Epithelial-to-mesenchymal transition is a phenomenon necessary for embryonic development and also seen during certain pathological conditions. We show here for the first time that reduction in miR-30 family microRNAs, is responsible for mesenchymal transition of primary cultures of human pancreatic epithelial cells. We found that miR-30 family microRNAs target mesenchymal gene transcripts and maintain them in a translationally inactive state. Forced depletion using miR-30 family specific anti-miRs leads to mesenchymal transition while ectopic overexpression maintains the epithelial phenotype. We also show that miR-30 family microRNAs increase in abundance during differentiation of pancreatic islet-derived mesenchymal cells into hormone-producing islet-like cell aggregates. Our studies in human adult diseased pancreas also demonstrate that miR-30 family microRNAs are expressed at lower abundance in fibrotic lesions during pancreatitis. Together, our data confirm that miR-30 family microRNAs form a part of the regulatory signaling events involved in cellular response of pancreatic epithelial cells during mesenchymal transition.

Background and study aim Peroral endoscopic myotomy (POEM) has emerged as an effective treatment modality for achalasia. Prior treatment may affect the outcomes of subsequent management. In this study, we aimed to compare the safety and efficacy of POEM in treatment-naïve patients vs. those with prior treatment failure (PTF). Patients and methods The data of consecutive patients with achalasia who underwent POEM at a single tertiary care center from January 2013 to November 2016 were analyzed retrospectively. A comparative analysis was performed between treatment-naïve and PTF cases. Technical and clinical success, adverse events, and operative time for POEM were compared between the two groups. Results Overall, 502 patients with achalasia underwent POEM during the study period: 260 patients (51.8 %) in the treatment-naïve group and 242 patients (48.2 %) in the PTF group. The mean operative time was significantly longer in the PTF group compared with the treatment-naïve group (74.9 ± 30.6 vs. 67.0 ± 27.1 minutes; P = 0.002). On multivariate analysis, type of achalasia, dilated esophagus ( > 6 cm), disease duration, prior treatment, occurrence of adverse events, and type of knife used were significant predictors of operative time. Technical success (98.1 % vs. 97.1 %; P = 0.56) and clinical success (92.4 % vs. 92.5 %; P = 0.95) were comparable in the treatment-naïve and PTF cases, respectively. Occurrence of gas-related events and mucosotomy were similar in both groups. Elevated DeMeester score was found in 17 /53 patients (32.1 %) in the PTF group and in 11 /44 patients (25.0 %) in the treatment-naïve group (P = 0.50). Conclusion POEM is safe and equally effective for treatment-naïve patients and for those in whom prior treatment has failed. POEM should be considered the treatment of choice in patients in whom prior treatment has failed.