Combined treatment with endovenous laser ablation and compression therapy of incompetent perforating veins for treatment of recalcitrant venous ulcers

Abstract

Objective

Patients with healed venous ulcers often experience recurrence of ulceration, despite the use of long-term compression therapy. This study examines the effect of closing incompetent perforating veins (IPVs) on ulcer recurrence rates in patients with progressive lipodermatosclerosis and impending ulceration.

Methods

Patients with nonhealing venous ulcers of >2 months’ duration underwent duplex ultrasound to assess their lower extremity venous system for incompetence of superficial, perforating, and deep veins. Endovenous laser ablation (EVLA) of perforating veins was performed on patients with CEAP 6 disease with increasing hyperpigmentation, lipodermatosclerosis, and/or progressive malleolar pain. A minimum of 2 months of compressive therapy was attempted before endovenous ablation of IPVs. Demographic data, risk factors, CEAP classification, procedural details, and postoperative status were all recorded.

Results

Forty ulcers with 46 associated IPVs were treated with EVLA in 36 patients with CEAP 6 recalcitrant venous ulcers. Treated incompetent perforator veins were located in the medial ankle (85.7%), calf (10.7%), and lateral ankle (3.5%). Endovenous laser ablation was successful in 76% (35/46) with the first laser treatment of incompetent perforator veins and 15.2% (7/46) additional ablation procedures were performed. Of the 46 treated IPVs, 42 (91.3%) were occluded on the duplex examination at 12 months. The average energy administrated per perforating vein treated was 162 joule. Two patients reported localized paresthesia, which subsided spontaneously, but no deep venous thrombosis or skin burn was observed.

Conclusion

Especially in the case of liposclerotic or ulcerated skin in the affected region, PAP of IPVs is highly effective, safe, and appears to be feasible. Patients with active venous ulcers appear to benefit from EVLA of incompetent perforators in order to reduce the risk of ulcer recurrence.

Introduction

Incompetent perforating veins (IPVs) have been implicated in the development of venous ulcers since the relationship was first proposed by Homans in 1916.¹

Treatment of IPVs in severe chronic venous insufficiency (CVI) to reduce superficial venous hypertension has been suggested as one of the possible therapeutic options, and this treatment has been shown to result in more rapid healing of ulcers and lower recurrence rates.^2,3

Procedures to eliminate incompetence and reflux in the perforating veins have been advocated using surgical ligation,⁴ subfascial surgical approaches⁵ and sclerotherapy.⁶ The approach has shifted toward minimally invasive techniques, due to the fragility of the skin around the ulcer and the risk of creating new nonhealing wounds with surgical procedures. Recently, endovascular ablation has been advocated to close refluxing perforating veins.⁷ Furthermore, reports have demonstrated good technical success and low complication rates,⁸ although most reports have focused primarily on successful ablation of the vein, rather than venous ulcer healing.

We conducted this study to evaluate patients who had chronic venous ulcers that had received optimal therapy with compression and wound care for at least 2 months and therefore were considered to be refractory to conventional treatment. These patients were optimal candidates for our study to determine the impact of perforator ablation on the healing of recalcitrant venous ulcers.

Materials and methods

Patients

Our retrospective study included 36 consecutive patients with 40 nonhealing venous ulcers in 38 legs, which underwent endovenous laser treatment of incompetent varicose veins. Patients who have either healed ulcers (CEAP 5) or lipodermatosclerosis (CEAP 4) were not included in this study, although we have encountered many CEAP 4/5 patients who have reflux in the perforating veins. We are currently looking at outcomes in these patients to determine if ablations of incompetent perforating veins prevent recurrent ulceration. All patients were referred to our vascular diagnostics unit by their general practitioner for symptomatic varicose veins. Data were collected from the regular case records. Informed consent for participation in the study was obtained according to the guidelines of the institutional review boards and the local ethics committee approved the study protocol.

