Abstracts 54S. SUMMARY OF EVIDENCE OF EFFECTIVENESS OF PRIMARY CHRONIC VENOUS DISEASE TREATMENT William Marston, MD, Chapel Hill, NC

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1 54S 29. Moffat CJ, Franks PJ, Oldroyd M, Bosanquet N, Brown P, Greenhalg RM, et al. Community clinics for leg ulcers and impact on healing. BMJ 1992;305: Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous disease: patient compliance and efficacy. Ann Vasc Surg 2007; 21: Eklof B, Perrin M, Delis KT, Rutherford RB, Gloviczki P; American Venous Forum, et al. Updated terminology of chronic venous disorders: the VEIN-TERM Transatlantic Interdisciplinary consensus document. J Vasc Surg 2009;49: Marston WA, Brabham VW, Mendes R, Berndt D, Weiner M, Keagy B. The importance of deep venous reflux velocity as a determinant of outcome in patients with combined superficial and deep venous reflux treated with endovenous saphenous ablation. J Vasc Surg 2008;48: 400-5; discussion Puggioni A, Lurie F, Kistner RL, Eklof B. How often is deep venous reflux eliminated after saphenous vein ablation? J Vasc Surg 2003;38: Masuda EM, Kessler DM, Lurie F, Puggioni A, Kistner RL, Eklof B. The effect of ultrasound-guided sclerotherapy of incompetent perforator veins on venous clinical severity and disability scores. J Vasc Surg 2006;43:551-6; discussion Neglen P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg 2007;46: SUMMARY OF EVIDENCE OF EFFECTIVENESS OF PRIMARY CHRONIC VENOUS DISEASE TREATMENT William Marston, MD, Chapel Hill, NC COMPRESSION AFTER DEEP VENOUS THROMBOSIS TO PREVENT POST- THROMBOTIC SYNDROME AND ULCERATION A Cochrane review of non-pharmaceutical measures for prevention of postthrombotic syndrome identified three randomized controlled trials (RCTs) evaluating compression stockings to no compression or sham compression in patients after an episode of deep vein thrombosis (DVT). 1 The use of compression stockings in each study was associated with a significant reduction of the development of postthrombotic syndrome (PTS; odds ratio 0.39). Because the incidence of venous ulceration after DVT is low ( 10%) and may not present for more than 10 years after the initial event, randomized studies on the prevention of ulceration after DVT are unlikely to be performed. The use of compression hosiery to prevent PTS after DVT can be given a 1A recommendation based on the clear benefit and low-risk of complications, but for prevention of ulceration, a 1C grade is recommended as a prevention of PTS is only a surrogate for ulcer prevention. It may also be argued that a treatment modality that suffers from poor patient compliance (fewer than 50% of DVT patients are estimated to routinely wear compression stockings longterm) should not be assigned a 1 grade because patients frequently decide that the therapy is not worth the supposed treatment benefit. COMPRESSION FOR VENOUS ULCER HEALING AND PREVENTION OF RECURRENCE The Cochrane Collaboration recently (January 2009) updated their extensive review of the literature on the use of compression for venous leg ulcers. 2 After a review of 39 RCTs examining various forms of compression in venous leg ulcers, they concluded that compression clearly increases ulcer healing rates compared to no compression. Multi-component systems are more effective than single-component systems, and most studies found that multi-component systems with an elastic bandage were more effective than those composed mainly of inelastic components. An RCT of 153 patients compared the effectiveness of compression hosiery in reducing the incidence of ulcer recurrence after healing. 3 Significantly fewer patients using compression routinely developed ulcer recurrence at 6 months of follow-up (21%) than did those not using compression hosiery (46%; P.05). Another RCT compared the relative benefit of class 2 compression stockings compared to class 3 stockings in preventing ulcer recurrence. 