Search

Background and Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients., Methods: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model., Results: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups., Conclusions: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Sphincter of Oddi dysfunction (SOD) is managed primarily by endoscopic sphincterotomy (ES); however, surgical transduodenal sphincteroplasty (TDS) is a treatment option for select patients. In our high-volume pancreatico-biliary practice, we have observed variable outcomes among TDS patients; therefore, we sought to determine preoperative predictors of durable improvement in quality of life., Methods: SOD patients treated by TDS between January 2006 and December 2015 were studied. The primary outcome measure was long-term changes in quality of life after sphincteroplasty. The secondary outcome measure examined postoperative outcomes, including postoperative complications, need for repeat procedures, and readmission rates. Perioperative data were abstracted, and the SF-36 quality-of-life (QoL) survey was administered. Standard statistical analysis included non-parametric methods to examine bivariate associations., Results: Eighty-eight patients had an average follow-up duration of 6.7 (± 2.9) years. Thirty (34%) patients were naïve to endoscopic therapy. Patients with prior endoscopy averaged 2.1 procedures (range 1 to 13) prior to surgery. Perioperative morbidity was 27%; one postoperative death was caused by severe acute pancreatitis. Twenty-nine (33%) patients required subsequent biliary-pancreatic procedures. QoL analysis from available patients showed that 66% were improved or much improved. With multivariable analysis including SOD type and prior endoscopic instrumentation, freedom from surgical complication was the only variable that correlated significantly with a good outcome (p < 0.02)., Conclusion: Surgical transduodenal sphincteroplasty provides durable symptom management for select patients with sphincter of Oddi dysfunction. Minimizing surgical complications optimizes long-term outcomes., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background and Aims: Post-ERCP pancreatitis (PEP) is the most frequent adverse event of ERCP. Various prophylactic measures are endorsed by the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy to both lower the incidence of PEP and to decrease its severity. The extent to which these interventions are practiced throughout the United States is unclear. The aim of this study was to describe the utilization pattern of various PEP measures and determine factors that affect utilization of these measures., Methods: A 27-question electronic survey was distributed using a cloud-based program (Qualtrics). The questions assessed ERCP training, practice setting, experience, practice patterns, and perceptions for PEP prophylaxis interventions. Endoscopists with practices based in the United States listed in the American Society for Gastrointestinal Endoscopy member directory received a survey invitation via e-mail. The invitation outlined the study and contained a link with instructions to complete the voluntary survey if they had an active ERCP practice. Data were de-identified for the purposes of analysis., Results: Of survey respondents (N = 319), 46% reported therapeutic endoscopy fellowship training and 37% practiced in teaching programs. Annualized ERCP volume of >100 cases per year were reported by 47%, with pancreatic ERCP comprising ≤5% of procedure volume reported by the majority of respondents (61%). The majority of respondents used prophylactic pancreatic stent (PPS), and 54% reported frequent use during high-risk ERCP. The most common indications for PPS were difficult cannulation, to assist biliary access, and multiple pancreatic duct injections. Most respondents reported frequent use of indomethacin (89%). Of physicians who did not use PPS, use of indomethacin was the most common reason (80%). Variables associated with frequent use of PPS were ERCP fellowship training (P ≤ .001), practice at a teaching program (P ≤ .001), <10 years in practice (P = .005), higher procedure volume (P ≤ .001), and higher proportion of pancreatic cases (P ≤ .001)., Conclusions: Physicians with higher annual ERCP volume, who teach at hospital-based ERCP practices, and who regularly perform pancreatic ERCP are more likely to use PPS. Therapeutic ERCP fellowship training and recent entry into practice were also associated with PPS utilization. Indomethacin use seems to be more frequent than PPS. Our findings suggest that indomethacin is supplanting PPS as the preferred method of PEP prophylaxis., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Abstract: Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study., Competing Interests: E.A. is on the advisory board for Nestle. M.D.B. receives research support from Viacyte and Dexcom and is on advisory board for Insulet. K.M.D. receives research support from Sanofi, Viacyte, Abbott, and Dexcom; has consulting activities with Eli Lilly, Boehringer Ingelheim, Elsevier; and receives honoraria from UptoDate, Elsevier, Medscape, and Academy for Continued Healthcare Learning. C.E.F. receives research support from AbbVie and has consulting activities with Nestle. G.I.P. receives research support from AbbVie and has consulting activities with Nestle. C.S. is on the advisory board for Vertex Pharmaceuticals. F.G.S.T. receives research support from Dompé Pharmaceuticals and has consulting activities with Sanofi, Eli Lilly, and AstraZeneca. The other authors declare no conflict of interest., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Abstract: Recruitment and retention of patients with acute pancreatitis (AP) in clinical studies can be challenging. While some obstacles are similar to other clinical conditions, some are unique to AP. Identifying potential barriers early and developing targeted solutions can help optimize recruitment and retention in AP studies. Such pre-emptive and detailed planning can help prospective, longitudinal studies focus on exocrine and endocrine complications of AP in accurately measuring outcomes. This article highlights the challenges in recruitment and retention strategies in AP studies and reviews available resources to create opportunities to address them. We describe the multifaceted approach used by the Recruitment and Retention Committee of the Type 1 Diabetes in Acute Pancreatitis Consortium, which builds upon earlier experiences to develop a recruitment and retention plan for the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) study., Competing Interests: E.A. is part of advisory board for Nestle. M.D.B. receives research support from Viacyte and Dexcom and is part of advisory board for Insulet. AC is part of advisory board for GSK and expert opinion for Guidepoint. P.J.L. is part of advisory board for AbbVie. G.I.P. receives research support from AbbVie, has consulting activities with Olympus and Nestle, and receives equity with Ariel Precision Medicine. The other authors declare no conflict of interest., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Abstract: This core component of the Diabetes RElated to Acute pancreatitis and its Mechanisms (DREAM) study will examine the hypothesis that advanced magnetic resonance imaging (MRI) techniques can reflect underlying pathophysiologic changes and provide imaging biomarkers that predict diabetes mellitus (DM) after acute pancreatitis (AP). A subset of participants in the DREAM study will enroll and undergo serial MRI examinations using a specific research protocol. The aim of the study is to differentiate at-risk individuals from those who remain euglycemic by identifying parenchymal features after AP. Performing longitudinal MRI will enable us to observe and understand the natural history of post-AP DM. We will compare MRI parameters obtained by interrogating tissue properties in euglycemic, prediabetic, and incident diabetes subjects and correlate them with metabolic, genetic, and immunological phenotypes. Differentiating imaging parameters will be combined to develop a quantitative composite risk score. This composite risk score will potentially have the ability to monitor the risk of DM in clinical practice or trials. We will use artificial intelligence, specifically deep learning, algorithms to optimize the predictive ability of MRI. In addition to the research MRI, the DREAM study will also correlate clinical computed tomography and MRI scans with DM development., Competing Interests: Besides the funding support from NIH listed about, C.E.F. receives consultant fee or honorarium from Nestle HealthCare Nutrition, Inc, Parexel International Corp, and Medialis, Ltd. M.D.B. is an advisory board member of Insulet and receives research support from Dexcom and Viacyte. S.J.P. owns stock options of Avenzoar Pharmaceuticals, Phyteau, and Lucid Sciences. W.G.P. is a consultant for AbbVie. B.S. is a consultant for Francis Medical and Botimage. T.T. receives royalties from Springer Nature. J.R.G. receives royalties from Elsevier, Inc. D.K.A. receives royalties from McGraw-Hill. R.E.P. is consultant for Bayer AG, Corcept Therapeutics Incorporated, Dexcom, Gasherbrum Bio, Inc, Hanmi Pharmaceutical Co, Hengrui (USA) Ltd, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Inc, Sanofi, Scohia Pharma Inc, and Sun Pharmaceutical Industries and receives speaker fees from Novo Nordisk. The other authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

MicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found a decrease in miR-29a in experimental and human chronic pancreatitis, leading us to investigate the regulatory role of the miR-29a/b1 cluster in acute pancreatitis (AP) utilizing a conditional miR-29a/b1-KO mouse model. miR-29a/b1-sufficient (WT) and -deficient (KO) mice were administered supramaximal caerulein to induce AP and characterized at different time points, utilizing an array of IHC and biochemical analyses for AP parameters. In caerulein-induced WT mice, miR-29a remained dramatically downregulated at injury. Despite high-inflammatory milieu, fibrosis, and parenchymal disarray in the WT mice during early AP, the pancreata fully restored during recovery. miR-29a/b1-KO mice showed significantly greater inflammation, lymphocyte infiltration, macrophage polarization, and ECM deposition, continuing until late recovery with persistent parenchymal disorganization. The increased pancreatic fibrosis was accompanied by enhanced TGFβ1 coupled with persistent αSMA+ PSC activation. Additionally, these mice exhibited higher circulating IL-6 and inflammation in lung parenchyma. Together, this collection of studies indicates that depletion of miR-29a/b1 cluster impacts the fibroinflammatory mechanisms of AP, resulting in (a) aggravated pathogenesis and (b) delayed recovery from the disease, suggesting a protective role of the molecule against AP.

