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A systematic review and meta-analysis of mechanochemical endovenous ablation using Flebogrif for varicose veins

Open AccessPublished:June 03, 2021DOI:https://doi.org/10.1016/j.jvsv.2021.05.010

      Abstract

      Objective

      In the present study, we reviewed and analyzed the currently available data on the Flebogrif device (Balton, Warsaw, Poland) to define its role in the global varicose vein treatment devices market.

      Methods

      A systematic literature search was performed in MEDLINE, Embase, and the Cochrane Library. Studies were eligible if they had included patients treated using the Flebogrif for saphenous vein incompetence, had been reported in English, and had the full text available. The methodologic quality of the studies was assessed using the methodologic index for nonrandomized studies (MINORS) score. A random effects model was used to estimate the primary outcome of anatomic success, defined as the occlusion rate of the treated vein. The estimates are reported with the 95% confidence intervals (CIs). The secondary outcomes were clinical success, complication rate, pain during and after the procedure, and time to return to work.

      Results

      Five articles met the inclusion criteria, reporting 348 procedures in 392 patients. Four studies reported the 3-month anatomic success, and three studies reported the 12-month anatomic success. The pooled 3-month anatomic success rate was 95.6% (95% CI, 93.2%-98.0%). The 12-month anatomic success rate was 93.2% (95% CI, 90.3%-96.1%). The only major complication reported within 3 months was deep vein thrombosis, which developed in 0.3% of the patients. The minor complications of thrombophlebitis and hyperpigmentation had occurred in 13.3% to 14.5% and 3.3% to 10.0% of patients, respectively, within 3 months. The methodologic quality of the included studies was moderate.

      Conclusions

      Mechanochemical ablation using the Flebogrif device is a safe and well-tolerated procedure for the treatment of saphenous vein insufficiency. However, well-designed studies of sufficient sample size and follow-up are required to compare the effectiveness with other endovenous treatment modalities and define the definitive role of the Flebogrif device.

      Keywords

      Chronic venous insufficiency of the lower limbs is a common disease, with a prevalence of superficial vein reflux of 21%, which increases linearly with age.
      • Maurins U.
      • Hoffmann B.H.
      • Lösch C.
      • Jöckel K.H.
      • Rabe E.
      • Pannier F.
      Distribution and prevalence of reflux in the superficial and deep venous system in the general population—results from the Bonn Vein Study, Germany.
      Chronic venous insufficiency is mainly caused by saphenous vein insufficiency and has been associated with decreased general and disease-specific quality of life.
      • Eklöf B.
      • Rutherford R.B.
      • Bergan J.J.
      • Carpentier P.H.
      • Gloviczki P.
      • Kistner R.L.
      • et al.
      Revision of the CEAP classification for chronic venous disorders: consensus statement.
      • Carradice D.
      • Mazari F.A.
      • Samuel N.
      • Allgar V.
      • Hatfield J.
      • Chetter I.C.
      Modelling the effect of venous disease on quality of life.
      • Andreozzi G.M.
      • Cordova R.M.
      • Scomparin A.
      • Martini R.
      • D'Eri A.
      • Andreozzi F.
      • et al.
      Quality of life in chronic venous insufficiency: an Italian pilot study of the Triveneto region.
      Minimally invasive techniques with local anesthesia, such as radiofrequency ablation (RFA) and endovenous laser ablation (EVLA), have replaced the traditional saphenofemoral ligation and stripping.
      • Marsden G.
      • Perry M.
      • Kelley K.
      • Davies A.H.
      Guideline Development Group
      Diagnosis and management of varicose veins in the legs: summary of NICE guidance.
      However, the use of these endothermal ablation techniques has been associated with the risk of skin burns, nerve injury, and prolonged pain. Furthermore, tumescent anesthesia can be painful.
      • Bakker N.A.
      • Schieven L.W.
      • Bruins R.M.
      • van den Berg M.
      • Hissink R.J.
      Compression stockings after endovenous laser ablation of the great saphenous vein: a prospective randomized controlled trial.
      To avoid these risks and reduce pain, nonthermal treatment methods, such as ultrasound-guided foam sclerotherapy (UGFS), cyanoacrylate, and mechanochemical ablation (MOCA), have been developed. MOCA is a recently introduced therapy that combines mechanical endothelial damage with the infusion of sclerosant. In addition to the ClariVein device (Merit Medical, South Jordan, Utah), which consists of a rotating wire causing endothelial damage, a new device, Flebogrif (Balton, Warsaw, Poland), has entered the market. It combines endothelial damage performed by radial retractable cutting hooks with chemical ablation through sclerosant foam injection. The major benefit of MOCA is the pain reduction during and after treatment, because no heat is used and tumescence anesthesia is not required.
      The Flebogrif device is available worldwide, and the reports from prospective follow-up studies are becoming available. Therefore, the present systematic review was conducted to investigate the currently available data on the Flebogrif and define its role in the global varicose vein treatment devices market.

      Methods

      The present report was written in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for reporting systematic reviews and meta-analyses.
      • Moher D.
      • Shamseer L.
      • Clarke M.
      • Ghersi D.
      • Liberati A.
      • Petticrew M.
      • et al.
      Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.

       Literature search

      A systematic search was performed using the MEDLINE, Embase, and Cochrane Library. The following keywords or abbreviations were used: varicose veins, varix, varices, venous insufficiency, saphenous vein, mechanochemical, Flebogrif, Phlebogriffe, and mechanical occlusion chemically assisted ablation. The final search was performed on October 13, 2020. The reference lists of the retrieved articles, Google Scholar, and the website of the company that developed the Flebogrif device (available at: https://balton.pl) were also used to identify studies not found in the original search. A full search strategy can be found in Supplementary Table I (online only). The individual investigators of the included studies were not contacted.

       Inclusion and exclusion criteria

       Studies

      Studies were eligible if they had included patients treated for varicose veins with Flebogrif, had been reported in English, and had the full text available. The exclusion criteria were the use of another MOCA device (eg, ClariVein), case reports, commentaries, letters to the editor, and conference abstracts.

