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Objective The early twenty first century witnessed a decrease in mortality from abdominal aortic aneurysms (AAA), which was associated with variations in the prevalence of cardiovascular risk factors. This study investigated whether these trends continued into the second decade of the twenty first century. Methods Information on AAA mortality (2001 − 2015) using International Classification of Diseases codes was extracted from the World Health Organization (WHO) mortality database. Data on risk factors were extracted from the Institute of Health Metrics and Evaluation and WHO InfoBase, and data on population from the World Development Indicators database. Regression analysis of temporal trends in cardiovascular risk factors was done independently for correlations with AAA mortality trends. Results Seventeen countries across four continents met the inclusion criteria (Australasia, two; Europe, 11; North America, two; Asia, two). Male AAA mortality decreased in 13 countries (population weighted average: −2.84%), while female AAA mortality decreased in 11 countries (population weighted average: −1.64%). The decrease in AAA mortality was seen in both younger ( 65 years) patients. The decrease in AAA mortality was more marked in the second decade of the twenty first century (2011 – 2015) compared with the first decade (2001 – 2005 and 2006 – 2010). Trends in AAA mortality positively correlated with smoking (males: p = .03X, females: p = .001) and hypertension (males: p = .001, females: p = .01X). Conversely, AAA mortality negatively correlated with obesity (males: p = .001, females: p = .001), while there was no significant correlation with diabetes. Conclusion AAA mortality has continued to decline and seems to have declined at an even faster rate in the second decade of the twenty first century, albeit with heterogeneity among countries. These variations are multifactorial in origin but further efforts targeting smoking cessation and blood pressure control will probably contribute to continued reductions in AAA mortality.

Summary: Background: The aim was to evaluate the safety and efficacy of a high pressure, non-compliant balloon in the treatment of infrapopliteal occlusive disease in Asian patients with chronic limb threatening ischaemia (CLTI) from Singapore. Patients and methods: Prospective, multi-centre, single arm, non-randomized study. Immediate technical success, 6-month primary vessel patency (determined by Duplex ultrasonography), limb salvage, one-year clinically driven target lesion re-intervention (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. Results: 86 patients (63% males, mean age 68.9 ± 9.9 years) were enrolled over a 15-month period. Diabetes mellitus (DM) and end-stage renal failure (ESRF) were present in 94% and 38% of patients respectively. All had some degree of tissue loss at baseline (Rutherford scale 5 and 6 = 91% and 9% respectively). Of the 86 legs, 72% had 3 crural vessel disease and 84% had moderate/severe vessel wall calcification. 90% had > = 1 TASC D tibial lesion. Acute technical success was 89%. One month mortality was 3.5% and one-year freedom from TLR was 91%. 6-month tibial patency was 73%. 54/66 (82%) patients had at least one target treated tibial artery open at 6 months. A lower baseline toe pressure (OR 1.03, 95%CI 1.00–1.05) and elastic recoil post angioplasty (OR 0.20, 95%CI 0.05–0.79) were associated with a worse 6 month tibial patency. One-year AFS was 67%. 47/66 (71%) patients had a clinical improvement of at least one Rutherford class at 6 months and 52/59 (88%) experienced complete wound healing at 12 months. Conclusions: Use of a high pressure non-compliant balloon is safe and efficacious in treating highly complex infra-popliteal atherosclerotic lesions in an otherwise challenging population of CLTI patients with a high incidence of DM and ESRF. It is associated with highly satisfactory acute technical success, 6-month target lesion patency and one-year limb salvage.

Objective/Background The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. Methods Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. Results Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease ( p p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques ( p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques ( p = .03). CCL19 also co-localised with CD3 + T-cell lymphocytes in the core region, around where CCL19 was expressed. Conclusions CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Background Screening for abdominal aortic aneurysm (AAA) has reduced the rate of AAA rupture. However, cardiovascular disease is still a major cause of death in men with an AAA. The aim of this study was to assess cardiovascular risk in patients with a small AAA. Methods Standard PRISMA guidelines were followed. Analysis was performed of studies reporting cardiovascular outcomes in patients with a small AAA (30–54 mm). Weighted metaregression was performed for cardiovascular death in patients with a small AAA, and the prevalence of cardiovascular disease was reviewed. Results Twenty-one articles were identified describing patients with an AAA, and the prevalence of, and death from, cardiovascular disease. Ten of these reported cardiovascular death rates in patients with a small AAA. Some 2323 patients with a small AAA were identified; 335 cardiovascular deaths occurred, of which 37 were due to AAA rupture. Metaregression demonstrated that the risk of cardiovascular death was 3·0 (95 per cent c.i. 1·7 to 4·3) per cent per year in patients with a small AAA (R2 = 0·902, P < 0·001). The prevalence of ischaemic heart disease (44·9 per cent), myocardial infarction (26·8 per cent), heart failure (4·4 per cent) and stroke (14·0 per cent) was also high in these patients. Conclusion The risk of cardiovascular death in patients with a small AAA is high and increases by approximately 3 per cent each year after diagnosis. Patients with a small AAA have a high prevalence of cardiovascular disease. Patients a small AAA should be considered for lifestyle modifications and secondary cardiovascular protection.

