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Radiofrequency ablation (RFA) has become a valued weapon in the phlebologist's armoury. It offers ease of use and reproducibility with good outcomes. However, as with all interventions, complications arise. In this review we examine the complications inherent with RFA and their relative risk, with their avoidance measures if available. Overall, we find that RFA offers a very safe procedure with rare severe complications.

Varicose veins are an extremely common condition causing morbidity; however, with current financial pressures, treatment of such benign diseases is controversial. Many procedures allow the treatment of varicose veins with minimal cost and extensive literature supporting differing approaches. Here we explore the underlying evidence base for treatment options, the effect on clinical outcome and the cost-benefit economics associated with varicose vein treatment. The method of defining clinical outcome with quality-of-life assessment tools is also investigated to explain concepts of treatment success beyond abolition of reflux.

Purpose: To quantify a pseudoenhancement phenomenon observed during dynamic contrast material-enhanced ultrasonography (US) of the carotid artery, both in vitro and in vivo., Materials and Methods: Ethical approval was obtained prior to commencing this prospective case series, and each patient gave written informed consent. Thirty-one patients with 50%-99% internal carotid artery stenosis underwent dynamic contrast-enhanced US of the carotid bifurcation with use of 2 mL of microbubbles. In the final 10 patients, an additional 1 mL bolus was administered after 15 minutes. Raw linear digital imaging and communications in medicine data were analyzed offline. Regions of interest were drawn within the common carotid artery lumen and immediately adjacent to the lumen in the near and far wall adventitia. Peak intensity was measured. An in vitro experiment with a single-channel flow phantom was also performed. This apparatus consisted of an 8-mm-diameter latex tube placed in a tissue-mimicking fluid. Microbubble concentrations of 0.02%, 0.1%, 0.5%, 1%, and 2% were pumped into the tube. Regions of interest were drawn in a similar fashion to the in vivo experiments, and peak intensity was measured. The Wilcoxon signed rank and paired t tests were used to compare the difference between the near and far wall signal intensities at each dose; a multiplication factor comparing near and far wall signal intensity was derived., Results: The far wall of the common carotid artery was significantly more echogenic than the near wall at 2 mL contrast agent doses (P<.0001, n=31), and the far wall signal intensity increased synchronously with that of the lumen. The difference in signal intensity between near and far wall regions was significantly greater at 2 mL than at 1 mL (P=.012, n=10). In vitro, the phantom tubing demonstrated a similar pattern and magnitude of enhancement to that seen in vivo., Conclusion: A dose-dependent, nonlinear propagation artifact known as pseudoenhancement occurs in the far wall adventitia of the carotid artery and should not be mistaken as a marker of plaque vulnerability., (© RSNA, 2011)

High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications., (Copyright © 2012 S. Karger AG, Basel.)

Background: Sclerotherapy has been shown to be an effective and increasingly popular therapeutic strategy for the treatment of varicose veins. However, recent reports of serious side effects, including cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), as well as speech and visual disturbances, have caused serious concern regarding its use. This review evaluated the reported incidences of neurological side effects associated with the use of sclerotherapy., Methods: A systematic search of the data bases MEDLINE, OVID Embase, and Google Scholar was undertaken by two independent reviewers. Articles reporting neurological side effects in humans following foam and liquid sclerotherapy were included; animal studies, laboratory studies, and review articles were excluded. Additional references were also obtained using the related articles function., Results: The search yielded 1023 articles, of which 41 studies were found to meet the inclusion criteria. A total of 10,819 patients undergoing sclerotherapy were reviewed. There were 12 case reports of CVA with confirmatory brain imaging and nine reports of TIA. There were 97 (0.90%) reports of neurological events overall, including TIA, visual and speech disturbances, and 29 cases of reported migraine (0.27%). Symptoms occurred at times ranging from minutes to several days following sclerotherapy. Eleven patients with TIA or CVA were found to have a right to left cardiac shunt, usually a patent foramen ovale., Conclusions: Neurological side effects following sclerotherapy are a rare occurrence; however, CVA associated with the use of sclerotherapy is clearly documented. The pathologic mechanisms resulting in CVA are likely to be different to those leading to migraine and visual disturbances; however, care should be exercised in patient selection, particularly in those with known cardiac defects., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Venous thromboembolism is a concern in the paediatric population and its incidence seems to be increasing. Symptoms and signs may be subtle so a high degree of suspicion is needed. Paediatric patients represent a unique challenge in the provision of anticoagulation due to their unique physiology.

Background and Purpose: Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology., Methods: Subjects awaiting carotid endarterectomy (n=31) underwent axial LP-CEUS and diseased intimal segments were symmetrically divided in the long axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68 (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma cell culture and supernatant collected at 24 hours for multianalyte profiling for 34 analytes., Results: Percentage area immunopositivity was significantly higher in subjects in which normalized plaque late-phase intensity was ≥0 versus <0 (CD68 mean 11.8 versus 6.68, P=0.004; CD31 mean 9.45 versus 4.82, P=0.025). Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were significantly higher by multianalyte profiling when LP-CEUS was ≥0., Conclusions: LP-CEUS reflects biological features of inflammation and angiogenesis, key features predisposing to plaque rupture. Further investigation of LP-CEUS as a tissue-specific marker of inflammation for risk stratification of carotid atherosclerosis is warranted.