       Participants

      Studies reporting the outcomes of patients who were treated with Flebogrif for saphenous vein insufficiency were included.

       Outcome measures

      The primary outcome was anatomic success, defined as successful occlusion with no flow through the treated vein. The secondary outcomes were clinical success measured by the mean values of improvement in the standardized venous clinical severity score (VCSS), complication rates, pain during and after the procedure, and time to return to work.

       Data collection and quality assessment

      After the duplicates had been removed, two of us (T.A., E.H.) had screened the titles and abstracts of the identified studies for relevance. Of the relevant studies, the two of us (T.A., E.H.) read the full text and made a final selection. The methodologic quality of the studies was assessed using the methodologic index for nonrandomized studies (MINORS) score, with a global ideal score of 16 for noncomparative studies and 24 for comparative studies.
      • Slim K.
      • Nini E.
      • Forestier D.
      • Kwiatkowski F.
      • Panis Y.
      • Chipponi J.
      Methodological index for non-randomized studies (MINORS): development and validation of a new instrument.
      The MINORS score is reported as a percentage of the global ideal score. For the present review, a score of ≤8 was considered poor quality, 9 to 14 moderate quality, and ≥15 good quality for noncomparative studies. For comparative studies, a score of ≤15 was considered poor quality, 16 to 22 moderate quality, and ≥23 good quality. A discrepancy between the authors during the search, selection, and quality assessment were resolved by discussion. If necessary, a third author (C.Ü.) was consulted until agreement was reached.

       Data extraction

      Two of us (T.A., E.H.) independently performed the data extraction. Standardized forms were used to extract the year of publication, study design, sample size, study period, inclusion criteria, exclusion criteria, age, sex, treated vein diameter, type and concentration of foam sclerosant, visual analog scale for pain, VCSS, CEAP (clinical, etiology, anatomy, pathophysiology), occlusion, recanalization, or recurrence rate, complication rate, and the follow-up duration.

       Statistical analysis

      OpenMetaAnalyst software (CEBM, Brown University, Providence, RI) was used for analysis. Data were pooled if the following criteria were met: randomized trial, comparative study, or case series; anatomic success defined as occlusion rates at 3 or 12 months, or both; and polidocanol (POL) or sodium tetradecyl sulfate (STS) concentration of 2% or 3%. If only the recanalization or recurrence rates were presented, the occlusion rates were calculated. If recanalization had been further divided into segmental or partial, the overall recanalization rate was used to calculate the occlusion rate. Two separate analyses were performed to calculate the anatomic success rates at 3 and 12 months. Loss to follow-up was not included in the calculation of the anatomic success rates. The DerSimonian-Laird random effects model was used for pooled data analysis. The results are presented as odds ratios (ORs) with the 95% confidence intervals (CIs). Heterogeneity between studies was determined using forest plots and the I2 index.

