Effectiveness of foam sclerotherapy for the treatment of varicose veins

Transcription

1 Effectiveness of foam sclerotherapy for the treatment of varicose veins Vascular Medicine 15(1) The Author(s) 2009 Reprints and permission: sagepub.co.uk/journalspermission.nav DOI: / X Raha Nael and Suman Rathbun Guest Editor: Teresa Carman Abstract Varicose veins (VVs) are associated with lifestyle-limiting symptoms and complications. Patients who fail compression therapy are candidates for more invasive treatments. This study evaluates the efficacy and safety of endovenous foam sclerotherapy (EFS) for the treatment of VVs in a US academic center. We reviewed medical records of a consecutive cohort of patients who underwent EFS over a 2-year period. The primary outcome measure was obliteration of VVs. The secondary outcome measures were symptomatic improvement, ulcer healing, recurrence, and adverse events. A total of 166 patients (217 legs) underwent EFS for pain (81%), pruritis (41%), swelling (17%), ulcerations (17%), thrombophlebitis (14%), and varix rupture (3%). Complete (65%) or near-complete (34%) obliteration was achieved in 215 (99%) legs after one injection. Additional injections achieved complete obliteration in 39 of 53 legs. Ninety-three percent (27/29) of active ulcers healed or were decreasing in size. Five ulcers and 11 VVs recurred. Common adverse events included pain and hyperpigmentation. Thrombosis, hematoma, skin necrosis, and neurologic events were rare. In conclusion, EFS appears to be a safe and effective outpatient therapy for the treatment of symptomatic and complicated VVs. Keywords chronic venous insufficiency; foam sclerotherapy; varicose veins Introduction Chronic venous insufficiency (CVI) is a common and under-recognized problem, affecting greater than 20% of the general population. 1 Varicose veins (VVs), the most common manifestation of CVI, affect up to 25% of women and 15% of men. 1 Additionally, more than 80% of women and men have telangiectasias (spider veins) and reticular veins. 2 It has been estimated that 1% of the general population suffers from venous ulcerations with a United States (US) healthcare cost of three billion dollars per year. 2 The risk of developing VVs is increased in females, with advancing age, family history of venous insufficiency, pregnancy, occupations with prolonged standing, increased body mass index, vascular malformations, and prescription of hormone therapy (oral contraceptives or hormone replacement therapy). 2,3 While VVs have traditionally been regarded as simply a cosmetic problem, more commonly they produce symptoms of heaviness, fatigue, pain, swelling, restlessness, burning, and itching. 2,3 Symptoms often interfere with activities of daily living and result in lost time from work. 3 VVs are associated with a number of complications including spontaneous varix rupture with hemorrhage, superficial thrombophlebitis, deep vein thrombosis (DVT), and venous ulceration. 3 Venous ulcerations are particularly troublesome for the patients since many may take more than 9 months to heal, with 66% lasting more than 5 years. 2 In 2004, the American Venous Forum updated the standardized diagnostic evaluation and classification of patients with CVI, known as the CEAP (Clinical Etiologic Anatomic Pathophysiologic) classification. 4 This classification categorizes the clinical signs of CVI into seven classes and allows objective comparison of disease severity. Despite emphasis on the diagnostic evaluation of patients with CVI, the modern treatment of CVI and complicating VVs has not been rigorously studied. Traditional treatment modalities for VVs include conservative measures using external compression therapy and, if unsuccessful, surgical ligation and stripping of VVs and incompetent deep perforating veins. While surgical treatment of VVs Department of Internal Medicine: Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Presented at the Society for Vascular Medicine 18th Annual Meeting, Effectiveness of Endovenous Foam Sclerotherapy for Treatment of Varicose Veins, Baltimore, MD, June 7, Corresponding author: Suman Rathbun University of Oklahoma Health Sciences Center WP 3010, 920 Stanton L. Young Boulevard Oklahoma City, OK USA suman-rathbun@ouhsc.edu

