Current Treatment of Varicose Veins François Becker, MD, PhD Address Department of Vascular Surgery and Vascular Medicine, University Hospital Jean Minjoz, 03 Boulevard Fleming, Besançon 25030, France. E-mail: [email protected] Current Treatment Options in Cardiovascular Medicine 2006, 8:97–103 Current Science Inc. ISSN 1092-8464 Copyright © 2006 by Current Science Inc.

Opinion statement Varicose veins (VVs) of the lower limbs are a common complaint that can take many forms, ranging from a nonpathologic condition to an invalidating chronic disorder. When they have not been neglected, uncomplicated VVs have often been treated by sclerotherapy or surgery, with variably successful results. Currently, the best way of assessing VVs has been to carry out routine ultrasound investigations. The approach to VVs has changed due to recent awareness of cosmetic considerations and the way they can affect quality of life, as well as the development of new treatments (ie, echo-guided sclerotherapy, foam sclerotherapy, endovascular obliteration) and ambulatory care practices. In some cases, the evolution of the disease can be disconcerting, if not entirely hopeless. However, in most cases, poor results have been obtained because of perfunctory assessment, inappropriate treatment, and lack of follow-up. The treatment of complicated VVs has been improved by combining clinical and ultrasound examinations, which make for a quick, accurate diagnosis, pointing the way to the right treatment. Venous ulcers resulting from primary saphenous vein insufficiency, which account for 50% of all venous ulcers, and recurrent venous ulcers should all be a thing of the past, apart from those associated with deep valvular insufficiency disease. The quality of care and the scientific standard of clinical studies on chronic venous insufficiency and VVs have both increased considerably. Although there is still a need to set up scales for assessing symptoms and quality of life, progress is being made in clinical studies that now meet the standards of evidence-based medicine.

Introduction Varicose veins in the lower limbs are a frequent cause of medical consultation in Western countries, where there is a very high prevalence of varicose veins in the general population: 50% of the women and 30% to 50% of the men in these countries suffer from varicose veins of various kinds, one third of which are overt varicose veins [1•,2]. Although the prevalence of symptomatic varicose veins is certainly high, it is more difficult to assess. The prevalence of vein-related trophic skin changes is much lower (around 5%), but the effects of these disorders in terms of disability and health care costs are considerable. In Europe, the annual cost of chronic venous disorders has been estimated at 10 million euros per million inhabitants, taking only the direct costs into account [2].

Despite the high costs involved, these disorders have attracted very little attention so far. The reason for this situation is that varicose veins are not really regarded as a proper disease, and that vein-related trophic changes are known to be difficult to treat and to have a high recurrence rate, especially in the case of venous leg ulcers. The following facts are worth recalling: 1) there exist many different kinds of varicose veins, from spider veins to large trunk varicose veins; 2) although it is difficult to describe and quantify vein symptoms and complaints in cosmetic terms, they can seriously affect quality of life [3,4]; 3) little high level clinical research has been carried out until quite recently on chronic venous disease, partly because clinical studies are very

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difficult to perform in this field; 4) Bauer’s [5] dogma, according to which vein ulcers are mostly sequelae of deep vein thrombosis (DVT), has had a long career, although it has been established that half of all these cases result from primary saphenous varicose veins or incompetent distal perforators [6]; and 5) appropriate treatment for large trunk varicose veins reduces the patient’s risk of developing trophic changes and results in rapid healing of venous ulcers due to saphenous vein insufficiency [7,8]. As far as the latest methods of treating varicose veins are concerned, the issue can be summarized as follows: making accurate anatomic and clinical assessments, taking the cosmetic factors into account, and applying the most cost-efficient treatment. Here I propose to deal with the following points in turn: the various anatomic types of varicose veins, the signs and symptoms of superficial vein insufficiency, and the various therapeutic approaches available. This paper focuses on primary varicose veins, especially large primary varicose veins, leaving aside those that are obviously secondary to deep vein lesions (eg, post-thrombotic syndrome, primary deep venous insufficiency, deep venous obstruction) or to congenital or acquired arteriovenous shuntings.

