Venous Stasis Disease and Venous Ulcers

• Alpagut, U: Importance and Advantages of Intermittent External Pneumatic Compression Therapy in Venous Stasis Ulceration. Angiology 56: 19-23, 2005. Venous ulcers are seen following postthrombophlebitic syndrome with venous insufficiency and can begin as a result of minor trauma. In this retrospective study the authors examined the value of external intermittent pneumatic compression therapy in chronic venous ulcers. Results in 1,250 patients with postthrombophlebitic syndromes, 235 of these patients with leg ulcers, revealed that this modality of therapy shortens the therapy duration, lowers the total therapy cost, and hastens the return to active life in comparison to the classical therapy with compression stockings and antiaggregant or low-dose oral anticoagulant therapy. In the light of their findings they propose the wider use of this adjuvant therapy.

• Amann-Vesti BR, Ruesch C, Gitzelmann G, Hafner J, Koppensteiner R: Microangiopathy of split-skin grafts in venous ulcers. Dermatol Surg 30:399-402, 2004. BACKGROUND: In patients with chronic venous insufficiency, microangiopathy of blood and lymph capillaries caused by venous hypertension plays a major role in the development of venous ulceration. Conservative treatment of venous leg ulcers often fails, and split-skin grafting is sometimes performed. OBJECTIVE: To evaluate the microcirculation and especially the regeneration and function of lymphatic vessels in skin grafts in patients with chronic venous insufficiency. METHODS: The microcirculation of 15 split-skin grafts was studied by fluorescence microlymphography and measurement of transcutaneous oxygen tension (tcpO2) in 13 patients. RESULTS: The mean age of the skin grafts was 70.9 months. In only two skin grafts were a few intact lymph meshes found. In all other cases, only fragments of lymphatic capillaries have been detected. In seven skin grafts, cutaneous backflow of dye through insufficient deeper lymph channels was observed. The maximal spread of the dye in the lymphatic network was increased in the skin grafts (17.6 +/- 22.9 mm). The mean value of tcpO2 was only 27.1 +/- 18.1 mm Hg. CONCLUSIONS: In split-skin grafts of patients with venous ulcers, severe microcirculatory changes are present and characterized by hypoxia and abnormal regeneration and function of lymphatic vessels.

• Belcaro G, Cesarone MR, Ledda A et al: 5-Year control and treatment of edema and increased capillary filtration in venous hypertension and diabetic microangiopathy using O-(beta-hydroxyethyl)-rutosides: a prospective comparative clinical registry. Angiology 59 Suppl 1:14S-20S, 2008. This independent prospective controlled trial evaluates the efficacy of O-(beta-hydroxyethyl)-rutosides (HR) during 5 years of administration against signs and symptoms and further degeneration of microcirculatory disturbances. The protective effect of HR in preventing end-point complications such as venous ulceration is evaluated. This study is based on evaluation of edema and the capillary filtration rate (CFR) in association with a clinical score scale. Patients having a severe degree of chronic venous insufficiency (CVI) and venous microangiopathy and completing at least 5 years of treatment are included. The following 4 groups are considered: group A (patients with CVI but without diabetes mellitus, receiving 1500 mg/d of HR), group B (patients with CVI and diabetes mellitus, receiving 2 g/d of HR), group C (control subjects receiving no pharmacologic or compression treatment), and group D (patients using elastic compression stockings only). All patients received the "best" available treatment. No adverse effects or intolerance is noted, with good compliance (>85%). In group A, there is a statistically significant decrease in the CFR during 5 years of follow-up. In group B, the decrease in the CFR is greater than that in group A. Reductions in edema, swelling, and the CFR during 5 years are notable, and values approach normal levels. During 5 years, HR is effective in treating venous edema and hypertension and in preventing deterioration of the distal venous system. The prevention of ulcerations with HR is another important observation. The effects of HR seem to be partially dose related, and tolerability and compliance are good. Comments: The report entails 378 patients in their registry. "HR" has been available as "Paroven" or "Venoruton". Hr and rutin contain flavonoids which are noted for their strong antioxidant properties and are usually found in vegetables. This report and the one below suggest HR may become a important agent in the treatment of venous stasis disease.

• Belcaro G, Rosaria Cesarone M, Ledda A et al: O-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative study. Angiology 59 Suppl 1: 7S-13S, 2008. O-(beta-hydroxyethyl)-rutosides (HR) is used to treat chronic venous disease and signs and symptoms of chronic venous insufficiency (CVI), varicose veins, and deep venous disease. This independent prospective controlled trial (a registry study) evaluates how the efficacy of HR at the local level (perimalleolar region) can be increased by the administration of a topical HR gel. The study is based on evaluation of microcirculatory variables in patients with severe CVI (ambulatory venous pressure, > 56 mm Hg) and venous microangiopathy. Patients are treated using 1 of the following 3 regimens: oral treatment with 1 g sachets of HR (2 g/d total) plus topical HR 2% gel applied 3 times daily at the internal perimalleolar region; oral treatment only (same dosage), or light elastic compression stockings. Laser Doppler skin flux at rest, skin flux at the perimalleolar region, and transcutaneous PO2 and PCO2 are measured at baseline and at the end of the treatment period. A comparable group of healthy individuals without treatment is observed for 8 weeks. In the treatment groups, flux is increased, PO2 is decreased, and PCO2 is increased compared with normal skin. At 4 and 8 weeks, the improvement in skin flux (which is decreased by all measurements), the increase in PO2, and the decrease in PCO2 (indicating microcirculatory improvement) are statistically significantly greater in the combined oral plus topical treatment group (P < .05). No adverse effects, tolerability problems, or compliance issues are noted. These results indicate an important role of HR in the treatment and control of CVI and venous microangiopathy.

• Bjellerup M: Determining venous incompetence: a report from a specialised leg ulcer clinic. J Wound Care 15:429-30, 433-6, 2006. OBJECTIVE: To analyse the diagnosis, treatment and prognosis in patients attending a specialised leg ulcer clinic at a dermatology department. METHOD: In total, 345 patients were investigated and 332 registered and followed up prospectively. All patients had their arterial and venous circulation assessed with a hand-held Doppler ultrasound. RESULTS: The most frequent diagnosis was venous ulceration (153 patients, 46%) followed by hydrostatic ulceration (70 patients, 21%). Venous incompetence was classified as isolated superficial (n=86) or deep venous incompetence (n=57) in 143 out of the 153 patients. Previous deep vein thrombosis (DVT) was more frequent in patients with deep venous incompetence. Of patients with venous ulcers, 38 (25%) healed within 92 days, 77 (50%) within 155 days and 115 (75%) within 329 days. Healing time was influenced by patient age, ulcer duration and ulcer area, but not by type of venous incompetence or ankle brachial pressure index. After healing, 19% of venous patients (28/144), dominated by those with superficial disease, were subject to venous vascular surgery. CONCLUSION: Classification of venous insufficiency should be mandatory in patients with venous ulcers since it determines suitability for venous surgery. Comments: In this clinic specializing in leg ulcers, about 50% of the venous ulcers were not healed in five months and 25% were not healed in close to a year! Reading on, the reader will find that they could have benefited from a rapid-acting intermittent pneumatic boot program. Perhaps, some of the patients might have also benefited from vein ligation earlier in their course.

• Blackshear WM Jr, Prescott C, LePain F et al: Influence of sequential pneumatic compression on postoperative venous function. J Vasc Surg 5:432-6, 1987. Sequential external pneumatic compression (SEPC) has been reported to decrease the incidence of acute deep venous thrombosis in postoperative patients by a direct mechanical action on the lower extremity veins and/or by inducing alterations in systemic fibrinolysis. To evaluate the effect of SEPC on venous function in the postoperative patient, pre- and postoperative venous capacitance (VC) and outflow (VO) were measured in a series of general surgical patients. In phase I, 17 limbs were evaluated in patients who had been fully ambulatory preoperatively and at complete bed rest postoperatively. VC decreased from 3.19 +/- 0.43 cc/100 cc of tissue (mean +/- standard error of the mean) preoperatively to 2.08 +/- 0.34 cc/100 cc of tissue postoperatively (p less than 0.05) and VO decreased from 87.2 +/- 10.6 cc/100 cc of tissue/min preoperatively to 58.1 +/- 8.7 cc/100 cc of tissue/min postoperatively (p less than 0.025). In phase II SEPC was begun preoperatively and continued for 24 hours postoperatively on one limb of 20 patients. SEPC prevented the decrease in VC and VO both in the pumped leg (VC-2.65 +/- 0.26 cc/100 cc of tissue preop, 2.40 +/- 0.18 cc/100 cc of tissue postop, p greater than 0.2; VO-72.3 +/- 5.9 cc/100 cc of tissue/min preop, 66.2 +/- 5.3 cc/100 cc of tissue/min postop, p greater than 0.2) and in the unpumped limb (VC-2.85 +/- 0.18 cc/100 cc of tissue preop, 2.41 +/- 0.24 cc/100 cc of tissue postop, p greater than 0.05; VO-66.1 +/- 5.2 cc/100 cc of tissue/min preop, 66.7 +/- 6.7 cc/100 cc of tissue/min postop, p greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS) Comments: Here we see that the normal postoperative falloff in venous capacitance and outflow are lessened/prevented by postoperative sequential pneumatic compression therapy. Circulator Boot therapy (CBRX)is more vigorous than the devices used in this study. One expects such studies to improve with CBRX. Years ago we enlisted several healthy young student nurses to undergo vascular testing before and after CBRX. A marked increase in their pulse volume measurements was noted and attributed to a reduction of interstitial fluid volume and pressure. Such fluid loss, of course, increases venous capacitance. In patients with venous stasis, CBRX may likewise improve venous testing. Such follow-up testing is rarely necessary, however, as obvious clinical signs document the effects of therapy: edema is lessened; the leg becomes more compliant; pigment is lessened; palpable thrombi may disappear; and the ulcers heal.
• Blessing K: Malignant melanoma in stasis dermatitis. Histopathology 30:135-9, 1997. Two cases of malignant melanoma arising in established stasis dermatitis are described. One case was clinically thought to be melanocytic whereas the other was not. Histologically, both showed similar features with background varicose change of epidermal atrophy, sloughing of the epidermis, intense proliferation of small thick walled blood vessels, lymphocytic infiltrate and dermal fibrosis. In the superficial aspects of the biopsies there was little clue to the diagnosis of melanoma. In the deeper aspects of case 1, groups of melanocytes were present in the reticular dermis which mimicked benign naevus cells. S-100 protein staining confirmed the melanocytic nature of these lesions, their extent and the epidermal involvement. The latter features supported a malignant diagnosis. These lesions can be overlooked clinically as well as histologically. Comments: Such reports are frightening. One can imagine how easy it would be to overlook a melanoma in a deeply pigmented leg.