2 28 Vascular Medicine 15(1) has proven effective, it has fallen out of favor due to high cost, time away from work, and procedural complications of wound infection, hematoma, and nerve paresis. 5 More recently, percutaneous interventional therapies including endovenous laser therapy (EVLT), radiofrequency ablation (RFA) followed by microphlebectomy, and chemical sclerotherapy using foam have become available for outpatient treatment of VVs. 3 Despite the availability of endovenous foam sclerotherapy (EFS) for the obliteration of VVs since 1944 and widespread use within the US, there is no commercial foam product available, and the use of this procedure in the US is not FDA-approved. 6 Moreover, few studies in the US have systematically evaluated the efficacy of this procedure in a large series of patients. 7 The purpose of this study is to report the efficacy and safety of EFS for the treatment of symptomatic VVs, venous ulcerations, and venous angiomata in a diverse group of patients at a US academic vascular center. Materials and methods This study reviewed the results of a consecutive cohort of patients who underwent EFS from November 2004 through June 29, 2007 at the University of Oklahoma Vascular Center. The study was approved by the local institutional review board. Patients were initially seen by one of three vascular internists who followed a standardized protocol for management of CVI and VVs, including assessment for failure of conservative management with compression therapy or recurrence of VVs after surgical or other endovenous procedures, foam preparation and delivery techniques, post-procedure observation, and follow-up surveillance. Using Duplex ultrasound examination of the deep and superficial venous systems, all major truncal branches of the venous system were examined for size and evidence of venous incompetence, including the presence of incompetent perforating veins. Patency of the deep venous system was confirmed during the ultrasound examination. Each patient chart was reviewed for demographic characteristics, indication for EFS, previous conservative and/ or surgical treatments for VVs, ultrasound testing evaluation of VVs, procedural characteristics, adverse effects, and long-term follow-up to 1 year using a standardized data collection form in accordance with the published reporting standards for endovenous ablation for the treatment of venous insufficiency. 8 Patients were categorized by severity of venous insufficiency: uncomplicated VVs (CEAP class C2-3: VVs and edema) or severe venous insufficiency (CEAP class C4-6: lipodermatosclerosis, healed ulceration, active ulceration). Patients with venous angiomas and congenital venous malformations, including patients with Klippel-Trenaunay (KT) syndrome, were analyzed in a separate category. The primary outcome measure was the frequency of obliteration (complete, partial, or minimal) of injected varicosities at 1 week post procedure, and on long-term followup. Obliteration of varicosities was characterized using Duplex ultrasound as follows: complete obliteration represented sclerosis of all visualized varicosities and/or tributaries with no evidence of residual patency, partial obliteration referred to greater than 80% sclerosis of the originally visualized VVs with minimal residual patency, and minimal obliteration described less than 80% sclerosis with persistence of the majority of the varicosities and/or its tributaries. The secondary outcome measures were frequency of improvement in venous insufficiency symptoms as reported by the patient, ulcer healing, recurrent ulcers, recurrent VVs, and adverse events following the procedure and on long-term follow-up to 1 year. Description of procedure Immediately prior to the procedure, duplex ultrasound was used to localize the most superficial, accessible segment of the great or small saphenous veins or their tributaries in which the catheter could be easily inserted. Foam was prepared combining sodium tetradecyl sulfate 3% (one part) with room air (three to four parts) using the Tessari method. 9 Foam (average volume 10 ml) was injected under ultrasound guidance with visualization of the foam into the affected vessel followed by manual compression of the saphenofemoral junction for 2 3 minutes while the foam was massaged distally into the venous tributaries to prevent microbubble entry into the deep venous system. Ultrasound examination of the venous systems was performed immediately after procedure to document the presence of foam in the superficial venous tributaries and exclude evidence of DVT. A mmhg thigh-high compression stocking and/or short-stretch bandage were applied to the treated leg. The patient was observed for minutes postprocedure for evidence of immediate adverse events. The patient returned for follow-up at 1 week for ultrasound evaluation of sclerosed VVs and to exclude DVT. Followup ultrasound at 1 week included perforator veins if a DVT was detected. Patients were then seen at weeks 