Gallstones account for majority of acute pancreatitis in the Western world. Increase in number and smaller size of the stones increases the risk for biliary pancreatitis. In addition to features of acute pancreatitis, these patients also have cholestatic clinical picture. Fluid therapy and enteral nutrition are vital components in management of any case of acute pancreatitis. During initial evaluation, a right upper quadrant ultrasonogram is particularly important. On a case-bycase basis, further advanced imaging studies such as magnetic resonance cholangiopancreatography or endoscopic ultrasound may be warranted. Acute management also involves monitoring for local and systemic complications. Patients are triaged based on predictors of ongoing biliary obstruction in order to identify who would need endoscopic retrograde cholangiopancreatography. Index cholecystectomy is safe and recommended, with exception of cases with significant local and systemic complications where delayed cholecystectomy may be safer.

Background/aims: A calcineurin inhibitor may alter pancreatic function and inflammatory reaction. This study aimed to determine the possible pharmacologic effect of the calcineurin inhibitor, tacrolimus, on pancreatic function, and to determine its preventive effect on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in liver transplantation (LT) patients., Methods: The serum amylase and lipase values before and after LT were compared. The frequency of post-ERCP pancreatitis was compared between non-LT and LT patients, using propensity score matching method., Results: Median serum amylase values (normal range, 19 to 86 U/L) were 49.0 U/L (38.0 to 68.0) before LT and 27.0 U/L (19.3 to 36.8) after LT, and median serum lipase values (normal range, 7 to 59 U/L) were 40.0 U/L (26.5 to 54.0) before LT and 10.5 U/L (6.0 to 21.0) after LT. Both serum amylase and lipase values significantly decreased after LT (p < 0.001), and to a level comparable to chronic pancreatitis. There was a marginal significant difference between the non-LT and LT groups before the propensity score matching with respect to frequency of post-ERCP pancreatitis (16 [3.2%] in non-LT group vs. 2 [0.9%] in LT group, p = 0.069). After propensity score matching, a marginal significant difference still existed with respect to frequency of post-ERCP pancreatitis (7 [4.8%] in non-LT group vs. 1 [0.7%] in LT group, p = 0.067)., Conclusion: The immunosuppression with calcineurin inhibitor may reduce not only the pancreatic enzyme dynamics but also inciting inflammatory event including post-ERCP pancreatitis.

Acute pancreatitis is the most common and feared adverse event associated with performance of endoscopic retrograde cholangiopancreatography (ERCP). Unremitting effort has been made for over 40 years to minimize the frequency and severity of this complication. Recently, the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs) have opened a new era for its prevention. This review focuses on the role of NSAIDs in pancreatitis, the pharmacokinetics of these agents, and summarizes the results of clinical trials with rectal NSAIDs alone and combination regimens in the prevention of post-ERCP pancreatitis.

