The present status of surgery of the superficial venous system in the management of venous ulcer and the evidence for the role of perforator interruption
2008; Elsevier BV; Volume: 48; Issue: 4 Linguagem: Inglês
10.1016/j.jvs.2008.06.017
ISSN1097-6809
Autores Tópico(s)Central Venous Catheters and Hemodialysis
ResumoSuperficial venous hypertension has been cited as the putative etiologic factor in advanced chronic venous insufficiency with venous ulcer (CEAP C 5/6). For over a century, influenced by this belief, surgeons have ablated the superficial venous system as a treatment for venous ulcer. Incompetent perforating veins (ICPVs) have become a particular focus of this therapeutic strategy. This review examines the evidence for the surgical approach. A MEDLINE search of the literature identified only four randomized controlled trials (RCTs) directed at the surgical reduction of superficial venous hypertension. Risk ratios for ulcer healing and prevention of recurrence were calculated to determine benefits for these four RCTs, while mortality and morbidity, where available, was used to determine risk from the procedure. In addition, the quality of the trials (design and outcomes) was assessed. While two trials compared ICPV ligation to compression, the great saphenous vein (GSV) was also treated in many of these limbs, which confounds the results. By contrast, two RCTs, which compared treatment of the GSV alone to compression, demonstrated a significant reduction in the incidence of ulcer recurrence. Case series that employed hemodynamic or surrogate outcomes showed little effect on the addition of ICPV treatment to GSV stripping, while GSV ablation alone was associated with a reduction in the number of ICPVs in several studies. This review suggests a grade 1A recommendation for the treatment of venous ulcer by GSV ablation to reduce ulcer recurrence. The role of ICPV ablation alone or concomitant with GSV treatment awaits results of properly conducted RCTs. Superficial venous hypertension has been cited as the putative etiologic factor in advanced chronic venous insufficiency with venous ulcer (CEAP C 5/6). For over a century, influenced by this belief, surgeons have ablated the superficial venous system as a treatment for venous ulcer. Incompetent perforating veins (ICPVs) have become a particular focus of this therapeutic strategy. This review examines the evidence for the surgical approach. A MEDLINE search of the literature identified only four randomized controlled trials (RCTs) directed at the surgical reduction of superficial venous hypertension. Risk ratios for ulcer healing and prevention of recurrence were calculated to determine benefits for these four RCTs, while mortality and morbidity, where available, was used to determine risk from the procedure. In addition, the quality of the trials (design and outcomes) was assessed. While two trials compared ICPV ligation to compression, the great saphenous vein (GSV) was also treated in many of these limbs, which confounds the results. By contrast, two RCTs, which compared treatment of the GSV alone to compression, demonstrated a significant reduction in the incidence of ulcer recurrence. Case series that employed hemodynamic or surrogate outcomes showed little effect on the addition of ICPV treatment to GSV stripping, while GSV ablation alone was associated with a reduction in the number of ICPVs in several studies. This review suggests a grade 1A recommendation for the treatment of venous ulcer by GSV ablation to reduce ulcer recurrence. The role of ICPV ablation alone or concomitant with GSV treatment awaits results of properly conducted RCTs. Reduction of venous hypertension by surgical ablation of the incompetent superficial venous system (great saphenous vein [GSV], small saphenous vein [SSV], branch tributaries and perforators) has been a fundamental approach to the treatment of venous ulcer for nearly a century.1Homans J. The etiology and treatment of varicose ulcer of the leg.Surg Gynecol Obstet. 