Background Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently. The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size. Methods and results Literature review identified 106 studies suitable for inclusion. Meta-analysis demonstrated a significant difference between matrix metalloproteinase (MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C-reactive protein (CRP), α1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor α, osteoprotegerin, osteopontin, interferon γ, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level. Conclusion A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically.

Background The National Vascular Registry Report on Surgical Outcomes (NVSRO) coincided with the update of the National Health Service Standard Contract for Specialized Vascular Services in Adults (NHSSCSVS). The latter promises patients minimum standards for vascular centres. The present study aimed to determine whether current data support the standards proposed in the NHSSCSVS. Methods Numbers of abdominal aortic aneurysm (AAA) repairs and carotid endarterectomies (CEAs) performed by hospital Trust and surgeon, and their outcomes were obtained from the NVRSO. These were assessed against NHSSCSVS recommendations that included: more than 60 AAA repairs per year per Trust, over 50 CEAs per year per Trust and at least six vascular surgeons per Trust. Results Based on NVRSO data, 107 hospital Trusts (92·2 per cent) would fail to meet the minimum standards required to achieve vascular centre status. Outcomes were poorer in these hospitals (overall mortality rate after AAA: 2·7 versus 1·3 per cent; P = 0·007). There were strong associations between number of AAA repairs or CEAs per Trust and better outcomes (AAA repair, P < 0·001; CEA, P = 0·004). These remained significant when analysed by individual surgeon (AAA repair, P < 0·001; CEA, P < 0·001). Trusts undertaking 60 or fewer elective AAA repairs per year had significantly higher elective AAA mortality rates (2·7 versus 1·7 per cent; P = 0·010). Trusts performing a minimum of 50 CEAs per year had significantly lower perioperative mortality/morbidity rates (1·9 versus 3·0 per cent; P = 0·032). Trusts with seven or more surgeons demonstrated lower AAA-related mortality rates (1·7 versus 2·7 per cent; P = 0·018). Conclusion Data from the NVRSO suggest that the majority of hospital Trusts presently fail to meet the standards for vascular centre status. NVRSO data support a standard of more than 60 elective AAA repairs and 50 CEAs per Trust per year. A minimum of seven vascular surgeons per unit was associated with better outcomes. These data support the ongoing remodelling of vascular services in the UK.

Lifelong surveillance is not cost-effective after endovascular aneurysm repair (EVAR), but is required to detect aortic complications which are fatal if untreated (type 1/3 endoleak, sac expansion, device migration). Aneurysm morphology determines the probability of aortic complications and therefore the need for surveillance, but existing analyses have proven incapable of identifying patients at sufficiently low risk to justify abandoning surveillance. This study aimed to improve the prediction of aortic complications, through the application of machine-learning techniques. Patients undergoing EVAR at 2 centres were studied from 2004–2010. Aneurysm morphology had previously been studied to derive the SGVI Score for predicting aortic complications. Bayesian Neural Networks were designed using the same data, to dichotomise patients into groups at low- or high-risk of aortic complications. Network training was performed only on patients treated at centre 1. External validation was performed by assessing network performance independently of network training, on patients treated at centre 2. Discrimination was assessed by Kaplan-Meier analysis to compare aortic complications in predicted low-risk versus predicted high-risk patients. 761 patients aged 75 +/− 7 years underwent EVAR in 2 centres. Mean follow-up was 36+/− 20 months. Neural networks were created incorporating neck angu- lation/length/diameter/volume; AAA diameter/area/volume/length/tortuosity; and common iliac tortuosity/diameter. A 19-feature network predicted aor- tic complications with excellent discrimination and external validation (5-year freedom from aortic complications in predicted low-risk vs predicted high-risk patients: 97.9% vs. 63%; p < 0.0001). A Bayesian Neural-Network algorithm can identify patients in whom it may be safe to abandon surveillance after EVAR. This proposal requires prospective study.

Mortality after lower limb amputation is high, with UK 30-day mortality rates of 9-17%. We performed a retrospective analysis of factors affecting early and late outcome after lower limb amputation for peripheral vascular disease or diabetic complications at a UK tertiary referral vascular centre between 2003 and 2010. Three hundred and thirty-nine patients (233 male), of median (IQR [range]) age 73 (62-79 [26-92]) years underwent amputation. Thirty-day mortality was 12.4%. On regression modelling, the risk of 30-day mortality was increased in patients of ASA grade ≥ 4 (OR 4.23, 95% CI 2.07-8.63), p 79 years (HR 2.78, 95% CI 1.82-4.25), p