• Bohannon WT, McLafferty RB, Chaney ST et al: Outcome of venous stasis ulceration when complicated by arterial occlusive disease. Eur J Vasc Endovasc Surg 24:249-54, 2002. OBJECTIVE: to report the outcome of patients with venous stasis ulceration (VSU) and severe arterial occlusive disease (AOD). DESIGN: retrospective study. METHODS: using the International Classification of Diseases (ICD-9), codes for VSU and AOD were cross-matched to identify patients from 1989 to 1999 at two tertiary hospitals. Entry into the study required the presence of a VSU and an ipsilateral procedure to improve AOD or major amputation during the same hospitalisation. RESULTS: fourteen patients (15 extremities) with a mean age of 80 years (range: 47-93) were identified as having VSU and AOD. Mean duration of VSU up to the time of revascularisation or amputation was 6.4 years (range: 4 months-21 years). The mean number of VSUs per extremity was 2.1 and mean wound area was 71 cm(2). Mean ankle-brachial index was 0.46 (range: 0.10-0.78). Nine extremities (60%) had a bypass procedure, 3 (20%) had an interventional procedure, 1 (0.6%) had a lumbar sympathectomy, and 2 (13%) had an amputation. Over a mean follow-up of 2.8 years, 3 extremities (23%) healed of which 2 recurred. On last review, 11 patients with 12 afflicted extremities had expired. Nine of the remaining 10 extremities were not healed at the time of death. Eight of nine bypass grafts remained patent in follow-up or at death and subsequent limb salvage was 100%. CONCLUSIONS: combined VSU and AOD represents a rare condition predominantly found in elderly patients with multiple comorbidities. Few patients had complete healing despite an arterial inflow procedure and mortality was high over the short term.

• Brkljacic B, Misevic T, et al: Duplex-Doppler ultrasonography in the detection of lower extremities deep venous thrombosis and in the detection of alternative findings.Coll Antropol 28:761-7, 2004. The diagnoses observed in patients referred for the Doppler ultrasonographic examination of peripheral and iliac veins for suspected deep venous thrombosis (DVT) are presented in this study. During 48 months 2,610 patients were examined by duplex Doppler ultrasonography (US). Among these, 1,879 were women (72%) and 731 men (28%), with the age-range 16-91 (mean 56, 2) years. Ultrasonic scanners Acuson 128 XP 10, ATL HDI 5000, GE Logiq 7, and GE Logiq 9 were used, with transducers in the frequency range from 2.5-14 MHz. Findings were categorized into four main categories: (1) deep venous thrombosis (DVT); (2) pathology predominantly related to superficial veins without DVT, (3) pathology of adjacent structures; (4) normal findings. 562 patients had DVT (21.5%). 1,108 patients (42.5%) had predominant pathology of superficial veins: postthrombotic syndrome, superficial thrombophlebitis and varicose veins. 390 patients (14.9%) had pathology of surrounding structures, unrelated to veins, the most common pathology being popliteal cysts and muscular hematomas. These lesions must be properly diagnosed by US to avoid erroneous anticoagulant treatment.

• Cesarone MR, Belcaro G, Pellegrini L, et al: Venoruton vs Daflon: evaluation of effects on quality of life in chronic venous insufficiency. Angiology 57:131-8, 2006. The aim of this independent study was to investigate differences in efficacy between oxerutins (Venoruton) and 500 mg micronized diosmin + hesperidin (D+H) (Daflon) in patients with chronic venous insufficiency (CVI), evaluating venous-related quality of life (Ve-QOL). A first group of 90 patients with severe venous hypertension (CVI, ankle swelling) was randomized to treatment with oxerutins or D+H. The oxerutins group received oral oxerutins (2 g/day); the D+H group received 3 (500 mg) tablets daily every 8 hours for 8 weeks. A second group of 122 comparable patients was included in a registry following the same study format. The 2 treatments were administered with the same methods and procedures. Clinical conditions were comparable. All patients completing 8 weeks of treatment were included in a registry. Specialists or general practitioners included patients when they considered that clinical conditions were compatible with treatment indications using 1 of the 2 treatments on the basis of their evaluation and experience. When cases were compatible with the registry, the prescribing physician communicated the case to our monitoring center. Patients were evaluated without interfering with their treatment. The main target of evaluation for this study was the change in Ve-QOL (range, 0-100) induced by treatment. A specific Ve-QOL questionnaire was used for this study. Ve-QOL score is a specific expression of the changes in QOL induced by CVI in patients between 35 and 75 years old (defined in our population studies) in which no other significant clinical disease is present (as a confounding factor affecting QOL). Two hundred twelve patients completed the 2 parts of the study. The 2 treatment groups were comparable for age and gender distribution. The mean age was 42 years (SD +/-5.5) in the oxerutins group and 41.5 (SD +/-6) in the D+H group. There were no differences in the severity of CVI between the treatment groups at inclusion. A significant decrease (46.8%, p <0.05) in Ve-QOL score; that is, improvement, was observed in the oxerutins group. The change in Ve-QOL was significantly less in the D+H group (15.5%). In conclusion, CVI, venous microangiopathy, and edema were significantly improved by the treatment with oxerutins; the improvement in QOL was significantly greater in the oxerutins group. The comparison with D+H indicates that oxerutins is comparatively more effective on Ve-QOL and on signs/symptoms of CVI.

• Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, Ricci A, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cacchio M, Di Renzo A, Hosoi M, Stuard S, Corsi M: Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology 57: 569-576, 2006. The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous insufficiency. Patients with severe venous hypertension (chronic venous insufficiency, ankle swelling) and history of venous ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls (no treatment during the observation period). All 21 patients (age 53 years; range, 42-60 years; M:F=11:10) in the treatment group completed the 8-week study. Also the 18 controls completed the follow-up period. There were no drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68) with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients. The duration of the disease-from the first signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated a progressive decrease in skin flux, indicating an improvement in the level of microangiopathy; a significant decrease in capillary filtration; a significant improvement in the symptomatic score; and a reduction in edema. There were no visible effects in controls. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol in the management, treatment and control of this common clinical problem. The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy. Comments: An interesting study involving 21 patients, 18 controls and 17 authors. Pycnogenol is derived from the bark of French maritime pine. As a natural product, it may be sold over the counter without FDA regulation. To date it has a good press and appears to be a panacea for aging, vascular disease, athletic endurance etc. Few complications or side effects have been described.

• Chang HY, Wong KM, Bosenberg M et al: Myelogenous leukemia cutis resembling stasis dermatitis. J Am Acad Dermatol 49:128-9, 2003. Leukemia cutis may clinically mimic many inflammatory dermatoses. A patient with myelodysplastic syndrome presented with an acute eruption of bilateral, lower-extremity, tender, indurated, brown plaques that clinically resembled chronic stasis dermatitis. Histologic study revealed a dermal myeloblastic leukemic infiltrate.

• Christen Y, Reymond MA, Vogel JJ et al:Hemodynamic effects of intermittent pneumatic compression of the lower limbs during laparoscopic cholecystectomy.Am J Surg 170:395-8, 1995. BACKGROUND: The effects of surgical pneumoperitoneum on lower-limb venous hemodynamics have already been studied; however, the effects of intermittent compression boots are not known in such venous-stasis conditions. METHODS: In 12 volunteers and 12 patients, the venous hemodynamic effects of intermittent leg compression were studied under external abdominal pressure or during laparoscopic cholecystectomy, respectively. Femoral venous diameter and velocity were measured. Venous pressure was monitored during the surgical procedures. RESULTS: External abdominal pressure of 50 mm Hg and pneumoperitoneum were found to increase the diameter (17% in the volunteers and 14% in the patients) and decrease peak velocity (49% and 32%, respectively) in the femoral vein. Femoral pressure was increased (106%) during pneumoperitoneum. In both venous-stasis circumstances, intermittent compression of the legs restored venous flow velocity, but had no effect on vessel diameter and pressure. CONCLUSIONS: The lower-limb venous hemodynamic changes were similar during external abdominal pressure or pneumoperitoneum, and the flow velocity decrease was intermittently reversed by pneumatic compression boots.Comments: Here external or internal abdominal pressure obstructed venous outflow from the legs. The same happens with the application of pressure to the groin which is commonly applied to prevent bleeding after the removal of catheters from the femoral artery. In this situation, pneumatic boots may again play a helpful role.

• Cirujeda JL, Granado PC: A study on the safety, efficacy, and efficiency of sulodexide compared with acenocoumarol in secondary prophylaxis in patients with deep venous thrombosis.Angiology 57:53-64, 2006. This study was carried out to study the safety and efficacy of a fixed dosage of sulodexide compared to adjusted dosages (INR) of acenocoumarol as secondary prophylaxis in patients with deep vein thrombosis (DVT) in lower limbs. An economic evaluation based on the criteria of use in normal clinical practice was also performed. One hundred and fifty patients of both sexes were included, all over 18 years of age and diagnosed with proximal DVT of the lower limbs by color echo-Doppler, and with clinical evolution of less than 1 month. The patients were initially treated with low-molecular-weight heparin (LMWH) and urokinase in accordance with the established protocol. They were then randomized to continue treatment with acenocoumarol and INR adjustments every 30 days, or with sulodexide. Treatment was extended for 3 months with monthly follow-up visits and a final visit at 3 months posttreatment. No differences between the groups were detected concerning demographic or basal characteristics in clinical evolution or adverse reactions. In the group treated with sulodexide, no major/minor hemorrhagic complications were detected. On the other hand, in the acenocoumarol group, 1 major hemorrhage and 9 minor hemorrhages were produced (13.3%), reaching statistical difference in relation to the sulodexide group (p = 0.014; CI from 95% of 4.7% to 19.4%). Regarding the economic impact, treatment costs with sulodexide are much less than those with acenocoumarol, the data confirmed by the sensitivity analyses performed. The results prove the efficacy, safety, and efficiency of sulodexide as a secondary prophylaxis in thromboembolic disease, avoiding hemorrhagic risks and the monitoring of patients, and providing significant savings to the health system.

• Daroczy J: Quality control in chronic wound management: the role of local povidone-iodine (Betadine) therapy. Dermatology 212 Suppl 1:82-7, 2006. BACKGROUND: The treatment of venous leg ulcers is often inadequate, because of incorrect diagnosis, overuse of systemic antibiotics and inadequate use of compression therapy. Stasis dermatitis related to chronic venous insufficiency accompanied by infected superficial ulcers must be differentiated from erysipelas, cellulitis and contact eczema. OBJECTIVES: To assess the effectiveness of (1) topical povidone-iodine with and (2) without compression bandages, (3) to compare the efficacy of systemic antibiotics and topical antimicrobial agents to prevent the progression of superficial skin ulcers. PATIENTS AND METHODS: 63 patients presenting ulcerated stasis dermatitis due to deep venous refluxes were included in the study. The clinical stage of all patients was homogeneous determined by clinical, aetiological, anatomical and pathological classification. They were examined by taking a bacteriological swab from their ulcer area. Compression bandages were used in a total of 42 patients. Twenty-one patients with superficial infected (Staphylococcus aureus) ulcers were treated locally with povidone-iodine (Betadine), and 21 patients were treated with systemic antibiotics (amoxicillin). Twenty-one patients were treated locally with Betadine but did not use compression. The end point was the time of ulcus healing. The healing process of the ulcers was related to the impact of bacterial colonization and clinical signs of infection. RESULTS: Compression increases the ulcer healing rate compared with no compression. Using the same local povidone-iodine (Betadine) treatment with compression bandages is more effective (82%) for ulcus healing than without compression therapy (62%). The healing rate of ulcers treated with systemic antibiotics was not significantly better (85%) than that of the Betadine group. Using systemic antibiotics, the relapse rate of superficial bacterial infections (impetigo, folliculitis) was significantly higher (32%) than in patients with local disinfection (11%). CONCLUSION: Compression is essential in the mobilization of the interstitial lymphatic fluid from the region of stasis dermatitis. Topical disinfection and appropriate wound dressings are important to prevent wound infection. Systemic antibiotics are necessary only in systemic infections (fever, lymphangitis, lymphadenopathy, erysipelas).