4 Whereas no significant difference in the incidence of ulcer recurrence was found (32% recurred using class 3 and 39% recurred using class 2), 42% of patients randomized to class 3 hosiery were unable to comply with their use, potentially masking the ability to prevent recurrence in this group. In the class 2 group, 28% of patients were noncompliant with routine use. Based on this analysis, it seems appropriate to assign a 1A grade to the use of compression bandaging for the healing of venous leg ulcers. A grade of 1B seems reasonable for the recommendation of compression hosiery to prevent recurrent ulceration. There is little risk to compression bandaging and hosiery as long as patients with arterial insufficiency are identified and appropriate stocking sizing and training is performed. However, it must be acknowledged that compliance with high-grade compression hosiery is poor, and in many cases lower amounts of compression may be preferable to achieve compliance. MEDICAL THERAPIES FOR TREATMENT OF PRIMARY CHRONIC VENOUS DISEASE AND ACCELERATION OF ULCER HEALING: PHLEBOTONIC AGENTS The category of phlebotonic agents contains a variety of natural and synthetic compounds believed to have venoactive properties that will reduce the symptoms of venous disease. These properties include a reduction of capillary permeability, improvement of venous tone, inhibition of inflammation or leukocyte activation, and others. Flavonoids, natural extracts from plants such as grape seed and French maritime pine bark, are included in this category, as are horse chestnut seed extract (HCSE) and rutosides. In a recent review by the Cochrane Collaborative on phlebotonic agents, 5 it was concluded that there is some evidence of a reduction in limb edema with phlebotonic agents, but overall there is not sufficient evidence to recommend their use with the exception of HCSE.

2 Volume 52, Number 14S 55S Two RCTs have studied the benefit of flavonoids in addition to compression for venous leg ulcer healing. Both found a significant benefit for flavonoid treatment compared to control. 6,7 Currently, flavonoids are not approved by the Food and Drug Administration for use in the United States. It is difficult to assign a grade to this category of medications for treatment of the symptoms of chronic venous insufficiency (CVI) and for ulcer healing due to the multitude of compounds studied and extensive variability in the method of study and outcomes measured. HORSE CHESTNUT SEED EXTRACT The HCSE contains escin, which has been shown to inhibit the activity of elastase and hyaluronidase, enzymes involved in proteoglycan degradation. These are postulated to be involved in the inflammatory pathway translating venous hypertension to tissue damage. Other reports have suggested that escin inhibits leukocyte activation in patients with CVI. 8 In a review of RCTs studying the effects of HCSE on the symptoms of CVI, the Cochrane Collaborative reported that 6 of 7 trials reported a significant reduction of leg pain in patients treated with HCSE compared to placebo-treated groups. 9 A meta-analysis of the studies noted significantly better edema reduction in HCSEtreated patients compared to control. In summary, HCSE seems to have evidence from multiple RCTs of benefit in reducing symptoms in patients with CVI. No evidence of efficacy in preventing ulceration or accelerating ulcer healing is available. Side effects with treatment seem to be uncommon. HCSE can be assigned as a 2A grade recommendation for the reduction of the symptoms of CVI. The magnitude of benefits, in my opinion, is not sufficient to provide a grade 1 recommendation. PENTOXIFYLLINE In a review of RCTs, Jull et al 10 found five trials in which pentoxifylline was added to compression compared to placebo and compression. Pooling this data resulted in the conclusion that more patients healed in the pentoxifylline group. In one of the studies, Falanga et al 11 reported a median time to healing of 100 days for placebo, compared to 71 days for pentoxifylline at 800 mg three times a day. Treatment of patients with this dose of pentoxifylline is occasionally limited by gastrointestinal side effects which have been reported in 10% to 20% of patients. For this reason, a grade of is recommended for pentoxifylline in accelerating ulcer healing. THERAPIES FOR SUPERFICIAL VENOUS INSUFFICIENCY Saphenous stripping. For patients with active or healed venous leg ulcers (VLUs), Barwell et al 12 performed a randomized study comparing the efficacy of saphenous stripping plus compression compared to compression alone for healing and prevention of VLUs. Termed the ESCHAR study, 500 patients with isolated superficial reflux (60%) or