12, 24, and 48 for follow-up. Patients with active ulcerations received optimal wound care with compression therapy before and after the EFS procedure. Results A total of 166 patients (217 legs) underwent EFS. The study population was divided into three categories: uncomplicated VVs (n = 127), severe CVI (n = 86), and venous angiomata (n = 4). Patient demographic information and CEAP classification are given in Table 1. Patients suffered from symptoms of pain with prolonged standing and at rest (81%), pruritis (41%), swelling (17%), recurrent or non-healing ulcerations (17%), superficial thrombophlebitis (14%), and spontaneous varix rupture (3%). Fifty-nine percent of the legs treated were indicated for uncomplicated VVs (CEAP class 2-3), 40% had complicated CVI (CEAP class 4-6), and 2% had venous angiomata. Seventy-seven percent of the patients had

3 Nael R and Rathbun S 29 Table 1. Demographic information No. of patients 166 Male 63 (38%) Female 103 (62%) Mean age (years) 56.7 (18 89) No. of legs 217 Left leg 104 (48%) Right leg 113 (52%) Symptoms Pain 175 (81%) Pruritis 89 (41%) Swelling 36 (17%) Ulcers 36 (17%) Phlebitis 30 (14%) Varix rupture 6 (3%) CEAP class C (59%) C (40%) Congenital 4 (2%) Previous treatments Conservative 167 (77%) Endovascular 10 (5%) Surgical 40 (19%) failed conservative therapy (stockings and compression hose), 5% had undergone endovascular therapy (EVLT, RFA, subfascial endoscopic perforator surgery (SEPS), and previous EFS), and 19% surgical therapy (venous stripping) prior to presenting for EFS. The majority of treated varicosities involved the great saphenous vein (94%) and its tributaries (92%). Eight percent of the treated varicosities included the small saphenous vein and its tributaries (6%). The saphenofemoral junction demonstrated incompetence in 59% of legs. Fiftyfour percent of the legs had incompetent below the knee perforating veins and 12% had incompetent above the knee perforating veins. The mean diameter of the treated varicose veins was 5.83 mm (range: 3 10 mm). Post-sclerotherapy results Patient follow-up is reported for an average of 33 weeks (range weeks; median 24 weeks). Of the 217 legs that underwent EFS, 142 (65%) achieved complete obliteration, 73 (34%) achieved near-complete obliteration, and two (0.9%) had minimal obliteration after the initial injection. The percent obliteration for uncomplicated VVs (CEAP 2 3), complicated CVI (CEAP 4 6), and congenital angiomata is given in Table 2. Thirty-nine of the 53 legs (74%) requiring re-injection (median 1.0) achieved complete obliteration. The remaining 14 legs were not re-injected since these patients had complete relief of their symptoms despite having some residual patency of their VVs. At 1 year, in the 41 legs (19%) that were seen for follow-up, 95% continued to have complete or near complete obliteration of the treated varicose veins (Figure 1A and B). Table 2. Summary of results Obliteration rate Follow-up (weeks) Total: n (%) with f/u 217 (100%) 164 (76%) 122 (56%) Complete obliteration after 1 injection 141 (65%) 109 (66%) 78 (64%) Partial obliteration 74 (34%) 53 (32%) 42 (34%) Minimal obliteration 2 (0.9%) 2 (1%) 2 (2%) Complete after re-injection CEAP 2-3: n (%) with f/u 127 (100%) 90 (71%) 68 (54%) Complete 87 (69%) 65 (72%) 49 (72%) Partial 40 (31%) 25 (28%) 19 (28%) Minimal Complete after re-injection CEAP 4-6: n (%) with f/u 86 (100%) 71 (83%) 52 (60%) Complete 52 (60%) 43 (61%) 28 (54%) Partial 32 (37%) 26 (37%) 22 (42%) Minimal 2 (2%) 2 (3%) 2 (4%) Complete after re-injection Congenital: n (%) with f/u 4 (100%) 3 (75%) 2 (50%) Complete 2 (50%) 1 (33%) 1 (50%) Partial 2 (50%) 2 (67%) 1 (50%) Minimal Complete after re-injection Symptomatic improvement, ulcer healing, recurrence Symptomatic improvement 203/217 (94%) 153/164 (93%) 111/122 (91%) Ulcers healed 23/29 (79%) 21/25 (84%) 17/19 (89%) Ulcers healing 4/29 (14%) 3/25 (12%) 1/19 (5%) Non-healing ulcers 2/29 (7%) 1/25 (4%) 1/19 (5%) Recurrent ulcers 5/29 (17%) 5/25 (20%) 5/19 (26%) Recurrent varicose veins 11/217 (5%) 11/164 (7%) 10/122 (8%)

