Servier – Phlebolymphology

Introduction to the UIP Consensus Project

By E. Rabe

Scientific and educational progress in phlebology in recent years has led to a higher demand for communication between phlebologists worldwide. At the same time specialization in phlebology by medical associations and the setting up of master degree programs in phlebology are increasing. For these reasons the Executive Committee of the UIP decided to establish a common platform to promote phlebology worldwide.

The first steps in this direction were taken by means of the consensus papers of the UIP on anatomy, definition of terms in the CEAP classification, evidencebased compression treatment and duplex consensus documents. In a further step, a number of consensus groups worked hard over several months to prepare a curriculum in phlebology and to finish various consensus papers in time for the World Congress in Monaco. These consensus papers define the accepted standards in phlebology.

Each group of 5-12 members worked mainly by the Internet with one chairman per group who coordinated the discussion in the consensus group in cooperation with the President and the Executive Committee of the UIP. Each paper has the same structure with definition of the topic, diagnosis, and treatment. The proposals made in the different documents are evidence-based with an evaluation of the literature according to the ACCP grading system.

UIP Consensus. Venous symptoms and clinical assessment

Chairperson: B. Eklöf
Moderator: P. Carpentier

Venous symptoms: evolution of the concept
P. Carpentier

Symptoms traditionally ascribed to chronic venous disease (CVD) include aching, heaviness, a feeling of swelling, cramps, itching, tingling, and restless legs. Prolonged standing, high temperature, and sexual hormones usually enhance them. Venous symptoms are associated with reduced quality of life. The proportion of patients presenting with venous symptoms increases with increasing CEAP class. Nevertheless, there are no strong correlations of venous symptoms with CEAP classes. New techniques for the objective evaluation of venous symptoms are necessary for international epidemiological studies and assessment of treatment modalities.

Pathophysiology of pain in chronic venous disease
N. Danziger
Current hypotheses on pain mechanisms in venous disease are focused on a local inflammatory origin, related to venous stasis. The starting point for this mechanism is probably local hypoxia associated with capillary stasis. Hypoxia induced by capillary stasis has the effect of activating endothelial cells. Such activation is manifest in the synthesis of proinflammatory mediators (bradykinin, prostaglandins E2 and D2, PAF, and leukotriene B4). Some proinflammatory mediators can activate nociceptors located in the venous wall (between endothelial cells and smooth muscle cells of the media). The pathophysiological mechanisms involved in venous pain are now better understood, but the causal relationship between venous disease and pain remains difficult to explain by experimental methods.
N. Danziger

Our obligation to monitor clinical outcomes in venous disease
M. Vasquez, J.J. Guex

The Venous Severity Scoring (VSS) system was derived from the CEAP classification to provide for evaluation purposes. The VSS comprises the venous disability score (VSD), the venous segmental disease score (VSDS), and the venous clinical severity score (VCSS). The VCSS responds to features of venous disease that change with treatment. Each of these scores has been validated, and each has strengths and weaknesses. Maintaining the dynamic nature of assessment with periodic review and revision is the way forward for generating universal applicability. VCSS is in the process of revision in order to incorporate quality-of-life tools. Although the choice of instrument is debatable, our obligation is to improve treatment outcomes by examining our results and sharing them in a meaningful way.

CEAP classification: what is the future?
B. Eklof

The CEAP classification is accepted and actively used around the world by venous experts in America, Asia, Australia, and Europe. It was originally intended that it should be amended progressively in the light of experience with its use. After the first 10 years, the CEAP classification underwent critical review with the aim of revision in 2004 by a new international subcommittee of the American Venous Forum (AVF). In this revision the fundamental structure of the CEAP categories was affirmed and retained. There are several conditions that are not included in the CEAP classification but that can influence the management of patients with chronic venous disease: combined arterial and venous etiology, postthrombotic lymphedema, ankle ankylosis with atrophy of the calf, venous aneurysms, venous neuropathy, corona phlebectatica, pelvic congestion syndrome, and morbid obesity. They can be incorporated into the CEAP classification in the future.

