Ultrasound-Guided Sclerotherapy of the Great Saphenous Vein with 1% vs. 3% Polidocanol Foam: A Multicentre Double-Blind Randomised Trial with 3-Year Follow-Up

Article Outline

• Abstract
• Study objectives
• Materials and methods
  • Sample size
  • Statistical methods
• Results
• Discussion
• Funding
• Conflict of Interest
• Ethical approval
• Acknowledgements
• References
• Copyright

Abstract 

Objectives

The aim of this study was to compare the efficacy and side effects of ultrasound-guided foam sclerotherapy of the great saphenous vein using 1% and 3% polidocanol foam with a 3-year follow-up.

Design

A multicentre prospective double-blind randomised clinical trial comparing the efficacy of 1% vs. 3% polidocanol sclerosant foam.

Materials and methods

Patients with incompetence of the great saphenous vein (GSV) in CEAP clinical classes C2–5 (CEAP, Clinical–Etiology–Anatomy–Pathophysiology), with or without incompetence of the sapheno-femoral junction, were included. The Turbofoam^® method was used to create 1% and 3% polidocanol foam, which was injected into the GSV under ultrasound guidance, with a volume not exceeding 10 ml. Further foam sclerotherapy was carried out at 6 weeks, 3 and 6 months if required to abolish persistent venous reflux. The main outcome measure was the absence of saphenous reflux as assessed by ultrasound imaging at 6 months, 1, 2 and 3 years. Clinical severity (Venous Clinical Severity score (VCSS)) and quality of life (the Chronic Venous Insufficiency Questionnaire (CIVIQ)) scores were assessed.

Results

A total of 143 patients were included; 1% group men = 18, women = 55, 3% group men = 19, women = 51. The abolition of venous reflux was: 1% group, 69% and 3% group, 85% at 6 months; 1% group, 79% and 3% group, 78% at 3 years (including additional injections at 6 months). Three asymptomatic thrombo-embolic events (2%) occurred. Local side effects (principally pigmentation and matting) were 9% in the 3% group and 6% in the 1% group at 3 years (N.S.). Clinical severity and quality of life scores improved by more than 20% at 6 months in both the groups, with no difference between the groups.

Conclusions

This is the first randomised clinical trial of ultrasound-guided foam sclerotherapy which is a 3-year follow-up and shows equivalent efficacy of 1% and 3% sclerosant foam.

Clinical trial registration number: 2006-07-05.

Keywords: Superficial venous incompetence, Ultrasound-guided foam sclerotherapy, Polidocanol, Great saphenous vein

Foamed sclerosant drugs are effective in the management of incompetent saphenous veins. Although it is recognised that foamed sclerosants are superior in efficacy to liquid sclerosants, the technique has not yet been standardised and there are wide variations in clinical practice, both in the concentrations used and in the volumes of foam injected. While the initial studies employed foam concentrations of 3%, the maximum concentration that can be used, some preliminary studies have demonstrated that the lower concentrations may have similar efficacy. Furthermore, few studies have been published concerning the long-term outcome of this treatment.

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Study objectives 

The aim of the study was to assess the efficacy and tolerance of sclerotherapy with 1% and 3% polidocanol foam in the treatment of great saphenous vein (GSV) incompetence. The primary objective was the efficacy of abolition of venous reflux at 6 months. The main outcome measure was the abolition of venous reflux in the GSV at 6 months assessed by colour duplex ultrasonography (absence of saphenous reflux in the thigh lasting more than 1 s).

Secondary objectives concerned the clinical outcome and ultrasound assessment of saphenous vein obliteration at 3 years, as well as tolerance of the treatment. The secondary outcomes included clinical evaluation using the Venous Clinical Severity score (VCSS), the quality of-life score using the Chronic Venous Insufficiency Questionnaire (CIVIQ) both at 6 months and 3 years, and absence reflux in the GSV at 3 years. Tolerance to treatment was assessed from local and systemic side effects, which occurred immediately and after 6 months and 3 years of follow-up.

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Materials and methods 

This was a multicentre prospective randomised, double-blind clinical trial with two arms and no placebo group, with direct benefit to the patient. Patients considered for inclusion in this trial had primary incompetence of the GSV with or without incompetence of the sapheno-femoral junction. Details of the inclusion and exclusion criteria are presented in Table 1. The study was approved on 12 November 2003 by the South East France regional ethics committee (registration number 03/ARMV/1) and conforms to the Helsinki declaration (1964, version Hong Kong, 1989). All the patients were given a copy of the written study information document approved by the Ethics Committee and gave written informed consent before inclusion in the trial. The clinical trial registration number is 2006-07-05.

