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Objective: Cyanoacrylate closure of refluxing saphenous veins has demonstrated excellent safety and effectiveness results in feasibility and pivotal studies. This article provides the 36-month follow-up results of a prospective, multicenter, nonrandomized cohort study., Methods: A total of 70 patients were enrolled in a prospective, multicenter study conducted at seven centers in four European countries and underwent treatment of a solitary refluxing great saphenous vein with endovenous cyanoacrylate embolization without the use of tumescent anesthesia or postprocedure compression stockings. The primary effectiveness end point was freedom from recanalization (closure rate) of the great saphenous vein at 6 months. Safety was assessed by occurrence of adverse events after the procedure and during the 6-month follow-up period. Quality of life and clinical improvement parameters were measured before and after the procedure and through a 12-month follow-up period. Anatomic success and clinical improvement were assessed through 36 months after the procedure., Results: Of 70 treated patients, 64 (91%) were available for the 3-year follow-up. The closure rates by Kaplan-Meier life table methods at 6-, 12-, 24-, and 36-month time points were 91.4%, 90.0%, 88.5%, and 88.5%, respectively. Through 36 months, the improvement in change of the mean venous clinical severity score over time was statistically significant by dropping from 4.3 at baseline to 0.9 at the 36-month follow-up (P < .001)., Conclusions: The 3-year follow-up results of the prospective, multicenter eSCOPE study demonstrated the continued anatomic and clinical effectiveness of cyanoacrylate embolization over an extended follow-up period., (Copyright © 2020. Published by Elsevier Inc.)

Objective: The ambulatory selective variceal ablation under local anesthesia (ASVAL) technique subscribes to the "ascending" theory of varicose vein etiology, which recommends primary ambulatory phlebectomy as a treatment for tributary varicosities and truncal vein incompetence. This systematic review explores the efficacy and safety of the ASVAL technique for the treatment of symptomatic varicose veins., Methods: A comprehensive search of the Medline and Embase databases and the Cochrane Register of Controlled Trials in May 2019 revealed 11 original articles that were qualitatively reviewed. The primary outcome was the absence from recurrent varicose veins at 1-year follow-up. Secondary outcomes were resolution of great saphenous vein (GSV) reflux on duplex ultrasound, change in GSV diameter, objective and subjective clinical improvement in chronic venous disease, and patient-reported outcome measures., Results: A total of 2106 limbs underwent intervention in 1734 patients reported in two randomized controlled trials, one case control study, three cohort studies, and five case series. Varicosity recurrence at 1 year ranged from 0.5% to 13.5% in patients. Of 1622 limbs with diagnosed GSV incompetence before intervention, 1114 were competent at 1 year (mean, 68.2% [±12.62%]). All studies measuring GSV diameter reported statistically significant reductions in vein size., Conclusions: ASVAL may be considered as a minimally invasive treatment for early stages of chronic venous disease in the presence of truncal reflux. The evidence base should be strengthened by prospective randomized controlled trials that follow standardized procedures and report according to recognized measures of quality of life alongside clinical and hemodynamic data., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Ambulatory phlebectomies and foam sclerotherapy are two of the most common treatments for varicose vein tributaries. Many studies have been published on these treatments, but few comparative studies have attempted to determine their relative effectiveness., Methods/design: This is a prospective single-centre randomised clinical trial. Patients with primary truncal vein incompetence and varicose vein tributaries requiring treatment will be assigned randomly to either ambulatory phlebectomies or foam sclerotherapy. The primary outcome measure is the re-intervention rate for the varicose vein tributaries during the study period. The secondary outcomes include the degree of pain during the first two post-operative weeks and the time to return to usual activities or work. Improvements in clinical scores, quality of life scores, occlusion rates and cost-effectiveness for each intervention are other secondary outcomes. The re-intervention rate will be considered from the third month., Discussion: This study compares ambulatory phlebectomies and foam sclerotherapy in the treatment of varicose vein tributaries. The re-intervention rates, safety, patient experience and the cost-effectiveness of each intervention will be assessed. This study aims to recruit 160 patients and is expected to be completed by the end of 2019., Trial Registration: ClinicalTrials.gov, NCT03416413 . Registered on 31 January 2018.