After an interview and a physical examination, all patients underwent preoperative duplex venous mapping in our vascular surgery clinic, performed by experienced phlebologist. For this purpose, Toshiba Xario SSA-660A series (Toshiba Medical system corporation Nasu-Tokyo Japan) color Doppler ultrasound system was used with a 4.8–11 MHz (Toshiba PLT 704 AT) linear transducer. Scanning was performed with the patients sitting on a high examining couch, with their feet resting on a low stool and their knees partially flexed. Reflux times were measured on the release of manual compression of the foot, calf, or thigh, always distal to the evaluated venous segment. A perforator was considered to be incompetent when outward flow exceeding 1 s in duration was documented immediately after the release of manual compression. Inclusion criteria for the study were incompetent perforating veins >4 mm with sonographical proven reflux >1 s in one or multiple perforator veins. Their diameters at the level of the fascial plane were measured. Legs with one or more incompetent perforating veins in the affected area of the leg were treated by EVLA. In addition, all remaining incompetent saphenous trunks in the limb were also treated simultaneously.

Ulcer management prior to endovenous ablation

Patients underwent treatment in our dedicated wound care center for a minimum of 2 months and a mean of 14 months prior to endovenous ablation of incompetent perforator veins. In addition to twice weekly three- or four-layer compression therapy, patients had debridement, topical and systemic antibiotic treatment, topical growth factors, and skin substitutes. When patients completed two months of compression therapy, those with persistent ulcers that did not show evidence of healing by measurement using the software system underwent repeat duplex ultrasound to re-evaluate for any remaining reflux in the superficial system, and if none were found, to specifically evaluate the limb for incompetent perforating veins. The wound area was determined by means of planimetry (greatest width x greatest length). Patients with incompetent perforating veins were offered endovenous ablation to treat their perforator reflux and potentially heal their venous ulcer.

Endovenous ablation technique

Patient was positioned on the operation table in a reverse trendelenburg to enhance venous fill and dilate veins. IPVs were identified by transverse scanning starting from the medial malleolus to the knee. When the target vein was localized, the probe was slowly rotated to achieve the image including the entire perforator length from its most superficial to the deepest end below the muscle fascia. The IPVs are marked on the skin where they penetrate the fascia (Figure 1a). We used a 21-gauge seldinger needle to puncture and access the IPVs. After puncturing, a guide wire was inserted in to the vein (Figure 1b). A 5-Fr dilator of a micropuncture introducer set was placed over the guide wire in to the vein (Figure 1c). Then, the 400 µm diameter, radial emitting laser fiber was inserted through the 5-Fr dilator (Figure1d).

Figure 1.

(a) Doppler image of incompetent calf perforating vein. (b) Reflux of the perforator before ablation and (c) one week after ablation. (d) Occluded perforator vein two months after EVLA.

Perivascular local tumescent anesthesia (500 ml saline 0.9%, 10 ml Bupivacaine hidroclorure, 0,5%, 1 ml Epinenephrine 1:1000, 10 mEq NaHCO3) was given under US control, which also had the advantage of compressing the vessel wall around the laser fibre. A 1470 nm diode laser and slim radial fibre (Elves-radial slim kit™, biolitec biomedical technology GmbH, Jena, Germany) was used at a power of 10 W in the continuous pullback mode. Laser energy was administrated over the straight section of the vessel, by pulling back slowly under ultrasound control. Additional EVLA of all incompetent truncal saphenous veins was then performed in the same session when necessary.

At the first week of follow-up; duplex ultrasonography was used to confirm occlusion of the treated vein segment and patency of the deep veins. If there is residual flow in the IPV, retreatment is performed at that time. All patients had folded 4 × 4 gauze applied over treated perforators and elastic bandage wrapped around the leg from the ankle to the knee. Compression after the treatment was the same before the treatment with moderate pressure in a multilayer fashion. After treatment and ulcer healing, all patients wore 20–30 mmHg compression stockings. Patients were advised to walk regularly (at least three times daily for 20 min) and instructed to ambulate for a minimum of 30 min daily and to refrain from prolonged sitting or standing for three to five days.