1917; 24: 300-311Google Scholar Incompetent perforating veins (ICPVs) in particular have been cited frequently as an important etiologic factor in the pathogenesis of venous ulcer and the focal point for therapy.2Negus D. Friedgood A. The effective management of venous ulceration.Br J Surg. 1983; 70: 623-627Crossref PubMed Scopus (118) Google Scholar Therefore, the interruption of ICPVs by subfascial endoscopic perforator surgery (SEPS) has been recommended as an essential element in the reduction of superficial hypertension and the “cure” of venous ulcer.3O'Donnell T.F. Lessons from the past guide the future: is history truly circular?.J Vasc Surg. 1999; 30: 776-786Abstract Full Text Full Text PDF Scopus (18) Google Scholar What is the supporting data for this belief and how valid is it? Evidence-based medicine is a helpful tool to the clinician for assessing the optimal treatment, based on the best available current knowledge.4Wente M.N. Seiler C.M. Uhl W. Buchler M.W. Perspectives of evidence-based surgery.Dig Surg. 2003; 20: 263-269Crossref PubMed Scopus (125) Google Scholar This method has provided a way to analyze the statistical strength or “quality” of various studies, which supports a treatment choice and allows the clinician to assess the bias and strength of evidence surrounding that therapeutic recommendation. Evidence-based medicine has evolved from merely an assessment of study(s) qualities to combining study strength with an estimate of the risk to benefit trade off of a particular therapy in order to make an overall recommendation.5Guyatt G. Schumemann H. Cook D. Jaeschke R. Pauker St. Bucher H. Grades of recommendation for antithrombotic agents.CHEST. 2001; 119: 3S-7SCrossref PubMed Scopus (95) Google Scholar It is the purpose of this paper to review the evidence for treating the superficial venous system, especially the perforators, in advanced chronic venous insufficiency (CVI) (CEAP C5/6) by performing a systematic review. Treatment risk will be derived from the interventions mortality and morbidity (requirement for hospitalization) while the promotion of ulcer healing and/or reduction in ulcer recurrence will represent the benefit. This review will assess the few randomized controlled trials (RCTs), which explore the effect of superficial venous surgery on the clinical outcomes of venous ulcer healing and recurrence. This review in particular will examine if there is compelling evidence for the treatment of ICPVs. We had performed a previous systematic review on the efficacy of SEPS in general, which covered the period from 1966 through December 2002 and failed to identify any RCTs with ulcer healing or recurrence as their outcomes.6TenBrook J.A. Iafrati M.D. O'Donnell T.F. Wolf M.P. Hoffman D.O. Pauker S.G. et al.Systematic review of outcomes after surgical management of venous disease incorporating subfascial endoscopic perforator surgery.J Vasc Surg. 2004; 39: 583-589Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The current review was restricted to the period January 2003 through December 30, 2007. Studies cited in the previous review as well as new non-RCTs will be incorporated into the discussion of the current systematic analysis. A MEDLINE search, which employed the search key terms “venous insufficiency/surgery; varicose ulcer surgery; leg ulcer/surgery”, or the Keyword “perforator” was performed.6TenBrook J.A. Iafrati M.D. O'Donnell T.F. Wolf M.P. Hoffman D.O. Pauker S.G. et al.Systematic review of outcomes after surgical management of venous disease incorporating subfascial endoscopic perforator surgery.J Vasc Surg. 2004; 39: 583-589Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar The search was restricted to human and English language studies. To be included in this review, the study had to have the following characteristics: (1) a RCT study design, (2) a patient population that was restricted to active and/or healed ulcers (CEAP Clinical Classification C5/6) and (3) express the study outcome as ulcer recurrence. Ulcer healing was a desirable outcome, but not an essential component for a study to be included in this review. An analysis of treatment effects was performed on those trials that met the inclusion criteria by calculating the risk ratio and the corresponding 95% confidence intervals from data presented in the original trials. Using desirable elements of clinical trials as reported by others7Moher D. Schulz K.F. Altman D.G. For the Consort Group The Consort Statement: revised recommendations for improving the quality of reports of parallel-group randomized trials.Lancet. 