Search

Presents several books on cutaneous pathology. 'Sclerotherapy: Treatment of Varicose and Telangiectatic Leg Veins,' by M.P. Goldman and J.J. Bergan; 'Text Atlas of Pediatric Dermatology,' by R. Dawber, I. Bristow and W. Turner; 'Comprehensive Dermatology Drug Therapy,' by S.E. Wolverton.

Venous hypertension is associated with microvascular inflammation, restructuring, and apoptosis, but the cellular and molecular mechanisms underlying these events remain uncertain. In the present study, we tested the hypothesis that elevated venous pressure and reduction of shear stress induce elevated enzymatic activity. This activity in turn may affect endothelial surface receptors and promote their dysfunction. Using a rodent model for venous hypertension using acute venular occlusion, microzymographic techniques for enzyme detection, and immunohistochemistry for receptor labeling, we found increased activity of the matrix metalloproteases (MMPs) -1, -8, and -9 and tissue inhibitors of metalloproteases (TIMPs) -1 and -2 in both high- and low-pressure regions. In this short time frame, we also observed that elevated venule pressure led to two different fates for the vascular endothelial growth factor receptor-2 (VEGFR2); in higher-pressure upstream regions, some animals exhibited higher VEGFR2 expression, while others displayed lower levels upstream compared to their downstream counterparts with lower pressure. VEGFR2 expression was, on average, more pronounced upon application of MMP inhibitor, suggesting possible cleavage of the receptor by activated enzymes in this model. We conclude that venous pressure elevation increases enzymatic activity which may contribute to inflammation and endothelial dysfunction associated with this disease by influencing critical surface receptors., (2010 Elsevier Inc. All rights reserved.)

Objectives: To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response., Material and Methods: A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP)., Results: The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals., Conclusions: Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.

Background: Reflux of blood through incompetent venous valves is a major cause of the venous hypertension that underlies clinical manifestations of chronic venous disease, including varicose veins, lipodermatosclerosis, and venous ulcers., Objective: To review published literature relating to animal models in which venous hypertension has been produced and which have yielded information on the mechanisms by which venous hypertension may trigger inflammation and cause changes in the skin and venous valves., Methods: Medline searches, with additional papers identified from reference lists in published papers., Results: At least three types of animal model were identified that have contributed to a better understanding of the trigger mechanisms and role of inflammatory processes in chronic venous disease. These models involve venous hypertension induced either by acute venular occlusion, placement of a chronic arteriovenous fistula, or ligation of several large veins. Model results suggest that elevated venous pressure and altered flow can trigger inflammatory cascades in the vein wall and venous valves which can cause progressive valvular incompetence and eventual valvular destruction, and which are also important in the skin changes associated with venous disease. Treatment with agents that reduce oxidative stress by scavenging free radicals and that inhibit the inflammatory cascade can prevent the progressive deterioration of function in valves exposed to elevated venous pressure and can prevent the development of reflux blood flow., Conclusions: Understanding these processes suggests potential therapeutic targets that could be effective in slowing or preventing progression, and could help promote a more positive and proactive attitude towards treatment of the underlying disease process, rather than the later manifestations of chronic venous disease.

Our objective was to chronicle our experience in using sclerosant foam to treat severe chronic venous insufficiency (CVI). Forty-four patients with 60 limbs severely affected by severe CVI were entered into the study. They had lipodermatosclerosis, CEAP 4 (seven limbs); atrophie blanche or scars of healed venous ulcerations, CEAP 5 (18 limbs); and frank, open venous ulcers, CEAP 6 (35 limbs). Patients and limbs were collected into three groups. In group I, all limbs were treated with compression without intervention. Group II consisted of crossover patients who failed compression treatment. Group III consisted of patients treated promptly with sclerosant foam therapy without a waiting period of compression. A standing Doppler duplex reflux examination was done in all cases. Compression was by Unna boot or long stretch elastic bandaging. Foam was generated from Polidocanol 1%, 2%, or 3% by the two-syringe technique and administered under ultrasound guidance. Posttreatment compression was used for 14 days. In addition to clinical and ultrasound evaluation at 2, 7, 14, and 30 days, venous severity scoring was noted at entry and discharge. In group I, 12 patients were discharged from care within 6 weeks of initiating compression. All eight of the class 6 limbs had healed. Group II consisted of four CEAP class 5 limbs and eight class 6 limbs that had failed to heal with compression. Five of eight venous ulcers healed within 2 weeks, two more healed by 4 weeks, and one required 6 weeks to heal. In group III, 7 of 11 venous ulcers healed within 2 weeks and four more within 4 weeks. Venous severity scores reflected the success of treatment, with the greatest change occurring in group III and the least in group I. Limbs treated with foam had a statistically better outcome than those without (p = 0.041). One patient failed foam sclerotherapy, another had pulmonary emboli 4 months after foam treatment, and a single medial gastrocnemius thrombus was discovered 24 hr after treatment. Treatment of severe CVI with compression and foam sclerotherapy causes more rapid resolution of the venous insufficiency complications and does so without an increase in morbidity.

