Servier – Phlebolymphology

Chairpersons: E. Rabe, A. Scuderi

K. Parsi (Australia)

K. Parsi presented a brief resume of the structure of the consensus document from the International Union of Phlebology that was published in International Angiology last year (Int Angiolog 2010 December; 29(6): 533-59). The aims of this consensus about Training Curriculum in Phlebology were to be incorporated in a Training Program by member countries, to act as a guide and to be adopted and modified to suit local needs for a 4-year training program. The different chapters were related to Anatomy, Basic Sciences, Pharmacology, Clinical Sciences, Consultation, Diagnostic Evaluation, Treatment Modalities, Adjunctive Education and Literature Reading.

• He also referred to the example of the Australian College of Phlebology and what is now its training program.

• Parsi concluded his presentation with reference to future directions: the curriculum should be used in training programs, the committee must receive feedback from members societies about the implementation of the program so that the consensus document can be revised every 2-4 years.

F. Lurie (USA)

Deep venous disease includes primary and/or secondary pathological changes in the deep venous system. These may consist of valve insufficiency, complete or incomplete vein obliteration and/or functional impairment. Regarding pathophysiology, it was emphasized that the deep veins constitute the outflow track of the lower extremities. In healthy individuals the blood flow is unidirectional from the superficial into the deep veins. This is possible due to pressure gradient directed towards central veins, low resistance of deep veins and the muscle pump in the presence of competent valves. Recent studies have revealed substantial deficiencies in current understanding of venous physiology regarding pressure changes in veins during muscle activity, regarding relationships between the flow in major veins and their tributaries and additional functional roles of venous valves. Disruption of the venous blood flow plays the key role in the natural history of venous disease, which includes one or more of the following: incompetence of venous valves, acute or chronic occlusion of the vein, and increased resistance to blood flow as a result of stenosis, synechia, or increased rigidity of the venous wall. A cascade of biological reactions results from interaction of disturbed flow and endothelium. Changes in collagen in patients with chronic venous disease appear to be systemic and not limited to the venous wall. Management of chronic deep vein disease requires accurate objective diagnosis of the venous tree from the lower calf to the diaphragm. Segment by segment diagnosis of reflux and obstruction is the standard and is achieved by means of duplex scanning. Venography is required for definitive diagnosis in the iliac and inferior vena cava vessels. Physiologic studies with pressure and volume methods are useful to evaluate global function and differentiate dominant obstruction from reflux. These studies are all complementary. New diagnostic modalities (B-flow ultrasound, intravenous ultrasound, MRI) provide information that is potentially useful for identification and evaluation of venous abnormalities. The CEAP classification is necessary for the definitive workup. Partial correction of venous defects may have enormous influence on the clinical state, allowing the extremity to achieve a clinically compensated state consistent with improved or normal function for the future. In advanced disease, unfortunately, the veins can seldom be restored to a totally normal state. Concomitant axial reflux in the superficial veins is poorly tolerated by the skin and must be corrected surgically. Axial deep vein reflux need not be corrected as the initial step when deep and superficial refluxes co-exist. In the short term, deep axial reflux appears to be better tolerated than superficial axial reflux. There are limited data indicating that correction of deep reflux can improve clinical outcomes and if not corrected can contribute to recurrence of varicose veins. Failure of the extremity to thrive following correction of superficial reflux is an indication for deep vein reconstruction. Correction of deep venous reflux in primary disease can be accomplished by internal and external repair. Correction of postthrombotic reflux can be achieved by direct repair when the valves have not been destroyed. When the valves have been deformed, transposition or transplantation of a competent valve may be successful. The longterm durability of these repairs is less than that of internal valve repairs in primary disease. Recent reports of open surgical creation of an autogenous valve (creation of a flap by dissecting the vein wall) provide the alternative of long-term success in the postthrombotic extremity with reflux. While not impeding the normal flow of blood, this method is able to withstand the reflux. Early restoration of iliac vein patency at the time of acute iliofemoral deep vein thrombosis has shown improved long-term results and is becoming the norm for treatment in the acute phase. Iliac vein obstruction is often present in silent form in the general population. Such lesions are present in >90% of symptomatic primary and postthrombotic CVI patients when examined with intravenous ultrasound. Iliac vein obstructive disease has been treated effectively with balloon angioplasty and stenting, which has replaced most of the attempts to bypass iliac obstructions, with good mediumterm results, minimal morbidity, less than 5% restenosis, and significant improvement of pain, swelling, and quality of life. The indications for deep vein reconstruction are limited at this time to cases in which simpler forms of venous repair have failed to control the problem and the patient is healthy enough to benefit from the correction. The risk of vein surgery has proven to be surprisingly low. Mortality has been rare throughout the 40- to 50-year history of reporting from around the world. The morbidity of operating inside the veins includes several considerations. Thromboembolic complications are rare in primary disease, and more frequent in postthrombotic disease.

