Lymphedema Byung-Boong Lee Stanley G

Lymphedema Byung-Boong Lee Stanley G. Rockson John Bergan Editors Lymphedema

A Concise Compendium of Theory and Practice

Second Edition Editors Byung-Boong Lee Stanley G. Rockson Center for the Lymphedema and Falk Cardiovascular Research Center Vascular Malformations Stanford University School Division of Vascular Surgery of Medicine Department of Surgery Stanford, CA George Washington University USA Washington, DC USA John Bergan† Department of Surgery La Jolla, CA Uniformed Services University of the USA Health Sciences Bethesda, MD USA

†John Bergan is now deceased

ISBN 978-3-319-52421-4 ISBN 978-3-319-52423-8 (eBook) https://doi.org/10.1007/978-3-319-52423-8

Library of Congress Control Number: 2017956936

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Foreword

In the foreword of the first edition of this book, I wrote, «If venous diseases are the Cinderella of the vascular field as the late Michael Hume, former President of the American Venous Forum, called them, then the lymphatics are Cinder- ella’s poor cousin.» This second edition of Lymphedema: A Compendium of Theory and Practice, which will be published only a few years after the first edition, is a welcome evidence of the great interest and acceptance that the subject of lymphedema and its challenging pathology has received among the students of vascular disorders. The lymphatics are no more the poor cousin of the vascular system. How pleased would have been the late John Bergan, coau- thor of the first edition, to see that the field that he chose and made seminal contributions to during the last two decades of his life is now in its second edition and in the limelight of most vascular meetings. Even a prestigious jour- nal is dedicated solely to diseases of the venous and lymphatic systems!

This book is a welcome update of the first edition and has been elevated to the category of textbook. The addition to every chapter of an abstract, a summary of basic concepts, and a few annotated relevant references is an important con- tribution to its contents. Almost every chapter has been expanded and revised to include an update of our current knowledge on the subject.

The critically important work of early investigators in the field of the lymphatic physiology and pathophysiology, such as Servelle, Kinmonth, Casley-Smith, Olszewski, Nielubowicz, Földi, and others, established the basis and served as a stepping-stone for many of the subjects covered by recognized specialists in this book. As recognized by all investigators, one of the most important obsta- cles in the study of the lymphatics has been its visualization. The technique of visual lymphography using intradermal injections of Patent Blue (alphazurine) to study cutaneous and deeper lymphatics followed the technique of oil lymphography and lymphadenography as described by Professor John Kinmonth. These techniques were a useful tool in the study of the lymphatic vasculature and served as the basis for an early classification of lymphedemas. The tedious and time-consuming lymphography has been replaced by new nuclear medicine imaging techniques, radionuclide lymphoscintigraphy, multislice CT scan, magnetic resonance imaging, and computerized axial tomography. These techniques have contributed to guide the clinician in the process of establishing a rational diagnosis and dictating appropriate treatment. Advances in diagnosis have been followed by an array of therapeutic techniques. Many of them are described in this book by their original authors.

At this point, I will take the liberty to narrate a pertinent anecdote that hap- pened during my fellowship at the Peter Bent Brigham Hospital in Boston. It was my fortune that, in the fall of 1957, Professor John Kinmonth from St. VI Foreword

Thomas’ Hospital in London came to Boston as a visiting professor invited by my mentor Professor Richard Warren. Mr. Kinmonth gave us a great lecture on lymphatic disorders and the lymphangiography procedure that he pioneered and had performed in more than 2000 patients in London.

During a break, Mr. Kinmonth pulled me aside and gave me a small bag con- taining one ounce of a blue powder that was his «Patent Blue Violet,» a vital dye that diffuses readily and is absorbed promptly by the lymphatic vessels. He had used it extensively to visualize the lymphatics. He gave me detailed instructions on how to use it and told me: «young fellow, take this powder and prepare an 11% distilled water solution, sterilize it, and start using it!»

Professor Kinmonth’s visit to the Brigham sparked the flame of a lifetime interest in the lymphatic system. I became fascinated with the elusive little channels and their physiopathology. The reflections of my mentor’s friendship with Pro- fessor Kinmonth led him to study the lymphatics. Doctor Warren and I designed an instrument to measure lymphatic pressures and perform direct lymphangiography that is described in this book.