Postinterventional care

Immediately after the procedure, prophylaxis of venous thromboembolism was started with enoxaparin 40 mg subcutaneously and prescribed for the following five days. A non-steroidal anti-inflammatory drug (diclofenac-sodium 75 mg 3–5 days twice daily) was prescribed for optional use. The patient was told to resume routine daily activities, but to avoid strenuous exercise for about one week. Follow-up examinations were performed at one week, 1, 3, 6, 12, and 18 months after the procedure, to determine the treatment outcome. Venous Clinic Severity Score (VCSS),⁹ patient satisfaction, recurrence rates were recorded in a written form by the patients during the follow-up visits. All patients were asked to record a pain score on a visual analog score (VAS) after the procedure, describing the average pain perceived during the procedure.¹⁰ Patients were asked to fill out a questionnaire to record pain scores and the use of pain medication in the first week following the procedure. Patients were also asked to record when daily activities were resumed. If normal activities were not possible, patients were asked if pain was the cause. The aim of the sonography was to examine the treated veins and the surrounding area for venous reflux and the treated veins for re-canalization and to exclude deep vein thrombosis (DVT) in the extremity. Signs for superficial vein thrombosis/phlebitis were also checked. All patients were requested to be present in our vascular unit or contact us by phone if symptoms of DVT or pulmonary embolism (PE) developed.

Statistical analysis

A statistical analysis was performed using GraphPad Instat software (version 11.5 for Mac, GraphPad Software Inc., La Jolla, CA, USA). Discrete variables are reported as numbers with percentages and continuous data as mean and standard deviation for normally distributed data otherwise median and range preferred. For normally distributed data, the groups were compared by unpaired Student’s t-test, for non-normally distributed data, Mann–Whitney U-test was employed. The VAS scores were analyzed using a paired t-test. A P < 0.05 was considered statistically significant.

Results

Between May 2010 and July 2014, 122 patients had venous ulcers treated in our center; 58 were managed with compression therapy, 28 patients were treated with a saphenous ablation procedure alone, and 36 patients had perforator ablation. Figure 2 shows the flow diagram of the study. The 36 patients had 40 nonhealing venous ulcers in 38 legs for >3 months; all patients had CEAP 6 clinical classification on entry into the study. There were 14 females and 22 males with a mean age of 45.7 ± 9.6 years (31–65 years). The clinical severity of the examined limbs was stratified according to the CEAP (Clinical, Etiology, Anatomy and Pathophysiology classification of venous insufficiency). The demographic and clinical characteristics of the patients are presented in Table 1.

Figure 2.

Flow diagram of the study shows algorithm of management of patients with CEAP 6 disease. GSV, great saphenous vein; SSV, small saphenous vein; IPV, incompetent perforating vein.

Table 1.

Demographic data and comorbidities.

Variable	Number
Patients	36
Mean age (years)	45.7 ± 9.6
Mean BMI (kg/m²)	28.1 ± 1.7
Sex (male:female)	22:14
ABI (<0.9)	8.3%
Anticoagulation therapy	27.7%
Deep venous reflux	44.4%
Etiology
Post-thrombotic	15 (42%)
Severe venous insufficiency	21 (58%)
Perforating vein incompetence	13 (62%)
Perforating and superficial vein incompetence	8 (38%)
Level of DVT
Iliofemoral	66.6%
Femoro-popliteal	33.3%
Distribution of superficial venous reflux
GSV	6
SSV	2
Location of the ulcers
Medial ankle	85%
Lateral Ankle	2.5%
Calf	12.5%
Average diameter of IPVs	4.6 ± 0.3
Mean Duration of ulcers (months)	16.7 ± 5.2

Note: Data’s are expressed mean ± standard deviation.

ABI: Ankle brachial index, BMI: Body mass index, CEAP: clinical, etiology, anatomy and pathophysiology classification of venous insufficiency, DVT: Deep vein Thrombosis.

The location of the ulcers was medial ankle in 85%, calf in 12.5%, and lateral ankle in 2.5%. The etiology of the venous ulcer was post-thrombotic in 42%, and severe venous insufficiency in 58%. Eight patients (38%) had both perforating and superficial vein incompetence whereas 13 patients had only perforating vein incompetence in the severe venous insufficient group. The number of incompetent perforating veins ranged from one to four in each leg with a venous ulcer. Patients had their ulcer for a mean of 18.6 ± 5.7 months (range 11–47 months). The average diameter of incompetent perforator was 4.6 ± 0.4 mm. Patients had undergone procedures at other institutions to treat the venous ulcers, including great saphenous vein strippings, small saphenous vein strippings, and surgical procedure on a perforating vein (Table 2). Patients had concomitant diseases that might interfere with wound healing, including two patients with chronic liver disease, three patients with leg edema due to congestive heart failure, one undergoing chemotherapy for a neoplasm, and one with renal insufficiency that was dialysis dependent.