UIP Consensus in Varicose Veins

Chairpersons: P. Gloviczki , H. Neumann

P. Gloviczki presented the guidelines of the AVF on diagnosis and treatment of varicose veins. Varicose veins have a high prevalence in the general population (more than 20% in the Western population). Varicose vein evaluation, grade C2 of the CEAP classification, can be done correctly by clinical and physical examination complemented by duplex sonography. Duplex scan determines vein patency, valvular competency, presence of incompetent perforators, the varicose map and evaluates the complications and efficacy of therapy. Duplex scanning is recommended as the first diagnostic test for patients with suspected valvular incompetence or obstruction (AVF grade recommendation 1 – grade of evidence A). Venous management of varicose veins can be conservative, with compression garments, correction of lifestyle and risk factors, and phlebotrophic drugs, or invasive with open surgery, minimally invasive endoscopic surgery, or endovenous procedures like sclerotherapy, radiofrequency ablation, and endovenous laser therapy. Great saphenous vein (GSV) high ligation and vein stripping have several disadvantages: invasive procedure, pain, delayed return to work, deep vein thrombosis (DVT) in 5.3% and recurrence rate of 6% – 66%. For treatment of the incompetent GSV high ligation and inversion stripping of the saphenous vein to the level of the knee is recommended (AVF grade recommendation 1 – grade of evidence B). Endovenous ablation of GSV has some advantage compared with open surgery: minimally invasive percutaneous access, no incisions, ambulatory procedure under local/tumescent anesthesia, and rapid return to full activity with a low complications rate (paresthesia 3%, thrombophlebitis 1.87%, skin burns 0.5%, DVT 0.27%, and pulmonary embolism [PE] 0.023%). Radiofrequency ablation results in less pain, earlier return to work, and reduces costs to society when compared with conventional surgery. Endovenous laser therapy and surgery were comparable in abolition of GSV reflux and in disease-specific quality of life, but return to normal activity following endovenous laser therapy was earlier than after surgery. Radiofrequency and EVL are safe and effective and have a better patient acceptance than conventional surgery. Foam sclerotherapy is an effective, safe, and minimally invasive endovenous treatment for varicose veins with a low rate of complications. Polidocanol microfoam was non-inferior to surgery or conventional sclerotherapy. Foam caused less pain and was followed by earlier return to work than surgery. Radiofrequency ablation of the GSV is safe and effective and we recommend it for treatment of saphenous incompetence (AVF grade recommendation 1 – grade of evidence A). Endovenous laser therapy of the GSV is safe and effective and we recommend it for treatment of saphenous incompetence (AVF grade recommendation 1 – grade of evidence A).
Finally, P. Gloviczki stressed that the use of guidelines is essential to practice evidence-based medicine and play a major, but not unique, role in determining the best management of patients with varicose veins, because as William Mayo recalled in 1910 “The best interest of the patient is the only interest to be considered”.

UIP Consensus in Venous Edema and Skin Changes

Chairperson: J. Strejcek
Moderator: I. Staelens

This session was dedicated to the UIP Consensus on venous edema and skin changes. Particular attention was paid by the UIP to reaching a consensus on common definitions for venous disease, and on common tools to evaluate the burden and severity of disease, for both patient care and clinical research.

Development of a questionnaire to evaluate the burden of venous disease in daily life
J-J. Guex

J-J. Guex presented a new questionnaire aimed at evaluating the burden of venous disease in daily life. The objective was to provide a tool able to explore and measure the overall disability of patients with venous disease, and the burden of the disease in their daily lives. Authors followed the recommended methodology for questionnaire construction. After a literature review and exploratory face-to-face interviews, they defined 5 possible dimensions to explore: pain, daily life, interpersonal relationship, work, psychological aspect. They eventually included 36 questions and three visual analogue scales in the ABC-V questionnaire (ABCV standing for ‘Assessment of Burden in Chronic Venous disease). In the discussion, J-J. Guex stressed the difference between quality of life questionnaires and the ABC-V, the goal of the latter being to take into account all aspects of disability caused by venous disease.

Recommendations for evaluation of outcomes after treatment of C0s-C4 patients
A. Davies

In the same quest for common and reproducible tools for evaluating venous disease, A. Davies gave recommendations for the evaluation of outcomes after treatment of C0s to C4 chronic venous disease patients. The outcomes range from absence of reflux to improvement of symptoms or clinical signs, and to patients’ and/or physicians’ satisfaction. It is important to reach a consensus on reporting standards for publication, comparing treatment modalities, and eventually determining the best patient care. A. Davies described several possible ways of assessing venous disease: 1) anatomy, which can be explored by ultrasonography, 2) hemodynamics (plethysmography), 3) clinical evaluation, including CEAP or VCSS scoring systems, and 4) functional evaluation, using either generic (SF-36, SF-12, EQ-5D) or disease-specific (AVVQ, SQOR-V, CIVIQ-2, VEINES) questionnaires. However, there are some issues when using these tools. For example, reflux does not always correlate with symptoms and quality of life, and changes in hemodynamics do not correlate with other parameters. A. Davies also reminded the audience that CEAP is only a classification scale, is not sensitive to improvements following interventions and therefore can not be used as a followup tool. Finally, in the context of increasing competition for health care resources, these scales could be used by insurance companies to identify patients eligible for treatment, though the cost-effectiveness of interventions is hard to assess accurately.
The take-home message was that beside ultrasonographic assessment, current recommendations to assess outcomes in venous disease are the use of VCSS score, and of both generic and a disease-specific quality of life questionnaires.