combined superficial and deep venous disease (40%) were enrolled. Compression in both groups was performed using multilayered compression bandaging. Surgical treatment included high ligation and stripping of the great and/or small saphenous vein and calf varicosity avulsion as needed based on preprocedure duplex scans. Data analysis was performed on an intention-to-treat basis such that patients randomized to the surgery plus compression group who did not proceed with surgery (n 47) were kept in the surgery group for data analysis. Three patients initially randomized to compression alone requested surgery. Demographic factors were similar in the two groups. Ulcer healing was no different with 65% healed in each group by life table analysis at 24 weeks after randomization (Fig 3). In the group with healed ulcers, mean follow-up time was 14 months. Significantly fewer patients in the surgery group experienced recurrent ulceration (15%) compared to the compression alone group (34%; Fig 4. Adverse events were infrequent ( 5% in each group) primarily comprised of compression bandage injuries in the conservative group and wound infection (n 5) in the surgical group. In a second report, longer term follow-up of the enrolled patients was reported with up to 4 years of observation after randomization. 13 Ulcer healing rates did not vary at 3 years between the two groups at 89% for the compression group and 93% for the compression plus surgery group (P.73). The rate of ulcer recurrence 4 years after randomization was 56% for the compression group and 31% for the compression plus surgery group (P.01). Based on this prospective randomized analysis, I recommend superficial venous stripping procedures be assigned a grade of for the outcome of ulcer healing and 2A for prevention of ulcer recurrence. Although it seems that there is a reduction of recurrence that is significant, many patients choose against surgical stripping procedures (nearly 20% in this study) based on risk, personal preference, or other reasons. There has been no credible data to suggest that superficial stripping operations accelerate wound healing and, in this study, randomizing all patients with venous ulcerations did not yield a healing benefit. A study that eliminated the patients who respond rapidly to compression therapy, randomizing delayed healers to compression or compression plus surgery is necessary to further define the role of superficial intervention in wound healing. Alternatives to conventional saphenous surgery. Numerous alternatives to conventional saphenous surgery have been promoted to effectively eliminate saphenous reflux without the need for surgical incisions or saphenous removal. These include: Hemodynamic correction of varicose veins (CHIVA) External banding to restore saphenous competence Endovenous ablation ΠRadiofrequency ΠLaser Sclerotherapy ΠUltrasound-guided ΠFoam Endovenous ablation (radiofrequency or laser). Of the listed alternatives to saphenous ligation and stripping

3 56S procedures, endovenous ablation has been the most widely studied, including randomized comparisons to stripping. The goal of radiofrequency ablation (RFA) or endovenous laser ablation is to ablate the saphenous vein percutaneously eliminating saphenous reflux, thereby producing the same hemodynamic benefit as high ligation and saphenous stripping with no incisions, fewer complications, and faster recovery to full activity. Early studies with both techniques have demonstrated initial saphenous closure rates of over 90%. Long-term reports on the incidence of saphenous recanalization are now emerging, with acceptable 3 to 5 year results. In the EVOLVeS study, RFA was compared to ligation and stripping in 86 limbs including quality of life measures and follow-up ultrasound scan examinations at routine intervals. Initial success rates at elimination of saphenous reflux were 100% in the stripping group and 95% in the RFA group. 