Background: Although rectal indometacin 100 mg is effective in reducing the frequency and severity of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients, the optimal dose is unknown, and pancreatitis incidence remains high. The aim of this study was to compare the efficacy of two dose regimens of rectal indometacin on the frequency and severity of pancreatitis after ERCP in high-risk patients., Methods: In this randomised, double-blind, comparative effectiveness trial, we enrolled patients from six tertiary medical centres in the USA. Eligible patients were those at high risk for the development of pancreatitis after ERCP. We randomly assigned eligible patients (1:1) immediately after ERCP to receive either two 50 mg indometacin suppositories and a placebo suppository (standard-dose group) or three 50 mg indometacin suppositories (high-dose group). 4 h after the procedure, patients assigned to the high-dose group received an additional 50 mg indometacin suppository, whereas patients in the standard-dose group received an additional placebo suppository. The randomisation schedule, stratified according to study centre and with no other restrictions, was computer generated by an investigator who was uninvolved in the clinical care of any participants, distributed to the sites, and kept by personnel not directly involved with the study. These same personnel were responsible for packaging the drug and placebo in opaque envelopes. Patients, study personnel, and treating physicians were masked to study group assignment. The primary outcome of the study was the development of pancreatitis after ERCP. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01912716, and enrolment is complete., Findings: Between July 9, 2013, and March 22, 2018, 1037 eligible patients were enrolled and randomly assigned to receive either standard-dose (n=515) or high-dose indometacin (n=522). Pancreatitis after ERCP occurred in 141 (14%) of 1037 patients-76 (15%) of 515 patients in the standard-dose indometacin group and 65 (12%) of 522 patients in the high-dose indometacin group (risk ratio [RR] 1·19, 95% CI 0·87-1·61; p=0·32). We observed 19 adverse events that were potentially attributable to study drug. Clinically significant bleeding occurred in 14 (1%) of 1037 patients-six (1%) of 515 patients in the standard-dose indometacin group and eight (2%) of 522 patients in the high-dose indometacin group (p=0·79). Three (1%) of 522 patients in the high-dose indometacin group developed acute kidney injury versus none in the standard-dose group (p=0·25). A non-ST elevation myocardial infarction occurred in the standard-dose indometacin group 2 days after ERCP. A transient ischaemic attack occurred in the high-dose indometacin group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed pancreatitis after ERCP, were considered serious as all required admission to hospital. We observed no allergic reactions or deaths at 30 day follow-up., Interpretation: Dose escalation to rectal indometacin 200 mg did not confer any advantage compared with the standard 100 mg regimen, with pancreatitis incidence remaining high in high-risk patients. Current practice should continue unchanged. Further research should consider the pharmacokinetics of non-steroidal anti-inflammatory drugs to determine the optimal timing of their administration to prevent pancreatitis after ERCP., Funding: American College of Gastroenterology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: In patients with acute recurrent pancreatitis (ARP), pancreas divisum, and no other etiologic factors, endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) is often performed to enlarge the minor papillary orifice, based on limited data. The aims of this study are to describe the rationale and methodology of a sham-controlled clinical trial designed to test the hypothesis that miES reduces the risk of acute pancreatitis., Methods: The SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) trial is a multicenter, international, sham-controlled, randomized trial comparing endoscopic ultrasound + ERCP with miES versus endoscopic ultrasound + sham for the management of ARP. A total of 234 consented patients having 2 or more discrete episodes of acute pancreatitis, pancreas divisum confirmed by magnetic resonance cholangiopancreatography, and no other clear etiology for acute pancreatitis will be randomized. Both cohorts will be followed for a minimum of 6 months and a maximum of 48 months., Results: The trial is powered to detect a 33% risk reduction of acute pancreatitis frequency., Conclusions: The SHARP trial will determine whether ERCP with miES benefits patients with idiopathic ARP and pancreas divisum. Trial planning has informed the importance of blinded outcome assessors and long-term follow-up.

Characteristic features of chronic pancreatitis (CP) may be absent on standard imaging studies. Quantitative Magnetic Resonance Imaging (MRI) techniques such as T 1 mapping, extracellular volume (ECV) fraction, diffusion-weighted imaging (DWI) with apparent diffusion coefficient map (ADC), MR elastography (MRE), and T 1 -weighted signal intensity ratio (SIR) have shown promise for the diagnosis and grading severity of CP. However, radiologists still use the Cambridge classification which is based on traditional ductal imaging alone. There is an urgent need to develop new diagnostic criteria that incorporate both parenchymal and ductal features of CP seen by MRI/MRCP. Designed to fulfill this clinical need, we present the MINIMAP study, which was funded in September 2018 by the National Institutes of Health. This is a comprehensive quantitative MR imaging study which will be performed at multiple institutions in well-phenotyped CP patient cohorts. We hypothesize that quantitative MRI/MRCP features can serve as valuable non-invasive imaging biomarkers to detect and grade CP. We will evaluate the role of T 1 relaxometry, ECV, T 1 -weighted gradient echo SIR, MRE, arteriovenous enhancement ratio, ADC, pancreas volume/atrophy, pancreatic fat fraction, ductal features, and pancreatic exocrine output following secretin stimulation in the assessment of CP. We will attempt to generate a multi-parametric pancreatic tissue fibrosis (PTF) scoring system. We anticipate that a quantitative scoring system may serve as a biomarker of pancreatic fibrosis; hence this imaging technique can be used in clinical practice as well as clinical trials to evaluate the efficacy of agents which may slow the progression or reverse measures of CP.