The tedious and time-consuming Kinmonth’s lymphography has been replaced by new nuclear medicine imaging techniques, radionuclide lymphoscintigraphy, multislice CT scan, magnetic resonance imaging, and computerized axial tomography. These techniques have contributed to guide the clinician in the process of establishing a rational diagnosis and dictating appropriate treatment. Advances in diagnosis have been followed by an array of therapeutic techniques. Many of them are described in this book by their original authors. Because of my longtime interest on the subject, I have had personal experience with some of the diagnostic and surgical techniques described in this book such as oil lymphography, lymphoscintigraphy, lymphovenous anastomosis, and debulking procedures for massive lymphedema. I consider however that, at present, a program of complex manual decongestive techniques, associated with properly applied intermittent pneumatic compression and followed by a closely supervised compression therapy program in a compliant patient, may achieve long-lasting edema control without the need for surgery. The role of surgery, as described in surgical books and texts of vascular surgery, has been relegated to severe cases of chronic fibro-lymphedema treated by reconstructive plastic surgery to excise the fibrous tissue and remodel the redundant skin folds resulting from a good lymphatic manual decompression program of the extremities.

The science of genetics has found fertile ground in the pathology of the lymphatic vasculature. I am certain that as genetic research on the phenotypes of different lymphedema conditions progresses, our thoughts and concepts on the nature and classification of some primary lymphedemas will change. The same will occur in those cases of lymphedemas associated to other vas- VII Foreword cular and nonvascular anomalies. We are on the threshold of a true revolution in our understanding of the Kinmonth lymphedemas for the benefit of our own understanding of the disease and, hopefully, for the benefit of the many unfortunate patients suffering from the disabling pathology of the lymphatic system.

J. Leonel Villavicencio, MD, FACS Bethesda, MD, USA IX

Preface

It is indeed gratifying that, a scant 5 years after the first publication of this compendium, we find ourselves in need of a revision and expansion of the text. This fact is testimony to the continued and growing renaissance that is being experienced in the realm of lymphatic science and, specifically, as it impacts the vexing problem of lymphedema and related disorders. The transformation that we sensed in 2011 is far from over.

The last 5 years have witnessed substantial growth of insights within the genetics, developmental biology, and physiology of the lymphatic system, as evi- denced by the steady growth of publications devoted to this subject and by the 15% growth in the number of manuscripts indexed by the National Library of Medicine.

While the translation of biomedical science into diagnostic and therapeutic advances can be frustratingly slow, the last 5 years have indeed witnessed a substantial evolution in the evaluation and medical care of these patients. Spe- cifically, significant progress has been made in diagnostic imaging and in reconstructive surgical interventions, with increasing utilization of the various approaches that have been developed. One can say, optimistically, that greater numbers of lymphedema patients now have access to appropriate evaluation and therapeutic interventions. There is substantially greater awareness of the problem, which translates into more effective surveillance mechanisms for the at-risk population.

It has been our intent that this second edition of our compendium accurately reflects the exponential growth in the content of this subject matter. We have had the opportunity to work with our distinguished colleagues in generating new and expanded subject matter. Given the increasing need for clinicians to embrace this material, we have added features that allow this work to be uti- lized as a textbook of lymphatic medicine, including summaries of the basic concepts inherent in each chapter, and highlighted references that reflect the most important primary sources of information.

For the first edition of this book, we had the honor and privilege to work edito- rially with our colleague Dr. John Bergan. It is our fervent hope that this edition serves as a fitting tribute to him and to his distinguished career.

Stanley G. Rockson, MD Stanford, CA, USA

Byung-Boong Lee, MD Washington, DC, USA XI

Preface to the First Edition

It is truly fortunate that, as we enter the twenty-first century, the fields of lymphatic biology and medicine are experiencing a highly anticipated renaissance. This much-needed emphasis upon the study of the lymphatic system is pre- dicted to have a transformative impact upon our understanding of physiology, health, and disease.