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Structured follow-up after revascularisation for chronic critical limb ischaemia (CLI) aims at sustained treatment success and continued best patient care. Thereby, efforts need to address three fundamental domains: (A) best medical therapy, both to protect the arterial reconstruction locally and to reduce atherosclerotic burden systemically; (B) surveillance of the arterial reconstruction; and (C) timely initiation of repeat interventions. As most CLI patients are elderly and frail, sustained resolution of CLI and preserved ambulatory capacity may decide over independent living and overall prognosis. Despite this importance, previous guidelines have largely ignored follow-up after CLI; arguably because of a striking lack of evidence and because of a widespread assumption that, in the context of CLI, efficacy of initial revascularisation will determine prognosis during the short remaining life expectancy. This chapter of the current CLI guidelines aims to challenge this disposition and to recommend evidentially best clinical practice by critically appraising available evidence in all of the above domains, including antiplatelet and antithrombotic therapy, clinical surveillance, use of duplex ultrasound, and indications for and preferred type of repeat interventions for failing and failed reconstructions. However, as corresponding studies are rarely performed among CLI patients specifically, evidence has to be consulted that derives from expanded patient populations. Therefore, most recommendations are based on extrapolations or subgroup analyses, which leads to an almost systematic degradation of their strength. Endovascular reconstruction and surgical bypass are considered separately, as are specific contexts such as diabetes or renal failure; and critical issues are highlighted throughout to inform future studies., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Objective: The sonographic findings of chronic cerebrospinal venous insufficiency (CCSVI) are used by some as selection criteria for venography. We performed a systematic review to establish the prevalence and strength of association between sonographic CCSVI and multiple sclerosis (MS)., Method: Two reviewers searched PubMed and EMBASE from 1948 to date using the keywords 'chronic cerebrospinal venous insufficiency' according to PRISMA guidelines., Results: Four cross-sectional studies met the criteria for inclusion. The prevalence of CCSVI ranged from 7% to 100% in MS patients and from 2% to 36% in healthy controls. Diagnostic odds ratios for MS varied between 2 and 26, 499 (I(2) = 94%). Sensitivities of CCSVI for MS varied between 7% and 100% (I(2) = 98%). Specificities varied between 64% and 100% (I(2) = 95%)., Conclusion: There is substantial variation in the strength of association between CCSVI and MS beyond that explained by demographic differences or sonographer training. Reliable evidence on which to base decisions requires sonographic consensus and assessment of the reproducibility of individual criteria between trained sonographers.

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Ulcerated diabetic foot is a complex problem. Ischaemia, neuropathy and infection are the three pathological components that lead to diabetic foot complications, and they frequently occur together as an aetiologic triad. Neuropathy and ischaemia are the initiating factors, most often together as neuroischaemia, whereas infection is mostly a consequence. The role of peripheral arterial disease in diabetic foot has long been underestimated as typical ischaemic symptoms are less frequent in diabetics with ischaemia than in non-diabetics. Furthermore, the healing of a neuroischaemic ulcer is hampered by microvascular dysfunction. Therefore, the threshold for revascularising neuroischaemic ulcers should be lower than that for purely ischaemic ulcers. Previous guidelines have largely ignored these specific demands related to ulcerated neuroischaemic diabetic feet. Any diabetic foot ulcer should always be considered to have vascular impairment unless otherwise proven. Early referral, non-invasive vascular testing, imaging and intervention are crucial to improve diabetic foot ulcer healing and to prevent amputation. Timing is essential, as the window of opportunity to heal the ulcer and save the leg is easily missed. This chapter underlines the paucity of data on the best way to diagnose and treat these diabetic patients. Most of the studies dealing with neuroischaemic diabetic feet are not comparable in terms of patient populations, interventions or outcome. Therefore, there is an urgent need for a paradigm shift in diabetic foot care; that is, a new approach and classification of diabetics with vascular impairment in regard to clinical practice and research. A multidisciplinary approach needs to implemented systematically with a vascular surgeon as an integrated member. New strategies must be developed and implemented for diabetic foot patients with vascular impairment, to improve healing, to speed up healing rate and to avoid amputation, irrespective of the intervention technology chosen. Focused studies on the value of predictive tests, new treatment modalities as well as selective and targeted strategies are needed. As specific data on ulcerated neuroischaemic diabetic feet are scarce, recommendations are often of low grade., (Copyright © 2011 European Society for Vascular and Endovascular Surgery Urology. Published by Elsevier Ltd. All rights reserved.)