Background— Contemporary data from Western populations suggest steep declines in abdominal aortic aneurysm (AAA) mortality; however, international trends are unclear. This study aimed to investigate global AAA mortality trends and to analyze any association with common cardiovascular risk factors. Methods and Results— AAA mortality (1994–2010) using International Classification of Diseases codes were extracted from the World Health Organization mortality database and age standardized. The World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Nineteen World Health Organization member states were included (Europe, 14; Australasia, 2; North America, 2; Asia, 1). Regression analysis of temporal trends in cardiovascular risk factors (1946–2010) was done independently for correlations to AAA mortality trends. Global AAA mortality trends show substantial heterogeneity, with the United States and United Kingdom recording the greatest national decline, whereas internationally, male individuals and those P ≤0.03), cholesterol ( P ≤0.03), and smoking prevalence ( P ≤0.02) in males and females. Body mass index demonstrated a negative linear association with AAA mortality ( P ≤0.007), whereas fasting blood glucose showed no association. Conclusions— AAA mortality has not declined globally, and this study reveals that differences between nations can be explained by variations in traditional cardiovascular risk factors. Declines in smoking prevalence correlate most closely with declines in AAA mortality, and a novel obesity paradox has been identified that requires further investigation. Public health measures could therefore further reduce global AAA mortality, with greatest benefits in the younger age group.

Screening for abdominal aortic aneurysm (AAA) has been shown to be effective at reducing AAA-related mortality and is cost-effective. There are, however, significant variations in AAA screening protocols between healthcare systems and numerous challenges to be overcome. Further evidence of cost- and clinical effectiveness is likely to be required before there is widespread international adoption of AAA screening.

To report a systematic review and meta-analysis of outcomes following endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA) vs. those with favorable neck anatomy (FNA).Systematic review and meta-analysis of data on EVAR in patients with HNA and FNA was performed by 2 reviewers in February 2013. An eligible study was required to have at least 50 participants and to incorporate one or more of the HNA criteria of neck length15 mm, neck diameter28 mm, and/or angulation60°. Of the 24 full-length articles ultimately reviewed, 8 were excluded, resulting in 16 articles that were suitable for inclusion in the meta-analysis. The study size ranged from 55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039 patients in the HNA group. Mean follow-up ranged from 9 to 49 months.Analysis of the pooled data revealed a significant increase in 30-day mortality (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p0.01), intraoperative adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30-day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8% HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria were used to define HNA. For outcomes at30 days, the increase in secondary interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but aneurysm-related mortality, all-cause mortality, migration, and aortic rupture did not achieve statistical significance. There was no difference in rates of sac expansion. Analysis of endoleak rates revealed a significant increase in 30-day type I endoleaks (OR 2.92, 95% CI 1.61 to 5.30; p0.001) and late type I endoleaks (OR 1.71, 95% CI 1.31 to 2.23; p0.0001) in patients with HNA.These results suggest that performing EVAR in patients with HNA increases the technical difficulty and results in poorer short-term outcomes. The higher rates of early and late type I endoleaks, along with secondary interventions, suggest that increased monitoring should be performed in this category of patient to ensure rapid treatment.

Background Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm (EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance. Methods Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan–Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre. Results Some 761 patients, with a median age of 75 (interquartile range 70–80) years, underwent EVAR. Median follow-up was 36 (range 11–94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter (P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002). Conclusion The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits.

Objective Abdominal aortic aneurysm (AAA) is a condition that mainly affects elderly men. At present, there is no effective medical therapy that can retard aneurysm growth or prevent aneurysm rupture. There is evidence that angiogenesis within the wall of an aortic aneurysm may play key roles in aneurysm progression as well as rupture. The use of anti-angiogenic therapy as potential medical therapy in AAA is a promising strategy but has never been studied in detail. Design This paper discusses the basic mechanisms of angiogenesis, the role played by angiogenesis in aortic aneurysms and the potential therapeutic role of anti-angiogenic drugs against aneurysm expansion or rupture. Results Angiogenesis is a multi-step process which is fundamental for growth and differentiation of various tissues within a multi-cellular organism. Hypoxia and inflammation are key stimuli for activation of neoangiogenesis. Investigations in both human tissues and animal models of AAA have shown that angiogenesis is a pathological hallmark of AAA and appears to play a role in the development and progression of the condition. Pre-clinical studies have shown that anti-angiogenic drugs can potentially be effective in reducing the intensity of aneurysm formation, suggesting that such drugs may potentially be useful as novel drug therapy for AAA in humans. Conclusion Current evidence suggests that angiogenesis contributes to the destructive processes within aneurysmal aortic wall. As novel drug therapy for aortic aneurysms (for use in humans) is still eluding researchers, anti-angiogenic pathway appears to be an attractive approach.

