Efficiency of endovenous laser and glue ablation methods in comparison with conventional surgery for the treatment of venous ulcers

Introduction

Chronic venous disease which is highly prevalent and estimated incidence reaching to 45% in general population is an increasing worldwide health problem associated with significant morbidity. The clinical manifestations range from telengiectasias, distended lower extremity veins, edema, pigmentation, and to the latter extent ulceration in longstanding severe cases.^1,2

The definition of venous ulcers is made in 2004 according to the CEAP classification as follows: a defect comprising the full thickness of the skin, occurring usually around the ankle which does not heal spontaneously in the presence of chronic venous disease.^3,4 Gillespie et al. ⁴ summarize the definition of the pathology as full thickness skin defect together with pigmentation and dermatitis around the ankle region that is present for more than 30 days, associated with venous hypertension and without an associated arterial or systemic cause. The venous hypertension leading to ulceration in general is secondary to superficial veins in 90%, perforating veins in 80%, and deep veins in 70% of the cases. ⁴

The estimated incidence of venous ulceration is around 1–1.5% in affected patients.^4,5 Venous ulcers are troublesome. The treatment of venous ulcers is usually long lasting and complicated with recurrences. The rationelle beyond the treatment of the disease is mainly based on the relief of venous hypertension. ⁴ It may be accomplished by non-invasive compression methods or invasively by conventional surgical procedures or percutaneous endovascular ablation techniques. The two main primary goals for the venous ulcer disease are treatment of the ulcer and prevention of recurrence after treatment. ⁴

In this manuscript, we sought to investigate the efficiency of two different endovascular techniques, the endovenous laser and glue ablation methods combined with perforating vein ligation on venous ulcer treatment and compared the results with conventional surgical stripping method.

Patients and methods

Between January 2005 and January 2020, 3133 consecutive patients superficial venous reflux disease underwent treatment at our institution. Among the patients, there were 112 consecutive patients with active venous stasis ulcers and they were reviewed and included into this non-randomized retrospective study. Data regarding the patients were obtained from the institutional records. Patients were divided into 3 groups as receiving conventional open surgical treatment (Group 1), endovenous glue ablation (Group 2), and endovenous laser ablation (Group 3).

All the patients were examined thoroughly and sizes of the ulcers were measured. A detailed Doppler ultrasonography examination of the symptomatic leg(s) was performed before the interventions. Lower extremity superficial, deep, and perforating venous systems were mapped. Saphenous vein variations, deep venous insufficiency or thrombosis, perforating vein insufficiency and small saphenous vein reflux disease, and other venous diseases were also checked and recorded. The severity of the venous reflux disease was graded according to the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification. The clinical findings were assessed with the Venous Clinical Severity Score in the preoperative period.

Patients with saphenofemoral junctional and/or greater saphenous vein reflux in response to standing manual compression and release or Valsalva maneuver for more than 0.5 s were electively scheduled for the interventional treatment either with conventional surgical techniques or endovascular methods. According to the social security reimbursement strategies of the national healthcare system, patients with refluxing saphenous vein diameter larger than 5.5 mm with Doppler ultrasonography could be treated with percutaneous saphenous vein ablation methods, that is, endovenous laser or glue ablation. The choice of laser ablation or glue ablation techniques has depended on the availability of the catheter at the institution. Patients with chronic superficial venous reflux disease with saphenous vein diameters lower than 5.5 mm underwent stripping. Endovenous techniques were prioritized. When institution lacked catheters or when the size of the greater saphenous vein was not suitable for endovenous techniques according to the regulations of the social security system, conventional stripping was performed. In addition to truncal vein treatment, the other varicose paquets were resected with microphlebectomy. Refluxing perforating veins, especially around the ulcer are marked preoperatively, controlled with Doppler ultrasonography perioperatively and subfascially ligated. One leg was treated at one session for better patient comfort. When the patients had bilateral disease, the leg with a bigger size ulcer was treated first followed by the intervention for the contralateral side which was postponed at least 15 days to see improvement of leg ulcer in the treated leg. The sizes of the ulcers were roughly determined in cm² by multiplying the length and width of the ulcers. The patients with signs and symptoms of infection with active ulcers including fever, erythema of the affected leg, and inguinal lymph nodes were first treated with appropriate antibiotic and wound dressing.