Background and Study Aim: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a significant and potentially life-threatening adverse event and is common in patients with suspected sphincter of Oddi dysfunction (SOD). Here we aimed to identify predictors of the risk in this population., Patients and Methods: The Evaluating Predictors and Interventions in SOD (EPISOD) study prospectively enrolled 214 post-cholecystectomy patients with SOD type III in seven US centers. Patients were randomized, using a 2:1 allocation, to sphincterotomy or sham procedure, irrespective of the results of sphincter of Oddi manometry. Patients in the sphincterotomy arm who had elevated pancreatic sphincter pressure were randomized to biliary only or to dual (biliary and pancreatic) sphincterotomy. All but one patient received prophylactic pancreatic stents, but none received pharmacological prophylaxis. Post ERCP pancreatitis (PEP) was defined as acute pancreatitis within the subsequent 7 days. Blinded research coordinators at each site called patients at 1 week post-procedure., Results: PEP occurred in 26 patients, in 10.6 % (15/141) in the sphincterotomy arm and 15.1 % (11/73) in the sham arm; unadjusted relative risk 0.71 (95 % confidence interval [95 %CI] 0.34 - 1.46). PEP rate was not significantly different in patients who received sphincterotomy compared with those undergoing sham treatment. In addition, the proportion was not statistically different in those who received biliary sphincterotomy alone (12/94; 12.8 % [95 %CI 6.0 % - 19.5 %]) compared with dual sphincterotomy (3/47; 6.4 % [95 %CI 0.0 % - 13.4 %]). Multivariate analysis identified an interaction between duration of ERCP and sedation type (P < 0.02)., Conclusion: The performance of biliary or dual sphincterotomy does not increase the risk of PEP in patients suspected of SOD. However, the high rate of PEP in patients with suspected SOD, despite pancreatic stenting in expert centers, is confirmed in this prospective study. The combined effect of duration of ERCP and sedation type on the development of PEP should be further explored.Clinicaltrials.gov registration: NCT00688662., (© Georg Thieme Verlag KG Stuttgart · New York.)

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.)

Objectives: In adults with unexplained pancreatitis, the yield of complete gene versus select exosome sequencing on mutation detection and distinguishing clinical characteristics associated with mutations requires clarification. We sought to (1) compare frequency of mutations identified using different techniques and (2) compare clinical characteristics between adults with and without mutations., Methods: This is a cohort study of adults with unexplained pancreatitis who underwent genetic testing between January 2008 and December 2012. We compare probabilities of having a positive mutation with complete gene sequencing versus alternatives and describe differences in characteristics among patients with and without mutations., Results: Of the 370 patients, 67 (18%) had a genetic mutation; 24 (6%) were of high risk. Mutations were significantly more prevalent with use of complete sequencing (42%) versus other approaches (8%, P < 0.0001). Most (44/67, 66%) with a mutation had no family history. Those with high-risk mutations were more likely to have a family history of chronic pancreatitis (21% vs 4%, P = 0.002). Patients with pancreas divisum were more likely to have mutations (27% vs 14%, P = 0.0007)., Conclusion: Among individuals with adult-onset pancreatic disease, the probability of finding any mutation, including high risk, is significantly higher using complete gene sequencing. The impact on patients and providers requires further investigation.

Background: It is believed, based on limited observational data, that an unsuccessful attempt to place a prophylactic pancreatic stent substantially increases the risk of post-ERCP pancreatitis (PEP)., Objective: To better understand the risk of PEP in patients with failed pancreatic stent placement (FPS) and the impact of rectal indomethacin on this risk., Design: Secondary analysis of randomized, controlled trial data., Setting: University of Michigan and Indiana University., Patients: A total of 577 clinical trial participants at elevated risk for PEP., Interventions: Pancreatic stent placement., Main Outcome Measurements: Within the placebo group, we compared PEP rates in patients with FPS, patients who underwent successful stent placement, and in those without a stent attempt. We also performed a regression analysis evaluating the association between FPS and PEP. To define the protective effect of indomethacin, we repeated these analyses in the indomethacin group and in the full study cohort., Results: The incidence of PEP among patients in the placebo group who experienced FPS was 34.7%, significantly exceeding rates in patients who underwent successful stent placement (16.4%) and in those without a stent attempt (12.1%). After we adjusted for known PEP risk factors, FPS was found to be independently associated with PEP. Among the indomethacin group and in the full cohort, FPS was not associated with a higher risk of PEP., Limitations: Low event rate, FPS not prospectively captured., Conclusion: FPS appears to confer an increased risk of PEP, which is attenuated by rectal indomethacin administration. These findings highlight the importance of adequate training and proficiency before endoscopists attempt pancreatic stent placement and the routine use of rectal indomethacin in high-risk ERCP cases., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Hereditary pancreatitis is a rare cause of chronic pancreatitis. In recent years, genetic mutations have been characterized. The rarity of this disorder has resulted in a gap in clinical knowledge. The aims were to characterize patients with hereditary pancreatitis and establish clinical guidelines., Methods: Pediatric and adult endoscopic, surgical, radiologic, and genetic databases from 1998 to 2012 were searched. Patients with recurrent acute or chronic pancreatitis and genetic mutation for either PRSS-1, SPINK-1, or CFTR or those who met the family history criteria were included. Patients with pancreatitis due to other causes, without a positive family history, familial pancreatic cancer, or cystic fibrosis, were excluded., Results: Eighty-seven patients were identified. Genetic testing confirmed the diagnosis in 54 patients (62 %). Eighty-five patients (98 %) underwent 263 endoscopic procedures including sphincterotomy (72 %), stone removal (49 %), and pancreatic duct stenting (82 %). Twenty-eight patients (32 %) have undergone 37 operations which included 19 resections and 18 drainage procedures. The interval between procedures for recurrent pain was longer for surgery than for endoscopic therapy (9.1 vs. 3.4 years, p < 0.05)., Conclusions: Most children and young adults with hereditary pancreatitis can be managed initially with endoscopic therapy. When surgery is undertaken, the procedure should be tailored to the pancreatic anatomy and cancer risk.