Inexplicably, the lymphatic system has been the subject of passive neglect for centuries of medical development. This is, indeed, paradoxical, considering that such a very important component of the human circulation plays an equally important role in the normal functioning of the immune apparatus. Awareness of the importance of lymphatic mechanisms to the continuum of human biology and disease is growing. This «lymphatic continuum» now easily encompasses cardiovascular disease, obesity, autoimmune disease, respiratory and other forms of chronic inflammation, and chronic transplant rejection, among many other expressions of human pathology.

Lymphedema is a central manifestation of both peripheral and visceral diseases of the lymphatic circulation. Any pathological condition of the lymphatic vasculature, whether superficial or internal, regional, or systemic, is predominated by the appearance of the characteristic type of tissue edema that occurs when lymphatic dysfunction supervenes. While there is a broad spectrum of lymphatic vascular diseases, the most common diagnosis in lymphatic medicine is, of course, lymphedema.

This patient population is large and, historically, underserved by the medical community. At last, after decades and centuries of relative neglect, these patients are increasingly receiving attention. It is very timely, and gratifying, that there is now a clinical need for a comprehensive textbook that addresses the problem of lymphedema, and it is equally gratifying to acknowledge that this compendium has called upon the expertise of so many authorities to con- tribute their collective wisdom.

I am especially honored to collaborate with such an inspiring group of colleagues and, in particular, to have had the privilege to work so closely with my esteemed coeditors, Drs. John Bergan and Byung-Boong Lee.

It is an honor to dedicate this volume to the current and future well-being of our patients with lymphedema.

Stanley G. Rockson, MD Stanford, CA, USA XIII

Contents

I Introduction

1 General Considerations...... 3 Stanley G. Rockson

2 Etiology and Classification of Lymphatic Disorders...... 9 Stanley G. Rockson

3 Hereditary and Familial Lymphedemas...... 29 Peter S. Mortimer, Kristiana Gordon, Glen Brice, and Sahar Mansour

II Embryology, Anatomy, & Histology

4 Embryology of the Lymphatic System and Lymphangiogenesis...... 47 Stanley G. Rockson

5 Anatomy of the Lymphatic System and Its Structural Disorders in Lymphoedema...... 57 Hiroo Suami and Seiji Kato

III Physiology, Pathophysiology, and Lymphodynamics

6 General Overview...... 81 Stanley G. Rockson

7 Lymphodynamics...... 87 Stanley G. Rockson

8 Physiology: Lymph Flow...... 91 Anish Mukherjee, Joshua Hooks, and J. Brandon Dixon

9 Biomechanics of the Lymphatic Circulation...... 113 James E. Moore Jr. and Lowell T. Edgar

10 Pathology and Histochemistry...... 125 Waldemar L. Olszewski, Marzanna T. Zaleska, and Marta Jakimowicz-Cakala XIV Contents

11 Lymph Formation and Composition...... 139 Laura Santambrogio

IV Clinical Diagnosis

12 General Overview...... 155 Stanley G. Rockson

13 Lymphedema Epidemiology...... 165 Vaughan Keeley and Christine Moffatt

14 Clinical Staging...... 177 Sandro Michelini, Marco Cardone, Alessandro Failla, and Giovanni Moneta

15 Combined Clinical and Laboratory (Lymphoscintigraphic) Staging...... 187 Kendal Endicott, James Laredo, and Byung-Boong Lee

16 Early Diagnosis in Latent Phase...... 197 Leigh C. Ward

17 Cutaneous Manifestations of Edema...... 205 Peter S. Mortimer

18 The Diagnosis of Edema and Its Pathogenesis...... 221 Stanley G. Rockson

19 Differential Diagnosis: Venous Edema...... 229 Eri Fukaya

20 Differential Diagnosis: Lipedema...... 239 Győző Szolnoky

V Laboratory/Imaging Diagnosis

21 General Guidelines...... 253 Andrzej Szuba

22 Radionuclide Lymphoscintigraphies...... 257 Pierre Bourgeois XV Contents

23 Duplex Ultrasonography...... 315 Attilio Cavezzi

24 Oil Contrast Lymphangiography...... 329 J. Leonel Villavicencio

25 Microscopic Lymphangiography...... 337 Claudio Allegra, Michelangelo Bartolo, and Anita Carlizza

26 Near-Infrared Fluorescent Lymphography...... 345 Takumi Yamamoto

27 MR Lymphangiography...... 357 Ningfei Liu

28 Combined Role of Lymphoscintigraphy, X-ray Computed Tomography, Magnetic Resonance Imaging, and Positron Emission Tomography in the Management of Lymphedematous Disease...... 367 Pierre Bourgeois and Stanley G. Rockson