The techniques of endovenous laser, glue ablation^6,7 and conventional saphenous vein stripping; briefly as saphenopopliteal ligation and/or saphenofemoral ligation and limited stripping of great saphenous vein or resection from saphenofemoral junction to below the knee level, ⁸  were previously explained in details. The endovenous laser ablations were performed with 1470 nm diode laser (ELVeS®, Biolitec^® AG, Vienna, Austria). Endovenous glue ablations were performed with n-butyl cyanoacrylate (VenaBlock; Invamed, Ankara, Turkey). 0.014^″ diameter guidewire (Inwire; Invamed, Ankara, Turkey) was introduced under ultrasound guidance into the trunk of the target vein at the distal point of the axial reflux using a 6-F introducer (Invaducer; Invamed, Ankara, Turkey).

Patients were kept at the hospital overnight, received prophylaxis against deep vein thrombosis and followed against bleeding or other wound problems, and discharged home after 1 day of hospitalization as a standard policy. Exercise, especially walking, was strongly advised. Ambulatory based wound care was scheduled at the outpatient clinic. Debridement, when required, was only performed during intervention session and was not repeated. Special wound dressing products were not used. Wound rehabilitation was performed with cleaning the wound surrounding with povidone-iodine solution and irrigation of the wound with 0.9% isotonic saline solution. Wound dressing was repeated every 48 h. Elastic bandage was applied to the treated leg until ulcer healing. Change of CEAP 6 to CEAP 5 and ensuring skin integrity was accepted as healing whereas decrease in ulcer size was not accepted. After venous ulcer healing, patients were advised high pressure compression stockings, were distracted from follow up, and were requested to readmit if they experience wound recurrence. All the patients underwent control venous Doppler ultrasonography examination at 3, 6 and 12 months follow up.

The patients were informed about the risks and benefits of the procedures. Patients were clearly explained that venous ulcer treatment is long lasting and may be complicated with recurrences. Procedures were executed after their consent. Patients with deep or superficial venous thrombosis, patients receiving anticoagulants, those with concomitant peripheral arterial disease, serious systemic disease, immobile or pregnant patients, patients with short life expectancy, and patients with previous venous interventions including perforating and superficial venous reflux disease surgery for great and small saphenous vein or scleroterapy were excluded from this study. A complete superficial venous disease treatment including greater saphenous vein, small saphenous vein, and perforating veins were performed in one leg at the same session. The same treatment method which is used for the treatment of greater saphenous vein was preferred for the treatment of the smaller saphenous vein.

Statistical analysis

The data were analyzed with computer software Statistical Package for Social Sciences, SPSS 20. Descriptive statistics (absolute frequencies and percentages for categorical variables; means and standard deviation for continuous variables) were used to evaluate demographic and clinical characteristics of the population. Values are expressed as mean ± standard deviation or frequency and percentage. Conformity of normal distribution and homogeneity were tested with the “Kolmogorov–Smirnov test” for continuous variables. Categorical values were evaluated with “chi-square test.” Normally distributed variables are analyzed with paired samples T test to compare continuous variables. Continuous values without normal distribution were analyzed with Wilcoxon signed rank test and Mann–Whitney U test. Spearman rank and Pearson correlation coefficients were used for correlation analysis. A p value less than 0.05 was considered statistically significant.

Results

There were 3133 patients who underwent treatment for chronic superficial venous reflux disease between January 2005 and January 2020 at our institution. Among the 3133 patients, 1925 patients received conventional open surgical treatment, 228 patients underwent endovenous glue ablation, and 980 patients received endovenous laser ablation. Procedures were performed by the same attending physician with same standard techniques. Among 3133 patients, there were 112 patients with long lasting, first time, or recurrent active venous ulcers (CEAP C6) (Figure 1). The study was conducted with this particular patient population with CEAP C6 venous disease (3.5% of the cohort), 7.46 patients per year. Group 1, the surgical treatment group, consisted of 70 patients (62%), the glue ablation group (Group 2) consisted of 20 patients (18%), and Group 3 (laser ablation group) contained 22 patients (20%). There were 6 patients with bilateral venous leg ulcers in Group 1, 1 patient in Group 3, and no patients had bilateral disease in Group 2. A total of 119 legs were intervened. Deep venous insufficiency was present in 23 patients (33%) in Group 1, 7 patients (35%) in Group 2, and 8 patients (36%) in Group 3. Demographic features of the patients including age, gender, history of diabetes mellitus, hypertension, history of previous treatment, diameters of the great and small saphenous veins, number of refluxing perforating veins, and size of the ulcers are presented on Table 1.