2001; 357: 1191-1194Abstract Full Text Full Text PDF PubMed Scopus (3077) Google Scholar and us8O'Donnell T.F. Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer.J Vasc Surg. 2006; 44: 1118-1125Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar previously, we assessed the quality of both study design and outcomes. Our current systematic review of RCTs for ulcer recurrence following treatment of ICPVs revealed 44 reports on the treatment of ICPVs between 1980 and 2007. From this review, we identified two level II trials (small subject population)9Stacey M.C. Burnand K.G. Layer G.T. Pattison M. Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.Br J Surg. 1988; 75: 436-439Crossref PubMed Scopus (101) Google Scholar, 10Zamboni P. Cisno C. Marchetti F. Mazza P. Fogato L. Carandina S. et al.Minimally invasive surgical management of primary ulcers vs compression treatment: a randomized trial.Eur J Vasc Endovasc Surg. 2003; 25: 313-318Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar and two level I trials (large subject population),11van Gent W.B. Hop W.C. van Pragg M.C. MacKaay A.J. deBoer E.M. Wittens C.H. Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial.J Vasc Surg. 2006; 44: 563-571Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 12Barwell J.R. Davies C.E. Deacon J. Harvey K. Minor J. Sassano A. et al.Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomized controlled trial.Lancet. 2004; 363;: 1854-1859Abstract Full Text Full Text PDF PubMed Scopus (468) Google Scholar which satisfied the criteria. In addition, one of the level I RCTs published a subsequent paper with a longer follow-up period than its original study.13Gohel M.S. Barwell J.R. Taylor M. Chant T. Foy C. Earnshaw J.J. et al.Long term results of compression plus surgery in chronic venous ulceration (ESCHAR): randomized controlled trial.BMJ. 2007; 335: 83Crossref PubMed Scopus (320) Google Scholar Two RCTs addressed the effect of ICPV treatment on ulcer healing and recurrence,9Stacey M.C. Burnand K.G. Layer G.T. Pattison M. Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.Br J Surg. 1988; 75: 436-439Crossref PubMed Scopus (101) Google Scholar, 11van Gent W.B. Hop W.C. van Pragg M.C. MacKaay A.J. deBoer E.M. Wittens C.H. Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial.J Vasc Surg. 2006; 44: 563-571Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar while the other two examined the effect of GSV treatment on the same outcomes.10Zamboni P. Cisno C. Marchetti F. Mazza P. Fogato L. Carandina S. et al.Minimally invasive surgical management of primary ulcers vs compression treatment: a randomized trial.Eur J Vasc Endovasc Surg. 2003; 25: 313-318Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 12Barwell J.R. Davies C.E. Deacon J. Harvey K. Minor J. Sassano A. et al.Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomized controlled trial.Lancet. 2004; 363;: 1854-1859Abstract Full Text Full Text PDF PubMed Scopus (468) Google Scholar The characteristics of these four studies are presented in Table I and will be summarized briefly here.Table IClinical characteristics of four RCTsStacey (1988)Van Gent (2006)Zamboni (2003)Barwell (2004)Number pts/limbs30/41170/20045/47500Male (%)57624042Age-years (mean)61656373C5 (%)1000032C6(%)010010068Ulcer diameter (mms)—225110 m200Ulcer duration (months)—4—5Previous DVT (%)503108DVI (%)5052035Diabetes (%)—7/17—38Compression typeClass? Elastic stockingDual-layer short-stretch→ Class II/IIIInelastic bandage & Aqua cellMultilayer comp → class IIISurgical RXICPV/GSVICPV/GSVCHIVAGSVMorbidity (%)None reported——Surg→2.4%Comp→2.2%Mortality (%)None——12 mo→8%Outcome-ulcer (%)Healing-comp739676Healing-surg8310082Recurr-comp24233834Recurr-surg522915DVT, Deep venous thrombosis; DVI, deep venous insufficiency; RX, treatment; ICPV, incompetent perforating veins; GSV, greater saphenous vein; CHIVA, hemodynamic-based minimally invasive surgery to prevent reflux, but maintaining GSV drainage. Open table in a new tab DVT, Deep venous thrombosis; DVI, deep venous insufficiency; RX, treatment; ICPV, incompetent perforating veins; GSV, greater saphenous vein; CHIVA, hemodynamic-based minimally invasive surgery to prevent reflux, but maintaining GSV drainage. Putative evidence for the effect of ICPV ligation on ulcer recurrence: the first RCT by Stacey,9Stacey M.C. Burnand K.G. Layer G.T. Pattison M. Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.Br J Surg. 1988; 75: 436-439Crossref PubMed Scopus (101) Google Scholar which included 41 limbs with healed venous ulcer, had as its principle outcome hemodynamic improvement (calf pump function), with treatment by either elastic compression alone or compression and open subfascial ligation (many limbs also had treatment of the GSV and SSV).9Stacey M.C. Burnand K.G. Layer G.T. Pattison M. Calf pump function in patients with healed venous ulcers is not improved by surgery to the communicating veins or by elastic stockings.Br J Surg. 1988; 75: 436-439Crossref PubMed Scopus (101) Google Scholar By foot volumetry, the half volume refilling time was comparable between the surgical and compression group, but the expelled volume was improved significantly in the surgical group. Ulcer recurrence was not reported in the results section, but rather in the Patients and Methods section as treatment failure. Only one ulcer recurred in the surgical arm, while five developed in the compression alone group. No statistical analysis was provided for the later clinical findings. There was no differentiation as to how many limbs underwent concomitant treatment of the superficial system (GSV and SSV), nor obviously any stratification or post-hoc analysis. A very important large RCT (level I), the Dutch ulcer trial, was based on 200 C6 limbs, which were randomized into either treatment with elastic compression alone or SEPS (+/−GSV treatment) with elastic compression (Table I).11van Gent W.B. Hop W.C. van Pragg M.C. MacKaay A.J. deBoer E.M. Wittens C.H. Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial.J Vasc Surg. 2006; 44: 563-571Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar This trial, which putatively focused on the effect of SEPS on ulcer healing/recurrence, was conducted in 12 centers with the ulcer-free period, as determined by Kaplan-Meier analysis, the primary outcome. The secondary endpoints included ulcer healing, ulcer recurrence, quality of life (QOL), and cost-effectiveness. The investigators stratified patients into: (1) new or recurrent ulcer; (2) presence of deep venous reflux; and (3) the specific center where the treatment (medical or surgical) was carried out. Concomitant superficial venous surgery of the GSV or SSV was performed in 54% and an additional 40 patients had previous treatment of their GSV so that only 6% of patients apparently had treatment of ICPVs alone. Thus, it would be impossible to separate the effect of treating the GSV and ICPVs from treating the ICPVs alone in this RCT. Over a median follow-up length of 27 months, the ulcer-free period was comparable between the SEPS group (72%) and the compression group (53%), as were ulcer recurrence and ulcer healing. The authors conducted a post-hoc analysis, however, that identified certain factors in favor of the SEPS arm for ulcer-free survival: (1) ulcers of less than 4 month's duration; and (2) medial located ulcer (also favored earlier healing). Of the stratified factors both (1) recurrent ulcer and (3) surgery carried out in a specialized center favorably influenced ulcer-free survival, while deep-venous reflux had no influence. The effect of GSV treatment alone: Zamboni, et al,10Zamboni P. Cisno C. Marchetti F. Mazza P. Fogato L. Carandina S. et al.Minimally invasive surgical management of primary ulcers vs compression treatment: a randomized trial.Eur J Vasc Endovasc Surg. 2003; 25: 313-318Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar RCT compared ambulatory conservative management of varicose veins (CHIVA) (hemodynamic-based minimally invasive surgery to prevent reflux, but maintaining GSV drainage) to compression and wound care in 47 C6 limbs