Objective/background: The aim was to summarise the evidence for the relationship between vein diameters and clinical severity, and elucidate the relationship between diameters and health related quality of life (HRQoL) METHODS: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The MEDLINE and Embase databases were searched from 1946 to 31 August 2018. Reference lists of included studies were searched for further relevant papers. Full text studies in English reporting the relationship between great and small saphenous vein diameters and clinical severity and/or HRQoL scores measured using validated instruments were included. All study designs were included. Studies that did not include relationships between these parameters, non-English studies, and studies focusing on non-truncal veins were excluded. Two reviewers independently performed the study selection, data extraction, and risk of bias assessment., Results: Eleven eligible studies were identified, reporting on 2,732 limbs (range 22-681). Four studies correlated truncal vein diameter with both clinical severity and HRQoL, while seven reported only on clinical severity measures. Multiple instruments were used to quantify HRQoL and clinical severity. Seven studies assessed the relationship with CEAP class, with the majority observing a positive correlation between vein diameter and disease severity. Four studies found weak correlations with VCSS, with one showing correlations with VCSS components. No significant relationship between diameters and HRQoL scores was reported. One study also revealed no correlation with Aberdeen Varicose Vein Questionnaire improvements post-treatment. The majority of studies failed to include C 0 and C 1 participants., Conclusions: While further studies are required to improve the level of evidence, the existing literature suggests that truncal vein diameters correlate with clinical severity. Diameters are a poor predictor of HRQoL, with no relationship to patients' perceived impact of chronic venous disease. As such, vein diameter should not be used as a measure to decide who needs venous intervention., (Copyright © 2019. Published by Elsevier B.V.)

Background: Varicose veins and chronic venous disease are common, and some funding bodies ration treatment based on a minimum diameter of the incompetent truncal vein. This study assessed the effect of maximum vein diameter on clinical status and patient symptoms., Methods: A prospective observational cohort study of patients presenting with symptomatic varicose veins to a tertiary referral public hospital vascular clinic between January 2011 and July 2012. Patients underwent standardized assessment with venous duplex ultrasonography, and completed questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated. Regression analysis was used to investigate the relationship between QoL, symptoms and vein diameter., Results: Some 330 patients were assessed before surgery. The median maximum vein diameter was 7·0 (i.q.r. 5·3-9·2) mm overall, 7·9 (6·0-9·8) mm for great saphenous vein and 6·0 (5·2-8·9) mm for small saphenous vein. In linear regression analysis, vein diameter was shown to have a significant association with VCSS (P = 0·041). For every 1-mm increase in vein diameter, there was a 2·75-fold increase in risk of being in CEAP class C4 compared with C2. No other QoL or symptom measures were related to vein diameter., Conclusion: Incompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective Mechanochemical ablation is a novel technique for ablation of varicose veins utilising a rotating catheter and liquid sclerosant. Mechanochemical ablation and radiofrequency ablation have no reported neurological side-effect but the rotating mechanism of mechanochemical ablation may produce microbubbles. Air emboli have been implicated as a cause of cerebrovascular events during ultrasound-guided foam sclerotherapy and microbubbles in the heart during ultrasound-guided foam sclerotherapy have been demonstrated. This study investigated the presence of microbubbles in the right heart during varicose vein ablation by mechanochemical abaltion and radiofrequency abaltion. Methods Patients undergoing great saphenous vein ablation by mechanochemical abaltion or radiofrequency ablation were recruited. During the ablative procedure, the presence of microbubbles was assessed using transthoracic echocardiogram. Offline blinded image quantification was performed using International Consensus Criteria grading guidelines. Results From 32 recruited patients, 28 data sets were analysed. Eleven underwent mechanochemical abaltion and 17 underwent radiofrequency abaltion. There were no neurological complications. In total, 39% (11/28) of patients had grade 1 or 2 microbubbles detected. Thirty-six percent (4/11) of mechanochemical abaltion patients and 29% (5/17) of radiofrequency ablation patients had microbubbles with no significant difference between the groups ( p=0.8065). Conclusion A comparable prevalence of microbubbles between mechanochemical abaltion and radiofrequency ablation both of which are lower than that previously reported for ultrasound-guided foam sclerotherapy suggests that mechanochemical abaltion may not confer the same risk of neurological events as ultrasound-guided foam sclerotherapy for treatment of varicose veins.

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., (© The Author(s) 2014.)

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein device, without adverse sequelae.