• Dillon RS: Treatment of resistant venous stasis ulcers and dermatitis with the end-diastolic pneumatic compression boot.. Angiology 37:47-56, 1986. The end-diastolic pneumatic compression boot was used to treat 17 patients with difficult or refractory stasis dermatitis and ulcers. Decreases in induration, pigmentation, and palpable thrombi were observed and all patients were improved or healed. The boot treatment allowed effective local administration of antibiotics on gauze wrappings. Removal of the latter after treatments provided a means of nonsurgical debridement. Healing was maintained by periodic outpatient boot treatments in patients with close followup. Ulcers recurred in patients lost to followup but responded again to boot treatment. One diabetic man with knee contractures and both severe venous and arterial disease relapsed repetitively and lost both legs in spite of bilateral femoral-popliteal bypasses and his boot treatments.

• Eklöf B, Rutherford RB, Bergan JJ et al (American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification): Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 40:1248-52, 2004. The CEAP classification for chronic venous disorders (CVD) was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995. Today most published clinical papers on CVD use all or portions of CEAP. Rather than have it stand as a static classification system, an ad hoc committee of the American Venous Forum, working with an international liaison committee, has recommended a number of practical changes, detailed in this consensus report. These include refinement of several definitions used in describing CVD; refinement of the C classes of CEAP; addition of the descriptor n (no venous abnormality identified); elaboration of the date of classification and level of investigation; and as a simpler alternative to the full (advanced) CEAP classification, introduction of a basic CEAP version. It is important to stress that CEAP is a descriptive classification, whereas venous severity scoring and quality of life scores are instruments for longitudinal research to assess outcomes. Comment: ... C3 = edema, C4 = skin changes and C5-6 = venous ulcers

• Flota-Cervera F, Flota-Ruiz C et al: Randomized, double blind, placebo-controlled clinical trial to evaluate the lymphagogue effect and clinical efficacy of calcium dobesilate in chronic venous disease. Angiology 59:352-6, 2008. The aims of the present study were to investigate the effect of calcium dobesilate on lymph flow and lymphovenous edema in patients with chronic venous disease. It was a randomized, placebo-controlled, double-blind clinical trial. Patients received 1 capsule of 500 mg calcium dobesilate every 8 hours (1.5 g/day) or placebo by 49 days. By the end of the treatment period, only the patients treated with calcium dobesilate had normalization of lymphogammagraphy (capture index and speed of lymph flow; 80 and 78%, respectively). Only patients treated with calcium dobesilate had statistically significant reduction in the perimeter of leg, calf, and ankle. Twenty-two out of 25 (88%) calcium dobesilate-treated patients presented clinical improvement versus 5 out of 24 (20.8%) in the placebo group. One patient on calcium dobesilate developed rash and one patient on placebo complained of vomiting. In the present study, calcium dobesilate normalized lymph physiology and improved symptoms in patients with chronic venous disease.

• Gupta AK, Koven JD, et al.: Open-label study to evaluate the healing rate and safety of the Profore Extra Four-Layer Bandage System in patients with venous leg ulceration.J Cutan Med Surg 4(1):8-11, 2000. BACKGROUND: Venous ulcers are increasing in prevalence, especially since these are observed more frequently in the elderly, and the number of individuals in this age group is becoming a larger portion of the population. OBJECTIVE: To determine the healing rate and safety of the Profore Extra Four-Layer Bandage System in the management of venous leg ulcers. METHODS: In an open-label study, patients aged 18 years or older with venous leg ulcers were treated with a high compression four-layer bandage system in which a hydrocellular dressing was placed in contact with the wound. The combination is designated the "Profore Extra Four-Layer Bandage System." Follow-up visits took place weekly unless there was heavy exudation from the ulcer or if there was marked edema of the leg at the start of the study requiring reapplication of the bandage system. RESULTS: Fifteen patients were entered into the study (men 8, women 7, mean age 66 years, mean duration of ulcers 1.3 years). Thirteen of the 15 patients completed the study, with two withdrawals. In one patient who withdrew, the ulcer became infected and required treatment with antibiotics. The other termination from the study occurred for reasons unrelated to treatment. The ulcer in this patient healed in 7 weeks. Ten of the 13 patients (77%) who completed the study, and 10 (67%) of 15, who had enrolled experienced complete (100%) healing. Healing of > 80% of the ulcers occurred in 11 of 13 patients (85%) who completed the study and in 12 (80%) of 15 enrolled patients. No patient experienced a study-related adverse event. One patient developed contact dermatitis and was later found to have stasis dermatitis. It is unclear whether the initial event was contact or stasis dermatitis. CONCLUSION: In this open-label study, a high compression system, using the Profore Extra Four-Layer Bandage with a hydrocellular dressing in contact with the wound, was found to be effective and safe for the treatment of venous leg ulcers.

• Heit JA, Silverstein MD, Mohr DN et al: The epidemiology of venous thromboembolism in the community. Thromb Haemost 86:452-63, 2001. The incidence of venous thromboembolism exceeds 1 per 1000; over 200,000 new cases occur in the United States annually. Of these, 30% die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has been constant since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving cases develop recurrent venous thromboembolism within ten years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of cases develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis. Comments: Venous thromboembolism and venous stasis disease are obviously not the same thing; not all patients with stasis disease have or will get thromboembolism. Still, it is a significant complication and deserves consideration especially in those listed here with increased risk.

• Ikeda M, Kambayashi J, Iwamoto S, et al: The coagulofibrinolytic state of patients with primary varicose veins of the lower legs. The relationship between a local hypercoagulable state and primary varicose veins of the lower legs was investigated by measuring the plasma levels of D-dimer (DD) and the thrombin-antithrombin-III complex (TAT) in 122 consecutive patients before treatment, and in 46 patients after surgical intervention and compression sclerotherapy. Elevated levels of DD and TAT were found in 25% and 20%, respectively, of the 122 patients, being significantly elevated in the patients with thrombophlebitis compared to the patients with no dermal symptoms, pigmentation, or stasis dermatitis. There was no significant difference in either parameter among eight groups of patients classified according to their valvular incompetence. The levels of DD and TAT were elevated before treatment in 25% and 20%, respectively, of 45 treated patients, but became significantly reduced after treatment. These results indicate that even though the local hypercoagulable state in varicose veins without thrombophlebitis is too subtle to be detected by systemic parameters such as DD and TAT, a local hypercoagulable state can be detected in a certain proportion of patients with venous stasis by these parameters.

• Leu AJ, Leu HJ, Franzeck UK, Bollinger A: Microvascular changes in chronic venous insufficiency--a review. Cardiovasc Surg 3:237-45, 1995. Chronic venous insufficiency is the result of an impairment of the main venous conduits, causing microvascular changes. The driving force responsible for the alterations in the microcirculation is probably the intermittently raised pressure propagated from the deep system into the capillaries. The capillaries are dilated, elongated and tortuous and their endothelium is injured (irregular luminal surface, increased cytopempsis, dilated interendothelial spaces). Through the latter an increased extravasation can be observed, leading to an enlarged pericapillary space, oedema in the interstitial tissue and to the clinical finding of swelling. Haemoglobin from extravasated erythrocytes and erythrocyte fragments in the pericapillary space is degraded to haemosiderin which is responsible for hyperpigmentation. Microthrombosis in the capillaries causes microinfarction and micronecrosis. Skin areas with severe microangiopathy have reduced numbers of perfused nutritional capillaries and are characterized by a low transcutaneous (tc) PO2. The increased blood flow in the deeper skin layers does not contribute to nutrition of the superficial skin layers. The microvascular ischaemia is patchy and appears to be the main factor determining trophic changes and venous ulceration. The process of microinfarction and micronecrosis is followed by the formation of a granulation tissue, proliferation of capillaries and fibroblasts and finally wound healing by formation of scar tissue destroying the microlymphatic network. Clinically this process leads to lipodermatosclerosis, atrophy and in its most extreme form to ulceration where the compensating mechanisms are no longer able to repair the damage.

• Malanin K, Kolari PJ, Havu VK: The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers. Acta Derm Venereol 79:156-60. 1999. In an attempt to clarify the pathophysiology of haemodynamics in legs with venous ulcer we investigated the effect of a single intermittent pneumatic compression treatment on the peripheral resistance of leg arteries and the cutaneous laser Doppler flux in the leg. Eight patients with venous leg ulcers and 10 subjects with healthy legs were investigated. Doppler waveforms of the leg arteries and laser Doppler flux of the leg skin were recorded before and after a single intermittent pneumatic compression treatment with the subjects in a recumbent position. In the legs with venous ulcer, the peripheral resistance of the arteries was lower and the laser Doppler flux was greater, compared with healthy legs (p = 0.003 and p = 0.002, respectively). A single intermittent pneumatic compression treatment raised the peripheral resistance in the arteries of legs with ulcer and laser Doppler flux of the skin more in ulcer legs than in healthy legs (p = 0.046 and p = 0.034, respectively). These findings suggest that removal of oedema causes redistribution of skin blood flow in the legs with venous ulcer favouring the superficial capillary perfusion. This could explain why compression treatment promotes the healing of venous leg ulcers. Comments: A single pneumatic leg compression is hardly a 40 minute Circulator Boot treatment which in 40 minutes would deliver 2800 compressions to a patient with a pulse of 70. Still reduction in edema is likely one mechanism whereby cutaneous flow is improved with Circulator Boot therapy. The rapid pulsations of the Circulator Boot also increase local production of nitric oxide, fibrinolysins, prostacyclin and vascular endothelial growth factors. In an earlier publication (Arch Phys Med Rehabil 72:667-70, 1991) this same group reported improvement in CT measurements and bedside tape measurements in patients with post-traumatic edema given intermittent pneumatic compression treatments. The latter decreased relative edema from 23% to 15.9% (p less than 0.01) as measured by CT, and from 23.5% to 13.2% as measured clinically. The density of muscle tissue increased 9% (p less than 0.01) and that of subcutaneous tissue decreased 5.6% (p less than 0.05). The IPC treatment influenced both the amount of edema and the density of tissue compartments.