Table 2.

Performed procedures of the patients.

Procedure	Number
Procedures performed before referral to our Center
Vein stripping	15 (11 GSV & 4 SSV)
Perforator procedure	4
Vein ligation/phlebectomy	11
Procedures performed at our center prior to perforator ablation
Tributary vein ligation	3
Vein stripping	0
SEPS	2
GSV ablation	8
SSV ablation	5
Skin graft	9

GSV, Great saphenous vein; SEPS, subfascial endoscopic perforator surgery; SSV, small saphenous vein.

Endovenous ablation results

Endovenous laser ablation was successful in 76% (35/46) with the first laser treatment of incompetent perforator veins and 15% (7/46) additional ablation procedures were performed at a mean of 76 ± 13 days (range 45–254 days); overall, the final closure rate was 91% (42/46). The closure success was independent of the site of the perforator, BMI of the patient, or age of the ulcer. The average energy delivered per perforating vein treated was 162 J. Operative data are shown in Table 3. Simultaneous treatment of truncal incompetence with EVLA was performed in eight patients (22%). Average of ulcer size before the first successful laser ablation was 13 ± 3.42 cm². Ulcers healed in patients with successful ablation of at least one perforator in 95% (38/40) at mean 11.5 ± 3.7 months, and 2 ulcers never healed. The nonhealing ulcers had a mean diameter of 11.5 cm ± 5.7 and a mean age of 39 months.

Table 3.

Operative data.

Parameters
Laser power (W)	10
LEED (J/cm)	72 ± 12
Total energy/limb (J)	162 (range 98–255)
TLA volume/limb (ml)	45 (range 25–55)
Procedure duration/limb (min)	16.4 ± 5.9
Simultaneous Treatment of Truncal incompetence	8 (22.2%)
Number of phlebectomies/limb	3.7 ± 1.8
Immediate postoperative closure rate (%)	91.3% (42/46)

LEED: Linear endovenous energy density, J: Joule, TLA: Tumescent local anesthesia, W: Watt

Post ablation therapy, recurrence and follow up

After ablation, 94% of patients (34/36) continued to wear their compression stockings. Two patients, who did not comply preoperatively, also declined postoperatively, due to inability to pull the stocking onto his legs. Ulcer recurrence rates, measured from time of ulcer healing, were 0% at 6 months, 2.7% (1/36) at 12 months, and 5.5% at 18 months. Median follow-up time from final ablation was 20 months (range, 13–43 months).

Patients were followed up after the procedure for healing of their ulcers at 7th day, and at 1, 3 and 6 months, with the VCSS administered at each visit. The overall mean VCSS for all 10 components decreased from 16.5 ± 3.6 to 7.3 ± 2.2 at the first follow-up visit. During the follow-up period, all VCSS components continued to improve, reaching a significant mean of 3.4 ± 1.1 at the third month of visit (P < 0.001), except for the pigmentation component, which varied throughout the follow-up period. At the initial postprocedure visit, the greatest improvement was noted in the pain, varicosity, edema, and inflammation components (Figure 3). The ulcer components of the VCSS proved useful in tracking the number, size, and duration of stasis ulcers after EVLA of IPVs.

Figure 3.

Scores for each Venous Clinical Severity Scoring component showed significant improvement at each time interval, except for the pigmentation component, over the course of follow-up.

Complications

Minor complications consisted of pain in five patients of which one had not been prescribed postoperative analgesia. Two patients complained of paresthesia, which subsided spontaneously and, in another four cases, ecchymosis was observed.

Skin burn was not recorded. Mean duration of pain was 2.3 ± 0.6 days and duration of analgesia need was 2.0 ± 0.5 days. There was not seen any symptomatic or asymptomatic deep venous thrombosis with Doppler ultrasound in patients at this assessment. Table 4 summarizes the side effects and other assessments of the outcome of this study.

Table 4.

Side effects and postoperative data.