Although deep venous insufficiency is common and important, the anatomy of deep vein valves is poorly understood. The aim of this study was to investigate the location, number and consistency of venous valves in the femoral and popliteal veins in normal subjects. A detailed literature search of PubMed was performed. Abstracts and selected full text articles were scrutinised and relevant studies published between 1949 and 2010 reporting anatomical details of deep vein valves were included. From 7470 articles identified by the initial search strategy, nine studies with a total of 476 legs were included in this review. All studies were cadaveric and subjects ranged from stillborn fetuses to 103 years of age. Studies suggested that femoral veins contain between one and six valves, and popliteal veins contain between zero and four valves. Deep vein valves were consistently located in the common femoral vein (within 5 cm of the inguinal ligament), the femoral vein (within 3 cm of the deep femoral vein tributary) and in the popliteal vein near the adductor hiatus. Valves are consistently located at specific locations in the deep veins of the leg, although there is often significant variability between subjects. Further anatomical and functional studies using new imaging modalities available should target these areas to identify whether certain valves play a more important role in venous disease. This may guide us in the development of new treatment options for patients with deep venous disease., (© 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.)

Chronic cerebrospinal venous insufficiency (CCSVI) is a hypothesis through which cerebral venous drainage abnormalities contribute towards the pathogenesis of multiple sclerosis. CCSVI venoplasty is already practised worldwide. We report the case of a 33-year-old lady with multiple sclerosis who underwent left internal jugular venoplasty resulting in iatrogenic jugular thrombosis requiring open thrombectomy for symptom relief. This occurred without insertion of a stent and while fully anticoagulated. Clinicians should be aware that endovenous treatment of CCSVI could cause paradoxical deterioration of cerebral venous drainage. Patients with complications post venoplasty are now presenting to geographically distant vascular units.

Y-box binding protein-1 (YB-1) expression in the mammary gland promotes breast carcinoma that demonstrates a high degree of genomic instability. In the present study, we developed a model of pre-malignancy to characterize the role of this gene during breast cancer initiation and early progression. Antibody microarray technology was used to ascertain global changes in signal transduction following the conditional expression of YB-1 in human mammary epithelial cells (HMEC). Cell cycle-associated proteins were frequently altered with the most dramatic being LIM kinase 1/2 (LIMK1/2). Consequently, the misexpression of LIMK1/2 was associated with cytokinesis failure that acted as a precursor to centrosome amplification. Detailed investigation revealed that YB-1 localized to the centrosome in a phosphorylation-dependent manner, where it complexed with pericentrin and γ-tubulin. This was found to be essential in maintaining the structural integrity and microtubule nucleation capacity of the organelle. Prolonged exposure to YB-1 led to rampant acceleration toward tumorigenesis, with the majority of cells acquiring numerical and structural chromosomal abnormalities. Slippage through the G(1)/S checkpoint due to overexpression of cyclin E promoted continued proliferation of these genomically compromised cells. As malignancy further progressed, we identified a subset of cells harboring HER2 amplification. Our results recognize YB-1 as a cancer susceptibility gene, with the capacity to prime cells for tumorigenesis.

Introduction: There is a need to develop methods of vascular hemostasis, which limit vessel trauma. LeGoo is a reverse thermosensitive polymer (poloxamer) which is a viscous liquid at room temperature, becoming a firm plug at body temperature. We aimed to describe early single center experience in clampless peripheral vascular surgery., Methods: Single surgeon experience using LeGoo during peripheral vascular surgery between February and October 2010 was analyzed., Results: LeGoo was used in 13 anastomoses in 11 patients. A satisfactory bloodless field without the use of conventional occlusion devices was achieved in 92% of anastomoses. At a median of 36 weeks follow-up, total conduit patency was 91%., Conclusions: In this small series, LeGoo was seen to be safe and effective in the provision of a clamp-free bloodless field in the context of peripheral vascular surgery. Prospective comparative study is necessary to determine performance against conventional vascular clamps., (© The Author(s) 2011)

