Servier – Phlebolymphology

IV. Phlebolymphology forum

Functional relationship of the lymphatic and venous systems in clinical aspect
Waldemar L. Olszewski (Poland)

The blood and lymph circulation systems arise simultaneously in the embryo. The lymph sacs are formatted from the venous endothelial cells. Peripheral blood (arteries and veins) and lymphatic vessels originate from the same tissue mesenchymal cells. They differentiate into the hematological (blood vessels) or tissue fluid channel (lymphatic channels) structures. Eventually the lymphatic vessels join veins in the subclavian-jugular angle and hundreds of lymphovenous communications in the limbs and the retroperitoneal space. This order of events indicates that both systems are functionally dependent. This dependence is particularly important in lower limbs, as their skin, subcutaneous tissue, and muscles undergo continuing microtrauma (gait, runs) and penetration of microbes from the foot and perineum (skin microabrasions). Waldemar L. Olszewski raised the question about whether venous insufficiency with incompetent valves and local thrombi affect limb tissue and draining lymphatic vessels. Today, venous ultrasonography and fluorescent indocyanine green lymphography can be performed simultaneously or one immediately after the other to depict sites of venous and lymphatic changes. The obtained pictures give insight into the venous blood and tissue fluid/lymph flow impairment and the clinical consequences as edema, inflammation, dermatoliposclerosis, and ulceration. We can see that both the venous and lymphatic vasculature are simultaneously affected. In conclusion, Waldemar L. Olszewski emphasized that leg venous system insufficiency is followed by changes in the microcirculation (excess capillary filtration), excess fluid/lymph in the tissue, retention of metabolites, cellular debris, and microorganisms. Subsequently damage to lymphatic vessels, fibrosis of skin and fascia, and total depletion of lymphoid tissue from lymph nodes develops. This pathological chain of events shows the functional relationship between the venous and lymphatic systems in case of venous insufficiency.

Contemporary methods of visualization and functional evaluation of lymphatics and veins in limbs-hints for therapy
Marzanna T. Zaleska (Poland)

Impaired venous blood and tissue fluid/lymph flow away from limb tissues causes retention of fluid in the extravascular and extracellular space, which is called edema. The effects are major changes in epidermis, dermis, subcutaneous tissue, fascia, and in muscles (to a lower extent, but it is still present), including hyperkeratosis, dermatofibrosis, subcutaneous and fascia fibrosis, and a dilated muscle vein network. Evidence of fluid accumulation sites and the fluid volume is crucial for effective treatment to prevent development of tissue changes. Marzanna T. Zaleska listed examples of methods used to evaluate limb edema, such as skin water concentration, skin tonometry, tissue fluid pressures during compression, fluid movement measure, bio impedance, effective compression force measurement, and inflated cuff edema fluid movement. She concluded that lymphatic and venous edema is not only an excess of water in the interstitial space, but also an increased mass of cells and ground matrix. Evaluation of the changes in edema requires measurements of fluid volume, pressure, movement through the tissue space, tissue cells, fibers, and blood vessel mechanical structure and resistance to compression force. Massaging out fluid does not decrease the limb volume to normal values, as the increased cell and matrix mass remains unchanged. Measurements help to understand changes in lymphedematous tissue.

Lymphedema: where we are today?
Tanja Planinsek Rucigaj (Germany)

The incidence of lymphedema after lymphadenectomy for melanoma can be up to 44% after therapeutic groin dissection for palpable disease, but the incidence following sentinel lymph node biopsy is much less. The estimated incidence of breast-cancer related lymphedema ranges from 13% to 50%. The incidence of lower limb lymphedema following radical hysterectomy alone is estimated at 5% to 10%, but can be as high as 49% by 10 years of follow-up in patients who also received adjuvant radiation treatment. The average time from appearance of lymphedema to the start of therapy was 7 years in Slovenia. Only 3 patients received therapy for lymphedema as soon as the edema started. The maximal time from beginning of lymphedema to therapy was 28 years. In Slovenia, secondary lymphedema makes up 74.4% of cases; following cancer therapy it is 56.2% and due to other causes it is 43.8%. Primary lymphedema makes up 25.6% of patients with lymphedema. Tanja P. Rucigaj presented her study in patients with secondary lymphedema in which the edema was quicker, soft, and small in patients where underpadding materials were used in comparison with short-stretch bandages without underpadding. Patients with lymphedema have a poor quality of life and, at a higher stage of lymphedema, the quality is lower. Patients are less mobile and often have associated diseases, such as obesity, degenerative changes in the joint, heart diseases, and carcinomas. It is important to prevent complications and disease progression as soon as possible and as complete a treatment as possible. In a clinical study, two different short-stretch systems were compared from the viewpoint of patients and of staff, showing no differences in slippage, both systems were very comfortable, and patients did not have any problems with mobility and wearing their usual footwear. Compliance was slightly better in the patients with one-layer, adhesive, short-stretch system. The staff said that experience with applying both compression systems is the most important.

