BACKGROUND:Arteriovenous malformations (AVMs) are developmental defects in the vascular system with abnormal connections between arteries and veins. A minority of AVMs are characterized by aggressive growth and continue to proliferate despite maximal surgical and interventional therapy. We report our outcomes with the use of thalidomide as the only UK specialist center adopting this novel approach for the management of AVMs refractory to conventional therapy.METHODS:This was a retrospective case series which included only complex and proliferative AVM lesions (Schobinger grade III and IV). All patients prescribed thalidomide on a compassionate basis between September 2006 and August 2022 after attempts at embolosclerotherapy without satisfactory response were reviewed.RESULTS:Eleven patients were included in our study. The median total duration of thalidomide use was 10 months. Two thirds of patients with pain (six of nine) reported an improvement, three quarters reported a reduction in swelling (six of eight) and all who presented with bleeding reported improvement in overall volume or frequency (four of four). Over the study period, 45% achieved a non-proliferative state with no further target vessel demonstrable on angiography. Mild, tolerable side effects such as fatigue were common (73%). There was only one major adverse reaction (neutropenia) necessitating cessation of therapy.CONCLUSIONS:We can conclude that thalidomide is able to reduce the symptom burden for patients with complex and proliferative AVMs that were refractory to established treatment modalities. Adverse effects are common, but the benefit achieved from taking thalidomide in otherwise treatment resistant cases outweighs the risks, most of which are manageable.

The presentation of symptomatic inferior vena cava (IVC) occlusion is variable, and no clear guidance exists on indications for invasive treatment. We describe the first documented case in the literature of IVC occlusion and venous congestion of the spine with associated neurological symptoms, successfully treated with endovascular IVC reconstruction. Case report A 31 year-old male presented with a long history of reduced sensation and motor function in his lower limbs upon waking every morning, lasting 30-50 minutes during which he was unable to ambulate. He was involved in a severe road traffic accident as a child, and was born prematurely requiring prolonged neonatal hospitalisation. Both duplex ultrasonography and magnetic resonance venography identified an occlusion of the IVC, with patent common femoral and iliac veins draining into large spinal collaterals. No other cause was identified for his symptoms. After appropriate multidisciplinary team discussion and patient counselling, the patient proceeded to have endovenous recanalization of his IVC and common iliac veins with dedicated venous stents. Post-operatively, the patient reported an immediate resolution of neurological symptoms, with an improvement in quality of life questionnaire scores and with stent patency at 9-month follow up. Conclusion IVC occlusion with symptomatic spinal venous congestion is a rare condition which may be successfully treated with endovascular iliocaval recanalization, although long-term outcomes of this treatment are still unknown.

Post-thrombotic syndrome (PTS) has variable clinical presentation with significant treatment costs and gaps in the evidence-base to support clinical decision making. The contribution of variations in venous anatomy to the risk of complications following treatment has yet to be characterized in detail. We report the development of a steady-state, 0D model of venous anatomy of the lower limb and assessments of local sensitivity (10% radius variation) and global sensitivity (50% radius variation) of the resulting flows to variability in venous anatomy. An analysis of orthogonal sensitivity was also performed. Local sensitivity analysis was repeated with four degrees of thrombosis in the left common iliac vein. The largest normalised sensitivities were observed in locations associated with the venous return. Both local and global approaches provided similar ranking of input parameters responsible for the variation of flow in a vessel where thrombosis is typically observed. When a thrombus was included in the model increase in absolute sensitivity was observed in the leg affected by the thrombosis. These results can be used to inform model reduction strategies and to target clinical data collection.

Chronic obstruction of the iliac veins or inferior vena cava can occur as a result of deep vein thrombosis, or owing to extrinsic compression in nonthrombotic iliac vein lesions (NIVLs). This obstruction can manifest as post-thrombotic syndrome (PTS) after deep vein thrombosis or as chronic venous disease (CVD) in NIVL. Little evidence exists to support the use of deep venous stents in established PTS or NIVLs, and the evidence for its use in the prevention of PTS is inconclusive. A provisional health economic analysis over 5 years found that the incremental cost-effectiveness ratio of stenting versus no stenting over a 5-year period was between £7,500 and £52,000 per quality-adjusted life-year for treatment of established PTS.