Background: Guidelines and protocols assist in the clinical management of patients, helping to utilise available resources efficiently, however, there is limited documented guidance on surveillance of patients following open arterial surgery. The frequency of clinical follow up, Doppler ultrasound measurements and radiological imaging should all be justified. Here we review the available literature to offer an evidenced based approach to postoperative care., Method: An electronic search was made of Medline and Embase databases through September 2009 revealing over 2300 studies in the initial searches. Following title and abstract screening, the relevant medical literature concerning post-operative surveillance of open vascular procedures was reviewed (300 papers). 42 papers were included in this review. Surveillance recommendations were constructed from the evidence presented., Results and Conclusion: Detailed anatomical imaging is available for the technical assessment in the majority of patients' postoperative management; however there is little Level 1 evidence to guide modality or timing. Grades B and C recommendations form the majority of surveillance recommendations. Clinical review remains the mainstay of surveillance following open peripheral arterial surgery. Duplex scanning is the imaging modality of choice when indicated in most instances. Minimal data exists to quantify quality of life or intervention efficacy., (Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Approximately 20% of strokes are attributable to carotid stenosis. However, the number of asymptomatic patients needed to prevent one stroke or death with endarterectomy is high at 17 to 32. There is a clear need to identify asymptomatic individuals at high risk of developing future ischemic events to improve the cost-effectiveness of surgery. Our aim was to examine the evidence for subclinical microembolization and silent brain infarction in the prediction of stroke in asymptomatic carotid stenosis using transcranial Doppler (TCD), computed tomography (CT), and magnetic resonance imaging (MRI)., Methods: The review was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Articles regarding humans between 1966 and 2010 were identified through systematic searches of Pubmed, MEDLINE, and EMBASE electronic databases using a predetermined search algorithm., Results: Fifty-eight full text articles met the inclusion criteria. A median of 28% of microemboli positive patients experienced a stroke or transient ischemic attack during follow-up compared with 2% of microemboli negative patients (P = .001). The same was true for the end point of stroke alone with a median of 10% of microemboli positive patients experiencing a stroke vs 1% of microemboli negative patients (P = .004). A specific pattern of silent CT infarctions was related to future stroke risk (odds ratio [OR] = 4.6; confidence interval [CI] = 3.0-7.2; P < .0001). There are no prospective MRI studies linking silent infarction and stroke risk., Conclusions: There is level 1 evidence for the use of TCD to detect microembolization as a risk stratification tool. However, this technique requires further investigation as a stroke prevention tool and would be complemented by improvements in carotid plaque imaging., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Clostridium difficile, a highly infectious bacterium, is the leading cause of antibiotic-associated pseudomembranous colitis. In 2009, the number of death certificates mentioning C. difficile infection in the U.K. was estimated at 3933 with 44% of certificates recording infection as the underlying cause of death. A number of virulence factors facilitate its pathogenicity, among which are two potent exotoxins; Toxins A and B. Both are large monoglucosyltransferases that catalyse the glucosylation, and hence inactivation, of Rho-GTPases (small regulatory proteins of the eukaryote actin cell cytoskeleton), leading to disorganization of the cytoskeleton and cell death. The roles of Toxins A and B in the context of C. difficile infection is unknown. In addition to these exotoxins, some strains of C. difficile produce an unrelated ADP-ribosylating binary toxin. This toxin consists of two independently produced components: an enzymatic component (CDTa) and the other, the transport component (CDTb) which facilitates translocation of CDTa into target cells. CDTa irreversibly ADP-ribosylates G-actin in target cells, which disrupts the F-actin:G-actin equilibrium leading to cell rounding and cell death. In the present review we provide a summary of the current structural understanding of these toxins and discuss how it may be used to identify potential targets for specific drug design.

Background: Despite extensive use in practice, the impact of noninvasive cardiovascular imaging in primary prevention remains unclear., Methods: We searched for randomized trials that compared imaging with usual care and reported any of the following outcomes in a primary prevention setting: medication prescribing, lifestyle modification (including diet, exercise, or smoking cessation), angiography, or revascularization., Results: Seven trials were included. Trials screened patients for inducible myocardial ischemia (2 trials), coronary calcification (3 trials), carotid atherosclerosis (1 trial), or left ventricular hypertrophy (1 trial). Imaging had no effect on medication prescribing overall (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.76-1.33) or on provision of lipid-modifying agents (OR, 1.08; 95% CI, 0.58-2.01), antihypertensive drugs (OR, 1.05; 95% CI, 0.75-1.47), or antiplatelet agents (OR, 1.05; 95% CI, 0.84-1.32). Similarly, no effect was seen on dietary improvement (OR, 0.78; 95% CI, 0.22-2.85), physical activity (0.02 vs -0.08 point change for imaging vs control on a 5-point scale; P = .23), or smoking cessation (OR, 2.24; 95% CI, 0.97-5.19). Imaging was not associated with invasive angiography (OR, 1.26; 95% CI, 0.89-1.79)., Conclusions: We found limited evidence suggesting that noninvasive cardiovascular imaging alters primary prevention efforts. However, given the imprecision of these results, further high-quality studies are needed.