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Figure 1.

Active venous ulcer.

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Table 1.

Demographic features of the patients.

	Age (mean, years)	Gender [male (n)/female (n)]	BMI (mean, kg/m2)	DM (n)	HT (n)	Smoking (n)	Bilateral venous ulcers (n)	Deep venous insufficiency (n)	SSV incompetence (n)	Diameter of the GSV (mean/mm)	Diameter of the SSV (mean/mm)	Ulcer size (mean, cm2)	Duration of healing (days)	Ulcer recurrence
Group 1	43.7 ± 11.9	56/14	27.3 ± 2.4	7	11	42	6	23	11	8.71 ± 3.69	4.09 ± 1.01	71.51 ± 57.13	53.28 ± 22.1	23
Group 2	39.05 ± 11.6	16/4	25.46 ± 1.78	2	2	15	0	7	3	7.31 ± 1.4	4.39 ± 0.62	73.25 ± 62.74	73.7 ± 39.6	7
Group 3	42.3 ± 11.1	17/%	25.5 ± 1.8	1	4	14	1	8	4	7.48 ± 1.7	4.13 ± 0.72	67.55 ± 45.26	62.59 ± 19.65	5

DM: diabetes mellitus, HT: hypertension, GSV: great saphenous vein; SSV: small saphenous vein.

Mean age of the patients were 43.7 ± 11.9 (range: 22–68) years in Group 1, 39.05 ± 11.6 (range: 19–59) years in Group 2, and 42.3 ± 11.1 (range: 27–63) years in Group 3. There were 56 male and 14 female patients, 16 male and 4 female patients and 17 male and 5 female patients in Group 1, Group 2 and Group 3, respectively. There were 7 diabetic and 11 hypertensive patients in Group 1, 2 diabetic and 2 hypertensive cases in Group 2, and 1 diabetic and 4 hypertensive cases in Group 3. Active smoking or history of smoking was 42/70 patients (60%) in the stripping group, 15/20 patients (75%) in the glue ablation group, and 14/22 patients (64%) in the laser ablation group. Body mass indexes were calculated 27.3 ± 2.4 (range: 22.14–31.44) kg/m² in Group 1, 25.46 ± 1.78 (range: 20.92–27.16) kg/m² in Group 2, and 25.5 ± 1.8 kg/m² (range: 20.92–27.16) in Group 3.

When the age, gender, comorbidities (diabetes mellitus and hypertension), smoking, diameter of the small saphenous vein, number of refluxing perforating veins, size of the ulcer, and ulcer recurrence ratio were compared between groups, there was not statistically significant difference (Table 1). Mean of body mass indexes was significantly higher in Group 1 than Group 2 and Group 3 (p: 0.00044, Group 1 and Group 2; p: 0.00056, Group 1 and Group 3). Body mass indices did not significantly differ between Group 2 and Group 3 (p: 0.85). Rate of deep venous insufficiency was significantly higher in Group 3 than Group 1 (p: 0.014); however, Group 1 and Group 2, and Group 2 and Group 3 did not differ significantly (p: 0.86, Group 1 and Group 2; p: 0.066, Group 2 and Group 3).