Objectives A recent GWAS demonstrated an association between low density lipoprotein receptor related protein 1 (LRP1) and Abdominal Aortic Aneurysm (AAA). This review aims to identify how LRP1 may be involved in the pathogenesis of abdominal aortic aneurysm. Design and materials A systematic review of the English language literature was undertaken in order to determine whether LRP1 and associated pathways were plausible candidates for contributing to the development and/or progression of AAA. Methods and results A comprehensive literature search of MEDLINE (since 1948), Embase (since 1980) and Health and Psychological Instruments (since 1985) was conducted in January 2012 identified 50 relevant articles. These studies demonstrate that LRP1 has a diverse range of biological functions and is a plausible candidate for playing a central role in aneurysmogenesis. Importantly, LRP1 downregulates MMP (matrix metalloproteinase) activity in vascular smooth muscle cells and regulates other key pathways involved in extracellular matrix remodelling and vascular smooth muscle migration and proliferation. Crucially animal studies have shown that LRP1 depletion leads to progressive destruction of the vascular architecture and aneurysm formation. Conclusions Published evidence suggests that LRP1 may play a key role in the development of AAA.

Background It is common for authors to introduce a paper by demonstrating the importance of the clinical condition being addressed, usually by quoting data such as mortality and prevalence rates. Abdominal aortic aneurysm (AAA) epidemiology is changing, and therefore such figures for AAA are subject to error. The aim of this study was to analyse the accuracy of AAA prevalence and mortality citations in the contemporaneous literature. Methods Two separate literature searches were performed using PubMed to identify studies reporting either aneurysm prevalence or mortality. The first 40 articles or those published over the last 2 years were included in each search to provide a snapshot of current trends. For a prevalence citation to be appropriate, a paper had to cite an original article publishing its own prevalence of AAA or a national report. In addition, the cited prevalence should match that published within the referenced article. These reported statistics were compared with the most recent data on aneurysm-related mortality. Results The prevalence of AAA was reported to be as low as 1% and as high as 12.7% (mean 5.7%, median 5%). Only 47.5% of studies had referenced original articles, national reports or NICE, and only 32.4% of cited prevalences matched those from the referenced article. In total 5/40 studies were completely accurate. 80% of studies cited aneurysm mortality in the USA, with the majority stating 15,000 deaths per year (range 9,000 to 30,000). Current USA crude AAA mortality is 6,289 (2010). Conclusion References for AAA mortality and prevalence reported in the current literature are often inaccurate. This study highlights the importance of accurately reporting mortality and prevalence data and using up-to-date citations.

The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) pathogenesis is well described. However, a clear role for the MMPs in disease prediction has not been established. The aim of this study was to determine if circulating levels of MMPs correlated with AAA diameter and with MMP concentrations within the aneurysm wall. Preoperative plasma samples and intraoperative infrarenal AAA sac biopsies were taken in a standard fashion from 31 patients undergoing elective repair. The concentrations of MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2 were quantified in plasma and aneurysm wall homogenates using enzyme-linked immunosorbent assay. Comparison used the Spearman correlation. There were no correlations between the paired plasma and aneurysm wall concentrations for any MMP or TIMP. Correlation between MMP-9 levels in the aneurysm wall and aneurysm diameter was negative ( r = −.42, p = .019). Other correlations between plasma and tissue levels with aneurysm diameter were nonsignificant.

Background The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) formation is well established. However the changes in plasma MMP levels with AAA rupture have not been reported. The aim of this study was to determine circulating levels of MMPs in non-ruptured and ruptured AAA immediately prior to open repair. Methods Concentrations of MMPs and their endogenous tissue inhibitors (TIMPs) were quantified using ELISA in pre-operative plasma samples from non-ruptured and ruptured AAA. Results MMP1 and MMP9 were elevated in the plasma of ruptured AAA versus non-ruptured AAA. A four-fold elevation in pre-operative plasma MMP9 was associated with non-survival at 30 days from rupture surgery compared with those surviving for greater than 30 days. Conclusion In conclusion, these findings support the role of MMPs in AAA pathogenesis. Elevation of MMP9 was associated with ruptured aneurysm related 30-day mortality and may represent a survival indicator in this group.

Objectives Patients with aortic aneurysms have significant comorbidities which influence outcome. Our practice includes comprehensive assessment to identify comorbidities, allowing subsequent medical optimisation prior to aneurysm repair. The aim of this study was to assess this process and to identify any factors predictive of outcome. Design Prospective observational study. Materials Medical case notes of 200 patients referred with aortic pathology. Methods Data analysed included preoperative, perioperative and postoperative factors. Multiple logistic regression analysis was performed to identify predictors of outcome. Results Following assessment 17 patients (8.5%) were found to be unfit for intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group assessment uncovered previously undiagnosed cardiac, respiratory and renal comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic regression analysis indicated that optimisation by a renal physician reduced post-operative renal impairment (OR 0.12, 95% CI 0.03–0.45, P = 0.002) while optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI 0.05–0.99, P = 0.049). An abnormal echocardiogram was associated with pneumonia (OR 6.9, 95% CI 1.6–29, P = 0.01) and death (OR 7.9, 95% CI 1.15–54, P = 0.036). Conclusion Pre-operative assessment identifies previously undiagnosed comorbidity in a significant proportion of patients. Subsequent medical optimisation may reduce post-operative morbidity and mortality.