Table 1. Inclusion and exclusion criteria for the study patients.

The sclerosant drug used was polidocanol (Kreussler Pharma, Wiesbaden, Germany) and patients were randomised to receive a concentration of 1% or 3% (Fig. 1). The randomisation was centralised and coordinated by a computer system. Randomisation and the management of the stocks for double-blind use were performed by the Clinical Research Centre in collaboration with Kreussler Pharma who supplied the ampoules of polidocanol without commercial labels. The randomisation list was computer centralised, without stratification, equilibrated and with blocks of variable size. Envelopes were distributed to the investigating centres with numbers corresponding to the sclerosant lots. Double blinding was thus maintained for all the injections and until the end of patient follow-up (3 years in total).

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• Figure 1 

  Study Flow Chart.

Sclerosant foam was obtained using a Turbofoam^® system (Kreussler Pharma, Wiesbaden, Germany). The sclerosant liquid was mixed with sterile air to obtain a liquid-to-air ratio of 1:5. The foam was injected immediately after production or within 170 s.

Nine investigation centres were selected with investigating physicians who were experienced in the practice of ultrasound-guided sclerotherapy. They had personally performed at least 300 sclerotherapy procedures during the previous 3 years. In addition, each investigating physician was trained in the study procedure. The colour Doppler ultrasound apparatus used had to be fitted with a high-resolution probe with an imaging frequency of 7.5 MHz or higher and a system for the reproduction and/or storage of images.

The initial treatment consisted of placing a short intravenous catheter (20-G 1.1 × 48 mm or butterfly 22-G 0.9 × 22 mm) in the lower third of the GSV in the thigh under ultrasound guidance. In this region, the GSV is at its closest to the fascia superficialis. The treatment was performed under ultrasound control with gel and sterile gloves. The volume of foam to be injected was estimated from the quantity that produced venous spasm, but did not exceed 10 ml. Compression of 34–49 mmHg was achieved by applying an adhesive foam bandage (Elastomousse^®, BSNmedical, Le Mans, France) and followed by a further layer of Elastoplast^® (BSNmedical, Le Mans, France). Bandages were applied immediately after the treatment to be worn continuously for 3 days. They were then removed and a class 2 elastic compression stocking (Oedema Twin 25, Kreussler Pharma, Wiesbaden, Germany; 23–32-mmHg compression) was worn during the day for 15 days.

During the follow-up period, patients were assessed clinically and by duplex ultrasound imaging at 8 days, 6 weeks, 3 months, 6 months, 1 year, 2 years and 3 years. Further ultrasound-guided foam sclerotherapy was allowed by the protocol at 6 weeks, 3 and 6 months. The investigators performed both sclerotherapy and vascular sonography. During these additional sclerotherapy sessions, a volume of up to 4 ml of foam was allowed to be injected into veins with a persistent lumen of at least 2 mm in diameter and 50 mm in length. A re-canalised vein without the presence of venous reflux or with reflux lasting less than 1 s was not considered a failure and was not re-injected. The investigator and patient remained blinded to the treatment that was administered throughout the 3-year study period. In the event of a side effect (including thrombo-embolic events), there was no need for unblinding as knowledge of the concentration used would in no respect change what is to be done.

Systematic clinical and ultrasound surveillance were performed at 8 days, 6 weeks, 3 months, 6 months, 1 year, 2 years and 3 years. At 8 days, a duplex ultrasound investigation was performed. Three views were taken: the sapheno-femoral junction and the sural veins, with and without compression. The following items were noted: obliteration or not flush with the sapheno-femoral junction, persistence of patent collaterals, persistence of a venous stump and its length and whether any reflux persisted. Each segment of the GSV was studied (the proximal, middle and distal portions) noting whether obliteration had been achieved or not, and whether this was complete or not, its diameter, the presence of reflux or not and its extent. In the case of thrombosis, the event had to be systematically documented by photography. At the other visits (6 weeks, 3 months, 6 months, 1 year, 2 years and 3 years), clinical examination was performed, the Clinical–Etiology–Anatomy–Pathophysiology (CEAP) score determined and observations regarding pain, superficial thrombosis, pigmentation, cutaneous inflammation, matting and induration had to be systematically recorded (Table 3).