Objectives: Carotid stenosis accounts for 20% of ischemic strokes and can be managed with pharmacotherapy alone or in conjunction with carotid endarterectomy or stenting. The management of asymptomatic carotid stenosis is controversial amongst physicians. The aim of this study was to explore patient preferences for the potential management options using a standardized scenario to minimize clinician bias. These data will then be used to facilitate comparison with existing published data on physicians' preferences in the management of asymptomatic carotid stenosis., Methods: A patient information booklet and questionnaire was developed, validated, and distributed to patients who were identified as candidates for carotid screening duplex based on the presence of peripheral arterial, coronary, or aneurismal disease. Patients were asked to imagine their duplex revealed a 70% unilateral carotid stenosis. Five-year stroke or death risks of 11% were quoted for best medical therapy. The perioperative stroke or death rates quoted were 3% for endarterectomy and 3% to 5% for stenting, based on best current evidence. No physician interaction was allowed to minimize clinician bias. Responses for treatment preference and reasoning were analyzed using appropriate statistical methods. Results from this survey were then compared with a previously published poll of physician preference., Results: One hundred two questionnaires were analyzed with a 94% response rate: 48% chose pharmacotherapy alone, 30% selected carotid endarterectomy, and 22% opted for stenting. The preference for pharmacotherapy alone over either intervention, and for endarterectomy, over stenting was consistent in subgroup analyses by age, gender, prior stroke, family history of stroke, and smoking status., Conclusion: In this scenario, patients were split equally between medical and surgical treatment of asymptomatic carotid stenosis. This was identical to a recent poll of physicians. Tools for risk assessment and the results of the SPACE2, ACST2, and ACT1 trials would benefit patients and physicians making this important treatment decision., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques., Methods and Results: A chip-based robotic nanoelectrospray platform interfaced to a triple quadrupole mass spectrometer was adapted to analyze lipids in tissue sections and extracts from human endarterectomy specimens by shotgun lipidomics. Eighteen scans for different lipid classes plus additional scans for fatty acids resulted in the detection of 150 lipid species from 9 different classes of which 24 were detected in endarterectomies only. Further analyses focused on plaques from symptomatic and asymptomatic patients and stable versus unstable regions within the same lesion. Polyunsaturated cholesteryl esters with long-chain fatty acids and certain sphingomyelin species showed the greatest relative enrichment in plaques compared to plasma and formed part of a lipid signature for vulnerable and stable plaque areas in a systems-wide network analysis. In principal component analyses, the combination of lipid species across different classes provided a better separation of stable and unstable areas than individual lipid classes., Conclusions: This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.

Hypoxia-inducible factor-1 (HIF-1) is a nuclear transcription factor that is upregulated in hypoxia and co-ordinates the adaptive response to hypoxia by driving the expression of over 100 genes. In facilitating tissues to adapt to hypoxia, HIF-1 may have a role in reducing the cellular damage induced by ischaemia, such as that seen in peripheral arterial disease (PAD), or following acute ischaemic insults such as stroke and myocardial infarction. This therefore raises the possibility of HIF-1 modulation in such contexts to reduce the consequences of ischaemic injury. HIF1 has further been implicated in the pathogenesis of atherosclerosis, abdominal aortic aneurysm (AAA) formation, pulmonary hypertension and systemic hypertension associated with obstructive sleep apnoea. Through a better understanding of the role of HIF-1 in these disease processes, novel treatments which target HIF-1 pathway may be considered. This review summarises the role of HIF-1 in arterial disease, specifically its role in atherosclerosis, ischaemic heart disease, in-stent restenosis following coronary revascularisation, stroke, PAD, AAA formation, pulmonary artery hypertension and systemic hypertension. The potential for exploiting the HIF-1 signalling pathway in developing therapeutics for these conditions is discussed, including progress made so far, with attention given to studies looking into the use of prolyl-hydroxylase inhibitors.

The treatment of superficial venous disease (commonly described as varicose veins by the general public) has remained relatively constant over the past 100 years until the refinements of endovenous treatments such as sclerotherapy and more recently, the development of endovenous ablation. This has radically changed the treatment profile of this disease with treatments easily administered and well tolerated even in those patients who would not be considered fit for open surgery previously. With the advent of day surgery and improved general and local anaesthetic techniques, venous surgery has forged a path towards the end goal of outpatient treatment with no requirement for inpatient stay. The end goal of all superficial venous surgery is an improvement in quality of life, and with such new treatments reducing the impact of the actual intervention, such gains are easier to make. This review assesses and presents the current literature describing superficial venous disease treatments covering all treatment modalities. With endovenous treatment, true ambulatory treatment is available, providing high quality treatment at speed and convenience for patients.

Surprisingly little is known about the underlying genetic events that trigger the progression of a normal cell into a cancerous cell. We recently developed a YB-1-driven model of pre-malignancy where we uncovered that the oncogene promotes genomic instability through cell cycle checkpoint slippage and centrosome amplification. In this research perspective, we describe a possible mechanism by which YB-1 instigates preneoplastic transformation. Using Kinex antibody microarrays with coverage of 800 proteins, we discovered that pre-malignant cells exhibit deregulated signal transduction along the HER2-MAPK-RSK axis. We will discuss the implications of these finding in regard to early intervention strategies.

Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

Background: Decreased venous tone and vein wall dilation may contribute to varicose vein formation. We have shown that prolonged vein wall stretch is associated with upregulation of matrix metalloproteases (MMPs) and decreased contraction. Because hypoxia-inducible factors (HIFs) expression also increases with mechanical stretch, this study tested whether upregulation of HIFs is an intermediary mechanism linking prolonged vein wall stretch to the changes in MMP expression and venous contraction., Methods: Segments of rat inferior vena cava (IVC) were suspended in tissue bath under 0.5-g basal tension for 1 hour, and a control contraction to phenylephrine (PHE, 10(-5)M) and KCl (96 mM) was elicited. The veins were then exposed to prolonged 18 hours of tension at 0.5 g, 2 g, 2 g plus HIF inhibitor U0126 (10(-5)M), 17-[2-(dimethylamino)ethyl] amino-17-desmethoxygeldanamycin (17-DMAG, 10(-5)M), or echinomycin (10(-6)M), or 2 g plus dimethyloxallyl glycine (DMOG; 10(-4)M), a prolyl-hydroxylase inhibitor that stabilizes HIF. The fold-change in PHE and KCl contraction was compared with the control contraction at 0.5-g tension for 1 hour. Vein tissue homogenates were analyzed for HIF-1α, HIF-2α, MMP-2, and MMP-9 messenger RNA (mRNA) and protein amount using real-time reverse transcription polymerase chain reaction and Western blots., Results: Compared with control IVC contraction at 0.5-g tension for 1 hour, the PHE and KCl contraction after prolonged 0.5-g tension was 2.0 ± 0.35 and 1.1 ± 0.06, respectively. Vein contraction to PHE and KCl after prolonged 2-g tension was significantly reduced (0.87 ± 0.13 and 0.72 ± 0.05, respectively). PHE-induced contraction was restored in IVC exposed to prolonged 2-g tension plus the HIF inhibitor U0126 (1.38 ± 0.15) or echinomycin (1.99 ± 0.40). U0126 and echinomycin also restored KCl-induced contraction in IVC exposed to prolonged 2-g tension (1.14 ± 0.05 and 1.11 ± 0.15, respectively). Treatment with DMOG further reduced PHE- and KCl-induced contraction in veins subjected to prolonged 2-g tension (0.47 ± 0.06 and 0.57 ± 0.01, respectively). HIF-1α and HIF-2α mRNA were overexpressed in IVC exposed to prolonged 2-g tension, and the overexpression was reversed by U0126. The overexpression of HIF-1α and HIF-2α in stretched IVC was associated with increased MMP-2 and MMP-9 mRNA. The protein amount of HIF-1α, HIF-2α, MMP-2, and MMP-9 was also increased in IVC exposed to prolonged 2-g wall tension., Conclusions: Prolonged increases in vein wall tension are associated with overexpression of HIF-1α and HIF-2α, increased MMP-2 and MMP-9 expression, and reduced venous contraction in rat IVC. Together with our report that MMP-2 and MMP-9 inhibit IVC contraction, the data suggest that increased vein wall tension induces HIF overexpression and causes an increase in MMP expression and reduction of venous contraction, leading to progressive venous dilation and varicose vein formation., (Copyright © 2011 Society for Vascular Surgery. All rights reserved.)

The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored in recent years. The capacity of about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles to TLRs, in particular to TLR2 and TLR4, in immune and cardiovascular disease. Using human and murine systems, we have investigated the consequence of TLR3 signaling in vascular disease. We compared the responses of human atheroma-derived smooth muscle cells (AthSMC) and control aortic smooth muscle cells (AoSMC) to various TLR ligands. AthSMC exhibited a specific increase in TLR3 expression and TLR3-dependent functional responses. Intriguingly, exposure to dsRNA in vitro and in vivo induced increased expression of both pro- and anti-inflammatory genes in vascular cells and tissues. Therefore, we sought to assess the contribution of TLR3 signaling in vivo in mechanical and hypercholesterolemia-induced arterial injury. Surprisingly, neointima formation in a perivascular collar-induced injury model was reduced by the systemic administration of the dsRNA analog Poly(I:C) in a TLR3-dependent manner. Furthermore, genetic deletion of TLR3 dramatically enhanced the development of elastic lamina damage after collar-induced injury. Accordingly, deficiency of TLR3 accelerated the onset of atherosclerosis in hypercholesterolemic ApoE(-/-) mice. Collectively, our data describe a protective role for TLR signaling in the vessel wall.