We present the first case of retrograde ablation of the small saphenous vein to treat active venous ulceration. A 73-year-old gentleman with complicated varicose veins of the left leg and a non-healing venous ulcer despite previous successful endovenous treatment to his left great saphenous vein underwent mechanochemical ablation of his small saphenous vein with the ClariVein® system, under local anaesthetic, using a retrograde cannulation technique. Post-operatively the patient had improved symptomatically and the ulcer size had reduced. This report highlights that patients with small saphenous vein incompetence and active ulceration can be treated successfully with retrograde mechanochemical ablation., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

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.

The significance of short saphenous vein (SSV) reflux is an under-explored territory in chronic venous disease (CVD). We have examined the origin and significance of SSV reflux in primary and secondary CVD. While the natural history of SSV incompetence remains uncertain, its prevalence has been shown to approximate 3.5%, rising with progressing clinical venous insufficiency, and bears an association with lateral malleolar venous ulceration. The most common pattern of reflux extends throughout the SSV. Patterns of incompetence in recurrent disease are highly variable, but SSV reflux may itself pose a risk for recurrence, in part due to the complex anatomy of the saphenopopliteal system. Further studies are required to delineate the impact of SSV reflux in secondary venous disease and deep venous incompetence.

Background: Doxycycline and micronized purified flavonoid fraction (MPFF) modulate vein wall remodeling that may be associated with hypoxia in varicose veins (VVs), vein graft stenosis, and deep venous thrombosis. We recently reported that in vitro exposure of non-VV (NVVs) and VVs to hypoxic conditions activates the hypoxia-inducible factor (HIF) pathway. This study investigated the in vitro effects of doxycycline and MPFF on the HIF pathway in hypoxic NVVs and VVs., Methods: Six NVVs and six VVs obtained from surgery were used to prepare vein organ cultures, which were exposed to hypoxia (1% O(2)), with and without MPFF (10(-5) mol/L) or doxycycline (5 μg/mL) for 16 hours. The veins were analyzed for HIF-1α, HIF-2α, and their target gene expression, with real-time polymerase chain reaction and Western blot. The differences between gene expressions were tested with one-way analysis of variance with repeated measures, followed by the Dunnett test for multiple comparisons. P < .05 was considered significant., Results: Treatment of NVV organ cultures exposed to hypoxia with doxycycline or MPFF did not significantly alter the expression of HIF-1α and HIF-2α messenger (m)RNA and protein compared with untreated. Doxycycline also did not significantly affect the expression of HIF-1α and HIF-2α mRNA and protein in VVs exposed to hypoxia compared with untreated VVs. However, MPFF significantly reduced the expression of HIF-1α but not HIF-2α mRNA in VVs exposed to hypoxia compared with untreated VVs. Interestingly, the reduction of the expression of HIF-1α mRNA in VVs by MPFF was not reflected at the protein level. The mRNA expression of HIF target genes, namely glucose transporter-1, carbonic anhydrase-9, vascular endothelial growth factor, B-cell lymphoma 2/adenovirus E1B 19-kDa protein-interacting protein 3, prolyl hydroxylase domain-2, and prolyl hydroxylase domain-3, was not significantly altered in NVVs and VVs exposed to hypoxia and treated with doxycycline or MPFF compared with those untreated., Conclusions: Doxycycline and MPFF at a concentration corresponding to a therapeutic dose do not alter the activation of the HIF pathway in NVV and VV organ cultures exposed to hypoxia. Our findings suggest vein wall remodeling actions in NVVs and VVs are likely not HIF-dependent., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: Nuclear magnetic resonance (NMR) spectroscopy is an established tool for metabolic profiling of tissues or biofluids with utility in identifying disease biomarkers and changes in enzymatic or gene expression. This pilot study aims to compare the metabolic profiles of intact varicose and non-varicose vein tissue via magic angle spinning (MAS) NMR spectroscopy with a view to promoting the understanding of the pathogenesis of varicose vein formation., Methods: Varicose vein tissue (n = 8) was collected from patients undergoing varicose veins surgery. Control non-varicose great saphenous vein samples were collected from patients undergoing lower limb amputation (n = 3) and peripheral arterial bypass surgery (n = 5). Intact tissue samples (average weight 10.33 ± 0.8 mg) from each vein segment were analysed using 1D MAS (1)H NMR (600 MHz) spectroscopy. For selected vein samples, two-dimensional (2D) NMR experiments were performed. Differences between spectra from varicose and non-varicose tissues were elucidated using a variety of multivariate statistical analyses., Results: The metabolic profiles of varicose veins samples were clearly differentiated from non-varicose veins samples. Lipid metabolites were present at a higher concentration in the non-varicose veins group whilst creatine, lactate and myo-inositol metabolites were more characteristic of the varicose veins group., Conclusion: We demonstrate differential metabolic profiles between varicose veins and non-varicose veins. Elucidating the metabolic signature underlying varicose veins can further improve our understanding of the biological mechanisms of disease initiation, progression, and aid in identifying putative therapeutic targets., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate postoperative pain following endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) and identify risk factors for increased pain., Methods: Patients undergoing either segmental RFA (VNUS Closure Fast, VNUS Medical Technologies, San Jose, California) or EVLA (980 nm) for varicose veins completed a preoperative disease-specific quality-of-life questionnaire (Aberdeen Varicose Vein Questionnaire [AVVQ]) and a diary card recording postoperative pain, return to normal activities, and return to work. Median 3- and 10-day pain scores were calculated., Results: In all, 81 patients returned diary cards (RFA = 45, EVLA = 36). Patients receiving RFA reported less postoperative pain than those receiving EVLA at 3 days (14.5 vs 25.8 mm, P = .053, Mann-Whitney U test) and 10 days (13 vs 23.3 mm, P = .014, Mann-Whitney U test) and returned to work earlier than those receiving EVLA (median 5 vs 9 days, P = .022)., Conclusions: Patients treated with segmental RFA had less postoperative pain and returned to work quicker than those treated with EVLA.