UIP consensus in diagnosis and treatment of venous edema
A. Scuderi

UIP consensus in diagnosis and treatment of CVI-related skin changes
A. Cornu-Thénard

The two subsequent talks by A. Scuderi and A. Cornu-Thénard reported on the work currently conducted by the Union Internationale de Phlébologie on the diagnosis and treatment of C3 (edema) and C4 (skin changes) classes of chronic venous disease. Precise definitions will be provided for edema (C3), eczema and pigmentation (C4a) and lipodermatosclerosis and atrophie blanche (C4b). Recommendations for diagnosis include assessment of the full CEAP score. Three levels of diagnostic investigations have been defined: level 1 comprises office visit, medical history, and clinical examination, and hand-held ultrasound; level 2 includes color duplex ultrasonography, whereas level 3 refers to additional more invasive and/or complex testing, phlebography, varicography, magnetic resonance imaging, intravascular ultrasonography, computed tomography, etc. which are not required in all patients. Reflux and obstruction should be searched for. The best method for measuring edema is water displacement volumetry, though perimetry may be used in routine practice. Treatment options are: 1) Basic recommendations: change in habits, postural drainage; 2) Physical treatments: manual drainage, compression therapy (elastic stockings, bandage, intermittent pneumatic compression); 3) Pharmacological treatments (venoactive drugs, topical treatments). The underlying venous disease should also be treated. These therapeutic strategies are used in C3 and C4 patients, although as stressed by the second speaker, the level of evidence is low in C4 patients, for whom more research is needed.

UIP Consensus Curriculum in Phlebology

Chairperson: S. Raju
Moderator: K. Parsi

UIP Consensus Curriculum in Phlebology
K. Parsi

Recently, the UIP has made a considerable effort to define an inaugural training curriculum in phlebology which should be implemented and incorporated in the future in a training program by member countries. This document was presented in summary by K. Parsi who was the chairman of the Curriculum Committee, together with S. Zimmet. The Committee consisted of several international experts. The document is a guide to be adopted and modified to suit local needs. We need a training curriculum in phlebology to define phlebology, to set minimum training standards across the globe and to help practitioners identify gaps in expertise. It addresses the needs of future trainees in phlebology and existing practitioners who need to acquire extra skills/expertise. Phlebology was defined as a specialty with surgical, interventional, and medical activity to help patients with acute and chronic venous disorders. Therefore, phlebology covers not just varicose veins, but skin manifestations, venous malformations, superficial thrombophlebitis, DVT, and PE. Phlebology is an evolving specialty and a phlebologist is a medical specialist competent in the diagnosis and management of all aspects of venous disease. Phlebology may have roots in surgery in many countries, but has evolved beyond its traditional origins. There is no “super-phlebologist” competent in everything covered in this curriculum. The standards have been set mainly for the future. The UIP Training Curriculum has 8 sections with many subsections including: anatomy (core venous anatomy and broader topics), basic sciences (physics, rheology, venous physiology, genetics, embryology, vascular histology, vascular biology, coagulation system, inflammation, detergent biochemistry, lymphatic biology), pharmacology (general principles, vascular pharmacology), clinical sciences (core clinical phlebology, pediatric phlebology, other venous conditions, vascular malformations, phlebology in other disciplines, lymphology), diagnostic evaluation (basic modalities, duplex ultrasound, venography, venous function tests, other imaging and laboratory investigations), treatment modalities (patient education and referrals, conservative interventions, nonsurgical treatment of CVI, surgical treatment of CVI, treatment of venous thromboembolism [VTE), other treatments), additional education (laser and safety, life support, research design, venous outcome assessment, infection control, legal issues), and reference reading (textbooks and journals). This training handbook was developed on a model based on the Australian College of Phlebology Training Handbook 2009 and with inspiration from the following documents: Australian College of Dermatologists Training Handbook 2009, American College of Phlebology, Phlebology Fellowship Curriculum, Phlebology education in France, proposed Phlebology Training Curriculum University of California, San Diego and the Vein Institute of La Jolla, 2008.

