Plastic Surgery: Volume 1: Principles (Plastic Surgery, 1) [5 ed.] 9780323810388, 9780323873772, 9780323810371, 0323810381

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Fifth Edition

Plastic Surgery Principles Volume One

Cover illustration “The Plastic Surgery Huddle” The concept and inspiration for the cover art was derived from a situation that we as plastic surgeons are all familiar with. It is that special time when you know there is a new or interesting case happening down the hall in your hospital. It might be a complex reconstruction, a new flap design or an unusual presentation. There is a buzz and a crowded OR with extra residents, Fellows, students, and colleagues around the table. The “Plastic Surgery huddle” includes additional hands scrubbed-in to assist, wanting to be involved, to learn, and to experience the innovation that is being performed. It is always dynamic, and it is always a learning situation. The color arrangement of the surgical caps/hats around the OR table is intentional. It borrows from the artist’s color wheel, which includes primary colors (red, yellow, and blue) and the secondary colors (orange, purple, and green). All the different colours are meant to represent the dynamic and unique diversity of our discipline as well as the sharing of ideas and collaboration that we all strive to promote in our wonderful specialty of Plastic Surgery. John L. Semple MD, MSc, FRCSC, FACS, LLD Head, Division of Plastic Surgery Women’s College Hospital Professor, Department of Surgery University of Toronto

Content Strategist: Lauren Boyle, Belinda Kuhn Content Development Specialists: Kathryn DeFrancesco, Rebecca Gruliow, Grace Onderlinde, Kevin Travers Project Managers: Anne Collett, Joanna Souch, Julie Taylor Designer: Miles Hitchen Marketing Manager: Mary McCabe-Dunn Video Liaison: Nicholas Henderson

Fifth Edition

Plastic Surgery Principles Volume One Volume Editors

Geoffrey C. Gurtner

Andrea L. Pusic

MD, FACS

MD

Professor and Chair, Department of Surgery Professor of Biomedical Engineering College of Medicine University of Arizona Tucson, AZ, United States

Chief, Division of Plastic and Reconstructive Surgery Brigham and Women’s Hospital Boston, MA, United States

Editor-in-Chief

Multimedia Editor

Peter C. Neligan

Daniel Z. Liu

MB, FRCS(I), FRCSC, FACS

MD

Professor Emeritus Surgery, Division of Plastic Surgery University of Washington Seattle, WA, United States

Reconstructive Microsurgeon Oncoplastic and Reconstructive Surgery City of Hope Chicago Zion, IL, United States

For additional online figures, videos, and video lectures visit Elsevier eBooks+

London, New York, Oxford, Philadelphia, St Louis, Sydney 2024

Elsevier 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

PLASTIC SURGERY, FIFTH EDITION Copyright © 2024, Elsevier Inc. All rights reserved.

First edition 1990 Second edition 2006 Third edition 2013 Fourth edition 2018 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www. elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Volume 1 ISBN: 978-0-323-81038-8 Volume 1 Ebook ISBN: 978-0-323-87377-2 6 volume set ISBN: 978-0-323-81037-1

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Last digit is the print number: 9

1

220

19 Repair, grafting, and engineering of cartilage

235

20 Repair and grafting of bone

265

21 Repair and grafting of peripheral nerve

295

22 Repair and grafting fat and adipose tissue

309

23 Vascular territories

321

24 Flap physiology, classification, and applications

346 414



18 Tissue engineering



206









Ramin Shayan and Karl-Anton Harms











17 Skin grafting

Shawn Loder, Benjamin Levi, and Audra Clark



xxvii xxviii xxix l li



Preface to the Fifth Edition List of Editors List of Contributors Acknowledgments Dedication



Contents



442

27 Principles of radiation therapy

452

28 Lymphedema: pathophysiology and basic science

472

29 Benign and malignant nonmelanocytic tumors of the skin and soft tissue

490

30 Melanoma

521

31 Implants and biomaterials

544

32 Transplantation in plastic surgery

555

33 Technology innovation in plastic surgery: a practical guide for the surgeon innovator

568

34 Robotics in plastic surgery

582

35 Digital technology in plastic surgery

594

36 Aesthetic improvement through noninvasive technologies

613

37 Education and teaching in plastic surgery

619

Joon Pio Hong and Peter C. Neligan









186

















Stelios C. Wilson and Charles H. Thorne





Michelle F. Griffin, Evan Fahy, Michael S. Hu, Elizabeth R. Zielins, Michael T. Longaker, and H. Peter Lorenz





16 Scar prevention, treatment, and revision

Kristo Nuutila, David E. Varon, and Indranil Sinha

Lynn Jeffers, Hatem Abou-Sayed, and Haley M. Jeffers



163

Stav Brown and Babak J. Mehrara

Karim A. Sarhane and Jesse C. Selber 

15 Wound healing



153

David Perrault, Leila Jazayeri, and Geoffrey C. Gurtner



14 Principles of cancer management



146



13 Health services research in plastic surgery Jacqueline N. Byrd and Kevin C. Chung



135



Sophocles H. Voineskos, Danny Young-Afat, Madelijn Gregorowitsch, Jonas A. Nelson, Anne F. Klassen, and Andrea L. Pusic

Yannick F. Diehm, Valentin Haug, Martin Kauke-Navarro, and Bohdan Pomahac







12 Patient-reported outcomes in plastic surgery





115





Sophocles H. Voineskos, Lucas Gallo, Andrea L. Pusic, and Achilleas Thoma





Dharshan Sivaraj, Dominic Henn, Timothy W. King, and Kellen Chen



11 Evidence-based medicine and health services research in plastic surgery



Paul N. Afrooz and Franklyn P. Cladis

Sydney Ch’ng and Alexander H.R. Varey





101











Rei Ogawa



10 Anesthesia and pain management in plastic surgery

Stav Brown, Michelle Coriddi, and Babak J. Mehrara



94



9 Patient safety in plastic surgery



Stephanie K. Schaub, Joseph Tsai, and Gabrielle M. Kane





83







Britta A. Kuehlmann, Eva Brix, and Lukas M. Prantl

66

8 Pre- and intra-operative imaging for plastic surgery









7 Digital photography in plastic surgery

Fu-Chan Wei, Sherilyn Keng Lin Tay, and Nidal F. Al Deek













26 Tissue expansion and implants

Jessica Erdmann-Sager and Christopher J. Pannucci





60



6 Value-based healthcare

Arash Momeni and Lawrence Cai





37

Daniel Z. Liu





5 Business principles for plastic surgeons

25 Principles and techniques of microvascular surgery

Justin M. Broyles, Clifford C. Sheckter, and Anaeze C. Offodile 2nd









32

C. Scott Hultman



24

4 The role of ethics in plastic surgery and medico-legal issues in plastic surgery Michele A. Manahan and B. Aviva Preminger



Steven F. Morris and G. Ian Taylor





Nichola Rumsey and Alex Clarke









3 Applying psychology to routine plastic surgery practice

J. Peter Rubin



9

Riccardo F. Mazzola and Isabella C. Mazzola



2 History of reconstructive and aesthetic surgery

Peter C. Neligan

Hollie A. Power, Kirsty Usher Boyd, Stahs Pripotnev, and Susan E. Mackinnon



1



1 Plastic surgery and innovation in medicine





edited by Geoffrey C. Gurtner and Andrea L. Pusic





Iris A. Seitz, Chad M. Teven, Bryce Hendren-Santiago, and Russell R. Reid



Volume One: Principles





Wei Liu, Guangdong Zhou, and Yilin Cao

Lydia Helliwell and Johanna N. Riesel

Contents

vi

38 Global plastic surgery





625



Johanna N. Riesel, Peter Nthumba, George Ho, and Amanda Gosman





634



Shane D. Morrison, William M. Kuzon Jr., and Jens U. Berli

Index





Miles G. Berry, James D. Frame III, and Dai M. Davies

39 Gender-affirming surgery



9.5 Facelift: Platysma-SMAS plication

652



9.6 Facelift: Lateral SMASectomy facelift

212

9.7 Facelift: The extended SMAS technique in facial rejuvenation

219

9.8 High SMAS facelift: combined single flap lifting of the jawline, cheek, and midface

236

9.9 The lift-and-fill facelift

282





Daniel C. Baker and Steven M. Levine









James M. Stuzin

Volume Two: Aesthetic



edited by J. Peter Rubin and Alan Matarasso





9.10 Neck rejuvenation

301

9.11 Male facelift

319



13



Ashley N. Amalfi, Josef G. Hadeed, and Smita R. Ramanadham









9.12 Secondary facelift irregularities and the secondary facelift

345

9.13 Perioral rejuvenation, including chin and genioplasty

390

9.14 Facial feminization

404







Timothy Marten and Dino Elyassnia

Jeremy T. Joseph, Gabriele C. Miotto, Felmont F. Eaves III, and Galen Perdikis





Anna R. Schoenbrunner and Jeffrey E. Janis



33



Stelios C. Wilson and Barry Zide

6 Local anesthesia





42



Malcolm D. Paul



47



Zoe Diana Draelos



8.1 Editors’ perspective: injectables and non-surgical resurfacing techniques

53

8.2 Injectables and resurfacing techniques: Soft-tissue fillers

54

8.3 Injectables and resurfacing techniques: Botulinum toxin/neurotoxins

73



11 Forehead rejuvenation

425

12 Endoscopic brow lift

441

13 Blepharoplasty

453



8.4 Injectables and resurfacing techniques: Lasers in aesthetic surgery

96

8.6 Minimally invasive multimodal facial rejuvenation

16 Facial fat grafting

559









Francesco M. Egro, Sydney R. Coleman, and J. Peter Rubin



567



18 Nasal analysis and anatomy

568

19 Open technique rhinoplasty

581



118

Luiz S. Toledo





Rod J. Rohrich and Paul N. Afrooz





Rod J. Rohrich and Paul N. Afrooz



20 Closed technique rhinoplasty





607



Mark B. Constantian

9.1 Editors’ perspective: surgical facial rejuvenation

130

9.2 Facial anatomy and aging

131





Alan Matarasso



Bryan Mendelson and Chin-Ho Wong

9.3 Principles and surgical approaches of facelift



21 Airway issues and the deviated nose

647

22 Secondary rhinoplasty

662







Ali Totonchi, Bryan Armijo, and Bahman Guyuron







David M. Kahn, Danielle H. Rochlin, and Ronald P. Gruber

149

23 Otoplasty and ear reduction

681

24 Hair restoration

690



9.4 Facelift: Facial rejuvenation with loop sutures: the MACS lift and its derivatives 180





Charles H. Thorne





484



513





Patrick Tonnard, Alexis Verpaele, and Rotem Tzur



Alan Matarasso







17 Editors’ perspective: nose



Richard J. Warren



Jong Woo Choi, Tae Suk Oh, Hong Lim Choi, and Clyde Ishii



8.5 Injectables and resurfacing techniques: Chemical peels





15 Asian facial cosmetic surgery

84

Richard H. Bensimon and Peter P. Rullan





Seth Z. Aschen and Henry M. Spinelli









14 Secondary blepharoplasty





Jonathan Cook, David M. Turer, Barry E. DiBernardo, and Jason N. Pozner





Renato Saltz and Eric W. Anderson



Rawaa Almukhtar and Sabrina G. Fabi





Richard Warren







424



Julius Few Jr., and Marco Ellis

Kavita Mariwalla



10 Editors’ perspective: brow and eye











Patrick R. Keller, Matthew Louis, and Devin Coon











J. Peter Rubin





Alan Matarasso

Section II: Aesthetic Surgery of the Face 7 Non-surgical skin care and rejuvenation



Ali Totonchi and Bahman Guyuron

5 Anatomic blocks of the face and neck





25





Timothy Marten and Dino Elyassnia



4 Pain management in plastic surgery



James E. Zins and Jacob Grow



Section I: Aesthetic Anesthesia Techniques 3 Essential elements of patient safety in aesthetic plastic surgery 18





Stav Brown, Justin L. Bellamy, and Rod J. Rohrich

2 Principles of practice management and social media for cosmetic surgery



Timothy Marten and Dino Elyassnia

1



Michelle B. Locke and Foad Nahai







1 Managing the aesthetic surgery patient



203







Alfonso Barrera and Victor Zhu

Contents

Section III: General Aesthetic Surgery 25.1 Editors’ perspective: liposuction





700

Volume Three: Craniofacial, Head and Neck Surgery and Pediatric Surgery

701

Part 1: Craniofacial, Head and Neck Surgery: edited by Richard A. Hopper



J. Peter Rubin

25.2 Liposuction: a comprehensive review of techniques and safety







Gianfranco Frojo, Jayne Coleman, and Jeffrey Kenkel

25.3 Correction of liposuction deformities with the SAFE liposuction technique

723

26 Editors’ perspective: abdominal contouring

731

27 Abdominoplasty

732







Simeon H. Wall Jr. and Paul N. Afrooz





Alan Matarasso









28 Lipoabdominoplasty with anatomical definition: a new concept in abdominal aesthetic surgery 775







785

30 Bra-line back lift

786

31 Belt lipectomy

792







Joseph Hunstad and Saad A. Alsubaie





110



5 Secondary treatment of acquired cranio-orbital deformities 138

155

6.2 Three-dimensional virtual planning in orthognathic surgery

157

6.3 Computerized surgical planning in head and neck reconstruction

173



Richard A. Hopper





Pradip R. Shetye and Srinivas M. Susarla



Maureen Beederman, Adam S. Jacobson, David L. Hirsch, and Jamie P. Levine





834



34 Circumferential approaches to truncal contouring: lower bodylift with autologous gluteal flaps for augmentation and preservation of gluteal contour

841



9 Post-oncologic midface reconstruction: the Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center approaches

217



35.2 Buttock augmentation with implants

855





Jose Abel De la Peña Salcedo, Jocelyn Celeste Ledezma Rodriguez, and David Gonzalez Sosa





854



J. Peter Rubin

10 Local flaps for facial coverage

229

11 Lip reconstruction

256

12 Oral cavity, tongue, and mandibular reconstructions

275

13 Hypopharyngeal, esophageal, and neck reconstruction

302

14 Secondary facial reconstruction

336

15 Facial paralysis

359

16 Surgical management of facial pain, including migraines

390

17 Facial feminization

400





Nicholas Do and John Brian Boyd





Julian J. Pribaz and Mitchell Buller









Ming-Huei Cheng

869



Constantino G. Mendieta, Thomas L. Roberts III, and Terrence W. Bruner

190



Matthew M. Hanasono and Peter G. Cordeiro

35.1 Editors’ perspective: buttock augmentations

35.3 Buttock shaping with fat grafting and liposuction

8 Overview of head and neck soft-tissue and bony tumors







Robert F. Centeno and Jazmina M. Gonzalez



188



Sydney Ch’ng, Edwin Morrison, Pratik Rastogi, and Yu-Ray Chen





7 Introduction to post-oncologic reconstruction Zoe P. Berman and Eduardo D. Rodriguez

Joseph P. Hunstad and Nicholas A. Flugstad











4 Auricular construction

6.1 Computerized surgical planning: introduction

819

33 Circumferential approaches to truncal contouring: autologous buttocks augmentation with purse-string gluteoplasty

















32 Circumferential approaches to truncal contouring in massive weight loss patients: the lower lipo-bodylift Dirk F. Richter and Nina Schwaiger



52







Amitabh Singh and Al S. Aly



3 Aesthetic nasal reconstruction





J. Peter Rubin



39



Allan B. Billig and Oleh M. Antonyshyn

29 Editors’ perspective: truncal contouring

2 Scalp and forehead reconstruction

Dale J. Podolsky, Leila Kasrai, and David M. Fisher





2



Frederick J. Menick



Osvaldo Ribeiro Saldanha, Andrés F. Cánchica Cano, Taisa Szolomicki, Osvaldo Saldanha Filho, and Cristianna Bonetto Saldanha



Alexander F. Mericli and Jesse C. Selber



Alan Matarasso

1 Management of craniomaxillofacial fractures Srinivas M. Susarla, Russell E. Ettinger, and Paul N. Manson





vii









36 Upper limb contouring



Margaret Luthringer, Nikita O. Shulzhenko, and Joseph F. Capella



37 Medial thigh





39 Energy devices in aesthetic surgery

919

40 Aesthetic genital surgery

926





David Turer, Jonathan Cook, Jason Pozner, and Barry DiBernardo





Gary J. Alter

Index





951







Simeon C. Daeschler, Ronald M. Zuker, and Gregory H. Borschel

898



Jonathan W. Toy and J. Peter Rubin



Afaaf Shakir and Lawrence J. Gottlieb



38 Post-bariatric reconstruction



891



Samantha G. Maliha and Jeffrey Gusenoff



Min-Jeong Cho and Peirong Yu

878





Anna Schoenbrunner and Jeffrey E. Janis







Luis Capitán, Daniel Simon, and Fermín Capitán-Cañadas

Contents

viii

Part 2: Pediatric Surgery: edited by Joseph E. Losee

25.2 Nonsyndromic craniosynostosis



18 Embryology of the craniofacial complex





451



Joseph E. Losee and Michael R. Bykowski

19.2 Rotation advancement cheiloplasty

456

19.3 Extended Mohler repair

488









Roberto L. Flores



19.4 Anatomic subunit approximation approach to unilateral cleft lip repair



Alexandra Junn, John T. Smetona, Michael Alperovich, and John A. Persing

26 Craniofacial microsomia





27 Idiopathic progressive hemifacial atrophy

887

28 Robin sequence

902



519

21.1 Cleft palate: introduction

538





John B. Mulliken and Daniel M. Balkin





Michael R. Bykowski and Joseph E. Losee





29 Treacher Collins syndrome





Section III: Pediatrics 30 Congenital melanocytic nevi

542

21.3 Double opposing Z-palatoplasty

549



21.4 Buccal myomucosal flap palate repair

557



21.5 The buccal fat pad flap

567

Brian Sommerlad





Jordan N. Halsey and Richard E. Kirschner







Robert Joseph Mann







James D. Vargo and Steven R. Buchman











21.8 Orthodontics in cleft lip and palate management



Alvaro A. Figueroa, Alexander L. Figueroa, Gerson R. Chinchilla, and Marta Alvarado



21.9 Velopharyngeal dysfunction

592

974

33 Pediatric tumors

988

34 Conjoined twins

1001







Matthew R. Greives, George Washington, Sahil Kapur, and Michael Bentz





Anna R. Carlson, Gregory G. Heuer, and Jesse A. Taylor

1011



Volume Four: Lower Extremity, Trunk and Burns 1 Comprehensive lower extremity anatomy





1



Rajiv P. Parikh and Grant M. Kleiber

2 Management of lower extremity trauma

52

Section I: Lower Extremity Surgery 3.1 Lymphedema: introduction and editors’ perspective

76



21.10 Secondary deformities of the cleft lip, nose, and palate



Han Zhuang Beh, Andrew M. Ferry, Rami P. Dibbs, Edward P. Buchanan, and Laura A. Monson

edited by David H. Song and Joon Pio Hong

618



Richard E. Kirschner, Hannah J. Bergman, and Adriane L. Baylis



32 Pediatric chest and trunk deformities

Index



952



Arin K. Greene and John B. Mulliken

583



Katelyn Kondra, Eloise Stanton, Christian Jimenez, Erik M. Wolfswinkel, Stephen Yen, Mark Urata, and Jeffrey Hammoudeh







21.7 Alveolar clefts

31 Vascular anomalies

575



Mirko S. Gilardino, Sabrina Cugno, and Abdulaziz Alabdulkarim

935



Sara R. Dickie, Neta Adler, and Bruce S. Bauer



21.6 Oral fistula closure

923



Irene Mathijssen







Sofia Aronson, Chad A. Purnell, and Arun K. Gosain

21.2 Straight line repair with intravelar veloplasty (IVVP)



Peter J. Taub, Kathryn S. Torok, Daniel H. Glaser, and Lindsay A. Schuster

499

20 Repair of bilateral cleft lip



859



Craig B. Birgfeld and Scott P. Bartlett







849





Raymond W. Tse and David M. Fisher



25.4 Neurosurgical and developmental issues in craniosynostosis





Philip Kuo-Ting Chen and Lucia Pannuto



827



Richard A. Hopper and Benjamin B. Massenburg

Section I: Clefts 19.1 Unilateral cleft lip: introduction

25.3 Multisutural syndromic synostosis





808



Sameer Shakir and Jesse A. Taylor

442



Jingtao Li and Jill A. Helms









Hyunsuk Peter Suh





Han Zhuang Beh, Rami P. Dibbs, Andrew M. Ferry, Robert F. Dempsey, Edward P. Buchanan, and Larry H. Hollier Jr.

21.11 Cleft and craniofacial orthognathic surgery





Stephen B. Baker, Brian L. Chang, and Anusha Singh

Section II: Craniofacial 22 Pediatric facial fractures













747





James P. Bradley and Henry K. Kawamoto Jr.

25.1 Craniosynostosis: introduction





Christopher R. Forrest and Johanna N. Riesel

3.3 Lymphaticovenular bypass

92



Wei F. Chen, Lynn M. Orfahli, and Vahe Fahradyan

24 Craniofacial clefts



Eric Arnaud, Giovanna Paternoster, Roman Khonsari, Samer E. Haber, and Syril James



3.2 Imaging modalities for diagnosis and treatment of lymphedema 78 Balazs Mohos and Chieh-Han John Tzou

708 726



Joon Pio Hong and David H. Song

661

23 Orbital hypertelorism







John T. Smetona, Jesse A. Goldstein, Michael R. Bykowski, and Joseph E. Losee



636



102

3.5 Debulking strategies and procedures: liposuction of leg lymphedema

111





Rebecca M. Garza and David W. Chang



775

3.4 Vascularized lymph node transplant



Håkan Brorson



3.6 Debulking strategies and procedures: excision 120

Hung-Chi Chen and Yueh-Bih Tang



Contents

4 Lower extremity sarcoma reconstruction

128

5 Reconstructive surgery: lower extremity coverage

154







Andrés A. Maldonado, Günter K. Germann, and Michael Sauerbier





15 Reconstruction of acquired vaginal defects

452

16 Pressure sores

462







6.1 Diagnosis, treatment, and prevention of lower extremity pain 180



17 Perineal reconstruction



6.2 Targeted muscle reinnervation in the lower extremity



Section III: Burn Surgery 18 Burn, chemical, and electrical injuries





190





6.3 Lower extremity pain: regenerative peripheral nerve interfaces



19 Extremity burn reconstruction

203







210



Marco Innocenti, Stephen Kovach III, Elena Lucattelli, and L. Scott Levin



589



Section I: Aesthetic Breast Surgery 1 Preoperative assessment and planning of the aesthetic breast patient









9.3 Diabetic foot: management of vascularity and considerations in soft-tissue reconstruction 296











11 Reconstruction of the chest



12 Reconstruction of the posterior trunk



13 Abdominal wall reconstruction

28



4 Autologous fat transfer: fundamental principles and application for breast augmentation 52

388



Gregory A. Dumanian

14.1 Gender confirmation surgery: diagnosis and management

407



414

Kaylee B. Scott, Dana N. Johns, and Cori A. Agarwal

8 Short scar breast reduction

102

9 Reduction mammaplasty with inverted-T techniques

131







10 Breast implant illness: diagnosis and management

154



421

14.4 Breast, chest wall, and facial considerations in gender affirmation 439 

92



Caroline A. Glicksman and Patricia McGuire





7 Prevention and management of complications following breast augmentation and mastopexy







Alexander Y. Li, Walter C. Lin, and Bauback Safa

83



Maurice Y. Nahabedian



Loren Schechter and Rayisa Hontscharuk

6 Mastopexy after massive weight loss

Elizabeth Hall-Findlay, Elisa Bolletta, and Gustavo Jiménez Muñoz Ledo



14.3 Gender affirmation surgery, female to male: phalloplasty; and correction of male genital defects

69







14.2 Gender confirmation surgery, male to female: vaginoplasty



M. Bradley Calobrace and Chester J. Mays



Loren Schechter and Rayisa Hontscharuk

5 Augmentation mastopexy

Francesco M. Egro and J. Peter Rubin

354



Reuben A. Falola, Nicholas F. Lombana, Andrew M. Altman, and Michel H. Saint-Cyr





Justin L. Perez, Daniel J. Gould, Michelle Spring, and W. Grant Stevens

327



Brian L. Chang, Banafsheh Sharif-Askary, and David H. Song



3 Primary breast augmentation with implants

Roger Khalil Khouri, Raul A. Cortes, and Daniel Calva-Cerquiera

311



J. Andres Hernandez, Andrew Nagy Atia, and Scott Thomas Hollenbeck



13





Section II: Trunk, Perineum, and Transgender 10 Trunk anatomy





Charles Randquist



Paige K. Dekker, Kevin G. Kim, and Karen K. Evans

2 Current status of breast implants Patrick Mallucci and Giovanni Bistoni

270

Jayson N. Atves, John D. Miller, and John S. Steinberg



1









Kiya Movassaghi and Christopher N. Stewart

9.2 Diabetic foot: management of wounds and considerations in biomechanics and amputations



610

edited by Maurice Y. Nahabedian

265



Kevin G. Kim, Paige K. Dekker, John D. Miller, Jayson N. Atves, John S. Steinberg, and Karen K. Evans





Sebastian Q. Vrouwe and Lawrence J. Gottlieb

Volume Five: Breast

9.1 Diabetic foot: introduction





228





21 Pediatric burns





Romina Deldar, Zoe K. Haffner, Adaah A. Sayyed, John S. Steinberg, Karen K. Evans, and Christopher E. Attinger



561



Index

8 Foot reconstruction



20 Management of the burned face and neck Vinita Puri and Venkateshwaran Narasiman

7 Skeletal reconstruction



538



S. Raja Sabapathy, R. Raja Shanmugakrishnan, and Vamseedharan Muthukumar



Nishant Ganesh Kumar, Theodore A. Kung, and Paul S. Cederna

501



Raphael C. Lee and Chad M. Teven



Brian L. Chang and Grant M. Kleiber

489



Ping Song, Hakim Said, and Otway Louie



Brian L. Chang and Grant M. Kleiber



Ibrahim Khansa and Jeffrey E. Janis



Joon Pio Hong



Leila Jazayeri, Andrea L. Pusic, and Peter G. Cordeiro





ix



11 Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): diagnosis and management 160



Mark W. Clemens, Eliora A. Tesfaye, and Anand Deva

x

Contents

12 A critical analysis of irrigation solutions in breast surgery Grace Keane, Marissa M. Tenenbaum, and Terence M. Myckatyn

13 Imaging and surveillance in patients with breast implants Bradley Bengtson, Patricia McGuire, Caroline Glicksman, and Pat Pazmiño

174

182

191

15 Management strategies for gynecomastia

200

Michele Ann Manahan

16 Management options for gender affirmation surgery of the breast Ara A. Salibian, Gaines Blasdel, and Rachel Bluebond-Langner

Section II: Reconstructive Breast Surgery 17 Preoperative evaluation and planning for breast reconstruction following mastectomy Saïd C. Azoury and Liza C. Wu

18 Perfusion assessment techniques following mastectomy and reconstruction Alex Mesbahi, Matthew Cissell, Mark Venturi, and Louisa Yemc

19 Introduction to prosthetic breast reconstruction Maurice Y. Nahabedian

20 One- and two-stage prepectoral reconstruction with prosthetic devices

Alberto Rancati, Claudio Angrigiani, Maurizio Nava, Dinesh Thekkinkattil, Raghavan Vidya, Marcelo Irigo, Agustin Rancati, Allen Gabriel, and Patrick Maxwell

21 One-stage dual-plane reconstruction with prosthetic devices Brittany L. Vieira and Amy S. Colwell

22 Two-stage dual-plane reconstruction with prosthetic devices Ara A. Salibian and Nolan S. Karp

23 Two-stage prosthetic reconstruction with total muscle coverage Colleen M. McCarthy and Peter G. Cordeiro

24 Skin reduction using “smile mastopexy” technique in breast reconstruction Kiya Movassaghi and Christopher N. Stewart

25 Management of complications of prosthetic breast reconstruction Nima Khavanin and John Y.S. Kim

26 Secondary refinement procedures following prosthetic breast reconstruction Roy de Vita and Veronica Vietti Michelina

27 Introduction to autologous breast reconstruction with abdominal free flaps Maurice Y. Nahabedian

28 Breast reconstruction with the pedicle TRAM flap Jake C. Laun and Julian J. Pribaz

355

30 Autologous breast reconstruction with the DIEP flap

371

Dennis C. Hammond

Adrian McArdle and Joan E. Lipa

31 Autologous breast reconstruction with the free TRAM flap 396

14 Breast implant explantation: indications and strategies to optimize aesthetic outcomes Connor Crowley, M. Bradley Calobrace, Mark W. Clemens, and Neil Tanna

29 Breast reconstruction with the latissimus dorsi flap

207

Jin Sup Eom and Hyunho Han

32 Autologous breast reconstruction with the superficial inferior epigastric artery (SIEA) flap

413

33 Introduction to autologous reconstruction with alternative free flaps

420

34 Gluteal free flaps for breast reconstruction

424

Pierre Chevray

Maurice Y. Nahabedian

Salih Colakoglu and Gedge D. Rosson

35 Autologous breast reconstruction with medial thigh flaps 433 222 234

Venkat V. Ramakrishnan and Nakul Gamanlal Patel

36 Autologous breast reconstruction with the profunda artery perforator (PAP) flap

450

37 Autologous reconstruction with the lumbar artery perforator (LAP) free flap

461

38 Hybrid breast reconstruction: combining flaps and implants

468

39 Innervation of autologous flaps

475

40 Stacked and conjoined flaps

481

41 Management of complications following autologous breast reconstruction

488

42 Enhanced recovery after surgery (ERAS) protocols in breast surgery: techniques and outcomes

498

43 Secondary procedures following autologous reconstruction

516

44 Introduction to oncoplastic breast surgery

526

45 Partial breast reconstruction using reduction and mastopexy techniques

533

46 Oncoplastic breast reconstruction: local flap techniques

547

47 Surgical and non-surgical management of breast cancer-related lymphedema

556

Adam T. Hauch, Hugo St. Hilaire, and Robert J. Allen, Sr.

Phillip Blondeel and Dries Opsomer

239

Arash Momeni, Hani Sbitany, and Suhail K. Kanchwala

247

Aldona J. Spiegel and Janak A. Parikh Nicholas T. Haddock and Sumeet S. Teotia

265

Anne C. O’Neill, Vincent J. Choi, and Stefan O.P. Hofer

280 293 298

Nicholas F. Lombana, Reuben A. Falola, John C. Cargile, and Michel H. Saint-Cyr

Jian Farhadi and Vendela Grufman Maurice Y. Nahabedian

304

Albert Losken, Nusaiba F. Baker, and Alexandre Munhoz

317

Moustapha Hamdi and Claudio Angrigiani

336 340

Ketan M. Patel, Emma C. Koesters, Rachel Lentz, and Orr Shauly

Contents



48 Breast reconstruction and radiotherapy: indications, techniques, and outcomes

567



Jaume Masià, Cristhian D. Pomata, and Javier Sanz



49 Robotic-assisted autologous breast reconstruction

337

16 Tumors of the hand

356



581

50 Total breast reconstruction by external vacuum expansion (EVE) and autologous fat transfer (AFT)

590

51 Current options for nipple reconstruction

603













Kashyap K. Tadisina, Justin M. Sacks, and Mitchell A. Pet







Andrzej Piatkowski and Roger K. Khouri



Section III: Specific Disorders 15 Infections of the hand



Andrew O’Brien, Ryan P. Calfee, Jana Dengler, and Amy M. Moore

Karim A. Sarhane and Jesse C. Selber



xi





David Chi and Justin M. Sacks

Index



610

17 Dupuytren’s disease

384



James K-K. Chan, Paul M.N. Werker, and Jagdeep Nanchahal



18 Osteoarthritis in the hand and wrist

411

19 Rheumatologic conditions of the hand and wrist

449

20 Occupational disorders of the hand

491





Paige M. Fox, J. Henk Coert, and Steven L. Moran







Douglas M. Sammer and Kevin C. Chung

Volume Six: Hand and Upper Extremity



liii



James Chang





1



James Chang, Anais Legrand, Francisco J. Valero-Cuevas, Vincent R. Hentz, and Robert A. Chase



3 Diagnostic imaging of the hand and wrist

70



Alphonsus K.S. Chong, Janice Liao, and David M.K. Tan





147

8 Fractures and dislocations of the wrist and distal radius

173





Steven C. Haase and Kevin C. Chung

9 Flexor tendon injuries and reconstruction

193



Jin Bo Tang

10 Extensor tendon injuries

230

11 Replantation

250



Kai Megerle and Karl-Josef Prommersberger







Dong Chul Lee and Eugene Park



12 Reconstructive surgery of the mutilated hand

272



S. Raja Sabapathy and Hari Venkatraman











27 Free-functioning muscle transfer







14 Thumb reconstruction: Microsurgical techniques

320



704

30 The stiff hand

716







31 The painful hand



735





Michael Tonkin and Kerby C. Oberg

33 Congenital hand II: Malformations – whole limb

770

34 Congenital hand III: Malformations – abnormal axis differentiation – hand plate: proximodistal and radioulnar

790





Aaron Berger, Soumen Das De, Bhaskaranand Kumar, and Pundrique Sharma





680

Section VI: Congenital Disorders 32 Congenital hand I: Embryology, classification, and principles 746



305

Jeffrey B. Friedrich, Nicholas B. Vedder, and Elisabeth Haas-Lützenberger

665

29 The spastic hand

Hazel Brown, Anna Berridge, Dennis Hazell, Parashar Ramanuj, and Tom J. Quick

­

Nidal F. Al Deek and Fu-Chan Wei

638



David T. Netscher, Rita E. Baumgartner, Kimberly Goldie Staines, and Logan W. Carr





26 Nerve transfers







13 Thumb reconstruction: Non-microsurgical techniques

605



Caroline Leclercq, Nathalie Bini, and Charlotte Jaloux





25 Tendon transfers

Hee Chang Ahn, Jung Soo Yoon, and Neil F. Jones

Warren C. Hammert and Randy R. Bindra





Section V: Challenging Disorders 28 The ischemic hand



7 Hand fractures and joint injuries



585



Kirsty Usher Boyd, Ida K. Fox, and Susan E. Mackinnon

123





24 Tetraplegia



Simeon C. Daeschler, Kristen M. Davidge, Leila Harhaus, and Gregory H. Borschel

Amanda Brown, Brian A. Mailey, and Michael W. Neumeister



552



Neil F. Jones



Section II: Trauma Reconstruction 6 Nail and fingertip reconstruction

23 Brachial plexus injuries: adult and pediatric

Carina Reinholdt and Catherine Curtin

109



Margaret Fok, Jason R. Kang, Christopher Cox, and Jeffrey Yao







5 Principles of internal fixation

526



Johnny Chuieng-Yi Lu and David Chwei-Chin Chuang

95



Eugene Park, Jonay Hill, Vanila M. Singh, and Subhro K. Sen





Simon Farnebo, Johan Thorfinn, and Lars B. Dahlin



4 Anesthesia for upper extremity surgery



499



22 Peripheral nerve repair and reconstruction

49



Ryosuke Kakinoki







2 Examination of the upper extremity





Elisabet Hagert and Donald Lalonde

Section I: Principles of Hand Surgery 1 Anatomy and biomechanics of the hand



Section IV: Nerve Disorders 21 Nerve entrapment syndromes

 





Celine Yeung and Steven J. McCabe

Introduction: Plastic surgery contributions to hand surgery







Brinkley K. Sandvall and Charles A. Goldfarb

xii

Contents

35 Congenital hand IV: Malformations – abnormal axis differentiation – hand plate: unspecified axis

824

36 Congenital hand V: Deformations and dysplasias – variant growth

842

Christianne A. van Nieuwenhoven

Wee Leon Lam, Xiaofei Tian, Gillian D. Smith, and Shanlin Chen

868

38 Congenital hand VII: Dysplasias – congenital contractures

898

Ellen Satteson, Paul C. Dell, Xiao Fang Shen, and Harvey Chim

39 Growth considerations in the pediatric upper extremity Marco Innocenti and Sara Calabrese

930

41 Upper extremity composite allotransplantation

949

42 Aesthetic hand surgery

963

43 Hand therapy

983

Gregory Ara Dumanian, Sumanas W. Jordan, and Jason Hyunsuk Ko

Christopher D. Lopez, Joseph Lopez, Jaimie T. Shores, W.P. Andrew Lee, and Gerald Brandacher

37 Congenital hand VI: Dysplasias – tumorous conditions Amir H. Taghinia and Joseph Upton

Section VII: New Directions 40 Treatment of the upper extremity amputee

David Alan Kulber and Meghan C. McCullough Wendy Moore, Minnie Mau, and Brittany N. Garcia

Index

909

999

Video Contents Volume One Chapter 8: Pre- and intra-operative imaging for plastic surgery 8.1: Injection and monitoring of indocyanine green (ICG) using SPY for real-time lymphatic mapping in patients with lymphedema Arash Momeni and Lawrence Cai

Chapter 15: Wound healing 15.1: Treatment of left ischial pressure ulcer Kristo Nuutila, David E. Varon, and Indranil Sinha

Chapter 17: Skin grafting 17.1: Harvesting a split-thickness skin graft Dennis P. Orgill

Chapter 19: Repair, grafting, and engineering of cartilage 19.1: Surgical procedure of the implantation of in vitro engineered human ear cartilage 19.2: Follow-up analysis of auricular shape and structure, and mechanical property Wei Liu, Guangdong Zhou, and Yilin Cao

Chapter 27: Principles of radiation therapy 27.1: CT simulation and patient setup 27.2: Treatment planning Stephanie K. Schaub, Joseph Tsai, and Gabrielle M. Kane

Chapter 34: Robotics in plastic surgery 34.1: Robotic microsurgery 34.2: Robotic rectus abdominis muscle flap harvest 34.3: Trans-oral robotic surgery 34.4: Robotic latissimus dorsi muscle harvest 34.5: Robotic lymphovenous bypass Jesse C. Selber

Chapter 39: Gender-affirming Surgery 39.1: Pre-operative markings for double incision and free nipple grafting mastectomy. 39.2: Surgical approach to double incision and free nipple grafting mastectomy Edwin Wilkins, Shane D. Morrison, and Martin P. Morris 39.3: Creation of tube-in-tube phalloplasty Jens Urs Berli and Srdjan Kamenko 39.4: Surgical approach to penile inversion vaginoplasty Shane D. Morrison, Martin P. Morris, and William M. Kuzon

Volume Two

Chapter 9.3: Principles and surgical approaches of facelift 9.3.1: Parotid masseteric fascia 9.3.2: Anterior incision 9.3.3: Posterior incision 9.3.4: Facelift skin flap 9.3.5: Buccal fat pad elevation 9.3.6: Facial fat injection Richard J. Warren 9.3.7: Anthropometry, cephalometry, and orthognathic surgery Jonathon S. Jacobs, Jordan M.S. Jacobs, and Daniel I. Taub

Chapter 9.4: Facelift: Facial rejuvenation with loop sutures: the MACS lift and its derivatives 9.4.1: Loop sutures MACS facelift Patrick L. Tonnard

Chapter 9.5: Facelift: Platysma-SMAS plication 9.5.1: Platysma-SMAS plication Dai M. Davies and Miles G. Berry

Chapter 9.9: The lift-and-fill facelift 9.9.1: Adjunctive fat grafting during facelift 9.9.2: Face-lift incision planning Rod J. Rohrich and Erez Dayan

Chapter 9.10: Neck rejuvenation 9.10.1: Intraoperative dissection demonstrating the location of the great auricular nerve during facelift surgery 9.10.2: Intraoperative demonstration of facelift maneuvers in the midface that contribute to neck rejuvenation 9.10.3: Simulated components of neck rejuvenation approached through the submental incision on a fresh cadaver dissection James E. Zins and Jacob Grow 9.10.4: The anterior only approach to the neck James E. Zins, Colin M. Morrison, and C.J. Langevin

Chapter 9.14: Facial feminization 9.14.1: Markings for hairline lowering surgery 9.14.2: Burring of lateral orbital rim 9.14.3: Burring of mandibular body Patrick R. Keller, Matthew Louis, and Devin Coon

Chapter 11: Forehead rejuvenation 11.1: Traditional open brow lift 11.2: Endoscopic brow lift 11.3: Modified lateral brow lift 11.4: Gliding brow lift Richard Warren

Chapter 8.3: Injectables and resurfacing techniques: Botulinum toxin/neurotoxins

Chapter 13: Blepharoplasty

8.3.1: Botulinum toxin injection technique Rawaa Almukhtar and Sabrina G. Fabi

13.1: Perioribital rejuvenation Julius Few Jr. and Marco Ellis

xiv

Video Contents

Chapter 15: Asian facial cosmetic surgery

Chapter 38: Post-bariatric reconstruction

15.1: Nonincisional double eyelidplasty Yeon Jun Kim 15.2: Incisional double eyelidplasty – pretarsal preparation Hong Lim Choi 15.3: Double fold fixation Hong Lim Choi 15.4: Lateral canthal lengthening Yeon Jun Kim 15.5: Medial epicanthoplasty 15.6: Eyelidplasty: Non-incisional method 15.7: Rhinoplasty 15.8: Subclinical ptosis correction (total) 15.9: Secondary rhinoplasty: septal extension graft and costal cartilage strut fixed with K-wire Kyung S. Koh, Jong Woo Choi, and Clyde H. Ishii

38.1: Post-bariatric reconstruction – bodylift procedure J. Peter Rubin and Jonathan W. Toy

Chapter 16: Facial fat grafting 16.1: Structural fat grafting of the face Sydney R. Coleman and Alesia P. Saboeiro

Volume Three Chapter 3: Aesthetic nasal reconstruction 3.1: The three-stage folded forehead flap for cover and lining 3.2: First-stage transfer and intermediate operation Frederick J. Menick

Chapter 4: Auricular construction 4.1: Total auricular construction Akira Yamada

Chapter 5: Secondary treatment of acquired cranio-orbital deformities

Chapter 19: Open technique rhinoplasty

5.1: Temporalis muscle flap 5.2: Orbitozygomatic osteotomy Oleh M. Antonyshyn

19.1: Open technique rhinoplasty Allen L. Van Beek

Chapter 8: Overview of head and neck soft-tissue and bony tumors

Chapter 23: Otoplasty and ear reduction 23.1: Setback otoplasty Leila Kasrai

Chapter 24: Hair restoration 24.1: My preferred hair transplantation technique: A 28 year experience Alfonso Barrera and Victor Zhu

Chapter 27: Abdominoplasty 27.1: Abdominoplasty markings 27.2: Secondary abdominoplasty Alan Matarasso

Chapter 28: Lipoabdominoplasty with anatomical definition: a new concept in abdominal aesthetic surgery 28.1: Lipoabdominoplasty (including secondary lipo) Osvaldo Ribeiro Saldanha, Sérgio Fernando Dantas de Azevedo, Osvaldo Ribeiro Saldanha Filho, Cristianna Bonetto Saldanha, and Luis Humberto Uribe Morelli

Chapter 35.2: Buttock augmentation with implants 35.2.1: Buttock augmentation Terrence W. Bruner, José Abel De la Peña Salcedo, Constantino G. Mendieta, and Thomas L. Roberts

Chapter 36: Upper limb contouring 36.1: Brachioplasty Joseph F. Capella, Margaret Luthringer, and Nikita Shulzhenko 36.2: Upper limb contouring Joseph F. Capella, Matthew J. Travato, and Scott Woehrle

8.1: Surgical approaches to the facial skeleton Yu-Ray Chen, You-Wei Cheong, and Alberto Cordova-Aguilar

Chapter 10: Local flaps for facial coverage 10.1: Facial artery perforator flap 10.2: Local flaps for facial coverage Peter C. Neligan

Chapter 12: Oral cavity, tongue, and mandibular reconstructions 12.1: Profunda artery perforator flap for tongue, inferior maxilla and lower lip defects 12.2: Osteomyocutaneous peroneal artery-based combined flap for reconstruction of type II mandibular defects Ming-Huei Cheng

Chapter 13: Hypopharyngeal, esophageal, and neck reconstruction 13.1: Reconstruction of pharyngoesophageal defects with the anterolateral thigh flap Peirong Yu

Chapter 15: Facial paralysis 15.1: Facial paralysis Eyal Gur 15.2: Facial paralysis 15.3: Cross facial nerve graft 15.4: Gracilis harvest Peter C. Neligan 15.5: Intraoperative gracilis stimulation 15.6: Intraoperative facial nerve stimulation Simeon C. Daeschler, Ronald M. Zuker, and Greogry H. Borschel

Chapter 37: Medial thigh

Chapter 16: Surgical management of facial pain, including migraines

37.1: Thighplasty Samantha G. Maliha and Jeffrey Gusenoff

16.1: Frontal trigger site injection Jeffrey E. Janis and Anna Schoenbrunner

Video Contents

Chapter 17: Facial feminization

Chapter 23: Orbital hypertelorism

17.1: Forehead reconstruction 17.2: Lower jaw and chin contouring Fermin Capitán-Cañadas, Luis Capitán, and Daniel Simon

23.1: Box-shift osteotomy Eric Arnaud

Chapter 19.2: Rotation advancement cheiloplasty 19.2.1: Repair of unilateral cleft lip Philip Kuo-Ting Chen, M. Samuel Noordhoff, Frank Chun-Shin, Chang, and Fuan Chiang Chan 19.2.2: Unilateral cleft lip and palate Philip Kuo-Ting Chen and Lucia Pannuto

Chapter 19.4: Anatomic subunit approximation approach to unilateral cleft lip repair 19.4.1: Medial lip checkpoints David M. Fisher and Raymond W. Tse 19.4.2: Unilateral cleft lip repair – anatomic subunit approximation technique David M. Fisher

Chapter 21.2: Straight line repair with intravelar veloplasty (IVVP) 21.2.1: Straight line repair of the palate with intravelar veloplasty (IVVP) Brian Sommerlad

xv

Chapter 28: Robin sequence 28.1: Tongue lip adhesion technique demonstrated and narrated by the senior author 28.2: Mandibular distraction Arun K. Gosain and Chad A. Purnell

Chapter 29: Treacher Collins syndrome 29.1: Lateral canthotomy 29.2: Ptosis correction 29.3: Dermisfat graft cheek Irene Mathijssen

Chapter 31: Vascular anomalies 31.1: Lip hemangioma Arin K. Greene

Chapter 32: Pediatric chest and trunk deformities 32.1: Cleft sternum 32.2: Thoracic ectopia cordis Han Zhuang Beh, Andrew M. Ferry, Rami P. Dibbs, Edward P. Buchanan, and Laura A. Monson

Chapter 21.3: Double opposing Z-palatoplasty 21.3.1: The Furlow double-opposing Z-palatoplasty Richard E. Kirschner and Jordan N. Halsey

Chapter 21.6: Oral fistula closure 21.6.1: Mobilization of the BFP flap for interposition Mirko S. Gilardino, Sabrina Cugno, and Abdulaziz Alabdulkarim

Volume Four Chapter 3.2: Imaging modalities for diagnosis and treatment of lymphedema

21.7.1: Alveolar bone graft: bone morphogenic protein & demineralized bone matrix Katelyn Kondra, Eloise Stanton, Christian Jimenez, Erik M. Wolfswinkel, Stephen Yen, Mark Urata, and Jeffrey Hammoudeh

3.2.1: ICG lymphangiography for lymphatic mapping before LVA procedure 3.2.2: Microscope-integrated NIRF imaging confirms LVA patency after the anastomosis 3.2.3: UHF-US records the contraction of a functional lymph vessel Balazs Mohos and Chieh-Han John Tzou

Chapter 21.9: Velopharyngeal dysfunction

Chapter 3.3: Lymphaticovenular bypass

21.9.1: Adequate velopharyngeal closer for speech 21.9.2: Velopharyngeal incompetence 21.9.3: Velopharyngeal insufficiency Richard E. Kirschner and Adriane L. Baylis

3.3.1: Supermicrosurgical lymphaticovenicular anastomosis Wei F. Chen, Lynn M. Orfahli, and Vahe Fahradyan

Chapter 21.7: Alveolar clefts

Chapter 21.10: Secondary deformities of the cleft lip, nose, and palate 21.10.1: Abbé flap Larry H. Hollier Jr. and Han Zhuang Beh 21.10.2: Complete takedown 21.10.3: Definitive rhinoplasty Evan M. Feldman, John C. Koshy, Larry H. Hollier Jr., and Samuel Stal 21.10.4: Thick lip and buccal sulcus deformities Evan M. Feldman and John C. Koshy

Chapter 21.11: Cleft and craniofacial orthognathic surgery 21.11.1: Le Fort I BSSO and genioplasty 21.11.2: Genioplasty 21.11.3: Patient recovery from orthognathic surgery Stephen B. Baker

Chapter 3.4: Vascularized lymph node transplant 3.4.1: Supraclavicular lymph node flap harvest Rebecca M. Garza and David W. Chang 3.4.2: Recipient site preparation for vascularized lymph node transfer – axilla David W. Chang

Chapter 3.5: Debulking strategies and procedures: liposuction of leg lymphedema 3.5.1: Liposuction of leg lymphedema: tips and tricks for a successful surgery Håkan Brorson

Chapter 3.6: Debulking strategies and procedures: excision 3.6.1: Charles procedure Peter C. Neligan

xvi

Video Contents

Chapter 4: Lower extremity sarcoma reconstruction

14.3.6: Radial forearm phalloplasty: venous anastomoses and closure Alexander Y. Li, Walter C. Lin, and Bauback Safa

4.1: Case example of a synovial sarcoma in the proximal leg. 4.2: Result 11 years after tumor removal and latissimus dorsi transplantation. Andrés A. Maldonado, Günter K. Germann, and Michael Sauerbier

Chapter 14.4: Breast, chest wall, and facial considerations in gender affirmation

Chapter 5: Reconstructive surgery: lower extremity coverage

14.4.1: Facial feminization: operative technique Kaylee B. Scott, Dana N. Johns, and Cori A. Agarwal

5.1: Anterolateral thigh flap harvest Michel Saint-Cyr

Chapter 17: Perineal reconstruction

Chapter 6.2: Targeted muscle reinnervation in the lower extremity 6.2.1: Targeted muscle reinnervation in the lower extremity Brian L. Chang and Grant M. Kleiber

Chapter 6.3: Lower extremity pain: regenerative peripheral nerve interfaces 6.3.1: Intraoperative demonstration of sciatic nerve neuroma 6.3.2: Demonstration of autologous free skeletal muscle grafts harvested from the lower extremity for RPNIs Nishant Ganesh Kumar, Theodore A. Kung, and Paul S. Cederna

Chapter 7: Skeletal reconstruction 7.1: Harvesting technique of fibular free flap 7.2: Harvesting technique of iliac crest free flap Marco Innocenti, Stephen Kovach III, Elena Lucattelli, and L. Scott Levin 7.3: Medial femoral condyle/medial geniculate artery osseocutaneous free flap dissection Stephen Kovach III and L. Scott Levin

Chapter 9.2: Diabetic foot: management of wounds and considerations in biomechanics and amputations 9.2.1: AT and PT tendon transfers 9.2.2: Cadaver dissection lab: percutaneous tendo-achilles lengthening and vertical contour calcanectomy Jayson N. Atves

Chapter 11: Reconstruction of the chest 11.1: Sternal rigid fixation David H. Song and Michelle C. Roughton

Chapter 12: Reconstruction of the posterior trunk 12.1: Posterior trunk reconstruction with keystone flap Reuben A. Falola, Nicholas F. Lombana, Andrew M. Altman, and Michel H. Saint-Cyr

Chapter 13: Abdominal wall reconstruction 13.1: Ventral hernia repair using narrow well-fixed retrorectus mesh 13.2: “Pumpkin-teeth” flaps for creation of neo-umbilicus Gregory A. Dumanian

Chapter 14.3: Gender affirmation surgery, female to male: phalloplasty; and correction of male genital defects 14.3.1: Right radial forearm phalloplasty: history and markings 14.3.2: Radial forearm phalloplasty: flap donor nerve harvest 14.3.3: Radial forearm phalloplasty: flap shaping 14.3.4: Radial forearm phalloplasty: flap harvest 14.3.5: Radial forearm phalloplasty: vascular anastomoses

17.1: Discovering the role of robotically harvested rectus abdominis muscle flaps in the management of pelvic defects Geraldine T. Klein, Chad M. Bailey, John C. Pederson, Jesse C. Selber, and Louis L. Pisters

Chapter 20: Management of the burned face and neck 20.1: Application of collagen sheet on a partial thickness burn of face 20.2: Resurfacing a post burn scarred face with large full thickness grafts from expanded lower abdominal skin Vinita Puri and Venkateshwaran Narasiman

Chapter 21: Pediatric burns 21.1: Fractional CO2 laser for hypertrophic burn scars Sebastian Q. Vrouwe and Lawrence J. Gottlieb

Volume Five Chapter 3: Primary breast augmentation with implants 3.1: Skin incision and mono-polar needle electrocautery 3.2: Dissection through the deep dermis and subcutaneous fat 3.3: Entrance into the subpectoral space 3.4A: Insertion of the implant – Keller funnel 3.4B: Insertion of the implant – Motiva funnel 3.5: Marking, before performing lucky-8-stitch Charles Randquist

Chapter 5: Augmentation mastopexy 5.1: Preoperative markings for a single-stage augmentation mastopexy 5.2: Augmentation mastopexy W. Grant Stevens

Chapter 8: Short scar breast reduction 8.1: Breast mobility Elizabeth Hall-Findlay, Elisa Bolletta, and Gustavo Jiménez Muñoz Ledo 8.2: SPAIR technique Dennis C. Hammond

Chapter 14: Breast implant explantation: indications and strategies to optimize aesthetic outcomes 14.1: Demonstration of capsulotomy 14.2: Demonstration of a partial capsulectomy 14.3: Demonstration of total capsulectomy showing intact capsule and implant after removal Connor Crowley, M. Bradley Calobrace, Mark W. Clemens, and Neil Tanna

Chapter 15: Management strategies for gynecomastia 15.1: Surgical management of gynecomastia Michele Ann Manahan

Video Contents

15.2: Ultrasound-assisted liposuction Charles M. Malata

Chapter 16: Management options for gender affirmation surgery of the breast 16.1: Preoperative markings and surgical technique for gender affirming double-incision mastectomy Ara A. Salibian, Gaines Blasdel, and Rachel Bluebond-Langner

Chapter 18: Perfusion assessment techniques following mastectomy and reconstruction 18.1: Perfusion imaging as a decision-making tool within the operating room 18.2: ICG fluorescence imaging to determine the extent of perfusion for a perforator flap Alex Mesbahi, Matthew Cissell, Mark Venturi, and Louisa Yemc

Chapter 21: One-stage dual-plane reconstruction with prosthetic devices 21.1: Intraoperative technique: Immediate subpectoral direct-to-implant reconstruction with ADM Brittany L. Vieira and Amy S. Colwell

Chapter 24: Skin reduction using “smile mastopexy” technique in breast reconstruction 24.1: Marking for smile mastopexy 24.2: Operative procedure for smile mastopexy Kiya Movassaghi and Christopher N. Stewart

Chapter 25: Management of complications of prosthetic breast reconstruction

xvii

26.10: Balcony technique for reduction/augmentation mastopexy. Roy de Vita and Veronica Vietti Michelina

Chapter 28: Breast reconstruction with the pedicle TRAM flap 28.1: Unilateral breast reconstruction with a pedicled TRAM flap 28.2: Bilateral breast reconstruction with pedicled TRAM flaps 28.3: Abdominal donor site closure for bilateral TRAM flap Julian Pribaz and Jake Laun 28.4: The bikini inset Jake Laun Paul D. Smith, and Julian Pribaz 28.5: Demonstration of a bipedicled folded TRAM design Julian Pribaz, Jake Laun, Alex Girardot

Chapter 29: Breast reconstruction with the latissimus dorsi flap 29.1: Immediate latis marks 29.2: Delayed latis marks Dennis C. Hammond

Chapter 30: Autologous breast reconstruction with the DIEP flap 30.1: Incision of the anterior rectus fascia 30.2: Incision between the fascial rents 30.3: Intramuscular dissection of the perforator 30.4: Microvascular flap transfer, part 1 30.5: Microvascular flap transfer, part 2 30.6: Drainless progressive tension closure Adrian McArdle and Joan E. Lipa

25.1: Intra-operative video demonstrating poorly incorporated ADM along the inferolateral breast pocket following tissue expander removal 25.2: Patient presents following left sided mastectomy and tissue expander placement with a palpable seroma and fluid wave along the medial breast pocket 25.3: Patient underwent bilateral breast reconstruction following left skin-sparing mastectomy and prophylactic right nipple-sparing mastectomy Nima Khavanin and John Kim

Chapter 31: Autologous breast reconstruction with the free TRAM flap

Chapter 26: Secondary refinement procedures following prosthetic breast reconstruction

34.1: Superior gluteal artery perforator (SGAP) flap 34.2: Inferior gluteal artery perforator (IGAP) flap Peter C. Neligan

26.1: Preoperative 26.2: Postoperative 26.3: Lipoaspiration for lipofilling 26.4: Lipofilling on multiple plane with a fanning technique 26.5: Complete resolution of bilateral animation deformity and capsular contracture in a right breast reconstruction following radiotherapy and left simmetrization 26.6: Complete resolution of bilateral animation deformity and capsular contracture in a right breast reconstruction following radiotherapy and left simmetrization 26.7: Complete resolution of animation deformity after exchange of implant and change of implant placement with prepectoral implant based breast reconstruction. 26.8: Complete resolution of animation deformity after exchange of implant and change of implant placement with prepectoral implant based breast reconstruction. 26.9: Postoperative result in motion after nipple sparing mastectomy with prepectoral implant based breast reconstruction.

Chapter 35: Autologous breast reconstruction with medial thigh flaps

31.1: Elevation of the free TRAM flap Hyunho Han and Jin Sup Eom 31.2: Inset of TRAM flap in delayed breast reconstruction Jin Sup Eom

Chapter 34: Gluteal free flaps for breast reconstruction

35.1: Transverse upper gracilis (TUG) flap 1 Peter C. Neligan 35.2: Transverse upper gracilis (TUG) flap 2 Venkat V. Ramakrishnan

Chapter 36: Autologous breast reconstruction with the profunda artery perforator (PAP) flap 36.1: Profunda artery perforator flap. Adam T. Hauch, Hugo St. Hilaire, and Robert J. Allen Sr.

Chapter 42: Enhanced recovery after surgery (ERAS) protocols in breast surgery: techniques and outcomes 42.1: Traditional transversus abdominis plane block administration by chapter’s senior author

xviii

Video Contents

42.2: Serratus anterior plane and PECS I block administration by chapter’s senior author Nicholas F. Lombana, Reuben A. Falola, John C. Cargile, and Michel H. Saint-Cyr

Chapter 44: Introduction to oncoplastic breast surgery 44.1: Partial breast reconstruction using reduction mammoplasty Maurice Y. Nahabedian

Chapter 47: Surgical and non-surgical management of breast cancer-related lymphedema 47.1: Lymphovenous bypass for BCRL 47.2: Composite SCIP vascularized lymph node transplant Ketan Patel

Volume Six Chapter 1: Anatomy and biomechanics of the hand 1.1: The extensor tendon compartments 1.2: The contribution of the interosseous and lumbrical muscles to the lateral bands 1.3: Extrinsic flexors and surrounding vasculonervous elements, from superficial to deep 1.4: The lumbrical plus deformity 1.5: The sensory and motor branches of the median nerve in the hand James Chang, Vincent R. Hentz, Robert A. Chase, and Anais Legrand

Chapter 2: Examination of the upper extremity 2.1: Flexor profundus test in a normal long finger 2.2: Flexor sublimis test in a normal long finger 2.3: The milking test of the fingers and thumb in a normal hand 2.4: Dynamic tenodesis effect in a normal hand 2.5: Eichhoff test 2.6: Extensor pollicis longus test in a normal person 2.7: Test for the extensor digitorum communis (EDC) muscle in a normal hand 2.8: Test for assessing thenar muscle function 2.9: The “cross fingers” sign 2.10: Scaphoid shift test 2.11: Ulnar fovea sign 2.12: Static two-point discrimination test (s-2PD test) 2.13: Moving 2PD test (m-2PD test) performed on the radial or ulnar aspect of the finger 2.14: Semmes Weinstein monofilament test: The patient should sense the pressure produced by bending the filament 2.15: Allen’s test in a normal person 2.16: Digital Allen’s test 2.17: Adson test 2.18: Roos test Ryosuke Kakinoki

Chapter 3: Diagnostic imaging of the hand and wrist 3.1: Scaphoid lunate dislocation Alphonsus K.S. Chong, David M.K. Tan 3.2: Right wrist positive midcarpal catch up clunk

3.3: Wrist ultrasound Alphonsus K.S. Chong

Chapter 4: Anesthesia for upper extremity surgery 4.1: Supraclavicular block Subhro K. Sen

Chapter 5: Principles of Internal Fixation 5.1: Dynamic compression plating and lag screw technique Christopher Cox 5.2: Headless compression screw 5.3: Locking vs. non-locking plates Jeffrey Yao and Jason R. Kang

Chapter 7: Hand fractures and joint injuries 7.1: PIP volar approach for ORIF Warren C. Hammert and Randy R. Bindra 7.2: Hemi-hamate arthroplasty Warren C. Hammert 7.3: MCP dislocation Warren C. Hammert and Randy R. Bindra 7.4: Metacarpal shaft ORIF narrated 7.5: Bennet reduction Warren C. Hammert

Chapter 9: Flexor tendon injuries and reconstruction 9.1: Zone II flexor tendon repair 9.2: Incision and feed tendon forward 9.3: Distal tendon exposure 9.4: Six-strand M-Tang repair 9.5: Extension-flexion test – wide awake 9.6: How to pass FDP tendon through a palm incision Jin Bo Tang

Chapter 10: Extensor tendon injuries 10.1: Secondary suture of central slip 10.2: Sagittal band reconstruction 10.3: Setting the tension in extensor indicis transfer Kai Megerle

Chapter 11: Replantation 11.1: Replantation Dong Chul Lee 11.2: Hand replantation James Chang

Chapter 12: Reconstructive surgery of the mutilated hand 12.1: Debridement technique James Chang

Chapter 13: Thumb reconstruction: Nonmicrosurgical techniques 13.1: First dorsal metacarpal artery (FDMA) flap 13.2: Osteoplastic thumb reconstruction Jeffrey B. Friedrich

Chapter 14: Thumb reconstruction: Microsurgical techniques 14.1: Trimmed great toe 14.2: Second toe for index finger

Video Contents

14.3: Combined second and third toe for metacarpal hand Nidal F. Al Deek

Chapter 17: Dupuytren’s disease 17.1: Surgical technique of PNF 17.2: Surgical technique of LF James K-K. Chan, Paul M.N. Werker, and Jagdeep Nanchahal

Chapter 18: Osteoarthritis in the hand and wrist 18.1: Ligament reconstruction tendon interposition arthroplasty of the thumb carpometacarpal joint James W. Fletcher

Chapter 19: Rheumatologic conditions of the hand and wrist 19.1: Silicone metacarpophalangeal arthroplasty Kevin C. Chung and Evan Kowalski 19.2: Extensor tendon rupture and end-side tendon transfer James Chang

Chapter 21: Nerve entrapment syndromes 21.1: The manual muscle testing algorithm 21.2: Scratch collapse test – carpal tunnel Elisabet Hagert 21.3: Injection technique for carpal tunnel surgery Donald Lalonde 21.4: Carpal tunnel and cubital tunnel releases in the same patient in one procedure with field sterility: Part 1 – local anesthetic injection for carpal tunnel Donald Lalonde and Michael Bezuhly 21.5: Wide awake carpal tunnel surgery Donald Lalonde 21.6: Endoscopic carpal tunnel release 21.7: Clinical exam and surgical technique – Lacertus syndrome Elisabet Hagert 21.8.1: Triple nerve release 1 21.8.2: Triple nerve release 2 21.8.3: Triple nerve release 3 Donald Lalonde 21.9: Carpal tunnel and cubital tunnel releases in the same patient in one procedure with field sterility: Part 2 – local anesthetic injection for cubital tunnel Donald Lalonde and Michael Bezuhly 21.10: Injection technique for cubital tunnel surgery 21.11: Wide awake cubital tunnel surgery Donald Lalonde 21.12: Clinical exam and surgical technique – Radial tunnel syndrome 21.13: Clinical exam and surgical technique – Lateral intermuscular syndrome 21.14: Clinical exam and surgical technique – Axillary nerve entrapment Elisabet Hagert

Chapter 22: Peripheral nerve repair and reconstruction 22.1: Suture repair of the cut digital nerve 22.2: Suture repair of the median nerve Simon Farnebo, Johan Thorfinn, and Lars B. Dahlin

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Chapter 23: Brachial plexus injuries: adult and pediatric 23.1: Supraclavicular brachial plexus dissection Johnny Chuieng-Yi Lu and David Chwei-Chin Chuang 23.2: Nerve transfer results 1 23.3: Nerve transfer results 2 23.4: Operative demonstration of 1) Contralateral C7 to innervate injured median nerve via free vascularized ulnar nerve graft, 2) 3rd to 5th intercostal nerve transfer to musculocutaneous nerve for a patient with right total root avulsion 23.5: Nerve transfer results 3 23.6: Nerve transfer results 4 David Chwei-Chin Chuang 23.7: Long-term result after total left brachial plexus palsy reconstruction Johnny Chuieng-Yi Lu and David Chwei-Chin Chuang 23.8: Nerve transfer results 5 David Chwei-Chin Chuang

Chapter 24: Tetraplegia 24.1: The single-stage grip and release procedure 24.2: Postoperative results after single-stage grip release procedure in OCu3-5 patients 24.3: Postoperative function after grip release procedure Carina Reinholdt and Catherine Curtin

Chapter 26: Nerve transfers 26.1: Guyon’s canal release and carpal tunnel release – extended Susan E. Mackinnon and Andrew Yee

Chapter 27: Free-functioning muscle transfer 27.1: Gracilis functional muscle harvest Gregory H. Borschel

Chapter 28: The ischemic hand 28.1: Extended sympathectomy of the radial, ulnar and common digital arteries for Raynaud’s phenomenon Neil F. Jones 28.2: Radial artery reconstruction with cephalic vein graft 28.3: Ulnar artery reconstruction with DIEA graft Hee Chang Ahn and Jung Soo Yoon

Chapter 29: The spastic hand 29.1: Hyperselective neuroectomy musculo-cutaneous Caroline Leclercq, Nathalie Bini, and Charlotte Jaloux

Chapter 30: The stiff hand 30.1: Volkmann angle allowing finger extension 30.2: Post-Operative demonstration 30.3: Joint demonstration after three days in a resting splint 30.4: Full function of joints during hockey practice 30.5: Weak grip strength, enough to impact work efficiency 30.6: Improved grip after elevating the original flap David T. Netscher, Rita E. Baumgartner, Kimberly Goldie Staines, and Logan W. Carr

Chapter 31: The painful hand 31.1: Surgical intervention: nerve root avulsion injuries 31.2: Surgical intervention: decompression and neurolysis Hazel Brown, Anna Berridge, Dennis Hazell, Parashar Ramanuj, and Tom J. Quick

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Video Contents

Chapter 32: Congenital hand I: Embryology, classification, and principles

Chapter 39: Growth considerations in the pediatric upper extremity

32.1: Pediatric trigger thumb release James Chang

39.1: Epiphyseal transplant harvesting technique Marco Innocenti and Sara Calabrese

Chapter 33: Congenital hand II: Malformations – whole limb

Chapter 41: Upper extremity composite allotransplantation

33.1: Function of left hand of patient in Figure 33-4 33.2: Congenital radioulnar synostosis of the right forearm and narrowing of the proximal radioulnar joint on the left forearm Aaron Berger, Soumen Das De, Bhaskaranand Kumar, and Pundrique Sharma

41.1: Upper extremity composite tissue allotransplantation W.P. Andrew Lee and Vijay S. Gorantla

Chapter 36: Congenital hand V: Deformations and dysplasia – variant growth 36.1: Surgical release of trigger thumb 36.2: Surgical release of trigger finger Wee Leon Lam, Xiaofei Tian, Gillian D. Smith, and Shanlin Chen 36.3: Thumb hypoplasia Amir H. Taghinia and Joseph Upton III

Chapter 37: Congenital hand VI: Dysplasia – tumorous conditions 37.1: Excision of venous malformation Joseph Upton III and Amir H. Taghinia

Chapter 42: Aesthetic hand surgery 42.1: Injection of radiesse using a bolus technique 42.2: Post-injection massage 42.3: Markings for autologous fat grafting 42.4: A fanning technique is used to maximize surface area contact between the fat and recipient tissues David Alan Kulber and Meghan C. McCullough

Chapter 43: Hand therapy 43.1: Fabrication of the RMA orthosis Wendy Moore, Minnie Mau, and Brittany N. Garcia

Lecture Video Contents Volume One Chapter 1: Plastic surgery and innovation in medicine Plastic surgery and innovation in medicine Peter C. Neligan

Chapter 25: Principles and techniques of microvascular surgery Principles and techniques of microvascular surgery Fu-Chan Wei, Sherilyn Keng Lin Tay, and Nidal F. Al Deek

Chapter 26: Tissue expansion and implants

Chapter 7: Digital photography in plastic surgery

Tissue expansion and implants Britta A. Kuehlmann, Eva Brix, and Lukas M. Prantl

Digital photography in plastic surgery

Chapter 27: Principles of radiation therapy

Daniel Z. Liu Chapter 8: Pre-and intra-operative imaging for plastic surgery Pre- and intra-operative imaging in plastic surgery Arash Momeni and Lawrence Cai

Chapter 16: Scar prevention, treatment, and revision Scar prevention, treatment, and revision Michelle F. Griffin, Evan Fahy, Michael S. Hu, Elizabeth R. Zielins, Michael T. Longaker, and H. Peter Lorenz

Principles of radiation therapy Stephanie K. Schaub, Joseph Tsai, and Gabrielle M. Kane

Chapter 29: Benign and malignant nonmelanocytic tumors of the skin and soft tissue Benign and malignant nonmelanocytic tumors of the skin and soft tissue Rei Ogawa

Chapter 39: Gender-affirming surgery Gender-affirming surgery Shane D. Morrison, William M. Kuzon Jr., and Jens U. Berli

Chapter 17: Skin grafting Skin grafting Shawn Loder, Benjamin Levi, and Audra Clark

Chapter 19: Repair, grafting, and engineering of cartilage Repair, grafting, and engineering of cartilage Wei Liu, Guangdong Zhou, and Yilin Cao

Chapter 20: Repair and grafting of bone Repair and grafting of bone Iris A. Seitz, Chad M. Teven, Bryce Hendren-Santiago, and Russell R. Reid

Chapter 21: Repair and grafting of peripheral nerve Repair and grafting of peripheral nerve Hollie A. Power, Kirsty Usher Boyd, Stahs Pripotnev, and Susan E. Mackinnon

Chapter 22: Repair and grafting fat and adipose tissue Repair and grafting fat and adipose tissue J. Peter Rubin

Chapter 23: Vascular territories Vascular territories Steven F. Morris and G. Ian Taylor

Chapter 24: Flap physiology, classification, and applications Flap physiology, classification, and applications Joon Pio Hong and Peter C. Neligan Flap pathophysiology and pharmacology Cho Y. Pang and Peter C. Neligan

Volume Two Chapter 5: Anatomic blocks of the face and neck Anatomic blocks of the face and neck Stelios C. Wilson and Barry Zide

Chapter 7: Non-surgical skin care and rejuvenation Non-surgical skin care and rejuvenation Zoe Diana Draelos

Chapter 8.2: Injectables and resurfacing techniques: Soft-tissue fillers Injectables and resurfacing techniques: soft-tissue fillers Kavita Mariwalla

Chapter 8.3: Injectables and resurfacing techniques: Botulinum toxin/neurotoxins Injectables and resurfacing techniques: botulinum toxin/neurotoxins Rawaa Almukhtar and Sabrina G. Fabi

Chapter 8.4: Injectables and resurfacing techniques: Lasers in aesthetic surgery Injectables and resurfacing techniques: Lasers in aesthetic surgery Jonathan Cook, David M. Turer, Barry E. DiBernardo, and Jason N. Pozner

Chapter 8.5: Injectables and resurfacing techniques: Chemical peels Injectables and resurfacing techniques: Chemical peels Richard H. Bensimon and Peter P. Rullan

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Lecture Video Contents

Chapter 9.2: Facial anatomy and aging

Chapter 11: Forehead rejuvenation

Facial anatomy and aging Bryan Mendelson and Chin-Ho Wong

Forehead rejuvenation Richard Warren

Chapter 9.3: Principles and surgical approaches of facelift

Chapter 12: Endoscopic brow lift

Principles and surgical approaches of facelift Richard J. Warren

Endoscopic brow lifting Renato Saltz and Eric W. Anderson

Chapter 13: Blepharoplasty

Chapter 9.4: Facelift: Facial rejuvenation with loop sutures: the MACS lift and its derivatives

Blepharoplasty Julius Few Jr. and Marco Ellis

Facelift: Facial rejuvenation with loop sutures: the MACS lift and its derivatives Patrick Tonnard, Alexis Verpaele, and Rotem Tzur

Chapter 14: Secondary blepharoplasty

Chapter 9.5: Facelift: Platysma-SMAS plication

Chapter 15: Asian facial cosmetic surgery

Facelift: Platysma-SMAS plication Miles G. Berry, James D. Frame III, and Dai M. Davies

Asian facial cosmetic surgery Jong Woo Choi, Tae Suk Oh, Hong Lim Choi, and Clyde Ishii

Chapter 9.6: Facelift: Lateral SMASectomy facelift

Chapter 16: Facial fat grafting

Facelift: Lateral SMASectomy facelift Daniel C. Baker and Steven M. Levine

Secondary blepharoplasty Seth Z. Aschen and Henry M. Spinelli

Facial fat grafting Francesco M. Egro, Sydney R. Colman, and J. Peter Rubin

Chapter 18: Nasal analysis and anatomy

Chapter 9.7: Facelift: The extended SMAS technique in facial rejuvenation

Nasal analysis and anatomy Rod J. Rohrich and Paul N. Afrooz

Facelift: The extended SMAS technique in facial rejuvenation James M. Stuzin

Chapter 19: Open technique rhinoplasty

Chapter 9.8: High SMAS facelift: Combined single flap lifting of the jawline, cheek and midface High SMAS facelift: combined single flap lifting of the jawline, cheek and midface Timothy Marten and Dino Elyassnia

Chapter 9.9: The lift-and-fill facelift The lift-and-fill facelift Stav Brown, Justin L. Bellamy, and Rod J. Rohrich

Chapter 9.10: Neck rejuvenation Neck rejuvenation James E. Zins and Jacob Grow

Chapter 9.11: Male facelift Male facelift Timothy Marten and Dino Elyassnia

Open technique rhinoplasty Rod J. Rohrich and Paul N. Afrooz

Chapter 20: Closed technique rhinoplasty Closed technique rhinoplasty Mark B. Constantian

Chapter 21: Airway issues and the deviated nose Airway issues and the deviated nose Ali Totonchi, Bryan Armijo, and Bahman Guyuron

Chapter 22: Secondary rhinoplasty Secondary rhinoplasty David M. Kahn, Danielle H. Rochlin, and Ronald P. Gruber

Chapter 23: Otoplasty and ear reduction Otoplasty and ear reduction Charles H. Thorne

Chapter 24: Hair restoration

Chapter 9.12: Secondary facelift irregularities and the secondary facelift

Hair restoration Alfonso Barrera and Victor Zhu

Secondary facelift irregularities and the secondary facelift Timothy Marten and Dino Elyassnia

Chapter 25.2: Liposuction: a comprehensive review of techniques and safety

Chapter 9.13: Perioral rejuvenation, including chin and genioplasty

Liposuction: A comprehensive review of techniques and safety Gianfranco Frojo, Jayne Coleman, and Jeffrey Kenkel

Perioral rejuvenation, including chin and genioplasty Ali Totonchi and Bahman Guyuron

Chapter 25.3: Correction of liposuction deformities with the SAFE liposuction technique

Chapter 9.14: Facial femininization Facial feminization Patrick R. Keller, Matthew Louis, and Devin Coon

Correction of liposuction deformities with the SAFE liposuction technique Simeon H. Wall Jr. and Paul N. Afrooz

Lecture Video Contents

Chapter 27: Abdominoplasty Abdominoplasty Alan Matarasso

Volume Three

Chapter 30: Bra-line back lift

Chapter 1: Management of craniomaxillofacial fractures

Bra-line back lift Joseph Hunstad and Saad A. Alsubaie

Management of craniomaxillofacial fractures Srinivas M. Susarla, Russell E. Ettinger, and Paul N. Manson

Chapter 31: Belt Lipectomy

Chapter 2: Scalp and forehead reconstruction

Belt lipectomy Amitabh Singh and Al S. Aly

Scalp and forehead reconstruction Alexander F. Mericli and Jesse C. Selber

Chapter 32: Circumferential approaches to truncal contouring in massive weight loss patients: the lower lipo-bodylift

Chapter 3: Aesthetic nasal reconstruction

Circumferential approaches to truncal contouring in massive weight loss patients: the lower lipo-bodylift Dirk F. Richter and Nina Schwaiger

Chapter 33: Circumferential approaches to truncal contouring: autologous buttocks augmentation with purse-string gluteoplasty Circumferential approaches to truncal contouring: autologous buttocks augmentation with purse-string gluteoplasty Joseph P. Hunstad and Nicholas A. Flugstad

Chapter 34: Circumferential approaches to truncal contouring: Lower bodylift with autologous gluteal flaps for augmentation and preservation of gluteal contour Circumferential approaches to truncal contouring: Lower bodylift with autologous gluteal flaps for augmentation and preservation of gluteal contour Robert F. Centeno and Jazmina M. Gonzalez

Chapter 35.2: Buttock augmentation with implants Buttock augmentation with implants Jose Abel De la Peña Salcedo, Jocelyn Celeste Ledezma Rodriguez, and David Gonzalez Sosa

Chapter 35.3: Buttock shaping with fat grafting and liposuction

Aesthetic nasal reconstruction Frederick J. Menick

Chapter 4: Auricular construction Auricular construction Dale J. Podolsky, Leila Kasrai, and David M. Fisher

Chapter 8: Overview of head and neck soft-tissue and bony tumors Overview of head and neck soft-tissue and bony tumors Sydney Ch'ng and Edwin Morrison

Chapter 9: Post-oncologic midface reconstruction: the Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center Approaches Post-oncologic midface reconstruction: the MSKCC and MDACC approaches Matthew M. Hanasono and Peter G. Cordeiro

Chapter 10: Local flaps for facial coverage Local flaps for facial coverage Nicholas Do and John Brian Boyd

Chapter 11: Lip reconstruction Lip reconstruction Julian J. Pribaz and Mitchell Buller Complex lip reconstruction: local flaps Julian J. Pribaz Total lip reconstruction Julian J. Pribaz

Buttock shaping with fat grafting and liposuction Constantino G. Mendieta, Thomas L. Roberts III, and Terrence W. Bruner

Chapter 12: Oral cavity, tongue, and mandibular reconstructions

Chapter 36: Upper limb contouring

Oral cavity, tongue, and mandibular reconstructions Ming-Huei Cheng

Upper limb contouring Margaret Luthringer, Nikita O. Shulzhenko, and Joseph F. Capella

Chapter 38: Post-bariatric reconstruction Post-bariatric reconstruction Jonathan W. Toy and J. Peter Rubin

Chapter 40: Aesthetic genital surgery Aesthetic genital surgery Gary J. Alter

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Chapter 13: Hypopharyngeal, esophageal, and neck reconstruction Hypopharyngeal, esophageal, and neck reconstruction Min-Jeong Cho and Peirong Yu

Chapter 15: Facial paralysis Facial paralysis Simeon C. Daeschler, Ronald M. Zuker, and Gregory H. Borschel

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Lecture Video Contents

Chapter 19.1: Unilateral cleft lip: introduction

Chapter 12: Reconstruction of the posterior trunk

Unilateral cleft lip Joseph E. Losee and Michael R. Bykowski

Reconstruction of the posterior trunk Reuben A. Falola, Nicholas F. Lombana, Andrew M. Altman, and Michel H. Saint-Cyr

Chapter 20: Repair of bilateral cleft lip Repair of bilateral cleft lip John B. Mulliken and Daniel M. Balkin

Chapter 21.1: Cleft palate: introduction Cleft palate Michael R. Bykowski and Joseph E. Losee

Chapter 21.4: Buccal myomucosal flap palate repair Buccal myomucosal flap palate repair Robert Joseph Mann

Chapter 25.2: Nonsyndromic craniosynostosis Nonsyndromic craniosynostosis Sameer Shakir and Jesse A. Taylor

Chapter 28: Robin sequence Robin sequence Sofia Aronson, Chad A. Purnell, and Arun K. Gosain

Chapter 31: Vascular anomalies Vascular anomalies Arin K. Greene and John B. Mulliken

Volume Four Chapter 2: Management of lower extremity trauma Management of lower extremity trauma Hyunsuk Peter Suh

Chapter 3.3: Lymphaticovenular bypass Lymphaticovenular bypass Wei F. Chen, Lynn M. Orfahli, and Vahe Fahradyan

Chapter 3.4: Vascularized lymph node transplant Vascularized lymph node transplant Rebecca M. Garza and David W. Chang

Chapter 3.6: Debulking strategies and procedures: excision Debulking strategies and procedures: excision Hung-Chi Chen and Yueh-Bih Tang

Chapter 5: Reconstructive surgery: lower extremity coverage Reconstructive surgery: lower extremity coverage Joon Pio Hong

Chapter 11: Reconstruction of the chest Reconstruction of the chest Brian L. Chang, Banafsheh Sharif-Askary, and David H. Song

Chapter 13: Abdominal wall reconstruction Abdominal wall reconstruction Gregory A. Dumanian

Chapter 14.1: Gender confirmation surgery: diagnosis and management Gender confirmation surgery: diagnosis and treatment Loren Schechter and Rayisa Hontscharuk

Chapter 15: Reconstruction of acquired vaginal defects Reconstruction of acquired vaginal defects Leila Jazayeri, Andrea L. Pusic, and Peter G. Cordeiro

Chapter 16: Pressure sores Pressure sores Ibrahim Khansa and Jeffrey E. Janis

Chapter 17: Perineal reconstruction Perineal reconstruction Ping Song, Hakim Said, and Otway Louie

Volume Five Chapter 3: Primary breast augmentation with implants Primary breast augmentation with implants Charles Randquist

Chapter 4: Autologous fat transfer: Fundamental principles and application for breast augmentation Autologous fat transfer: fundamental principles and application for breast augmentation Roger Khalil Khouri, Raul A. Cortes, and Daniel Calva-Cerquiera

Chapter 5: Augmentation mastopexy Augmentation mastopexy Justin L. Perez, Daniel J. Gould, Michelle Spring, and W. Grant Stevens

Chapter 9: Reduction mammaplasty with inverted-T techniques Reduction mammaplasty with inverted-T techniques Maurice Y. Nahabedian

Chapter 20: One- and two-stage prepectoral reconstruction with prosthetic devices One- and two-stage prepectoral reconstruction with prosthetic devices Alberto Rancati, Claudio Angrigiani, Maurizio Nava, Dinesh Thekkinkattil, Raghavan Vidya, Marcelo Irigo, Agustin Rancati, Allen Gabriel, and Patrick Maxwell

Lecture Video Contents

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Chapter 21: One-stage dual-plane reconstruction with prosthetic devices

Chapter 48: Breast reconstruction and radiotherapy: indications, techniques, and outcomes

One-stage dual-plane reconstruction with prosthetic devices Brittany L. Vieira and Amy S. Colwell

Breast reconstruction and radiotherapy: indications, techniques, and outcomes Jaume Masià, Cristhian D. Pomata, and Javier Sanz

Chapter 27: Introduction to autologous breast reconstruction with abdominal free flaps Introduction to autologous breast reconstruction with abdominal free flaps Maurice Y. Nahabedian

Volume Six Chapter 1: Anatomy and biomechanics of the hand

Chapter 29: Breast reconstruction with the latissimus dorsi flap

Anatomy and biomechanics of the hand James Chang, Anais Legrand, Francisco J. Valero-Cuevas, Vincent R. Hentz, and Robert A Chase

Breast reconstruction with the latissimus flap Dennis C. Hammond

Chapter 7: Hand fractures and joint injuries

Chapter 30: Autologous breast reconstruction with the DIEP flap Autologous breast reconstruction with the DIEP flap Adrian McArdle and Joan E. Lipa

Chapter 34: Gluteal free flaps for breast reconstruction Gluteal free flaps for breast reconstruction Salih Colakoglu and Gedge D. Rosson

Chapter 35: Autologous breast reconstruction with medial thigh flaps Autologous breast reconstruction with medial thigh flaps Venkat V. Ramakrishnan and Nakul Gamanlal Patel

Chapter 36: Autologous breast reconstruction with the profunda artery perforator (PAP) flap Autologous breast reconstruction with the profunda artery perforator (PAP) flap Adam T. Hauch, Hugo St. Hilaire, and Robert J. Allen Sr.