Recent histological and immunocytochemical analyses of venous leg ulcers suggest that lesions observed in the different stages of chronic venous insufficiency (CVI) may be related to an inflammatory process. This inflammatory process leads to fibrosclerotic remodeling of the skin and then to ulceration. The vascular network of the most superficial layers of the skin appears to be the target of the inflammatory reaction. Hemodynamic forces such as venous hypertension, circulatory stasis, and modified conditions of shear stress appear to play an important role in an inflammatory reaction accompanied by leukocyte activation which clinically leads to CVI: venous dermatitis and venous ulceration. The leukocyte activation is accompanied by the expression of integrins and by synthesis and release of many inflammatory molecules, including proteolytic enzymes, leukotrienes, prostaglandin, bradykinin, free oxygen radicals, cytokines, and possibly other classes of inflammatory mediators. The inflammatory reaction perpetuates itself, leading to liposclerotic skin and subcutaneous tissue remodeling. In light of the mechanisms of venous ulcer formation cited above, therapy in the future might be directed against leukocyte activation in order to diminish the magnitude of the inflammatory response. With this in mind, the attention of many investigators has been drawn to two different drugs with an anti-inflammatory effect: pentoxifylline and flavonoids.

We have developed new clinical (C) and laboratory (L) staging systems to improve the clinical management of chronic lymphedema. These systems were retrospectively assessed in 220 chronic lymphedema patients followed up for 4 years. Clinical evaluation of the treatment response/disease progression was performed at 6 month intervals and laboratory evaluation at a yearly interval except for recurrent sepsis cases. The reliability of C-stage and L-stage for the progression of disease were analyzed separately. The C-staging was based on the subjective and objective findings of local and systemic conditions, while L-staging was based on lymphoscintigraphicfindings. Clinical implementation of this new staging system facilitated interpretation of the progress/deterioration of the clinical response to CDT treatment, and it was found to be a useful guideline for the decision/selection of further surgical treatment. We propose that these two separate staging systems could now become a new guideline for improved management of lymphedema with a better prediction of treatment outcome and decision point for additional medical/surgical therapy. Further clinical implementation and evaluation is necessary to demonstrate clinical usefulness especially to guide surgical therapy and L-staging in followup.

Chronic venous insufficiency is linked to venous hypertension and forces of shear stress on the endothelium. Venous hypertension depends upon two forces: the weight of a column of blood from the right atrium transmitted through the valveless vena cava and iliac veins to the femoral vein, and pressure generated by contracting skeletal muscles of the leg transmitted through failed perforating veins. When valve failure occurs in superficial axial veins and perforating veins, the venous pressure in the veins and venules of the skin and subcutaneous tissue is raised. The skin changes in chronic venous insufficiency are directly related to the severity of the venous hypertension. Also, pathologic changes in the valves are linked to venous hypertension and leukocyte infiltration and activation. It is hypothesized that acute venous pressure elevations cause a shift in the venous hemodynamics with changes in wall shear stress. This initiates the inflammatory cascade. Daflon 500 mg ameliorates the effects of chronic inflammation. In randomized trials, 60 days of therapy with Daflon at a dosage of 500 mg 2 tablets daily was effective, in addition to elastic compression, in accelerating venous ulcer healing. Because venous insufficiency is linked to venous hypertension and an inflammatory reaction, it appears that Daflon 500 mg 2 tablets daily shows a great potential for accomplishing blockade of the inflammatory cascade.

Venous angiomata, or venous malformations, are often present at birth, although they may not be evident until later. They consist of a spongy tangle of veins, and these lesions usually vary in size. Treatment of venous angiomata is often requested for cosmetic reasons, but painful ulcerations, nerve compression, functional disability can command care. This presentation describes management using sclerosant foam as the treating agent. During a 30-month period ending March 2004, 1,321 patients were investigated for venous disorders at the Vein Institute of La Jolla. Fourteen (incidence 1%) were found to have venous angiomata (: nine women). The age range was 15-76 years (mean 30.8 +/- 18.6). Lesions were classified by the Hamburg system and were primarily venous, extratruncular in 12 patients and combined extratruncular and truncular in two patients. Eight patients, three males, had manifestations of lower extremity Klippel-Trenaunay (syndrome; six had only venous angiomas. Only 10 of the 14 patients were treated. All patients were studied by Doppler duplex examination. Selected lesions were chosen for helical computed tomographic studies. Magnetic resonance venography was also used to image the lesions, define the deep circulation, note connections with normal circulation, identify vessels for therapeutic access, and determine infiltration of the lesion into adjacent soft tissue. Foam was produced by the Tessari two syringes one three-way stopcock teclinique, with the air to Polidocanol ratio being 4 or 5 to 1. This was used at 1% or 2% concentration, specific for each patient. The SonoSite 190 plus Duplex Doppler was used for ultrasound guidance, whenever deep access was required and to monitor progress and effects of treatment. A goal was set for each patient before treatment was begun. Ten patients were treated, and four await treatment. The mean number of treatments was 3.6 +/- 2.8 (range 1-10). A primary goal of pain-free healing was set in patients with nonhealing, painful ulceration or symptomatic varicose veins. This was achieved in all treated patients. Cosmetically, all of the patients were improved, and symptomatic patients were relieved of pain. The single complication was formation of a cutaneous ulcer following injection of telangiectasias. Sclerosant foam is a satisfactory tool to use in treating venous angiomata including the Klippel-Trenaunay syndrome. Use of foam sclerotherapy in this experience has proven the technique to be effective, essentially pain-free, and durable in the short term.