UIP consensus on diagnosis and treatment of deep venous insufficiency

F. Lurie

A Consensus Group on Deep Venous Disease was created on behalf of the XVI World Congress of UIP. The summary document was presented by the chairman of this Group, F. Lurie. 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 activities, 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 is 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 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 DVT 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 medium-term 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 40-50 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. Several questions remain unanswered: relationship between changes in deep, superficial and perforator veins in the natural history of chronic venous disease, the impact of the presence, severity, and extent of reflux and obstruction on venous function and their interaction when present in the same extremity.

DAPS-dalteparin in patients with superficial leg vein phlebitis in addition to compression treatment – a placebo-controlled phase III study
E. Rabe

E. Rabe talked about the results of a randomized, double-blind, multicenter, phase III trial which assessed the efficacy and safety of dalteparin in patients with superficial leg vein phlebitis (SVP). A total of 276 patients with SVP used compression stockings (30 mm Hg) for 3 months and either dalteparin 10 000 IU (group A) or placebo (group B) for 14 days. The primary end point was progression of the thrombotic process during the treatment period as confirmed by compression ultrasound. Sonographic assessment was planed in all patients on days 1, 7, 14, and 90. Secondary end points were pain assessment by visual analogue scale (VAS) and calculation of symptom scores (tension, heaviness, swelling). In each treatment group, 138 patients received at least one dose of study medication. Progression of the thrombotic process after 14 days was detected in 8% (95% CI: 4%-13.8%) of patients in group A and in 17.4% (95% CI: 11.5%-24.8%) of patients in group B. DVT rates were 0.7% in each group. No symptomatic PE occurred during the treatment period. Progression rates during posttreatment follow-up were 3.1% (A) versus 7% (B) (p=0.168). One patient in group A (0.7%) and two patients in group B (1.5%) developed symptomatic DVT during followup. Another patient in group A experienced PE (0.7%). Symptom scores decreased in both groups without significant differences. During the first 14 days adverse events were reported in 7.2% (2.2% serious) of patients treated with dalteparin versus 13% (6.5% serious) of patients treated with placebo. The author concluded that combined dalteparin/compression therapy in patients with SVP is safe and results in a decreased progression rate of the thrombotic processes. No rebound phenomenon was observed after cessation of dalteparin. Comparing this study with others (STENOX study in 2003 with enxaparin, and Prandoni’s study with nadroparin in 2005), the speaker remarked that in these studies there was no strict compression applied and no differentiation between varicophlebitis and SVP of other origin. That’s why the comparison of data is difficult.

Updated terminology of chronic venous disorders: the VEIN-Term transatlantic interdisciplinary consensus document.

Michel Perrin for the transatlantic interdisciplinary group

A transatlantic interdisciplinary faculty of experts under the auspices of the Union Internationale de Phlébologie, together with the European Venous Forum, the American Venous Forum, the American College of Phlebology, the International Union of Angiology, and the Society for Vascular Surgery met in order to provide recommendations for fundamental venous terminology. The above organizations have endorsed these recommendations, which were recently published in the VEIN-Term consensus document.
The raison d’être of such recommendations came from the many terms that still pose problems of interpretation, highlighting the need for a common scientific language in the investigation and management of chronic venous disorders. Venous terms related to the management of chronic venous disorders of the lower extremities that are widely used and recognized to vary in applicability and interpretation in reports in the venous literature were summarized.
Terms previously defined in CEAP documents1-3 and prior venous nomenclature refinements,4-5 and those pertaining to a congenital etiology, were excluded. The terms selected for inclusion in the VEIN-Term consensus document are divided into three different groups: clinical, physiological, and descriptive.
Regarding clinical terms, a definition of chronic venous disease is, “morphological and functional abnormalities of the venous system of long duration manifested either by symptoms and/or signs indicating the need for investigation and/or care”, Chronic venous insufficiency (C3-C6), “a term reserved for advanced chronic venous disorders, which is applied to functional abnormalities of the venous system producing edema, skin changes, or venous ulcers”, or venous symptoms, “complaints related to venous disease, which may include tingling, aching, burning, pain, muscle cramps, swelling, sensations of throbbing or heaviness, itching skin, restless legs, leg tiredness and/or fatigue. Although not pathognomonic, these may be suggestive of chronic venous disease, particularly if they are exacerbated by heat or dependency in the day’s course, and relieved with leg rest and/or elevation”. Besides these frequently used terms, thirty others were defined.
The whole set of terms is published in J Vasc Surg, (Eklof B, Perrin M, Delis KT, Rutherford RB, Gloviczki P et al. Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg. 2009;49:498-501.)