TYPES OF VEINS It is necessary to distinguish telangiectases or spider veins and reticular veins, which differ from large varicose veins. It is also worth outlining the role of the perforating veins or perforators. Telangiectases have been defined as dilated intradermal venules less than 1 mm in size [9]: when distal and bluish in color, these veins are a sign of chronic venous insufficiency, and when they are proximal and purple or red the problems to which they give rise are of a more cosmetic nature. Reticular veins have been defined as dilated, nonpalpable, immediately subdermal veins less than 4 mm in size [9]. Both kinds are extremely frequent (they occur in 80% to 90% of the general population). They are sometimes concomitant with large trunk varicose veins, but the two forms are not usually linked.

Telangiectases

Varicose veins Varicose veins are defined as dilated, palpable, subcutaneous veins larger than 4 mm [9] caused by valvular incompetence and weakness of the vein wall. They are sometimes not even visible or palpable in the subcutaneous fatty tissue, but conversely all veins that are too conspicuous or palpable are not necessarily varicose veins. Trunk varicose veins involve the main stem or major tributaries of the great saphenous vein or those of the small saphenous vein. Ultrasound investigations (hand-held Doppler, Bmode echography, ultrasound duplex) have shown that varicose veins cannot simply be defined as either great or

small saphenous vein insufficiency. There exist various anatomic forms and it is practically indispensable these days to carry out detailed Doppler ultrasound investigations, at least whenever surgical or endovascular treatment is envisaged [10]. For example, the great saphenous vein can be either partly or entirely duplicated or bordered by accessory saphenous veins running parallel to the saphenous trunk. Saphenofemoral incompetence is not necessarily propagated to the great saphenous trunk: sometimes only the thigh anterolateral or posteromedial accessory saphenous vein is incompetent, and sometimes all three show various levels of incompetence. Great saphenous vein insufficiency can be associated not with a saphenofemoral reflux but with a reflux arising from the internal iliac vein and transiting via pudendal or perineal varicose veins, or with a reflux originating from anteromedial thigh perforating veins. The position of the saphenopopliteal junction is normal in only 50% of all cases. What is taken to be a saphenopopliteal reflux is often a reflux from a vein of the popliteal fossa, called the Thiery perforator, which is independent of the small saphenous vein. The distal half of the small saphenous vein can receive a reflux originating from muscular veins and transiting via the perforator at the gastrocnemius or soleus point, or resulting from great saphenous vein insufficiency and transiting via the intersaphenous veins. Lastly, varicose veins can also be either diffuse and nonsystematic or linked to a perforating vein, which is not part of the saphenous network. Generally speaking, all varicose veins located on the thigh or on the internal leg are not necessarily due to great saphenous vein insufficiency, nor are all varicose veins with a postero-external leg location necessarily due to small saphenous vein insufficiency. Based on studies on series from noninvasive vascular laboratories, the rate of nonsaphenous vein reflux is 10% to 40% of all varicose vein syndromes [11,12]. Perforating veins Pe rf or atin g ve in s ca n ei t he r be directly associated with a saphenous vein (eg, great saphenous vein, small saphenous vein, or accessory) or they can be an independent source of reflux. In the former case, dilatation and insufficiency of the perforating veins usually occur concomitantly with the saphenous trunk insufficiency. Distal perforating veins (ankle/ Cockett’s perforators) play an important role in the genesis of venous ulcers, and these should generally be diagnosed and treated whenever saphenous vein insufficiency–related skin trophic changes are encountered.

SYMPTOMS AND SIGNS The symptoms in lower limbs often mentioned by patients with varicose veins (ie, aching, pain, heaviness and tension, a feeling of swelling, night cramps, restless legs, and itching) are not clearly correlated with the pattern or severity of venous disorders. If they are of venous origin, they usually result from lower-limb venous dysfunction

Current Treatment of Varicose Veins Becker (chronic venous insufficiency) rather than from the varicose veins themselves. Clinical scores are needed to be able to check whether or not these symptoms are venous symptoms and quantify the degree of discomfort. The pains attributable to varicose veins are those located along the course of the varicose vein or where a pathologic perforating vein penetrates aponevrosis. The signs of chronic venous disorders are easier to diagnose (they are mainly the following: pitting ankle edema, skin pigmentation, lipodermatosclerosis, venous ulcers). They have been codified by Widmer [13], the subcommittee on reporting standards in venous disease [14], and more recently in the C code of the Clinical Epidemiological Anatomic and Physiologic (CEAP) classification [15], which is still being validated and improved [16,17]. We hope the ankle flare and corona phlebectatica described by Van der Molen [18] will be included in the CEAP classification,

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because along with ankle edema these are the first signs of decompensated venous insufficiency.

