From January 2011 to November 2016, a total of 546 patients were diagnosed or treated with ERCP at the First Affiliated Hospital of Dalian Medical University. The study was conducted in compliance with the Helsinki Declaration and in accordance with local legislation, was approved by the Ethics Committee of First Affiliated Hospital, Dalian Medical University. (Ethics References No: YJ-KY-FB-2019-01). Written informed consent was obtained from all of the patients or their relatives before the procedure.
The inclusion and exclusion criteria were as follows:
Inclusion criteria: (1) preoperative serum amylase and lipase levels were normal; (2) age ≥18 years; (3) serum amylase level was measured 3 hours after ERCP; (4) patients have not used trypsin inhibitor before the diagnosis of PEP.
Exclusion criteria: (1) preoperative diagnosis of acute and chronic pancreatitis (2) abnormal renal function (serum creatinine > 92umol / L) (3) pregnant women
According to the inclusion and exclusion criteria above, a total of 206 patients were enrolled, including 92 males and 114 females, among them, 84 cases were simultaneously detected for serum lipase.
The diagnosis of pancreatitis after ERCP is based on the consensus reached by Cotton et al[4, 13], and the international consensus on the classification of acute pancreatitis in Atlanta in 2012.
(1) Acute pancreatic abdominal pain within 24 hours after ERCP;
- Serum amylase more than 3 times the upper limit of normal within 72 hours after ERCP(normal value is 30-110U/L) or lipase greater than 3 times the upper limit of normal within 96h after ERCP(normal reference range 23-300U/L) ;
- Contrast-enhanced CT, MRI, abdominal ultrasound showing acute pancreatitis changes (pancreatic enlargement, exudation, necrosis and other AP signs); having two of the three criteria will lead to a diagnosis of PEP.
- The necessity for new or continued hospitalization for at least 2 nights.
1.2 Equipment Description
Duodenoscope（JF-260, Olympus Optical Corporation, Tokyo, Japan), guide wire (Hydra Jagwire 0.035 inch, Boston Scientific Microvasive. Cork, Ireland), triple lumen sphincterotome (Papillotome, ENDO-FLEX GmbH, Germany), CRE balloon catheter (Boston Scientific Microvasive, Cork, Ireland), retrieval balloon catheter (Extractor Three Lumen Retrieval Balloon, Boston Scientific Microvasive. Cork, Ireland), Dormia basket (Web™ extraction basket, Wilson-Cook Medical Inc. Winston-Salem, North Carolina, United States), Percuflex Biliary Stent(Boston Scientific Corporation,One Boston Scientific Place, Natick, MA 01760-1537, USA), nasal biliary drainage tube (nasobil.Sonde, ENDO-FLEX GmbH, Germany), WallFlex Biliary RX Fully Covered Stent System(Boston Scientific Corporation,One Boston Scientific Place, Natick, MA 01760-1537, USA),Mechanical lithotripsy (BML-4Q; Olympus Optical, Tokyo, Japan).
Some ERCP procedures were accomplished under ECG monitoring. Tetracaine was given for local anesthesia of the pharynx. The patients were sedated and relieved pain by intramuscular administration of diazepam and meperidine. 20 mg of butyl scopolamine bromide was injected intramuscularly prior to the procedure to inhibit duodenal peristalsis.
A sphincterotome with a guide wire was used for selective cannulation. Difficulties in selective cannulation including stenosis and sclerosis of the papillary, incarceration of common bile duct (CBD) stone at papilla, and periampullary diverticulum，especially the papilla is located at bottom of the diverticulum.
For some cases difficulty in bile cannulation, precut through pancreatic duct was applicated. For cases with incarceration of CBD stone at papilla, needle knife was used for precut sphincterotomy. For papilla located at the bottom of diverticulum, it was exposed by eversion diverticulum through biopsy forceps, or fixation by metal clip, or submucosal injection of saline.
For patients with CBD stones, small endoscopic sphinecterotomy (EST) alone or EST combined with endoscopic papillary balloon dilation(EPBD) was performed. For biliary tract benign stricture or biliary fistula, ERBD was given. For biliary or pancreatic malignant tumor, a self-expanding metal stent was placed.
Mechanical lithotripsy was used for large common bile duct stones. However, if patient was in poor condition and cannot tolerate long procedure time, just ERBD was placed for drainage and to relieve symptoms. And a next ERCP was performed for removal of cholelithiasis three months later.
Serum amylase, lipase, biochemical liver function and renal function were detected by Johnson & Johnson's VITROS FS5.1 automatic biochemical analyzer.
1.4 statistical methods
According to the inclusion and exclusion criteria above, a total of 206 patients were enrolled, and each patient's progress note was reviewed by the medical record system. Sudden pancreatitis-like mid-abdominal pain within 24 hours after ERCP was marked positive, otherwise negative; combined with CT, serum amylase, lipase levels, comprehensive estimation was made according to the PEP diagnostic criteria .
Statistical methods: 1. Descriptive analysis of the enrolled patients, a preliminary understanding of the basic situations of the study objects. 2. The ROC curve was plotted according to the 3-hour post-ERCP serum amylase level of the enrolled patients and PEP diagnosis. According to the area under the ROC curve and the 95% confidence interval of the area, the accuracy of the tests was evaluate based on statistical tests. The Youden index was calculated according to the sensitivity and specificity of each level and the optimal cut-off value was obtained. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio, Youden index of different cut-off sites were calculated, comprehensively evaluated the accuracy and predictive value of the predictive diagnostic method. 3. According to gender, they were divided into two groups, and the ROC curves were drawn and analyzed separately aimed to find best cut-off in different gender. As a same lab test whose diagnosis accuracy（be showed as AUC in ROC） should have no difference between genders or other classifications of subjects. So we use Z test to test the reliability of data，then obtain the optimal diagnostic cut-off value according to these two curves. 4. Matched-pair analysis of ROC curves in patients who were simultaneously tested for both serum amylase levels and lipase levels 3 hours after ERCP. According to the two test Methods, the ROC curves were drawn and statistically tested, and the difference test (Z test) was performed to compare and analyze the diagnostic accuracy and diagnostic value in the two groups.
Statistical software: Medcalc was applied to perform matched-pair analysis. The ROC curve of serum amylase of different gender patients were plotted using SPSS software, and then the difference test was performed according to the standard error and the area under the curve. The Z value was manually calculated, and the P value was looked up in the table .
Related formula: (see Supplemental Files for Formulas)