A critical events committee made up of three non-investigator physicians classified the adverse events with respect to the treatment received. Every reported event was examined by the committee. Events were classified as expected local side effects or systemic (visual symptoms, etc.) and serious adverse events (deep vein thrombosis, pulmonary embolism, stroke, etc.). Following consultation of the patient's medical records, the committee decided on the imputability. Patients completed the VCSS and CIVIQ questionnaires of quality of life at inclusion, 6 months, 1 year, 2 and 3 years.², ³

Sample size 

The initial hypothesis assumed 90% success for the main outcome measure (abolition of reflux) in the two groups. The definition of therapeutic equivalence was with a δ value of 10%. A one-sided test was used with an α risk of 0.05 and β risk of 0.10. We obtained a sample size of 150 patients using the nQuery Advisor program version 7.0.

Statistical methods 

The statistical analysis was performed on an intention-to-treat basis. Categorical variables are expressed as frequencies and percentages, and continuous variables as the mean and standard deviation. The principal outcome and efficacy at 6 months and 3 years were tested using a test of equivalence by the Hauck–Anderson method. Secondary outcomes were tested by a chi-square test without correction for continuity for the qualitative variables and by a Student's t-test for the continuous variables. An analysis of variance (ANOVA) for repeated measurements was also performed (comparison M0/M6/1y/2y/3y). The statistical tests used a type 1 error of α = 0.05. Statistical analysis was performed using Stata (version 10.0; Stata Corp, College Station, TX, USA). The equivalence tests were performed with Equiv Test (Statistical Solutions).

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Results 

Between March 2004 and May 2005, 143 patients were included (Fig. 1). At 3 years, 3.5% were lost to follow-up. Table 2 gives the characteristics of the population. The abolition of significant reflux in the GSV was 69% for 1% foam and 85% for 3% foam at 6 months and 82% for 1% foam and 90% for 3% foam at 1 year (including the additional injection at 6 months) and 79% for 1% foam and 78% for 3% foam at 3 years. The results are equivalent at 3 years (p = 0.05).

Table 2. Baseline characteristics of the treated population.

VCSS = Venous Clinical Severity Score; CIVIQ 2 = a French Quality of Life questionnaire.

Table 3. Local side effects (6 months and 3 years) and thrombo-embolic complications in the 1% and 3% groups.

The volumes of foam injected initially were a mean of 6.1 ml for the 1% group and 6.4 ml for the 3% group. At least one additional injection was required for 49% of patients in the 1% group and 31% in the 3% group, which is a significant difference (p = 0.04). The percentage of patients requiring an additional injection in the 1% and 3% groups, respectively, was 24% and 12% at 6 weeks, 14% and 12% at 3 months and 31% and 19% at 6 months. The presence or absence of sapheno-femoral junction incompetence did not influence the efficacy of treatment.

The clinical severity scores assessed by VCSS and of quality of-life measured by the CIVIQ questionnaire improved following the initial treatment session (Fig. 2), with a reduction of more than 20% in the scores in each group after 6 months and no significant difference between the two groups.

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• Figure 2 

  Changes in VCSS and CIVIQ scores between inclusion and 3 year visit for the two treated groups.

At 3 years, local side effects were 9% in the 3% group and 6% in the 1% group (p = 0.46) (Table 3). Patients who had at least one local complication at 6 months had a VCSS score that was significantly higher compared to those with no complication (p < 0.01). By contrast, the CIVIQ test score is similar (p = 0.73). At 3 years, there is no significant difference for either test.

Three thrombo-embolic events (2%) were reported, two of which were in the 1% group. Three cases of asymptomatic deep vein thrombosis were detected at day 8 and no patient suffered pulmonary embolism: one proximal thrombosis (femoral vein), one thrombosis of a distal perforating vein associated with a muscle vein thrombosis (soleal vein) and one distal muscle vein thrombosis (medial gastrocnemius vein).

In all the three cases, tests revealed associated thrombophilia (one heterozygous mutation of factor V Leiden gene mutation, one heterozygous prothrombin gene mutation and one of acquired anti-thrombin III deficiency). After anticoagulant treatment for 6 weeks, the thrombi completely disappeared in all three cases. No case of migraine or other neurological event occurred during the study.