INDICATIONS FOR HOSPITALIZATION The vast majority of varicose vein treatments do not require hospitalization. Medical treatment and sclerotherapy can be given in the ambulatory setting. Endovascular obliteration, minimally invasive surgery, and stripping for uncomplicated varicose veins can be performed during day hospitalization (except for small saphenous vein surgery with complex reflux in the popliteal fossa). The indications for longer hospitalization are mainly trunk saphenous varicose veins complicated by lipodermatosclerosis or ulcers requiring surgery for distal perforating veins, or in a few rare cases complicated with ascending thrombophlebitis and freefloating thrombus close to the saphenofemoral or popliteal junction, or complicated by bleeding.

Treatment Diet and lifestyle • Epidemiologic studies have not identified any strong and consistent lifestyle risk factors responsible for varicose veins and venous reflux [1•,2,19]. However, sedentary activities and those involving long standing or long sitting positions are factors contributing to venous stasis. Physical exercise, particularly walking and swimming, has positive effects on the lower-limb venous hemodynamics. Being overweight has not been confirmed as a risk factor, but because being overweight is generally linked to lack of exercise, its reduction should be encouraged.

Pharmacologic treatment • No drugs have been found so far to result in varicose vein resolution, but some venoactive drugs help to alleviate venous symptoms, especially pains and aching [20].

Interventional procedures Compression treatment: elastic stockings The benefits of compression treatment (eg, bandages and elastic stockings) for venous ulcers and for preventing post-thrombotic syndrome have been well documented [21]. The advantages of gradual elastic compression have been less well documented in the case of varicose veins (small and large varicose veins, asymptomatic or with so-called venous symptoms, as a single treatment or postsclerotherapy or postsurgery treatment). However, compression therapy is regarded as the best available treatment for chronic venous insufficiency. Some studies have shown that elastic compression stockings reduce venous symptoms and evening edema wearing only class I (10- to 20-mm Hg) stockings [22,23].

Sclerotherapy Sclerotherapy [24–26] is the targeted elimination of telangiectases, reticular veins, or subcutaneous varicose veins by injection of a sclerosant, which irritates and damages the endothelium and even the entire wall of the treated vein, causing

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Vascular Disease it to thrombose, fibrose, and be absorbed by surrounding tissues. The goal of sclerotherapy is not only to induce thrombosis of the treated vein but to transform it into a fibrous cord. Varicose veins of all kinds can be sclerotized. Sclerotherapy is the first-choice treatment for telangiectases, spider veins, and reticular veins. Subcutaneous varicose veins without saphenous vein insufficiency, residual varicose veins after surgery for saphenous vein insufficiency, and varicose veins associated with incompetent perforators are also common indications for sclerotherapy. In these cases, the alternatives to sclerotherapy are percutaneous phlebextraction and ligation of perforating veins. Although surgery is generally held to be the best means of treating saphenous vein insufficiency, sclerotherapy is also possible. The use of sclerotherapy in the treatment of varicose veins in the lower limbs is spreading thanks to the development of echo-guided sclerotherapy and foam sclerotherapy techniques. Standard procedure Echo-guided sclerotherapy makes it possible to puncture and to inject the vein to be sclerosed, and to assess the progression and the effect of the sclerosant under echographic control. In skilled hands, this method provides a safer and more efficacious means of performing large varicose vein sclerotherapy, including trunk saphenous vein sclerotherapy. Sclerotherapy with foamed sclerosant is a new development of an old idea (Sigg, 1949). The indications and contraindications are the same as those applying in the case of conventional sclerotherapy with fluid sclerosants. This method requires less sclerosant and fewer injections per session, while giving stronger sclerosing effects on larger distances. Depending on the technique and the concentration used to produce the foam, the sclerosant can be either fine bubbled and fluid or rather viscous. The fluid form is employed on spider veins and the viscous form on large varicose veins. In the hands of a skilled phlebologist, combined with echo-guided sclerotherapy in the case of large varicose veins, foam sclerotherapy offers better controllability and better efficacy than conventional sclerotherapy. In both cases, a compression bandage or a stocking with local padding is applied for a few hours to a few weeks after a session of sclerotherapy, depending on the type of varicose veins treated and the technique used. Contraindications A known allergy to the sclerosant, severe systemic disease, acute superficial or DVT or severe arterial insufficiency affecting the same leg, and pregnancy. Relative contraindications are bronchial asthma and allergic diathesis, known thrombophilia, a documented history of DVT or arterial insufficiency, or degenerative complications of diabetes affecting the same leg. Complications Although properly performed sclerotherapy rarely leads to complications, a series of adverse events can occur: allergic reactions (from minor reactions to anaphylactic shock), excessive sclerosing reactions (superficial thrombophlebitis), extensive thrombosis spreading to the deep veins (thromboembolism), orthostatic collapse, transient visual disturbances especially in patients with migraine (foam sclerotherapy), skin necroses or nerve damage (paravascular injection), and extended necroses (intra-arterial injection). The most common side effect is pigmentation (up to 10%), the risk of which can be reduced by performing microthrombectomy [27].

