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Background: No randomized controlled trials have substantiated endoscopic decompression of the pancreatic duct in patients with painful chronic pancreatitis., Objective: To investigate the pain-relieving effect of pancreatic duct decompression in patients with chronic pancreatitis and intraductal stones., Design: 24-week, parallel-group, randomized controlled trial (ClinicalTrials.gov: NCT03966781)., Setting: Asian Institute of Gastroenterology in India from February 2021 to July 2022., Participants: 106 patients with chronic pancreatitis., Intervention: Combined extracorporeal shock-wave lithotripsy (ESWL) and endoscopic retrograde pancreatography (ERP) compared with sham procedures., Measurements: The primary end point was pain relief on a 0- to 10-point visual analog scale (VAS) at 12 weeks. Secondary outcomes were assessed after 12 and 24 weeks and included 30% pain relief, opioid use, pain-free days, questionaries, and complications to interventions., Results: 52 patients in the ESWL/ERP group and 54 in the sham group were included. At 12 weeks, the ESWL/ERP group showed better pain relief compared with the sham group (mean difference in change, -0.7 [95% CI, -1.3 to 0] on the VAS; P  = 0.039). The difference between groups was not sustained at the 24-week follow-up, and no differences were seen for 30% pain relief at 12- or 24-week follow-up. The number of pain-free days was increased (median difference, 16.2 days [CI, 3.9 to 28.5 days]), and the number of days using opioids was reduced (median difference, -5.4 days [CI, -9.9 to -0.9 days]) in the ESWL/ERP group compared with the sham group at 12-week follow-up. Safety outcomes were similar between groups., Limitation: Single-center study and limited duration of follow-up., Conclusion: In patients with chronic pancreatitis and intraductal stones, ESWL with ERP provided modest short-term pain relief., Primary Funding Source: Asian Institute of Gastroenterology and Aalborg University Hospital., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0210.

Background and Aims: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs)., Methods: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality., Results: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48)., Conclusions: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin., Methods: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP., Results: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002)., Conclusions: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users., Methods: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas., Conclusions: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs., Trial Registration: NCT05252754, registered on February 14, 2022., Competing Interests: Declaration of competing interest Mouen Khashab reports advisory board member and consultant for Boston Scientific. Erwin J.M. van Geenen reports grants from Mylan and Olympus, personal fees from MTW-Endoskopie, outside the submitted work. Vikesh Singh reports personal fees from Abbvie, advisory board participant for Cook Medical, and grants from Orgenesis and Theraly. Venkata Akshintala is co-founder and chief medical officer of Origin Endoscopy Inc. All other authors declare no competing interests., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure for the management of pancreaticobiliary disorders. ERCP is, however, associated with the risk of complications including pancreatitis, bleeding, perforation, infection, and instrument failure, which can often be fatal. It is, therefore, necessary to recognize the risk of ERCP-associated complications and understand the methods to prevent and treat such complications., Competing Interests: Disclosure The authors have no disclosures relevant to this publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis., Methods: We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606., Findings: We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons., Interpretation: This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis., Funding: None., Competing Interests: Declaration of interests JPHD reports grants from Gilead, outside the submitted work. BJE reports personal fees from Takeda Pharmaceuticals, outside the submitted work. MK is an advisory board member and consultant for Boston Scientific, outside the submitted work. ANK is an equity holder for Apollo Endosurgery, outside the submitted work. EJMvG reports grants from Mylan and Olympus and personal fees from MTW-Endoskopie, outside the submitted work. VKS reports personal fees from AbbVie, grants from Orgenesis and Theraly, and is an advisory board participant for Cook Medical, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Aims: The accurate measurement of technical skill in ERCP is essential for endoscopic training, quality assurance, and coaching of this procedure. Hypothesizing that technical skill can be measured by analysis of ERCP videos, we aimed to develop and validate a video-based ERCP skill assessment tool., Methods: Based on review of procedural videos, the task of ERCP was deconstructed into its basic components by an expert panel that developed an initial version of the Bethesda ERCP Skill Assessment Tool (BESAT). Subsequently, 2 modified Delphi panels and 3 validation exercises were conducted with the goal of iteratively refining the tool. Fully crossed generalizability studies investigated the contributions of assessors, ERCP performance, and technical elements to reliability., Results: Twenty-nine technical elements were initially generated from task deconstruction. Ultimately, after iterative refinement, the tool comprised 6 technical elements and 11 subelements. The developmental process achieved consistent improvements in the performance characteristics of the tool with every iteration. For the most recent version of the tool, BESAT-v4, the generalizability coefficient (a reliability index) was .67. Most variance in BESAT scores (43.55%) was attributed to differences in endoscopists' skill, indicating that the tool can reliably differentiate between endoscopists based on video analysis., Conclusions: Video-based assessment of ERCP skill appears to be feasible with a novel instrument that demonstrates favorable validity evidence. Future steps include determining whether the tool can discriminate between endoscopists of varying experience levels and predict important outcomes in clinical practice., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. All rights reserved.)