• Margolis DJ, Berlin JA, Strom BL: Which venous leg ulcers will heal with limb compression bandages? Am J Med 109:15-9, 2000. PURPOSE: To develop a simple prediction rule to identify patients in whom a venous leg ulcer will heal using a limb compression bandage (eg, Unna's boot).SUBJECTS AND METHODS: We performed a retrospective cohort study of patients with venous leg ulcers who received a limb compression bandage applied weekly. Prognostic factors were assessed from the patient's history before the start of treatment. The outcome of interest was a healed wound within 24 weeks of treatment. The final model was validated in another data set.RESULTS: Several accurate prognostic models were developed. The simplest model summed the size and duration of the wound before treatment, with 1 point given for a wound with an area >5 cm(2) and another if the wound was >6 months old. In the development data set, ulcers healed in 93% (110 of 118) of patients with a score of 0, but in only 13% (9 of 67) of those with a score of 2. In the validation data set, ulcers healed in 95% (19 of 20) of patients with a score of 0, and 37% (44 of 120) of those with a score of 2.CONCLUSIONS: This simple prognostic model can be used to discriminate between patients with a venous leg ulcer that will or will not heal within 24 weeks of care with a limb compression bandage. The model may be useful in determining which patients to treat with a limb compression, and which patients should be referred or considered for alternative treatments. Comments: Size and duration count! More of the same below.

• Margolis DJ, Allen-Taylor L, Hoffstad O, Berlin JA: The accuracy of venous leg ulcer prognostic models in a wound care system.. Wound Repair Regen 12:163-8, 2004. Venous leg ulcers are among the most common chronic wounds. Treatment is commonly with a limb compression bandage. Previous small, often single-center, studies have shown that it is possible to predict which wounds are likely to respond to compression therapy. We designed this cohort study using a dataset of over 20,000 individuals with a venous leg ulcer to investigate the accuracy of several prognostic models. Creating complex models using logistic regression, as well as simply counting prognostic factors, we show that initial measures of wound size and duration accurately predict, as measured by area under the receiver operator curve and Brier score, who will heal by the 24th week of care. For example, a wound that is less than 10 cm(2) and less than 12 months old at the first visit has a 29 percent chance of not healing by the 24th week of care, while a wound greater than 10 cm(2) and greater than 12 months old has a 78 percent chance of not healing. Ultimately, these models can be applied by a clinician to help determine whom to continue to treat with standard care and perhaps whom to treat with adjuvant therapies. They may also aid in the design of clinical trials. Comments: These models might also command the attention of the insurance industry. Commonly, the latter deny reimbursement for boot therapy unless the patient has failed six months of standard care. Large ulcers even of short duration prove difficult to heal by standard measures. As large ulcers are commonly of long duration, however, adoption of this model to allow boot therapy would be appropriate for most patients.

• Margolis DJ, Knauss J, Bilker W: Medical conditions associated with venous leg ulcers. Br J Dermatol 150:267-73, 2004. BACKGROUND: In patients who have a venous leg ulcer, very little is known about the frequency of their concomitant medical conditions. OBJECTIVES: To evaluate the frequency that other medical conditions are associated with a new venous leg ulcer. METHODS: We studied a 10% random sample of elderly patients registered in the General Practice Research Database between 1988 and 1996. We describe the frequency of medical conditions using simple percentages. In order to assess the associations between medical conditions and the onset of a venous leg ulcer, we used logistic regression models. RESULTS: Several medical conditions occur commonly in patients who develop venous leg ulcers, including anaemia, angina, asthma, cellulitis of the lower extremity, depression, diabetes, limb oedema, hypertension, osteoarthritis, pneumonia and urinary tract infection. After statistical adjustment many medical conditions were significantly associated with those who had recent onset of a venous leg ulcer, including asthma, cellulitis of the lower extremity, congestive heart failure, diabetes, deep venous thrombosis, lower limb oedema, osteoarthritis, peripheral vascular arterial disease of the lower extremity, rheumatoid arthritis, history of hip surgery, and history of venous surgery/ligation. Unexpectedly, some illnesses were inversely associated with those that had recent onset of a venous leg ulcer, including angina, cerebral vascular accident, depression, malignancy, myocardial infarction, pneumonia and urinary tract infection. CONCLUSIONS: Physicians caring for individuals with venous leg ulcers need to be aware that it is likely that these individuals may have one of the comorbid illnesses listed above.

• McCulloch JM, Marler KC, Neal MB, Phifer TJ: Intermittent pneumatic compression improves venous ulcer healing.Adv Wound Care 7:22-4, 26, 1994. The effects of intermittent pneumatic compression on the healing rates of ulcers in patients with chronic venous insufficiency were examined in a prospective, controlled study of 22 patients. Patients were randomly assigned to the experimental or the control group. Both groups received local wound care followed by application of an Unna boot. In addition, subjects in the experimental group received intermittent pneumatic compression (IPC) twice weekly for one hour each session. Healing rates were reported in square centimeters per day. Data analysis revealed a mean healing rate of 0.08 cm2 per day for control subjects and 0.15 cm2 per day for experimental subjects. Statistical analysis, demonstrated the healing rates of the two groups to be statistically different. The results appear to indicate that intermittent pneumatic compression is beneficial in the management of venous insufficiency ulcers.

• Min RJ, Khilnani NM: Endovenous laser ablation of varicose veins. J Cardiovasc Surg 46(4): 395-405, 2005. Readily available non-invasive diagnostic tests now allow physicians to accurately map out abnormal venous pathways and identify all sources of reflux. Minimally invasive alternatives to surgical removal of incompetent truncal veins have been developed with impressive RESULTS: Endovenous laser treatment can be performed in the office under local anesthesia and is associated with virtually no recovery period. Better understanding of the primary mechanism of energy transfer by direct contact between the laser fiber tip and vein wall has underscored the importance of vein emptying. Improved utilization of tumescent anesthesia has helped facilitate circumferential laser fiber to vein wall contact and virtually eliminated the incidence of heat-related complications. Further refinements in the technique and optimization of laser energy parameters have improved success rates of vein closure from 90% to nearly 100%. Compared to surgery, endovenous laser has also demonstrated lower rates of recurrence largely due to the absence of neovascularity. This review of endovenous laser treatment should validate this exciting technique as a scientifically acceptable option for eliminating truncal vein reflux. If measured by patient acceptance and satisfaction, endovenous laser and other minimally invasive methods have already supplanted traditional surgery as the treatment of choice for superficial venous insufficiency.

• Moosa HH, Falanga V, Steed DL et al: Oxygen diffusion in chronic venous ulceration. J Cardiovasc Surg (Torino). 28:464-7, 1987. A diffusion barrier to oxygen caused by fibrin deposition around dilated, proliferating capillaries in patients with venous hypertension may contribute to the development of venous ulceration. This diffusion barrier was studied in 18 patients with venous ulcers using the transcutaneous oxygen (TcPO2) monitor (TCM204 Radiometer, America). TcPO2 sensors were placed adjacent to venous ulcers on lower limbs and on the chest and foot of each patient. Readings were taken after a sensor temperature of 44 degrees C was reached (10-15 minutes). TcPO2 values were markedly decreased in skin adjacent to the ulcers (10 +/- 2 mmHg) compared with those of the chest (64 +/- 2 mmHg) and foot (43 +/- 2 mmHg). Inhalation of 100% oxygen for 10 minutes increased chest TcPO2 in all patients (145 +/- 8 mmHg) and increased TcPO2 in skin around the ulcers in 17 of 18 patients (61 +/- 13 mmHg). This study supports the existence of a local pathologic barrier to oxygen diffusion in patients with venous ulcers. Comments: Among our venous boot referrals, such low levels were associated a history of nonhealing, the presence of pain, and the presence of infection (especially if erythema and with a detectable PPG pulse found next to the ulcer). Again, patients returning with pain after having healed their ulcers were commonly found to have low TcPO2 levels at the site of the pain possibly signifying incipient tissue breakdown. The pain was relieved and the TcPO2 raised with a repeat short course of boot therapy.

• Neumann HA, van den Broek MJ, Boersma IH, Veraart JC: Transcutaneous oxygen tension in patients with and without pericapillary fibrin cuffs in chronic venous insufficiency, porphyria cutanea tarda and non-venous leg ulcers. Vasa 25:127-33, 1996. To evaluate the influence of fibrin cuffs on the transcutaneous oxygen tension in patients with chronic venous insufficiency (CVI) we performed a prospective comparative study in an out-patient dermatological department of a district hospital in the Netherlands. 16 patients with CVI grade II or III, 6 patients with porphyria cutanea tarda (PCT) without any sign of CVI, 4 patients with clinical ecthyma type ulcers without CVI and 10 healthy volunteers were studied. Skin biopsies for fibrinogen staining, transcutaneous oxygen tension measurements (TcPO2) and light reflexion rheography (LRR) were performed. TcPO2 readings were significantly lower in patients with CVI compared to patients of the other groups. Fibrin cuffs were found in 8 out of 16 patients with CVI, all PCT patients and 3 out of 4 ecthyma-ulcer patients. On the basis of these results we conclude that the fibrin cuff alone does not act as a barrier for oxygen transport. Fibrin cuffs in CVI are not the cause of venous ulceration but only a part of the complicated mechanism of the altered microcirculation induced by reflux in the venous macrocirculation. Fibrin cuffs are not unique for CVI but an indication of a disturbed microcirculation. Comments: Fibrin cuff are not unique to chronic venous disease.

• Nikolovska S, Arsovski A, Damevsky K, Gocev G, Pavlova L: Evaluation of two different intermittent pneumatic compression cycle settings in the healing of venous ulcers: a randomized trial. Med Sci Monit 11:CR337-43. 2005. BACKGROUND: Intermittent pneumatic compression (IPC) has been successfully used in the treatment of venous ulcers, although the optimal setting of pressure, inflation and deflation times has not yet been established. The aim of this study was to compare the effect of two different combinations of IPC pump settings (rapid vs slow) in the healing of venous ulcers. MATERIAL/METHODS: 104 patients with pure venous ulcers were randomized to receive either rapid IPC or slow IPC for one hour daily. The primary and secondary end points were the complete healing of the reference ulcer and the change in the area of the ulcer over the six months observational period, respectively. RESULTS: Complete healing of the reference ulcer occurred in 45 of the 52 patients treated with rapid IPC, and in 32 of the 52 patients treated with slow IPC. Life table analysis showed that the proportion of ulcers healed at six months was 86% in the group treated with the fast IPC regimen, compared with 61% in the group treated with slow IPC (p=0.003, log-rank test). The mean rate of healing per day in the rapid IPC group was found to be significantly faster compared to the slow IPC group (0.09 cm2 vs 0.04 cm2, p=0.0002). CONCLUSIONS: Treatment with rapid IPC healed venous ulcers more rapidly and in more patients than slow IPC. Both IPC treatments were well tolerated and accepted by the patients.These data suggest that the rapid IPC used in this study is more effective than slow IPC in venous ulcer healing.