Surgery Conventional surgery (stripping) Standard procedure Conventional surgery (stripping) is still the reference method for dealing with large varicose veins with proximal incompetence located either in the groin or at the back of the knee. The patient is generally admitted on the day of the operation (or in the late afternoon the day before) and discharged home the following morning. Simple problems can be dealt with in the day hospitalization setting. Performing ultrasound duplex preoperative mapping can be most useful before great saphenous vein surgery; this procedure is practically mandatory prior to small saphenous vein surgery, given the variability of the anatomy and the inaccuracy of the clinical examination in this case. It is preferable to perform the ultrasound mapping before premedication of the patient to prevent lipothymia from occurring during cutaneous mapping in the standing position.

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These operations are performed under general or regional anesthesia or even under local anesthesia, depending on the surgeon’s and the patient’s preferences, and on the extent and the complexity of the varicose veins to be treated. The patient is operated on in the supine position for great saphenous vein surgery, and in the prone position for small saphenous vein surgery. The complete operation involves ligation of the saphenous vein near its ending or flush with the femoral or the popliteal vein, stripping the saphenous trunk (short or long stripping in the case of the great saphenous vein), ligation and excision of tributaries, and ligation of large perforating veins. In cases where there are many distal incompetent perforating veins to be treated (which rarely occurs in the case of primary varicose veins), ligature is performed by performing subfascial endoscopic ligation rather than open surgery, to avoid obtaining a long, unattractive, and often poorly healing wound. Compression bandaging is applied to the operated limb at the end of the operation. After the patient’s discharge, class II elastic compression is worn during the day. There is no consensus as to the type, strength, and duration of postoperative compression therapy. Residual varicose veins are treated by sclerotherapy a few weeks later. If well indicated, well documented, well performed, and combined with sclerotherapy in the follow-up, saphenous varicose vein surgery gives good results. Contraindications Contraindications to saphenous vein surgery are rare and simply require good clinical sense, balancing the indications for surgery versus the patient’s general state of health. Bleeding disorders, hypercoagulable states, severe arterial insufficiency, major obesity, or major lymphedema are the main contraindications and limitations. Complications The complication rate is low. Femoral/popliteal artery or femoral/popliteal vein damage is exceptional in skilled hands. Nerve injuries can occur even in the best hands, especially in cases involving long saphenous vein stripping from the ankle [28]. Postoperative DVT is mainly low-risk DVT confined to the calf veins and there is no consensus about DVT prophylaxis for patients having varicose vein surgery [29,30]. Nevertheless, caution should be exercised in small saphenous vein surgery, particularly in the case of complex reflux or redo surgery in the popliteal fossa. The main disadvantages of varicose vein surgery are postoperative pains and discomfort, bruising and hyperpigmentation, lymphoceles and hematomas (mainly in obese patients and in the case of redo surgery in the groin), inesthetic scars, and a 20% to 60% rate of incidence of recurrent varicose veins [31,32]. Usually, inappropriate or incomplete ligation at the saphenofemoral/popliteal junction level, or more generally an inappropriate or incorrect original operation, an incorrect assessment of the varicose vein network, and lack of phlebologic follow-up are generally thought to be the main causes of recurrent varicose veins. However, an increasing amount of data stress the modes of saphenofemoral/popliteal junction ligation used: flush ligation seems to not always be necessary and may favor neovascularization processes [33,34•]. The above complications and criticisms argue in favor of the development of new methods of treatment, but these in turn are not devoid of criticism [35].