Objective: Cerebral hyperperfusion syndrome is a preventable cause of stroke after carotid endarterectomy (CEA). It manifests as headache, seizures, hemiparesis or coma due to raised intracranial pressure or intracerebral haemorrhage (ICH). There is currently no consensus on whether to control blood pressure, blood pressure thresholds associated with cerebral hyperperfusion syndrome, choice of anti-hypertensive agent(s) or duration of treatment., Method: A systematic review of the PubMed database (1963-2010) was performed using appropriate search terms according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: A total of 36 studies were identified as fitting a priori inclusion criteria. Following CEA, the incidence of severe hypertension was 19%, that of cerebral hyperperfusion 1% and ICH 0.5%. The postoperative mean systolic blood pressure of patients, who went on to develop cerebral hyperperfusion syndrome, was 164 mmHg (95% confidence interval (CI) 150-178 mmHg) and the cumulative incidence of cases rose appreciably above a postoperative systolic blood pressure of 150 mmHg. The mean systolic blood pressure of cerebral hyperperfusion cases was 189 mmHg (95% CI 183-196 mmHg) at presentation. The incidence of cerebral hyperperfusion in the first week was 92% with a median time to presentation of 5 days (interquartile range (IQR) 3-6 days). 36% of patients presented with seizures 31% with hemiparesis and 33% with both. The proportion of patients with severe hypertension was significantly higher in cases than in post-CEA controls (p < 0.0001, Odds ratio 19 (95% CI 9-41)). Three large case-control studies identify postoperative hypertension as a risk factor for ICH., Conclusion: There is currently level-3 evidence for the prevention of ICH through control of postoperative blood pressure. From the available data, we suggest a definition for cerebral hyperperfusion syndrome, blood pressure thresholds, duration of monitoring and a postoperative blood pressure control strategy for validation in a prospective study. The implications of this are that one in five patients would need intravenous anti-hypertensives and home blood pressure monitoring for 1 week., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: The wide variety of outcome measures to evaluate patients with varicose veins poses significant difficulties when comparing clinical trials. In addition, the relationship between different outcome measures is poorly understood. The aim of this study was to compare anatomical, hemodynamic, and clinical outcomes with disease-specific quality-of-life tools in patients undergoing treatment for varicose veins., Methods: Patients undergoing treatment for symptomatic veins in a single unit were studied. Assessments included duplex ultrasonography, digital photoplethysmography, evaluation of Venous Clinical Severity Scores and CEAP scores, generic (Short Form 12 [SF12]) and disease-specific (Aberdeen Varicose Vein Questionnaire [AVVQ], and Specific Quality-of-life and Outcome Response-Venous [SQOR-V]) questionnaires. Patients were reviewed at 6 weeks when hemodynamic, clinical, and quality-of-life assessments were repeated. The relationships between these outcomes were assessed., Results: The AVVQ showed a strong positive correlation with the SQOR-V (Spearman coefficient 0.702; P < .001) and weaker, but significant correlations with the SF12 physical and mental component scores and the Venous Clinical Severity Score (VCSS) (P < .001, P = .019, and P < .001, respectively, Spearman correlation). No correlations were observed between the AVVQ and photoplethysmography results (Spearman coefficient -0.042; P = .606), and weak correlations were observed with the AVVQ and anatomical reflux. At 6 weeks, functional, clinical, and hemodynamic measurements were all responsive to changes following interventions; however, correlations observed between changes in disease-specific quality-of-life and generic, clinical, and hemodynamic outcomes were weak., Conclusions: Both the AVVQ and SQOR-V questionnaire are sensitive and responsive disease-specific questionnaires, which correlate with generic and clinical outcomes to some extent. Anatomical and hemodynamic measurements correlated poorly with functional outcomes both preoperatively and following interventions., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Introduction: Ambiguity in the literature concerning potential benefits of carotid artery stenting (CAS) as an alternative to carotid endarterectomy (CEA) necessitated a 5-year Delphi-type survey, gauging the changing views over this period of relevant experts undertaking carotid intervention., Methods: Delphi surveys performed in 2004 and 2009 involved 2 rounds of questions combined with feedback of results from the first round between them. The questionnaire was e-mailed to UK vascular surgeons, neurosurgeons, interventional radiologists, and cardiologists., Results: In 2004 and 2009, the second round response rates were 69% and 51%, respectively. Over 5 years, there was a statistically significant reduction in support for ''general anesthesia risk'' and ''contralateral occlusion'' as indications for CAS and views that CAS ''increased patient satisfaction'' and ''decreased the length of hospital stay.'' Concerning the impact of recent trials on the professionals' treatment routines for symptomatic and asymptomatic patients with carotid disease, 65.8% and 76.3%, respectively, had not changed their overwhelming non-CAS routines, with 32.9% and 19.7% saying clinical trial results moved them toward CEA., Conclusions: A 2009 survey of vascular experts found no increase in preference for CAS as a treatment option for advanced carotid bifurcation atherosclerosis. This, in combination with the lack of change from and indeed move toward the ''gold-standard'' CEA, demonstrates a general decline in confidence with CAS.