Objectives: A variety of endovenous therapies for the treatment of superficial venous incompetence are currently available. The aim of this study was to evaluate the prevalence of endovenous techniques used by consultant vascular surgeons in the United Kingdom., Methods: An anonymous online survey of 16 multiple choice questions relating to the nature and provision of treatment for varicose veins was devised. Consultant members of the Vascular Society of Great Britain and Ireland were invited to participate by email., Results: A total of 108/352 (31%) surgeons completed the survey. The majority offered surgery as the first-line treatment for primary great saphenous vein (GSV) and small saphenous vein (SSV) incompetence (69% and 74%, respectively). Endovenous procedures were offered as first-line treatment by 32/108 (29.6%) for GSV reflux, 36/51 (70.6%) surgeons performed these under local anaesthetic and 21/51 (41.2%) were performed as an outpatient procedure. The most important factor influencing treatment decisions was considered to be patient preference by 77/108 (71.3%) surgeons, although 48/61 (78.7%) respondents were restricted by primary care trusts with regard to endovenous treatments, and 33/108 (30.6%) offered different treatments to private patients., Conclusion: Traditional surgery remains the most commonly offered treatment for patients with varicose veins. The provision of endovenous therapies varies greatly, and there are significant differences in local availability regarding these treatments.

Purpose: We investigated the hypothesis that fibrinogen increased DNA synthesis (and cell proliferation) of smooth muscle cells (SMCs) cultured from human saphenous vein and that the increased DNA synthesis was attenuated when cells were cultured on polymeric collagen., Methods: SMCs were cultured from human saphenous vein on plastic, fibronectin, monomeric, and polymeric collagen. Fibrinogen products were prepared by proteolytic digestion. DNA synthesis was measured by bromodeoxyuridine incorporation into DNA, cell proliferation by cell counting, cyclic adenosine monophosphate by enzyme-linked immunosorbent assay, and fibrinopeptide B labeled with iodine 125 used for binding studies., Results: Fibrin monomer (0.003-0.1 micromol/L) stimulated a concentration-dependent increase in DNA synthesis of up to 10-fold, which could be inhibited by the peptide Bbeta15-42. The stimulation of DNA synthesis was highest for cells cultured on plastic and lowest for cells cultured on type I collagen polymer. Much higher concentrations of fibrinogen (0.3-1 micromol/L) were required to effect similar increases in DNA synthesis. Fibrinogen had a particular effect to augment DNA synthesis, up to 14-fold, when cells were cultured on monomeric type I collagen. This augmented DNA synthesis was inhibited by a neutralizing antibody to urokinase-type plasminogen activator. Incubation of cells cultured on collagen monomer with fibrinogen resulted in production of fibrinopeptide B. Fibrinopeptide B (5 micromol/L) increased DNA synthesis by fourfold and had additive effects with fibrin monomer to increase DNA synthesis. Iodinated tyrosine fibrinopeptide B bound to SMCs (dissociation constant 0.6 micromol/L)., Conclusion: Cultured human saphenous vein SMCs appear to have high-affinity receptors for fibrin monomer and fibrinopeptide B, the engagement of which stimulates DNA synthesis. These mechanisms may be pertinent to the association between fibrinogen and vein graft stenosis in vivo.