New procedures • I will not discuss laser treatment for telangiectasia. After a period of enthusiasm, the adverse effects have been too frequent and the efficacy has been too low; this method has therefore been abandoned. New lasers are now being developed. • Transilluminated-powered phlebectomy (Trivex procedure [Smith & Nephew, London, UK]) is competing with conventional stab incision phlebectomy. Trivex combines endoscopic-powered vein resection and ablation of superficial varicosities with tumescent anesthesia and irrigated illumination. In a recent, randomized controlled trial, no significant differences were observed in cosmesis or recurrence during follow-up [36], but the risk of necrotizing fasciitis associated with tumescent anesthesia needs to be taken into account [37].

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Vascular Disease • Radiofrequency or laser endovenous obliteration methods use controlled thermic energy to close large varicose veins [38–41,42•]. The radiofrequency technique is performed using a single device (Closure; VNUS Medical Technologies, San Jose, CA) and is beginning to be well codified and well documented unlike the endovascular laser technique, which can be performed using different devices. In both cases, the procedure is performed under local or regional anesthesia, the catheter/fiber is introduced percutaneously or via a minisurgical access point, and the progression of the extremity of the catheter/fiber is followed under echographic control (radiofrequency) or detected through the skin (laser). Additional phlebectomies and scleroses are performed as with conventional surgery. Using the radiofrequency method, high ligation of the saphenous vein does not seem to be necessary. The endovenous laser technique can be used on collateral veins of the saphenous vein treated. These techniques are mainly applied to treat great and small saphenous vein insufficiency, especially the former, and are performed in a day hospitalization setting. The complications rate and the short- and mid-term results have been more fully documented in the case of the radiofrequency method. The results obtained are similar to those of conventional surgery. The rate of incidence of recurrent varicose veins seems to be lower with radiofrequency. The cost-effectiveness ratio may be in favor of radiofrequency. • Further well-defined, prospective, randomized studies are now required comparing echo-guided foam sclerotherapy, endovenous obliteration, and conventional surgery in terms of safety, short- and long-term efficacy, and costeffectiveness. However, the new techniques, at least radiofrequency obliteration, could replace conventional surgery as first-choice methods of treatment for dealing with the most common forms of saphenous vein insufficiency.

References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.• Adhikari A, Criqui MH, Wool V, et al.: The epidemiology of chronic venous diseases. Phlebology 2000, 15:2–18. A major review of epidemiologic studies on varicose veins and chronic venous insufficiency. 2. Carpentier PH, Maricq HR, Biro C, et al.: Prevalence, risk factors, and clinical patterns of chronic venous disorders of lower limbs: a population-based study in France. J Vasc Surg 2004, 40:650–659. 3. Smith JJ, Garrat AM, Guest M, et al.: Evaluating and improving health-related quality of life in patients with varicose veins. J Vasc Surg 1999, 30:710–719. 4. Kaplan RM, Criqui MH, Denenberg JO, Greenhalgh RM: Quality of life in patients with venous disease: San Diego population study. J Vasc Surg 2003, 37:1047–1053. 5. Bauer G: A roentgenological and clinical study of the sequels of thrombosis. Acta Chir Scand 1942, 86(suppl 74):5–116. 6. Magnusson MB, Nelzen O, Risberg B, Sivertsson R: A colour Doppler ultrasound study of venous reflux in patients with chronic leg ulcers. Eur J Vasc Endovasc Surg 2001, 21:353–360.