Objectives: A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach., Methods: We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both., Results: After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP., Conclusions: This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

Background: Pancreatitis is the most common major complication of ERCP and precut endoscopic sphincterotomy (ES). Prophylactic pancreatic duct (PD) stent placement has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk settings., Objective: To determine whether leaving a main PD stent in place after precut ES would reduce the incidence and severity of PEP., Design: Single-center, randomized, prospective study., Setting: Tertiary care ERCP referral center., Patients: Consecutive patients who underwent ERCP with a clear indication for biliary access and standard biliary ES whereby free cannulation of the bile duct was not possible and precut ES was undertaken., Interventions: When free bile duct cannulation for ES was not possible and selective PD cannulation was achieved, a PD stent was placed. Using the PD stent as a guide, we used a needle-knife sphincterotome to perform precut ES. The patients were then randomized to either leaving the PD stent in place for 7 to 10 days (stent group) or immediate removal after the procedure (stent removed group). The remaining patients who did not undergo selective PD cannulation and stent placement were not randomized (no stent group) and had a free-hand needle-knife ES performed., Main Outcome Measurements: Patients were prospectively followed for the development of complications. Standardized criteria were used to diagnose and grade the severity of PEP., Results: A total of 151 patients were enrolled. The groups were similar with regard to patient demographics and patient and procedure risk factors for PEP. The overall incidence of PEP was 13.2% (20/151). It occurred in 4.3% (2/46), 21.3% (10/47), and 13.8% (8/58) of patients in the stent, stent removed, and no stent groups, respectively. The stent group had a significantly lower frequency and severity of PEP compared with the stent removed group (4.3% vs 21.3%; P = .027 for frequency and 0% vs 12.8%; P = .026 for moderate and severe pancreatitis)., Limitations: Single center. Randomization scheme not optimal., Conclusions: These data suggest that placing and maintaining a PD stent for needle-knife precut ES reduces the frequency and severity of postprocedure pancreatitis., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP)., Methods: In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights., Results: A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03)., Conclusions: Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Background: Limited data are available on complication rates of ERCP in patients with pancreas divisum (PD), and it is unclear whether traditional risk factors for post-ERCP pancreatitis (PEP) apply., Objectives: To describe the rates of ERCP complications in patients with PD and assess patient and procedure-related risk factors for PEP., Design: Retrospective cohort study., Setting: Tertiary care referral center., Patients: A total of 2753 ERCPs performed in 1476 patients with PD from 1997 to 2010., Main Outcome Measurements: Rates of PEP, hemorrhage, perforation, cholecystitis, and hospitalization directly attributable to ERCP., Results: Early complications occurred after 7.8% of procedures, with PEP, hemorrhage, perforation, cholecystitis, and cardiorespiratory complications in 6.8%, 0.7%, 0.2%, 0.1%, and 0.1% of procedures, respectively. PEP was uncommon in patients who did not undergo attempted dorsal duct cannulation, occurring in 1.2% of procedures. With dorsal duct cannulation and cannulation with minor papilla sphincterotomy (MiS), the rates of PEP increased significantly to 8.2% and 10.6%, respectively (P<.01 for each comparison). Significant predictors of PEP after multivariate logistic regression included age younger than 40 (odds ratio [OR] 1.8; 95% CI, 1.27-2.59), female sex (OR 1.94; 95% CI, 1.25-3.01), previous PEP (OR 2.02; 95% CI, 1.32-3.1), attempted dorsal duct cannulation (OR 7.45; 95% CI, 3.25-17.07), and MiS (OR 1.62; 95% CI, 1.05-2.48). Presence of severe chronic pancreatitis was a protective factor (OR 0.46; 95% CI, 0.22-0.98)., Limitations: Retrospective analysis of prospectively collected data., Conclusions: Among patients with PD, the rate of PEP is low (1.2%) if dorsal duct cannulation is not attempted. However, patients with PD undergoing dorsal duct cannulation with or without MiS are at high risk of PEP (8.2% without and 10.6% with). Traditional PEP risk factors apply to patients with PD., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Placement of prophylactic pancreatic stents (PPS) is a method proven to reduce the rate and severity of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk patients; however, PPS do not eliminate the risk completely. Early PPS dislodgement may occur prematurely and contribute to more frequent or severe PEP., Objective: To determine the effect of early dislodgement of PPS in patients with moderate or severe PEP., Methods: A total of 27,176 ERCP procedures from January 1994 to September 2007 for PPS placement in high-risk patients were analyzed. Patient and procedure data were analyzed to assess risk factors for PEP, and to evaluate the severity of pancreatitis, length of hospitalization and subsequent complications. Timing of stent dislodgment was assessed radiographically., Results: PPS were placed in 7661 patients. Of these, 580 patients (7.5%) developed PEP, which was graded as mild in 460 (6.0%), moderate in 87 (1.1%) and severe in 33 (0.4%). Risk factors for developing PEP were not different in patients who developed moderate PEP compared with those with severe PEP. PPS dislodged before 72 h in seven of 59 (11.9%) patients with moderate PEP and five of 27 (18.5%) patients with severe PEP (P=0.505). The mean (± SD) length of hospitalization in patients with moderate PEP with stent dislodgement before and after 72 h were 7.43 ± 1.46 days and 8.37 ± 1.16 days, respectively (P=0.20). The mean length of hospitalization in patients with severe PEP whose stent dislodged before and after 72 h were 21.6 ± 6.11 and 22.23 ± 3.13 days, respectively (P=0.96)., Conclusion: Early PPS dislodgement was associated with moderate and severe PEP in less than 20% of cases and was not associated with a more severe course. Factors other than ductal obstruction contribute to PEP in high-risk patients undergoing ERCP and PPS placement.

