The Mechanism Of NSAIDs In Preventing Post-ERCP Pancreatitis And Related Research

Background: ERCP(Endoscopic retrograde cholangiopancreatography,ERCP)is an important method for diagnosis and treatment of biliary and pancreatic diseases,complications include hemorrhage,cholangitis,pancreatitis,perforation,etc.But the most common complication is post-ERCP pancreatitis.The pancreatitis rate is 1-10%,in high-risk groups is as high as 30-40%,early identification of risk factors of post-ERCP pancreatitis,early diagnosis and early treatment of high-risk patients are important ways to reduce the incidence and mortality of post-ERCP pancreatitis.In recent years,many reports have reported non-steroidal anti-inflammatory drugs to prevent the occurrence of post-ERCP pancreatitis,and European guidelines suggest that 100 mg of non-steroidal anti-inflammatory drugs can be effectively prevented post-ERCP pancreatitis before or after operation.However,this method has not been widely used in China,and its dosage,mode and whether it can reduce the incidence of postoperative pancreatitis are still controversial,and its mechanism of action is also rarely studied.Part I The mechanism of non-steroidal anti-inflammatory drugs to prevent post-ERCP pancreatitis Objctive: Exploring whether preoperative rectal administration of non-steroidal anti-inflammatory drugs reduces the incidence of post-ERCP pancreatitis and whether non-steroidal anti-inflammatory drugs can down-regulate the expression of inflammatory factors such as HMGB1 and TNF-? and the activation of leukocytes and neutrophils to reduce the incidence of post-ERCP pancreatitis.Method: A prospective case-control study was conducted to collect 100 patients who were scheduled to undergo ERCP from July 2017 to April 2018.They were randomly divided into case group and control group.The patients in case group were treated with 100 mg indomethacin suppository,in control group were treated with the same dose of glycerol enema.Blood samples were collected before operation,3 hours and 24 hours after operation,and then detect the serum levels of HMGB1 and TNF-alpha by ELISA.The incidence of pancreatitis and the expression of inflammatory factors were analyzed.Results: Six patients(12%)developed pancreatitis after ERCP in the indomethacin group and 16 patients(32%)in the control group.The difference was statistically significant(P<0.05).The expression level of serum TNF-?(183.65±6.77ng/L)in the indomethacin group was lower than that in the control group(184.78±6.98 ng/L).There was no significant difference between the two groups(P>0.05).The level of serum TNF-? expression in the indomethacin group(236.70±7.34 ng/L)was lower than that in the control group(263.56±7.44 ng/L),and the difference was statistically significant(P<0.05).The level of serum TNF-?(148.48±14.95ng/L)in the indomethacin group was lower than that in the control group(204.62±30.00 ng/L)24 hours after operation.The difference was statistically significant(P<0.05).The serum HMGB1 expression level(20.75±0.79?g/L)was lower in the indomethacin group than in the control group(21.04±2.64?g/L).There was no significant difference between the two groups(P>0.05).Serum HMGB1 expression level(30.68±2.67?g/L)was lower in the indomethacin group than in the control group(37.22±7.56?g/L),and the difference was statistically significant(P<0.05).Serum HMGB1 expression level(20.19±1.38?g/L)was lower in the indomethacin group than in the control group(22.83±2.30?g/L)24 hours after operation.The difference between the two groups was statistically significant(P<0.05).There was no significant difference in the white blood cell count between the indomethacin group and the control group at 3 hours before and after operation(P>0.05).The blood white blood cell count was significantly lower in the indomethacin group than in the control group at 24 hours after surgery.Statistical significance(P <0.05).There was no significant difference in the percentage of neutrophils between the indomethacin group and the control group before and after 3 hours(P>0.05).The percentage of blood white neutrophils was compared with the indomethacin group at 24 hours after operation.The difference was statistically significant(P<0.05).There was no significant difference in blood CRP concentration between the indomethacin group and the control group before operation,3 hours after operation and 24 hours after operation(P>0.05).Conclusion: Preoperative prophylactic administration of 100 mg indomethacin suppository can reduce the incidence of post-ERCP pancreatitis.Non-steroidal anti-inflammatory drugs can reduce the incidence of post-ERCP pancreatitis by down-regulating the expression of inflammatory factors such as HMGB1 and TNF-? and the activation of leukocytes and neutrophils.Part II A clinical analysis about risk factors of post-ERCP pancreatitis Objective: To further clarify the high risk factors of post-ERCP pancreatitis,so as to better prevent the occurrence of post-ERCP pancreatitis.Methods: The age of the patients,the history of previous cholecystectomy,the gender,the diameter of stones,the number of stones,the history of previous ERCP surgery,the operation time and other clinical data were collected.Using Chi-square test for univariate analysis and Logistic regression model for multivariate analysis to identification of high risk factors for post-ERCP pancreatitis.Result: A total of 100 patients were enrolled in the study.Twenty-two patients had pancreatitis after surgery,with an incidence of 22%.Univariate analysis showed that age,hypertension,operation time,and whether or not the drug was associated with post-ERCP pancreatitis(P<0.05).Multivariate analysis showed that the operation time and whether the drug was an independent risk factor for post-ERCP pancreatitis(P <0.05).Conclusion:Post-ERCP pancreatitis is associated with a variety of factors.The operation time and whether the drug is an independent risk factor for pancreatitis after ERCP should be taken to prevent pancreatitis after ERCP.