29 Alternative Assessment and Measurement Tools...... 387 Neil Piller

VI Physical and Medical Management

30 General Overview...... 397 Stanley G. Rockson

31 Complete Decongestive Physiotherapy...... 403 Etelka Földi, Martha Földi, and Stanley G. Rockson

32 Decongestive Lymphatic Therapy...... 413 Kristiana Gordon and Peter S. Mortimer

33 Compression Therapy...... 431 Hugo Partsch and Stanley G. Rockson

34 Intermittent Pneumatic Compression Therapy...... 443 Stanley G. Rockson

35 Other Contemporary Treatment Modalities...... 449 Neil Piller XVI Contents

36 Medical Treatment Options...... 459 Stanley G. Rockson

37 Diagnosis and Management of Infection in Lymphedema...... 465 Waldemar L. Olszewski and Marzanna T. Zaleska

38 The Prospect for Genetic and Growth Factor Therapy...... 483 Stanley G. Rockson

39 Adherence and Quality of Life...... 493 Sheila Ridner, Jie Deng, and Bethany Andrews Rhoten

40 Lymphedema Within the Healthcare System...... 503 Jane M. Armer, Joseph L. Feldman, Pamela L. Ostby, Janet S. Chance-Hetzler, Yuanlu April Sun, Nathan C. Armer, and Ya-Chen Tina Shih

VII Practical Issues in the Physiotherapeutic Approach to Lymphedema

41 Lower Limb Lymphedema...... 527 Győző Szolnoky

42 Upper Limb Lymphedema...... 537 Robert J. Damstra

43 Head, Face, and Neck Lymphedema...... 547 Anne-Marie Vaillant-Newman and Stanley G. Rockson

44 Genital Lymphedema...... 559 Stéphane Vignes

VIII Surgical Treatment: Reconstructive Surgery

45 Surgical Treatment - Reconstructive Surgery General Overview...... 571 Peter Gloviczki and Ying Huang

46 Principles of Patient Selection for Surgical Management of Lymphedema...... 589 Joseph H. Dayan XVII Contents

47 Lymphatic-Venous Derivative and Reconstructive Microsurgery...... 599 Corradino Campisi, Corrado Cesare Campisi, and Francesco Boccardo

48 Lymphatic-Lymphatic Reconstructive Microsurgery...... 619 Ruediger G.H. Baumeister

49 Lymph Node-Venous Microvascular Reconstructive Surgery: Filariasis Lymphedema...... 631 Gurusamy Manokaran

50 Vascularized Lymph Node Transfer for the Treatment of Lymphedema...... 637 Laurence S. Paek, Joseph M. Baylan, Corrine Becker, and Dung H. Nguyen

51 A Combined Microsurgical Reconstruction Approach for Lymphedema...... 653 Akitatsu Hayashi, Giuseppe Visconti, Yukio Seki, Guido Giacalone, Hidehiko Yoshimatsu, Nobuko Hayashi, and Takumi Yamamoto

52 Current Dilemmas and Controversies in Reconstructive Surgery for Lymphedema...... 673 Byung-Boong Lee and James Laredo

53 Future Prospects in Lymphatic Reconstructive Surgery...... 681 Chad M. Teven and David W. Chang

IX Surgical Treatment: Excisional and Debulking Tech- niques

54 Contemporary Indications and Controversies in Excisional Surgery...... 695 James Laredo and Byung-Boong Lee

55 Debulking Surgery for Lymphatic Filariasis...... 703 Gurusamy Manokaran

56 From Lymph to Fat: Liposuction as a Treatment for Complete Reduction of Lymphedema...... 707 Håkan Brorson

57 Surgical Management of Lipedema...... 717 Mark L. Smith and Bianca J. Molina XVIII Contents

X Congenital Vascular Malformation with Lymphatic Involvement

58 General Overview...... 729 K. Benjamin Lee, James Laredo, and Byung-Boong Lee

59 Primary Lymphedema and Lymphatic Malformation...... 743 Ningfei Liu

60 Molecular Genetics of Lymphatic and Complex Vascular Malformations...... 753 Matthieu J. Schlögel, Pascal Brouillard, Laurence M. Boon, and Miikka Vikkula