      Results

       Study selection

      The search identified 266 studies. After the duplicates had been removed and the titles and abstracts screened for relevance, 49 reports were eligible for the full-text review. The full-text reading and application of the inclusion and exclusion criteria resulted in the inclusion of five studies in the present systematic review. The included studies consisted of three prospective case series,
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      one prospective comparative study,
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      and one randomized trial.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      We excluded 44 studies for the following reasons (Supplementary Table II, online only): case reports,
      • Jindal R.
      • Verma D.
      • Kaur T.
      • Dhillon S.
      • Kaur N.
      • Chaudhary P.
      Mechanochemical endovenous ablation: latest varicose vein treatment.
      conference abstracts,
      • Babin Z.I.
      • Badar M.
      Literature review and results comparison of mechanochemical endovenous ablation.
      • Belramman A.
      • Bootun R.
      • Tang T.Y.
      • Lane T.R.A.
      • Davies A.H.
      Mechanochemical ablation versus cyanoacrylate adhesive for the treatment of varicose veins: study protocol for a randomised controlled trial.
      • Belramman A.
      • Bootun R.
      • Yip Tang T.
      • Lane T.R.A.
      • Davies A.H.
      Randomized clinical trial of mechanochemical ablation versus cyanoacrylate adhesive for the treatment of varicose veins.
      • Chung J.K.
      • Kim S.
      • Zygmunt J.
      • Watercott A.
      • Singh K.P.
      • Syeda S.S.
      Indirect comparison and cost-effectiveness analysis of minimally invasive endovenous cyanoacrylate glue occlusion, surgical and other treatment options in chronic venous insufficiency.
      • Gupta A.
      • Fernandez E.
      • Lakhanpal S.
      • Pappas P.
      Clinical effectiveness of mechanochemical ablation versus radiofrequency ablation for symptomatic great or small saphenous vein reflux.
      • Halmesmaki K.
      • Vähäaho S.
      • Mahmoud O.
      • Albäck A.
      • Vikatmaa P.
      • Aho P.
      Mechanochemical ablation vs. thermal ablation in GSV insufficiency: results of a RCT after 3-year follow-up.
      • Ibrahim M.I.
      • Nabil K.A.
      • Abdalmageed A.M.
      • Hussein G.K.
      Great saphenous vein mechanochemical sclerotherapy versus laser ablation in treatment of varicose vein.
      • Jindal R.
      A single center randomized controlled trial comparing radiofrequency and mechanical occlusion chemically assisted ablation of varicose veins in patients with bilateral involvement: initial experience.
      • Kawanishi D.
      • Tappin K.
      • Aschan S.
      Decrease of number of chemical ablation procedures required to achieve ablation of varicose vein tributaries with ≥3mm diameter following non-thermal, nontumescent ablation compared to thermal, tumescent ablation: single-center noninvestigational initial experience with nonthermal non-tumescent techniques.
      • Kawanishi D.
      • Tappin K.
      • Willy L.
      • Afrasiabi M.
      • Schofield M.
      • Loussararian A.
      Incidence of segments with complete or partial compressibility and of extension of thrombus into a deep vein at early follow-up ultrasound examination following ablation using non-thermal non-tumescent techniques.
      • Kim S.Y.
      • Vanegas A.A.
      • Png C.Y.M.
      • Ting W.
      • Faries P.L.
      • Marin M.L.
      Mechanochemical ablation improves venous ulcer healing compared to thermal ablation.
      • Lajos P.
      • Weiss R.
      • Weber J.
      • Marin M.
      • Faries P.
      Use of compression wraps immediately after venous closure: does it matter?.
      • Sinha Y.
      • Busuttil A.
      • Onida S.
      • Davies A.
      Quality of life assessment using validated measures after endovenous intervention for varicose vein disease—a systematic review.
      • Tal M.
      • Sivek G.
      • Avrahami R.
      Inframalleolar access for endovascular treatment of venous insufficiency ulcers.
      • Tal M.
      • Avrahami R.
      • Sivak G.
      03:36 PM Abstract No. 155: inframalleolar venous access for endovascular treatment of venous insufficiency ulcers.
      • Teichert C.
      Two-year outcome after MOCA.
      • Teßarek J.
      The mechano-chemical endovenous ablation (MOCA) for the treatment of varicosal veins: technique and results.
      reviews with overlapping data,
      • Bootun R.
      • Lane T.R.
      • Davies A.H.
      The advent of non-thermal, non-tumescent techniques for treatment of varicose veins.
      • Bootun R.
      • Lane T.R.A.
      • Davies A.H.
      A comparison of thermal and non-thermal ablation.
      • Bootun R.
      • Onida S.
      • Lane T.R.A.
      • Davies A.H.
      Varicose veins and their management.
      • Hassanin A.
      • Aherne T.M.
      • Greene G.
      • Boyle E.
      • Egan B.
      • Tierney S.
      A systematic review and meta-analysis of comparative studies comparing nonthermal versus thermal endovenous ablation in superficial venous incompetence.
      • Néaume N.
      • Josnin M.
      Endovenous treatments of lower limbs varicose veins: a review (part 2).
      • Neaume N.
      Management of small saphenous vein varices with perspectives from a recent meta-analysis and recommendations.
      • Nugroho J.
      • Wardhana A.
      • Ghea C.
      Mechanical occlusion chemically assisted ablation (MOCA) for saphenous vein insufficiency: a meta-analysis of a randomized trial.
      • Singhal S.
      • Uthappa M.C.
      Endovascular management of varicose veins: a review of literature.
      • Sun J.J.
      • Chowdhury M.M.
      • Sadat U.
      • Hayes P.D.
      • Tang T.Y.
      Mechanochemical ablation for treatment of truncal venous insufficiency: a review of the current literature.
      • Vos C.G.
      • Ünlü Ç.
      • Bosma J.
      • van Vlijmen C.J.
      • de Nie A.J.
      • Schreve M.A.
      A systematic review and meta-analysis of two novel techniques of nonthermal endovenous ablation of the great saphenous vein.
      • Vuylsteke M.E.
      • Klitfod L.
      • Mansilha A.
      Endovenous ablation.
      the use of ClariVein,
      • Bishawi M.
      • Bernstein R.
      • Boter M.
      • Draughn D.
      • Gould C.F.
      • Hamilton C.
      Mechanochemical ablation in patients with chronic venous disease: a prospective multicenter report.
      • Boersma D.
      • Kornmann V.N.
      • van Eekeren R.R.
      • Tromp E.
      • Ünlü Ç.
      • Reijnen M.M.
      Treatment modalities for small saphenous vein insufficiency: systematic review and meta-analysis.
      • Elias S.
      • Lam Y.L.
      • Wittens C.H.
      Mechanochemical ablation: status and results.
      • Hartmann K.
      Varicosis: crossectomy and stripping versus endovenous techniques: when to use which method and why—a categorisation attempt.
      • Hartmann K.
      Mechano-chemical ablation in the treatment of small saphenous vein varicosis.
      • Kim P.S.
      • Bishawi M.
      • Draughn D.
      • Boter M.
      • Gould C.
      • Koziarski J.
      Mechanochemical ablation for symptomatic great saphenous vein reflux: a two-year follow-up.
      • Sadek M.
      • Kabnick L.S.
      Are non-tumescent ablation procedures ready to take over?.
      • Vähäaho S.
      • Mahmoud O.
      • Halmesmäki K.
      • Albäck A.
      • Noronen K.
      • Vikatmaa P.
      Randomized clinical trial of mechanochemical and endovenous thermal ablation of great saphenous varicose veins.
      • Vähäaho S.
      • Halmesmäki K.
      • Mahmoud O.
      • Albäck A.
      • Noronen K.
      • Venermo M.
      Three-year results of a randomized controlled trial comparing mechanochemical and thermal ablation in the treatment of insufficient great saphenous veins.
      overlapping data with an already included report by same author,
      • Zubilewicz T.
      • Terlecki P.
      • Terlecki K.
      • Przywara S.
      • Rybak J.
      • Iłźecki M.
      Application of endovenous mechanochemical ablation (MOCA) with Flebogrif™ to treat varicose veins of the lower extremities: a single center experience over 3 months of observation.
      ,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Urbanek T.
      • Pedrycz-Wieczorska A.
      • Dave S.
      A new device for minimally invasive mechanochemical method of saphenous vein ablation: report of 12 months of follow up.
      other outcomes,
      • Hirsch T.
      Varicose vein therapy and nerve lesions.
      no data reported,
      • Milleret R.
      What is the future of treatment of varices by endovenous procedures?.
      and data not yet available.
      • Jprn U.
      Mechanical occlusion chemically assisted ablation (MOCA) for varicose vein: a metaanalysis of randomized-trial.
      A flow chart of the selection procedure is shown in Fig 1.
      Figure thumbnail gr1
      Fig 1PRISMA (preferred reporting items for systematic reviews and meta-analyses) flow diagram for literature search to identify studies reporting on mechanochemical endovenous ablation using Flebogrif (Balton, Warsaw, Poland).