To search for novel transcriptional pathways that are activated in abdominal aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA expression at the aneurysm rupture edge to anterior sac, and selected results were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR). This study identified apoptosis, angiogenesis, and inflammation as potentially important participants during the process of aneurysm rupture.

Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.

Abdominal aortic aneurysm (AAA) rupture is the 13th commonest cause of death in the Western World. Although considerable research has been applied to the aetiology and mechanism of aneurysm expansion, little is known about the mechanism of rupture. Aneurysm rupture was historically considered to be a simple physical process that occurred when the aortic wall could no longer contain the haemodynamic stress of the circulation. However, AAAs do not conform to the law of Laplace and there is growing evidence that aneurysm rupture involves a complex series of biological changes in the aortic wall. This paper reviews the available data on patient variables associated with aneurysm rupture and presents the evidence implicating biological factors in AAA rupture.

Introduction Biomarkers have the potential to improve the clinical management of patients with AAA. Report A prospective, proteomics discovery study was undertaken to compare patients with AAA ( n = 20) to matched screened controls ( n = 19) for plasma protein expression. Surface-Enhanced-Laser-Desorption-Ionization Time of Flight Mass Spectrometry (SELDI ToF MS) coupled with Artificial Neural Networks (ANN) analysis identified six protein related diagnostic biomarker ions with a combined AUC of 0.89. Discussion This study discovered a signature plasma protein profile for patients with AAA and demonstrated that mass spectrometric based research for disease specific biomarker of AAA is feasible.

Background— Temporal trends in mortality from thoracic aortic disease are unclear. This study examined trends in mortality from thoracic aortic aneurysm (TAA) and aortic dissection (AD) with the aim of identifying associations with trends in established cardiovascular risk factors. Methods and Results— TAA and AD mortality (1994–2010) using International Classification of Diseases codes was extracted from the World Health Organization mortality database and age standardized. World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Eighteen World Health Organization member states were included (Europe=13, Australasia=2, North America=2, Asia=1). Ecological regression was performed of temporal trends in cardiovascular risk factors (1946–2010) and independent correlations to mortality trends. TAA and AD mortality trends show substantial heterogeneity but are generally declining. TAA mortality has increased in Hungary, Romania, Japan, and Denmark, and AD mortality has increased in Romania and Japan; therefore, the mortality decline is not universal. A linear relationship exists between trends in systolic blood pressure, cholesterol, and body mass index and mortality from TAA. Body mass index demonstrated a negative linear association with female AD mortality, whereas trends in systolic blood pressure demonstrated a positive linear relationship with male AD mortality. Trends in smoking prevalence were not associated with TAA or AD mortality trends. Conclusions— This population-level ecological regression provides evidence that mortality secondary to TAA and mortality secondary to AD are both in decline. Differences between countries could be explained by population-level changes in common cardiovascular risk factors. Public health measures could further reduce mortality from TAA and AD.

Interleukin-6 (IL-6) is associated with abdominal aortic aneurysm (AAA) development and is an independent risk factor for cardiovascular mortality. We tested the hypothesis that aneurysm repair reduces circulating IL-6 by comparing concentrations in patients with large AAA awaiting repair ( n =50) with patients having undergone open ( n =34) or endovascular ( n =66) repair. Only open repair was associated with a significant reduction in IL-6 ( p =0.025). These results suggest that AAAs remain biologically active following endovascular repair. Aneurysm-derived IL-6 may have serious implications for cardiovascular health, and attention should be directed to modifying cardiovascular risk factors in these patients, even after successful aneurysm repair.

Studies suggest that aneurysm-derived cytokines perpetuate the cycle of inflammation and proteolysis that is the pathological hallmark of abdominal aortic aneurysms (AAA). As interleukin (IL)-6 is an independent risk factor for cardiovascular mortality, such cytokines may also have important systemic effects. The purpose of this study was to investigate the effect of aneurysm repair on circulating levels of cytokines. Inflammatory cytokines were measured in 99 patients with AAA and 100 patients who had undergone AAA repair in the past. There was a significant reduction in IL-10 in the postoperative group, and a nonsignificant trend toward reduction in IL-6 and CRP in the postoperative group. Subgroup analysis of the postoperative group revealed significantly lower levels of IL-6 and CRP in the open group compared to endovascular aneurysm repair (EVAR). These results suggest that aneurysm repair may have an effect upon chronic levels of circulating inflammatory cytokines, and that the type of repair may exert some influence.