INTRODUCTION: Many challenges posed by the venous outflow obstruction (VOO) are unique to the venous system which require specific mechanical characteristics of stents to overcome them. Therefore, this article aims to review and discuss these challenges and the stent mechanical characteristics required to overcome them.EVIDENCE ACQUISITION: A literature search was performed with Pubmed with the terms "mechanical characteristics of venous stents" and "mechanical properties of venous stents".EVIDENCE SYNTHESIS: The venous system poses unique anatomical, physiological and pathological challenges when compared to the arterial counterpart. Several mechanical characteristics specific to venous stents which include the size, inherent forces, and flexibility are important to overcome these unique challenges when treating VOO. The most important stent inherent forces for venous stents include the chronic outward force, radial resistive force, and crush resistance. Various stent materials and designs, particularly laser-cut versus braided-structure stents, and open-cell versus closed-cell stents, determine the mechanical characteristics including the inherent forces of the venous stents. The desired mechanical characteristics of stents needed to overcome the venous system challenges often in conflict or with opposing effects. Therefore, it is important to fine adjust and optimize these characteristics.CONCLUSIONS: There are many anatomical, physiological, and pathological challenges unique to the venous system which need to be overcome by the stent system mechanically when treating VOO. Therefore, dedicated venous stents with optimal mechanical characteristics are being developed with different designs and properties to treat VOO. Further research and innovations are needed to improve the stent technology that targets the venous system specifically.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Venous disease is common in the general population, with chronic venous disorders affecting 50–85% of the western population and consuming 2–3% of healthcare funding. It, therefore, represents a significant socioeconomic, physical and psychological burden. Acute deep vein thrombosis, although a well-recognised cause of death through pulmonary embolism, can more commonly lead to post-thrombotic syndrome (PTS). This article summarises the pathophysiology and risk factor profile of PTS, and highlights various strategies that may reduce the risk of PTS, and the endovenous management of iliofemoral deep vein thrombosis. The authors summarise the advances in PTS risk reduction strategies and present the latest evidence for discussion.

Aneurysmal disease involving the origins of supra aortic vessels often requires complex open and/or endovascular repair that is not only associated with significant risk of mortality and morbidity but also often with perioperative blood loss requiring transfusion. We report a successful repair of a large thoracic aortic aneurysm (TAA) involving the aortic arch with a custom-made Bolton Relay 2-vessel branched thoracic aortic endograft in a 42-year-old Jehovah's Witness who would otherwise be very unlikely to survive an open repair. Branched thoracic aortic endografting offers a potentially safe, minimally invasive, and effective alternative for TAA disease involving the supra-aortic arteries, especially in patients who are at high risk of open surgery.

