I. Venous and lymphatic challenges: superficial veins
I. Venous and lymphatic challenges:
Foam sclerotherapy can replace phlebectomy for the management of varicosities
Claudine Hamel-Desnos (Caen, France)
A review of the literature on truncal vein ablation showed no difference in terms of recurrences between concomitant and delayed treatment; moreover, Sutton et al1 showed that deep vein thrombosis occurred more when concomitant phlebectomy is performed. International guidelines are not all in accordance. An important factor for foam sclerotherapy is a relevant choice of access site. Key points before starting are disconnection of the large tributaries and a precise duplex ultrasound examination. Sclerotherapy is possible for large veins remaining dilated at the end of the procedure; however, the doses are decreased because of the inflammation caused by thermal ablation. A “wait and see” option is preferable, especially for the elderly; in fact, Claudine Hamel-Desnos recommends waiting 3 to 6 months for most patients. One of the indications where sclerotherapy can replace phlebectomies is when the subcutaneous part of an anterior accessory saphenous vein is implicated. Some physicians prefer phlebectomies because of the fear of thrombophlebitis. In the management of tributaries, there is no strong evidence supporting the superiority of the options, such as concomitant or delayed sclerotherapy and/or phlebectomies. Hamel-Desnos states that minimal sclerotherapy is a credible option and all extensive treatments of tributaries should be avoided. A new paradigm may be that glue will change habits and make phlebectomies disappear as Dr Kathleen Gibson stressed in her talk.
1. Sutton PA, El-Dhuwaib Y, Dyer J, Guy AJ. The incidence of post operative venous thromboembolism in patients undergoing varicose vein surgery recorded in Hospital Episode Statistics. Ann R Coll Surg Engl. 2012;94(7):481-483.
The benefit of non-thermal modalities
Steve Elias (Englewood, NJ, US)
Emerging endovenous technologies are divided into either thermal tumescent ablation or nonthermal nontumescent ablation. Thermal tumescent ablation techniques are subdivided into three categories, ie, radiofrequency ablation, laser ablation, and steam ablation, while nonthermal nontumescent ablation techniques are subdivided into mechanochemical (Clariven, Flebogrif), cyanoacrylate, and endovenous foams (polidocanol endovenous microfoam, Varithena) we are waiting for the results on hyaluronic acid (HIFU). When we focus on nonthermal nontumescent ablation, it looks beneficial for patients (less pain, faster, lower risk), for doctors (faster, lower risk), families (faster return to normal activities), and society (faster return to work). Tumescence is the most discomforting aspect of thermal tumescent ablation, the hardest part to learn, and the most time-consuming aspect. As of 2019, the rules for venous ablation can be outlined as follows: treat the lowest point of incompetence, to treat closer to the point of incompetence, and to increase the implementation of techniques, such as tributary and perforator ablation, for later stages of the disease. The application of these rules can be done while minimizing injury to nerves and skin. Benefits of the technique depend on the size, length, location, the neighboring nerves, surrounding tissues, and veins, disease state, and the patient type. Below the knee is challenging due to (i) the number of nerves (including saphenous, sural, tibial, and peroneal nerves); (ii) the sensory nerve location due to the proximity of the veins to the skin, which is the end organ to be damaged; and (iii) the difficulty in visualizing the veins in patients with clinical class C5 and C6. Especially in advanced disease states, tumescence is difficult from the great saphenous vein or small saphenous vein to the ankle and because of the feasibility of retrograde use, nonthermal nontumescent ablation methods should be preferred in the ulcer bed. As no nerve injuries are reported with nonthermal nontumescent ablation in the suprafascial part of the veins, it should be the preferred technique. The future of endovenous ablation is nonthermal nontumescent ablation technologies.
Technique and strategy are as important as modality in the treatment of superficial reflux
Manj Gohel (Cambridge, UK)
Older patients with more advanced disease are more likely to have recurrent veins and deep venous disease. Patient preference, patient variation, and the importance of below-the-knee great saphenous vein reflux must all be taken into consideration before performing a procedure. Better quality of life improvements and lower reintervention rates were obtained with both above- and below-the-knee ablations. Truncal ablation alone may be adequate for some patients, as varicosity treatment is associated with potentially serious complications. However, residual varicosities may be considered a treatment failure by the patient. There may be an argument for prophylactic ablation of a clinically insignificant anterior accessory saphenous vein. Significantly lower procedural pain scores were obtained when using buffered tumescence. Controversial areas can include the following: (i) treatment of perforators; (ii) treatment of superficial venous reflux in patients with a chronic venous disease classification of C3; (iii) when and how to investigate the obstruction; and (iv) treatment of superficial reflux in patients with a mixed-etiology disease. In conclusion, the enormous choice of endovenous modalities should not distract from important strategic and technical factors. The incompetent below-the knee segment should be ablated when feasible. These interventions remain more of an art than a science.