The relative deficiency of the official Terminologia Anatomica with regard to the veins of the lower limbs was responsible for a nonuniform anatomic nomenclature in the clinical literature. In 2001, an International Interdisciplinary Committee updated and refined the official Terminologia Anatomica regarding the veins of the lower limbs. Recommendations for terminology were included in an updating document that appeared in the Journal of Vascular Surgery (2002;36:416-22). To enhance further the use of a common scientific language, the committee worked on the present document, which includes (1) extensions and refinements regarding the veins of the lower limbs; (2) the nomenclature of the venous system of the pelvis; (3) the use of eponyms; and (4) the use of terms and adjectives of particular importance in clinical vascular anatomy.

Venous insufficiency, for practical purposes, can be divided into primary venous insufficiency and chronic venous insufficiency. The latter is characterized by advanced skin changes of hyperpigmentation, edema, ulceration, scarring from healed ulcers or open ulcerations. These are summarized in the CEAP classification as Classes 4, 5 and 6. Pretreatment evaluation is done with a standing ultrasound reflux examination. Thorough mapping of the extremity reflux is desirable. Physiologic tests of venous function, such as plethysmography, are unnecessary. Treatment is directed at closing refluxing axial veins as well as controlling those perforating veins with outward flow. Varicose veins contribute to axial reflux and must be obliterated. Arterial occlusive disease may complicate venous ulceration in as many as 15% of cases. Initial treatment of severe chronic venous insufficiency is usually carried out by controlling the edema with elastic bandaging or nonelastic support, such as the Unna boot or the CircAid dressing. Surgical intervention has been successful but the advent of foam sclerotherapy has proven to be an attractive alternative to surgery and has added a new tool for the treatment of severe chronic venous insufficiency. In this preliminary experience, the results are quite satisfactory and the technique has been shown to be effective, pain-free, inexpensive, with very little morbidity. Guidelines for obtaining sclerosants for use in foam sclerotherapy legally are provided.

Venous aneurysms are not rare. But most attention has been paid to deep venous aneurysms. Because of their propensity to thrombose and cause pulmonary embolization. Increased availability of duplex Doppler ultrasound has allowed total evaluation of all venous segments in patients undergoing surgery for chronic venous insufficiency. In this study, patients were recorded consecutively and the venous reflux examination was carried out with the patient standing. The superficial venous system was studied with special interrogation of the great and small saphenous veins and their tributaries. Reflux >0.5 sec was recorded as positive. Data were analyzed using the Spearman's correlation index and the student's t-test. A strong correlation was considered for values of rho > 0.6. A total of 65 superficial venous aneurysms of the saphenous vein systems were found in 43 patients (33 women and 10 men) with an average age of 53 years (range, 34-70). The mean body mass index (BMI) overall was 25 +/- 4.6. The BMI in men was 29.5 +/- 2.5. The BMI in women was 23.6 +/- 4 (p < 0.05). Aneurysms of the saphenous systems were classified into four types. Type I aneurysms (52%) were located in the proximal third of the saphenous vein, not at the saphenofemoral junction but instead just distal to the subterminal valve. Type II aneurysms were located in the shaft of the saphenous vein in the distal third of the thigh (35%). The third classification (type III) of superficial saphenous vein aneurysms was an occurrence of types I and II in the same lower extremity (3 patients/43 patients). Superficial venous aneurysms of the short saphenous system were found and were classified as type IV (6%.) Strong correlations were found with female gender and a very strong correlation of larger aneurysms was found with an elevated BMI in men. There was a so a strong correlation between type III aneurysms of the proximal and distal thigh greater saphenous vein and greater saphenous vein reflux. Aneurysms of the saphenous veins are common and this may have an impact on choice of surgical treatment.

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.

Objectives: To identify possible mechanisms for destruction of valves in chronic venous hypertension and the results of treatment with an anti-inflammatory micronized purified flavonoid fraction., Material and Methods: The saphenous vein valves in a rat model of venous hypertension caused by a femoral arterial-venous fistula were studied. Studies included femoral venous pressure, valve morphology, femoral venous reflux and selected molecular inflammatory markers as examined by immunohistochemistry. The effects of treatment with the anti-inflammatory micronized purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day) were investigated., Results: The femoral venous pressure was elevated close to arterial values for a period of 3 weeks. We then examined the morphology of the veins and selected molecular inflammatory markers were assessed. The results show that in this model venous reflux develops in response to venous hypertension. This can be inhibited by the administration of the anti-inflammatory micronized purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day). The valve becomes incompetent by a combination of venous dilation and shortening of the valve leaflets. This is not inhibited by treatment with S 5628. The valve leaflets are infiltrated with granulocytes, monocytes and T-lymphocytes, and the endothelial cells express enhanced levels of P-selectin and ICAM-1. Cells in the valves are subject to extensive apoptosis although no enhancement of MMP 2,9 expression could be detected at the three-week time point examined in this study., Conclusions: These results indicate that in this model chronic elevation of venous pressure is associated with an inflammatory reaction in venous valves, a process that may lead to their dysfunction, reflux, and upstream elevation of venous pressure. These effects are mitigated by the anti-inflammatory micronized purified flavonoid fraction in a dose dependent manner.

