Abstract
Objectives
This study aimed to analyze the clinical outcomes of ultrasound-guided foam sclerotherapy (UGFS) in patients with lower limb symptoms and pathological reflux localized to the great saphenous vein (GSV) below the knee.
Methods
This study is a retrospective analysis of patients diagnosed with valve dysfunction limited to the area below the knee of the GSV who underwent UGFS with physician-compounded sclerosing foam between March 2014 and March 2024. Patients who did not have duplex ultrasonography follow-up after UGFS were excluded.
Results
A total of 49 patients (53 lower limbs) were included in the study, with a male-to-female sex ratio of 1:1.8. The mean age was 53 years (26–84 years), and the mean body mass index was 23.5 kg/m2. The distribution of clinical–etiological–anatomical–pathophysiological clinical class was C0 in 11 patients, C1 in 17 patients, C2 in 23 patients, C4a in 1 patient, and C6 in 1 patient. The mean follow-up was 23 months. There were three cases of thrombophlebitis after the procedure, and no major complications. Recanalization with reflux was noted in 3 of 53 lower limbs (5.7%). None of the patients with recanalized lower limbs complained of lower limb symptoms.
Conclusions
UGFS performed on the below-knee segment of the GSV appears to be associated with a low rate of complications and a favorable mid-term recanalization profile.
Introduction
For patients with symptomatic great saphenous vein (GSV) valvular insufficiency and a clinical–etiological–anatomical–pathophysiological (CEAP) classification 1 of C2 or higher, the preferred treatment options include endovenous thermal ablation—such as radiofrequency ablation or endovenous laser treatment—and non-thermal, non-tumescent modalities, such as cyanoacrylate closure (CAC) or mechanochemical ablation (MOCA). When endovenous thermal ablation is performed for GSV with axial reflux, it is usually treated from the groin to the knee because there is a possibility of thermal damage to the saphenous nerve located close to the vein. 2 If follow-up after endovenous closure of the GSV in the above-knee segment reveals residual reflux in the below-knee segment and symptoms in the lower extremities, CAC or MOCA can be used to close the below-knee segment of the GSV. However, these are expensive treatments, and applying them to the below-knee segment may be unaffordable if endovenous thermal or endovenous non-thermal treatments were previously performed in the above-knee segment.
Ultrasound-guided foam sclerotherapy (UGFS) is a non-thermal, non-tumescent technique reported to have inferior occlusion rates compared to other treatments3–7 and is not the first choice. However, it is a low-cost, easy-to-apply, and cost-effective treatment that can be repeated. Most studies on UGFS have focused on the treatment of the above-knee segment, with few reports on outcomes of treatment of the below-knee segment.3–8
This study aimed to analyze the clinical outcomes of UGFS for symptomatic lower extremity patients with pathologic reflux localized to the below-knee segment of the GSV and to analyze the technical success rate.
Methods
This retrospective cohort study was approved by the Institutional Review Board of the National Health Insurance Service Ilsan Hospital on September 12, 2024 (IRB No. NHIMC 2024-08-030), and the requirement for informed patient consent was waived. We have de-identified all patient details. This study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 2024. The reporting of this study conforms to STROBE guidelines. 9
Patients who consecutively underwent UGFS between March 2014 and March 2024 for chronic venous disease, with valvular incompetence in the below-knee segment of the GSV confirmed by duplex ultrasonography (DUS), were included in the study. None of the previously published studies included the patient cohort analyzed in the present study. Patients who did not have DUS follow-up after UGFS were excluded. Patients with lower extremity symptoms that could be caused by chronic venous disease were classified according to the CEAP classification. In addition, gender, weight, height, and past medical history were recorded. DUS was performed with a LOGIQ S7 Expert (GE Healthcare, Sungnam, South Korea) using a 3.6–12 MHz linear probe and was performed in an upright position with weight bearing on the contralateral lower limb of the lower extremity being examined. The GSV was examined for reflux at the saphenofemoral junction (SFJ), proximal thigh, knee, and proximal calf, and the deep veins were examined for reflux in the common femoral vein at the SFJ and the popliteal vein at the popliteal fossa. Pathologic reflux was defined as a reflux duration of greater than 0.5 s for saphenous veins and greater than 1.0 s for deep veins. 10 If there was pathologic reflux localized to the below-knee segment of the GSV on DUS and accompanied by lower extremity symptoms, but the clinical class was C0 or C1, conservative treatment such as compression stockings or medication was performed for at least 3 months, followed by UGFS if the patient preferred invasive treatment. If the clinical class was C2 or higher, UGFS was performed rather than conservative treatment.