VeClose extension study five-year results
Nick Morrison (Scottsdale, AZ, US)
The VenaSealTM closure system uses an advanced nonthermal nontumescent venous ablation therapy that has no risk of thermal injury, with a rapid return to normal activity, and no need for postprocedural compression stockings. The eSCOPE study, a prospective, multicenter study that included 7 European sites, assessed the safety and efficacy of this system with follow-up visits at day 2 and months 1, 3, 6, 24, and 36. The VeClose trial, a US multicenter, randomized controlled study conducted under investigational device exemption, assessed the safety and efficacy of this system for the treatment of lower extremity truncal reflux compared with radiofrequency ablation. The trial assessed the noninferiority of anatomical closure at 3 months in 242 subjects and 10 sites with follow-up visits at day 3 and months 1, 3, 6, 12, 24, and 36. The WAVES trial, a postmarket evaluation of the VenaSealTM closure system conducted in a single center in the US with 5 providers, assessed vein closure, venous clinical severity score, Aberdeen Varicose Vein Questionnaire, pain, and return to normal activities and work in 50 subjects with follow-up visits at week 1 and months 1, 3, and 12.
The VeClose 5-year follow-up extension study was conducted to continue assessing the safety and efficacy of this system for the long-term effect on closure of the great saphenous vein with a follow-up 5 years after the index procedure enrolment in the VeClose study; 89 patients completed the 60-month visit. The primary outcome measure was complete closure and the secondary outcome measures were venous clinical severity score (VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), EuroQol-5D (EQ-5D), clinical, etiological, anatomical, and pathophysiological (CEAP) classification, satisfaction with treatment, adverse events, and adjunctive procedures. Baseline demographics were similar in both groups. Closure rates were sustained over the long term, with no new failures reported and noninferiority demonstrated through 60 months. Of the patients treated with the VenaSeal closure system, 53 maintained a closure rate of 94.6% at 60 months. Long-term durability in the group randomized to the VenaSeal closure system has been demonstrated with a closure rate of 93.6% at 60 months. The signs and symptoms associated with venous reflux disease (VCSS) improved over time, which was maintained through 60 months. There was a 55% reduction in the signs and symptoms in the VenaSeal closure system group vs 67.5 in the radiofrequency ablation group. Subjects reported a slight improvement in their current health state over time through 60 months with a 22% and 15% increase from baseline in VenaSeal closure system and radiofrequency ablation groups, respectively. Fewer subjects were classified as CEAP C3- 4b at 60 months than at baseline in the VenaSeal closure system group. All 47 patients in the VenaSeal closure system were somewhat or very satisfied with treatment at the 60-month follow-up, with 93.6% stating that they would definitely choose the VenaSeal closure system again. No long-term sequelae were reported in this cohort for VenaSeal closure system and radiofrequency ablation between the 36-month and the 60-month follow-up.
Post-procedure care after cyanoacrylate glue closure
Kathleen Gibson (Bellevue, WA, US)
An ideal patient can be defined as young with a healthy lifestyle, active, able to don compression stockings, eager to be back to work at once, and primarily with CEAP C2 disease. However, today’s patients are elderly with limited mobility, have difficulty donning compression stockings, need to maintain mobility and strength by walking right away, and have comorbidities and advanced venous disease. Kathleen Gibson’s aftercare for endothermal ablation includes not stopping anticoagulation (except in cases where there is bruising while on anticoagulation), using compression for up to 2 weeks, going back to work the next day, waiting to work out for 48 hours, using nonsteroidal anti-inflammatory drugs for analgesia, and not driving the same day if not taking sedatives. On the contrary, they can start driving the next day. For cyanoacrylate glue closure aftercare, she suggests immediate ambulation, not stopping anticoagulation if the patient is already taking them, usually no compression is needed, going back to work the same day, no restrictions on working out, taking nonsteroidal anti-inflammatory drugs for analgesia, and not driving the same day. She defines her usual follow-up procedure as to stage treatment of the tributaries/branches and perform a duplex ultrasound at the end of the case. The follow-up visit at 1 to 2 weeks and at 3 months consists of assessing for complications and tributaries and using duplex ultrasound as indicated. Potential common complications can include infection, deep vein thrombosis, phlebitis of a truncal vein, and phlebitis/ thrombosis of tributaries. Complications unique to cyanoacrylate glue closure can be systemic allergy, hypersensitivity reaction, and retained foreign body (glue in SQ [ethyl cyanoacrylate adhesive]).