14 The time required to return to normal activities and return to work were significantly less in the RFA group. Quality of life surveys revealed a significantly better global score and a significantly better pain score for RFA 1-week postprocedure, but these differences progressively decreased over time. At 2 years of follow-up, 2 patients in the RFA group had developed recanalization of an initially closed saphenous vein (4%), but global quality of life scores still favored RFA. One patient in the RFA group and 4 treated with ligation and stripping were found to have evidence of neovascularization on ultrasound scan examination. Recurrent varicose veins (VVs) occurred in 14% of RFA limbs and 21% of stripped limbs (P NS). No studies have compared the outcome of endovenous ablation to saphenous stripping for patients with VLUs, and little information is available on the incidence of ulcer recurrence after saphenous ablation using any of the above methods. Most data on endovenous ablation has been reported on procedures performed in patients with CEAP class 2 and 3 disease. One study reported the hemodynamic results of patients in CEAP classes 3 to 6 treated with RFA or laser saphenous ablation. It included 29 patients in CEAP classes 5 and 6, and found that ablation resulted in reliable correction in venous hypertension. 15 Seventy-eight percent of limbs demonstrated a normal venous filling index (VFI) postablation and 95% had a VFI 4 ml/second. Based on previous studies of poststripping VFI, these patients would be expected to have a low incidence of recurrent ulceration unless saphenous recanalization were to develop. Currently, all information relating endovenous ablation to ulcer healing or recurrence is through surrogate outcomes. Therefore, endovenous ablation can be given no better than a recommendation for healing venous ulcers or preventing their recurrence. Sclerotherapy for superficial venous insufficiency. In general, studies with liquid sclerotherapy for saphenous reflux have reported high rates of recurrent reflux. More recently, saphenous sclerotherapy has been performed with foam-based sclerosants with a lower rate of recurrence. Most reports on the results of foam sclerotherapy have focused on the success in saphenous ablation in CEAP clinical class 2 or 3 limbs based on posttreatment duplex scan examination of the vein. Gonzalez-Zeh et al 16 reported a 1-year follow-up study of 98 patients after foam sclerotherapy or endovenous laser ablation for saphenous reflux. The study was not randomized, but venous clinical severity scores were measured in both groups at follow-up visits. At 1 year of follow-up, 93% of laser-treated great saphenous veins (GSVs) remained occluded, compared to 77% of foam-treated GSVs (P.05). Venous clinical severity scores improved significantly in both groups with no difference at 1 year of follow-up. Pascarella et al 17 reported on the use of this method in the treatment of 19 patients with VLUs in combination with compression bandaging. Excellent results were obtained with a suggestion that ulcers healed more rapidly than in a comparator group of 12 limbs treated with compression alone. This trial was not randomized and did not achieve statistical significance in demonstrating a benefit for the addition of sclerotherapy to compression in improving ulcer management significantly. We may consider a grade of for foam sclerotherapy for the outcome of symptom relief in patients with CEAP class 2 and 3 superficial venous insufficiency. However, given the lack of more specific data in larger series of patients with leg ulcers, foam sclerotherapy can only be assigned a recommendation for ulcer healing or prevention of recurrence. Combined superficial and deep venous insufficiency. In patients with CEAP class 5 and 6 disease, superficial insufficiency is often identified in combination with deep disease. Nearly 30% of these limbs have been reported as having combined reflux. In this situation, the clinician must determine whether benefit is likely from treatment of superficial reflux alone, or if the patient is more likely to require deep venous reconstruction. Several authors have reported that when superficial reflux in the GSV or small saphenous vein is present, the more proximal deep vein segment will occasionally reflux solely due to the superficial vein incompetence. Correction of the superficial reflux reliably results in resolution of the deep vein segment reflux. 