61 Syndromic Lymphedema and Complex Vascular Malformations with Lymphatic Involvement...... 765 Francine Blei

62 An Atlas of Neonatal and Infantile Lymphedema...... 777 Cristóbal Miguel Papendieck and Miguel Angel Amore

XI Management of Chyle Reflux and Effusions

63 Pathophysiology and Medical Management of Chylous Disorders...... 799 Francine Blei

64 Surgical Management of Chylous Reflux and Effusions...... 807 Ying Huang and Peter Gloviczki

65 Endovascular Catheter-Based Management of Chylous Effusions...... 823 Max Itkin

XII Lymphatic Filariasis

66 Epidemiology...... 841 Stanley G. Rockson

67 Etiology and Pathophysiology...... 849 Sasisekhar Bennuru, Subash Babu, and Thomas B. Nutman XIX Contents

68 Clinical Overview: Diagnosis and Management...... 865 Gurusamy Manokaran

XIII Oncology and Lymphedema

69 Breast Cancer...... 879 Sharon L. Kilbreath and Elizabeth S. Dylke

70 Lower Extremity Cancers...... 887 Mi-Joung Lee and Stanley G. Rockson

71 Radiation Considerations...... 899 Kathleen Horst and Jie Jane Chen

XIV Phlebolymphedema

72 Diagnosis and Management of Primary Phlebolymphedema...... 913 Kendal Endicott, James Laredo, and Byung-Boong Lee

73 Diagnosis and Management of Secondary Phlebolymphoedema...... 925 A Cavezzi

74 Management of Phlebolymphedema Ulcer...... 937 Sergio Gianesini, Erica Menegatti, and Paolo Zamboni

Supplementary Information Index...... 957 XXI

Contributors

Claudio Allegra Ruediger G.H. Baumeister Angiology Department Ludwig Maximilians University Munich San Giovanni Hospital Munich, Germany Rome, Italy [email protected] [email protected] Joseph M. Baylan, MD Miguel Angel Amore, MD, FACS Stanford University Phlebology and Lymphology Unit Palo Alto, CA, USA Central Military Hospital Buenos Aires, Argentina Corrine Becker, MD American Hospital of Paris Laboratory of Vascular Anatomy Paris, France University of Buenos Aires [email protected] Buenos Aires, Argentina [email protected] K. Benjamin Lee George Washington University Jane M. Armer, PhD, RN, FAAN, CLT Washington, DC, USA Sinclair School of Nursing [email protected] Nursing Research Ellis Fischel Cancer Center Sasisekhar Bennuru University of Missouri Laboratory of Parasitic Diseases Columbia, MO, USA National Institute of Allergy and [email protected] Infectious Diseases, NIH Bethesda, MD, USA Nathan C. Armer, MEd [email protected] Sinclair School of Nursing Francine Blei, MD University of Missouri Vascular Anomalies Program Columbia, MO, USA Lenox Hill Hospital of Northwell Health [email protected] New York, NY, USA [email protected] Subash Babu Laboratory of Parasitic Diseases Francesco Boccardo National Institute of Allergy and Department of Surgery Infectious Diseases, NIH Unit of Lymphatic Surgery Bethesda, MD, USA University of Genoa Genova, GE, Italy NIH-NIRT- ICER, Chennai, India [email protected] Michelangelo Bartolo Angiology Department San Giovanni Hospital Rome, Italy XXII Contributors