Chapter 37: Autologous reconstruction with the lumbar artery perforator (LAP) free flap Autologous reconstruction with the lumbar artery perforator (LAP) free flap Phillip Blondeel and Dries Opsomer

Chapter 40: Stacked and conjoined flaps

Hand fractures and joint injuries Warren C. Hammert and Randy R. Bindra

Chapter 8: Fractures and dislocations of the wrist and distal radius Fractures and dislocations of the wrist and distal radius Steven C. Haase and Kevin C. Chung

Chapter 11: Replantation Replantation Dong Chul Lee and Eugene Park

Chapter 13: Thumb reconstruction: Nonmicrosurgical techniques Thumb reconstruction: Non-microsurgical techniques Jeffrey B. Friedrich, Nicholas B. Vedder, and Elisabeth Haas-Lützenberger

Chapter 14: Thumb reconstruction: Microsurgical techniques Thumb reconstruction: Microsurgical techniques Nidal F. Al Deek and Fu-Chan Wei

Chapter 21: Nerve entrapment syndromes Nerve entrapment syndromes Elisabet Hagert and Donald Lalonde

Chapter 22: Peripheral nerve repair and reconstruction Peripheral nerve repair and reconstruction Simon Farnebo, Johan Thorfinn, and Lars B. Dahlin

Stacked and conjoined flaps Nicholas T. Haddock and Sumeet S. Teotia

Chapter 24: Tetraplegia

Chapter 43: Secondary procedures following autologous reconstruction

Tetraplegia Carina Reinholdt and Catherine Curtin

Secondary procedures following autologous reconstruction Jian Farhadi and Vendela Grufman

Chapter 25: Tendon transfers Tendon transfers Neil F. Jones

Chapter 44: Introduction to oncoplastic breast surgery

Chapter 26: Nerve transfers

Introduction to oncoplastic breast surgery Maurice Y. Nahabedian

Nerve transfers Kirsty Usher Boyd, Ida K. Fox, and Susan E. Mackinnon

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Lecture Video Contents

Chapter 30: The stiff hand The stiff hand David T. Netscher, Rita E. Baumgartner, Kimberly Goldie Staines, and Logan W. Carr

Chapter 31: The painful hand Clinical assessment of the function of the sympathetic nervous system Clinical assessment of the function of the nervous system: Hoffman-Tinel Test Hazel Brown, Anna Berridge, Dennis Hazell, Parashar Ramanuj, and Tom J. Quick

Chapter 39: Growth considerations in the pediatric upper extremity Growth considerations in the Pediatric upper extremity Marco Innocenti and Sara Calabrese

Chapter 40: Treatment of the upper extremity amputee Treatment of the upper extremity amputee Gregory Ara Dumanian, Sumanas W. Jordan, and Jason Hyunsuk Ko

Preface to the Fifth Edition This is the 5th edition of Plastic Surgery but the third and last edition for which I have been lucky enough to be Editor-in Chief. Looking back on the almost 15 years I have been involved in this series, I marvel at how many advances have been made in the specialty in that relatively short time. My predecessors, Drs. McCarthy and Mathes, who edited the 1st and 2nd editions, did so by themselves. When I took over the 3rd edition I realized that the specialty had become so complex that one person could not possibly have the bandwidth to do justice to all the information that an encyclopedic series such as this demands. I therefore introduced separate editors for each volume, bringing their subspecialty expertise to each volume, helping to highlight advances in their areas of subspecialty as well as identifying leaders in the field and up-and-coming authorities to author the various chapters. In this edition we have increased the number of volume editors. This reflects the ever-increasing complexity as well as the most recent advances in each area. In this 5th edition, Andrea Pusic joins Geoff Gurtner in Volume 1; Alan Matarasso teams up with Peter Rubin in Volume 2; Richard Hopper has replaced Ed Rodriguez (who did an outstanding job but, because of increased work demands, had to step down) and edited Volume 3 with Joe Losee; JP Hong joined David Song in Volume 4. Mo Nahabedian in Volume 5 and Jim Chang in Volume 6 updated both of those volumes. Developments continue within the specialty and we have endeavored to capture them in this edition. Dr. Daniel Liu, the multimedia editor has, once again, done an amazing job in compiling and editing the media content. In the 3rd edition we compiled multiple movies to complement the text. In the 4th edition we considerably expanded the list of videos and added lectures to accompany selected chapters. Many of these presentations were done by the chapter authors; the rest were compiled by Dr. Liu and myself from the content of the individual chapters. We have kept many of the movies and lectures from the previous editions and added to them yet again. A significant feature in this edition is the artwork on the cover. I am truly indebted to John Semple, a friend and former colleague of mine in Toronto, for providing this original piece of art. As well as being a talented and widely published plastic surgeon, John is an artist and a musician as well as being Fellow of the Canadian National Geographic Society, well known for his research on climate change in the Himalayas. I asked John if he would consider doing a painting for the cover of this edition and was delighted when he accepted.

In both the 3rd and 4th editions, we started the process of organizing the content with face-to-face meetings with the volume editors as well as the Elsevier team. Because of COVID, this was not possible for this edition so it was all planned via video conferencing. We held regular online meetings between Elsevier and the volume editors during the whole production process. This proved not only to be convenient, but extremely efficient. We went through the 4th edition volume by volume, chapter by chapter, decided what needed to stay, what needed to be added, what needed to be revised, and what needed to be changed. We also decided who should write the various chapters, keeping many existing authors, replacing others, and adding some new ones; we did this in order to really reflect the changes occurring within the specialty. Apart from the updated content, there is a lot that is new in each volume of this edition. We have new chapters on patient-reported outcome measures (PROMs), on education and teaching in Plastic Surgery, on gender affirmation surgery, lymphedema, local anesthetic blocks in aesthetic surgery, facial feminization, diabetic foot management, to name but some. We have also added multiple algorithms for various conditions, all in an effort to make the text easier to use and more approachable. In my travels around the world since the 3rd edition was published, I’ve been struck by the impact this publication has had on the specialty and, more particularly, on training. Everywhere I go, I’m told how the text is an important part of didactic teaching and a font of knowledge. It was gratifying to see the 3rd edition translated into Portuguese, Spanish, and Chinese. The 4th edition has been equally successful. When I first took over as Editor-in-Chief of this series, Elsevier wanted a new edition to be produced every 5 years. At first I thought that was too ambitious, but as this 5th edition is published I am struck, once again, by the extent of what has changed and how the specialty has continually developed, as evidenced by the number of completely new chapters (34), not to mention all the updated ones. I hope this 5th edition continues to contribute to the specialty, remains a resource for practicing surgeons, and continues to prepare our trainees for their future careers in Plastic Surgery. Peter C. Neligan Phoenix, AZ March, 2023

List of Editors Volume 3: Pediatric Surgery Joseph E. Losee, MD Ross H. Musgrave Professor of Pediatric Plastic Surgery Department of Plastic Surgery University of Pittsburgh Medical Center Chief, Division of Pediatric Plastic Surgery UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA, United States

Volume 1: Principles Geoffrey C. Gurtner, MD, FACS Professor and Chair, Department of Surgery Professor of Biomedical Engineering College of Medicine University of Arizona Tucson, AZ, United States

Volume 4: Lower Extremity, Trunk and Burns David H. Song, MD, MBA, FACS Physician Executive Director and Chairman Plastic Surgery Georgetown University Washington, DC, United States

Andrea L. Pusic, MD Chief, Division of Plastic and Reconstructive Surgery Brigham and Women’s Hospital Boston, MA, United States

Joon Pio Hong, MD, PhD, MMM Professor, Plastic Surgery Asan Medical Center University of Ulsan Seoul, Republic of Korea Adjunct Professor Plastic and Reconstructive Surgery Georgetown University Washington, DC, United States

Volume 2: Aesthetic J. Peter Rubin, MD, FACS Professor and Chair, Department of Plastic Surgery Professor of Bioengineering University of Pittsburgh Pittsburgh, PA, United States

Volume 5: Breast Maurice Y. Nahabedian, MD, FACS Former Professor of Plastic Surgery Johns Hopkins University, Georgetown University, and the Virginia Commonwealth University Private practice – National Center for Plastic Surgery McLean, VA, United States

Alan Matarasso, MD, FACS Clinical Professor of Surgery Systems Chief of Cosmetic Surgery Hofstra School of Medicine-Northwell Health System New York, NY, United States

Volume 6: Hand and Upper Extremity James Chang, MD Johnson & Johnson Distinguished Professor and Chief Division of Plastic Surgery Stanford University Medical Center Palo Alto, CA, United States

Volume 3: Craniofacial, Head and Neck Surgery Richard A. Hopper, MD, MS Chief, Division of Craniofacial and Plastic Surgery Surgical Director, Craniofacial Center Seattle Children’s Hospital Marlys C. Larson Professor Department of Surgery University of Washington Seattle, WA, United States

Multimedia editor Daniel Z. Liu, MD Reconstructive Microsurgeon Oncoplastic and Reconstructive Surgery City of Hope Chicago Zion, IL, United States



Editor-in-Chief Peter C. Neligan, MB, FRCS(I), FRCSC, FACS Professor Emeritus Surgery, Division of Plastic Surgery University of Washington Seattle, WA, United States

List of Contributors The editors would like to acknowledge and offer grateful thanks for the input of all previous editions’ contributors, without whom this new edition would not have been possible. VOLUME ONE Hatem Abou-Sayed, MD, MBA, FACS Private Practice Plastic Surgeon Tim Sayed MD, P.C. La Jolla and Newport Beach, CA; Co-Founder and Chief Medical Officer YesDoctor Irvine, CA; Co-Founder and Chief Medical Officer Elevai Labs Newport Beach, CA, United States Paul N. Afrooz, MD Resident Plastic and Reconstructive Surgery University of Pittsburgh Medical Center Pittsburgh, PA, United States Nidal F. Al Deek, MD, MSc Associate Professor of Surgery Division of Plastic and Reconstructive Microsurgery Cleveland Medical Center, University Hospitals Case Western Reserve School of Medicine Cleveland, OH, United States; Chang Gung Memorial Hospital, and Chang Gung School of Medicine Taipei, Taiwan Jens U. Berli, MD Associate Professor Division Chief Plastic Surgery Department of Surgery Oregon Health and Science University Portland, OR, United States Kirsty Usher Boyd, MD, FRCSC Associate Professor Division of Plastic Surgery The Ottawa Hospital University of Ottawa Ottawa, ON, Canada Eva Brix, MD Consultant Plastic Surgeon Department of Plastic, Hand, and Reconstructive Surgery University Hospital Regensburg Regensburg, Germany Stav Brown, MD Research Fellow Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer Center New York, NY, United States Justin M. Broyles, MD Assistant Professor of Surgery Plastic and Reconstructive Surgery Harvard Medical School, Brigham and Women’s Hospital Boston, MA, United States

Jacqueline N. Byrd, MD, MPH, MS Research Fellow Surgery, Center for Health Outcomes and Policy University of Michigan Ann Arbor, MI; Resident Surgery University of Texas Southwestern Dallas, TX, United States Lawrence Cai, MD Division of Plastic and Reconstructive Surgery Stanford University Medical Center Palo Alto, CA, United States Yilin Cao, MD, PhD Professor Shanghai 9th People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai, China Kellen Chen, PhD Assistant Research Professor Department of Surgery Department of Biomedical Engineering College of Medicine University of Arizona – Tucson Tucson, AZ, United States Sydney Ch’ng, MBBS, PhD, FRACS Associate Professor Faculty of Medicine and Health The University of Sydney Sydney, NSW, Australia Kevin C. Chung, MD, MS Professor of Surgery Section of Plastic Surgery University of Michigan; Chief of Hand Surgery University of Michigan; Assistant Dean for Faculty Affairs University of Michigan Ann Arbor, MI, United States Franklyn P. Cladis, MD, FAAP Associate Professor of Anesthesiology Department of Anesthesiology The Children’s Hospital of Pittsburgh of UPMC; Program Director, Pediatric Anesthesiology Fellowship The Children’s Hospital of Pittsburgh of UPMC Pittsburgh, PA, United States Audra Clark, MD Assistant Professor General Surgery University of Texas Southwestern Dallas, TX, United States

Alex Clarke, DSc honoris causa, DClinPsych, MSc, BSc (Hons), AFBPS Visiting Professor, Chartered Clinical and Health Psychologist Centre for Appearance Research UWE Bristol Bristol, United Kingdom Michelle Coriddi, MD Attending Plastic Surgery Memorial Sloan Kettering Cancer Center New York, NY, United States Yannick F. Diehm, MD, MSc Resident Doctor Department of Hand, Plastic and Reconstructive Surgery BG Trauma Center Ludwigshafen Ludwigshafen, Germany Jessica Erdmann-Sager, MD, FACS Assistant Professor Harvard Medical School Division of Plastic Surgery Brigham and Women’s Hospital Newton, MA, United States Evan Fahy, MD Clinical Research Fellow Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States Lucas Gallo, MD, MSc, PhD(c) Resident Physician Clinician Investigator Program; Division of Plastic Surgery, Department of Surgery McMaster University Hamilton, ON, Canada Amanda Gosman, MD Professor and Chief of Plastic Surgery Director of Craniofacial and Pediatric Plastic Surgery UC San Diego School of Medicine San Diego, CA, United States Madelijn Gregorowitsch, MD, PhD, MHSc General Practitioner in Training and Clinical Epidemiologist The Julius Center, University Medical Center Utrecht Utrecht, The Netherlands Michelle F. Griffin, MBChB, PhD Clinical Research Fellow Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States

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List of Contributors

Geoffrey C. Gurtner, MD Professor and Chair Department of Surgery Professor of Biomedical Engineering College of Medicine University of Arizona Tucson, AZ, United States Karl-Anton Harms, MBBS O’Brien Institute Department St Vincent’s Institute for Medical Research Melbourne, VIC, Australia Valentin Haug, MD Resident Doctor Department of Hand, Plastic and Reconstructive Surgery BG Trauma Center Ludwigshafen Ludwigshafen, Germany Lydia Helliwell, MD Plastic, Hand and Reconstructive Surgeon Brigham and Women’s Hospital Harvard Medical School Boston, MA, United States Bryce Hendren-Santiago, BS Medical Student Pritzker School of Medicine University of Chicago Chicago, IL, United States Dominic Henn, MD Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas, TX, United States George Ho, MD Division of Plastic, Reconstructive and Aesthetic Surgery Department of Surgery University of Toronto Toronto, ON, Canada Joon Pio Hong, MD, PhD, MMM Professor Plastic Surgery Asan Medical Center, University of Ulsan Seoul, Republic of Korea; Adjunct Professor Plastic and Reconstructive Surgery Georgetown University Washington, DC, United States Michael S. Hu, MD Clinical Research Fellow Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States C. Scott Hultman, MD, MBA Professor and Vice Chair Department of Plastic Surgery Johns Hopkins University School of Medicine; Director Burn Center Johns Hopkins Bayview; Fellowship Director Burn Surgical Critical Care Johns Hopkins Bayview Baltimore, MD, United States

Leila Jazayeri, MD Microsurgery Fellow Plastic and Reconstructive Surgery Memorial Sloan Kettering New York, NY, United States

Daniel Z. Liu, MD Reconstructive Microsurgeon Oncoplastic and Reconstructive Surgery City of Hope Chicago Zion, IL, United States

Haley M. Jeffers Student Harvard University Boston, MA, United States

Wei Liu, MD, PhD Professor Plastic and Reconstructive Surgery Shanghai 9th People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai, China

Lynn Jeffers, MD, MBA, FACS Chief Medical Officer CommonSpirit/Dignity Health St. John’s Regional Medical Center and St. John’s Hospital Camarillo, CA Plastic Surgery Private Practice Oxnard and Camarillo, CA, United States Gabrielle M. Kane, MB, BCh, EdD, FRCPC Professor Emeritus Radiation Oncology University of Washington Seattle, WA, United States Martin Kauke-Navarro, MD Resident Physician Department of Surgery, Division of Plastic Surgery Yale School of Medicine New Haven, CT, United States Timothy W. King, MD, PhD, MSBE, FAAP, FACS Stuteville Division Chief of Plastic and Reconstructive Surgery Professor, Department of Surgery Loyola Stritch School of Medicine Maywood, IL; Plastic Surgery Site Director Department of Surgery Hines VA Hospital Hines, IL, United States Anne F. Klassen, BA(Hons), DPhil Professor Department of Pediatrics McMaster University Hamilton, ON, Canada Britta A. Kuehlmann, Dr. med. Postdoctoral Research Fellow Plastic Surgery Stanford University Palo Alto, CA, United States; Plastic Aesthetic Surgeon, Scientist and Founder, CEO and MD of CINEOLUX Düsseldorf, North Rhine-Westphalia, Germany WiIliam M. Kuzon Jr., MD, PhD Reed O. Dingman Professor of Surgery Department of Surgery University of Michigan Ann Arbor, MI, United States Benjamin Levi, MD Dr. Lee Hudson-Robert R. Penn Chair in Surgery Associate Professor in the Department of Surgery University of Texas Southwestern Medical Center, Dallas, TX, United States

Shawn Loder, MD Resident Department of Plastic Surgery University of Pittsburgh Pittsburgh, PA, United States Michael T. Longaker, MD, MBA, FACS Deane P. and Louise Mitchell Professor of Plastic Surgery Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States H. Peter Lorenz, MD Pediatric Plastic Surgery Service Chief and Professor Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States Susan E. Mackinnon, MD, FRCSC, FACS Minot Packer Fryer Professor of Surgery Director of the Center for Nerve Injury and Paralysis Professor of Plastic and Reconstructive Surgery Division of Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis, MO, United States Michele A. Manahan, MD, MBA, FACS Professor of Clinical Plastic and Reconstructive Surgery Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States Isabella C. Mazzola, MD Attending Plastic Surgeon Klinki für Plastiche und Ästhetische Chirurgie Klinikum Landkreis Erding Erding, Germany Riccardo F. Mazzola, MD Plastic Surgeon Department of Specialistic Surgical Sciences Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan, Italy Babak J. Mehrara, MD Chief Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer Center; Member Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer Center New York, NY; Professor Plastic and Reconstructive Surgery Weill Cornell Hospital New York, NY, United States

List of Contributors

Arash Momeni, MD Director, Clinical Outcomes Research Division of Plastic and Reconstructive Surgery Stanford University Medical Center Palo Alto, CA, United States

David Perrault, MD Division of Plastic and Reconstructive Surgery Stanford University Stanford, CA, United States

Steven F. Morris, MD, MSc, FRCS(C) Professor Department of Surgery Dalhousie University Halifax, NS, Canada

Bohdan Pomahac, MD Professor of Surgery Chief, Division of Plastic and Reconstructive Surgery Frank F. Kanthak Professor of Surgery Department of Surgery Yale School of Medicine New Haven, CT, United States

Shane D. Morrison, MD, MS Assistant Professor Division of Plastic Surgery, Department of Surgery Seattle Children’s Hospital; Division of Plastic Surgery, Department of Surgery University of Washington Medical Center Seattle, WA, United States

Hollie A. Power, MD, FRCSC Assistant Professor Division of Plastic Surgery, Department of Surgery University of Alberta Edmonton, AB, Canada

Peter C. Neligan, MB, FRCS(I), FRCSC, FACS Professor Emeritus Surgery, Division of Plastic Surgery University of Washington Seattle, WA, United States

Lukas M. Prantl, MD, PhD University Center for Plastic, Reconstructive, and Hand Surgery University Hospital Regensburg Regensburg, Germany

Jonas A. Nelson, MD, MPH Assistant Professor Department of Surgery Memorial Sloan Kettering New York, NY, United States

B. Aviva Preminger, MD, MPH, FACS Preminger Plastic Surgery New York, NY, United States

Peter Nthumba, MD, MSc AIC Kijabe Hospital Department of Plastic Surgery Vanderbilt University Medical Center Nashville, TN, United States Kristo Nuutila, MSc, PhD Principal Research Scientist US Army Institute of Surgical Research San Antonio, TX; Associate Professor of Surgery Uniformed Services University of the Health Sciences Bethesda, MD, United States Anaeze C. Offodile 2nd, MD, MPH Assistant Professor Department of Plastic and Reconstructive Surgery University of Texas MD Anderson Cancer Center; Assistant Professor Department of Health Services Research University of Texas MD Anderson Cancer Center Houston, TX, United States Rei Ogawa, MD, PhD, FACS Professor Department of Plastic, Reconstructive and Aesthetic Surgery Nippon Medical School Tokyo, Japan Christopher J. Pannucci, MD, MS Plastic and Microvascular Surgeon Private Practice Plastic Surgery Northwest Spokane, WA, United States

Karim A. Sarhane, MD, MSc General, Laparoscopic, and Peripheral Nerve Surgeon Burjeel Royal Hospital, Al Ain Abu Dhabi United ArabEmirates Stephanie K. Schaub, MD Assistant Professor Department of Radiation Oncology University of Washington School of Medicine Seattle, WA, United States Iris A. Seitz, MD, PhD Edward-Elmhurst Healthcare Naperville, IL, United States Jesse C. Selber, MD, MPH, FACS Professor, Vice Chair, Director of Clinical Research Department of Plastic Surgery MD Anderson Cancer Center Houston, TX, United States Ramin Shayan, MBBS, PhD, FRACS(Plast) Associate Professor O’Brien Institute Department St. Vincent’s Institute for Medical Research Melbourne, VA, Australia

Stahs Pripotnev, MD, FRCSC Assistant Professor Division of Plastic Surgery Roth | McFarlane Hand and Upper Limb Centre Western University London, ON, Canada

Clifford C. Sheckter, MD Assistant Professor Plastic and Reconstructive Surgery Stanford University Stanford, CA; Associate Director Regional Burn Center Santa Clara Valley Medical Center San Jose, CA, United States

Andrea L. Pusic, MD Professor Chief, Division of Plastic and Reconstructive Surgery Brigham and Women’s Hospital Boston, MA, United States

Indranil Sinha, MD Plastic and Reconstructive Surgery Brigham and Women’s Hospital; Associate Professor Harvard Medical School Boston, MA, United States

Russell R. Reid, MD, PhD Professor Surgery/Section of Plastic and Reconstructive Surgery University of Chicago Medicine Chicago, IL, United States

Dharshan Sivaraj, BS Research Fellow Division of Plastic Surgery, Department of Surgery Stanford University University of Arizona – Tucson Tucson, AZ, United States

Johanna N. Riesel, MD Pediatric Craniofacial and Plastic Surgery The Hospital for Sick Children Toronto, ON, Canada J. Peter Rubin, MD Professor and Chair Department of Plastic Surgery University of Pittsburgh; Professor Bioengineering University of Pittsburgh Pittsburgh, PA, United States Nichola Rumsey, BSC, MSc, PhD Professor Emerita Centre for Appearance Research UWE Bristol Bristol, United Kingdom

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Sherilyn Keng Lin Tay, MRCS, MSc, FRCS(Plast) Consultant Plastic Surgeon Plastic Surgery Glasgow Royal Infirmary Glasgow, United Kingdom G. Ian Taylor, AO, FRACS Professor Department of Anatomy and Physiology University of Melbourne; Department of Plastic Surgery Royal Melbourne Hospital Melbourne, VIC, Australia Chad M. Teven, MD, MBA, FACS, HEC-C Assistant Professor of Surgery (Clinical) Northwestern University Feinberg School of Medicine Chicago, IL, United States

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List of Contributors

Achilleas Thoma, MD, MSc, FRCS(C), FACS Clinical Professor, Department of Surgery Associate Member, Department of Health Research Methods, Evidence and Impact (HEI) McMaster University Hamilton, ON, Canada Charles H. Thorne, MD Chairman Department of Plastic Surgery Lenox Hill Hospital New York, NY, United States Joseph Tsai, MD, PhD Department of Radiation Oncology University of Washington School of Medicine Seattle, WA, United States Alexander H.R. Varey, MBChB, MRCS, FRACS, FRCS(Plast), PhD Clinical Associate Professor Faculty of Health and Medicine University of Sydney; Faculty Member Melanoma Institute Australia Sydney; Staff Specialist Plastic and Reconstructive Surgery Westmead Hospital Sydney, NSW, Australia David E. Varon, BS University of Michigan Medical School Ann Arbor, MI, United States Sophocles H. Voineskos, MD, MSc Assistant Professor Division of Plastic Surgery, Department of Surgery University of Toronto Toronto, ON, Canada Fu-Chan Wei, MD, FACS Professor Plastic and Reconstructive Surgery Chang Gung Memorial Hospital Kweishan, Taoyuan, Taiwan Stelios C. Wilson, MD Private Practice Charles H. Thorne MD Plastic Surgery New York, NY, United States Danny Young-Afat, MD, PhD, MHSc Plastic Surgeon and Clinical Epidemiologist Department of Plastic and Reconstructive Surgery Amsterdam University Medical Center Amsterdam, The Netherlands Guangdong Zhou, MD, PhD Professor Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering Research Shanghai 9th People’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai, China Elizabeth R. Zielins, MD Clinical Research Fellow Stanford University School of Medicine Division of Plastic and Reconstructive Surgery Stanford, CA, United States

VOLUME TWO Paul N. Afrooz, MD Private Practice Miami, FL, United States Rawaa Almukhtar, MD, MPH Scripps Medical Group Dermatology San Diego, CA, United States Saad A. Alsubaie, MD, FACS, FRCSC Asthetic Plastic Surgeon North Texas Plastic Surgery Dallas, TX, United States Gary J. Alter, MD Assistant Clinical Professor Division of Plastic Surgery University of California Los Angeles, CA, United States Al S. Aly, MD Professor of Plastic Surgery Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas, TX, United States Ashley N. Amalfi, MD Board Certified Plastic Surgeon Quatela Center for Plastic Surgery Rochester, NY; Clinical Assistant Professor of Surgery Division of Plastic Surgery University of Rochester School of Medicine Rochester, NY, United States Eric W. Anderson, MD Resident Plastic Surgery University of Utah Salt Lake City, UT, United States Bryan Armijo, MD Plastic Surgery Dallas Plastic Surgery Institute Dallas, TX, United States Seth Z. Aschen, MD Weill Cornell Medical College Division of Plastic and Reconstructive Surgery Weill Cornell Medicine New York, NY, United States Daniel C. Baker, MD Professor of Surgery Institute of Reconstructive Plastic Surgery New York University Medical Center Department of Plastic Surgery New York, NY, United States Alfonso Barrera, MD, FACS Clinical Assistant Professor Plastic Surgery Baylor College of Medicine Houston, TX, United States Justin Bellamy, MD Board Certified Plastic Surgeon West Palm Beach, FL, United States Richard Hector Bensimon, MD Medical Director Plastic Surgery Bensimon Center Portland, OR, United States

Miles G. Berry, MS, FRCS (Plast) Aestheticus Plastic and Aesthetic Surgery London Welbeck Hospital London, UK Stav Brown, MD Research Fellow Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer Center New York, NY, United States Terrence W. Bruner, MD, MBA AnMed Health Cosmetic and Plastic Surgery Anderson, SC, United States Andrés F. Cánchica Cano, MD Plastic and Reconstructive Surgeon Private Practice Medellín, Colombia Joseph Francis Capella, MD Chief, Post-bariatric Body Contouring Division of Plastic Surgery Hackensack University Medical Center Hackensack, NJ, United States Robert F. Centeno, MD, MBA Medical Director St. Croix Plastic Surgery & MediSpa; Chief Medical Quality Officer Governor Juan F. Luis Hospital & Medical Center Christiansted, US Virgin Islands Sydney R. Coleman, MD Assistant Clinical Professor Plastic Surgery University of Pittsburgh Medical Center Pittsburgh, PA, United States Mark B. Constantian, MD Adjunct Clinical Professor Surgery (Plastic Surgery) University of Wisconsin School of Medicine Madison, WI; Visiting Professor Department of Plastic Surgery University of Virginia Health System Charlottesville, VA, United States Jonathan Cook, MD Plastic Surgeon Private Practice Sanctuary Plastic Surgery Boca Raton, FL, United States Hong Lim Choi JW Plastic Surgery Clinic Seoul, Republic of Korea Jong Woo Choi, MD, PhD, MMM Professor Department of Plastic and Reconstructive Surgery University of Ulsan College of Medicine Asan Medical Center Seoul, Republic of Korea Jayne Coleman Professor Department of Anesthesiology and Pain Medicine University of Texas Southwestern Medical Center Dallas, TX, United States  

List of Contributors

Devin Coon, MD, MSE Associate Professor of Plastic Surgery and Biomedical Engineering Department of Plastic and Reconstructive Surgery Johns Hopkins University Baltimore, MD, United States Dai M. Davies, FRCS Consultant and Institute Director Institute of Cosmetic and Reconstructive Surgery London, UK Jose Abel De la Pena Salcedo, MD, FACS Plastic Surgeon Director Instituto de Cirugia Plastica SC Huixquilucan, State of Mexico, Mexico Daniel A. Del Vecchio, MD, MBA Instructor in Surgery Massachusetts General Hospital Boston, MA, United States Zoe Diana Draelos, MD Consulting Professor Department of Dermatology Duke University School of Medicine Durham, NC, United States Barry DiBernardo, MD, FACS Clinical Associate Professor, Plastic Surgery Rutgers, New Jersey Medical School Newark, NJ; Director, New Jersey Plastic Surgery Montclair, NJ, United States Felmont F. Eaves, III, MD, FACS Adjunct Professor of Surgery (Plastic), Emory University ME Plastic Surgery Founder, Executive Chair, and Chief Medical/ Technical Officer, Brijjit Medical, Inc. Atlanta, GA, United States Francseco M. Egro, MD, MSc, MRCS Associate Professor Department of Plastic Surgery University of Pittsburgh Medical Center Pittsburgh, PA, United States Dino Elyassnia, MD, FACS Plastic Surgeon Private Practice Marten Clinic of Plastic Surgery San Francisco, CA, United States Marco Ellis, MD Assistant Professor Plastic Surgery Northwestern Medicine, Feinberg School of Medicine Chicago, IL, United States Sabrina G. Fabi, MD Volunteer Assistant Clinical Professor Department of Dermatology University of California San Diego, San Diego, CA; Associate Dermatology Cosmetic Laser Dermatology San Diego, CA, United States

Julius Few Jr., MD Director Plastic Surgery The Few Institute for Aesthetic Plastic Surgery Chicago, IL Clinical Professor Plastic Surgery University of Chicago Pritzker School of Medicine Chicago, IL Health Science Clinician Northwestern University Plastic Surgery Chicago, IL, United States Nicholas A. Flugstad, MD Plastic Surgeon Denton Plastic Surgery Denton, TX, United States James D. Frame III, MBBS, FRCS, FRCSEd, FRCS(Plast) Professor of Aesthetic Plastic Surgery Anglia Ruskin University Chelmsford, Essex, UK Gianfranco Frojo, MD Plastic Surgeon Private Practice Virginia Beach, VA, United States Jazmina M. Gonzalez, MD Plastic and Cosmetic Surgery Younger Image Plastic Surgery Center Vienna, VA, United States David Gonzalez Sosa, MD Plastic and Reconstructive Surgery Hospital Quirónsalud Torrevieja Alicante, Spain Jacob Grow, MD Plastic Surgery Associate Plastic Surgery Southern Indiana Aesthetic & Plastic Surgery Columbus, IN, United States Ronald P. Gruber, MD Adjunct Clinical Professor Division of Plastic and Reconstructive Surgery Stanford University Stanford, CA; Clinical Professor Division of Plastic and Reconstructive Surgery University of California San Francisco San Francisco, CA, United States Jeffrey Gusenoff, MD Professor of Plastic Surgery Department of Plastic Surgery University of Pittsburgh Pittsburgh, PA, United States Bahman Guyuron, MD Emeritus Professor Plastic Surgery Case Western Reserve University Cleveland, OH, United States Josef G. Hadeed, MD, FACS Plastic Surgeon Hadeed Plastic Surgery Beverly Hills, CA, United States

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Joseph Hunstad, MD Plastic Surgeon Plastic Surgery Hunstad-Kortesis-Bharti Center for Cosmetic Plastic Surgery and Medical Spa Huntersville, NC, United States Clyde Ishii, MD John A. Burns School of Medicine Department of Surgery University of Hawaii Honolulu, HI; Assistant Clinical Professor of Surgery University of Hawaii Honolulu, HI; Chief, Plastic Surgery Department of Surgery Shriners Hospital Honolulu, HI, United States Jeffrey E. Janis, MD Professor of Plastic Surgery, Neurosurgery, Neurology, and Surgery Department of Plastic and Reconstructive Surgery Chief of Plastic Surgery, University Hospital Department of Plastic and Reconstructive Surgery Ohio State University Wexner Medical Center Columbus, OH; Past President, American Society of Plastic Surgeons, American Council of Academic Plastic Surgeons, American Hernia Society, and Migraine Surgery Society United States Jeremy T. Joseph, MD Plastic and Reconstructive Surgery Resident Department of Surgery Eastern Virginia Medical School Norfolk, VA, United States David M. Kahn, MD Associate Professor of Plastic Surgery Division of Plastic Surgery Stanford University, Palo Alto, CA, United States Patrick R. Keller, MD Resident Physician Department of Plastic and Reconstructive Surgery Johns Hopkins University Baltimore, MD, United States Jeff Kenkel, MD Professor and Chair Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas, TX, United States Jocelyn Celeste Ledezma Rodriguez, MD Private Practice Guadalajara, Jalisco, Mexico Steven Levine, MD Assistant Professor of Surgery Department of Surgery Hofstra Medical School – Northwell Health System, New York, NY, United States

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List of Contributors

Michelle Locke, MBChB, MD, FRACS (Plastics) Plastic and Reconstructive Surgeon Department of Plastic Surgery Middlemore Hospital Auckland; Associate Professor Department of Surgery University of Auckland Auckland, New Zealand Matthew Louis, MD Resident Physician Department of Plastic and Reconstructive Surgery Johns Hopkins University Baltimore, MD, United States Margaret Luthringer, MD Resident Division of Plastic and Reconstructive Surgery Rutgers New Jersey Medical School Newark, NJ, United States Samantha G. Maliha, MD,MS Resident Physician Plastic Surgery University of Pittsburgh Pittsburgh, PA, United States Kavita Mariwalla Director Dermatology Mariwalla Dermatology West Islip, NY, United States Timothy Marten, MD, FACS Private Practice Founder and Director Marten Clinic of Plastic Surgery San Francisco, CA, United States Alan Matarasso, MD, FACS Clinical Professor of Surgery Systems Chief of Cosmetic Surgery Hofstra School of Medicine-Northwell Health System New York, NY, United States Bryan Christopher Mendelson, AM, FRCSE, FRACS, FACS, Diplomate American Board of Plastic Surgery Plastic Surgeon Aesthetic Plastic Surgery The Centre for Facial Plastic Surgery Melbourne, VIC, Australia Constantino G. Mendieta, MD Board Certified Plastic and Reconstructive Surgeon Miami, FL, United States Gabriele C. Miotto, MD Private Practice Adjunct Associate Professor, Division of Plastic Surgery Emory School of Medicine Atlanta, GA, United States Foad Nahai, MD Professor of Surgery Emory University Atlanta, GA, United States

Tae Suk Oh, MD, PhD Professor Department of Plastic and Reconstructive Surgery University of Ulsan College of Medicine Asan Medical Center Seoul, Republic of Korea Sabina Paiva, MD Serviço de Cirurgia Plástica Dr. Osvaldo Saldanha Santos, São Paulo, Brazil Malcolm Paul, MD Clinical Professor of Surgery Department of Plastic Surgery University of California, Irvine, CA, United States Galen Perdikis, MD Chair, Professor Department of Plastic Surgery Vanderbilt University Medical Center Nashville, TN, United States Jason Pozner, MD Adjunct Clinical Faculty Plastic Surgery Cleveland Clinic Florida, Weston, FL; Sanctuary Plastic Surgery Boca Raton, FL, United States Smita R. Ramanadham, MD, FACS Board-certified Plastic Surgeon SR Plastic Surgery P.C Montclair and East Brunswick, NJ, United States Dirk F. Richter, MD Institut ID Aesthetic Surgery and Regenerative Medicine Cologne, Germany Danielle H. Rochlin, MD Plastic Surgery Resident Division of Plastic and Reconstructive Surgery Stanford University Palo Alto, CA, United States Thomas L. Roberts, III Plastic Surgery Center of the Carolinas Spartanburg, SC, United States Rod J. Rohrich, MD Clinical Professor of Plastic Surgery Baylor College of Medicine Past Chair/Distinguished Professor of Plastic Surgery University of Texas Southwestern Medical Center Founding Partner Dallas Plastic Surgery Institute Dallas, TX, United States Peter J. Rubin, MD Professor and Chair Plastic Surgery University of Pittsburgh Pittsburgh, PA; Professor Bioengineering University of Pittsburgh Pittsburgh, PA, United States

Peter P. Rullan, MD Medical Director, Dermatology Institute Chula Vista, CA; Volunteer Clinical Faculty Department of Dermatology University of California San Diego, CA, United States Cristianna Bonetto Saldanha, MD Plastic and Reconstructive Surgeon Santos, São Paulo, Brazil Osvaldo Ribeiro Saldanha, MD, PhD Plastic Surgery Service Osvaldo Saldanha Santos, São Paulo, Brazil; Director of Plastic Surgery Services Department Metropolitan University of Santos – UNIMES São Paulo, Brazil Osvaldo Saldanha Filho, MD Plastic and Reconstructive Surgeon Santos, São Paulo, Brazil Renato Saltz, MD, FACS Adjunct Professor University of Utah Saltz Plastic Surgery and Spa Vitoria Salt Lake City and Park City, UT, United States Anna Schoenbrunner, MD, MAS Department of Plastic and Reconstructive Surgery Ohio State University Columbus, OH, United States Nina Schwaiger, Dr. Plastic and Aesthetic Surgery Clinic Dr. Reba Hanover, Germany Nikita O. Shulzhenko, MD Resident Division of Plastic and Reconstructive Surgery Rutgers New Jersey Medical School Newark, NJ, United States Amitabh Singh, MBBS, MS, DNB, MCh Plastic Surgery Fortis Memorial Research Institute Gurgaon, India Henry M. Spinelli, MD Clinical Professor Surgery and Neurological Surgery Plastic Surgery and Neurological Surgery New York Presbyterian Weill Cornell Medicine New York, NY, United States James M. Stuzin, MD Clinical Professor (Voluntary) Plastic Surgery University of Miami School of Medicine Miami, FL, United States Taisa Szolomicki, MD Plastic and Reconstructive Surgeon Balneário Camboriú, Santa Catarina, Brazil Charles H. Thorne, MD Chairman Department of Plastic Surgery Lenox Hill Hospital New York, NY, United States

List of Contributors

Luiz Toledo, Prof., Dr. Private Practice Plastic Surgery MMC Polyclinic Dubai, United Arab Emirates; Private Practice Plastic Surgery Hospital Saint Louis Lisbon, Portugal Patrick Tonnard, MD, PhD Plastic Surgeon Coupure Centre for Plastic Surgery Ghent, Belgium Ali Totonchi Professor Case Western Reserve University Plastic Surgery MetroHealth Medical Center Cleveland, OH, United States Jonthan W. Toy, MD, FRCSC Associate Clinical Professor Plastic Surgery University of Alberta Edmonton, AB, Canada Rotem Tzur, MD Private Practice Tel Aviv, Israel David Turer, MD, MS Assistant Professor Plastic Surgery University of Pittsburgh Pittsburgh, PA, United States Alexis Verpaele, MD, PhD Plastic Surgeon Coupure Centre for Plastic Surgery Ghent, Belgium Simeon Wall Jr., MD, FACS Director The Wall Center for Plastic Surgery Shreveport, LA; Assistant Clinical Professor Department of Plastic Surgery UT Southwestern Medical Center Dallas, TX; Assistant Clinical Professor Department of Surgery LSU Health Sciences Center at Shreveport Shreveport, LA, United States Richard J. Warren, MD, FRCSC Clinical Professor Division of Plastic Surgery University of British Columbia Vancouver, BC, Canada Stelios C. Wilson, MD Plastic Surgeon Charles H. Thorne MD Plastic Surgery New York, NY, United States Chin-Ho Wong, MBBS, MRCSE, MMed (Surg), FAMS (Plast Surg) Plastic Surgeon Plastic Surgery W Aesthetic Plastic Surgery Singapore

Victor Zhu, MD, MHS Department of Plastic Surgery Kaiser Permanente San Francisco San Francisco, CA, United States Barry M. Zide, MD, DMD Professor Plastic Surgery NYU Langone Health New York, NY, United States James E. Zins, MD Chair, Department of Plastic Surgery Cleveland Clinic Cleveland, OH, United States

VOLUME THREE Neta Adler, MD Plastic Surgeon Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, IL, United States Abdulaziz Alabdulkarim, MD, FRCSC Craniofacial Surgery Fellow Division of Plastic, Reconstructive and Aesthetic Surgery McGill University Health Center Montreal, QC, Canada; Department of Plastic Surgery Prince Sattam Bin Abdulaziz University Kharj, Riyadh, Saudi Arabia Michael Alperovich, MD, MSc Division of Plastic Surgery Yale School of Medicine New Haven, CT, United States Marta Alvarado, DDS, MS Orthodontist Department of Orthodontics Facultad de Odontología Universidad de San Carlos de Guatemala Guatemala City, Guatemala Oleh M. Antonyshyn, MD Professor Plastic Surgery University of Toronto Toronto, ON, Canada Eric Arnaud, MD Unité fonctionnelle de chirurgie craniofaciale, Service de Neurochirurgie Pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris, Centre de Référence Maladies Rares CRANIOST, Filière Maladies Rares TeteCou, ERN Cranio Paris, France; Clinique Marcel Sembat, Ramsay Générale de Santé Boulogne-Billancourt, France Sofia Aronson, MD Resident Physician Division of Plastic Surgery Northwestern University Feinberg School of Medicine Chicago, IL, United States

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Stephen B. Baker, MD, DDS Professor and Program Director Plastic Surgery Medstar Georgetown University Hospital Washington, DC; Medical Director Craniofacial Program Inova Children’s Hospital Falls Church, VA; Attending Physician Plastic Surgery Children’s National Medical Center Washington, DC, United States Daniel M. Balkin, MD, PhD Instructor in Surgery Harvard Medical School Department of Plastic and Oral Surgery Boston Children’s Hospital Boston, MA, United States Scott P. Bartlett, MD Professor of Surgery Department of Surgery University of Pennsylvania Philadelphia, PA; Mary Downs Endowed Chair in Craniofacial Treatment and Research Division of Plastic Surgery Children’s Hospital of Philadelphia Philadelphia, PA, United States Bruce S. Bauer, MD Chief Division of Plastic Surgery NorthShore University HealthSystem Highland Park, IL; Clinical Professor of Surgery Department of Surgery University of Chicago Pritzker School of Medicine Chicago, IL, United States Adriane L. Baylis, PhD, CCC-SLP Speech Scientist Department of Plastic and Reconstructive Surgery Nationwide Children’s Hospital Columbus, OH; Director, VPD Program and Co-Director, 22q Center Department of Plastic and Reconstructive Surgery Nationwide Children’s Hospital Columbus, OH; Associate Professor-Clinical Department of Plastic Surgery Ohio State University College of Medicine Columbus, OH, United States Maureen Beederman, MD Assistant Professor Department of Surgery, Section of Plastic and Reconstructive Surgery University of Chicago Chicago, IL, United States Han Zhuang Beh, MD Cleft, Craniofacial and Pediatric Plastic Surgeon Plastic Surgery Cook Children’s Hospital Fort Worth, TX, United States

List of Contributors

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Michael Bentz, MD, FAAP, FACS Chairman, Division of Plastic Surgery Department of Surgery University of Wisconsin Madison, WI; Vice Chair of Clinical Affairs Department of Surgery University of Wisconsin Madison, WI, United States Hannah J. Bergman, MD Plastic and Reconstructive Surgery The Center for Plastic Surgery at CoxHealth Springfield, MO; Clinical Instructor of Surgery University of Missouri School of Medicine Columbia, MO, United States  

Zoe P. Berman, MD Postdoctoral Research Fellow Hansjörg Wyss Department of Plastic Surgery NYU Langone Health New York, NY; Resident Physician Department of General Surgery Maimonides Medical Center Brooklyn, NY, United States Allan B. Billig, MD Department of Plastic, Reconstructive, and Hand Surgery Hadassah University Medical Center Jerusalem, Israel Craig B. Birgfeld, MD Associate Professor Department of Surgery Division of Plastic and Reconstructive Surgery University of Washington Craniofacial Fellowship Director Seattle Children’s Hospital Seattle, WA, United States Gregory H. Borschel, MD, FACS, FAAP James Joseph Harbaugh, Jr. Professor of Plastic Surgery Department of Plastic Surgery Riley Hospital for Children Indianapolis, IN, United States John Brian Boyd, MB, ChB, MD, FRCS, FECSC, FACS Chief of Plastic Surgery Department of Surgery Harbor-UCLA Torrance, CA; Professor of Surgery Department of Surgery University of California, Los Angeles Los Angeles, CA, United States James P. Bradley, MD Professor and Vice Chairman Plastic and Reconstructive Surgery Northwell Health New York, NY, United States Edward P. Buchanan, MD, FACS Professor, Director of Cleft Care, Program Director Craniofacial Fellowship Department of Surgery Baylor College of Medicine Houston, TX, United States

Steven R. Buchman, MD M. Haskell Newman Professor in Plastic Surgery Department of Surgery University of Michigan Medical School Ann Arbor, MI; Professor of Neurosurgery (Joint Appointment) Department of Neurosurgery University of Michigan Medical School Ann Arbor, MI; Director, Craniofacial Anomalies Program Department of Surgery University of Michigan Medical Center Ann Arbor, MI; Chief, Pediatric Plastic Surgery CS Mott Children’s Hospital Ann Arbor, MI, United States Mitchell Buller, MEng, MD Resident Physician Plastic Surgery University of South Florida Tampa, FL, United States Michael R. Bykowski, MD Assistant Professor, Department of Plastic Surgery Surgical Director, Vascular Anomalies Center Surgical Director, Craniofacial Scleroderma Center Division of Pediatric Plastic Surgery UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA, United States Luis Capitán, MD, PhD Director and Head Surgeon Surgical Department The Facialteam Group Marbella, Málaga, Spain Fermín Capitán-Cañadas, PhD R&D Director Department of Research and Development The Facialteam Group Marbella, Málaga, Spain Anna R. Carlson, MD Fellow in Craniofacial Surgery Plastic Surgery Children’s Hospital of Philadelphia Philadelphia, PA, United States Sydney Ch’ng, MBBS, PhD, FRACS Associate Professor Faculty of Medicine and Health University of Sydney Sydney, NSW, Australia Brian L. Chang, MD Resident Department of Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States Philip Kuo-Ting Chen, MD Director Craniofacial Center Taipei Medical University Hospital Taipei; Professor of Surgery Taipei Medical University Taipei, Taiwan

Yu-Ray Chen, MD Professor of Surgery Gung University Chang Gung Memorial Hospital Taipei, Taiwan Ming-Huei Cheng, MD, MBA Professor A+ Surgery Clinic Taoyuan, Taiwan Gerson R. Chinchilla, DDS, MS Director Department of Orthodontics Facultad de Odontología Universidad de San Carlos de Guatemala Guatemala City, Guatemala Min-Jeong Cho, MD Assistant Professor Department of Plastic and Reconstructive Surgery The Ohio State University Columbus, OH, United States Peter G. Cordeiro, MD The William G Cahan Chair in Surgery Plastic and Reconstructive Surgery Service Memorial Sloan Kettering Cancer Center Professor of Surgery Weil Medical College of Cornell University New York, NY, United States Sabrina Cugno, MD, MSc, FRCSC, FACS, FAAP Division of Plastic, Reconstructive and Aesthetic Surgery Montreal Children’s Hospital McGill University Health Center Montreal, QC, Canada Simeon C. Daeschler, MD, Dr. med Postdoctoral Fellow Neuroscience and Mental Health Program SickKids Research Institute The Hospital for Sick Children (SickKids) Toronto, ON, Canada Robert F. Dempsey, MD, FACS, FAAP Assistant Professor Division of Plastic Surgery Department of Surgery Texas Children’s Hospital Baylor College of Medicine Houston, TX, United States Rami P. Dibbs, MD Plastic Surgery University of Texas Medical Branch Galveston, TX, United States Sara R. Dickie, MD Clinician Educator Surgery University of Chicago Hospital, Pritzker School of Medicine Chicago, IL; Attending Surgeon Section of Plastic and Reconstructive Surgery NorthShore University HealthSystem Northbrook, IL, United States Nicholas Do, MD Assistant Professor Plastic Surgery Harbor-UCLA Medical Center Torrance, CA, United States

List of Contributors

Russell E. Ettinger, MD Assistant Professor Craniofacial & Plastic Surgery Seattle Children’s Hospital Seattle, WA; Assistant Professor Plastic Surgery University of Washington Seattle, WA, United States Andrew M. Ferry, MD Clinical Research Fellow Division of Plastic Surgery, Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston, TX; Clinical Research Fellow Division of Plastic Surgery, Department of Surgery Texas Children’s Hospital Houston, TX, United States

Mirko S. Gilardino, MD, MSc, FRCSC, FACS Chief Division of Plastic, Reconstructive and Aesthetic Surgery McGill University Health Center Montreal, QC; Director, H.B. Williams Craniofacial and Cleft Surgery Unit Montreal Children’s Hospital Montreal, QC, United States Daniel H. Glaser, MD, MPH Clinical Fellow Division of Pediatric Rheumatology UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA; Assistant Professor of Clinical Pediatrics (Rheumatology) Department of Pediatrics Yale University School of Medicine New Haven, CT, United States

Alexander L. Figueroa, DMD Adjunct Attending Orthodontist Rush Craniofacial Center Division of Plastic Surgery, Department of Surgery Rush University Medical Center Chicago, IL, United States

Jesse A. Goldstein, MD Associate Professor, Department of Plastic Surgery Craniofacial Surgery Fellowship Director Division of Pediatric Plastic Surgery UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA, United States

Alvaro A. Figueroa, DDS, MS Adjunct Associate Professor Rush Craniofacial Center Division of Plastic Surgery, Department of Surgery Rush University Medical Center Chicago, IL, United States

Arun K. Gosain, MD Children’s Service Board Professor and Chief Stanley Manne Children’s Research Institute Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, IL, United States

David M. Fisher, MB, BCh, FRCSC, FACS, MFA Medical Director, Cleft Lip and Palate Program Plastic Surgery The Hospital for Sick Children (SickKids) Toronto, ON; Professor Department of Surgery University of Toronto Toronto, ON, Canada Roberto L. Flores, MD Joseph G. McCarthy Associate Professor of Reconstructive Plastic Surgery Hansjörg Wyss Department of Plastic Surgery NYU Langone Health New York, NY, United States Christopher R. Forrest, MD, MSc, FRCSC, FACS Chief, Division of Plastic and Reconstructive Surgery The Hospital for Sick Children (SickKIds) Professor and Chair, Division of Plastic, Reconstructive and Aesthetic Surgery Department of Surgery, Temerty Faculty of Medicine University of Toronto Toronto, ON, Canada

Lawrence J. Gottlieb, MD Professor of Surgery Section of Plastic and Reconstructive Surgery, Department of Surgery University of Chicago Chicago, IL, United States Arin K. Greene, MD, MMSc Vascular Anomalies and Pediatric Plastic Surgery Endowed Chair Department of Plastic and Oral Surgery Boston Children’s Hospital Boston, MA; Professor of Surgery Harvard Medical School Boston, MA, United States Matthew R. Greives, MD, MS Thomas D. Cronin Chair of Plastic Surgery Division of Plastic Surgery, Department of Surgery McGovern Medical School at the University of Texas Health Sciences Center at Houston Houston, TX, United States Samer E. Haber, MD Unité fonctionnelle de chirurgie craniofaciale, Service de Neurochirurgie Pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Centre de Référence Maladies Rares CRANIOST, Filière Maladies Rares TeteCou, ERN Cranio Paris, France  

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Jordan N. Halsey, MD Assistant Professor Plastic Surgery Johns Hopkins All Children’s Hospital Saint Petersburg, FL, United States Jeffrey Hammoudeh, DDS, MD, FACS Associate Chief Plastic and Maxillofacial Surgery University of Southern California Children’s Hospital Los Angeles Los Angeles, CA, United States Matthew M. Hanasono, MD Professor, Deputy Chair, and Fellowship Program Director Department of Plastic Surgery University of Texas MD Anderson Cancer Center Houston, TX, United States Jill A. Helms, DDS, PhD Professor Department of Surgery Stanford University Stanford, CA, United States Gregory G. Heuer, MD, PhD Associate Professor of Neurosurgery Perelman School of Medicine at the University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, PA, United States David L. Hirsch, MD, DDS, FACS Professor of OMFS/dental Medicine Zucker School of Medicine at Hofstra-Northwell SVP, Dental Medicine Service Line, Northwell Health System Chair of Dental Medicine/OMFS at Long Island Jewish, North Shore, Lenox Hill Hospital New York, NY, United States Larry H. Hollier Jr., MD Surgeon in Chief Texas Children’s Hospital Professor Department of Surgery Baylor College of Medicine Houston, TX, United States Richard A. Hopper, MD, MS Chief Division of Craniofacial and Plastic Surgery Seattle Children’s Hospital Seattle, WA; Surgical Director Craniofacial Center Seattle Children’s Hospital Seattle, WA; Marlys C. Larson Professor Department of Surgery University of Washington Seattle, WA, United States Adam S. Jacobson, MD, FACS Chief, Division of Head and Neck Surgery Co-Director, Head and Neck Center Director, Fellowship in Head and Neck Oncologic and Reconstructive Surgery Department of Otolaryngology – Head and Neck Surgery New York University – Langone Health New York, NY, United States

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List of Contributors

Syril James, MD Unité fonctionnelle de chirurgie craniofaciale, Service de Neurochirurgie Pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Centre de Référence Maladies Rares CRANIOST, Filière Maladies Rares TeteCou, ERN Cranio Paris, France; Clinique Marcel Sembat, Ramsay Générale de Santé Boulogne-Billancourt, France Jeffrey E. Janis, MD Department of Plastic and Reconstructive Surgery Ohio State University Wexner Medical Center Columbus, OH; Past President, American Society of Plastic Surgeons, American Council of Academic Plastic Surgeons, American Hernia Society, and Migraine Surgery Society, United States Christian Jimenez, BS Medical Student Plastic and Reconstructive Surgery Keck School of Medicine of USC Los Angeles, CA, United States

Jamie P. Levine, MD Associate Professor Plastic Surgery NYU Langone Medical Center New York, NY; Chief of Microsurgery New York, NY, United States Jingtao Li, DDS, PhD Associate Professor Oral & Maxillofacial Surgery West China Hospital of Stomatology Sichuan University Chengdu, Sichuan, China Joseph E. Losee, MD Vice Dean for Faculty Affairs, University of Pittsburgh School of Medicine Dr. Ross H. Musgrave Endowed Chair in Pediatric Plastic Surgery Professor and Executive Vice Chair, Department of Plastic Surgery Division Chief, Pediatric Plastic Surgery, UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA, United States

Alexandra Junn, MD Department of Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States

Robert Joseph Mann, MD, FACS Senior Surgeon & Surgical Committee Member, Global Smile Foundation Executive Director of the Michigan / Ohio Chapter of Healing the Children Grand Rapids, MI, United States

Sahil Kapur, MD Resident Physician Division of Plastic Surgery University of Wisconsin Madison, WI, United States

Paul N. Manson, MD Distinguished Service Professor Plastic Surgery Johns Hopkins University Baltimore, MD, United States

Leila Kasrai, MD, MPH, FRCSC Division of Plastic Surgery St Joseph’s Health Centre Toronto, ON, Canada

Benjamin B. Massenburg, MD Resident in Plastic and Reconstructive Surgery Department of Surgery Division of Plastic and Reconstructive Surgery University of Washington Seattle, WA, United States

Henry K. Kawamoto Jr., MD, DDS Clinical Professor, Emeritus Surgery, Division of Plastic Surgery University of California, Los Angeles Los Angeles, CA, United States Roman Khonsari, MD, PhD Unité fonctionnelle de chirurgie craniofaciale Service de chirurgie maxillofaciale et chirurgie plastique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Centre de Référence Maladies Rares CRANIOST, Filière Maladies Rares TeteCou, ERN Cranio; Faculté de Médecine, Université Paris Cité Paris, France Richard E. Kirschner, MD Chair Department of Plastic and Reconstructive Surgery Nationwide Children’s Hospital Columbus, OH; Professor Pediatrics and Plastic Surgery Ohio State University College of Medicine Columbus, OH, United States Katelyn Kondra, MD Department of Plastic and Maxillofacial Surgery Children’s Hospital Los Angeles Los Angeles, CA, United States

Irene Mathijssen, MD, PhD, MBA-H Professor and Head of Department Plastic and Reconstructive Surgery and Hand Surgery Erasmus Medical Center Rotterdam, The Netherlands Frederick J. Menick, MD Medical Director, Cleft Lip and Palate Program Plastic Surgery The Hospital for Sick Children (SickKids) Toronto, ON; Professor Department of Surgery University of Toronto Toronto, ON, Canada Alexander F. Mericli, MD, FACS Associate Professor Plastic Surgery University of Texas MD Anderson Cancer Center Houston, TX, United States Laura A. Monson, MD Assistant Professor Department of Surgery Division of Plastic Surgery Houston, TX, United States

Edwin Morrison, LLB, BComm (Hons Eco), MBBS, FRACS Plastic and Reconstructive Surgery St Vincent’s Hospital Melbourne, VIC; Plastic and Reconstructive Surgery Peter Mac Hospital Melbourne, VIC, Australia John B. Mulliken, MD Professor of Surgery Harvard Medical School Department of Plastic and Oral Surgery Boston Children’s Hospital Boston, MA, United States Lucia Pannuto, MD Fellow Craniofacial surgery Taipei Medical University Hospital Taipei, Taiwan Giovanna Paternoster, MD Unité fonctionnelle de chirurgie craniofaciale, Service de Neurochirurgie Pédiatrique, Hôpital Necker – Enfants Malades, Assistance Publique – Hôpitaux de Paris; Centre de Référence Maladies Rares CRANIOST, Filière Maladies Rares TeteCou, ERN Cranio Paris, France  

John A. Persing, MD Emeritus Professor of Surgery Division of Plastic Surgery Yale School of Medicine New Haven, CT, United States Dale J. Podolsky, BSc, BESc, MD, PhD, FRCSC Surgeon Craniofacial Surgery The Hospital for Sick Children (SickKids) Toronto, ON, Canada Julian J. Pribaz, MD Professor of Surgery Department of Plastic Surgery University of South Florida Tampa, FL, United States Chad A. Purnell, MD Assistant Professor Division of Plastic, Reconstructive, and Cosmetic Surgery University of Illinois-Chicago Chicago, IL; Craniofacial Surgeon Department of Plastic Surgery Shriners Hospitals for Children – Chicago Chicago, IL, United States Pratik Rastogi, MBBS (Hons), GDAAD, MS, FRACS (PRS) Consultant Plastic and Reconstructive Surgeon St George Hospital Sydney, Australia Johanna N. Riesel, MD Assistant Professor, Division of Plastic and Reconstructive Surgery The Hospital for Sick Children (SickKIds) Division of Plastic, Reconstructive and Aesthetic Surgery Department of Surgery, Temerty Faculty of Medicine University of Toronto Toronto, ON, Canada  

 

List of Contributors

Eduardo D. Rodriguez, MD, DDS Professor and Chair Hansjörg Wyss Department of Plastic Surgery NYU Langone Health New York, NY, United States

Eloise Stanton, BA Medical Student Plastic and Reconstructive Surgery Keck School of Medicine of USC Los Angeles, CA, United States

Anna Schoenbrunner, MD, MAS Department of Plastic and Reconstructive Surgery The Ohio State University Columbus, OH, United States

Srinivas M. Susarla, DMD, MD, FACS, FAAP Associate Professor Oral and Maxillofacial Surgery University of Washington School of Dentistry Seattle, WA; Associate Professor Surgery (Plastic) University of Washington School of Medicine Seattle, WA, United States

Lindsay A. Schuster, DMS, MS Director, Cleft-Craniofacial Orthodontics Pediatric Plastic Surgery UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA; Associate Professor of Plastic Surgery Department of Plastic Surgery University of Pittsburgh School of Medicine Pittsburgh, PA, United States Jesse C. Selber, MD, MPH, FACS Associate Professor Plastic Surgery University of Texas MD Anderson Cancer Center Houston, TX, United States Afaaf Shakir, MD Resident Section of Plastic and Reconstructive Surgery Department of Surgery University of Chicago Chicago, IL, United States Sameer Shakir, MD Assistant Professor Division of Pediatric Plastic Surgery, Children’s Wisconsin Department of Plastic Surgery, Medical College of Wisconsin Milwaukee, WI, United States  

 

Pradip R. Shetye, DDS, BDS, MDS Associate Professor (Orthodontics), Director of Craniofacial Orthodontics, and Director of Craniofacial Orthodontic Fellowship Hansjörg Wyss Department of Plastic Surgery NYU Langone Health New York, NY, United States Daniel Simon, DMD Director and Head Surgeon Surgical Department The Facialteam Group Marbella, Málaga, Spain Anusha Singh, MD, MSc Resident Physician Department of Plastic Surgery MedStar Georgetown University Hospital Washington, DC, United States John T. Smetona, MD Craniofacial and Pediatric Plastic Surgery Director of Orthognathic Surgery Advocate Health Oak Lawn, IL, United States Brian Sommerlad, MBBS, DSc(Med) UCL(Hon), FRCS, FRCSE(Hon), FRCPCH, FRCSLT(Hon) Honorary Consultant Plastic Surgeon Department of Plastic Surgery Great Ormond Street Hospital for Children London, United Kingdom

Peter J. Taub, MD, MS Professor and System Chief Division of Plastic and Reconstructive Surgery Icahn School of Medicine at Mount Sinai New York, NY; Director, Cleft and Craniofacial Center Division of Plastic and Reconstructive Surgery Icahn School of Medicine at Mount Sinai New York, NY, United States Jesse A. Taylor, MD Chief, Division of Plastic, Reconstructive, and Oral Surgery Department of Surgery Children’s Hospital of Philadelphia Philadelphia, PA, United States Kathryn S. Torok, MD Co-Director, Pediatric Craniofacial Scleroderma Center UPMC Children’s Hospital of Pittsburgh Pittsburgh, PA; Associate Professor of Pediatrics Pediatric Rheumatology University of Pittsburgh School of Medicine Pittsburgh, PA, United States Raymond W. Tse, MD, FRCSC Associate Professor Craniofacial and Plastic Surgery Seattle Children’s Hospital Seattle, WA, United States Mark Urata, MD, DDS Chief Division of Plastic and Reconstructive Surgery Keck School of Medicine of USC Los Angeles, CA; Chair Division of Oral and Maxillofacial Surgery Ostrow School of Dentistry of USC Los Angeles, CA; Associate Dean of Surgery and Hospital Affairs Ostrow School of Dentistry of USC Los Angeles, CA; Division Head Division of Plastic and Maxillofacial Surgery Children’s Hospital Los Angeles Los Angeles, CA, United States James D. Vargo, MD Craniofacial and Pediatric Plastic Surgeon Plastic Surgery Children’s Hospital and Medical Center Omaha, NE; Assistant Professor of Plastic Surgery Department of Surgery University of Nebraska Medical Center Omaha, NE, United States

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George Washington, MD Resident Plastic and Reconstructive Surgery University of Texas Health Science Center at Houston Houston, TX, United States Erik Wolkswinkel, MD Assistant Professor Division of Plastic and Reconstructive Surgery Oregon Health & Science University Portland, OR, United States Stephen Yen, DMD, PhD Division of Dentistry and Orthodontics Children’s Hospital Los Angeles Los Angeles, CA, United States Peirong Yu, MD Professor Plastic Surgery University of Texas MD Anderson Cancer Center Houston, TX, United States Ronald M. Zuker, MD, FRCSC, FACS, FRCSEd(Hon) Professor of Surgery Department of Surgery University of Toronto Toronto, ON; Staff Plastic and Reconstructive Surgeon Department of Surgery The Hospital for Sick Children (SickKids) Toronto, ON, Canada

VOLUME FOUR Cori A. Agarwal, MD Associate Professor Plastic Surgery University of Utah Salt Lake City, UT, United States Andrew M. Altman, MD Associate Professor Department of Surgery Baylor Scott & White/Texas A&M Temple, TX, United States Andrew Nagy Atia, MD Department of Surgery Division of Plastic, Maxillofacial, and Oral Surgery Duke University Hospital Durham, NC, United States Christopher E. Attinger, MD Chief, Division of Wound Healing Department of Plastic Surgery Georgetown University Hospital Washington, DC, United States Jayson N. Atves, DPM, AACFAS Assistant Professor Plastic Surgery Georgetown University Washington, DC; Program Director MedStar Georgetown University Hospital Foot and Ankle Research Fellowship Washington, DC, United States

List of Contributors

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Håkan Brorson, MD, PhD Professor, Senior Consultant Plastic Surgeon Department of Clinical Sciences Lund University Plastic and Reconstructive Surgery Skåne University Malmö, Sweden; Professor Faculty of Medicine Esculera de Graduados, Asociación Médica Buenos Aires, Argentina; Professor Lund University Cancer Centre Lund, Sweden Paul S. Cederna, MD Chief of Plastic Surgery Robert Oneal Professor of Plastic Surgery Professor of Biomedical Engineering Section of Plastic Surgery, Department of Surgery University of Michigan Ann Arbor, MI, United States  

Brian L. Chang, MD Resident Department of Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States David W. Chang, MD Professor Department of Surgery University of Chicago Chicago, IL, United States Hung-Chi Chen, MD, PhD, FACS Professor Department of Plastic Surgery China Medical University Hospital Taichung, Taiwan Wei F. Chen, MD, FACS Professor of Plastic Surgery Head, Regional Microsurgery and Supermicrosurgery Co-director, Center for Lymphedema Research and Reconstruction Department of Plastic Surgery Cleveland Clinic Cleveland, OH, Unites States Peter G. Cordeiro, MD, FACS Professor of Surgery Weil Medical College of Cornell University New York, NY; William G. Cahan Chair in Surgery Plastic and Reconstructive Surgery Service Memorial Sloan Kettering Cancer Center Westfield, NJ, United States Paige K. Dekker, MD Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States Romina Deldar, MD PGY-4, General Surgery MedStar Georgetown University Hospital Washington, DC, United States

Gregory A. Dumanian, MD Stuteville Professor of Surgery Division of Plastic Surgery Northwestern Feinberg School of Medicine Chicago, IL, United States Karen K. Evans, MD Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States Vahe Fahradyan, MD Assistant Professor Division of Plastic and Reconstructive Surgery Mayo Clinic Rochester, MN, United States Reuben A. Falola, MD, MPH Postdoctoral Research Fellow Plastic & Reconstructive Surgery Baylor Scott & White Temple, TX, United States Rebecca M. Garza, MD Rebecca Garza Plastic Surgery Schererville, IN, United States Günter K. Germann, MD, PhD Professor of Plastic Surgery Department of Plastic, Reconstructive, Hand and Aesthetic Surgery ETHIANUM Clinic Heidelberg Heidelberg, Germany Lawrence J. Gottlieb, MD, FACS Professor of Surgery Section of Plastic & Reconstructive Surgery University of Chicago Chicago, IL, United States Zoe K. Haffner, BS Medical Student Georgetown University School of Medicine Washington, DC, United States J. Andres Hernandez, MD, MBA Resident Physician Division of Plastic, Maxillofacial and Oral Surgery Duke University Hospital Medical Center Durham, NC, United States Scott Thomas Hollenbeck, MD, FACS Plastic and Reconstructive Surgery Duke University Durham, NC, United States Joon Pio Hong, MD, PhD, MMM Professor Plastic Surgery Asan Medical Center University of Ulsan Seoul, Republic of Korea; Adjunct Professor Plastic and Reconstructive Surgery Georgetown University Washington, DC, United States Rayisa Hontscharuk, MD, MSc, FRCSC Plastic, Reconstructive and Aesthetic Surgeon Private Practice Toronto Plastic Surgery Toronto, ON, Canada

Marco Innocenti, MD Chairman and Professor of Plastic Surgery University of Bologna Director of Orthoplastic Surgery Department Rizzoli Institute Bologna, Italy Jeffrey E. Janis, MD Professor of Plastic Surgery, Neurosurgery, Neurology, and Surgery Department of Plastic and Reconstructive Surgery Ohio State University Wexner Medical Center Columbus, OH; Chief of Plastic Surgery, University Hospital Department of Plastic and Reconstructive Surgery Ohio State University Wexner Medical Center Columbus, OH, United States Leila Jazayeri, MD Microsurgery Fellow Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer Center New York, NY, United States Dana N. Johns, MD Assistant Professor Plastic Surgery University of Utah Salt Lake City, UT, United States Ibrahim Khansa, MD, FAAP, FACS Assistant Professor of Plastic and Reconstructive Surgery Department of Plastic and Reconstructive Surgery Nationwide Children’s Hospital Columbus, OH, United States Kevin G. Kim, MD Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States Grant M. Kleiber, MD Attending Surgeon, Assistant Professor Plastic and Reconstructive Surgery MedStar Georgetown University Hospital MedStar Washington Hospital Center Washington, DC, United States Stephen Kovach III, MD Herndon B. Lehr Endowed Associate Professor Division of Plastic Surgery, Department of Orthopaedic Surgery University of Pennsylvania Philadelphia, PA; Assistant Professor Department of Orthopaedic Surgery University of Pennsylvania Philadelphia, PA, United States Nishant Ganesh Kumar, MD House-Officer Section of Plastic Surgery, Department of Surgery University of Michigan Ann Arbor, MI, United States Theodore A. Kung, MD Associate Professor Section of Plastic Surgery Department of Surgery University of Michigan Ann Arbor, MI, United States

List of Contributors

Raphael C. Lee, MS (BmE), MD, ScD, FACS, FIAMBE Paul and Allene Russell Distinguished Service Professor Emeritus Departments of Surgery, Medicine, Molecular Engineering and Molecular Biosciences University of Chicago Chicago Electrical Trauma Rehabilitation Institute Chicago, IL, United States L. Scott Levin, MD, FACS Chair Orthopaedic Surgery Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA, United States Alexander Y. Li, MD, MS Surgeon Plastic and Reconstructive Surgery Stanford Hospital and Clinics Palo Alto, CA, United States Walter C. Lin, MD, FACS Attending Surgeon Reconstructive Microsurgery The Buncke Clinic San Francisco, CA, United States Nicholas F. Lombana, MD, BS Associate Professor Department of Surgery Baylor Scott & White/Texas A&M Temple, TX, United States Otway Louie, MD Associate Professor Surgery University of Washington Medical Center Seattle, WA, United States Elena Lucattelli, MD Breast Unit A. Franchini Hospital Santarcangelo di Romagna, Italy Andrés A. Maldonado, MD, PhD Plastic Surgery University of Getafe Madrid, Spain; Department of Plastic, Hand and Reconstructive Surgery BG Unfallklinik Frankfurt Frankfurt, Germany John D. Miller, DPM Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States Balazs Mohos, MD Microsurgery Fellow Plastic and Reconstructive Surgery, Department of Surgery Hospital of Divine Savior (Göttlicher Heiland Krankenhaus) Vienna, Austria; Heart and Vascular Center, Semmelweis University Budapest, Hungary; Plastic and Reconstructive Surgery, Department of Surgery County Hospital Veszprem Veszprem, Hungary  

Vamseedharan Muthukumar, DNB, M Ch, DrNB, MRCS Junior Consultant, Department of Plastic Surgery Ganga Hospital Coimbatore, Tamil Nadu, India  

Venkateshwaran Narasiman, MS, MCh. Plastic Surgery Consultant Plastic Surgeon Director- Wound Clinic Jupiter Hospital, Thane, Maharashtra, India; Hon. Visiting Consultant Seth G S Medical College and KEM Hospital Mumbai, India Lynn M. Orfahli, MD Resident Division of Plastic and Reconstructive Surgery University of Colorado Aurora, CO, United States Rajiv P. Parikh, MD, MPHS Attending Surgeon, Assistant Professor Plastic and Reconstructive Surgery MedStar Georgetown University Hospital MedStar Washington Hospital Center Washington, DC, United States  

Vinita Puri, MS (General Surgery), MCh (Plastic Surgery) Professor and Head Department of Plastic Surgery Seth G S Medical College and KEM Hospital Mumbai, Maharashtra, India Andrea L. Pusic, MD Chief Plastic and Reconstructive Surgery Brigham and Women’s Hospital Boston, MA, United States S. Raja Sabapathy, MS, MCh, DNB, FRCSE, FAMS, Hon FRCSG, Hon FRCS (Eng), Hon FACS, DSc (Hon) Chairman Department of Plastic Surgery, Hand Surgery, Reconstructive Microsurgery, and Burns Ganga Hospital Coimbatore, Tamil Nadu, India Hakim Said, MD, FACS Clinical Associate Professor Division of Plastic Surgery University of Washington Seattle, WA, United States Bauback Safa, MD, MBA, FACS Attending Surgeon Reconstructive Microsurgery The Buncke Clinic San Francisco, CA; Adjunct Clinical Faculty Division of Plastic and Reconstructive Surgery Stanford University Palo Alto, CA, United States Michel H. Saint-Cyr, MD, FRCSC Professor Plastic Surgery Banner MD Anderson Cancer Center Phoenix, AZ, United States

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Michael Sauerbier, MD, PhD PROFESSOR SAUERBIER Private Practice for Hand and Plastic Surgery Bad Homburg v.d. Höhe, Germany Adaah A. Sayyed, BS Medical Student Georgetown University School of Medicine Washington, DC, United States Loren Schechter, MD Professor of Surgery Division of Plastic Surgery Rush University Medical Center Chicago, IL, United States Kaylee B. Scott, MD Resident Physician Division of Plastic Surgery University of Utah Salt Lake City, UT, United States R. Raja Shanmugakrishnan, MS, DNB, MRCS Consultant, Department of Plastic and Burns Surgery Ganga Hospital Coimbatore, Tamil Nadu, India  

Banafsheh Sharif-Askary, MD Resident Department of Plastic and Reconstructive Surgery MedStar Georgetown University Hospital Washington, DC, United States David H. Song, MD, MBA Physician Executive Director and Chairman Plastic Surgery Georgetown University Washington, DC, United States Ping Song, MD Virginia Hospital Center Department of Plastic and Reconstructive Surgery Arlington, VA, United States John S. Steinberg, DPM Professor Plastic Surgery Georgetown University School of Medicine Washington, DC, United States Hyunsuk Peter Suh, MD, PhD Associate Professor Plastic Surgery Asan Medical Center Seoul, Republic of Korea Yueh-Bih Tang, MD, PhD Professor in Plastic Surgery National Taiwan University Hospital Taipei; Attending Plastic Surgeon Far Eastern Memorial Hospital New Taipei City, Taiwan Chad M. Teven, MD, MBA, FACS, HEC-C Assistant Professor of Surgery (Clinical) Division of Plastic Surgery Northwestern University Feinberg School of Medicine Chicago, IL, United States

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List of Contributors

Chieh-Han John Tzou, MD, PhD, MBA Director of Plastic and Reconstructive Surgery Hospital of Divine Savior (Göttlicher Heiland Krankenhaus) Vienna; Associate Professor of Plastic and Reconstructive Surgery Faculty of Medicine Sigmund Freud University Vienna; Director Lymphedema and Facial Palsy Center TZOU MEDICAL Vienna, Austria  

Bradley P. Bengtson, MD, FACS Founder and CEO Bengtson Center for Aesthetics and Plastic Surgery Grand Rapids, MI; Associate Professor Department of Surgery Michigan State University Grand Rapids, MI, United States Giovanni Bistoni, MD Department of Surgery “Pietro Valdoni” Plastic Surgery Unit Policilinico Umberto I, University of Rome “Sapienza” Rome, Italy  

 

Sebastian Q. Vrouwe, MD, FRCSC Assistant Professor of Surgery Section of Plastic & Reconstructive Surgery University of Chicago Chicago, IL, United States

VOLUME FIVE Allen Gabriel, MD, FACS Plastic Surgeon Vancouver, WA; Clinical Professor Plastic Surgery Loma Linda University Medical Center Loma Linda, CA, United States Robert J. Allen Sr., MD Director Microsurgical Breast Reconstruction Department Ochsner Baptist Hospital New Orleans, LA; Clinical Professor of Plastic Surgery Department of Plastic and Reconstructive Surgery Louisiana State University New Orleans, LA, United States Claudio Angrigiani, MD Director Oncoplastic Surgery Hospital de Clínicas José de San Martín University of Buenos Aires Buenos Aires, Argentina Eric Michel Auclair, MD Plastic Surgeon Clinique Nescens Paris, France Saïd C. Azoury, MD Assistant Professor of Surgery (Plastic Surgery) Division of Plastic Surgery University of Pennsylvania Philadelphia, PA; Assistant Professor of Orthopaedic Surgery Orthopedic Surgery University of Pennsylvania Philadelphia, PA, United States Nusaiba F. Baker, PhD MD PhD Student Medicine Emory University Atlanta, GA, United States

 