Background: Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent studies have suggested that obesity may serve as a prognostic indicator of poor outcome in non-ERCP-induced acute pancreatitis. However, to our knowledge, no one has ever investigated the potential association of obesity and ERCP-induced pancreatitis. Thus, the purpose of our study was to determine whether obesity conferred an increased risk and/or more severe course of post-ERCP pancreatitis., Methods: A 160 variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study, evaluating whether prophylactic corticosteroids reduces the incidence of post-ERCP pancreatitis. Body mass indices (BMIs) were available on 964 of the 1115 patients from the original study. A BMI > or = 30 kg/m2 was defined as obese (World Health Organization) and used as a cutoff point in this study. BMIs were analyzed in a retrospective fashion to determine whether obesity confers an increased risk and/or more severe course of post-ERCP pancreatitis. Data were collected before the ERCP, at the time of procedure, and 24 to 72 hours after discharge. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis., Results: Nine hundred sixty four patients were enrolled in the study. Pancreatitis occurred in 149 patients (15.5%) and was graded as mild in 101 (67.8%), moderate in 42 (28.2%), and severe in 6 (4.0%). The patients were categorized by BMI (kg/m2) using the following breakdowns: BMI < 20, 20 to < 25, 25 to < 30, and > or = 30, as well as BMI < 30 or > or = 30. The groups were similar with respect to the patient and procedure risk factors for post-ERCP pancreatitis except the group with BMI > or = 30 had a higher frequency of females, were younger, had less frequent chronic pancreatitis, a lower number of pancreatic duct injections, and fewer patients received more than 2 pancreatic duct injections. Of the patients with a BMI < 30, 119 (16.4%) developed post-ERCP pancreatitis compared with 30 (12.5%) of those with a BMI > or = 30 (P=0.14). There was no association between the presence of obesity and the severity of pancreatitis (P=0.74). Patients with a BMI < 20, 20 to < 25, 25 to < 30, and > or = 30 had a similar incidence of post-ERCP pancreatitis., Conclusions: Obesity did not seem to confer an increased risk for ERCP-induced pancreatitis. A statistically significant association between obesity and the severity of ERCP-induced pancreatitis was not apparent.

Gallstone disease is encountered commonly in clinical practice. The diagnosis of biliary stones has become less problematic with current, less-invasive imaging methods. The relatively invasive endoscopic techniques should be reserved for therapy and not used for diagnosis. Acute cholangitis and gallstone pancreatitis are two major complications that require prompt recognition and timely intervention to limit morbidity and prevent mortality or recurrence. Appropriate noninvasive diagnostic studies, adequate monitoring/supportive care, and proper patient selection for invasive therapeutic procedures are elements of good clinical practice.