References
1. Porter IP, Moneta GM, an International Consensus Committee on Chronic Venous Disease. Reporting standards in venous disease: an update. J Vasc Surg. 1995;21:635-645. – 2. Allegra C, Antignani PL, Bergan JJ, Carpentier PH, Coleridge-Smith P, Cornu-Thenard A, et al. The “C” of CEAP: Suggested definitions and refinements: An international Union of Phlebology conference of experts. J Vasc Surg. 2003;37(1):129-131. – 3. Eklöf B, Rutherford RB, Bergan JJ, Carpentier PH, Gloviczki P, Kistner RL, et al, for the American Venous Forum’s International ad hoc committee for revision of the CEAP classification. Revision of the CEAP classification for chronic venous disorders. A consensus statement. J Vasc Surg. 2004;40:1248-1252. – 4. Caggiati A, Bergan JJ, Gloviczki P, Jantet G, Coleridge Smith P, Partsch H, and an International Interdisciplinary Consensus Committee on Venous Anatomical Terminology. Nomenclature of the veins of the lower limbs: An international interdisciplinary consensus statement. J Vasc Surg. 2002;36:416-422. – 5. Caggiati A, Bergan JJ, Gloviczki P, Eklof B, Allegra C, Partsch H and An International Interdisciplinary Consensus Committee on Venous Anatomical Terminology. Nomenclature of the veins of the lower limb: Extensions, refinements, and clinical application. J Vasc Surg. 2005;41:719-724.

UIP News, Awards

Chairpersons: E. Rabe, J-J. Guex

BAUERFEIND Fellowships

How to utilize compression therapy after ultrasound-guided sclerotherapy (USGS) with foam for the treatment of varicose veins – a randomized controlled trial
R. Ceulen (Austria), winner 2007-2009

Main conclusions:
• Obliteration is achieved in >80% of all patients
• Compression does not influence the outcome of USGS
• Compression prevents the development of side effects, but:
– When compression is completed, phlebitis will arise
– It does not reduce the incidence of hyperpigmentation
• Patients suffer from less pain when phlebitis occurs and compression is applied
• This suggests that for the patient’s comfort compression therapy should be recommended at least to reduce pain after phlebitis

Compression therapy for superficial vein thrombophlebitis
K. Bohler, S. Stolkovich, H. Kittler (Austria), winners 2009-2011

Main outcome variables:
• Reduction of spontaneous pain measured using a VAS
• Reduction of induced pain (modified Lowenberg test)

Additional outcome variables:
• Reduction of erythema in square cm
• Duplex sonographic change of thrombus length
• Duplex sonographic confirmation of new DVT
• Influence of treatment on quality of life SF-36
• Number of analgesics needed (pill counting)

KREUSSLER Fellowship

Catheter-directed foam sclerotherapy of varicose veins under tumescent anesthesia
N. Tetsch, B. Kahle (Germany)

Objective:
to investigate whether intrafascial tumescent anesthesia (TA) around the insufficient vein treated by duplex-guided catheter-directed foam sclerotherapy (DGCDS) improves therapeutic outcome.

SERVIER Fellowships

Erythrocyte diapedesis during chronic venous insufficiency
C. Rosi (Italy), UIP/SERVIER winner 2007/09

Considerations:
Erythrodiapedesis is currently considered the cause of the abnormal iron deposition occurring in legs with CVI. Historically, Myers (1965) was the first to affirm that stasis pigmentation around venous ulcers is due to deposition of hemosiderin (Fe+++) resulting from disintegrated red blood cells.

Methods:
The author evaluated the occurrence of erythrocyte diapedesis in 110 skin biopsies from legs with CVI at different clinical stages of the CEAP classification.

Results:
Erythrodiapedesis was NEVER found in samples of apparently normal skin, even in cases of long-lasting and severe CVI.
Erythrodiapedesis was found in biopsies from: skin overlying varicophlebitis, skin with acute dermatitis, skin around the ulcer and in the ulcer base.

Preliminary conclusions:
1. In most cases skin iron overload is not due to erythrodiapedesis (cellular mechanism)
2. Skin iron overload is likely to occur by means of a molecular mechanism

The role of soluble uPAR fragments in venous ulcer healing
A. Ahmad (UK), UIP/SERVIER winner 2009/11

Hypothesis:
The cleavage of uPAR into its fragments (D1 and D2-3) is an important mechanism in ulcer healing. Preliminary studies have shown a positive effect of suPAR in keratinocyte migration towards the ulcer wound that might help in venous ulcer re-epithelisation

Aims:
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.