Background: The association between raised levels of homocysteine, fibrinogen and lipoprotein (a), and the presence of pre-existing intimal hyperplasia (IH) in vein has not been assessed. The positive association between such hyperplasia and graft failure following infrainguinal arterial reconstruction, and between lipoprotein (a) and graft failure, is disputed. The influence of homocysteine on outcome has not been investigated prospectively., Methods: Fifty-seven patients (63 grafts) undergoing infrainguinal arterial reconstruction with saphenous vein were studied. Homocysteine, fibrinogen and lipoprotein (a) levels were measured, and a vein biopsy was taken at operation. Patients underwent graft surveillance and outcome at 12 months was determined., Results: Fifty-seven per cent of patients had hyperhomocysteinaemia. Patients with pre-existing IH had significantly higher homocysteine levels. There was no association between homocysteine and outcome, or between fibrinogen and pre-existing IH or outcome. Lipoprotein (a) levels were significantly lower in patients with pre-existing disease, and were lower, but not significantly, in those whose grafts failed. The correlation between pre-existing IH and vein graft failure was highly significant., Conclusion: Hyperhomocysteinaemia is associated with peripheral vascular disease and the development of pre-existing IH in vein, which itself is associated with vein graft failure.

Objectives: To assess the sensitivity of saphenous vein to potassium channel opening drugs (KCOs)., Methods: Saphenous vein, harvested at bypass surgery or high ligation for correction of varicose veins, was exposed to an in vitro flow circuit and vasomotor responses assessed by organ bath pharmacology., Outcome Measures: Effective drug concentrations for 50% reduction in vein ring tension (IC50)., Results: Vein rings pre-contracted with phenylephrine showed a concentration-dependent relaxation to all the KCOs tested with a potency ranking of HOE 234 > cromakalim > pinacidil > diazoxide. The relaxation to cromakalim was endothelium-independent and was inhibited by glibenclamide (an ATP-sensitive K+ channel blocker). The sensitivity of vein rings to cromakalim increased after exposure to arterial flow conditions for 90 minutes (IC50 before 1.7 +/- 0.25 microM and after 0.25 +/- 0.08 microM, p > 0.001). This effect was not evident after 90 min of venous flow conditions, 2.19 +/- 0.49 microM. When the workload on vein, exposed to arterial flow conditions, was reduced mechanically by external stenting with PTFE the increased sensitivity to cromakalim was abolished., Conclusions: Saphenous vein has ATP-sensitive K+ channels responsive to KCOs. The increased sensitivity to cromakalim, induced by arterial flow conditions, may represent an endogenous protective mechanism limiting ischaemic damage resulting from the higher workload imposed on grafted vein.

Objectives: The severity of pre-existing pathological changes in human saphenous vein (HSV) correlates with the development of vein graft stenosis and graft patency. The aim of this study was to investigate the influence of pre-existing intimal hyperplasia on development of the neointima in vitro, using an organ culture model., Materials and Methods: Segments of HSV were harvested during coronary artery bypass surgery. Histology was performed on part of the vein; the remainder was maintained in culture. Pre-existing intimal thickness (PIT) in HSV from day 0 and neointimal thickness (NIT) in cultured HSV were measured using computerised image analysis on histological sections. Day 0 and 14 veins were compared with respect to intimal hyperplasia., Results: Twelve pairs of veins were examined. A mean tissue ATP of 297 nmoles/g wet weight for cultured. HSV confirmed cell viability. Mean PIT was 180 microns (CI: 86-274) and mean NIT was 60 microns (CI: 48-72), with a significant correlation between them using the Spearman Rank test (Rs = 0.72; p = 0.008)., Conclusions: Pre-existing vein quality as measured by PIT correlates with the development of neointimal hyperplasia in culture, adding further support to clinical evidence that poor vein quality predisposes to vein graft stenosis due to an inherent susceptibility to intimal hyperplasia.