18 Several of these studies reported symptomatic improvement and one reported improvement in venous hemodynamics. With these patterns of reflux, superficial ablative procedures are recommended using the same criteria used for superficial incompetence alone. Treatment of limbs demonstrating true deep venous insufficiency, defined as reflux in the femoral and/or popliteal veins, combined with superficial reflux is controversial. Puggioni et al 19 recently reported a study of 38 limbs with combined deep and superficial reflux studied with duplex ultrasound scan before and after saphenous stripping. Deep venous reflux was corrected in one-third of patients, and femoral vein reflux corrected more frequently when only segmental reflux was present in that vein rather than axial reflux throughout the deep venous system. In another study, patients with deep and superficial reflux were studied using maximal reflux velocities in the

4 Volume 52, Number 14S 57S deep venous system as a determinate of outcome after superficial venous ablation. When the deep venous reflux velocities were low, patients had significant improvement in their venous clinical severity scores and the air plethysmography derived VFI after superficial saphenous ablation. 20 In summary, it is reasonable to consider superficial ablative intervention in patients with CVI due to combined deep and superficial insufficiency to reduce their symptoms. Those most likely to benefit are those with proximal or segmental reflux and those with low velocity reflux in the deep venous system. There is no direct evidence that superficial ablation will improve ulcer healing or prevent ulceration in patients with CVI, but surrogate outcomes such as the VFI suggest that these procedures may reduce the risk of ulceration or ulcer recurrence. I suggest a grade of for the reduction of CVI symptoms and for prevention of ulceration. Incompetent perforator veins. The incidence of incompetent perforator veins (IPVs) increases as the clinical severity of CVI worsens. Unfortunately, it is difficult to clearly determine the hemodynamic significance of IPVs because they are usually seen in limbs that also display superficial and/or deep system incompetence. There clearly are cases where IPVs are seen in a limb previously treated with saphenous stripping with persistent leg ulceration. In these patients, perforator interruption is necessary. But it is unclear whether perforators should routinely undergo ligation in patients with VLU at the time of saphenous ablation. Conventional surgical ligation of perforator veins (Linton procedure). Although the Linton procedure was effective at eliminating perforator reflux, it has been associated with a high incidence of complications, mostly occurring at the incision site in the area of hyperpigmented, scarred skin typical of advanced CVI. In a report of 37 limbs treated with the Linton procedure, Stuart et al 21 reported that calf wound complications occurred in 7 patients (19%), and the average hospital time was 9 days. Recurrent ulceration was reported in 7% to 22% of treated limbs at varying lengths of follow-up after the Linton procedure. This technique seems to be primarily of historic interest. Subfascial endoscopic perforator ligation. In a retrospective comparison of subfascial endoscopic perforator ligation (SEPS; n 27) to the Linton procedure (n 29), Sato et al 22 reported similar rates of ulcer healing and recurrence, and a similar improvement in venous dysfunction scores in the two groups. In the Linton group, 45% of patients developed incision-related complications, compared to only 7% in the SEPS group (P.005). In a prospective comparison of the Linton procedure to SEPS, Pierik et al 23 randomized 39 patients to open or endoscopic perforator ligation. In the open group, 53% of patients developed postoperative wound infection compared to 0% in the SEPS group (P.001). Ulcer healing rates and recurrence rates were similar in the two groups. Iafrati et al 24 reported on the treatment of 51 limbs with perforator reflux and leg ulcers using SEPS. Venous disability scores improved significantly after the procedure, and 74% of limb ulcers healed within 6 months. The recurrent ulceration rate was low at 13%. Excellent results were obtained, but 35 of 51 limbs were treated concomitantly with saphenous or varicose vein removal. Of note, SEPS performed without saphenous surgery was associated with delayed ulcer healing. Tawes et al 25 reported a large retrospective multicenter experience using