Introduction: In human beings, chronic venous insufficiency is linked to venous hypertension. This in turn is associated with venous valve incompetence. This study was designed to test the hypothesis that venous hypertension serves to initiate a process that results in the venous valve and venous wall damage observed in venous insufficiency. Material and methods Acute venous hypertension was produced by creation of an arteriovenous (AV) fistula between the femoral artery and vein in Wistar rats. At specified intervals pressure in the veins was recorded. The proximal valve containing saphenous vein was exposed, and reflux was measured from reverse blood flow through the first proximal valve. The vein was excised, valve parameters were measured, a portion was taken for morphologic investigation, and the remaining specimen was frozen in liquid nitrogen for investigation of leukocyte infiltration, expression of adhesion molecules, matrix metalloproteinase (MMP) levels, and apoptotic markers. Contralateral nonpressurized saphenous veins were used as control specimens., Results: The saphenous and femoral veins were immediately distended by pulsatile blood flow from the arterial system. Pressure was significantly increased from 11 +/- 2 mm Hg to 94 +/- 9 mm Hg. At 2 days no reflux was detected in the saphenous veins. At 1 week, one of four rats exhibited reflux; at 2 weeks, two of four rats had reflux; and at 3 weeks, three of four rats showed reflux. Contralateral saphenous veins were uniformly competent. Compared with control specimens, the veins were dilated; leaflet length and leaflet width were significantly reduced. Granulocytes, monocytes, and macrophages were identified in all regions of the vein wall, and the number was increased by the presence of the AV fistula. The number of T-lymphocytes was increased, and B-lymphocytes were present. P-selectin was upregulated in the saphenous vein walls, as was intercellular adhesion molecules. MMP-2 and MMP-9 expression in the veins was not enhanced. In the nuclear factor kappabeta family, Ikappabeta was not increased in any hypertensive veins. The number of apoptotic cells in the vein wall was increased in the presence of the AV fistula., Conclusion: This study indicates that acute venous hypertension is accompanied by significant venous distention and some valve damage as early as 3 weeks after fistula creation. There is development of inflammatory markers, with leukocyte infiltration and increased adhesion molecule expression. We could not detect significant enhancement of MMP levels or nuclear transcription factors. It is uncertain whether this lack of evidence may be partially due to enhanced apoptosis in venous valves and vein walls. A detailed definition of the inflammatory reaction produced by venous hypertension should be the subject of further study. Clinical relevance Saphenous vein valves when observed at the time of vein stripping show deformities of shortening, scarring, and tearing. The current model of induced venous hypertension demonstrates early venous valve changes similar to those observed in human beings and links them to a venous hypertension-induced inflammatory reaction. Thus the model could be useful in pharmacologic testing to prevent or treat venous insufficiency and for defining the fundamental mechanisms that cause varicose veins.

Introduction: Management of congenital vascular malformations (CVM) remains a major challenge because treatment carries a substantial risk of morbidity and recurrence of the fundamental problem. The new classification of CVM allows a multidisciplinary approach to the treatment with full integration of the several treatment modalities. The multidisciplinary approach was introduced at our CVM Clinic in 1995 and this report summarizes our results to date., Patients and Methods: The CVM Clinic is attended by 15 different specialties. These allow application of advanced diagnosis and treatments. The interdisciplinary consultation allows proper application of the various treatment modalities including embolosclerotherapy and surgical therapy. The embolosclerosants utilized are absolute ethanol and N-butyl cyanoacrylate (NBCA). These are used for venous malformations (VM), arteriovenous shunting malformations (AVM), and hemolymphatic malformations (HLM). These agents are used independently and as preoperative adjuncts. Among the 438 patients treated between September 1995 and September 1999, there were 99 patients treated with combinations of embolosclerotherapy. There were 286 sessions, 252 of which were for ethanol sclerotherapy and 247 of these employed ethanol alone and five were combined with NBCA. Independent embolotherapy with NBCA was instituted more recently and has been used in 28 sessions. Perioperative embolosclerotherapy has been performed in 43 sessions, mostly as preliminary preparation to reduce subsequent surgical morbidity. Followup assessment of immediate and interim results after completion of multisession therapy has been done using combinations of noninvasive diagnostic testing., Results: The immediate success rate of embolosclerotherapy has been 94.7% (271/286 sessions). There has been an immediate 5.2% failure (15/286 sessions). Failures have largely been due to forced abandonment of the sclerosing procedure due to risk of deep venous thrombosis. Interim results though short-term success following completion of multisession therapy, average 3.2 sessions per patient, were satisfactory. Complications, mostly skin damage from embolosclerotherapy were experienced in 31 patients during the 286 sessions performed on 99 patients. These skin complications were discussed and accepted by the multidisciplinary team which recognized unavoidable morbidity accompanying the ethanol therapy when applied to superficially located lesions. The overall morbidity included complication rate per session (14.7%, 42/286) and 31.3% per patient (31/99). Recovery from the skin complications has been mostly spontaneous but one case in which peroneal nerve palsy occurred became permanent. There has been no recurrence of the lesions treated successfully, and this has been confirmed through a battery of noninvasive testing. The average follow-up period after completion of multisession therapy is relatively short with 10.6 months (6.0-32 months) only to meet the condition as interim results. Fourteen patients have undergone surgical ablation after preoperative embolosclerotherapy and the surgical morbidity has been minimal., Conclusion: An accurate diagnosis and multidisciplinary treatment strategy for management of CVMs can improve overall treatment success with a reduced morbidity and recurrence over conventional approaches. This study reviews current trends in contemporary diagnosis and clinical management of congenital vascular malformations (CVM) of the peripheral vascular system emphasizing our new multidisciplinary approach.

