Early experience of thalidomide therapy for high-grade peripheral and facial arteriovenous malformations.

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.

Lower Limb Weakness due to Spinal Venous Congestion in Chronic Inferior Vena Cava Occlusion: A Case Report.

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.

Mechanical characteristics of venous stents to overcome challenges of venous outflow obstruction.

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.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

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.

Two-Vessel Branched Stent Graft for Severely Angulated Aortic Arch Aneurysm in a Jehovah's Witness.

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.

A Summation Analysis of Compliance and Complications of Compression Hosiery for Patients with Chronic Venous Disease or Post-thrombotic Syndrome.

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.

Post thrombotic syndrome following deep vein thrombosis in paediatric patients.

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.

Improving Patient Compliance With Post-EVAR Surveillance May Prevent Late Rupture.

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.

A multi-centre randomised controlled trial comparing radiofrequency and mechanical occlusion chemically assisted ablation of varicose veins - Final results of the Venefit versus Clarivein for varicose veins trial.

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.

Successful endovascular treatment of duodenal obstruction caused by large abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) causing duodenal obstruction is not a common presentation. Our literature review demonstrated that open surgery was often used to treat such problem. Here, we describe the first case of an endovascular approach to treat acute duodenal obstruction caused by a massive infrarenal AAA. CASE REPORT: An 84-year-old man presented with acute abdominal pain and distension, vomiting, decreasing appetite, and weight loss. Computed tomography scan confirmed a large infrarenal AAA causing duodenal obstruction. The patient was started on total parenteral nutrition, and the aneurysm treated by endovascular aneurysm repair (EVAR). Postoperatively, the patient's symptoms of duodenal obstruction gradually resolved. CONCLUSIONS: EVAR is a viable treatment option for patients presenting with duodenal obstruction caused by AAA.

A study to evaluate patterns of superficial venous reflux in patients with primary chronic venous disease.

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.

Coronary stent embolization of peroneal artery.

Embolization of coronary artery stents is a rare but well-recognized complication of percutaneous coronary intervention. Although intracardiac stent migration carries a significant risk to the patient, peripheral embolization is largely benign despite carrying a theoretical risk of distal ischemia. Furthermore, stents lost to the periphery are often never found. Here, we describe a case of an embolized stent to the peroneal artery which was accurately located using on-table fluoroscopy and ultrasound duplex.

Hypoxia-inducible factor pathway and diseases of the vascular wall.

BACKGROUND: 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. METHODS: 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." RESULTS: 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. CONCLUSIONS: 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.

Cell death pattern of a varicose vein organ culture model.

The study aimed to investigate the viability of a varicose vein (VV) organ culture model by assessing cell death pattern. To assess pattern of cell death with time, VV organ cultures were incubated for up to 14 days with regular medium changed. To assess viability, cell death of VV organ cultures treated with sodium azide and their untreated counterparts was assayed. Increased cell death was measured in VV organ cultures from day 0 to 2. Cell death decreased gradually after day 2 and plateaued from day 8 to 14.VV organ cultures treated with sodium azide demonstrated significantly more cell death in tissue (P = 0.001). Cell death measured in cultures treated with sodium azide continued to increase until day 7. In conclusion, this study demonstrated the viability of a VV organ culture model with most cell death occurred within the first two days and then declined to a relatively low level.

Unsuspected iatrogenic vertebral artery cannulation with a dialysis catheter.

Internal jugular vein cannulation is a common clinical procedure but not without risks including inadvertent artery puncture. The incidence of vertebral artery puncture during internal jugular vein cannulation is unclear but is thought to be much less than carotid artery involvement. Here, we describe an unsuspected case of vertebral artery cannulation with a Vas Cath dialysis catheter which was used for hemofiltration before the inadvertent artery cannulation was discovered later during open surgical retrieval.

Pathogenesis and etiology of recurrent varicose veins.

BACKGROUND: Recurrent varicose veins (RVV) occur in 13% to 65% of patients following treatment, and remain a debilitating and costly problem. RVV were initially thought largely to be due to inadequate intervention, however, more recently neovascularization and other factors have been implicated. This review aims to provide an overview of the current understanding of the etiology and pathogenesis of RVV. METHODS: A systematic search of the PubMed database was performed using the search terms including "recurrent," "varicose veins," and "neovascularization." RESULTS: Three types of RVV have been reported, namely residual veins, true RVV, and new varicose veins, although the definitions varied between studies. RVV are attributable to causes including inadequate treatment, disease progression, and neovascularization. Using duplex ultrasonography, neovascularization has been observed in 25% to 94% of RVV. These new vessels appear in various size, number, and tortuosity, and they reconnect previously treated diseased veins to the lower limb venous circulation. Histologically, these vessels appear primitive with incomplete vein wall formation, decreased elastic component, and lack of valves and accompanying nerves. Although the rate of RVV following open surgery and endovenous treatment appears similar, neovascularization seems less common following endothermal ablation. Other causes of RVV following endovenous treatment include recanalization and opening of collaterals. CONCLUSIONS: Recurrence remains poorly understood following treatment of varicose veins. Neovascularization is an established and common cause of RVV, although other factors may contribute.