Gaines Blasdel, BS Research Associate Department of Urology NYU Langone Health New York City, NY; University of Michigan Medical School Ann Arbor, MI, United States Phillip Blondeel, MD, PhD, FCCP Professor Plastic and Reconstructive Surgery Ghent University Ghent, Belgium Rachel Bluebond-Langner, MD Associate Professor of Plastic Surgery Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of Medicine New York, NY, United States Elisa Bolletta, MD, MRBS (Master’s Degree in Surgical Oncology, Reconstructive and Aesthetic Breast Surgery) Department of Plastic and Reconstructive Surgery Policlinico Sant’Orsola-Malpighi IRCCS Bologna, Italy M. Bradley Calobrace, MD Gratis Clinical Faculty Department of Plastic Surgery University of Louisville; CaloAesthetics Plastic Surgery Center Louisville, KY, United States Daniel Calva-Cerquiera, MD Miami Breast Center Miami, FL, United States John C. Cargile, MD Department of Anesthesiology Baylor Scott & White Memorial Hospital Temple, TX, United States Pierre Chevray, MD, PhD Plastic Surgeon Institute for Reconstructive Surgery Houston Methodist Hospital Houston, TX; Associate Professor Surgery Weill Cornell Medical College New York, NY; Adjunct Associate Professor Surgery Baylor College of Medicine Houston, TX, United States

David Chi, MD, PhD Resident Physician Division of Plastic and Reconstructive Surgery Washington University in St. Louis St. Louis, MO, United States Vincent J. Choi, BSc (Med), MBBS, MS, FRACS (Plast) Plastic Surgery University Health Network, University of Toronto Toronto, ON, Canada Matthew Cissell, DHSc, PA-C Surgical Physician Assistant National Center for Plastic Surgery McLean, VA, United States Salih Colakoglu, MD Assistant Professor Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States Amy S. Colwell, MD Professor Division of Plastic Surgery Massachusetts General Hospital, Harvard Medical School Boston, MA, United States Raul A. Cortes, MD Miami Breast Center Miami, FL, United States Mark W. Clemens II, MD, MBA, FACS Professor Plastic Surgery MD Anderson Cancer Center; Associate Vice President Perioperative Services MD Anderson Cancer Center Houston, TX, United States Peter G. Cordeiro, MD Attending Surgeon Department of Surgery Memorial Sloan Kettering Cancer Center; Professor of Surgery Weil Medical College of Cornell University New York, NY, United States Connor Crowley, MD Resident Doctor Department of Surgery Northwell New Hyde Park, NY, United States Anand Deva, MBBS(Hons), MS, FRACS Professor Plastic and Reconstructive Surgery Integrated Specialist Healthcare Miranda, NSW, Australia Roy de Vita Chief Plastic and Reconstructive Surgery Department Regina Elena National Cancer Institute Rome, Italy Francesco M. Egro, MD, MSc, MRCS Associate Professor, Department of Plastic Surgery Associate Professor, Department of Surgery University of Pittsburgh Pittsburgh, PA, United States

List of Contributors

Jin Sup Eom, MD, PhD Professor Plastic Surgery Asan Medical Center University of Ulsan, College of Medicine Seoul, Republic of Korea Reuben A. Falola, MD, MPH Postdoctoral Research Fellow Division of Plastic and Reconstructive Surgery Baylor Scott & White Medical Center Temple, TX, United States Jian Farhadi, MD, PD Professor Plastic Surgery Group Zurich; Professor University of Basel Basel, Switzerland Caroline A. Glicksman, MD, MSJ Assistant Clinical Professor Department of Surgery Hackensack Meridian School of Medicine Nutley, NJ, United States Daniel J. Gould, MD, PhD Surgeon, Private Practice Gould Plastic Surgery Beverly Hills, CA, United States Vendela Grufman, MD Consultant Plastic Surgery Plastic Surgery Group Zurich, Switzerland Nicholas T. Haddock VC Business Affairs, Associate Professor Department of Plastic Surgery University of Texas Southwestern Dallas, TX, United States Elizabeth J. Hall-Findlay, MD, FRCSC Private Practice Banff Plastic Surgery Banff, AB, Canada Moustapha Hamdi, MD, PhD Professor Plastic and Reconstructive Surgery Brussels University Hospital Brussels, Belgium Dennis C. Hammond, MD Assistant Program Director Grand Rapids Plastic Surgery Residency Spectrum Health Grand Rapids, MI, United States Hyunho Han, MD, PhD Associate Professor Asan Medical Center University of Ulsan, College of Medicine Seoul, Republic of Korea Adam T. Hauch, MD, MBA Assistant Professor of Clinical Surgery Department of Surgery Louisiana State University New Orleans, LA, United States Stefan O.P. Hofer, MD, PhD, FRCSC Professor of Plastic Surgery University Health Network, University of Toronto Toronto, ON, Canada

Marcelo Irigo, MD Chief Plastic Surgery Hospital Italiano La Plata La Plata, Argentina Suhail K. Kanchwala, MD Associate Professor of Surgery Division of Plastic Surgery University of Pennsylvania Philadelphia, PA, United States Nolan S. Karp, MD Professor of Plastic Surgery Hansjörg Wyss Department of Plastic Surgery NYU Grossman School of Medicine, New York, NY, United States Grace Keane, MD Resident Physician Plastic and Reconstructive Surgery Washington University School of Medicine Saint Louis, MO, United States Nima Khavanin, MD Resident Physician Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States Roger Khalil Khouri, MD, FACS Medical Director Miami Breast Center Miami, FL; Professor Department of Surgery Florida International University School of Medicine Miami, FL, United States John Y.S. Kim, MD, MA Professor Department of Surgery Northwestern University Chicago, IL, United States Emma C. Koesters, MD Assistant Professor Plastic and Reconstructive Surgery University of Southern California Los Angeles, CA, United States Jake C. Laun, MD Assistant Professor Department of Plastic Surgery University of South Florida Tampa, FL, United States Patricia McGuire, MD, FACS Clinical Instructor of Surgery Washington University St Louis, MO, United States Gustavo Jiménez Muñoz Ledo, MD Private Practice Phi Aesthetics León Guanajuato, México Anne C. O’Neill, MBBCh, MMedSci, FRCS(Plast), MSc, PhD Associate Professor of Plastic Surgery University Health Network, University of Toronto Toronto, ON, Canada

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Andrzej Piatkowski, MD, PhD Associate Professor Department of Plastic and Reconstructive Surgery Maastricht University Medical Centre, MUMC+ Maastricht, The Netherlands Rachel Lentz, MD Assistant Professor Plastic and Reconstructive Surgery University of Washington Seattle, WA, United States Joan E. Lipa, MD, MSc, FRCSC, FACS Associate Professor Department of Surgery, Division of Plastic, Reconstructive & Aesthetic Surgery University of Toronto; Active Staff Sunnybrook Health Sciences Centre Toronto, ON, Canada Nicholas F. Lombana, MD Plastic Surgery Resident Division of Plastic and Reconstructive Surgery Baylor Scott & White Medical Center Temple, TX, United States Albert Losken, MD, FACS Emory University Division of Plastic and Reconstructive Surgery Emory University Hospital Atlanta, GA, United States Patrick Mallucci, MD Director of Plastic Surgery Mallucci London London, United Kingdom Michele Ann Manahan, MD, MBA, FACS Professor of Clinical Plastic and Reconstructive Surgery Vice Chair of Faculty and Staff Development and Well-Being Department of Plastic and Reconstructive Surgery Johns Hopkins Hospital Baltimore, MD, United States Past President, MedChi, The Maryland State Medical Society Jaume Masià, MD, PhD Chief and Professor Plastic Surgery Sant Pau University Hospital (Universitat Autonoma de Barcelona) Barcelona, Spain Chester J. Mays, MD Plastic Surgeon CaloAaesthetics Plastic Surgery Center CaloAesthetics Plastic Surgery Louisville, KY, United States Patrick Maxwell, MD Plastic Surgeon Assistant Professor of Surgery Vanderbilt University Nashville, TN, United States

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List of Contributors

Adrian McArdle, MBBCh, MD, FRCSI, FEBOPRAS Assistant Professor Department of Surgery, Division of Plastic, Reconstructive and Aesthetic Surgery University of Toronto; Division of Plastic and Reconstructive Surgery Trillium Health Partners Toronto, ON, Canada Colleen M. McCarthy, MD, MHS Attending Surgeon Department of Surgery Memorial Sloan Kettering Cancer Center New York, NY, United States Alexandre Munhoz, MD, PhD Plastic Surgery Hospital Sírio-Libanês São Paulo; Professor Plastic Surgery Instituto do Câncer do Estado de São Paulo São Paulo, SP, Brazil Alex Mesbahi, MD, FACS Founding Partner National Center for Plastic Surgery McLean, VA, United States Arash Momeni, MD, FACS Director, Clinical Outcomes Research Division of Plastic & Reconstructive Surgery Stanford University Medical Center Palo Alto, CA, United States Kiya Movassaghi, MD, DMD, FACS Assistant Clinical Professor; Director, Aesthetic Surgery Fellowship at Movassaghi Plastic Surgery Division of Plastic Surgery Oregon Health & Science and University Portland, OR, United States Terence M. Myckatyn, MD, FACS, FRCSC Professor, Plastic and Reconstructive Surgery Washington University School of Medicine Saint Louis, MO, United States Maurizio Nava, MD Breast & Plastic Surgeon Assistant Professor of Surgery University of Milan Milan, Italy Maurice Y. Nahabedian, MD, FACS Former Professor of Plastic Surgery Johns Hopkins University, Georgetown University and the Virginia Commonwealth University Private practice- National Center for Plastic Surgery Mclean, VA, United States Dries Opsomer, MD Plastic Surgery OLV Aalst Aalst, Belgium Janak A. Parikh, MD, MSHS Resident Plastic Surgery Houston Methodist Houston, TX, United States

Ketan M. Patel, MD Assistant Professor Plastic and Reconstructive Surgery University of Southern California Los Angeles, CA, United States Nakul Gamanlal Patel, BSc(Hons), MBBS(Lond), FRCS(Plast) Consultant Plastic Surgeon Department for Plastic Surgery and Burns University Hospitals of Leicester Leicester, United Kingdom Pat Pazmiño Associate Professor Division of Plastic Surgery University of Miami Miller School of Medicine Miami, FL, United States Justin L. Perez, MD Plastic Surgeon Medical Director, Marina Plastic Surgery MarinaRox Aesthetic Fellowship Marina del Rey, CA, United States Cristhian D. Pomata, MD, MSc Associate Plastic Surgery Clinica Planas Barcelona, Spain Julian J. Pribaz, MD Professor of Surgery Department of Plastic Surgery University of South Florida Tampa, FL, United States

Justin M. Sacks, MD, MBA, FACS Chief Division of Plastic and Reconstructive Surgery Sidney M. Jr. and Robert H. Shoenberg Professor of Surgery Washington University in St. Louis School of Medicine St. Louis, MO, United States Michel H. Saint-Cyr, MD, MBA, FRCSC Professor Department of Plastic and Reconstructive Surgery Banner M.D. Anderson Cancer Center Phoenix, AZ, United States Javier Sanz, MD, PhD Associate Professor Pompeu Fabra University Barcelona Radiation Oncologist Radiation Oncology Department Hospital del Mar Barcelona, Spain Hugo St. Hilaire, MD, DDS, FACS Clinical Professor of Surgery Division Chief Plastic and Reconstructive Surgery Louisiana State University Baton Rouge, LA, United States Ara A. Salibian, MD Assistant Professor Plastic & Reconstructive Surgery University of California, Davis School of Medicine Sacramento, California, United States

Venkat V. Ramakrishnan, MS, FRCS, FRACS (Plastic Surgery) Consultant Plastic Surgeon St. Andrews Centre for Plastic Surgery Broomfield Hospital UK Chelmsford, Essex, United Kingdom

Karim A. Sarhane, MD, MSc General, Laparoscopic and Peripheral Nerve Surgeon Burjeel Royal Hospital, Al Ain Abu Dhabi, UAE

Agustin Rancati, MD Department of Surgery Hospital Británico Buenos Aires Buenos Aires, Argentina

Hani Sbitany, MD Professor of Surgery Division of Plastic Surgery Mount Sinai Medical Center New York, NY, United States

Alberto Rancati, MD, PhD Breast & Plastic Surgery Assistant Professor Surgery Florida International University – FIU Miami, FL, United States Charles Randquist, MD Plastic Surgeon Victoriakliniken Saltsjöbaden, Sweden Gedge D. Rosson, MD Associate Professor Department of Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States J. Peter Rubin, MD, MBA, FACS Chair, Department of Plastic Surgery at UPMC and the University of Pittsburgh UPMC Endowed Professor of Plastic Surgery Professor of Bioengineering University of Pittsburgh Pittsburgh, PA, United States

Jesse C. Selber, MD, MPH, FACS Professor, Vice Chair, Director of Clinical Research Department of Plastic Surgery MD Anderson Cancer Center Houston, TX, United States Orr Shauly Resident Physician Plastic and Reconstructive Surgery Emory University School of Medicine Atlanta, GA, United States Aldona J. Spiegel, MD Houston Methodist Institute for Reconstructive Surgery Houston Methodist Hospital Houston, TX, United States Michelle Spring, MD, FACS Mountain West Plastic Surgery Kalispell, MT, United States Sandpoint, ID, United States

 

 

List of Contributors

Grant Stevens, MD Professor Emeritus of Surgery Founder, Marina Plastic Surgery Associates Keck School of Medicine of USC Los Angeles, CA, United States Christopher N. Stewart, MD Plastic Surgeon Private Practice New Beautiful You Casper, WY, United States Neil Tanna, MD, MBA Professor Plastic Surgery Zucker School of Medicine at Hofstra/Northwell Hempstead, NY; Associate Program Director Plastic Surgery Northwell Health; Vice President, Women’s Surgical Services Northwell Health Great Neck, NY, United States Marissa Tenenbaum, MD Associate Professor of Surgery Director of Aesthetic Surgery Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis, MO, United States Sumeet S. Teotia, MD, FACS Professor, Department of Plastic Surgery Director, Breast Reconstruction Program Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TX, United States Eliora A. Tesfaye, MD Plastic Surgery M.D. Anderson Cancer Center Houston, TX; Virginia Commonwealth University Richmond, VA, United States Dinesh Thekkinkattil, MD Oncoplastic Breast Surgeon Lincoln County Hospital Lincoln, UK Mark L. Venturi, MD, FACS Founding Partner National Center for Plastic Surgery McLean, VA, United States Raghavan Vidya, MD Oncoplastic Breast Surgeon Royal Wolverhampton Hospital Birmingham University Birmingham, UK Brittany L. Vieira, MD Resident Physician Division of Plastic and Reconstructive Surgery Massachusetts General Hospital Boston, MA, United States Veronica Vietti Michelina, MD Plastic and Reconstructive Surgery Department Regina Elena National Cancer Institute Rome, Italy

Liza C. Wu, MD Associate Professor PRIVÉ Plastic Surgery Boca Raton, Florida, United States Louisa Yemc, PA-C Surgical Physician Assistant National Center for Plastic Surgery McLean, VA, United States VOLUME SIX Hee Chang Ahn, MD, PhD Professor Plastic and Reconstructive Surgery CHA University Bundang Medical Center Seongnam, Gyeonggi-do, Republic of Korea Nidal F. Al Deek, MD, MSc Consultant Plastic and Reconstructive Surgery Chang Gung Memorial Hospital Taipei, Taiwan Rita E. Baumgartner, MD Attending Physician Panorama Summit Orthopedics Frisco, CO, United States Aaron Berger, MD, PhD Chief/Medical Director of Programs in Pediatric Hand, Brachial Plexus and Peripheral Nerve Division of Plastic Surgery Nicklaus Children’s Hospital Miami, FL; Clinical Assistant Professor Division of Plastic Surgery Florida International University School of Medicine Miami, FL; Voluntary Assistant Professor Department of Orthopedic Surgery University of Miami Miller School of Medicine Miami, FL, United States Anna Berridge, MBBS, BSc, FRCS (Tr & Orth) Consultant Orthopaedic Hand and Wrist Surgeon Ipswich Hospital East Suffolk and North Essex Foundation Trust Ipswich, United Kingdom Randy R. Bindra, MChOrth, FRCS Professor Orthopaedic Surgery Griffith University and Gold Coast University Hospital Gold Coast, QLD, Australia Nathalie Bini, MD Pediatric Orthopedics Regina Margherita Hospital Turin, Italy Gregory H. Borschel, MD, FACS, FAAP, FAAPS James Harbaugh Professor of Surgery Indiana University School of Medicine Chief of Plastic Surgery, Riley Hospital for Children Indianapolis, Indiana, United States

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Kirsty Usher Boyd, MD, FRCSC Associate Professor Division of Plastic Surgery The Ottowa Hospital University of Ottawa Ottawa, ON, Canada Gerald Brandacher, MD Scientific Director Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States Amanda Brown, MD Division of Plastic and Reconstructive Surgery St. Louis University School of Medicine St. Louis, MO, United States Hazel Brown, MSc Advanced Physiotherapy, BSc Hons Physiotherapy, Post Grad Dip Orthopaedic Medicine Clinical Specialist Physiotherapist Peripheral Nerve Injury Unit Royal National Orthopaedic Hospital Stanmore, United Kingdom Sara Calabrese, MD Plastic Reconstructive and Aesthetic Surgery Resident Plastic, Reconstructive and Aesthetic Surgery Department Careggi University Hospital Florence, Italy Ryan P. Calfee, MD, MSc Professor Orthopedic Surgery Washington University School of Medicine in St. Louis St. Louis, MO, United States Logan W. Carr, MD Attending Physician Division of Plastic Surgery Westchester Medical Center Valhalla, NY; Associate Professor of Surgery New York Medical College Valhalla, NY, United States James K-K. Chan, MA(Cantab), DPhil(Oxon), FRCS(Plast) Consultant Hand, Plastic and Reconstructive Surgeon Department of Plastic Surgery Stoke Mandeville Hospital Aylesbury; Clinical Lecturer Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford, United Kingdom James Chang, MD Johnson & Johnson Distinguished Professor and Chief Division of Plastic Surgery Stanford University Medical Center Palo Alto, CA, United States

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List of Contributors

Robert A. Chase, MD Emile Holman Professor of Surgery (Emeritus) Department of Surgery Stanford University Stanford, CA, United States

Lars B. Dahlin, MD, PhD Professor Hand Surgery Department of Translational Medicine Malmö, Sweden

Paige M. Fox, MD, PhD Department of Surgery, Division of Plastic and Reconstructive Surgery Stanford University School of Medicine Stanford, CA, United States

Shanlin Chen, MD, PhD Professor and Consultant Orthopaedic Surgeon Chief, Department of Hand Surgery Beijing Ji Shui Tan Hospital National Center for Orthopedics Beijing, China

Soumen Das De, MBBS, FRCS, MPH Consultant Department of Hand and Reconstructive Microsurgery National University Health System Singapore

Jeffrey B. Friedrich, MD, FACS Professor of Surgery and Orthopedics Department of Surgery University of Washington Seattle, WA, United States

Harvey Chim, MD Professor Plastic and Reconstructive Surgery University of Florida College of Medicine Gainesville, FL, United States

Kristen M. Davidge, MD, MSc, FRCSC Plastic and Reconstructive Surgeon Department of Surgery Hospital for Sick Children Toronto; Assistant Professor Department of Surgery University of Toronto; Associate Scientist Child Health and Evaluative Sciences Sick Kids Research Institute Toronto, ON, Canada

Alphonsus K.S. Chong, MBBS Associate Professor Department of Orthopaedic Surgery National University of Singapore; Group Chief and Senior Consultant Department of Hand and Reconstructive Microsurgery National University Health Systems Singapore David Chwei-Chin Chuang, MD Professor Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Branch Gueishan District, Taoyuan City, Taiwan Kevin C. Chung, MD, MS Professor of Surgery Section of Plastic Surgery University of Michigan; Chief of Hand Surgery University of Michigan Ann Arbor, MI, United States J. Henk Coert, MD, PhD Professor Plastic Surgery UMC Utrecht Utrecht, The Netherlands Christopher Cox, MD Orthopedic Hand Surgery Kaiser Permanente Walnut Creek, CA, United States Catherine Curtin, MD Professor Department of Surgery Palo Alto VA Palo Alto, CA; Professor Department of Surgery Stanford University Palo Alto, CA, United States Simeon C. Daeschler, MD, Dr. med Postdoctoral Fellow Neuroscience and Mental Health Program SickKids Research Institute, Hospital for Sick Children (SickKids) Toronto, ON, Canada

Paul C. Dell, MD Professor Department of Orthopaedic Surgery and Sports Medicine University of Florida College of Medicine Gainesville, FL, United States Jana Dengler, MD, MASc Assistant Professor Department of Surgery University of Toronto; Staff Physician Department of Surgery Sunnybrook Health Sciences Program Toronto, ON, Canada Gregory Ara Dumanian, MD Stuteville Professor of Surgery Division of Plastic Surgery Northwestern Feinberg School of Medicine Chicago, IL, United States Simon Farnebo, MD, PhD Professor Department of Biomedical and Clinical Sciences and Department of Plastic Surgery, Hand Surgery, and Burns Faculty of Medicine and Health Sciences Linköping University Linköping, Sweden Margaret Fok, MBChB, FRCSE(Ortho), FHKAM (Orthopaedic Surgery) Associate Consultant Department of Orthopaedics and Traumatology Queen Mary Hospital Hong Kong; Honorary Clinical Assistant Professor Department of Orthopaedics and Traumatology The University of Hong Kong Hong Kong Ida K. Fox, MD Professor of Plastic Surgery Department of Surgery Washington University School of Medicine in St. Louis St. Louis, MO, United States

Brittany N. Garcia, MD Hand and Upper Extremity Surgery University of Utah Department of Orthopedic Surgery Salt Lake City, UT, United States Charles A. Goldfarb, MD Executive Vice Chair Orthopedic Surgery Washington University School of Medicine in St. Louis; Professor Orthopedic Surgery Washington University School of Medicine in St. Louis St Louis, MO, United States Kimberly Goldie Staines, OTR, CHT Visiting Researcher Michael E. DeBakey Veterans Affairs Medical Center Houston, TX; Adjunct Faculty Department of Immunology, Allergy, and Rheumatology Baylor College of Medicine Houston, TX, United States Elisabeth Haas-Lützenberger, MD Division of Hand, Plastic and Aesthetic Surgery University Hospital LMU Munich Munich, Germany Steven C. Haase, MD, FACS Professor Surgery University of Michigan Health Ann Arbor, MI, United States Leila Harhaus, MD, Prof. dr. med. Chief, Department for Handsurgery, Peripheral Nerve Surgery and Rehabilitation Vice Chair, Department for Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center BG Trauma Hospital Ludwigshafen; Chair, Section Upper Extremity, Orthopedic University Hospital Heidelberg University of Heidelberg Heidelberg, Germany Elisabet Hagert, MD, PhD Associate Professor Department of Clinical Science and Education Karolinska Institute Stockholm, Sweden; Head of Hand Surgery Department of Surgery Aspetar Orthopedic- and Sports Medicine Hospital Doha, Qatar

List of Contributors

Warren C. Hammert, MD Professor of Orthopedic and Plastic Surgery Orthopedic Surgery Duke University Durham, NC, United States Dennis Hazell, RN, MChiro, Independent Prescriber Clinical Nurse Specialist Peripheral Nerve Injury Unit Royal National Orthopaedic Hospital Stanmore, United Kingdom Vincent Henta, MD Professor of Surgery, Emeritus Plastic Surgery Stanford University Stanford, CA, United States

Jason Hyunsuk Ko, MD, MBA, FACS Associate Professor Division of Plastic and Reconstructive Surgery Northwestern University Feinberg School of Medicine Chicago; Associate Professor Department of Orthopedic Surgery Northwestern University Feinberg School of Medicine Chicago, IL, United States

Vincent R. Hentz, MD Professor of Surgery, Emeritus Department of Plastic Surgery Stanford University Stanford, CA, United States

David A. Kulber, MD Professor of Surgery Cedars Sinai Medical Center and USC Keck School of Medicine; Director of Hand and Upper Extremity Surgery Program Director Marilyn and Jeffrey Katzenberg Hand Fellowship Department of Orthopedic Surgery, Cedars Sinai Medical Center; Director of the Plastic Surgery Center of Excellence Cedars Sinai Medical Center Los Angeles, CA, United States

Charlotte Jaloux, MD Assistant Professor Hand and Limb Reconstructive Surgery Timone University Hospital - APHM Marseille, France

Bhaskaranand Kumar, MBBS, MS (Ortho) Formerly Professor and Head Department of Orthopaedic Surgery Kasturba Medical College Manipal, India

Neil F. Jones, MD, FRCS, FACS Distinguished Professor of Plastic and Reconstructive Surgery Distinguished Professor of Orthopedic Surgery Ronald Reagan UCLA Medical Center and David Geffen School of Medicine University of California, Los Angeles; Consultant in Hand Surgery and Microsurgery Division of Plastic and Reconstructive Surgery Shriners Hospital for Children Los Angeles, CA, United States

Donald Lalonde, HonsBSc, MSc, MD, FRCSC, DSc Professor Plastic Surgery Dalhousie University Saint John, NB, Canada

Jonay Hill, MD Private practice Park City, Utah, United States

Sumanas W. Jordan, MD, PhD Division of Plastic and Reconstructive Surgery Northwestern University Chicago, IL, United States Ryosuke Kakinoki, MD, PhD Professor of Hand Surgery and Microvascular Reconstructive Surgery Orthopedic Surgery Kindai University Osaka-sayama Osaka, Japan Jason R. Kang, MD Kaiser Permanente Physician Orthopedics Department Garfield Specialty Care Center San Diego, CA, United States Marco Innocenti, MD Chairman and Professor of Plastic Surgery University of Bologna; Director of Orthoplastic Surgery Department Rizzoli Institute Bologna, Italy

Wee Leon Lam, MBChB, FRCS(Plast) Consultant Plastic and Hand Surgeon Department of Plastic and Reconstructive Surgery Royal Hospital for Children and Young People Edinburgh; Honorary Clinical Senior Lecturer University of Edinburgh Edinburgh, United Kingdom Caroline Leclerq, MD Consultant Hand Surgeon Institut de la Main Clinique Bizet Paris; Consultant Hand Surgeon Neuro-orthopaedic Rehabilitation CRN Coubert Coubert; Consultant Hand Surgeon Neuro-paediatric Rehabilitation Hôpital National Saint Maurice Saint Maurice, France Dong Chul Lee, MD Attending Physician Plastic and Reconstructive Surgery Gwangmyeong Sungae Hospital Gwangmyeong, Gyeonggi-do, Republic of Korea

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W.P. Andrew Lee, MD Provost and Dean Office of Provost University of Texas Southwestern Medical Center Dallas, TX, United States Anais Legrand, MD Postdoctoral Research Fellow Plastic & Reconstructive Surgery Stanford University Medical Center Palo Alto, CA, United States Janice Liao, MBBS, MRCS, FAMS Consultant Department of Hand and Reconstructive Microsurgery National University Health Systems Singapore Christopher D. Lopez, MD Resident Physician Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States Joseph Lopez, MD, MBA Chief of Pediatric Head and Neck Surgery Head and Neck Surgery AdventHealth for Children Orlando, FL, United States Johnny Chuieng-Yi Lu, MD, MSCI Associate Professor Department of Plastic and Reconstructive Surgery Chang Gung Memorial Hospital, Linkou Branch Gueishan District, Taoyuan City, Taiwan Susan E. Mackinnon, MD, FRCSC, FACS Minot Packer Fryer Professor of Surgery Director of the Center for Nerve Injury and Paralysis Professor of Plastic and Reconstructive Surgery Division of Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis, MO, United States Brian A. Mailey, MD Associate Professor of Surgery Division Chief Plastic and Reconstructive Surgery Chief Pediatric Plastic Surgery Cardinal Glennon Children’s Hospital Pandrangi Family Endowed Professor of Plastic Surgery St. Louis University School of Medicine St. Louis, MO, United States Minnie Mau, OT, CHT/L Occupational Therapist, Certified Hand Therapist Hand Therapy Stanford Health Care Redwood City, CA, United States Steven J. McCabe, MD, MSc, FRCS(C) Director of Hand Program Department of Surgery University of Toronto Toronto, ON, Canada Meghan C. McCullough, MD, MS Plastic and Reconstructive Surgery Cedars Sinai Hospital Los Angeles, CA, United States

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List of Contributors

Kai Megerle, MD, PhD Professor and Chief Center for Hand Surgery, Microsurgery and Plastic Surgery Schoen Clinic Munich Munich, Germany Amy M. Moore, MD Professor and Chair Plastic and Reconstructive Surgery The Ohio State University Columbus, OH, United States Wendy Moore, OTR/L, CHT Assistant Manager Rehab Services Hand Therapy Stanford Health Care Redwood City, CA, United States Steven L. Moran, MD Professor of Plastic Surgery and Orthopedic Surgery Mayo College of Medicine and Science Mayo Clinic, Rochester, MN, United States Jagdeep Nanchahal, BSc, PhD, FRCS(Plast) Professor Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford, United Kingdom David T. Netscher, MD Professor Division of Plastic Surgery, Department of Orthopedic Surgery Baylor College of Medicine Houston, TX, United States Michael W. Neumeister, MD Professor and Chairman Surgery SIU School of Medicine; The Elvin G. Zook Endowed Chair in Plastic Surgery SIU School of Medicine, Springfield, IL, United States Christianne A. van Nieuwenhoven, MD, PhD Plastic Surgeon/Hand Surgeon Plastic and Reconstructive Surgery and Hand Surgery Erasmus Medical Center Rotterdam Rotterdam, The Netherlands Kerby C. Oberg, MD, PhD Professor and Vice Chair Pathology and Human Anatomy Loma Linda University Loma Linda, CA, United States Andrew O’Brien, MD, MPH Clinical Instructor, Housestaff Plastic and Reconstructive Surgery The Ohio State University Medical Center Columbus, OH, United States

Eugene Park, MD Pediatric Hand and Plastic Surgeon Plastic Surgery Shriners Children’s Philadelphia; Clinical Assistant Professor Orthopedic Surgery Sidney Kimmel Medical Center of Thomas Jefferson University Philadelphia, PA, United States Mitchell A. Pet, MD Assistant Professor Surgery Washington University School of Medicine in St. Louis St. Louis, MO, United States Karl-Josef Prommersberger, Prof. dr. Professor Krankenhaus St. Josef Clinic for Elective Hand Surgery Schweinfurt, Germany Tom J. Quick, MB, MA(hons)Cantab, FRCS(Tr & Orth) Associate Professor Institute of Orthopaedics and Musculoskeletal Science University College London London; Consultant Surgeon Peripheral Nerve Injury Unit Royal National Orthopaedic Hospital London, United Kingdom Parashar Ramanuj, MBBS, BSc(Hons) London Spinal Cord Injury Centre Royal National Orthopaedic Hospital Stanmore; Clinical Director Mental Health and Community Programmes Imperial College Health Partners London; Senior Research Fellow RAND Europe Cambridge, United Kingdom Carina Reinholdt, MD, PhD Senior Consultant in Hand Surgery Center for Advanced Reconstruction of Extremities Sahlgrenska University Hospital Mölndal; Assistant Professor Department of Hand Surgery Institute for Clinical Sciences Sahlgrenska Academy Göteborg, Sweden Justin M. Sacks, MD, MBA, FACS Shoenberg Professor of Plastic Surgery Chief, Division of Plastic and Reconstructive Surgery Director – Microsurgery Fellowship Division of Plastic and Reconstructive Surgery Department of Surgery Washington University in St. Louis School of Medicine St. Louis, MO, United States

Douglas M. Sammer, MD Professor Plastic Surgery and Orthopedic Surgery University of Texas Southwestern Medical Center at Dallas Dallas, TX, United States Brinkley K. Sandvall, MD Assistant Professor Department of Plastic Surgery Texas Children’s Hospital Baylor College of Medicine Houston, TX, United States Ellen Satteson, MD Assistant Professor, Research Director Plastic and Reconstructive Surgery University of Florida Gainesville, FL, United States Subhro K. Sen, MD Clinical Associate Professor Plastic Surgery Stanford University Medical School Palo Alto, CA, United States Pundrique Sharma, BSc(Hons) PhD, MBBS, FRSC(Plast) Consultant Plastic Surgeon Alder Hey Children’s Hospital Liverpool, United Kingdom Xiao Fang Shen, MD Vice-Director Pediatric Orthopedic (Hand Surgery) Children’s Hospital Affiliated to Soochow University Suzhou, Jiangsu, China Jamie T. Shores, MD Clinical Director of Hand and Upper Extremity Transplantation Plastic and Reconstructive Surgery Johns Hopkins University School of Medicine Baltimore, MD, United States S. Raja Sabapathy, MS, MCh, DNB, FRCSE, FAMS, Hon FRCSG, Hon FRCS, Hon FACS, DSc (Hon) Chairman Department of Plastic Surgery, Hand and Reconstructive Microsurgery and Burns Ganga Hospital Coimbatore, Tamil Nadu, India Vanila M. Singh, MD, MACM Clinical Associate Professor Anesthesiology, Perioperative, and Pain Medicine Stanford University Stanford, CA, United States Gillian D. Smith, MBBCh Consultant Hand and Plastic Surgeon Plastic Surgery Great Ormond Street Hospital London, United Kingdom Kashyap K. Tadisina, MD Assistant Professor Division of Plastic and Reconstructive Surgery Department of Surgery University of Miami Miller School of Medicine Miami, FL, United States

List of Contributors

Amir H. Taghinia, MD, MPH Attending Surgeon Department of Plastic Surgery Boston Children’s Hospital; Associate Professor of Surgery Harvard Medical School Boston, MA, United States David M.K. Tan, MBBS, MMED (Surgery) Senior Consultant Department of Hand and Reconstructive Microsurgery National University Health Systems Singapore Jin Bo Tang, MD Professor and Chair Department of Hand Surgery Affiliated Hospital of Nantong University; Chair The Hand Surgery Research Center Affiliated Hospital of Nantong University Nantong, Jiangsu, China Johan Thorfinn, MD, PhD Associate Professor Department of Biomedical and Clinical Sciences and Department of Plastic Surgery, Hand Surgery, and Burns Faculty of Medicine and Health Sciences Linköping University Linköping, Sweden Xiaofei Tian, MSc Professor Department of Burns and Plastic Children’s Hospital of Chongqing Medical University Chongqing, China

Michael Tonkin, MBBS, MD, FRACS, FRCSE(Orth) Professor Emeritus University of Sydney Medical School University of Sydney Sydney, NSW, Australia Joseph Upton, MD Attending Surgeon Shriners Children’s Hospital; Professor of Surgery Harvard Medical School Boston, MA, United States Francisco J. Valero-Cuevas, PhD Professor of Biomedical Engineering Professor of Biokinesiology and Physical Therapy The University of Southern California Los Angeles, CA, United States Hari Venkatramani, MS, MCh, DNB, EDHS Senior Consultant Plastic Surgery, Hand and Reconstructive Microsurgery Ganga Hospital Coimabatore, Tamil Nadu, India Nicolas B. Vedder, MD Professor of Surgery and Orthopedics Chief of Plastic Surgery Department of Surgery University of Washington Seattle, WA, United States

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Celine Yeung, MSc, MD, FRCSC Plastic, Reconstructive and Aesthetic Surgery Department of Surgery University of Toronto Toronto, ON, Canada Fu-Chan Wei, MD, FACS Professor Plastic and Reconstructive Surgery Chang Gung Memorial Hospital Kweishan, Taoyuan, Taiwan Paul M.N. Werker, MD, PhD, FEBOPRAS, FEBHS Professor and Chair Plastic Surgery University Medical Centre Groningen Groningen, The Netherlands Jeffrey Yao, MD Professor Orthopedic Surgery Stanford University Medical Center Menlo Park, CA, United States Jung Soo Yoon, MD, PhD Assistant Professor Plastic and Reconstructive Surgery Dongguk University Ilsan Hospital Goyang, Gyeonggi-do, Republic of Korea

Acknowledgments My wife, Gabrielle Kane, continues to encourage me in my work but gives constructive criticism bolstered by her medical expertise as well as by her knowledge and training in education. I can never repay her. The editorial team at Elsevier have made this series possible. Belinda Kuhn, once again, leads the group and is the Content Strategist. Through the years I’ve been involved with this project Belinda has been a constant support, an amazing resource, and a good friend. Unlike the previous editions which were managed through the London office, this edition has been directed through the Philadelphia office led by Katie De Francesco. The Elsevier production team, as always, has been vital in moving this project along. The volume editors, Geoff Gurtner and Andrea Pusic in Volume 1, Peter Rubin and Alan Matarasso in Volume 2, Richard Hopper and Joe Losee in Volume 3, David Song and JP Hong in Volume 4, Mo Nahabedian in Volume 5, and Jim Chang in Volume 6, have shaped and refined this 5th edition,

making vital changes to keep the series relevant and up to date. Dan Liu has, once again, taken masterful charge of the media content. This series is a team effort and wouldn’t exist without these wonderful people. This is the last edition I will edit. It has been an honor, an enormous privilege, and a work of love to do so. Peter C. Neligan, MB, FRCS(I), FRCSC, FACS I would like to thank my wife, Kathryn, and my three sons, Cole, Jack, and Pierce. I could never have edited this book or done anything else without their steadfast support and good cheer when I was absent. I love them all and will be forever grateful that they are able to put up with me. Geoffrey C. Gurtner, MD, FACS

Dedication

Dedicated to all teachers, peers, and trainees in Plastic Surgery

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1 Plastic surgery and innovation in medicine Peter C. Neligan

 

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Introduction What is different about plastic surgery compared to other areas of specialty practice? I pointed out in the last edition of this textbook that plastic surgeons do not own a disease like oncologists do, or a body part like heart surgeons do. We do not concentrate on a system like orthopedists or urologists do, we are everywhere, operating from head to toe and flitting between systems; peripheral nerves, lymphatics, tendons, moving tissue from one place to another, enhancing function, features, and appearances. Our specialty is also dynamic, constantly changing and evolving. Just in the past 15–20 years the areas of vascularized composite allotransplantion, perforator flaps, fat grafting, distraction osteogenesis in the craniofacial skeleton, just to name a few, have been developed and become mainstream. These areas and others continue to evolve. This is one of the reasons why this textbook needs constant revision (Video Lecture 1.1 ). This endless development and evolution has followed a pattern. The pattern has been that plastic surgery develops solutions for a given problem, we perfect these techniques and not infrequently other specialties adopt these procedures and ultimately take them over. Meanwhile we move on to another problem. This has already happened in many different areas in different parts of the world. For example, head and neck surgery, particularly in the US, is most frequently performed by head and neck surgeons, most of whom are trained in otolaryngology. Initially otolaryngologists did the resections and partnered with plastic surgeons to do the reconstructions. Personally, head and neck reconstruction consisted of approximately 70% of my practice at one time. Gradually, head and neck surgeons took over the reconstructions, including microsurgical reconstructions, with the result that currently, in the US, most head and neck cases, resection and reconstruction, are done by head and neck surgeons. When I trained in Ireland in the 1970s, plastic surgeons did the head and neck resection as well as the reconstruction. Now many plastic

surgery programs in the US and elsewhere no longer do head and neck surgery in any appreciable volume; we do less and less head and neck reconstruction, let alone resection. The same is true of hypospadias. Again, when I trained, plastic surgery did all the hypospadias repairs, an area that has now been taken over by urologists. Surgeons were reconstructing eyelids but the specialty of oculoplastic surgery did not exist. Otolaryngologists had not yet branched into facial plastic surgery. Part of the reason for these developments is that plastic surgeons are generally not the gatekeepers for most diseases. Patients with breast cancer see a breast surgeon, patients with skin cancer see a dermatologist. Plastic surgeons are consulted by these other specialties to reconstruct whatever defect the patient is left with and, in many cases, we are referred patients after a failed attempt at reconstruction by the other specialty, some of whom have little surgical training.

Adaptation and change This ability to change and adapt is a strength and we can see this in other spheres. For example, this ability to adapt, change, and incorporate new ideas is what has made English such a dominant language. It is the reason that Apple has become an industry leader. The same is true of Amazon. This is the essence of innovation. There are numerous examples in Biology that underline how the power of adaptation is the power of survival. For plastic surgery the same holds true and while some fear the demise of the specialty, I would argue that while we adapt and develop, there will always be a place for plastic surgery. This pattern of change and adaptation has been the blueprint of plastic surgery and we are stronger for it. Why is this? To answer that question, we need to look at what has happened historically. When we look back, we realize that what has been the hallmark of development in plastic surgery is innovation. While it is true that we are not the only ones who innovate, it is something that is in our culture and is something we have seen in all subspecialty areas of plastic surgery.

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CHAPTER 1 • Plastic surgery and innovation in medicine  

Innovation and research We see innovation in all spheres of life. What is innovation? There are several definitions. Baregheh et al. in their definition said that “Innovation is the multi-stage process whereby organizations transform ideas into new/improved products, services or processes, in order to advance, compete and differentiate themselves successfully in their marketplace”.1 We innovate all the time. Most of the time this innovation is incremental. We change the way we put a suture in, we modify an incision, we design a flap differently. We do this to improve what we do and we adopt those innovations into our practice. Sometimes we innovate to deal with a specific problem that we have not been faced with before. What all these innovations have in common is the desire to improve things or to treat conditions that we were hitherto unable to tackle. This is something we all want. While the majority of innovations are incremental, some innovations are more radical, completely changing an approach, often developing new techniques that seem to break the rules we have lived by up until that point. Innovation has been responsible for many of the great advances in surgery and while research has, of course, played a key role in development, innovation is at least as important. What is the difference between innovation and research? We have already defined innovation as the transformation of ideas into new/improved processes. On the other hand research is creative and systematic work undertaken to increase the stock of knowledge.2 It involves the collection, organization, and analysis of information to increase understanding of a topic or issue. The two can co-exist. For example, innovation of an existing laboratory technique may open the door to a new line of investigation. While it would make sense that research comes before innovation, often in practice it is the other way around. I did my first IMAP (internal mammary artery perforator) flap on a patient in whom I had planned a pectoralis major flap. This was for coverage of a neck defect. However, the patient was a large man and I wondered whether we could raise a similar flap without the bulk of the pectoralis. Using a hand-held Doppler I found two robust internal mammary perforators. Taking out a segment of costal cartilage, just like we do for access to the internal mammary arteries for breast reconstruction, I divided the internal mammary distal to the run-off of the two perforators and pedicled the flap up to the neck.3 Subsequently we went to the anatomy lab and did dye injection studies of the internal mammary system to define the limits of the flap,4 thereby putting innovation before research. The two editors of this volume are prominent researchers and illustrate how research has also adapted and changed. Dr. Gurtner is a basic science and translational researcher, bringing his laboratory findings to the bedside and advancing the specialty in that way. He introduced us to the concept of “biologic brachytherapy”,5,6 combining his knowledge of vascular anatomy with knowledge of genetic engineering. Using genetic engineering we can program cells to perform certain tasks. We can suppress certain functions, stimulate others, in other words we can manipulate cells. This is a very powerful science and has potential applications across all of medicine. The process of transfection, whereby DNA or RNA is introduced into cells to modify gene expression, is widely used in molecular research. Using techniques of viral transfection, he has been able to design flaps that not only close a surgical

defect but introduce a therapeutic element to the reconstruction by having the flap produce peptides appropriate to the disease entity being treated, producing probiotics for infected wounds, or anti-angiogenic peptides for oncologic reconstructions. This innovative approach combines the best of plastic surgery with the best of genetic engineering to provide a new and better solution to an existing clinical problem. Biologic brachytherapy represents the melding of anatomic knowledge with tissue engineering principles and is a very exciting development. Dr. Pusic has championed clinical research and has devised tools that allow us to measure patient-reported outcome measures (PROM), an aspect of outcomes that we shamefully never measured in a meaningful way before. The first of these validated tools was the BreastQ.7,8 This has been adopted world-wide and has been translated into numerous languages. Dr. Pusic has since developed several similar tools to cover other conditions. This is painstaking work and involves countless hours of questions and interviews in order to validate each tool. So plastic surgery research has evolved to include high-quality clinical as well as basic research.

Major innovations In our history as a specialty there have been several major innovations. One example is the work of Paul Tessier (Fig. 1.1). His innovation would be best described as radical. He broke all the rules of surgical dogma by combining an intracranial and extracranial approach for the treatment of hypertelorbitism.9 This was a heretical approach and despite the fact that some of his early patients died, he had the courage of his convictions and proceeded to develop his techniques. He is the founding father of craniofacial surgery. His obituary in the British newspaper the Independent underscores his importance as well as the impact his innovation had on surgery. It read: “Paul Tessier was

Figure 1.1 Dr. Paul Tessier.  

Innovation and research

a great innovator in the medical profession, the creator of a new surgical speciality which brought hope to many with severe facial deformities that had previously been untreatable. He is acknowledged as the father of craniofacial surgery and his contribution is recognized internationally, crossing the boundaries of the related specialities of plastic, maxillofacial, ophthalmic and neurosurgery”.10 Others after him continued to innovate. Paul Manson and the late Joe Gruss (Fig. 1.2) independently developed the concept of rigid fixation and primary bone grafting for treating trauma of the craniofacial skeleton; a concept that was decried at the time and that now has become the standard of care for the management of facial fractures.11,12 Harry Buncke (Fig. 1.3), working in his garage, figured out how to suage a small needle on to a fine suture by metallizing the suture-end and helped develop

Figure 1.2 Drs. Joe Gruss (left) and Paul Manson.  

Figure 1.3 Dr. Harry Buncke.  

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microsurgery as we know it today. He also experimented with replanting tissue in animals and did a free omental transfer for a scalp defect in 1972.13,14 These are major innovations leading to significant advances. However, as I have said, most innovations are far less momentous. We come up with a solution to treat an unusual or a unique problem. Each little change gets adopted if it is successful and dropped if it is not. Innovation is seen at its most extreme extent in certain situations; situations of conflict, times of natural disaster, when we are faced with devastating injuries in such numbers and of such extreme that we have to find a means to deal with them. The recent SARS-CoV-2 pandemic is another example of this phenomenon and of course these advances are not confined to plastic surgery. One of the innovations that has resulted from the COVID crisis is the development of telemedicine. While this is not new, it has advanced rapidly during the pandemic at a pace far beyond what would have otherwise happened. Remote learning has also been boosted in an unprecedented way. Personally, I gave 33 virtual lectures between March 2020 and May 2021, the height of the COVID pandemic. Eric Santamaria in Mexico City organized two annual meetings (Microsurgery Masters for Residents) during the pandemic. These were initially planned for his own residents, but Eric opened it to residents from all over the world. Major international figures gave outstanding lectures and attendance was in the thousands. Tommy Nai-Jen Chang from Taiwan founded a Facebook group, the International Microsurgery Club (IMC), which meets every Saturday and Sunday for a lecture. These lectures are given by experts from all over the world and virtually attended by surgeons globally. The club is free and currently there are over 18,000 members. These are advances that are here to stay. What about some other clinical advances? Tissue expansion was devised as a method of recruiting extra skin for reconstruction. As with anything new, it was treated with suspicion. In fact the first use of tissue expansion was for reconstruction of an ear. Neumann used a Foley catheter to expand skin for this reconstruction.15 This idea was not revisited for another 20 years when Radovan presented the concept again.16,17 His initial presentation was greeted with skepticism and unfortunately he died before realizing that tissue expansion had become a mainstream technique in plastic surgery. Innovation happens in all aspects of what we do, whether reconstructive or aesthetic. Some innovations in aesthetic surgery have been game-changers, like Syd Coleman’s (Fig. 1.4) introduction of structural fat grafting.18 This technique has been applied equally successfully to reconstructive surgery. While we used to treat cases of hemifacial atrophy with buried free flaps, we can now achieve the same result with fat grafting (Fig. 1.5A–D). This underlines the fact that the two aspects of the specialty, aesthetic and reconstructive, are really inseparable and innovations in one field are often adopted by the other. The story of fat grafting illustrates another feature that we not-infrequently see with innovations, unanticipated benefits. Fat grafting, it transpires, has effects other than volume augmentation. It has also been observed that grafted fat appears to have a rejuvenating effect on skin, presumably acting through stem cells.19 Rigotti brought to our attention that fat grafting seems to reverse or at least ameliorate the effects of radiation on tissues.20 In fact it has also been reported to ameliorate pain associated with radiation fibrosis in lumpectomy defects, something I have observed in my own practice.21

CHAPTER 1 • Plastic surgery and innovation in medicine

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Figure 1.4 Dr. Sydney Coleman.

So, a technique that was originally conceived as a volume filler, turned out to have multiple previously unrecognized benefits. The same is true of vacuum-assisted closure, or the VAC as it is commonly known. Originally conceived as a form of dressing, it transpires that the application of suction to a wound not only removes debris and secretions from the wound but also promotes neo-angiogenesis and cell proliferation.22,23 Khouri ultimately put all of these concepts together. He devised the Brava bra. This is basically a suction cup that was designed to be placed over the breast to produce swelling; a temporary augmentation mammoplasty. The swelling would last for several hours.24,25 However what was really happening was a form of tissue expansion, external tissue expansion, and Khouri recognized that this swollen tissue was an excellent medium for the injection and retention of fat. By injecting fat in multiple vectors a large volume of could be introduced and breast reconstruction could be achieved with the combination of external expansion and fat grafting alone.26,27 In radiated patients the prior injection of fat could create a situation that would allow expander/implant reconstruction, something that most people shy away from in the radiated patient.28

 

A

C

B

D

Figure 1.5 (A) Preop hemifacial atrophy. (B) Postop following free groin flap. (C) Preop hemifacial atrophy. (D) Postop following fat grafting.  

Innovation and research

5

Figure 1.7 Drs. Foad Nahai (left) and Stephen Mathes.  

Figure 1.6 Dr. Joseph McCarthy (left) with the author.  

While we celebrate the key innovations that give rise to major changes in the practice of our specialty, we also must acknowledge innovations in other specialties. Innovations in these other specialties also lead to innovations in our field. One of the great examples of this is the application of bone lengthening to the craniofacial skeleton. The possibility of lengthening bone was discovered by Gavril Ilizarov in 1951. This proved a revolutionary advance. Joseph McCarthy (Fig.  1.6), editor of the first edition of this textbook, subsequently adapted that technique to the craniofacial skeleton and distraction osteogenesis, as it is now called, has changed the way we treat many craniofacial anomalies,29–32 making obsolete some of the more morbid operations with which we used to treat these conditions in the past.

Making innovation safe To the uninitiated, the thought of just winging it and trying something new is shocking. However, whether consciously or unconsciously, we base our innovations on past experience and knowledge so it is a lot more than just “winging it”. Of course, this type of surgical innovation raises ethical issues and it is something with which many institutions are struggling, not merely in the domain of plastic surgery but in the field of surgery in general. Many institutions already have processes and protocols in place to oversee and regulate innovation.33 When is innovation in surgery ethical and when is it

not? This has already been the source of much discussion in the literature.34–36 How far can we safely push the envelope? That particular discussion is beyond the scope of this chapter. Suffice it to say that it is important to strike a balance between necessary oversight of research practices and a supportive environment where research can flourish. All these innovations, whether big or small, have led to the evolution of our specialty. I have already mentioned the difference between research and innovation. While innovation has played a vital role in our development, research has had a similar impact. Sometimes it is a mixture of the two, in whatever order, as I illustrated with the IMAP example. In fact, the history of flaps illustrates this relationship very well. Flaps were all random initially. We did not know what the blood supply was, just that it was at the base of the flap. We followed all sorts of rules such as the length to width ratio until Milton came along and disproved that theory.37 Amazingly, I still hear people talk about the length to width ratio today. It just proves how difficult it is to dispel an incorrect belief. McGregor and Jackson introduced the groin flap in 1972 and gave us our first axial flap, one in which we knew the blood supply and axis of flow.38 The groin flap is still used today and has found new life as the SCIP flap based on a perforator from the superficial circumflex artery, which Isao Koshima introduced in 2004.39 The discovery of the axiality of flaps opened up a new era in flap surgery. Many people started experimenting with flaps but it was not until Mathes and Nahai (Fig. 1.7) did their anatomic dissections and gave us the precise information on how to use muscle flaps that myocutaneous flaps became mainstream.40 Pontén went a step further and introduced the fasciocutaneous flap.41 Cormack and Lamberty did similar anatomic dissections as had been done by Mathes and Nahai and described the vascular supply of fasciocutaneous flaps.42,43 In 1987 Ian Taylor (Fig. 1.8) published his angiosome theory and in a series of elegant lead oxide injection studies mapped out the blood supply of the integument.44 Since then there has been an explosion in the development of flaps, with Koshima (Fig. 1.9) introducing us to the perforator flap concept in 1989.45 Even still flaps continue to evolve and with

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Figure 1.8 Dr. Ian Taylor.  

Dr. Murray was a plastic surgeon. He got into transplantation because he was researching immunity and the pathophysiology of skin graft failure, because this was a problem in his clinical practice after the Second World War. Because of the antigenicity of skin, he moved to a single organ experimental model, the kidney. There were fewer compounding factors to deal with antigenically in a single organ than in the skin. He went on to perform the world’s first kidney transplant between two identical twins, the Herrick brothers, in 1954. He subsequently performed the world’s first successful allograft in 1959 and the world’s first cadaveric renal transplant in 1962.47 Dr. Murray ultimately returned to his roots, the practice of plastic surgery, and was awarded the Nobel Prize in Physiology or Medicine in 1990 for his contribution to the science of transplantation. Transplantation more recently has returned to plastic surgery in the form of vascularized composite allotransplantation (VCA) with the first hand transplant being performed in 199848 and the first face transplant being performed in 2005.49 Though the field is expanding, the restriction of immunosuppression still hampers progress and raises one of the major ethical dilemmas in VCA. Once this roadblock is breached, the potential for transplantation is boundless. While we can do a pretty good job at reconstructing some defects, we are still woefully inadequate at others. For example, reconstructing functioning eyelids is difficult and the results are often crude. Similarly, total nasal reconstruction is something that is usually done in multiple stages over several months or years and even with that, the results are not great. There are a handful of surgeons around the world who can do a spectacular job of nasal reconstruction but for most of us, their results are unattainable. The same is true of ear reconstruction. Imagine being able to do a nasal or ear reconstruction in one operation with spectacular results by transplanting the part rather than reconstructing it. This will demand a whole new approach to the detailed anatomy of each part. How for example would one go about transplanting functioning eyelids, which vessels, which nerves etc.?50 Doing these anatomic investigations now will prove to be important for achieving these transplants when immunosuppression becomes less hazardous. This gets back to the ethical question of whether it is justifiable to give a potentially dangerous drug to treat a non life-threatening condition. We have already seen the beginnings of this spare-parts surgery with uterine transplants,51,52 penile transplants,53,54 and others. I think this will be the future of composite tissue allo-transplantation(CTA), restoring form and function to areas where our reconstructive efforts are currently lacking.

Collaboration and teamwork

Figure 1.9 Dr. Isao Koshima.  

advances in imaging techniques we can now raise superthin flaps and subdermally dissected pure skin perforator flaps.46 In previous editions of this book I have talked about Dr. Joe Murray, one of the founding fathers of transplant surgery.

I have mentioned that innovation in one field gives rise to advances in related fields. The example of distraction osteogenesis and the facial skeleton illustrates this. However, many of the advances we now take for granted could not have happened but for the collaboration between surgeon and industry. This is another area in which there are ethical minefields and there has been much regulation in disclosure and transparency to ensure that the relationship between physician and industry is principled. When I arrived in Toronto as a Fellow in 1983, Joe Gruss was developing his techniques for reducing and bone grafting facial fractures. At that time he was wiring

Conclusion

little fracture fragments together, as can be seen in illustrations in his publications, because there were no plating systems for the craniofacial skeleton.11 He, and others, worked with industry to develop such systems.55 There has been a strong relationship between industry and surgeons, particularly throughout the past century, and this continues. The plating systems, various implants, anastomotic devices, sutures, all of these have been made possible because of the collaboration between surgeons and industry. Collaboration also exists between specialty groups This was brought home to me many years ago. At head and neck tumor boards one Monday afternoon in Toronto General Hospital, Dr. Fred Gentili, a skull base surgeon, presented a case which he said was probably resectable but he could not access it. Dr. Pat Gullane, head of the head and neck service, said he could give Dr. Gentili access but it would leave “a hell of a hole”. I then interjected that I could fix the hole. That was an “aha” moment for all three of us when we realized that, working together, we could achieve what none of us could accomplish alone. Furthermore, with the addition of free tissue transfer, we discovered that the incidence of the most common and potentially most lethal complications of skull base surgery, brain abscess, meningitis and CSF leak, were all significantly reduced by the addition of well-vascularized tissue into the resected bed to seal the dura and separate the intracranial contents from the upper aerodigestive tract.56 Many years later, amid much controversy, endoscopic resection of skull base tumors was introduced.57 We started to see the same problems with the endoscopic approach as we had seen with the open approach 20 years before, i.e., brain abscess meningitis and CSF leaks. We knew what the solution was, flaps. However, we no longer had access because we no longer had the open approach. This gave rise to the development of new intra-nasal flaps, modified peri-cranial flaps and the trans-pterygoid approach to the anterior skull base.58–60 That is the essence of collaboration and the nub of teamwork. I once had to give a talk on teamwork which I titled “There is no ‘I’ in TEAM”. The concept of a team is often misrepresented. I have heard surgeons say “I have a great team” when what they really mean is “I have all these people working for me who do things exactly as I want them because I am a great man”. Now while there is a place for such a team to improve efficiency, the real concept of a team is accomplishing together what no one individual on the team could do alone. Playing in a team sometimes means compromise, standing back, and letting someone else do something that you think you could do yourself. As surgeons, we are not very good at that, however, as I have experienced over my career, it pays off hugely.

Documentation, data-gathering, and regulation It is important to document change. If one asks a surgeon how many procedures he or she has done, the answer is usually a gross exaggeration. Similarly, we tend to underestimate our complications. We are not good at remembering things, though we think we are. It is surprising when one starts to keep a database how sobering it is to see the actual numbers. It is also surprising how much information one can glean, and

7

this information is vital if we are to change and improve. This was brought home to me in my own practice. I have kept a database of my cases and over the years residents and fellows have added to it, used it as a resource for studies etc. Several years ago, a new fellow asked if he could look at my head and neck database as he was keen to write some papers. I told him that he was welcome but said that I thought we had got as much information out of it as we could. He got back to me about a week later and said that he had found several things and we started working on them. The result was that that fellow published five papers from the database during the year he spent with me.61–65 Innovation implies change and in times of change it is imperative to document results. How else can one evaluate the effects of the innovation? So, documentation and data-gathering are important aspects of innovation and a discipline that is worth instigating in your practice. The difficulty with innovation arises in that gray zone between innovation and research. Small changes are easy to effect, large changes more difficult! Most institutions regulate change through the institutional review board (IRB). Regulation is necessary yet it is also restrictive. The IRB process varies from institution to institution but, in general, is getting more and more stringent. This can have a significant effect on the development of medicine as a whole. It is widely believed, for example, that the reason the first heart transplant did not occur in the US was because of the strict regulations governing experimental surgery in the US as compared to South Africa, where Dr. Christiaan Barnard, an American trained cardiac surgeon, performed this operation.66 Institutions also grapple with the dilemma of allowing some degree of innovation yet controlling quality and risk exposure. The latter is an important consideration for institutions and individuals alike. Apart from protecting the individual and the institution, regulation also introduces and enforces an element of objectivity. When one is involved in developing a theory, an operation, or some sort of change, it is very easy to lose objectivity and that is a serious issue. Regulation enforces objectivity and the difficulty lies in the balance between creativity and objectivity. Just as one can become obsessed with creativity and freedom of expression however, one can also become obsessed with objectivity and regulation. Finding a balance between the two is sometimes difficult. Added to that is the conflict of interest that is sometimes introduced to the process when a commercial value is associated with the innovation, and particularly when a significant sum may already have been invested in developing it. That introduces the ethics of practice and this subject is covered in another chapter of this textbook. So, we have seen that innovation is an important part of medicine. It is separate from research though often stimulates research. It is as difficult to regulate as it is to define and, at least in some instances may be stifled by regulation. From all of the innovations I have touched on in this chapter we can see that innovation is vital to the development of medicine in general and to the evolution of plastic surgery in particular.

Conclusion As this is the last time I will be writing this chapter and the last time I will edit this textbook, I would like to leave you with some advice, whether you are a resident or a practicing

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CHAPTER 1 • Plastic surgery and innovation in medicine  

surgeon. You are a member of an extraordinary specialty. Enjoy it. However, don’t rest on your laurels. 1. Make plastic surgery better, whether you do it by introducing something new and revolutionary or by incrementally changing and improving what you do. The vast majority of you will fall into the latter category and that is totally fine. 2. Document what you do and share it with others. Publish and present in order to share information. Publish and present your good results but more importantly, publish your complications. This is something I have tried to do in my career. We all make mistakes and mistakes are almost always well intentioned; occasionally they are because of carelessness or lack of focus. However, the vast majority of them67,68 are honest mistakes. The reason to let people know about your mistakes is to try to prevent someone else from making the same mistake. Some people fear that doing so shows weakness, but I think the opposite. Publishing or presenting your complications and mistakes enhances your character and gives you the reputation of being an honest broker. 3. Listen to the people around you. When I was a fellow, working with Dr. Ralph Manktelow in Toronto, we were planning to do a free flap for a lower extremity patient. The patient had some exposed hardware. A











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medical student in the room asked Dr. Manktelow why he would not use some of the muscle in the wound to cover the metal and skin graft it. Much to my surprise, Dr. Manktelow thought about it and said “You know, I think you’re right” and that is what we did. Here was a professor of surgery listening to a suggestion from a medical student. I have never forgotten that. In Seattle we had a scrub-technician who had been a surgeon in China. I loved working with him. He would often say something like “why don’t you try such and such” and he was often right. I was always amazed to see some residents scoff at his advice and plod on with whatever their original plan was. Go to meetings, attend webinars. Present your material but also listen to what else is being presented. Don’t become isolated. I started practice in a small town in rural Ontario in Canada and it was difficult to get to meetings but it was worth it. Not only do you learn new things, but you also validate your own practice. As well as that, you network. You get to know people with similar practices, similar attitudes. Always ask the question “why”. This is something that my friend JP Hong, himself a master preacher and master surgeon, preaches. Always question yourself and others and not infrequently you will find that there is a better way.

References

References 1. Baregheh A, Rowley J, Sambrook S. Towards a multidisciplinary definition of innovation. Management Decision. 2009;47(8):1323–1339. 2. OECD (Organisation for Economic Co-operation and Development) Guidelines for Collecting and Reporting Data on Research and Experimental Development: The Measurement of Scientific, Technological and Innovative Activities. Frascati Manual. 2015 3. Neligan PC, Gullane PJ, Vesely M, Murray D. The internal mammary artery perforator flap: new variation on an old theme. Plast Reconstr Surg. 2007;119(3):891–893. 4. Vesely MJ, Murray DJ, Novak CB, Gullane PJ, Neligan PC. The internal mammary artery perforator flap: an anatomical study and a case report. Ann Plast Surg. 2007;58(2):156–161. 5. Michaels J 5th, Dobryansky M, Galiano RD, et al. Ex vivo transduction of microvascular free flaps for localized peptide delivery. Ann Plast Surg. 2004;52(6):581–584. 6. Michaels J 5th, Levine JP, Hazen A, et al., Biologic brachytherapy: ex vivo transduction of microvascular beds for efficient, targeted gene therapy. Plast Reconstr Surg. 2006;118(1): 54-65; discussion 66-8. 7. Pusic AL, et al. Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. Plast Reconstr Surg. 2009;124(2):345–353. 8. Pusic AL, Chen CM, Cano S, Klassen A, et al. Measuring quality of life in cosmetic and reconstructive breast surgery: a systematic review of patient-reported outcomes instruments. Plast Reconstr Surg. 2007;120(4):823–837. 9. Tessier P, Guiot G, Rougerie J, Delbet JP, Pastoriza J. [Cranio-nasoorbito-facial osteotomies. Hypertelorism] [in French]. Ann Chir Plast. 1967;12(2):103–118. 10. Britto JA, Jones BM. Dr Paul Tessier: Plastic surgeon who revolutionised the treatment of facial deformity. Independent. June 23, 2008. 11. Gruss JS, Mackinnon SE, Kassel EE, Cooper PW. The role of primary bone grafting in complex craniomaxillofacial trauma. Plast Reconstr Surg. 1985;75(1):17–24. 12. Manson PN, Crawley WA, Yaremchuk MJ, Rochman GM, Hoopes JE, French JR. Midface fractures: advantages of immediate extended open reduction and bone grafting. Plast Reconstr Surg. 1985;76(1):1–12. 13. Buncke HJ, Schulz WP. Total ear reimplantation in the rabbit utilising microminiature vascular anastomoses. Br J Plast Surg. 1966;19(1):15–22. 14. McLean DH, Buncke HJ. Autotransplant of omentum to a large scalp defect, with microsurgical revascularization. Plast Reconstr Surg. 1972;49(3):268–274. 15. Neumann CG. The expansion of an area of skin by progressive distention of a subcutaneous balloon; use of the method for securing skin for subtotal reconstruction of the ear. Plast Reconstr Surg (1946). 1957;19(2):124–130. 16. Radovan C. Breast reconstruction after mastectomy using the temporary expander. Plast Reconstr Surg. 1982;69(2):195–208. 17. Radovan C. Tissue expansion in soft-tissue reconstruction. Plast Reconstr Surg. 1984;74(4):482–492. 18. Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthetic Plast Surg. 1995;9(5):421–425. 19. Charles-de-Sa L, Ferreira Gontijo-de-Amorim N, Maeda Takiya C, et al. Antiaging treatment of the facial skin by fat graft and adipose-derived stem cells. Plast Reconstr Surg. 2015;135(4):999–1009. 20. Rigotti G, MArchi A, Galiè M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg. 2007;119(5):1409–1422. discussion 1423–4. 21. Maione L, Vinci V, Caviggioli F, et al. Autologous fat graft in postmastectomy pain syndrome following breast conservative surgery and radiotherapy. Aesthetic Plast Surg. 2014;38(3): 528–532. 22. Malsiner CCM, Schmitz M, Horch RE, Keller AK, Leffler M. Vessel transformation in chronic wounds under topical negative pressure









































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therapy: an immunohistochemical analysis. Int Wound J. 2015;12(5):501–509. Saxena V, Hwang C-W, Huang S, Eichbaum Q, Ingber D, Orgill DP. Vacuum-assisted closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg. 2004;114(5):1086–1096. discussion 1097–8. Khouri RK, Schlenz I, Murphy BJ, Baker TJ. Nonsurgical breast enlargement using an external soft-tissue expansion system. Plast Reconstr Surg. 2000;105(7):2500–2512. discussion 2513-4. Smith CJ, Khouri RK, Baker TJ. Initial experience with the Brava nonsurgical system of breast enhancement. Plast Reconstr Surg. 2002;110(6):1593–1595. author reply 1595–8. Khouri R, Del Vecchio D. Breast reconstruction and augmentation using pre-expansion and autologous fat transplantation. Clin Plast Surg. 2009;36(2):269–280. viii. Khouri RK, Eisenmann M, Cardoso E, et al. Brava and autologous fat transfer is a safe and effective breast augmentation alternative: results of a 6-year, 81-patient, prospective multicenter study. Plast Reconstr Surg. 2012;129(5):1173–1187. Salgarello M, Visconti G, Farallo E. Autologous fat graft in radiated tissue prior to alloplastic reconstruction of the breast: report of two cases. Aesthetic Plast Surg. 2010;34(1):5–10. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH. Lengthening the human mandible by gradual distraction. Plast Reconstr Surg. 1992;89(1):1–8. discussion 9–10. McCarthy JG. The role of distraction osteogenesis in the reconstruction of the mandible in unilateral craniofacial microsomia. Clin Plast Surg. 1994;21(4):625–631. McCarthy JG, Staffenberg DA, Wood RJ, Cutting CB, Grayson BH, Thorne CH. Introduction of an intraoral bone-lengthening device. Plast Reconstr Surg. 1995;96(4):978–981. McCarthy JG, Williams JK, Grayson BH, Crombie JS. Controlled multiplanar distraction of the mandible: device development and clinical application. J Craniofac Surg. 1998;9(4):322–329. Neumann U, Hagen A, Schönermark M. Procedures and criteria for the regulation of innovative non-medicinal technologies into the benefit catalogue of solidly financed health care insurances. GMS Health Technol Assess. 2008:3 Doc13. McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374(9695):1105–1112. Ergina PL, Cook JA, Blazeby JM, et al. Challenges in evaluating surgical innovation. Lancet. 2009;374(9695):1097–1104. Barkun JS, Aronson JK, Feldman LS, et al. Evaluation and stages of surgical innovations. Lancet. 2009;374(9695):1089–1096. Milton SH. Pedicled skin-flaps: the fallacy of the length: width ratio. Br J Surg. 1970;57(7):502–508. McGregor IA, Jackson IT. The groin flap. Br J Plast Surg. 1972;25(1):3–16. Koshima I, Nanba Y, Tsutsui T, et al. Superficial circumflex iliac artery perforator flap for reconstruction of limb defects. Plast Reconstr Surg. 2004;113(1):233–240. Mathes SJ, Nahai F. Classification of the vascular anatomy of muscles: experimental and clinical correlation. Plast Reconstr Surg. 1981;67(2):177–187. Pontén B. The fasciocutaneous flap: its use in soft tissue defects of the lower leg. Br J Plast Surg. 1981;34(2):215–220. Cormack GC, Lamberty BG. Fasciocutaneous vessels. Their distribution on the trunk and limbs, and their clinical application in tissue transfer. Anat Clin. 1984;6(2):121–131. Cormack GC, Lamberty BG. A classification of fascio-cutaneous flaps according to their patterns of vascularisation. Br J Plast Surg. 1984;37(1):80–87. Taylor GI, Palmer JH. The vascular territories (angiosomes) of the body: experimental study and clinical applications. Br J Plast Surg. 1987;40(2):113–1141. Koshima I, Soeda S. Inferior epigastric artery skin flaps without rectus abdominis muscle. Br J Plast Surg. 1989;42(6):645–648. Yamamoto T, Yamamoto N, Fuse Y, Kageyama T, Sakai H, Tsukuura R. Subdermal dissection for elevation of pure skin perforator flaps

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and superthin flaps: the dermis as a landmark for the most superficial dissection plane. Plast Reconstr Surg. 2021;147(3):470–478. Murray JE, Merrill JP, Dammin GJ, Dealy Jr JB, et al. Kidney transplantation in modified recipients. Ann Surg. 1962;156:337–355. Dubernard JM, Owen E, Lefrançois N, et al. First human hand transplantation. Case report. Transpl Int. 2000;13(Suppl 1):S521–S524. Devauchelle B, Badet L, Lengelé B, et al. First human face allograft: early report. Lancet. 2006;368(9531):203–209. Mathes DW, Edwards JA, Anzai Y, et al. A functional periorbital subunit allograft: vascular, anatomic, and technical considerations for future subunit facial transplantation. J Plast Reconstr Aesthet Surg. 2014;67(10):1371–1377. Dahm-Kähler P, Kvarnström N, Rodriguez EA, Skogsberg Dahlgren U, Brännström M. Uterus transplantation for fertility preservation in patients with gynecologic cancer. Int J Gynecol Cancer. 2021;31(3):371–378. Malasevskaia I, Al-Awadhi AA. A new approach for treatment of woman with absolute uterine factor infertility: a traditional review of safety and efficacy outcomes in the first 65 recipients of uterus transplantation. Cureus. 2021;13(1):e12772. Jonczyk MM, Tratnig-Frankl P, Cetrulo CL. Genitourinary vascularized composite allotransplantation: a review of penile transplantation. Curr Opin Organ Transplant. 2019;24(6):721–725. Kohn TP, Peña V, Redett RJ 3rd, Burnett AL. Penile allotransplantation: early outcomes from reported cases and survivorship considerations. Minerva Urol Nephrol. 2021;73(3):333–341. Gruss JS. Internal fixation of bone by screws. Plast Reconstr Surg. 1985;76(4):655. Neligan PC, Mulholland S, Irish J, et al. Flap selection in cranial base reconstruction. Plast Reconstr Surg. 1996;98(7):1159–1166. discussion 1167–1168. Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg. 1997;87(1):44–51. Fortes FS, Carrau RL, Snyderman CH, et al. The posterior pedicle inferior turbinate flap: a new vascularized flap for skull base reconstruction. Laryngoscope. 2007;117(8):1329–1332.

59. Hadad G, Rivera-Serrano CM, Bassagaisteguy LH, et al. Anterior pedicle lateral nasal wall flap: a novel technique for the reconstruction of anterior skull base defects. Laryngoscope. 2011;121(8):1606–1610. 60. Fortes FS, Carrau RL, Snyderman CH, et al. Transpterygoid transposition of a temporoparietal fascia flap: a new method for skull base reconstruction after endoscopic expanded endonasal approaches. Laryngoscope. 2007;117(6):970–976. 61. Lannon DA, Ross GL, Addison PD, Novak CB, Lipa JE, Neligan PC. Versatility of the proximally pedicled anterolateral thigh flap and its use in complex abdominal and pelvic reconstruction. Plast Reconstr Surg. 2011;127(2):677–688. 62. Ross GL, Ang EE SW, Lannon D, et al. A ten-year experience of multiple flaps in head and neck surgery: how successful are they? J Reconstr Microsurg. 2008;24(3):183–187. 63. Ross GL, Ang E SW, 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(8):1086–1089. 64. Ross GL, Ang E SW, Golger A, et al. Which venous system to choose for anastomosis in head and neck reconstructions? Ann Plast Surg. 2008;61(4):396–398. 65. Ross G, Yla-Kotola TM, Goldstein D, et al. Second free flaps in head and neck reconstruction. J Plast Reconstr Aesthet Surg. 2012;65(9):1165–1168. 66. Barnard CN. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S Afr Med J. 1967;41(48):1271–1274. 67. Addison PD, Lannon D, Neligan PC. Compartment syndrome after closure of the anterolateral thigh flap donor site: a report of two cases. Ann Plast Surg. 2008;60(6):635–638. 68. Lannon DA, Novak CB, Neligan PC. Arteriovenous fistula complicating an inferior gluteal artery perforator flap donor site. J Reconstr Microsurg. 2008;24(4):227–229.







































2 History of reconstructive and aesthetic surgery Riccardo F. Mazzola and Isabella C. Mazzola

SYNOPSIS

ƒ Closure of wounds represents one of the first gestures of reparative surgery. ƒ History shows that almost every possible local flap has been described in the past and that the ingenuity of plastic surgeons was unlimited. ƒ The lesson drawn from history reveals that the so-called new flaps are variations of what has already been published. ƒ We have to be humble and recognize that “nothing is new under the sun”.

and (4) pain. Attempts to transform a defect that heals slowly by secondary intention into one healing quicker by primary intention may well account for the first example of a reparative procedure. However, this must have been quite complex without appropriate tools, in the presence of hemorrhage and without anesthesia. There is no documentation of stitching of wounds among primitive people.2 We may extrapolate from what was reported in ancient Hindu medicine, where wound edges were sewn with simple means like fibers or strips of tendon, or pinned together using insect mandibles. Later, bronze pins were used (Fig. 2.1).

Historical definition of plastic surgery

In Ancient Egypt

In 1597, the Bolognese Gaspare Tagliacozzi (1545–1597), considered the founder of plastic surgery, gave the following definition of our discipline: plastic surgery is the art devoted to “restore what Nature has given and chance has taken away. The main purpose of this procedure is not the restoration of the original beauty of the face, but rather the rehabilitation of the part in question”,1 in other terms repair of congenital or acquired defects, restoration of an appearance as close as possible to normality, but also improvement of functional impairment. The term “plastic” comes from the Greek πλαστικóς (plasticós), moldable.

We are well informed about Egyptian surgery thanks to the Edwin Smith papyrus, the most ancient medical text. The papyrus is a later transcription (about 1650 BCE) of an original manuscript dating from the Old Kingdom (between 3000 and 2500 BCE). It describes 48 surgical cases, including wounds, fractures, dislocations, sores, and tumors, and suggests their potential management. Fresh wounds were treated conservatively with the application of grease and honey using linen and swabs. Adhesive strips of cloth, stitches or a combination of clamp and stitches were advocated to bring together the margins of the wound. A surgical knife was never mentioned, as wounds already existed in the cases presented.2 Treatment of nasal fractures is accurately explained. First, clots should be removed from the inside of the nostrils, then the bony fragments repositioned; two stiff rolls of linen were applied externally “by which the nose is held fast” and finally “two plugs of linen saturated with grease placed into the nostrils”.3

Origin of plastic surgery The distant past – the wound as a problem The ancient origin of plastic surgery relates to the healing of wounds. Management of wounds caused by stones, weapons, arrows, and animal bites goes back millions of years, when primitive humans had to face four major problems: (1) closing post-traumatic defects; (2) bleeding; (3) infection;

In Mesopotamia Mesopotamia is the region between the rivers Tigris and Euphrates (now approximately Iraq), cradle of the Sumerian civilization. Medicine was well developed, although strongly

CHAPTER 2 • History of reconstructive and aesthetic surgery

10

 

Figure 2.1 Bronze pin to approximate wound margins. (Reproduced from Rodius J. De Acia Dissertatio. Padua: Frambotto; 1639.)  

influenced by astrology and divination. During excavations of the Nineveh palace, a great library containing more than 30,000 clay tablets with cuneiform inscriptions was discovered, 800 of them of a medical nature. They were written about 600 BCE, although the text dates from around 2000 BCE. A few of them deal with wound healing or congenital anomalies. “If a man is sick with a blow on the cheek, pound together turpentine, tamarisk, daisy, flour of Inninnu […] mix in milk and beer in a small copper pan; spread on skin and he shall recover.”4 Another tablet suggests the use of a dressing with oil for an open wound. Monsters (congenital malformations) had a key role in predicting future events and in determining their course. “When a woman gives birth to an infant […] whose nostrils are absent, the country will be in affliction, and the house of the man ruined; that has no tongue the house of the man will be ruined; that has no lips affliction will strike the land and the house of the man will be destroyed.”5 Interestingly, surgery is never mentioned in clay tablets, although surgery was certainly performed. In the King Hammurabi Code,2 dating from about 1700 BCE, surgical malpractice was recognized with precise laws: “If a physician carried out a major operation on a seignior with a bronze lancet and has caused the seignior’s death or he opened the eye socket of a seignior and has destroyed the seignior eye, they shall cut off his hand.” “If a physician carried out a major operation on a commoner’s slave with a bronze lancet and has caused [his] death, he shall make good slave for slave.”

In India In the Samhita, a Sanskrit text on surgery attributed to Sushruta and possibly dating 600 BCE, the description of several reconstructive procedures related to the face are discussed. In particular, management of eyelid anomalies like entropion, trichiasis, or ingrown eyelashes and repair of the nose is reported. Certain Indian populations had the habit of cutting the nose of adulterers, thieves, and prisoners of war as a sign of humiliation. In an attempt to improve this terrible disfigurement, surgeons invented different solutions over the centuries. Repair of the nose was carried out by the Koomas, a low caste of priests, or, according to others, a guild of potters. Local flaps, outlined in the cheek, were used, and accurate description of blunt (yantra) and sharp (sastra) instruments to perform nasal reconstruction was supplied.6

Figure 2.2 Indian forehead flap nasal reconstruction. (Reproduced from BL. Letter to the editor. Gentleman’s Magazine. 1794;64:891–892.)  

When was the forehead skin used? There is no mention of it. In the second half of the seventeenth century, the Venetian adventurer Nicolò Manuzzi (1639–1717) wrote a manuscript about the Moghul empire in which an account of forehead rhinoplasty is supplied. Regrettably the manuscript, kept in the Marciana Library in Venice, was not published until 1907.7 Information on the forehead flap in nasal reconstruction only reached the Western world at the end of the eighteenth century, thanks to a letter signed BL, addressed to Mr. Urban, editor of the Gentleman's Magazine, and published in October 1794 (Fig. 2.2).8 A friend of mine has transmitted to me, from the East Indies, the following very curious and, in Europe, I believe unknown chirurgical operation, which has long been practiced in India with success; namely, affixing a new nose on a man’s face. There follows the accurate description of the two-step procedure carried out on Cowasjee, a bullock driver of the English

Plastic surgery after the decline of the Roman Empire

11

army, who fell under the disfavor of Tippoo Sultan and had his nose amputated. It demonstrated the high level of surgery reached by the Indians in performing an operation, without anesthesia, in a very similar way to what we do nowadays.

