Servier – Phlebolymphology

Veins and their impact on the cardiovascular system
Chairman: A.T. Guillaumon (Brazil)
Lecture by D. Clement (Belgium)

The venous system returns blood from various organs and tissues to the heart. The venous circulation is regulated at two levels. Local control is achieved by neurohormones (noradrenaline, histamine, serotonin, etc.), physical factors (temperature change), and the mechanical properties of the venous wall (valves, flexibility, deformability). A number of these mechanisms have genetic determinants. Central regulation of the venous circulation is carried out by the reflex arcs including peripheral baroreceptors and muscle receptors. For example, rhythmic muscle contraction activates muscle receptors, thus causing generalized venoconstriction in turn. As a result, blood return to the heart is increased. Cardiac output is also increased, as required for maintenance of adequate circulation during muscular contractions. Peripheral and central regulation of the venous circulation change venous tonus and venous pressure. Lasting increase in venous pressure can lead to disturbances of the microcirculation and development of varicosities. Disturbances of venous tone lead to specific clinical signs, such as orthostatic hypotension, edema, venous stasis. Venous stasis can activate inflammation, the coagulation cascade, and thrombus formation. Many drugs used for treatment of cardiac diseases (nitrates, digitalis, diuretics etc.) have a negative effect on venous tonus, and their long-term use can provoke venous disturbances. There is an association between atherosclerosis and spontaneous venous thrombosis (Prandoni et al., 2003). Also, Poredos and Jezonik (2007) found a relation between arterial and venous thromboembolism. Lastly, the author emphasized that venous disease is very important socioeconomically, and this must be considered when formulating insurance policy in public health services.

Life with chronic venous insufficiency
Participants: JJ Guex (France), E Bouskela (Brazil), A Nicolaides (Cyprus)

In the first lecture of this satellite symposium, JJ Guex dealt with the role of quality of life (QoL) score and patient-reported outcome (PRO) in evaluation and global assessment of chronic venous disease patients before and after any type of treatment in everyday life. A global assessment is possible through PRO measures. In relation to the evaluation of treatment results, self-report questionnaires and visual analogue scales provide data independent of the physician’s appraisal. Dr Guex recently conducted a study (QUALITY) with a combination of Ruscus aculeatus, hesperidin, and ascorbic acid and, using both a generic QoL scale (SF 12) and a specific QoL scale (CIVIQ1), demonstrated that QoL scales correlate with CEAP grades and also that this phlebotropic drug improved QoL. However, the CIVIQ1 score was also correlated with body mass index and age, which could result in confusion. Therefore it has been considered that an improved PRO would be necessary for the less severe cases, assuming that a satisfactory PRO should be used alone, and that this approach would simplify the assessment. A group of specialists from the French Society of Phlebology, American College of Phlebology, and American Venous Forum devised a questionnaire which took into account all relevant questions. Comprising 46 items in 5 dimensions, the Specific Quality Of life and outcome Response-Venous (SQORE-V) has been developed, field-tested and validated in French and Spanish, and is freely available for translation into any other languages. Its sensitivity is less affected by age and body mass index.

E Bouskela presented the usefulness of microcirculatory evaluation in the assessment of chronic venous disease (CVD), by studying the effect of severity of CVD on capillary network. She and her team used a newly developed noninvasive technique—orthogonal polarization spectral (OPS) imaging—to identify capillary morphology, capillary and dermal papilla diameter as important morphological parameters in detecting early stages of microangiopathy. Using OPS and duplex ultrasound, they evaluated the changes in cutaneous microangiopathy in chronic venous disease (C2-C3s) after the use of Ruscus aculeatus, elastic stockings, or no treatment for 4 weeks and found in the group treated with Ruscus aculeatus a decrease on capillary diameter for both limbs and an improvement in capillary morphology in the left limb. The results confirmed the role of capillary diameter in microcirculatory dysfunction observed in CVD and the usefulness of this new noninvasive method in capillary evaluation in CVD.