Increased activation of the hypoxia-inducible factor pathway in varicose veins.

BACKGROUND: Venous hypoxia has been postulated to contribute to varicose vein (VV) formation. Direct measurements of vein wall oxygen tension have previously demonstrated that the average minimum oxygen tensions were significantly lower in VVs compared with non-varicose veins (NVVs). Hypoxia-inducible factors (HIFs) are nuclear transcriptional factors that regulate the expression of several genes of oxygen homeostasis. This study aimed to investigate if hypoxia was associated with VVs by assessing the expression of HIF-1α, HIF-2α, HIF target genes, and upstream HIF regulatory enzymes in VVs and NVVs, and their regulation by hypoxia. METHODS: VVs and NVVs were surgically retrieved and immediately snap-frozen or used for organ culture preparation. The relative expression of HIF-1α, HIF-2α, HIF target genes, and HIF regulatory enzymes in VVs and NVVs was analyzed with quantitative polymerase chain reaction (Q-PCR) and Western blot. VV and NVV organ ex vivo cultures were exposed to 16 hours of normoxia, hypoxia (oxygen tension 1%), or the hypoxia mimetic dimethyloxallyl glycine (DMOG) 1 mM in normoxia. The vein organ cultures were then analyzed for HIF-1α, HIF-2α, and their target gene expression with Q-PCR and Western blot. RESULTS: HIF-1α and HIF-2α mRNA were significantly upregulated in VVs compared with NVVs (89.8 ± 18.6 vs 10.4 ± 7.2 and 384.9 ± 209.4 vs 8.1 ± 4.2, respectively). HIF target gene mRNA expression was also significantly elevated in VVs compared with NVVs, namely glucose transporter-1 (GLUT-1; 8.7 ± 2.1 vs 1.0 ± 0.3), carbonic anhydrase-9 (CA9; 8.5 ± 2.1 vs 2.8 ± 1.2), vascular endothelial growth factor (VEGF; 7.5 ± 2.1 vs 0.9 ± 0.2), and BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP-3; 4.5 ± 0.7 vs 1.4 ± 0.3). The upregulation of HIF-1α, HIF-2α, and HIF target genes in VVs was also reflected at protein level. Of the HIF regulatory enzymes, the expression of prolyl-hydroxylase domain (PHD)-2 and PHD-3 was found to be elevated in VVs compared with NVVs. Exposure of VV and NVV organ cultures to hypoxia or DMOG was associated with increases in HIF-1α and HIF-2α protein and HIF target gene expression compared with normoxia only. CONCLUSIONS: The study concluded, we believe for the first time, an increased activation of the HIF pathway, with upregulation of the expression of HIF-1α and HIF-2α transcription factors, and HIF target genes, in VVs compared with NVVs. Exposure of VVs and NVVs to hypoxic conditions was associated with increased expression of HIF-1α and HIF-2α protein and HIF target genes. The data suggest that the HIF pathway may be associated with several pathophysiologic changes in the VV wall, and that hypoxia may be a feature contributing to VV pathogenesis.

Metastatic bladder transitional cell carcinoma presenting as a vascularised cutaneous right arm lesion.

A 65-year-old man presented to the emergency department with a 3-week history of a fast-growing and painful mass in his right antecubital fossa. He felt otherwise well. Four months earlier, he had undergone a radical cystectomy for transitional-cell carcinoma (TCC) of the bladder (grade 3, stage pT1). Two months after the cystectomy, at another hospital, he was diagnosed with, and treated for, a pseudoaneurysm in his right antecubital fossa. Duplex ultrasonography of the presenting lesion revealed a highly vascularised mass with no pseudoaneurysm. Histological and immunohistochemical analysis preceded a diagnosis of cutaneous metastatic TCC. Whole-body CT revealed widespread metastases. This is the first reported case of a highly vascularised cutaneous lesion being the presenting feature of metastatic bladder TCC.