For UGFS, the course of the GSV below the knee was first marked under ultrasound guidance. A 20-gauge angio-catheter was then inserted into the GSV at the distal calf under ultrasound guidance, and the patient's leg was elevated at least 30 degrees. Sclerosant was sodium tetradecyl sulfate (Fibrovein™; STD Pharmaceutical Products, Hereford, UK) at a concentration of 1.0% for saphenous vein external diameter greater than or equal to 2 mm and less than 3 mm, 1.5% for greater than or equal to 3 mm and less than or equal to 4 mm, and 3% for greater than or equal to 4 mm. The sclerosant was stored in a refrigerator for approximately 5 min before use. It was immediately injected after 30 agitations using the Tessari technique to create foam using a 1:3 ratio of sclerosant to air. 11 During the procedure, the patient was asked to move the ankle of the treated lower limb to perform dorsi flexion and plantar flexion.
After the procedure, an eccentric compression dressing was applied by wrapping cotton gauze along the course of the GSV below the knee, which was pre-marked before the procedure, followed by a self-adhesive bandage (ROGG Latexfree Haft-Crepp; KOB GmbH, Germany), and then a short stretch compression bandage (CEB Ideal Cohesive Bandage: Karl Otto Braun GmbH & Co. KG, Germany) was applied on top of it, and the patient was allowed to walk for 15 min, checked for complications, and sent home. Patients were asked to visit the outpatient clinic on post-operative day 2 to remove the compression bandage and apply a knee-high compression stocking of 20–30 mmHg, which was advised to be worn 24 h a day for 1 week. Thereafter, they were instructed to wear compression stockings from morning to evening for 2 weeks. Outpatient visits were arranged 6 and 12 months post-procedure for DUS follow-up. At baseline and during each follow-up visit, quality of life was appraised by the Aberdeen Varicose Vein Questionnaire (AVVQ). 12 Beyond 12 months, follow-up DUS examinations were performed during outpatient visits at intervals of no less than 6 months, generally prompted by patient-reported recurrence of lower extremity symptoms. Technical success was defined as complete occlusion of the treated segment.
The data were analyzed using software Statistical Package for the Social Sciences (IBM SPSS Statistics, version 21, SPSS Inc., Chicago, IL), and Paired-sample t-tests were conducted to compare mean AVVQ scores before the procedure and at 1-year follow-up.
Results
During the study period, 78 patients (85 limbs) underwent UGFS, but after excluding 29 patients who were lost to follow-up, 49 patients (53 limbs) were included. The median follow-up was 23 months (range 6 months to 116 months). Twelve cases were followed for 6 months, 24 cases were followed for 12 months, and 17 limbs were followed for more than 24 months. One lower limb was analyzed as a single case, and the demographic data of the included limbs are shown in Table 1. Among the eligible lower limbs, 18 cases had reflux confined to the below-knee segment and underwent UGFS of the below-knee segment without treatment of the above-knee segment. Thirty-five cases were lower extremities with axial reflux within the GSV. They were treated with UGFS when DUS follow-up 6 months after treatment of the above-knee segment showed residual reflux in the below-knee segment and lower extremity symptoms.
Demographic data.
BMI: body mass index; CEAP: clinical etiological anatomical pathological classification; GSV: great saphenous vein; EVLT: endovenous laser treatment; RFA: radiofrequency ablation; CAC: cyanoacrylate closure; HLS: high ligation and stripping.
Pre-procedural ultrasound results are shown in Table 2. All of the deep vein refluxes (DVRs) had valvular failure of the popliteal vein.
Result of the duplex ultrasonography prior to the UGFS.
UGFS: ultrasound-guided foam sclerotherapy; DVR: deep vein reflux; GSV: great saphenous vein.
There were no major complications, including deep vein thrombosis, with thrombophlebitis observed in three cases (5.7%) after the procedure.
Only 21 patients, representing 43% of the total cohort, completed both pre- and post-procedure AVVQ assessments. However, the mean AVVQ score decreased from 4.31 points pre-procedure to 1.96 points at final follow-up, demonstrating a statistically significant improvement (p < 0.01).
At follow-up, no evidence of recanalization or new-onset reflux was observed in the above-knee segment of the GSV. In contrast, recanalization of the below-knee segment of the GSV was confirmed in 3 of 53 lower limbs (5.7%), all of which were associated with reflux. The follow-up time before diagnosis of recanalization was 6 months in one case, 12 months in one case, and 28 months in one case. Of the three lower limbs with confirmed recanalization, one had popliteal vein reflux, and the other two had no DVR. All three cases with confirmed recanalization were female, with a mean body mass index of 23.3 kg/m2 and a mean age of 49. The pre-procedure diameter of the target vein averaged 2.9 mm (2–4 mm), and the mean duration of reflux was 4.4 s (1.86–5.90 s). The pre-procedure clinical classes of the recanalized lower limbs were one C0s, one C1s, and one C4as. None of the recanalized lower limb patients complained of lower limb symptoms, so no further treatment was given.