Background Any possible long-term benefit from endovascular (EVAR) versus open surgical repair for abdominal aortic aneurysm (AAA) remains unproven. Long-term data from the Open Versus Endovascular Repair (OVER) trial add to the debate regarding long-term all-cause and aneurysm-related mortality. The aim of this study was to investigate 30-day and long-term mortality, reintervention, rupture and morbidity after EVAR and open repair for AAA in a systematic review. Methods Standard PRISMA guidelines were followed. Random-effects Mantel–Haenszel meta-analysis was performed to evaluate mortality and morbidity outcomes. Results The existing published randomized trials, together with information from Medicare and SwedVasc databases, were included in a meta-analysis. This included 25 078 patients undergoing EVAR and 27 142 undergoing open repair for AAA. Patients who had EVAR had a significantly lower 30-day or in-hospital mortality rate (1·3 per cent versus 4·7 per cent for open repair; odds ratio (OR) 0·36, 95 per cent confidence interval 0·21 to 0·61; P < 0·001). By 2-year follow-up there was no difference in all-cause mortality (14·3 versus 15·2 per cent; OR 0·87, 0·72 to 1·06; P = 0·17), which was maintained after at least 4 years of follow-up (34·7 versus 33·8 per cent; OR 1·11, 0·91 to 1·35; P = 0·30). There was no significant difference in aneurysm-related mortality by 2 years or longer follow-up. A significantly higher proportion of patients undergoing EVAR required reintervention (P = 0·003) and suffered aneurysm rupture (P < 0·001). Conclusion There is no long-term survival benefit for patients who have EVAR compared with open repair for AAA. There are also significantly higher risks of reintervention and aneurysm rupture after EVAR.

Background— Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom. Methods and Results— All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years. Conclusions— In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base.

Objective Type II endoleak is the most common complication after endovascular abdominal aortic aneurysm repair (EVAR); however, its natural history is unclear. The aim of this study was to examine the incidence and outcomes of type II endoleak, at a single institution after EVAR. Methods A total of 904 consecutive patients who underwent EVAR between September 1995 and July 2013 at a single centre were entered onto a prospective database. All patients were followed up by duplex ultrasound (DUSS). Patients who developed type II endoleak were compared for preoperative demographics, mortality, and sac expansion. Results A total of 175(19%) patients developed type II endoleak over a median follow-up of 3.6 years (1.5-5.9 years); 54% of type II endoleaks spontaneously resolved within 6 months (0.25-1.2 years). No difference was found in preoperative demographics or choice of endograft between the two groups. Survival was significantly higher in the group with type II endoleak (94.1% vs. 85.6%; p = .01) and this effect was most pronounced in those with late type II endoleaks (97.7% vs. 85.6% p = .004). No difference was seen in aneurysm-related mortality or rate of type I endoleak between the two groups. Freedom from sac expansion (>5 mm from preoperative diameter) was significantly lower in the group of patients with type II endoleak (82.5% vs. 93.2%, p = .0001); however, at a threshold of >10 mm from preoperative diameter no difference was seen. Conclusions Patients with isolated type II endoleak demonstrate equivalent aneurysm-related mortality and an improved survival.

Death from abdominal aortic aneurysm (AAA) rupture can be significantly lowered through single screening with ultrasound scan in men aged 65e74 years. Nevertheless, AAA screening is not without risks. It is therefore a mandatory requirement that AAA screening programmes inform potential participants of any possible adverse outcomes. In the UK the National Health Service Abdominal Aortic Aneurysm Screening Program summarises the risks involved clearly and unambiguously in its standard national information leaflet sent to all men on invitation. Historically, there were concerns over the implementation of a national AAA screening programme in the UK owing to high mortality after elective AAA repair (7.5%d double the average for the rest of Europe). Following an agreed action plan to reduce mortality from elective AAA repair through a quality improvement framework consisting of best practice standards for aortic surgery, the 30-day mortality after elective AAA surgery improved to 2.4%. It is imperative that the low mortality be maintained so that AAA screening will continue to be effective. In this issue, Linne et al. compared postoperative mortality and morbidity between patients with screendetected versus nonscreen-detected AAAs. They reported low postoperative mortality after AAA surgery and their data revealed no differences in postoperative mortality (at 30 days, 90 days, and 1 year) or morbidity between patients with screen-detected AAAs and agematched controls. The effectiveness of AAA screening is clearly dependent on the safe management of any AAA detected, and the low postoperative mortality and morbidity in screen-detected AAA patients from the Swedish National Registry for Vascular Surgery (Swedvasc) are therefore very encouraging. Linne et al. postulated that nonscreen-detected male patients with AAA will have more comorbidities that those detected through screening. Intuitively, this would seem reasonable, and Linne et al. suggested that nonscreened patients are more likely to be demographically