of 45 patients. Of the 23 limbs undergoing CHIVA, 16 had high ligation of the GSV and division of its tributaries. Seven limbs had ligation of the GSV tributaries only. Direct treatment of the ICPVs was not carried out. QOL improved in the CHIVA group, while venous filling index, ejection fraction, and residual volume fraction normalized postoperatively. Most importantly, ulcer recurrence was significantly lower in the surgical group (9%) in comparison to the compression group (38%–P < .05). The authors did not provide a separate analysis of the two surgical groups and reported the results as a whole, which can lead to heterogeneity. In the large multi-center effect of surgery and compression on healing and recurrence (ESCHAR) Trial ligation and stripping of the GSV +/− the SSV and compression was compared to compression alone and wound care, where the clinical outcomes of ulcer healing and recurrence were employed.12Barwell J.R. Davies C.E. Deacon J. Harvey K. Minor J. Sassano A. et al.Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomized controlled trial.Lancet. 2004; 363;: 1854-1859Abstract Full Text Full Text PDF PubMed Scopus (468) Google Scholar Of the 500 limbs, 68% were class VI and 32% class V. Deep venous reflux was evenly distributed in both arms—37% vs 38%. Of the 195 limbs in the surgical arm, 141 underwent treatment of the GSV alone; 27 the SSV alone, and 21 the GSV and SSV combined. Only six limbs (3.1%) had treatment of the perforators, presumably as the authors stated in their introduction “reserved for the few (2-3%) legs with isolated calf perforator incompetence.” There was no statistical significance between the two treatment arms in ulcer healing –76% in the compression group and 82% in the compression and surgery group. On the other hand, there was a two-fold reduction of ulcer recurrence in the surgical arm (15%) over the compression alone group (34%). The study clearly showed the superiority of GSV ablation to compression for the prevention of ulcer recurrence. The risk reduction of the risk of ulcer recurrence is portrayed in Fig. Only the two studies where the GSV alone was treated (Zamboni and ESCHAR) showed a significant reduction in ulcer recurrence for the surgical arm. The basis for the surgical approach: the Boston surgeon, John Homans, formulated our modern concept of venous pathophysiology nearly a century ago and emphasized the role of ICPVs in the production of superficial venous hypertension.1Homans J. The etiology and treatment of varicose ulcer of the leg.Surg Gynecol Obstet. 1917; 24: 300-311Google Scholar Homans' surgical plan for venous ulcer was based on eradication of both the GSV and particularly the ICPVs.14Homans J. The operative treatment of varicose veins and ulcers, based upon a classification of these lesions.Surg Gynecol Obstet. 1916; 22: 143-159Google Scholar In 1938, Beecher, et al,15Beecher H.K. Field M.E. Krogh A. The effect of walking on the venous pressure at the ankle.Skand Arch F Physiol. 1936; 73: 133-140Crossref Scopus (19) Google Scholar as well as Warren, et al,16Warren R. White D. Venous pressures in the saphenous system in normal, varicose and post-phlebitic extremities.Surgery. 1948; 26: 435-441Google Scholar provided the hemodynamic basis of superficial venous hypertension and its potential relationship with venous ulcer. In his seminal article in 1938, Linton17Linton R.R. The communicating veins of the lower leg and the operative technique for their ligation.Ann Surg. 1938; 107: 582-593Crossref PubMed Google Scholar proposed a new surgical approach for ligating ICPVs through a long medial calf incision and he stated, “It's necessary to interrupt communicating veins to affect a cure”. The British surgeon, Frank Cockett, further refined some of Linton's concepts18Linton R.R. The post-thrombotic ulceration of the lower extremity: its etiology and surgical treatment.Ann Surg. 1953; 138: 415-433PubMed Google Scholar into what Cockett called the “blow out theory”—an ulcer was the end result of a local rise in venous pressure in the peri-ulcer area.19Cockett F.B. Elgan Jones D.E. The ankle blow-out syndrome A new approach to the varicose ulcer problem.Lancet. 