A Nicolaides in his short overview presented highlights from the 2008 Guidelines on Management of Chronic Venous Disorders of Lower Limbs, recently published in International Angiology 2008L,27:1-59. The document was drawn up under the auspices of the world’s leading venous societies. It has 20 sections, levels of evidence I, II, III,, and more than 800 references. Part I deals with pathophysiology, symptoms, and investigations, and stresses that 30% of deep venous reflux is due to primary valvular incompetence, spontaneous lysis of deep veins after deep vein thrombosis occurs in 50% to 70% of cases, and early recanalization preserves valve function after deep vein thrombosis. Part II presents evidence for the efficacy of the therapeutic method. Part III deals with management of symptomatic individuals, and also with prevention of postthrombotic syndrome. The last section consists of key questions that need to be answered. This presentation stimulated interest in the auditorium and a desire to read and “digest” in detail the written consensus.

Varicose veins. Is there any evolution?
Moderators: C. Allegra (Italy)-A. Giannoukas (Greece)
Participants: E. Kalodiki (UK), P. Gloviczki (USA), M. Vasquez (USA), D. Kontothanassis (Italy), R. Simkin (Argentina)

Three reports of a strictly practical nature were presented during this session. Kalodiki presented the detailed description of foam sclerotherapy. She used the Tessari technique and mixed 1.2 mL of 1% or 3% sodium tetradecyl sulfate solution with 4.8 mL of air. Six mL of the sclerosing foam was produced after 20 pump movements. Sclerosing foam was injected into varicose vein after previous ultrasound mapping. The patient was in the upright position during injection. Second class compression stockings were applied just after injection. Compression was prescribed for 5 weeks ( day and night – 2 weeks; day- 3 weeks). Kontothanassis reported experience in endovenous laser therapy of the 104 small saphenous veins. There were low postoperative complications. Vasquez presented a series of 402 patients (602 limbs) who underwent radiofrequency ablation and convincingly showed that the venous clinical severity score (VCSS) can be used to estimate early and long-term results after radiofrequency ablation. The average VCSS was 8.3 before procedure and significantly decreased to 4.9 during 3-4 weeks of followup. The author underlined that VCSS does not consider cosmetic complaints. Simkin et al presented 487 cases of combination treatment with endoluminal laser and ambulatory phlebectomy. All operations were performed under tumescent anesthesia. There were low postoperative complications. The author concluded that combination treatment is appropriate for all cases.

Gloviczki recalled that incompetent perforating veins (IPVs) play an important role in chronic venous disease (CVD). There is a correlation between the number of IPVs and severity of CVD. There are three basic methods for IPV dissection. The most widely performed is subfascial endoscopic perforator vein surgery (SEPS). The primary benefits of this technique have been reported to include more rapid ulcer healing, fewer perioperative complications, and lower recurrence rate. In the Mayo Clinic’s experience, 80% of ulcers had healed 90 days after SEPS. Median time to ulcer healing was 35 days. A meta-analysis confirmed that SEPS in class 5-6 patients (CEAP classification) has recurrence rate of 10% to 20% over 3-5 years. Duplex-guided hook interruption of IPV is under consideration. The healing rate after this procedure is 100%, with a 20% recurrence rate during five-year followup. Percutaneous ablation of perforators is an innovative technique, which includes ultrasound-guided sclerotherapy, and radiofrequency and laser ablation.

Deep venous disease. New concepts.
Moderators: F.H.A. Maffei (Brazil)-S. Vasdekis (Greece)
Participants: A. Nicolaides (Cyprus), M. De Castro Silva (Brazil), D. Christopoulos (Greece), N. Angelides (Cyprus), Z.G. Wang (China)