Parameters
Pain duration (day)	2.3 ± 0.6
Duration of analgesia need (day)	2.0 ± 0.5
Induration (number of limbs)	3
Ecchymosis (number of limbs)	4
Skin necrosis (number of limbs)	0
Skin burn (number of limbs)	0
Paresthesia (number of limbs)	2
Deep vein thrombosis	0
Pulmonary embolus	0

Discussion

Our results show that treatment of incompetent perforating veins with the slim radial fibre and a 1470 nm diode laser is effective and safe. When focusing on the closure rate of perforators after ablation, initially not all veins could be successfully treated. Endovenous laser ablation was successful in 76% (35/46) with the first laser treatment of incompetent perforator veins and 15% (7/46) additional ablation procedures were performed. This might be due to the very short ablation distance in comparison with an ablation in the saphenous veins. It is conceivable that blood flow on both ends of the short intra-perforator thrombus can lead more easily to re-canalization than in longer distances. The venous high blood pressure on the muscle side towards the closed perforator while standing and walking may be another mechanism for re-canalization. In addition, the mechanical destruction of the thrombus when walking might cause an unstable occlusion.

Many methods of treating IPVs have been described. Until the turn of the century, surgery was the only widely used option to prevent venous reflux. Surgical techniques such as that of Linton’s or its modifications leave noticeable surgical scars and lead to high complication rates, such as wound site infection, nerve injury, postoperative pain, especially in patients with CVI-induced skin changes.¹¹ Subfascial endoscopic perforator surgery (SEPS) tackled the problem of the direct surgical approach and avoided the need for an incision in the damaged skin overlying the perforating vein to be treated. This proved to be a step forward in the reduction of wound problems compared to the open surgical technique. Other authors have evaluated interventions such as sclerotherapy, laser ablation, or endovenous ablation, combined with leg compression.^7,8,12

The Effect of Surgery and Compression on Healing and Recurrence (ESCHAR) study¹³ highlighted the benefit of vein interruption combined with leg compression on recurrence rates, reporting recurrence rates of 24% with compression plus superficial vein surgery and 52% with leg compression alone at three-year follow-up. However, the study only evaluated patients who underwent great saphenous vein interruption; incompetent perforating veins were not treated. Wittens and colleagues compared conservative versus surgical treatment both at ulcer healing and ulcer recurrence in Dutch SEPS study.¹⁴ A total of 97 ulcers were allocated to the surgical group and 103 to the conservative group. During follow-up of a mean of 29 months, they found that in the surgical group, the ulcer-free rate was 72%, whereas in the conservative group this rate was 53%. They suggest that patients with medial and/or recurrent ulceration should receive surgery combined with ambulatory compression therapy same as recently published van Gent study.¹⁵ They have followed up ulcerated legs mean of 97 months, and 80 (41%) out of 196 legs could be inspected. The incidence of “ulcer-free”, the main outcome, was significantly (p = 0.007) higher in the surgical group (58.9%), compared to the conservative group (39.6%). Observed ulcer recurrence was 48.9% for the surgical group and 94.3% for the conservative group. They conclude that, addition of surgical treatment in patients with venous ulceration leads to a significantly higher chance of being ulcer-free, than just ambulatory compression therapy.

Most of the literature to date has primarily focused on a conservative approach to preventing ulcer recurrence, by advocating the use of lifelong leg compression to correct venous hypertension.^16–19 However, Nelzen²⁰ reported that leg compression alone does not prevent recurrence and advocated additional therapeutic options.

Although SEPS has been the most popular way to treat IPVs, ultrasound-guided endovenous ablation may demonstrate several potential advantages. This technique is not limited to perforating vein location, and can easily be accessed at various locations with lower access site complication rates, including those that are more proximal, such as paratibial or posterior tibial perforators or the mid-thigh perforators or laterally located perforators, and perimalleolar vessels. SEPS is, however, not recommended for very distally located perforators or thigh perforators. EVLA also allows the flexibility of retreatment of persistent or newly developed IPVs. As long as IPVs can be visualized by Doppler ultrasound, they can be ablated with a laser. Theoretical disadvantages of EVLA of perforator veins can be summarized as missed IPVs, skin, nerve, and deep vessel injuries, and recanalization of ablated IPVs.²¹

We have debated how many incompetent perforators should be closed at a single sitting, and currently believe that the best approach is to pick the incompetent perforator veins immediately adjacent to and above the ulcer ones that are likely to reflux into the ulcer when the patient is sitting or standing as the initial veins for closure. Once these veins are closed, then a search for other large incompetent perforating veins in the region should be made. Frequently, other nearby perforators will be difficult to visualize once the first perforator has been ablated due to the infiltration of lidocaine throughout the adjacent tissue. If refluxing and close to the ulcer, a second incompetent vein should also be considered for ablation.