SEPS in over 800 limbs with CVI. The majority of patients (532) had active or previous leg ulceration. Concomitant GSV removal was performed in 55% of cases. Reported results were excellent with 92% of limb ulcers healing at 4 to 14 weeks after SEPS. Recurrent ulceration occurred in only 4% at a mean follow-up of 15 months. From this review, the authors concluded that until definitive level I evidence is available, SEPS is advocated as optimal therapy for patients with CVI and IPVs. A randomized prospective study compared the benefit of SEPS (and superficial venous ablation when necessary) compared to compression in patients with CVI-related leg ulcers. In this patient group, deep venous incompetence was present in 52% of limbs. Superficial venous procedures were performed in 54%. Ulcer healing rates were not significantly different in the two groups, and ulcer recurrence occurred in 22% in the surgical group compared to 23% in the compression group. Healing rates in medial leg ulcers and recurrent ulcers were significantly better in surgically treated limbs. The effect of adding SEPS to saphenous stripping was studied in patients with superficial and perforator reflux only. In a prospective randomized study, 70 patients were randomized to saphenofemoral ligation and stripping or the same with SEPS. The majority of patients in both groups were CEAP clinical class 2, with no open ulcers in either group. Outcomes examined included the presence of IPVs after surgery on duplex ultrasound scan, and quality of life as evaluated by the Short Form Health Survey and the Aberdeen Varicose Vein Symptom Score. A significantly higher proportion of patients in the stripping alone group had IPVs at 1 year of follow-up (78%) than did those undergoing stripping plus SEPS (32%). However, there were no differences between the two groups in postprocedure pain, mobility, or quality of life scores. Based on the currently available information, most venous practitioners believe that there are specific cases in which perforator ligation is useful to reduce symptoms or address difficult cases of recurrent ulceration. However, the benefit of perforator interruption has been difficult to demonstrate in systematic study. I recommend a grade of for SEPS for both symptom reduction and ulcer-related outcomes. Percutaneous perforator ablation and foam sclerotherapy. Recently, alternate options have been reported for treatment of refluxing perforators. Initial reports of the use of endoluminal techniques using radiofrequency or laser heat sources have suggested that percutaneous ablation of perforator veins is feasible. Currently available reports have described success in 80% to 90% of cases attempted at eliminating reflux in IPVs. Studies reporting

5 58S patient-relevant outcomes and longer follow-up are not yet available. Similarly, successful perforator ablation has been reported using ultrasound-guided foam sclerotherapy injection. The current literature does not allow a grade assignment to these techniques, but they should be observed with interest. Summary of grade recommendations: Compression after DVT to prevent PTS Compression after DVT to prevent ulceration Compression for venous ulcer healing Compression for prevention of ulcer recurrence HCSE for reducing CVI symptoms Pentoxifylline for healing venous leg ulcers Saphenous stripping for healing venous ulcers Saphenous stripping for prevention of recurrent ulcers Endovenous saphenous ablation for reducing CVI symptoms Endovenous saphenous ablation for healing or preventing recurrent ulcers Ultrasound-guided foam sclerotherapy for reducing CVI symptoms Ultrasound-guided foam sclerotherapy for healing or preventing recurrent ulcers SEPS for reducing CVI symptoms SEPS for venous ulcer healing or preventing recurrent ulcers 1A 1C 1A 1B 2A 2A REFERENCES 1. Kolbach DN, Sandbrink MW, Hamulyak K, Neumann M, Prins MH. Non-pharmaceutical measures for prevention of post-thrombotic syndrome. Cochrane Database Syst Rev 2004:CD O Meara S, Cullum NA, Nelson EA. Compression for venous leg ulcers. Cochrane Database Syst Rev 2009:CD Vandongen YK, Stacey MC. Graduated compression elastic stockings reduce lipodermatosclerosis and ulcer recurrence. Phlebology 2000;15: Nelson EA, Harper DR, Prescott RJ, Gibson B, Brown D, Ruckley CV. Prevention