K. Böhler (Austria)

Preliminary results of the still ongoing randomized, unblinded, controlled trial were presented. Adult patients with superficial thrombophlebitis (ST) are included (ST at least 5 cm long, not closer than 2 cm to saphenofemoral or saphenopopliteal junction, with clinical symptoms of inflammation). Those with concomitant deep vein thrombosis (DVT), known thrombophilia, cancer, immobility, peripheral artery disease or with ST after sclerotherapy are excluded. All patients receive lowmolecular- weight heparin in a prophylactic dose and nonsteroidal antiinflammatory drugs (NSAIDs) on demand. Patients are randomized to Group I (compression stockings, tailored to fit to every patient with the help of special 3D video imaging system) or to Group II (no compression used).

The main outcome is the reduction of pain – spontaneous pain (visual analogue scale), induced pain (Löwenberg test), and the consumption of NSAIDs. Additional outcomes are: reduction of erythema, change of thrombus length, development of DVT, and impact on quality of life.

So far, 36 patients have been included. Spontaneous pain and induced pain as well as the consumption of NSAIDs decreased significantly over time, but there were no significant differences between the compression and noncompression groups, only a tendency to slightly faster relief of induced pain and less consumption of NSAIDs after day 7 in the compression group. So far, the effectiveness of compression therapy in pain reduction in ST has not been proven in this study. More patients are needed before any definitive conclusions can be drawn.

D. Milic (Serbia)

This project is an open, prospective study with three parallel study groups. The primary objective is to determine if use of Class 2 (23-27 mm Hg) or Class 1 (18- 20 mm Hg) compression stockings reduces the incidence of venous disorders during pregnancy: emergence of varicose veins of any kind, hemorrhoids, leg swelling, VTE (thrombophlebitis, deep vein thrombosis, pulmonary embolism), and symptoms of venous hypertension (pain, night cramps, numbness, tingling, ache, itching, and heaviness). The secondary objective is to determine if regular use of Class 1 or 2 compression stockings reduces dilatation of superficial veins (great saphenous and small saphenous) and deep veins (femoral and popliteal) or decreases the incidence and level of reflux in the superficial and deep vein systems.

For this purpose, there will be follow-up of 300 pregnant women assigned to three different groups:
• 100 Pregnant women who will wear compression stockings (23-27 mm Hg- Class 2) during pregnancy and 6 months after delivery
• 100 Pregnant women who will wear compression stockings (18-20 mm Hg- Class 1) during pregnancy and 6 months after delivery
• 100 Pregnant women who will be without compression hosiery during pregnancy and after delivery.

The participants will be evaluated using both clinical and quality of life parameters.

N. Tetsch (Germany)

Sclerotherapy in the treatment of varicose veins is a minimally invasive procedure, economical, with no general anesthesia, good aesthetic results, and various treatment options.