Corcos et al.²² reported on treating 534 IPVs of 303 limbs with EVLA. EVLA was performed using a 808 nm diode laser and 27.5 months follow-up of 467 limbs demonstrated with high rates of occlusion. Furthermore, Lawrence et al. reported on 45 patients with CEAP 6 recalcitrant venous ulcers¹⁶ and 86 IPVs treated with percutaneous endovenous radiofrequency ablation. It was found that 90% of ulcers healed when at least one perforator was closed; no ulcer healed without at least one perforator being closed. Similar to our study, they conclude that, ablation of the IPV both the feasible and effective technique for a selected group of patients with venous ulcers who fail conventional therapy with compression.

Hissink et al.²³ reported on 28 patients with 58 IPVs treated percutaneously. Depending on the available straight length of the perforator vein, total mean energy delivered was 187 J (range 87–325 J). However, in our study, a 1470 nm diode laser was used at a power of 10 W in the continuous pullback mode with cold tumescent fluid (+4℃) and average energy administrated per perforating vein treated was 162 J. An occlusion rate of 78% achieved at 3 months in Hissink study is comparable to our results; however, our complication rates, duration of pain, and need for analgesia were less than those for the studies mentioned above. We have used a higher wavelength laser whose target is water rather than hemoglobin. This may be an advantage for thermal-related complications, while also effective at ablating the IPVs. Tarhan et al. experimented on the effects of two different laser wavelengths in EVLA procedures.²⁴ They observed that, perforation rates and complication rates were much better with higher wavelength of the laser.

Most EVLA series describe the use of local anesthetic infiltration of the perivenous stroma for tumescent analgesia and protection against thermal injury to the nearby structures.^14,19,21 Despite this anesthesia, heat-induced complications such as skin burns, nerve damage, and prolonged pain may occur. Low temperature of the tumescence fluid might cause additional venous constriction and a cooling effect around the vein. This might reduce perivascular thermal injury and postoperative pain.^24,25

In the case of liposclerotic or ulcerated skin in the affected region where the perforator treatment needs to take place, a percutaneous approach by EVLA seems a safe treatment option. Another benefit is that retreatment is easily performed should recurrence of incompetent perforating veins arise. Finally, imaging of the vein by ultrasound during the entire procedure may overcome the problem of poor accuracy reported for surgical treatment of incompetent perforating veins.^7,8

The most compelling argument that perforator ablation facilitates ulcer healing is that we had no patient in our series who healed an ulcer following failed ablation, so simply improving wound care intensity and patient compliance was only successful when at least one perforator was closed. In addition, when at least one perforator was closed, a very high percentage of patients (>90%) had complete healing of their ulcer and that is similar to van Gent study.¹⁵

Even when all incompetent veins have been closed, it still is imperative that the patient remains compliant with wearing compression hose, because failure to do so often leads to progressive skin deterioration and ulceration. One of the limitations to our study is that it was a single center retrospective experience. Our study did not have a control group, because all patients with progressive symptoms were offered vein ablation and lacked the large patient numbers necessary for level 1 or 2 evidence; such limitations could be addressed through a randomized controlled trial. The excellent results in our trial should lead to consideration of a prospective, randomized, controlled clinical trial.

Conclusion

This experience demonstrates both the feasibility and effectiveness of perforator ablation in patients with nonhealing venous ulcers who fail a 2-month trial of compression therapy. In comparison to previous series of patients with CEAP 6 in which long-term compression therapy was used, we found that a subset of patients with active or healed venous ulcers and progressive lipodermatosclerosis experienced lower than expected ulcer recurrence rates at a median follow-up of 20 months when endovenous ablation of IPVs was used in conjunction with compression therapy.

Footnotes

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.

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