Indomethacin down-regulating HMGB1 and TNF-α to prevent pancreatitis after endoscopic retrograde cholangiopancreatography.

Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). However, studies revealed inconsistent results. The mechanism of NSAIDs in preventing PEP is still little known. Therefore, the aim of our study was to evaluate the efficacy of NSAIDs for PEP prophylaxis and further to explore the mechanism of NSAIDs for prevention of PEP. Methods: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to receive 100 mg rectal indomethacin or glycerin suppository 15-20 min before ERCP. The primary outcome was the rate of PEP. And the levels of serum HMGB1 and TNF-α were also measured before ERCP and 3 and 24 h after ERCP. Univariate analysis and multivariate analysis were carried out to estimate the independent risk factors for PEP. Results: Totally, 100 patients were enrolled, 50 received indomethacin and 50 with placebo (glycerin suppository). PEP developed in six patients in indomethacin group and 16 in the control group, the difference was significant (p = .016). The levels of HMGB1 and TNF-α were significantly decreased in indomethacin group at 3 (p < .0001) and 24 h (p < .0001) after ERCP, compared to the control group. Multivariate analysis revealed that duration of ERCP (OR, 0.221; 95% CI, 0.072-0.680; p = .008) and usage of NSAIDs (OR, 0.278; 95% CI, 0.090-0.861; p = .026) were independent predictors of PEP. Conclusions: Rectal indomethacin could significantly reduce the risk of PEP by down-regulating the levels of HMGB1 and TNF-α.

Nonsteroidal anti-inflammatory drugs reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis.

BACKGROUND: Several recent studies suggested that nonsteroidal anti-inflammation drugs (NSAIDs) could prevent the pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the routes of administration, the dosages of NSAIDs and the potential efficacy in reducing the severity of pancreatitis remain controversial. The aim of this meta-analysis was to evaluate the efficacy of NSAIDs for post-ERCP pancreatitis (PEP) prophylaxis. METHODS: We systematically searched PubMed, Embase, EBSCO, Elsevier and Web of Science databases up to 1 October 2016 for relevant studies. RESULTS: A total of 24 studies met the inclusion criteria. Compared to the controls, the risk of pancreatitis was much lower in the NSAIDs group (OR = 0.57, 95% CI: 0.48-0.67, P < 0.0001). However, NSAIDs were not effective in reducing the risk of moderate to severe pancreatitis compared with placebo (OR = 0.75, 95% CI: 0.57-1.00). In the subanalyses, rectal administration was the only effective route (OR = 0.51, 95% CI: 0.42-0.62), and the risk of PEP was reduced in both randomized controlled trials (RCTs) (OR = 0.63, 95% CI: 0.52-0.76) and case-control articles (C-Cs) (OR = 0.40, 95% CI: 0.28-0.58). CONCLUSIONS: Prophylactic administration of NSAIDs reduced the incidence of PEP in both RCTs and C-Cs, especially when rectally administered, but was not effective in reducing the risk of moderate to severe pancreatitis.

Clinical research for delayed hemorrhage after endoscopic sphincterotomy.

To analyze the effect of delayed hemorrhage after endoscopic sphincterotomy (EST) and compare the efficacy in improving complication between medicine treatment alone and medicine combined with endoscopic treatment. 1741 patients with EST admitted in Yijishan hospital of Wannan medical college from September 2009 to May 2014 were enrolled in this study. 32 cases suffered from delayed hemorrhage. The patients with delayed hemorrhage were evaluated through incision length of duodenal papilla, clinical manifestation, stool occult blood test and the difference of hemoglobin concentration between pre and post operation. 32 patients were divided into mild bleeding group, mild serious group and serious group through the speed and amount of bleeding. All cases in mild group accepted medicine treatment. Mild serious group were divided into medicine therapy group and medicine combined with endoscopic therapy group randomly. Serious group accepted vascular intervention therapy even traditional operation. The different treatments for delayed hemorrhage were judged by efficiency. The dates were analyzed by t-test or chi-square test. Nobody endured delayed hemorrhage who accepted small incision. Delayed hemorrhage was found in 7 patients out of 627 cases who accepted medium-large incision, 25 patients of 920 cases who accepted large incision. The patients who accepted lager EST were more dangerous than small EST (χ(2)=4.718, P=0.030) concerning delayed hemorrhage. 32 cases in 1741 patients suffered from delayed hemorrhage. 14 patients only have passed black stool after EST. Among 14 cases, 13 patients stop bleeding after medical therapy, and 1 case received endoscopic hemostasis. 15 cases with hematemesis or melena after EST, 7 patients who received combination therapy stop bleeding. 3 patients from 8 cases stop bleeding after single chemical treatment, 5 cases had to receive endoscopic hemostasis after ineffectual medical therapy. There are significant difference for concerning effect between combination therapy group and medical therapy group (P=0.026). 3 patients repeatedly vomited blood and develop to peripheral circulatory failure. Those patients all received vascular intervention therapy, 2 patients stop bleeding, 1 patient failed in vascular intervention therapy and given up emergency rescue and died. Large EST has more risks than small EST in concerning delayed hemorrhage. Delayed bleeding after EST should be treated by different levels. Adapted therapy should be recommend for patients with different levels bleeding.