4 30 Vascular Medicine 15(1) (A) Table 3. Adverse events (n/%) Pain 97 (45%) Hyperpigmentation 51 (23%) Thrombophlebitis 11 (5%) Trapped coagulum 8 (4%) Deep vein thrombosis 5 (2%) Neurologic 2 (0.9%) Skin necrosis 3 (1%) Hematoma 1 (0.4%) Allergic reaction 0 Chest tightness 0 n = 217. (B) incidence of serious adverse events, including hematoma, superficial thrombophlebitis or trapped coagulum, DVT, skin necrosis, and transient neurologic symptoms was low (Table 3). Two patients suffered neurologic side effects: one 62-year-old patient who received an injection of greater than 20 cc of foam when both legs were treated at a single visit as per the patient s request developed visual changes and headache that resolved within 30 minutes. A second 87-year-old patient developed transient confusion and dysarthia that resolved within 2 hours. Both patients were later discovered to have patent foramen ovale (PFO). Discussion Figure 1. (A) Before EFS; (B) 3 months post-efs. Symptomatic improvement and ulcer healing Of the 217 legs treated, 203 (94%) resulted in symptomatic improvement of the patient s initial complaints as reported by the patient at the 1-week follow-up. Twenty-three (79%) of the 29 active ulcers healed and four (14%) were decreasing in size after the procedure. The average time to ulcer healing was 14 weeks (range 1 48 weeks, median 8 weeks). Five legs (17%) developed recurrent ulcerations and 11 legs (5%) developed recurrent VVs (Table 2). Adverse events There were minimal side effects associated with EFS. Ninety-seven (45%) complained of minimal pain, 79 (81%) did not require any pain medications and 18 (19%) required over-the-counter pain medication. Fifty-one (23%) had mild skin hyperpigmentation over the sclerosed VVs. The Our results demonstrate the efficacy of EFS for obliteration of symptomatic VVs in the outpatient setting. Overall, 99% of our patients achieved complete (65%) or near complete (34%) obliteration of their VVs after the initial injection, irrespective of their CEAP classification. Symptomatic improvement was achieved in 93% of the legs injected. Twenty-three of the 29 active ulcers (79%) healed and four (14%) reduced in size at 1 48 weeks (mean 14 weeks) after treatment. Five legs (17%) developed recurrent ulcerations and 11 (5%) had recurrent VVs. These results are comparable to those achieved with surgical or other interventional endovascular procedures. 7,10 19 Our study consisted of a representative number of patients with uncomplicated VVs (59%) and severe venous insufficiency (41%) referred to a vascular outpatient clinic. We have demonstrated that the rate of complete and partial obliteration does not differ between these patients. We observed that few patients with long-term follow-up had recurrent patency of VVs after initial obliteration. There were few adverse effects associated with EFS, the most common being mild post-procedure pain and discomfort that did not require pain medications in most cases, and skin hyperpigmentation, which faded over weeks to months. More serious complications, including hematoma, DVT, superficial thrombophlebitis or trapped coagulum, skin necrosis, and transient neurologic events (headache, visual changes) rarely occurred. Limbs that developed DVT (2%) after the procedure were treated with anticoagulation for 3 months with resolution of their DVT on followup ultrasound examination. One patient with DVT had occlusion of her perforator vein. It is unclear whether this

5 Nael R and Rathbun S 31 represented foam sclerosis of the perforator vein or thrombus since the perforator vein ultimately occluded. There were no suspected cases of pulmonary embolus (PE). There are a number of limitations of our study. This study was not a randomized trial but included a consecutive cohort of patients in a closed practice who underwent EFS at the University of Oklahoma Vascular Center during a defined period of time. No treatment other than EFS for the treatment of VVs was performed during this time, limiting direct comparisons to other therapies. Microphlebectomy was not used. Although the severity of the patients symptoms was not quantified using a standardized questionnaire before or after the procedure, and the severity of symptoms and clinical improvement was determined based on the patients report, all patients were evaluated by one of three trained vascular internists who followed a standardized protocol for management of VVs, EFS procedure, and frequency of follow-up. Follow-up included Duplex ultrasound in all patients to document obliteration of treated VVs. There are a number of unique characteristics in performing EFS. The procedure requires some physician training. Ultrasound guidance is necessary for venous mapping and achieving endovenous access. The foam must be prepared immediately prior to the procedure to limit microbubble coalescence and decay. The procedure is typically performed in Trendelenburg s position to theoretically prevent microbubble entry into the deep venous system and to avoid the potential neurologic sequelae, although this advantage has never been confirmed in clinical studies. Other limitations of EFS include the need for more than one injection in some cases to achieve complete obliteration of the affected VVs and for treatment of recurrent varicosities. However, the procedure is simple with minimal discomfort without the need for anesthesia or hospital admission. Most patients who undergo EFS resume their normal daily activity within 24 hours of the procedure. While no formal analysis has been performed, it is likely to be more cost-effective than other more invasive therapies. Other studies have reported comparable success rates in patients undergoing EFS at similar follow-up intervals after the procedure. 