Background and Aims: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield., Methods: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders., Results: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement., Conclusions: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT., Competing Interests: Declaration of competing interest M. Bellin discloses research funding from Viacyte and Dexcom, and medical advisory role (DSMB) for Insulet., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Deep pancreatic cannulation (DPC) failure during endoscopic retrograde cholangiopancreatography (ERCP) in patients with chronic pancreatitis (CP) can occur in the presence of ductal obstruction due to strictures and/or stones. There are currently no simple preprocedure clinical or laboratory tests that can predict DPC failure during ERCP., Methods: All adult patients with definite CP by M-ANNHEIM criteria referred to the pancreatitis clinic between 2010 and 2017 were evaluated. Serum trypsin levels were obtained to assess the morphologic severity of disease and/or exocrine insufficiency. Univariable and multivariable logistic regression analyses were performed to identify factors associated with DPC failure., Results: There were 346 patients, of whom 100 underwent trypsin measurements and ERCP for symptomatic CP. Deep pancreatic cannulation failure occurred in 32 (32%). There were no significant differences with regard to age, sex, etiology, smoking, and alcohol use. Deep pancreatic cannulation failure was more likely to occur in patients with low trypsin levels (53.1% vs 25%, P = 0.007) compared with those with successful DPC. Low trypsin levels were independently associated with DPC failure in adjusted analysis (odds ratio, 3.7; 95% confidence interval, 1.2-11; P = 0.02)., Conclusions: Low serum trypsin levels independently predict DPC failure during ERCP in patients with symptomatic obstructive CP.

Objectives: We compared outcomes of acute alcoholic pancreatitis (AAP), acute biliary pancreatitis (ABP), and post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP)., Methods: This was a retrospective cohort study conducted at a tertiary care center between June 2007 and June 2012., Results: A total of 300 (68%) patients were diagnosed with AAP, 88 (20%) with ABP, and 55 (12%) with PEP. Longer length of hospital stay (LOHS) was more common in ABP (23%) as compared with AAP (10%) and PEP (7%, P = 0.025). Pseudocyst (P = 0.048), organ failure (OF) (P = 0.01), need for interventions (P ≤ 0.001), and mortality (P = 0.002) occurred more in ABP as compared with other groups. Systemic inflammatory response syndrome was associated with LOHS of more than 10 days (P = 0.01) and multi-OF (P = 0.05). Chronic pancreatitis was associated more with pseudocyst (P < 0.001) and mortality (P = 0.03). Serum urea nitrogen of greater than 25 g/dL predicted LOHS of more than 10 days (P = 0.02), OF (P < 0.001), multi-OF (P < 0.001), and persistent OF (P < 0.001)., Conclusions: Acute biliary pancreatitis is a more severe disease compared with PEP and AAP. Chronic pancreatitis, systemic inflammatory response syndrome, and high serum urea nitrogen are important predictors of morbidity.

Introduction: Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone., Methods: We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group., Results: A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar between the 2 groups. Women <50 years of age (25.4%) and difficult cannulation (84.9%) were the most common PEP risk factors. The incidence of PEP was 6.4% in the indomethacin alone group (n = 482) compared to 6.7% in the combination group (n = 477; P = 0.87). Severe PEP was found in 5 (12%) and 7 (16%) patients in the indomethacin alone and combination groups, respectively (P = 0.88). The overall mortality was 0.6%, which was unrelated to the primary outcome., Conclusions: The combination of rectal indomethacin and topical spray of epinephrine does not reduce the incidence of PEP compared to rectal indomethacin alone in high-risk patients; https://clinicaltrials.gov/ct2/show/NCT02116309.

Background: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO)., Methods: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded., Discussion: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial., Trial Registration: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Purpose of Review: Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis., Recent Findings: The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy., Summary: The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery.