Purpose: Angioscopy for in situ vein graft preparation has been criticized on the basis that the trauma of instrumentation may predispose to accelerated intimal hyperplasia, jeopardizing patency rates following infrainguinal revascularization. The aim of this study was to assess the effects of angioscopic preparation on endothelial integrity and smooth muscle cell (SMC) behavior in an established organ culture model of human saphenous vein (HSV)., Methods: HSV was harvested from 12 patients during bypass surgery before and after angioscopic preparation. Endothelial integrity was evaluated by immunohistochemical staining with JC-70 and scanning electron microscopy (SEM); remaining segments of pre- and postangioscopy vein were maintained in culture for 14 days in medium supplemented with 30% fetal calf serum. Viability was confirmed by measurement of tissue adenosine triphosphate on day 14 and thickness of the neointima was measured by computerized image analysis of histologic sections. Monoclonal antibodies to proliferating cell nuclear antigen (PCNA) were used as an immunohistochemical marker for proliferating SMCs., Results: There was a significant reduction in the percentage staining by JC-70 (71.3% versus 20.4%) in pre- versus postangioscopy vein (p = 0.002 by Wilcoxon's rank test; n = 12). This was supported by SEM images. Despite this, there were no significant differences between the pre- and postangioscopy HSVs after 14 days of culture with respect to neointimal thickness (61 versus 56 microns) and staining with PCNA (4.80 versus 4.08 nuclei per 10 microns), all according to Wilcoxon's rank test., Conclusions: Angioscopic vein graft preparation is associated with endothelial cell loss but does not induce additional neointimal hyperplasia in HSV in vitro. These results suggest that angioscopic manipulation does not alter SMC behavior.

Objectives and Study Design: The diagnostic capability of angioscopy for endoluminal evaluation is established and its superiority over arteriography for completion studies has been confirmed. The therapeutic use of angioscopy in vein graft preparation is more controversial. The aim of this prospective study was to establish whether angioscopic vein preparation confers real benefits over existing techniques., Methods: Forty-seven patients were randomised to either full angioscopic (ANG) vein preparation (23 patients) or conventional (CON) in situ grafting (19 patients). All patients underwent completion studies with arteriography and angioscopy and postoperatively, entered a Duplex graft surveillance programme., Results: There was a significant difference in the incidence of wound morbidity: 26% in the ANG group as against 63% in the CON group (Fisher's exact test: p = 0.043), but no significant differences with respect to duration of operation, duration of vein graft preparation, length of hospital stay and both 30 day and 12 month secondary cumulative patencies (log rank test: p > 0.5). Completion angioscopy detected eight persistent valve cusps in six patients, all missed at arteriography, but failed to detect arteriovenous fistulae., Conclusions: Angioscopic preparation reduces wound morbidity and complements arteriography for detecting intraoperative defects. A large, prospective, randomised trial is now warranted to fully evaluate the potential therapeutic role of angioscopy with respect to current vascular practice.

Objectives: Although autogenous vein is the conduit of choice for infrainguinal bypass grafting, some 20-30% of vein grafts fail during the first year postoperatively. Many of these failed veins are now known to have pre-existing pathological changes. Angioscopy enables intraoperative endoluminal visualisation of veins and can reveal anomalies, some previously unsuspected, despite preoperative Duplex ultrasound mapping and normal external appearances. The aim of this study was to compare angioscopic findings with contemporary histological appearances and with subsequent graft outcome and ultimately, to identify those endoluminal features which might be predictive for failure., Methods: Angioscopic vein inspection was carried out using Olympus 1.4 and 2.2mm angioscopes in patients undergoing femoropopliteal/distal bypass. Severe disease in the veins of five patients led to preferential use of polytetrafluoroethylene (PTFE) for above-knee bypasses. The remaining 38 videotaped sequences were reviewed by two surgeons and scored using a scale of 0 to 3, based on frequency and distribution of angioscopically detected lesions. These included haemorrhagic mural plaques, flimsy intraluminal strands, webs/bands and mobile/adherent thrombus. Vein harvested at operation was assessed by a pathologist according to the level of pre-existing abnormality., Results: There were significant associations between angioscopy/histology scores and graft survival (chi 2 = 22.00; df:3; p < 0.001; chi 2 = 22.43; df:3; p < 0.001 respectively). There was a significant correlation between angioscopy and histology scores (R8 = 0.725; p < 0.001)., Conclusions: Angioscopy allows immediate identification of the at risk, poor quality vein graft at the time of surgery, without the delays inherent with histological preparation and assessment. Recognition of abnormalities at angioscopy may ultimately improve graft outcome by prospectively eliminating use of poor vein.

