Eight year results of patients with varicose vein underwent endovenous occlusion using n-butyl cyanoacrylate

Abstract

Objective

To present the 8-year results of 180 patients on whom we performed endovenous occlusion using N-butyl cyanoacrylate in 2014.

Methods

We have previously published the 30-month results for 168 patients available for follow-up. Thirteen more patients were lost to follow-up in the 8-year research period. The remaining 155 patients underwent clinical examinations and their Venous Clinical Severity Score (VCSS) values were recorded. Doppler ultrasonography was performed, and whether the saphenous vein was occluded, or whether partial or complete recanalization were present was evaluated.

Results

The mean age of the 155 patients we were able to follow-up was 47.4 ± 11.8 years. Sixty-eight of the patients were men, and 87 were women. Mean VCSS scores were 10.2 before the procedure, 2.7 at 30 months, and 2.6 ± 0.7 at 8 years. Complete recanalization was observed in seven patients over the 8 years, and partial recanalization in six. Occlusion rates were 94.1% at 30 months and 91.7% at 8 years.

Conclusion

The long-term results of the use of N-butyl cyanoacrylate in the treatment of patients with varices are highly satisfying in terms of a high ablation rate.

Keywords

N-butyl cyanoacrylate glue ablation varicose vein

Introduction

Endovenous ablation techniques are currently widely used in the treatment of varicose veins. Thermal ablation methods began being widely employed after the first use of laser ablation in 1999 and radiofrequency ablation in 2002, and are still in use today. Advances have taken place in these methods over the years. However, the application of tumescent anesthesia is essential in thermal ablation techniques. This can sometimes be uncomfortable for patients. A trend toward non-thermal ablation has therefore developed in order to avoid this. One of the most important of these methods is chemical occlusion using N-butyl cyanoacrylate (NBCA), a glue.

The first study in which NBCA was used in humans was published in 2013.¹ It subsequently began being widely employed on a global basis. Glue occlusion was found to be equivalent to thermal ablation in terms of early period results.^2–5 We also began applying glue occlusion after 2014. We previously published our early period results,⁶ followed by our mid-period outcomes.⁷ These results were no terms inferior to those of thermal ablation. They were in fact superior in terms of patient comfort and time to return to work.

However, the greatest deficiency in comparing glue occlusion and thermal ablation was that longer-term results were uncertain. We therefore intended to present our 8-year results for 180 patients on whom we performed glue occlusion in 2014 in order to make good this gap in the literature.

Methods

Patients

In this prospective study, endovenous glue occlusion was performed on 180 patients with saphenous vein incompetence using VariClose (FG Group, Ankara, Turkey) between May and October 2014. Patients with incompetent great and/or small saphenous veins diagnosed using colored Doppler ultrasonography (USG) were included in the study. The inclusion criteria were a great saphenous vein diameter greater than 5.5 mm and a small saphenous vein diameter greater than 4 mm in conjunction with reflux for longer than 0.5 s. The exclusion criteria are given in Table 1. No maximum vein size was imposed during patient selection. The patients were re-assessed with colored Doppler USG immediately before the procedures by the surgeon who performed them. All patients were informed about the study, and their consent was obtained. They were then taken to the operating room.

Table 1.

Exclusion criteria.

1	Patients under the age of 18
2	Patients with obstruction in the deep venous system
3	Patients who have previously used another invasive treatment method (thermal and chemical ablation, surgery)
4	Patients with cardiac and renal failure
5	Immobile patients
6	Patients with secondary varicose vein
7	Hypercoagulability status
8	Local or systemic infection
9	Obesity (body mass index>35)

Following the occlusion procedure, the occlusion of the vein was immediately verified by the surgeon using duplex ultrasound to assess the success of the procedure. Patients were asked to return for a follow-up visit 2 days after the procedure. Additional follow-up visits were conducted one, three, six, 12, 30 months, and 8 years after the procedure, during which the patients underwent clinical and duplex ultrasound examinations. Doppler USG assessment was performed by a radiologist. Additionally, patients were told to return to hospital immediately in case of edema, rash, pain in the legs, or shortness of breath.

No patients received postoperative antiaggregant or anticoagulant therapy. Paracetamol was prescribed for pain; the patients being asked to report this if it occurred.

We were able to contact 180 of the patients who underwent follow-ups at 30 months, but only 155 patients at 8 years. These patients underwent clinical examinations, and their VCCSs were recorded. At Doppler USG, the saphenous veins subjected to ablation were classified as occluded, partial recanalization, or complete recanalization.