Laurence M. Boon Corrado Cesare Campisi Human Molecular Genetics Department of Surgery de Duve Institute, Université catholique Unit of Lymphatic Surgery de Louvain University of Genoa Brussels, Belgium Genova, GE, Italy Center for Vascular Anomalies Marco Cardone Division of Plastic Surgery San Giovanni Battista Hospital, ACISMOM Cliniques universitaires Saint-Luc Rome, Italy Université catholique de Louvain Brussels, Belgium Anita Carlizza Pierre Bourgeois, MD, PhD Angiology Department Institut Jules Bordet, Brussels, Belgium San Giovanni Hospital [email protected] Rome, Italy

J. Brandon Dixon Attilio Cavezzi Parker H. Petit Institute for Bioengineering Eurocenter Venalinfa and Bioscience, Georgia Institute of San Benedetto del Tronto, AP, Italy Technology [email protected] Atlanta, GA, USA [email protected] Janet S. Chance-Hetzler, DNP,MSN,RN,APRN, Glen Brice ACNS-BC,AOCNSCNE Lymphovascular Research Unit Sinclair School of Nursing St George’s University of London University of Missouri London, UK Columbia, MO, USA [email protected] Håkan Brorson Department of Clinical Sciences in Malmö David W. Chang, MD, FACS Lund University Section of Plastic and Reconstructive Plastic and Reconstructive Surgery Surgery Skåne University Hospital The University of Chicago Medicine SE-205 02 Malmö, Sweden Chicago, IL, USA [email protected] [email protected]

Pascal Brouillard Jie Jane Chen Human Molecular Genetics, de Duve Department of Radiation Oncology Institute, Université catholique de Louvain Stanford University School of Medicine Brussels, Belgium and Stanford Cancer Institute Stanford, CA, USA Corradino Campisi [email protected] Department of Surgery Unit of Lymphatic Surgery University of Genoa Genova, GE, Italy [email protected] XXIII Contributors

Robert J. Damstra Etelka Földi Department of Dermatology Clinic for Lymphology Expert Center on Lympho-Vascular Földiklinik, Hinterzarten Medicine, Nij Smellinghe Hospital Baden-Württemberg, Germany Drachten, The Netherlands [email protected] [email protected] Martha Földi Joseph Dayan, MD Clinic for Lymphology Division of Plastic and Reconstructive Földiklinik, Hinterzarten Surgery Baden-Württemberg, Germany Memorial Sloan Kettering Cancer Center New York, NY, USA Eri Fukaya, MD, PhD [email protected] Vascular Medicine, Stanford University Stanford, CA, USA Jie Deng, PhD, RN, OCN [email protected] Vanderbilt University School of Nursing Nashville, TN37240, USA Guido Giacalone [email protected] Department of Lymphatic Surgery AZ Sint- Maarten Hospital Elizabeth S. Dylke Mechelen, Belgium University of Sydney Sydney, Australia Sergio Gianesini Vascular Diseases Center Lowell T. Edgar University of Ferrara Department of Bioengineering Ferrara, FE, Italy Imperial College London, London, UK Uniformed Services University of the Health Sciences, Bethesda, MD, USA Kendal Endicott [email protected] George Washington University Washington, DC, USA Peter Gloviczki, MD [email protected] Division of Vascular and Endovascular Surgery Alessandro Failla Mayo Clinic San Giovanni Battista Hospital, ACISMOM Rochester, MN, USA Rome, Italy [email protected] Joseph L. Feldman, MD, CLT-LANA Kristiana Gordon NorthShore University HealthSystem, Dermatology and Lympho-vascular Pritzker School of Medicine, Medicine Department University of Chicago St George’s University Hospital Chicago, IL, USA London, UK [email protected] [email protected] XXIV Contributors