       Quality assessment

      The included studies were of moderate quality as assessed using the MINORS score. None of the included studies had reported a prospective calculation of the study size, and none of the studies had described an unbiased assessment of the endpoint. One study had a substantial loss to follow-up of 44% (Table I).
      Table IQuality appraisal (MINORS score)
      Items 9-12 only for comparative studies.
      ItemAmmollo et al,
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      2020
      Ciostek et al,
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      2015
      Iłźecki et al,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      2019
      Soliman et al,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      2019
      Tawfik et al,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      2020
      1. Clearly stated aim22202
      2. Inclusion of consecutive patients22122
      3. Prospective data collection22222
      4. Endpoint appropriate to study aim22222
      5. Unbiased assessment of study endpoint00000
      6. Follow-up period appropriate to study aim22212
      7. Loss to follow-up <5%22022
      8. Prospective calculation of study size00000
      9. Adequate control group20002
      10. Contemporary groups00002
      11. Baseline equivalence of groups00002
      12. Adequate statistical analysis10002
      Total MINORS score15129920
      Maximum possible score2416161624
      0, Not reported; 1, reported but inadequate; 2, reported and adequate; MINORS, methodologic index for nonrandomized studies.
      a Items 9-12 only for comparative studies.

       Study and patient characteristics

      Five articles met the inclusion criteria, reporting 348 Flebogrif procedures in 392 patients. The study period of the included reports ranged from January 2011 to May 2019. In three of the five studies, the purpose was to investigate the efficacy and safety of Flebogrif.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      The purpose of one study was to evaluate the efficacy of Flebogrif by varying the POL foam concentrations.
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      In one study, the results of EVLA using a 1470-nm diode laser and a radial fiber were compared with results of Flebogrif.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      Two of the five studies had included patients who had been treated for great saphenous vein (GSV) incompetence.
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      The other three studies had included patients with GSV or small saphenous vein (SSV) incompetence.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      The characteristics of the included studies are summarized in Table II, and the baseline data of the included studies for the analysis are summarized in Table III.
      Table IICharacteristics of included studies
      InvestigatorDesignPeriodAimInclusion criteriaExclusion criteria
      Ammollo et al,
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      2020
      Prospective comparative1/2019-5/2019To assess efficacy of Flebogrif by varying POL foam concentrationsChronic venous disease symptoms; reflux at SFJ; linear GSV without large, tortuous truncular collaterals; GSV diameter at SFJ level of ≤60 mmNR
      Ciostek et al,
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      2015
      Prospective case series2011-2013To assess efficacy and safety of FlebogrifPrimary GSV or SSV incompetence; CEAP C2-C6NR
      Iłźecki et al,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      2019
      Prospective case series2013-2015To assess efficacy and safety of FlebogrifPrimary GSV or SSV incompetenceNR
      Soliman et al,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      2019
      Prospective case series10/2018-5/2019To assess efficacy and safety of FlebogrifAge ≥18 years; primary GSV or SSV incompetence; CEAP C2-C6Allergy to sclerosant; severely tortuous GSV or SSV; history of deep venous thrombosis, peripheral arterial disease (ABPI <0,8); pregnancy or lactating; anticoagulation with warfarin
      Tawfik et al,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      2020
      Randomized trial1/2017-10/2018To compare Flebogrif and EVLAPrimary GSV incompetence with or without incompetent perforators based on DUS; CEAP C2-C4Pregnancy; history of superficial thrombophlebitis, deep vein thrombosis, pulmonary embolism; venous ulcers (healed or active); severe medical illness (cardiac, hepatic, renal, cancer, bleeding disorders); recurrent VV; anticoagulant therapy; peripheral arterial disease; vasculitis; internal pacemaker
      ABPI, Ankle brachial pressure index; CEAP, clinical, etiology, anatomy, pathophysiologic; DUS, duplex ultrasound; EVLA, endovenous laser ablation; GSV, great saphenous vein; POL, polidocanol; SFJ, saphenofemoral junction; SSV, small saphenous vein; VV, varicose veins.
      Table IIIBaseline data of included studies
      CharacteristicInvestigator
      Ammollo et al,
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      2020
      Ciostek et al,
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      2015
      Iłźecki et al,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      2019
      Soliman et al,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      2019
      Tawfik et al,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      2020
      Patients, No.23 (100)39 (100)200 (100)30 (100)50 (100)
      Male sex4 (17)6 (15)30 (15)10 (33)17 (34)
      Legs, No.24392003550
      Age, yearsNR52 ± 1651NR34 ± 10
      CEAPNRNRNR
       C250
       C3916
       C41234
       C570
       C660
       Mean total scoreNRNR7.6NRNR
      Mean total VCSSNR5.910.7NR11
      Treated vein
       GSV24NR17233
      Nineteen unilateral GSV, five bilateral GSV, two unilateral SSV, four unilateral GSV and SSV.
      50
      Forty-five unilateral GSV and five unilateral GSV and SSV.
       SSV0NR286
      Nineteen unilateral GSV, five bilateral GSV, two unilateral SSV, four unilateral GSV and SSV.
      5
      Forty-five unilateral GSV and five unilateral GSV and SSV.
       GSV diameter, mm4.6 ± 0.56.2 ± 2.06.2 (3.8-17.1)6.211.3 ± 3.9
       SSV diameter, mmNR5.6 ± 2.76.2 (3.8-17.1)NRNR
      Polidocanol concentration, %NR
      Soliman et al11 reported the use of polidocanol 2% for veins with a diameter of 15 mm and polidocanol 3% for veins of a larger diameter; the specific number of patients in each group was not reported.
       1.512000
       2.01239050
       3.0002000
      Post-treatment compression, daysNR21-242810NR
      Ultrasound surveillance31, 3, 6, and 12 months1 week; 1, 3, 6, 12, and 24 months1 and 3 months1 week; 1, 6, and 12 months
      CEAP, Clinical, etiology, anatomy, pathophysiologic; GSV, great saphenous vein; NR, not reported; SSV, small saphenous vein; VCSS, venous clinical severity score.
      Data presented as number (%) or mean ± standard deviation, unless stated otherwise.
      a Nineteen unilateral GSV, five bilateral GSV, two unilateral SSV, four unilateral GSV and SSV.
      b Forty-five unilateral GSV and five unilateral GSV and SSV.
      c Soliman et al
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      reported the use of polidocanol 2% for veins with a diameter of 15 mm and polidocanol 3% for veins of a larger diameter; the specific number of patients in each group was not reported.