• Noppeney T, Noppeney J, Winkler M, Kurth I: Acute superficial thrombophlebitis--therapeutic strategies. Zentralbl Chir 131:51-6, 2006. Thrombophlebitis (TP) of the superficial venous system is associated to a high percentage with deep venous thrombosis (DVT). References in literature vary between 5 and 65 %, pulmonary embolisms (LE) were described in up to 33 %. PATIENTS: In a retrospective study, 114 patients who had presented themselves with a TP of the superficial venous system between January 1 (st) and December 31 (st) 2004, were analysed in our institution. 50 % (n = 57) exhibited a TP in side branches of the superficial venous system. 19.3 % (n = 22) showed a TP of the great saphenous vein (GSV) of the calf or of the small saphenous vein (SSV) distally, in 28.1 % (n = 32) the GSV or SSV were affected at the thigh or proximally or in total length, 3 patients (2.6 %) exhibited a TP of the arm vein. 11 patients (9.6 %) showed a concomitant DVT. The frequency of DVT depended on the localisation and extension of the TP, and also on additional basic and acute risks for DVT. The incidence of a concomitant DVT was 5.2 % when side branches were affected and amounted to 15.6 % with TP in the area of the GSV or SSV. With varicosis as single risk factor, the frequency of a concomitant DVT was 6 %, varicosis combined with further risks showed a DVT frequency of 15.4 %. RESULTS: All patients were treated with low molecular weight heparin either with prophylactic or therapeutic dosage, depending on localisation, extension and concomitant diseases. 10.5 % of the patients (n = 12) had to undergo urgent surgery with ligation of the sapheno-femoral junction or popliteal junction, if the TP had reached the junction into the deep venous system. By this therapy, we had not to observe any additional DVT. In 9 cases, an extension, respectively a recurrence of the TP could be observed. In each of these cases the dosage of the LMWH had not been adapted to the concomitant risks or had been terminated too early. DISCUSSION: TP of the superficial venous system should be considered and treated as DVT. Consequent anticoagulation is needed, surgery should be performed when the TP reaches the junction into the deep venous system. The duration of the anticoagulation is not quite clear, but is carried out in our institution for three months with therapeutic intention.

• Ogawa T, Hoshino S, Midorikawa H, Sato K: Intermittent pneumatic compression of the foot and calf improves the outcome of catheter-directed thrombolysis using low-dose urokinase in patients with acute proximal venous thrombosis of the leg. J Vasc Surg 42(5):940-4, 2005. OBJECTIVE: Catheter-directed thrombolysis (CDT) is a promising treatment of acute proximal deep vein thrombosis (DVT) to prevent the postthrombotic syndrome by early removal of thrombus. During CDT for DVT patients, the calf muscle pump is compromised because of immobility. Intermittent pneumatic compression (IPC) can be used to increase venous flow during bed rest. The CDT with IPC may lyse venous thrombus better than CDT alone. The purpose of this study was to evaluate the efficiency and safety of IPC during CDT for DVT using low-dose urokinase. METHODS: Twenty-four patients with proximal DVT confirmed by duplex ultrasonography underwent CDT alone (10 cases) and CDT with IPC and a temporary inferior vena cava filter (14 cases) for 3 to 6 days. Pulmonary emboli (PEs) were assessed by pretreatment and posttreatment pulmonary angiogram or spiral computed tomography of the chest, and in the CDT/IPC patients, a posttreatment inferior vena cavogram was performed. The initial results were evaluated by venogram immediately after CDT, and the late results were evaluated by venous disability score and duplex ultrasonography 6 to 36 months after treatment. RESULTS: There was no symptomatic PE in either group. In CDT with IPC, one new asymptomatic PE was found, but there was no large thrombus in the inferior vena cava. The initial thrombolytic results of CDT with IPC were better than those of CDT alone (five cases of complete lysis in the CDT/IPC group and none in the CDT alone group). In the follow-up, the deep veins were patent and competent in 43% (6/14) in the CDT/IPC group, compared with 17% (1/6) in the CDT-alone group. The venous disability score showed that the CDT/IPC group had less disability than the CDT-alone group. CONCLUSIONS: This pilot study showed that adding IPC to CDT using low-dose urokinase for DVT treatment of the leg resulted in better early and late outcomes compared with CDT alone and was not associated with an increased risk of symptomatic PEs. Comments: We have anecdotal reports of Circulator Boot therapy associated with the successful administration of Urokinase given both by the systemic intravenous route and by the catheter-directed intravenous route. The risk of pulmonary emboli has slowed interest in treating deep vein thrombi.

• Pascarella L, Penn A, Schmid-Schonbein GW: Venous hypertension and the inflammatory cascade: major manifestations and trigger mechanisms. Angiology 56 Suppl 1:S3-10, 2005. Recent histologic and immunocytochemical evidence of venous leg ulcers supports the hypothesis that lesions observed at different stages of chronic venous insufficiency may be associated with, and possibly caused by, an inflammatory process. Evidence has been obtained that venous valve deficiency may be associated with leukocyte infiltration into valve leaflets; therefore, it is hypothesized that an essential event in the inflammatory cascade is the enzymatic degradation of the valve leaflets and venous wall. The metalloproteinases (MMP) in veins exposed to elevated pressures up to 6 weeks were examined in a rat femoral fistula model with venous hypertension. Zymography shows increased activity of pro-MMP-2 at 3 and 6 weeks. MMP-2 and MMP-9 activity was predominantly observed at days 7 and 21 after creation of the fistula. The degree of extracellular matrix remodeling correlates with the morphological finding of macroscopic lesions. Therefore, the MMP-2 and MMP-9 activation is already present in veins days after exposure to elevated blood pressure and coincides with periods of early alterations in the valve morphology and early forms of reflux.

• Patel KR and Paidas CN: Phlegmasia cerulea dolens: the role of non-operative therapy. Cardiovasc Surg 1:518-23, 1993. Thrombectomy and thrombolysis are often advocated in the treatment of phlegmasia cerulea dolens, but frequently result in incomplete clot removal, recurrence of thrombosis, local and systemic hemorrhagic complications and chronic venous stasis; this state is associated with a rate of major amputation and death of up to 50%. Non-operative therapy includes elevation, hydration and heparinization and excludes all methods aimed at surgical removal or chemical lysis of the thrombus. In 1982 it was decided to use non-operative therapy as the first line of treatment for phlegmasia cerulea dolens. In the last 9 years seven extremities in six patients with this condition have been treated. One patient had advanced gangrene on presentation and one underwent emergency thrombectomy. Five extremities (in five patients) were treated with non-operative therapy. Ischemia was rapidly corrected in all five patients. Edema resolved completely after 3-4 days in four patients. There were no complications attributable to the therapy. Two of six (33%) patients died from terminal disease. Non-operative therapy appears to be effective in preventing limb loss and avoiding the risks of thrombectomy and thrombolysis in critically ill patients. Comment: The diagnosis of phlegmasia cerulea dolens may be delayed in patients with advanced chronic stasis disease who, of course, may have swollen, uncomfortable and discolored legs.

• Peschen M, Rogers AA, Chen WY, Vanscheidt W: Modulation of urokinase-type and tissue-type plasminogen activator occurs at an early stage of progressing stages of chronic venous insufficiency. Acta Derm Venereol 80:162-6, 2000. Chronic venous insufficiency (CVI) progresses through a series of clinical stages, from healthy skin to poorly healing leg ulcers. The aim of this study was to analyse the distribution pattern and activity level of urokinase-type (uPA) and tissue-type plasminogen activators (tPA) in normal skin and in tissue biopsies of progressing stages of CVI, prior to and including venous ulceration. Biopsies 6 mm thick were taken from 14 healthy volunteers and 37 patients with 5 different stages of CVI: telangiectases; stasis dermatitis; hyperpigmentation; lipodermatosclerosis; and leg ulcer. Changes in the enzymatic activity and spatial localization of uPA and tPA during the progression of CVI were examined using in situ histological zymography. Normal skin and skin with telangiectases showed a punctate PA activity, consisting of both uPA and tPA activity. As CVI progressed, an increase in the distribution of uPA and a decrease in tPA activity was observed. The spatial localization of uPA was widespread within the dermis of biopsies from stasis dermatitis and lipodermatosclerosis and was associated in particular with the dermoepidermal junction. Hyperpigmented skin revealed a pattern of PA expression similar to that of healthy skin. However, leg ulcer specimens exhibited peak levels of uPA with little tPA. Furthermore, a plasminogen-independent protease activity that was not present in any of the earlier stages of CVI appeared. Our results indicate that there are profound changes in PA activity during the progression of CVI and that these changes begin early in CVI, for example, in stasis dermatitis. We hypothesize that the balance or imbalance of the PA activity in the later stages of CVI is an important pathogenic factor for the development of venous leg ulcer.

• Raffetto JD, Mendez MV, Phillips TJ, Park HY, Menzoian JO: The effect of passage number on fibroblast cellular senescence in patients with chronic venous insufficiency with and without ulcer. Am J Surg 178:107-12, 1999. BACKGROUND: Fibroblasts (fb) cultured from venous ulcer patients and patients with venous reflux disease without ulcer demonstrate characteristics of cellular senescence, such as increased fibronectin level and senescence-associated beta-galactosidase (SA beta-gal) positive cells. Cellular senescence is an in vitro event characterized by the progressive loss of proliferative capacity with increased passage number, and has been associated with impaired healing in vivo. This report examines progressive stages of cellular senescence in fb from the distal area (du-fb) and proximal fb (pu-fb) of patients with venous ulcer, as well as in distal fb (dr-fb) and proximal fb (pr-fb) from patients with venous reflux without ulcer, by comparing the population doubling time (T) and percent SA beta-gal expression. RESULTS: The mean value of T over 6 passages for fb in the ulcer group was 132.5 +/- 29.0 hours for pu-fb and 492.9 +/- 146.2 hours for du-fb (P = 0.0009). For fb in the reflux group the mean value of T over 5 passages was 79.3 +/- 12.8 hours for pr-fb and 94.2 +/- 16.8 hours for dr-fb (P = 0.8). Comparing ulcer and reflux fb, no difference in T was observed between pu-fb and pr-fb (P = 0.6), but a difference was noted between du-fb and dr-fb (P = 0.0004). The mean percent SA beta-gal activity for fb in the ulcer group was 11.2% +/- 3.1% for pu-fb and 63.8% +/- 8.9% for du-fb (P = 0.0001). Individual passages demonstrated significant difference (P <0.05) in SA beta-gal activity between pu-fb and du-fb at early and late passages. No difference was noted in SA beta-gal activity for fb in the reflux group or between pu-fb and pr-fb, but comparison between du-fb and dr-fb was significant (63.8% +/- 8.9% versus 7.8% +/- 2.9%; P = 0.0001). CONCLUSIONS: The in vitro passage of du-fb and pu-fb in chronic venous ulcer patients has an effect on T and cellular senescence as measured by SA beta-gal activity. Our data further suggest that du-fb are at a more progressive stage of cellular senescence when compared with pu-fb, and more importantly with fb cultured from patients with venous reflux without ulcer. These findings are consistent with impaired wound healing of venous stasis ulcer. The accumulation of senescent fb and a more advanced stage of cellular senescence of du-fb may explain why repeated episodes of venous ulceration are resistant to conservative treatment and require more aggressive measures of therapy.