Lower extremity venous insufficiency is a highly prevalent condition. Now it is understood that telangiectasias, reticular varicosities, and true varicose veins are physiologically similar and etiologically identical. The four main influences causing these abnormalities are heredity, female sex, gravitational hydrostatic forces, and hemodynamic muscular compartment pressure. There are clear indications and goals for intervention. A cornerstone in the treatment of venous insufficiency is elimination of sources of venous hypertension. One of these is the refluxing greater saphenous vein. Minimally invasive saphenous ablation can be achieved by radiofrequency energy and laser light energy. These new techniques eliminate the psychologic barrier to treatment caused by the term "stripping" and allow the objectives of surgery to be achieved with minimal invasion and quick recovery. Endovenous techniques show great promise. They provide minimal invasion, often under local anesthesia and intravenous sedation, thereby eliminating the need for general anesthesia. Objectives of venous insufficiency have been established and the endoluminal minimally invasive techniques developed in recent years appear to accomplish their goals.

Elevated venous pressure can be associated with severe tissue injury. Few links, however, between venous hypertension and tissue damage have been established. We examined here the effects of micropressure elevation on the outcome of venular occlusion/reperfusion in the mesenteric microvasculature of male Wistar rats. One hour of venular occlusion (diameter approximately 50 microm) by micropipette occlusion followed by reperfusion were carried out with sham surgery without occlusion as control. Leukocyte rolling, adhesion, and migration, oxygen radicals detected by dichlorofluorescein (DCF), and parenchymal cell death detected by propidium iodide (PI) were recorded simultaneously in the same vessel at a location upstream of the occlusion site with elevated micropressure and at a downstream location with low micropressure. The number of rolling, adhering, and migrating leukocytes increased on the upstream side of the occlusion to a higher level than downstream of the occlusion site. During occlusion, DCF intensity on the venular endothelium was greater on the upstream side than in the downstream side, but there were no differences during reperfusion. The number of PI-positive cells adjacent to the venules increased significantly compared with controls, and it remained greater on the upstream higher-pressure side than the downstream side. Leukocyte adhesion and transvascular migration in postcapillary venules as well as parenchymal cell death could be significantly reduced by the hydroxyl radical scavenger dimethylthiourea. Microhemorrhages of blood cells into the mesentery interstitium were observed only on the upstream side of the occlusion. These results indicate that an elevation of the venular blood pressure during occlusion/reperfusion exacerbates the inflammatory cascade and tissue injury. Venous occlusion may constitute an important mechanism for tissue injury.

Surgical principles that guided varicose vein surgery for nearly 75 years have been time honored and taught to generations of surgeons. Each of these principles has been challenged successfully, and, as a result, varicose vein surgery has changed markedly. The fundamental principle of totally removing varicose clusters from the circulation remains firmly established. However, methods of accomplishing this have changed and continue to change. Hook phlebectomy and clamp phlebectomy have replaced open dissection and tributary ligation. The place of tumescent anesthesia, transilluminated-powered phlebectomy, and sclerotherapy remain unsettled. However, there now are a number of alternatives in planning patient care., (Copyright 2002 by W.B. Saunders Company)

Carotid artery angioplasty with stenting (CAS) is being increasingly used in the treatment of extracranial carotid artery stenosis. As in other catheter-based approaches to the treatment of arterial disease, surgical intervention may be required because of either acute complications or correct critical restenosis. We have reviewed our experience managing early complications and critical in-stent restenoses after CAS in a tertiary care university hospital and a Veterans Affairs Medical Center. During the last 5 years, 22 carotid arteries (21 patients) underwent CAS. One patient developed thrombosis and rupture of the carotid artery during stenting. Two other patients (3 arteries) developed critical restenosis within 12 months. Subsequent surgical reconstructions included an internal carotid artery (ICA)-to-external carotid artery (ECA) transposition and a common carotid artery (CCA)-to-ICA bypass with reversed saphenous vein (RSV). The patient who underwent CCA-to-ICA bypass later required subclavian-to-ICA bypass because of rapidly progressive intimal hyperplasia and subsequent occlusion of the CCA. The other patient has not had surgical repair because of his deteriorating condition and significant co-morbidities. During the same time period, two additional patients were referred from outside institutions specifically for surgical intervention after carotid stenting. One had delayed rupture of the carotid artery 1 day after stenting and underwent urgent surgical repair. Another patient had early, critical restenosis within the stent and underwent placement of a CCA-to-ICA interposition graft using RSV. Acute treatment failures after CAS can be successfully managed using standard surgical techniques. Patients who develop critical in-stent restenosis requiring surgical repair may need more challenging surgical reconstructions to maintain cerebral perfusion.