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Discussion 

Several studies have shown that foamed sclerosant drugs are more effective in obliterating saphenous trunks than liquid sclerosants.⁴, ⁵, ⁶, ⁷ Foam sclerotherapy has revolutionised the practice of sclerotherapy, permitting effective obliteration of saphenous trunks as well as varices. There is great variation in the way in which this technique is used in clinical practice. Many variations in technique have not been evaluated as to their influence on the final outcome. The meta-analysis published by Jia gives poorer results for foam sclerotherapy compared to surgery (relative risk 0.86).⁸ Nevertheless, she points out that there are many limitations in the methods used for comparing the techniques.

An important factor in determining the outcome is the experience of the physician performing the treatment and the method he uses. This is demonstrated in the study by Wright et al. when assessing the efficacy of Varisolve^®,⁹ which is a microfoam containing a 1% aqueous solution of polidocanol incorporating oxygen and carbon dioxide to create a foam. It may not be strictly comparable to polidocanol foam made using the Turbofoam^® method of our study. Excellent efficacy was reported in the patient group treated by a phlebologist experienced in sclerotherapy (94%) but was considerably lower when performed by a surgeon (68%).⁴, ⁶ In our study, we minimised this bias by ensuring all investigating physicians were experienced sclerotherapists.

Other variables, such as the type and concentration of the sclerosant drug, the type of gas, the liquid/gas ratio, the method of foam preparation (temperature and pH), the time needed for foam preparation and use and bubble size, could influence the efficacy. To improve foam quality, techniques have been developed.¹⁰ In our study, the foam was produced in an automated manner with a Turbofoam^® apparatus to be as reproducible and homogeneous as possible.¹¹ The aim of the study was focussed on the quantity of sclerosant injected, which can vary in two parameters: the volume injected and the concentration used.

Patients included in this study had incompetence of the GSV with or without incompetence at the sapheno-femoral junction. The efficacy of sclerosant foam treatment for saphenous trunk incompetence that includes the sapheno-femoral junction has been reported previously.¹², ¹³ We chose to limit the diameter of the GSV in this study to ≤8 mm and to exclude affected perforating or small saphenous veins so as to make the characteristics of the treated veins as homogeneous as possible. The volume of foam injected was defined as the volume that produced venous spasm. Hamel-Desnos reported a positive predictive value of 100% for this criterion in predicting abolition of reflux in the sclerosed vein.¹³ The latest European consensus on sclerotherapy with foam has questioned the appropriateness of this predictive value: it does not appear to be a good indicator of the long-term outcome.¹⁴ We used this criterion to indicate when sufficient foam had been injected, and limited the maximum volume to 10 ml per injection session, a volume in agreement with the recommendations of several consensus reports.¹⁵, ¹⁶ Using this strategy, we consider that we performed a double-blind randomised trial that included assessment of the injected volume required at each concentration, whilst limiting biases associated with foam production and operator-dependent factors.

We found equivalence of outcome in the 1% and 3% treatment groups at 3 years, although at 6 months the outcome appeared to be slightly less successful in the 1% group. The improvement for the 1% group at 3 years could possibly be explained by additional at 6 months where venous reflux persisted. There was no significant difference in efficacy whether the sapheno-femoral junction was competent or not and whatever the treatment group was. The volumes injected at inclusion in the two groups were similar. To our knowledge, this is the only double-blind study to assess the efficacy of foam with a follow-up at 3 years. In a prospective double-blind study of 80 patients, Ceulen concluded that sclerosant foam at 3% (80%) was more effective than 1% foam (70%) at 1 year.¹⁷ In a comparative study, Hamel-Desnos shows an efficacy at 68% with 1% and 69% with 3% sclerosant foams at 2 years.¹ In this study, venous spasm was the criterion defining the volume of sclerosant to be injected. The first injection consisted of a volume of 2.5 ml to be repeated a maximum of three times, depending on the occurrence of a spasm. Efficacy was assessed at up to 2 years but without the possibility of additional injections, in contrast to our procedure.¹ Similar efficacy was observed in the two treatment groups, the mean volume injected was similar (4.4 ml in the 3% group and 4.6 ml in the 1% group). Our study provides additional information on the longer-term results compared to these studies. It suggests equivalent efficacy between 1% and 3% at medium term, with fewer injections for the 3% group.

Quality of life has been assessed in few studies of foam sclerotherapy. Some studies have included legs, and not patients, irrespective of the functional improvement to the patient.¹⁸ Furthermore, the scales used for evaluation are not always specified.¹² We have assessed the functional improvement achieved by foam sclerotherapy, which is already apparent 6 months after treatment in both the groups. The scales we have used were the VCSS² and the CIVIQ test, a French quality of life questionnaire for patients with chronic lower limb venous insufficiency.³ In our study, we found significant correlation between patients having at least one local complication at 6 months and a higher VCSS score compared to those having no complication. No such correlation was found for the quality of life.