7,10 17 In the only published US study, Bergan et al. demonstrated the efficacy of EFS for the management of CVI in 332 patients (261 uncomplicated VVs, 56 severe CVI, six venous angiomata, and nine KT syndrome), with satisfactory obliteration in all treated veins (average of 2.89 treatments/limb) and a 99% ulcer healing rate at the 6-week follow-up. 7 O Hare et al. achieved 93% obliteration in 165 patients (185 truncal veins) at 2 weeks and 74% complete and 10% partial obliteration at 6 months post-treatment with EFS. Ninety-one percent of these patients had a single treatment session. There was no significant difference in obliteration rate between those with complicated (CEAP C4-6) and uncomplicated (CEAP C1-3) VVs. 10 Myers et al. reported a primary success rate of 52.4% and a secondary success rate of 76.8% by ultrasound surveillance at 36 months in 489 patients (807 saphenous veins) treated with EFS. 11 In a systematic review of foam sclerotherapy for the treatment of VVs, Jia et al. reported an 87% occlusion rate and an 8.1% recurrence rate of the treated veins. 12 Other studies report similar results Two recent systematic reviews and meta-analyses including randomized controlled trials, prospective cohort studies and retrospective case series have evaluated the efficacy of EFS compared with other endovenous ablation and surgical stripping. 18,19 The first review evaluated 10 studies using EFS, most involving less than 100 patients all performed outside the US, and found that it was as effective as surgical stripping for the treatment of VVs, but less effective than EVLT. 18 However, this analysis reported anatomic outcomes only and did not evaluate adverse events or patient satisfaction. A second larger meta-analysis included 22 studies using EFS, with one report from the US, 7 and found complete occlusion of treated veins in 86% with 84% of patients venous ulcers healing. 19 The rate of adverse events was similarly low as with our experience. Although EFS was associated with a slightly lower complete occlusion rate compared to EVLT, it was similar or better than RFA or surgical stripping, and patients undergoing EFS had fewer adverse events, particularly DVT and paresthesia. Despite these favorable reviews, there has been some concern about the occurrence of neurological events after EFS. One recent report described two patients who experienced a transient neurological event. 20 The first was an elderly man who underwent perforator vein treatment with foam and suffered altered consciousness and arm weakness that resolved. The patient was later found to have a small intracardiac shunt. In a second patient, it was unclear whether the foam sclerotherapy procedure caused her presyncopal event since she admitted to intentional altered breathing during the procedure that resulted in her becoming dizzy and striking her head against a side table resulting in loss of consciousness. She also recovered fully after the event. Another case reported a patient who developed right upper extremity weakness, frontal headache, and sweating after injection with 20 ml of polidocanol foam (0.5%). 21 The patient s weakness improved after 10 minutes and completely resolved within 2 weeks. The patient was later found to have a PFO. Most studies report an incidence of transient neurologic events after EFS of less than 1% without long-term sequelae. 7,12 16,22 Currently, the presence of PFO is not considered a contraindication to EFS, although a restricted amount of foam is recommended in patients with symptomatic PFO. 23 Screening for PFO in patients undergoing EFS is considered unnecessary. 24 However, the lack of well-controlled studies has limited the acceptance of EFS as standard treatment for VVs despite being used widely in the US and abroad. While the use of liquid sclerosant with sodium tetradecyl sulphate (STS) has been approved by the FDA for the treatment of VVs, foam preparation and injection has not owing to a lack of randomized trials. However, it has been shown that using foam sclerosant is more effective in achieving obliteration of VVs than the injection of liquid sclerosant. 25,26 Currently, a phase III trial using a commercially prepared microfoam is underway in the US (Varisolve: ClinicalTrials.gov NCT ). If found safe and effective, FDA approval is anticipated. While these phase III studies are in progress, there is an