Background and Aims: Perforation is a rare but serious adverse event of ERCP. There is no consensus to guide the clinician on the management of ERCP-related perforations, with particular controversy surrounding the immediate surgical management of postprocedurally detected duodenal perforation because of overextension of a sphincterotomy. Our aim was to assess patient outcomes using a predetermined algorithm based on managing ERCP-related duodenal perforations according to the mechanism of injury., Methods: A retrospective single-center study of all consecutive patients with Stapfer type I and II perforations between 2000 and 2014 were included. Our institutional algorithm since 2000 dictated that Stapfer type I perforations (duodenal wall perforation, endoscope related) should be managed surgically unless prohibited by underlying comorbidities and Stapfer type II perforations (periampullary, sphincterotomy related) managed nonsurgically unless a deterioration in clinical status necessitated surgery., Results: Sixty-one patients (mean age, 51 years; 80% women) were analyzed with Stapfer type I perforations diagnosed in 7 (11%) and type II in 54 (89%). A postprocedural diagnosis of perforation was made in 55 patients (90%). Four patients (7%) had Stapfer type II perforations that failed medical management and required surgery. The mean length of stay (LOS) in the entire cohort was 9.6 days with a low mortality rate of 3%. Systemic inflammatory response syndrome was observed in 18 patients (33%) with Stapfer type II perforations and was not associated with the need for surgery. Concurrent post-ERCP pancreatitis was diagnosed in 26 patients (43%) and was associated with an increased LOS., Conclusions: Stapfer type II perforations have excellent outcomes when managed medically. We validate an algorithm for the management of ERCP-related perforations and propose that it should function as a guide., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP., Methods/design: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked., Discussion: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough., Trial Registration: NCT02476279, registered June 2015.

Background. Consensus guidelines recommend that patients at high risk for choledocholithiasis undergo endoscopic retrograde cholangiopancreatography (ERCP) without additional imaging. This study evaluates factors and outcomes associated with performing magnetic resonance cholangiopancreatography (MRCP) prior to ERCP among patients at high risk for choledocholithiasis. Methods. An institutional administrative database was searched using diagnosis codes for choledocholithiasis, cholangitis, and acute pancreatitis and procedure codes for MRCP and ERCP. Patients categorized as high risk for choledocholithiasis were evaluated. Results. 224 patients classified as high risk, of whom 176 (79%) underwent ERCP only, while 48 (21%) underwent MRCP prior to ERCP. Patients undergoing MRCP experienced longer time to ERCP (72 hours versus 35 hours, p < 0.0001), longer length of stay (8 days versus 6 days, p = 0.02), higher hospital charges ($23,488 versus $19,260, p = 0.08), and higher radiology charges ($3,385 versus $1,711, p < 0.0001). The presence of common bile duct stone(s) on ultrasound was the only independent factor associated with less use of MRCP (OR 0.09, p < 0.0001). Conclusions. MRCP use prior to ERCP in patients at high risk for choledocholithiasis is common and associated with greater length of hospital stay, higher radiology charges, and a trend towards higher hospital charges.

Background & Aims: There is controversy over the efficacy of pharmacologic agents for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). We performed a systematic review of PEP pharmacoprevention to evaluate safety and efficacy., Methods: We performed a systematic search of the literature for randomized controlled trials (RCTs) and meta-analyses of PEP pharmacoprevention through February 2014. After identifying relevant studies, 2 reviewers each extracted information on study characteristics, clinical outcomes, and risk of bias. A research classification scale was developed to identify pharmacologic agents ready for clinical use, agents for which a confirmatory RCT should be considered a high priority, agents for which exploratory studies are still necessary, and agents for which additional research should be of low priority. Clinical and research recommendations for each agent were made by consensus after considering research classification results and other important factors such as magnitude of benefit, safety, availability, and cost., Results: After screening 851 citations and 263 potentially relevant articles, 2 reviewers identified 85 RCTs and 28 meta-analyses that were eligible. On the basis of these studies, rectal nonsteroidal anti-inflammatory drugs were found to be appropriate for clinical use, especially for high-risk cases. Sublingual nitroglycerin, bolus-administered somatostatin, and nafamostat were found to be promising agents for which confirmatory research is warranted. Additional research was found to be required to justify confirmatory RCTs for topical epinephrine, aggressive intravenous fluids, gabexate, ulinastatin, secretin, and antibiotics., Conclusions: On the basis of a systematic review, NSAIDs are appropriate for use in prevention of PEP, especially for high-risk cases. Additional research is necessary to clarify the role of other pharmacologic agents. These findings could inform future research and guide clinical decision-making and policy., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Anastomotic biliary strictures (ABS) are a significant clinical problem associated with decreased survival post-liver transplantation (LT). Contributing to the morbidity of ABS is the need for early (i.e. emergent or unplanned) repeat endoscopic retrograde cholangiopancreatographies (ER-ERCPs). Our aim was to determine clinical, operative, and endoscopic predictors of ER-ERCP in patients with ABS., Material and Methods: Medical records of 559 patients who underwent LT at our institution from 2000-2012 were retrospectively reviewed for pertinent data. The primary endpoint was need for ER-ERCP. Seventeen potential predictors of ER-ERCP were assessed in bivariate analyses, and those with p < 0.20 were included in multivariate regression models., Results: Fifty-four LT patients developed ABS and underwent a total of 200 ERCPs, of which 40 met criteria for ER-ERCP. Predictors of ER-ERCP in bivariate analyses included balloon dilation within 3 months post-LT and donation after cardiac death (both p < 0.05). Balloon dilation within 3 months post-LT was also associated with shorter ER-ERCP-free survival (p = 0.02). Moreover, a significantly higher proportion (67%) of patients who underwent balloon dilation within 3 months post-LT subsequent experienced ≥ 1 ER-ERCP (p = 0.03), and those who experienced ≥ 1 ER-ERCP had lower stricture resolution rates at the end of endoscopic therapy compared to those who did not (79 vs. 97%, p = 0.02). In multivariate analyses, balloon dilation within 3 months post-LT was the strongest predictor of ER-ERCP (OR 3.8, 95% CI 1.7-8.6, p = 0.001)., Conclusions: Balloon dilation of ABS within 3 months post-LT is associated with an increased risk of ER-ERCP, which itself is associated with lower ABS resolution rates. Prospective studies are needed to confirm these findings and their implications for endoscopic management and follow-up of post-LT ABS.

Background: Early systemic inflammatory response syndrome (SIRS) has been associated with severe non-iatrogenic acute pancreatitis. The aims of this study were to determine whether early SIRS could be used to predict severe post-ERCP pancreatitis (PEP) and to determine the effect of prophylactic-pancreatic stenting (PS) on SIRS and severe PEP., Methods: Between 1/2000 and 6/2012, all patients admitted for PEP after an outpatient ERCP and who had ≥1 abdominal CT scan during hospitalization were retrospectively evaluated. The presence of SIRS was assessed between 0 and 24 h and 24 and 48 h after the time of ERCP completion. SIRS was evaluated as a predictor of severe PEP using area under receiver operating characteristic (AUROC) curve analysis., Results: There were 113 patients with PEP of whom 22 (19.5%) had severe PEP. SIRS was present in 44 (38.9%) and 33 (29.2%) patients between 0 and 24 h and 24 and 48 h, respectively. SIRS between 24 and 48 h had a higher predictive accuracy for severe PEP compared to SIRS between 0 and 24 h (AUROC = 0.7 vs. 0.5, p = 0.002). The prevalence of SIRS between 24 and 48 h was significantly less among the 19 patients who underwent PS (11% vs. 37%, p = 0.03). There was no difference between the prophylactic stenting and no stenting groups with regards to acute fluid collection(s), pancreatic necrosis, organ failure or mortality during hospitalization., Conclusions: SIRS between 24 and 48 h after ERCP is an accurate, easy to obtain, and inexpensive predictor of severe PEP. PS is associated with a decreased prevalence of SIRS between 24 and 48 h after ERCP., (Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Endoscopic ultrasound-guided biliary drainage (EGBD) may be a safe, alternative technique to percutaneous transhepatic biliary drainage (PTBD) in patients who fail ERCP. However, it is currently unknown how both techniques compare in terms of efficacy, safety, and cost. The aims of this study were to compare efficacy, safety, and cost of EGBD to that of PTBD., Methods: Jaundiced patients with distal malignant biliary obstruction who underwent EGBD or PTBD after failed ERCP were included. Technical success, clinical success, and adverse events between the two groups were compared., Results: A total of 73 patients with failed ERCP subsequently underwent EGBD (n = 22) or PTBD (n = 51). Although technical success was higher in the PTBD group (100 vs. 86.4 %, p = 0.007), clinical success was equivalent (92.2 vs. 86.4 %, p = 0.40). PTBD was associated with higher adverse event rate (index procedure: 39.2 vs. 18.2 %; all procedures including reinterventions: 80.4 vs. 15.7 %). Stent patency and survival were equivalent between both groups. Total charges were more than two times higher in the PTBD group (p = 0.004) mainly due to significantly higher rate of reinterventions (80.4 vs. 15.7 %, p < 0.001)., Conclusion: EGBD and PTBD are comparably effective techniques for treatment of distal malignant biliary obstruction after failed ERCP. However, EGBD is associated with decreased adverse events rate and is significantly less costly due to the need for fewer reinterventions. Our results suggest that EGBD should be the technique of choice for treatment of these patients at institutions with experienced interventional endosonographers.