       Technical details

      The key technical aspects of the procedure were comparable between all four studies that had reported the technical details of the Flebogrif procedure.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      With the patient under local anesthesia, the vein was punctured with an 18-guage needle using ultrasound guidance. A 0.035-in. guidewire was introduced into the vein, and a 4F to 6F vascular sheath was inserted over the guidewire. The Flebogrif catheter was placed through the vascular sheath, and its tip was positioned 2 to 5 cm from saphenofemoral junction (GSV) or saphenopopliteal junction (SSV) to prevent the application of the obliterating agent into the femoral vein.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      By retracting the outer sheath, five cutting elements with sharp hooks on the end were released, and scarification of the vein was performed by withdrawing the system with continuous movement. Simultaneously, POL foam was injected. The technical differences between the studies were the speed at which the system slid and the POL concentration. The pullback speed varied from 1 to 5 cm/second.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      Ammollo et al
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      compared POL at 1.5% and POL at 2.0%. Iłźecki et al
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      used POL at 2% for veins with a diameter of 15 mm and POL at 3% for veins with a larger diameter. The other three studies used POL at 3%.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      ,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      The volume of the injected foam amounted to 1 mL/5 cm of vein.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      After the procedure, an elastic bandage or class 2 compression stockings were applied for 10 to 28 days, reported by three studies.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      Postoperative anticoagulation was only administered in the study by Iłźecki et al.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      Enoxaparin was chosen for patients with an increased risk of thromboembolism at a dose of 1 × 40 mg subcutaneously for 10 days postoperatively.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      Adjunctive treatment, in addition to GSV or SSV ablation, was reported in two studies.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      In 16 of 30 patients reported in the study by Soliman et al,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      complementary foam sclerotherapy was performed during the 4 weeks of follow-up. The volume of sclerosant foam ranged from 5 to 10 mL, and the POL concentration was 2%. In the study by Tawfik et al,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      complementary UGFS using POL at 3% to treat incompetent perforating veins and superficial varicosities was performed in 44 and 32 of the 50 patients, respectively.

       Primary outcomes

       Anatomic success

      One study reported anatomic success at 1 month, which was 97%.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      Four studies reported anatomic success at 3 months, which ranged from 83% to 100%.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      Ammollo et al
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      reported a greater occlusion rate in the POL 3.0% group compared with the POL 1.5% group (100% vs 83%, respectively). The 6-month occlusion rate was assessed by Ciostek et al,
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      which was 90%. Three studies had reported the 12-month occlusion rates, which varied from 90% to 96%.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      ,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      One study compared Flebogrif with EVLA and reported occlusion rates of 96% vs 98% after 12 months.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      Iłźecki et al
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      performed the longest follow-up, with an occlusion rate of 93% after 24 months.

       Pooled analysis

      Data from three prospective case series, one comparative study, and one randomized trial were included in the analysis. Four of the five studies reported the 3-month anatomic success, and three of five studies reported the 12-month anatomic success. The pooled 3-month anatomic success rate was 95.6% (95% CI, 93.2%-98.0%). The 12-month anatomic success rate was 93.2% (95% CI, 90.3%-96.1%; Fig 2).
      Figure thumbnail gr2
      Fig 2Forest plots of pooled data on 3- (A) and 12-month (B) anatomic success. CI, Confidence interval. Solid squares denote the mean difference; horizontal lines, the 95% CI; diamonds, the weighted mean differences; and tips, the 95% CI.

       Secondary outcomes

       Clinical success

      Three studies reported the VCSS, which is a system used to score the severity of venous disease and allows for the monitoring of the response to treatment.
      • Rutherford R.B.
      • Padberg Jr., F.T.
      • Comerota A.J.
      • Kistner R.L.
      • Meissner M.H.
      • Moneta G.L.
      Venous severity scoring: an adjunct to venous outcome assessment.
      The mean VCSS improved from 9.21 ± 2.86 at baseline to 3.02 ± 1.20 at the 12-month follow-up.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      ,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.

       Intraprocedural and postprocedural pain

      Three studies reported patients' pain before, during, or after the procedure using a 10-point visual analog scale. Only Soliman et al
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      assessed intraprocedural pain and reported a mean pain score of 6. The mean pain scores were 3.2 after 1 week and 1.2 after 1 month. After 3 months, the patients reported no pain.
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      Iłźecki et al
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      reported a mean pain score of 3.2, 1.9, 0.7, and 0.6 before the procedure and at 1, 6, and 12 months after the procedure, respectively. Tawfik et al
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      observed a mean pain score of 7.4, 1.3, 0.4, and 0.2 measured before and at 1, 6, and 12 months after the procedure, respectively. The 24-month mean pain score was reported by Iłźecki et al
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      and was 0.64.

       Complications

      Complications within 3 months were reported by two studies. One study reported a deep vein thrombosis rate of 0.5%,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      thrombophlebitis in 13.3% to 14.5%,
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      and hyperpigmentation in 3.3% to 10.0%.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      ,
      • Soliman M.D.
      • Ahmed H.
      Mechano-chemical endo-venous ablation of varicose veins with Flebogrif occlusion catheter.
      The two other studies reported the 12-month complications. Ciostek et al
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      reported aching along the course of the vein in 20.5% of the patients, hyperpigmentation in 5.1%, telangiectasia in 7.7%, and thrombophlebitis in 35.9%. Tawfik et al
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      reported bruising in 2.0% of the patients after Flebogrif vs 4.0% after EVLA and phlebitis in 0.0% after Flebogrif vs 14.0% after EVLA. No hematoma was seen in any of the groups. One study did not evaluate the risk of complications.
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.