s / International Journal of Surgery 23 (2015) S15eS134 S19 Aim: Review mortality, infections and CSF sampling in EVD patients. Methods: Theatre shunt register and laboratory results were used to collect data from August 2012 to b2014. Results: 141 EVDs were inserted in 117 patients. The mortality rate within 2 months of operation was 36%. Mortality was highest in patients with intra-ventricular haemorrhage (69%) and malignant tumours (67%). 258 CSF samples were taken for analysis costing £4,987.14. 38% of patients had an intra-operative sample sent, none of which grew an infective organism without pre-existing shunt or infection. The iatrogenic infection rate was 7% however 4 of these were potential contaminant organisms (coagulasenegative staphylococcus), and a further 4 contaminants were not treated. Neither the number of samples taken from EVDs, nor the CSF cell counts were associated with infection. Conclusion: We have demonstrated the high mortality associated with patients requiring EVDs, knowledge of which has been incorporated into our practise when counselling patients and families. We have also highlighted the lack of value of cell count intra-operative sampling in predicting infection. To improve efficiency our microbiologists are reviewing use of routine cell counts, favouring culture only. We also recommend only sampling patients with a high index of suspected infection to avoid overtreating contaminants. 0562: OPPORTUNITY FOR CARDIOVASCULAR RISK FACTOR REDUCTION IN AAA SURVEILLANCE PROGRAMS: A SYSTEMATIC REVIEW AND METAANALYSIS OF CARDIOVASCULAR MORTALITY IN PATIENTS WITH SMALL AAA M. Bath , V. Gokani , D. Sidloff , L. Jones , E. Choke , R. Sayers , M. Bown . 1 Leicester Medical School, UK; University of Leicester, UK Aim: Screening for abdominal aortic aneurysm (AAA) has dramatically reduced the rate of AAA-rupture, yet cardiovascular mortality remains a major cause of death in this patient group. A diagnosis of AAA is a powerful marker of cardiovascular risk, yet only 12.4% of patients use statins. The aim of this study was to assess the cardiovascular risk in patients with small AAA. Methods: Standard PRISMA guidelines were followed. A meta-regression analysis was performed for cardiovascular mortality in small AAA patients and a qualitative synthesis of the prevalence of concurrent cardiovascular diseases. Results: A total 2323 patients with small AAA were identified (median follow-up 5 years). A total of 335 cardiovascular deaths occurred, 37 of which from AAA-rupture, showing a cardiovascular mortality risk of 3.00% per year in small AAA patients (R2 1⁄4 0.902, p < 0.001). The prevalence of ischaemic heart disease (44.9%), myocardial infarction (26.8%), heart failure (4.4%) and cerebrovascular disease (14.0%) were high in this patient group. Discussion: There is high cardiovascular risk in patients with small AAA, yet manymay not be taking advantage of optimal cardiovascular risk factor modification. The diagnosis of a small AAA should be seen as a red-flag sign, triggering lifestyle change and pharmaco-vigilance against cardiovascular risk factors. 0726: PATTERNS OF DISEASE PERSISTENCE AND RECURRENCE IN REOPERATIVE PARATHYROIDECTOMY J.L. Allen , C. McIntyre , V. Constantinides , J. Jackson , N. Tolley , F. Palazzo . 1 Imperial College London, UK; Hammersmith Hospital, UK Aim: Parathyroidectomy is the definitive cure for primary hyperparathyroidism. Re-operative parathyroidectomy is required when the first operation has been unsuccessful, however, re-operative surgery has a higher complication rate and a higher rate of failure to cure. Our study looked at our departmental experience of re-operative parathyroidectomy. Methods: Using an internal database we identified all patients who had undergone re-operative parathyroidectomy between 2006 and 2014. We reviewed results from the pre-operative work up, the operative note, and the post-operative biochemistry and histology for the initial and reoperative procedure. Results: During this time period over 700 parathyroidectomies were performed. Of these, we identified 46 re-operative patients for whom we had the relevant data to include them in the study. A large proportion of patients had negative, equivocal or discordant conventional imaging and therefore went on to have more invasive localisation studies. Most abnormal parathyroid glands were found in eutopic locations. Of the ectopic glands, the most common locations were: intra-thyroidal, intrathymic, and mediastinal. 10 patients were found to have multiple adenomas and 4 patients had supernumerary parathyroid glands. 28% of the patients had concurrent thyroid disease. Conclusion: This study has identified patterns of disease persistence and recurrence in patients who have undergone re-operative parathyroidectomy. 0911: EXPRESSION PATTERNS OF HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR PROTEINS IN EARLY GASTRIC CANCER A. Mohamed , M. Gandy , A. Butt , V. Sehgal , I. Puccio , R. Hamoudi , R. Haidry , M. Novelli , M. Banks , L. Lovat , M. RodriguezJusto . University College London, UK Aim: The human epidermal growth factor receptor (HER) molecules are therapeutic targets in epithelial derived cancers. This study investigated their co-expression in early gastric neoplasia. Methods: Specimens from 22 suspected early gastric cancer patients were selected. Tissues were immunostained for EGFR, HER2, HER3 and HER4 overexpression on the Bond immunostainer. EGFR and HER2 were evaluated by interacellular (ICD) and extracellular binding (ECD) antibodies. Interpretation was performed as per clinical HER2 and EGFR scoring criteria. Results: ICD EGFR overexpression was seen in 9% (2/22) of samples but no overexpression against the EGFR ECD epitope. 13.6% (3/22) showed ECD HER2 overexpression and 9% (2 of 22) showed overexpression against the HER2 ECD epitope (3/3 with gene amplification). 50% (1 of 2) of overexpressing showed co-expression of EGFR and HER2. The coexpressed case showed significant disease progression. The pattern of distribution was heterogeneous in all EGFR cases but uniform in all of the HER2 cases. HER3 and HER4 overexpression was not seen in any cases. Conclusion: This pilot study suggests a relationship between EGFR and HER2. Interestingly, HER3 and HER4 lacked correlatation with either of these in contrast to reported relationships. The prognostic utility EGFR and HER2 co-expression to predict an aggressive early gastric cancer phenotype warrants further investigation. Society of Academic & Research Surgery Short Paper Session 0021: EFFECTS OF PLASMA SURFACE MODIFICATION ON SURFACE PROPERTIES OF POLYHEDRAL OLIGOMERIC SILSESQUIOXANE POLY(CARBONATE-UREA) URETHANE (POSS-PCU) FOR NASAL RECONSTRUCTION A. Abdul-Hamid. University College London, UK Aim: An unmet need exists for the development of tissue-engineered materials for biomedical applications, particularly in the field of nasal reconstruction. This study aims to alter the surface properties of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSSPCU), using plasma surface modification. Methods: The surface of porous POSS-PCU was modified using the plasma surface modification (PSM) technique with ammonia (NH3) and carbon dioxide (CO2) gases. Surfaces were analysed by comparing the water contact angle and using attenuated total reflectanceeFourier transform infrared (ATReFTIR) spectroscopy. Results: Both NH3 and CO2 gases using PSM significantly changed the surface characteristic of POSS-PCU from hydrophobic to hydrophilic (p < 0.05), with NH3 making the surface more hydrophilic than CO2 (control: 83 CO2: 61 NH3: 6 ). Comparison of ATReFTIR spectra samples post PSM demonstrated no changes in material characteristics compared to controls. Conclusion: This study demonstrated the ability of PSM to alter the surface of POSS-PCU for desirable characteristics. By achieving the desired surface

Objective The purpose of this study was to summarize the current evidence of the association between markers of hemostasis and both the presence and size of abdominal aortic aneurysms (AAAs). Methods A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines by use of the search terms "aneurysm AND abdominal AND aortic AND coagulation" NOT "thoracic." Outcome data including concentration of hemostatic marker, number of patients, and significance level were recorded. Results A total of 22 nonrandomized studies were included in the analysis, with a total of 9862 patients. Fibrinogen mean difference (MD) (0.43 g/L; 95% confidence interval [CI], 0.28-0.58 g/L; P ≤ .00001), D-dimer MD (325.82 ng/mL; 95% CI, 199.74-451.89 ng/mL; P ≤ .00001), and thrombin-antithrombin III complex MD (5.58 g/L; 95% CI, 3.34-7.83 g/L; P ≤ .0001) were significantly elevated in the presence of AAAs. Tissue plasminogen activator, prothrombin fragments F1+F2, and platelet count were not shown to be significantly different between patients with and those without AAAs. Meta-regression of studies reporting plasma D-dimer concentration and aneurysm diameter suggests a strong and significant association ( r 2 = 0.94; P ≤ .0001). Conclusions This study suggests that the presence of AAAs is associated with increased fibrin turnover, fibrinolysis, and thrombin generation, as shown by increased levels of fibrinogen, D-dimer, and thrombin-antithrombin III complex. This is clinically relevant because markers of hemostasis are independent risk factors for cardiovascular events, highlighting the necessity of addressing all modifiable cardiovascular risk factors in patients with AAAs. Furthermore, the finding that plasma D-dimer concentration appears to have a linear relationship with aneurysm diameter may be useful as a future biomarker of AAAs.

Objective Type II endoleak is the most common complication after endovascular abdominal aortic aneurysm repair (EVAR); however, its natural history is unclear. The aim of this study was to examine the incidence and outcomes of type II endoleak, at a single institution after EVAR. Methods A total of 904 consecutive patients who underwent EVAR between September 1995 and July 2013 at a single centre were entered onto a prospective database. All patients were followed up by duplex ultrasound (DUSS). Patients who developed type II endoleak were compared for preoperative demographics, mortality, and sac expansion. Results A total of 175(19%) patients developed type II endoleak over a median follow-up of 3.6 years (1.5–5.9 years); 54% of type II endoleaks spontaneously resolved within 6 months (0.25–1.2 years). No difference was found in preoperative demographics or choice of endograft between the two groups. Survival was significantly higher in the group with type II endoleak (94.1% vs. 85.6%; p = .01) and this effect was most pronounced in those with late type II endoleaks (97.7% vs. 85.6% p = .004). No difference was seen in aneurysm-related mortality or rate of type I endoleak between the two groups. Freedom from sac expansion (>5 mm from preoperative diameter) was significantly lower in the group of patients with type II endoleak (82.5% vs. 93.2%, p = .0001); however, at a threshold of >10 mm from preoperative diameter no difference was seen. Conclusions Patients with isolated type II endoleak demonstrate equivalent aneurysm-related mortality and an improved survival.