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Bello M, Scriven M, Hartshone T, et al.: Role of superficial venous surgery in the treatment of venous ulceration. Br J Surg 1999, 86:755–759. Iafrati MD, Pare GJ, O’Donnel TF, Estes J: Is the nihilistic approach to surgical reduction of superficial and perforator vein incompetence for venous ulcer justified? J Vasc Surg 2002, 36:1167–1174. Porter JM, Moneta GL: Reporting standards in venous disease, an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg 1995, 21:635–645. Mercer KG, Scott DJA, Berridge DC: Preoperative duplex imaging is required before all operations for primary varicose veins. Br J Surg 1998, 85:1495–1497. Labropoulos N, Kang SS, Mansour MA, et al.: Primary superficial vein reflux with competent saphenous trunk. Eur J Vasc Endovasc Surg 1999, 18:201–206. Jiang P, van Rij AM, Christie RA, et al.: Non-saphenofemoral venous reflux in the groin in patients with varicose veins. Eur J Vasc Endovasc Surg 2001, 21:550–557. Widmer LK, ed: Peripheral Venous Disorders. Basle Study III. Berne, Switzerland: Hans Huber Publishers; 1978.

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Enoch S, Woon E, Blair SD: Thromboprophylaxis can be omitted in selected patient undergoing varicose vein surgery and hernia repair. Br J Surg 2003, 90:818–820. 30. van Rij AM, Chai J, Hill B, Christie RA: Incidence of deep vein thrombosis after varicose vein surgery. Br J Surg 2004, 91:1582–1585. 31. Blomgren L, Johansson G, Dahlberg-Akerman A, et al.: Recurrent varicose veins: incidence, risk factors and groin anatomy. Eur J Vasc Endovasc Surg 2004, 27:269–274. 32. Kostas T, Ioannou CV, Touloupakis E, et al.: Recurrent varicose veins after surgery: a new appraisal of a common and complex problem in vascular surgery. Eur J Vasc Endovasc Surg 2004, 27:275–282. 33. van Rij AM, Jones GT, Hill GB, Jiang P: Neovascularization and recurrent varicose veins: more histologic and ultrasound evidence. J Vasc Surg 2004, 40:296–302. 34.• Frings N, Nelle A, Tran PH, et al.: Reduction of neoreflux after correctly performed ligation of the saphenofemoral junction. A randomized trial. Eur J Vasc Endovasc Surg 2004, 28:246–252. Prospective, randomized study comparing four methods of ligating the saphenofemoral junction. Important contribution to the understanding of neovascularization and recurrence at the groin level. 35. Campbell B: New treatments for varicose veins. Lack of robust evidence, longer operating time, and greater expense are limitations [editorial]. BMJ 2002, 324:689–690. 36. Aremu MA, Mahendran B, Butcher W, et al.: Prospective randomized controlled trial: conventional versus powered phlebectomy. J Vasc Surg 2004, 39:88–94. 37. Hubmer MG, Koch H, Haas FM, et al.: Necrotizing fasciitis after ambulatory phlebectomy performed with use of tumescent anesthesia. J Vasc Surg 2004, 39:263–265. 38. Crane J, Cheshire N: Recent developments in vascular surgery. Clinical review. BMJ 2003, 327:911–915. 39. Perkowski P, Rajagopalan R, Gowda RCN, et al.: Endovenous laser ablation of the saphenous vein for treatment of venous insufficiency and varicose veins: early results from a large single-center experience. J Endovasc Ther 2004, 11:132–138. 40. Lurie F, Creton D, Eklof B, et al.: Prospective randomized study of endovenous radiofrequency obliteration (Closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study). J Vasc Surg 2003, 38:207–214. 41. Pichot O, Kabnick LS, Creton D, et al.: Duplex ultrasound scan findings two years after great saphenous vein radiofrequency endovenous obliteration. J Vasc Surg 2004, 39:189–195. 42.• Perrin M: Endovenous therapy for varicose veins of the lower extremities [in French]. Ann Chir 2004, 129:248–257. Excellent presentation and analysis of the news methods of endovascular treatment of varicose veins by a vascular surgeon expert in the treatment of varicose veins. (See also Perrin M: Endoluminal treatment of lower limb varicose veins by endovenous laser and radiofrequency techniques. Phlebology 2004, 19:170–178.)