Akitatsu Hayashi Marta Jakimowicz-Cakala Department of Plastic and Mossakowski Medical Research Center Reconstructive Surgery Department of Epigenetics Asahi General Hospital Polish Academy of Sciences Tomari, Japan Warsaw, Poland [email protected] Seiji Kato, PhD Nobuko Hayashi Professor Emeritus, Faculty of Medicine Department of Plastic and Oita University Reconstructive Surgery Oita, Japan Asahi General Hospital [email protected] Tomari, Japan Vaughan Keeley Joshua Hooks Derby Teaching Hospitals NHS Parker H. Petit Institute for Bioengineering Foundation Trust and Bioscience Derby, UK Georgia Institute of Technology University of Nottingham Atlanta, GA, USA Nottingham, UK [email protected] Kathleen Horst Department of Radiation Oncology Sharon L. Kilbreath Stanford University School of Medicine Health Sciences and Stanford Cancer Institute University of Sydney Stanford, CA, USA Sydney, Australia [email protected] [email protected] Ying Huang, MD, PhD James Laredo Division of Vascular and Endovascular Center for the Lymphedema and Vascular Surgery Malformations, Division of Vascular Surgery Mayo Clinic Department of Surgery Rochester, MN, USA George Washington University [email protected] Washington, DC, USA [email protected] Max Itkin, MD, FSIR Radiology and Pediatrics Byung-Boong Lee CHOP/HUP Center for Lymphatic Center for the Lymphedema and Vascular Imaging and Interventions Malformations, Division of Vascular Philadelphia, PA, USA Surgery, Department of Surgery Children’s Hospital of Philadelphia, George Washington University Penn Medicine Washington, DC, USA Philadelphia, PA, USA Department of Surgery Hospital of University of Pennsylvania Uniformed Services University of the 3400 Spruce Street, Philadelphia, Health Sciences, Bethesda, MD, USA PA19004, USA [email protected] [email protected] XXV Contributors

Mi-Joung Lee Erica Menegatti The University of Sydney, Faculty of Health Vascular Diseases Center Sciences, Discipline of Physiotherapy University of Ferrara Sydney, New South Wales, Australia Ferrara, FE, Italy [email protected] [email protected]

J. Leonel Villavicencio Sandro Michelini Distinguished Professor of Surgery San Giovanni Battista Hospital, ACISMOM Department of Surgery, Uniformed Services Rome, Italy University School of Medicine, Director [email protected] Emeritus Venous and Lymphatic Teaching Clinics, Walter Reed Army and National Christine Moffatt Naval Medical Centers School of Health Sciences, University of Washington DC and Bethesda, MD, USA Nottingham, Nottingham, UK [email protected] Derby Teaching Hospitals NHS Foundation Trust Ningfei Liu, MD, PhD Derby, UK Lymphology Center of Dept. Plastic & Reconstructive Surgery, Cardiff Wound Healing Institute; Shanghai Ninth People’s Hospital, Kanasawa University; Western Ontario Shanghai Jiao Tong University School of University, LOROS, UK, Glasgow University Medicine, Glasgow, UK 639 Zhi Zao Ju Road, Shanghai, 200011, [email protected] China [email protected] Bianca J. Molina Department of Plastic Surgery Wexner Medical Center, Ohio State University Gurusamy Manokaran, MS, Columbus, OH, USA MCh., (Plastic), FICS, FRCS Senior Consultant Plastic & Reconstructive Giovanni Moneta Surgeon & Lymphologist, San Giovanni Battista Hospital, ACISMOM Apollo Hospitals Rome, Italy 21, Greams Road, Chennai, India

Past President “International Society of James E. Moore Jr. Lymphology”, Tucson, Department of Bioengineering Arizona, USA Imperial College London London, UK Honorary Associate Prof. Macquarie [email protected] University Sydney, NSW, Australia Peter S. Mortimer [email protected]; Dermatology and Lympho-vascular [email protected] Medicine Department St George’s University Hospital Sahar Mansour London, UK Lymphovascular Research Unit [email protected] St George’s University of London London, UK XXVI Contributors

Anish Mukherjee Hugo Partsch Parker H. Petit Institute for Department of Dermatology Bioengineering and Bioscience University of Wien Georgia Institute of Technology Baumeistergasse, Wien, Austria Atlanta, GA, USA [email protected]

Dung H. Nguyen, MD Neil Piller Stanford University Lymphoedema Clinical Research Unit Palo Alto, CA, USA Department of Surgery [email protected] Flinders University Adelaide, South Australia Thomas B. Nutman [email protected] Laboratory of Parasitic Diseases, National Institute of Allergy and Bethany Andrews Rhoten, PhD, RN Infectious Diseases, NIH Vanderbilt University School of Nursing Bethesda, MD, USA Nashville, TN37240, USA [email protected] [email protected]