Minimally invasive, embolosclerotherapy (EST) for upper extremity vascular malformations (VMs) carries significant risk of serious complications, such as ischemia, infarction, amputation, nerve injury, contracture, and ulceration, with as high as 61% rates for hand treatments most recently reported. Despite improved care in specialist centers, up-to-date estimates of complication risk for audit and informed consent are scarce; recent literature focuses on high-flow VMs (HFVM) with a paucity of data for low-flow VMs (LFVM). This study reviews the 5-year serious complications following EST of all upper extremity VM in our tertiary referral center for vascular anomalies. All VM patients underwent multidisciplinary review directed intervention, and demographic, procedural, follow-up, and complication data collected prospectively in a dedicated database. Treatment outcomes for upper extremity VM from January 1, 2013, to December 31, 2017, were analyzed (Figures 1 and 2). EST interventions were performed under fluoroscopic guidance. All ESTs of HFVM were performed under selective catheter angiography and direct injection, but LFVM with direct injection only. Serious complications were defined as any tissue or functional damage caused by direct injection, distal embolization, or tissue reaction. There were 70 patients who had a total of 150 EST procedures for upper extremity VMs (median age, 24.5 years; range, 1-73 years; 44 male, 26 female). Of these, 28 (40%) had EST for HFVM and 42 (60%) for LFVM (total 78 and 72 procedures, respectively). Most used agents were foam sclerosant (STD 3% mixed in ratio 2:8 with air), dehydrated absolute ethanol, and coils. Serious complications as follows: HFVM in five patients (17.9%) or 6.4% of total procedures; three ischemia of fingers and/or hand requiring amputation (Figs 1 and 2), and two skin ulcerations. Serious complication in LFVM occurred in five patients (11.9%) or 6.9% of total procedures: one median nerve injury causing wrist drop requiring nerve grafting and hand therapy, one hand contracture requiring tendon release, and three skin ulcerations. All ulcerations resolved without significant long-term disability. However, the nerve and tendon injuries carried degrees of long-term functional disability. Current EST is relatively safe for upper extremity HFVM where our complication rate of 17.9% compares favorably with the recent literature, possibly owing to the selective use of foam versus alcohol, and improved classification and targeted treatment. For LFVM, significant complications resulted in 11.9% of patients from local toxicity after direct injection. These outcomes will direct treatment strategies to avoid local toxic complications in the hand for both HFVM and LFVM, and to informed consent.Fig 2After amputations.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Objectives: Compression stockings are commonly prescribed for patients with a range of venous disorders, but are difficult to don and uncomfortable to wear. This study aimed to investigate compliance and complications of compression stockings in patients with chronic venous disease (CVD) and post-thrombotic syndrome (PTS). Methods: A literature search of the following databases was carried out: MEDLINE (via PubMed), EMBASE (via OvidSP, 1974 to present), and CINAHL (via EBSCOhost). Studies evaluating the use of compression stockings in patients with CVD (CEAP C2-C5) or for the prevention or treatment of PTS were included. After scrutinising full text articles, compliance with compression and associated complications were assessed. Compliance rates were compared based on study type and degree of compression. Good compliance was defined as patients wearing compression stockings for >50% of the time. Results: From an initial search result of 4303 articles, 58 clinical studies (37 randomised trials and 21 prospective studies) were selected. A total of 10,245 limbs were included, with compression ranging from 15 to 40 mmHg (not stated in 12 studies) and a median follow-up of 12 months (range 1-60 months). In 19 cohorts, compliance was not assessed and in a further nine, compliance was poorly specified. Overall, good compliance with compression was reported for 5371 out of 8104 (66.2%) patients. The mean compliance, weighted by study size, appeared to be greater for compression <= 25 mmHg (77%) versus > 25 mmHg (65%) and greater in the randomised studies (74%) than in prospective observational studies (64%). Complications of stockings were not mentioned in 43 out of 62 cohorts reviewed. Where complications were considered, skin irritation was a common event. Conclusions: In published trials, good compliance with compression is reported in around two thirds of patients, with inferior compliance in those given higher degrees of compression. Further studies are required to identify predictors of non-compliance, to help inform the clinical management of these patients. Complications of compression are not documented in many studies and should be given more consideration in the future. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Catheter thrombolysis of acute deep venous thrombosis (DVT) of the upper extremity (UE) and lower extremity (LE) is being increasingly carried out following emerging evidence to support that it reduces the risk for development of post-thrombotic syndrome. Such intervention and its potential secondary procedures may expose the patients to significant cumulative radiation over time. Furthermore, these patients are often relatively younger than those with arterial diseases. The study aimed to assess the cumulative radiation exposure to patients who had thrombolysis for acute DVT of the LE and UE.

Background Although well characterised in adults, less is known about post-thrombotic syndrome in children. In this review, current knowledge regarding paediatric post-thrombotic syndrome is summarised, with particular emphasis on pathophysiology, aetiology, diagnosis and management. Methods A Medline literature review was performed using search terms ‘post thrombotic syndrome’, ‘post phlebitic syndrome’, paediatric and children. Relevant articles were identified and included for summation analysis. Results The incident of paediatric venous thromboembolism is rising. Deep vein thrombosis can cause venous hypertension through a combination of venous reflux, venous obstruction and impairment of the calf muscle pump, leading to development of post-thrombotic syndrome. In children, this is more likely to occur if deep vein thrombosis diagnosis and treatment are delayed, if a higher number of vessels are involved, and if factors such as D-dimer are elevated at diagnosis and throughout treatment. Post-thrombotic syndrome occurs in about 26% of paediatric deep vein thrombosis, though the results of individual studies vary widely. A number of tools exist to diagnose paediatric post-thrombotic syndrome, including the modified Villalta scale and Manco-Johnson instrument. Once post-thrombotic syndrome develops, the mainstay of treatment remains supportive, with little evidence of benefit from pharmacological measures. Conclusion Surgical or interventional treatment is not advised except in exceptional cirumstances, due to variable prognosis of PTS in paediatric populations with rising incidence of paediatric venous thromboembolism, it follows that the prevalence of post-thrombotic syndrome in children may also increase. Evidence-based venous thromboembolism prevention strategies need to be implemented for prevention of deep vein thrombosis, but when it does occur, deep vein thrombosis requires prompt and effective treatment to prevent post-thrombotic syndrome. Optimum treatment strategies for post-thrombotic syndrome require further investigation.

Endovascular aneurysm repair (EVAR) has gained increasing popularity in the treatment of infrarenal abdominal aortic aneurysm. Despite its favorable early outcomes, the long-term efficacy of EVAR remains a concern. Late rupture is the ultimate treatment failure and continues to complicate EVAR. Univariate and multivariate analyses have identified factors predictive of late rupture. The importance of EVAR surveillance to prevent late complications is equally widely acknowledged. This article aims to present our current understanding of the precipitating factors of late rupture after EVAR and explores whether the key to its prevention lies within improving patient factors, particularly compliance to follow-up appointments or whether physicians hold the solution.