Daily practice in diagnosis and therapy of veno-lymphatic disease of limbs
Andrzej Szuba (Poland)

Venolymphatic edema can be caused by chronic venous insufficiency, vein compression/ occlusion, and congenital venolymphatic abnormalities. Andrzej Szuba presented the pathophysiology of venolymphatic edema. A venous valve damage/obstruction leads to chronic venous hypertension with the consequences of lymphatic system overload, damaged lymphatic capillaries/vessels, occlusion of lymphatic capillaries, damaged anchoring filaments and lymphatic valves, increased lymphatic capillary permeability, lymph reflux to superficial lymphatic plexus with lymph stasis, and impairment in local immune defense. These consequences cause skin, subcutaneous tissue, and venous wall inflammation, edema, lipodermatosclerosis, and ulcers. In daily clinical practice, medical history, clinical exams, and treatment are the three most important pillars. Medical causes of peripheral edema should be excluded. The general examination includes blood pressure, heart and lung auscultation, jugular vein assessment, and abdominal assessment. A focused examination includes edema, peripheral pulse control, skin condition, and Stemmer sign. If necessary additional tests can be performed, such as Ratschow, ankle brachial index, venous ultrasound, lymphoscintigraphy, etc. The next step is the selection of optimal therapy, including appropriate skin/wound care, compression therapy (the most important), pharmacotherapy (flavonoids, sulodexide, antibiotics, antifungal, etc). This seminar finished with a discussion on venous obstruction and lymphedema. The clinical course is characterized by sudden onset, rapid worsening, or edema not responding to compression therapy. Signs of venous congestion are delayed emptying of superficial veins, venous collaterals, telangiectasias and, bluish discoloration. As a diagnostic method, color Doppler can be often misleading, MRI venography is promising, and a CT scan is very useful.

Complex lymphedema treatment in the dedicated centre – lesson learned
Franz Josef Schingale (Germany)

Lymphedema treatment can be subdivided in two phases. Phase 1 aims to reduce the edema and consists of manual lymphatic drainage, skin care, bandaging, exercises, self-management. Phase 2 aims for optimization and conservation and consists of manual lymphatic drainage, skin care, made to measure stockings, exercises, and selfmanagement. Franz J. Schingale mentioned additional therapies, such as intermittent pneumatic compression, pulsed magnetic field, CO2 gas and ozone, Hivamat (electrostatic field, produces deep oscillation), Flowave (hearable sound waves, produce bio resonance to the molecules), infrared cabin, and soft laser.

Contemporary surgical treatment of lymphedema of limbs and other organs-practical hints
Waldemar L. Olszewski (Poland)

Waldemar L. Olszewski elucidated the present state of clinical experience in the surgical treatment of lymphedema. In the early stage I, afferent lymphatic vessels are present on lymphograms. Recommended procedures include lymph node–saphenous vein shunts, lymphatic-saphenous vein branch through vein wall puncture, or end-to-end shunt. In advanced stages II and III, no afferent lymphatics are present on lymphograms. In these stages, the treatment methods are excision of fibrotic lymph nodes and obliterated afferent lymphatic vessels, silicone tubing implant bypassing the sites of lymph flow obstruction. In advanced stage IV, fibrotic skin, subcutaneous tissue, and fascia are present. The treatment of choice for advanced stage IV is debulking by excision of wide skin, subcutaneous tissue, and fascia strips. Compression and long-term penicillin are recommended in all stages.