Aim: To evaluate angioscopy in this Unit with respect to its application in lower limb vascular reconstructions. By providing magnified, colour images of the luminal surfaces of vein grafts, anastomoses and native arteries, angioscopy allows direct visualisation of imperfections and is sensitive in diagnosing technical problems. However, assessment is qualitative and magnification of the image can distort the operator's impression of true size. Angioscopy would be more versatile if it were possible to quantify the observed images., Method: A new technique has been developed to measure intra-luminal diameter from the angioscopic images. A linear displacement transducer is attached to the angioscope and accurately monitors its axial shift. Signals from the transducer are received by a personal computer equipped with a video frame grabber and analogue digital converter, together with appropriate software. The computer generates calculated dimensions based on geometrical principles, once each angioscope has been appropriately calibrated at the outset., Results: Laboratory studies examining tubes of known dimensions have confirmed the reproducibility and accuracy of the technique. Simultaneous angioscopic and Duplex ultrasound measurements of the internal diameters of segments of vein suspended in a water bath were then carried out. Using the Duplex results as the 'gold standard', there was a strong correlation between the measurements obtained with the two techniques (Rs = 0.92)., Conclusions: In the clinical context, this system has the capability to generate accurate endoluminal measurements during angioscopy. This has application for quality control in the selection of veins and inspection of run-off vessels during bypass grafting and in completion studies, following both operative and percutaneous procedures.

The aetiology of vein graft stenosis is poorly understood. In a cohort of 88 patients, the mean internal diameter of the vein grafts that developed a stenosis was 3.7 (3.1-4.2) mm compared to 4.7 (4.4-5.0) mm in those that did not (p = 0.006). The mean lowest compliance value in the 11 patients who developed a stenosis was 0.1 (0.07-0.13) % per mmHg compared to 0.21 (0.19-0.23) % per mmHg in the rest (p < 0.001). The presence of vein incompetence, site of tributaries or valves and the degree of endothelial cell loss were not related to the development of vein graft stenoses. The presence of a macrophage infiltrate (p < 0.001), lymphocyte infiltrate (p < 0.025) and subendothelial smooth muscle cells (p < 0.05) were all significantly more common in those grafts that developed a stenosis. Vein quality is an important factor in the development of graft stenoses.

The ability of vein to dilate may allow smaller veins to be used for bypass if this change could be predicted. Sixty patients undergoing femorodistal popliteal or infrapopliteal bypass have had their long saphenous vein studied. Diameter measurements of the long saphenous vein have been performed using an ATL Duplex scanner at the groin, mid-thigh and knee. Measurements were performed preoperatively both at rest and with a venous occlusion cuff to dilate the vein and subsequently at 7 days and 3, 6, 9, 12 months after implantation. The mean diameter of the vein at the mid thigh was 4.2 mm non dilated, 5.1 mm with occlusion, 5.4 mm 7 days postoperatively and 5.5 mm at 12 months (p < 0.01 ANOVA). The mean diameter of the vein at the knee was 3.8 mm non-dilated, 4.8 mm with occlusion, 4.8 mm at 7 days and 5.0 mm at 12 months after operation (p < 0.01 ANOVA). If the minimum resting internal diameter of vein regarded as being suitable for bypass was 3 mm, this technique would have increased the vein utilisation rate by 22%. These results show that by using a technique of venous occlusion at the time of preoperative vein mapping the adaptive response of the vein can be predicted and this can result in an increased rate of vein utilisation.

Random vein samples taken prior to bypass surgery have shown certain pathological features. Long saphenous vein was taken from the groin (proximal) and knee to mid-calf (distal) of 85 patients undergoing femoro-distal bypass over a 2-year period. During this period only four patients had cephalic arm vein used; this was also studied. Histological examination was performed using haematoxylin and eosin and van Geison stains. Intimal hyperplasia was seen in 62 (73%) proximal and 74 (87%) distal samples. There were significantly more distal veins with moderate to severe focal hyperplasia and circular muscle hypertrophy (p < 0.05 and p < 0.001). Changes of diffuse intimal hyperplasia were seen in three of the cephalic veins. Muscle hypertrophy occurred in 58 (68%) of proximal segments compared to 75 (88%) of distal segments (p < 0.005). This study shows that significant pathological changes are seen in long saphenous and cephalic veins thought to be "normal". These changes are more evident in the distal long saphenous vein. These changes may have a significant effect on the outcome of vein bypass.