A Nicolaides presented convincing data confirming a key role of leukocytes in damage to the venous wall. Leukocyte activation, adhesion, and migration through the endothelium as a result of altered shear stress contribute to the inflammation and subsequent remodeling of the venous wall and valves. Entrapment of leukocytes in the microcirculation reduces local capillary perfusion. All these reactions have a clinical manifestation. M de Castro Silva presented several Brazilian epidemiological studies that show a high prevalence of varicose veins in females (84.3%), 72.2% in pregnant women. Open ulcers were noted in 3.2% of respondents (male-2.3%; female- 4.1%). D Christopoulos described various diagnostic procedures in at patients with chronic venous disease (CVD). There are three levels of investigation of patients with CVD: Level I: Clinical examination, Doppler or a color flow duplex. Level II: Duplex color flow scanning, with or without plethysmography. Level III: Phlebography, varicography, venous pressure measurements, CT scan, venous helical scan, magnetic resonance imaging, and intravascular ultrasound. The choice of the diagnostic level depends on clinical class according to the CEAP classification.

ZG Wang reported a very aggressive treatment strategy in patients with proximal DVT. The author prefers open surgical thrombectomy after preliminary implantation of the removable cava-filter.

Moderators: J Fernandes e Fernandes (Portugal), JL Nascimento Silva (Brazil)
Participants: AT Guillaumon , I Merlo, IMMER Castro Santos, SP Marques, C Belczak, H Guedes (Brazil)

Gene Therapy in Vascular Ulcer
A.T. Guillaumon (Brazil)

Gene therapy may have a role to play in possible intervention on target tissues. Gene therapy takes three forms: proliferation and transcription of an active unit to one cell or tissue, amplification of the local or systemic expression of one protein, and inhibition or regulation of endogenous gene expression in the cells and tissues.

In venous stasis ulcers, cell proliferation therapy is used using various factors such as vascular endothelial growth factor [VEGF], fibroblast growth factor, human growth factor, hypoxia-inducible factor.

The therapeutic vascular growth of new vessels is based on the use of angiogenic factors or stem cells or their combination to promote neovascularization. New vessel formation is an important aspect of tissue recovery because it supplies oxygen, nutrients, humoral growth factors, and enzymes to cells. VEGF as a key regulator of the amplification of local or systemic expression of one protein, and the inhibition or regulation of endogenous gene expression in the cells or tissues. VEGF/VEGF-R is a complex of various ligands which has an important relationship with angiogenesis.

Surgical Treatment of the Varicose Veins with Endolaser
I. Merlo (Brazil)

This author reported the experience of the Brazilian working group on laser ablation in great and small saphenous veins. Laser ablation is indicated in patients with saphenofemoral and saphenopopliteal pathologic reflux, vein diameter <11 mm, and in patients without previous sclerotherapy of the saphenous vein.

The technique was described as follows: pulsed mode, energy applied 3 J/mm of diameter (80-100 J/cm2), after the injection of tumescent cold saline solution around the saphenous vein, Laser Diode 810/980 (if necessary), Introducer 5Fr (if necessary), fiber 600 Ìm diameter, and frequent duplex monitoring. All varicose tributary veins were removed through stab incisions under local or regional blockage anesthesia.

The results Merlo’s personal experience—early occlusion 100%, late occlusion 99.6%—were identical to those of the Brazilian working group. Their experience with endovenous laser treatment of incompetent small and great saphenous veins proved that this is a safe, efficient surgical technique and at the same time a good alternative to traditional surgery.

Thrombophilia States and Venous Disease in the Woman
I.M.E.R. Castro Santos (Brazil)

Venous thromboembolic disease is the most prevalent vascular disease in young women, with an incidence of 2 to 5 per 100 000 women-years between the ages of 20 and 49 years.

The higher venous thromboembolism frequency in the female gender is explained by the exposure to known risk factors such as oral contraceptives, hormone replacement therapy, selective estrogen receptor modulator, pregnancy, and postpartum period.

The prothrombotic effects observed with the use of oral contraceptives and hormone replacement therapy are mainly due to the estrogens present in their composition.

The risk of thromboembolic events in users of oral contraceptives remains high even with the use of low-estrogen preparations. The first episode of thromboembolism occurs in 3 to 4 women per 10 000 users of oral contraceptives versus 5 to 10 in 100 000 women during the reproductive age.