Procedure

All procedures were performed by physicians experienced in EVLA and RFA. No problems occurred during catheterization and ablation in any case. The saphenous vein was accessed using a 6F introducer set with the assistance of Doppler USG. A 0.035″x150 cm guidewire was passed through the 6F introducer sheath to the saphenofemoral junction (SFJ) or the saphenopopliteal junction (SPJ). Once the presence of the guidewire in the SFJ or SPJ was confirmed via Doppler USG, a 5F catheter was advanced to the SFJ or SPJ over the guidewire. Following confirmation of the position of the 5F catheter at the beginning of the SFJ or SPJ, it was retracted back from the SFJ or SPJ by 6 cm. This distance was employed because the tip of the 4F delivery catheter emerges 3 cm from the 5F marker catheter. The 4 F delivery catheter therefore had to be positioned 3 cm distal to the SFJ or SPJ. Once the position of the 4F delivery catheter was confirmed, the NBCA injection groundwork was complete.

In patients who underwent VSM procedure, the above knee segment was occluded. This depends on our personal experience. We believe that a significant portion of patients can recover by treating only the above-knee segment. Even the varicosities that formed in the below-knee segment disappeared or became smaller over time.

The procedure then began. First, pressure over the SFJ was applied with Doppler USG, and the closure of the SFJ was confirmed. The delivery catheter was primed prior to the injection of NBCA inside the vein lumen. One trigger push was applied for one second for this priming. After priming, the trigger was pushed again for 5 s, and this time the delivery catheter was pulled back at 2 cm/s. The delivery catheter was set up for the injection of 0.03 cc of NBCA/cm. Continuous pressure was applied over the target vein segment simultaneously with the retraction of the delivery catheter by the Doppler USG probe without releasing the pressure from the SFJ. The trigger had to be pressed every 5 s or 10 cm. This trigger-pressing and pressure application routine was performed continuously until the target vein segment was fully sealed. Once the entire vein segment was injected with NBCA with the continued application of pressure during the procedure, a final pressure was applied for 30 s over the entire target vein segment.

No adjunctive procedure was applied to any patient during the procedure.

Statistical analysis

Patient demographics, venous insufficiency characteristics, results, and complications were described for all patients. Frequency and percentage values of categorical variables as well as mean, standard deviation, median, and range values for continuous variables were determined. Non-normally distributed Venous Clinical Severity Scores (VCSS) data were analyzed using Friedman’s test. Wilcoxon’s signed-rank test was used for post hoc pairwise comparisons. Venous occlusion level at 8-year follow-up was determined using Kaplan–Meier analysis. A probability value less than 5% was considered significant. Statistical analysis was performed on SPSS version 20.0 for Windows software (SPSS Inc., Chicago, IL, USA).

Results

The ages of the 155 patients available for follow-up at the end of 8 years ranged between 27 and 67, with a mean age of 47.4 ± 11.8 years. Sixty-eight patients were men and 87 were women. Procedures were performed on the great saphenous vein in 148 cases and on the small saphenous vein in seven. Saphenous vein diameters ranged between 5.5 mm and 14 mm (mean 7.6 ± 2.4 mm). Procedures were performed on the right leg in 82 cases and the left leg in 73. The mean length of the saphenous veins subjected to procedures was 26.3 ± 6.5 cm (range 9–43 cm). The mean length of procedure was 15.3 ± 2.5 min (range 10–25 min), and the volume of glue injected was 2 cc, up to a maximum of 3 cc.

Occlusion was observed in 100% of saphenous veins at post-procedural USG controls.

No severe pain was observed in any patient, with 5% experiencing only mild pain. Superficial phlebitis was observed in 11 patients (6%). No hematoma or deep vein thrombosis was observed in any case. Patients returned to work within an average of 1 day after the procedures.

The occlusion rate at 5.5-month follow-ups of the 180 patients included in the study was 100%. However, only 168 of these patients could be contacted during 30-month evaluations, and the occlusion rate decreased to 94.1%. Complete recanalization was detected in seven of the available patients at the end of 8 years, and partial recanalization in six. The occlusion rate was 91.7%. The relevant Kaplan-Meier analysis is shown in Figure 1.

Figure 1.

The Kaplan-Meier analysis.

Mean VCSS scores were 10.2 ± 1.5 before the procedures, 3.9 ± 1.6 at 3 months, 2.7 ± 0.7 at 30 months, and 2.6 ± 0.7 at 8 years. The preoperative values and those at three and 30 months postoperatively differed significantly, while no significant difference was observed between the values at 30 months and 8 years. The patient characteristics are compared in Table 2.

Table 2.

The patient characteristics.

	Preoperative	Postoperative 5 months	Postoperative 30 months	Postoperative 8 years
Number of patients followed	180	180	168	155
Age (years)	47.7±11.7	47.7±11.7	47.7±11.8	47.4±11.8
Sex (F/M)	94/86	94/86	89/79	87/68
Occlusion rate (%)		100	94.1	91.7
VCSS	10.2	3.9	2.7	2.6

VCSS: venous clinical severity score.