During femorodistal bypass angioscopy can be used in vein graft preparation allowing valve lysis and the identification of tributaries under direct vision. A total of 30 patients have undergone angioscopic assisted femorodistal bypass using either an Olympus or Stortz system. Nineteen patients have undergone full vein mobilisation and valve lysis under direct vision. Eleven patients had in situ bypass with ligation of tributaries, identified by the angioscope, through small stab incisions. No evidence of fistula or retained valve cusps was found by subsequent duplex scanning and arteriography. One of these grafts failed at 6 days due to an unrecognised outflow stenosis. The mean hospital stay after operation for this latter group of patients was 5.2 days (range 4.4-6.0 days) compared with 9.5 days (8.6-10.3 days) in a historical group of 30 patients (P < 0.001). Angioscopy is a useful aid in the performance of femorodistal bypass. Early experience suggests that hospital stay may be reduced by angioscope assisted in situ femorodistal bypass because of the minimal dissection involved.

Compliance measurements of 53 long saphenous veins before femorodistal bypass have been performed using a duplex scanner with venous occlusion for distension. These have been compared with the histological features of the veins. There was significantly more moderate or severe focal hyperplasia and circular muscle hypertrophy in distal long saphenous vein than in its proximal counterpart (P < 0.01 and P < 0.05 respectively). The mean (95 per cent confidence interval) compliance of distal vein with moderate or severe hyperplasia was 0.16 (0.13-0.19) compared with 0.29 (0.22-0.36) for that with no, minimal or mild hyperplasia (P = 0.001). The mean compliance of distal vein with moderate or severe muscle hypertrophy was 0.19 (0.17-0.21) and of vein with no, minimal or mild hypertrophy 0.25 (0.21-0.29) (P = 0.14). The mean lowest compliance in seven patients who developed stenosis was 0.10 (0.07-0.13) compared with 0.21 (0.16-0.26) in the rest (P < 0.001). Preoperative measurement of vein compliance can be used to identify vein with marked pre-existing intimal hyperplasia and as a predictor of future graft stenosis.

In 30 patients undergoing femoro-distal bypass the effect of papaverine and praxilene on blood flow in the graft was measured. The mean resting flow was 129 ml min-1 (range: 91-167) and after papaverine was 202 ml min-1 (142-262) and after praxilene was 205 ml min-1 (143-267). Praxilene has a similar effect to papaverine in the augmentation of blood flow, and further investigation is needed to see if long-term praxilene administration might improve graft survival.

Donor homograft vein is sometimes used in vascular surgery when autograft vein is not available. The optimum mode of storage remains controversial. An ideal solution would cause cellular disruption and thus decrease the immunogenicity of the donor vein, and allow a preserved collagen matrix and basement membrane, required to maintain the structure. Human donor vein was stored in normal saline at 4 degrees C, glycerol at 4 degrees C, liquid nitrogen and at -50 degrees C. The veins were examined at 1, 3, 7, 14, 21, 28, 35, 42, 49 and 56 days of storage using light microscopy, histochemistry, transmission and scanning electron microscopy. Vein stored at 4 degrees C in normal saline fulfilled the two requirements of preservation of the basement membrane and collagen matrix of the vein with loss of the cellular elements. We conclude, that in morphological terms this is the best mode of preservation. However further in vitro and in vivo studies are necessary.

The diameter of the long saphenous vein has been shown to affect the outcome of femoro-distal bypass. Many surgeons regard a vein with a diameter of less than 3 mm as being unsuitable. The long saphenous vein was studied in 35 patients undergoing femoro-distal bypass. Diameter measurements of the vein were performed using an ATL duplex scanner at the groin, mid-thigh and knee. Measurements were performed preoperatively both at rest and with a venous occlusion cuff to dilate the vein, and subsequently at 7 days and 2 months after implantation. The mean diameter of the vein at the mid-thigh was 4.1 mm non-dilated, 5.1 mm with occlusion, 5.0 mm 7 days postoperatively and 5.2 mm at 2 months (ANOVA, p less than 0.05). The mean diameter of the vein at the knee was 3.9 mm non-dilated, 4.8 mm with occlusion, 4.8 mm at 7 days and 4.9 mm at 2 months after operation (ANOVA, p less than 0.025). In all five patients whose preoperative resting vein diameter at the knee or mid-thigh was less than 3 mm, preoperative dilatation occurred, such that the diameter became greater than 3 mm. These results suggest that by using a technique of venous occlusion at the time of pre-operative vein mapping, the functional diameter of the vein can be predicted and vein utilisation may be increased.