Abstracts LymphForsch 2/2019

– full text in German –

The relationship between skin fold thickness on the abdomen and thigh and the compressibility of the subcutaneous skin layer are objective criteria for diagnosing lipedema

R. Kasseroller, E. Brenner
LymphForsch 23 (2) 2019, 76-82

Summary
Introduction: Lipedema is diagnosed based on clinical findings. No objective parameters are available for diagnosis at present. The aim of this study is to show a possible correlation between standardized, sonographically measured compressibility of the subcutaneous fat layer and the comparison of the skin fat folds on the abdomen and thighs and the clinical diagnosis of lipedema.

Materials and methods: The basic patient for the selection of subjects consisted of 1,100 patients. Of these individuals, 1,016 patients were excluded on the basis of the relevant exclusion criteria. The remaining 84 (female) patients were examined for the clinical diagnosis “Lipedema of the legs”. The clinical diagnosis “lipedema” was positive in 71 patients and negative in 13 patients. Three patients declined to participate (1 with negative diagnosis, 2 with positive diagnosis); 69 patients in the group of lipedema patients and 12 patients in the control group were examined. In addition, 7 “healthy” male volunteers were measured and compared as a further control group using the same technique. The data collected for all subjects included age, BMI, ratio of abdominal to thigh skin fat fold (right only), and subcutis thickness at the thigh uncompressed and compressed on both sides.
Results: The assumption that the subcutaneousskin layer in lipedema patients is significantly less compressible was verified in 69 (female) patients with lipedema but without signs of lymphedema. The results of the control groups (7 men, 12 women) were negative in this respect. The mean value of this compressibility of the subcutaneous skin layer was 7 % in the lipedema group and 22 % (men) and 16% (women without lipedema) in the control groups. The ratio of skin fat folds on the abdomen and thighs in lipedema patients was 0.43 on average, significantly below that of the other groups (men: 1.45; women without lipedema: 1.16).
Discussion: The sonographically measured compressibility of the subcutis is an important objective parameter for the diagnosis of lipedema. An additional positive statement is provided by the comparison of skin fat fold thickness on the abdomen and thighs with statistically significant differences.

Keywords:
lipedema, lipohyperplasia, sonography, compression, subcutis, skin fat folds
E-mail: erich.brenner@i-med.ac.at

Lipiodol Lymphography - Tracing its history from 1961 to 2019

H. Weissleder
LymphForsch 23 (2) 2019, 83-87

Summary: 
Visualization of the human lymphatic system by means of intravascular injection of the oily contrast agent Lipiodol UF® provides insights into the structure and function of lym­phatic vessels and lymph nodes. During the pre-CT and MRI period prior to the 1980s, the method served as a valuable diagnostic tool, particularly for detecting abnormal changes in inguinal, pelvic, lumbar and axillary lymph nodes.
After the introduction of non-invasive cross-sectional imaging techniques such as ultra­sound, computed tomography, and magnetic resonance imaging, as well as the lym­phoscintigraphic function test, ICG fluorescence lymphography, and indirect lymphan­giography, lipiodol lymphography as an invasive method largely lost its original significance as a valuable routine diagnostic method.
At present, both the old intravascular and the new intranodal technique of Lipiodol UF® injection is limited to the detection, location, and treatment of lymphatic vessel defects as a cause of thoracic and/or abdominal chylous disorders. In this group of diseases, the method is also used to locate the cisterna chyli for subsequent interventional procedures.

Keywords:
lipiodol lymphography, visualization of the human lymphatic system, detection of post-traumatic lymphatic vessel defects, locating cisterna chyli.
E-mail: horstwei@gmx.de

