Lymphovenous Canada: Highlights from the XXth International Congress of Lymphology in Salvador Brazil

This year's bi-annual International Society of Lymphology (ISL) conference held in Salvador Brazil, was hosted by the Brazilian Congress of Lymphology (Sociedade Sociedade Brasileira de Linfologia), of the Latin American Chapter of Lymphology in Salvador Bahia Brazil.

It is the 34st year of existence for the International Society of Lymphology (ISL) which was founded in Zurich in 1966. The Society now has some 375 members from 42 nations. Affiliated groups are: The Japanese Society of Lymphology, The North American Society of Lymphology, The German Speaking Section of Lymphology, The Groupement Europeen de Lymphologie, the Association de Lymphologie de Langue Français, the British Lymphology Interest Group, Club de Linfologia (Spain), Asociation Argentina de Linfologia, and the Latin-Mediterranean Chapter.

Salvador's 85% Afro-brazilian population is credited for making this area the stimulous of Brazil's top musicians and artisans. Salvador has the second largest Carnaval in the country (next to Rio de Janeiro); its colourful historic colonial district (Pelourinho) is a Unesco-declared World Heritage site - and the area has some of Brazil's most beautiful beaches.

The Sociedade Brasilerira de Linfologia made the most of this fertile environment throughout the conference: local music was performed at several evening happy hours, including the final gala dinner which had delegates dancing until the wee hours to the songs of some of Brazil's top international groups such as Olodum and the international hit album Tribalistas. President of the organizing committee, Brazilian Dr. Mauro Andrade (credited with developing the ISL concensus document on treatment for lymphedema), was a charming presence throughout the conference, and made everyone feel at home.

About 150 delegates attended the conference from as far away as Russia, China, Japan, Sweden, Australia and India, with delegates also hailing from many European countries, the U.S. and Latin America, representing both the public and private health care systems. This made for spirited discussions at a number of workshops on the challenges of providing cost effective health care to people with limited resources.

The conference honoured some of the pioneers of lymphology such as Brazilian phlebolymphologist, Dr. Rubens Carlos Mayall, France's Dr. Robert Victor Cluzan, U.S. Dr. Charles Witte, while providing a forum for new theories in treatment and research to be discussed.

Discussions related to genetic research played a critical and important role at the conference. Dr. Peter Mortimer, Michael Bernas and Dr. Marlys Witte gave delegates a mini course on the genetics of lymphatic disorders. Presentations were also made on research into Foxc2 gene insufficiency, the unsuccessful search (so far) for a gene responsible for lipedema; the lymphatic phenotype of the Chy-3 mice in comparison to mice with Vegfc+/-, and the potential use of tissue growth genetics (lymphangiogenesis) through Vegfc and Vegfd, to restrict the spread of cancerous tumors.

The acceleration of new information on the lymphatic system as a result of genetic research has given new hope to professionals who have worked in this area for many years. It has also been encouraging to consumers who yearn to see improvements in treatments for lymphatic disorders. These relevations have forced practitioners to re-think their assumptions in this area.

One of the areas which is undergoing some major rethinking, is the relationship between lymphatic system, lipids and adipose tissue. (Note: lipids (fat) are absorbed by lymphatics in the bowel; adipose tissue is a specialized connective tissue that functions as the major storage site for fat.) A number of researchers presented some interesting findings on this topic.

In the Sept. 18, 2005 on-line issue of Nature Genetics (http://www.stjude.org/genetics-tumor-cell-biology/0,2524,416_2043_19189,00.html), St. Jude Children's Research Hospital reported findings that the abnormal leakage of lymph fluid from the ruptured lymphatic vessels stimulates the accumulation of fat, particularly in regions of the body rich in lymphatics (abdomen and thorax/chest). The findings - which look at the role of the Pox1 gene which is necessary for the normal development of the lymphatic system - suggest that leaky lymphatic vessels could be the leading cause of adult onset obesity. It also suggests that some obese patients might be suffering from a problem that can't be solved by eating less and exercising more.

Leaky lymphatic vessels could be the
leading cause of adult onset obesity

Dr. Hakan Brorson, with the Lymphedema Unit at the Department of Plastic and Reconstructive Surgery, Malmo University Hospital, Sweden, reported his observations of increased adipose tissue content in the involved areas of patients with chronic non-pitting lymphedema. Dr. Brorson has been using liposuction to treat patients with non-pitting lymphedema who do not respond to more conventional forms of treatment, for 11 years.

Dr. Brorson studied 44 women who had received liposuction in his clinic for breast cancer related lymphedema and found a very high level of adipose tissue. He noted that increased adipose tissue in intestinal segments "fat wrapping" in patients with Crohn's disease have shown that inflammation plays an important role and suggested that further research be undertaken to determine whether anti-inflamatory medication might reduce the development of excess adipose tissue in patients with lymphedema.

There may be a sub-type of fat cell necessary for the
metabolism of lymphocytes and dendritric cells in lymphoid tissue

Ryan noted a recent theory by Catherine Pond and her colleagues that there may be a sub-type of fat cell necessary for the metabolism of lymphocytes and dendritric cells in lymphoid tissue. He asked whether the sequestered lymphoid tissue in the skin might stimulate a peripheral enlargement of adipose tissue there. He suggested that perhaps that the filariasis worm might be attracted to the lymphatic nodes because of their metabolic relationship with fatty deposits.

These observations were echoed by Dr. Andrzej Szuba and his research team from the Medical University of Wroclaw, Poland. Szuba presented findings which suggested that the migration of lipid loaded macrophages from the arterial wall through adventitial lymphatics is a physiological process present also in persons without significant atherosclerosis. This process may represent an important mechanism of physiological regression of atherosclerosis (the buildup of fatty deposits called plaque on the inside walls of arteries which leads to diseases of the heart and blood vessels).