The local and systemic side effects of sclerosant foam are well known. However, there is disagreement in the literature regarding any link between the concentration or the volume of foam and local side effects. Some authors consider that local side effects are related to the volume of foam injected¹² but this does not seem to be the case in our study. In the study by Ceulen, pigmentation was more frequent in the 3% group (18% vs. 8.1%) for similar total volumes injected in the two groups (5.3 ml for the 1% group vs. 5.1 ml for the 3% group).¹⁷ The side effects appear to be more closely linked to the concentration used rather than to the volume injected. The results of our study are consistent with this, with similar volumes resulting in more pigmentation at 3 years in the 3% group.

The general complications of this technique are the same as those for conventional sclerotherapy. Limited data are available in the literature on the rate of complications as a function of concentration used. The passage of sclerosant foam into deep veins is less when small volumes of foam are used.¹⁹ The occurrence of complications varies depending on the studies considered. Jia undertook a meta-analysis of 69 studies of treatment by sclerotherapy for venous insufficiency.⁸ Serious side effects are estimated to be between 0% and 5.7%, with one case of pulmonary embolism in a series of 1316 patients treated and a percentage of deep vein thrombosis of between 0.1% and 18%.²⁰, ²¹ The disadvantages are mainly characterised by the occurrence of venous thrombo-embolic reactions due to undiagnosed thrombophilia, as in our study. It should be noted that no neurological event that could be attributed to the possible presence of a foramen ovale was reported during our study.¹⁴

Our study shows equivalent efficacy of 1% and 3% sclerosant foam used to treat truncal incompetence of the GSV as assessed by ultrasound imaging and by clinical severity score and the CIVIQ quality- of-life questionnaire. The trial concerned only treatment of GSV reflux and excluded other associated conditions such as the perforating or small saphenous veins that are encountered in clinical practice. The protocol allowed additional injections if necessary, to reflect clinical practice, while at the same time limiting bias. The assessment of the efficacy of sclerotherapy used a completely different approach to that of other vein ablation treatments, such as surgery, radiofrequencies or laser, which usually require a single treatment session. From the scientific point of view, this makes sclerotherapy more difficult to compare with the other techniques.

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Funding 

Grant from the French association for vascular medicine, donation of Turbofoam machines for each investigating centre (8) and batches of polidocanol at 1% and 3% without commercial labels by Kreussler Pharma.

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Conflict of Interest 

None.

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Ethical approval 

The study was approved on 12 November 2003 by the South East France regional ethics committee (registration number 03/ARMV/1) and conforms to the Helsinki declaration (1964, version Hong Kong, 1989).

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Acknowledgements 

We thank the Rhone Alps Vascular Physicians Association for sponsoring the study; Kreussler Pharma for donating 8 Turbofoam machines and providing polidocanol at 1% and 3% without commercial labels; the investigating physicians: Addala A, Bucci F, Gachet G, Gillet JL, Gobbin JP, Lebrun D, Laurent Spini; Proust M for data collection, Genty C for the statistical analysis, Foote A for translating and critically reading the manuscript, and Pichot O, MD, Hamel-Desnos C, MD for their help in conception and study design.