6 32 Vascular Medicine 15(1) urgent need for US consensus guidelines to clarify the use of EFS for the treatment of patients with VVs. In conclusion, we report the safe and effective use of EFS in a large series of patients for the treatment of symptomatic and complicated VVs in a US academic vascular center. Additional prospective, well-controlled studies are needed in the US to clarify the role of EFS for the treatment of VVs and associated complications of CVI. References 1. Callam MJ. Epidemiology of varicose veins. Br J Surg 1994; 81: Bergan JJ, Schmid-Schonbein GW, Smith PDC, Nicolaides AN, Boisseau MR, Eklof B. Mechanism of disease: chronic venous disease. N Engl J Med 2006; 355: Bartholomew JR, King T, Avisesh S, Vidimos AT. Varicose veins: newer, better treatments available. Cleve Clin J Med 2005; 72: Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg 1995; 21: Rigby KA, Palfreyman SJ, Beverley C, Michaels JA. Surgery versus sclerotherapy for the treatment of varicose veins. Cochrane Database Syst Rev 2004; (4): CD Orbach EJ. Sclerotherapy of varicose veins: utilization of an intravenous air block. Am J Surg 1944; 66: Bergan J, Pascarella L, Mekenas L. Venous disorders: treatment with sclerosant foam. J Cardiovasc Surg 2006; 47: Kundu S, Lurie F, Millward SF, et al. Recommended reporting standards for endovenous ablation for the treatment of venous insufficiency: joint statement of The American Venous Forum and The Society of Interventional Radiology. J Vasc Interv Radiol 2007; 18: Tessari L. Nouvelle technique d obtention de la scléromousse. Phlebologie 2000; 53: O Hare JL, Parkin D, Vandenbroeck CP, Earnshaw JJ. Mid term results of ultrasound guided foam sclerotherapy for complicated and uncomplicated varicose veins. Eur J Vasc Endovasc Surg 2008; 36: Myers KA, Jolley D, Clough A, Kirwan J. Outcome of ultrasound-guided sclerotherapy for varicose veins: medium term results assessed by ultrasound surveillance. Eur J Vasc Endovasc Surg 2007; 33: Jia X, Mowatt G, Burr JM, Cassar K, Cook J, Fraser C. Systematic review of foam sclerotherapy for varicose veins. Br J Surg 2007; 94: Darke SG, Baker SJA. Ultrasound-guided foam sclerotherapy for the treatment of varicose veins. Br J Surg 2006; 93: Barrett JM, Allen B, Ockelford A, Goldman MP. Microfoam ultrasound-guided sclerotherapy of varicose veins in 100 legs. Dermatol Surg 2004; 30: Frullini A, Cavezzi A. Sclerosing foam in the treatment of varicose veins and telangiectases: history and analysis of safety and complications. Dermatol Surg 2002; 28: Cavezzi A, Frullini A, Ricci S, Tessari L. Treatment of varicose veins by foam sclerotherapy: two clinical series. Phlebology 2002; 17: Kahle B, Leng K. Efficacy of sclerotherapy in varicose veins - a prospective, blinded, placebo-controlled study. Dermatol Surg 2004; 30: Van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg 2009; 49: Luebke T, Brunkwall J. Systematic review and meta-analysis of endovenous radiofrequency obliteration, endovenous laser therapy, and foam sclerotherapy for primary varicosis. J Cardiovasc Surg 2008; 49: Bush RG, Derrick M, Manjoney D. Major neurological events following foam sclerotherapy. Phlebology 2008; 23: Forlee MV, Grouden M, Moore DJ, Shanik G. Stroke after varicose vein foam injection sclerotherapy. J Vasc Surg 2006; 43: Guex JJ, Allaert FA, Gillet JL, Chleir F. Immediate and midterm complications of sclerotherapy: report of a prospective multicenter registry of 12,173 sclerotherapy sessions. Dermatol Surg 2005; 31: Breu F, Guggenbichler S. European Consensus Meeting on Foam Sclerotherapy, April 4-6, 2003, Tegernsee, Germany. Dermatol Surg 2004; 30: ; discussion Morrison N, Cavezzi A, Bergan J, Partsch H. Regarding Stroke after varicose vein foam injection sclerotherapy [Letter]. J Vasc Surg 2006; 44: ; author reply Rabe E, Otto J, Schliephake D, Pannier F. Efficacy and safety of great saphenous vein sclerotherapy using standardized polidocanol foam (ESAF): a randomized controlled multicenter clinical trial. Eur J Vasc Endovasc Surg 2008; 35: Hamel-Desnos C, Desmos P, Wollmann JC, Ouvry P, Mako S, Allaert FA. Evaluation of the efficacy of polidocanol in the form of foam compared with liquid form in the sclerotherapy of the greater saphenous vein: initial results. Dermatol Surg 2004; 29: