Peripheral artery disease: a marked lack of awareness in Ireland.

OBJECTIVES: Patients with symptomatic peripheral artery disease (PAD) have a 30% risk of death within 5 years. However, public awareness of vascular disease has been shown to be low. The aim of this study was to assess awareness regarding risk factors, significance and potential sequelae of PAD in an Irish population. DESIGN: A cross-sectional, anonymous survey of patients and members of the public. MATERIALS: An anonymous questionnaire was developed to collect details on basic demographics, presence of and treatment for risk factors for cardiovascular disease, awareness of PAD and its risk factors and sequelae. The local ethics committee granted ethical approval. METHODS: Two investigators in face-to-face interviews administered the survey with patients and members of the general public, older than 40 years of age, attending a range of outpatient clinics, day care services and in patients. RESULTS: A total of 336 questionnaires were administered. A post-secondary school course had been completed by 32% of respondents. Only 19% of patients reported familiarity with PAD, a figure considerably lower than those reporting familiarity with stroke (94%), coronary artery disease (78%) or diabetes (98%) (Chi Squared p<0.001). The only independent predictor of awareness of PAD was having a post-secondary school course with an odds ratio or 4.2. CONCLUSIONS: This study demonstrates a disturbing lack of awareness of PAD and highlight the need for a meaningful targeted public health awareness campaign on PAD in order to close the gap of knowledge in Irish patients, prior to any prevention campaign.

Predicting carotid artery disease and plaque instability from cell-derived microparticles.

OBJECTIVES: Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. METHODS: This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. RESULTS: Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. CONCLUSIONS: EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.

Eversion endarterectomy for external iliac artery occlusive disease.

INTRODUCTION: The advent of effective endovascular techniques has revolutionized the treatment of iliac occlusive disease. Long-segment iliac occlusions remain technically difficult to treat, particularly in the presence of femoral disease. Iliac endarterectomy is an established procedure for the treatment of iliac occlusive disease, but it has been suggested that in the era of effective endovascular intervention, its role is limited. METHODS: A review of all patients who had eversion endarterectomy of the external iliac artery from a single institution between 2000 and 2008. RESULTS: Twenty-one patients (18 male) underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal American Society of Anaesthesiologists (ASA) grade was 3. The indications were critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months). There were no technical failures. Seventeen patients had significant improvement in symptoms and three had moderate improvement. The cumulative primary patency at 1 year was 81%. One patient had no improvement (because of infrainguinal occlusive disease), and subsequently required femoro-popliteal bypass. There was no systemic morbidity within 30 days. There was 1 in-hospital death from sudden cardiac arrest (47 days postoperatively). Six patients died during follow-up (from unrelated illness). CONCLUSION: Eversion external iliac endarterectomy is an effective means of treating iliofemoral occlusive disease with excellent short-term outcomes and a low complication rate in a cohort with high levels of comorbidity.

Separation of components in fenestrated and branched endovascular grafting--branch protection or a potentially new mode of failure?

OBJECTIVES: Modular component separation following endovascular aortic repair is recognized as a potential source of late failure. The aim of this study was to establish the extent of component separation occurring in branched and fenestrated endografts and to ascertain any factors that predict its occurrence. DESIGN: An analysis of component relationships following fenestrated and branched endovascular aneurysm repair was conducted on all patients with >1 year of digital imaging data. A mathematical model was developed, and retrospectively applied, to determine the minimum stentgraft overlap required to preclude any risk of component separation. RESULTS: Of the 184 patients treated prior to 2006, data (for patients with greater than 1 year follow-up) were available for 106 patients. Fourteen (13%) had evidence of inter-component movement of which 8 developed component separation (<2 stent overlap). All 8 patients with component separation, in addition to 38% of the total cohort, were identified as being at risk for eventual component separation using the mathematical model. CONCLUSIONS: Component movement is commonly observed in modular devices, but clinical consequences are rare. The degree of overlap, aneurysm diameter, aneurysm length, and stentgraft diameter can be used to predict the risk of inter-component movement which may result in component separation.

Percutaneous endovascular abdominal aortic aneurysm repair leads to a reduction in wound complications.

INTRODUCTION: While endovascular aortic aneurysm repair (EVAR) has significantly reduced the morbidity associated with open surgery, efforts continue to minimise the surgical insult to the patient. We report our experience of percutaneous EVAR. PATIENTS AND METHODS: Since June 2005, 17/20 EVARs (85%) have been attempted percutaneously by deployment of two Perclose) devices into each femoral artery prior to passage of the device sheath. The sutures are left untied until the sheath is removed at the end of the procedure, when haemostasis is obtained. Patients were entered onto a prospectively maintained database and followed up at regular intervals in a dedicated EVAR clinic. RESULTS: Access and subsequent graft deployment was successful in all the 17 cases. The range of defects closed ranged from 12-24 Fr. Five patients (29%) required open groin exploration at the end of the procedure to achieve haemostasis. There was a significantly lower incidence of wound complications in the percutaneous EVAR group (6 vs. 10% open cutdown cases, P < 0.05, Mann-Whitney U test). CONCLUSION: Percutaneous EVAR is both a feasible and safe method of performing endovascular abdominal aortic aneurysm repair, which is associated with a reduction in wound complication rates.

Aorto-enteric fistula: changing management strategies.

BACKGROUND: Traditionally treatment of aorto-enteric fistulae involved placement of an extra-anatomic bypass and graft excision. This is associated with limb loss (10-40%) and high mortality (10-70%). More recently in situ revascularisation has been advocated. AIMS: To examine our experience with the changing management of aorto-enteric fistulae over a 22-year period. METHODS: Demographic, clinical, operative and pathological data were recorded retrospectively. RESULTS: Twenty-one patients were included. Seven had primary fistulae. Six died prior to intervention. Five had an extra-anatomical bypass (60% mortality, 40% limb loss), four had in-situ revascularisation (25% mortality), four had a primary repair (25% mortality) and two had insertion of a tube graft (primary fistulae). The overall survival rate was 38%. The postoperative survival rate was 6o%. CONCLUSION: Techniques for operative management continue to evolve. The current trend is towards a local surgical approach with prolonged and intensive postoperative antimicrobial therapy. In our experience this approach has yielded acceptable outcomes.

Linear stapling of the short gastric vessels reduces blood loss and splenectomy at oesophageal and gastric surgery.

BACKGROUND: Increased operative blood loss, blood transfusion and nontherapeutic splenectomy negatively influence postoperative morbidity and mortality following esophageal or gastric resection. A critical point at which blood loss and iatrogenic splenic injury occurs is at the time of division of the short gastric vessels. We examined the efficacy of using a laparoscopic linear cutting stapler (developed for minimal access surgery) to divide with the short gastric vessels at open surgery. METHODS: Fifty-six patients were included. In 28 consecutive patients the linear stapler was used when dividing the short gastric vessels. These were compared to 28 matched controls (short gastric vessels were divided between hemostats and ligated). In the two patient groups, patient age, body mass index, and preoperative hemoglobin levels were similar. RESULTS: Operation time, splenectomy rates, blood transfusion, and mean transfusion volume were all significantly reduced in the group where the stapler was used. CONCLUSION: Use of a linear cutting stapler reduced operation time, blood product use, and incidental splenectomy in patients undergoing radical open esophageal and gastric surgery.

Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury.

INTRODUCTION: Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain. MATERIALS AND METHODS: This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery. RESULTS: Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower. CONCLUSIONS: We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.

Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

Experience of surgery for rectal cancer with total mesorectal excision in a general surgical practice.

BACKGROUND: Results from specialist centres have shown that total mesorectal excision (TME) produces excellent control of local disease in patients with carcinoma of the rectum. METHODS: The results of TME were reviewed in a surgical practice in which patients with rectal cancer comprised 1 per cent of the total caseload and mean case numbers were less than 15 each year. RESULTS: Eighty-two consecutive patients underwent rectal excision with TME over a 72-month period (68 anterior resection, eight abdominoperineal excision and six Hartmann's procedure). Sixty-nine operations were deemed 'curative' at the time of surgery. Anastomotic leak occurred in two (3 per cent) of 68 patients, both of whom recovered without additional surgery. There were two local recurrences (3 per cent) among 69 patients who underwent 'curative' surgery. At a median follow-up of 190 weeks, the survival rate for Dukes' stage A, B, C and 'D' was 100, 83, 68 and 18 per cent respectively. CONCLUSION: Outcome as measured by perioperative morbidity and local disease control achieved in a surgical practice with a broad case mix and relatively low annual case volume was comparable to that from larger centres. Appropriate surgical training and attention to technical detail may be as important as case volume in determining outcome after surgery for rectal cancer.

Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline.

BACKGROUND: The immunomodulatory effects of hypertonic saline (HTS) provide potential strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that administration of intratracheal aerosolized HTS modulates the development of lung injury in pancreatitis. METHODS: Pancreatitis was induced in 24 male Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). At 24 and 48 h, intratracheal aerosolized HTS (7.5% NaCl, 0.5 mL) was administered to 8 rats, while a further 8 received 0.5 mL of aerosolized normal saline (NS). At 72 hours, pulmonary neutrophil infiltration (myeloperoxidase activity) and endothelial permeability (bronchoalveolar lavage and wet:dry weight ratios) were assessed. In addition, histological assessment of representative lung tissue was performed by a blinded assessor. In a separate experiment, polymorphonucleocytes (PMN) were isolated from human donors, and exposed to increments of HTS. Neutrophil transmigration across an endothelial cell layer, VEGF release, and apoptosis at 1, 6, 12, 18, and 24 h were assessed. RESULTS: Histopathological lung injury scores were significantly reduced in the HTS group (4.78 +/- 1.43 vs. 8.64 +/- 0.86); p < 0.001). Pulmonary neutrophil sequestration (1.40 +/- 0.2) and increased endothelial permeability (6.77 +/- 1.14) were evident in the animals resuscitated with normal saline when compared with HTS (0.70 +/- 0.1 and 3.57 +/- 1.32), respectively; p < 0.04). HTS significantly reduced PMN transmigration (by 97.1, p = 0.002, and induced PMN apoptosis (p < 0.03). HTS did not impact significantly upon neutrophil VEGF release (p > 0.05). CONCLUSIONS: Intratracheal aerosolized HTS attenuates the neutrophil-mediated pulmonary insult subsequent to pancreatitis. This may represent a novel therapeutic strategy.