In Greece Greek medicine was influenced by Hippocrates, the greatest physician of his time. Historians consider that Hippocrates was born on the island of Kos around the year 460 BCE, and probably trained in medicine at the Asklepieion of Kos. In ancient Greece and Rome, the Asklepieion (Latin: aesculapium) was a healing temple, sacred to Asklepios, the Greek god of medicine. Hippocrates rejected the views of his time that illness was due to supernatural influence, possession of evil spirits, or disfavor of the gods. He based his medical practice on the direct observation of disease and on an analysis of the human body, introducing scientific methods into medicine. Hippocrates taught and practiced medicine throughout his life, traveling in various Greek regions. He established the Great School of Medicine on the island of Kos. He probably died in Larissa (Greece) at the age of 83 or 90. About 70 medical treatises, assembled during the Alexandrian era (third century CE) were attributed to Hippocrates. They form the so-called Corpus Hippocraticum. Whether Hippocrates himself is the author of the Corpus and these works are authentic has been the matter of great dispute and controversy.9 The Corpus contains manuals, lectures, research, philosophical thoughts, and essays on different topics of medicine, without any logical order and even with significant contradictions among them. The works of Hippocrates were true best-sellers, reprinted numerous times over the centuries. The first printed edition of the Opera Omnia (Complete Works) was issued in Latin in Rome in 1525, and in Greek in Venice in 1526 by the Aldine Press. The surgical knowledge of Hippocrates was vast. He used cauterization for the management of raw surfaces, reduced malunited fractures, and practiced cranial trephination to evacuate hematomas.

In Rome In Rome, surgery was well developed, at least judging from the rather sophisticated bronze instruments discovered in Pompei and now kept at Naples National Museum. Many were stored in traveling kits to be used by surgeons for emergency or on the battlefields. The two most representative figures of Roman medicine were Celsus and Galen. Aulus Cornelius Celsus (25 BCE to 50 CE) was probably not a physician, but a writer from a noble family and the author, in about 30 CE, of De Medicina (On Medicine) in eight volumes. In book seven, chapter nine, vessel ligature and lithotomy as well as lip closure (cleft lip or lip tumor) by means of flaps are reported. It is explained how “defects of the ears, lips and nose can be cured [curta in auribus, labrisque ac naribus, quomodo sarciri et curare possint]”, followed by a description of wound closure by advancement flap.10 “The defect should be converted into a square [in quadratum redigere]. Then, from the inner angles transverse incisions are made [lineas transversas incidere], so that the part on one side is fully divided from that on the opposite side. … After that, the tissues which have been undermined,

Figure 2.3 Lip repair according to Celsus. (Reproduced from Nélaton C, Ombredanne L. Les Autoplasties. Paris: Steinheil; 1907.)  

are brought together [in unum adducer]”. … If this is not possible two additional semilunar incisions are made at some distance from the original [ultra lineas, quas ante fecimus, alias duas lunatas et ad piagam conversas immittere], but only sectioning the outer skin. … These latter incisions enable the parts to be easily brought together without using any traction” (Fig. 2.3). Celsus holds a key role in the history of plastic surgery, as he is considered the earliest writer on this particular topic. He introduced the four cardinal signs of acute inflammation, “redness and swelling with heat and pain [rubor et tumor, cum calore et dolore]”. A copy of Celsus’s manuscript was discovered in Milan in 1443, and printed for the first time in 1478 in Florence.11 De Medicina went through more than 50 editions. Claudius Galen (c. 129–201 CE) was born in Pergamon (Turkey), studied medicine at the Asklepieion (see above) in his native city and moved to Rome. He wrote about head traumas, techniques of trephination for evacuating hematomas and various types of bandaging. An excellent anatomist, he described more than 300 muscles, the seven pairs of cranial nerves and contributed to neurology, demonstrating that nerves arise from the brain or spinal cord. He observed that section of the laryngeal nerve resulted in dysphonia. For management of wounds he used sutures and cautery. Numerous works of Galen were lost, but 82 survived. Originally written in Greek, many were translated into Arabic and Latin. Galen’s Opera was first printed in Latin in Venice in 1490 and in Greek in Venice in 1525 by the Aldine Press.

Plastic surgery after the decline of the Roman Empire Byzantine surgery Oribasius (325–403 CE) wrote a collection of medical texts entitled Synagogae Medicae in which reconstructive procedures for cheek, nose, ears, and eyebrow defects are described.12 Paulus of

12

CHAPTER 2 • History of reconstructive and aesthetic surgery  

Aegina (625–690 CE), surgeon and obstetrician, was the author of a medical encyclopedia (Epitome) in seven volumes. In Book 6, which deals with surgery, a description of tracheotomy, tonsillectomy, ectropion, upper eyelid retraction, and lip repair is supplied.13,14 “Defects [Greek, colobomata] of the lips and ears are treated in this way. First the skin is freed on the underside. Then the edges of the wound are brought together and the callosity is removed. Finally, stitches holding the margins into position are applied.” This technique closely resembles that of Celsus.

The Middle Ages Arabian surgery Arabian medical writers came from different nations, such as Persia, Syria, and Spain. Their only common denominator was the language. The most representative figure was Abū-l-Qāsim or Albucasis (c. 936–1013 CE), whose famous treatise Al Tasrif (On Surgery) was translated into Latin and first published in 1500. It included more than 200 illustrations of surgical instruments, such as tongue depressor, tooth extractor, hooks, and cauteries, most invented by Albucasis himself, with an explanation of their use.15 Like most Arabian surgeons, Albucasis was a proponent of cautery, for different clinical applications and the management of wounds and cleft lip. He was the first to use a syringe with a piston.

The rise of the universities The founding of the universities is one of the most important events in the Middle Ages and a key factor in the development of modern culture. Originally, “universitas” denoted an aggregation of masters (magistri), students, or both, and the primary goal was teaching philosophy and theology. Lessons were practiced in the house of the masters or in small rooms. Students sat on the floor, whereas the professor was in the chair. The oldest university, at least in Europe, was Bologna, established in 1088, followed by Paris, Oxford, and Montpellier. In Bologna medicine was taught and cadaver dissection was accepted, thus significantly contributing to the development of the study of anatomy. Mondino de’ Luzzi (1270–1326) was the first anatomist to lecture directly in front of the cadaver (Fig. 2.4). As anatomists were also surgeons, such as Henry of Mondeville (1260–1320) or Guy of Chauliac (1300–1368), surgery was part of the teaching program of anatomy.

The invention of printing The invention of the printing press and movable type around 1440 by Gutenberg enabled the spread of medical knowledge and considerably enlarged the libraries of universities and monasteries. The first printed textbook on surgery was La Ciroxia (On Surgery), by William of Saliceto (1210–1277), issued in Venice in 1474. This text has particular relevance in the history of surgery because it reintroduced the use of the surgical knife to replace cautery, strongly advocated by Arabian surgeons. The first printed textbook on anatomy was Anatomia by Mondino de’ Luzzi, issued in Padua about 1476, which remained the reference text for numerous years. The printed works of Hippocrates, Galen, Celsus, and Arabian writers played a key role in educating medical students.

Figure 2.4 Mondino in the chair supervising a cadaver dissection. (Reproduced from Ketham J. Fasciculo de Medicina. Venice: Gregorio de' Gregorii; 1493.)  

The Renaissance Renaissance surgery The most celebrated surgeon of the Renaissance period was the Frenchman Ambroise Paré (1510–1590) (Fig. 2.5). A humble but very talented barber–surgeon, Paré amassed considerable experience from his tireless work in the battlefields. At that time, gunshot wounds were considered poisoned and were barbarically cauterized either with red-hot iron or with boiling oil poured directly into the wound. To the contrary, Paré used simple dressings and soothing ointment made of egg yolk, oil of roses, and turpentine with great benefit for the soldiers. The conclusion was that less invasive methods were far superior to the traditional ones. In 1545 he published his observation in La Méthode de traicter les playes … (The Method of Treating Wounds …). Paré’s works were collected in a single folio volume, Les Oeuvres …, first published at Paris in 1575 and dedicated to Henry III, King of France.16 Paré’s contributions to plastic surgery were significant. He showed the first image of a cleft lip suture in medical literature (Fig. 2.6). To facilitate healing avoiding potential wound breakdown and reducing the risk of unpleasant wide scar formation on the

Plastic surgery after the decline of the Roman Empire

Figure 2.5 Portrait of Ambroise Paré (1510–1590).  

face, he applied adhesive and fastened the wound margins (Fig. 2.7). He described and illustrated a vast number of congenital malformations, some real and others the result of fantasy, the so-called monstrosities. The year 1583 marks a great breakthrough in ophthalmology and eyelid surgery with Ophthalmodouleia, das ist Augendienst (Ophthalmodouleia, or the Service of the Eyes) by Georg Bartisch (1535–1607), oculist to the Elector August of Saxony.17 The book constitutes the first comprehensive treatise on the care and management of the diseases of eye and adnexa and is embellished by dozens of detailed anatomical images of the eye, eyelids, and brain, as well as of surgical instruments. Besides this, it includes the first clinical illustration of blepharochalasis and baggy eyelid (Fig. 2.8) and the report of an original technique for surgical excision of the overhanging skin fold above the tarsus for correcting blepharochalasis, using a curved clamp in the form of a guillotine (Fig. 2.9). The beginning of plastic surgery is usually associated with De Curtorum Chirurgia per Insitionem (On the Surgery of Injuries by Grafting),1,18 published in Venice in 1597, by Gaspare Tagliacozzi (1544–1599), Professor of Surgery at Bologna University, in which the procedure for nasal reconstruction is shown step by step and skillfully illustrated. The instruments necessary for the operation are presented first, followed by the indications, flap outlining on the arm, flap inset, the bandage necessary to secure the arm into position, resection of the vascular pedicle, final result, as well as the different clinical

13

Figure 2.6 Cleft lip repair. (Reproduced from Paré A. Les Oeuvres. Paris: Buon; 1575.)  

applications of the technique for lip and ear defects (Fig. 2.10). The book was well received and reprinted in a pocket edition at Frankfurt the following year, directed specifically at military surgeons who were often confronted with the problems of nasal repair in the battlefields. But when did nasal reconstruction start in the Western world and from whom did Tagliacozzi learn the technique? The operation was performed by members of the Branca family from Catania (Sicily). Gustavo (early 15th century) used skin taken from the cheek. His son, Antonio, made considerable improvements to the operation. He selected the arm as the donor site, to avoid further scars on the face. About 1460, at Antonio’s death, the Branca method, which was kept as a family secret and passed on by word of mouth, was discontinued in Sicily. It was resumed by Vincenzo Vianeo in Calabria (southern Italy). His sons Pietro (about 1510–1571) and Paolo (about 1505–1560) established a flourishing clinic for rhinoplasty in Tropea (Calabria). Evidence of their reconstructive work comes from the Bolognese army surgeon Leonardo Fioravanti (1517–1588), who assisted in Vianeo’s operations and issued a detailed report in Il Tesoro della Vita Humana (Treasure of Human Life), issued in Venice in 1570.19 I moved to Tropea where at that time there were two brothers Pietro and Paolo, who made a nose for anyone who had lost his by some accident […]. I went every day to the house of these

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Figure 2.8 Blepharochalasis and baggy eyelids. (Reproduced from Bartisch G. Ophthalmodouleia, das is Augendienst. Dresden: Stöckel; 1583.)  

Figure 2.7 Facial wound suture. A piece of linen is stitched to the skin to facilitate wound edge approximation. (Reproduced from Paré A. Les Oeuvres. Paris: Buon; 1575.)  

surgeons, who had five noses scheduled for repair and when they wanted to perform these operations they called me to watch and I, pretending I had not the courage to look at, I turned my face away, yet my eyes saw perfectly. Thus, I observed the whole secret from top to toe, and learned it. Then follows the description of the arm flap procedure. Possibly Fioravanti’s book came to the attention of Gaspare Tagliacozzi, who successfully applied the technique on some patients and published his famous textbook in 1597. Although Tagliacozzi was not the discoverer of rhinoplasty, and the arm flap operation is now rarely performed, he deserves credit for being the first to make a work of art out of a surgical practice, for systematizing and promulgating nasal reconstruction. He is rightly considered the founder of plastic surgery.

Figure 2.9 First illustration of blepharochalasis correction. (Reproduced from Bartisch G. Ophthalmodouleia, das is Augendienst. Dresden: Stöckel; 1583.)  

The decline of plastic surgery After Tagliacozzi’s death, apart from his pupil G. B. Cortesi (1554–1634), who published a book on nasal reconstruction in 1625,20 the operation, which was difficult to perform,

The nineteenth century

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Figure 2.10 Nasal reconstruction with the arm flap. (A) Preoperative view of the patient. The missing nose and flap are outlined. (B) The flap sutured into position. (C) Final result. (Reproduced from Tagliacozzi G. De Curtorum Chirurgia per Insitionem. Venice: Bindoni; 1597.)  

became obsolete for almost two centuries. Sporadic cases were reported in seventeenth- or eighteenth-century literature. Instead of recommending autologous tissue for restoring a missing nose, surgeons like Fallopio (1523–1562), Heister (1683–1758), Camper (1722–1789), and others advocated the application of a prosthesis, convinced that noses made out of wood or silver were far superior to those of skin.

The rebirth of plastic surgery The 1794 letter to the editor of the Gentleman's Magazine (see above) holds a key position in the revival of plastic surgery. The English surgeon Joseph Constantine Carpue (1764–1846) read it and made practical and successful use of its contents. In 1814, he carried out the first forehead flap rhinoplasty of modern time at St. Bartholomew’s Hospital, London, on an officer of His Majesty’s Army, who had his nose amputated during a battle. The operation lasted 35 minutes, “it was no child’s play, extremely painful – the officer said – but it was no use complaining”. At the end he exclaimed: “My God, there is a nose!” In 1816, Carpue issued an account of nasal reconstruction, which marks the prelude to the rebirth of modern plastic surgery (Fig. 2.11).21  

The nineteenth century The golden age of plastic surgery Carpue’s work was immediately translated into German, and Carl Ferdinand von Gräfe (1787–1840), Professor of Surgery at Berlin University, promptly initiated the operation. In 1818,

he published Rhinoplastik oder die Kunst den Verlust der Nase organisch zu ersetzen (Rhinoplasty: or the Art of Reconstructing the Nose), where he compared the Italian and Indian procedures.22 Von Gräfe supported the arm flap, as he was unhappy about forehead donor site scar morbidity. The publications of Carpue and von Gräfe stimulated the interest of European surgeons to carry out nasal and other reconstructions. In Germany, Johann F. Dieffenbach (1794– 1847), head of surgery at La Charité Hospital in Berlin, performed rhinoplasty, facial restorations, and cleft lip and palate repairs. He reported his contributions in Chirurgische Ehrfahrungen (Surgical Experiences), issued in 1829.23 In France, Jacques Mathieu Delpech (1777–1832), chief surgeon at Montpellier, wrote Chirurgie Clinique de Montpellier in 1828, with a detailed section on rhinoplasty.24 Outstanding works on the rediscovered art were presented by Pancoast (1805–1882)25 in the US, Balassa (1814–1868)26 in Hungary, and Sabattini (1810–1864)27 in Italy. A review of the state of the art of nasal reconstruction in Europe in the mid-nineteenth century was published by Nélaton and Ombrédanne in 1904,28 and more recently by McDowell,29 Rogers,30 and Mazzola.31 With the advent of anesthesia (1846) and the possibility of closing the donor site primarily, leaving a scar that was often unnoticeable, forehead rhinoplasty became the procedure of choice due to its simplicity, good color match, and excellent results. The first attempt to close a cleft palate goes back to the second decade of the nineteenth century. The priority is shared between Carl Ferdinand von Gräfe32 and Philibert Roux (1780– 1854) from France.33 However, the greatest advance was made in 1862 by Bernard von Langenbeck (1810–1887), who outlined two mucoperichondrial flaps obtaining a more reliable closure.34 Refinements in cleft lip repair were published by the

CHAPTER 2 • History of reconstructive and aesthetic surgery

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Figure 2.11 Nasal reconstruction with the forehead flap. (A) Preoperative view. (B) The flap transposed into position. (Reproduced from Carpue JC. An Account of Two Successful Operations for Restoring a Lost Nose from the Integuments of the Forehead, in the Case of Two Officers of His Majesty's Army. London: Longman, Hurst; 1816.)  

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Figure 2.12 The lip switch technique for upper lip repair. (A) Flap outlining. (B) Final result. (Reproduced from Sabattini P. Cenno storico dell'origine e progressi della Rinoplastica e Cheiloplastica seguita dalla descrizione di queste operazioni praticamente eseguite sopra un solo individuo. Bologna: Belle Arti; 1838.)  

Frenchmen Joseph Malgaigne (1806–1865)35 and Germanicus Mirault (1796–1879) in 1844.36 Reconstructive procedures for lip37 were reported by Pietro Sabattini in 1838, using the lip switch technique27,38 (Fig. 2.12), and by Victor von Bruns (1812–1883) in 1857, using double lateral flaps for oral sphincter restoration39 (Fig. 2.13), whereas eyelid repair was reported by Johann Fricke (1790–1841) in 1829, who described a pedicled skin flap from the ipsilateral temple or cheek region to correct upper or lower eyelid defects, respectively40 (Fig. 2.14).

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Figure 2.13 (A,B) The double lateral flaps for lower lip repair. (Reproduced from von Bruns V. Chirurgischer Atlas. Tübingen: Laupp; 1857.)  

The twentieth century

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Figure 2.14 (A–D) Upper and lower eyelid repair with a temporal and cheek flap, respectively, according to Fricke. (Reproduced from Fritze HE, Reich OFG. Die plastische Chirurgie. Berlin: Hirschwald; 1845.)  

split-thickness skin, which included the superficial layers and underlying dermis.45 Carl Thiersch (1822–1895)46 and John R. Wolfe (1824–1904)47 made further advances in the procedure. In the late 1800s, skin grafting became the preferred solution for the management of chronic and granulating wounds.

The twentieth century The origin of modern plastic surgery Figure 2.15 First autologous skin graft in a ram. (Reproduced from Baronio G. Degli innesti Animali. Milan: Stamperia del Genio; 1804.)  

One of the greatest advances in nineteenth-century surgery was the demonstration that a piece of skin, fully separated from its original site, might survive when transplanted to another part of the body to cover a granulating raw surface.41 This became possible through the pioneering work of Giuseppe Baronio (1758–1811) from Milan, who performed the first autologous skin graft in a ram in 1804 (Fig. 2.15).42,43 Sixty-five years later, Jacques Reverdin (1842–1929) carried out the first successful epidermic graft on a human being at Hôpital Necker in Paris, opening a new era in wound-healing management.44 The route for skin grafting was traced. A few years later, Louis Ollier (1830–1900) transferred a large piece of

Trenches played an important role during World War I. Created for shielding purposes, they actually only protected soldiers’ lower body and trunk, whereas the head and neck remained exposed to enemy weapons. As they returned home, soldiers with major maxillofacial mutilations found it impossible to step back into society, and this constituted a new social problem. Treatment of these devastating facial wounds urged the development of a new discipline, reconstructive surgery. The first plastic surgeons came from general surgery, oto laryngology, or orthopedics during the first two decades of the twentieth century. Associations were created all over the world to help these poor individuals. The most famous was Les Gueules Cassées (The Facial Cripples), founded in France in 1921, by Colonel Picot. In addition to these associations, France, the UK, Germany, Italy, and Czechoslovakia established specialized centers to manage injuries that had never been seen before. The key to success was the cooperation between plastic surgeons, ­

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trained in soft-tissue defect management, and oral surgeons, expert in stabilizing bone fractures using dental appliances. Hippolyte Morestin (1868–1919), who worked with the dentist Charles Auguste Valadier (1873–1931) at Hôpital Valde-Grâce (Paris), first realized the importance of such a team approach. For this he is considered the pioneer in facial reconstructive surgery. In 1915, the New Zealand otolaryngologist Harold Gillies (1882–1960), at that time working in France on behalf of the Red Cross, visited Val-de-Grâce military hospital. He was much impressed by the work of Hippolyte Morestin and Valadier pushed him to take care of facial disfigurements. Upon his return to the UK, Gillies established a center for the management of face and jaw injuries at Queen’s Hospital, Sidcup, which opened in August 1917. It became the referral center in Europe. Treatment was provided to British and allied soldiers wounded in the battlefields on the Somme, where Britain suffered hundreds of thousands of casualties with an enormous number of dramatic facial mutilations (Fig. 2.16). Gillies operated among a multidisciplinary team with William Fry (1889– 1963) and Henry Pickerill (1879–1956) as dental surgeons, and a qualified group of anesthesiologists. He systematized new reconstructive procedures, like the tubed flap, described by the Russian Vladimir Filatov (1875–1956),48 which allowed the coverage of large skin defects, but also skin flaps, bone, cartilage, and skin grafts (Fig. 2.17). Gillies reported his experiences in Plastic Surgery of the Face, issued in 1920.49

In Germany, Erich Lexer (1867–1937), one of the founders of maxillofacial surgery, built up a vast experience on the repair of the face, mandible, and eye socket using cartilage, bone, skin, and fat graft. He published a book on reconstructive surgery in 1920.50 The Dutch surgeon Johannes Esser (1877–1946) was active at Tempelhof Hospital, Berlin, and in Vienna. Between 1916 and 1918 Esser codified some of the flaps currently used today: cheek rotation51 (Fig. 2.18), bilobed, island, and arterialized flaps, which he called biological flaps.52 In Italy, Gustavo Sanvenero Rosselli (1897–1974) was appointed head of the Padiglione per i Mutilati del Viso (Pavilion for Facial Cripples) in Milan (Fig. 2.19). It became a European referral center for reconstructive surgery and was visited by surgeons from all over the world. Frantisek Burian (1881–1965) headed an important plastic surgery unit in Prague, Czechoslovakia. In the US the specialty only grew after World War I. Vilray Blair (1871–1955), trained at Sidcup, established the first independent unit in the US for the care of complex maxillofacial injuries at Walter Reed Hospital. Other renowned reconstructive surgeons were Robert Ivy, Truman Brophy, John Staige Davis, and the Armenian Varaztad Kazanjian.

The training programs By the end of World War I, reconstructive techniques had achieved surprising results. Transfer of skin flaps (tubed or pedicled) and use of grafts (skin, cartilage, bone, fat) became routine procedures. New units were established all over the world. Thus, the need for training programs, where young doctors could become familiar with reparative methods, was essential. Queen’s Hospital at Sidcup, headed by Sir Harold Gillies, was probably the most famous for the management of facial injuries. Anesthesia improved considerably thanks to Ivan Magill, who developed nasal and endotracheal intubation. Other training programs in the UK were organized by Sir Archibald McIndoe, Rainsford Mowlem, and Pomfret Kilner. In Paris, the otorhinolaryngologist Fernand Lemaître (1880– 1958) established a residency at the International Clinic of Oto-Rhino-Laryngology and Facio-Maxillary Surgery, having Eastman Sheehan (1885–1951), Professor of Plastic Surgery at Columbia University New York, as course director (Fig. 2.20). The 2-year fellowship included an intense program of lectures and practical surgical demonstrations. Attendees from various parts of Europe and the US were numerous. Among them was the Italian Gustavo Sanvenero Rosselli, later appointed head of the Plastic Surgery Clinic in Milan. In the US the first training program was organized by Vilray Blair at Washington University in St. Louis.

The birth of the scientific societies

Figure 2.16 Dramatic facial mutilations from World War I. (Reproduced from Pickerill HP. Facial Surgery. Edinburgh: Livingstone; 1924.)  

The aim of the scientific societies was to improve the scientific level of the specialty and to defend the public from charlatans. The first society was the American Association of Oral and Plastic Surgeons, established in 1921 by Truman Brophy (1848–1928), who strongly supported close cooperation between oral and plastic surgeons. Initially membership required the MD and DDS degrees. In Europe, the first society was the Société Française de Chirurgie Réparatrice Plastique et Esthétique, established in

The twentieth century

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Figure 2.17 Sequelae of facial burn from World War I. Repair using the tubed flap. (A) Preoperative view of the patient. (B) Outlining of the tubed flap. (C) The flap in position. (D) Final result. (Reproduced from Gillies H. Plastic Surgery of the Face. London: Frowde, Hodder and Stoughton; 1920.)  

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Figure 2.18 Cheek flap transposition for closing of an orbitopalpebral defect. (Reproduced from Esser JFS. Die Rotation der Wange. Leipzig: Vogel; 1918.)  

Figure 2.19 The Pavilion for Facial Cripples in Milan, headed by G. Sanvenero Rosselli (1897–1974).  

Figure 2.20 Fernand Lemaître and Eastman Sheehan at the International Clinic in Paris, in 1927.  

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Figure 2.21 Executive Council members of the Société Européenne de Chirurgie Structive, Brussels, 1936. From left to right: Sir H. Gillies, J. F. S. Esser, M. Coelst, P. Kilner, G. Sanvenero Rosselli.  

1930 by Charles Claoué (1897–1957) from Bordeaux and Louis Dartigues (1869 –1940) from Paris. It only lasted 2 years. In 1931, Jacques Maliniak (1889–1976) founded the American Society of Plastic Surgeons. The first supranational society was the Société Européenne de Chirurgie Structive, created in 1936 by the Belgian Maurice Coelst (1894–1963) (Fig. 2.21), with the aim of gathering annually all those international specialists interested in the new discipline.53 The term structive was coined by Johannes Esser, as he considered it more appropriate than “plastic” to emphasize the repairing concept. In 1937, Vilray Blair organized the American Board to certify real plastic surgeons.

The scientific journals At the time of the foundation of the American Society (1931), the Belgian Maurice Coelst established and edited the Revue de Chirurgie Plastique (Fig. 2.22). The journal, the first one on this topic, played an important role in the history of plastic surgery between the two wars. Thanks to an international editorial board, which included the most prestigious plastic surgeons, the journal published high-quality papers written by Gillies, Maliniak, and Rethi, the proceedings of the American Society of Plastic Surgery and those of the Société Française de Chirurgie Réparatrice Plastique et Esthétique.54 Papers appeared in the author’s preferred language and were summarized in English, French, and German. In 1935, the Revue de Chirurgie Plastique changed its name into Revue de Chirurgie Structive, becoming the official journal of the Société Européenne de Chirurgie Structive. The Revue lasted until the end of 1938 (8 years), when it ceased publication, due to the advent of World War II. In 1946, the Plastic and Reconstructive Surgery Journal was established and Warren B. Davis was appointed as an editor. The bases for the official recognition of plastic surgery as an independent specialty were settled.

Postwar plastic surgery More recent history has seen an incredible development of new reconstructive procedures, initiated in the 1960s with the recognition of arterialized flaps, continuing with the clinical definition of the cutaneous vascular territories nourished by

Figure 2.22 The first issue of the Revue de Chirurgie Plastique, established by M. Coelst in 1931.  

a single vessel, first identified by Carl Manchot (1866–1932) in 188955 (Fig. 2.23), and culminating with their microvascular transfer. The application in surgical practice of musculocutaneous flaps, originally described by the Italian Iginio Tansini (1855–1943)56 (Fig. 2.24), the introduction of craniofacial techniques, developed in the late 1960s by Paul Tessier (1917–2008),57 the systematization of breast reconstruction, the use of fat grafting for numerous aesthetic and reconstructive indications,58 and even the most recent face transplantation, constitute further achievements of our specialty.

Aesthetic surgery The origin The history of aesthetic surgery begins in 1845, when Johann F. Dieffenbach (1794–1847) described external incisions to reduce large, hanging noses with the dual purpose of modifying the nasolabial angle and decreasing the size of the nose.59 No illustration was provided. The same operation was undertaken a few years later by the Latvian surgeon Julius von Szymanowski (1829–1868), who reported it in his “Operatzij poverchnosti …” (Handbook of Operative Surgery),60 showing the illustration of the procedure. The change of the nasolabial angle and the aesthetic goal of the procedure were emphasized. Correction of prominent ears, performed in 1881 by the New York surgeon Edward Ely (1850–1885), and modifications of nasal appearance are considered among the first purely cosmetic procedures.61

Aesthetic surgery

21

In 1887, John Orlando Roe (1848–1915), an otolaryngologist from Rochester, NY, showed members of the New York Medical Society that reduction of a bulbous or “pug nose”, as he named it, under local anesthesia and on outpatient basis, was feasible.62 Four years later, he presented hump removal using scissors at the same society.63 The following year, Robert Weir (1838–1927), a general surgeon from New York, described alar base excision, now eponymously named the “Weir operation”, to lower an overprojected nose.64 On the other side of the ocean, in Europe, aesthetic rhinoplasty started in Berlin, in about the same period, with Jacques Joseph (1865–1934), who codified the steps of the technique in a rigorous sequence, still used today after almost 100 years, with minimal variations (Fig. 2.25). For at least 20

Figure 2.23 The cutaneous vascular territories nourished by a single vessel. (Reproduced from Manchot C. Die Hautarterien des menschlichen Körpers. Leipzig: Vogel; 1889.)  

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Figure 2.25 Jacques Joseph (1865–1934), carving a piece of ivory, before inserting it into the nasal dorsum. (Reproduced from Joseph J. Nasenplastik und sonstige Gesichtsplastik nebst einem Anhang über Mammaplastik. Leipzig: Kabitzsch; 1931.)  

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Figure 2.24  The latissimus dorsi musculocutaneous flap according to Tansini. (A) Flap outlined. (B) Flap transposition. (C) Final result. (Reproduced from Tansini I. Sopra il mio nuovo processo di amputazione della mammella. Gazz Med It. 1906;57:141.)

22

CHAPTER 2 • History of reconstructive and aesthetic surgery  

years, Joseph managed the aesthetic rhinoplasty scenario in Europe, receiving the most famous patients from every part of the world. His experience was included in a monumental work, Nasenplastik und sonstige Gesichtsplastik (Rhinoplasty and Other Facial Plasties), published in 1931, which remained an unsurpassed text for several decades.65

The development The problem of the beauty doctors The real explosion of aesthetic surgery took place in Europe and in the US between the two world wars. The importance given to personal appearance produced, in the early twentieth century and especially during the interwar period, a horde of quacks, charlatans, and beauty doctors often working in beauty salons, exclusively on a commercial basis. They advertised in newspapers, women’s magazines, and yellow pages as cosmetic surgeons. They appealed to popular naïvety by promising a more attractive look with simple, fast procedures on an outpatient basis, at relatively high cost and by insisting on how beautiful faces and noses were crucial in creating a favorable first impression for finding a job, or expanding social relationships.66 To establish a barrier against beauty doctors and in an attempt to isolate them, true plastic surgeons, practicing reconstructive as well as aesthetic procedures, founded plastic surgical societies (see above). However, it was not an easy task because the general public was more interested in the achievements of cosmetic surgery than in the outcome of reconstructive procedures. An example is given by Charles C. Miller (1880–1950), regarded as an “unscrupulous charlatan” by some or “the father of modern cosmetic surgery” by others for having published in 1907 The Correction of Featural Imperfections, a pioneering work on aesthetic procedures, where facial operations, such as double-chin excision, eyelid and nasolabial fold modification, were illustrated.67 Miller made extensive use of paraffin injections, considered the ideal filler for improving saddle nose and cutaneous depressions. When paraffin was abandoned because of devastating local and systemic sequelae (paraffinomas, pulmonary embolism, phlebitis), he replaced it with crude rubber mixed with gutta-percha and ground in a mill.68 Another borderline cosmetic surgeon was Henry J. Schireson (1881–1949), who knew a moment of fame in the US for having successfully operated on a British actress. Apart from this episode, he faced a series of lawsuits for malpractice which culminated in having his license revoked for a period of time. In 1944, Time defined him as the “king of quacks”. Trained surgeons made considerable efforts to establish a positive view of plastic surgery. Their talent contributed to the transformation of a field regarded with suspicion into an accepted branch of surgery. Eastman Sheehan (1885–1951), Jacques Maliniak (1889–1976), Jerome P. Webster (1888–1974), Vilray Blair (1871–1955), Ferris Smith (1884–1957), and others all played important roles in creating plastic surgery’s professional and public image during the years the specialty was taking shape. Sheehan, course director at Lemaître’s International Clinic in Paris (see Fig. 2.20), was elected President of the American Association of Plastic Surgeons in 1935, despite the controversial view of him by many American colleagues,

who regarded Sheehan as a publicity-seeking skilled operator. Maliniak is best remembered as the founding member of the American Society of Plastic Surgeons in 1931. He was a prolific writer; Sculpture in the Living (1934)69 and Rhinoplasty and Restoration of Facial Contour (1947)70 are some examples. He had an important aesthetic surgical practice in New York, mainly for nose and breast. Webster was one of the founding fathers of US plastic surgery and a talented surgeon in the reconstructive as well as aesthetic fields. Smith, like Sheehan, was course director at Lemaître’s International Clinic in Paris, and author of Reconstructive Surgery of the Head and Neck, issued in 1928 with a section devoted to aesthetic rhinoplasty.71 In Paris, Suzanne Noël (1878–1954), active feminist and founder of the Soroptimist Club of Europe, established a successful solo practice in the very exclusive 16th arrondissement. Her operations were simple but effective, mainly related to facial rejuvenation and entirely performed on an outpatient basis (Fig. 2.26). Major surgery, such as abdominoplasty or mammoplasty, was executed in a private clinic. In 1926, she published La Chirurgie esthétique: Son rôle sociale, one of the first textbooks on this topic and the first written by a woman.72 In 1928 she was awarded the Legion of Honour. Raymond Passot (1886–1933), a leading Parisian aesthetic surgeon, added innovative techniques for breast ptosis, abdomen, and facial rejuvenation. His book La Chirurgie esthétique pure, dating from 1931, showed a wide range of operations in the field of aesthetic surgery73 (Fig. 2.27). Julien Bourguet (1876–1952), another Parisian cosmetic surgeon, became renowned for having first presented the transconjunctival approach for baggy eyelid correction in 1929.74 In Berlin, Jacques Joseph carried out a wide variety of cosmetic operations from rhinoplasty to reduction of prominent ears, facelifting and reduction mammoplasty.65 Eugen

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Figure 2.26 Result of a facelift carried out by Suzanne Noël (1878–1954) about 1925. (Reproduced from Noël S. La Chirurgie esthétique. Son rôle Sociale. Paris: Masson, 1926.)  

Aesthetic surgery

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Holländer (1867–1932) is credited with being the first to report on a facelifting. “Victim myself of the art of feminine persuasion, a few years ago, I performed the excision of a piece of skin along the hairline and the natural folds of the ageing wrinkles and I rejuvenated the drooping cheek for the satisfaction of the beholder.”75 In a later publication he affirmed that this occurred in 1901 and that the patient was a Polish aristocrat. In the same paper, Holländer showed two cases of facial atrophy treated by him with fat injection, and this was the first account reported in the literature.

Postwar aesthetic surgery After World War II and in more recent years, aesthetic surgery grew significantly. The number of plastic surgeons around the world increased and the specialty expanded. Techniques for the correction of noses, faces, necks, eyelids, ears, chins, breasts, and abdomens improved considerably. New operations for solving a myriad of cosmetic problems developed. A typical example is management of the hypoplastic breast. Over the years it was treated with paraffin, sponge implants, fat grafts, and liquid silicone, with poor or unpleasant results. In the mid-1960s the silicone mammary prosthesis appeared on the market, representing the first convincing solution. Liposuction, introduced in the mid-1980s, soon became one of the most popular procedures. Faceliftings, fillers, botulinum toxin, and fat injection favorably improved the demand for facial rejuvenation. Figure 2.27 The cover of the book on aesthetic surgery by Raymond Passot (1886–1933), published in 1931.  

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References

References 1. Tagliacozzi G. De Curtorum Chirurgia per Insitionem. Venice: Bindoni; 1597:43. 2. Majno G. The Healing Hand. Man and Wound in the Ancient World. Cambridge, MA: Harvard University Press; 1982. 3. Breasted JH. The Edwin Smith Surgical Papyrus: Published in facsimile and hieroglyphic transliteration with translation and commentary. Chicago: University of Chicago Press; 1930. 4. Thompson RC. Assyrian prescriptions for treating bruises or swellings. Am J Semitic Lang Lit. 1930;47:1–25. 5. Ballantyne JW. The teratological records of Chaldea. Teratologia. 1894;1:127–142. 6. Keegan DF. Rhinoplastic Operations with a Description of Recent Improvements in the Indian Method. London: Baillière Tindall & Cox; 1900. 7. Sykes PJ, Santoni-Rugiu P, Mazzola RF. Nicolò Manuzzi (1639– 1717) and the first report of the Indian Rhinoplasty. J Plast Reconstr Aesth Surg. 2010;63:247–250. 8. B.L. Letter to the editor. Gentleman's Magazine. 1794;64:891–892. 9. Dunkas N, ed. The Works of Hippocrates. Athens: Diachronic Publications; 1998. 10. Gurlt EJ. Geschichte der Chirurgie und ihrer Ausübung. Berlin: Hirschwald; 1898. 11. Celsus A.C. De Medicina, Libri VIII. Florence: Nicolaus Laurentius; 1478. 12. Lascaratos J, Cohen M, Voros D. Plastic surgery of the face in Byzantium in the fourth century. Plast Reconstr Surg. 1998;102:1274–1280. 13. Briau R. La Chirurgie de Paul d'Égine. Texte Grec… avec traduction Française en regard. Paris: Masson; 1855. 14. Gurunluoglu R, Gurunluoglu A. Paulus Aegineta, a seventh century encyclopedist and surgeon: his role in the history of plastic surgery. Plast Reconstr Surg. 2001;108:2072–2079. 15. Tabanelli M. Tecniche e Strumenti Chirurgici del XIII e XIV secolo. Florence: Olschki; 1973. 16. Paré A. Les Oeuvres. Paris: Buon; 1575. 17. Bartisch G. Ophthalmodouleia, das is Augendienst. Dresden: Stöckel; 1583. 18. Gnudi MT, Webster JP. The Life and Time of Gaspare Tagliacozzi. New York: Reichner; 1950. 19. Fioravanti L. Il Tesoro della Vita Humana. Venice: Sessa; 1570. 20. Cortesi G.B. Miscellaneorum Medicinalium Decades Denae. Messina: Brea; 1625. 21. Carpue JC. An Account of Two Successful Operations for Restoring a Lost Nose from the Integuments of the Forehead, in the Case of Two Officers of his Majesty's Army. London: Longman, Hurst; 1816. 22. Gräfe CF. Rhinoplastik: oder die Kunst den Verlust der Nase organisch zu ersetzen. Berlin: Realschulbuchhandlung; 1818. 23. Dieffenbach JF. Chirurgiche Erfahrungen. Berlin: Enslin; 1829–1834. 24. Delpech JM. Sur l’opération de la rhinoplastique. In: Delpech JM, editor. Chirurgie Clinique de Montpellier. Vol. II. Paris: Gabon; 1828:221. 25. Pancoast J. A Treatise on Operative Surgery; comprising a Description of the Various Processes of the Art, including All New Operations. Philadelphia: Carey and Hart; 1844. 26. Balassa J. Uj Mütétmodorok az Orrképlés Körül két Kòresettel és Tizenegy Köre rajzolt Tàblàval. Pest: Emich; 1863. 27. Sabattini P. Cenno storico dell'origine e progressi della Rinoplastica e Cheiloplastica seguita dalla descrizione di queste operazioni praticamente eseguite sopra un solo individuo. Bologna: Belle Arti; 1838. 28. Nélaton C, Ombrédanne L. La Rhinoplastie. Paris: Steinheil; 1904. 29. McDowell F. History of rhinoplasty. Aesth Plast Surg. 1978;1:321–348. 30. Rogers BO. Nasal reconstruction 150 years ago: aesthetic and other problems. Aesth Plast Surg. 1981;5:283–327. 31. Mazzola RF. Reconstruction of the nose. A historical review. Handchir Mikrochir Plast Chir. 2007;39:181–188.











32. Gräfe CF. Die Gaumennaht, ein neuentdecktes Mittel gegen angeborene Fehler der Sprache. J Chir Augenheilk. 1820;1:1–54. 33. Roux PJ. Observation sur une division congénitale du voile du palais et de la luette guérie au moyen d’une opération analogue à celle du bec de lièvre. J Univers Sci Med. 1819;16:356. 34. Langenbeck BRC. Die Uranoplastik mittelst Ablösung des mucösperiostalen Gaumenüberzuges. Arch Klin Chir. 1862;2:205–287. 35. Malgaigne JF. Nouvelle méthode pour l’opération du bec de lièvre. J Chir. 1844;2:1–6. 36. Mirault G. Lettre sur l’opération du bec de lièvre. J Chir. 1844;2:257–263. 37. Mazzola RF, Lupo G. Evolving concepts in lip reconstruction. Clin Plast Surg. 1984;11:583–617. 38. Mazzola RF, Hueston JT. A forgotten innovator in facial reconstruction: Pietro Sabattini. Plast Reconstr Surg. 1990;85:621–626. 39. Bruns V. von. Chirurgischer Atlas. Bildliche Darstellung der chirurgischen Krankheiten und der zu ihrer Heilung erforderlichen Instrumente, Bandagen und Operationen. II Abt. Kau- u. Geschmaks-Organ. Tübingen: Laupp; 1857–1860. 40. Fricke JCG. Die Bildung neuer Augenlider (Blepharoplastik) nach Zerstörungen und dadurch hervorgebrachten Auswärtswendungen derselben. Hamburg: Perthes und Besser; 1829. 41. Klasen HJ. History of Free Skin Grafting. Berlin: Springer; 1981. 42. Baronio G. Degli Innesti Animali. Milan: Stamperia del Genio; 1804. 43. Baronio G. On Grafting of Animals. Boston, MA: Boston Medical Library; 1985. 44. Reverdin JL. Greffe Epidermique. Expérience faite dans le Service de M. le Docteur Guyon à l’Hôpital Necker. Bull Soc Imp Chir Paris. 1870;10:511–515. 2 sér. 45. Ollier LXEL. Greffes Cutanées ou Autoplastiques. Bull Acad Méd. 1872;1:243–250. 46. Thiersch C. Über die feineren anatomischen Veränderungen bei Aufheilung von Haut auf Granulationen. Verh deutsch Ges Chir. 1874;3:69–75. 47. Wolfe JR. A new method of performing plastic operations. Br Med J. 1875;2:360–361. 48. Filatov VP. Plastika na kruglom steb (Plastic procedure using a round pedicle). Vestnik Oftalmol. 1917;34:149–158. 49. Gillies HD. Plastic Surgery of the Face. London: Frowde, Hodder and Stoughton; 1920. 50. Lexer E. Wiederherstellungschirurgie. Leipzig: Barth; 1920. 51. Esser JFS. Die Rotation der Wange und allgemeine Bemerkungen bei chirurgischer Gesichtsplastik. Leipzig: Vogel; 1918. 52. Esser JFS. Biological or Artery Flaps of the Face. Monaco: Institut Esser de Chirurgie Structive; 1935. 53. Mazzola RF, Kon M. EURAPS at 20 years. A brief history of European Plastic Surgery from the “Société Européenne de Chirurgie Structive” to the “European Association of Plastic Surgeons” (EURAPS). J Plast Reconstr Aesthet Surg. 2010;65:888–895. 54. Rogers BO. U.S. plastic surgeons who contributed to the Revue de Chirurgie Plastique and the Revue de Chirurgie Structive (1931– 1938): “Giants” in our specialty. Aesthetic Plast Surg. 1999;23:252–259. 55. Manchot C. Die Hautarterien des menschlichen Körpers. Leipzig: Vogel; 1889. 56. Tansini I. Sopra il mio nuovo processo di amputazione della mammella. Gazz Med It. 1906;57:141. 57. Tessier P, Guiot G, Rougerie J, et al. Ostéotomies cranio-naso-orbitofaciales. Hypertélorisme Ann Chir Plast. 1912:669–712. 58. Mazzola RF, Mazzola IC. History of fat grafting. From ram fat to stem cells. Clin Plast Surg. 2015;42:147–153. 59. Dieffenbach JF. Die operative Chirurgie. Leipzig: Brockhaus; 1845. 60. Szymanowski J. von. Operatzij na poverchnosti Tchelovetcheskago Tela. Kiev: Davidenko; 1865. 61. Rogers BO. A chronologic history of cosmetic surgery. Bull NY Acad Med. 1971;47:265–302. 62. Roe JO. The deformity termed “Pug-Nose” and its correction by a simple operation. Med Rec. 1887;31:621–623.













































































































































































































































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63. Roe JO. The correction of angular deformities of the nose by a sub-cutaneous operation. Med Rec. 1891;40:57–59. 64. Weir RF. On restoring sunken noses without scarring the face. NY Med J. 1892;56:449–454. 65. Joseph J. Nasenplastik und sonstige Gesichtsplastik nebst einem Anhang über Mammaplastik. Leipzig: Kabitzsch; 1931. 66. Haiken E. Venus Envy. A History of Cosmetic Surgery. Baltimore, MD: Hopkins University Press; 1997. 67. Miller CC. Cosmetic Surgery. The Correction of Featural Imperfections. Chicago: Oak Printing; 1907. 68. Miller CC. Rubber and Gutta-Percha Injections. Chicago: Oak Printing; 1923. 69. Maliniak JW. Sculpture in the Living. New York: Pierson; 1934. 70. Maliniak JW. Rhinoplasty and Restoration of Facial Contour. Philadelphia: Davis; 1947. 71. Smith F. Reconstructive Surgery of the Head and Neck. New York: Nelson; 1928. 72. Nöel S. La Chirurgie esthétique. Son rôle sociale. Paris: Masson; 1926.

73. Passot R. La Chirurgie esthétique pure. Technique et résultats. Paris: Doin; 1931. 74. Bourguet J. Notre traitement chirurgical de “poches” sous les yeux sans cicatrice. Arch Fr Belg Chir. 1928;31:133–136. 75. Holländer E. Die kosmetische Chirurgie. In: Joseph M, ed. Handbuch der Kosmetik. Leipzig: Von Veit; 1912.





















































Further reading Aufricht G. Development of plastic surgery in the United States. Plast Reconstr Surg. 1946;1:3–25. Mazzola RF. History of esthetic rhinoplasty. In: Peled IJ, Manders EK, eds. Esthetic Surgery of the Face. London: Taylor & Francis; 2004:171–189. McDowell F. The Source Book of Plastic Surgery. Baltimore: Williams & Wilkins; 1977. Santoni-Rugiu P, Sykes PJ. A History of Plastic Surgery. Berlin: Springer; 2007.

3 Applying psychology to routine plastic surgery practice Nichola Rumsey and Alex Clarke

Introduction Until now, research on the psychology of plastic surgery has coalesced around two main themes; firstly, the motivation to undergo appearance-altering surgery, and secondly, the prevalence of psychopathology in the population of prospective patients.1 Findings have been contradictory and difficult to apply in routine practice. Progress in improving understanding has been hampered by the lack of data in this sector, however, recent studies of the increasing prevalence of dissatisfaction with appearance in the general population have provided useful insights. It is now clear that a substantial majority of prospective patients are motivated to undergo appearance-altering surgery by the anticipation of psychosocial gains. Psychological factors also influence expectations about the process and likely outcomes of treatment and satisfaction with the postoperative result. An appreciation of the psychology of appearance-altering surgery is therefore crucial in enabling surgeons to provide effective care and treatment. To facilitate the application of current understanding to practice, the sections of this chapter have been structured as responses to questions we are asked frequently by plastic surgeons. We have supplemented research findings with clinical insights when appropriate.

What motivates people to seek appearance-altering surgery? The prevalence of appearance dissatisfaction in the general population An interest in looks amongst artists, sculptors, and affluent social groups has been evident since records began. Over the years, codes governing self-presentation within these groups have been prescriptive, but largely achievable. During the past decade, however, the internet and social media have provided

a platform for the sharing of appearance ideals across the globe. Crossing social and cultural boundaries, these ideals are less achievable for the vast majority of the population than has previously been the case. Influenced by a heavy diet of appearance-focused content in broadcast and print media2 and of digitally enhanced images on social media,3 in excess of two-thirds of young people and adults of all ages experience dissatisfaction (and for many, distress) with a particular feature or multiple aspects of their looks. The prevalence of appearance dissatisfaction among people of all ages is increasing year on year and is now considered normative.4 We all experience at least some degree of pressure to correct “faults” in our appearance and are encouraged to believe that our looks are key in the way we are judged by others and in how we should judge ourselves. Achieving looks closer to current ideals will open doors to “the good life”. In contrast to these messages in our sociocultural context, however, a substantial body of evidence now attests to troubling associations between appearance dissatisfaction and key aspects of living, including psychological wellbeing (for example, lowered self-esteem and body image), mood (anxiety; depression5; suicidal ideation6) and patterns of behavior (disordered eating7; unhealthy exercise behaviors; the misuse of alcohol and drugs7; and self-harm7). Negative impacts also extend to education, work aspirations, and performance in occupational settings.8,9 Recent evidence that appearance dissatisfaction is far from benign has led to calls from health professionals, researchers, politicians, policy-makers, and third sector organizations to recognize the phenomenon as a pressing public health, gender, and social justice issue. These calls are of particular relevance to plastic surgeons and their teams as dissatisfaction with appearance is the most commonly cited reason for seeking appearance-altering surgery10 and plastic surgery is the route portrayed in the media and perceived by the public to be amongst the most effective methods of closing the gap with appearance ideals and improving quality of life.

What motivates people to seek appearance-altering surgery?

What are the characteristics of people who seek cosmetic interventions? As evidence indicates that the majority of the population are dissatisfied with their looks, what differentiates those who present for cosmetic surgery from those who do not? As with other questions in this sector, a major impediment to understanding is the lack of data and as a result, a paucity of research. During the wait for data, researchers have gleaned insights from studies of the reported intentions of general population samples. Two key psychological processes – a person’s degree of susceptibility to messages in their sociocultural context – and internalization – the degree to which people perceive these messages to be personally relevant – appear to characterize those who intend to seek surgery. People who consume a large amount of social and broadcast media have more favorable attitudes about undergoing cosmetic surgery as a means of achieving appearance ideals than less frequent users of these media.11,12 These media encourage users to compare their own looks with digitally enhanced and retouched images of celebrities and influencers. People with a stronger tendency to choose unrealistic targets of comparison and to aspire to unrealistic appearance ideals are also more likely to have positive attitudes towards cosmetic surgery.3 Although the results of these studies are illuminating, the gap between intention and actual behavior is widely recognized in psychology and limits confidence in the generalizability of the findings. Research with people who have translated their intention into behavior offers more authoritative insights on the motivation of prospective patients. Margraf and colleagues13 measured the preoperative expectations of a large sample of patients who had made the decision to undergo surgery, comparing this group with those still considering surgery and a further representative general population sample. Both of the groups actively considering surgery attributed a greater importance to improving their body image, rated their current appearance more negatively and reported a lower level of satisfaction with life generally than the general population group. The goals most commonly endorsed by the surgical group were “to feel more comfortable in my own skin”, “to eliminate a long-felt blemish”, and “to increase self-esteem”. Remaining goals focused on “external” rather than “internal” motives, including the desire to please a partner, or to have more professional success. These findings are in line with other reports about the psychosocial nature of the changes that cosmetic surgery patients hope to achieve.14,15 Taken together, these results highlight a critical issue for surgeons. Prospective patients are motivated to seek surgery by psychosocial factors and also hold expectations of psychosocial gains as the result of an altered appearance over which the surgeon has no control. At one level, the reasons offered by prospective patients seem straightforward, but the drivers behind these reasons involve complex interactions between key psychological and social processes. For example, in saying “I just want to look normal”, prospective patients may be referring to the desire to regain a previous appearance (such as a pre-pregnancy body shape), the desire to remove a feature they perceive to be stigmatizing (for example, the visible signs of weight loss), or to achieve the size and shape of genitalia perceived as “normal” through exposure to images on the internet or social media. Their motivation

25

will draw on their body image and/or a recollection of their appearance at an earlier life stage (this, in turn, will be biased by psychological processes) and the degree to which they buy-in to appearance ideals and perceived social norms prevalent in social and mass media, family, and peers. A prospective patient’s susceptibility to perceived or real pressure in the sociocultural environment also extends to the business practices of some cosmetic surgery providers. Advertising and marketing strategies promoting new products and interventions as the solution to “faults” in appearance can fuel existing insecurities and create new appearance concerns. Promotional materials often include glamorous images with explicit or implicit messages about the likely psychological and lifestyle gains associated with surgery. The décor of a clinic, the “before” and “after” photos on display, and the language used by clinic staff to describe the likely outcomes of surgery will influence not only the prospective patient’s desire to undergo an intervention, but also their expectations of the likely psychosocial outcomes.16

Visible differences (disfigurement) and reconstructive surgery Living with an unusual appearance, whatever the cause, presents significant challenges. The motivation of patients to undergo reconstructive surgery and their responses to treatment will be influenced by their experiences of these challenges and by pressures in the sociocultural context described above. Research indicates that the most frequently reported difficulties for this group of people relate to social situations. First encounters with others can be particularly troubling, either as the result of a lack of confidence, or because of perceived negativity in the reaction of others to their appearance. Moving to a new job, geographical neighborhood or social group can be particularly stressful, requiring multiple first encounters and the need to establish new social networks.17 Anxieties about the potentially negative impact of a disfigurement on forming friendships or establishing longer-term relationships are also common.16 Recently, research has also highlighted these anxieties in sexuality and intimate relationships.18 These issues are rarely raised by the patient and are topics commonly avoided by professionals. As this driver for treatment frequently remains undisclosed, it is rarely factored into a treatment plan. Widespread reports of detrimental effects of a visible difference on self-perceptions are also common. These include low levels of self-esteem and body image, aversive emotions such as perceptions of stigma (resulting from stereotyping by others on the basis of appearance) and shame. Specific cultural or religious beliefs may increase the perceived pressure to “improve” appearance. Prospective patients commonly articulate their desire to achieve a “normal” appearance to avoid attention from strangers, but their aspirations often include improved self-esteem and confidence. While surgery can directly address the goal of achieving an unremarkable appearance, broader psychological gains are likely to require a more comprehensive treatment plan. The proportion of people who experience significant levels of distress varies between studies, conditions, and situations, but overall, about one-third seem to experience significant

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difficulties, either on a transitory or more enduring basis. However, perhaps the most striking aspects of adjustment to an unusual appearance are the extent of the variation in adjustment and the factors accounting for these differences. Early studies focussed on condition-specific effects, such as the etiology, severity, and extent of a disfigurement, and the body parts affected. Results have demonstrated clearly that these “physical” parameters are, in fact, poor predictors of adjustment.16 Neither is time necessarily a great healer. Difficulties and distress can wax and wane over the years, triggered by developmental challenges such as the imperative to form a lasting relationship, the physical or psychological changes in midlife, stressful life events, or even a casual comment that, for one reason or another, takes root. The visible difference can become a “hook” – blamed for real or imagined negativity from others, or the cause of the crisis in hand. A disfigurement resulting from trauma may leave a legacy of distress or PTSD, and the patient’s mental health before the trauma will influence how well she or he copes with the aftermath in both the short and longer term. In sum, the influence of condition-specific factors and the passage of time is smaller than many clinicians expect and assumptions about the patient’s wellbeing should not be made on this basis. Adjustment does not rely on appearance alone and the preconception that the patient’s anomaly is the root cause of psychological difficulties should be avoided. The strongest predictors of adjustment include the degree to which the person’s disposition and outlook on life are optimistic or pessimistic, the extent to which their sense of selfworth relies on their perceptions of the reactions and opinions of others, the degree of satisfaction they report with their social connections and social support, and the extent to which they believe their life has meaning and purpose. Their level of social skill (the ability to successfully navigate social interactions with others) is also a contributory factor.16 In a similar way to cosmetic procedures, psychological factors and processes play a part in all stages of reconstructive surgery. Patients may need encouragement to get off the treatment treadmill and to focus on attributes other than appearance which are more likely to lead to improvements in quality of life.19 People who have significant body image concerns independent of their disfiguring conditions, or mental health conditions such as depression or PTSD (e.g., after traumatic injury) may be over-invested in surgery to provide “solutions” to their broader psychological distress. Careful assessment of the anticipated benefits of surgery is crucial in guarding against unrealistic expectations of outcome.

Does cosmetic surgery meet patients’ needs? The psychological benefits and limitations of cosmetic surgery The majority of patients and providers assert that cosmetic interventions have positive impacts, however, the evidence about what works for whom and under what circumstances is still lacking, leaving many who are vulnerable to unrealistic expectations at risk of poor outcome. We are able to come to these tentative conclusions by synthesizing the most

recent research findings as below. Surgery is more likely to be effective:   Where a particular feature is targeted. Patients tend to report better outcomes under these circumstances than for expectations of a general improvement in body image.20   Where signs of Body Dysmorphic Disorder (BDD) with a significant disruption of day-to-day activities have been fully investigated. All BDD patients are at very high risk and are more appropriately managed via alternative interventions.21,22   Where patients have clear, measurable, and achievable goals agreed between them and their surgeon.23   Where motivation is intrinsic (i.e., undertaken for personal reasons without undue pressure from others).16   Where psychological vulnerabilities have been identified and managed. (This includes but is not limited to those meeting the diagnostic criteria for BDD.)24   Where no complications are incurred.25   Where cosmetic surgery is not presented as a first-line treatment for mental health disorders, e.g., depression.14 Margraf and colleagues,26 reporting longitudinal data showing generally positive outcomes after surgery, highlight the need for better knowledge of how surgery results in gains, including any significant mediational processes. For example, what psychological changes are important to becoming socially at ease after a rhinoplasty? Has the level of rumination and worry about the feature declined? Or is the opportunity to engage in social activity postoperatively responsible for the positive outcomes? If so, would it be helpful to support patients to increase social activity following surgery? There is certainly evidence from studies of people with visible differences that demonstrate the benefits of teaching positive social behaviors in reducing anxiety and promoting self-confidence.27 If so, might this form part of rehabilitation postoperatively? Understanding cosmetic surgery outcomes better requires a commitment to assessment and audit from all providers. We need to understand better what works for whom and therefore how to manage the next generation of patients we are starting to see for whom appearance is an over-valued commodity. We should also consider how to manage current patients returning for repeat procedures, as aging alters the ratio of risks and benefits in relation to the surgical interventions on which they have come to depend.

Who is psychologically vulnerable – does vulnerability lead to poorer outcomes? Interest has grown in the influence of a broad range of psychological vulnerabilities on the motivation of prospective patients to seek appearance-altering surgery and less invasive cosmetic procedures, and in their response to the outcomes. Young people are particularly prone to pressure to conform to social norms. They are also heavy consumers of social media. Their sense of identity and their self-esteem are likely to be fluid. In addition, their physical development (for

How can I manage my patients more effectively?

example, their breast size) may not be complete until early adulthood. There is a consensus from professional bodies28–30 and from social commentators in the UK31 that esthetic procedures are contraindicated for people under the age of 18. Young adults should also be assessed very thoroughly. With a generation of people worried about their appearance and for whom plastic surgery is perceived to be a quick fix for psychosocial discomfort, together with the likelihood of a higher prevalence of a range of psychological vulnerabilities, the risk of disappointment and dissatisfaction postoperatively is very real – even when there is an excellent technical result. New ways of working are needed to manage the risks of this disappointment to both the surgeon and the patient.

Mental health problems Reviews have noted the higher prevalence of a range of psychiatric issues in cosmetic settings, of which the body image issues, including BDD, are of particular concern.14,20 Paradoxically, cosmetic procedures are often considered a solution to some of these mental health issues despite the lack of evidence to support the benefits of cosmetic surgery in treating mental health issues.14 With the exception of BDD, there is very little evidence about whether people with mental health issues comprise a significant proportion of those who are dissatisfied or return for multiple procedures, but we do know from the general literature that they are at potentially greater risk. For example, depression is associated with a withdrawal from rewarding behaviors. This can mean that decisions are being made at a time when judgments are impaired (life seems lonelier and less hopeful than usual). Surgery may seem a tantalizing option. All patients are required to make complex decisions about treatment, but depression directly impairs attention, memory, and the capacity to process and absorb procedural and risk information. A severely depressed patient, where logical reasoning is impacted, may lack capacity to give informed consent. The ability to adapt to changing situations (for example, unexpected complications of treatment) and to comply with appropriate rehabilitation (such as physiotherapy, massage or wound management) may also be impaired, feeding into postoperative dissatisfaction. Anxiety has a higher prevalence in cosmetic settings, with reports of up to 18% of patients taking an anxiolytic or antidepressive medication at the time of referral, compared with 5% of the general population.32 Anxiety is associated with changes in behavior, including overestimation of the likelihood of negative events. Cosmetic surgery may appear to have many answers for these patients, from feeling more confident in social situations to a reduction in rumination and worry, but the data so far do not support these outcomes. With regard to social anxiety, which often forms the basis of the motivation for appearance change, it is important that patients clearly understand what is within the surgeon’s power and what is more likely to improve as a result of experiencing positive outcomes in social settings. BDD is an extreme form of body image anxiety, with symptoms sufficiently severe to result in significant distress and impairment in day-to-day life. With the prevalence of BDD around 15% and higher in rhinoplasty clinics, there is potentially one patient per clinic or more. In its milder forms, it can be difficult to distinguish from other body image issues.

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Although the benefits of surgery for mild BDD cannot be ruled out,33 the balance of evidence is in favor of a psychological approach to treatment. Because people with BDD are very clearly over-represented in groups reporting postoperative dissatisfaction, risk of postoperative dissatisfaction is high and screening out of the surgical pathway is recommended. Specific management guidance in the UK recommends evidence-based psychological treatments in the form of Cognitive Behavior Therapy (CBT) and or medication.22 More broadly, and likely to vary between practices, surgeons may become increasingly aware of psychological vulnerabilities in their patients, despite the fact that they may not have a formal psychiatric diagnosis. These factors are associated with a disadvantaged background, chaotic lifestyle, history of domestic violence, generally poor wellbeing and current substance abuse.20 These patients often present with a history of multiple or repeat procedures to the same feature and/or dissatisfaction with previous outcome. Their behavior suggests excessive internalization of unrealistic messages about the value of appearance in their life prospects, excessive rumination, and unrealistic comparisons between their own looks and images of celebrities, which maintain their feelings of low self-worth. Their high consumption of social media and investment in appearance-related behaviors sees them increasingly drawn to cosmetic surgery with its offer of easily achieved solutions. Management of these patients can be challenging: there are no evidence-based guidelines relevant to their care. However, it is possible to draw on clinical experience, itself evidence-based, to design a systematic approach to patient assessment and the identification of known risks, and to suggest a management pathway for surgeons to assist them in their decisions about care.

How can I manage my patients more effectively? The psychology of cosmetic surgery is a relatively new (but growing) field of interest for psychologists. As yet, with the exception of BDD, we are unable to offer an evidence base for effectiveness of our interventions. However, we have refined some principles, based on many years of clinical observation and engagement, which have been popular with surgeons in our teaching. These are offered here in the form of practical tips (and avoidable pitfalls) that we have found to be helpful in preparing patients for surgery and reducing the risks of dissatisfaction.

Communicating effectively A surgeon’s behavior is a major contributory factor to levels of patient satisfaction with the process and outcomes of surgery.34 Communication skills are key in encouraging the prospective patient to share the detail of their motivation to change their appearance, in facilitating the processing of procedural and risk information, in promoting their involvement in treatment decision-making, and in achieving meaningful consent to surgery. While many surgeons develop an appropriate “script” for their consultations, some fail to understand that their nonverbal behavior is more powerful than their words. Rapport with the patient is established through facial expression, eye

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contact, posture, and spatial orientation (consider, for example, the effect of sitting behind a large desk, compared with a more accessible seating arrangement). Facilitative, unrushed, and interested behavior is central to this patient-focussed approach. Hints and tips It is really important not to rush. Patients may take some time to really explain what concerns them. They may be tearful at times; often this has been something that has troubled them all their lives and this is a big moment for them. Silence is okay. Don’t rush to fill the silence with a menu of procedures for them to choose from. If necessary, suggest that they do some reading and come back another time when their thoughts are clearer. Dissatisfied patients often report feeling hurried and agreeing to something they had not really thought about.

Screening and assessment An acknowledgement of the key role of psychological factors and processes in plastic surgery has shone a spotlight on the need for the effective assessment of prospective patients. Furthermore, evidence of the prevalence and range of psychological vulnerabilities in the population of patients seeking cosmetic interventions has led to calls for a shift away from a focus on identifying known risk factors for poor outcomes such as BDD, to a model in which the relative vulnerability of all prospective patients is assessed.20,31 Although this recommendation is widely supported, progress in producing an accurate, evidence-based screening tool has been slow. Hampered by the dearth of good quality longitudinal data in this sector, it has not yet been possible to identify definitively the key psychosocial predictors of good and sub-optimal outcomes. These data are necessary to develop a generic psychometrically sound screening tool appropriate for patients undergoing a broad range of cosmetic procedures.20,35 Until the necessary data are forthcoming, dilemmas in how best to assess patients remain. The current “list” of possible risk factors for postoperative dissatisfaction is long. Existing scales capture individual factors, but a comprehensive assessment would require a large battery of these scales and multiple assessments are not a feasible option in routine practice. Examples include the Cosmetic Procedures Screening Questionnaire (COPS),36 a 9-item scale designed to identify signs and symptoms of BDD. However, the COPS is not designed to identify other types of psychological vulnerability flagged as additional risk factors for poorer outcomes following aesthetic surgery. In the interim, researchers have focussed on the development of evidence-based frameworks for assessment and follow-up, designed to generate a common dataset between users. Available in versions for patients undergoing cosmetic or reconstructive surgery, the Patient Assessment Tools (PATs) offer the potential to identify and manage the patient’s psychosocial agenda through the medium of a structured interview. The initial assessment identifies patients’ aesthetic and psychosocial goals, while flagging risk factors for poorer outcomes. The profile of responses is linked to evidence-based suggestions for appropriate management. The post-procedure versions assess progress towards agreed goals and clarify any areas of postoperative dissatisfaction. Together, the pre- and

post-surgery versions provide a framework for the routine collection of data that can be used in-house for audit or shared with other clinics to facilitate research. The PATs and a suite of training modules on key aspects of the psychology of cosmetic and reconstructive surgery are available from Triskelion (Sweden).37 Despite the delays in producing an authoritative screening tool, significant progress has been made in appropriate ways to assess satisfaction with outcomes as judged by the patient. Patient reported outcome measures (PROMS) assess the impacts of surgery and level of postoperative satisfaction in individual patients. Widely recommended are the QPROMS. Available in procedure-specific versions (including the FACEQ, BODYQ and BREASTQ), they are not designed for use as a generic screening tool for psychological vulnerability.

Understanding motivation and modifying expectations of outcome As we have seen, our increasing understanding of patients’ motivation for surgery illustrates the predominance of psychosocial factors. Indeed, some have argued that cosmetic procedures are essentially a quest for psychosocial change.14,15,38 This presents a real challenge for surgeons in that psychosocial expectations are outcomes over which a surgeon has no control. How, for example, is a surgeon to influence the concept of “feeling comfortable in one’s own skin”? A surgeon can make a feature bigger, smaller, or more symmetrical and potentially reduce a scar or remove a skin lesion; but surgeons can only have both indirect and unpredictable impact on psychological factors such as self-confidence, self-esteem, happiness, “feeling more feminine” or more “attractive”, all of which are entirely subjective. Direct impacts on the patient’s behavior (or the behavior of others) are particularly unlikely, despite the patient’s assumptions that these changes will result from surgical intervention. Even when there is an excellent

Hints and tips One way to make outcomes clear and specific is to divide up physical goals (the ones that you can have some control over) and the psychosocial or emotional goals that the patient assumes will follow surgery.

Physical

Psychosocial

Remove bump on nose

Increase confidence

Lift the tip

Reduce anxiety

Increase breast size

Make me feel more feminine

Reduce breast size

Improve my attractiveness

It can also be helpful to assign a probability of achieving outcome, e.g., Probability of increasing or reducing breast size – High. Probability of reducing anxiety – Low or unknown. In this way you are assisting the patient to focus on their priorities whilst gently modifying their expectations of the surgery you can provide. This is a nice way of operationalizing shared decision-making and sharing planning and responsibility for different outcomes. For example, whilst you can increase breast size, your patient can choose new clothes and engage in activities to enhance her self-esteem.

How can I manage my patients more effectively?

technical result, expectations may be unmet and patients can, understandably, be disappointed.

Facilitating the understanding of risk When expectations are high, this can impact on how risks are evaluated. The resulting tension can lead to distancing from risks, which are downplayed: “It’s worth taking the risk – I could be knocked down by a car tomorrow.” Similarly, where risks are perceived to be very high, the resulting potential benefits can be perceived as greater.16 Getting the balance right and establishing that risk information has been processed and retained is critical to obtaining consent.

29

risks involved in the surgical procedure. The role of the clinician is to explore treatment options in the context of the patient’s priorities. The Box shows how we described this process to patients in an intervention to promote shared decision-making in breast reconstruction. Hints and tips Promoting shared decision-making “Whilst we [the breast care team] are the experts in breast cancer and reconstruction, we don’t know anything about you yet. You are the expert on that. So we hope that by working together we can come to a shared understanding of what is important for you and how we can support you to achieve it.”

Hints and tips It can be helpful to ask the patient to explain risk information back to you in the first person. So, for example, “I understand that immediate infection around my implant is a very small risk and that this happens to just under one women in 100; but if it happens to me, I may need the implant removed whilst the infection is treated”, is more salient than “There is a 1% infection risk”. This simple technique helps to locate the risk as a personal one rather than a population risk and gives you a chance to modify any errors early on.

If people hear information that they cannot understand they will be unable to retain it. Use of jargon, phrases with an emotional overtone, such as the suggestion of abnormality (e.g., tubular breast deformity) can impair attention to the central message and cause the patient to switch off. Even terms such as “correction” imply an underlying problem whereas “change” is neutral. Avoiding percentages is recommended, as these can be difficult to interpret (“He said I had a 30% chance of a 50% improvement”). Being specific and avoiding value judgments is important. Terms such as “bigger”, “smaller”, “symmetrical” can be measured, recorded and agreed. “Normal”, “better” and “more attractive” are subjective values which are difficult to measure and outside the surgeon’s control. Providing information about what to do if a risk is incurred helps with the patient’s sense of agency and control and supports a shared approach to responsible management. Having a clear, documented plan which everyone agrees with and sticking to it is helpful. Last-minute changes can cause last-minute uncertainty. Sometime patients respond to risk information by stating that they are willing to accept any risk even when you are reluctant to proceed: “Anything is better than the way I look now.” This can be an example of unrealistic expectations of outcome; where the potential benefits are inflated to avoid internal conflict because the risks are high. The probability of a good outcome is reduced.

Promoting patient involvement in treatment decision-making There is an association between active engagement by patients in treatment decision-making and higher levels of postoperative satisfaction and better health outcomes.15 Shared decision-making involves the exchange of information from the patient about their motivation, expectations, and relevant medical history, and from the surgeon about the options and

Research using this approach demonstrated higher levels of satisfaction and less decisional regret in situations where patients were making complex, preference-sensitive decisions. Health professionals similarly reported positive experience of using this intervention.23,39 Shared decision-making is a practical way of operationalizing the factors cited as important by cosmetic surgery patients who post positive ratings and testimonials on line, including good communication skills, not feeling rushed during consultations, and levels of patient involvement in decisions.34 A full disclosure of medical history by the patient is part of the shared decision-making approach. However, some patients request secrecy. In weighing up these requests, concerns include the potential for non-disclosure of relevant medical history, lack of social support during recovery, and underlying shame about treatment decisions

Incorporating psychological care into routine practice in cosmetic surgery Whilst incorporating psychological care into routine management means a more thorough assessment for all patients, it does not imply that all patients need referral to a psychologist: indeed, this group comprises a minority of those requesting surgery. The surgeon and team can help the patient to tackle psychological challenges by directing them to authoritative sources of information and support.40–42 Good psychological care can be provided by the clinic team via a commitment to excellent communication, assessment of motivation and expectations, management of risk and shared decision-making Hints and tips Explaining a psychology referral to the patient “In this practice, we are committed to fully understanding all the reasons that people consider cosmetic treatments. Ensuring that we have fully understood your goals and expectations is key to achieving a good result. Helping us to do this we have a psychologist and I would like you to see them before we plan any further ahead.” “Normalize” referral: stress that this is a common part of a preoperative assessment. Introduce this as an opportunity to explore goals and expectations, understanding of risk and decision-making.

CHAPTER 3 • Applying psychology to routine plastic surgery practice

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as outlined in this chapter. However, when assessment highlights concerns and suggests that a more comprehensive psychological assessment is needed, it is useful to have this process well established within the routine patient pathway. In the UK, the British Association of Aesthetic Plastic Surgeons has sponsored the development of a Special Interest Group of psychologists working within cosmetic surgery practice. This ensures that surgeons can access professionals with the relevant training and experience to support their practice. Rather than wait until they encounter problems, surgeons are encouraged to make contact with someone who can offer assessment to assist them in treating patients who are psychologically vulnerable, have a mental health issue of concern or are unhappy with the outcome postoperatively. In addition to assessment, psychologists may offer supervision or training to clinic staff, advice on clinic literature, and debriefing for surgeons themselves, in addition to offering evidence-based interventions for patients. Models of working include occasional referral for assessment, to regular referrals, and in some cases, joint working with all patients (although the latter is rare). Algorithm 3.1 illustrates a typical treatment pathway. Patients are seen for a first appointment by the surgeon where

they complete their assessment (for example by using PATs) as part of the pre-surgical consultation. Where issues of concern are highlighted these are managed initially in the clinic, with the option of onward referral for psychological assessment. Following this, patients either return to the surgical pathway or have some adjuvant sessions alongside surgery or, in the minority of cases, are offered alternative treatment or referred on to other appropriate providers. Cooling off periods are advised but have no psychological value on their own. These should be used constructively, for example asking patients to consult appropriate information, or asking them to discuss the proposed treatment with others. Failure to engage with suggestions made by the surgeon at this stage is likely to be predictive of failure to engage at other stages of the pathway (e.g., in relation to postoperative recovery).

Managing mental health issues The significant numbers of patients with BDD who present in cosmetic clinics is well established.14 Screening out of the surgical pathway is recommended. Psychological input in the form of Cognitive Behavior Therapy (CBT) and/or

Hints and tips

Hints and tips Considerations in making a referral to the psychologist The golden rule in referral is to ask what you [the surgeon] want to know. If you just ask for an opinion, we [psychologists] don’t necessarily understand the issues that most concern you. The more you can tell us about what you want to know the better we can try to answer it. Don’t rush! Please don’t book the patient for surgery before we have seen them. Taking someone off a surgical list is far harder than delaying putting them on in the first place. Think about inviting the psychologist to the practice to discuss the kinds of issues you commonly encounter. Highlight any technical issues and be honest in your assessment. If you feel reluctant to offer surgery, even if this is just a gut feeling, it is helpful to let the psychologist know.

Declining surgery Many surgeons find it hard to decline surgery. They may worry that patients will end up with an unscrupulous provider: “If I say no, the patient will seek out another provider.” They may feel that although they cannot do all the patient is asking, perhaps a more modest alternative treatment might be helpful. However, if surgery carries too great a risk (either of a poor technical outcome or dissatisfaction) then you should not proceed. Patients sometimes say that they are willing to accept any risk: but you have to make it clear if you will not. It can be easier to frame your response in terms of your own skills rather than the patient’s expectations: “I don’t feel that I have the skills or expertise to achieve the outcomes you are hoping for” is more likely to avoid confrontation than “I don’t think you will be happy with the results”.

Algorithm 3.1 C O OO L F I F N G

FINAL REVIEW • Treatment decisions • Consent

SURGERY

FOLLOW-UP PATs postsurgery

PATs presurgery assessment

Psychological assessment

Implementing pathways for referral and the appropriate management of patients.

Psychological intervention

FOLLOW-UP with psychologist

Summary

medication has well-evidenced benefits and is the procedure of choice.21,22 Although some believe that mild BDD patients can do well, they often need considerably more time and input from clinic staff. Although it is tempting to offer surgery to the patient if you think you can make a physical difference, it is a risky choice. For a start, where there is significant body image distortion, you are not seeing the feature that concerns them as they are seeing it. Even the best technical result may not satisfy the patient, leading to even greater concern and worry. Given the numbers of patients seeking cosmetic surgery who are taking antidepressive or anxiolytic medication at the time of referral,32 the surgeon should ensure the patient is stable on their medication and that surgery is not being considered as a primary treatment for the underlying condition. If it is, then surgery is unlikely to achieve the expected outcomes. Patients and those supporting them (including some health professionals without a background in cosmetic surgery) may draw their expectations from the popular media and genuinely believe that surgery offers a means of managing mood or potentially giving up medication. It is helpful to explore whether others support the request; has the physical feature of concern been a problem for the patient for some time? If not, is the patient under pressure from well-meaning others who assume a positive impact of a change in appearance on mood? It is important to explain that, so far, the evidence does not suggest these psychological gains will be likely. An assessment should be made about the capacity of the individual to assimilate risk and cope with any complications of the procedure. Postoperative dissatisfaction can be devastating for someone already inclined to catastrophize. Should treatment go ahead, careful preparation is advised. Pressure to offer surgery quickly should be resisted. Other mental health issues that require additional assessment include eating disorders where the request for surgery (e.g., liposuction) may be a reflection of the underlying disorder. (For a full discussion of mental health issues that present most commonly in cosmetic settings, see reference 14.) Even though many patients may turn down the offer of psychological support as an alternative or an adjunct to surgery, it is still important to stress that for those with expectations of significant psychosocial change, this is the procedure of

Access the reference list online at

  

Elsevier eBooks+

31

choice and the most likely way to achieve the goals they are anticipating. Whilst there is a lack of evidence to support the benefits of cosmetic surgery for the psychologically vulnerable, including those with mental health issues, there is similarly no evidence yet to suggest that all these patients should be screened out of the surgical pathway. But it is clear that the risks for dissatisfaction and decision regret are higher and that the next generation of cosmetic surgery patients may be more vulnerable than previous cohorts for all the reasons discussed in this chapter. We therefore need to mitigate these risks, by ensuring that every patient is managed in a routine pathway that can identify their expectations (and modify these if necessary), facilitate their understanding of the potential risks of surgery, promote their active engagement in treatment decision-making and provide additional support when needed.

Summary Psychological factors and processes are key at all stages of plastic surgery interventions. The ability to effectively assess the expectations and needs of patients and to incorporate these into an appropriate management plan is widely acknowledged and becomes more important as a new generation of patients with appearance concerns and largely psychosocial expectations emerges. In view of the dearth of evidence regarding the psychological impacts of appearance-altering surgery, there is an imperative for plastic surgeons to commit to the routine collection of pre- and post-procedural data using an agreed framework for data collection. These data will underpin the development of definitive assessment and screening tools and can also facilitate the development and evaluation of effective methods of psychological support and intervention, either as an adjunct or, in a small minority of cases, an alternative to surgery. Behavior change is notoriously difficult. The decision to augment existing patterns of clinical care to include attention to the psychosocial needs of patients requires energy, planning, and commitment. Feedback from surgeons who are undertaking this process suggests this will be a worthwhile endeavor for clinicians as well as their patients.23,39,43

References

References 1. Sarwer D, Constantian M. Psychological aspects of cosmetic surgical and minimally invasive procedures. In: Gurtner G, Neligan P, eds. Plastic Surgery. Volume 1. 4th ed. London: Elsevier; 2017:24. 2. Holland G, Tiggemann M. A systematic review of the impact of the use of social networking sites on body image and disordered eating outcomes. Body Image. 2016;7:100–110. 3. Fardouly J, Pinkus RT, Vartanian LR. The impact of appearance comparisons made through social media, traditional media, and in person in women’s everyday lives. Body Image. 2017;20:31–39. 4. Rumsey N, Diedrichs P. Part of the problem or part of the solution? Plastic surgeons and body image dissatisfaction. AJOPS. 2018;1(2):74–84. 5. Sharpe H, Patalay P, Choo TH, et al. Bidirectional associations between body dissatisfaction and depressive symptoms from adolescence through early adulthood. Dev Psychopathol. 2018;30(4):1447–1458. 6. duRoscoat E, Legleye S, Guignard R, Husky M, Beck F. Risk factors for suicide attempts and hospitalizations in a sample of 39,542 French adolescents. J Affect Disord. 2016;190:517–521. 7. Bornioli A, Lewis-Smith H, Smith A, Slater A, Bray I. Adolescent body dissatisfaction and disordered eating: predictors of later risky health behaviours. Soc Sci Med. 2019;238:112458. 8. Halliwell E, Diedrichs P. Orbach. Literature review: examining the links between body image, aspirations and workplace confidence. Bristol, UK: University of the West of England; 2014. Retrieved from. http:// eprints.uwe.ac.uk.ezproxy.uwe.ac.uk/24438/GoogleScholar. 9. Griffiths S, Murray S, Bentley C, Gratwick-Sarll K, Harrison C, Mond J. Sex differences in quality of life impairment associated with body dissatisfaction in adolescents. J Adolesc Health. 2017;61(1):77–82. 10. VonSoest T, Kvalem I, Skolleborg K, Roald H. Psychosocial changes after cosmetic surgery: a 5 year follow-up study. Plast Reconstr Surg. 2011;128:765–772. 11. de Vries DA, Peter J, Nikken P, de Graaf H. The effect of social network site use on appearance investment and desire for cosmetic surgery among adolescent boys and girls. Sex Roles. 2014;71(9–10):283–295. 12. Walker CE, Krumhuber EG, Dayan S, Furnham A. Effects of social media use on desire for cosmetic surgery among young women. Curr Psychol. 2019:1–10. 13. Margraf J, Lavallee K, Meyer A. Psychological health and aims of aesthetic surgery seekers. Clin Psychol Sci. 2015;3(6):877–891. 14. Sarwer DB. Body image, cosmetic surgery, and minimally invasive treatments. Body Image. 2019;31:302–308. 15. Guest EF, Paraskeva N, Griffiths C, et al. The nature and importance of women’s goals for immediate and delayed breast reconstruction. J Plast Reconstr Aesthet Surg. 2021;74(9):2169–2175. 16. Clarke A, Thompson A, Jenkinson E, Rumsey N, Newall R, eds. CBT for Appearance Anxiety: Psychosocial Interventions for Anxiety due to Visible Differences. London: Wiley–Blackwell; 2014. 17. Rumsey N, Harcourt D. Visible difference amongst children and adolescents: issues and interventions. Dev Neurorehabil. 2007;10(2):113–123. 18. Sharratt N, Jenkinson E, Moss T, Clarke A, Rumsey N. Understandings and experiences of visible difference and romantic relationships: a qualitative exploration. Body Image. 2018;27:32–42. 19. Rumsey N, Stock N. Living with a cleft: psychological challenges, support and intervention. In: Berkowitz S, ed. Cleft Lip and Palate: Diagnosis and Management. 3rd ed. New York: Springer Verlag; 2013. ch. 45. 20. Brunton G, Paraskeva N, Caird J, et al. Psychosocial predictors, assessment and outcomes of cosmetic procedures: a systematic rapid evidence assessment. Aesthet Plast Surg. 2014;38:1030–1040. 21. Veale DB, Neziroglu F. Body Dysmorphic Disorder: A Treatment Manual. Wiley–Blackwell; 2010.





















































































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22. National Institute for Health and Care Excellence. Obsessive– compulsive disorder and body dysmorphic disorder: treatment. Clinical guideline [CG31]. https://www.nice.org.uk/guidance/ cg31. 23. Tollow P, Paraskeva N, Clarke A, et al. “They were aware of who I was as a person”: Patients’ and health professionals’ experiences of using the PEGASUS intervention to facilitate decision-making around breast reconstruction. Eur J Cancer Care. 2021 https://doi. org/10.1111/ecc.13464. 24. Rumsey N, Clarke N. The PATs Companion Module. 2020. Available from https://triskelion.learnworlds.com/. For access contact [email protected]. 25. Crerand C, MacGee L, Sarwer D. Cosmetic procedures. In: Rumsey N, Harcourt D, eds. The Oxford Handbook of the Psychology of Appearance. Oxford: Oxford University Press; 2012:330–352. 26. Margraf J, Meyer A, Lavallee K. Well-being from under the knife. Clin Psychol Sci. 2013;1(3):239–252. 27. Bessell A, Brough V, Clarke A, Harcourt D, Moss T, Rumsey N. Evaluation of FACE IT, a computerised psychosocial intervention for disfigurement related distress. Psychol Health Med. 2012;17(5):565–577. 28. Royal College of Surgeons: Professional Standards for Cosmetic Practice. https://www.rcseng.ac.uk/standards-and-research/ standards-and-guidance/service-standards/cosmetic-surgery/ professional-standards-for-cosmetic-surgery/. 29. Medical Board of Australia. Guidelines for registered medical practitioners who perform cosmetic medical and surgical procedures. 2016. https://plasticsurgery.org.au/wp-content/ uploads/2020/08/2.5-AHPRA-MBA-Guidelines-for-RegisteredMedical-Practitioners-Who-Perform-Cosmetic-Medical-andSurgical-Procedures-2016.pdf. 30. General Medical Council. Guidance for doctors who offer cosmetic interventions. 2016. https://www.gmc-uk.org/ethical-guidance/ ethical-guidance-for-doctors/cosmetic-interventions. 31. Nuffield Council on Bioethics. Cosmetic procedures: ethical issues. 2017. www.nuffieldbioethics.org/project/cosmetic-procedures. 32. Sarwer D, Crerand C. Body image and cosmetic medical treatments. Body Image. 2004;1:99–111. 33. Bowyer L, Krebs G, Mataix-Cols D, Veale D, Monzani B. A critical review of cosmetic treatment outcomes in body dysmorphic disorder. Body Image. 2016;19:1–8. 34. Chen K, Conjuista S, Nash IS, Coppa G. Factors influencing patient satisfaction in plastic surgery: a nationwide analysis. Plast Reconstr Surg. 2018;142(3):820–825. 35. Ericksen W, Billick S. Psychiatric issues in cosmetic plastic surgery. Psychiatr Q. 2012;83(3):343–352. 36. Veale D, Ellison N, Werner T. Development of a cosmetic procedure screening questionnaire (COPS) for Body Dysmorphic Disorder. J Plast Reconstr Aesthet Surg. 2011;65:530–532. 37. Kinnunen T. “A second youth”: Pursuing happiness and respectability through cosmetic surgery in Finland. Sociol Health Illness. 2010;32:258–271. 38. The Patient Assessment Tools (PATs). Available from https:// triskelion.learnworlds.com/. For access contact martin.j.persson@ hkr.se. 39. Paraskeva D, Tollow P, White P, Clarke A, Powell J, Harcourt D. A multi-centred sequential trial comparing PEGASUS, an intervention to promote shared decision making about breast reconstruction, with usual care. J Plast Reconstr Aesthet Surg. 2022;75(4): 1342–1351. 40. The Dove Self-Esteem Project. https://www.dove.com/uk/ dove-self-esteem-project.html. 41. Be Real Campaign. https://www.berealcampaign.co.uk. 42. Veale D, Willson R, Clarke A. Overcoming Body Image Problems, including Body Dysmorphic Disorder. Hachette UK; 2013. 43. Paraskeva N, Clarke A, Rumsey N. The routine screening of cosmetic surgery patients. Aesthetics. 2014;1(12):28–32.























































































4

The role of ethics in plastic surgery and medico-legal issues in plastic surgery Michele A. Manahan and B. Aviva Preminger

Better is possible. It does not take genius. It takes diligence. It takes moral clarity. It takes ingenuity. And above all, it takes a willingness to try. Atul Gawande

Introduction Consideration of topics pertaining to ethics in the field of plastic and reconstructive surgery is frequently provocative. With ongoing clinical, technological, and interpersonal evolution, and the emphasis on innovation that drives this specialty, one may assume that new decision-making quagmires will constantly arise. This situation is only compounded by the novel ethical issues created by a specialty that is, for better or worse, often driven by advertising and commercialism. The connection of aesthetic plastic surgery to advertising has become even more complex in the age of the internet and social media. Somewhat ironically, despite the overwhelming ethical questions to be considered, the attention given to these issues within the plastic surgery literature is somewhat lacking. Presented here are some current areas of interest with an emphasis on the varied perspectives that may be brought to bear upon them. As authors, we will refrain from defining right and wrong, as subjectivity and differences of opinion are the sine qua non of ethical debates.

History of ethics and plastic surgery The early ethical questions and concerns pertaining to the field of plastic surgery were largely religious rather than truly ethical in nature. Plastic surgeons were considered quacks rather than healers, and religious authorities voiced vociferous objections to cosmetic and even reconstructive procedures. Plastic surgery was thought to be used to hide the advanced

stigmata of syphilis, and nasal mutilation that was sometimes inflicted as punishment. Across the board, religious authorities – Christian, Catholic, Jewish, and Muslim – expressed the concerns that plastic surgery involved interfering with divine creation. Church authorities excommunicated Gaspare Tagliacozzi (widely considered one of the fathers of our specialty) after his death and exhumed his body from the church cemetery, moving it to unconsecrated ground. Plastic surgery was further considered by Jewish authorities to fall under a prohibition of self-mutilation and was thought to be inherently feminine and therefore potentially prohibited to men. The field only gained true legitimacy during the two World Wars with the need for reconstructive procedures.1 However, as pointed out by the historian Elizabeth Haiken, the history of the specialty is forever colored by standards that could be thought to be frankly racist and anti-semitic.2 Aesthetic plastic surgery, to this day, often serves as a relief from the social anxieties created from living in a world with unrealistic beauty standards. Thus, from the very outset, that aspect of our specialty has presented unique ethical dilemmas that seem only to burgeon.

Core ethical principles and plastic surgery The field of medical ethics in the US most commonly adheres to the moral theory of principlism, first described by Beauchamp and Childress in 1979. Within this framework, reasoning about ethical issues is based upon four moral principles: respect for autonomy, beneficence, nonmaleficence, and justice.3 Respect for autonomy describes a patient’s right to self-determination and self-governance and to accept or refuse care. Beneficence is the principle that one ought to do and promote good for the patient while preventing harm. Nonmaleficence dictates that a physician must not intentionally inflict harm on a patient. Distributive justice dictates that patients be treated similarly

Conflict of interest

and fairly, with the result that benefits, risks, and costs are equally distributed among them.3 Plastic surgeons must carefully consider these principles when caring for patients. These four core principles are not given equal attention in the plastic surgery literature. Respect for autonomy encompasses discussions of informed consent for procedures, photography, and marketing and has been shown to be the most fully explored ethics core principle within plastic surgery publications.4 The next most commonly publicized theme in plastic surgery is beneficence.4 Conversations of risks and benefits fall within the purview of both respect for autonomy and beneficence. Often related to beneficence is nonmaleficence, which is the third most common principle discussed.4 Distributive justice in plastic surgery is considered least often4 but still is an important ethical principle in the practice of medicine, particularly as diversity, equity, and inclusion initiatives proliferate.

Patient communication, education, informed consent, and disclosure Surgical informed consent is a cornerstone of the patient–physician relationship and an important expression of respect for patient autonomy. However, the constant struggle by plastic surgeons to bridge the gap between acceptable surgical outcomes and patient expectations complicates educational efforts. The elective nature of many procedures, the potential vulnerability of patients, and subjectivity of beauty standards, particularly in aesthetic surgery, place plastic surgeons at particular risk. These issues have been compounded by questions of device and procedure safety. These device safety issues and the discussions surrounding them are often flavored with questions of the surgeon’s obligation to respect the aforementioned principles of beneficence and nonmaleficence. Patient communication, education, and the process of informed consent have been highlighted recently, due to evolving breast implant regulations. Specifically, the discussion relates to the gap between perceptions and physician disclosure of information. While informed consent documents are routinely provided, the process leading to completion of these forms may vary. Many styles of communication exist. It is likely that no one “right” answer will rise to the fore. However, external regulation is increasing as regulatory agencies have concluded that plastic surgeons and device companies cannot be relied upon to police themselves. The FDA now requires that a checklist be completed by the patient and the operating surgeon prior to prosthetic breast implantation. Institutions have developed policies to address patient understanding of the composition and responsibilities of their treatment teams. When examining the language used in public sessions at the FDA related to breast implants, patients expressed feeling blind-sided, duped, and deceived. Doctors were accused of failing to stay up to date, wanting to hide the truth, withholding information, not taking the time, and failing women. When reviewing comments on the FDA website related to this issue, nearly half expressed concern over inadequacy of informed consent, nearly one-third denigrated the content and language of existing forms and documents, and about one-quarter disparaged physician-provided patient education.

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Recommendations for best practices pertaining to preoperative education will continue to evolve, but basics include a full discussion of the current state of clinical understanding. One might also incorporate education as to the evolving nature of medical knowledge and the likelihood that future understanding will be greater and may contradict current thinking. Standard risks, benefits, alternatives, and timing to proposed interventions remain a mainstay in the informed consent process. Often the manner of the discussion impacts understanding as well. Validation of patients’ own health concerns can strengthen patient–clinician relationships.5 This intentional effort to build trust could also encourage patients’ sense of agency to seek care about their future concerns and increase patient ownership of and responsibility for their health.5 Presenting patient-reported outcomes may assist patients, but the variability of patient opinions may make decision-making more difficult.5 Patient education can also build trust by demonstrating physician concern, knowledge, and interest in patients’ concerns.5

Conflict of interest The struggle for true informed consent is often tied to the questions regarding conflict of interest (COI) and the surgeon’s ability and willingness to fully disclose risks, benefits, and alternatives. Decision-making in plastic surgery may be subject to conflict of interest related to a variety of competing interests such as facility ownership, profit, device company ownership, and research productivity.6 In a field such as plastic surgery where innovation and creativity are the defining traits, relationships with industry, profit centers, and research efforts will be pervasive. Estimates are that well over half of plastic surgeons have these relationships.7 Review of historical literature reveals routine absence of disclosure of potential conflicts.8 Despite much recent attention, authors have noted that a majority of recent, breast implant-based studies have undisclosed COIs.9 Financial COIs have come under considerable scrutiny, particularly regarding potential impacts on patient care. A recent example is the variable beliefs and practices employed during the COVID-19 pandemic related to definitions of “elective” surgery that were often curtailed.10 Furthermore, there is evidence that investigators with a financial COI were significantly more likely to publish positive conclusions compared with their nonfunded couterparts.11 In response to these concerns, the field has demonstrated a rapid alteration in practice over the last several years. Much current discussion and many current and recently developed policies attempt to address the ethics of conflict of interest. Solutions look to disclosure and management of COIs, rather than elimination of these. Disclosure of conflicts before and during presentations and in journal publications embodies these efforts.10 Likewise, routine prompting for disclosure of COIs during the business of plastic surgery groups allows group leaders to implement conflict management strategies such as complete recusal, removal from discussion, and abstention from voting. Often the management of conflicts in professional organizations varies based on position in the leadership hierarchy to ensure that top leaders may be viewed by membership as more purely devoted to the group. More difficult to ascertain may be the influence of conflict of interest on individuals who have

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CHAPTER 4 • The role of ethics in plastic surgery and medico-legal issues in plastic surgery  

become “key opinion leaders” with industry sponsorship.7 Further efforts will likely continue to emphasize transparency and active management.

Concurrent and overlapping surgery Pursuant to media attention, surgical practices have been scrutinized regarding attribution of responsibilities within treatment teams. A practice known as concurrent surgery, in which critical portions of more than one procedure would occur simultaneously under the guidance of a single senior surgeon, has been curtailed with very limited emergency exceptions. A more nuanced situation pertains to overlapping surgery in which non-critical portions of more than one procedure occur at the same time. The US Senate Finance Committee issued a report several years ago, highlighting the potential for increasing government and other external agency regulation of the practice of medicine. This, in combination with popular media and medical literature, has highlighted the ethical conundrums associated with these practices. One issue relates to informed consent as previously discussed in this chapter. Some will assert that these practices are acceptable as long as the patient understands who comprises their treatment team and the responsibilities of each. Variations in practice exist with regard to the extent of disclosure felt to be sufficient for patient education regarding their care experience. Another issue relates to erosion of patient trust in the physician–patient relationship when surgeons seem overcommitted to more than one patient. Questions arise pertaining to the extent of physicians’ obligations to their patients.12 Authors have raised questions about whether it is “right or safe”.12 Some consider this a profit-driven practice at the expense of patient safety.11 Insurance payments may be impacted by these decisions.13 One might ask if anybody really wants a surgeon to be gone for any part of a procedure. Yet other problems include disagreement over definitions of “critical portions,” uncertainty over who should be empowered to create definitions, prompt availability for transitions in care, creating feasible backup systems to protect against unforeseen availability challenges, and ensuring compliance. Over-reliance upon backup systems may further promulgate patient concern related to absence of a physician–patient relationship with a substitute. Defenders of physician extender use point to quality of outcomes and the benefits of expanding access to surgeons.14,15 Others suggest benefits regarding trainee education and operating room resource use efficiency. However, data in these realms may lack relevancy if the tide of public sentiment rises in anger, distrust, and dismay. Many ethical considerations have yet to be solved related to boundaries of safe practice, who should set them, unpredictable timing of crucial changes like intra-operative consults, and the consideration given to individual skills.15

Medical errors Questions of whether and how to disclose information arise in the setting of medical errors. What is the surgeon’s ethical obligation to disclose, and what are the potential legal

ramifications? Patient awareness of medical imperfections has increased over time, particularly following the Institute of Medicine’s report To Err Is Human: Building a Safer Health System in 2000.16 The sociologist Charles Bosk studied ways to reduce errors in medicine. He concluded that some level of medical error was inevitable and maintaining a humane environment for patients and providers alike was essential.17 While physicians persist with concern that apologies may prompt litigation, increasing adoption of policies requiring disclosure, apology, and offer of compensation attempt to increase transparency in medical care which may benefit both quality improvement and medical professional well-being.18 Authors frequently reference biomedical ethics principles related to patient autonomy, beneficence, nonmaleficence, and justice, all of which impact difficult discussions related to outcomes.3,18 Efforts to offload the blame to promote medical error reporting with the goal of education and improvement in quality and safety include the Patient Safety and Quality Improvement Act of 2005.18,19 However, the ambiguity of liability for the event can lead to shifting of responsibility for the disclosure.18 Reliance upon the surgeon’s honesty, compassion, and fidelity can ease these encounters.18

Expert witness testimony Malpractice litigation often strikes fear into the hearts of physicians, though doctors recognize that this can serve as a mechanism of patient protection, particularly given that the US system, in contradistinction to many other countries, tries these cases before a jury of laypersons.20 To protect all parties involved, both plaintiff and defendant, due process requires fair evaluation of the facts based on sound understanding and unbiased interpretation of science.21 Therefore, one might argue that physicians possess a moral, social, or at least professional, obligation to serve as “expert witnesses” in these situations to support both our peers and to advocate for our patients. Ronquillo however, when considering the role of physicians as “expert witnesses” in malpractice litigation, points out that several potential pitfalls exist.21 The definition of “expert” stands as one such hazard. Many physicians would agree that becoming a professional expert witness at the expense of clinical practice, as sometimes happens, may corrupt the intent of having a contemporary colleague who understands standard practices and the spectrum of acceptable deviations from such. Many specialty societies’ codes of ethics address these issues.20 However, high fees paid for these services can be appealing and call into question the impetus spurring individuals to participate.20 More debate occurs when considering how closely an expert’s specialization must match the case under review. Should a plastic surgeon who performs solely aesthetic surgery opine on microsurgical breast reconstruction? Should a plastic surgeon who performs hand surgery only when on call be considered an expert for elective hand surgery? Does the burden of determination rest with the physician volunteering to become an expert witness, or should consensus criteria be developed to address volume or recency standards related to the expert’s own performance of similar cases? How could these criteria ever feasibly be developed or implemented? In 1993, the Supreme Court set the standard for expert testimony admissibility in the seminal case Daubert v. Merrell

Social media and advertising

Dow Pharmaceuticals, Inc. Under the Daubert standard, the court provided guidelines for determining whether an expert’s methodology is valid. The Daubert guidelines consist of five factors of consideration: (1) Whether the theory or technique in question can be and has been tested; (2) Whether it has been subjected to peer review and publication; (3) Its known or potential error rate; (4) The existence and maintenance of standards controlling its operation; (5) Whether it has attracted widespread acceptance within a relevant scientific community. These criteria intend to prevent unreliable or otherwise “junk science” from being heard as evidence in an expert’s substantive testimony. The burden is on the proponent of the testimony to establish its admissibility by a preponderance of proof. Under Federal Rule 702, persons that are qualified as experts based on knowledge, skill, experience, training, or education are permitted to offer expert opinion testimony if the following conditions have been met: (1) The expert’s scientific, technical, or other specialized knowledge will help the trier of fact to understand the evidence or to determine a fact in issue; (2) The testimony is based on sufficient facts or data; (3) The testimony is the product of reliable principles and methods; and (4) The expert has reliably applied the principles and methods to the facts of the case.22 Another hazard relates to physicians’ selection of cases with which to become involved. Some might argue that both plaintiffs and defendants should have access to the same pool of expert witnesses to ensure equity and the opportunity for careful consideration of the evidence without bias. Should expectations exist that expert witnesses be willing to testify on behalf of both parties, according to the evidence? When considering embarking on an expert witness journey, prudence requires cautious consideration of the extent to which the witness will be “put on trial”. Past journal articles, published opinions, and quotations may be used in attempts to discredit the witness.20 If testifying against peers, one must recognize and prepare for potential ill will, retaliatory complaints, and damaged interpersonal relationships, a by-product of the stress and emotions when one’s skills and outcomes are questioned. Plaintiff’s attorneys maintain that malpractice litigation is routine business, but physicians often suffer self-doubt regarding integrity and values when their competence and decision-making is faulted.20 Regardless, a potential expert witness must evaluate the results with respect to inherent risk, unexpected complications, or incompetence by using an understanding of standard of care and careful consideration of possible extenuating circumstances.20 Understanding medical malpractice litigation benefits physicians regardless of one’s plans for participation in the expert witness business. Liability arises in a variety of areas, including negligence (the most common), insufficiently informed consent, purposeful misconduct, breach of contract, defamation, breach of confidentiality, and failure to prevent foreseeable injury.21 The case hinges on violation of a standard of care causally related to a distinct injury within a physician–patient relationship and must be demonstrated with a preponderance of the evidence (or 51%).20 Poor outcomes alone do not define malpractice.21 Determinations of standard of care, often defined as reasonable or ordinary care provided by local peers with similar practices, are aided by published guidelines, literature, and professional society outputs.21

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Social media and advertising Social media has become a touchstone for all of the above ethical issues. When one communicates, one runs the risk of misspeaking and misunderstanding. With the explosion of social media, these opportunities have exponentially multiplied. The potentially enduring nature of these communications magnifies the risk. Medical professionals may be further susceptible to risk as practitioners strive to surpass competitors in meeting patients’ interest in these channels for information dissemination and communication. However, social media, generally considered to be Web-based and mobile technology allowing for interactive communication, possesses little likelihood of disappearing.23 Therefore, the ethical concerns must be addressed rather than ignored. Those who step away from social media use may risk obsolescence. Plastic surgeons may look to social media as a practice building tool to amplify their spheres of influence.24 Through this, patients may gain easier access both to educational information as well as to opportunities to communicate with their surgeons’ practices.23 In this fashion, social media usage becomes both a patient service and a professional service and potential tool for informed consent. However, some might argue that there is less ability to assist patients in understanding the information when it is disseminated and less ability to rely upon the way the information is received and interpreted by the intended audiences.23 One may also argue that social media may expand access to care within certain populations of patients who may have previously experienced barriers. Without question, practice building benefits surgeons through profits, particularly given that a large majority of posts have been judged to be purely promotional rather than educational.23 While studies have shown that the majority of patients believe social media sources to be unbiased and reliable,23 most physicians can probably agree that social media resources currently represent a wide spectrum of quality and impartiality. Expressed opinions may depart from scientific soundness, and paid sponsorship may call into question conflicts of interest.23 The wide variety of tools encompassed in the umbrella term “social media” further adds to the confusion: consider before and after photographs, testimonials, ratings, treatment videos, physician videos, and blogs. Additionally, the volume of posts weighs much more heavily to those by patients than those by medical professionals, and those by medical professionals related to plastic surgery are often not by board certified or board eligible plastic surgeons.25 Patient confidentiality may be very difficult to preserve when using images on social media.26 Currency of patient consent for dissemination of images may be difficult to maintain. Lines blur between education and entertainment.27,28 Provocative and titillating content may flirt with pornography; however this has been historically difficult to judge. The widely quoted, “You know it when you see it” pornography criterion does not inspire confidence in reliable application of widely accepted standard criteria across time and space. The rapid expansion of social media has outpaced professional societies’ ability to revise codified ethical and professional guidelines.26,29 Most would agree that social media platforms defy easy regulation.23 Increasing focus centers on training related to “appropriate” social media use.30

CHAPTER 4 • The role of ethics in plastic surgery and medico-legal issues in plastic surgery

36

 

Conclusions Clearly, our specialty presents unique ethical dilemmas and concerns. Though the challenges presented may seem daunting, like anything else, solutions begin with a first step.

Access the reference list online at



Elsevier eBooks+

Renewed focus on these issues begins the process. While societies and regulatory bodies have increased their involvement, we must ultimately rely upon the goodwill of the members of our specialty to uphold the oaths that we all took our first year of medical school to “First, do no harm”.

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References 1. Preminger BA, Fins JJ. Plastic surgery, aesthetics, and medical professionalism: beauty and the eye of the beholder. Ann Plast Surg. 2009;62(4):340–343. 2. Haiken E. Venus Envy: A History of Cosmetic Surgery. Baltimore: Johns Hopkins University Press; 1997. 3. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 5th ed. New York, NY: Oxford University Press; 2001. 4. Chung KC, Pushman AG, Bellfi LT. A systematic review of ethical principles in the plastic surgery literature. Plast Reconstr Surg. 2009;124(5):1711–1718. 5. Manahan MA. What do clinicians and organizations owe patients with recalled implanted devices or materials? AMA J Ethics. 2021;23(9):E678–E684. 6. Zbar RIS, Taylor LD, Canady JW. Ethical issues for the plastic surgeon in a tumultuous health care system: Dissecting the anatomy of a decision. Plast Reconstr Surg. 2008;122(4):1245–1252. 7. Gray R, Tanna N, Kasabian AK. Conflict of interest at plastic surgery conferences: Is it significant? Plast Reconstr Surg. 2019;144(2):308e–313e. 8. Voineskos SH, Coroneos CJ, Ziolkowski NI, et al. A systematic review of surgical randomized controlled trials: Part 2. Funding source, conflict of interest, and sample size in plastic surgery. Plast Reconstr Surg. 2016;137(2):453e–461e. 9. Tian T, Sekigami Y, Char S, Bloomenthal M, Aalberg J, Chen L, Chatterjee A. Assessment of conflicts of interest in studies of breast implants and breast implant mesh. Aesthet Surg J. 2021;41(11):1269–1275. 10. Mercer NSG. Invited EURAPS JPRAS editorial conflict of interest in plastic surgery. J Plast Reconstr Aesthet Surg. 2021;74(1):1–3. 11. Lopez J, Lopez S, Means J, et al. Financial conflicts of interest: An association between funding and findings in plastic surgery. Plast Reconstr Surg. 2015;136(5):690e–697e. 12. Abelson J, Slatzman J, Allen S. Clash in the name of care. Boston Globe. October 25, 2015. https://apps.bostonglobe.com/spotlight/ clash-in-the-name-of-care/story/. 13. Hamill SD. Feds in rare battle with UPMC, star doctor. Pittsburgh Post-Gazette. October 9, 2021. https://www.post-gazette.com/ news/crime-courts/2021/10/10/Feds-lawsuit-against-UPMC-starsurgeon-stuns-experts/stories/202109110038. 14. Beasley GM, Pappas TN, Kirk AD. Procedure delegation by attending surgeons performing concurrent operations in academic medical centers: balancing safety and efficiency. Ann Surg. 2015;261(6):1044–1045.























































15. Mello MM, Livingston EH. Managing the risks of concurrent surgeries. JAMA. 2016;315(15):1563–1564. 16. Kohn LT, Corrigan JM, Donaldson MS, eds. To Err Is Human: Building a Safer Health System. Committee on Quality of Health Care in America, Institute of Medicine. Washington DC: National Academy Press; 2000. 17. Bosk CS. Forgive and Remember: Managing Medical Failure. Chicago, IL: Chicago University Press; 1979. 18. Vercler CJ, Buchman SR, Chung KC. Discussing harm-causing errors with patients: an ethics primer for plastic surgeons. Ann Plast Surg. 2015;74(2):140–144. 19. Rohrich RJ. Patient Safety and Quality Improvement Act of 2005: what you need to know. Plast Reconstr Surg. 2006;117:671–672. 20. Gorney M. The dilemma of the expert witness. Plast Reconstr Surg. 2008;121(5):1845–1846. 21. Ronquillo Y, Robinson KJ, Nouhan PP. Expert witness. 2022 Jun 27. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan– 2022. 22. Daubert v. Merrell Dow Pharmaceuticals. https://en.m.wikipedia.org/ wiki/Daubert_v._Merrell_Dow_Pharmaceuticals,_Inc. 23. Atiyeh BS, Chahine F, Ghonam FA. Social media and plastic surgery practice building: a thin line between efficient marketing, professionalism, and ethics. Aesthet Plast Surg. 2021;45(3):1310–1321. 24. Gould DJ, Nazarian S. Social media return on investment: how much is it worth to my practice? Aesthet Surg J. 2018;38(5):565–574. 25. Branford OA, Kamali P, Rohrich RJ, et al. #PlasticSurgery. Plast Reconstr Surg. 2016;138(6):1354–1365. 26. Hetzler PT, Makar KG, Baker SB, Fan KL, Vercler CJ. Time for a consensus? Considerations of ethical social media use by pediatric plastic surgeons. Plast Reconstr Surg. 2020;146(6):841e–842e. 27. Gupta N, Dorfman R, Saadat S, Roostaeian J. The plastic surgery social media influencer: ethical considerations and a literature review. Aesthet Surg J. 2020;40(6):691–699. 28. Bennett KG, Vercler CJ. When is posting about patients on social media unethical “medutainment”? AMA J Ethics. 2018;20(4):328–335. 29. Hetzler PT III, Wang J, Fan KL, Song DH. Conceptualizing professionalism in social media: a framework for evaluation. Plast Reconstr Surg. 143(6):1318e–1319e. 30. Hamilton KL, Kim R, Savetsky IL, Avashia YJ, Maricevich R, Rohrich RJ. Social media guidelines for young plastic surgeons and plastic surgery training programs. Plast Reconstr Surg. 2021;148(2):459–465.































































5 Business principles for plastic surgeons C. Scott Hultman

SYNOPSIS

ƒ This chapter provides a broad overview of the essential principles that characterize what a business does and how a business does its work. ƒ The ability to apply business concepts is of paramount importance if plastic surgeons are to become and remain leaders in healthcare. ƒ Plastic surgeons should understand and use strategy, accounting, finance, economics, marketing, and operations to help guide decisions about their practice. ƒ Innovation, entrepreneurship, and human resource management are three areas where plastic surgeons can add value to their practice and distinguish themselves from their competition.

Introduction Make everything as simple as possible, but not simpler. Albert Einstein

Not only is healthcare business, it is big business. The healthcare–industrial complex incorporates multiple sectors to deliver health and depends on an expanding group of interdisciplinary teams, services, and institutions to achieve this value proposition. Business sectors involved in the delivery of healthcare include not only professionals such as doctors, nurses, and administrators, but also hospitals, nursing homes, and home healthcare groups; drug manufacturers and developers; manufacturers of medical equipment and instruments; diagnostic laboratories; biomedical researchers; and biotechnological entrepreneurs. Recent estimates from 2020 place healthcare spending at 19.7% of the United States’ gross domestic product, an increase from 17.7% in 2017.1 For every dollar spent in the US on healthcare, 31% goes to hospital services, 21% to physicians, 10% to pharmaceuticals, 6% to nursing homes, 4% to dental services,

and 28% to other categories, such as diagnostics laboratories, medical equipment, and medical devices. Of note, 7% of total spending is assigned to administrative overhead costs. If healthcare provided by physicians is not business, then physicians are certainly surrounded by business; they must navigate a complex environment that is full of paradoxes, inefficiency, and bureaucracy. Unfortunately, physicians receive no formal education in business but must learn on the job, through mistakes and successes, often one patient and one business problem at a time. Although many critics argue that healthcare has been tainted by the intersection with big business, which places the bottom line at the top and undermines the physician–provider relationship, many other thought leaders contend that healthcare needs business, to help solve problems of inconsistent quality, rising costs, limited access to care, and disparities in outcomes. Indeed, business thinking and business processes are desperately needed to transform our current system, so that healthcare can be available to all people, at fair-market prices, to improve the health of our community. Why should plastic surgeons care about the business of healthcare? From an individual perspective, every plastic surgeon must either run a business or be part of a business, if the surgeon’s practice is to thrive, grow, change, and continue to provide high-quality care. Whether one works for oneself, for a hospital or health maintenance organization (HMO), for an academic institution, for a non-profit or non-governmental organization (NGO), for a free community clinic, or for an overseas volunteer mission trip, plastic surgeons are involved with organizations that utilize business principles and interface with business entities. From a broader perspective, however, plastic surgeons are uniquely situated to serve as leaders of healthcare systems and healthcare businesses. Given our extensive training, our collaboration with multiple specialties, our diverse portfolio of services that we provide, our problem-solving skills, and our entrepreneurial spirit, plastic surgeons have the leadership skills, influence, and positioning within the healthcare

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CHAPTER 5 • Business principles for plastic surgeons  

system to effect real change. Just as the Greek word plastikos, which means to shape or to mold, was chosen to describe what we do as surgeons, this word could also impart upon us the ability to shape or mold our systems of healthcare delivery. The knowledge and application of business principles is of paramount importance if plastic surgeons are to become and remain leaders in healthcare. The purpose of this chapter is to provide a broad overview of the essential principles that characterize what a business does and how a business does its work. Each section offers a topical overview, and readers are strongly encouraged to explore in more depth the following components of this chapter: 1. Strategy 2. Accounting 3. Finance 4. Economics 5. Marketing 6. Operations 7. Innovation 8. Entrepreneurship 9. Sustainable enterprise 10. Human resource management 11. Legal and regulatory considerations 12. Negotiation 13. Ethics 14. Leadership  



 



 



 



 



 



 



 



 























BOX 5.1 Idea watch: Strategy  

Reference: Wade M, Joshi A, Teracino EA. Six principles to build your company’s strategic agility. Harvard Business Review, SeptemberOctober, 2021. https://hbr.org/.2 Over the past few years, business leaders have been reminded of the interconnectedness and unpredictability of commerce, economies, and societies. Humanitarian disasters such as the coronavirus pandemic, the war in Ukraine, and climate change have impacted geopolitics, trade, energy, supply chains, and markets in ways not anticipated. Although many companies have succumbed to these crises, some businesses have survived and even thrived in these conditions. Agility and resilience may not only protect companies from black swan events, but may offer a strategic advantage in such times of volatility. The key to navigating these challenges and adapting to rapidly changing environments may be due to three qualities: • •

Staying nimble enough to avoid the worst impacts of a crisis Remaining robust enough to absorb direct hits from an overwhelming challenge • Being resilient enough to accelerate forward, while competitors fall backward To achieve these qualities, the authors recommend the following six principles:





1. 2. 3. 4. 5. 6.











The end of each section will spotlight an “Idea Watch”, as a forum to present novel, emerging, and occasionally controversial topics related to business and healthcare. Featured topics will be drawn from cutting-edge articles published in the Harvard Business Review, with the goal of promoting further reflection, analysis, and inquiry by the reader. Plastic surgeons, at the very least, must learn the language of business, to have meaningful interactions with hospital administrators, insurance carriers, salespeople, and marketing firms. Hopefully, though, plastic surgeons can utilize the principles of business to improve the care that we provide, and in the end, to transform the industry in which we practice our science, and our art.

Strategy Long-range planning does not deal with future decisions. It deals with the future of present decisions … Significant competitive advantage lies with those organizations and individuals who anticipate well in turbulent times. Peter F. Drucker

Competitive advantage begins and ends with strategy (Box 5.1). Nearly all of the components of business are affected by strategy, from finance to operations, from marketing to managing human capital, and therefore a review of business principles should commence with an understanding of how strategy guides decision-making within an organization. Strategy can be characterized as the art of inducing your competitor to do something else, while you focus on doing what you do well. In more academic terms, strategy is the process of forming, implementing, and evaluating decisions that



Prioritize speed over perfection Prioritize flexibility over planning Prioritize diversification and “efficient slack” over optimization Prioritize empowerment over hierarchy Prioritize learning over blaming Prioritize resource modularity and mobility over resource “lock-in”

These principles do not apply to all businesses in all markets but may provide a roadmap for corporate survival in turbulent times. Sometimes, perfection is the enemy of good.

enable an organization to achieve its long-term goals. Strategy is dictated by (and, in turn, can influence) the organization’s mission, vision, and values, which serve as a foundation to guide policy, projects, and programs. Furthermore, strategy is about competing on differentiation – creating a value proposition – in which a firm provides the consumer with a product or service of greater quality or at less cost than its competitor, deliberately choosing a different set of activities to deliver a unique mix of outputs. Before examining specific strategic principles, one should become familiar with how the business environment affects the flow of inputs to outputs, along the supply chain. Because value is added at various points along this process, the entire axis, from supplier to consumer, is called the value chain. Primary activities of the company, which include inbound logistics, operations, outbound logistics, marketing and sales, and ultimately customer service, each create value that manifests in the final product; these processes are guided by strategic priorities and are coordinated by support activities that include technological development, human resource management, and firm infrastructure. The most established and respected model of the business environment is Michael Porter’s 5-Forces model of competition (Fig. 5.1).3 Each industry contains: (1) previously established competitors; (2) the potential for new entrants; (3) the threat of substitute rivals, who often compete on

Accounting

demand. Previous “settlers” will “migrate” to this new market space and become “pioneers”. Apple has done this over and over with the personal computer market, introducing new devices that expand the functionality of their operating system and hardware, evidenced by the transition from desktop to laptop to iPhone to iPad. True value innovation comes when a company jumps out of its industry and creates an entirely new market, often in a different industry.7,8 This foray into uncharted territory, which is referred to as “white space”, typically occurs when a company develops a disruptive technology that permits the use of core competencies to produce a radically different product or service. Apple was successful in capturing the dominant position in the digital music market by designing and offering iTunes, despite being a computer company. Inherent to this success was the fact that Apple also changed the business model for purchasing music; consumers could buy singles or albums, listen to samples, and of course, use the website for free. As the music industry shifts again, from purchasing content to subscription services as a major revenue model, Apple is determined to remain the dominant player. The acquisition of the Beats music platform will allow Apple to compete with Pandora and Spotify, but also serve to stream video content for gaming and on-demand viewing of television and film. In summary, strategy involves the following steps: 1. Industry analysis – assess industry profitability today and tomorrow. 2. Positioning – identify sources of competitive advantage. 3. Competitor analysis – study current competitors, future entrants, and substitutes. 4. Assessment of current strategy – predict effectiveness and sustainability. 5. Option generation – search for new customers, new segments, new markets. 6. Development of capabilities – planning now for future opportunities. 7. Refining strategy – assess uniqueness, trade-offs, compatibility with vision and values.

Threat of new entrants HMOs/PPOs, accountable care organizations, out-of-state healthcare systems

Bargaining power of suppliers Insurers, state

Rivalry among existing competitors UNC/Rex, Duke, Wake Med

Bargaining power of consumers Patients

Supply chain Threat of substitute products or services Alternative medicine, medical tourism

Figure 5.1 Strategy: Porter’s 5-Forces model of competition. HMOs, Health maintenance organizations; PPOs, preferred provider organizations.  

price; (4) suppliers, who can have significant bargaining power; and (5) buyers, who create demand for the outputs. Understanding the environment of a specific industry, such as healthcare, can strengthen decision-making and help with strategic planning. For example, how should an academic plastic surgery practice respond to the influx of recently graduated residents into the community? How should the solo private practitioner attract new patients in a fixed market, when a group practice dominates the landscape? How should surgeons challenge scope of practice with non-surgeon physicians and non-physician providers? What is the optimal portfolio of services, specifically the mix of reconstructive surgery, cosmetic procedures, and skin care, to achieve the goals of the organization? Once the dynamics and landscape of the business environment are defined, specific decisions can be made regarding change in operations, marketing, investment in new assets, alliances, or supply chain.4–6 Most mature industries, such as the automotive industry or the personal computer industry, settle into a competitive scenario in which one firm dominates with 60% market share, while a second firm contains 30% of the market share, and the remaining competitors occupy 10%. Because of barriers to entry, new entrants may not be able to successfully compete, unless disruptive technology lowers production costs or the market shifts, due to cultural, social, economic, or political forces. In fact, significant competitive advantage is conferred to small, nimble firms that focus their product line or services and offer a unique selling proposition, to a targeted segment of the market. When executed correctly, this activity, termed “judo strategy”, has the power to undermine dominant businesses and increase market share substantially. A major limitation of competitive strategy is that most efforts deal with gaining a larger portion of a fixed market or attracting new customers via the “rising tide” of a slowly growing market. If companies in search of sustained, profitable growth compete with multiple rivals, then differentiation becomes difficult, price wars may ensue, and the total profit pool shrinks. Instead, companies may pursue a “blue ocean strategy”, in which uncontested but related market space is discovered, rendering rivals obsolete and generating new

39





























Accounting Nowadays, people know the price of everything and the value of nothing. Oscar Wilde

Business management must be based upon a common language that is used to objectively communicate information related to the quantitative metrics of an organization. That language is accounting (Box 5.2). This section will review the tools that accountants use to assess the financial health of a business: income statement, balance sheet, summary of cash flows, and financial ratios.10–12 The nuances of accounting are beyond the scope of this overview, but healthcare providers must have a basic comprehension of these instruments and how they represent the financial standing of their practice, their hospital, and their healthcare system. Furthermore, these instruments are used in budgeting to construct pro forma predictions of future performance.

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BOX 5.2 Idea watch: Accounting  

Reference: Gallo A. Contribution margin: What it is, how to calculate it, and why you need it. Harvard Business Review, SeptemberOctober, 2017. https://hbr.org.9 Although hospitals and healthcare systems typically cite profit margin and operating income as some of the most important indicators of the financial viability of the organization, contribution margin provides more granular information about value created by products or services. Amy Gallo reminds us that contribution margin allows analysts to determine the profitability of a specific product or service, independent of overhead and fixed costs (real estate, debt repayment, administrators’ salaries, marketing), which are often allocated incorrectly, based on faulty assumptions, and subject to manipulation. Contribution margin, defined as revenue less variable costs, permits us to compare different products or service lines within a portfolio of offerings. As long as a product or service has a positive contribution margin, and the system is not at capacity, that product or service brings value to the enterprise, which can be used to pay down operating expenses. When the system is at capacity, then the product or service with the highest contribution margin creates the most value. For surgical procedures, ranging from abdominal wall reconstruction to facial rejuvenation, contribution margin can be significantly affected by the cost of the materials used, as well as direct variable overhead from capital equipment and labor. If procedures have a negative contribution margin, then the institution faces three choices: (1) improve efficiency and decrease costs to obtain a positive contribution margin, (2) eliminate the procedure, or (3) continue the procedure as a mission-critical “loss leader”. Procedures with positive contribution margins can be ranked according to importance and prioritized based on the financial needs of the institution and clinical needs of the patients.

Revenue less

Operating costs

= Grossprofit less less

Fixed overhead Depreciation (a assets) and amortization (leases)

= Operating income (EBIT) less Interest expenses = Pre - tax income less Income taxes

= Net income

Balance sheet The balance sheet is a snapshot of what the company owns and owes, at a single point in time. On one hand, the balance sheet summarizes the cumulative impact of all transactions, but the balance sheet does not provide much useful information on the operational performance of the firm. The net worth of the company, referred to as owner’s equity, is defined as the difference between the assets and the liabilities. Equity = Assets − Liabilities

However, balance sheets usually frame this relationship slightly differently, but again, the following equation must always balance: Assets = Liabilities + Equity or Assets = Debt + Equity

The field of accounting is governed by generally accepted accounting principles, also known as GAAP, which are rules used to prepare, present, and report financial statements for various entities, such as non-profit organizations, publicly-traded companies, and privately-held firms. Although the government does not set these standards, the US Securities and Exchange Commission does require that public firms follow these rules. Managerial accounting, which is used to allocate cost and assign overhead, does not follow GAAP and is dependent upon institutional culture and practice.

Income statement The income statement, also known as the profit/loss statement, describes financial transactions within a defined period of time, which may be quarterly or annually. Revenue refers to the gross income that a company receives from normal business activities, typically the sales of goods or services, but may also include rent, dividends, or royalties. In accrual accounting, revenue occurs at the time of the transaction, not when receipts are collected. Net income is expressed as a profit or loss, after deducting expenses, which usually include operating expenses (cost of goods sold, variable overhead expenses), depreciation of assets and amortization of leases, fixed overhead (selling and administrative expenses, research and development), interest expenses, and taxes.

The actual worth of a company, the equity, is difficult to ascertain, but one method to calculate value is market capitalization, which is (share price) × (shares outstanding); this represents the public consensus of the value of the firm’s equity. Assets are defined as resources with probable future economic benefit, obtained or controlled by the entity, as a result of past transactions, that are expected to contribute to positive net cash flows. Examples of assets include cash and cash equivalents (pre-paid expenses, bonds, stock), accounts receivable (the money that is owed but has not been collected), inventory (raw materials, work-in-process, and finished goods), property/plant/equipment (purchase price less depreciation), goodwill (intangible value of brand), and intellectual property. Liabilities refer to what a company owes, or from a different perspective, how the assets were obtained. Liabilities include short-term loans (credit lines) current portion of longterm debt, accounts payable (the money a company owes its vendors), and long-term debt. Owners’ equity – the difference between assets and liabilities – can be allocated into several categories: preferred shares (which usually receive periodic dividends), common stock, and retained earnings (accumulated earnings that have been reinvested into the business, instead of being distributed as dividends).

Summary of cash flows An assessment of a company’s cash flows is critical in determining the financial viability of the firm, because profit is NOT

Finance

the same as cash. This disconnect is due to multiple reasons: (1) cash may be coming in from investors or loans; (2) revenue is booked at time of sale, not collection; (3) expenses are matched to revenue, not when they are actually paid; and (4) capital expenditures do not count against profit (because only the depreciation is charged against revenue) but require cash or debt to pay for the assets. As a result of this discrepancy between when a good or service is provided and when cash is exchanged, following the flow of cash can be very complicated. Fortunately, we have accountants. For mature, stable, and well-managed companies, cash flow does approximate net profit. But for younger, growing, and poorly managed companies, profit can occur without gaining cash (resulting in bankruptcy, because bills cannot be paid) or cash can accrue without being profitable (which bodes poorly for long-term success, if expenses cannot be controlled). Overall cash flows are further subdivided into three categories – operations, investing, and financing – based upon the conduit for the flow. Cash flows from operating activities (CFO) indicate how much cash was generated from operations: selling goods and services. Cash flows from investing activities (CFI) indicate how much cash the company spent (or received) from buying and selling businesses, property, plant, and equipment. Finally, cash flows from financing activities (CFF) indicate how much cash the firm borrowed, received from selling stock, or used to pay down debt or repurchase stock. Total cash flow represents the true flow of money through a firm and is a composite of the operations, investing, and financing, represented by the following equation: Totalcash flow = CFO + CFI + CFF

41

Four types of ratios help managers and stakeholders analyze a company’s performance: profitability, leverage, liquidity, and efficiency. These ratios can be used to follow the performance of a firm over time or to compare several firms across related industries.

Profitability ratios Gross margin = gross profit / revenue Operatingmargin = operatingprofit / revenue Net margin = net profit /revenue

Returnonassets = net profit / totalassets = (net income / revenue )× (revenue /assets )

Returnonequity = net profit / shareholders’equity

Contribution margin = revenue − variable direct costs ( technically not a ratio, but lovedby CFOs everywhere )

Leverage ratios Debt-to-equity ratio = total liabilities / shareholders’equity Interest coverage = operating profit /annual interest charged

Liquidity ratios



Many financial analysts believe that total cash flow myopically focuses on earnings while ignoring “real” cash that a firm generates and retains for future investments. Therefore, another measure of the ability of a firm to create value is free cash flow (FCF), which is defined numerically as: Free cash flow = CFO – capital expenditures or alternatively: Free cash flow = net income + amortization + depreciation – changein working capital − capitalexpenditures

In other words, free cash flow represents the total cash that a company is able to generate after laying out the funds required to maintain or grow its asset base. FCF is very important to investors because this allows a firm to pursue opportunities that increase shareholder value. This is the best source of capital for development of new products and services, acquiring new companies, paying stock dividends, and reducing debt. Cash really is king, and this is why.

Financial ratios Because companies even within a single industry can vary in size and maturity, such instruments as the income statement, balance sheet, and summary of cash flows may not permit a valid comparison of those companies. Instead, financial ratios – the numerical relationship between two categories – can provide powerful insight into the financial health of a company. Jonathan Swift observed that “vision is the art of seeing what is invisible to others,” and financial ratios provide that vision.

Current ratio = current assets /current liabilities Quick ratio = ( current assets − inventory )/current liabilities



Efficiency ratios Days ininventory = average inventory / ( cost of goods sold [COGS]/ day ) Inventory turns = 360 /days in inventory Days sales outstanding = accounts receivable /(revenue /day ) Days payable outstanding = accounts payable /(COGS/day ) Property, plant, equipment ( PPE) turnover = revenue/PPE Totalasset turnover = revenue / totalassets

Finance Markets are constantly in a state of uncertainty and flux and money is made by discounting the obvious and betting on the unexpected. George Soros

The goal of finance (Box 5.3) is to maximize corporate value while minimizing the firm’s financial risks.13 If accounting is the language and grammar of business, then finance is a combination of poetry and theoretical physics, with some rock ‘n’ roll added to keep the mix interesting. The central thesis

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BOX 5.3 Idea watch: Finance  

Reference: Harris M, Tayler B. Don’t let metrics undermine your business. Harvard Business Review, September-October 2019. https:// hbr.org.14 Although tying performance metrics to strategy has become a standard practice in business, focusing too narrowly on the numbers can sink the best strategic plans. Companies can lose sight of their strategic goals when focusing on the metrics that are meant to represent achieving that strategy. The authors note that “people have a behavioral tendency—known as surrogation—to confuse what’s being measured with the metric being used. To reduce the risk of surrogation, make sure that the people executing your strategy had a role in formulating it, don’t link incentives too tightly to strategy metrics, and use multiple metrics to assess performance.” For example, the most successful physician compensation models are usually tied to multiple metrics, including case volume, total wRVUs, patient revenue, grant support, clinic attendance, teaching evaluations, academic performance, and citizenship. Multiple metrics are ideal for institutions that are committed to the tripartite mission of clinical care, education, and research. Compensation models that rely heavily on just one or two parameters incentivize productivity in only those metrics. Indeed, every system is perfectly designed to get the results it gets.

of finance is that risk can be managed successfully, in such a way that wealth is created, by combining the variables of cash, assets, supply chain, and human capital, to produce a good or service that is more valuable than the cost of production. The consumer, however, is the final arbiter who decides if the good or service is more valuable than the cost of the inputs, and if the output is more valuable than the price the consumer is willing to pay. If so, the consumer exchanges money for the good or service. Risk can be measured statistically and therefore, given assumptions that are known with certainty, the outcome of decision-making can be predicted with specific probability. Thus, the decision to make an investment in a new piece of equipment, a new employee, a new product line, or to purchase another company, can be made with a certain level of confidence. However, when some variables are unknown (ambiguity) or when no variables are known (true uncertainty), sound financial management may not be possible, to the point that flipping a coin may provide more insight regarding outcomes. This section will introduce common tools used by financial managers when analyzing a financial scenario, to determine go/no-go decisions about acquiring and allocating assets. While understanding the mechanics of such calculations is not essential, understanding the logic behind the decision-making is critical, as well as understanding the significance of the results. We will review the following concepts: time value of money, opportunity cost, net present value (NPV), discounted cash flows (DCF), weighted average cost of capital (WACC) and the hurdle rate, return on investment (ROI), and internal rate of return (IRR).

Time value of money Money increases in value over time, and such appreciation is actually logarithmic (although it takes a while to get going!). Even Einstein conceded, “The most powerful force in the

universe is compound interest.” Essentially, a dollar today is worth slightly more tomorrow and a lot more in 10 years. A dollar invested in a money market account with an annual return of 2% will yield 2 pennies next year, increasing the value of this investment to $1.02, which is the future value of today’s dollar. The formula for the time value of money is:

Present value (PV ) = future value /(1 + interest rate )# of periods

Why does money have a time value? Economists attribute this to two factors: postponement of consumption and expectations of inflation. Interest rates are a hedge against this type of depreciation. As risk of an investment increases, then the reward to the investor needs to increase, to convince the investor to part with one dollar today, in hopes of having possibly $1.20 next year (which would be a 20% return). The actual rate that money can appreciate is determined by multiple factors, such as the risk of the specific investment, the performance of the stock market, the return on US Treasury bonds, and the monetary policy established by the Federal Reserve, which sets the overnight lending rates to commercial markets. Consequently, obtaining capital costs money. If one borrows money from the bank, this loan creates risk for that institution, so the bank will need to collect more money from the borrower, when the debt is repaid, at some point in the future. But here is the catch: banks need to charge not only for the time value of money, which is their expected rate of return (also called the discount rate), but the bank must also hedge against your riskiness as a borrower, driving up the cost of capital and increasing the interest rate that you must pay. In fact, if the bank can make a safer investment, with a possibly higher rate of return, then the bank should not pursue the loan.

Opportunity cost When considering a new project or purchasing a piece of equipment, one should proceed if the intrinsic value of the asset equals or exceeds its cost. What one must also consider, though, is the opportunity cost of tying up precious time, money, and energy in that project or asset, when those resources could be invested elsewhere. The definition of opportunity cost is the potential benefit forgone from not following the financially optimal course of action. Rather than thinking in yes/no parameters, the investor should make either/or decisions, searching for other opportunities, until he or she can compare the proposed course of action with the next best alternative. In the world of surgery, where most of physician revenue is generated from procedures, any activity that takes the surgeon out of the operating room should be carefully compared to what the surgeon could accomplish by staying in the OR.

Net present value (NPV) and discounted cash flows (DCF) The decision to pursue a project, when economic considerations are important, involves determining the net present value of that opportunity. NPV is calculated by adding a time-series of cash flows, both incoming and outgoing, that

Economics

the project is expected to produce, over a series of future periods. This calculation would include the initial cost of purchasing the asset, at DCF0, plus the anticipated revenue that the asset would generate, from DCF1 to DCFn. Each future cash flow must be discounted back to its present value.

NPV0 -n = DCF0 + DCF1 + DCF2 + …+ DCFn where n = number of periods

If the NPV is >0, then the investment would add value to the firm, and the project may be accepted. If the NPV is 2.4 Gy per day). Radiosurgery or SBRT consists of using 1–5 fractions (up to 8 fractions is commonly used in Canada and Europe) using highly conformal treatment-planning techniques to prescribe to a lower isodose line which allows for internal dose escalation and hetero geneity to achieve ablative doses with a steep gradient to safely spare adjacent critical organs at risk, such as the spinal cord or esophagus. This is only possible with image guidance of CBCT to ensure precision as described above. To facilitate comparison between these different fractionation regimens, calcula ting an equivalent dose in 2 Gy fractions (EQD2) or a biological equivalent dose (BED) demonstrates how higher dose per fraction can result in similar or higher effective doses in a shorter treatment duration. Similarly, hyperfractionation (twice daily fractions, 6 hours apart) takes advantage of the maximal repair of normal tissues and can allow for gentler radiotherapy for late responding tissues, yet still provide dose escalation and increased tumor cell death, particularly for rapidly dividing tumors. Hyperfractionation is often also considered for normal tissue protection in re-irradiation, and for head and neck  

 

 

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malignancies to intensify therapy when a patient may not be able to tolerate cisplatin-based chemotherapy. The dose is determined by the intention of the treatment. Radiation can be used as the primary modality of therapy or adjuvant when combined with surgery and/or chemotherapy. When the treatment intent is curative, radical doses, such as 66 Gy for early (and 70 Gy for late) laryngeal cancer or 80 Gy for prostate cancer, are delivered in conventional fractionation sizes of 1.8–2.0 Gy per daily fraction, 5 days a week, over periods of 7 weeks or more. Typically, the maximum dose is applied to known tumor, but lower doses (45–50 cGy) are used to treat tissues that have the potential for microscopic disease, for example, the peritumoral edema around a soft tissue sarcoma. However, when resection margins are histologically positive, a higher dose is needed, e..g., to 70 Gy, and the context is no longer adjuvant. In non-curative situations, treatment may be used to palliate symptoms such as pain or bleeding, employing hypofractionated regimens that use smaller total doses but a larger dose per fraction to facilitate decreased logistical burden of treatment and minimize potential breaks from systemic therapy. Common palliative regimens include: 8 Gy in 1 fraction, 20 Gy in 5 fractions, and 30 Gy in 10 fractions. However, there are also non-curative situations when a patient has known metastatic disease, but bulky or aggressive tumor at the primary site that is, or will shortly become, very symptomatic and impair quality of life. Radical radiation approaches are used to optimize local control, for example, an unresectable fungating breast cancer even in the presence of bone metastases. For patients with an excellent performance status and small volume tumor burden, ablative radiotherapy such as SBRT is sometimes employed for a durable local control, and sometimes curative benefit, even in the metastatic setting, and may have an abscopal effect – shrinking tumor deposits outside of the target volume.15,16  

 

 

 

 

Hints and tips • For all patients, but particularly for young people, potential benefit of radiation must be weighed against the late sequelae of radiation, including the risk of second malignancy. • Chromosomal fragility syndromes such as Li–Fraumeni syndrome, and Rb or ATM gene carriers, are relative contraindications to radical or curative radiation therapy. • Previous radiation therapy is a relative contraindication and should be assessed by a radiation oncologist to determine if further radiotherapy would justify the potential increased risk in morbidity.





 

 

 

 

Patient selection As in any branch of medicine, careful patient selection and informed consent is essential. Multidisciplinary tumor boards and clinics allow for consideration of all treatment modalities. Patients are often referred to radiation oncology when surgery or chemotherapy options are not feasible because of comorbidities or poor performance status. There are some basic principles to follow. For all patients, but particularly for young people, potential benefit of radiation must be weighed against the late sequelae of radiation, including the risk of second malignancy. Poor performance status and patient preferences can shift a potentially curative scenario into one of observation, or non-radical radiotherapy. However, chromosomal fragility syndromes such as Li–Fraumeni syndrome and Rb or ATM gene carriers are relative contraindications to radical or curative RT. Previous RT is only a relative contraindication, and requires careful assessment of the current tumor in relationship to the prior radiotherapy field, the total dose delivered, the length of time between treatment for some functional recovery, and the potential radiosensitivity of the tumor requiring treatment. Pregnancy testing in women of child-bearing age is essential as the risk of fetal damage is high.

Breast cancer Until 1997, it was widely believed that RT for breast cancer only offered local control, and that any improvement in

survival was related to the effect of adjuvant systemic therapy. Any survival advantage of radiation was negated by deaths that may have been caused by cardiotoxicity from large fractions and older, less precise techniques. Two landmark studies examining the role of RT in node-positive breast cancer demonstrated significantly improved survival with RT and changed breast cancer practice dramatically.17–19 The impact on overall survival has been confirmed in subsequent meta-analyses.20,21 Although not as dramatic a finding as for nodal RT, radiation to the intact breast alone also confers a small survival advantage.22

Breast conservation therapy Adjuvant breast irradiation allows breast conservation by reducing the risk of breast cancer recurrence. The evidence for the effectiveness of post-lumpectomy radiation is strong, and derived from many randomized clinical trials,23,24 and provides equivalent25 or even improved26 survival for younger women in modern series. It is one of the commonest radiotherapy treatments in RT practice.27 Cosmesis was also found to be satisfactory in a large European study that used rigorous assessment methods.28 It is a relative contraindication with multicentric disease involving multiple quadrants, which would likely result in significant cosmetic deformity, positive margins, prior chest wall or breast irradiation, and is an absolute contraindication for pregnant women or those with inflammatory breast disease. Women with active connective tissue diseases, especially scleroderma,29 may have an increased risk of acute and late toxicities; however, these patients were not excluded from many of the trials and there is little data to support if conventional fractionation results in decreased toxicity compared to hypofractionation.27 Historically, women with larger breasts or larger tumors were at risk of a poorer cosmetic result due to large lumpectomy cavity deficits, but with the advent of oncoplastic closure to minimize seroma accumulation and radiotherapy advancements for improving the homogeneity of the treatment plan, this is less of a concern.

Indications for postmastectomy radiation (PMRT) PMRT is indicated for circumstances where the tumor is 5 cm or larger based on prechemotherapy extent of disease if used in the neoadjuvant setting (cT3); when the margins are positive, or closer than 1 mm; or when there are regional lymph node metastases, since these are all strong predictors of chest  

 

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Algorithm 27.1

cN0

1–2 nodal metastases

SLNB

Management of nodepositive breast cancer cN1 (palpable) -> Needle biopsy with clip placed for confirmation at time of surgery

Breast conservation therapy, no need for ALND

Consider high-tangents (low axillary coverage)

Mastectomy, ALND. Consider omission if N1mic**

Selective nodal irradiation for high-risk patients*

If cN1 direction prior to surgery +/- neoadjuvant chemotherapy

ALND

If cN1 converts to cN0 after neoadjuvant chemotherapy

SLNB

If positive, ALND. Ongoing ALLIANCE A011202 trial randomizing ALND and regional nodal irradiation (omitting RT to dissected axilla) vs. regional nodal irradiation without ALND

If negative, no ALND. Ongoing NSABP B-52 trial randomizing +/- regional nodal irradiation

Multidisciplinary clinical decision-making algorithm for axillary management for breast cancer. *High-risk features: extent of nodal involvement, microscopic extracapsular extension, larger primary tumor size, lymphovascular space invasion. **Two randomized trials (IBCSG 23-01 and AATRM 048/13/2000) showed ALND vs. no further surgical treatment in mastectomy patients for those with micrometastases had no disease-free survival difference, even in the absence of RT. Abbreviations: ALND, axillary lymph node dissection; cNx, clinical node status; RT, radiotherapy; SLNB, sentinel lymph node biopsy.

wall recurrence.30 Radiation should also be considered when the lymph node status is uncertain, and the histology shows that the tumor has evidence of lymphovascular involvement, which predicts for local recurrence.31,32 Conversely, it is not indicated when the tumor size is less than 5 cm with negative margins and without spread to the lymph nodes. The role for PMRT is widely established for those with four or more lymph nodes, with controversy regarding the role of one to three lymph nodes,33 particularly in the setting of disease less than 5 cm and remains important to have an individualized discussion regarding the known benefits for locoregional control with the potential toxicities.30 Importantly, PMRT chest wall irradiation is always indicated even in the setting of nodal involvement and even if the primary tumor is small, as the most common pattern of failure is local chest wall failure in all settings.  

 

Radiation of the nodal draining areas For patients undergoing breast conservation therapy, the ACOSOG Z0011 study demonstrated that completion axillary lymph node dissection (ALND) could be omitted in select patients with limited sentinel node-positive disease.34 This trial compared sentinel lymph node resection with versus without ALND in patients with T1–2 tumors with up to three

positive sentinel lymph nodes. All of the patients underwent breast-conserving surgery with whole breast irradiation. The study required no dedicated axillary lymph node irradiation. There was no difference in local or regional recurrence, supporting omission of ALND in this population. The AMAROS trial (which randomized patients with a positive sentinel lymph node to ALND or axillary RT) show excellent 5-year local control and survival with less lymphedema in the radiotherapy arm.35 The inclusion of nodal irradiation is indicated when four or more lymph nodes are positive; RT for 1–3 nodes is still a grey area, even though it has become fairly routine practice. When there has been an adequate sampling, the upper axilla is usually not included in the volume, although the supraclavicular area, i.e., the next echelon of nodes, is included. Internal mammary (IM) nodal RT is controversial, and subject to institutional bias.36 IM nodal involvement is known to be more common in medial and central breast cancers, and to be present when axillary lymph nodes are positive,37 although IM clinical failure is rare. Positive IM nodes detected on imaging such as positron emission tomography (PET) fludeoxyglucose scan are rarely resectable, unlike axillary nodes, and thus need a higher dose of RT,38 as this situation is no longer one of adjuvant therapy. Algorithm 27.2 highlights the multidisciplinary clinical decision-making for axillary management of breast cancer.

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Algorithm 27.2 < 5 cm, low grade (May not require RT)

Upfront oncologic resection with pathology review to determine if high-risk features are present to necessitate postoperative radiation

> 5 cm, intermediate -high-grade (likely will require RT)

Multidisciplinary evaluation to see if neoadjuvant chemotherapy would be of benefit

Soft-tissue sarcoma clinical decision algorithm

Preop RT considerations: Lower dose (50 Gy) Shorter treatment duration: 5-5.5 weeks Smaller field size Reduced fibrosis Reduced edema Increased wound healing complications

Discussion with oncologic surgical team regarding clinical experience with preop vs. post RT Equivalent local control Postop RT considerations: Higher dose (60-66 Gy) Longer treatment duration: 6-6.5 weeks Larger field size Increased fibrosis Increased edema Decreased wound complications

Multidisciplinary clinical decision-making algorithm for management of soft-tissue sarcoma. Abbreviations: RT, radiotherapy.

RT indications, dose, and techniques The target volume includes the breast, subcutaneous tissues, and chest wall. In any technique used to cover these tissues, the lower axilla is usually within the high-dose volume. The classic technique is breast “tangents”, using medial and lateral beams (Fig. 27.17) that are either angled or blocked to reduce the dose to the heart and lungs. The beam can be modified with a wedge-shaped device or a step-and-shoot technique to strategically position collimator leaves to reduce the “hot spot” of radiation dose that can result from this technique. For select patients, IMRT, proton therapy, and other conformal approaches are used to provide more homogeneous dose distribution, particularly in the setting of large breasts, left-sided breast cancer, or when nodal irradiation is indicated. The same techniques are used to treat the chest wall, although the scar and drains have traditionally been in the high-dose volume, necessitating bolus to ensure that the scar receives an adequate dose (Fig. 27.18). The use of bolus on the entire chest wall is debatable, except in the case of inflammatory breast cancer, where tumor cells, by definition, invade the dermis, and so it is essential to achieve full dose on the chest wall skin. Apart from the lower axilla, which is incidentally covered in breast or chest wall techniques, additional planning is required to ensure that the targeted lymph node areas match carefully to the breast/chest wall volumes to avoid overlap of the radiation fields, which could result in increased toxicity to the normal tissues, including the brachial plexus. With a traditional supraclavicular field, the small apex of the ipsilateral

Figure 27.17 Conserved breast treated with classic breast tangents; the internal mammary chain (IMC) is not covered.  

lung receives a full dose when treating the supraclavicular lymph node basin. If overlap of fields happens, a portion of the brachial plexus may receive almost a double dose of radiation,

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B

Figure 27.18 Postmastectomy radiation treatment plan. (A) Including the IMC nodal area using a wide tangent technique, resulting in a larger volume of irradiated lung. (B) The use of bolus to bring the surface dose to 100%, and losing the skin-sparing effect.  

and thus be at very high risk of brachial plexopathy. If treating the IM nodal chains, there are two main techniques: the first uses an extra-wide “deep” tangent arrangement, which can result in a significantly larger volume of lung tissue being damaged. The addition of an electron field patched on to the medial aspect of the tangent fields delivers a fairly homogeneous dose over the IM nodes, but still can result in increased lung, and cardiac dose, if the tumor is located on the left side. Getting adequate dosing into the IM nodes, and avoiding critical structures, can be especially challenging when an expander has already been placed in the chest wall prior to using this technique (Fig. 27.19), sometimes causing the electron dose to “splash” onto the contralateral breast. This does not happen often on the flat chest wall of PMRT, or when the breasts are natural and fall to the side, leaving the ipsilateral parasternal area flat. Advanced treatment techniques have improved our ability to spare critical organs at risk, particularly the heart for left-sided breast cancer as we have learned that even low doses can result in meaningful increased risk of long-term cardiac toxicity.39 Treatment using a breath-hold technique allows for the chest wall to move anterior with lung expansion, and the mediastinum to narrow and be pulled inferior increasing the separation of the heart from the chest wall (Fig. 27.20). In this setting, radiotherapy is administered in sequential breath-holds of 20–30 seconds over the course of a few minutes only when in position. Proton beam therapy can be particularly beneficial for patients with locally advanced left-sided breast cancers, particularly necessitating regional nodal irradiation, as typically a single en-face beam is delivered to the chest wall, and due to the dosimetric advantage, the dose to the heart and lung beyond the target can be significantly reduced (Fig. 27.21). For this reason, an ongoing randomized clinical trial of proton versus photon radiotherapy (RADCOMP) has the primary endpoint of reducing the 10-year incidence of cardiac toxicity. The traditional conventional fractionated adjuvant dose to the chest wall or breast is 50 Gy (clinical trials have used ranges  

 

from 45 to 60 Gy), given in 1.8–2 Gy/fraction, depending on practice, with the same dose used for the nodal areas. For breast conservation patients, the Ontario Clinical Oncology group and the UK START A and B trials have demonstrated long-term randomized evidence of the efficacy and similar to improved cosmesis using a hypofractionated region of 40 Gy in 15 fractions or 42.5 Gy in 16 fractions40–42 and therefore has become standard of care for breast conservation therapy when additional regional nodal irradiation is not required.27 For PMRT, conventional fractionation remains standard of care with promising randomized data from China43 and phase II data from the US44 demonstrating the potential safety of hypofractionation, and an ongoing phase III ALLIANCE A221505 clinical trial. Even in the absence of positive margins, local recurrence is most likely to occur in the operative bed, or tumor cavity. The use of a shrinking field boost to this volume can reduce this risk, and is recommended in patients at higher risk for local failure (age 40. Boosts are typically delivered sequentially after whole breast irradiation or to the chest wall/scar after PMRT, for an additional dose of 10 Gy for low risk factors and 14–16 Gy in 2 Gy fractions for high-risk factors (particularly a positive margin, or combination of close margin and multiple high-risk features). Patient selection is of importance given the addition of a boost can result in increased fibrosis and compromise cosmesis.45 Another approach for early-stage breast cancer has been to treat only the area most at risk, i.e., the cavity plus a margin, and not treat the whole breast, called accelerated partial breast irradiation (APBI).46 NSABP B-39 recently published a phase III randomized equivalence trial for conventional whole breast irradiation versus APBI to 34 Gy of  

 

 

 

 

 

 

 

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A

B

Figure 27.19 (A) Treating a right breast mound with inflated expander in place can mean that the medial aspect of the contralateral breast may be “splashed”. (B) The expander in situ is more problematic for the contralateral breast when the IMC lymph nodes are treated.  

A

C

B

Figure 27.20 Representative photon radiotherapy plan for left-sided breast cancer using a breath-hold technique. One can see how the breath-hold technique narrows the mediastinum and pulls the heart inferiorly and away from the chest wall (pink outline) compared to the free breathing heart (shaded yellow) as seen on the representative axial (A), coronal (B), and sagittal (C) views. (Courtesy of Janice N Kim, MD.)  

brachytherapy (catheter-based applicator) or 38.5 Gy in 10 fractions, twice daily, of external beam radiation therapy.47 While APBI did not meet criteria for equivalence due to the large eligibility criteria, the absolute difference of less than 1% in the 10-year cumulative incidence of ipsilateral breast-tumor recurrence, still makes APBI an acceptable  

alternative in a properly selected patient. Current guidelines support the use of ABPI for women age 50 or above, margins >2 mm, staged Tis or T1, and for DCIS (ductal carcinoma in situ) if all are met (size ≤2.5 cm, low–intermediate grade, screen-detected, widely negative margins ≥3 mm).46  

 

 

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A

B

C

Figure 27.21 (A–C) Postmastectomy radiation treatment plan to a total dose of 6040 cGy (5040 initial field, 1000 cGy chest wall boost) to the chest wall and comprehensive regional nodes using proton beam therapy. Protons enabled a low mean heart dose of 76 cGy which should decrease the long-term risk of heart disease in the future. (Courtesy of Li Ming Christine Fang, MD.)  

 

 

 

Breast: Spotlight on upfront multidisciplinary evaluation topics For patients with breast cancer, particularly with planned or anticipated mastectomy and/or axillary lymph node dissection, we strongly recommend upfront multidisciplinary evaluation with the surgical oncologist, radiation oncologist, medical oncologist, plastic surgeon, and physical therapist. If there are indications upfront or a high likelihood of requiring PMRT, coordination with the patient’s reconstruction plans is of utmost importance to design an individualized staged reconstruction plan due to increased rate of complications in the reconstructed breast and increased complexity of radiation delivery.48 Typically, after radiation, an autologous-based reconstruction option (e.g. DIEP [deep inferior epigastric perforator], latissimus flap) is the preferred treatment of choice rather than implant-based which can be more prone to contracture and reconstructive failure.49 Often at the time of surgery, if a skin-sparing mastectomy is performed, either an entirely delayed approach is planned or a two-staged approach with an expander placed after coordination with the radiation oncologist (institutional preference), then with expansion of the skin to promote memory, then deflation is often (but not always) desired prior to treatment for improved dosimetry. If an uninvolved contralateral breast expander is also placed, this may also need to be partially deflated to improve radiation beam angles and minimize potential unintentional irradiation of this uninvolved tissue. For proton

beam therapy specifically, if an expander is placed at the time of mastectomy, the port must be outside of the treatment field as it has the potential to cause uncertainty in dose distribution beyond or adjacent to the port; however, this is not a significant issue with photon (X-ray)-based radiation. The optimal timing for reconstruction after radiation remains controversial and based on institutional preference, however, data supports that an interval for autologous-based reconstruction of at least 12 months minimizes complications and optimizes the outcomes in patients receiving PMRT.50 (Refer to Volume 5 for further details on breast reconstruction options.) Lastly, if an axillary nodal dissection is anticipated, coordination with a plastic surgeon to perform a lymphatic microsurgical preventing healing approach (LYMPHA) to prevent lymphedema has been demonstrated to dramatically lower the rate of lymphedema51–53 (refer to Volume 5, Chapter 47 for further details).

Head and neck cancer Head and neck cancers are mostly squamous cell carcinomas (HNSCCs). Radiation has an important role in the primary, postoperative, and palliative aspect of their management. Previously, a general principle of minimizing toxicity by using either surgery or radiation, and keeping the other modality for salvage, was preferred. However, increasingly, especially in locally advanced disease, combined modality, particularly postoperative radiation treatment, is used because it has been shown to reduce the incidence of recurrence, especially if

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there is a large primary tumor and/or cervical lymph node involvement. The use of concurrent chemotherapy has shown a benefit in both survival and local control;54 as a result, platinum-based therapy has become the standard of care in the management of all but the most favorable – early disease that has a high cure rate with RT alone. However acute toxicity is considerably worsened by concurrent chemotherapy, and some patients are not optimal candidates for cisplatin due to competing comorbidities or poor performance status. In the RTOG 9501 trial,55 cetuximab concurrently with radiotherapy for locally advanced head and neck squamous cell carcinomas showed improved in survival and local control compared to radiation alone and appeared to have less toxicity compared to cisplatin based on historical trials. The incidence of human papilloma virus (HPV)-associated oropharyngeal cancers has been increasing, with a decrease in rates in smokers. HPV-associated oropharyngeal SCC clinically behaves differently with a better prognosis.56 De-intensification of therapy for HPV-positive tumors is being investigated in multiple ongoing trials with the overall goal to reduce morbidity in HPV-related HNSCC without a detriment in survival and local control. However, recent attempts to de-escalate therapy for HPV-positive HNSCC serve as a cautionary tale with two recent phase III clinical trials (RTOG 1016, De-ESCALaTE) showing inferior cancer control outcomes in this patient population.57–59 SCC head and neck cancers have lower local control rates if treatment time is extended, due to repopulation of tumor cells.60 In order to overcome this effect, efforts have to be made to deliver five fractions per week even if it requires treating twice a day to do so, and to aim to start postoperative therapy within 6 weeks of surgical resection after adequate wound healing. Approaches that further intensify the course of treatment by giving it over a shorter period of time (accelerated fractionation) or giving treatment more than once a day using a smaller dose per fraction over the same time period (hyperfractionation) can improve outcome but result in severe acute toxicity so that breaks in treatment may be necessary, thus negating the benefit of altering the fractionation schedule. Doses used for gross tumor are in the 66–72 Gy range. Subclinical disease is treated to 50–60 Gy. Before the introduction of IMRT, these areas were usually treated sequentially, covering the larger volume to a “microscopic” dose, before boosting the smaller volume or volumes containing gross disease, although a concomitant boost was sometimes used. However, IMRT allows a technique of “dose painting” or differential dosing so that the areas at higher risk are programmed to receive a slightly higher dose per day than the areas of low risk. It can also reduce the dose to the parotid, reducing the risk of permanent xerostomia.61 Submandibular gland-sparing IMRT has also been utilized in select patients to reduce xerostomia with excellent locoregional control.62 Proton therapy can be considered when treating a unilateral neck to minimize the contralateral neck fibrosis and impact on salivary glands (Fig. 27.22). In addition, for patients with locally advanced tumors with intracranial extension and/ or cranial nerve extension to the base of skull, protons can achieve adequate target coverage while minimizing dose to the temporal lobes, brainstem, and potentially sparing the optic structures, or at least contralateral structure in hope to preserve vision.  

 

Figure 27.22 A 55-year-old man with a resected Merkel cell carcinoma, stage IIIB s/p wide local excision and sentinel lymph node biopsy with a pathologic node. Shown is a postoperative radiation treatment plan to 50 Gy fractions to the resection bed and ipsilateral at-risk neck. Proton therapy was used to minimize dose to the contralateral neck and salivary glands. (Courtesy of Upendra Parvathaneni, MD.)  

 

Acute toxicities occur during the course of treatment and resolve 2–3 months following completion of treatment. They are reversible unless the acute damage is confluent, causing damage to the basal membrane and depleting the supply of stem cells. Mucositis, which is exacerbated by smoking and alcohol, starts during weeks 2–3, becoming confluent by the end. It affects the mucous membranes within the high-dose volume and results in difficulty in swallowing. Because of concerns about nutritional status, percutaneous endoscopic gastrostomy tubes are often inserted before the start of treatment, particularly if bilateral neck irradiation and concurrent platinum chemotherapy is anticipated. Mucositis is painful and mouthwashes containing local anesthetic help this, but usually narcotics are also required. The skin develops erythema by weeks 3–4, even with the aggressive use of topical aloe vera gels, other unguents, and steroids. Reaction is inevitably brisk with moist desquamation by completion of treatment. Because of dose to the parotid, patients will also experience change in taste; radiation causes xerostomia, changing the consistency of saliva by drying the water component, which results in thick mucoid secretions that are difficult to clear. During treatment patients often lose weight and experience fatigue. Late toxicities depend on the size of dose per fraction given. They occur 6 months to 3 years following the completion of treatment and unfortunately are permanent and

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progressive. The primary problem is fibrosis that can affect the subcutaneous tissues, musculature, and joints. The patient can experience trismus, neck stiffness, aching, and swallowing difficulties as a result. If the parotid or submandibular glands have been treated to more than 26 Gy the patient may be left with permanent xerostomia, which can exacerbate dental problems. The patient may also experience voice changes due to chronic laryngeal edema and/or cartilage damage. Patients are also at risk of osteoradionecrosis (ORN), as described later.  

Head and neck: Spotlight on upfront multidisciplinary evaluation topics Multidisciplinary evaluation with the medical, surgical, and radiation oncology team prior to treatment is instrumental to avoid unnecessary morbidity of multimodal treatment, if feasible. For example, if a patient has clear clinical evidence of lymph node extracapsular extension that would necessitate the recommendation for concurrent chemotherapy with radiotherapy, definitive chemoradiation may be the treatment of choice, as upfront surgical resection would not allow for radiotherapy dose and/or concurrent chemotherapy treatment de-intensification. Furthermore, if radiotherapy is planned, coordination with dental clearance with consideration of creating a custom stent for optimal tongue immobilization away from the radiotherapy field, can allow for decreased delays to treatment initiation since we know the time package of total treatment completion can meaningfully impact local control. Furthermore, a known history of radiotherapy to the head and neck region should prompt discussion with the radiation oncologist of how much dose each tooth has received if dental work is required to minimize the risk of osteoradionecrosis.

Sarcoma Sarcomas comprise a heterogeneous group of more than 150 bone and soft-tissue mesenchymal subtypes. Soft-tissue sarcomas (STS) are rare (10,000 cases diagnosed annually in the US) mesenchymal malignancies arising from connective tissue. They can arise anywhere in the body but most commonly affect the extremities and trunk. Because of the rarity and diversity in histology, treatment outcomes are improved with management in a specialized multidisciplinary group that includes dedicated sarcoma radiation oncologists.63 Prognosis and treatment recommendations depend on size, grade, histological subtype, and superficiality of the tumor. Location is also important; retroperitoneal sarcomas have an independently worse outcome, but usually do not present until tumors are very large. Although the primary treatment of STS is surgery, pre- or postoperative radiation allow for limb preservation in extremity sarcoma and reduce the risk of local recurrence.64,65 Overall, local control rates are approximately 80–90% at 5 years.66 Upfront evaluation in a multidisciplinary setting with a biopsy planned in coordination with the surgical oncologist/orthopedist is necessary, as “whoops” non-oncologic surgeries or biopsies violating uninvolved tissue compartments result in inferior local control, even in the setting of proper subsequent multimodal therapy.67 If the patient is unfit for surgery, primary RT can provide useful local control.68

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The role of RT in treatment of osteosarcoma or chondrosarcoma is less well defined, but is typically considered for axial-based tumors, such as involving the spine or base of skull where a wide negative margin surgery may not be feasible to decrease the risk of local recurrence,69 or in the palliative setting. The role of radiotherapy is well established for chordomas, radioresistant tumors that can arise anywhere from the base of skull to the coccyx from the embryologic notochord remnant. For chordomas, radiotherapy is typically administered in the postoperative setting after maximal safe resection, and/ or in the definitive setting if surgery is deemed to be too morbid. Emerging evidence suggests the potential for improved outcomes using a combined preoperative radiotherapy followed by oncologic excision and an individualized postoperative boost based on the margin status.70 Due to the need for dose-escalation adjacent to critical organs at risk such as the spinal cord, pelvic organs, and/or other anterior structures to the spine, proton therapy has been demonstrated to allow for dose escalation with acceptable treatment-related morbidity and excellent long-term outcomes.71

RT indications, dose, and techniques For STS, RT is indicated for tumors >5 cm, intermediate or high grade regardless of margin status, or low-grade STS with positive margins, local recurrence s/p surgery alone, or a tumor location-sensitive and challenging location for surgical salvage. The Canadian NCIC-SR-2 clinical trial demonstrated the same local control with preoperative (50 Gy in 25 fractions) versus postoperative radiotherapy (60–66 Gy in 30–33 fractions), with decreased permanent late grade 2 or greater fibrosis, joint stiffness, and edema.64,72,73 The lower preoperative dose and smaller field size was thought to result in these reduced late toxicities, since a higher dose is required in the postoperative setting due to decreased oxygenation and vascularity of the tumor bed along with the need to cover the whole operative “footprint” which can result in larger field sizes (fusing a postoperative diagnostic MRI to identify the surgical bed along with the operative report is essential. The tradeoff was that preoperative RT resulted in a higher rate of major wound healing complications than postoperative RT (35% vs. 17%). Wound complications varied dramatically by anatomic site with nearly no major wound complications in the upper extremity, but a more pronounced rate of complications in the lower extremity with preoperative radiation. Despite this increased risk, given wound healing complications are generally considered reversible, many institutions favor a preoperative approach. Algorithm 27.2 summarizes the multidisciplinary clinical decision-making for STS in regard to pre- versus postoperative radiotherapy. It is important to realize that the NCIC-SR-2 trial was conducted before IMRT was in common use. Subsequent data supports that more conformal radiotherapy techniques such as IMRT and reduced treatment field size can result in improved local control,74,75 along with decreased wound healing complications particularly with collaboration with the surgical team,76 and late complications, which can lead to more cost-effective care.77 Proton therapy is considered for inguinal or pelvic sarcomas, particularly in young or adolescent patients to minimize  

 

 

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the radiotherapy dose to the pelvic organs to maximize the opportunity for fertility sparing (Fig. 27.23). Optimal immobilization is important in the RT planning process. It is also necessary to delineate bones, joints, perineum, gonadal and pelvic structures so that dose to these sites can be minimized. It is also necessary to spare a longitudinal strip of skin and subcutaneous tissue so that lymphatic drainage remains intact to reduce the risk of chronic lymphedema.