Clinical observations and information-sharing continues to play an important role at ISL conferences, however there is now an acknowledgement that while less intrusive conventional forms of treatment (compression, massage and exercise) can be helpful to many people, there are some people who do not respond to them.

Dr. Alexandre Pissas of France's General Hospital Louis Pasteur raised this point in his summarizing the study his institute undertook over a five year period between 2000 - 2004 of patients with lymphedema in: "Lymphedema is a frequent Horse of Troy of numerous Pathological Situations". Of the 553 women and 256 men his clinic saw during that period, Dr. Pissas noted that in numerous cases where lymphedema existed its treatment did not resolve the problem resulting in a real problem for the patient.

Professors Jose Maria Pereira de Godoy and Maria Fatima Guerreiro Godoy made an impressive number of presentations and poster presentations singly and apart on their rehabilitative clinical work with adults and children with lymphedema in Brazil. Dr. Waldemar Olszewski from Poland was also prodigious presence throughout the conference, discussing his on-going case studies on infection-control, clinical rehabilitation and surgical interventions in extreme situations of lymphedema.

Alternative forms of therapy:

• the external application of Antimicrobiotic (Nadifloxacine) lotion for lymphedema-related dermatitis;
• the treatment of hyperkeratosis associated with lymphedema by external application of Maxacalcitol (vitamin D3 derivative) ointment

Drs. Masuzawa, Madea, Miyata and Katsuoka from the Department of Dermatology, Kitasato University School of Medicine in Japan, also presented findings on the successful treatment of lymphorrhea with the oral administration of the antiplatelet drug Cilostazol (Pletal). Their poster discussion elaborated on an efficacy study of Cilostazol on 30 people, which they presented at the ISL conference in 2003. The drug appears to significantly reduce the leakage of lymph in some individuals. These researchers conclude that Cilostazol dilates blood vessels and promotes the increase of blood flow. As a result there may be greater absorption of lymph in the blood vessels. (Note to readers: Cilostazol should not be used by patients with congestive heart failure as it has shown increased mortality in well controlled studies. Source: FDA Centre for Drug Evaluation and Research www.fda.gov/cder/news/cilostazol/default.htm)

Dr. S. Narahari from Kerala state in India reported on an evidence-based study which looked at a low cost integrated system of managing filarial lymphedema in rural communities using Indian Ayuredic herbal medicines in a treatment regime of skin care, compression bandaging, yoga and massage. (Lymphedema resulting from filariasis is known as Shleepada in Ayuredic medicine)

The study took place between October 2003 and 2005. 51 patients with lymphedema of one or both lower limbs of any duration were involved in the study. A patient advocacy group assisted with the study which met the requirements of the Institute of Applied Dermatology's ethics committee.

Patients were trained in the hospital for two weeks on how to undertake these procedures which they then carried out for another six month period following discharge. One week after review they were called in for a review. In addition patients were advised to take two oral medications of Ayurveda described for lymphedema: Kanchanaraguggula and Mahamanjishtadi kwatha as recommended by the Ayurvedic formulary of India. While on these medications they were required to observe certain diet restrictions such as avoiding cold water and cool drinks, milk and milk products, and to be strictly vegetarian in diet. Significant differences among disease categories were found for end of calf bulk, maximal bulk, maximum bulk on stand and volume. Since the study took place, the Institute of Applied Dermatology has treated 115 patients with this program. Results from the study will be published in the Lymphology Journal.

Other interesting highlights of the conference included:

• A report from scientist Eric Bridenbaugh of the A&M University System Health Science Center in Texas, who has undertaken research with Calgary's Pierre Yves Von Der Wied, to better understand how the receptors (transient reception potential channels of the V subfamily - TRPV) control the contraction of lymphatic vessels in temperature change.
• Australia's Mercy Hospital for Women's young people's peer group which helped encourage young people to improve their self-management and reduced some of the psychological issues related to coping with the condition.
• Saskia Thiadens, Executive Director of the U.S. National Lymphedema Network (NLN), reported on a 4-year Internet patient survey electronic study her organization undertook, in conjunction with between March 2001 and May 2005. 4389 patients responded to the survey, 67% with secondary lymphedema. While the majority of patients were females (88.4%) and residing in the U.S. (94.8%), the collected data included 228 patients from 53 other countries. Surprisingly, Thiadens noted that less than 50% of respondents used compression garments. Plenty of material here for further follow-up research and analysis.
• Dr. Pecking of the Centre Rene Hugeenin in France reported on a new method of lymphatic imaging using a fusion of anatomic and functional imaging. Lymphoscintigraphic images were obtained using a hybrid gammacamera, combining a dual head gamma and an integrated CT. Emission tomography and CT were simultaneously performed and precisely registered during the same time and fused to provide a more accurate anatomic location of detected abnormalities. Pecking has suggests that the fusion of techniques provides a more accurate picture of the lymphatic system and its compensatory pathways and also enables practitioners to more accurately locate the sentinel node in breast cancer.

The Lymphatic Research Foundation (LRF) spoke to delegates on their continuing success in securing funding for scientific research in the U.S. on the lymphatic system from the National Institutes for Health. The LRF has initiated the launching of the scientific journal Lymphatic Research and Biology and has been instrumental in ensuring a segment of the prestigious Gordon Research Conference Series has been dedicated to scientific research into the lymphatic system.

A number of presenters at the ISL conference also made a point of noting that their studies had been undertaken in compliance with the ethical research guidelines of their institution, and that they had received informed consent from their patients before proceeding with trials. These included Brazilian researcher Marcelo Araujo who highlighted the Helsinki Declaration (2002) and resolution 196/96 of the Brazilian Ministry of Health on informed consent.