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Background: We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials., Methods: The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients., Results: Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results., Conclusion: APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials., Competing Interests: None

Benign esophageal strictures refractory to the conventional balloon or bougie dilatation may be subjected to various adjunctive modes of therapy, one of them being endoscopic incisional therapy (EIT). A proper delineation of the stricture anatomy is a prerequisite. A host of electrocautery and mechanical devices may be used, the most common being the use of needle knife, either standard or insulated tip. The technique entails radial incision and cutting off of the stenotic rim. Adjunctive therapies, to prevent re-stenosis, such as balloon dilatation, oral or intralesional steroids or argon plasma coagulation can be used. The common strictures where EIT has been successfully used are Schatzki's rings (SR) and anastomotic strictures (AS). Short segment strictures (< 1 cm) have been found to have the best outcome. When compared with routine balloon dilatation, EIT has equivalent results in treatment naïve cases but better long term outcome in refractory cases. Anecdotal reports of its use in other types of strictures have been noted. Post procedure complications of EIT are mild and comparable to dilatation therapy. As of the current evidence, incisional therapy can be used for management of refractory AS and SR with relatively short stenosis (< 1 cm) with good safety profile and acceptable long term patency.

Aim: To study the role of needle knife assisted ampullary biopsy in the diagnosis of periampullary carcinoma., Methods: In this study the authors retrospectively analyzed clinical records of patients with periampullary tumors diagnosed by ampullary biopsy taken after needle knife papillotomy in whom surface ampullary biopsies were non contributory., Results: Between January 2008 and December 2010, 38 patients with periampullary tumors were seen by us and initial side viewing endoscopy with surface biopsy from the papilla was positive for malignancy in 25 patients. Thirteen patients with a negative surface biopsy for malignancy underwent a repeat ampullary biopsy following needle knife papillotomy. There were 8 (61.5%) males and 5 (38.5%) females. The most common presenting symptom was jaundice (100%), followed by fever (46.2%), melena (38.5%), abdominal pain (30.8%) and weight loss (30.8%). All the patients had hyperbilirubinemia with a mean ± SD serum bilirubin of (11.2 ± 1.9) mg/dL (normal value < 1 mg%) and the mean ± SD serum alkaline phosphatase was (288.0 ± 94.3) IU/L (normal value < 129 IU/L). Serum CA 19.9 level estimation was done in 11 patients; it was elevated (cut off value > 70.5 IU/L) in all of them with a median of 1200 IU/L (inter quartile range 274-3500). Side viewing endoscopy showed a bulky papilla in all of them. Adequate tissue was obtained in all of the 13 patients for histological evaluation; 12 of the 13 patients were reported to have adenocarcinoma while one patient had adenoma. There were no complications from the needle knife papillotomy in any of the patients., Conclusion: Needle knife assisted ampullary biopsy appears to be a safe and effective diagnostic modality for periampullary carcinoma.

Aim: To investigate p16 gene methylation and its expression in 30 patients with sporadic colorectal adenocarcinoma in a North Indian population., Methods: Methylation specific polymerase chain reaction was used to detect p16 gene methylation and immunohistochemistry was used to study the p16 expression in 30 sporadic colorectal tumors as well as adjoining and normal tissue specimens., Results: Aberrant promoter methylation of p16 gene was detected in 12 (40%) tumor specimens, whereas no promoter methylation was observed in adjoining and normal tissue. Immunohistochemistry showed expression of p16 protein in 26 (86.6%) colorectal tumors whereas complete loss of expression was seen in 4 (13.3%) and reduced expression was observed in 12 (40%) tumors. In the adjoining mucosa, expression of p16 was in 11 (36.6%) whereas no clear positivity for p16 protein was seen in normal tissue. There was a significant difference in the expression of p16 protein in tumor tissue and adjoining mucosa (P < 0.001). The methylation of the p16 gene had a significant effect on the expression of p16 protein (P = 0.021). There was a significant association of methylation of p16 gene with the tumor size (P = 0.015) and of the loss/reduced expression of p16 protein with the proximal site of the tumor (P = 0.047). Promoter methylation and expression of p16 had no relation with the survival of the patients (P > 0.05)., Conclusion: Our study demonstrated that promoter hypermethylation of the p16 gene results in loss/reduced expression of p16 protein and this loss/reduced expression may contribute to tumor enlargement.

Esophageal strictures are a problem frequently encountered by gastroenterologists. Dilation has been the customary treatment for benign esophageal strictures, and dilation techniques have advanced over the years. Depending on their characteristics and the response to treatment, esophageal strictures can be classified into two types: 1, simple (Schatzki rings, webs, peptic injury, and following sclerotherapy) - these are easily amenable to dilation, with a low recurrence rate after initial treatment; and 2, complex (caused by caustic ingestion, radiation injury, anastomotic strictures, and photodynamic therapy) - these are difficult to dilate and are associated with higher recurrence rates. Refractory strictures are those in which it is not possible to relieve the anatomic restriction successfully up to a diameter of 14 mm over five sessions at 2-weekly intervals, due to cicatricial luminal compromise or fibrosis; and recurrent strictures are those in which it is not possible to maintain a satisfactory luminal diameter for 4 wk once the target diameter of 14 mm has been achieved. There are no standard recommendations for the management of refractory strictures. The various techniques used include intralesional steroid injection combined with dilation; endoscopic incisional therapy, with or without dilation; placement of self-expanding metal stents, Polyflex stents, or biodegradable stents; self-bougienage; and endoscopic surgery. This review discusses the indications, technique, results, and complications of the use of intralesional steroid injections combined with dilation and endoscopic incisional therapy with dilation in refractory strictures.

Gastric outlet obstruction (GOO) includes obstruction in the antropyloric area or in the bulbar or post bulbar duodenal segments. Though malignancy remains the most common cause of GOO in adults, a significant number of patients have benign disease. The latter include peptic ulcer disease, caustic ingestion, post-operative anastomotic state and inflammatory causes like Crohn's disease and tuberculosis. Peptic ulcer remains the most common benign cause of GOO. Management of benign GOO revolves around confirmation of the etiology, removing the offending agent Helicobacter pylori (H. pylori), non-steroidal anti-inflammatory drugs, etc. and definitive therapy. Traditionally, surgery has been the standard mode of treatment for benign GOO. However, after the advent of through-the-scope balloon dilators, endoscopic balloon dilation (EBD) has emerged as an effective alternative to surgery in selected groups of patients. So far, this form of therapy has been shown to be effective in caustic-induced GOO with short segment cicatrization and ulcer related GOO. In the latter, EBD must be combined with eradication of H. pylori. Dilation is preferably done with wire-guided balloon catheters of incremental diameter with the aim to reach the end-point of 15 mm. While it is recommended that fluoroscopic control be used for EBD, this is not used by most endoscopists. Frequency of dilation has varied from once a week to once in three weeks. Complications are uncommon with perforation occurring more often with balloons larger than 15 mm. Attempts to augment efficacy of EBD include intralesional steroids and endoscopic incision.