Background: Data regarding the incidence and severity of post-ERCP pancreatitis (PEP) are primarily from nonrandomized studies., Objective: To determine the incidence, severity, and mortality of PEP from a systematic review of the placebo or no-stent arms of randomized, controlled trials (RCTs)., Design: MEDLINE, EMBASE, and Cochrane databases were searched to identify RCTs evaluating the efficacy of drugs and/or pancreatic stents to prevent PEP., Setting: Systematic review of patients enrolled in RCTs evaluating agents for PEP prophylaxis., Patients: Patients in the placebo or no-stent arms of the RCTs, Intervention: ERCP., Main Outcome Measurements: Incidence, severity, and mortality of PEP., Results: There were 108 RCTs with 13,296 patients in the placebo or no-stent arms. Overall, the PEP incidence was 9.7% and the mortality rate was 0.7%. Severity of PEP was reported for 8857 patients: 5.7%, 2.6%, and 0.5% of cases were mild, moderate, and severe, respectively. The incidence of PEP in 2345 high-risk patients was 14.7% and the severity of PEP was mild, moderate, and severe in 8.6%, 3.9%, and 0.8%, respectively, with a 0.2% mortality rate. The incidence of PEP was 13% in North American RCTs compared with 8.4% in European and 9.9% in Asian RCTs. ERCPs conducted before and after 2000 had a PEP incidence of 7.7% and 10%, respectively., Limitations: Difference in PEP risk among patients in the included RCTs., Conclusion: The incidence of PEP and severe PEP is similar in high-risk patients and the overall cohort. Discrepancies in the incidence of PEP across geographic regions require further study., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the CT severity of post-ERCP pancreatitis (PEP) and determine the association between radiographic and clinical severity., Methods: There were 1332 patients admitted to the hospital with suspicion for PEP after undergoing ERCP as outpatients over a 10-year period, of whom 84 (6.3%) patients underwent at least one contrast-enhanced CT scan while hospitalized were evaluated. All CT scans were evaluated by two radiologists, and the modified CT severity index (MCTSI) score was calculated. Demographic, clinical, and procedural data as well as clinical severity parameters including systemic inflammatory response syndrome, organ failure, need for ICU, need for intervention, length of hospital stay, and mortality were recorded. Statistical analysis was performed using the χ (2) and Student's t test or ANOVA and logistic regression analysis., Results: Patients were predominantly females (70%) with a mean age of 46.5 years (range 20-86). The most common indication for ERCP was sphincter of Oddi dysfunction. MCTSI was graded as mild in 45 (53.6%), moderate in 36 (42.8%), and severe in 3 (3.6%) patients. The interobserver agreement was excellent (κ: 0.91, p < 0.0001) for MCTSI. The duration of ERCP (p = 0.005) was the only risk factor for PEP that significantly correlated with the MCTSI score. Increasing MCTSI was significantly associated with hospital length of stay., Conclusions: PEP is typically a mild disease by radiologic and clinical criteria. Longer duration of ERCP is a risk factor for severe radiologic PEP. Severe radiographic PEP is associated with significantly longer hospital length of stay.