VeClose (VenaSeal sapheon CLOSurE system vs radiofrequency ablation for incompetent great saphenous veins) and WAVES (Lake WAshington Vascular VenaSeal Post-Market Evaluation) are the first two trials evaluating cyanoacrylate glue closure. Both trials noted that some patients developed a self-limited cutaneous/dermal reaction within the first several weeks after the procedure, a reaction not typical for the one seen after the endothermal ablation. In the WAVES trial, patients with a reaction did not experience an impact on their return to work, normal activities, or pain scores at 1 month, but higher at 1 week. Kathleen Gibson presented her single-site VeClose trial, WAVES trial, and retrospective chart review from 2016 to 2018. Hypersensitivity was defined as a distinctive dermal reaction with erythema, itching, and variable edema and/or pain, where mild reactions required steroids, and severe and recurring reactions lasting more than 30 days required removal of the vein. No patient had a hypersensitivity reaction after treating the second limb if no reaction was observed after treating the first limb. A severe reaction was one with a recurrent rash and, in this case, the vein was excised with ultrasound guidance via small incisions. In Kathleen Gibson’s protocol, important steps to take are screening for an adhesive allergy, waiting a full 30 seconds after the last injection before removing the catheter, resheathing the delivery catheter prior to removal, and testing selective skin patches. Hypersensitivity reactions occurred in 6% of patients treated with cyanoacrylate glue, but the majority of cases were mild and self-limited. Patients classified as CEAP C4-6 showed a decreased reaction. Previous cyanoacrylate treatment was not a predictive factor for a hypersensitivity reaction. The value of screening/skin testing was not proven, but it was used selectively in this cohort.
The evolution of superficial venous management has moved away from thermal techniques
Kursat Bozkurt (Istanbul, Turkey)
Available alternatives to nonthermal nontumescent ablation are foam, mechanochemical ablation, and cyanoacrylate glue. If you take a close look at foam, it has a similar complication profile to that of endovenous laser ablation, radiofrequency ablation, ultrasound-guided foam sclerotherapy, and stripping, but foam has a 25% lower occlusion rate compared with the others. Neurologic events reported make this method less attractive. In other reports, no difference in Aberdeen Varicose Vein Questionnaire (AVVQ), venous clinical severity score (VCSS), EuroQol-5D (EQ-5D), and short form 36 (SF36) were reported. Varithena® may overcome the inconsistency of physician compounded foam, but its use is limited due to a fixed concentration and cost. Clinical trials have demonstrated equivalent or better efficacy and safety outcomes compared with physician-compounded foam.
Studies analyzing mechanochemical ablation revealed a 92%, 90%, and 87% anatomic success at 1, 2, and 3 years, respectively. Clinical success at 3 years was 83%. The AVVQ and SF36 scores showed improvement, and a significant deterioration was observed in VCSS between 12 and 36 months, which was accompanied by a worsening of disease specific and general quality of life. On the contrary, 3-month closure rates for glue were reaching up to 99%, compared with 96% for radiofrequency ablation. Pain scores were mild and similar between treatment groups. At day 3, less ecchymosis in the treated region was present after cyanoacrylate glue adhesion compared with radiofrequency ablation. In the VeClose trial, the complete closure rates at 3 years were 94.4% for VenaSeal and 91.9% for radiofrequency ablation. Studies conducted to show the efficacy of VenaBlock revealed a 99.4% occlusion rate at the 12-month follow-up, and the VCSS and AVVQ scores decreased significantly. In another study conducted for VenaBlock in 573 patients, no adverse events were observed, including deep vein thrombosis, pulmonary embolism, and paresthesia. The clinical recurrence-free rate at 2 years was 99.38% and the VCSS and AVVQ scores decreased significantly. An analysis of 7 studies that included 1000 limbs and consisted of 53 cases of small saphenous vein involvement revealed an average procedure duration of 11.7 minutes, an occlusion rate at 12 and 30 months of 96.8% and 94.1%, respectively. Another study with 456 patients compared n-butyl cyanoacrylate, radiofrequency ablation, and endovenous laser treatment showed that, at the 2-year follow-up, n-butyl cyanoacrylate appeared superior with respect to periprocedural pain, time to return to work, and a decreased VCSS. For the small saphenous vein, endovenous laser treatment showed higher pooled anatomic success rates compared with surgery, while neurologic complications were also lower in the endovenous laser treatment group.
Questions regarding nonthermal nontumescent ablation emerged due to a lack of long-term data about the occurrence of phlebitis, granuloma, and long residual stumps. Phlebitis seems to occur less frequently with Turkish glue (4.5%) compared with VenaSeal (14% to 20%), which can be explained by the composition of n-butyl cyanoacrylate, the continuous delivery method, and the fast polymerization that allows getting cyanoacrylate into each cm of the vein to leave no empty space without glue and no residual blood inside the vessel. Kursat Bozkurt stated that they had full reimbursement for glue for over 5 years in Turkey. The overall experience in Turkey and in other countries (>27) is around 8000 cases with no reported granuloma, albeit long-term data is necessary.