Blue toe syndrome commonly occurs as a result of aneurysmal or atherosclerotic disease in the iliac arteries. Surgery, angioplasty, or intraarterial stent placement are the most common treatment options but the optimal management has not been defined. Here we report managing distal microembolization from iliac artery atherosclerosis associated with aneurysmal dilation with the Wallgraft Endoprosthesis, a self-expanding metallic stent covered with Dacron. Three common iliac arteries in two patients were treated using this device. A 79-year-old male presented with unilateral symptoms and an 83-year-old female with bilateral disease. Arteriography demonstrated complex plaque at the aortic bifurcation associated with aneurysmal dilation of the distal common iliac artery in both patients. This complex disease was successfully covered using the Wallgraft Endoprosthesis. Postoperatively the patients received aspirin, their toe lesions healed, and neither has had a recurrence after 16 months. Covered stents offer the theoretic advantage of completely excluding the diseased segment, preventing the escape of thrombus or plaque debris, and covering aneurysmal dilation in the artery.

Chronic venous insufficiency (CVI) and its complications of chronic pain, intractable ulceration, and infection are important conditions to treat by modern surgical techniques. As early as the 1930s, perforating veins with outward flow were implicated in the pathogenesis of this condition. Recognition that such outward flow promotes leukocyte adhesion and activation as the principal microcirculatory cause for the cutaneous changes has explained the importance of perforating vein interruption? Because of disability of CVI, surgeons and patients reluctantly tolerated the open Linton perforator interruption operation with its morbid knee-to-ankle incisions. It was tolerated because it worked. Modifications to reduce the morbidity of the procedure eliminated two of the three incisions used in the explorations of the 1930s. Other modifications such as DePalma's modification of the incisions further reduced wound complications. However, the most significant surgical alteration was to utilize the endoscopic techniques introduced in Europe by Fischer and Hauer. Very quickly it was obvious that the endoscopic technique minimized postoperative complications. Application of endoscopic perforator interruption to varicose vein surgery validated the safety of the procedure but did not contribute to knowledge about treating CVI.

Reduction in the thrombogenicity of small-caliber synthetic vascular grafts by lining them with mesothelial cell has been suggested as a method to reduce thrombosis. The purpose of this research is to determine whether creation of a mesothelial lining on the inner surface of a synthetic vascular graft would improve the patency rate of a small-caliber vascular grafts. Carotid interposition grafting was performed using mesothelial-lined grafts (MLG) in 30 New Zealand rabbits and compared with similar carotid interposition grafts using non-mesothelial-lined grafts (NLG) on the contralateral side. The mesothelial lining was created by suturing a piece of harvested peritoneum with the visceral surface toward the lumen onto a 2-mm polytetraflouroethylene (PTFE) graft. Graft patency was studied by in vivo Dopler. In vitro evaluations were done with hematoxylin-eosin stains, broadband cytokeratin staining, and monoclonal antibodies for macrophages. Explanation of the grafts was done in terminal operation at 7, 14, and 21 days. The MLG showed progressive fibroblastic proliferation in direct proportion to the age of the graft, but this did not lead to graft occlusion. However, a significant number of NLG were not patent at each time period studied. We concluded that mesothelial cell lining of smallcaliber PTFE grafts could enhance the short-term patency more than using the PTFE without the mesothelial lining. The use of such hybrid small-caliber grafts has a potential for improving the patency of these artificial vascular graft substitutes.

Generally, when the origin of the word saphenous is discussed, most affirm that the term derives from the Greek word safaina, which means "evident." The ancient Greeks knew only the caudal portion of the vein, and neither the Greeks nor the Romans used the term saphena. In fact, the term first appeared in the writings of Avicenna. In contrast, the term saphenous is derived from the Arabic el safin, which means "hidden" or "concealed." Ancient Arabic physicians knew the anatomy of superficial veins of the human body and its extremities because they performed therapeutic bleeding. Arabic physicians phlebotomized the distal portion of the greater saphenous vein (GSV) at the ankle. Such phlebotomies were never performed on the proximal portions of the GSV because they were not superficial enough to be clearly evident. As a consequence, the proximal GSV was called el safin, or "the concealed." The modern reader will recognize that based on duplex examination, the GSV is correctly identified on the basis of its deep position with the superficial fascia covering it. This information may be useful in modern saphenous vein surgery in identifying the proximal portion of the GSV.