• Raju S, Neglen P: Popliteal vein entrapment: a benign venographic feature or a pathologic entity? J Vasc Surg 31:631-41, 2000. PURPOSE: Asymptomatic morphologic popliteal vein entrapment is frequently found in the healthy population (27%). In our institution, popliteal vein compression on plantar flexion was observed in 42% of all ascending venograms. Some authorities consider the lesion benign, without pathologic significance. This study examines the pathophysiologic importance in select patients, describes treatment with surgery, and suggests a diagnostic tool. METHOD: Thirty severely symptomatic patients with venographic evidence of popliteal entrapment were selected to have popliteal vein release after a process of elimination (ie, other causes of chronic venous insufficiency [CVI] were ruled out by means of comprehensive hemodynamic and morphologic studies). In the last nine limbs, popliteal vein pressure was also measured by means of the introduction of a 2F transducer tip catheter. Patients were clinically and hemodynamically assessed before and after surgery, and anatomical anomalies encountered during surgery were recorded. RESULTS: Popliteal vein release was performed without mortality or serious morbidity. Anomalies of the medial head of the gastrocnemius muscle caused entrapment in 60% of the patients; anatomic course venous anomalies were infrequent (7% of the patients). Significant relief of pain and swelling occurred in the patients who had surgery. Stasis ulceration/dermatitis resolved in 82% of patients. Popliteal venous pressures had normalized in the six patients who were studied postoperatively. CONCLUSION: Popliteal vein entrapment should be included in the differential diagnosis of CVI in patients in whom other, more common etiologies have been excluded on the basis of comprehensive investigations. Popliteal vein compression can be demonstrated venographically in a large proportion of patients with CVI, but the lesion is likely pathological only in a small fraction of these patients. A technique for popliteal venous pressure measurement is described; it shows promise as a test for functional assessment of entrapment. Immediate results of popliteal vein release surgery are encouraging; long-term follow-up is necessary to judge the efficacy of surgical lysis of entrapment in symptomatic patients who fail to improve with conservative treatment measures.

• Recek C: Conception of the venous hemodynamics in the lower extremity. Angiology 57:556-63, 2006. Contradictory reports on the significance of several hemodynamic phenomena, such as femoral vein incompetence and incompetent calf perforators, impede orientation in venous hemodynamics. Venous pressure difference arising between the popliteal and the posterior tibial vein during the activity of the calf muscle venous pump was reported for the first time about 50 years ago, but regrettably, this important discovery continues to be unrespected. The venous pressure difference has since been termed ambulatory pressure gradient and seems to be the key factor triggering the venous reflux in the lower limb as well as the process leading to varicose vein recurrence. On the other hand, simultaneous recordings of the mean venous pressure in the posterior tibial and long saphenous veins demonstrated that the pressure curves have been identical at rest, during ambulation, and in the recovery period, a finding typical of conjoined vessels. Bidirectional flow within calf perforators taking place both in healthy subjects and in patients with varicose veins enables a quick equilibration of pressure changes between deep and superficial veins of the lower leg. Reflux disturbing the venous hemodynamics is in various degrees dependent on the quantity of retrograde flow; abolition of reflux restores normal venous hemodynamics. Reflux in superficial veins, if large enough, may cause the most severe form of chronic venous insufficiency. Femoral vein incompetence and incompetent calf perforators per se do not produce ambulatory venous hypertension and do not cause hemodynamic disturbance. This study discusses the controversial issues, tries to define and appraise the principal hemodynamic phenomena (ambulatory venous hypertension, ambulatory pressure gradient, venous reflux, superficial and deep vein incompetence, incompetent perforators), mentions a possible relation between deep vein incompetence and varicose veins, and attempts to present, based on proved facts, a comprehensive picture of the venous hemodynamics in the lower extremity.

• Rivera MR, Ishihara M, Mihara M: A case of non-selective phagocytosis of hemosiderin and melanin of dermal histiocytes in stasis dermatitis. Arch Dermatol Res 295:19-23, 2003. A case study was undertaken to determine whether or not the same dermal histiocytes could phagocytose both melanin and hemosiderin simultaneously. A biopsy specimen was taken from a pigmented lesion of the lower leg of a 57-year-old woman with stasis dermatitis. The specimen was processed for histology, conventional transmission electron microscopy and electron-probe X-ray microanalysis. Histologically, numerous histiocytes with their cytoplasm packed with either Prussian blue-positive granules or Fontana-Masson-positive granules were distributed almost equally in the dermis. Electron microscopically, the dermis had many histiocytes with their cytoplasm containing solitary or compound electron-dense substances. The electron-dense substances were classified into three types according to their degree of electron density. By electron-probe X-ray microanalysis, these electron-dense substances were classified into iron-containing and non-iron-containing substances. Both substances were seen in the cytoplasm of the same histiocytes and even in the same compound electron-dense substance. The former were siderosomes and the latter were probably melanosomes. These results show that the same dermal histiocytes probably phagocytose non-selectively both hemosiderin and melanin granules.

• Rosziski S, Schmeller W: Differences between intracutaneous and transcutaneous skin oxygen tension in chronic venous insufficiency. J Cardiovasc Surg (Torino) 36:407-13, 1995. Data obtained from transcutaneously measured PO2 (tcPO2) were taken as an indication for a decreased oxygen supply to the skin in patients with chronic venous insufficiency III. Direct (invasive) measurements in LDS have not yet been performed. We therefore measured the intracutaneous PO2 (icPO2) in healthy skin and LDS (8 healthy volunteers and 18 patients with CVI III) with needle probes (250 microns tip diameter). The icPO2 values were compared with data of tcPO2 (37 degrees C and 44 degrees C electrode temperature). In healthy skin the mean icPO2 was about 50 mmHg and no steep PO2 gradients were found. In LDS (ulcer edge) mean PO2 values were lower than in healthy skin, however, no hypoxia or anoxia was observed. At the same site most tcPO2 (44 degrees C) values were between 0 and 5 mmHg. The mean icPO2 values from ulcer edges of different patients ranged from 6 mmHg to 42 mmHg (mean 22 mmHg). In LDS very different PO2 profiles were seen. There was no correlation between tcPO2 and icPO2 data. Our present results may suggest that skin damage in patients with CVI is not necessary associated with hypoxia. Comments: The authors have increased the number of patients from an earlier publication and report the same result: healthy patients have higher transcutaneous and subcutaneous oxygen tensions than do patients with stasis disease. TcPO2 values between 0-5 mm HG with the 44 degree probe sound like hypoxia to most investigators. They had poor correlation between their icPO2 and TcPO2 data which comes as no surprise; platinum wire electodes and the polarographic method are hard to standardize. Or again, as pointed out by Liu et al above, the superficial (where TcPO2 is measured) and deeper layers of the skin (where a needle probe measures O2) differ in their supply of nutritive vessels in patients with chronic venous insufficiency..

• Sindrup JH, Avnstorp C, Steenfos HH, Kristensen JK: Transcutaneous PO2 and laser Doppler blood flow measurements in 40 patients with venous leg ulcers. Acta Derm Venereol 67:160-3, 1987. The study included 40 patients with clinically venous leg ulcer(s) in one leg only and with a systolic toe blood pressure above 50 mmHg in both legs. Transcutaneous oxygen tension was measured on both lower legs at equivalent sites, on the affected leg immediately proximal to the ulcer(s). Similarly, skin blood flow was measured in both legs at a skin temperature of 32 degrees C and 44 degrees C by means of laser Doppler velocimetry, and for each leg the index of blood flow 44 degrees C/flow 32 degrees C was calculated to express the degree of blood flow increment following local hyperthermia. Transcutaneous oxygen tension measurements were significantly lower on affected legs (p less than 0.01) as was flow increment (p less than 0.01), mainly due to a high flow measurement at 32 degrees C on affected legs rather than to a low measurement at 44 degrees C. The results of our flow measurements suggest a state of (relative) hyperemia in the vicinity of venous leg ulcers, also confirmed by the clinical findings. This could be interpreted as an arteriolar response to lowered oxygen tension or (it could) be part of reactive reparative processes leading to increased O2 consumption in the tissues. Comments: Hyperemia and hypoxia! Easy to see why there can be confusion here.

• Smith PC: Daflon 500 mg and venous leg ulcer: new results from a meta-analysis.Angiology 56 Suppl 1:S33-9, 2005. The objective of this study was to assess the effect of oral treatment with Daflon 500 mg (micronized purified flavonoid fraction [MPFF]) on leg ulcer healing. This study was conducted as a meta-analysis of randomized prospective studies using Daflon 500 mg as an adjunct to conventional treatment. Medical literature databases and the manufacturer's records were searched for relevant clinical trials. Five prospective, randomized, controlled studies in which 723 patients with venous ulcers were treated between 1996 and 2001 were identified. Conventional treatment (compression and local care) in addition to Daflon 500 mg 2 tablets daily was compared with conventional treatment plus placebo in two studies (n = 309), or with conventional treatment alone in three studies (n = 414). The primary end point was complete ulcer healing at 6 months. The results are expressed as a reduction in the relative risk (RRR) of healing with 95% confidence intervals (CI). Since, in the present case, the desired treatment effect is increased ulcer healing, RRR should be positive to indicate a benefit of adjunctive Daflon 500 mg over conventional therapy alone. Type 1 error was set at 5%. At 6 months, the chance of ulcer healing was 32% better in patients treated with adjunctive Daflon 500 mg than in those managed by conventional therapy alone (RRR, 32%; 95% CI, 3% to 70%). This difference was present from month 2 (RRR, 44%; 95% CI, 7% to 94%), and was associated with a shorter time to healing (16 weeks vs 21 weeks; p = 0.0034). The benefit of Daflon 500 mg was found in the subgroup of ulcers between 5 and 10 cm2 in area (RRR, 40%; 95% CI, 6% to 87%), as well as in patients with ulcers of 6 to 12 months' duration (RRR, 44%; 95% CI, 6% to 97%). These results confirm that venous ulcer healing is accelerated by Daflon 500 mg treatment. Daflon 500 mg might be a useful adjunct to conventional therapy in large and longstanding ulcers that might be expected to heal slowly.

• Smith PC, Sarin S, Hasty J, Scurr JH: Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial.Surgery 108(5):871-5, 1990. The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers.

