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Background Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. Methods This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. Results 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. Conclusions The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Backgrounds Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. Methods We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). Results Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P Conclusions The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

While drug-induced pancreatitis from corticosteroids has been well described in the medical literature, the exact mechanism is unclear. We present the first reported case of drug-induced pancreatitis from beta-sitosterol, a naturally occurring plant sterol structurally similar to cholesterol, obtained primarily through Western diet and supplementation. A 57-year-old male with a history of situs inversus and benign prostatic hyperplasia presented from an outside facility with a two-day history of worsening epigastric pain radiating to the right upper quadrant. Lipase was markedly elevated at 572 U/L. CT scan and ultrasound of the abdomen were remarkable for acute pancreatitis with acute necrotic collections and normal appearing gallbladder and bile ducts without the presence of gallstones. The patient was managed with aggressive intravenous hydration and supportive management and had resolution of symptoms. At his follow-up appointment, the patient disclosed that he had started a new herbal supplement, beta-sitosterol, on the morning after his symptoms began. Abdominal magnetic resonance cholangiopancreatography obtained at follow-up appointment showed interval resolution of pancreatitis and normal biliary anatomy. In the absence of classical risk factors for acute pancreatitis, a diagnosis of drug-induced pancreatitis secondary to beta-sitosterol was made. The patient was advised to avoid beta-sitosterol, and thus continued to remain asymptomatic. We describe the first reported case of drug-induced pancreatitis from beta-sitosterol, a common phytosterol found in many over the counter supplements worldwide. After a thorough workup to exclude other causes, our case demonstrates consistent resolution of symptoms and pancreatic enzymes along with normal imaging following discontinuation of the offending agent.

AIM: An increased prevalence of irritable bowel syndrome has been reported in obese individuals. Factors important in weight loss after bariatric surgery are incompletely understood, and small intestinal bacterial overgrowth in individuals with type 2 diabetes mellitus is a potential risk factor. Our aims are to examine whether the increased prevalence of irritable bowel syndrome in obese individuals seeking bariatric surgery is associated with diabetes mellitus and whether weight loss after bariatric surgery is altered by irritable bowel syndrome. METHODS: This is a single-center, retrospective study performed in a large, urban community teaching hospital. Individuals seen in gastrointestinal bariatric clinic prior to bariatric surgery from 2010 to 2013 completed a Manning symptom criteria questionnaire prior to their medical evaluation; ≥3 Manning criteria is accepted as diagnostic of irritable bowel syndrome. Percent excess weight loss at 6-, 12-, and 24-months after bariatric surgery is recorded. RESULTS: Thirty percent of 278 individuals seeking bariatric surgery have ≥3 Manning criteria. There is no relationship between type 2 diabetes mellitus and the presence of ≥3 Manning criteria (p>.05), nor is body mass index a significant risk factor for irritable bowel syndrome (p>.05). At 6-, 12-, and 24-months after Roux-en-Y gastric bypass or vertical sleeve gastrectomy, there is no difference in percent excess weight loss in individuals with ≥3 Manning criteria compared to individuals with ≤2 Manning criteria (for both surgical procedures: p>.05). CONCLUSION: A diagnosis of diabetes mellitus or body mass index do not explain the high prevalence of irritable bowel syndrome identified in individuals with obesity seeking bariatric surgery, and irritable bowel syndrome does not alter weight loss after bariatric surgery.

There has been a worldwide rise in the prevalence of overweight and obese individuals. Due to this increase, there has been a related rise in the number of individuals with non-alcoholic fatty liver disease or NAFLD, a condition that is becoming a more common cause for cirrhosis leading to liver transplantation. Diet and activity program provide modest weight loss and are poor treatments for maintenance of weight loss. Multiple studies have shown that Roux-en-Y gastric bypass surgery can lead to histological improvement in both non-alcoholic fatty liver disease as well as in the subset of individuals who also have steatohepatitis. This editorial explores the potential for the newer bariatric surgery, vertical sleeve gastrectomy, to function as a surgical option for the treatment of non-alcoholic fatty liver disease and steatohepatitis.

The Ca2+ release channel ryanodine receptor 2 (RyR2) is required for excitation-contraction coupling in the heart and is also present in the brain. Mutations in RyR2 have been linked to exercise-induced sudden cardiac death (catecholaminergic polymorphic ventricular tachycardia [CPVT]). CPVT-associated RyR2 mutations result in “leaky” RyR2 channels due to the decreased binding of the calstabin2 (FKBP12.6) subunit, which stabilizes the closed state of the channel. We found that mice heterozygous for the R2474S mutation in Ryr2 (Ryr2-R2474S mice) exhibited spontaneous generalized tonic-clonic seizures (which occurred in the absence of cardiac arrhythmias), exercise-induced ventricular arrhythmias, and sudden cardiac death. Treatment with a novel RyR2-specific compound (S107) that enhances the binding of calstabin2 to the mutant Ryr2-R2474S channel inhibited the channel leak and prevented cardiac arrhythmias and raised the seizure threshold. Thus, CPVT-associated mutant leaky Ryr2-R2474S channels in the brain can cause seizures in mice, independent of cardiac arrhythmias. Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death.