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References 

1. Hamel-Desnos C, Ouvry P, Benigni J-P, Boitelle G, Schadeck M, Desnos P, et al. Comparison of 1% and 3% polidocanol foam in ultrasound guided sclerotherapy of the great saphenous vein: a randomized double-blind trial with 2 year-follow-up. “The 3/1 study”. Eur J Vasc Endovasc Surg. 2007;34:723–729
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (659 KB)
   • CrossRef
2. Rutherford RB, Padberg FT, Comerota AJ, Kistner RL, Meissner MH, Moneta GL. Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg. 2000;31:1307–1312
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (33 KB)
   • CrossRef
3. Launois R, Reboul-Marty J, Henry B. Construction and validation of a quality of life questionnaire in chronic lower limb venous insufficiency (CIVIQ). Qual Life Res. 1996;5:539–554
   • View In Article
   • MEDLINE
   • CrossRef
4. Rabe E, Otto J, Schliephake D, Pannier F. Efficacy and safety of great saphenous vein sclerotherapy using standardized polidocanol foam (ESAF): a randomized controlled multicentre clinical trial. Eur J Vasc Endovasc Surg. 2007;35:238–245
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (169 KB)
   • CrossRef
5. Alos J, Carreno P, Lopez JA, Estadella B, Serrat-Prat M, Marinel-Lo J. Efficacy and safety of sclerotherapy polidocanol foam: a controlled clinical trial. Eur J Vasc Endovasc Surg. 2006;31:101–107
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (109 KB)
   • CrossRef
6. Hamel-Desnos C, Desnos 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 sclerotherapy of the greater saphenous vein: initial results. Dermatol Surg. 2003;29(12):1170–1175
   • View In Article
   • MEDLINE
   • CrossRef
7. Ouvry P, Allaert FA, Desnos P, Hamel-Desnos C. Efficacy of polidocanol foam versus liquid in sclerotherapy of the great saphenous vein: a multicentre randomised controlled trial with a 2 year follow-up. Eur J Vasc Endovasc Surg. 2008;36:366–370
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (186 KB)
   • CrossRef
8. Jia X, Mowatt G, Burr JM, Cassar K, Cook J, Fraser C. Systematic review of foam sclerotherapy for varicose veins. Br J Surg. 2007;94:925–936
   • View In Article
   • CrossRef
9. Wright D, Gobin JP, Bradbury AW, Coleridge-Smith P, Spoelstra H, Berridge D, et al. Varisolve^® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial. Phlebology. 2006;21:180–190
   • View In Article
   • CrossRef
10. Rao J, Goldman MP. Stability of foam in sclerotherapy: differences between sodium tetradecyl sulfate and polidocanol and the type of connector used in the double-syringe system technique. Dermatol Surg. 2005 Jan;31(1):19–22
    • View In Article
    • MEDLINE
    • CrossRef
11. Hamel-Desnos C, Desnos P. L'écho-sclérothérapie à la mousse en 2004. Technique de la ponction-injection directe. Phlébologie. 2004;57:289–300
    • View In Article
12. Barrett JM, Allen B, Ockelford A, Goldman MP. Microfoam ultrasound-guided sclerotherapy treatment for varicose veins in a subgroup with diameters at the junction of 10 mm or greater compared with a subgroup of less than 10 mm. Dermato Surg. 2004;30:1386–1390
    • View In Article
13. Hamel-Desnos C, Allaert FA, Benigni J-P, Boitelle G, Chleir F, Ouvry P, et al. Etude 3/1.Mousse de Polidocanol 3% versus 1% dans la grande veine saphène: premiers résultats. Phlébologie. 2005;58:165–173
    • View In Article
14. Breu FX, Guggenbichler S, Wollmann JC. Duplex ultrasound and efficacy criteria in foam sclerotherapy from the 2nd European consensus meeting on foam sclerotherapy 2006, Tegernsee, Germany. VASA. 2008;37:90–95
    • View In Article
15. Breu FX, Guggenbichler S. European consensus meeting on foam sclerotherapy, April, 4–6, 2003, Tegernsee, Germany. Dermatol Surg. 2004;30:709–717
    • View In Article
    • MEDLINE
    • CrossRef
16. Gachet G, Spini L. Référentiel sur le traitement endovasculaire des varices par injections échoguidées de mousses fibrosantes: le consensus d'experts de Grenoble. Phlébologie. 2008;61(2):196–206
    • View In Article
17. Ceulen RPM, Bullens-Goessens YIJM, Pi-Van De Venne SJA, Nelemans PJ, Veraart JCJM, Sommer A. Outcomes and side effects of duplex-guided sclerotherapy in the treatment of great saphenous veins with 1% versus 3% polidocanol foam: results of a randomized controlled trial with 1-Year follow-up. Dermatol Surg. 2007;33:276–281
    • View In Article
    • MEDLINE
    • CrossRef
18. Barrett JM, Allen B, Ockelford A, Goldman MP. Microfoam ultrasound-guided sclerotherapy of varicose veins in 100 legs. Dermatol Surg. 2004;30:6–12
    • View In Article
    • MEDLINE
    • CrossRef
19. Myers KA, Jolley D. Factors affecting the risk of deep venous occlusion after ultrasound-guided sclerotherapy for varicose veins. Eur J Vasc Endovasc Surg. 2008;36(5):602–605
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (99 KB)
    • CrossRef
20. 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(2):123–128
    • View In Article
    • MEDLINE
    • CrossRef
21. 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(1):116–121
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (182 KB)
    • CrossRef