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Abstract: Background: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed. Aims: We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers. Methods: Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer. All tumours underwent an MisMatch Repair test combining microsatellite instability analysis and MisMatch Repair immunohistochemistry. Patients with an MisMatch Repair-deficient tumour were offered germline testing. Results: Of the 307 patients fulfilling the clinical criteria, 46 (15%) had a MisMatch Repair-deficient tumour. Amongst them 27 were identified as Lynch carriers (20 with germline mutation: 12 MLH1, 7 MSH2, 1 MSH6; 7 highly suspected cases despite failure of genetic testing). The simplified clinical criteria selected a population whose MisMatch Repair-deficient status was highly predictive (59%) of Lynch syndrome. Conclusion: This bio-clinical strategy based on simplified clinical criteria combined with an MisMatch Repair test efficiently detected LS cases and is easy to use in clinical practice, outside expert centres. [Copyright &y& Elsevier]

Background: Studies of risk factors after pancreatoduodenectomy are few: some concern restricted populations and others are based on administrative data. Methods: Multicenter clinical data were collected for 300 patients undergoing pancreatoduodenectomy to determine (by univariate and multivariate analysis) preoperative and intraoperative risk factors for mortality and intra-abdominal complications (IACs), including pancreatic fistula. Fourteen factors including the center and volume effect were analyzed. Results: In univariate analysis, mortality was increased with age 70 years or more, extended resection(s), and volume and center effects. IACs occurred more often with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, extended resection(s), and the center effect. Pancreatic fistula was more frequent with main pancreatic duct diameter of 3 mm or less, normal parenchyma texture, and the center effect. In multivariate analysis, independent risk factor(s) for mortality were age greater than 70 years (odds ratio [OR], 3; 95% confidence interval [CI], 1.3-8) and extended resection (OR, 5; 95% CI, 1.2-22), risk factors for IACs were extended resection (OR, 5; 95% CI, 1.2-22) and main pancreatic duct diameter of 3 mm or less (OR, 2; 95% CI, 1.1-3), and the risk factor for pancreatic fistula was main pancreatic duct diameter of 3 mm or less (OR, 2.5; 95% CI, 1.2-4.6). Conclusions: Age more than 70 years, extended resections, and main pancreatic duct diameter less than 3 mm are independent risk factors that should be considered in indications for and techniques of pancreatoduodenectomy. [Copyright &y& Elsevier]

Colonic macrophages are considered to be major effectors of inflammatory bowel diseases (IBDs) and the control of gut inflammation through C-type lectin receptors is an emerging concept. We show that during colitis, the loss of dectin-1 on myeloid cells prevents intestinal inflammation, while the lack of mannose receptor (MR) exacerbates it. A marked increase in dectin-1 expression in dextran sulfate sodium (DSS)-exposed MR-deficient mice supports the critical contribution of dectin-1 to colitis outcome. Dectin-1 is crucial for Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon as precursors of inflammatory macrophages. Dectin-1 also promotes inflammasome-dependent interleukin-1β (IL-1β) secretion through leukotriene B4 production. Interestingly, colonic inflammation is associated with a concomitant overexpression of dectin-1/CCL2/LTA4H and downregulation of MR on macrophages from IBD patients. Thus, MR and dectin-1 on macrophages are important mucosal inflammatory regulators that contribute to the intestinal inflammation. • Colitis is attenuated in mice with dectin-1−/− macrophages and severe in mice with MR−/− macrophages • Dectin-1 on macrophages mediates recruitment of inflammatory classical monocytes in the gut • Dectin-1 positively controls inflammatory phenotype of intestinal macrophages during colitis • Gut inflammation in IBD patients is linked to dectin-1 induction and reduced MR Rahabi et al. show a critical contribution of dectin-1 on macrophages in intestinal inflammation. Dectin-1 is involved in Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon, macrophage differentiation toward inflammatory phenotype, and inflammasome-dependent IL-1β secretion through LTB4. [ABSTRACT FROM AUTHOR]