The case of a 49-year-old male patient who presented with recurrent pulmonary emboli secondary to a calcified lesion within his inferior vena cava is presented. The diagnosis and relevant literature is reviewed. This is the first time that calcification within the inferior vena cava has presented this way in adults, and it is important to consider this diagnosis in patients presenting with recurrent pulmonary emboli., (Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Venous hypoxia has long been postulated as a potential cause of varicosity formation. This article aimed to review the development of this hypothesis, including evidence supporting and controversies surrounding it. Vein wall oxygenation is achieved by oxygen diffusing from luminal blood and vasa vasorum. The whole media of varicosities is oxygenated by vasa vasorum as compared to only the outer two-thirds of media of normal veins. There was no evidence that differences exist between oxygen content of blood from varicose and non-varicose veins, although the former demonstrated larger fluctuations with postural changes. Studies using cell culture and ex vivo explants demonstrated that hypoxia activated leucocytes and endothelium which released mediators regulating vein wall remodelling similar to those observed in varicosities. Venoactive drugs may improve venous oxygenation, and inhibit hypoxia activation of leucocytes and endothelium. The evidence for hypoxia as a causative factor in varicosities remains inconclusive, mainly due to heterogeneity and poor design of published in vivostudies. However, molecular studies have shown that hypoxia was able to cause inflammatory changes and vein wall remodelling similar to those observed in varicosities. Further studies are needed to improve our understanding of the role of hypoxia and help identify potential therapeutic targets., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP., Methods: Varicose veins (n=26) were compared with great saphenous vein (GSV) segments (n=11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n=13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry., Results: There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3)., Conclusions: This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate the cost-effectiveness of traditional and endovenous treatments for patients with primary great saphenous varicose veins., Methods: A Markov model was constructed to compare costs and quality-adjusted life years (QALYs) for great saphenous vein (GSV) reflux. Eight popular treatment strategies were compared up to 5 years. Estimates for the effectiveness of treatments were obtained from published randomized studies and cost values were obtained from published National Health Service (NHS) healthcare resource group tariffs and device manufacturers. Parameter uncertainty was tested using sensitivity analysis and Monte Carlo simulation., Results: Ultrasound-guided foam sclerotherapy (UGFS) had the lowest initial cost, but a higher requirement for further interventions. Day-case surgery (with concomitant treatment of varicosities), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) performed in an outpatient or office setting (with staged treatment of varicosities) were likely to be cost-effective treatment strategies. The incremental cost-effectiveness ratio (ICER) for UGFS (versus conservative care), EVLA (versus UGFS) and RFA (versus EVLA) were £1366, £5799 and £17 350 per QALY respectively. The ICER for traditional surgery (performed on a day-case basis) was £19 012 compared with RFA. Other strategies were not cost-effective using the NHS threshold of £20 000 per QALY., Conclusion: Day-case surgery or endovenous ablation using EVLA or RFA performed as an outpatient are likely to be cost-effective treatment strategies for patients with primary unilateral GSV reflux requiring treatment., (Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Aims: The efficacy of endovenous treatments for venous reflux has been demonstrated in numerous randomised clinical trials, although significant heterogeneity may exist between studies. The aim of this study was to assess the heterogeneity in reporting between randomised clinical trials investigating endovenous treatments for patients with varicose veins., Methods: A literature search of the Pubmed, Cochrane and Google Scholar databases was performed using appropriate search terms. Randomised clinical trials published between January 1968 and June 2009 evaluating endovenous interventions for varicose veins were included and relevant abstracts and full text articles were reviewed. Published study reports were evaluated against recommended reporting standards published by the American Venous Forum in 2007., Results: Twenty-eight randomised trials fulfilled the inclusion criteria. Median patient age (reported in 20/28 studies) ranged from 33 to 54 years. The CEAP classification was presented in 17/28 studies and the proportion of patients with C2 disease ranged from 6.3% to 83.5%. A total of 31 different outcome measures were utilised. This included 13 different questionnaires, varicose vein recurrence at 38 time points and 30 categories of complications. Duplex ultrasonography was used in 21/28 trials to assess recurrence. Quality of life was only evaluated in 11 studies and the follow-up period ranged from 3 weeks to 10 years., Conclusions: Meaningful comparison across randomised studies of endovenous treatments is made difficult by considerable variations in study populations and outcome measures between trials. This highlights the need for the use of prospectively agreed population selection, and reporting standards for outcome measures in randomised clinical assessments of new treatments., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: A range of surgical, endovenous, physical and medical treatments are available for patients with chronic venous disease. The aim of this review was to evaluate the evidence for pharmacological agents used for the treatment of chronic venous disease., Methods: A literature search was performed using Pubmed, Embase, Cochrane and Google Scholar databases. The initial search terms 'varicose vein', 'venous ulcer', 'venous disease' and 'lipodermatosclerosis' were used to identify relevant clinical studies of pharmacotherapy in patients with chronic venous disease (C4-C6)., Results: A huge range of naturally occurring and synthetic drugs have been studied in patients with chronic venous disease. For patients with C4 venous disease, micronized purified flavonoid fraction (MPFF), oxerutin, rutosides and calcium dobesilate may reduce venous symptoms and oedema. MPFF and pentoxifylline have been shown to improve venous ulcer healing when used in addition to multilayer compression bandaging. The clinical benefits of other medications remain unproven. Reliability of meta-analyses was limited by study heterogeneity, small sample sizes and lack of long-term follow-up., Conclusions: In prospective randomized studies, MPFF (Daflon(®)), other flavonoid derivatives and pentoxifylline have demonstrated clinical benefits in patients with C4-C6 venous disease. Pharmacotherapy should be part of a range of treatment options in the modern management of patients with chronic venous disorders.