Waldemar L. Olszewski Sheila Ridner, PhD, RN, FAAN Mossakowski Medical Research Vanderbilt University School of Nursing Center, Department of Surgery Nashville, TN37240, USA and Applied Physiology, [email protected] Polish Academy of Sciences Warsaw, Poland Stanley G. Rockson Falk Cardiovascular Research Center Central Clinical Hospital Stanford University School of Medicine Warsaw, Poland Stanford, CA, USA [email protected] [email protected]

Pamela L. Ostby, Laura Santambrogio PhD, RN, OCN®, CLT Department of Pathology Sinclair School of Nursing Microbiology & Immunology University of Missouri Albert Einstein College of Medicine Columbia, MO, USA 1300 Morris Park Avenue, New York [email protected] NY10461, USA [email protected] Laurence S. Paek, MD Stanford University Matthieu J. Schlögel Palo Alto, CA, USA Human Molecular Genetics, de Duve Institute, Université catholique de Louvain Cristóbal Miguel Papendieck, Brussels, Belgium MD, PhD, FACS Angiopediatria Buenos Aires, Argentina [email protected] XXVII Contributors

Yukio Seki Andrzej Szuba, MD, PhD Department of Plastic and Professor of Medicine Reconstructive Surgery Division of Angiology St. Marianna University School of Wroclaw Medical University and Medicine Hospital Department of Internal Medicine Kawasaki, Japan Wroclaw, Poland [email protected] Ya-Chen Tina Shih, PhD Section of Cancer Economics and Chad M. Teven, MD Policy, Department of Health Services Section of Plastic and Reconstructive Research Surgery University of Texas MD Anderson The University of Chicago Medicine Cancer Center Chicago, IL, USA Houston, TX, USA [email protected] [email protected] Anne-Marie Vaillant-Newman Mark L. Smith, MD, FACS Stanford Center for Lymphatic Northwell Health System and Venous Disorders, Stanford University Lake Success, NY, USA School of Medicine [email protected] Stanford, CA, USA [email protected] Hiroo Suami, MD, PhD Associate Professor, Australian Lymphoe- Stéphane Vignes, MD dema Education, Research and Treatment Department of Lymphology (ALERT), Faculty of Medicine and Health Hôpital Cognacq-Jay Sciences, Macquarie University, 15, rue Eugène-Millon75015, Paris, France Sydney, Australia [email protected] [email protected] Miikka Vikkula Yuanlu April Sun, BSN, CLT Human Molecular Genetics Sinclair School of Nursing de Duve Institute, Université University of Missouri catholique de Louvain Columbia, MO, USA Brussels, Belgium [email protected] Center for Vascular Anomalies Győző Szolnoky, MD, PhD Division of Plastic Surgery Department of Dermatology and Allergology Cliniques universitaires Saint-Luc University of Szeged Université catholique de Louvain Korányi fasor, Szeged, Hungary Brussels, Belgium [email protected] Walloon Excellence in Life sciences and Biotechnology (WELBIO) Université catholique de Louvain Brussels, Belgium [email protected] XXVIII Contributors

Giuseppe Visconti Hidehiko Yoshimatsu Centre for Surgical Treatment of Department of Plastic and Reconstructive Lymphedema, Department of Plastic Surgery Surgery, University Hospital “Agostino University of Tokyo Hospital Gemelli” Università Cattolica del Sacro Tokyo, Japan Cuore Milan, Italy Marzanna T. Zaleska Mossakowski Medical Research Center Leigh C. Ward Department of Surgery and Applied Metabolic Biochemistry, School of Physiology, Polish Academy of Sciences Chemistry and Molecular Biosciences Warsaw, Poland The University of Queensland Central Clinical Hospital Brisbane, Australia Warsaw, Poland [email protected] Paolo Zamboni Takumi Yamamoto Vascular Diseases Center Plastic and Reconstructive Surgery University of Ferrara National Center for Global Health and Ferrara, FE, Italy Medicine, Toyama 1-21-1, Shinjuku-ku, [email protected] Tokyo 162-8655, Japan [email protected]