• Somers P, Knaapen M: The histopathology of varicose vein disease. Angiology 57:546-55, 2006. Varicosity is a complex venous pathology affecting the lower extremities. The exact etiology and physiopathology of varicose vein disease remain, however, unclear. Several theories exist from incompetence of the valves to a disturbance of the smooth muscle cells (SMC) and extra-cellular matrix (ECM) organization providing a weakness of the venous wall. Multiple studies have been performed to explain the underlying mechanisms of varicosity inducing alterations in the expression patterns of the endothelium, SMC, and ECM. In that respect, most attention has been focused on the alteration of the endothelium due to blood stasis and hypoxia inducing migration/proliferation of the medial SMC into the intima. Also, studies in the deformation of the ECM induced by alterations of the expression patterns of the metalloproteinases (MMP) and their inhibitors (TIMPs) have been put forward to explain the etiology of varicosity. However, less attention has been paid to the hormonal changes that occur during pregnancy and menopause, crucial factors to be involved in the etiology of varicosity. Since alteration of the estrogen receptor-b (ERb) expression could enhance directly the cellular volume of SMC and thus the disorganization of the contractile-elastic units, hypertrophy of SMC must be accounted a pivotal role that could induce the weakness of the venous wall. Altogether, this review summarizes an overview of the latest findings of varicosity with respect to the histopathological changes of the different cellular components of the varicose vein wall related to functional and morphologic alterations.

• Sottiurai VS: Surgical correction of recurrent venous ulcer. J Cardiovasc Surg (Torino) 32(1):104-9, 1991. Seventy-six limbs from 46 patients with comparable superficial and deep venous valve incompetence underwent surgical correction for recurrent venous ulcers of the leg that were refractory to various modes of nonsurgical and surgical treatments. A follow-up of 10 to 73 months (mean = 37 months), revealed the venous ulcer healed with perforator ligation and saphenous vein stripping in 14 of 33 (44%), stripping plus valvuloplasty 17 of 21 (80%), stripping plus vein transposition 11 of 14 (78%) and stripping plus valve transplantation 6 of 8 (75%). In patients with incompetent deep venous valve and perforators, the disassociation of the superficial from the deep venous system (stripping) plus correction of the deep venous valvular incompetence (valvuloplasty, transposition or valve transplant) produced superior results in the treatment of recurrent venous ulcer when compared to perforator ligation and saphenous vein stripping alone (p less than 0.005). Adjunctive usage of elastic stockings and intermittent compression pneumatic boots in the perioperative period was helpful in controlling leg swelling and promoting wound healing. Comments: The inclusion of such studies in a website on the Circulator Boot might be questioned. Like many such studies, the authors were not using cardiosynchronous boots that provide the vigorous therapy delivered by the Circulator Boot systems.

• Sottiurai VS: Comparison of surgical modalities in the treatment of recurrent venous ulcer. Int Angiol 9:231-5, 1990. Recurrent leg ulcer secondary to superficial and deep venous valve incompetence that are refractory to non-surgical treatment can be healed with the following surgical modalities. Perforator ligation and saphenous vein stripping (PLSVS) healed 4/16 (25%) of the ulcer. PLSVS and correction of deep venous valve incompetence healed 14/16 (87.5%) of the ulcer (p less than 0.005). The mean follow-up was 32 months (8-62 mon). This prospective comparison of the 2 surgical treatments (PLSVS versus PLSVS and correction of deep venous valve) demonstrated that disassociation of theCardiovasc Surg 8:372-80, 2000. superficial from the deep venous system with PLSVS and correction of the deep valve (valvuloplasty, transposition or valve transplant) produced promising results in the treatment of recurrent venous ulcer. Adjunctive usage of elastic stocking and intermittent compression pneumatic boot to reduce swelling in the paraoperative period improved long term result in venous reconstructive surgery.

• Stacey MC, Burnand KG, Bhogal BS, Black MM: Pericapillary fibrin deposits and skin hypoxia precede the changes of lipodermatosclerosis in limbs at increased risk of developing a venous ulcer. Cardiovasc Surg 8:372-80, 2000. his study investigated the possibility that pericapillary fibrin deposition, found in the calf skin of patients with venous ulceration and lipodermatosclerosis, might already be present in the dermis of the gaiter area of apparently healthy limbs before any skin changes were visible. The apparently healthy limbs of 19 consecutive patients with a healed venous ulcer on one leg and no history of ulceration or clinical evidence of lipodermatosclerosis in the opposite calf, were studied. Bipedal ascending phlebography and foot volume plethysmography were performed, and systemic fibrinolytic activity and fibrinogen levels were calculated. Transcutaneous oxygen measurements were expressed as a ratio of levels from a fixed position in the gaiter skin over a control site on the arm. Biopsies of a standard site in the gaiter skin and the thigh were assessed for the presence of laminin, fibrinogen and fibronectin using immunofluorescent microscopy. The extent of pericapillary fluorescence was expressed as a ratio of the number of capillaries with deposits divided by the total number of capillaries staining with laminin (fibrin and fibronectin scores).Pericapillary fibrin deposits were observed in the dermis in 16 of the biopsies of the gaiter region (median score 0.20), and in eight of the biopsies from the thigh (median score 0.0). This difference was highly significant (P<0.01, Wilcoxon signed rank test). The transcutaneous oxygen ratio correlated negatively with the fibrin score (Spearman rank correlation coefficient -0.62, P<0.01), and there was a weak negative correlation between the half volume refilling time on foot volume plethysmography (an indicator of venous reflux) and the fibrin score (Speraman rank correlation coefficient -0.47, P<0.05). No such correlation could be shown between the fibrin score and the indicators of calf pump function, the euglobulin clot lysis time or the plasma fibrinogen. The presence of significant numbers of pericapillary fibrin deposits within the dermis of the gaiter skin has been demonstrated in 84% of this cohort of 'at risk' limbs before there is any evidence of clinical lipodermatosclerosis.

• Sugerman HJ, Sugerman EL, Wolfe L et al: Risks and Benefits of Gastric Bypass in Morbidly Obese Patients With Severe Venous Stasis Disease. Ann Surg 234: 41-46, 2001. Objective: To determine the risks and benefits of gastric bypass-induced weight loss on severe venous stasis disease in morbid obesity. Summary Background Data: Severe obesity is associated with a risk of lower extremity venous stasis disease, pretibial ulceration, cellulitis, and bronze edema. Methods: The GBP database was queried for venous stasis disease including pretibial venous stasis ulcers, bronze edema, and cellulitis. Result: Of 1,976 patients undergoing GBP, 64 (45% female) met the criteria. Mean age was 44 ± 10 years. Thirty-seven patients had pretibial venous stasis ulcers, 4 had bronze edema, 23 had both, and 17 had recurrent cellulitis. All had 2 to 4+ pitting pretibial edema. Mean preoperative body mass index (BMI) was 61 ± 12 kg/m2 and weight was 179 ± 39 kg (270 ± 51% ideal body weight), significantly greater than in patients who underwent GBP without venous stasis disease. Two patients had a pulmonary embolus and four had Greenfield filters in the remote past. Additional comorbidities included obesity hypoventilation syndrome, sleep apnea syndrome, hypertension, gastroesophageal reflux, degenerative joint disease symptoms, type 2 diabetes mellitus, pseudotumor cerebri, and urinary incontinence. Comorbidities were significantly more frequent in the patients with venous stasis disease than for those without. At 3.9 ± 4 years after surgery, patients lost 55 ± 21% of excess weight, 62 ± 33 kg, reaching 40 ± 9 kg/m2 BMI or 176 ± 41% ideal body weight. Venous stasis ulcers resolved in all but three patients. Complications included anastomotic leaks with peritonitis and death, fatal pulmonary embolism, fatal respiratory arrest, wound infections or seromas, staple line disruptions, marginal ulcerations treated with acid suppression, stomal stenoses treated with endoscopic dilatation, late small bowel obstructions, and incisional hernias. There were six other late deaths. Conclusions: Severe venous stasis disease was associated with a significantly greater weight, BMI, male sex, age, comorbidity, and surgical risk (pulmonary embolus, leak, death, incisional hernia) than in other patients who underwent GBP. Surgically induced weight loss corrected the venous stasis disease in almost all patients as well as their other obesity-related problems.Comment: Take-home messages: Gastric bypass surgery is risky. Severe obesity is risky. Stasis disease associated with severe obesity may be cured with significant weight reduction. Risk of death in the severe obese undergoing gastric bypass is significantly increased when stasis disease is also present (8% vs 0.5%).

• Tallman P, Muscare E, Carson P, Eaglstein WH: Initial rate of healing predicts complete healing of venous ulcers. Arch Dermatol 133:1231-4, 1997. BACKGROUND: Venous ulcers represent a clinical problem with considerable morbidity, especially in the elderly population. Standard treatment is the use of leg compression bandages to improve the underlying venous hypertension, but not every ulcer heals in a timely fashion with this treatment modality. Methods are needed to predict the outcome of standard treatment as soon as possible to institute alternative therapy. OBJECTIVE: To prospectively study the rate of healing in a group of elderly patients with venous ulcers, based on a previously described equation that takes into account the size and perimeter of the ulcer. METHODS: We studied by computerized planimetry 15 elderly patients with venous ulcers treated with leg compression bandages for up to 24 weeks or until complete healing. We determined weekly healing rate by comparing ulcer size at each visit to initial baseline size (baseline-adjusted healing rate). Also, we used a novel way to calculate the healing rate at a given week by taking the mean of all previous healing rates between each visit (mean-adjusted healing rate). RESULTS: When using the baseline-adjusted healing rate, we noted what we describe as a healing rate instability from week to week, which decreases the ability to predict complete healing. However, the mean-adjusted healing rate allowed us to predict complete healing as early as 3 weeks from starting therapy (P<.001). CONCLUSION: In this prospective study of elderly patients with venous ulcers, we describe a novel and more powerful method for predicting complete healing of venous ulcers with compression therapy alone. Comments: Common sense! Margolis et al above told us that ulcers that are large and long-lasting are tough to cure. These authors tell us that patients who do not initially respond to standard therapies are tough to cure. Obviously, such patients do well to be diverted to Circulator Boot therapy.