of recurrence of venous ulceration: randomized controlled trial of class 2 and class 3 elastic compression. J Vasc Surg 2006;44: Martinez-Zapata MJ, Bonfill Cosp X, Moreno RM, Vargas E, Capella D. Phlebotonics for venous insufficiency (Review). The Cochrane Library 2009, Issue Guilhou JJ, Dereure O, Marzin L, Ouvry P, Zuccarelli F, Debure C, et al. Efficacy of Daflon 500 mg in venous leg ulcer healing: a doubleblind, randomized, controlled versus placebo trial in 107 patients. Angiology 1997;48: Glinski W, Chodynicka B, Roszkiewicz J, Ouvry P, Zuccarelli F, Debure C, et al. [Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized.] [Article in Italian] Minerva Cardioangiol 2001;49: Facino RM, Carini M, Stefani R, Aldini G, Saibene L. Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency. Arch Pharm (Weinheim) 1995;328: Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2006:CD Jull AB, Waters J, Arroll B. Pentoxifylline for treating venous leg ulcers. Cochrane Database Syst Rev 2002.CD Falanga V, Fujitani RM, Diaz C, Hunter G, Jorizzo J, Lawrence PF, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Wound Repair Regen 1999;7: Barwell JR, Davies CE, 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: Gohel MS, Barwell JR, Taylor M, Hunter G, Jorizzo J, Lawrence PF, et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ 2007;335: Lurie F, Creton D, Eklof B, Kabnick LS, Kistner RL, Pichot O, et al. Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected population (EVOLVeS Study). J Vasc Surg 2003;38: Marston WA, Owens LV, Davies S, Mendes RR, Farber MA, Keagy BA. Endovenous saphenous ablation corrects the hemodynamic abnormality in patients with CEAP clinical class 3-6 CVI due to superficial reflux. Vasc Endovascular Surg 2006:40: Gonzalez-Zeh R, Armisen R, Barahona S. Endovenous laser and echoguided foam ablation in great saphenous vein reflux: one-year follow-up results. J Vasc Surg 2008;48: Pascarella L, Bergan JJ, Mekenas LV. Severe chronic venous insufficiency treated by foamed sclerosant. Ann Vasc Surg 2006;20: Padberg FT Jr, Pappas PJ, Araki CT, Back TL, Hobson RW 2nd. Hemodynamic and clinical improvement after superficial vein ablation in primary combined venous insufficiency with ulceration. J Vasc Surg 1996;24: Puggioni A, Lurie F, Kistner RL, Eklof B. How often is deep venous reflux eliminated after saphenous vein ablation? J Vasc Surg 2003;38: Marston WA, Brabham VW, Mendes R, Berndt D, Weiner M, Keagy B. Importance of deep venous reflux velocity as a determinant of outcome in patients with combined superficial and deep venous reflux treated with endovenous saphenous ablation. J Vasc Surg 2008;48:400-5; discussion Stuart WP, Asam DJ, Bradbury AW, Ruckley CV. Subfascial endoscopic perforator surgery is associated with significantly less morbidity and shorter hospital stay than open operation (Linton s procedure). Br J Surg 1997;84: Sato DT, Goff CD, Gregory RT, Walter BF, Gayle RG, Parent FN 3rd, et al. Subfascial perforator vein ablation: comparison of open versus endoscopic techniques. J Endovasc Surg 1999;6: Pierik EG, van Urk H, Hop WC, Wittens CH. Endoscopic versus open subfascial division of incompetent perforating veins in the treatment of venous leg ulceration; a randomized trial. J Vasc Surg 1997;26: Iafrati MD, Pare GJ, O Donnell TF, Estes J. Is the nihilistic approach to surgical reduction of superficial and perforator vein incompetence for venous ulcer justified? J Vasc Surg 2002;36: Tawes RL, Barron ML, Coello AA, Joyce DH, Kolvenbach R. Optimal therapy for advanced chronic venous insufficiency. J Vasc Surg 2003;37: DEFINITION OF POSTTHROMBOTIC DISEASE Suresh Vedantham, MD, St. Louis, Mo The postthrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT; grade: high/ concordant prospective trials and registries), 1-5 but its prevention and treatment are often neglected by physicians as key DVT treatment objectives. Achievement of consensus within the scientific community on what exactly constitutes PTS would be helpful in developing the research, provider education, and public awareness initiatives that are needed to drive collective action to reduce the disease burden of PTS upon patients and society with DVT. The process of developing a uniform definition of PTS must be informed by its expected utility. Among key po-