Background Individuals with a very high lifetime risk of developing pancreatic ductal adenocarcinoma; for example, hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous... Show moreBackground Individuals with a very high lifetime risk of developing pancreatic ductal adenocarcinoma; for example, hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm, may wish to discuss prophylactic total pancreatectomy but strategies to do so are lacking. Objective To develop a shared decision-making programme for prophylactic total pancreatectomy using decision tables. Methods Focus group meetings with patients were used to identify relevant questions. Systematic reviews were performed to answer these questions. Results The first tables included hereditary pancreatitis and main-duct or mixed-type intraductal papillary mucinous neoplasm. No studies focused on prophylactic total pancreatectomy in these groups. In 52 studies (3570 patients), major morbidity after total pancreatectomy was 25% and 30-day mortality was 6%. After minimally invasive total pancreatectomy (seven studies, 35 patients) this was, respectively, 13% and 0%. Exocrine insufficiency-related symptoms occurred in 33%. Quality of life after total pancreatectomy was slightly lower compared with the general population. Conclusion The decision tables can be helpful for discussing prophylactic total pancreatectomy with individuals at high risk of pancreatic ductal adenocarcinoma. Show less
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide... Show moreGenome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis. Show less
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association... Show moreWe undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease. Show less