All the patients had saphenous vein insufficiency in all groups. In addition small saphenous vein incompetence was detected in 11 patients (16%) in Group 1, 3 patients (15%) in Group 2, and 4 patients (18%) in Group 3. The mean number of detected refluxing perforating veins was 1.71 ± 0.95 (range: 1–4), 2.35 ± 2.5 (range: 1–5), and 1.59 ± 1.18 (range: 0–4), in Group 1, Group 2, and Group 3, respectively. The mean diameter of the saphenous vein was 8.71 ± 3.69 (range: 4.3–16) mm in the stripping group, 7.31 ± 1.4 (range: 5.5–9.4) mm in the glue ablation group, and 7.48 ± 1.7 (range: 5.5–11.6) mm in the laser ablation group. Mean diameter of the great saphenous vein was significantly higher in Group 1 than Group 2 and Group 3 (p: 0.012, Group 1 and Group 2; p: 0.035, Group 1 and Group 3) and it was not significantly different between Group 2 and Group 3 (p: 0.367). The corresponding values for the insufficient small saphenous vein were 4.09 ± 1.01 (range: 2.1–6) mm, 4.39 ± 0.62 (range: 3.5–4.9) mm and 4.13 ± 0.72 (range: 3.5–4.9) mm, which were not significantly different between groups (p > 0.05 for all groups). All the interventions could be performed successfully in all groups confirmed with the periprocedural control Doppler ultrasonography examinations in Group 2 and 3.

The ulcer sizes at the time of intervention ranged between 5 and 220 (mean: 71.51 ± 57.13) cm² in Group 1, 8–240 (mean: 73.25 ± 62.74) cm² in Group 2, and 4–200 (mean: 67.55 ± 45.26) cm² in Group 3. Complete healing could be achieved in all patients in different duration of follow up (Figure 2). All the patients could be followed regularly and no patients were lost at the follow up. Mean duration of follow up was 18.24 ± 4.64 months. Mean durations for complete ulcer healing were 53.28 ± 22.1 (range: 26–94) days, 73.7 ± 39.6 (range: 43–164) days, and 62.59 ± 19.65 (range: 49–108) days, in Group 1, Group 2, and Group 3, respectively. Mean durations for complete ulcer healing were significantly lower in Group 1 than Group 2 (p: 0.037); however, duration for complete ulcer healing did not differ significantly between Group 1 and Group 3, and Group 2 and Group 3 (p: 0.067, Group 1 and Group 3; p: 0,26, Group 2 and Group 3). Thirty-four patients (48%) in Group 1, 6 patients (30%) in Group 2, and 6 patients (27%) in Group 3 experienced healing and recurred ulcers at least once in the preoperative period (p > 0.05 for all groups). After the interventions, ulcers recurred in 23 patients (33%) in the stripping group at a mean follow up of 14.42 ± 4.6 months, in 7 patients (35%) in the glue ablation group at a mean follow up of 11.97 ± 2.94 months, and in 5 patients (23%) in the laser ablation group at a mean follow up of 12.66 ± 3.48 months (p > 0.05 for all groups).

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Figure 2.

Healed venous ulcer.

The correlation analysis was performed between demographic features of the patients (age, gender, diabetes mellitus, hypertension, smoking status, body mass index, deep venous insufficiency, diameters of the great and small saphenous veins, and number of refluxing perforating veins) and ulcer size, and mean durations for complete ulcer healing and ulcer recurrence. Increased body mass index, deep venous insufficiency, diameters of the great saphenous vein, diabetes mellitus, hypertension, and smoking were not correlated with ulcer size. Diameters of the small saphenous vein and number of refluxing perforating veins were weakly correlated with ulcer size and mean durations for complete ulcer healing. Size of the ulcer (cm²) was significantly correlated with mean durations for complete ulcer healing. Other factors such as deep venous insufficiency, diabetes mellitus, smoking, and diameters of the great saphenous vein were not correlated with mean durations for complete ulcer healing. Increased body mass index, deep venous insufficiency, diameters of the great and small saphenous veins, number of refluxing perforating veins, size of the ulcer, diabetes mellitus, and hypertension as well as the treatment method were not correlated with recurrence. Smoking was mildly correlated with ulcer recurrence.

Mortality did not occur during or after the procedures or at the follow up. None of the patients experienced deep venous thrombosis. Recanalization was not observed in patients treated with endovenous ablation methods. Two patients (one in Group 1 and one in Group 3) experienced neurologic deficit which was presumed to occur during perforating vein ligation. Patients in Group 1, the conventional stripping group, experienced hematoma more commonly. Significant infectious complications did not occur. Minor infections were treated with oral antibiotheraphy and local wound care. Amputation was not performed and skin grafting was not required after the interventions during initial wound healing; however, recurrent patients were advised plastic and reconstructive surgery admission for chronic wound therapy.