       Time to return to work

      The time to return to work, which was only assessed by Tawfik et al,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      was shorter after Flebogrif compared with EVLA (3.8 ± 1.0 days vs 8.0 ± 1.4 days; P < .001).

      Discussion

      The present systematic review evaluated the currently available data for MOCA using the Flebogrif device in the treatment of saphenous vein insufficiency. The pooled anatomic success of Flebogrif after 3 and 12 months was 96% and 93%, respectively.
      Owing to the quality of the included studies, the ability to compare these results with other endovenous ablation options was limited, and the data must be interpreted with caution. Only one study compared Flebogrif with EVLA in a randomized controlled trial, with occlusion rates of 96% vs 98%, respectively.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      A randomized study comparing EVLA, RFA, UGFS, and surgical stripping reported 12-month success rates of 94.2%, 95.0%, 83.7%, and 95.2%, respectively.
      • Rasmussen L.H.
      • Lawaertz M.
      • Bjoern B.
      • Vennits B.
      • Blemings A.
      • Eklof B.
      Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous veins.
      Boersma et al
      • Boersma D.
      • Kornmann V.N.
      • van Eekeren R.R.
      • Tromp E.
      • Ünlü Ç.
      • Reijnen M.M.
      Treatment modalities for small saphenous vein insufficiency: systematic review and meta-analysis.
      reported a pooled anatomic success rate of 98.5% after EVLA, with a mean follow-up of 12.5 months. More recent studies have reported 12-month anatomic success rates of 75.0%, 92.2%, and 97.3% after EVLA.
      • Hamann S.A.S.
      • Timmer-de Mik L.
      • Fritschy W.M.
      • Kuiters G.R.R.
      • Nijsten T.E.C.
      • van den Bos R.R.
      Randomized clinical trial of endovenous laser ablation versus direct and indirect radiofrequency ablation for the treatment of great saphenous varicose veins.
      • Koramaz İ.
      • El Kılıç H.
      • Gökalp F.
      • Bitargil M.
      • Bektaş N.
      • Engin E.
      • et al.
      Ablation of the great saphenous vein with nontumescent n-butyl cyanoacrylate versus endovenous laser therapy.
      • Bozkurt A.K.
      • Yılmaz M.F.
      A prospective comparison of a new cyanoacrylate glue and laser ablation for the treatment of venous insufficiency.
      Two meta-analyses of MOCA using ClariVein reported anatomic success rates varying from 84.5% to 91.7% after a follow-up period of >6 months but <12 months and 12 months, respectively.
      • Singhal S.
      • Uthappa M.C.
      Endovascular management of varicose veins: a review of literature.
      ,
      • Sun J.J.
      • Chowdhury M.M.
      • Sadat U.
      • Hayes P.D.
      • Tang T.Y.
      Mechanochemical ablation for treatment of truncal venous insufficiency: a review of the current literature.
      The anatomic success rates of the nonthermal VenaSeal technique (Medtronic, Santa Rosa, Calif) using cyanoacrylate glue to occlude the vein lumen varied from 92% to 100% at 1 year.
      • Lam Y.L.
      • De Maeseneer M.
      • Lawson J.
      • De Borst G.J.
      • Boersma D.
      Expert review on the VenaSeal® system for endovenous cyano-acrylate adhesive ablation of incompetent saphenous trunks in patients with varicose veins.
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      • Morrison N.
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      • Kolluri R.
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      • Morrison N.
      Roll-in phase analysis of clinical study of cyanoacrylate closure for incompetent great saphenous veins.
      Because most of the endovenous treatments have comparable anatomic success rates, outcome measures, such as clinical success, intraprocedural and postprocedural pain, complications, and return to normal activities, become more interesting. However, these outcomes were not analyzed because of poor documentation by the included studies. Clinical success after Flebogrif demonstrated by improvement of VCSS was described in three studies. However, in one of three studies, the patients had undergone adjunctive complementary ultrasound-guided foam sclerotherapy to treat incompetent perforating veins and superficial varicosities.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      Therefore, the postoperative VCSS scores obtained after adjunctive ultrasound-guided foam sclerotherapy might have been affected.
      The potential benefit of MOCA reported in previous reviews of ClariVein is the reduced intraprocedural and postprocedural pain and, thereby, an earlier return to work.
      • Vos C.G.
      • Ünlü Ç.
      • Bosma J.
      • van Vlijmen C.J.
      • de Nie A.J.
      • Schreve M.A.
      A systematic review and meta-analysis of two novel techniques of nonthermal endovenous ablation of the great saphenous vein.
      ,
      • Boersma D.
      • Kornmann V.N.
      • van Eekeren R.R.
      • Tromp E.
      • Ünlü Ç.
      • Reijnen M.M.
      Treatment modalities for small saphenous vein insufficiency: systematic review and meta-analysis.
      ,
      • van Eekeren R.R.
      • Boersma D.
      • Holewijn S.
      • Werson D.A.
      • de Vries J.P.
      • Reijnen M.M.
      Mechanochemical endovenous ablation for the treatment of great saphenous vein insufficiency.
      No firm conclusions from the present review can be drawn in this regard because only one study assessed the effect on the time for the patient to return to work.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      However, the observation that patients treated with MOCA resume their work earlier might have a significant effect on the total health care burden of varicose vein treatment. Additional studies are indicated to confirm this finding.
      The development of deep vein thrombosis after Flebogrif occurred in 0.3% of the patients within 12 months of follow-up. The data on ClariVein reported deep vein thrombosis in 0.0% to 1.0% of patients.
      • Vos C.G.
      • Ünlü Ç.
      • Bosma J.
      • van Vlijmen C.J.
      • de Nie A.J.
      • Schreve M.A.
      A systematic review and meta-analysis of two novel techniques of nonthermal endovenous ablation of the great saphenous vein.
      A previous meta-analysis reported deep vein thrombotic events in 1.7% of patients after treatment with EVLA or RFA. This probably resulted from heat-induced vessel wall injury with thrombotic occlusion.
      • Healy D.A.
      • Kimura S.