3RF trial: randomised trial of three radiofrequency devices for great saphenous vein ablation
Isaac Nyamekye (Worcester, UK)
The 3RF study was conducted to compare the clinical efficacy of Venefit, radiofrequency induced thermal therapy device (RFiTT®), and endovenous radiofrequency (EVRF) in a randomized controlled trial. The radiofrequency energy delivery protocol was defined for these three modalities according to the size of the vein to be ablated. Postoperative treatment management was immediate ambulation, discharge after 30 minutes, compression stockings for up to 2 weeks, and recording pain scores for 7 days. The primary outcome was great saphenous vein ablation, and the secondary outcomes were complications, treatment time, 7-day pain scores, health-related quality of life (EuroQol-5D [EQ-5D] and Aberdeen Varicose Vein Questionnaire [AVVQ]). Venefit and RFiTT resulted in a 100% and 98% ablation, respectively, at 6 months, whereas EVRF resulted in inferior ablation rates (21% failure at 6 months). EQ-5D and AVVQ did not differ at 12 months. Existing EVRF users should take special measures for consent and must study and audit their outcomes. One should be more critical before accepting new unproven endovenous technologies into clinical practice.
Current theories on indications and techniques for perforator ablation
Kathleen Gibson (Bellevue, WA, US)
In the US, up to 6 million patients with venous disease per year account for 70% of leg ulcers. The direct costs of leg ulcers reach close to 2.5 billion US dollars per year, while indirect costs include time off work for wound care and disability. Substantial evidence supports a role for incompetent perforator veins in chronic venous insufficiency. Approximately, two-thirds of limbs with skin changes have incompetent perforator veins as well as superficial or deep reflux; 63% of recurrent varicose veins are associated with incompetent perforator veins. A pathologic incompetent perforator vein is described as having an outward flow ≥500 msec, a diameter ≥3.5 mm, and a location that is beneath a healed or open venous ulceration.
The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) guidelines suggest ablating incompetent superficial veins and perforator veins, as well as using compression therapy to aid in ulcer healing and prevent recurrence in grade 2C patients with ulcers. In patients at risk for an ulcer (C4b) or a healed ulcer (C5), the guidelines suggest ablating the incompetent superficial veins to prevent ulcer development or recurrence. Perforator ablation can be performed simultaneously or staged if still incompetent on reevaluation with grade 2C patients. Treatment options are the Linton procedure, subfascial endoscopic perforator surgery, direct perforator ligation, percutaneous radiofrequency ablation, percutaneous laser ablation, foam sclerotherapy, and nonthermal ablation. Radiofrequency ablation for an incompetent perforator vein delivers bipolar radiofrequency energy to the treatment site. Laser ablation for incompetent perforator veins can go directly through a needle or sheath (method supported by data from the SECURE trial [SeCure Endovenous Laser Treatment Study]). Key points to preoperative duplex assessment imaging are positioning the patient in a supine position with reverse Trendelenburg to dilate the perforator veins, performing medial or lateral imaging from the malleolus to the knee (longitudinal orientation shows a path of tortuous perforators and assists with access, alternates between cross-sectional and longitudinal views, often one or several perforators underneath or adjacent to active ulcers), and marking of the incompetent perforator veins on the skin where they penetrate the fascia. Local tumescence is injected to surround the perforator. Drawbacks to endothermal techniques can include nerve injury, arteriovenous fistula, difficulty in positioning once tumescence is in, the need for more tumescence in case of pain, and nonsatisfying closure rates. Possible complications are thrombosis, pulmonary embolism, foot drop/nerve damage, skin burn, phlebitis, hematoma, arteriovenous fistula, and infection. The usefulness of cyanoacrylate and polidocanol endovenous microfoam can be explained by the avoidance of tumescence in damaged skin and avoidance of nerve injury for below the knee procedures. Kathleen Gibson’s personal experience includes 30 perforators in patients with advanced disease with 100% technical success at the day of the procedure. The CAPE feasibility study (Cyanoacrylate Adhesive Perforator Embolization) of cyanoacrylate for incompetent perforator veins included 33 perforators, which showed a 76% closure rate; there were 2 infections and no deep vein thromboses. The potential for proprietary foam arises from the truncal ablation with branch treatment, possible direct perforator injection, ulcer bed treatment, and an ongoing clinical trial.
In conclusion, the current guidelines suggest a role for incompetent perforator vein ablation in patients with pathologic perforator veins. Closure rates remain lower for incompetent perforator veins compared with truncal veins. Nonthermal techniques may offer some advantages over thermal techniques.