Sarcoma: Spotlight on upfront multidisciplinary evaluation topics Multidisciplinary decision- making is essential for STS management; centralized expertise in a dedicated sarcoma program is preferred due to the relative rarity of the cancer, the heterogeneity of the pathologic subtypes and anatomic distributions. Collaboration with plastic surgery is increasingly common to coordinate upfront in anticipation of potential wound healing challenges for planned flap or graft-based closure and/or reconstruction of anatomic deficits, when necessary. This can potentially allow for a radiotherapy plan to be designed to preferentially avoid or minimize dose to areas of vascular supply or tissue that would be used for wound closure. While it is uncommon for most STS subtypes to spread to regional nodal basins, when nodal dissection is required for known involvement, advanced techniques such as the LYMPHA procedure can be considered to further reduce the long-term risk of lymphedema. For patients who have already undergone treatment and are suffering with chronic challenges with lymphedema, advanced surgical procedures such as lymph node transposition or further surgical lymphatic manipulation may be of benefit (refer to Chapter 28 for further details). Lastly, for select patients where proton therapy is under consideration, careful upfront discussion should occur

if hardware reconstruction is anticipated and if a carbonfiber-based hardware solution is available to maximize the opportunity of being able to use proton therapy. If hardware is necessary, it would be important to consider if a preoperative approach would be feasible to provide all or most of the therapeutic dose prior to hardware placement.

Skin cancers This group encompasses basal cell carcinoma (BCC), squamous cell carcinomas (SCC), Merkel cell carcinoma (MCC), cutaneous angiosarcoma, and melanoma. Of these, the commonest are BCC and SCC. The majority are radiation-related, albeit mostly solar radiation! Due to their chronic immunosuppression, patients who have undergone transplantation are more likely to develop SCC, which tends to behave more aggressively.

RT indications, dose, and techniques Primary radiation is indicated when the patient is not a surgical candidate (due to comorbidities, anticoagulation, or patient preference) or when surgery may risk function or cosmesis, and in the adjuvant setting to reduce the risk of local recurrence. It can provide good palliation for locally advanced unresectable disease, often with high doses over a short duration (hypofractionation) to optimize local control. Decisions about the extent of the RT target volume are based on the risk of lymph node metastases, and inclusion of the regional nodes in high-risk disease. An important consideration is the presence of perineural invasion, which may involve treating extended volumes along neural pathways. In all, 30–40% of incompletely incised BCCs recur but they can be salvaged equally with surgery or radiation.78 Doses for the primary treatment of BCC are in the range of 40–50 Gy delivered in 10–20 fractions, but higher doses are  

A

B

C

Figure 27.23  (A-C) Representative treatment plan of a young man undergoing preoperative radiotherapy to 50.4 Gy in 28 fractions to his left inguinal region for soft-tissue sarcoma using proton therapy for decreased integral dose of radiation and fertility sparing. The light green (5 Gy) isodose line represents 10% of the prescription dose and below this represents scatter dose. This plan demonstrates how the testicles (orange) are spared to even the lowest doses of radiation since 1–2 Gy or greater can result in infertility.

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needed for SCC in the range of 60–66 Gy in 2 Gy fractions, similar to those for head and neck squamous cell cancers.79 Small lesions without risk for nodal or peurineural involvement can be treated with hypofractionation. When delivering radiotherapy for skin cancers it is necessary to achieve a high dose superficially. One of the best ways to do this is to use superficial kV equipment that provides 100% of the dose at the surface and a very tight penumbra resulting in smaller fields. However, this equipment has now been largely supplanted by electrons, which have a larger penumbra due to their propensity to scatter. Furthermore, low-energy electrons do not provide 100% of the dose at the surface, which is corrected with the use of bolus (tissue equivalent material). Although treatment with RT is highly curative, late toxicities of treatment result in cosmetic changes related to change in pigmentation, fatty necrosis, subcutaneous fibrosis, and dermal telangiectasias. These tend not to arise for 2 years or more after treatment and not all patients suffer these, since many of these cancers are small, and the patient population is, by and large, elderly and frail, one can still get away with using hypofractionated treatment over a shorter period of time. Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor that has a lethal potential for spread. MCC is traditionally treated with a wide oncologic surgical excision with sentinel lymph node sampling for pathologic staging. Adjuvant radiotherapy is typically recommended for nearly all non-metastatic patients except those with the lowest risk of recurrence (stage I extremity MCCs with widely negative margins) with some institutional preference for stage I/II patients.80–83 When adjuvant radiotherapy is used, it is typically to doses of 45–50 Gy in conventional fractionation with a tumor bed boost to 60–66 Gy if there is evidence of microscopic or gross residual disease. Given the propensity of MCCs to spread through the in-transit and regional lymphatics, large treatment fields of 3–5 cm with consideration of coverage of the regional lymphatic basin or in-transit nodes based on individualized risk assessment and informed discussion regarding the potential additive morbidity (see Fig. 27.23). Definitive doses of 50–66 Gy conventional fractionation have also demonstrated excellent local control for patients opting for a non-surgical approach.84–86 Two emerging areas include extrapolation from highly effective palliative treatment with single fraction (8 Gy) radiation therapy87 to the adjuvant setting, where excellent local control has been shown in a small series of stage I/II head and neck patients.88 In addition, new data support that if adjuvant radiotherapy is anticipated, one may consider a narrow margin surgery for similar local control,89 therefore minimizing the risk of wound healing complications that could result in delay to postoperative radiotherapy, which has the potential to influence long-term locoregional control outcomes. Angiosarcoma is primarily treated with surgery. When this is not possible or when there is recurrence or presence of positive margins, radiation is necessary, with higher doses between 66 and 70 Gy. Tumor location can be an important issue in planning treatment. Treating the entire scalp but avoiding the brain requires sophisticated treatment planning. One technique is called the “German helmet”, in which a combination of photons and electrons is used to minimize penetration to the brain and subsequent cognitive dysfunction, or more recently with newer volumetric adaptations of IMRT.  

 

 

 

 

 

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Malignant melanoma is generally thought to be relatively radioresistant. In vivo studies show that the cell survival curve has a very broad shoulder, indicating that these cells have a large capacity to repair sublethal damage. The way to overcome this is to hypofractionate with large doses per fraction. Adjuvant radiation can reduce the risk of local recurrence in high-risk adjuvant situations. At the MD Anderson Cancer Center, criteria for this include desmoplastic histology, depth >4 mm with ulceration or satellite lesions, positive margins, or recurrent disease.90 Radiation to involved or high-risk but clinically negative lymph nodes can improve control. Hypofractionated radiotherapy is effective; 6 Gy twice a week for a total of 30–36 Gy regimens are commonly used,91 albeit with a higher risk of lymphedema, improving local control from 50% to 87%92 without affecting survival. The Trans Tasmanian Group (TROG 96.06) also demonstrated the potential benefit of adjuvant radiotherapy to the lymph node basin for patients with known regional nodal involvement to 48 Gy in 20 fractions with improved local control by 15% with an increase in late effects, including lymphedema.93 Due to the emergency of immunotherapy, the role of adjuvant radiotherapy in the immunotherapy era has become more controversial and less common. For melanoma, radiation also plays a major role in palliation of brain and bone metastases, and uncontrolled tumor.  

 

 

 

Skin cancers: Spotlight on upfront multidisciplinary evaluation topics Many of the patients with skin malignancies have many lesions over the course of their lifetime throughout different parts of their body, and each type of lesion and location will require a thoughtful and individualized approach that is best facilitated by multidisciplinary evaluation to determine the most effect and least morbid options, particularly for tumors in delicate areas. Prior radiotherapy can impact the ability for wound healing should a surgical procedure occur at a future date and awareness of past radiation treatment fields may help provide guidance for wound closure.

Pediatrics

 

 

Unlike adult cancers, pediatric malignancies are not usually caused or related to exposure history (tobacco use, dietary habits, sun), but happen due to underlying mutations and cancer predisposition syndromes.94 Remarkably, the mortality rate for pediatric malignancies has fallen dramatically, which is due in a large part due to the collaborative nature and culture of the pediatric cooperative groups to encourage many patients to enroll on clinical trials. Due to the growing population of childhood cancer survivors, importance needs to be placed on incorporating functional recovery, psychological adaptability, and minimizing childhood survivors’ long-term treatment morbidities. For this reason, particularly in this vulnerable population undergoing physical and mental growth and development, strategies to omit, reduce dose, or minimize target volumes of radiotherapy treatment is of utmost importance. Yet, despite this effort many pediatric brain and spine tumors, and general tumors, still require radiotherapy as an integral part of their treatment course for cure.

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RT indications, dose, and techniques Of key importance for deciding upon the optimal RT modality (e.g., photons vs. protons) is if there is a clinically meaningful reduction in: (1) integral (low-dose bath) of radiation that may increase the risk of secondary malignancy; (2) proximity of adjacent critical organs-at-risk.95 While discussion regarding the indications and dose for all pediatric malignancies is beyond the scope of this chapter, we want to provide a few illustrative examples to highlight the treatment planning considerations. For example, for patients with medulloblastoma who require craniospinal irradiation, proton beam therapy allows for a posterior beam to be used to treat the entire length of the spine, and due to the dosimetric advantage of protons having no exit dose, this allows for maximal sparing of anterior organs such as the heart, lungs, thyroid, bowel, liver, kidneys, and pelvic organs which may help preserve fertility (see Fig. 27.3). Importantly, during the sequential cone-down boost phase where only the posterior fossa mass is treated, this allows for improved sparing of the supratentorial fossa critical learning structures such as the hippocampi and the pituitary gland that can further help minimize the risk of long-term endocrine deficiencies. To build upon our discussion of sarcoma in the adult population, two specific subtypes of sarcoma that are prevalent in the pediatric population but can happen at any age are Ewing sarcoma and rhabdomyosarcoma. Both are far more chemosensitive and radiosensitive than many sarcoma histologies that tend to occur more frequently in the adult population.94 For Ewing sarcoma, local control is important in the localized or metastatic setting, and given current data does not support an additive benefit for surgery and radiotherapy, we favor local control being planned as a single modality to minimize the morbidities of both.96–98 For this reason, for tumors located in areas of expendable bones or potentially resectable with a reasonable rehabilitation pathway, we favor a surgical approach. However, if surgery would result in undue morbidity, which is often the case for spinal or pelvic tumors, then a definitive radiotherapy approach may be more appropriate, balancing careful consideration of the risk of arresting growth, fertility, and the potential of a secondary malignancy within the RT field. Fig. 27.4 is an example of a patient with Ewing sarcoma treated with definitive radiotherapy to 55.8 Gy in conventional fractionation with proton therapy deemed medically necessary to reduce her uterine and contralateral ovary dose. Lastly, while many of the pediatric malignancies tend to be more radiosensitive and can be treated to lower doses of 10–30 Gy (e.g., Wilms, neuroblastoma, Hodgkin lymphoma), their treatments often involve large fields. Careful attention is needed when designing a radiation therapy plan for skeletally immature patients where the uninvolved but directly vertebral bodies touching the radiation field should have uniform coverage with a dose no less than 3–5 Gy decrease from the prescription dose to avoid steep dose gradients in order to minimize the risk of scoliosis.99 There is a tradeoff as well regarding using more sophisticated planning techniques such as IMRT that can have a larger low-dose “bath” versus using 3D conformal radiotherapy or proton radiation therapy which only uses a few select beam angles but may have less conformality at the tumor itself of the higher dose radiotherapy lines. Another careful area of consideration for pediatric  

 

 

patients is to try to minimize the dose to the developing breast buds using the ALARA (As Low As Reasonably Achievable) principle to reduce the effect on breast development and secondary malignancy.

Pediatrics: Spotlight on upfront multidisciplinary evaluation topics When designing a local control plan for a patient with a pediatric cancer, it is important to discuss in a team-based setting the potential benefits and toxicities for each patient’s case, presenting all options to the patient and their family as part of the informed consent process. While the functional change from a surgical procedure is often immediately apparent, it is important to realize the long-term effects from radiotherapy are gradual and manifest over years to decades and may be irreversible. A pediatric radiation oncologist addresses the dose received to specific structures as this can speak to important screening needs (i.e., cardiac, breast cancer, hormone) and influence future treatment decisions.

Benign disorders RT was historically used to treat many benign conditions, such as ankylosing spondylitis, tinea capita, and eczema, that fortunately now are treated with other therapies. However, it is still used in the treatment of noncancerous conditions such as prevention of heterotopic ossification after hip replacement surgery and keloid scars.100 Doses used are low, so unlikely to cause significant problems with fibrosis. However, especially in a younger person, the concerns about development of a radiation-induced malignancy must be weighed against the potential gain of using radiation for benign disease.

Specific toxicities and complications Bony injury Osteoradionecrosis (ORN) is a necrotic wound manifested in irradiated bone that persists without healing for 3–6 months, in the absence of tumor recurrence.101 It presents as clinically exposed bone, sometimes without any pain, and radiologic evidence of necrosis on both CT and MRI between 1 and 3 years following radiation. Radiologic findings may mimic disease recurrence. ORN is mostly seen as a result of treating head and neck cancer and most frequently affects the mandible. Radiation-related risk factors include fraction size (>2 Gy), the volume of bone irradiated, a total dose to the bone of >60 Gy, and re-irradiation. The modality of radiation used is also important, because particle therapy (electrons, neutrons, and protons), brachytherapy, and kilovoltage energy can result in higher absorbed doses within bone than from megavoltage RT, e.g., photons. The use of 3D treatment-planning systems, improvements in immobilization, as well as conformal techniques such as IMRT and higher precision with IGRT for localization, help to minimize the volume of bone in the target, as well as the dose. Other risk factors in the head and neck region include poor oral hygiene and dental extraction, making careful dental preparation an integral part of treatment planning. Prior to initiation of radiation therapy, patients undergo dental clearance. Dental extractions, if indicated, are done prior  

 

Specific toxicities and complications

to the start of RT. During RT planning, the radiation oncologist delineates the mandible, maxilla, and salivary glands and identifies dose constraints. After completion of radiotherapy, patients proceed with life-long daily fluoride treatments and maintain a pristine dental hygiene regimen. Concurrent chemotherapy causes mucositis and xerostomia, further increasing the risk, as does the xerostomia resulting from relatively low doses to the parotid. ORN arising in other sites can also be associated with trauma and surgery. Although ORN in the head and neck region had an incidence of 6.8% in 1968,102 it is fortunately now quite rare, with more recent series reporting incidences of 0–2%.103,104 Bisphosphonates can cause osteonecrosis without radiation,105 but it is still unclear what increased risks are incurred with concurrent radiation and bisphosphonate therapies. Bone fractures occurring within the irradiated volume are more common. Rib fractures tend to be the result of coughing. Limb fractures can happen with minimal trauma. No intervention is necessary for clavicles or ribs, but long bones usually require an intramedullary nail and there can be long delays in union. An analysis of fractures associated with soft-tissue sarcoma identified that the total dose to the bone and the volume irradiated were critical factors, leading to recommendations that the maximum dose to the bone should be 59 Gy, and that the volume of bone receiving >40 Gy be limited to 64%,106 in addition, circumferential irradiation of the bone to 50 Gy.107  

 

 

Bone growth in children It is widely recognized early on that radiation impedes bone development in children, leading to limb shortening, truncal shortening (if abdominal RT is given), asymmetry (including scoliosis), deformity and functional impairment. It was difficult initially to quantify dose constraints as treatments and dosimetry were very heterogeneous. Radiologically, there are changes on the growth plate that resemble rickets, with metaphyseal sclerosis, metaphyseal fraying, and epiphyseal plate widening, reflecting the radiosensitivity of rapidly proliferating cells in this region. Awareness of the child’s skeletal maturity is of importance when deciding if elective coverage of the adjacent vertebral bodies is required for symmetric growth.99 Most girls complete their accelerated growth phase between age 11 and 13 while most boys complete this from ages 13 to 15; after this pubertal acceleration phase all gradients are acceptable. If the clinical history is ambiguous regarding growth, one can consider wrist radiographs to assess. The most important radiotherapy factors are the total dose and volume of bone irradiated. Although 30 Gy is considered the tolerance threshold dose, growth effects are seen with as low a dose as 15 Gy, suggesting a very steep dose–response curve in this range.108 If the spine is within the high-dose volume, uniform dose across the whole vertebral body is recommended to reduce the risk of scoliosis.94 Craniofacial growth is different to long bones, since these bones develop through intramembranous ossification, resulting in a complex 3D pattern of growth.109 Disruption of this growth by radiation in all or any part of the head and face can cause significant clinical problems, including distorted appearance and functional problems related to eating. Dentition is also affected.  

 

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Cranial irradiation is used for prophylaxis against central nervous system relapse in leukemia and for many embryonal CNS malignancies. Not only can this affect cognition and bone growth, it can also impair the production of growth hormone, which results in decreased bone mineralization.110 Genetic factors are important, for example, in the treatment of retinoblastoma, where there may be much greater sensitivity to RT. Biological factors that are disrupted by RT include remodeling of the extracellular matrix in response to paracrine and endocrine signaling that affects chondrocyte production. Radioprotective agents, such as amifostine, have been studied clinically and found to protect a number of cell lines, such as osteoblast-like, endothelial, and fibroblastic, from harmful effects of radiation.111

Cardiovascular disease There has been a well-established correlation between radiation and risk of cardiac morbidity and mortality, particularly well studied in survivors of breast cancer and Hodgkin lymphoma. Radiation therapy for left-sided breast tumors has an increased risk of subsequent ischemic cardiac disease by 7.4% per Gy mean heart dose that follows a linear, no-threshold relationship.112 Several techniques have been developed to reduce heart and coronary vessel dose. Deep inspiratory breath-hold (DIBH) is a technique to reduce the heart dose for left-sided breast cancer irradiation with current data showing clinical benefit based on modeled risk estimates, most notably in patients with high-baseline cardiac risk.113 With this technique, which displaces the heart away from the chest wall, CT simulation involves both DIBH and free breathing scans for dosimetric comparisons of the heart and chest wall separation with breath-hold technique. Proton therapy is another technique that can be used to treat the chest wall and regional nodes, including IM nodes, while minimizing exit dose to the underlying heart.

Lymphedema The mechanics of RT-related lymphedema are due to the radiation-induced fibrosis causing compression of the lymph vessels. When assessing lymphedema in someone who has had a previous cancer diagnosis, it is important to exclude recurrent disease before assuming that the edema is related to treatment. However, lymphedema after breast cancer is common. Norman et al. identified 42% 5-year accumulative incidence in a 5-year prospective, population-based study of breast cancer survivors. However, the majority (23%) described only mild lymphedema, and only 2% had developed chronic, severe edema.114 Independent risk factors for breast cancer-associated lymphedema include radiation treatment of the axilla, the extent of axillary lymph node dissection, the type of breast surgery, and the presence of regional lymph node metastases.115 A history of infection and injuries, and the patient’s body mass index are also associated factors. The combination of RT and axillary lymph node dissection confers the greatest risk.116 A large series from Massachusetts General Hospital reported lymphedema rates of 10% in women who had breast-conserving surgery and RT to the axilla,117 although historically, higher rates have been reported. It has also been suggested115 that, with survival and longevity, this late toxicity becomes

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more prevalent. However, as sentinel lymph node biopsy has become the standard of care in early breast cancer, this will result in a lower risk of lymphedema than conventional axillary lymph node dissection risks.118

Brachial plexopathy Brachial plexopathy is most commonly due to metastatic disease involving the brachial plexus, and it can be very difficult to distinguish between the late side effect of RT versus recurrence. PET has been reported to be helpful.119 However, it is also a rare (1%) complication of radiation treatment.120 Its development is dependent not just on total dose, with a marked increase above 60 Gy, but also on the dose per fraction. RT technique is also a very important factor, as older breast RT techniques that extended to the lymph nodes could result in overlapping fields just above the clavicle immediately above the brachial plexus, meaning that the plexus received up to twice the prescribed dose. Concurrent chemotherapy also increased the risk.  

Radiation-induced malignancies Radiation has been shown to induce malignant transformation in vitro, for example, in laboratory mice, and in vivo, for example, from atom bomb survivors, as well as long-term follow-up studies of treated patients. Estimations of risk are not easy, due to the heterogeneity of variables. Three mechanisms for radiation-induced malignancy have been suggested: (1) DNA damage and subsequent mutation; (2) disturbances of multiple defense or control mechanisms within the cell at the molecular level; and (3) the chronic ongoing damage of irradiated tissue.121 Radiation-induced malignancies are rare within the first 5 years after treatment, and, in the absence of chromosomal fragility syndrome, usually present many years after treatment. As more cancers are cured, and the number of long-term survivors increases, so does the risk of radiation-induced malignancies.122 Although a second malignancy rate of 1 per 100,000 patients treated is often cited, this figure is only an estimate, and may be misleading. Many different mathematical models are used to standardize the doses, dose per fraction and quality of radiation, as well as the volume of the target, the organs treated, and the age of the patient. Second primary tumors are more common in those who have already had a malignancy, with a relative risk (RR) of 1.12, regardless of treatment. Chemotherapy, especially alkylating agents, is also carcinogenic, although more likely to induce leukemia than a solid tumor, and within a much shorter latency period. The addition of chemotherapy during RT also increases the risk. Some of the best data on pediatric radiation-associated malignancy comes from the very comprehensive Childhood Cancer Survivor Study childhood survivors; in particular, the long-term outcomes of a cohort of 5-year survivors identified a relatively small risk of adverse events, including second cancers, as well as pulmonary and pregnancy complications,123 although also identifying large variations in findings. In children, susceptibility varies according to age and the type of tissue irradiated, with leukemia developing after 5–8 years, and solid tumors, the commonest of which are thyroid cancers, breast cancers, and bone and central nervous system

malignancies, usually occurring many years later. These survivors require vigilant screening for these malignancies, as well as cataracts, thyroid disease, and osteoporosis.124 Some second primary malignancies, especially carcinomas, arise around the periphery of the target within the lower-dose volume. Concerns have been expressed about the risk of techniques such as IMRT: although they have very conformal high-dose volumes and can minimize dose to critical structures, there is a large lower-dose volume from the multiple-beam entry through normal tissues.125,126 Thyroid cancer is unlikely when the gland has received doses over 30 Gy. Conversely, sarcomas tend to arise in heavily irradiated tissues, and appear to have a dose–response effect. Survivors of Hodgkin lymphoma treated with mantle radiation (i.e., mediastinal, cervical, and axillary nodal RT with shields over the lungs) have four times the risk of developing breast cancer. The woman’s age at the time of RT is extremely important: adolescent girls aged 10–16 years have as much as a 136-fold greater risk of developing breast cancer than their non-irradiated peers.127 Factors such as smoking can markedly increase the risk of developing primary lung cancer, even in parts of the lung that received only a tiny, scattered dose. Some genetic predispositions, such as Li–Fraumeni syndrome, which is linked to germline mutations of the p53 suppressor gene, or ATM and RB gene carriers, are exquisitely susceptible to damage from any form of radiation, and subsequent malignancies present frequently and earlier.  

Exposure to radiation Radiation accident studies have shown that there is a proportional relationship between the amount of radiation exposure and the risk of developing cancer. The sievert (Sv) is the SI unit that measures the biological effect of absorbed dose, taking into consideration the relative biological effectiveness of the radiation (e.g., 1 for photons and electrons, 20 for high-dose neutrons and α-particles) and the biological effect on different organs. When all of these weightings are 1, then 1 Sv = 1 Gy. The gray is a unit of absorbed dose in any material defined only by physical, not biological, properties of radiation. The sievert is used to quantify risk of radiation damage, including cancer. To put this into perspective, on average, a chest X-ray is 0.34 mSv, mammogram 0.48 mSv, and CT thorax 6 mSv. The biggest contributor of background radiation source is radon, which is approximately 2 mSv annually. There is background cosmic radiation of 0.24 mSv per year, and a passenger on a return flight between Seattle, WA and Toronto, ON would be exposed to 0.085 Sv. Radiation oncologists are limited to an occupational exposure of 50 mSv per year, excluding medical and background sources of radiation, but after the March 2011 earthquake and subsequent explosion in a nuclear reactor, the emergency nuclear workers at Fukushima, Japan were exposed to up to 400 mSv per hour. The Japanese public already has a 20–25% lifetime risk of cancer, and exposure to 400 mSv increases that risk by 2–4%. Survivors of the atom bombs in Hiroshima and Nagasaki have an excess risk of cancer (RR 1.42 at 1 Sv) that persists through their lifetime. Exposure to 1 Sv increases the lifetime risk of fatal cancer by approximately 5%. The most sensitive organs to this sort of accidental exposure are bone marrow and thyroid, and leukemia is the most common resulting malignancy. Radiation sickness is an acute effect of radiation exposure, causing nausea,  

 

 

 

 

 

 

 

 

 

 

 

 

Conclusion and future trends

headache, and bone marrow suppression, and is rarely experienced at exposures of less than 1 Sv. Regardless of the regulatory safety requirements, the ALARA principle is the mantra of all who work with ionizing radiation in their efforts to reduce the risk of harm. Ways to minimize radiation exposure include reducing time of exposure, increasing the distance from the radiation source, and utilizing adequate shielding.  

Conclusion and future trends Radiation treatment uses ionizing radiation to treat malignancies as a primary therapy, or often, as part of a planned collaborative multidisciplinary approach, used in combination with systemic therapy and surgery. Like surgery, it is a local therapy, and has a curative, adjuvant, or palliative role in managing most cancers. Although acute toxicities are reversible, late toxicities are not, and are related mostly to the loss

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of normal fibrosis mechanisms. The risk of radiation-induced malignancy, as well as other late side effects, becomes more important as more cancers are cured, and the proportion of survivors grows. Dramatic advances in radiation treatment-planning, delivery, and verification technology have increased the accuracy and precision of treatment, allowing higher doses to tumor, and reducing the risk of radiation injury by sparing more normal tissue. Improvements in RT-planning systems provide not only the ability to apply dose constraints to specified structures, but also to provide data that help quantify risk of toxicity, in tandem with better reporting and collection of data and outcomes. Improved patient selection, risk factor identification and biomarkers may help guide those at increased risk of toxicity and/or eligible for consideration of therapeutic de-escalation to further minimize the potential morbidity of radiation therapy. However, access to site-specific multidisciplinary oncologic decision-making and care remains the cornerstone of individual patient management.

Bonus images for this chapter can be found online at Elsevier eBooks+ Fig. 27.5 Incident photon knocks an electron off the outer ring and scatters it along a pathway through a distance before the electron energy is absorbed. Fig. 27.6 (A) Depth dose distribution for 6 MV photons: Only approximately 30% of the dose is absorbed at the skin surface; the maximum dose (100%) is absorbed at a depth of 1.5 cm, and then attenuates by less than 5% per cm. (B) When two beams are opposed, depth doses can be added, resulting in an even distribution across the target volume. (C) If a higher dose is required at the skin surface, a strip of bolus material is placed on the skin. Fig. 27.7 Multileaf collimators (photographed looking into the head of the machine) are used to provide static shielding, or, when programmed dynamically, differential dose absorption for intensity-modulated radiation therapy. Fig. 27.8 (A) Axial intensity modulated radiation treatment plan of a sarcoma involving the mediastinum extending into a thoracic vertebral body. The technique allowed a radical dose (66 Gy) to be delivered to the target volume, but constrained the cord dose to a safe dose of 52 Gy. (B,C) Coronal and sagittal distributions. Fig. 27.9 A 51-year-old male with metastatic sarcoma to the spine resulting in cord compression, s/p surgical decompression and fixation, followed by postoperative SBRT to 30 Gy in 5 fractions for durable local control. Fig. 27.10 Intraoperative radiation therapy (IORT) delivering a large single fraction of RT to the operative bed in the retroperitoneum. This photograph shows the cone, or electron applicator (the metal cylinder) after it has been positioned over the target volume. It will now be secured into place, the position verified, the monitor units and dose rate calculated, before personnel leave the room and RT is delivered. Set-up takes approximately 15–20 minutes, but the treatment is delivered in only 2–3 minutes.  

 

 

 

 

 

Access the reference list online at

  

Elsevier eBooks+

Fig. 27.11 Therapeutic ratio curves. (A) In an ideal situation, a tumor response would be almost complete before causing any tissue reaction. (B) More commonly, the dose required to achieve adequate tumor response also causes an unacceptably high risk of normal tissue reaction. (C) An acceptable trade-off is that one allows adequate tumor control and less than 5% probability of normal tissue complications. Fig. 27.12 Acute skin reactions can be severe, depending on multiple factors, including the volume and total dose. (A) Clinical photograph of the posterior thigh of a woman with a large (28 cm) sarcoma, treated with postoperative radiation to a total dose of 66 Gy. She had a history of over 240 lb (109 kg) intentional weight loss, and had marked skin redundancy, resulting in multiple folds, exacerbating her acute reaction. (B) Rapid improvement after just 7 days of conservative management with application of saline soaks. The white patches are healthy islands of new skin. (C) 14 days post completion of RT. Fig. 27.13 Acute skin reaction on the neck. (A) An acute skin reaction at the base of the neck at a completion dose of 70 Gy. (B) 1 week later, again demonstrating rapid recovery and the skin islands. This reaction at the base of the neck is fairly typical, and is a result of the obliquity of the surface and narrowness of the shoulder. Fig. 27.14 A severe late skin reaction as a result of fast neutron therapy 22 years earlier following excision of a large dermatofibrosarcoma protuberans (DFSP) tumor from the shoulder. It demonstrates characteristic telangiectasia, hypopigmentation, subcutaneous fibrosis and, medially, delayed healing of a minor skin abrasion.  

 

 

 

 

References

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99. Hoeben BA, Carrie C, Timmermann B, et al. Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group. Lancet Oncol. 2019;20(3):e155–e166. 100. Laramore GE, Stelzer KJ. Radiation therapy for benign disease: an old area revisited. Lancet. 1998;352(9131):834–835. 101. Schwartz HC, Kagan AR. Osteoradionecrosis of the mandible: scientific basis for clinical staging. Am J Clin Oncol. 2002;25(2):168–171. 102. Clayman L. Clinical controversies in oral and maxillofacial surgery: Part two. Management of dental extractions in irradiated jaws: a protocol without hyperbaric oxygen therapy. J Oral Maxillofac Surg. 1997;55(3):275–281. 103. Ben-David MA, Diamante M, Radawski JD, et al. Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions. Int J Radiat Oncol Biol Phys. 2007;68(2):396–402. 104. Studer G., Graetz K.W., Glanzmann C. In response to Dr. Merav A. Ben-David et al. ("Lack of osteoradionecrosis of the mandible after IMRT," Int J Radiat Oncol Biol Phys 2007:In Press). Int J Radiat Oncol Biol Phys. 2007;68(5):1583-1584. 105. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7(6):508–514. 106. Dickie CI, Parent AL, Griffin AM, et al. Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose. Int J Radiat Oncol Biol Phys. 2009;75(4):1119–1124. 107. Bishop AJ, Zagars GK, Allen PK, et al. Treatment-related fractures after combined modality therapy for soft tissue sarcomas of the proximal lower extremity: can the risk be mitigated? Pract Radiat Oncol. 2016;6(3):194–200. 108. Eifel PJ, Donaldson SS, Thomas PR. Response of growing bone to irradiation: a proposed late effects scoring system. Int J Radiat Oncol Biol Phys. 1995;31(5):1301–1307. 109. Gevorgyan A, La Scala GC, Neligan PC, Pang CY, Forrest CR. Radiation-induced craniofacial bone growth disturbances. J Craniofac Surg. 2007;18(5):1001–1007. 110. Sala A, Barr RD. Osteopenia and cancer in children and adolescents: the fragility of success. Cancer. 2007;109(7): 1420–1431. 111. Daniel M, Luby AO, Buchman SR. Overcoming nuclear winter: the cutting-edge science of bone healing and regeneration in irradiated fields. Plast Reconstr Surg Open. 2021;9(6):e3605. 112. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–2106. 113. Eldredge-Hindy HB, Duffy D, Yamoah K, et al. Modeled risk of ischemic heart disease following left breast irradiation with deep inspiration breath hold. Pract Radiat Oncol. 2015;5(3):162–168. 114. Norman SA, Localio AR, Potashnik SL, et al. Lymphedema in breast cancer survivors: incidence, degree, time course, treatment, and symptoms. J Clin Oncol. 2009;27(3):390–397. 115. Tsai RJ, Dennis LK, Lynch CF, Snetselaar LG, Zamba GK, Scott-Conner C. The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors. Ann Surg Oncol. 2009;16(7):1959–1972. 116. Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer. Am J Surg. 2004;187(1):69–72. 117. Coen JJ, Taghian AG, Kachnic LA, Assaad SI, Powell SN. Risk of lymphedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys. 2003;55(5):1209–1215. 118. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98(9):599–609.















































































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119. Eubank WB, Mankoff D, Bhattacharya M, et al. Impact of FDG PET on defining the extent of disease and on the treatment of patients with recurrent or metastatic breast cancer. AJR Am J Roentgenol. 2004;183(2):479–486. 120. Pierce SM, Recht A, Lingos TI, et al. Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys. 1992;23(5):915–923. 121. Suit H, Goldberg S, Niemierko A, et al. Secondary carcinogenesis in patients treated with radiation: a review of data on radiationinduced cancers in human, non-human primate, canine and rodent subjects. Radiat Res. 2007;167(1):12–42. 122. Tubiana M. Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol. 2009;91(1):4–15. discussion 1-3.















123. Robison LL, Green DM, Hudson M, et al. Long-term outcomes of adult survivors of childhood cancer. Cancer. 2005;104(11 Suppl): 2557–2564. 124. Neglia JP, Nesbit Jr. ME. Care and treatment of long-term survivors of childhood cancer. Cancer. 1993;71(10 Suppl): 3386–3391. 125. Brenner DJ. Extrapolating radiation-induced cancer risks from low doses to very low doses. Health Phys. 2009;97(5):505–509. 126. Hall EJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65(1):1–7. 127. Deniz K, O’Mahony S, Ross G, Purushotham A. Breast cancer in women after treatment for Hodgkin’s disease. Lancet Oncol. 2003;4(4):207–214.



















28 Lymphedema: pathophysiology and basic science Stav Brown, Michelle Coriddi, and Babak J. Mehrara

SYNOPSIS

ƒ Lymphedema is a progressive disease that can occur as a result of congenital defects, iatrogenic injury, or infection of the lymphatic system. ƒ The lymphatic system is comprised of capillary lymphatics that drain into progressively larger collecting vessels. ƒ Lymphedema can develop due to genetic/developmental abnormalities of the lymphatic system (i.e., primary lymphedema) or more commonly, after trauma or infection of the lymphatic system (secondary lymphedema). ƒ The pathophysiology of lymphedema is complex and involves multiple processes driven by chronic inflammatory reactions, including pumping failure, impaired collateral vessel formation, fibroadipose deposition, and epidermal changes. ƒ Obesity and lymphedema are intimately related. ƒ Although there is currently no definite cure for lymphedema and its late changes are likely not reversible, early identification and comprehensive evaluation are key for improved outcomes.

Introduction Lymphedema is a progressive disease of the lymphatic system characterized by chronic inflammation, adipose deposition, hyperkeratosis, and fibrosis.1,2 Although the precise mechanisms regulating the development of lymphedema remain unknown, a key inciting event is lymphatic dysfunction and impaired clearance of interstitial fluids. Lymphedema can develop due to genetic or developmental abnormalities of the lymphatic system (i.e., primary lymphedema) in which lymphatic vessels are absent or poorly developed.3 More commonly, lymphedema develops after trauma or infection of the lymphatic system (secondary lymphedema).4 These inciting events set off a cascade of tissue changes that in some cases ultimately result in massive accumulation of adipose tissue and the classic findings of elephantiasis (Fig. 28.1).5

Estimates of the incidence of lymphedema vary widely. It is estimated that 200 million patients in low-income countries suffer from lymphedema secondary to parasitic infections by Wuchereria bancrofti.6 This disease has a variable course, with smoldering disease in some and rapidly progressive/ disabling lymphedema in others. Patients with filariasis may develop massive swelling of the limbs and genitals due to direct lymphatic obstruction by the parasites and inflammatory reactions resulting in significant morbidity and mortality.6 In high-income countries, the most common cause of lymphedema is cancer treatment.7 Breast cancer survivors comprise the largest group of affected individuals due to the high incidence of breast cancer in these regions. It is estimated that 15–40% of all patients who undergo axillary lymph node dissection go on to develop lymphedema (ALND).8–10 The variability in rate is due, at least in part, to differences in the diagnostic criteria and the length of follow-up.1 Recent advances in sentinel lymph node biopsy (SLNB) have decreased the requirement for full ALND and therefore the incidence of lymphedema. However, lymphedema does develop even after SLNB in 5–7% of patients.11,12 In addition to lymph node dissection, extensive skin resections, radiation therapy, obesity, and infections have also been identified as significant risk factors for disease development.13–15 Lymphedema is not exclusively a disease of breast cancer survivors and occurs as a complication of treatment of most other solid tumors, with reported incidence of 16% in melanoma, 30% in sarcoma, 20% in gynecologic tumors, 10% in genitourinary tumors, and 4% in head and neck cancers.16 In fact, a recent meta-analysis estimated that nearly 1 in 6 patients treated for a variety of solid tumors go on to develop lymphedema.16,17 The development of lymphedema in patients with sarcomas is an interesting phenomenon since lymph nodes are rarely removed in these tumors, suggesting that widespread injury to the superficial lymphatic system (as would occur with a wide excision of a skin sarcoma in combination with radiation therapy) is sufficient to disrupt the lymphatic

Anatomy and physiology

vasculature and lead to the development of lymphedema even when the regional lymph nodes are not injured. Cancer survivors with lymphedema are severely impacted by the disease, suffering chronic pain and decreased ability to perform activities of daily living as well as being at high

473

risk for developing severe infections necessitating prolonged hospitalization.6,18 Given that the prevalence of lymphedema is expected to increase with increasing incidence of its predisposing factors such as obesity and radiation, lymphedema represents a substantial biomedical burden.6,17,19–21 Based on both clinical and laboratory experience, this chapter overviews the cellular mechanisms that regulate the pathophysiology of lymphedema, as well as the basic principles of evaluation and management of lymphedema patients.

Anatomy and physiology Lymphatic circulation

Figure 28.1 Severe (grade III) lymphedema of the left leg after melanoma resection.  

The lymphatic system plays a key role in many physiologic processes, including interstitial fluid and immune cell transport, regulation of inflammation, responses to host or foreign antigens, and fat absorption, among others.22 The transport of immune cells and interstitial fluid from the periphery begins in capillary lymphatics located in the dermis (Fig. 28.2). These thin-walled, relatively large vessels are comprised of a single layer of lymphatic endothelial cells (LECs) with little to no basement membrane, are physically tethered to the surrounding tissues by anchoring filaments and to each other by overlapping or intercalating button-like junctions.23 Minute changes in tissue fluid content cause adjacent LECs to separate due to the physical connections of these cells with the surrounding tissues by anchoring filaments, thus enabling entrance of cells and interstitial fluid into the initial lymphatics. Once the interstitial fluid has entered the lymphatic

Normal

Skin Lymph capillaries and pre-collectors

Subcutaneous tissue

Lymph collecting vessels

Deep tissue

A

Figure 28.2 Microscopic anatomy of the lymphatic system. (A) Schematic of superficial and deep lymphatics of the skin. (B) Fluorescent immunehistological depiction of mouse ear skin lymphatic tree. Mouse ear skin whole mount stained for Prox1 (pan LEC marker) and Smooth muscle actin alpha to identify the capillary, pre-collecting and collecting lymphatic vessels in a single plane (upper panel). High magnification images 1, 2, 3, and 4 from the upper panel image showing spatial separation of capillaries at the ear tips to collectors at ear base. Note the collecting lymphatic vessels being tightly wrapped by SMA cells enabling them to pump the lymph. (A, Adapted from Suami H, Pan WR, Taylor GI. Changes in the lymph structure of the upper limb after axillary dissection: radiographic and anatomical study in a human cadaver.  

Collectors

Pre-collectors

Initial capillaries

Base

Tip of the ear 4

SMA α

3

2 1

PROX1

4

B Plast Reconstr Surg. 2007;120:982–991.)

3

2

1

474

CHAPTER 28 • Lymphedema: pathophysiology and basic science  

system, the overlapping regions between LECs is reestablished, maintaining the fluid within the lymphatic vessel. Fluid is propelled passively to pre-collectors and collecting lymphatics located in the deeper dermis and subcutaneous tissues. The LECs in collecting vessels, in contrast to the capillary lymphatics, have continuous, “zipper like”, endothelial cell junctions that prevent fluid leak with physical changes in the microenvironment. In addition, collecting lymphatics have a basement membrane and are covered by smooth muscle cells that can contract to propel lymphatic fluid forward. Lymphatic collectors also have bicuspid valves located every 1–2 mm that ensure one-way flow of interstitial fluid blocking backflow into the capillary lymphatic system.24 The functional lymphatic unit is defined as a lymphangion and contains a region of collecting lymphatic vessels between two valves (Fig. 28.3). Lymphatic flow is determined by two factors.25,26 Passive compressive forces arise from external compressive forces such as muscle contractions, respiration, regional arterial pulsation, and gravity. These forces, as their name implies, passively propel interstitial fluid centrally. In normal limbs (i.e., without history of lymphatic injury), passive compressive forces such as massage or muscular contractions do not significantly increase lymphatic pressure in collecting lymphatics and do not increase flow. Active compressive forces arise from intrinsic contraction of smooth muscle cells surrounding the collecting lymphatics. These muscle cells are unique in that they have features of both smooth and striated muscles and have basal myogenic activity. Myogenic forces in the lymphatic system, similar to the heart, are responsive to preload and afterload pressure changes. In addition, the force and frequency of lymphatic pump contraction can be modulated by vasoactive substances such as histamine and substance P, among others.25 In general, increases in preload and afterload lead to an increase in contraction frequency and strength up to a point. Persistent increases beyond this point lead to lymphatic pump failure and vessel dilatation.  

A

Int α 9

PROX1

SMA α

Lymphangion

Valve Valve

SMA α Valve

Lymph nodes Lymph nodes filter lymphatic fluid as it is transported within the lymphatic system back to the venous circulation (Fig. 28.4). Although the number of lymph nodes is somewhat variable, a typical adult has 600 lymph nodes located in various regions and clustered in areas where body parts come together or in/ around intra-abdominal organs.27 Interstitial fluid is transported centrally by collecting lymphatics and enters the subcapsular sinus of the lymph node via afferent lymphatics. From there, the interstitial fluid (and the antigens, antigen-presenting cells, and inflammatory cells it contains) drain through lymph sinuses that surround lymph node follicles where B cells reside. Lymphatic sinuses are lined by reticular endothelial cells and antigen-presenting cells, enabling presentation and response to self/foreign antigens. Macrophages located in these regions can also phagocytose bacteria for processing and clearance. In addition, fluid exchange occurs through regional high endothelial venules that permeate the lymph node enabling hematogenous delivery of immune cells and cytokines to the lymph node. The lymphatic fluid exits the lymph node via efferent lymphatics located at the lymph node medulla progressing to the next lymph node chain or centrally for return back to the venous system.28

Int α 9

B

PROX1

Figure 28.3 Anatomy of a lymphangion. (A) Schematic representation of a lymphangion (segment of lymphatic collector between two valves). (B) Fluorescent immune-histological representation of a lymphangion (segment of lymphatic collector between two valves) in mouse ear skin (upper). Note the two valves immune-positive for integrin alpha 9 (a valve marker). High magnification image of a single valve showing SMA cells (green), valve leaflets (red), and PROX1-stained LECs (blue).  

Etiology of lymphedema Primary lymphedema Numerous genetic defects are associated with development of primary lymphedema (Table 28.1) and germline sequence variations have been identified in at least 20 human genes.3 These disorders have a highly variable natural history in terms of timing of presentation and severity of symptoms. In addition, primary lymphedema may be familial with known or suspected genetic defects, may occur as a result of spontaneous mutations, or in some cases develop without a known cause. Familial forms of primary lymphedema, even within

Etiology of lymphedema

475

Afferent lymphatics

Subcapsular sinus Lymphatic trabecula

Blood capillaries

Efferent lymphatic vessel

High endothelial venule

Artery Vein Hilum

B cell zone

Figure 28.4 Schematic representation of a lymph node. Lymph enters the lymph node subcapsular sinus via afferent lymphatics and drains through the node via lymph sinuses, eventually exiting the node via the efferent lymphatics in the hilum. Blood capillaries and high endothelial venules enable leukocytes to enter the lymph node and are a site of fluid exchange.

Capsule

T cell zone

 

Table 28.1 Genetic mutations and lymphedema  

Gene

Syndrome

Pathology

References

FLT4 (5q35) (coding region for vascular endothelial growth factor receptor 3)

Milroy disease

Primary lymphedema of the lower extremities. Upslanting “ski jump” toenails due to nail bed edema

38,136,137

FLT4 (4q34) (coding region for vascular endothelial growth factor C)

Milroy-like lymphedema

Congenital lower limb lymphedema

29

FOXC2

Lymphedema-distichiasis syndrome

Lower-limb lymphedema most often presents at puberty; double row of eyelashes

29,30,156

SOX18

Hypotrichosis–lymphedema– telangiectasia syndrome

Lymphedema, hair loss, and small dilated blood vessels near the surface of skin

31

GJC2 (coding for connexin 47 (CX47)

Meige’s disease

Impaired gap junction activity, increased risk of breast cancer-related lymphedema

32

CCBE1 (18q21) (encodes for collagen and calcium binding EGF domain 1)

Hennekam syndrome

Severe lymphedema in limbs, genitalia, and face; facial anomalies; seizures, mental retardation; and stunted growth. Symptoms often present in utero

33

KIF11 (10q24)

MCLMR syndrome

Microcephaly, congenital lower limb LE, ocular abnormalities, learning disabilities

34

GATA2 (3q21)

Emberger syndrome

Unilateral or bilateral lower limb lymphedema; presents in childhood; severe cutaneous warts; myelodysplasia

35

WILD syndrome

WILD syndrome (warts, immunodeficiency, lymphedema, and dysplasia)

36

Proteus syndrome

Lymphatic malformations, skeletal, cutaneous, and CNS abnormalities

37,38

AKT1

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CHAPTER 28 • Lymphedema: pathophysiology and basic science  

members of the same family, can have different presentation due to the penetrance of the genetic mutation or causative factors and interaction with environmental regulators.3,29–32 Thus, in some cases primary lymphedema may present shortly after birth (i.e., congenital lymphedema) or, more commonly, become manifest years later with progressive symptoms (lymphedema praecox or lymphedema tarda).33,34 In most cases of primary lymphedema, patients present with unilateral lower extremity lymphedema (~70%) at some point between birth and age 35.35 The lymphatic system is poorly developed with decreased numbers of lymphatic vessels (most commonly collecting lymphatics). However, it is unclear if patients with primary lymphedema have defects of the lymphatic system at birth or if these changes develop postnatally. The current evidence suggests that in most cases some degree of lymphatic dysfunction is present at birth and that these changes gradually worsen over time.29–31 The rate at which these changes occur is variable and can be altered by environmental factors leading to differential presentation of the disease. Studying these changes has been a challenge due to our inability to serially monitor the lymphatic system noninvasively; however, recent advances with lymphatic imaging have been helpful in this regard. Congenital lymphedemas occur more commonly in females, more commonly involve the lower extremities, and account for 10–25% of all primary lymphedemas.36 The degree of swelling of the limbs can be variable and, in some cases, may result in severe abnormalities in one limb and relatively mild or absent disease in the contralateral limb. Our knowledge of the molecular mechanisms affecting lymphangiogenesis has improved substantially over the past 20 years, mainly due to the identification of regulatory molecules and markers specific to the lymphatic endothelium. Several signal transduction pathways have been described in the differentiation and growth of LECs, and differentiate lymphatics from blood vessels.37 The signal-transduction system for LEC growth, migration, and survival is formed by vascular endothelial growth factors (VEGF) C and D and their receptor VEGFR-3, a key signaling molecule primarily expressed by LECs.38–41 VEGF-C and VEGF-D also bind to neuropilin-2 (Nrp2), a semaphorin receptor in the nervous system that is also expressed in lymphatic capillaries.42 Not surprisingly, Nrp2-deficient mice have lymphatic hypoplasia.43 Milroy’s disease is a familial, sex-linked disorder in which inactivating mutations occur in VEGF-R3.44 These mutations account for a relatively small number of patients with primary lymphedema (2–3%) and usually present shortly after birth with limb swelling and/or chylothorax. Activation of VEGF-R3 results in transmission of intracellular signals that regulate lymphatic endothelial cell differentiation, proliferation, migration, and endothelial-derived nitric oxide production. Consistent with these findings, patients with Milroy’s disease have hypoplastic lymphatic vessels with variable severity of dermal and collecting lymphatic vessel agenesis. In contrast to congenital lymphedemas in which the disease presents shortly after birth, patients diagnosed with lymphedema praecox present with mostly unilateral lower extremity lymphedema at some point before the age of 35.35 The vast majority of these patients develop unilateral lower extremity lymphedema and the disease has a 4:1 female to male ratio. Additional evidence implicating a sex-hormone link with this disease is the fact that most patients begin to become

symptomatic at the time of puberty.36 Histologic examination of patients with lymphedema praecox has shown variable pathologic findings; however, these patients often exhibit fewer capillary lymphatics and hypoplastic, low-caliber, collecting vessels. The diagnosis of lymphedema tarda refers to patients who develop primary lymphedema after the age of 35. This disease is a diagnosis of exclusion since secondary causes of lymphedema are much more common in this age group. In addition, lymphedema tarda is an infrequent presentation of primary lymphedema and occurs most commonly in the lower extremities of women. Although the pathophysiology of this disease remains largely unknown, recent studies have shown an association with loss-of-function mutations in the FOXC2 gene.45–47 The validity of classification schemes that categorize primary lymphedema based on the age at which symptoms present has been recently debated. This debate centers on the fact that presentation of these disorders is highly variable due to genetic and environmental factors and that this variability decreases the utility of these categories for diagnosis. As a result, recent studies have attempted to develop new classification schemes based on the presentation of disease and known genetic mutations.48 This approach categorizes congenital lymphedemas into five main groups: syndromic, systemic or visceral, disturbed growth, congenital onset, and late onset. The developers of this system contend that this diagnosis algorithm is more precise and as a result can be useful for developing and testing of diagnostic or therapeutic interventions. Due to the high genetic heterogeneity in primary lymphedema, a better understanding of the pathogenetic mechanisms of lymphedema along with accurate pheno typing may improve genotype–phenotype correlations and disease classification.49 ­

Secondary lymphedema Secondary lymphedemas develop after injury or obstruction of the lymphatic system. For example, infections with parasites in filariasis result in chronic obstruction of lymphatic channels and subsequent immune responses that impair lymphatic function leading to progressive disease.50 Filariasis is caused by roundworms (most commonly Wuchereria bancrofti, Brugia malayi, and Brugia timori) that are transmitted by mosquitos. The adult worms grow in the tissues and release larvae into the bloodstream (microfilariae) that are diagnostic for the disease. However, patients with clinical disease may be free of microfilariae in the blood, in which case the diagnosis is made either clinically, or by tissue biopsies, or serum antigen testing. Filariasis is a major cause of morbidity in low-income countries and treatment remains limited to antiparasitic medications that only kill the developing larvae rather than the adult worm. Iatrogenic lymphatic injury in the course of cancer treatment is another major cause of secondary lymphedema. In fact, lymphedema is the most common long-term complication of cancer treatment (even more common than radiation-induced sarcomas, or chemotherapy-induced renal or cardiac failure), with the potential to develop in the course of treatment for virtually all solid tumors. Lymphedema can even develop after extirpation of head and neck tumors resulting in cosmetic deformity and functional compromise.

Pathophysiology of lymphedema

Incidence of lymphedema (%)

80

60

40

20

0 0

25

50 75 Follow-up (months)

100

125

Figure 28.5 Timing of lymphedema (linear prediction) presented as a scatterplot of median follow-up times of various studies. Note that development of lymphedema occurs in a delayed fashion after surgery. (From Cormier JN, Askew RL, Mungovan KS, et al. Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer. 2010;116:5138–5149.)  

Secondary lymphedema in cancer survivors occurs most frequently months and sometimes years after the initial surgery (Fig. 28.5).51,52 This delayed presentation together with the fact that lymphedema develops in only a subset of patients who undergo lymphadenectomy is important since these findings suggest that lymphatic injury is necessary but not sufficient for the development of the disease. Thus, additional pathological changes are needed for patients to develop lymphedema after lymph node dissection. On average, secondary lymphedema in breast cancer survivors develops approximately 8 months after the initial surgery.13,53 In addition, the majority of patients (75%) are diagnosed within the first 3 years.54 In one unusual case report, a patient developed lymphedema after a seemingly innocuous injury 50 years after the initial lymphatic injury. Thus, in most cases the acute surgical swelling that develops after breast surgery and lymphadenectomy resolves within the first few weeks of surgery and, in most cases, never recurs. However, in some patients it recurs in a progressive and permanent manner 8–12 months later. This process appears to be accelerated somewhat in the lower extremity (perhaps due to the effect of gravity) with lymphedema developing on average 3–6 months after surgery.55,56

Pathophysiology of lymphedema Although lymphedema is common and morbid, surprisingly little is known about the pathophysiology of this disease. The histological hallmarks of the disease are edema, fibroadipose tissue deposition, chronic inflammation, and hyperkeratosis and recent studies have begun to shed light on how lymphatic injury leads to these protean symptoms (Fig. 28.6).1,57–59 A key concept in understanding the pathology of lymphedema is that lymphatic injury is only the initiating step and that additional pathological events are necessary for the development of lymphedema clinically. This concept is highlighted by the

477

fact that lymphedema only develops in a subset of patients who undergo lymphadenectomy, and even in these individuals does so in a delayed fashion usually months to years after surgery.1 Rockson and colleagues were one of the first groups to suggest that inflammation plays a key role in lymphedema development. It was previously known that inflammation was a histological characteristic of the disease but recent studies have shown that inflammation may play a causal role. This group has not only shown that inflammation is increased in lymphedema, but also that treatment with anti-inflammatory medications decreases the severity of the disease.60–62 Focusing on understanding the types of inflammatory reactions that occur in lymphedema, our lab has recently shown that activation and maintenance of chronic inflammatory mechanisms with resultant tissue fibrosis underlie these additional steps.1,58,59 We have shown that lymphedema develops after lymphatic injury in response to induced infiltration and differentiation of CD4+ cells into Th2 cells in the tissues, and that the degree of this inflammatory response correlates with the severity of lymphedema.63 Using antibody depletion studies and knockout mice, we have shown that CD4+ cell responses are necessary for the initiation and maintenance of lymphedema after lymphatic injury. Further, using mouse models and biopsy specimens, our group has demonstrated that Th2 cells critically influence the pathological mechanisms that translate lymphatic injury to the development of lymphedema, regulating multiple overlapping mechanisms, including lymphatic pump failure, impaired collateral vessel formation, adipose deposition and epidermal changes (Figs. 28.7 & 28.8).63–70 A better understanding of these pathological processes is therefore imperative for improved diagnosis and development of targeted treatments and prevention options. Although a number of studies have analyzed lymphatic vascular changes in primary lymphedema and have identified a wide variety of defects, the remainder of this discussion will be dedicated to pathophysiological changes that occur in secondary lymphedema following cancer therapy.

Lymphatic vascular defects in secondary lymphedema The International Society of Lymphology (ISL) staging system is the most widely used classification system for lymphedema.71 Although this classification is based on clinical findings including measurable swelling and presence or absence of pitting, each stage can be characterized by distinct imaging and histological findings (Table 28.2). Lymphangiographic studies performed acutely after axillary lymph node biopsy (i.e., before onset of lymphedema) demonstrate dilated collecting lymphatics and blockage of flow in these vessels in the axilla. Patients at this stage have subclinical interstitial fluid stasis that is either not clinically measurable (stage 0 or latent lymphedema) or resolves spontaneously with compression/ elevation and “pitting edema” resulting from fluid accumulation in the skin (stage I). Persistent subclinical interstitial fluid stasis results in further dilatation of the collecting lymphatics and irregular pulsation. Lymphatic dilatation occurs in part due to accumulation of CD4+ T cells around lymphatic vessels, which produce large amounts of nitric oxide (NO).69,72 This extrinsic source of NO causes lymphatic vessel dilatation

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Normal

Lymphedema

A

B

Figure 28.6 Histology of lymphedema. (A) H&E stain of forearm skin demonstrating characteristic hyperkeratosis of lymphedematous skin (white brackets). (B) Forearm skin sections stained for type I collagen (brown stain). Note dermal accumulation of type I collagen.  

and decreases the force that lymphatics generate for pumping. In an early stage disease, disruption of the endogenous NO gradient leads to reversible lymphatic vessels dilatation, while in a later stage disease, irreversible lymphatic obliteration develops, leading to permanent collecting lymphatic pumping impairment.73–77 Lymphatic valvular incompetence is an additional mechanism that contributes to lymphatic dilatation, resulting in localized areas of retrograde flow to capillary lymphatics located in the superficial dermis (i.e., dermal backflow).78,79 At this point, the collecting lymphatics maintain the ability to actively contract, however the pulsations become more irregular with loss of correlation between lymphatic pulse amplitude and stroke volume. In the early stages of injury following lymph node dissection, chronic inflammation and subclinical lymphatic fluid stasis promote proliferation and collateralization of capillary lymphatics in the superficial dermis. These vessels effectively bypass the zone of obstruction and prevent development of overt lymphedema (Fig. 28.9).80 However, increased VEGF-C concentrations mainly produced by macrophages, induce the formation of nonfunctional hyperplastic, irregularly shaped vessels (Fig. 28.10).20,81,82 These abnormal lymphatic vessels arise from existing lymphatic collecting vessels and proliferate around them, however, they do not bypass the zone of injury.67,83 The development of hyperplastic vessels alongside decreased collaterals can be explained by the presence of T-cell-derived growth cytokines including interleukin 4 (1L-4), interleukin 13 (IL-13), and interferon gamma (IFN-γ), causing direct anti-lymphangiogenic effects on LECs.69,84 While the expression of lymphangiogenic growth factors such as VEGF-C is highly upregulated in lymphedematous tissues, this effect is counterbalanced by the production of anti-lymphangiogenic cytokines, preventing functional lymphatics from forming.85 Histologically, stage I disease is characterized by minor hyperkeratosis, collagen deposition (particularly in the dermis),

inflammatory cell infiltration, and dilatated lymphatic capillaries and collectors.66,86 In the fraction of patients (30–50%) who go on to develop clinically measurable lymphedema, sustained interstitial fluid stasis and ongoing chronic inflammation lead to extracellular matrix collagen deposition with resultant obliteration of capillary lymphatics and smooth muscle cell proliferation around collecting lymphatics.87 Thus, we and others hypothesize that development of clinically evident lymphedema is dependent on the failure of both superficial and deep lymphatic systems (i.e., capillary and collecting lymphatics, respectively) (Fig. 28.11). Patients at this stage have overt accumulation of interstitial fluid in the subcutaneous tissues (stage II) and changes in limb volume or circumference become possible by conventional measures. The irreversible nature of swelling and lack of pitting in these patients can be explained by the proliferation and accumulation of adipocytes due to exposure of these cells to fatty acids in lymphatic fluid.88–93 Interstitial fluid accumulates primarily (60–70% of the total excess volume) in the subcutaneous tissues between adipose tissues and around small veins.94 To a lesser degree, fluid also accumulates above/below the muscular fascia and in the dermis. Collecting lymphatic vessels at this stage continue to actively contract; however, these contractions are ineffective and fail to propel lymphatic fluid forward. Indocyanine green (ICG) lymphography demonstrates loss of major lymphatic collectors, decreased or absent lymphatic pumping, hyperplastic lymphatic collectors, and more extensive dermal backflow.20,75–77 Histologically, stage II disease is characterized by sclerosed capillary and collecting lymphatics, type I collagen fibers accumulation, and lymphatic smooth muscle cells proliferation.86 Progression of lymphedema occurs as a result of accumulation of adipose tissues, hyperkeratosis, fibrosis, and progressive destruction/dysfunction of the remaining lymphatic vessels (i.e., late stage II to III disease). This stage is characterized clinically by severe and irreversible swelling with no recognizable lymphatic collectors in the limb and diffuse accumulation of dye on ICG lymphography (Fig. 28.12).20,71 Histologically, late stage II to III disease is characterized by hyperkeratosis, parakeratosis, chronic inflammation, fibrosis/sclerosis of lymphatic collectors, massive accumulation of adipose tissues and type I collagen fibers in the subcutaneous layers.65,67,86,95–98 The proportion of fluid versus fat accumulation is variable in different individuals and can have widely different patterns of deposition in the limb although some regions tend to swell more than others (i.e., medial elbow area). In addition, progressive fibrofatty deposition makes lymphedema therapy more resistant to compressive therapies. This problem is compounded by the presence of absent pulsations or completely sclerosed collecting lymphatics with loss of luminal diameter and absence of spontaneous lymph flow.99

Regulation of fibrosis Based on the evidence cited above, it is clear that extracellular matrix, fibrosis, and progressive sclerosis of collecting lymphatics play a key role in the pathology of lymphedema. Anatomic clinical research and animal studies suggest that lymphedema is a fibroproliferative disorder in which functional parenchyma (i.e., capillary and collecting lymphatics) ­

Pathophysiology of lymphedema

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Pump failure

Naïve CD4+ cells

Th2 cells

Impaired collateral vessel formation

Lymphedema

Lymphatic injury Fibroadipose deposition

Epidermal changes

Figure 28.7 The role of Th2 cells in the pathophysiology of lymphedema. Th2 cells critically influence the pathological mechanisms that translate lymphatic injury to the development of lymphedema, regulating multiple overlapping mechanisms, including: lymphatic pump failure, impaired collateral vessel formation, adipose deposition, and epidermal changes. (Created with BioRender.)  

Normal

Lymphedema

CD4

IL 4

IL 13

Figure 28.8 Role of CD4+ cells in lymphedema. Representative immunohistochemistry images demonstrating CD4+ (upper), IL-4+ (middle), and IL-13+ (lower) cells in matched human biopsy specimens comparing lymphedematous and contralateral normal upper extremities. (Reproduced with permission from Li CY, Kataru RP, Mehrara BJ. Histopathologic features of lymphedema: a molecular review. Int J Mol Sci. 2020;21(7):2546.)  

The fibroproliferative nature of lymphedema also provides a rationale for the increased risk of lymphedema in patients who have undergone radiation therapy and is supported by experimental studies demonstrating that fibrosis independently decreases lymphatic vessel regeneration.101,102 Using a variety of mouse models as well as clinical biopsy specimens, our lab has shown that lymphedema results in progressive fibrosis and that inhibition of this fibrotic response markedly increases lymphatic regeneration and function.101,103 In addition, we have shown that fibrosis in lymphedema is mediated by proliferation of CD4+ cells and their differentiation into Th2 cells which produce vast amounts of profibrotic cytokines such as IL-4, IL-13, and transforming growth factor beta-1 (TGF-β1).65,70,104–107 Macrophages, on the other hand, play an antifibrotic role that promotes extracellular matrix breakdown, thus decreasing fibrosis.108 The increased expression of TGF-β1 in clinical lymphedema specimens and mouse models of the disease suggest that this growth factor plays a role in regulating lymphedema-induced fibrosis.109 Inhibition of TGF-β1 with small-molecule inhibitors was shown to decrease fibrosis, increase collateral lymphatic formation, improve radiation-induced lymphatic dysfunction and decrease the severity of lymphedema in the animal models.101,106,109,110 However, further studies are needed for the development of effective pharmacological interventions that chronically decrease TGF-β1 activity without induction of autoimmune responses.

Regulation of adipose deposition is progressively replaced by scar tissue.86,87,100 A study by Mihara and colleagues looking at biopsies of collecting lymphatics in patients with varying degrees of lymphatic injury demonstrated obliteration of lymphatic vessels in patients with severe disease by proliferation of smooth muscle cells and deposition of collagen.86

The end stage of lymphedema is progressive adipose deposition. While the initial pathology of lymphedema is fluid accumulation in subcutaneous tissues, over time this fluid promotes chronic fibrofatty tissue deposition in the subcutaneous tissues rendering compressive treatments for lymphedema obsolete (Fig. 28.13).5 It is clear, therefore, that

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Table 28.2 International Society of Lymphology (ISL) staging system and characteristic indocyanine green (ICG) and histological findings  

ISL stage

Pathophysiology

Clinical findings

ICG findings

Histological findings

0

Latent lymphedema

• Lymphedema has not yet occurred or is not yet apparent

• Lymphatic vessels are injured. Capacity for fluid transport is impaired, but still sufficient to drain lymph as necessary

N/A

1

• Persistent interstitial fluid Spontaneously accumulation and localized reversible lymphedema swelling responsive to decongestive treatment and compression garments • “Pitting edema” (indentation of the affected area when pressure is applied to it) resulting from fluid accumulation in the skin

• Dilated lymphatics with irregular pulsation • Localized areas of dermal back flow • Formation of hyperplastic, irregularly shaped lymphatic vessels

• Modest hyperkeratosis • Inflammatory cell infiltration • Dilatation of lymphatic capillaries and collectors • Collagen deposition in some patients (dermis)

• Loss of major lymphatic collectors • More extensive dermal backflow • Decreased or absent lymphatic pumping • Hyperplastic lymphatic collectors

• Proliferation and accumulation of adipocytes • Sclerosed capillary and collecting lymphatics • Accumulation of type I collagen fibers • Proliferation of lymphatic smooth muscle cells

• No recognizable lymphatic collectors in the limb • Diffuse accumulation of dye in the skin

• Hyperkeratosis • Parakeratosis • Chronic inflammatory infiltrate • Fibrosis/sclerosis of lymphatic collectors • Massive accumulation of adipose tissues and type I collagen fibers in the subcutaneous layers







2

Spontaneously irreversible lymphedema

• Irreversible swelling • No pitting, spongy consistency • Limbs harden and increase in size





















3

Lymphostatic elephantiasis

• Severe and irreversible swelling • Heavily fibrosed tissues and significantly thickened skin

































lymphatic (interstitial) fluid accumulation and adipose deposition are closely related.111 Recent observations have demonstrated a strong reciprocal relationship between obesity and lymphedema on a molecular level demonstrating that fat induces inflammatory responses, adipose deposition and fibrosis after lymphatic injury resulting in a vicious cycle of lymphatic function impairment.54,107,112,113 The cellular mechanisms that regulate adipose deposition have been studied in mice with congenital lymphatic defects. Prox-1 is a transcription factor that is necessary for embryonic lymphatic differentiation and development. Prox-1 haploinsufficient mice suffering from impaired pumping and lymphatic leakiness were shown to gain more weight to become obese, compared to wild-type controls, suggesting a causal relationship between lymphatic abnormalities and weight gain.90 This idea is supported by previous studies demonstrating that fatty acids in the interstitial fluid potentially increase adipocyte proliferation and differentiation in vitro.90 Lymphatic

injury in vivo similarly results in upregulation of adipose differentiation, adipose hypertrophy, and fat deposition.90,97,114–116 Serum levels of adiponectin and leptin, hormones that play key roles in fat deposition and metabolism, were also shown to be increased in lymphedema patients.97,117 In addition, IL-6, a known regulator of adipose tissue homeostasis, was shown to be increased locally and systemically in both lymphedema patients and animal models. Interestingly, inhibition of this cytokine increases adipose deposition in lymphedema, implicating IL-6’s role in decreasing adipose tissue deposition.114,118 The relationship between adipocytes and lymphatic endothelial cells appears to be bidirectional in nature.119 This hypothesis is based on recent reports demonstrating that obesity markedly impairs lymphatic function both clinically and in animal models. Obesity is not only known to increase the risk for developing lymphedema after surgery, but was also shown to independently induce the spontaneous development of lymphedema in super-obese individuals (i.e.,

Pathophysiology of lymphedema BMI >59). This effect was shown to be permanent, with little improvement after gastric bypass and weight loss.11,120,121 Recently our lab has shown that obesity results in the development of leaky lymphatics and decreased lymphatic pumping and that lymphatic function is directly proportional

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to body weight in mice.113,122,123 More importantly, we found that the adverse effects of obesity on the lymphatic system are reversible with weight loss, calorie restrictive diet or exercise and lymphatic pumping can be restored back to normal due to these interventions.122,123 These findings provide a rationale for the fact that obesity is a major risk factor for lymphedema.

Epidermal changes Epidermal changes are another pathologic feature of lymphedema including hyperkeratosis and thickening of the epidermis. Our lab has previously shown that Th2 cytokines as IL-4 and IL-13 are necessary for the differentiation of naïve T cells to Th2 cells.70 Based on these findings, we conducted a phase I clinical trial to treat patients with IL-4 and IL-13 neutralizing antibodies.66 This was an open label, single arm study of 9 breast cancer-related lymphedema patients treated once

Surgery

Deep system injury

Figure 28.9 Photograph of lymphangiography performed in a canine model of right axillary lymph node dissection demonstrating hyperplastic superficial lymphatic vessels (black arrow) bypassing the right axilla to lymph nodes in the supraclavicular area bilaterally (white arrows). (Adapted from Suami H, Yamashita S, Soto-Miranda MA, Chang DW. Lymphatic territories (lymphosomes) in a canine: an animal model for investigation of postoperative lymphatic alterations. PLoS One. 2013;8:e69222.)

Superficial system fibrosis

Superficial system intact

Lymphedema

Asymptomatic

 

Figure 28.11 Hypothetical model for development of lymphedema after failure of both deep and superficial lymphatic function.  

A

C

B

D

Figure 28.10  Indocyanine green (ICG) lymphography showing anatomy of normal, stage I, II, and III lymphedema arms. (A) Patent, well-defined, linear collecting lymphatic vessels identified in the volar aspect of a healthy arm. No dermal backflow is observed. (B) Hyperplastic, irregularly shaped lymphatic vessels identified in the volar aspect of a stage I lymphedema arm (yellow arrow points to injection site). (C) Moderate number of collecting lymphatic vessels can be seen with segmental dermal back flow and hyperplastic lymphatic vessels in the dorsal aspect of a stage II lymphedema arm. (D) Diffuse dermal backflow can be seen throughout the entire arm in the dorsal aspect of a stage III lymphedema arm. No recognizable patent collecting lymphatic vessels can be seen.

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Cephalic vein

Cephalic vein

Elbow Basilic vein

Figure 28.12 Cadaver dissection and lymphangiography in a patient with a history of unilateral axillary lymph node dissection. Note loss of capillary (superficial) lymphatics stained green in the upper limb after lymph node dissection. (Adapted from Suami H, Pan WR, Taylor GI. Changes in the lymph structure of the upper limb after axillary dissection: radiographic and anatomical study in a human cadaver. Plast Reconstr Surg. 2007;120:982–991.)  

Thumb

Thumb

Pre-collector

Thumb

Superficial lymph collecting vessel

Thumb

Deep lymph collecting vessel

monthly with IL-4 and IL-13 neutralizing antibodies injections with a subsequent 4-month washout period. While there was no effect on limb volumes, we demonstrated a significant decrease in skin stiffness measured by skin tonometry. This was associated with improvement in quality of life (QoL) as measured by a validated lymphedema-specific QoL tool. The scores went back to normal after the washout period, suggesting that this may not have been a placebo effect. In biopsies from the unaffected arm and lymphedema arm after treatment, we found that Th2 blockade significantly decreased epidermal thickness, skin collagen deposition, and infiltration of mast cells and T cells. We also found that keratinocytes produced Th2 cytokines (TSLP [thymic stromal lymphopoietin], IL-25, IL-33) that promote Th2 differentiation, decreased after treatment with IL-4 and IL-13 neutralizing antibodies. Interestingly, this suggests that keratinocytes may play a role in the pathophysiology of lymphedema and this area is actively under investigation in our lab.

Risk factors of lymphedema Figure 28.13 End-stage lymphedema is associated with subcutaneous adipose deposition and “regional” obesity. (Left) Bilateral magnetic resonance imaging scan of a patient with severe left leg lymphedema after groin lymph node dissection for melanoma 15 years previously. Note significant adipose deposition in the subcutaneous compartment of the affected leg (blue brackets) compared with the normal limb. (Right) Photograph of a young patient with grade II lymphedema of the left leg 2 years after treatment for cervical cancer. Note adipose deposition in the entire left leg. (Reproduced with permission from Mehrara BJ, Greene AK. Lymphedema and obesity: is there a link? Plast Reconstr Surg. 2014;134:154e–160e.)  

A variety of genetic and environmental factors have been shown to increase the risk of developing lymphedema, including obesity, radiation, infection, and genetic factors.11,13,124–129

Obesity Obesity is among the first recognized risk factors for lymphedema and has since been shown to increase the risk of disease in patients treated for a variety of solid tumors.130

Clinical presentation, evaluation, and diagnosis

Prospective studies have shown that patients with a body mass index (BMI) of >30 have at least a threefold increased risk of developing lymphedema as compared with patients with a similar stage breast cancer but a BMI of 59) in some cases spontaneously develop lower extremity lymphedema.120 Even postoperative weight gain in previously lean patients increased the risk of lymphedema development.119,131–133 Further, randomized clinical trials have shown that diet-induced weight loss over a 12-week period resulted in a significant reduction in arm volumes as compared to controls who did not lose weight.134 Finally, exercise studies have shown monitored exercise programs in lymphedema patients not only led to weight loss but also markedly decreased lymphedema symptoms as compared to a sedentary control group.131 Thus, it is clear that patients who are scheduled for lymphadenectomy or lymphatic surgery should be counseled to first lose weight prior to proceeding with invasive interventions.

Radiation Radiation therapy (RT) in combination with surgery is also a well-known risk factor for development of lymphedema, increasing the risk of disease development by as much as fivefold.135–138 Interestingly, lymphedema is significantly more prevalent in obese patients treated with surgery and radiation, suggesting that risk factors for lymphedema can act in an additive manner.139 Although some studies have failed to show a relationship between radiation and development of lymphedema after breast cancer treatments, some of these results may be confounded by the fact that radiation in some studies included only the chest wall and not the regional lymph node basins (e.g., supraclavicular or axilla). In addition, it appears that the negative effects of radiation on lymphedema development are largely additive to those of surgery since the development of the disease following radiation alone is unusual, occurring in less than 7% of patients.138 The increased risk of lymphedema in patients who have undergone RT is further supported by experimental studies demonstrating that fibrosis independently decreases lymphatic vessel regeneration and lymphatic function.101,102

Infection Postoperative infections and cellulitis have long been thought to be a risk factor for development of lymphedema,140,141 however the mechanisms that regulate this potential interaction remain unknown. About a third of patients with lymphedema develop recurrent soft-tissue infections,142,143 which often require hospitalization for intravenous antibiotics.142,144 It is unknown if development of an infection is a symptom of subclinical lymphedema that eventually blossoms into full- scale disease or if infection damages remaining lymphatics thus resulting in disease development.145 Several studies have demonstrated an interplay between bacteria and the

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lymphatic system on a molecular level, suggesting a direct role of bacteria in generating lymphatic dysfunction via the loss of lymphatic muscle cells (LMCs).146–148 Previous gynecological reports have shown that early infections following vulvar cancer surgery significantly increase the incidence of lower extremity lymphedema development.140 These findings have led some investigators to suggest that avoiding cellulitis is a major method to avoid lymphatic injury and disease progression, particularly in patients with a previous history of lymphedema.149 Lymphatic dysfunction also has detrimental effects on host humoral and innate immunity and peripheral tolerance via the increased infiltration of T-regulatory cells (Tregs) in lymphedematous tissues in response to lymphatic injury.150 Inhibition of these cells was shown to improve bacterial clearance and immune responses in lymphedema.150 Tregs regulate immune responses by inhibiting immune cell activation and have also been shown to play a role in suppressing the hallmark inflammatory response necessary for the development of lymphedema.151,152 However, inhibition of Treg cell function also increased tissue inflammatory responses in a preclinical model resulting in a more severe lymphedema phenotype. These interesting findings require further investigation into the dual role of Tregs in lymphedema inhibiting the inflammatory response that contributes to lymphatic dysfunction while also impairing host immunity.

Genetics Genetics have long been shown to cause primary lymphedema and lymphatic abnormalities. However, more recent studies have identified genetic factors that also predispose patients to developing secondary lymphedema. For example, Finegold et al. found that women with mutations in the gene encoding for connexin 47 or hepatocyte growth factor have a significantly increased risk of developing lymphedema after mastectomy and axillary lymph node dissection as compared with normal controls.153,154 Another study, of 157 single-nucleotide polymorphisms (SNPs) in 17 candidate genes, demonstrated that at least four genes and three haplotypes may contribute to development of secondary lymphedema.155 By providing evidence for genetic mutations as an important risk factor in secondary lymphedema, these new discoveries challenge the traditional perspective of secondary lymphedema being solely due to mechanical trauma.155

Clinical presentation, evaluation, and diagnosis Signs and symptoms of lymphedema The timing, severity, and rate of progression of primary and secondary lymphedema are highly variable. While some patients have mild disease that progresses slowly, some others have severe, rapidly progressive disease. Therefore, a detailed history should be taken of lymphedema onset, family history, surgical treatment, and, if relevant, travel to areas in which filariasis is endemic.49

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The most common presenting signs and symptoms of lymphedema are swelling or heaviness of the affected limb followed by pitting edema, as demonstrated in a recent review.156 Additional symptoms include pain, skin tightness, decreased limb function, fatigue, and overall decreased quality of life.156 More rarely, the presenting symptom is cellulitis or lymphangitis and rapid swelling of the affected extremity. Recurrent infections occur in approximately 40% of patients and usually require intravenous antibiotics. Some patients also require long-term antibiotic prophylaxis.156 With disease progression, pitting is decreased, and the skin becomes dry and firm with secondary cutaneous fibrosis and adipose deposition.1,57 Patients may develop hyperkeratosis, acanthosis, skin ulcerations, papillomatous plaques, and recurrent infections.157 In 1976, Stemmer described the inability to pinch the skin fold at the base of the second toe on the dorsal aspect of the foot or the webspace of the hand in patients with lymphedema.158 A positive Kaposi–Stemmer sign is a sensitive predictor for primary and secondary lymphedema of the arms or legs and thus is a useful part of the physical examination.159 However, a positive sign is not required for diagnosis since in some patients with extremity lymphedema the hands or feet are spared from swelling. Later stages of the disease are characterized by clinically apparent dermal thickening which progresses to hyperkeratosis, acanthosis, lichenification, and verrucae.57 A “cobblestoned” overlying skin appearance is characteristic. The skin becomes prone to fissures and recurrent infections57 such as: cellulitis, erysipelas, tinea pedis, and lymphangitis, commonly requiring intravenous antibiotics and long-term prophylaxis in selected cases.57

intra-operator validity of circumference measurements has been questioned, although several reports have shown that with training these measurements can be performed reproducibly. Further, the utility of circumferential measurements is limited in patients with a high body mass index (a 2-cm difference is much more significant in a thin patient than in someone who is morbidly obese).161,162 Nevertheless, measurements are a cornerstone of lymphedema diagnosis and follow-up. Volume measurements are more sensitive and specific and therefore considered superior to circumference measurements.156 These can be performed with water displacement which can be practically difficult (for example some hospitals require using sterile fluid for each patient) or limb scanners such as the perometer. The perometer is an infrared scanner that measures the limb circumference (arm or leg) in multiple areas and then uses the truncated cone formula to calculate limb volume and volume differentials (Fig. 28.15).163,164 This device is useful but is unfortunately expensive and not widely available in the United States. Limb volumes can also be calculated by measuring limb circumferences at 4 cm intervals from the wrist to 44 cm proximally and using the truncated cone formula as described by Brorson.156,165 This approach is simple to perform and is a good compromise between water displacement/perometer and limb circumference measurements. Volume differences of 200 mL or 10% are the threshold for lymphedema diagnosis.160  

 

 

Differential diagnosis The differential diagnosis of primary or secondary lymphedema includes venous insufficiency, deep vein thrombosis, congestive heart failure, recurrent or primary malignancy causing lymphatic obstruction, medications, and infections.6 Vascular obstruction is particularly important since nearly 70% of interstitial fluid is removed by the venous system. Thus, venous obstruction resulting from thrombosis or recurrent tumor compressing the venous system is a common cause of limb swelling in cancer patients and appropriate imaging studies to rule out this diagnosis are warranted in patients with unusual disease presentation.