• van Gent WB, Hop WC, van Praag MC, Mackaay AJ, de Boer EM: Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial. J Vasc Surg 44:563-71, 2006. BACKGROUND: The prevalence of venous leg ulcers is as high as 1% to 1.5%, and the total costs of this disease are 1% of the total annual health care budget in Western European countries. Treatment modalities are conservative or surgical. Subfascial endoscopic perforating vein surgery (SEPS) combined with superficial vein ligation is performed in many centers to address vein incompetence in patients with chronic venous leg ulcers. Several reports describe good healing and low recurrence rates, although a randomized trial to compare surgical treatment including SEPS and treatment of the superficial venous system to conservative modalities has never been performed. Therefore, a prospective, randomized, multicenter trial was conducted to study whether ambulatory compression therapy with venous surgery is a better treatment than just ambulatory compression therapy in venous leg ulcer patients. METHODS: Patients with an active (open) venous leg ulcer (CEAP C6) qualified for the study. The study consisted of two treatment groups. All patients were treated by standardized ambulatory compression therapy, and half of the patients received SEPS. Concomitant superficial venous incompetence was also treated in the second group. For allocation to both treatment groups, each patient was assigned by a computer program at the randomization center. The primary goal of the study was to compare the ulcer-free period during follow-up in both study groups. Secondary end points were ulcer healing and recurrence rates. RESULTS: From April 1997 until January 2001, 200 ulcerated legs (170 patients) were included in the study in 12 centers in The Netherlands. A total of 97 ulcers were allocated to the surgical group and 103 to the conservative group. Patient characteristics were similar in the two treatment groups at baseline, with the exception of a higher proportion in the conservative group of diabetes mellitus. Healing rates were 83% in the surgical group and 73% in the conservative group (not significant; median time to healing, 27 months). Recurrence rates were the same in both treatment groups (22% surgical vs 23% conservative). During follow-up of a mean of 29 months (median, 27 months) in the surgical group and 26 months (median, 24 months) in the conservative group, we found that in the surgical group, the ulcer-free rate was 72%, whereas in the conservative group this rate was 53% (P = .11; Mann-Whitney test). Patients with recurrent ulceration or medially located ulcers in the surgical group had a longer ulcer-free period than those treated in the conservative group (P = .02 for both). A first-time ulcer and one of the centers also had a positive effect on the ulcer-free period during follow-up (P < .001 and P = .02), independent of the treatment group. Deep vein incompetence did not affect the ulcer-free period. CONCLUSIONS: In conclusion, we suggest that patients with medial and/or recurrent ulceration should receive surgery combined with ambulatory compression therapy. A dedicated center should provide care for those patients. Comments: The surgical group unfortunately had both treatment of incompetence of the superficial veins (a proven benefit - Recek 2006) and SEPS which is technically more difficult and itself of unproven benefit.

• van Weert H, Dolan G, Wichers I et al: Spontaneous superficial venous thrombophlebitis: does it increase risk for thromboembolism? A historic follow-up study in primary care.. OBJECTIVE: To determine the risk of arterial and venous complications after a spontaneous superficial venous thrombophlebitis (SVTP) in the leg in a general practice population. STUDY DESIGN: Retrospective cohort study (LOE: 2b [CEBM]). Exposure consisted of the diagnosis of SVTP of the lower limbs on an index date. The exposed cohort was compared with an (unexposed) cohort of practice-, age-, and sex-matched controls without SVTP. POPULATION: Patients with spontaneous SVTP in the leg were identified through diagnostic coding in the medical registers of 40,013 patients, enlisted with 5 health centers in Amsterdam, The Netherlands. OUTCOMES: Primary outcomes were deep venous thrombosis (DVT), pulmonary embolism (PE), acute coronary events, or ischemic stroke over a 6-month follow-up period. Odds ratios (OR) were used to quantify the associations between SVTP and outcome events. RESULTS: No statistically significant odds ratios were found for PE, coronary events or stroke. DVT was the only primary outcome to show a significant relationship. DVT occurred in 2.7% of all SVTP patients as compared with 0.2% in the controls (OR=10.2; 95% confidence interval [CI], 2.0-51.6). When controlling for prior history of DVT, the OR decreased to 7.1 and the confidence interval crossed 1.0 (95% CI, 0.9-65.6). DISCUSSION: Spontaneous SVTP in the leg is a risk factor for DVT, but is less predictive in patients with prior DVT. Although effective treatments for the prevention of DVT are available, the absolute risk is too low to advocate prophylaxis in a general practice population. More research on prophylaxis is needed to stratify these patients at risk.

• Weiss SC, Nguyen J, Chon S, Kimball AB: A randomized controlled clinical trial assessing the effect of betamethasone valerate 0.12% foam on the short-term treatment of stasis dermatitis. J Drugs Dermatol 4:339-45, 2005. BACKGROUND: There are no published studies examining either the effectiveness of topical steroids in the treatment of stasis dermatitis or indicating what steroid strength or duration of treatment is optimal to treat this common condition. OBJECTIVE: To investigate the efficacy of twice-daily application of the topical steroid betamethasone valerate 0.12% foam for the treatment of stasis dermatitis. DESIGN: 42-day randomized, double-blinded, vehicle-controlled, pilot study. SETTINGS: Outpatient dermatology clinic at a university-affiliated clinic. SUBJECTS: 19 subjects, mean age of 73, with mild to moderate bilateral stasis dermatitis. INTERVENTION: Twice-daily application of betamethasone valerate 0.12% foam versus vehicle foam to bilateral randomly assigned lower legs for 28 days with follow-up to day 42. MAIN OUTCOME MEASURES: The primary clinical endpoints were the mean change in erythema, scale, swelling, petechiae, post-inflammatory hyperpigmentation, and self-reported pruritus, assessed on a 5-point Likert scale (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe). Secondary endpoints were changes in health related quality of life (HRQL) using the EuroQol-5D (EQ-5D) utility score and visual analog scale (VAS) and the Dermatology Life Quality Index (DLQI). RESULTS: Although there was no overall difference between the foam and vehicle-treated leg at days 14 and 28, the steroid-treated leg, but not the vehicle-treated leg, showed statistical improvement over baseline. Improvement in the steroid-treated leg was statistically better than vehicle at days 14 and 28 in terms of erythema (P < .05) and petechiae (P < .05). Improvement in VAS was notable at days 14 (7.1%), 28 (9.7%), and 42 (9.6%) (P < .001). Similarly, there was a statistically significant improvement in the DLQI compared to baseline on visit days 14 (188.9%) and 28 (126.1%) (P < .001). CONCLUSIONS: This study suggests that betamethasone valerate 0.12% foam is an effective and well-tolerated short-term treatment of stasis dermatitis, but that higher potency steroids may be needed to achieve better efficacy. Furthermore, these results are the first to suggest that the application of effective topical anti-inflammatory therapy can lead to improvement in HRQL. Comments: Confusing results. Baseline states are equal: A=B. Over time A progresses to AA and B to BB. AA is not different from BB. However, AA is better than A while BB is not better than B. So the treatment for A was better than the treatment for B????

• Williams, Robert: PW216 - Case Report: Novel Combined Therapy for Intractable Concomitant Venous and Arterial Disease. Poster at Third Congress of the World Union of Wound Healing Societies, Toronto, June 2008. Goals and Objectives: Venous insufficiency (VI) and peripheral artery disease (PAD) when present concurrently make lower extremity wounds extremely difficult to treat. Wound healing is impaired by both edema and ischemia. In this setting, each disease process limits effective therapy of the other. Purpose: Demonstrate the efficacy of combining a novel pneumatic intermittent compression device with a new collagen matrix to successfully close a lower extremity wound associated with combined VI and PAD. Methods: Intermittent pneumatic compression of 45 mm Hg was applied to the entire affected lower limb during cardiac diastole for duration of 0.40 to 0.45 seconds per compression. Compression was applied 40 min a day, 5 days a week. Local wound care consisted of applying a novel porcine collagen matrix containing carboxymethylcellulose, sodium alginate, and EDTA. The matrix was applied every other day. Results: Swelling caused by VI markedly improved with intermittent pneumatic compression therapy. Compression therapy administered as described above did not exacerbate ischemic pain, but rather, patient reported resolution of all pain attributable to both ischemia and ulceration. The wound closed within 6 weeks of initiating therapy. Discussion / Conclusion: The matrix composed of partially denatured porcine collagen, carboxymethylcellulose, sodium alginate, and EDTA introduces unique characteristics that optimize wound bed moisture, impair MMP activity, and facilitate cell migration. Because intermittent compression was timed with the diastole, venous return was improved and edema secondary to VI reduced, without impairing arterial blood flow. Improved venous return facilitated arterial blood flow through the capillary beds into the emptied venous system and enhanced cardiac output. Resolution of edema with enhanced blood flow in the face of optimal wound bed preparation facilitated prompt closure of this wound associated with concomitant venous insufficiency and peripheral artery disease.

• Williams, Robert: PW218 - Concurrent Venous Insufficiency and Peripheral Artery Disease Treated with Novel Pneumatic Intermittent Compression Device Timed with Cardiac Relaxation. Goals and Objectives: Wounds associated with combined venous insufficiency (VI) and peripheral artery disease (PAD) are extremely difficult to heal. The disease process of each entity limits effective therapy of the other. Can concomitant VI and PAD be safely and effectively treated with intermittent compression therapy (ICT) if timed with cardiac relaxation? Purpose: Assess the efficacy of a novel pneumatic intermittent compression device that is timed with cardiac diastole in treating wounds associated with concomitant VI and PAD. Methods: Intermittent pneumatic compression of 45 mm Hg was applied to the entire affected lower limb during cardiac diastole for a duration of 0.40 to 0.45 seconds per compression. Compression was applied to the affected limb for 40 min a day, 5 days a week. Local wound care consistent with principles of wound bed preparation were utilized during the course of therapy. Results: Swelling caused by VI improved in all three patients with intermittent pneumatic compression therapy. Compression therapy administered as described above did not exacerbate ischemic pain, but rather, patients reported resolution of all pain attributable to either ischemia or ulceration. Wounds in two of the three patients closed and the third patient's wound continues to improve but has not yet closed. Discussion / Conclusion: This novel ICT that is timed with the diastolic phase of the cardiac cycle improves venous return and reduces edema secondary to VI without impairing arterial blood flow, even in patients with severe peripheral artery disease. The improved venous return facilitates arterial blood flow through capillary bed into the emptied venous system and by enhancing cardiac output as expected according to Starling's Laws of Hemodynamics. Resolution of edema and enhanced blood flow facilitates closure of wounds in limbs that have combined venous insufficiency and peripheral artery disease that would otherwise not be expected to heal. Comments: A novel treatment in Texas but not in suburban Philadelphia.

• Zamboni P, Izzo M, Tognazzo S, Carandina S et al: The overlapping of local iron overload and HFE mutation in venous leg ulcer pathogenesis. Free Radic Biol Med 40:1869-73, 2006. Chronic venous stasis determines red blood cell extravasation and either dermal hemosiderin deposits or iron-laden phagocytes. Several authors have suspected that iron could play a role in the pathogenesis of venous leg ulcers. They hypothesized that local iron overload could generate free radicals or activate a proteolytic hyperactivity on the part of metalloproteinases (MMPs) or else down-regulate tissue inhibitors of MMPs. However, they were unable to explain why iron deposits, visible in the legs of patients with chronic venous disease (CVD), cause lesions in only some individuals, whereas in others they do not. We hypothesized that such individual differences could be genetically determined and investigated the role of the C282Y and H63D mutations of the HFE gene. C282Y mutation significantly increases the risk of ulcer in primary CVD more than six times (OR = 6.69; 1.45-30.8; p = 0.01). Patients carrying the H63D variant have an earlier age of ulcer onset, by almost 10 years (p > 0.004). The increased risk of skin lesion and the early age of onset of the disease in HFE carriers confirm in a clinical setting that intracellular iron deposits of mutated macrophages have less stability than those of the wild type. We hypothesize that the physiologic iron protective mechanisms are affected by the HFE mutations and should be investigated in all diseases characterized by the combination of iron overload and inflammation. Comments: One does not have to be in the business of treating stasis ulcers too long before encountering familes afflicted with stasis ulcers. Frequently, they are all superobese. Perhaps among them, however, are the genetic variants described by these authors.