Thromboembolic events are up to 30 times more frequent in thrombophilic women who use of oral contraceptives, especially associated with protein C, protein S, or antithrombin deficiency. A 20-fold greater risk is observed in users with the prothrombin gene mutation.

Hormone replacement therapy with low estrogen dose, combined or not with progestin, has been increasingly indicated for healthy women during and after the menopause. However, it has been proved that the risks exceed the benefits, with increased incidence of deep venous thrombosis and pulmonary embolism, in addition to the elevated incidence of acute myocardial infarction, cerebral ischemia, and breast cancer.

There is a 3- to 4-fold higher risk of venous thrombosis with the use of tamoxifen for treatment of breast cancer, and the increase in risk may be as much as 10-fold in advanced breast cancer and chemotherapy.

Pregnancy is an independent risk factor for deep venous thrombosis and pulmonary embolism. The risk is 6-fold higher when compared with women of the same age. The association with other risk factors elevated their incidence even further. Half of the thromboembolic events in pregnancy occur in thrombophilic patients.

The presence of a thrombophilic disorder confers on women a higher risk of venous thromboembolic disease at different periods of life. Large prospective studies are still needed to define the risks and establish the associations of thrombophilia with venous thromboembolic disease among groups with different thrombophilic defects. The real value of routine thrombophilia screening still needs to be determined.

Lymphoscintigraphic Visualization of the Thoracic Duct Confluence in patients with Lymphedema of the Lower Limbs
S.R. Marques (Brazil)

Lymphoscintigraphic Visualization (LSG) of the Thoracic Duct Confluence was used in 38 patients with lymphedema of the lower limbs are presented (26 unilateral and 12 bilateral). Females (46.2%) had a mean age of 41 years and males (53.8%) a mean age of 39 years.

Technique
Subcutaneous injection in the first space between the first and the second toe in each foot of 1.0 mL of a solution of dextran-500 labeled with TC-99m. The first gamma-camera image of the thoracic duct was obtained within 5 minutes after the injection. The images obtained were uploaded and stored using a software program.

Results
The thoracic duct was not visualized in 9 patients (34.2%), but was observed in 11 patients (91.7%) with bilateral lymphedema and in 18 (69.23%). with unilateral lymphedema.

Conclusions
LSG allows adequate analysis of the thoracic duct and the results are comparable with those of classic anatomic studies. LSG of the thoracic duct and its confluence reveals that lymph arrives at the venous confluence even when lymphodynamics are substantially compromised. These findings suggest that poor absorption could have a more important role than previously believed.

Compression Therapy in Lymphedema
C. Belczak (Brazil)

Among all conservative measures, ie, manual lymph drainage, compression, myolymphokinetic exercises and skin care, elastocompression is the most important since it is also effective when applied alone. Compression therapy reduces limb volume, restores limb shape, improves skin quality, enhances limb mobility, improves muscle pump activity, controls lymph formation, inhibits the development of fibrosclerotic tissue, and stimulates lymphatic transport. Compression therapy is not indicated in acute infection, acute contact eczema, acute thrombosis, peripheral arterial disease, neoplasia in situ, and cardiac insufficiency.

During lymphedema treatment, two phases are distinct: the first one, the socalled attack phase, reduces the edema quickly. The second phase starts immediately after the point where no more reduction can be achieved. During the first phase, firm bandages with short-stretching textile elastic material are usually applied. This must be always performed by highly qualified staff. For the maintenance phase in order to consolidate the results obtained during the first phase, medical elastic stockings are prescribed.

For severe grade IV lymphedema patients (elephantiasis), there is a useful inexpensive new kind of multilayer bandage that is applied in the first phase of lymphedema treatment with convincing results.

Compression therapy is the important and effective basic therapy for lymphedema. It acts on the effect, not on the cause of the disease, as it does not heal lymphedema but avoids the symptoms and progression of the disease.