Discussion

The lifetime risk of developing varicose veins is estimated 30–50% in humans. ⁹ Advanced disease secondary to chronic venous pathologies including skin changes and lipodermasclerosis may be seen in 5–10% of the affected patients and leg ulceration occurs approximately 1–1.5% in this particular patient group.^4,5,9 Venous ulcers are frequently long lasting, catarrhal, painful lesions requiring long time to heal and associated with high rates of recurrences. ⁴

Venous disorders are well known since ancient Greek times. Hippocrates noticed a correlation between varicose veins and leg ulcers. He also described a two-layer compression together with various herbs applied over the ulcers for the treatment. At that time, surgical treatment was performed by exposure of the veins and stab avulsion with a blunt hook. ¹⁰ The interventional treatment of superficial venous reflux disease has evolved greatly together with advances in medicine, medical technology, and better understanding of the underlying mechanisms of the disease. Conventional surgical saphenous vein stripping or high ligation of the great saphenous vein, although still performed in selected cases, was nearly replaced with endovenous ablation techniques which are performed minimally invasively for enhanced patient comfort. The endovenous techniques may be divided into thermal (laser or radiofrequency ablation) and non-thermal (polydocanol, mechanochemical, or cyanoacrylate glue ablation) methods. ¹¹ When excluding polidocanol endovenous microfoam therapy, the other methods including radiofrequency, laser, and cyanoacrylate glue occlusion methods are associated with >90% success rates similar to open surgical treatment but with less discomfort and early return to work and daily activities.^11,12 Regardless of the method, treatment performed against superficial venous reflux disease either for simple varicose veins or for complicated cases with skin changes is associated with improved patient quality of life. ⁹

Treatment of venous ulcers may be achieved with conservative or interventional methods. Conservative treatment comprises local wound therapy and compression bandages as well as rest and leg elevation.^5,14 Interventional approaches rely on correction of venous hypertension by treatment of refluxing superficial, deep and perforating venous systems. It is well known that interventional treatment of venous ulcers is associated with better patient comfort.^13–15 In the current study, we aimed to compare endovenous laser and glue ablation techniques with surgical treatment for the treatment of venous ulcer disease.

The laser ablation causes thermal damage to the vein wall proceeded by vessel obliteration. Mechanism of action of laser inside the vessel is through hemoglobin chromophore. The laser energy is absorbed from the wavelength energy leading to temperature increase resulting in thrombotic occlusion of the vessel throughout the burned segment. ¹¹ The cyanoacrylate glue briefly fills the lumen of the saphenous vein by polymerization when interacts with blood, causes inflammatory reaction, and ends up with fibrosis of the vessel. ¹⁶ Glue that is used in our cohort is a 3 mL of polymer-based cyanoacrylate. Following deployment of the catheter, saphenous vein is obliterated with 3 mL of cyanoacrylate that is injected through the delivery system. ¹⁷

Literature consists of reports presenting the results of different treatment options including sole compression therapy as well as comparison of alternatives. In addition, it should be reminded, regardless of the treatment method for the superficial venous reflux disease, importance of perforator vein surgery to prevent recurrences has been indicated, ⁵ despite historically it had been said that superficial venous surgery could provide ulcer healing without the need for perforator surgery. ¹⁸ Majority of patients usually possess incompetent venous tributaries around the ulcer in addition to superficial or deep venous pathologies. ¹⁹ Hence, refluxing perforating veins, especially around the ulcer were determined and subfascially ligated the tortuous, enlarged, and refluxing perforating veins routinely.

In our study, we compared the results of endovenous laser and glue ablation techniques and conventional saphenous vein stripping method. Howard et al. ¹⁸ in their systematic review in 2008 compared 21 studies investigating conservative therapy, 28 studies on surgical therapy, and 3 studies on both modalities. Authors concluded that superficial venous surgery had been associated with similar rates of ulcer healing as compression therapy alone, however, with lower rates of recurrence. ¹⁸ Hence, it should also be noted that multicomponent compression bandage systems are still the simplest and the gold standard options to treat venous ulcers. ²⁰ Although in the study by Bello et al. ¹⁸ in 2002, isolated superficial venous surgery in patients with venous ulceration had been promising in ulcer healing in majority of the patients without the need for perforating surgery, compression therapy, or skin grafting; recent evidence indicates perforator vein surgery reduced the recurrences by van Gent et al. ⁵ in 2010.