Professional medical networking in lymphology and phlebology – the patient is the focus
Oliver Gültig (Germany)

Manual lymph drainage is very effective, but only in conjunction with specialized compression bandages, decongestive exercises, professional skin care, and supportive self-management. In 2019, Germany had over 900 curricular-trained physicians in lymphology, 70 000 specialized physiotherapists, a large number of competent garment specialists, more than 90 lymphology-phlebology networks, cooperation with nursing professions, and founding of many lymphology self-help groups. The status quo in outpatient lymphology is the following: diagnose and treatment quality is under clinical conditions, countrywide seminars for patients about accompanying self-management, the nonprofit organization Lymphologicum German Network association, guides, and magazines for patients. As a result, treatment becomes cheaper, teamwork gives pleasure, and patients have more quality of life.

Translational/integrated medicine and lymphology
Attilio Cavezzi (Italy)

Science is provisional and we are by no means anywhere near the point of knowing all. Science is a constantly changing base of knowledge. We know about 4% of our reality and of science about health and diseases. Translational medicine is an interdisciplinary branch of the biomedical field supported by three main pillars: bench side, bedside, and community. The goal of translational medicine is to combine disciplines, resources, expertise, and techniques within these pillars to promote enhancements in prevention, diagnosis, and therapies. It is a highly interdisciplinary field that wants to join different biomedical cultures to improve the global health care system significantly.

Attilio Cavezzi presented the revised Starling principle, ie, microvascular fluid exchange. In steady state, a slight filtration prevails in most vascular beds. Lymph transport, but not venous capillary reabsorption, is the main process responsible for interstitial fluid balance. Chronic low-grade cellular inflammation is the root of all degenerative chronic diseases and of lymphedema as well. Microvascular tissue derangement in lymphedema includes edema, hypoxia, oxidative stress, inflammation, and fibrosis. Proper nutrition/ time-restricted feeding (intermitted fasting) must be included in the holistic treatment of lymphedema to improve anti-inflammatory, antiedema, and antioxidative stress role of the nutrients/fasting, obesity/overweight issue. Excessive carbohydrate intake is the key nutritional factor to generate inflammation. Bad nutrition habits (industrial country nutrition), degeneration of the Mediterranean diet, modern cereals, and industrialized food increase the chronic low-grade proinflammatory cellular processes, which generate and perpetuate edema. Overweight and obesity lead to metabolic syndrome and cardiac/renal edema-generating factors. Fat deposition in the tissues recalls fluids and it is accompanied by liver steatosis, which is related to edema. Antihypertension drugs generate venulodilatation and edema. Hormonal changes, which induce edema, are caused by higher cortisol, insulin, etc. Obesity is also accompanied by dysfunction in the diaphragm and in venolymphatic return. When examining nutrition and dietary interventions for lymphedema, positive effects were found in a systematic review for lymphedema volume reduction. An anti-inflammatory (antiedema) strategy, based on nutrition/nutraceuticals, includes balanced nutrition, integration with omega3, a low carbohydrate diet, and an increase in polyphenol intake.

Hormesis is a biological phenomenon where a beneficial effect (health improvement, improved stress tolerance, longevity) derives from the exposure to (low doses of) a chemical/physical agent that is, conversely, toxic or lethal at higher doses. The main beneficial processes for cell health are autophagy activation, mammalian target of rapamycin (mTOR) blockage, sirtuin activation, interferon gamma 1/leptin decrease, and misfolded protein removal/repair. Intermittent fasting also demonstrated benefits; it improves cardiovascular risk, reduces the risk of cancer, improves immunity, causes weight loss, increases longevity, increases insulin sensitivity, burns fat instead of sugar, reduces inflammation-inflammaging, improves cognitive function, and improves skin healing process.

Next, Attilio Cavezzi discussed a study with the conclusion that respiratory muscle pressure production is the predominant factor (2- to 3-fold) modulating venous return from the locomotor limb both at rest and during calf contraction even when the veins of the lower limb are distended due to the presence of a physiologic hydrostatic column.

The symposium finished with a review of the anti-inflammatory properties of the vagus nerve. Breathing increases the centripetal lymph drainage as a mechanical action and has an anti-inflammatory action (vagus activation) and a biochemical action.