Prospective Studies On Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis And Difficult Cannulation

Background Endoscopic retrograde cholangiopancreatography(ERCP)is an advanced endoscopic technique widely used as the first-line treatment of biliary and pancreatic diseases,and post-ERCP pancreatitis(PEP)is the most common complication of it.Prevention of PEP is a critical issue in clinical research of ERCP.In addition to pharmacological agents,multiple aspects such as risk factors,cannulation strategy,and operator training need to be considered for the prevention of PEP.Several studies have confirmed that difficult intubation is an independent risk factor for PEP,usually manifested by prolonged cannulation time,increased cannulation attempts,or inadvertent pancreatic duct cannulation.The incidences of PEP and difficult cannulation are influenced by several factors,including patient-related factors,procedurerelated factors,operator experience,and major papilla morphology etc.Certain types of duodenal major papilla may lead to difficult cannulation.The existing papilla classification criteria are based on differences in overall papilla morphology or opening morphology,and several studies suggest that small flat papilla and large protruding papilla may be associated with difficult cannulation or even PEP.On the one hand,these classification criteria are mostly based on subjective observations by endoscopists,and their inter-and intra-observer agreement needs to be improved;on the other hand,the relationship between papilla morphology and patient outcome events,such as complications including PEP,deserves further investigation.The influence of other variables of the papilla morphology,such as the position,axial orientation,transverse folds,and periampullary diverticulum(PAD),on PEP and difficult cannulation is unclear.Difficult cannulation with inadvertent pancreatic duct cannulation increased the risk of PEP.Double-guidewire technique(DWT)can effectively increase the cannulation rate to 90%,and in combination with pancreatic duct stenting,can also significantly reduce the incidence of PEP.In the hands of ERCP trainees,the success rate of selective cannulation is only 54.5%,which is partly due to the limited time allotted and the fact that they are only allowed to use the standard cannulation,in addition to being limited by their proficiency and inexperience.Compared to other advanced cannulation techniques,such as precut,the double-guidewire technique is less challenge and has a lower risk of bleeding and perforation,thus may be suitable for trainees to perform during hands-on ERCP training.Currently there are no study on the learning curve and safety of double-guidewire technique by trainees.Aims: 1.To investigate the influence of the major papilla morphology on the PEP and cannulation through a prospective multicenter cohort study.2.A prospective single-center cohort study was conducted to investigate the learning curve and safety of double-guidewire technique by trainees during ERCP hands-on training in difficult cannulation scenarios.Methods: 1.Patients with native major duodenal papilla who underwent ERCP were consecutively recruited in 4 study centers according to the inclusion/exclusion criteria.1)Papilla-related variables collection: pictures of each major papilla were taken endoscopically according to the set criteria before selective cannulation.The length of the long axis(L),short axis(S)and the opening width(OW)of each papilla were measured by Image J and the L/S ratio and L/OW ratio were calculated.Other papilla morphological variables such as transverse folds,periampullary diverticulum,orientation of the papilla,papilla swelling and duodenal stricture were documented.2)Other data collection: Clinical outcomes and complications of ERCP were documented;patient’s demographic data,disease history,and procedure-related variables were documented to investigate potential patient-related and procedurerelated PEP risk factors.3)Study endpoints: The primary outcome was the incidence of PEP;secondary outcomes included the rate of difficult cannulation,total cannulation time,total cannulation attempts,unintended PD cannulation,and overall ERCP-related complications.4)Statistical analysis: Risk factors for PEP were identified by univariate and multivariate logistic regression analysis.2.All ERCP patients with difficult cannulation were recruited consecutively in this study according to the inclusion/exclusion criteria.1)Basic ERCP training: 2 ERCP trainees A and B completed ERCP simulator training,case observation and initial hands-on training before entering the study.2)DWT training: 2 trainees were randomized to perform DWT on patients with difficult cannulation under verbal instruction and/or hands-on assistance from the trainer.Their performance scores(including assistance scores and skill scores),ERCP outcomes,and procedure-related variables were documented.3)Study endpoints: The primary outcome was the success rate of trainee’s DWT.The secondary outcomes were the assistance score and skill score,the time and attempts of DWT,precut rate,and the incidence of complications such as PEP.4)Statistical methods: Cumulative summation analysis(CUSUM)was used to generate visualized learning curves.logistic regression analysis was used to identify factors associated with the success of DWT.Results: 1.658 ERCP patients who met the inclusion/exclusion criteria were enrolled.1)PEP and cannulation: The incidence of PEP was 4.7%(31/658).the overall complication rate of ERCP was 6.4%.The final cannulation success rate was 98.5%.The incidence of difficult cannulation was 55.2%.The median total cannulation time was 469 seconds and the median total cannulation attempts was 5. 2)The impact of major papilla’s morphology on PEP: patients who developed PEP had a higher L/S ratio(OR 3.84,95% CI: 1.37-10.74,p=0.010),a higher L/OW ratio(OR 1.35,95% CI: 1.06-1.71,p=0.014),and a higher number of transverse folds(OR 2.53,95% CI: 1.02-6.26,p=0.044)and less periampullary diverticulum(OR 0.21,95% CI: 0.06-0.70,p=0.011).3)The impact of major papilla’s morphology on difficult cannulation: Patients with L/S ratio ≥1.5 had a higher incidence of difficult cannulation(69.1% vs.53.5%,p=0.015)and an increased cannulation attempts and unintended PD cannulation.However,there was no difference in final cannulation success rate(98.5% vs.98.5%,p=1.0).4)Risk factors for PEP: Multivariate logistic regression analysis showed that among the variables associated with papillary morphology,L/S ratio ≥1.5(OR 3.53,95% CI:1.48-8.47)was an independent risk factor for PEP,and periampullary diverticulum(OR 0.26,95% CI:0.08-0.89)was an independent protective factor for PEP.Patient-related factors(indications other than common bile duct stones,normal serum bilirubin)and procedure-related factors(unintended PD cannulation >1)were also independent risk factors for PEP.2.60 patients with difficult cannulation were included.The final cannulation success rate was 98.3%(59/60).The incidence of PEP and overall adverse events was 6.7% and 8.3%,respectively.1)Learning curve of DWT: to achieve a targeted DWT success rate of 70%,12 and 15 procedures were required for trainee A and B,respectively.Higher targeted success rate of DWT could be achieved if the number of DWT procedures increased.The success rate was significantly higher in the late stage(case 15-30)(36.7%(11/30)vs.80%(24/30),p=0.001).2)Trainee’s performance scores: trainees could achieve an assistance score of 3 after 12-14 DWT cases;and a skill score of 4 after 11-14 DWT cases.The assistance score and skill score also improved significantly in the late stage.3)Risk factors for trainee’s DWT success: trainee’s performance in the early stage was the only risk factor negatively associated with DWT success(OR 0.16,95% CI: 0.05-0.52,p=0.001).Conclusions: 1.The L/S ratio of the major papilla and the absence of PAD were found to be independent risk factors for PEP,suggesting that in addition to patient-related and procedure-related factors,the papilla-related variables can be considered as a third types of factors associated with PEP.2.Trainees may become competent with DWT after performing 15 cases during the ERCP hands-on training.