In the literature, occlusion rates vary after 3 months from 69% to 96% and after 1 to 2 years from 53% to 80%. The aim of this prospective, blinded, randomized, controlled trial was to achieve higher occlusion rates than those reported in the literature by adding perivenous tumescent solution (TA) during catheter-directed foam sclerotherapy (CDFS) of the great saphenous vein. The author presented preliminary data of 50 patients enrolled from August 2010 to August 2011 and divided into two groups. Group 1: 25 p CDFS +TA, group 2 CDFS with follow-up at 1, 6, and 12 months. Primary end point: 100% occlusion rate at 12 months with CDFS+TA, secondary end point: comparison of occlusion rates of great saphenous veins after treatment with CDFS with and without TA, comparison of patient satisfaction and symptom severity. Inclusion criteria: men and women age 18-89, diameter of incompetent great saphenous vein 5-10 mm measured 3 cm distal to the saphenofemoral junction. Exclusion criteria: symptomatic foramen ovale, pregnancy, ABI <0.9, severe cardiovascular disease, acute thromboembolic diseases, high risk of DVT (>3 of the following criteria: oral contraceptive, obesity, smoking, thrombophilia, long phases of immobility). The procedure included direct puncture of the GSV below the knee using duplex ultrasound guidance with application of 8 mL of 2% polidocanol foam (Easyfoam^®) and in group 1 infiltration of saline solution (TA) along the whole length of the GSV. Post-interventional class II compression stockings (4 weeks), 30-min walking, low-molecular-weight heparin for 10 days. Study closure in August 2012.

T. Willenberg (UK)

The study focuses on the systemic side effects that may appear after endovenous procedures and on whether the systemic side effects that may appear after foam sclerotherapy (FS) or radiofrequency ablation (RF) are related to the inflammatory response of the endothelial wall.

For this purpose, consecutive patients admitted to a unit of vascular surgery for treatment of varicose veins will be screened, with 15 patients undergoing RF and 15 FS. The exclusion criteria are pregnancy or breastfeeding, age <18 or > 80 y, inflammatory, infectious, or thrombotic disease, anti-inflammatory treatment, or obesity.

Blood will be sampled from the arm and from the common femoral vein in the treated limb, before, at the end of treatment, and 24 hours after treatment. Data will be collected for assessment of side effects.

Primary outcomes are levels of endothelin 1, tumor necrosis factor a, interleukin 1-b, and interleukins 4 and 5 before and 24 hours after FS or RF ablation. Secondary outcomes are leukocyte count, D-dimers, and any related adverse effect.

The results of this pilot study may provide key information for further investigation of venous endothelial damage and help understand the mechanism of FS.

A. Ahmad (UK)

Based on the hypothesis that the cleavage of uPAR into its fragments (D1 and D2-3) is an important mechanism in ulcer healing, the aim of the research was threefold:
1. To compare levels of suPAR fragments in healed venous ulcers with these of poorly healed ones.
2. To examine pattern of distribution of uPA, uPAR, PAI-1 & PAI-2 in healing and poorly healing ulcers.
3. To determine the effect of suPAR D1 & D2-D3 fragments and wound exudates on in vitro keratinocyte migration.

Preliminary studies have shown a positive effect of suPAR in keratinocyte migration towards the ulcer wound that might help in venous ulcer re-epithelialization Our initial results have confirmed the presence of uPA and its receptor within the environment of a venous ulcer. There was no uPA activity detected in any of the chronic wound fluids. Urokinase was detected in most of the wound fluids but not in tissue lysates. In contrast, suPAR immunoreactivity was present in both wound fluids and tissue lysates. Wound fluids showed increased amounts of all forms of suPAR (ie, DI-III, DII-III and DI) as compared with tissue lysates.

G. Szolnoky (Hungary)

A large number of putative genetic factors in the development of venous leg ulcer (VLU) have been described, most of them being involved in the mechanism of altered immune response in chronic wound healing. The role of humoral immunity remains to be elucidated. It is known that patients with VLU have a significantly weaker tuberculin skin test (TST) response than matched patients without VLU.

The aim of this study is to measure Candida albicans killing activity as a general and functional assessment of polymorphonuclear leukocyte (PMNL) function, to determine the expression of proinflammatory cytokines/chemokines along with the expression of TAM receptors.

40 patients with VLU and 40 controls (age- and sex-matched without VLU) will be compared in terms of isolation of PMNLs, total RNA isolation, and real-time quantitative PCR (QPCR) detection of the expression of TAM receptors (Tyro3, Axl, Mer), their ligands (Gas6 and proS), and pro- and anti-inflammatory cytokines/chemokines (TNFa, IL1, IL6, CXCL8, and IL10).

It is expected that in patients with VLU the baseline mean candida killing activity will be substantially lower than in subjects without VLU.