The proteolytic activation of vascular endothelial growth factor C

M. Lackner, C. Schmotz, M. Jeltsch
LymphForsch 23 (2) 2019, 88-98

Summary:
The enzymatic cleavage of the protein backbone (proteolysis) is integral to many biological processes, such as for the breakdown of proteins in the digestive system. Specific proteolytic cleavages are also used to turn on or off the activity of proteins. For example, lymphangiogenic vascular endothelial growth factor C (VEGF-C) is synthesized as a precursor molecule that must be converted to a mature form by the enzymatic removal of C- and N-terminal propeptides before it can bind and activate its receptors. The constitutive Cterminal cleavage is mediated by proproteinconvertases such as furin. The subsequent activating cleavage can be mediated by at least 4 different proteinases: by plasmin, ADAMTS3, prostate-specific antigen (PSA) and cathepsin D. Processing by different proteinases results in distinct forms of "mature" VEGF-C that differ in their affinity and their receptor activation potential. The CCBE1 protein regulates the activating cleavage of VEGF-C by ADAMTS3 and PSA, but not by plasmin. During embryonic development of the lymphatic system, VEGF-C is activated primarily by the ADAMTS3 proteinase. In contrast, it is believed that plasmin is responsible for wound-healing lymphangiogenesis and PSA for tumor-associated pathological lymphangiogenesis. Cathepsin D has also been implicated in tumor lymphangiogenesis. In addition, cathepsin D contained in saliva might activate latent VEGF-C upon wound licking, thereby accelerating wound healing. The molecular details of proteolytic activation of VEGF-C have only recently been extensively explored, and it is likely that not all activating proteinases are known as yet. It appears that the activity of VEGF-C is regulated for different specific functions by different proteinases. Although VEGF-C clearly plays a pivotal role for tumor progression and metastasis in experimental animal studies, the relevance of most correlative studies on the role of VEGF-C in human cancers has been quite limited until now, also due to the lack of methods for differentiating between inactive and active forms of VEGF-C.

Keywords:
VEGF-C, lymphangiogenesis, proteinases, proteolysis
E-mail: michael@jeltsch.org

The influence of mechanical forces on the developing lymphatic system

L. S. Hilger, E. Lammert
LymphForsch 23 (2) 2019, 99-103

Summary:
Lymphatic endothelial cells (LECs) form the inner lining of lymphatic vessels and are exposed to multiple different mechanical forces. Here we describe the role of mechanical forces on LECs in relation to several diseases, focusing specifically on mechanical stimuliduring lymphatic vascular growth. On a molecular level, we describe vascular endothelialgrowth factor receptor-3 (VEGFR3) and how it is activated via mechanical stimuli andβ1-integrin, leading to LEC proliferation, which can result in abnormal overgrowth of the lymphatic vessels.

Keywords:
Lymphatic endothelial cells, lymphangiogenesis, mechanical stimuli, VEGFR3, β1-integrinn
E-mail: lammert@uni-duesseldorf.de

Secondary lymphedema of the external genitalia and lower extremities after prostate cancer treatment: A case report

D. Bojinović-Rodić, T. Ivanković, J. Nikolić-Pucar, S. Kopčanski-Miljanović
LymphForsch 23 (2) 2019, 104-107

Summary:
Secondary lymphedema of the external genitalia is an uncommon and disabling side effect of pelvic radiation therapy for invasive prostate cancer. Therapy of lymphedema after prostate cancer treatment remains controversial. Currently, therapeutic concepts include conservative therapy (complex decongestive physical therapy) and surgery to reduce genital volume, however, no therapy standards exist at present. This paper describes a patient who developed secondary lymphedema of the external genitalia and the lower extremities after prostate cancer treatment and did not respond to conservative therapy.

Keywords:
lymphedema of the external genitalia, prostate cancer, conservative treatment
E-mail: dbojinovic@yahoo.com

Does defined padding as part of intermittent pneumatic compression (IPC) promote decongestion in patients with lymphedema?

M. Morand
LymphForsch 23 (2) 2019, 108-111

Summary:
Ideally, intermittent pneumatic compression (IPC) treatment should be initiated only by lymph drainage therapists and physicians experienced in lymphangiology. They have undergone adequate training in the latest iteration of decongestion therapy. IPC plus is a procedure in its own right and is only a limited replacement for manual lymph drainage (MLD) or complete physical decongestion therapy (CDT). Patients must be fully informed about IPC and must be made aware that medical devices are not intended for self-treatment.

Keywords:
intermittent pneumatic compression (IPC), compression, padding, lymphedema, complete physical decongestive therapy (CDT), edema
E-mail: morand@t-online.de