A

Diagnostic measurements The diagnosis of lymphedema is usually made by clinical exam and, in some cases, radiologic tests. Limb circumference and volume measures are useful means of analyzing the degree of swelling in unilateral cases and these measures are commonly used as a means of following disease progression (Fig. 28.14). Circumference measurements are performed at distinct anatomic locations (e.g., 5 cm above and below the olecranon) and a difference of more than 2 cm is considered diagnostic, with some schemes classifying patients based on measured differences. However, a wide range of measures have been reported.160 In addition, the inter and

B

 

 

Figure 28.14 Lymphedema measurements. (A) Circumference measurements for upper extremity lymphedema. (B) Water displacement method for calculating limb volume. (Adapted from Pitsch F. Benefit of daflon 500 mg in chronic venous disease related edema. Phlebology. 2006;13:17–21.)  

 

Clinical presentation, evaluation, and diagnosis

485

Figure 28.15 Lower limb (left) and upper limb (right) perometer measurements. (Adapted from Pero-systems Inc.)  

Figure 28.16 Bioimpedance measurement compares the rate of electrical transmission between the lymphedematous and normal limbs.  

Other diagnostic tools Various technologies are available for the diagnosis of lymphedema. For example, with bioimpedance spectroscopy, the rate of electrical current transmission through tissues is used to estimate the fluid content of the lymphedematous limb as compared with the normal limb (Fig. 28.16).166 Although this test can have variable results due to skin temperature, superficial skin dryness, and other factors, and therefore requires optimization for reproducible results, some studies have suggested that bioimpedance is helpful in the diagnosis of early-stage lymphedema in which volumetric or circumference differences are subtle or non-existent.156,166–168 Historically, an L-DEX score of 10 or greater was consistent with a diagnosis of lymphedema but more recently a score of 7 or higher has been used as the new threshold indicative of clinical lymphedema with subclinical lymphedema occurring at a score of 6.5 and higher.167–169

Radiologic diagnosis of lymphedema Radiologic tests can be useful in the diagnosis of lymphedema as well as treatment planning and follow-up. Lymphoscintigraphy is the most commonly used radiologic method of diagnosis; it measures the uptake of 99mTc by draining lymph node basins after a radiolabelled colloid peripheral injection.77 Lymphoscintigraphy can also be used to estimate dermal backflow, a condition in which lymphatic blockage proximally results in the redirection of lymphatic fluid from deep channels into the superficial lymphatics. However, recent reports have suggested that the sensitivity of lymphoscintigraphy (0.61) for early stage lymphedema is lower than other

methods, such as magnetic resonance imaging (MRI) and ICG lymphangiography.156,170 The lymphatic vessels and pathologic changes in lymphedema as well as abnormalities in venous outflow can be visualized using MRI (MRI lymphangiography) with a high degree of sensitivity and specificity.170–172 Venous pathology is important to identify because venous hypertension may not only contribute to limb swelling but also compromise the effects of lymphovenous bypass or lymph node transplant.173 MRI also directly reveals the degree of lymphedema-related fat hypertrophy which is a significant confounding variable when treating lymphedema patients, as well as occult metastatic disease.156,174,175

Near-infrared (NIR) lymphography with ICG dye Recent studies have advocated the use of ICG near-infrared (NIR) lymphangiography as the gold standard in the diagnosis and staging of lymphedema.156 In this test, ICG dye is injected in the dermis of the affected extremity and lymphatic vessels are visualized using a NIR camera. In contrast to previous methods used for lymphangiography, this approach is nontoxic and enables visualization of the superficial collecting lymphatics, dermal backflow, and abnormal lymphatic vasculature and is a helpful adjunct to the diagnosis of lymphedema. Although this is an off-label use of ICG, which is currently approved by the US Food and Drug Administration for intravenous injection, pathologic changes such as splash/stardust/diffuse patterns demonstrated on ICG were shown to be present even in early-stage disease in symptomatic patients who do not meet diagnostic criteria based

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on limb volume measurements or even biompedance or lymphoscintigraphy.86,170 In fact, some authors have developed qualitative lymphedema staging systems based on ICG lymphangiography (see below).20,86,170,176–178 Experimental reports have also shown that lymphatic pumping capacity (the rate of change in fluorescence intensity in a given vessel over time) can be a useful measure of lymphatic function; however, this analysis has not been widely adopted.179 Future studies should focus on more sensitive and quantitative methods that can be used to diagnose lymphedema, quantify lymphatic function and, more importantly, analyze responsiveness to treatments.

Patient-reported outcomes Since substantial lymphedema symptoms may be present prior to any clear evidence on clinical metrics, patient-reported outcomes measures (PROMs) are a critical component in diagnosis and management of lymphedema.156,180–185 However, there is a lack of consensus regarding the instrument to use after surgical treatment for lymphedema. The main PROMs used for Quality of Life (QoL) evaluation in patients with lymphedema include the lymph quality of life measure for limb lymphedema (LYMQOL), the upper limb lymphedema 27 scale (ULL27), the lymphedema functioning, disability, and health questionnaire (Lymph-ICF), and the lymphedema life impact scale (LLIS) and the short form 36 (SF-36), which is not specific for lymphedema.186–190 However, the majority of existing PROMs were developed with limited

input from patients and have relatively low reliability and validity.191 The LYMPH-Q Upper Extremity Module has recently been developed to address these limitations, complementing the BREAST-Q which measures QoL and patient satisfaction among women with breast surgery.191,192 New scales are also in development to measure lymphedema burden and impact on ability to work. The main PROMs used in lymphedema patients are outlined in Table 28.3.

Lymphedema classification Common classification systems for lymphedema rely primarily on the clinical features of the disease. The ISL staging system is the most widely used scheme and is based on measurable swelling and presence or absence of pitting (Fig. 28.17; see Table 28.2).71 However, recent reports have demonstrated lack of correlation between the ISL stage and other measures such as limb volume difference, bioimpedence, PROMs and ICG lymphography.193,194 Changes in limb circumference or volume as compared to the contralateral limb or preoperative values have also been used as a means of classifying the severity of lymphedema.149,195 Although there is variability in these studies, the majority of reports classify patients with limb circumference excess of 2 cm or 100 mL volume differential as mild lymphedema. Differences of 2–4 cm (or more than 200 mL volume) is considered moderate lymphedema. Patients who have measured differences of 4 cm or more are classified ­

 

 

 

 

 

Table 28.3 Main patient-reported outcome measures (PROMs) used in lymphedema patients  

Validated tool

Target population

Lymph quality of life measure for limb lymphedema (LYMQOL)

Subscales

Authors, year

Lower extremity Upper extremity

Pain Mood Function Appearance Overall quality of life

Keeley et al., 2010186

The upper limb lymphedema 27 scale (ULL27)

Upper extremity

Physical Psychological Social

Launois et al., 2002187

The lymphedema functioning, disability and health questionnaire (Lymph-ICF)

Lower extremity Upper extremity

Physical function Mental function Household activities Mobility activities Life and social activities

Devoogdt et al., 2011188

Lymphedema life impact scale (LLIS)

Lower extremity Upper extremity

Physical Psychosocial Functional Infection occurrence

Weiss et al., 2015189

LYMPH-Q

Upper extremity

Arm symptoms Function Appearance psychological function Satisfaction with information and arm sleeves

Klassen et al., 2021191,192

Summary

as having severe lymphedema. The utility of this classification scheme, however, is highlighted by the fact that it assumes that the limbs had equal circumference or volume preoperatively (a false assumption in many patients due to differences based on hand/leg dominance), and does not consider the patient’s body habitus. ICG lymphangiography has been proposed by some researchers as a useful means of classifying patients with lymphedema. These efforts are important since they attempt to use physiologic changes in addition to clinical exam findings. Koshima and colleagues have proposed a system based on their experience with lymphovenous bypass procedures (Table 28.4). These authors classified the progression of secondary lymphedema into four steps based on ICG findings and termed this scheme the NECST system (Fig. 28.18).86 The

487

initial step in the disease process is normal lymphatic vessels distal to the zone of lymphatic injury. This is followed by lymphatic ectasis (dilated lymphatics with flattening of lymphatic endothelial cells), followed by contraction (loss of intraluminal diameter in collecting lymphatics and thickening of smooth muscle cell covering), and finally sclerosis (obliteration of the lumen with proliferative smooth muscle cells). The M.D. Anderson classification scheme also classifies lymphedema into four stages based on ICG findings and degree of dermal backflow (Fig. 28.19; Table 28.5).20 In this scheme, stage 1 patients have numerous patent lymphatics and minimal/no dermal backflow. Stage 2 patients have a moderate number of lymphatics and segmental dermal backflow. Stage 3 patients have few patent lymphatics with significant dermal backflow throughout the entire arm. Finally, stage 4 patients have no patent lymphatics and severe dermal backflow of the entire arm and hand. Although this scheme is somewhat subjective, the authors have found that it is useful for classification and patient selection for lymphovenous bypass procedures. Clinical staging for lymphedema remains highly subjective and qualitative with a limited usefulness in stratifying patients and tracking changes following interventions. This emphasizes the need for a more accurate, quantitative staging system in the future.

Summary

Figure 28.17 Patient with pitting edema of the upper extremity resulting from breast cancer-related lymphedema.  

Lymphedema is a debilitating disease that occurs most commonly as a complication of cancer care. With an expected increase in prevalence, the development of effective preventative and therapeutic approaches is of paramount importance. The pathophysiology of lymphedema is related to lymphatic vessel dilation, valvular incompetence, chronic inflammation and fibrosis. A fundamental understanding of the cellular mechanisms underlying the disease is imperative for improved diagnosis and development of targeted preventative or therapeutic strategies.

Table 28.4 Koshima lymphedema staging system  

Type

Description

Normal type (Step 0)

Lymphatic vessels are normal and fully functional

Ectasis type (Step 1)

Endolymphatic pressure is noticeably increased, causing lymphatic endothelial cells to flatten. Lymphangiectasia, the dilation of lymphatic vessels, starts to occur

Contraction type (Step 2)

Smooth muscle cells are converted into synthetic cells, promoting collagenous fiber growth. The wall of the lymphatic vessel starts to thicken

Sclerosis type (Step 3)

Lumen of lymphatic vessels are narrowed if not completely obstructed. Most of the tissue is fibrosed, and lymphatic vessels have lost their ability to transport and concentrate lymphatic fluid

Data from Mihara M, Hara H, Hayashi Y, et al. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy. PLoS One. 2012;7:e41126.

CHAPTER 28 • Lymphedema: pathophysiology and basic science

488

 

A

B

Figure 28.18 (A) NECST (normal, ectasis, contraction, and sclerosis type) classification of lymphedema. Upper panel shows representative figures of patients with various stages of lymphedema. Lower panel shows collecting lymphatic vessels corresponding to these stages. Note progressive sclerosis of the collecting lymphatics. (B) Histological changes in collecting lymphatics in the NECST classification scheme. Note increasing deposition of smooth muscle actin around the lymphatic vessels with increasing stage. (Adapted from Mihara M, Hara H, Hayashi Y, et al. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy. PLoS One. 2012;7:e41126.)  

Summary

489

Table 28.5 M.D. Anderson ICG lymphedema classification system  

Stage

Description

1

Many patent lymphatic vessels present and minimal dermal backflow can be observed in localized areas

2

Moderate number of lymphatic vessels can be seen with segmental dermal backflow

3

Few patent lymphatic vessels can be seen and significant dermal backflow can be observed throughout the entire arm

4

No patent lymphatic vessels can be seen. Severe dermal backflow throughout the entire arm and hand is apparent

From Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr Surg. 2013;132:1305–1314.

A

B

C

D

Figure 28.19 M.D. Anderson indocyanine green (ICG) lymphedema classification system. (A) Stage 1: many patent lymphatic vessels and minimal dermal backflow. (B) Stage 2: moderate number of patent lymphatic vessels and presence of segmental dermal backflow. (C) Stage 3: few patent lymphatics and extensive dermal backflow in the entire arm. (D) Stage 4: no patent lymphatics and severe dermal backflow. (Adapted from Chang DW, Suami H, Skoracki R. A prospective analysis of a 100 consecutive lymphovenous bypass cases for the treatment of extremity lymphedema. Plast Reconstr Surg. 2013;132:1305–1314.)  

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116. Zampell JC, Aschen S, Weitman ES, et al. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg. 2012;129:825–834. 117. Zaleska MT, Olszewski WL. Serum immune proteins in limb lymphedema reflecting tissue processes caused by lymph stasis and chronic dermato-lymphangio-adenitis (cellulitis). Lymphat Res Biol. 2017;15:246–251. 118. Karlsen TV, Karkkainen MJ, Alitalo K, Wiig H. Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema. J Physiol. 2006;574:583–596. 119. Greene AK, Grant FD, Slavin SA. Lower-extremity lymphedema and elevated body-mass index. N Engl J Med. 2012;366:2136–2137. 120. Greene AK, Grant FD, Slavin SA, Maclellan RA. Obesity-induced lymphedema: clinical and lymphoscintigraphic features. Plast Reconstr Surg. 2015;135:1715–1719. 121. Helyer LK, Varnic M, Le LW, Leong W, McCready D. Obesity is a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J. 2010;16:48–54. 122. Nitti MD, Hespe GE, Kataru RP, et al. Obesity-induced lymphatic dysfunction is reversible with weight loss. J Physiol. 2016;594:7073–7087. 123. Torrisi JS, Hespe GE, Cuzzone DA, et al. Inhibition of inflammation and iNOS improves lymphatic function in obesity. Sci Rep. 2016;6:19817. 124. Ahmed RL, Schmitz KH, Prizment AE, Folsom AR. Risk factors for lymphedema in breast cancer survivors, the Iowa Women’s Health Study. Breast Cancer Res Treat. 2011;130:981–991. 125. Ridner SH, Dietrich MS, Stewart BR, Armer JM. Body mass index and breast cancer treatment-related lymphedema. Support Care Cancer. 2011;19:853–857. 126. Meeske KA, Sullivan-Halley J, Smith AW, et al. Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women. Breast Cancer Res Treat. 2009;113:383–391. 127. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev. 2007;16:775–782. 128. Sakorafas GH, Peros G, Cataliotti L, Vlastos G. Lymphedema following axillary lymph node dissection for breast cancer. Surg Oncol. 2006;15:153–165. 129. Norman SA, Localio AR, Kallan MJ, et al. Risk factors for lymphedema after breast cancer treatment. Cancer Epidemiol Biomarkers Prev. 2010;19:2734–2746. 130. Treves N. An evaluation of the etiological factors of lymphedema following radical mastectomy; an analysis of 1,007 cases. Cancer. 1957;10:444–459. 131. Kwan ML, Cohn JC, Armer JM, Stewart BR, Cormier JN. Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv Res Pract. 2011;5:320–336. 132. Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med. 2003;44:43–57. 133. Arngrim N, Simonsen L, Holst JJ, Bülow J. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation? Int J Obes (Lond). 2013;37:748–750. 134. Shaw C, Mortimer P, Judd PA. A randomized controlled trial of weight reduction as a treatment for breast cancer-related lymphedema. Cancer. 2007;110:1868–1874. 135. Armer JM. The problem of post-breast cancer lymphedema: impact and measurement issues. Cancer Invest. 2005;23:76–83. 136. Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Arm edema in breast cancer patients. J Natl Cancer Inst. 2001;93:96–111. 137. Kocak Z, Overgaard J. Risk factors of arm lymphedema in breast cancer patients. Acta Oncol. 2000;39:389–392. 138. Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg. 1986;73:580–584.



























































































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CHAPTER 28 • Lymphedema: pathophysiology and basic science  

139. Warren LE, Miller CL, Horick N, et al. The impact of radiation therapy on the risk of lymphedema after treatment for breast cancer: a prospective cohort study. Int J Radiat Oncol Biol Phys. 2014;88:565–571. 140. Gould N, Kamelle S, Tillmanns T, et al. Predictors of complications after inguinal lymphadenectomy. Gynecol Oncol. 2001;82:329–332. 141. Vignes S, Arrault M, Dupuy A. Factors associated with increased breast cancer-related lymphedema volume. Acta Oncol. 2007;46:1138–1142. 142. Moffatt CJ, Franks PJ, Doherty DC, et al. Lymphoedema: an underestimated health problem. QJM. 2003;96:731–738. 143. Ridner SH, Deng J, Fu MR, et al. Symptom burden and infection occurrence among individuals with extremity lymphedema. Lymphology. 2012;45:113–123. 144. Connor MP, Gamelli R. Challenges of cellulitis in a lymphedematous extremity: a case report. Cases J. 2009;2:9377. 145. Campanholi LL, Duprat Neto JP, Fregnani JH. Mathematical model to predict risk for lymphoedema after treatment of cutaneous melanoma. Int J Surg. 2011;9:306–309. 146. Soo JK, Bicanic TA, Heenan S, Mortimer PS. Lymphatic abnormalities demonstrated by lymphoscintigraphy after lower limb cellulitis. Br J Dermatol. 2008;158:1350–1353. 147. de Godoy JM, de Godoy MF, Valente A, Camacho EL, Paiva EV. Lymphoscintigraphic evaluation in patients after erysipelas. Lymphology. 2000;33:177–180. 148. Jones D, Meijer EFJ, Blatter C, et al. Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic vessel dysfunction. Sci Transl Med. 2018;10(424):eaam7964. 149. Vignes S, Blanchard M, Yannoutsos A, Arrault M. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg. 2013;45:516–520. 150. García Nores GD, Ly CL, Savetsky IL, et al. Regulatory T cells mediate local immunosuppression in lymphedema. J Invest Dermatolo. 2018;138:325–335. 151. Gousopoulos E, Proulx ST, Bachmann SB, et al. Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function. JCI Insight. 2016;1:e89081. 152. Sojka DK, Huang YH, Fowell DJ. Mechanisms of regulatory T-cell suppression – a diverse arsenal for a moving target. Immunology. 2008;124:13–22. 153. Finegold DN, Baty CJ, Knickelbein KZ, et al. Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment. Clin Cancer Res. 2012;18:2382–2390. 154. Finegold DN, Schacht V, Kimak MA, et al. HGF and MET mutations in primary and secondary lymphedema. Lymphat Res Biol. 2008;6:65–68. 155. Miaskowski C, Dodd M, Paul SM, et al. Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery. PloS One. 2013;8:e60164. 156. Wiser I, Mehrara BJ, Coriddi M, et al. Preoperative assessment of upper extremity secondary lymphedema. Cancers. 2020;12(1):135. 157. Olszewski WL, Jamal S, Manokaran G, Lukomska B, Kubicka U. Skin changes in filarial and non-filarial lymphoedema of the lower extremities. Trop Med Parasitol. 1993;44:40–44. 158. Stemmer R. [A clinical symptom for the early and differential diagnosis of lymphedema]. Vasa. 1976;5:261–262. 159. Goss JA, Greene AK. Sensitivity and specificity of the Stemmer sign for lymphedema: a clinical lymphoscintigraphic study. Plast Reconstr Surg Glob Open. 2019;7:e2295. 160. Armer JM, Stewart BR. A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population. Lymph Res Biol. 2005;3:208–217. 161. Stanton AW, Northfield JW, Holroyd B, Mortimer PS, Levick JR. Validation of an optoelectronic limb volumeter (Perometer). Lymphology. 1997;30:77–97. 162. Deltombe T, Jamart J, Recloux S, et al. Reliability and limits of agreement of circumferential, water displacement, and



































































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optoelectronic volumetry in the measurement of upper limb lymphedema. Lymphology. 2007;40:26–34. Chang SB, Askew RL, Xing Y, et al. Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients. Ann Surg Oncol. 2010;17:2764–2772. Lee KT, Lim SY, Pyun JK, Mun GH, Oh KS, Bang SI. Improvement of upper extremity lymphedema after delayed breast reconstruction with an extended latissimus dorsi myocutaneous flap. Arch Plast Surg. 2012;39:154–157. Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg. 2012;46:410–415. Ward LC. Bioelectrical impedance analysis: proven utility in lymphedema risk assessment and therapeutic monitoring. Lymphat Res Biol. 2006;4:51–56. Seward C, Skolny M, Brunelle C, Asdourian M, Salama L, Taghian AG. A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema. J Surg Oncol. 2016;114:537–542. Fu MR, Cleland CM, Guth AA, et al. L-dex ratio in detecting breast cancer-related lymphedema: reliability, sensitivity, and specificity. Lymphology. 2013;46:85–96. Ridner SH, Dietrich MS, Spotanski K, et al. A prospective study of L-dex values in breast cancer patients pretreatment and through 12 months postoperatively. Lymphat Res Biol. 2018;16:435–441. Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PLoS One. 2012;7:e38182. Kamble RB, Shetty R, Diwakar N, Madhusudan G. Technical note: MRI lymphangiography of the lower limb in secondary lymphedema. Indian J Radiol Imaging. 2011;21:15–17. Parihar A, Suvirya S, Kumar S, Singh R. Interstitial MRI lymphangiography of the lower limbs. Indian J Radiol Imaging. 2011;21:155. Hall JE. Guyton and Hall Textbook of Medical Physiology. 12 ed. Philadelphia: Saunders Elsevier; 2011. Bae JS, Yoo RE, Choi SH, et al. Evaluation of lymphedema in upper extremities by MR lymphangiography: comparison with lymphoscintigraphy. Magn Reson Imaging. 2018;49:63–70. Neligan PC, Kung TA, Maki JH. MR lymphangiography in the treatment of lymphedema. J Surg Oncol. 2017;115:18–22. Yamamoto T, Narushima M, Yoshimatsu H, et al. Dynamic indocyanine green (ICG) lymphography for breast cancer-related arm lymphedema. Ann Plast Surg. 2014;73:706–709. Mihara M, Hayashi Y, Hara H, et al. High-accuracy diagnosis and regional classification of lymphedema using indocyanine green fluorescent lymphography after gynecologic cancer treatment. Ann Plast Surg. 2014;72:204–208. Yamamoto T, Yamamoto N, Doi K, et al. Indocyanine green– enhanced lymphography for upper extremity lymphedema: a novel severity staging system using dermal backflow patterns. Plast Reconstr Surg. 2011;128:941–947. Sevick-Muraca EM, Kwon S, Rasmussen JC. Emerging lymphatic imaging technologies for mouse and man. J Clin Invest. 2014;124:905–914. Taghian NR, Miller CL, Jammallo LS, O’Toole J, Skolny MN. Lymphedema following breast cancer treatment and impact on quality of life: a review. Crit Rev Oncol Hematol. 2014;92:227–234. Pusic AL, Cemal Y, Albornoz C, et al. Quality of life among breast cancer patients with lymphedema: a systematic review of patient-reported outcome instruments and outcomes. J Cancer Surviv. 2013;7:83–92. Hormes JM, Bryan C, Lytle LA, et al. Impact of lymphedema and arm symptoms on quality of life in breast cancer survivors. Lymphology. 2010;43:1–13.

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29

Benign and malignant nonmelanocytic tumors of the skin and soft tissue Rei Ogawa

Access video lecture content for this chapter online at Elsevier eBooks+

SYNOPSIS

All typical skin and skin-associated soft-tissue tumors apart from malignant melanocytic tumors are described from the point of view of the plastic surgeon. Topics covered include: ƒ Diagnosis: inspection and palpation, dermoscopy, imaging ƒ Pathologic diagnosis: TNM classification and clinical staging ƒ Treatment modalities, including wide excision, lymph node dissection, reconstructive surgery, radiation therapy, chemotherapy, laser therapy ƒ Benign cutaneous and soft-tissue tumors ƒ Malignant cutaneous and soft-tissue tumors

Diagnosis Inspection and palpation The diagnosis of skin tumors starts with inspection and palpation. The following information should be recorded: the number of lesions (solitary or multiple), the shape of the lesions (e.g., round, oval, polygonal, geographic, linear, annular), its size, its elevation status (e.g., narrow-pedicled, wide-pedicled, dome-like, hemispherical, flat elevated, umbilicated), its surface status (e.g., smooth, rough, papillary, granular, transudatory, xerophily, ulcerative, erosive, atrophic, lustrous, necrotic), its color (e.g., normal, yellow, pale yellow, erythematous, blackish brown, black, blue, depigmented, pigmented, hyperemic, livid), its hardness (e.g., soft, elastic soft, elastic hard, hard, bone-like hard, fluctuating), its alignment (e.g., localized, disseminated, centrifugal, systematized, singular, symmetric, asymmetric, bilateral), its site, whether there are any subjective symptoms (e.g., pain, itch, contracture sensation, numbness, burning sensation, cold sensation), and the time course of the appearance of the lesion (e.g., acute, subacute, chronic, temporary, recurrent). Color plays a particularly important role in the diagnosis of skin lesions (Box 29.1). The possibility of malignant tumors should be suspected at all times. If the shape, size, elevation status, or color of a lesion changes rapidly, a biopsy should be considered. ­

Introduction

In this chapter, all typical skin and skin-associated soft-tissue tumors apart from malignant melanocytic tumors (malignant melanoma) are described from the point of view of the plastic surgeon (Video Lecture 29.1 ).

The skin consists of the epidermis, which is derived during ontogeny from the superficial ectoderm, and the dermis, which is derived from the mesenchyme. Starting in the first 3–4 weeks of human ontogeny, cells derived from the neural crest migrate into the epidermis (Fig. 29.1) where they become melanocytes and Schwann cells; the latter associate with peripheral nerves in the skin. Later, the cutaneous appendages develop. These include hair, which originates from epidermal cells, and hair papillae, which are filled with mesenchyme; vessels and peripheral nerve endings also develop in the papillae. Other cutaneous appendages are the sebaceous glands, which are derived from the epithelial wall of the hair papillae, and the eccrine and apocrine sweat glands, which are also epidermal in origin. There are also soft tissues that are associated with skin, namely fat, muscles, and blood vessels (all of which have a mesenchymal lineage) and nerves (derived from neural crest cells). Thus, skin and skin-associated soft-tissue tumors can be classified simply into those that are of epithelial, cutaneous appendage, neural crest, and mesenchymal origin (Fig. 29.2).

Dermoscopy Dermoscopy is a specialized technique that employs a binocular microscope to observe the skin surface. It is useful for diagnosing pigmented lesions and is necessary for differentially

Diagnosis

491

Surface ectoderm Neural tube Neural crest cells

Notocord Melanocytes

Figure 29.1 The human embryo at 3–4 weeks.

Digestive tract

Enteric neural plexus

 

Ectoderm Stratum corneum

Mesenchyme A

Stratum granulosum

Periderm Stratum germinativum Stratum spinosum B Stratum germinativum

Stratum intermedium

Dermis D

Melanocyte

C

Figure 29.2 Development of the skin. (A) The 5th week of fetal life. (B) The 7th week of fetal life. (C) The 4th month of fetal life. (D) At birth.  

diagnosing malignant melanoma and nevus. It is also required for the diagnosis of seborrheic keratosis, basal cell carcinoma (BCC), and vascular lesions. Marghoob et al.1 have recommended the use of a revised two-step diagnostic algorithm, in which the first step is to differentiate melanocytic from nonmelanocytic pigmented lesions by using specific dermoscopic criteria. The second step is to differentiate between the various nonmelanocytic lesions by using other specific dermoscopic criteria (Algorithm. 29.1). The dermoscopic criteria that are used to diagnose melanocytic lesions, seborrheic keratosis, BCC, and vascular lesions are shown in Box 29.2.

Ultrasound and Doppler imaging To observe skin lesions, high-frequency ultrasound around 20–50 MHz is needed.2 However, if the lesion shows extension perpendicular to the skin surface that exceeds a depth of  

20 mm, the standard ultrasound (3–10 MHz) should be used. In such cases, computed tomography (CT) and magnetic resonance imaging (MRI) can provide additional information. Ultrasound can be used to determine tumor thickness, its relationship with adjacent structures, and the presence of lymph node metastasis. A variety of ultrasound devices are suitable for this purpose, including mechanical or electron scanning, one-dimensional A-mode, two-dimensional B-mode, and three-dimensional C-mode devices. Doppler imaging using color Doppler imaging (CDI) or power Doppler imaging is useful for the differential diagnosis of benign and malignant skin tumors, assessing inflammatory reactions, and detecting lymph node metastases. This is because 90% of malignant skin tumors exhibit a high blood flow rate of 3–20 cm/s that is not observed in more than 95% of benign skin tumors. The resolution of power Doppler imaging is higher than that of CDI. M-mode and duplex (a combination  

 

 

CHAPTER 29 • Nonmelanocytic tumors of the skin and soft tissue

492

 

BOX 29.2 Dermascopic criteria used to diagnose melanocytic lesions, seborrheic keratosis, basal cell carcinoma, and vascular lesions

BOX 29.1 Typical skin tumor colors

 

 

Normal color Epidermal origin (e.g., epidermoid cyst) Mesenchymal origin (e.g., lipoma, soft fibroma, leiomyoma) Neural crest origin (e.g., schwannoma)

Yellow–pale yellow Appendage origin (e.g., sebaceous nevus, xanthoma, milia)

Erythematous Epidermal origin (e.g., inflammatory atheroma, squamous cell carcinoma) Mesenchymal origin (e.g., keloid and hypertrophic scars, vascular malformations, hemangioma, dermatofibrosarcoma protuberans, angiosarcoma)

Blackish brown–black Epidermal origin (e.g., basal cell carcinoma) Neural crest origin (e.g., pigmented nevus, melanoma)

Blue Epidermal origin (e.g., epidermoid cyst) Neural crest origin (e.g., nevus of Ota, mongolian spot, blue nevus)

Algorithm 29.1 Criteria for melanocytic lesion

Pattern analysis

Yes

No Criteria for seborrheic keratosis

Yes

Seborrheic keratosis

No Criteria for BCC

Yes

BCC

No Criteria for vascular lesion

Yes

Malignant melanoma Clark’s nevus Unna nevus Miescher’s nevus Spitz/Reed nevus Congenital nevus Blue nevus Others

Vascular lesion

No

Two-step diagnosis using dermoscopy. BCC, Basal cell carcinoma. Modified from Consensus Net meeting on Dermoscopy. Available at http://www. dermoscopy.org/consensus/.

of B- and M-mode) scanning are useful for observing hemangiomas or vascular malformations.

X-ray, CT, MRI, angiography, scintigraphy, and positron emission tomography (PET) X-ray analysis is useful for detecting calcifying lesions such as pilomatricoma and malignant tumors that have necrosis-induced calcifications. Moreover, bone deformation associated with malignant or nonmalignant tumor invasion into bones can be observed by using X-rays.

Criteria for melanocytic lesions Pigment network Negative network Aggregated globules Streaks Homogeneous blue pigmentation Pseudonetwork Parallel pattern

Criteria for seborrheic keratosis Multiple milia-like cysts Comedo-like openings Light-brown fingerprint-like structures Fissures/ridges

Criteria for basal cell carcinoma Pigment network is absent, and one of: Arborizing vessels Leaf-like areas Large blue–gray ovoid nests Multiple blue–gray globules Spoke wheel areas Ulceration

Criteria for vascular lesions Red–blue lacunas Red–bluish to red–black homogeneous areas Reproduced from the Consensus Net meeting on Dermoscopy. Available at http:// www.dermoscopy.org/consensus/.

CT detects metastatic lesions in the bone, lymph nodes, and lungs better than MRI. Helical CT or multidetector low CT can generate three-dimensional and high-resolution images. Contrast-enhanced CT and CT angiography are useful for detecting malignant tumors, vascular regions, and adjacent vascular structures. MRI detects soft tissues better than CT. In general, malignant tumors present with low-iso signal intensity on T2-weighted images (T2WI) and low-signal intensity on T1weighted images (T1WI), while benign tumors exhibit high signal intensity on T2WI and low signal intensity on T1WI. Magnetic resonance angiography is superior to MRI in determining the nidus and exact nature of the collateral structures in hemangiomas and vascular malformations. Angiography is an invasive imaging method that was frequently used in the past to investigate vascular lesions. While it detects hemangiomas and vascular malformations readily, its use with pediatric patients requires general anesthesia. Scintigraphy can be used for metastatic lesion screening. 67 Ga and 201TiCl are used in tumor- or inflammation-seeking scintigraphy, while 99Tc-MDP and 99mTc-HMDP are used in bone scintigraphy. Scintigraphy suffers from low resolution, and this makes it difficult to detect lesions that are less than 2 mm in diameter by this method. PET is also useful for detecting the metastatic lesions of malignant skin tumors.3 2-deoxy-2-[18F] fluoro-d-glucose  

Treatment

(FDG) PET (FDG-PET) has been used for the diagnosis and staging of cancers and for monitoring treatment, particularly with regard to Hodgkin’s lymphoma, non-Hodgkin lymphoma, and lung cancer. PET can also sometimes detect many other types of solid tumors that occasionally show up as very highly labeled lesions. FDG-PET is particularly useful for searching for tumor metastasis, or for recurrence after the removal of a primary tumor that was known to be highly active. However, since PET can also detect inflammatory lesions, it will be necessary to exclude the possibility that a PET-detected apparent tumor is not an inflammatory, erosive, or ulcered area.

Pathologic diagnosis A definitive diagnosis requires a pathologic diagnosis. However, biopsies should only be performed for a clear purpose, such as for the differential diagnosis of benign tumors or to analyze the stage and grade of malignant tumors, which would allow the area to be resected to be determined. Moreover, biopsies should only take place after careful inspection, palpation, and imaging analyses. Depending on the purpose of a biopsy and the lesion characteristics, the surgeon can choose from a range of different biopsy techniques, including punch, incisional, excisional, and mapping biopsies. In the case of incisional biopsies, normal skin should be excised together with early-stage lesions and the characteristic areas of lesions (e.g., inflammatory, erosive, or ulcered areas). In the case of a possible malignant tumor, an excisional biopsy is recommended to prevent malignant cell dissemination into blood. However, surgeon judgment is needed to determine the amount of normal skin that should be removed. In general, the normal skin margin of an excisional biopsy should be as minimal as possible, especially if the tumor is suspected to be benign. However, if the margins of an excisional biopsy of a malignant tumor are wide enough, such biopsies could actually serve the same purpose as radical resections. Such extensive excisional biopsies could also reduce the number of operations that are needed to treat a tumor. Thus, if a low-grade malignant tumor (e.g., BCC) is suspected, an excisional biopsy that includes several millimeters of normal skin margin may be considered. For high-grade malignant tumors, excisional biopsies will often lead to a pathologic diagnosis that indicates the need for additional wide resection, radiation therapy, and/or chemotherapy. A way to detect lymph node metastasis that is increasingly being used is to perform sentinel node biopsy, which shows whether the cancer has spread to the very first lymph node.4 If the sentinel lymph node does not contain cancer, it is highly likely that the cancer has not spread to any other area of the body. However, this technique is only of therapeutic value for patients with positive nodes: for patients who have negative nodes, the possibility that the lymph node has undetectable cancerous cells should be considered. In addition, there is no compelling evidence that the survival of patients who have a full lymph node dissection as a result of a positive sentinel lymph node biopsy is better than that of those patients who do not have a full dissection until later in the disease, when the lymph nodes can be felt by a physician. Thus, such patients may be subjected unnecessarily to full dissection, which is associated with lymphedema.

493

The TNM clinical classification system and the pTNM pathologic classification system The TNM clinical classification5,6 applies only to malignant tumors (Figs. 29.3 & 29.4). T indicates the size of the tumor and whether it has invaded nearby tissue, N indicates whether regional lymph nodes are involved, and M indicates the presence of distant metastasis. The TNM classification system is based on clinical evidence acquired before definitive treatment. Once intraoperative and surgical pathologic data become available, the pathologic TMN (pTNM) classification system can be used. The pT, pN, and pM categories correspond to the T, N, and M categories. Regional lymph nodes are those that drain the site of the primary tumor (Fig. 29.5). The pN assessment of the regional lymph nodes requires that a sufficient number of lymph nodes are removed for histologic examination (usually six or more). If the examined lymph nodes are negative but fewer than six lymph nodes were resected, the pN classification is designated pN0. Box 29.3 shows examples of the TNM classification system, namely the systems used for carcinoma of skin and eyelid.

Clinical staging The TNM system5,6 is used to show the anatomical extent of malignant tumors. For purposes of tabulation and analysis, it is useful to condense these categories into stages (Table 29.1). To be consistent with the TNM system, carcinoma in situ is categorized as stage 0. In general, tumors that are localized to the organ of origin are categorized as stages I and II, while those that exhibit extensive local spread, particularly to the regional lymph nodes, are classified as stage III. The tumors that have distant metastasis are classified as stage IV. For pathological stage groups, if sufficient tissue has been removed for pathological examination to evaluate the highest T and N categor ies, M1 may be either clinical (cM1) or pathological (pM1). However, if only a distant metastasis has had microscopic confirmation, the classification is pathological (pM1) and the stage is pathological. ­

Treatment Wide excision With regard to wide resection of malignant tumors of skin, the horizontal and vertical margins vary depending on the type of tumor.7–9 Retrospective histopathologic studies have supported reductions in the horizontal margin in recent years. The horizontal margins that are recommended for particular tumor types are listed in Box 29.4. In the case of malignant soft-tissue tumors, the type of excision can vary with regard to the extent of the margins around the tumor: curative wide, wide, and marginal excisions indicate margins that are at least 5 cm outside the tumor-reactive layer, 1–2 cm outside the tumor-reactive layer, and within the tumor-reactive layer, respectively. It is now considered that wide excision is appropriate margin for soft tissue sarcoma. Moreover, Mohs micrographic surgery, where tumors undergo histologic analysis  

 

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T – Primary tumor* TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 The greatest dimension of the tumor is 2 cm or less T2 The greatest dimension of the tumor is more than 2 cm but less than 5 cm T3 The greatest dimension of the tumor is more than 5 cm T4 The tumor invades deep extradermal structures such as cartilage, skeletal muscle, or bone Tis

pTis

T4

pT4

Epithelium Papillary dermis Reticular dermis

Subcutaneous tissue

2–5 cm

>2–5 cm

>5 cm

T1

pT1

T2

pT2

T2(5)

pT2(5)

T3

pT3

* In the case of multiple simultaneous tumors, the tumor with the highest T category is used for the classification and the num ber of separate tumors is indicated in parentheses (e.g., T2 (5)).

Figure 29.3 The T factor of the TNM classification system, as described by the Union for International Cancer Control (UICC). (Modified from Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (UICC: Union for International Cancer Control). 8th ed. Wiley–Blackwell; 2017; and Wittekind CF, Greene FL, Hutter RVP, et al., eds. TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours. 5th ed. Springer; 2004.)  

during surgery in such a way that almost all of the surgical margins can be examined for tumor extensions, can help to obtain complete margin control during the removal of a skin cancer and soft-tissue sarcoma.10

Lymph node dissection Axillary lymph node dissection Since sentinel lymph node biopsy is now a widely practiced technique, there are fewer occasions where preventive axillary lymph node dissection is necessary. Metastatic squamous cell carcinoma (SCC) is an example of a malignant nonmelanocytic skin tumor that warrants axillary lymph node dissection. Axillary lymph nodes can be classified into levels I, II, and III,

which relate to the lateral and internal edges of the pectoralis minor muscle. Level I is the bottom level and lies below the lower edge of the pectoralis minor muscle. Level II lies underneath the pectoralis minor muscle, while level III is above the pectoralis minor muscle. Structures that should be preserved during axillary lymph node dissection are the pectoral nerves, the long thoracic nerve, the intercostobrachial nerves, the axillary artery and veins, the thoracoacromial artery and veins, and the subscapular artery and veins.

Inguinal lymph node dissection Widespread use of sentinel lymph node dissection has also reduced the frequency of inguinal lymph node dissection. Representative indications for inguinal lymph node

Treatment N – Regional lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis

495

M – Distant metastasis MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

N = pN M = pM M1

N1

M1 M1

Primary tumor M1 Primary tumor

M1

N1

M1

Primary tumor

M1

N1

N1

Primary tumor

Primary tumor N1

M1

N1

N1

N1

N1

Figure 29.4 The N and M factors of the TNM classification system, as described by the Union for International Cancer Control (UICC). (Modified from Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (UICC: Union for International Cancer Control). 8th ed. Wiley–Blackwell; 2017; and Wittekind CF, Greene FL, Hutter RVP, et al., eds. TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours. 5th ed. Springer; 2004.)  

dissection are metastatic SCC and extramammary Paget’s disease (EMPD). Traditionally, the area of dissection is a triangle composed of the inguinal ligament, the internal edge of the sartorius muscle, and the internal edge of the long adductor muscle. In the wide resection of inguinal lymph nodes, the femoral vein is identified along with the saphenous vein. After clamping the saphenous vein, the adductor longus muscle is identified and should be cleaned of all fatty nodal tissue by retracting the saphenous vein en bloc with the lymph nodes until the adductor canal is reached.

Reconstructive surgery Reconstruction via skin grafting is a basic surgical technique that is used to reconstruct the tissue defects that occur after tumor extirpation, that is also useful for early detection of local recurrence. The most ideal approach after tumor extirpation is to suture the wound margins directly together. However, this can only be performed if the wound is not too big and the adjacent skin can be extended sufficiently. One concern with this approach is that malignant cells may be left in the deep margins of the wound. Recent developments in reconstructive

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Tumors in the boundary zones

Unilateral tumors Head, neck

Ipsilateral preauricular, submandibular, cervical, and supraclavicular lymph nodes

Between Right / left midline

Thorax

Ipsilateral axillary lymph nodes

Head and neck / thorax

Clavicula–acromion–upper shoulder blade edge

Upper limb

Ipsilateral epitrochlear and axillary lymph nodes

Thorax / upper limb

Shoulder–axilla–shoulder

Abdomen, loins, and buttocks

Ipsilateral inguinal lymph nodes

Thorax / abdomen, loins, and buttocks

Front: middle between the navel and the costal arch. Back: lower border of the thoracic vertebrae (midtransverse axis)

Lower limb

Ipsilateral popliteal and inguinal lymph nodes

Groin–trochanter–gluteal sulcus

Anal margin and perianal skin

Ipsilateral inguinal lymph nodes

Abdomen, loins, and buttocks / lower limb

Parotid, preauricular and facial Submandibular (submaxillary) Lymph nodes overlying thyroid cartilage Inferior deep jugular, prelaryngeal and paratracheal

Axillary

Epitrochlear

Auricular and occipital Superior deep jugular Spinal accessory Supraclavicular

Inguinal

Retropharyngeal

A

B

Figure 29.5 (A,B) The regional lymph nodes, as described by the Union for International Cancer Control (UICC). (Modified from Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (UICC: Union for International Cancer Control). 8th ed. Wiley–Blackwell; 2017; and Wittekind CF, Greene FL, Hutter RVP et al., eds. TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours. 5th ed. Springer; 2004.)  

techniques, including thin flap-based techniques and wound coverage materials, mean that plastic surgeons can now choose from a wide and rapidly evolving variety of primary and aesthetic secondary reconstruction methods. Given this constantly altering medical (and social) environment, it is difficult to develop up-to-date reconstructive algorithms, and indeed, previous algorithms such as the reconstructive ladder, elevator, and triangle quickly lose favor. Consequently, the techniques that are chosen for primary and secondary reconstruction are largely determined on a case-by-case basis. However, one current and useful model is the reconstructive matrix,11 which helps plastic surgeons to determine the best reconstructive solutions for their patients in the context of particular medical and socioeconomic environments by considering aspects of surgical complexity, technological sophistication, and patient surgical risk.

Radiation therapy Malignant tumors vary in their sensitivity to radiation-induced damage, which directly affects the success of radiation therapy. For example, malignant melanomas are less sensitive to radiation and are therefore rarely treated with radiation therapy. Malignant skin tumors that are relatively sensitive to radiation and are therefore commonly treated with radiation therapy include BCC,12 SCC,13 and Merkel cell carcinoma of the skin.14 Acute skin reactions to radiation therapy occur during the first 7–10 days after treatment and are characterized initially by erythema that then progresses to pigmentation, epilation, and desquamation; this is particularly the case when higher doses are used. Subacute and late complications occur several weeks after radiation therapy and can progress for long periods of time.

Treatment

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BOX 29.3 The TNM classification systems for skin and eyelid (Union for International Cancer Control)  

Carcinoma of the skin (excluding eyelid, head and neck, perianal, vulva, and penis) TX T0 Tis T1 T2 T3

Primary tumor cannot be identified No evidence of primary tumor Carcinoma in situ Tumor >2 cm or less in greatest dimension Tumor >＞2 cm and ≦4 cm in greatest dimension Tumor ＞4 cm in greatest dimension or minor bone erosion or perineural invasion or deep invasion T4a Tumor with gross cortical bone/marrow invasion T4b Tumor with axial skeleton invasion including foraminal involvement and/or vertebral foramen involvement to the epidural space NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node 3 cm or less in greatest dimension N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension or in multiple ipsilateral nodes none more than 6 cm in greatest dimension N3 Metastasis in a lymph node more than 6 cm in greatest dimension M0 No distant metastasis M1 Distant metastatic disease











T2









 







T4











 

 

 

 



 



NX N0 N1







N2





Carcinoma of the skin of the eyelid TX T0 Tis T1









Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ Tumor 10 mm or less in greatest dimension

 







 



T3





 



 

 

 



 



T1a Not invading the tarsal plate or eyelid margin T1b Invades tarsal plate or eyelid margin T1c Involves full thickness of eyelid Tumor >10 mm, but 20 mm or less in greatest dimension T2a Not invading the tarsal plate or eyelid margin T2b Invades tarsal plate or eyelid margin T2c Involves full thickness of eyelid Tumor >20 mm, but 30 mm or less in greatest dimension T3a Not invading the tarsal plate or eyelid margin T3b Invades tarsal plate or eyelid margin T3c Involves full thickness of eyelid Any eyelid tumor that invades adjacent ocular, or orbital, or fascial structures T4a Tumor invades ocular or intraorbital structures T4b Tumor invades (or erodes through) the bony walls of orbit or extends to paranasal sinuses or invades the lacrimal sac/nasolacrimal duct or brain Regional lymph nodes cannot be assessed No evidence of lymph node involvment Metastasis in a single ipsilateral regional lymph node, 3 cm or less in greatest dimension Metastasis in a single ipsilateral lymph node more than 3 cm in greatest dimension or in bilateral or contralateral lymph nodes No distant metastasis Distant metastasis

M0 M1





 

 

Modified from Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (UICC:Union for International Cancer Control), 8th ed. Wiley–Blackwell; 2017.

 

These complications include scarring, permanent pigmentation, depigmentation, atrophy, telangiectasis, subcutaneous fibrosis, and necrosis.

Chemotherapy Chemotherapy can be either adjuvant or primary, and all chemotherapies can be administered either systemically or topically. Adjuvant chemotherapy is mainly used for malignant melanoma, while primary chemotherapy is indicated for SCC,15 angiosarcoma,16 and EMPD.17 However, the radical chemotherapy that malignant skin tumors are generally treated with can sometimes be seen as neoadjuvant chemotherapy before surgery for advanced stage cancer. Single-agent chemotherapies include peplomycin sulfate and CPT-1118 for SCC, pacitaxel for angiosarcoma, and docetaxel for angiosarcoma and EMPD. Multiagent chemotherapies includes cisplatin + doxorubicin and cisplatin + 5-fluorouracil (5-FU) + bleomycin for SCC; mesna + doxorubicin + ifosfamide + dacarbazine for angiosarcoma; and 5-FU + mitomycin C, 5-FU + carboplatin + leucovorin, and 5-FU + carboplatin + mitomycin C + epirubicin + vincristine for EMPD.

Laser therapy Dye lasers or neodymium-doped yttrium aluminum garnet (Nd: YAG) lasers can be used for lesions that are

characterized by neoplastic changes or malformations in capillary vessels or their overgrowth, such as hemangiomas,19 vascular malformations,20 and keloid/hypertrophic scars.21 Ruby and alexandrite lasers can be used to treat superficial pigmented lesions whose colors range from brown to black, while Q-switched ruby and alexandrite lasers are useful for intradermal pigmented lesions such as the nevus of Ota.22 CO2 lasers and erbium yttrium aluminum garnet (Er: YAG) lasers target the water contents of a lesion,23 which makes them suitable for lesions with various colors like seborrheic keratosis, telangiectatic granuloma, xanthoma, and fibroma.

Others (including immunotherapy, cryotherapy, electrocoagulation therapy, and sclerotherapy) At this stage, the only indication for immunotherapy is malignant melanoma. Cryotherapy and electrocoagulation therapy induce the freezing and melting of the tumor tissues, which results in their necrosis and/or apoptosis; these methods are suitable for superficial benign or malignant tumors like seborrheic keratosis, fibroma, and BCC. Sclerotherapy, where a sclerosant like ethanol, ethanolamine oleate, polidocanol, or OK-432 is injected into affected vessels, can be used to treat vascular malformations. Promising technologies that may

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Table 29.1 Clinical staging (Union for International Cancer Control)  

Carcinoma of the skin (general staging system) Stage 0

Tis

N0

M0

Stage I

T1

N0

M0

Stage II

T2

N0

M0

Stage III

T3

N0

M0

T1, 2, 3

N1

M0

BOX 29.4 Recommended surgical margins of wide excisions of nonmelanocytic tumors of the skin and soft tissues  

Horizontal margin Basal cell carcinoma Low risk: 4 mm High risk: 5–10 mm Squamous cell carcinoma Low risk: 4–6 mm High risk: 10 mm Merkel cell carcinoma 10–20 mm Sarcoma Low risk: 10 mm High risk: 20 mm  

 

 

 

Stage IVA Stage IVB

T1, 2, 3

N2, 3

M0

T4

Any T

M0

Any T

Any N

M1

Carcinoma of the skin of the eyelid

 

 

Stage 0

Tis

N0

M0

Stage IA

T1

N0

M0

Stage IB

T2a

N0

M0

Stage IIA

T2b, T2c, T3

N0

M0

Stage IIB

T4

N0

M0

Stage IIIA

Any T

N1

M0

Stage IIIB

Any T

N2

M0

Stage IV

Any T

Any N

M1

Modified from Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (UICC:Union for International Cancer Control). 8th ed. Wiley–Blackwell; 2017.

become useful in the near future include: hyperthermic infusion therapy, where the tumor is infused with a substance that makes it more susceptible to locally applied heat; molecular target therapy, which involves drugs or other substances that block the growth and spread of the tumor by interfering with specific tumor growth and progression molecules; and gene therapy and gene cell therapy, where genes are manipulated in target healthy cells (to enhance their cancer-fighting properties) or in target cancer cells (to kill them or inhibit their growth).

 

Vertical margin With fat layer Tumors that are limited to the dermis With deep fascia Tumors that extend into the fat layer With skeletal muscle Tumors that extend into the deep fascia With the membranes of deeper structures such as cartilage or bone Tumors that extend into skeletal muscle With deeper structures like cartilage or bone Tumors that extend into membranes of deeper structures like cartilage or bone Others The margins of wide tumor excisions that occur in anatomically complicated and special regions (e.g., eyelid, vulva, penis, finger/toe tip, and ear) will vary on a case-by-case basis. This is also true for soft-tissue tumors. In general, at least one layer of barrier structure should be excised. For example, for tumors that are limited to the fat layer, the deep fascia of skeletal muscle is considered as the barrier structure and should be removed with the tumor upon wide excision.

Benign cutaneous and soft-tissue tumors Benign epithelial-origin tumors Epidermal nevus (e.g., verrucous epidermal nevus and linear epidermal nevus)

Figure 29.6 Epidermal nevus of the upper arm.

This nevus is composed of skin cells that normally occur at the affected site but show hyperkeratosis and papillomatosis (Fig. 29.6). It can be considered to be a hamartoma, which is a benign focal, tumor-like malformation that is composed of a mixture of the cells that characterize the tissue of its origin; such nodules grow at the same rate as the surrounding tissues. The dermis below the epithelial nevus is usually normal. Epithelial nevi sometimes exhibit a diffuse or extensive distribution that affects a large area of the patient’s

body (termed systematized epidermal nevus); careful observation is necessary in these cases. Systematized epidermal nevus often occurs together with abnormalities in other organ systems. This condition is termed epidermal nevus syndrome,24 and has been described as a sporadic neurocutaneous linkage of congenital ectodermal defects in the skin, brain, eyes, and/or skeleton. Laser therapy, cryotherapy,

 

Benign cutaneous and soft-tissue tumors

499

Figure 29.7 Seborrheic keratosis on the temporal region.  

Figure 29.8 Keratoacanthoma on the nose.  

electrocoagulation, surgical abrasion, and excision are suitable for treating epithelial nevi. If abrasion therapy is used, it should be remembered that these lesions are usually limited to the epidermis; thus, to prevent heavy scarring, only the epidermis and the superficial layer of the dermis should be removed.

Seborrheic keratosis (also known as senile wart) This is a benign skin growth that originates from the basal and squamous cells in the epidermis (Fig. 29.7). It should be differentiated from nevus cell nevus, senile keratosis, BCC, and malignant melanoma. The sign of Leser–Trélat, which is the dramatic, sudden appearance of multiple seborrheic keratoses, can be a paraneoplastic syndrome, namely an ominous sign of an internal malignancy.25 In such cases, not only do new lesions suddenly appear, pre-existing lesions also frequently increase in size and become symptomatic. This sign should not be overlooked and screening for internal malignancy should be recommended to the patient. Laser therapy, cryotherapy, electrocoagulation, surgical abrasion, and excision are all suitable treatments for seborrheic keratosis. However, if the tumor invades the dermis, which can occur, surgical excision is recommended.

Figure 29.9 Epidermoid cyst with a central pore.  

Keratoacanthoma Keratoacanthoma has been a controversial entity for many years, mainly because it closely resembles SCC26 (Fig. 29.8). It grows rapidly and can sometimes self-heal. Upon histopathology, atypical squamous cells can be detected, which makes it difficult to distinguish from SCC. For this reason, excisional biopsy should be considered despite the fact that this lesion occasionally self-heals. If the lesion is on the nose and face, Mohs micrographic surgery is particularly suitable since it facilitates good margin control along with minimal tissue removal.

Epidermoid cyst (also known as epidermal cyst and atheroma) Epidermal cyst is a smooth, dome-shaped, freely movable, somewhat fluctuant subcutaneous swelling that is sometimes attached to the skin by a central pore (Fig. 29.9). It is covered with a stratified squamous epithelium that resembles the epidermis or the follicular infundibulum; thus, there is a granular cell layer adjacent to the keratin-containing cyst lumen. Epidermoid cysts can rupture spontaneously or be ruptured

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A

Figure 29.10 Giant atheroma.  

by external mechanical forces. Extremely large epidermoid cysts, also known as giant atheromas (Fig. 29.10), should undergo pathology to rule out malignant change,27 although such changes are rare. Epidermoid cysts that exhibit inflammation or recur should be removed by simple excision. In the case of large cysts, the contents can be removed first, after which the cyst walls can be removed with minimal incision (Fig. 29.11). In cases where pus and blood are excreted, the surgeon should consider incising the cyst and draining it first, and then excising it completely 1–2 weeks later.

B

Milia Milia are a smaller version of an epidermoid cyst (less than 4 mm in diameter). They may derive from the outer root sheath of vellus follicles. There are primary and secondary milia.28 Primary milia include congenital milia, benign primary milia of children and adults, milia en plaque, nodular grouped milia, multiple eruptive milia, nevus depigmentosus with milia, and genodermatosis-associated milia. Secondary milia are the disease-, medication-, and trauma-associated milia. Milia can be treated easily by making small holes in the surface with a needle or CO2 laser and then extruding the contents.  

Dermoid cyst A dermoid cyst is a congenital subcutaneous cyst that develops along the embryonic lines of closure (Fig. 29.12). It is most common on the head and neck area, particularly the supraorbital region, brow, upper eyelid, glabella, and scalp. These cysts can be easily removed surgically, but care should be taken not to injure the temporal branch of the facial nerve. The cyst lumen contains keratin debris and hair shaft fragments. Preoperative X-rays should be taken to distinguish it from pilomatricoma on the head and neck region, especially in pediatric patients. Since it has been reported that dermoid cysts can exhibit malignant changes, complete surgical removal is recommended.29

C

Figure 29.11 An epidermoid cyst (A) and the removal of the cyst with a minimal incision (B,C).  

Others Rare benign epidermal-origin skin tumors include clear cell acanthoma, large cell acanthoma, acantholytic acanthoma, warty dyskeratoma, traumatic inclusion cyst, human papillomavirus-associated cyst, proliferating epidermal cyst, and cutaneous keratocyst. The preoperative diagnosis of these tumors can be difficult, but many can be treated radically with a simple excision and suture.

Benign cutaneous and soft-tissue tumors

501

Figure 29.13 Nevus sebaceous on the scalp.  

A

Figure 29.14 Pilomatricoma on the upper eyelid.  

B

Figure 29.12 (A) Dermoid cyst on the supraorbital region; (B) the excised cyst.  

Benign appendage-origin tumors Nevus sebaceous Nevus sebaceous is a hamartoma rather than a neoplasm (Fig. 29.13). It is essentially confined to the head and neck regions, and can be found not only in the sebaceous gland but also in the epidermis, dermis, hair follicles, and sweat glands. Consequently, it is also referred to as organoid nevus. In appearance, it resembles an epidermal nevus. Since other tumors like BCC and trichilemmoma can arise from nevus sebaceous over time,30 complete surgical excision is recommended. If it is located in the hair, the hair stream should be carefully considered while performing the excision and suturing; moreover, dehairing caused by unnecessary buried or dermal sutures should be avoided.

Pilomatricoma (also known as calcifying epithelioma and pilomatrixoma) This is a cystic nodule that tends to occur on the head and neck regions of young patients (Fig. 29.14). Multiple pilomatricoma may be seen in a familial setting in patients who also have myotonic dystrophy. A calcified region can be seen by ultrasound, X-ray, CT, and MRI. This region will appear as a high-intensity signal on ultrasound, while on MRI it will show up as a low-intensity signal on both T1WI and T2WI. Since malignant tumors sometimes have a calcified lesion that is caused by necrosis, it is necessary to exclude this possibility when making a diagnosis of pilomatricoma. It is not associated with a clear capsule and thus should be excised carefully and completely to prevent recurrence. Malignant pilomatricoma has been reported,31 but there have been less convincing reports of the carcinomatous transformation of pre-existing benign pilomatricoma.

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Trichilemmal cyst This is a subcutaneous cyst that is derived from the outer root sheath of the hair follicle and arises most frequently on the hairy region on the head (Fig. 29.15). Clinically, it resembles an epidermoid cyst. Multiple cysts on the head are seen in 70% of cases. Complete excision is recommended. The conservative approach involves a small punch biopsy of the cyst that allows the cyst cavity to be entered. The contents of the cyst can then be emptied, leaving an empty cyst wall that can be grasped with a forceps and pulled out of the small incision. This method often results in a very small scar and very little, if any, bleeding. Proliferating trichilemmal cyst is an uncommon lesion that is characterized histologically by trichilemmal

keratinization. It is thought to originate from a trichilemmal cyst and to have the potential for malignant transformation, at which point it is termed a malignant proliferating trichilemmal cyst.32

Syringoma Syringoma is the result of intradermal eccrine proliferation that is malformative rather than neoplastic in most cases. It occurs mainly on the eyelids and presents as a 1–2-mm nodule. Since the main reason for treating syringoma is cosmetic, the tumor should be destroyed in such a way that there is minimal scarring and no recurrence. For this purpose, electrocoagulation, dermabrasion, CO2 lasers, Er:YAG lasers, and fractional photothermolysis33 can be used, although attention should be paid to preventing pigmentation and scarring.

Apocrine cystadenoma (also known as apocrine cysthidroma) Apocrine cystadenoma is characterized by the dilatation of an apocrine duct and secondary proliferation of the ductal epithelium that is architecturally bland (Fig. 29.16). Apocrine cystadenomas appear most commonly as solitary, soft, domeshaped, and translucent papules or nodules. They are located most frequently on the eyelids, especially the inner canthus. They grow slowly and usually persist indefinitely. They can be incised and drained, but electrosurgical destruction of the cyst wall is often needed to prevent recurrence. Punch, scissors, or elliptical excision can also remove these tumors. Multiple cystoadenomas can be treated with a CO2 laser. Trichloroacetic acid34 has also been used.

Chondroid syringoma (also known as cutaneous mixed tumor) A

Chondroid syringoma derives from the sweat glands and is most frequently seen on the head and neck, where it presents as an unexceptional dermal or subcutaneous nodule

B

Figure 29.15 Solitary trichilemmal cyst on the scalp (A) and after its excision (B).  

Figure 29.16 Apocrine cystadenoma on the earlobe.  

Benign cutaneous and soft-tissue tumors

Figure 29.17 Chondroid syringoma on the lower eyelid.  

503

Figure 29.18 Steatocystoma multiplex on the trunk.  

(Fig. 29.17). The tumor consists of a gland-like epithelial component that is set in a chondromyxoid stromal component. It is believed that there are both eccrine and apocrine variants. Hirsch and Helwig proposed the following five histologic criteria for diagnosis: (1) nests of cuboidal or polygonal cells; (2) intercommunicating tubuloalveolar structures lined with two or more rows of cuboidal cells; (3) ductal structures composed of one or two rows of cuboidal cells; (4) occasional keratinous cyst; and (5) a matrix of varying composition. Since malignant forms have been reported, although they are rare, complete surgical excision is recommended.35

Others Other benign appendage-origin tumors include steatocystoma multiplex (Fig. 29.18), trichofolliculoma, trichoepithelioma, poroma folliculare, trichilemmoma, sebaceous adenoma, eccrine nevus, and apocrine nevus. Moreover, hair follicles, sebaceous glands, and sweat glands (apocrine and eccrine glands) can undergo hyperplasia that results in a hamartoma; these skin appendages can also develop adenomas, benign epitheliomas, and primordial epitheliomas.

Benign neural crest-origin tumors

Figure 29.19 Lentigo simplex on the forearm.  

Lentigo simplex Lentigo simplex is a black-brown pigmented nevus, 2–3 mm in diameter. It is believed to be an acquired pigment cell nevus that is at an early stage (Fig. 29.19). Its margins can be either jagged or smooth. It is the result of the proliferation of melanocytes in the basal layer of epidermis. It is not induced by sun exposure and is not associated with systemic disease. The lesions are few in number and may occur anywhere on the skin or mucous membranes. They usually first appear in early childhood around 3 years of age, but they can also be present at birth or develop later. Cryosurgery, lasers,37 and simple excision can be tried.  

Pigment cell nevus (also known as pigmented nevus and nevus cell nevus) These are acquired and congenital nevi that originate from melanocytes. It has been suggested that healthy adults have on average 5–10 nevi. Dome-like elevated nevi sometimes bear hair. If an acquired nevus has a diameter of more than 7 mm and it is still growing, the possibility of malignant melanoma should be considered. It seems now that malignant melanomas do not originate from pigment cell nevus (except in the case of congenital giant nevus) but rather derive directly from epidermal melanocytes; this is known as the de novo carcinogenesis theory.36 There are five types of pigmented nevi, as follows.  

Acquired pigment cell nevus Acquired pigment cell nevi are due to the proliferation of melanocytes and can be divided into three types according to

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Figure 29.21 Medium-type congenital pigment cell nevus on the back.  

Figure 29.20 Intradermal nevus on the lower eyelid.  

the location of the melanocytes. In junction nevi, the melanocytes are mainly located at the junction between the epidermis and dermis. In compound nevi, the melanocytes are located in the dermis as well as at the junction between the epidermis and dermis. In intradermal nevi (Fig. 29.20), the melanocytes are in the dermis only. Laser treatment is ineffective for melanocytes located in the deeper layer of dermis because these cells lack the melanin pigment. Thus, simple surgical excision is recommended to prevent recurrence. The nevus that has a depigmented area around it is called Sutton’s halo nevus.38

Congenital pigment cell nevus The congenital pigment cell nevus is present at the time of birth and increases in size as the body grows, although its shape does not change. It is divided according to size into the small type (less than 1.5 cm in diameter), medium type (1.5–20 cm in diameter), and large or giant type (over 20 cm in diameter) (Fig. 29.21). Histology shows that the nevus cells tend to be diffusely distributed in the deep layer of the dermis. Careful observation is needed because malignant melanomas can arise from giant congenital pigmented cell nevi.39 Nevi that present on both the upper and lower eyelids are called divided nevi, while hairy giant nevi are called animal-skin nevi (Fig. 29.22). Giant nevi should be removed and reconstructed by the serial excision method, skin grafting, local flaps, or a combination of these.  

 

 

Dysplastic nevus (also known as Clark’s nevus and atypical mole) Clinically, dysplastic nevus resembles an early-stage malignant melanoma.40 It was initially thought to be a prodrome of malignant melanoma but is now suggested to be a type of acquired pigment cell nevus. Complete excision and pathologic examination should be performed. The US National Institutes of Health Consensus Conference on the diagnosis and treatment of early melanoma defined the familial atypical mole and melanoma syndrome,41 the criteria for which are the

Figure 29.22 Animal-skin nevus.  

occurrence of malignant melanoma in one or more first- or second-degree relatives, the presence of numerous (often >50) melanocytic nevi, some of which are clinically atypical, and the presence of certain histologic features in many of the associated nevi.

Juvenile melanoma (also known as Spitz nevus) This is a dome-like nodule that is about 1 cm in diameter and occurs on the face or legs of young patients (Fig. 29.23).42 The  

Benign cutaneous and soft-tissue tumors

Figure 29.23 Spitz nevus on the cheek.

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Figure 29.24 Solitary nevus spilus on the knee.

 

 

surface is smooth and sometimes exhibits telangiectasia. It may be nonpigmented or have a color that ranges from pink to orange-red. Some lesions are pigmented, especially those on the lower extremities. After its appearance, the lesion tends to grow rapidly and may reach a size of 1 cm within 6 months. After this rapid initial growth phase it tends to become static, although color changes may be observed. Bleeding and pruritus are rare. Complete excision and pathologic examination should be performed.  

Nevus spilus (also known as café-au-lait spot) This is a benign tumor of melanocytes that is characterized by the increased accumulation of melanin granules rather than the proliferation of melanocytes (Fig. 29.24). The whole nevus has a uniform café-au-lait color. The presence of six or more nevus spilus lesions that are greater than 5 mm in diameter in prepuberty and over 15 mm in diameter in postpuberty is indicative of neurofibromatosis type 1 (NF1), also known as von Recklinghausen’s disease (Fig. 29.25). NF1 is caused by a mutation of the chromosome band 17q11.2, which encodes neurofibromin. Neurofibromatosis type 2 (NF2) patients rarely have nevus spilus lesions and do not demonstrate the cutaneous neurofibromas that typically result in the early diagnosis of NF1, although they may have cutaneous schwannomas that resemble skin tags. Moreover, because symptoms from cranial nerve VIII schwannomas usually begin in the third decade of life, patients with NF2 are typically diagnosed later in life than patients with NF1.43  

 

Becker’s melanosis (also known as Becker’s pigmented hairy nevus) This lesion is characterized by the slight proliferation of melanocytes in the basal layer of the epidermis, the increasing accumulation of melanin granules, and the presence of hair. It mainly occurs in males and develops at puberty, which suggests that androgens may play a role in its development. This is supported by the fact that it is associated with hypertrichosis, the occasional development of acneiform lesions

Figure 29.25 Nevus spilus on the thigh of patient with neurofibromatosis type 1.  

within the patch, and, albeit rarely, with an accessory scrotum in the genital region. In addition, it has been reported that Becker melanosis lesional skin has significantly more androgen receptors than the normal surrounding skin. Ruby lasers, CO2 lasers, and Er:YAG lasers can be used to treat Becker’s melanosis.44

Nevus of Ota (also known as nevus fuscoceruleus ophthalmomaxillaris and oculodermal melanocytosis) This is a blue nevus that arises from the first and second branches of the trigeminal nerve (Fig. 29.26). It is common in Asians and rare in populations of European origin. Women are nearly five times more likely to be affected than men. It is not congenital but appears during early infancy and puberty.45 It is caused by the proliferation of melanocytes in the dermis. Bilateral nevus of Ota also exists: this is called acquired bilateral nevus of Ota-like macules or late-onset dermal

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Figure 29.27 Nevus of Ito.  

Figure 29.26 Nevus of Ota.  

melanocytosis. It has been suggested that nevus of Ota may be derived from melanocytes that have not migrated completely from the neural crest to the epidermis during embryogenesis. The variable prevalence among different populations suggests a genetic influence, but familial cases of nevus of Ota are exceedingly rare. The two peak ages of onset in early infancy and early adolescence suggest that hormones are a factor in the development of this condition. Q-switched ruby or alexandrite lasers have been used to treat nevus of Ota.46 After 4–8 treatments, the degree of skin pigmentation is reduced dramatically. Cryotherapy, dermabrasion, or peeling can also be used as a multimodal therapy on a case-by-case basis.

Nevus of Ito This dermal melanocytosis can be considered as a subtype of nevus of Ota (Fig. 29.27). It occurs on the acromiodeltoid region.47 Its pathogenesis is unclear, but the fact that the dermal melanocytes of the nevus of Ito are in close proximity with nerve bundles suggests the nervous system may be a factor in its development. Recommended treatments are the same as those for nevus of Ota.

Mongolian spot (also known as congenital dermal melanocytosis) More than 90% of Native American, 80% of Asian, and 70% of Hispanic infants have this proliferative disorder of dermal melanocytes, which presents as bluish-gray spots on the sacral and coccygeal region (Fig. 29.28). Fewer than 10% of infants of European descent have mongolian spots. These spots disappear before the age of 10 years. The blue–gray color is due

Figure 29.28 Typical mongolian spot on an Asian infant.  

to the melanocytes that are deep in the skin. It usually presents as multiple spots or one large patch covering the lumbosacral area (lower back), buttocks, flanks, and/or shoulders (Fig. 29.29). It results from the entrapment of melanocytes in the dermis during their migration from the neural crest to the epidermis during embryonic development.48 Treatment is usually not necessary, but Q-switched alexandrite laser can be used for severe cases.

Blue nevus Like the nevus of Ota and the mongolian spot, this is a dermal melanocytosis. However, it involves more cells, which means it has a nodular form. There are three types: common,

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Figure 29.29 Atypical mongolian spot on the back.

Figure 29.30 Schwannoma on the popliteal region.

cellular, and combined.49 The cellular lesion is usually larger than the common lesion and tends to invade the subcutaneous tissue. The combined lesion is a blue nevus that is combined with a pigment cell nevus or a juvenile melanoma. A biopsy should be performed to determine the proper diagnosis. For a solitary lesion, simple excision is usually curative. There are rare cases of persistent blue nevi that manifest as satellite lesions around the original excision site. These must be distinguished from malignant blue nevus and re-excision is recommended.

or palisading bundles of spindled Schwann cells with blunt, elongated nuclei. In each Verocay body, the long axes of the cells are all oriented toward the acellular area. Type B lacks Verocay bodies and consists of a loose, myxomatous stroma with fewer and more randomly arranged spindle cells. Neither type appears to have neurites. Schwannomas are typically encapsulated and the associated peripheral nerve may be seen in the microscopic section. Occasionally, older lesions show degenerative changes such as hemorrhage, hemosiderin deposition, mild chronic inflammatory cell infiltration, dense fibrosis, and nuclear pleomorphism. Such ancient schwannomas51 are benign but must be differentiated from neurofibrosarcoma and malignant schwannoma. Surgical removal is the first choice of treatment.

 

Neuroma Neuromas are hamartomas composed of peripheral nerve components, namely Schwann cells, fibroblasts, and axons; they arise as a result of ineffective, unregulated nerve regeneration that leads to neurofiber hyperplasia. They are often the result of nerve injury, especially injuries sustained during surgery; both superficial (skin or subcutaneous fat) and deep (e.g., cholecystectomy) surgery can induce neuromas. Neuromas are often very painful. It should be noted that neuroma is often used as a general term to describe any swelling of a nerve; thus, it does not necessarily mean neoplastic tumors. An example of this more general usage of the term is Morton’s neuroma, which is a mononeuropathy of the foot; to avoid confusing it with a tumor, this condition is now often referred to as Morton’s metatarsalgia.50 Surgical removal is the treatment of choice for neuromas.

Schwannoma (also known as neurilemmoma) This is a benign proliferation of Schwann cells in the dermis or subcutaneous tissues (Fig. 29.30). NF2 is associated with multiple schwannomas. Pathology shows that there are two basic histological types of schwannoma called Antoni types A and B. Type A is characterized by numerous Verocay bodies. These are acellular, eosinophilic areas that are oval, linear, or serpiginous in shape and are surrounded by parallel-lying

 

Neurofibroma A neurofibroma is a benign tumor of the peripheral nerve sheath. It is usually found in individuals with the genetically inherited diseases NF1 and NF2, and can result in symptoms that range from physical disfiguration and pain to cognitive disability (Figs. 29.31 & 29.32). Neurofibromas arise from Schwann cells but also incorporate many other types of cells and structural elements, which makes it difficult to identify and understand all the pathogenic mechanisms. Neurofibromas should be removed surgically or treated with a CO2 laser. However, once a plexiform neurofibroma52 has undergone malignant transformation, radiation and chemotherapy can be used as adjuvant therapies.

Others Other benign neural crest-origin tumors include the granular cell tumor and rudimentary polydactyly. The latter often have normal Merkel cells in the basal portion of the epidermis in addition to the proliferation of nerve fibers and encapsulated corpuscles. The proliferation of various neural components may be the essential feature of this condition.

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Figure 29.31 Mild neurofibroma on a patient with neurofibromatosis type 1.  

Figure 29.33 Sclerosing hemangioma.  

endothelial cell proliferation can sometimes be observed in both types, in which case a diagnosis of sclerosing hemangioma is made (Fig. 29.33). Moreover, if the cellular components are small and the tumor is composed of hyalinized collagenous fibers, it can be called a sclerotic fibroma. There are many other special dermatofibroma forms, including hemosiderotic histiocytoma, xanthomatous histiocytoma, atypical dermatofibroma, aneurysmal dermatofibroma, myxoid dermatofibroma, and keloidal dermatofibroma.53 Removal of the tumor is not necessary unless diagnostic uncertainty exists or particularly troubling symptoms are present.

Xanthoma

Figure 29.32 Severe neurofibroma on a patient with neurofibromatosis type 1.  

Benign mesenchymal-origin tumors Dermatofibroma (also known as fibrous histiocytoma) Dermatofibroma is a common cutaneous nodule that frequently develops on the extremities (mostly the lower legs). It is usually asymptomatic, although pruritus and tenderness are not uncommon. It is characterized by the proliferation in the dermis of both fibroblasts and other cell types, including histiocytes (skin macrophages) and vascular endothelial cells. It can be divided into the cellular type, which is mainly characterized by histiocyte proliferation, and the fibrous type, which predominantly shows fibroblast proliferation. Strong

Xanthoma is characterized by the aggregation of foamy histiocytes that have phagocytized lipids (Fig. 29.34). The most common xanthoma occurs on the upper eyelid and is often associated with hyperlipidemia. Xanthomas are not always associated with underlying hyperlipidemia but when they are, it is necessary to diagnose and treat the underlying lipid disorders to decrease the xanthoma size and reduce the risk of atherosclerosis. Treatment of the hyperlipidemia initially entails dietary changes and the use of lipid-lowering agents such as statins, fibrates, bile acid-binding resins, probucol, or nicotinic acid. Eruptive xanthomas usually resolve within weeks of initiating systemic treatment, while tuberous xanthomas usually resolve after a few months. However, tendinous xanthomas take years to resolve or may persist indefinitely. While the main goal of therapy for hyperlipidemia is to reduce the risk of atherosclerotic cardiovascular disease, in patients with severe hypertriglyceridemia the goal is to prevent pancreatitis. Surgery or locally destructive modalities, including lasers, can be used for idiopathic or unresponsive xanthomas.54

Juvenile xanthogranuloma This is a single or multiple dome-like tumor that occurs on the head and neck region, the body, or the limbs of young patients (Fig. 29.35). Approximately 35% of cases of juvenile

Benign cutaneous and soft-tissue tumors

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Figure 29.34 Xanthoma on the upper eyelid.

Figure 29.36 Touton giant cell in a juvenile xanthogranuloma.

Figure 29.35 An adult-onset juvenile xanthogranuloma on the elbow.

Figure 29.37 Acrochordon.

xanthogranuloma occur at birth, with as many as 70% of cases occurring in the first year. Most juvenile xanthogranulomas resolve by the age of 5 years. Despite the term “juvenile” in the disease name, 10% of cases manifest in adulthood. Histologic analysis can reveal the presence of Touton giant cells (Fig. 29.36). This tumor can be associated with NF1, Niemann– Pick disease, urticaria pigmentosa, and juvenile chronic myelomonocytic leukemia.55 The lesions can be excised for diagnostic and cosmetic reasons.

(Fig. 29.38), which is a large fibroma over 10 mm in diameter that has a narrow pedicle; and (3) any but (1) and (2). The color can vary between normal skin color and brownish-red. Small, pedunculated soft fibromas can be removed with curved or serrated blade scissors, while larger skin tags may simply require excision. For small, soft fibromas, aluminum chloride applied prior to removal will decrease the amount of bleeding, which is usually minor anyway. Anesthesia prior to electrodesiccation is another option. Other methods of removal include cryotherapy and ligation with a suture or a copper wire; however, freezing of the surrounding skin during liquid nitrogen cryotherapy may result in dyschromic lesions. Taking hold of the acrochordon with forceps and applying cryotherapy to the forceps may provide superior results.

 

 

Soft fibroma There are three types of soft fibroma: (1) acrochordon (also known as a skin tag) (Fig. 29.37), which occurs on the neck and axilla and increases after middle age; (2) fibroma pendulum56

 

 

 

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Figure 29.39 Typical keloids on the anterior chest of an Asian patient.  

Figure 29.38 Fibroma pendulum.  

Keloid and hypertrophic scars These scars are caused by the hyperproduction of collagen due to abnormal and prolonged cutaneous wound healing. It has been suggested that mechanical forces such as skin-stretching tension and mechanotransduction signaling pathways are associated with their generation and growth.57 The differential diagnosis of keloids (Fig. 29.39) and hypertrophic scars (Fig. 29.40) remains difficult; indeed, it is possible that they are manifestations of a fibroproliferative disorder of the skin58 that expresses a continuum of features. Nevertheless, for simplicity in clinical situations, the terms “hypertrophic scars” and “keloids” can still be used: hypertrophic scars are considered to be those that improve naturally and gradually, although the full maturation process may take up to 2–5 years, whereas keloids are considered to be those that rarely resolve naturally. To prevent the development of these scars and to treat them, multimodal therapy21 that includes steroid ointment/tape/ injection, taping fixation, silicone gel sheeting, surgery, radiation,59 cryotherapy, laser, and 5-FU is recommended.

Lipoma Lipoma is the most common of the mesenchymal soft-tissue tumors (Figs. 29.41 & 29.42). There are many subtypes, including lipoblastoma, angiolipoma, spindle cell lipoma, pleomorphic lipoma, and hibernoma. It was shown recently that these adipocellular tumors are characterized by specific chromosome and gene abnormalities and that these abnormalities can be used for diagnosis. Lipomas can be classified according to their location into entities such as intramuscular and intermuscular lipoma. Systemic lipoma is termed lipomatosis (Fig. 29.43). Diffuse lipomatosis sometimes affects the limbs, head and neck, and intestinal tract. Lipomatosis on the finger results in megadactyly. Multiple symmetric lipomatosis60 mainly occurs on the upper body (Fig. 29.44). Steroid-induced lipomatosis can be a side-effect of corticosteroid administration. A rapidly growing lipoma should be examined carefully to eliminate the possibility that it is actually a liposarcoma.

Figure 29.40 Typical hypertrophic scars on the thigh of an Asian patient.  

Complete surgical excision with the capsule is advocated to prevent local recurrence.