Teo et al. ²¹ and Abdul-Haqq et al. ²² assessed the efficacy of endovenous laser therapy for the treatment of lower extremity venous ulcers occurring in presence of venous reflux. They found out that healing processed with continuing obliteration of the great saphenous vein and loss of flow.^21,22 Puggina et al. ²⁰ conducted a randomized trial in Brazil on patients with venous ulcers without deep venous thrombosis receiving either radiofrequency ablation or two-layer compression bandage system. The results of their study showed venous ulcer healing rates had been higher in patients whom received endovenous radiofrequency ablation and two-layer compression bandages when compared with patients whom only received compression bandages alone. Similar results were achieved recently in VUERT Trial ²³ with combination of radiofrequency ablation and compression bandages in means of not only venous ulcer treatment but also prevention of recurrences. In addition, the efficacy of cyanoacrylate glue ablation ²⁴ and mechanochemical ablation methods ²⁵ has also been presented in the literature.

The rationelle beyond all invasive methods rely on reversal of venous hypertension by prevention of superficial and perforating venous reflux by obliteration of the affected great and/or small saphenous veins and/or perforating veins, and reconstructive surgery for the deep venous systems causing venous hypertension that is leading to venous ulcer on the affected leg. Various research studies compared the efficiency of different techniques in the literature.^25–30 However, none of the methods were significantly proven to be superior over the others as well as compression therapy alone in means of ulcer healing as well as duration of healing 31 . The choice of treatment has changed to less invasive methods in time rather than conventional surgical techniques for enhanced patient comfort, no necessity for general or spinal/epidural anesthesia, less pain, lesser wound complications, and less loss of work days. ¹³ In the current era of modern medicine, the optimal treatment should be minimally invasive, devoid of significant complications, could be repeatable when needed, low cost, cosmetic, associated with low work absence, and effective in eliminating venous reflux and decreasing venous hypertension.^13,32

Endovenous laser and glue ablations were the two less invasive techniques in our cohort. The ulcer healing in our patients in the glue ablation group had been slightly longer when compared with the other groups. It was attributed to brand of the glue that is used for ablation as the VenaBlock (Invamed, Ankara, Turkey) system contains 3 cc of polymer-based cyanoacrylate ¹⁷ ; hence, interventions ended up usually with partial proximal obliteration of the great saphenous vein unlike whole segment saphenous vein ablation with the marketed other opponent. However, ulcer healing proceeded together with distal obliteration of the saphenous vein in time in this particular patient subgroup which is in accordance with the results of the laser ablation subgroup.

Venous ulcer is a frequently relapsing health issue. It may take up to 6–12 months for complete ulcer healing. On the other hand, up to 70% may recur even after complete healing in 5 years.^4,8 The factors related with recurrence are usually not associated with successfully applied technique for the treatment of superficial venous reflux disease but rather related with various other factors such as body mass index, duration, size and depth of the ulcers, presence of deep venous reflux or occlusion, patient and ankle mobility, compliance with post-intervention recommendations, and socioeconomic factors.^31–33 Although complete ulcer healing could be provided in all patients in our cohort, we observed 33% recurrence rate in the stripping group, 35% in the glue ablation group, and 23% in the laser ablation group. Similar to the available literature, no applied treatment method was associated with recurrence but patient-related factors were found to be correlated with re-ulceration.

Conclusion

In conclusion, venous disorders are responsible for the majority of ulcers occurring on the legs. Although there are theories for venous leg ulcer occurrence and recurrence, none of them have been found to clearly explain the exact mechanisms. The rationelle beyond treatment of the venous ulcers as well as prevention of recurrence relies on relief of the venous hypertension by compression therapy or interventional methods and none of the methods have been superior over the others. Healing in short term without further recurrence may be achieved with successful intervention as well as good patient compliance.