1953; 1: 17-23Abstract PubMed Scopus (135) Google Scholar Subfascial vein ligation of ICPVs through a long medial calf incision was the standard approach for venous ulcer as typified by a leading 1970s article in the British Medical Journal.20The Hidden Perforating Vein.Br Med J. 1970; 1 (Editorial): 435-441PubMed Google Scholar “Venous ulcers could be treated by occluding the incompetent connecting vein between the superficial and deep system and so restore the pressure and flow to normal.”20The Hidden Perforating Vein.Br Med J. 1970; 1 (Editorial): 435-441PubMed Google Scholar This treatment was based on the concept that a reduction in the abnormally elevated ambulatory superficial venous pressure would, in turn, improve the abnormal microcirculation. To examine whether surgical ablation of ICPVs was associated with ulcer healing and prevention of recurrence, we carried out several studies to test this hypothesis. A 5-year retrospective follow-up study of ulcer recurrence examined whether ligation of ICPVs was effective in preventing recurrence. In a review of 40 limbs 5 years after ICPV ligation, 17 limbs with normal deep systems on phlebography had only one ulcer recur (6%), while all 23 limbs with postthrombotic signs on phlebography developed an ulcer.21Burnand K. O'Donnell T.F. Thomas M.L. Browse N.L. The relation between postphlebitic changes in the deep veins and results of surgical treatment of venous ulcers.Lancet. 1976; : 936-938Abstract PubMed Scopus (158) Google Scholar In a subsequent prospective study of 109 limbs, 40 limbs with phlebographically-proven postthrombotic syndrome treatment of ICPVs and +/− GSV, did not improve abnormal venous pressures.22Burnand K.G. O'Donnell T.F. Thomas M.L. Browse N.L. The relative importance of incompetent communicating veins in the production of varicose veins and venous ulcers.Surgery. 1977; 82: 9-14PubMed Google Scholar These two studies questioned the role of treating ICPVs in limbs with postthrombotic deep venous incompetence. Surgical options for incompetent perforating veins. Due to the high wound morbidity rate (4-44%) of the open approach combined with a significant recurrence of ulcers (2-55%), however, the open surgical treatment fell in popularity and use.3O'Donnell T.F. Lessons from the past guide the future: is history truly circular?.J Vasc Surg. 1999; 30: 776-786Abstract Full Text Full Text PDF Scopus (18) Google Scholar Several technical modifications were developed to minimize wound morbidity associated with subfascial ligation, which included placement of the incision away from the compromised skin and subcutaneous tissue to over the posterior calf—“the posterior stocking seam approach.”23Lim R.C. Blaisdell F.W. Zubrin J. Subfascial ligation of perforating veins in recurrent stasis ulceration.Am J Surg. 1970; 119: 246-249Abstract Full Text PDF PubMed Scopus (15) Google Scholar Minimally invasive approach. Hauer modified available endoscopic techniques to ligate ICPVs through a remote entry site on the upper medial calf using conventional instruments (mediastinoscope and liga-clips).24Hauer G. The endoscopic subfascial division of the perforating veins\em\preliminary report (in German).VASA. 1985; 14: 59-61PubMed Google Scholar In 1991, we developed a laparoscopic closed approach, which employed micro instruments and visualization of the operative field on a video screen.25O'Donnell T.F. Surgical treatment of incompetent perforating veins.in: Bergan J.J. Kistner R.L. Atlas of Venous Surgery. WB Saunders, Phila1992Google Scholar, 26O'Donnell T.F. Laparoendoscopic venous surgery in current critical problems in vascular surgery.in: Veith F.J. Quality Medical Publishing, 1992Google Scholar Both Glovicski27Gloviczki P. Cambria R.A. Rhee R.Y. Canton L.G. McKusick M.A. Surgical technique and preliminary results of endoscopic subfascial division of perforating veins.J Vasc Surg. 1996; 23: 517-523Abstract Full Text PDF PubMed Scopus (127) Google Scholar and Conrad28Conrad P. Endoscopic exploration of the subfascial space of the lower leg with perforator vein interruption using laparoscopic equipment: a preliminary report.Phlebology. 