Extracorporeal shock wave lithotripsy for pancreatic duct stones: an observational study.

INTRODUCTION: Previous studies suggest that fragmentation of pancreatic duct stones (PDS) using extracorporeal shock wave lithotripsy (ESWL) is associated with pain relief. However, the treatment may not be effective in certain subgroups. AIM: To evaluate predictors of pain relief after ESWL in patients with chronic pancreatitis and PDS. METHODS: Retrospective study including patients with chronic pancreatitis undergoing ESWL for painful PDS. Analgesic use before and after the ESWL procedure was registered. We defined adequate pain relief after ESWL as 'pain-free without analgesics or with use of weak analgesics as needed'. The study was approved by the Danish Data Protection Agency (approval number: AHH-2017-048). RESULTS: We included 81 patients (median age 58 years; 63% men; 68% alcoholic pancreatitis). Patients underwent one to seven ESWL procedures (mean 1.7). A concurrent ERCP was performed in 17%. All patients used analgesics before the ESWL procedure (68 used opioids). After ESWL, 43 still used opioids. Thirty-two patients achieved adequate pain relief. Univariable regression analysis showed that older age predicted adequate pain relief (OR 1.09;1.03-1.16; p = .002) as did location of the stone in the head or neck (OR 2.59;1.04-6.45; p = .041). In multivariable analysis, we found that the only two predictors of adequate pain relief were age (p = .002) and the location of the stones (p = .039). CONCLUSION: After the ESWL, about four out of ten patients are pain-free without medication or able to manage their pain with weak analgesics. Age and the location of the stones may be considered when evaluating if patients are eligible for referral to ESWL.

Differential expression of CK20, ß-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X.

BACKGROUND: Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. METHODS: We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and ß-catenin in Lynch syndrome and FCCTX. RESULTS: Differences were identified for CK20 and nuclear ß-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome (p < 0.001), whereas MUC2, MUC5AC and MUC6 were overexpressed in Lynch syndrome tumors compared with FCCTX tumors (p = 0.001, < 0.01, and < 0.001, respectively). We observed no differences in the expression patterns of CK7 and CDX2. CONCLUSIONS: In summary, we identified significant differences in the immunoprofiles of colorectal cancers linked to FCCTX and Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.

Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.