MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions

Pancreatic ductal adenocarcinoma(PDAC) is the 4^(th) deadliest cancer in the United States, due to its aggressive nature, late detection, and resistance to chemotherapy. The majority of PDAC develops from 3 precursor lesions, pancreatic intraepithelial lesions(PanIN), intraductual papillary mucinous neoplasm(IPMN), and mucinous cystic neoplasm. Early detection and surgical resection can increase PDAC 5-year survival rate from 6% for Stage Ⅳ to 50% for Stage Ⅰ. To date, there are no reliable biomarkers that can detect PDAC. MicroRNAs(miRNA) are small noncoding RNAs(18-25 nucleotides) that regulate gene expression by affecting translation of messenger RNA(mRNA). A large body of evidence suggests that miRNAs are dysregulated in various types of cancers. MiRNA has been profiled as a potential biomarker in pancreatic tumor tissue, blood, cyst fluid, stool, and saliva. Four mi RNA biomarkers(miR-21, miR-155, miR-196, and miR-210) have been consistently dysregulated in PDAC. MiR-21, miR-155, and miR-196 have also been dysregulated in IPMN and PanIN lesions suggesting their use as early biomarkers of this disease. In this review, we explore current knowledge of miRNA sampling, miR NA dysregulation in PDAC and its precursor lesions, and advances that have been made in using miRNA as a biomarker for PDAC and its precursor lesions.

One hundred and one over-the-scope-clip applications forsevere gastrointestinal bleeding,leaks and fistulas

AIM: To investigate the efficacy and clinical outcome of patients treated with an over-the-scope-clip(OTSC) system for severe gastrointestinal hemorrhage, perforations and fistulas.METHODS: From 02-2009 to 10-2012, 84 patients were treated with 101 OTSC clips. 41 patients(48.8%) presented with severe upper-gastrointestinal(GI) bleeding, 3(3.6%) patients with lower-GI bleeding, 7 patients(8.3%) underwent perforation closure, 18 patients(21.4%) had prevention of secondary perforation, 12 patients(14.3%) had control of secondary bleeding after endoscopic mucosal resection or endoscopic submucosal dissection(ESD) and 3 patients(3.6%) had an intervention on a chronic fistula. RESULTS: In 78/84 patients(92.8%), primary treatment with the OTSC was technically successful. Clinical primary success was achieved in 75/84 patients(89.28%). The overall mortality in the study patients was 11/84(13.1%) and was seen in patients with life threatning upper GI hemorrhage. There was no mortality in any other treatment group. In detail OTSC application lead to a clinical success in 35/41(85.36%) patients with upper GI bleeding and in 3/3 patients with lower GI bleeding. Technical success of perforation closure was 100% while clinical success was seen in 4/7 cases(57.14%) due to attendant circumstances unrelated to the OTSC. Technical and clinic success was achieved in 18/18(100%) patients for the prevention of bleeding or perforation after endoscopic mucosal resection and ESD and in 3/3 cases of fistula closure. Two application-related complications were seen(2%).CONCLUSION: This largest single center experience published so far confirms the value of the OTSC for GI emergencies and complications. Further clinical experience will help to identify optimal indications for its targeted and prophylactic use.