Background and Study Aims: Placement of a pancreatic stent is recommended for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatitis (ERCP) among high-risk patients. However, it is not known whether there is a particular feature of the pancreatic stent that is associated with a lower incidence of post-ERCP pancreatitis (PEP). This systematic review and network meta-analysis (NMA) aimed to examine whether a particular feature of pancreatic stents is associated with lower incidence of PEP., Patients and Methods: The MEDLINE, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that evaluated the efficacy of pancreatic stents in the prevention of PEP from September 1993 to June 2013. Trials that reported the incidence of PEP in high-risk patients randomized to one vs. another type of pancreatic stent or vs. no stent at all were included in the analysis., Results: Among the 1377 citations identified from the database searches, 6 RCTs involving 561 patients were included. Three RCTs evaluated 5-Fr straight, flanged pancreatic stents, two RCTs evaluated 5-Fr single-pigtail, unflanged stents, and three RCTs evaluated 3-Fr single-pigtail, unflanged stents. The probability of being ranked the best was 50.3 % (SD = 0.5, Markov chain error = 0.003) for 5-Fr single-pigtail, unflanged pancreatic stents, 46.5 % for 5-Fr straight, flanged stents, and 3.1 % for 3-Fr single-pigtail, unflanged stents., Conclusion: The 5-Fr pancreatic stent is superior to the 3-Fr pancreatic stent for the prevention of PEP in high-risk patients. The 5-Fr single-pigtail, unflanged pancreatic stent and 5-Fr straight, flanged pancreatic stent performed similarly and both performed better than the 3-Fr pancreatic stent in preventing PEP, suggesting that stent diameter is more important for the prevention of PEP than type of stent or the presence of flanges., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS)., Material and Methods: Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC., Results: 45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038)., Conclusions: Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

Background & Aims: Acute ascending cholangitis usually is treated with antibiotics, and biliary drainage is treated by endoscopic retrograde cholangiopancreatography (ERCP). We investigated the effects of the timing of ERCP on outcomes of patients with acute cholangitis factors that predict prolonged hospital stays, increased costs of hospitalization, and composite clinical outcomes (death, persistent organ failure, and admission to the intensive care unit)., Methods: We performed a retrospective analysis of data from 90 patients (mean age, 60 y; 48% female) admitted to Johns Hopkins Hospital from January 1994 to June 2010 who were diagnosed with acute cholangitis and underwent ERCP. A delayed ERCP was defined as one performed more than 72 hours after admission. Electronic and paper medical records were reviewed, and relevant data were abstracted., Results: ERCP was performed successfully in 92% of the patients, at a mean time period of 38 hours after admission (14% of ERCPs were delayed). Factors that were associated independently with prolonged length of hospital stay (top 10%) included unsuccessful ERCP (odds ratio [OR], 52.5; P = .002) and delayed ERCP (OR, 19.8; P = .008). Factors associated with increased hospitalization cost (top 10%) included unsuccessful ERCP (OR, 33.8; P = .004) and delayed ERCP (OR, 11.3; P = .03). Factors associated with composite clinical outcome included age (OR, 1.1; P = .01), total level of bilirubin (OR, 1.36; P = .002), and delayed ERCP (OR, 7.8; P = .04)., Conclusions: Delayed and failed ERCP are associated with prolonged hospital stays and increased costs of hospitalization. Delayed ERCP is associated with composite clinical outcome (death, persistent organ failure, and/or intensive care unit stay). Older age and higher levels of bilirubin also are associated with patients' composite end point., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: Conventional plastic stents with a lumen typically have limited patency. The lumenless wing stent was engineered to overcome this problem. The objective of this study was to compare the incidence of early stent occlusion (symptomatic occlusion/cholangitis necessitating re-insertion within 90 days) for wing stents and conventional plastic stents., Patients and Methods: Patients with biliary pathology treated with plastic biliary stenting during the period 2003-2009 comprised the study cohort. Patients who had at least one biliary wing stent placed comprised the wing stent group, whereas patients who underwent only conventional stent plastic placement comprised the conventional stent group. Patients were stratified by indication: benign biliary strictures (group 1), malignant biliary strictures (group 2), or benign biliary non-stricture pathology (group 3). The association of stent type with the occurrence of primary outcome by indication was analyzed by use of multivariable logistic regression., Results: Three-hundred and forty-six patients underwent 612 ERCP procedures with placement of plastic biliary stent(s). On multivariate analysis, early stent occlusion did not differ between the wing and conventional groups in groups 1, 2, and 3. Among patients who achieved primary outcome in group 2, significantly fewer patients in the wing group had cholangitis (6.7% vs. 39.1%, P = 0.03). Among patients who achieved primary outcome in group 3, significantly fewer patients in the wing group had cholangitis (10% vs. 50%, P = 0.03)., Conclusions: Early stent occlusion was similar for wing stents and conventional plastic stents. Wing stents, however, were associated with a lower incidence of cholangitis in patients with malignant biliary obstruction and benign non-stricturing biliary pathology.