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Diagnostic and Therapeutical Aspects of Lymphedema

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Diagnostic and Therapeutical Aspects of Lymphedema Diagnostic and therapeutical aspects of lymphedema Citation for published version (APA): Damstra, R. J. (2009). Diagnostic and therapeutical aspects of lymphedema. Stichting Lymfologie Centrum Nederland (SLCN). https://doi.org/10.26481/dis.20090626rd Document status and date: Published: 01/01/2009 DOI: 10.26481/dis.20090626rd Document Version: Publisher's PDF, also known as Version of record Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.umlib.nl/taverne-license Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 11 Oct. 2021 Diagnostic and therapeutical aspects of lymphedema Financial support for publication and distribution of this thesis by the SLCN was obtained from a grant by: Golden donation from Lomann & Rauscher, Medi, Varitex, Varodem, and by Bauerfeind, BSN, 3M, Doove, Juzo, Smith & Nephew, Thuasne Painting on the cover: “Blue excentrique” (1992). Kor Onclin (1918-1998) ISBN/EAN: 978-90-805399-2-1 © 2009, R.J. Damstra No parts of this thesis may be reproduced or transmitted in any forms by means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system, without permission in writing from the publisher Publisher: Stichting Lymfologie Centrum Nederland (SLCN). Postbus 696, 9200 AR, Drachten, NL Lay-out: P. van der Sijde, Groningen, NL Printed by drukkerij van Denderen, Groningen, NL Graphic design: Gravis ontwerpers, Groningen, NL Diagnostic and therapeutical aspects of lymphedema PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit Maastricht, op gezag van de Rector Magni!cus Prof. mr. G.P.M.F. Mols volgens besluit van het college van Decanen, in het openbaar te verdedigen op vrijdag 26 juni 2009 om 14.00 uur door Robert Jacobus Damstra geboren op 15 juli 1959 te Hengelo (ov) Promotiecommissie: Promotor: Prof. dr. P.M. Steijlen Copromotoren: Dr. M.A.M. van Steensel Dr. J.C.J.M. Veraart Beoordelingscommissie: Prof.dr. F.C.S. Ramaekers (voorzitter) Prof. dr. A. Gri"oen Prof.dr. H.A.M. Neumann (Erasmus universiteit, Rotterdam) Prof.dr. med. E. Rabe (University of Bonn, Germany) dr. G.W.H. Schurink A pessimist sees the di"culty in every opportunity; an optimist sees the opportunity in every di"culty. Sir Winston L.S. Churchill (1874 - 1965) Voor Jorine, Anne Marijn, Josephine en Hugo CONTENT List of abbreviations Chapter 1 general introduction and aim of the thesis 9 - Anatomy, physiology, pathophysiology and immunological aspects - Developmental and Genetic aspects of lymphatics - Epidemiology of lymphedema - Diagnosis of swelling and lymphedema - Therapeutic aspects of lymphedema - Aim of the thesis - References Chapter 2 Validation of the inverse water volumetry method: a new gold standard for 67 arm volume measurements Chapter 3 Novel missense mutations in the FOXC2 gene lead to increased 83 transcriptional activity and causes lymphedema Chapter 4 Erysipelas as a sign of subclinical primary lymphedema: A prospective 95 quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg Chapter 5 Cancer related secondary lymphedema due to cutaneous lymphangitis 109 carcinomatosa: clinical presentations and review of literature Chapter 6 Controlled, comparative study of relation between volume changes and 123 interface pressure under short-stretch bandages in leg lymphedema patients Chapter 7 Compression therapy in breast cancer related lymphedema. A randomized 133 controlled, comparative study of relation between volume and interface pressure changes Chapter 8 Lymphatic Venous Anastomosis (LVA) for treatment of secondary 151 lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature Chapter 9 Reduction surgery by Circumferential Suction-Assisted Lipectomy 167 (Brorson method) in end stage breast cancer related lymphedema: a prospective study Chapter 10 Multidisciplinary guidelines for early diagnosis and management of 183 lymphedema Chapter 11 Diagnosis and therapy in children with lymphedema 199 Chapter 12 General discussion, summary and future research 221 Chapter 13 Algemene discussie, samenvatting en toekomstig onderzoek 237 Chapter 14 Dankwoord / Words of thanks / Curriculum vitae / Bibliography 251 List of abbreviations ANG Angiopoietins BCRL Breast Cancer Related Lymphedema BMI Body Mass Index CPT Complex Physical therapy CSAL Circumferential Suction Assisted Lipectomy CT Compression Therapy ICC Intra-class correlation coe"cient IWV Inverse Water Volumetry LE Lymphedema LN Lymph nodes LVA Lymphatico Venous Anastomosis MLD Manual lymph drainage PL Primary lymphedema QoL Quality of life RT Radiotherapy SLD Simple lymph drainage VEGF Vascular Endothelial Growth Factor CHAPTER 1 General Introduction and Aim of the Thesis 9 Chapter 1 INTRODUCTION The blood circulation and the lymphatic system are the two vascular systems of the body. Besides the well know major role of the lymphatics in tissue $uid regulation, they are also important in tumor metastasis and immune system function. Lymphedema is de!ned as swelling of a body part due to the accumulation of interstitial tissue $uid. It is caused by insu"ciency, either physical or functional of the lymphatic system and has a wide range of clinical manifestations and causes. Over the past few years, lymphedema has enjoyed an ever-increasing interest in the national and international health communities, primarily because of the morbidity it causes in many cancer survivors. More vocal patient groups have also played an important role in increasing awareness. These developments are fortunate, because lymphedema is not rare and can have devastating medical, psychological and social consequences for patients. Despite the obvious need, most healthcare workers have relatively little knowledge of or experience in dealing with lymphedema. As a result, many patients are not adequately diagnosed and treated. Because many organ systems can be a%ected, several medical specialties can and should be involved in patient care. Multidisciplinary teams need a coordinator and it is the author’s conviction that in cases of lymphedema a dermatologist should !ll this position. Most lymphatic vessels in the extremities are situated between the muscular fascia and the epidermis and lymphedema often causes skin changes. Thus, a dermatologist will almost invariably be involved in diagnosis and treatment. That said, lymphology, the study of the lymphatic system and its diseases, is in need of systematic research e%orts to give it an evidence-based footing. This thesis addresses the !rst Dutch e%orts in this direction. To provide a basis for understanding the work presented here, an overview will be given in the following paragraphs of the current state of the art in lymphology, covering anatomy, (patho) physiology, genetics, epidemiology, diagnostic approaches and therapeutic aspects. ANATOMY The lymphatic system consists of vessels and lymphatic organs1. Lymph vessels are a one- 10 Introduction way system: there is no central pump, and the lymphatics start as minute, blind-ended, 1 endothelial sacs in the intercellular space of all tissues, with the exception of avascular structures such as hair, nails, cartilage and the retina. The brain and spinal cord likewise do not have lymphatics. The lymphatic system is divided into pre-lymphatic and lymphatic portions. The pre- lymphatic portion is de!ned as interstitial channels in the intercellular space without endothelial linings. The lymphatic portion is lined with endothelium and composed as follows, from small to large: 1. Initial lymphatics / lymph capillaries / lymph sacs. Endothelial lymphatic cells are connected to the surrounding elastic !bers in the extracellular matrix by !brillar anchoring !bers2. These !bers can pull the endothelial cells of the lymphatics apart because the initial lymphatics are very thin and lack an endothelial membrane and pericytes3. The blind initial lymphatics are called lymph sacs. The endothelial cells of these
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