For the 48th meeting of the International Society for Cardiovascular Surgery, North American Chapter in June 2000, we were asked to organize a presentation with the title displayed above. We welcomed this opportunity because the phrase 'growing the practice' literally means giving greater service to underserved patients with vascular disorders. Underserved individuals with vascular disorders include those with nonatherosclerotic arterial disorders, patients with lymphedema, and individuals with a variety of venous disorders including venous insufficiency. The majority of these conditions are not surgical, but venous insufficiency commands attention because its treatments are interventional. Therefore, this presentation will discuss prevalence of venous insufficiency, a unifying concept of its pathophysiology, how treatment may be selected, what the new technology provides, and then a description of coding issues and whether or not interventions are actually worthwhile from the point of view of the patient.

Chronic venous insufficiency (CVI) is inseparably linked to elevated venous pressure and is accompanied by vascular, dermal, and subcutaneous tissue damage and restructuring. Abundant evidence exists both in humans and in experimental models to suggest that the tissue damage may be initiated by generation of an inflammatory reaction. Inflammatory indicators include elevation of endothelial permeability; attachment of circulating leukocytes to the endothelium; infiltration of monocytes, lymphocytes, and mast cells into the connective tissue; and development of fibrotic tissue infiltrates and several molecular markers, such as growth factor or membrane adhesion molecule generation. Indicators of an inflammatory reaction are already detectable at early stages of CVI and may be involved in the development of primary venous valve dysfunction. One of the important questions is to identify trigger mechanisms for the inflammatory reaction in CVI. Current evidence suggests that, among several possible mechanisms (hypoxia, humoral stimulation), a shift in fluid shear stress from normal physiological levels and endothelial distension under the influence of elevated venous pressure may serve as trigger mechanisms for inflammation.

Early manifestations of chronic venous insufficiency (CVI) are edema, hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous ulceration and delayed healing. The specific hallmarks of this inflammation include CD68-positive infiltration into the dermal tissue, monocytes, and lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff" formation. In addition, membrane adhesion molecules are present and cytokine expression is seen. In one experimental model of mesenteric venous hypertension, the inflammatory process was detected in its earliest stages. This was evident in the form of neutrophilic leukocyte adhesion to venular endothelium as well as migration of cells across the endothelium and basement membrane into the interstitial space. Simultaneously, parenchymal cell death was detected. This suggests that the mechanism that triggers the inflammatory reaction is venous hypertension. This may cause venous distension and a shift in fluid shear stress. Our observations suggest that patients with venous insufficiency demonstrate circulatory humoral stimulators for leukocyte activation. Otherwise, there is evidence that the inflammatory reaction is limited to the region of the venous ulceration or at least to the skin areas with severe microangiopathy. It may be that activated leukocytes traverse perivascular cuffs and release active transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated exclusively in areas of clinically active CVI. Surgical intervention markedly decreases the number of dysfunctional vein segments and allows pharmacologic agents to protect normal structures from continuing damage. Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished. The action of micronized purified flavonoid fraction is beginning to be better understood, and as further knowledge is gained, better pharmacologic control of CVI is a tantalizing promise.

Recently, carotid artery stenting (CAS) has emerged as a treatment option for carotid artery stenosis. Since the procedure is new, management of its complications is not standardized. This case report describes one method of arterial reconstruction after failed CAS. A 64-year-old male underwent CAS of his right internal carotid artery (ICA) for an asymptomatic 65% stenosis. Seven months later the stented area had narrowed to 95%. Arteriography revealed that the common and external carotid arteries (ECA) were free of disease so we elected to perform a transposition of the distal ICA onto the proximal ECA. The ECA and its branches were completely mobilized and the ascending pharyngeal and lingual arteries divided. The ICA was divided distal to the stent. Transection of the occipital artery provided an arteriotomy for an end ICA to side ECA anastamosis, thus preserving ECA flow. Postoperative surveillance after 8 months has revealed no recurrent stenosis. Operative repair of restenosis after CAS may be challenging if standard endarterectomy is not possible. Other options for reconstruction are feasible but if the common and external carotid arteries are disease-free, an ICA to ECA transposition provides a simple all-arterial repair that avoids bypass and prosthetic material.

There is no consensus as to the single best approach to the treatment of varicose veins. There has been a trend toward less invasive procedures to reduce the number of incisions and provide more selective ablation of varicosities. Ultimately, therapeutic decisions have depended on surgeon preference and the patient population. The active duty military population presents a unique challenge in the treatment of varicose veins. This mobile and active population requires a treatment method that provides maximum relief with the lowest possible morbidity and rapid recovery. The authors previously reported their experience with 104 patients who underwent saphenofemoral ligation combined with perforator point ligation and staged sclerotherapy. This group was compared to 103 patients who underwent saphenofemoral ligation, point perforator ligation, and stab avulsion phlebectomy as a single procedure. Follow-up for the sclerotherapy group included patient satisfaction surveys and documentation of recurrent varicosities. All ambulatory phlebectomy patients responded positively with respect to symptomatic and cosmetic results. Overall satisfaction was favorable and there was no significant difference in patient satisfaction between the ambulatory phlebectomy and sclerotherapy groups. Twelve per cent of the sclerotherapy patients developed true recurrences or new varicosities compared to 11% in the ambulatory phlebectomy group. The most common complication was superficial thrombophlebitis (20% ambulatory phlebectomy, 16% sclerotherapy) which was mild in all cases. All but three patients in the ambulatory phlebectomy group returned to work within 7 days and 75% returned to full duty within 72 hours. Completion of therapy was accomplished in a much shorter period for the ambulatory phlebectomy group. Overall patient satisfaction was achieved for both ambulatory phlebectomy and sclerotherapy patients. Completion of therapy was achieved in a shorter period with fewer clinic visits in the ambulatory phlebectomy group and this has become our procedure of choice for active duty military patients.

