Search

Peutz–Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%–15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2–83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed. [ABSTRACT FROM AUTHOR]

Objective: Acute pancreatitis with walled‐off necrosis (WON) is associated with considerable morbidity and mortality. Previous studies have evaluated outcomes in WON collections of limited size, while data about large WON with long‐term follow‐up are lacking. We aimed to report our experience in managing large WON. Methods: Between 2010 and 2020, consecutive patients with large (>15 cm) WON were identified from a prospectively maintained database. Patients with chronic pancreatitis or an index intervention 90 days or more from the debut of symptoms were excluded. We registered clinical and technical outcomes following minimally invasive treatment in WON >15 cm. Follow‐up was a minimum of 1 year. Results: Overall, 144 patients with WON >15 cm, with a median age of 60 (interquartile range [IQR] 49–69) years, were included. The median WON size was 19.2 cm (IQR 16.8–22.1). Most patients were treated with endoscopic transluminal drainage (93%). The median length of stay was 53 days (IQR 39–76) and 61 (42%) patients needed intensive care support during their hospital stay. As 143 patients (99%) were managed using endoscopic or video‐assisted retroperitoneal techniques, only one (0.7%) patient needed an open necrosectomy. Procedure‐related adverse events occurred in 10 (7%) patients. Overall, 24 patients (17%) died during admission, all due to multiorgan failure. The median follow‐up was 35 months (IQR 15–63.5). Complete resolution was achieved in all remaining patients. Conclusion: Minimally invasive treatment of large WON is feasible, with a minimal need for surgery and acceptable rates of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN‐lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping. [ABSTRACT FROM AUTHOR]

Background. Small mothers against decapentaplegic (SMAD)4 and SMAD7 are key regulatory components in the immunosuppressive transforming growth factor- (TGF-) β signaling pathway, which is defective in inflammatory bowel disease (IBD). SMAD4 may play an important role in the pathogenesis of IBD as indicated in experimental models of colitis. Aims. To examine the ileal expression levels of SMAD4 and to correlate these with CD disease activity. Methods. The material comprised 29 CD patients (13 with active disease, 16 in remission) and 9 asymptomatic patients referred for ileocolonoscopy as part of an adenoma surveillance program serving as controls. Patients were examined with ileocolonoscopy. Corresponding ileal biopsies were obtained for histological analysis and assessment of SMAD4 and SMAD7 protein expression by immunohistochemistry (IHC). Results. The protein expression of SMAD4 was significantly downregulated in ileal tissue sections from CD patients as compared to healthy controls (p<0.001). Further, luminal SMAD4 expression was inversely correlated with endoscopic (rs=−0.315; p=0.05) and histopathological activity (rs=−0.40; p=0.013). Conclusions. The SMAD4 epithelial protein level was markedly downregulated in CD patients and inversely correlated with disease activity. This may contribute to defective mucosal TGF-β signaling in active IBD. [ABSTRACT FROM AUTHOR]