1994; 9: 154-157Google Scholar independently modified the laparoscopic technique with a tourniquet and CO2insufflation. The closed CO2 technique expanded the operating space and allowed the surgeon to visualize, dissect, and clip the ICPVs. Ruckley stated that, “Evidence-based medicine has not been so far a strong feature of phlebological practice” and that appears to be true for the data supporting SEPS.29Ruckley C.V. Editorial Brit J Surg. 1996; 83: 1492Crossref Google Scholar Levels of evidence and the strength can be divided into those which address single trials or those that are based on a compilation of trials-systematic reviews and Meta analysis. Single studies of therapy range from level 5, uncontrolled case series, with weak statistical power to a level 1 study, a large RCT with a low risk of error or bias and greater statistical strength.30Sackett D.L. Rules of evidence and clinical recommendations on the use of anti-thrombotic agents.Chest. 1989; 95: 25-45Google Scholar Even higher levels of evidence can be provided by systematic analyses of multiple studies and include the Cochrane Systematic Reviews, AHRQ evidence reports, and a standard systematic review. Level 1 evidence is important because it provides scientific validation of a treatment option and is statistically powerful. In addition, Center for Medicare Services (CMS) and other third party payors are strongly influenced on a decision to reimburse for a therapy by such data.8O'Donnell T.F. Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer.J Vasc Surg. 2006; 44: 1118-1125Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar While study design is an important component which determines the validity of a trial, the choice of appropriate outcomes is also essential. Unfortunately, many venous series report hemodynamic outcomes, such as valve closure times or air plethysmographic values, which are surrogate outcomes of lower evidentiary power. By contrast, the objective clinical outcomes specific for venous therapy include the Venous Clinical Severity Score,31Rutherford 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.J Vasc Surg. 2000; 31: 1307-1312Abstract Full Text Full Text PDF PubMed Scopus (617) Google Scholar while self-reported QOL assessments, such as the SF 36, address global quality outcomes. Finally, there are venous-specific QOL assessment tools such as the Aberdeen Varicose Vein Score.32Garrat A.M. MacDonald L.M. Ruta D.A. Russell I.T. Buckingham J.K. Krukowski Z.H. Toward measurements of outcomes for patients with varicose veins.Qual Health Care. 1993; 3: 5-10Google Scholar Outcome measurements appear more straightforward for the evaluation of treatment options for C5/C6 disease where ulcer healing and ulcer recurrence help to define the critical outcomes of treatment. Both outcomes define critical elements of the disease process and are capable of change while being reproducible. Finally, the “quality” of a trial can be rated based on established criteria.5Guyatt G. Schumemann H. Cook D. Jaeschke R. Pauker St. Bucher H. Grades of recommendation for antithrombotic agents.CHEST. 2001; 119: 3S-7SCrossref PubMed Scopus (95) Google Scholar This assessment is formalized in the GRADE recommendations for therapy, where the strength of the recommendation is “graded” on a scale from A-strong recommendation to C- weak recommendation.33GRADE Working GroupGrading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490-1505Crossref PubMed Google Scholar The sequence of proof that the treatment of ICPVs is important in ulcer healing and prevention of ulcer recurrence depends on four statements: (1) The treatment of ICPVs “cures” ulcers by promoting healing and reducing recurrence. (2) The treatment of ICPVs improves venous hemodynamics (less powerful than # 1, because surrogate outcome employed). (3) The treatment of the GSV alone cures ulcers by promoting healing and reducing recurrence. (4) The treatment of the GSV alone improves perforator function (less powerful than #3). When is a perforating vein incompetent? The criteria for determining by duplex scan whether a perforating vein is incompetent is essential for
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