Peripheral vascular disease, or peripheral arterial disease (PAD), is a common condition, particularly prevalent in the older adult population. The condition is caused by narrowing of the arteries, which causes numerous signs and symptoms, usually affecting the lower limb. The sequelae of PAD can lead to difficulty mobilizing, ulceration, and the need for intervention. As the general population is living longer, general practitioners and care of the elderly physicians are increasingly caring for older adults with PAD. The diagnostic principles and treatment considerations in older adults with PAD are similar to those for the general population, although additional attention must be paid to several factors including fitness for intervention, medications, mobility, and quality of life. These factors cause a significant burden to patients in terms of their quality of life. In this chapter we discuss PAD with resect to its history, presentation, diagnosis, and treatment modalities.

Background: Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal techniques such as mechanical occlusion chemically assisted endovenous ablation (MOCA) allow treatment of entire trunks with single anaesthetic injections. Previous non-randomised work has shown reduced pain post-operatively with MOCA. This study presents a multi-centre randomised controlled trial assessing the difference in pain during truncal ablation using MOCA and radiofrequency endovenous ablation (RFA) with six months' follow-up.Methods: Patients undergoing local anaesthetic endovenous ablation for primary varicose veins were randomised to either MOCA or RFA. Pain scores using Visual Analogue Scale and number scale (0-10) during truncal ablation were recorded. Adjunctive procedures were completed subsequently. Pain after phlebectomy was not assessed. Patients were reviewed at one and six months with clinical scores, quality of life scores and duplex ultrasound assessment of the treated leg.Results: A total of 170 patients were recruited over a 21-month period from 240 screened. Patients in the MOCA group experienced significantly less maximum pain during the procedure by Visual Analogue Scale (MOCA median 15 mm (interquartile range 7-36 mm) versus RFA 34 mm (interquartile range 16-53 mm), p = 0.003) and number scale (MOCA median 3 (interquartile range 1-5) versus RFA 4 mm (interquartile range 3-6.5), p = 0.002). 'Average' pain scores were also significantly less in the MOCA group; 74% underwent simultaneous phlebectomy. Occlusion rates, clinical severity scores, disease specific and generic quality of life scores were similar between groups at one and six months. There were two deep vein thromboses, one in each group.Conclusion: Pain secondary to truncal ablation is less painful with MOCA than RFA with similar short-term technical, quality of life and safety outcomes.

Malignancy and its associated management have long been recognised as significant risk factors for venous thromboembolism (VTE). The risk of VTE in cancer patients is increased by seven-fold, with approximately 5–20% of all cancer patients will develop VTE. Complex aetiology involving prothrombotic state of underlying tumour cells and the haemostatic sideeffects of oncological treatments including cytotoxic drugs, hormonal therapy, radiotherapy and surgery lead to difficulties in defining optimal VTE prevention and management in cancer patients. Nonetheless, the consequential morbidity and mortality dictate that its amelioration must remain a priority for clinicians. Currently, low-molecular weight heparins (LMWHs) are the preferred anticoagulants for the prophylaxis and treatment of VTE in cancer patients. Meanwhile, vitamin K antagonists (VKA) such as warfarin are advocated where high cost or poor renal function precludes the use of LMWHs in the treatment of VTE. Considering long-term treatment, LMWH demonstrates superior efficacy to warfarin. Recent meta-analysis by the Cochrane Collaboration on seven randomised controlled trials (RCTs) comparing LMWHs with VKAs found a statistically significant reduction in VTE (hazard ratio 0.47; 95% confidence interval, CI 0.32 to 0.71), but no significant difference in survival benefit, bleeding and thrombocytopenia. In addition, LMWHs hold a myriad of practical advantages over VKAs including fewer drug interactions, avoidance of frequent venepuncture and predictable effect especially in those with risk of gastrointestinal tract disturbance such as nausea, vomiting, diarrhoea and malabsorption. However, disadvantages include bruising and pain from daily injection, potential cost associated with requirement for district nurses and increased risk of thrombocytopenia and osteoporosis. The main advantages of VKAs are that they are effective in preventing recurrent VTE and are time proven. However, cancer patients have numerous complicating factors such that achieving and maintaining a therapeutic international normalised ratio is challenging; frequent venepuncture becomes unavoidable. Over recent years, several novel direct oral anticoagulant (DOAC) agents have emerged which specifically target key molecules within the coagulation cascade. These mainly include factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and direct thrombin inhibitors (e.g. dabigatran). Results emerging from phase three trials for both classes appear promising in the treatment of VTE. Both the EINSTEIN-DVT and EINSTEIN-PE RCTs demonstrated noninferiority of rivaroxaban when compared with standard treatment (enoxaparin for 5–10 days followed by an oral VKA) in preventing recurrent VTE. In a subgroup analysis of 207 (6%) and 223 (4.6%) cancer patients enrolled in the EINSTEIN-DVT and EINSTEIN-PE, respectively, similar results were found. Moreover, in the EINSTEIN-Ext trial, the superiority of rivaroxaban over placebo in long-term prevention of recurrent VTE was reported. Similar non-inferiority of apixaban and edoxaban when compared with standard treatment was reported in the AMPLIFY and HOKUSAI trials, respectively. The bleeding risk with the factor Xa inhibitors does not appear significantly different compared with LMWHs and warfarin. With regard to dabigatran, the RE-COVER and RE-MEDY trials demonstrated it to be non-inferior to warfarin in the prevention of recurrent VTE and VTE-related death in acute and long term, respectively. Similar conclusions were drawn from the subgroup analysis of 121 (4.7%) cancer patients in the RE-COVER study. Dabigatran was shown to have similar safety profile including bleeding although with more adverse events leading to drug discontinuation and dyspepsia when compared with warfarin in the RE-COVER study. Meanwhile, in the RE-MEDY study, dabigatran demonstrated a trend toward a lower risk of bleeding but significantly more acute coronary syndrome when compared to warfarin. A recent meta-analysis performed subgroup

