Cytokines in small bowel transplantation Expression during graft rejection

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Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma omega-3 polyunsaturated fatty acid levels: An analysis of the UK Biobank

Observational evidence linking dietary omega-3 polyunsaturated fatty acid (PUFA) intake and health outcomes is limited by a lack of robust validation of dietary intake using blood omega-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use, and plasma omega-3 PUFA levels in 121,650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma omega-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38% and 31% of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P<0.001). Oily fish intake ≥twice a week was the strongest predictor of high total omega-3 PUFAs (odds ratio [OR] 6.7 [95% confidence interval 6.3-7.1]) and DHA levels (6.6 [6.3-7.1). FOS use was an independent predictor of high plasma omega-3 PUFA levels (2.0 [2.0-2.1]) with a similar OR to that associated with eating oily fish <once a week (1.9 [1.8-2.0]). FOS use was associated with plasma omega-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma omega-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary omega-3 PUFA intake, blood levels of omega-3 PUFAs, and health outcomes

Colorectal Hepatic Metastases: Detection with SPIO-enhanced Breath-hold MR Imaging-Comparison of Optimized Sequences

PURPOSE: To compare the accuracy of four breath-hold magnetic resonance (MR) imaging sequences to establish the most effective superparamagnetic iron oxide (SPIO)–enhanced sequence for detection of colorectal hepatic metastases. MATERIALS AND METHODS: Thirty-one patients with colorectal hepatic metastases underwent T1-weighted gradient-echo (GRE) and T2-weighted fast spin-echo (FSE) MR imaging before and after SPIO enhancement. Four sequences were optimized for lesion detection: T2-weighted FSE, multiecho data image combination (MEDIC), T2-weighted GRE with an 11-msec echo time (TE), and T2-weighted GRE with a 15-msec TE. Images were reviewed independently by three blinded observers. The accuracy of each sequence was measured by using alternative free-response receiver operating characteristic analysis. All results were correlated with findings at surgery, intraoperative ultrasonography, or histopathologic examination. Differences between the mean results of the three observers were measured by using the Student t-test. RESULTS: Postcontrast T2-weighted GRE sequences were the most accurate and were significantly superior to postcontrast T2-weighted FSE and unenhanced sequences alone (p<.05). For all lesions that were malignant or smaller than 1 cm, respectively, mean accuracies of postcontrast sequences were 0.082 and 0.64 for T2-weighted FSE, 0.90 and 0.78 for MEDIC, 0.92 and 0.80 for GRE with an 11-msec TE, 0.93 and 0.82 for GRE with a 15-msec TE, and 0.81 and 0.62 for unenhanced sequences. CONCLUSION: Optimized SPIO-enhanced T2-weighted GRE combined with unenhanced T2-weighted FSE MR sequences were the most sensitive. Breath-hold FSE postcontrast sequences offer no improvement in sensitivity compared with unenhanced sequences alone

Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid

NoBackground Oral administration of the omega-3 fatty acid eicosapentaenoic acid (EPA), as the free fatty acid (FFA), leads to EPA incorporation into, and reduced growth of, experimental colorectal cancer liver metastases (CRCLM). Design: We performed a Phase II double-blind, randomised, placebo-controlled trial of EPA-FFA 2 g daily in patients undergoing liver resection surgery for CRCLM. The patients took EPA-FFA (n=43) or placebo (n=45) prior to surgery. The primary end-point was the CRCLM Ki67 proliferation index (PI). Secondary end-points included safety and tolerability of EPA-FFA, tumour fatty acid content and CD31-positive vascularity. We also analysed overall survival (OS) and disease-free survival (DFS). Results The median (range) duration of EPA-FFA treatment was 30 (12–65) days. Treatment groups were well matched with no significant difference in disease burden at surgery or preoperative chemotherapy. EPA-FFA treatment was well tolerated with no excess of postoperative complications. Tumour tissue from EPA-FFA-treated patients demonstrated a 40% increase in EPA content (p=0.0008), no difference in Ki67 PI, but reduced vascularity in ‘EPA-naïve’ individuals (p=0.075). EPA-FFA also demonstrated antiangiogenic activity in vitro. In the first 18 months after CRCLM resection, EPA-FFA-treated individuals obtained OS benefit compared with placebo, although early CRC recurrence rates were similar. Conclusions EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted. Trial Identifier: ClinicalTrials.gov NCT01070355.The Cancer Research UK Clinical Trials Awards and Advisory Committee approved the Trial. PML and ADR were supported by Department of Health/Cancer Research UK Yorkshire Experimental Cancer Medicine Centre funding. The Trial was adopted by the UKCRN Clinical Trials Portfolio (UKCRN ID 8946) allowing West Yorkshire Comprehensive Local Research Network funding of Pharmacy costs. SLA Pharma AG funded some of the experimental work and provided EPA-FFA and placebo. SLA Pharma AG played no role in the design or execution of the Trial. Laboratory costs were also supported by the Leeds Teaching Hospitals Charitable Foundation (Rays of Hope)

Non-operative management of pyogenic liver abscess

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Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol

Introduction There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. Methods and analysis The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. Ethics and dissemination Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. Trial registration number NCT0342847

Mirizzi's syndrome – results from a large western experience

Background. This paper reports a series of patients with Mirizzi's syndrome (MS) who were managed at our institution over an 11-year (1994–2005) period. Methods. Retrospective case note study of patients with a definitive or possible diagnosis of MS stated in radiology reports were identified using the hospital's radiology computer coding system. Results. 33 patients were identified with a median age of diagnosis of 70 (35–90) years and male to female ratio of 15:18. Liver function tests were deranged in all patients. Pre-operative radiological diagnosis was achieved in 28 patients: ultrasound scan (n = 4), computer tomography (n = 3), magnetic resonance cholangiopancreatography (n = 10) and endoscopic retrograde cholangiopancreatography (n = 11). Five patients were diagnosed intra-operatively. Type I MS was reported in 27 patients. Laparoscopic cholecystectomy was attempted in 18 patients with 6 being converted to open cholecystectomy. Six patients had biliary stent insertion only and 3 were conservatively managed. Six patients had type II MS, 4 were treated with open cholecystectomy and Roux-en-Y hepaticojejunostomy, 1 underwent an open subtotal cholecystectomy with fistula closure and 1 had percutaneous biliary stent insertion only. The median follow-up period was 2 (1–7) months (n = 18). 10 patients are currently under follow-up. Overall morbidity was 27% (n = 8) and mortality was 7% (n = 2). Conclusion. Pre-operative diagnosis of MS can be achieved using MRCP. Laparoscopic cholecystectomy for type I MS is a safe option and type II MS can be treated with Roux-en-Y hepaticojejunostomy or subtotal cholecystectomy with fistula closure