Objective: This study explores the added effect of extended saphenofemoral junction (SFJ) ligation when the greater saphenous vein (GSV) has been eliminated from participating in thigh reflux by means of endovenous obliteration. GSV obliteration, unlike surgical stripping, can be done with or without SFJ ligation to isolate and study SFJ ligation's specific contribution to treatment results., Methods: Sixty limbs treated with SFJ ligation and 120 limbs treated without high ligation were selected from an ongoing, multicenter, endovenous obliteration trial on the basis of their having primary varicose veins, GSV reflux, and early treatment dates., Results: Five (8%) high-ligation limbs and seven (6%) limbs without high ligation with patent veins at 6 weeks or less were excluded as unsuccessful obliterations. Treatment significantly reduced symptoms and CEAP clinical class in both groups (P =.0001). Recurrent reflux developed in one (2%) of 49 high-ligation limbs and eight (8%) of 97 limbs without high ligation by 6 months (P =.273). New instances of reflux did not appear thereafter in 57 limbs followed to 12 months. Recurrent varicose veins occurred in three high-ligation limbs and four limbs without high ligation by 6 months and in one additional high-ligation limb and two additional limbs without high ligation by 12 months. Actuarial recurrence curves were not statistically different with or without SFJ ligation (P >.156), predicting greater than 90% freedom from recurrent reflux and varicosities at 1 year for both groups., Conclusion: These early results suggest that extended SFJ ligation may add little to effective GSV obliteration, but our findings are not sufficiently robust to warrant abandonment of SFJ ligation as currently practiced in the management of primary varicose veins associated with GSV vein reflux.

The cases reported here demonstrate the variability of the clinical manifestations of left common iliac venous occlusive disease. In each instance, therapy must be adjusted to meet the symptomatic needs of the individual patient. The experience reported here should reinforce the fact that occlusions even 25 months or longer in duration may be reopened. Continuing patency can be enhanced by stent placement.

The objective of this study was to assess the relationship of signaling molecules to monocyte/ macrophages as a precursor to venous valve and venous wall dysfunction in patients with varicose veins. One of the hallmarks of venous dysfunction is destruction of venous valves with subsequent reflux and elevation of distal venous pressure. We recently observed that monocytes/macrophages migrate into the venous walls and valves of patients with venous insufficiency. There, they may play a role in the pathogenesis of primary venous insufficiency. If so, an important element in their performance would be the interaction between the monocytes and the endothelium as a precursor of damage to venous valves and the venous wall. To explore this interaction, immunohistochemistry was carried out to detect adhesion molecules and cytokines in surgical specimens removed during surgical therapy. Twenty-four surgical specimens consisting of proximal saphenous vein and subterminal valve were obtained using minimally traumatic technique in 6 males and 18 females who ranged in age from 31 to 79 years. Reflux was confirmed preoperatively by duplex technique, and severity was classified by the CEAP classification of the American Venous Forum. Ten patient limbs were class 2, eight were class 3, four were class 4, and two were class 6. The venous specimens were labeled using monoclonal antibody against ICAM-1, E-selectin, IL-1alpha, and TNF-alpha. CD68 was used for detection of monocytes/macrophages. Our results indicate that not only luminal venous endothelium but also endothelium in the vasa vasora of refluxing saphenous veins is activated, as indicated by the up-regulation of ICAM-1. However, IL-1alpha and TNF-alpha were increased in only selected specimens and are mainly detected in the vein wall. The factors that serve as trigger mechanisms to activate cells in the pathogenesis of primary venous dysfunction remain to be explored.

Background: Tissue necrosis after sclerotherapy has been observed, but is unexplained., Objective: To present the complication of extensive tissue necrosis following high-concentration sclerotherapy for varicose veins., Methods: Cases coming to the attention of the authors are presented briefly with commentary and discussion to explain the mechanisms of tissue destruction., Results: Although the complication of extensive tissue necrosis has been ascribed to intra-arterial injection, in fact, careful study of the cases described here shows that intravenous injection was present in each case. A theory of distribution of the sclerosant into the arterial arborization is proposed. This theory would explain the distribution of sclerosant into the arterial tree and would also explain the causation of extensive tissue necrosis. Mention is made of experimental work in which intra-arterial injection was not the mechanism of causation of tissue necrosis., Conclusion: Extensive tissue necrosis following high-concentration sclerotherapy may be rare, but its occurrence is serious and its treatment may be incomplete.