Objective This study assessed patterns of superficial reflux in patients with primary chronic venous disease.Methods Retrospective review of all patient venous duplex ultrasonography reports at one institution between 2000 and 2009. Legs with secondary, deep or no superficial reflux were excluded.Results In total, 8654 limbs were scanned; 2559 legs from 2053 patients (mean age 52.3 years) were included for analysis. Great saphenous vein reflux predominated (68%), followed by combined great saphenous vein/small saphenous vein reflux (20%) and small saphenous vein reflux (7%). The majority of legs with competent saphenofemoral junction had below-knee great saphenous vein reflux (53%); incompetent saphenofemoral junction was associated with combined above and below-knee great saphenous vein reflux (72%). Isolated small saphenous vein reflux was associated with saphenopopliteal junction incompetence (61%), although the majority of all small saphenous vein reflux limbs had a competent saphenopopliteal junction (57%).Conclusion Superficial venous reflux does not necessarily originate from a saphenous junction. Large prospective studies with interval duplex ultrasonography are required to unravel the natural history of primary chronic venous disease.

Hypoxia may contribute to the pathogenesis of various diseases of the vascular wall. Hypoxia-inducible factors (HIFs) are nuclear transcriptional factors that regulate the transcription of genes that mediate cellular and tissue homeostatic responses to altered oxygenation. This article reviews the published literature on and discusses the role of the HIF pathway in diseases involving the vascular wall, including atherosclerosis, arterial aneurysms, pulmonary hypertension, vascular graft failure, chronic venous diseases, and vascular malformation.PubMed was searched with the terms "hypoxia-inducible factor" or "HIF" and "atherosclerosis," "carotid stenosis," "aneurysm," "pulmonary artery hypertension," "varicose veins," "venous thrombosis," "graft thrombosis," and "vascular malformation."In atherosclerotic plaque, HIF-1α was localized in macrophages and smooth muscle cells bordering the necrotic core. Increased HIF-1α may contribute to atherosclerosis through alteration of smooth muscle cell proliferation and migration, angiogenesis, and lipid metabolism. The expression of HIF-1α is significantly elevated in aortic aneurysms compared with nonaneurysmal arteries. In pulmonary hypertension, HIF-1α contributes to the increase of intracellular K(+) and Ca(2+) leading to vasoconstriction of pulmonary smooth muscle cells. Alteration of the HIF pathway may contribute to vascular graft failure through the formation of intimal hyperplasia. In chronic venous disease, HIF pathway dysregulation contributes to formation of varicose veins and venous thromboembolism. However, whether the activation of the HIF pathway is protective or destructive to the venous wall is unclear. Increased activation of the HIF pathway causes aberrant expression of angiogenic factors contributing to the formation and maintenance of vascular malformations.Pathologic vascular wall remodelling of many common diseases of the blood vessels has been found to be associated with altered activity of the HIF pathway. Therefore, understanding the role of the HIF pathway in diseases of the vascular wall is important to identify novel therapeutic strategies in the management of these pathologies.