Leiomyoma Cutaneous or subcutaneous leiomyoma is a tumor that is derived from smooth muscles in the skin, including the arrector muscle of hair and vascular smooth muscle.61 These tumors are localized and are associated with pain. Leiomyomas can be categorized into four types: (1) multiple piloleiomyoma; (2) solitary piloleiomyoma; (3) angioleiomyoma; and (4) genital leiomyoma. Angioleiomyomas and genital leiomyomas usually occur as solitary lesions. In contrast, piloleiomyomas may be solitary or multiple; in the latter case, there may be thousands of lesions. This is because the arrector pili muscle from which piloleiomyomas originate has multiple points of insertion, such as those located proximal to the hair follicle, those located distal to the multiple attachment points within the papillary and reticular dermis, and those located in the basement

Benign cutaneous and soft-tissue tumors

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A A

B

Figure 29.41 Lipoma on the nape (A) and the lesion after excision (B).  

B

Figure 29.43 Multiple lipomatosis (A) and the lesions after excision (B).  

Figure 29.44 Multiple symmetric lipomatosis.  

Figure 29.42 Lipoma on the face.  

Rhabdomyoma membrane. Piloleiomyomas can emerge from each of these insertion points, thus occurring as multiple tumors. Angioleiomyoma often occurs on the distal area of the limbs, especially under the knee in women. In contrast, angiolipoma commonly occurs on the head in men and is often not associated with pain. Surgical excision or ablation of the leiomyoma may be helpful for some symptomatic individuals.

Rhabdomyoma is a benign tumor of striated muscle. It is most commonly associated with the heart and tongue but can also occasionally occur as a superficial mesenchymal tumor. There are adult, fetal, and genital types. The adult-onset type often occurs on the head and neck area, whereas the fetal type often occurs on the postauricular area of children under the age of 3 years. Patients with adult rhabdomyoma should have surgical resection of head and neck lesions, especially those

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lesions that compress or displace the tongue, or protrude and partially obstruct the pharynx or larynx. Fetal rhabdomyomas are usually located in the subcutaneous tissues.62 In most instances, they can be excised without much difficulty. Local excision is the treatment of choice for genital rhabdomyomas.

Osteochondrogenic tumors Chondromas and osteochondromas often occur in adults on the hand and foot. Osteochondromas are sometimes associated with calcification. Osteomas are composed of mature bone but can be considered to be reactive outgrowths. Osteoma cutis63 refers to the presence of bone within the skin in the absence of a pre-existing or associated lesion, as opposed to secondary types of cutaneous ossification that are the result of metaplastic reactions to inflammation, trauma, and neoplastic processes. Osteoma cutis can be removed by excision or laser resurfacing that ablates the overlying skin. Myositis ossificans, panniculitis ossificans, and fibrodysplasia ossificans progressiva are also reactive ossifications. Exostosis is also considered to be a reactive osteochondrogenic disorder (Fig. 29.45). This often occurs on the cranial and subungual regions. Exostosis can be removed easily by a chisel and hammer, and its recurrence is rare.

A

Accessory auricle (also known as nevus cartilagines) This congenital nevus arises from the area between the tragus and the lateral neck (Fig. 29.46). Nevi that are near the ear are largely composed of cartilage, while nevi that are distant from the ear are mainly composed of hair follicles. Multiple accessory auricles64 are sometimes associated with hemifacial microsomia. Surgical removal may be possible. If so, sufficient skin and cartilage should be removed so that flat and linear scars are the result rather than a dog-ear deformity.

Granuloma Granulomas can be broadly classified as infectious (Fig. 29.47) and noninfectious. Almost all noninfectious granulomas are foreign-body granulomas; some of these are associated with a type IV allergy. There are a number of causes of foreign-body granuloma. These can be divided into endogenous causes such as uric acid salt, cholesterol, and sebum production, and exogenous causes such as materials injected for aesthetic surgery65 (Fig. 29.48), vaccines, surgical sutures, and materials implanted by trauma (Fig. 29.49). Small pyogenic granulomas (telangiectatic granulomas) and foreign-body granulomas can be removed by surgery, but this may not be possible for large and multiple granulomas. In this case, systemic or local corticosteroid administration to reduce inflammation should be considered.

B

Figure 29.45 Exostosis on the frontal bone (A) and the excised specimen (B).  

Glomus tumor Glomus tumors arise from the arterial portion of the glomus body, or the Sucquet–Hoyer canal, which is an arteriovenous anastomosis in the dermis that participates in temperature regulation. Patients with solitary glomus tumors usually have paroxysmal pain that can be severe and exacerbated by pressure or temperature changes, especially cold. Multiple glomus

Figure 29.46 Accessory auricle.  

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A

Figure 29.47 Pyogenic granuloma on the back.  

B

Figure 29.49 Foreign-body granuloma caused by the implantation of a large wood splinter (A) and view of the patient just after surgery (B).  

Capillary malformation Hemangioma simplex

Figure 29.48 Foreign-body granuloma caused by a nasal implant.  

tumors can also be painful but are less common; the pain is also usually not severe. Two features that are useful for diagnosing glomus tumors, particularly solitary painful glomus tumors (especially those under a nail), are the Hildreth sign, which is the disappearance of pain after a tourniquet is placed on the proximal arm, and the Love test, where pain is elicited by pressing the skin overlying the tumor with the tip of a pencil. The treatment of choice for solitary glomus tumors is surgical excision. For multiple glomus tumors,66 excision may be more difficult because of their poor circumscription and the large number of lesions. In this case, excision should be limited to symptomatic lesions.

This is the result of the abnormal development or differentiation of capillary vessels in the dermis.67 According to its location, it can be classified into three types: (1) portwine stain (face, limbs, and upper body) (Figs. 29.50 & 29.51); (2) salmon patch (medial forehead, glabella, nasal tip, and upper lip); and (3) nevus Unna (nape). Portwine stains are sometimes associated with Sturge–Weber syndrome (face) and Klippel–Trenaunay syndrome (limb). Patients with solitary hemangioma simplex, regardless of whether they have these syndromes, should be subjected to brain examinations. Of the three types, only the salmon patch can disappear within a year after birth. A dye laser or Nd:YAG laser can be used to treat these lesions.

Strawberry hemangioma This tumor is derived from the endothelial cells of capillary vessels in the skin. It arises around 3–4 weeks after birth and its growth peaks at 6–7 months of age (Figs. 29.52 & 29.53). After this growth period, the volume rarely decreases naturally, although the color can become less livid spontaneously. Consequently, laser treatments with, for example, dye or Nd:YAG lasers should be performed at an early stage to prevent the capillaries from proliferating further.68 On a case-bycase basis, surgical excision, steroid injection, and compression therapy may also be suitable.

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Figure 29.50 Portwine stain on the face of an infant.

Figure 29.52 Strawberry hemangioma on the frontal head of an infant.

 

 

Figure 29.53 Strawberry hemangioma on the trunk.  

Arteriovenous fistula and arteriovenous malformation (AVM)

Figure 29.51 Portwine stain on the face of an adult.  

Venous malformation A representative type of venous malformation is a cavernous hemangioma, which is a blood-storing lesion with a low blood flow (Fig. 29.54). Histology shows the absence of endothelial cell proliferation. It is seen in Klippel–Trenaunay syndrome, which is characterized by various malformations, including capillary malformation and bony and soft-tissue hypertrophy. Venous malformation is best treated with sclerosing therapy, where sclerosing agents like absolute ethanol, polidocanol, sodium tetradecyl sulfate, or ethanolamine oleate are injected into the lesion under ultrasound or digital subtraction angio graphy guidance.69 ­

Arteriovenous fistula and AVM are high-flow pulsating lesions with an arteriovenous shunt; they are either acquired because of trauma or are congenital (Fig. 29.55). CDI is useful for detecting the blood flow in the tumor. Patients with Parkes–Weber syndrome who have a huge limb AVM sometimes exhibit congestive heart failure. The Schobinger classification allows AVMs to be classified into four clinical stages: (I) quiescence; (II) expansion; (III) destruction; and (IV) decompensation. Patients with heart failure are considered to have stage IV AVMs. Surgical removal is the first choice of treatment but is often hampered by the diffuse distribution of the vessels and the specific anatomy in the affected region (e.g., the local presence of a facial nerve). Incomplete resection results in the rapid regrowth of the remaining lesion. In cases

Malignant cutaneous and soft-tissue tumors

Figure 29.54 Cavernous hemangioma on the lower lip.  

515

Figure 29.56 Mucous cyst of the oral mucosa.  

Malignant cutaneous and soft-tissue tumors Malignant epithelial-origin tumors Actinic keratosis

Figure 29.55 Congenital mild arteriovenous malformation on the forearm.  

where surgical removal is difficult, embolosclerosing therapy can be used as a palliative therapy.70

Lymphatic malformation There are two main types of lymphatic malformation: lymphangioma and cystic hygroma. Clinically, lymphatic malformation can be classified into macrocyst (cystic hygroma and lymphangioma cystoides), microcyst (lymphangioma simplex), and combined (cavernous lymphangioma) types. The microcysts can be removed surgically, while the macrocysts and combined types should be treated by surgery or sclerotherapy using OK-43271 or absolute ethanol on a case-by-case basis.

Others There are many other benign mesenchymal-origin tumors. These include giant cell tumor, histiocystoma, reticulohistiocystoma, fibroxanthoma, desmoid tumor, mucous cyst of the oral mucosa (Fig. 29.56), cutaneous myxoma, Langerhans cell histiocytosis, Kimura disease, plasmacytosis, and mastocytosis.

Actinic keratosis is an intraepidermal early-stage SCC caused by long-term exposure to ulraviolet light (Fig. 29.57). It is mostly seen in the elderly, especially fair-skinned people who have been highly exposed to the sun. The areas that bear the lesions are those that have been most exposed. Over time, actinic keratoses develop into invasive SCC. They are epidermal lesions that are characterized by aggregates of atypical, pleomorphic keratinocytes at the basal layer that may extend upwards to involve the granular and cornified layers. Cutaneous horns72 sometimes occur in association with a hyperkeratotic actinic keratosis. Surgical removal is recommended but cryosurgery, CO2 lasers, 5-FU ointment, and chemical peeling may also be useful for selected cases.

Bowen’s disease Bowen’s disease is an intraepidermal carcinoma since it is a malignant tumor of keratinocytes. It can progress to invasive SCC. If the invasion is deep, it is termed Bowen’s carcinoma; this carcinoma can metastasize. The diagnosis of Bowen’s disease is often delayed because the lesion is asymptomatic and early skin changes may be subtle and overlap with the clinical features of many conditions, including tinea corporis, nummular eczema, seborrheic keratosis, Paget’s disease, superficial BCC, actinic keratosis, and psoriasis. A classic feature of the clinical history is the presentation of a nonsteroid-responsive dermatosis. Surgical removal is recommended but cryosurgery, CO2 lasers, 5-FU ointment, and imiquimode 5% cream73 may also be suitable for selected cases.

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Figure 29.57 Actinic keratosis on the cheek of an elderly patient.  

Figure 29.59 Squamous cell carcinoma on the sole that has arisen from traumatic scars.  

Figure 29.58 Squamous cell carcinoma on the cheek of an elderly patient.  

Squamous cell carcinoma SCC is a common cutaneous malignancy that often presents as an elevated, indurated lesion with varying degrees of ulceration and crusting (Fig. 29.58). SCC can arise on any site but is most common in damaged skin such as actinically damaged skin, postburn scars (Marjolin’s ulcer), traumatic scars (Fig. 29.59), stasis ulcers, chronic radiation dermatitis, lupus erythematosus lesions, lichen planus on the oral mucosa, and human papillomavirus infection lesions. One type of SCC is verrucous carcinoma. Since SCC can resemble BCC, it is important to make a differential diagnosis. One notable characteristic of SCC is the bad smell caused by the macerated keratin and bacterially infected necrotic tissues (Fig. 29.60). SCC should be removed by surgery. Mohs micrographic surgery74 is frequently used to remove SCCs. Radiotherapy given as external-beam radiotherapy or as brachytherapy (internal radiotherapy) can also be used.

Basal cell carcinoma BCC is the most common type of skin cancer (Fig. 29.61). It rarely metastasizes and kills, but is still considered malignant

Figure 29.60 Advanced squamous cell carcinoma on the face that shows necrosis and infection.  

because it can invade surrounding tissues and cause significant destruction and disfigurement. It most commonly affects the head and neck, and cosmetic disfigurement is not uncommon. It can be classified into 10 types75 (Box 29.5). It should be removed by surgery. Mohs micrographic surgery is frequently utilized. However, for selected cases of superficial BCC, CO2 lasers or cryosurgery can be used.

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517

Figure 29.62 Meibomian gland carcinoma on the upper eyelid.  

Figure 29.61 Basal cell carcinoma on the scalp.  

BOX 29.5 Histological classification of basal cell carcinoma (BCC)  

1. Multifocal superficial BCC (superficial multicentric) 2. Nodular BCC (solid, adenoid cystic) 3. Infiltrating BCC 3.1. Nonsclerosing 3.2. Sclerosing (desmoplastic, morpheic) 4. Fibroepithelial BCC 5. BCC with adnexal differentiation 5.1. BCC with follicular differentiation 5.2. BCC with eccrine differentiation 6. Basosquamous carcinoma 7. Keratotic BCC 8. Pigmented BCC 9. BCC in basal cell nevus syndrome 10. Micronodular BCC  



 



 







 



 



Figure 29.63 Malignant trichilemmal cyst.  





 



 



 



 





Reproduced from LeBoit PE, Burg G, Weedon D, et al., eds. World Health Organization Classification of Tumors. Pathology and Genetics of Skin Tumors. Lyon: IARC Press; 2006: 10–33.

Trichilemmal carcinomas are malignant tumors of these cells. They include malignant trichilemmoma, malignant pilomatricoma, and malignant proliferating trichilemmal cyst (Fig. 29.63). The latter is thought to be derived from proliferating trichilemmal cyst,32 while malignant pilomatrichoma is believed to be derived from pilomatricoma. Clinically, these tumors present as pale tan or reddish papules, indurated plaques, or nodules. Wide excision should be performed as a radical therapy.

Malignant appendage-origin tumors

Sweat gland carcinoma

Sebaceous carcinoma

There are many types of eccrine and apocrine carcinomas. These malignant primary cutaneous tumors exhibit glandular and/or ductal features that are thought to reflect their origin as eccrine or apocrine ducts and/or glands. The diagnosis of sweat gland carcinoma requires that the tumor shows sweat gland features, as shown by extracellular ductal or intracytoplasmic lumen formation. This can be indicated by resistance to diastase, staining with periodic acid–Schiff stain, and immunohistochemical positivity for epithelial membrane antigen and carcinoembryonic antigen. The presence of S100 protein may also indicate sweat gland differentiation. Conventional surgical excision has been associated with high recurrence rates but Mohs micrographic surgery is helpful.77 These carcinomas should be treated according to the guidelines for SCC.

Meibomian gland carcinoma (Fig. 29.62), Zeis gland carcinoma, and Montgomery’s gland carcinoma are all sebaceous carcinomas. These carcinomas often exhibit erosion and ulceration. A wide excision with a normal skin margin exceeding 5 mm is recommended. Lymph node dissection should be considered in T4 cases because of the high rate of lymph node metastasis associated with sebaceous carcinomas. Chemotherapy and radiation therapy may also be useful.76  

Trichilemmal carcinoma The outer hair root sheath consists of cells with clear vacuolated cytoplasm due to the presence of abundant glycogen.

CHAPTER 29 • Nonmelanocytic tumors of the skin and soft tissue

518

 

Figure 29.64 Mapping biopsy for extramammary Paget’s disease.  

Figure 29.65 Merkel cell carcinoma on the eyelid.  

Extramammary Paget’s disease Paget’s disease is an adenocarcinoma that is limited to the epidermis. Since mammary Paget’s disease is sometimes associated with invasive breast cancer, it can be considered as an intraepidermal proliferating breast carcinoma. In contrast, EMPD is only occasionally associated with an underlying invasive malignancy. It is usually found in the vulva, penis, and axilla. Since its invasive speed is relatively high, it can be difficult to detect early, especially if the lesion has been treated as eczema. Mohs micrographic surgery78 or mapping biopsy is helpful for determining the normal skin margin for wide excision (Fig. 29.64). Sentinel lymph node biopsy is also useful for deciding whether to remove the lymph nodes.

Merkel cell carcinoma Merkel cell carcinoma is a rare and highly aggressive cancer where malignant cancer cells develop on or just beneath the skin and in hair follicles (Fig. 29.65). The majority of Merkel cell carcinomas appear to be caused by the newly discovered Merkel cell polyomavirus. It occurs most often on the face, head, and neck, and usually appears as firm and painless nodules or tumors. A normal skin margin of 1–2 cm is needed for wide excision. Moreover, since this tumor tends to metastasize to lymph nodes, lymph node dissection and adjuvant radiation therapy may have to be implemented.79 Distant metastasis cases should also receive chemotherapy.79

Figure 29.66 Dermatofibrosarcoma protuberans on the abdomen.  

 

Malignant mesenchymal-origin tumors

treatment with corticosteroids. They metastasize rarely, but distant metastasis to the lung can result from local recurrence. Radical resection should include a normal skin margin of 5 cm. Mohs micrographic surgery with continuous histological margin control is needed to reduce local recurrence rates.80 Adjuvant chemotherapy and radiation therapy may be useful.

Dermatofibrosarcoma protuberans (DFSP)

Pleomorphic undifferentiated sarcoma (PUS)

DFSP is also called giant cell fibroblastoma. Over 90% of DFSP tumors have the chromosomal translocation t(17;22) that fuses the collagen gene COL1A1 with the platelet-derived growth factor gene. Typically, DFSP occurs as multiple or solitary tumors that have a red color, hemispherical elevation, and papillary vessels on the surface (Fig. 29.66). They have a keloidal appearance, which has sometimes led to misdiagnosis and

There are four types of MFH (which is more recently being classified as pleomorphic undifferentiated sarcoma81): (1) storiform-pleomorphic type; (2) myxoid type; (3) giant cell type; and (4) inflammatory type. Moreover, atypical fibroxanthoma is considered to be a superficial type (Fig. 29.67). Despite being called histiocytomas, these tumors are not believed to be derived from histiocytes. In fact, it is currently

 

Malignant cutaneous and soft-tissue tumors

Figure 29.67 Malignant fibrous histiocytoma on the axilla.  

519

Figure 29.68 Liposarcoma on the thigh.  

being argued on the basis of immunohistochemistry and electron microscopic observations82 that most of the storiform pleomorphic-type should be reclassified as liposarcomas, leiomyosarcomas, or rhabdomyosarcomas. Radical therapy involving wide excision is needed. Adjuvant chemotherapy and radiation therapy may also be useful.

Liposarcoma Liposarcoma is derived from the fat cells in deep soft tissues such as inside the thigh or the retroperitoneum (Fig. 29.68). They are generally large and bulky tumors with multiple smaller satellites located outside the main tumor. Diagnosis requires the detection of lipoblasts, which usually have an abundant, clear, multivacuolated cytoplasm and an acentric, darkly staining, vacuole-compressed nucleus. Dedifferentiated liposarcomas exhibit a dedifferentiated area in the tumor that sometimes results in osseous metaplasia.83 Radical therapy involving wide excision is needed. Adjuvant chemotherapy and radiation therapy may be useful.

Leiomyosarcoma This rare malignancy mainly occurs on the limbs of middle-aged and older patients (Fig. 29.69). It can be very unpredictable as it can remain dormant for long periods of time and recur after years. It is generally not very responsive to chemotherapy or radiation. However, neoadjuvant or adjuvant chemotherapies,84 or radiation, are recommended.

Rhabdomyosarcoma Rhabdomyosarcoma is thought to arise from skeletal muscle progenitors and occurs in many anatomic locations. Sometimes it is found attached to muscle tissue or wrapped around intestines. Mostly it occurs in areas that naturally lack skeletal muscle, such as the head, neck, and genitourinary

Figure 29.69 Leiomyosarcoma on the face.  

tract. Its three most common forms are embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, and pleomorphic rhabdomyosarcoma. Embryonal rhabdomyosarcoma is more common in younger children, where the cancer cells resemble those of a typical 6–8-week embryo. Alveolar rhabdomyosarcoma occurs more commonly in older children and teenagers, and the cells resemble those of a typical 10–12-week embryo. Pleomorphic rhabdomyosarcoma is a rare sarcoma that occurs most often in older patients. Radical therapy involving wide excision is needed. There is also evidence that rhabdomyosarcomas are the target of host immune responses.85

CHAPTER 29 • Nonmelanocytic tumors of the skin and soft tissue

520

 

Figure 29.70 Computed tomography of an osteosarcoma on the frontal bone.  

Osteosarcoma This aggressive cancerous neoplasm arises from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoids (Fig. 29.70). Complete radical surgical en bloc resection is the treatment of choice.86 Some recent studies have suggested that osteoclast inhibitors such as alendronate and pamidronate may improve the quality of life by reducing osteolysis, which decreases the pain as well as the risk of pathological fractures.

Chondrosarcoma At presentation, nearly all chondrosarcoma patients appear to be in good health as this form of cancer usually does not affect the whole body. Indeed, the patients are generally not aware of the growing tumor until there is a noticeable lump or pain. An earlier diagnosis is generally accidental, such as when a patient undergoes testing for another problem. Occasionally, the first symptom will be a broken bone at the cancerous site. Therefore, broken bones due to mild trauma warrant further investigation, even though there are many conditions that can lead to weak bones and this form of cancer is not a common cause of such breaks. Chemotherapy or traditional radiotherapy is not very effective for most chondrosarcomas, although proton beam radiation therapy is showing promise with regard to local tumor control.87 Complete surgical ablation is the most effective treatment but can be difficult to achieve. Proton beam radiation can facilitate the surgical removal of chondrosarcomas in awkward locations.

Angiosarcoma Angiosarcoma is the common name for malignant neoplasms of endothelial cells (Fig. 29.71) but it is replaced with the terms lymphangiosarcoma and hemangiosarcoma when more clinical precision is required. Haemangiosarcomas and lymphangiosarcomas of the skin are not uncommon. Given the location of angiosarcomas, metastasis to distant sites occurs often. Surgery, radiation therapy, chemotherapy, and immunotherapy using interleukin-288 should be used, but the prognosis of these tumors is poor. However, the prognosis

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Figure 29.71 Angiosarcoma on the axilla.  

of neoplasia of superficial vessel tissues such as those in the skin is generally better because the risk of malignancy is lower; moreover, these tumors are generally more accessible to treatment.

Kaposi’s sarcoma Kaposi’s sarcoma is caused by the Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8. It became widely known after its frequent appearance in acquired immune deficiency syndrome (AIDS) patients was noted in the 1980s. Although the viral cause of this cancer was discovered in 1994, this causal link remains poorly understood by the general populace, including by the groups that are at particular risk of contracting KSHV. Kaposi’s sarcoma lesions present as red, purple, brown, or black nodules or blotches that are usually papular (i.e., palpable or raised). They are typically found on the skin but can often spread elsewhere, especially to the mouth, gastrointestinal tract, and respiratory tract. Their growth can range from very slow to explosively fast, and they are associated with significant mortality and morbidity. Radiation therapy, cryotherapy, and chemotherapy may be useful. Surgery is not the primary choice of treatment, although it may be useful as supportive therapy. Highly active antiretroviral therapy should be combined with these therapies.89

Others Other malignant mesenchymal-origin tumors include epithelioid sarcoma, synovial sarcoma, extraskeletal Ewing’s sarcoma, histiocytic sarcoma, and Langerhans cell sarcoma. In general, treatment consists of induction chemotherapy, wide surgical excision, and then maintenance chemotherapy. Multiagent chemotherapy has improved survival rates.

References

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30 Melanoma Sydney Ch’ng and Alexander H.R. Varey

SYNOPSIS

 

 

 

 

 

 

 

ƒ Melanocytes usually exist as single cells in the basal layer of the epidermis, of which they represent approximately 1 in 8 cells. They function to export melanin via dendrites to the squamous cells which form a shield over the nucleus to absorb ultraviolet radiation. ƒ Melanoma occurs predominantly in fairer-skinned people as a result of ultraviolet radiation. The incidence has risen dramatically in recent decades in many countries but is now stable in some of those, including the US and Australia. ƒ Melanomas have an extremely varied appearance and may be amelanotic. ƒ The “ABCDE” screening tool has a good sensitivity and specificity but can be significantly increased by use of dermoscopy. ƒ Melanocytic nevi are mostly acquired, though can be congenital. They represent clonal proliferations of benign melanocytes. ƒ The risk of melanoma from a small congenital melanocytic nevus is very low, but around 2% for giant ones (>20 cm projected adult size). Excision of giant lesions does not completely remove the risk of developing a melanoma. Superficial removal techniques have no effect on the final skin color. ƒ The risk of malignant transformation of lentigo maligna (an in situ form of melanoma) is estimated to be up to 3.5% per year. ƒ The commonest histologic subtype of melanoma is superficial spreading. ƒ Acral and subungual melanomas occur with similar incidence across all skin types and are rarely caused by ultraviolet radiation. ƒ Accurate staging and prognosis requires sentinel node biopsy for tumors >1.0 mm thick. ƒ Suspicious pigmented/melanocytic (this may be amelanotic) lesions should have an excision biopsy with a 2 mm margin where possible; incomplete biopsies, including punch, incision, curette, and shave biopsies, can contribute to a pathologic misdiagnosis. ƒ Wide local excision margins of 1 and 2 cm appear adequate for melanomas ≤2 mm and >2 mm in Breslow thickness, respectively; for melanoma in situ, a 5–10 mm margin is recommended. ƒ Completion regional lymphadenectomy has been abandoned in favor of close observation with regular ultrasound plus/minus other imaging

modalities, including CT, PET-CT, and brain MRI, in sentinel node-positive patients. Sentinel node biopsy provides important staging information for prognostication, and identifying patients for adjuvant systemic therapy. ƒ For clinically detected regional nodal metastasis, therapeutic lymph node dissection remains the standard of care, although the extent of dissection is debatable in the era where more effective adjuvant systemic therapy has become routine; there is a trend towards more selective (less comprehensive) dissection. ƒ Immune checkpoint inhibitor immunotherapy and BRAF/MEK targeted therapies have revolutionized melanoma treatment resulting in much improved outcomes for unresectable stage III and stage IV disease. ƒ For patients with oligometastatic recurrence, or residual resectable metastases after most have responded to systemic therapy, salvage metastasectomy in carefully selected patients has been shown to be safe and associated with durable survival and local control.

Introduction Melanocytes are neuroectoderm-derived epithelial cells that represent approximately 10–20% of the basal layer in the cutaneous epidermis. These cells do not undergo proliferation under normal circumstances, but instead distribute melanin packaged as melanosomes via their dendrites to neighboring squamous cells. This melanin is then distributed within the squamous cells to form a protective shield from ultraviolet irradiation (UVR) over the external aspect of the nucleus. Melanoma is a cancer of melanocytes that occurs most commonly on the skin of fairer-skinned people due to UVRinduced genomic mutations. However, melanoma occasionally also occurs in non-sun-exposed sites such as mucosa, or sun-protected sites such as the glabrous skin of the palms and soles or subungually. The age-standardized incidence rates (SIR) of cutaneous melanoma have risen dramatically in the last few decades in many countries with a large proportion of fair-skinned people.

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CHAPTER 30 • Melanoma  

This is particularly where the UVR exposure is high, most notably in Australia and New Zealand, but also in regions with lower UVR exposure from which people often spend vacations in higher UVR regions and therefore have intermittent high doses, which is known to be a significant risk factor for melanoma. These increased SIRs for melanoma now place it amongst the top six cancers in many Western countries.1,2 Increased awareness of melanoma has led to substantial efforts to encourage sun safety through public health campaigns that appear to be taking effect in Australia, New Zealand, and the US, where the SIR has now plateaued, unlike many European countries where it is still increasing rapidly.3 With increased awareness has also come an increased detection of thin melanomas, which carry a better prognosis than thick ones. Accordingly, melanoma-specific mortality rates are remaining stable in most countries. Surgical excision of a primary melanoma remains the first line for curative treatment and is effective in around 80% of cases. Furthermore, sentinel lymph node biopsy (SLNB) is increasingly recognized as an important tool for accurate staging of patients with higher-risk melanomas. Such accurate staging is needed for prognostication and, increasingly, for selecting appropriate patients for adjuvant systemic therapy. The advent of these systemic therapies means that patients at high risk of recurrence and those with regional or distant recurrence now have effective treatment options available. More effective systemic therapy has led to a paradigm shift in the way melanoma is managed over the period from 2010 to 2020.

Clinical evaluation – dermoscopy and confocal The appearance of melanomas is extremely varied, hence they are known as the “great masqueraders”. As such, a low threshold for suspicion for melanoma is required when assessing any skin lesion even if it is not pigmented, as some melanomas are amelanotic. Important in assessing a skin lesion is the history, particularly focusing on risk factors for melanoma that include any recent change in the lesion and how long it has been there, any bleeding, any previous melanomas or non-melanoma skin cancers, where the patient has spent most of their life, episodes of significant sunburn, use of solariums, immunosuppression (due to disease or medications), and any family history of cancer (particularly melanoma). The “ABCDE” screening tool has been shown to have a sensitivity of 73% and specificity of 78% for melanomas when used by dermatologists (Table 30.1) to assess melanocytic lesions.4,5 This diagnostic accuracy can be increased further using dermoscopy to a sensitivity of 90%, whilst maintaining specificity. Furthermore, dermoscopy can reduce the benign to malignant biopsy rate by up to 64%.6,7 A dermatoscope provides 10–16 times magnification and typically a polarized light source, however it requires training and experience to be effective. A commonly used algorithm for dermatoscopic assessment of a lesion is the “two-step approach”, which first aims to classify a lesion as melanocytic or not in origin. For lesions that are thought to be melanocytic, the presence or absence of various features is then assessed (Algorithm 30.1) to determine whether the lesion is benign or possibly

Table 30.1 “ABCDE” rule  

A

Asymmetrical lesion

B

Border irregular

C

Color – multiple/variegated

D

Diameter >6 mm

E

Evolution – history of change

 

malignant. Commonly encountered non-melanocytic lesions include dermatofibroma, seborrheic keratosis, basal cell carcinoma (which may be pigmented), squamous cell carcinoma, and haemangioma. A newer technology that is also proving useful for melanocytic lesions is reflectance confocal microscopy (RCM), which uses a near-infrared LASER beam to image the skin in vivo at near histological resolution. The field of view is very small, up to 8 × 8 mm with a fixed ring system or 1 × 1 mm using a handheld system. However, the imaging has a “slice” thickness of 3–5 µm and the ability to visualize structures up to 350 µm in depth.8 This permits visualization of the epidermis in most areas of skin down to below the dermoepidermal junction, which typically lies at a depth of around 100 µm (Fig. 30.1). The sensitivity and specificity with which it can diagnose melanoma is 91–100% and 68–91%, respectively.9 Since RCM can detect very small amounts of melanin,10 it is also useful for detecting amelanotic lesions, especially on the face11 and also delineating the margins of lentigo maligna preoperatively.12 Unfortunately, the availability of RCM is very limited at present due to the training required to use it effectively.  

 

 

 

 

Benign melanocytic lesions Melanocytic nevi The name nevus derives from the Latin word for birthmark and is most associated with melanocytic hamartomas, although non-melanocytic hamartomas such as sebaceous nevi also exist. Some nevi are present at birth and so termed “congenital nevi”, however the majority are “acquired nevi” that develop later in life. Melanocytic nevi represent clonal proliferations of benign melanocytes.

Congenital nevi Congenital melanocytic nevi (CMN) are often classified according to their projected adult size as small (20 cm). They occur in approximately 1% of the population, however, the vast majority of these are small,13 with the prevalence of giant lesions being approximately 1/20,000 (0.005%) live births.14 The appearance of CMN is often irregular pigmentation with hyperpigmented papules and sometimes hair. The lesions are often deep and typically larger than acquired nevi but may be indistinguishable both clinically and histologically if small. Small nevi are round or ovoid in shape, symmetrical, slightly raised, and tan to brown in color. The risk of malignant transformation of a small congenital nevus has been found to be overall very low, while it is around 2% for giant ones.14 Importantly, the risk has  

 

 

Benign melanocytic lesions

523

Algorithm 30.1 Melanocytic?

Non-melanocytic

Dermatofibroma

Melanocytic

Benign nevus

Melanoma

Basal cell carcinoma

Diffuse reticular

Atypical network

Squamous cell carcinoma

Patchy reticular

Streaks (pseudopods & radial streaming)

Seborrheic keratosis

Peripheral reticular with central hypopigmentation

Negative pigment network

Hemangioma

Peripheral reticular with central hypopigmentation

Crytalline structures (shiny white lines)

Globular

Atypical dots/globules

Peripheral reticular with central globules

Off-centered blotch or multiple blotches

Two components

Peripheral tan structureless areas

Symmetric multicomponent

Blue-white veil

Homogenous

Regression structures

Peripheral globules/starburst

Atypical vascular structures

White: benign Orange: care needed - may be malignant Red: malignant

Polygonal lines

“Two-step” dermoscopic method for pigmented lesion assessment.

A

B

Figure 30.1  (A) A superficial spreading melanoma showing asymmetry of pattern and color, multiple colors, and irregular brown dots under dermoscopy. (B) For the same lesion, round and dendritic atypical cells can be seen at the level of the dermo-epidermal junction under reflectance confocal microscopy. (A, From National Cancer Institute, AV-8500-3850, created 1985, date entered 1/1/2001; B, from Sardá SP, Suárez, R, Malvehy Guilera J. Glowing in the dark: use of confocal microscopy in dark pigmented lesions. Dermatol Clin. 2016;34(4):431-442. © 2016.)

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been found to be highest (8%) in patients with giant CMNs that were greater than 60 cm projected adult size or those with multiple CMNs and no single large lesion, and even higher (12%) in those who also had an abnormal magnetic resonance imaging (MRI) screening of the central nervous system in the first year of life.15 However, surgical excision of the giant lesions does not completely remove the elevated risk of developing melanoma, as they can develop at other sites, including leptomeningeal.14 Furthermore, recent evidence has found that superficial removal techniques such as dermabrasion have no effect on the final color of the lesions, which is determined by the normal skin color in a normal process of spontaneous lightening.16  

Acquired naevi

Predisposing conditions There are some patients who are genetically susceptible to developing melanocytic nevi and cutaneous melanoma, with up to 15% of patients reporting a family history of melanoma. However, most of this apparent heritable risk is in fact due to shared patterns of sun exposure and susceptible skin phenotypes.27 This is particularly so with MC1R high-penetrance variants, which when biallelic usually results in a red hair color phenotype and an odds ratio for developing cutaneous melanoma of 4.4, however a single such allele does not result in a red hair color phenotype but still confers an increased risk of melanoma (odds ratio 2.6).28 Another significant contribution to the risk of melanoma comes from the total number of nevi being greater than 5 mm diameter. This is a more significant risk factor than the presence of high penetrance MC1R variants, such that those with a high total nevus count (TNC) of 20 or more but with no MC1R variants have an odds ratio of 4.8.28 The interaction of MC1R variants and TNC is multiplicative such that for people with both a high TNC and biallelic high penetrance MC1R variants the odds ratio for developing cutaneous melanoma is 25.1 compared to those with a TNC less than 5 and no MC1R variants.28 Of those patients with a true familial melanoma, around 45% of cases are due to a germline mutation of either CDKN2A or CDK4 genes. These are both linked to the familial atypical mole multiple melanoma (FAMMM) syndrome, formerly known as “dysplastic nevus syndrome”. Typical clinical features of this syndrome are an early age of onset of melanoma, multiple melanomas, family history of melanoma, many dysplastic nevi and pancreatic cancer.29  

Persons of European descent on average develop between 14 and 36 acquired nevi,17,18 predominantly in sun-exposed sites, and the incidence is reduced by sun protection, suggesting UVR as a causative factor.19 These typically appear before age 20 years, reaching a peak in the fourth decade20 and tending to undergo spontaneous regression in patients over age 60 years.20 Furthermore, recent research has found that development of acquired nevi appears to be initiated by a BRAFV600E gene mutation.19 The presence of acquired nevi increases the risk of melanoma development, with the risk rising with the total number.18 Although nevi themselves have an elevated risk of malignant transformation, the overall likelihood of a melanoma arising from a nevus is lower than from a normal area of skin21 due to the much greater body surface area this represents and therefore prophylactic excision is likely to be futile.22 The location of acquired nevi can be in the basal region of the epidermis, termed “junctional”, solely within the dermis, termed “intradermal” or in both locations, when it is termed “compound”. As the depth of the nevus increases, so the pigmentation will tend to become bluer in color due to the “Tyndall effect” in which blue light scatters more than red. Nevi that are intradermal will often produce a distortion of the overlying epidermis, whereas those that are junctional are typically flat. Spitz nevi are benign lesions that typically occur in children, presenting as a firm nodule that may be normal skin-colored, pink, reddish-brown or black in color. However, the histological resemblance of these nevi to melanoma led to their original description by Sophie Spitz as “juvenile melanomas”,23 but this was later revised by Spitz and Allen when they realized the lesions had a paradoxically benign behavior.24 Since Spitz nevi have histological and clinical features that are shared with melanoma, diagnosis is difficult, and although it is more likely that lesions in children are benign and those in adults are malignant, this is not always the case.25 Consequently, it is usually recommended that lesions are excised and examined by an expert dermatopathologist, particularly in patients over 12 years or with dermoscopic asymmetry.25 Some nevi are said to be atypical, a term that is not clearly defined but is used to refer to nevi that display some characteristics of melanoma but are not overtly malignant. An international definition often used for an atypical nevus is a lesion that has a macular component in one area and at least three of the following five clinical features: diameter ≥5 mm; poorly defined border; variegated color; uneven contour; erythema.26  

Melanoma The traditional cutaneous melanoma histologic subtype classification is superficial spreading melanoma (SSM), nodular melanoma (NM), lentigo maligna melanoma (LMM), and acral lentiginous melanoma (ALM).30 The commonest of these subtypes in populations of European descent is SSMs, comprising up to 80% of all melanomas, followed by NM (14%), LMM (5%), and ALM (1%).31 However, ALM occurs with equal incidence in all skin types,32 consistent with a non-UVR etiology. Although the histologic subtypes are generally considered unimportant prognostically, they are important to understand clinically due to the differences in presentation that need to be appreciated to ensure prompt diagnosis. More recently, the World Health Organization (WHO) published a revised classification of melanoma in 2018, which has nine subtypes defined by their distinct evolutionary pathways (Table 30.2).33 These are grouped into three categories: A – those associated with cumulative solar damage (CSD), B – those not associated with CSD, and C – those that can occur in most of the pathways.

In situ melanoma Melanoma in situ (MIS) is the presence of abnormal melanocytes that are confined to the epidermis. The features that are often present include proliferation of melanocytes, formation

Melanoma

525

Table 30.2 WHO classification of melanoma subtypes  

Group

Pathway

Subtype

CSD

A

I

SSM

Low

II

LLM

High

III

Desmoplastic melanomas (DM)

High

IV

Spitz melanomas

Not associated

V

Acral melanomas

Not associated

VI

Mucosal melanomas

Not associated

VII

Melanomas arising in congenital nevi

Not associated

VIII

Melanomas arising in blue nevi

Not associated

IX

Uveal melanomas

Not associated

Any

NM

±

B

C

Adapted from Elder DE, Bastian BC, Cree IA, MAssi D, Scolyer RA. The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: detailed analysis of 9 distinct subtypes defined by their evolutionary pathway. Arch Pathol Lab Med. 2020;144(4):500-522.

A

B

Figure 30.2 (A) Acral melanoma in situ on the glaborous skin of the lateral aspect of the left foot. (B) Parallel ridge pattern, asymmetrical structure and colors, diffuse pigmentation of various shades of brown color not respecting furrows or ridges can be seen on dermoscopy. (Courtesy of Sydney Diagnostic Melanoma Center.)  

of nests and migration of melanocytes to layers superficial to the basal layer termed “Pagetoid spread”. MIS occurring in the glabrous skin or nailbeds is known as “acral lentiginous” and at other cutaneous sites “superficial spreading” (Figs. 30.2 & 30.3). However, when MIS occurs in the presence of significant chronic sun damage to the skin, it is usually termed “lentigo maligna” (LM), or historically “Hutchinson’s melanotic freckle”. MIS lesions are concerning for two reasons: firstly, they signify a 5–10-fold elevated risk of developing further primary melanomas, thereby necessitating careful lifelong skin surveillance.34,35 Secondly, they are considered premalignant, although the risk of progression to invasive melanoma is unknown. However, for LM the risk of progression to lentigo maligna melanoma (LMM) is estimated to be up to 3.5% per year, resulting in a mean time to progression of 28 years.36 Importantly, without complete excision of an MIS lesion it is not possible to completely exclude an invasive component, particularly since invasive melanomas usually have an in situ component. Due to the extensive sun damage

found in LM the adjacent skin may well have some abnormality of the melanocytes, ranging from melanocytic hyperplasia through to definite LM. Furthermore, some areas may be amelanotic, thus determining the extent of the lesion for treatment and assessing adequacy of any surgical excision margins can both be problematic.

Superficial spreading melanoma The most commonly occurring type of melanoma is superficial spreading (SSM), which has a significant radial epidermal growth component, typically occurs in younger patients, and frequently has a BRAFV600E mutation.37,38 Importantly, these tumors may well have visible nodules of tumor within them. They typically fulfill the ABCDE criteria with asymmetry, irregular and sharply demarcated border, multiple colors, a diameter greater than 6 mm, and a history of evolution (Fig. 30.4). Nevi-associated melanomas are usually of the SSM type.39  

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A

B

C

Figure 30.3 Acral lentiginous melanoma in situ. (A) Irregular brown to black pigmented patch on the sole. (B) Dermoscopy shows a parallel ridge pattern with asymmetric distribution of pigment. (C) Histopathologic findings showing proliferation of scattered hyperchromatic melanocytes with lymphocytic infiltration in the papillary dermis. (C, Hematoxylin-eosin stain; original magnification: 3400.) (From Darmawan CC, Gwanghyun J, Montenegro SE, et al. Early detection of acral melanoma: a review of clinical, dermascopic, histopathologic, and molecular characteristics. J Am Acad Dermatol. 2019; 81(3):805-812. © 2019.)  

A

B

C

Figure 30.4 (A) A superficial spreading melanoma on the arm. (B,C) Under dermoscopy, the lesion shows classical signs of asymmetry of pattern, variegated colors and peripheral dots. (From Marino ML, Carrera C, Marchetti MA, Marghoob AA. Practice gaps in dermatology: melanocytic lesions and melanoma. Dermatol Clin. 2016;34(3):353362. © 2016.)  

Nodular melanoma Nodular melanomas are frequently ulcerated and amelanotic, presenting as pink and usually raised papules (Fig. 30.5). Since the NMs are mitotically active throughout, they grow rapidly and may have a considerable depth compared to their diameter. Melanomas of any anatomical location or histologic subtype can be nodular. They are defined as having no in situ component extending more than three rete ridges from the invasive component, otherwise they are classified under one of the other histologic subtypes. Although NMs typically have a worse prognosis than some other types of melanoma, on multivariable analysis this difference largely disappears, although is perhaps significant in thinner tumors.31

Lentigo maligna melanoma Melanomas arising in the setting of significant UVR-induced damage to the dermis (solar elastosis) are termed lentigo maligna melanomas (LMM). These should not be confused with the similarly named in situ melanoma termed lentigo maligna (LM), as LMM represents the progression of LM to dermal invasion. The lesions are often poorly circumscribed both clinically and histologically40 and may also be amelanotic or only slightly pigmented (Fig. 30.6). Both these factors increase the likelihood of

misdiagnosis and incomplete excision, as the tumor may extend well beyond the visible lesion.33 The lesions typically occur at sites of chronic sun exposure, e.g., face and forearms. The majority of these tumors have neither a BRAF nor NRAS mutation.

Desmoplastic melanoma Desmoplastic melanoma (DM) is a rare (~1%) subtype that is usually found in areas of skin with high CSD, especially the head and neck. They usually appear as firm “scar-like” lesions with minimal or no pigmentation and may therefore not be within the differential diagnosis of the clinician (Fig. 30.7).41 Hence, on average, these lesions have a higher Breslow thickness than other subtypes. Furthermore, the histologic appearance of sparse bland spindle cells separated by an abundance of collagen may not be recognized by a pathologist as DM, therefore a diagnosis of “scar” in the absence of a clear history of trauma should raise suspicion for clinicians.42 When at least 90% of the melanoma is desmoplastic it is said to be “pure”, whereas when there is 10–89% it is said to “mixed”. The clinical significance of “pure” DM is that it signifies a lower risk of sentinel lymph node positivity.43,44 Neurotropism in a melanoma is most frequently found in DM, which can be “perineural invasion”, “intraneural invasion” or rarely forming de novo nerve-like structures termed

Melanoma

A

527

B

Figure 30.5 (A,B) An amelanotic nodular melanoma of 2.3 mm Breslow thickness on the right upper back showing under dermoscopy structural asymmetry and regression with white areas, crystalline structures, and polymorphous vessels. (Courtesy of Sydney Diagnostic Melanoma Center.)  

 

Acral/subungual

Figure 30.6 A lentigo maligna melanoma on the nose with green ink markings showing extent of in situ changes extending beyond its clinical boundaries, as mapped with reflectance confocal microscopy. (Courtesy of Dr. Bruna M. Gouveia.)  

 

“neural transforming”. However, neurotropism also occurs in other subtypes of melanoma. Multivariable analysis of neurotropic melanomas have shown it is associated with an increased likelihood of close or involved histologic resection margins that increases the risk of local recurrence.45 In such cases, if greater surgical margins are not possible, then adjuvant radiotherapy may be indicated.43

Acral melanomas are those that occur on the glabrous (i.e., non-hair-bearing) skin found on the volar aspects of the hands and feet, and also the nailbeds. The etiology of acral melanomas is unknown, although they are rarely related to UVR exposure. However, trauma has been postulated as a causal mechanism.46 In contrast, melanomas arising in the skin on the dorsal aspect of these areas are likely to be CSD-related. The lack of UVR-mediated etiology of AM is due to the presence of a thick stratum corneum that scatters the UV light and thereby protects the underlying melanocytes from its damaging effects, which does not occur in other anatomical regions.33 Accordingly, the genomic mutational profile of AM is different to melanomas arising as a result of CSD, instead having frequent copy number variations and few point mutations (i.e., a low mutational burden).47 The clinical presentation of AM occurring on the palmar or plantar skin is well described by the ABCDE rule, usually starting as a patch that spreads radially and may not appear raised due to the presence of the thick stratum corneum. However, these lesions are frequently poorly circumscribed, which makes their extent hard to define both histologically and clinically (Fig. 30.8).40 The dermoscopic appearance of a ridge pattern is 86% sensitive and 98% specific for early AM and therefore this can significantly help with reducing the need for unnecessary biopsies.48 However, when a biopsy is required, it may be necessary to perform a punch or incisional type to avoid significant morbidity in diagnosing larger lesions that turn out to be benign. When lesions are subungual, they usually arise from the germinal matrix and therefore this region needs to be included in any nailbed biopsy to reduce the likelihood of false-negative results. They may demonstrate Hutchinson’s sign, which

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A

B

C

Figure 30.7 (A,B) A right forehead 0.6 mm Breslow thickness desmoplastic melanoma showing milky red areas and atypical linear and dotted vessels under dermoscopy. (C) Reflectance confocal microscopy is used to delineate the radial margins of an amelanotic melanoma on the right forehead. Complete destruction of the honeycomb pattern in the epidermis, junctional thickening and cerebriform nests with atypical cells in the epidermis and at the junction can be seen. The lesion ends abruptly at two margins and extends slightly beyond its clinical appearance at two other margins. Purple line marks the atypical cells with 1 mm margin. An additional 1 cm margin should be added for wide local excision as per clinical guidelines. (Courtesy of Sydney Diagnostic Melanoma Center.)  

 

 

A

B

 

C

Figure 30.8 (A) (Parallel ridge pattern typical of acral lentiginous melanoma. (B) Asymmetry of pattern and color with irregular black-grey and pink blotches, and some irregular black dots. (C) Irregular longitudinal melanonychia that is wider proximally than distally; concerning for subungual melanoma. (A, From Thomas L, Phan A, Pralong P, Poulalhon N, Debarbieux S, Dalle S. Special locations dermoscopy. Dermatol Clin. 2013; 31(4):615-624; B, from Deinlein T, Hofmann-Wellenhof R, Zalaudek I. Acral melanoma mimicking subungual hematoma. J Am Acad Dermatol. 2016; 75(5):e181-e183 © 2016; C, from Hirata SH, Yamada S, Enokihara MY, et al. Patterns of nail matrix and bed of longitudinal melanonychia by intraoperative dermatoscopy. J Am Acad Dermatol. 2011;65(2):297–303 © 2010.)  

is when there is hyperpigmentation of the proximal nailfold. In people with darker skin it is common for multiple benign longitudinal melanonychia streaks to occur, particularly with increasing age.49 However, concerning features for melanoma include a streak that is wider at its base than distally (representing rapid growth of the lesion), blurred rather than sharply demarcated edges, becomes suddenly darker or wider, is accompanied by nail dystrophy, and occurs in a single digit in a person in the fourth to sixth decade of life.49

Staging Staging of melanoma is done using the American Joint Committee on Cancer (AJCC) manual, which is currently in its 8th Edition.50 This system uses the tumor (T), node (N), and metastasis (M) system to assess the extent of disease. This system enables standardized comparisons for disease management and outcomes to be made across institutions around the world. Importantly, the prognosis of patients can

be determined using the survival curves provided by AJCC, however, these only apply to patients who had that stage at initial diagnosis and do not apply for patients who subsequently progress to stages III or IV. Importantly, in tumors greater than 1.0 mm thick (T2–T4) the N category can only be determined for if a sentinel node biopsy or a complete regional lymphadenectomy (usually for clinical or radiological evidence of regional nodal disease) has been performed. Otherwise, this category should be designated as “NX”. However, for T1 tumors where the regional nodes have not been pathologically staged, the designation “cN” should be used. The rationale for this is that clinical evaluation (including ultrasound assessment) of the regional lymph nodes is often inaccurate, detecting only around 24% of sentinel node biopsy-positive patients.51  

Tumor category The primary tumor category (T) is determined pathologically by biopsy of the lesion. The tumor Breslow thickness

Other histopathological features

is measured from the granular layer of the epidermis to the deepest part of the tumor in a direction that is perpendicular to the skin surface. If there is invasion from tumor extension down an adnexal structure, then it is the perpendicular distance from that surface that is measured. In the absence of the entire epidermal component due to ulceration, then the base of the ulcer is used as the reference point in place of the granular layer. Measurement should be reported to the nearest 0.1 mm, unlike in the 7th Edition of the AJCC staging manual, in which it was to the nearest 0.01 mm.52 The thickness should then be rounded down if the second decimal place is 0–4 and up if it is 5-–9, e.g., 1.04 mm becomes 1.0 mm (T1) whereas 1.05 mm becomes 1.1 mm (T2). If a tumor has been initially transected horizontally, e.g., by a shave biopsy, then the pathologist may be able to make an estimate of the true thickness of the tumor by assessing both the initial biopsy and the wider excision specimens, but this has not been validated and therefore should not be used for staging purposes.50  

529

Individual study estimates vary widely for the incidence of local recurrence and in-transit metastasis as first recurrence: 0.7–12.8% for local recurrence and 0.3–11% for in-transit metastasis.56 Microsatellitosis is rare, with rates of 5–10% in intermediate-thickness melanoma, and rates have been reported to be lower and higher in thin and thick melanomas, respectively.57

Distant metastasis category

 

 

 

 

 

Regional nodal category Metastatic spread of cutaneous melanoma is known to occur through lymphatic channels in approximately 90% of cases,53 while direct hematogenous dissemination is a less common route of metastasis. However, at present it is not entirely clear what clinicopathologic factors determine whether the lymphatic versus hematogenous pathways occur in melanoma metastasis.54 As the first sites of metastasis are typically regional lymph node basins, evaluation of the regional lymph node basins has become critical in the staging of melanoma. Consistent with this, evidence that melanoma has spread to the regional lymph nodes portends a poorer prognosis than for patients without such evidence. However, some tumor cells that spread via the lymphatics will first be detected within the lymphatic system en route to the regional nodes. Consequently, the nodal (N) category includes regional nodal disease together with in transit, satellite or microsatellite disease, with these latter three designations representing a continuum of intralymphatic metastases and portending a similarly relatively poor prognosis.55 Tumor deposits present in the cutaneous or subcutaneous tissue discrete from the main primary mass in either the initial excision biopsy or wide local excision specimen are termed “microsatellites” if they are pathologically or “satellites” if clinically detected within 2 cm of the primary tumor. Beyond this distance but proximal to the regional lymph nodes, such deposits are termed “in transit” metastases. Importantly, “microsatellites” should be truly separate and not just have an area of fibrosis or inflammation between them and the primary tumor, as this could simply represent regression. Additionally, deposits that are within the deep structures, e.g., muscle, are classified as distant metastases (stage IV) and not stage III. Nodal disease that is radiologically detected, e.g., using ultrasound, computed tomography (CT) or positron emission tomography (PET)-CT is classed as “clinically detected” and upstages the N subcategory to a “b” compared to that detected by sentinel node biopsy, which is termed “clinically occult” and are subcategory “a”. If there are microsatellites, satellites or in transit deposits without nodal disease, then a designation of N1c is given, whereas if there is also disease in a single node then it is termed N2c and if more than one node is involved then it is N3c.  

Metastatic disease is classified as either absent (M0) or present (M1), with M1 subcategorized into a, b, c, and d depending on the anatomical site of the metastases. The “d” subcategory is a new one that is specifically for central nervous system (CNS) metastases, as these carry the worst prognosis of all sites. However, the presence of an elevated serum LDH level does not change this subcategory, but is denoted instead by a suffix “(1)”, whereas a normal level is denoted as “(0)”, e.g., M1a(0). Where no LDH level has been recorded, then no suffix is used, e.g., M1a. Although the number of distant site metastases has been shown to have important prognostic information in multiple studies, the variability of the methods of detection employed and their respective sensitivities makes this information non-standardized and therefore unreliable for prognosis at present.50 When metastases are present at more than one site, then the highest subcategory site should be used for staging and prognosis.

Stage The overall stage that is given to a patient is determined by the combination of the “T’, “N”, and “M” categories. This can be used to determine prognosis, which is useful for both patients and clinicians advising them. The clinical stage is usually determined following the biopsy and the pathological stage following wide local excision and sentinel node biopsy for T2–4 tumors. In addition to the factors that are incorporated into the staging system there are various other clinically relevant factors that should be reported in the standardized reporting format, as these may also affect management of the disease.

Other histopathological features Clark’s level Clark’s level was removed from the AJCC staging system in the 7th Edition after it was found to have the lowest independent prognostic significance on a multivariable model for survival that included tumor mitotic rate.50,58 The Clark’s level is determined by the deepest of five anatomic levels the melanoma invades to (Table 30.3).

Neurotropism The presence of melanoma cells abutting nerve sheaths is termed “neurotropism”, which can take three forms: circumferentially (perineural), within the nerves (intraneural), or rarely forming de novo nerve-like structures (neural transformation). The presence of neurotropism should be determined

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Table 30.3 Clark’s levels for depth of melanoma invasion  

Clark’s level

Anatomical depth of melanoma invasion

I

Confined to the epidermis (melanoma in situ)

II

Into the papillary dermis, but do not fill or expand this layer

III

Fill or expand the papillary dermis and reach the junction with the reticular dermis

IV

Into the reticular dermis

V

Into subcutaneous tissue

by assessing for nerves at the periphery of the tumor, as its presence within the main tumor mass does not count as neurotropism. Neurotropism is mostly found in association with desmoplastic melanoma, however it can also be found with other cutaneous histologic subtypes. Although neurotropism does not appear to be an independent prognostic risk factor for recurrence, it does increase the likelihood of close or involved margins and in this situation can increase that risk of recurrence.45 Such a situation may require additional surgery to achieve adequate margins or adjuvant radiotherapy if further surgery is not feasible.43

Lymphovascular invasion The presence of melanoma cells within the lumina of lymphatics (lymphatic invasion) or blood vessels (vascular invasion) is collectively termed lymphovascular invasion (LVI). This is generally regarded as being a poor prognostic factor, though this association has not been consistent across all studies.59–66 The identification of LVI can be enhanced by staining with vascular endothelial cell markers, e.g., CD31 or CD34, and lymphatic endothelial cell markers, e.g., D2-40 or LYVE-1, particularly when double labelling is employed to also identify the tumor cells.67,68

Tumor infiltrating lymphocytes (TILs) Lymphocytes that are found directly opposing or to have infiltrated and disrupted nests of tumor cells are termed TILs. The degree of infiltration varies from “absent’, present in focal areas (“non-brisk”), to diffuse presence or presence along the entire base (“brisk”). The finding of a brisk TIL infiltrate is generally regarded as a good prognostic factor.69–73

Follow-up and imaging Patients who have had a melanoma completely resected are at risk both for recurrence and a lifelong five- to tenfold greater risk than the general population of developing a new primary melanoma.34 Since complete resection of recurrences is more likely to be possible when the tumors are detected early, there is a rationale for active follow-up. Similarly, since thinner melanomas carry a better prognosis than thicker ones, it would also seem logical that earlier detection of a new primary is likely to improve the outcome. Most recurrences become apparent within the first 3 years post diagnosis.74 However, thinner tumors are more likely to recur later though less likely to do so.75 Consequently, if

Table 30.4 Summary of NCCN recommendations for imaging in patients at diagnosis or resected with no evidence of residual diseasea  

Stage (AJCC 8th Edition)

Baseline imaging

Surveillance imaging

0 (in situ)

None

None

IA, IB, IIA

None

None

IIB, IIC

Consider crosssectional

IIIAb

Consider crosssectional

Consider crosssectional ± brain MRI every 3–12 months for 2 years followed by every 6–12 months until 5 years

IIIB,b IIIC,b

Cross-sectional ± brain MRI

IV

Cross-sectional ± brain MRI

Cross-sectional imaging is either computed tomography (CT) or positron emission tomography (PET)/CT (the latter may be more sensitive), with intravenous contrast for the CT unless contraindicated. b Consider adding ultrasound of nodal basin if completion regional lymphadenectomy not carried out. a

follow-up for thin melanoma recurrence is planned then it should be for a long time, but this will have a low yield and therefore the cost-benefit is perhaps questionable. Furthermore, while clinical examination by a specialist is likely to detect skin or subcutaneous tumor deposits at a small size, this is less likely for lymph nodes and they are unlikely to detect visceral metastases until they are large. Consequently, imaging needs to be considered for more sensitive detection of regional76 or distant metastases. However, there are significant implications for cost, radiation exposure, and harm from false-negative and false-positive results with routine surveillance imaging. The role of surveillance ultrasound imaging for sentinel node-positive patients in lieu of performing a completion lymphadenectomy has been demonstrated through the DeCOG-SLT and MSLT-II trials.77,78 However, the reliability of ultrasound is operator-dependent and may not be available to all patients. Consequently, in such circumstances patients may instead be recommended to have regular CT, though this has not been prospectively studied. Since there is a lack of evidence for any particular regimen of clinical follow-up or imaging, there are differences between the various national guidelines that exist.79 However, the National Comprehensive Cancer Network (NCCN) recommends at least yearly clinical history and physical examination, together with advice on self-examination, sun protection and avoidance. This should then be adjusted according to the patient’s particular circumstances, including the total number of nevi, presence of atypical nevi, number of primary melanomas, and the number of first-degree relatives who have had melanomas. For SLNB-positive patients who have not had a complete lymph node dissection (CLND), then ultrasound scan (USS) should be offered 4-monthly for the first 2 years followed by 6-monthly to 5 years post diagnosis. Imaging should not be routinely performed in stage I or IIA disease, but has a role in stages IIB/C, III, and IV disease (Table 30.4).

Surgical considerations and management

Where SLNB is not performed, USS surveillance of the nodal basin may be undertaken, but is not as sensitive as SLNB and therefore is not a substitute.80 In patients with stage IIB disease and above, NCCN recommends regular staging with cross-sectional imaging with or without brain MRI performed (see Table 30.4). Cross-sectional imaging is undertaken with either CT or flurodeoxyglucose (FDG) positron emission tomography (PET) combined with CT. The CT should be done with intravenous (IV) contrast unless contraindicated. Since the normal brain has a high glucose uptake, FDG-PET does not visualize brain metastases well. Consequently, an MRI of the brain is usually done in addition to the whole-body PET-CT if there are concerns about the possibility of a brain lesion.

531

anatomic site, may require skin graft or complex locoregional flap reconstruction. Surgical margin for melanoma has been the topic of many randomized clinical trials (Table 30.5).87–100 Based on the findings of these studies, the current recommendations can essentially be summarized as: for melanomas 2 mm in Breslow thickness, 1 cm and 2 cm margins, respectively, appear to be adequate. There is still some lingering uncertainty about the appropriate margin in the 1–2 mm subgroup. It is hoped that Melanoma Margins Trial-II (MELMART-II) (NCT03860883), a phase III, multicenter randomized controlled trial investigating 1 cm versus 2 cm wide surgical excision margins for pT2b-pT4b primary cutaneous melanoma will provide some clarity. No data exist that margins wider than 2 cm result in any superior disease-specific outcome. It is important to appreciate that all current treatment recommendations refer to surgical margins, i.e., the in vivo margins determined by the surgeon before wide local excision and before histologic examination of the specimen by the pathologist. This distinction is important because the macroscopic margins measured by the pathologist at the time of specimen cut-up will be less than the margins marked out by the surgeon prior to the wide local excision. This is due to a typical 14% tissue shrinkage rate after the specimen has been removed and fixed in formalin.101  

 

 

 

 

 

 

 

Surgical considerations and management Biopsy of a clinically suspicious melanocytic lesion Suspicious pigmented/melanocytic (this may be amelanotic) lesions should have an excision biopsy with a 2 mm margin where possible, as this offers the best opportunity for correct pathologic diagnosis.81,82 Incomplete biopsies of a lesion, including punch, incision, curette, and shave biopsies, may contribute to a significant pathologic misdiagnosis rate, with both false-positives and false-negatives.83 The rate of incomplete excision with shave biopsies has been shown to be up to 97%.83 There may be unrepresentative sampling of a heterogeneous tumor risking an incorrect diagnosis, or insufficient tissue for adequate assessment of the pathologic criteria necessary to permit correct diagnosis. In addition, a shave biopsy transecting the base of a melanoma precludes accurate measurement of the Breslow thickness.84,85 A patient might not have been offered SLNB due to this error. However, there are situations where an incisional biopsy is not feasible, e.g., for a large facial lentigo maligna, a very broad superficial shave biopsy may be more appropriate where the suspicion for dermal invasion is low.82 Importantly, the rate of false-negative diagnoses can be significantly reduced by writing the suspected diagnosis on the pathology request form.83 Since melanocytic tumors can be difficult to diagnose, they should be sent for histological assessment by an expert dermatopathologist.  

Wide local excision of primary melanoma Standard management of primary cutaneous melanoma involves wide local excision of the diagnostic excision biopsy scar or residual primary lesion with a surrounding margin of normal skin en bloc with the underlying subcutaneous tissue, usually down to the deep fascia. The optimal width of an excision margin has been a matter of controversy for decades. The vast majority of 1 cm surgical margins allow primary closure of the resultant surgical defect, and can be accomplished under local anesthesia, at minimal cost with little or no morbidity.86 On the other hand, wider excision margins of 2 cm and above are often performed with the patient under general anesthesia and, depending on the  

 

Wide excision of melanoma in situ There have been no randomized trials and only a limited number of case series to guide excision margins for melanoma in situ102–104and therefore treatment is based on consensus from clinical experience. Until recently, most guidelines suggested an excision margin of 5 mm for melanoma in situ. However, there is increasing evidence that 5 mm may be inadequate, leading to disease recurrence in some cases.103,105,106 European guidelines suggest 5 mm excision margins for melanoma in situ107–109 although a British Best Practice statement110 includes the caveat that 5 mm is inadequate in up to 50% of cases of melanoma in situ, particularly melanoma in situ of lentigo maligna subtype, and 10 mm margins, staged excision or Mohs surgery are alternatives. Dermatology guidelines from the US recommend 5–10 mm excision margins and state that wider margins may be necessary for lentigo maligna.111 Based on all the available evidence, it would seem most appropriate to recommend a minimum margin of 5 mm, but increasing it to 10 mm for melanoma in situ where feasible.112 One study reported that the use of in vivo confocal microscopy (see Fig. 30.7) may improve lesion boundary identification and allow for more effective excision.12 However, further studies are required to validate this technique.  

 

 

 

 

 

 

 

Sentinel lymph node biopsy The concept of melanoma metastasis to the regional lymph nodes is that this will occur in a consistent manner first to those nodes directly draining that area of skin, termed “sentinel lymph nodes”. The technique of sentinel lymph node biopsy (SLNB) was first described by Donald Morton and Alistair Cochrane’s team in melanoma patients.53 The sentinel nodes are identified by dual lymphatic mapping using a

CHAPTER 30 • Melanoma

532

 

preoperative lymphoscintogram and intraoperative blue dye. The sentinel nodes are then removed for careful histologic examination, which achieves unprecedented accuracy in staging the regional lymph nodes. The important role of lymphoscintigraphy in SLNB is to map the precise lymphatic pathway(s) to the draining sentinel lymph node(s) in each patient using radiolabeled tracers and real-time imaging. The lymphatic collecting vessels can be followed on dynamic imaging until a sentinel node is reached. More than one draining lymphatic collecting vessel is often

seen for a melanoma, which may go to the same or different sentinel lymph nodes. In the procedure of SLNB, only sentinel lymph nodes should be removed, and second-tier nodes that receive tracer upstream should be left in place to minimize surgical morbidity. Sappey demonstrated the lymphatic drainage patterns of the human body in 1874 by injecting mercury into the skin. The resultant Sappey’s lines (Fig. 30.9) are a helpful guide for determining the likely directions of lymphatic drainage from a skin site.113 They indicated that lesions located more than

Table 30.5 Prospective randomized trials addressing surgical excision margins for primary cutaneous melanoma  

Outcome time points, years (average follow-up)

Breslow thickness (mm)

Number of randomized patients (N analyzed)

Treatment comparisons, in cm (N patients)

French Cooperative Study (French)

≤2 ≤0.5 0.5–1.0 1.01–1.5 ≥1.5 Missing

337 (326) 18 141 105 61 1

2 vs. 5 (167 vs. 170)

Extremities, trunk, head, and neck

5 and 10 (16)

Local: 0.26 (0.03, 2.27) Nodal: 1.21 (0.56, 2.62) Distant: 0.41 (0.13, 1.28) Death: 1.13 (0.72, 1.78)

Khayat et al. (2003)87 Banzet et al. (1993)88

Swedish Melanoma Study Group I (SMSGI)

≤2 1–2

989 (989) 244 745

2 vs. 5 (476 vs. 513)

Trunk, limbs

5 and 10 (11)

Local: 0.65 (0.16, 2.69) Nodal: 1.24 (0.90, 1.70) Distant: 1.08 (0.79, 1.46) Death: 0.94 (0.76, 1.17)

Ringborg et al. (1996)89 CohnCedermark et al. (2000)90

WHO Melanoma Program (WHO)

≤2 ≤0.5 0.51–1.0 1.1–1.5 1.51–2.0 ≥2.1 Missing

703 (612) 112 244 148 97 9 2

1 vs. 3 (305 vs. 307)

Trunk, limbs

4, 8, 12 (>8)

Local: 2.68 (0.72, 10.02) Nodal: 0.88 (0.50, 1.55) Distant: 1.22 (0.61, 2.44) Death: 0.85 (0.57, 1.27)

Veronesi et al. (1988)91 Veronesi and Cascinelli (1991)92 Cascinelli (1998)93

1 (>1)

None reported

Moncrieff et al. (2018)94

Local: 0.83 (0.26, 2.67) Nodal: 0.96 (0.60, 1.53) Distant: 1.21 (0.87, 1.67) Death: 1.29 (0.95, 1.76)

Balch et al. (1993)95 Karakousis et al. (1996)96 Balch et al. (2001)97

Surgical trials

Primary site

Risk ratios (95%CIs) (narrow: wide)

References

Thin melanoma

Combined (1–4 mm)  

MelMarT

>1 1–2 2–4 >4

400 (377) 223 121 33

1 vs. 2 (185 vs. 192)

Trunk, extremities, head, and neck

Intergroup Melanoma Surgical Trial (Intergroup)

1–4 1–1.99 2–2.99 3–4.0

486 (470/468) 272 141 73

2 vs. 4 (244 vs. 242)

Trunk, 5 and 10 proximal limb (10)

(Continued)

Surgical considerations and management

533

Table 30.5 Prospective randomized trials addressing surgical excision margins for primary cutaneous melanoma —cont’d  

Surgical trials

Breslow thickness (mm)

Number of randomized patients (N analyzed)

Treatment comparisons, in cm (N patients)

Primary site

Outcome time points, years (average follow-up)

Risk ratios (95%CIs) (narrow: wide)

References

Thick melanoma UK Melanoma Study Group (UKMSG)a

>2 4 Missing

900 (900) 2 99 555 242 2

1 vs. 3 (453 vs. 447)

Trunk, limbs

5 and 10

Local: 1.14 (0.55, 2.37) In-transit/ regional: 1.41 (0.54. 3.67) Nodal: 1.13 (0.92, 1.39) Distant: 1.25 (0.79, 1.98) Death: 1.04 (0.92, 1.17)

Thomas et al. (2004)98 Hayes et al. (2016)99

Swedish Melanoma Study Group II (SMSGII)

>2 ≤3 >3–4 >4 Missing

936 (936) 460 204 270 2

2 vs. 4 (465 vs. 471)

Trunk, limbs

5 and 10

Local: 2.25 (1.04, 4.89) In-transit/regional: 1.28 (0.66, 2.49) Nodal: 0.89 (0.70, 1.13) Distant: 0.71 (0.48, 1.06) Death: 1.04 (0.88, 1.22)

Gillgren et al. (2011)100

Local and regional node recurrences were combined (this was not planned in the original trial protocol) and patients did not have regional node staging by SNB or ELND, so the groups may not have been balanced.

a

2 cm above or below a “belt line” drawn through the umbilicus usually drained to the axillary or groin nodes, respectively. Similarly, lesions located more than 2 cm on either side of the midline drained to the lymph nodes on their respective side. While lesions within the 4 cm central vertical and horizontal bands could drain to either or both sides, and either or both axillary/ groin nodes. Modern lymphoscintigraphy studies, however, have clearly demonstrated that there are many variations in the lymphatic drainage of human skin, and very few sites on the body actually have reliably predictable drainage.114,115 The original technique of lymphoscintigraphy has evolved with the use of various radioisotopes and tracers of various particle sizes over time. The ideal radiopharmaceutical for lymphoscintigraphy as a technique to locate and mark sentinel lymph nodes prior to their surgical removal would be rapidly cleared from the injection site, taken up in high concentration in the first lymph node that it enters without onward passage to second-tier nodes, have a high photon flux of gamma rays to make detection efficient, and have a short half-life with minimum radiation emission. It would also be painless on injection, easy to prepare, and inexpensive. Technetium99m is a commonly used radioisotope because of the convenience of its ready availability from a generator, its high photon flux and low radiation  

 

 

emission, and short half-life of 6 hours.116 It cannot be stated dogmatically which is the best tracer for the purpose of sentinel lymph node identification. Tilmanocept has been developed as an antibody-based tracer that specifically binds to CD206 receptors in lymph nodes, compared to the conventional sulfur colloids that are not receptor-specific. Antimony sulfide colloid, nanocolloid, or tilmanocept should be used in preference to sulfur colloid if available, as it is doubtful that all sentinel lymph nodes will be identified when using the latter agent.117 Single photon emission computed tomography (SPECT)/ CT is a new hybrid imaging technology that combines multiplanar gamma camera images with conventional CT imaging.118 The anatomical CT information is superimposed onto the excellent physiological resolution of the three-dimensional lymphoscintigraphy to reveal the precise anatomical location of the sentinel lymph nodes (Fig. 30.10), greatly aiding their surgical removal, especially in the head and neck and pelvis.119 Identification of the sentinel lymph nodes is achieved in more than 99% of patients with the combined use of preoperative radioactive colloid lymphoscintigraphy and intraoperative blue dye in patients with melanoma (Fig. 30.11).120 Correct determination of the nodal basin status is achieved in around 96% cases.120 The value of SLNB in melanoma was  

CHAPTER 30 • Melanoma

534

 

5 cm

5 cm

5 cm

L2

Figure 30.9 Lymphatic drainage pathways as predicted by Sappey’s lines.  

Figure 30.10 SPECT/CT hybrid imaging technology combines multiplanar gamma camera images with conventional CT imaging to reveal the precise anatomical location of the sentinel lymph nodes for a left forehead melanoma in the left parotid gland.  

evaluated in the landmark phase III Multicenter Selective Lymphadenectomy Trial (MSLT-I). MSLT-I randomized patients with ≥1.2 mm thick melanomas into two arms: to have either a wide local excision and SLNB (with completion lymphadenectomy for positive nodes) or instead to have wide local excision and observation of the regional nodes  

and therapeutic lymphadenectomy for those who developed clinically detected recurrence subsequently. The analysis was divided into intermediate thickness (1.2–3.5 mm) and thick (>3.5 mm) groups with the primary endpoint being melanoma-specific survival (MSS) in the intermediate thickness group. The final analysis at 10 years of follow-up  

 

Surgical considerations and management

A

B

C

D

535

Figure 30.11 (A) Sentinel node biopsy for a left temple melanoma. Preoperative lymphoscintgram mapped sentinel lymph nodes to left preauricular region and left neck level II. (B) Additional intraoperative mapping with intradermal patent blue injection allowed lymphatic pathways to be visualized. (C) Intraparotid blue and hot sentinel node identified. (D) Accessory nerve (green arrow) and internal jugular vein (blue arrow) visualized after removal of neck level II sentinel nodes.  

demonstrated no significant difference in outcomes between the two arms. However, an analysis of the subgroup with positive SLNB compared to nodal recurrences in the observation group demonstrated improved MSS in the SLNB arm for intermediate thickness melanomas (hazard ratio = 0.56 [95% CI, 0.37–0.84]; P = 0.006).120 This subgroup analysis was performed using a mathematical technique termed “latent subgroup analysis with accelerated time to failure” that should account for any unknown or unaccounted-for differences between the subgroups.121 The rationale for using this controversial analysis method was that the lower-than-expected event rate of nodal metastases in the study had resulted in underpowering as over 80% of patients could not derive a benefit and therefore this analysis approach was a reasonable practical solution. Unfortunately, due to the high costs associated with repeating a study similar to MSLT-1 but with a much larger sample size to achieve enough power, the question of whether there is any therapeutic benefit is likely to continue to be debated. Irrespective of the residual controversy over the potential therapeutic benefit of SLNB, it has largely become the standard of care in the initial evaluation of cutaneous melanoma, particularly for patients with melanoma thicker than 1 mm due to its staging and prognostic power.122 The NCCN advises that SLNB should be routinely offered for a melanoma where the risk of a positive node is estimated to be greater than 10% and considered where it is likely to be between 5% and 10%.123 Although guidelines have historically focused primarily on  

tumor thickness to estimate this risk, improved sentinel node positivity prediction tools have recently been published that consider multiple variables in a quantitative manner.124,125 Of particular importance is that increasing age is a negative predictor of sentinel node positivity. Individualized quantitative risk estimates of sentinel node positivity enable more informed decision-making by patients according to their personal circumstances and risk threshold than previous thickness-based thresholds.

Management of sentinel node metastases With the advent of SLNB, regional nodal management moved from elective lymph node dissection (ELND) for patients with high-risk melanomas to completion lymph node dissection (CLND) only for those patients who had positive sentinel nodes. However, this too has recently changed following the results of two landmark studies, Multicenter Selective Lymphadenectomy Trial – II (MSLT-II)78 and DeCOG-SLT,77 which were conducted to determine the utility of performing CLND for sentinel lymph node-positive patients. Patients were randomly assigned to either immediate CLND or nodal observation with regular (3- or 4-monthly) ultrasonography and only underwent therapeutic lymphadenectomy if recurrent disease was subsequently detected. Both studies found that immediate completion lymphadenectomy increased the rate of disease control within the nodal basin and provided prognostic information but did not increase MSS.77,78

536

CHAPTER 30 • Melanoma  

Consequently, completion lymphadenectomy has largely been abandoned in favor of close observation including with imaging of various modalities, including ultrasound surveillance, CT (brain, neck, chest, abdomen and pelvis) or PET/CT and brain MRI, with/without adjuvant medical therapy.126 In summary, the goals of SLNB are to identify patients with microscopic nodal metastases as early as possible so they might benefit from the early removal of these metastatic nodes before the disease can spread any further, to consider these patients for adjuvant systemic therapy, and to provide accurate staging for prognosis.

Management of clinically detected nodal metastases For patients with clinically detectable nodal disease, SLNB is irrelevant. However, the characteristics of the primary tumor, including Breslow thickness and ulceration have been shown in the latest edition of the AJCC staging (8th Edition) to remain relevant in addition to the number of nodes involved and any intralymphatic metastases with respect to predicting 5-year survival.127 Most patients today who have nodal metastases present with clinically occult disease, i.e., detected during SLNB. This is in contrast to clinically detected nodal metastases, which are detected by clinical or radiographic examination.127,128 Patients with clinically evident regional disease have a worse survival rate than patients with clinically occult disease.127,129 Risk factors for developing regional nodal metastases include thicker and ulcerated primary melanomas, frequent mitotic figures, and lymphatic invasion. Most such nodal metastases develop within 4 years but a significant minority of metastases develop later, occasionally even beyond 10 years after diagnosis of the primary melanoma,130 consequently it is important that patients monitor for recurrence for many years and have a low threshold for seeking expert medical advice if there is any such suspicion. Suspected nodal metastasis should be confirmed with fine needle aspirate (FNA) cytology or core biopsy histology. For biopsy-proven nodal metastases, therapeutic lymph node dissection of the entire nodal basin is still standard practice, following a comprehensive staging evaluation and discussion at a multidisciplinary team meeting with due consideration given to surgical morbidity, adjuvant medical therapy and clinical trial enrolment.78,126 More recently, emerging data from human translational and clinical research suggest an increased therapeutic efficacy of neoadjuvant (before surgery) over adjuvant (after surgery) medical therapy in the treatment of clinically evident regional metastasis (Table 30.6).131,132

Lymph node dissection (lymphadenectomy) The main nodal basins are the parotid/neck, axilla, and iliofemoral regions. The details for surgery and unique considerations for each are outlined below.

Neck dissection Patients with melanoma of the face and anterior scalp who are selected for neck dissection because of clinically detected regional metastasis should also be considered for superficial parotidectomy on the ipsilateral side because the parotid lymph nodes are the first echelon in lymphatic drainage. The commonest neck dissection performed is a comprehensive neck dissection, removing nodal tissue from levels I–V but preserving the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle (Fig. 30.12). For the posterior scalp and posterior neck primary melanomas, level I could probably be omitted,139 but the postauricular and occipital nodal basins might need to be included in the neck dissection. On the other hand, a patient diagnosed with clinically detected parotid lymph node metastasis should also be considered for neck dissection. Occult neck disease has been found in greater than 40% of patients undergoing parotidectomy and neck dissection for head and neck cutaneous melanoma.140 Shah et al. in 1981 proposed a simplified system that correlated with the surgical technique for neck dissection, in which numerical levels were assigned for different nodal groups.141 This system was updated and expanded by the American Head and Neck Society and by the American Academy of Otolaryngology-Head and Neck Surgery in 2002.142,143 More recently, in 2013 Gregoire et al. further updated the classification system, and divided the neck into 10 nodal groups creating levels for areas that are at risk of regional metastasis from malignancies arising in the skin.144 This system is in many ways more useful for the treatment of nodal disease in melanoma. The original six levels of the neck were described with a focus for metastatic disease from the upper aerodigestive tract. Therefore, nodal basins such as the parotid and postauricular nodes which are often involved with metastasis from head and neck cutaneous melanomas were overlooked in formal definition of levels with the prior neck dissection classification system (Tables 30.7 & 30.8). In the evolving era of more effective systemic therapies, where postoperative adjuvant medical therapy has become the standard of care, there is increasing debate regarding the type and extent of surgery required. There is increasing deviation from the uniform approach of a comprehensive neck dissection and/or parotidectomy for clinically apparent disease. Comprehensive or modified radical neck dissection involves complete dissection of all five neck levels, whereas selective neck dissection involves dissection of only certain node levels or groups. Based on some preliminary evidence, in the case of patients treated with neoadjuvant therapy who have radiologic evidence of a treatment response, a more selective neck dissection with preservation of nerves and blood vessels despite intraoperative observation of close association with gross nodal disease is probably oncologically sound.145,146 In such patients, it is not uncommon to encounter a final pathology of sheets or aggregates of pigmented macrophages without evidence of viable melanoma.147

Axillary dissection Once the decision to proceed with axillary lymph node dissection has been made, the goal of the procedure in patients

Lymph node dissection (lymphadenectomy)

537

Table 30.6 Modern neoadjuvant trials for stage III melanoma  

No. of patients

Duration of neoadj therapy (weeks)

Duration of adj therapy (weeks)

Median followup time (months)

Survival/ ORR

Pathological response

18.6

10 (71%) vs. 0 alive without disease HR 0.016 [95% CI 0.00012–0.14], P