Additional procedures were performed at different times of 21 patients after 30 months. Repeat glue occlusion was performed on five of the patients with complete recanalization, while foam sclerotherapy was applied in three cases with partial recanalization. Foam sclerotherapy was also applied to varicosities in different locations and at different times in 12 cases in which complete occlusion was achieved. In one case, the inferior epigastric vein was ligated due to collateral varicosities resulting from the enlarged inferior epigastric vein in the groin area

Discussion

Endovenous thermal methods have been widely employed in the treatment of varicose veins for the last 20years. EVLA and RF ablation are particularly proven techniques. However, the fact that thermal methods require the use of tumescent anesthesia and cause patient discomfort as a result has led to a search for new, non-thermal endovenous ablation techniques. One method that has become increasingly used for that purpose in recent years is glue occlusion using NBCA.

The first experimental study with that aim was published in 2011.⁸ It subsequently began being employed in the clinical setting, first in limited numbers of patients and later in larger numbers. NBCA entered the market and began being used in Turkey in 2014. Early period studies regarding procedures performed at that time began being published in 2016. We previously reported our early-period findings for 180 patients.⁶ In that study, we reported a complete ablation level of 100% in patients followed-up for at least 3 months. We subsequently published our 30-month results and determined an occlusion rate of 94.1%.⁷

The superiority of endovenous methods in the treatment of varicose veins has more and more evidence supporting. Interventional therapy in case of Class I, Level B is recommended in the treatment of symptomatic patients with varicose veins in the ESVS 2022 guideline.⁹ Thermal ablation in case of Class I, Level A and glue occlusion in Class IIa, Level A are also recommended in the same guideline. Yet glue occlusion is becoming increasingly used worldwide and the results are highly satisfactory. A recent systematic review study¹⁰ reported no difference in occlusion rates between thermal ablation and glue occlusion, and equal improvement of quality of life, although glue occlusion caused less postoperative pain and nerve injury. We also observed similar 2-year occlusion rates in a 525-patient randomized study comparing EVLA, RF ablation, and glue occlusion (glue 92.6%, RF ablation 90.9%, and EVLA 91.5%), while glue occlusion was found to be superior in terms of time to return to work and pain levels.¹¹

The greatest uncertainty concerning glue occlusion was the absence of published long-term results. Even recently published studies have reported 12- or 24-month outcomes^12–14

Longer-term follow-up results were published by Kilic et al. in 2022.¹⁵ Those authors published the 5-year outcomes of 467 patients receiving EVLA, RF, and glue ablation and reported occlusion rates of 70% for EVLA, 86% for RFA, and 80% for glue occlusion. However, the values were not statistically significantly different.

This study presents our 8-year follow-up results for patients who underwent glue occlusion. This, to the best of our awareness, is the longest follow-up time to date. We determined a 91.7% occlusion rate at the end of 8 years. This figure was same to those for patients undergoing thermal ablation. Complete recanalization was determined in seven of the 155 patients included. The adhesion disappeared in some areas of the treated vein, and venous flow was observed in those locations, while other areas were occluded in six patients.

The long-term results were highly satisfactory in terms of patient comfort. Two patients with complete recanalization were unwilling to undergo a repeat procedure, while repeat glue occlusion was performed on the remaining five. Glue occlusion was also performed on three of the patients with partial recanalization complaints. Foam scleropathy was performed at different times in 12 patients with complete occlusion. The great majority of these consisted of varicose structures that developed gradually with the expansion of the anterior accessory vein. We concluded that when the inferior epigastric vein or accessory saphenous veins remain patent using endovenous occlusion methods, these veins may expand in the future and new varicose structures may occur. This may be encountered more frequently, particularly in case of glue occlusion, when the catheter tip is left further back to avoid deep vein thrombosis.

As described above, glue occlusion was found to be superior to other thermal methods in terms of patients and return to work. The procedure itself caused less pain, and less pain was also experienced in association with tumescent anesthesia not being employed, thus representing another important advantage.

In short, glue occlusion has a very adequate treatment rate with a 91.7% occlusion rate in 8 years. In addition, it is at least as good as other methods as it is more comfortable during the procedure than thermal ablation methods and provides the opportunity to return to work in a short time.

Footnotes

Acknowledgements

We originally completed this research in 2022 and presented it at UIP 2022. However, a major earthquake struck the city of Kahramanmaraş, where we are based, during the preparation of the manuscript, and the writing of this article was delayed in consequence.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical statement

Guarantor

Contributorship

AY and EE conception and design, EE and MAc data collection and interpretation, MAr literature review, AY writing the article. All authors read and approved the final manuscript.

ORCID iD

Alptekin Yasim

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