      • Power D.
      • Elhaj A.
      • Abdeldaim Y.
      • Cross K.S.
      A systematic review and meta-analysis of thrombotic events following endovenous thermal ablation of the great saphenous vein.
      However, factors such as the wavelength, fiber type, and the position of the laser tip also should be considered in the interpretation of deep vein thrombosis occurrence. Phlebitis occurred in 14.9% of the patients after Flebogrif. This is an important consideration because phlebitis occurs with pain and contradicts the hypothesis that Flebogrif leads to less postprocedural pain. Lower rates of phlebitis have been described after endothermal ablation, such as 7.7% to 7.9% after EVLA reported within 12 months
      • Koramaz İ.
      • El Kılıç H.
      • Gökalp F.
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      • Bektaş N.
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      • et al.
      Ablation of the great saphenous vein with nontumescent n-butyl cyanoacrylate versus endovenous laser therapy.
      ,
      • Bozkurt A.K.
      • Yılmaz M.F.
      A prospective comparison of a new cyanoacrylate glue and laser ablation for the treatment of venous insufficiency.
      and 6% after RFA.
      • van Eekeren R.R.
      • Boersma D.
      • Holewijn S.
      • Werson D.A.
      • de Vries J.P.
      • Reijnen M.M.
      Mechanochemical endovenous ablation for the treatment of great saphenous vein insufficiency.
      The controversial definition of phlebitis after sclerotherapy leading to clot formation accompanied by an inflammatory infiltrate could be an explanation for the higher risk of phlebitis after Flebogrif compared with after endothermal ablation.
      • Shadid N.
      • Ceulen R.
      • Nelemans P.
      • Dirksen C.
      • Veraart J.
      • Schurink G.W.
      • et al.
      Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein.
      A comparison of the complication rates of Flebogrif with other techniques must be performed with caution because no conclusions can be drawn from the small dataset of the included studies. In addition, the diagnostic details, for example, whether thrombus extension into the common femoral vein was seen, and management of the reported case of deep vein thrombosis, were not reported.
      Some serious limitations exist regarding the strength of the conclusions that can be drawn from the present systematic review. First, we only performed an analysis for the anatomic success rate and not for clinical success, pain reduction, or quality of life owing to the lack of appropriate data from the included studies. In addition, anatomic success might have been influenced by the heterogeneity of the type of vein treated. Only two studies reported the closure rates of the GSV and SSV independently.
      • Ciostek P.
      • Kowalski M.
      • Woźniak W.
      • Miłek T.
      • Myrcha P.
      • Migda B.
      Phlebogriffe—a new device for mechanochemical ablation of incompetent saphenous veins: a pilot study.
      ,
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      Thus, the role of Flebogrif in the treatment of individual truncal veins could not be determined from these data. Furthermore, the different catheter tip positions might have influenced anatomic success as a residual saphenofemoral stump can be contribute to the formation of late recurrence.
      • Geier B.
      • Stücker M.
      • Hummel T.
      • Burger P.
      • Frings N.
      • Hartmann M.
      • et al.
      Residual stumps associated with inguinal varicose vein recurrences: a multicenter study.
      Other important determinants are the different POL foam concentrations and catheter pullback rates between the studies. However, the anatomic success of POL of 1.5%, only reported by Ammollo et al,
      • Ammollo R.P.
      • Petrone A.
      • Giribono A.M.
      • Ferrante L.
      • Del Guercio L.
      • Bracale U.M.
      Early results of mechanochemical ablation with Flebogrif® in great saphenous vein insufficiency: does polidocanol concentration affect outcome?.
      was not included in the pooled analysis to diminish the heterogeneity.
      An important drawback is the lack of well-designed comparative studies and sufficient sample sizes. Only one study compared Flebogrif and EVLA with an arbitrarily chosen small sample size of 50 patients per treatment group.
      • Tawfik A.M.
      • Sorour W.A.
      • El-Laboudy M.E.
      Laser ablation versus mechanochemical ablation in the treatment of primary varicose veins: a randomized clinical trial.
      Most patients were from the study by Iłźecki et al.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      In the present systematic review, the pooled data only included studies with follow-up periods not >12 months. Moreover, one of three studies with a follow-up of 12 months had a substantial loss to follow-up of 44%, thereby inducing potential bias regarding the calculation of anatomic success rates during follow-up.
      • Iłźecki M.
      • Terlecki P.
      • Przywara S.
      • Iłźecka J.
      • Dave S.
      • Zubilewicz T.
      The novel minimally invasive mechano-chemical technique of the saphenous vein ablation: our center experience: results of 24 months follow-up.
      Longer follow-up times are required because varicose veins might recur over time after treatment and could influence the choice of treatment.
      Other factors, including the diameter and length of the vein, duration of postoperative compression stockings, and costs, are also important considerations in the treatment decisions of the patient and clinician.
      Although the present systematic review had its limitations, a pressing need exists for an overview of evidence about this new technique. Because of the potential patient-friendly advantages compared with thermal ablation, the use of the Flebogrif device has been increasing in several countries. In implementing new techniques in daily practice, it is helpful to provide an overview of the reported data and attempting to draw conclusions in the form of a meta-analysis. This could be helpful in making clinical choices and saves time for clinicians because they would not need to perform their own search. In the present study, we collected data from a number of independent studies of the Flebogrif device to determine overall trends. In addition, we revealed the biases, strengths, and weaknesses of existing studies to form treatment recommendations and provide guidance in the design of future clinical trials.