Discussion
UGFS is an endovenous non-thermal treatment that involves the injection of a sclerosant into a vein under ultrasound guidance to induce vessel closure. Compared to surgical treatment or endovenous thermal ablation, such as radiofrequency ablation or endovenous laser treatment, technical success rates are reported to be low, with 1-year closure rates ranging from 51% to 84%,3,5 5-year closure rates ranging from 23% to 91.9%,4,7,8 and 8-year closure rates ranging from 33%. 6 The reason for the lower technical success rate of UGFS compared to endovenous thermal ablation or surgical treatment is that UGFS damages the intima of the vein to induce vein closure, whereas surgical treatment involves removal of the vein with valve failure, and endovenous thermal ablation can damage all layers of the vein wall using radiofrequency or laser, so the technical success rate is thought to be higher than UGFS. However, a literature review on UGFS shows considerable variation in technical success rates between researchers.3–8 Factors that may contribute to the variation in technical success rates include vein diameter, sclerosant concentration, differences in sclerosant injection methods, and the method and duration of post-procedure compression therapy. Hamel-Desnos et al. 13 showed that adding compression stockings after UGFS did not affect closure rates. However, this study evaluated outcomes at 28 days post-procedure, a very short observation period that is not comparable to other studies. A study that reported a 1-year technical success rate of 51% used a 24-h compression stocking for 3 days only, followed by 11 days of daytime compression stocking wear, 5 and a study that reported a 5-year closure rate of 23% used a 48-h compression bandage after the procedure, followed by 2 weeks of daytime compression stocking wear at 23–32 mmHg. 4 In contrast, a study that reported a 5-year occlusion rate of 90% or greater showed a somewhat higher intensity and longer duration of post-procedure compression therapy. Baeshko et al. reported a 5-year occlusion rate of 91.9% and used cotton wool padding along the treated vein route, followed by short stretch compression bandaging, and then Class 2 medical compression stockings worn 24 h a day for 7 days. After 7 days, the compression stocking was worn during the day for 4 weeks. 8 Therefore, based on previous reports, it is likely that the method and duration of compression during the post-procedure period significantly impact the venous closure rate due to the nature of UGFS, which only damages the endothelium in the vein. In this study, we applied a three-layered compression dressing including eccentric compression to the treated area for 48 h after UGFS, followed by a 24-h compression stocking for 1 week and then a daytime compression stocking only for 2 weeks, resulting in a closure rate of 94.3% at a mean 23-month follow-up, which we believe is relatively high compared to other reports.3–8
In addition to the method and duration of post-procedural compression therapy, three other factors may have influenced the technical success rate in this study. The first is the diameter of the vein being treated. Several studies have reported that UGFS has a good therapeutic effect when the diameter of the GSV is not large.14–16 The European Society for Vascular Surgery 2022 clinical practice guidelines recommend that UGFS be considered when the GSV diameter is less than 6 mm. 17 The diameter of the veins treated in this study ranged from 2 to 5 mm, and it is thought that the relatively small diameter (<6 mm) may have influenced the occlusion rate after UGFS. The second is the temperature of the sclerosant. In this study, the sclerosant was stored in the refrigerator for about 5 min before the procedure, and a lower temperature of the sclerosant may increase the stability of the foam and induce spasm of the vessel, which may increase the procedure's effectiveness. Third, the legs were kept elevated by 30 degrees during the procedure to reduce the diameter of the vein, which helps the foam to align the inner wall of the vein circumferentially and increases the residence time of the sclerosant in the target vein.
This study has several limitations. First, the UGFS procedure was confined to the below-knee segment of the GSV, making direct comparison with studies targeting the above-knee segment difficult. Second, the retrospective design, rather than a randomized approach, may have introduced unmeasured bias. Accordingly, future randomized prospective studies are warranted to evaluate the efficacy of UGFS for the below-knee GSV in comparison with endovenous thermal or non-thermal techniques, such as CAC. In addition, although the analysis suggested an improvement in quality of life after the procedure, only 21 patients (43% of the total) completed the follow-up questionnaire. As a result, drawing definitive conclusions regarding post-procedure quality-of-life changes was deemed inappropriate, and these findings were excluded from the conclusions. Instead, emphasis was placed on anatomical success rates. Further studies with larger patient cohorts are needed to investigate the relationship between quality-of-life outcomes and anatomical success rates following UGFS in the below-knee segment of the GSV.
Conclusions
UGFS performed on the GSV segment below the knee with valvular insufficiency demonstrated a low recanalization rate, comparable to that of endovenous thermal ablation. However, further prospective studies with larger patient cohorts are warranted to validate these treatment outcomes.
Footnotes
Author contributions
Ki-Pyo Hong was involved in writing the manuscript, developing the protocol, gaining ethical approval, and analyzing data.
Funding
The author disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: A research grant from NHIS Ilsan Hospital funded this study (grant number NHIMC-2024-CR-062).
Declaration of conflicting interest
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data availability statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.