      Conclusions

      MOCA using the Flebogrif device is a safe and well-tolerated procedure for the treatment of saphenous vein insufficiency. However, well-designed studies of sufficient sample size and follow-up are required to compare the effectiveness against other endovenous treatment modalities and to define the definitive role of the Flebogrif device.

      Author contributions

      Conception and design: TA, EH, MS, MM, CvV, WW, ÇÜ
      Analysis and interpretation: TA, EH
      Data collection: TA, EH
      Writing the article: TA
      Critical revision of the article: TA, EH, MS, MM, CvV, WW, ÇÜ
      Final approval of the article: TA, EH, MS, MM, CvV, WW, ÇÜ
      Statistical analysis: TA
      Obtained funding: Not applicable
      Overall responsibility: TA, ÇÜ

      Appendix (online only).

      Supplementary Table I (online only)Search strategy
      DatabaseSearch terms
      MEDLINE("Varicose Veins" [MeSH] OR varicose vein∗[tiab] OR varix∗[tiab] OR varice∗[tiab] OR "venous insufficiency"[MeSH] OR venous insufficienc∗[tiab] OR "saphenous vein"[MeSH] OR saphenous vein∗[tiab]) AND (mechanochemical∗[tiab] OR MOCA∗[tiab] OR Flebogrif∗[tiab] OR phlebogrif∗[tiab] OR mechano-chemical∗[tiab] OR Mechanical Occlusion Chemically Assisted Ablation∗[tiab])
      Embase('varicosis'/exp OR 'varicosis' OR 'vein insufficiency'/exp OR 'vein insufficiency' OR 'saphenous vein'/exp OR 'saphenous vein') AND ('mechanochemical ablation'/exp OR 'mechanochemical ablation' OR 'mechanochemical endovenous ablation'/exp OR 'mechanochemical endovenous ablation' OR moca OR flebogrif OR phlebogriffe OR 'mechano chemical' OR 'mechanical occlusion chemically assisted ablation' OR (mechanical AND ('occlusion'/exp OR occlusion) AND chemically AND assisted AND ablation))
      Cochrane("Varicose Veins"[MeSH] OR varicose vein∗[tiab] OR Varix∗[tiab] OR Varice∗[tiab] OR "Venous Insufficiency"[MeSH] OR Venous Insufficienc∗[tiab] OR "Saphenous Vein"[MeSH] OR Saphenous Vein∗[tiab]) AND (Mechanochemical∗[tiab] OR MOCA∗[tiab] OR Flebogrif∗[tiab] OR Phlebogrif∗[tiab] OR Mechano-Chemical∗[tiab] OR Mechanical Occlusion Chemically Assisted Ablation∗[tiab])
      Supplementary Table II (online only)Excluded studies
      First authorReason for exclusion
      Babin 2016Conference abstract
      Belramman 2019Conference abstract
      Belramman 2020Conference abstract
      Bishawi 2014Using ClariVein
      Boersma 2016Using ClariVein
      Bootun 2016Reviews with overlapping data
      Bootun 2016
      Bootun R, Lane TR, Davies AH. The advent of non-thermal, non-tumescent techniques for treatment of varicose veins. Phlebology 2016; 31:5-14.
      Reviews with overlapping data
      Bootun 2016
      Bootun R, Lane TRA, Davies AH. A comparison of thermal and non-thermal ablation. Rev Vasc Med 2016; 4:1-8.
      Reviews with overlapping data
      Chung 2018Conference abstract
      Elias 2013Using ClariVein
      Gupta 2019Conference abstract
      Halmesmaki 2019Conference abstract
      Hartmann 2016Using ClariVein
      Hartmann 2017Using ClariVein
      Hassanin 2019Reviews with overlapping data
      Hirsch 2017Other outcome
      Ibrahim 2020Conference abstract
      Iłźecki 2018Overlapping data with other (included) publication by same author
      Jindal 2018Conference abstract
      Jindal 2019Case report
      Jprn 2019Data not yet available
      Kawanishi 2018Conference abstract
      Kawanishi 2018
      Kawanishi D, Tappin K, Willy L, Afrasiabi M, Schofield M, Loussararian A. Incidence of segments with complete or partial compressibility and of extension of thrombus into a deep vein at early follow-up ultrasound examination following ablation using non-thermal non-tumescent techniques. Phlebology 2018; 33:40-2.
      Conference abstract
      Kim 2016Conference abstract
      Kim 2017Using ClariVein
      Kolluri 2020Reviews with overlapping data
      Lajos 2017Conference abstract
      Milleret 2019No data reported
      Néaume 2018Reviews with overlapping data
      Néaume 2020Reviews with overlapping data
      Nugroho 2020Reviews with overlapping data
      Sadek 2014Using ClariVein
      Singhal 2019Reviews with overlapping data
      Sinha 2017Conference abstract
      Sun 2017Reviews with overlapping data
      Tal 2018Conference abstract
      Tal 2019Conference abstract
      Teichert 2016Conference abstract
      Teßarek 2017Conference abstract
      Vähäaho 2019Using ClariVein
      Vähäaho 2020Using ClariVein
      Vos 2017Reviews with overlapping data
      Vuylsteke 2019Reviews with overlapping data
      Zubilewicz 2016Overlapping data with other (included) publication by same author
      a Bootun R, Lane TR, Davies AH. The advent of non-thermal, non-tumescent techniques for treatment of varicose veins. Phlebology 2016; 31:5-14.
      b Bootun R, Lane TRA, Davies AH. A comparison of thermal and non-thermal ablation. Rev Vasc Med 2016; 4:1-8.
      c Kawanishi D, Tappin K, Willy L, Afrasiabi M, Schofield M, Loussararian A. Incidence of segments with complete or partial compressibility and of extension of thrombus into a deep vein at early follow-up ultrasound examination following ablation using non-thermal non-tumescent techniques. Phlebology 2018; 33:40-2.

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