Background: Placement of a pancreatic duct (PD) stent reduces post-ERCP pancreatitis rates in high-risk patients. Patients with suspected sphincter of Oddi dysfunction (SOD) who are found to have normal manometry results (SOM) are also at high risk for this complication., Objective: Our purpose was to determine whether PD stent placement reduces pancreatitis rates in this patient population., Design: Non-randomized, retrospective study., Setting: Large, tertiary referral center., Patients: From January 1999 to December 2005, patients who underwent ERCP with normal SOM were identified from our ERCP database. Incidence of patient/procedure risk factors for post-ERCP pancreatitis, trainee participation, and prior sphincter therapy were evaluated., Interventions: PD stent placement., Main Outcome Measurement: Pancreatitis rates., Results: A total of 403 patients were available for analysis: 169 had a PD stent placed (group 1) and 234 did not (group 2). Overall, pancreatitis rates were 2.4% in group 1 and 9.0% in group 2 (P= .006, odds ratio 4.1, 95% CI 1.4-12.0). Other than increased PD opacification in group 1 (P< .001), the incidence of risk factors for pancreatitis, trainee participation, or prior sphincter therapy was similar between the 2 groups. In patients with an intact papilla, stent placement reduced the rate of pancreatitis from 11.5% to 2.7% (P= .012). In patients with prior sphincter therapy, no benefit was seen from stent placement, although there was a trend to decreased pancreatitis rates in stented patients with prior pancreatobiliary sphincterotomy., Limitations: Nonrandomized, retrospective design., Conclusion: Temporary PD stent placement reduces pancreatitis rates in patients with suspected SOD but normal SOM and an intact papilla. Their routine use is recommended when evaluating this difficult, high-risk patient population.

Background: Pancreatitis is one of the major complications of ERCP and endoscopic sphincterotomy. It has been shown that nonsteriodal anti-inflammatory drugs are potent inhibitors of phospholipase A(2), activity which is increased in pancreatitis. A previous study showed reduction of post-ERCP pancreatitis with administration of rectal diclofenac., Objective: The aim of this study was to determine whether prophylactic oral diclofenac will reduce the incidence and the severity of ERCP-induced pancreatitis, especially in high-risk patients., Design: Single-center, randomized, double-blinded, prospective study., Setting: Indiana University Medical Center., Patients: A total of 207 evaluable patients were randomized to receive either diclofenac 50 mg or placebo by mouth 30 to 90 minutes before and 4 to 6 hours after ERCP., Results: The groups were similar with regard to patient demographics and to patient and procedure risk factors for post-ERCP pancreatitis. The overall incidence of post-ERCP pancreatitis was 16.4%. It occurred in 17 of 102 patients in the control group (16.7%) and in 17 of 105 patients in diclofenac group (16.2%). The pancreatitis was graded mild in 9.8%, moderate in 5.9%, and severe 1.0% of the control group, and mild in 10.5%, moderate in 4.8%, and severe in 1.0% of the diclofenac group. In high-risk patients, the incidence of post-ERCP pancreatitis was 17.3%. It occurred in 18.0% (16/89) in the control group and in 17.8% (16/90) in the diclofenac group. There was no significant difference between the groups in the frequency or severity of post-ERCP pancreatitis in overall and high-risk patients; however, the power of the study was less than 45%., Conclusions: Prophylactic orally administered diclofenac was not observed to affect the frequency or severity of post-ERCP pancreatitis in high-risk patients.

Background: Pancreatitis is the most common complication of diagnostic and therapeutic ERCP. Almost certainly, the etiology of this pancreatitis is multifactorial., Objective: The primary objective of this study was to evaluate the relationship between the extent of pancreatic ductal opacification and the frequency of pancreatitis., Design: Retrospective study., Setting: The ERCP database at our institution was searched for prospectively collected data from 1994 to 2005., Patients and Interventions: A total of 14,331 ERCPs were included in the analysis. Patients were divided into 4 groups according to the extent of pancreatic duct opacification: group 1, no attempted opacification or failed cannulation of the pancreatic duct (n = 6739); group 2, opacification of head only (n = 845); group 3, opacification of head and body (n = 2061); and group 4, opacification to the tail (n = 4685). The incidence and severity of pancreatitis was compared between and within each group., Results: The overall pancreatitis rate was 4.0%. There was a progressively higher frequency of pancreatitis with increased extent of opacification to the pancreatic ductal system (P < .001). The overall pancreatitis severity was mild in 2.9%, moderate in 0.8%, and severe in 0.3% of cases. There was a significant difference in pancreatitis severity between patients with pancreatogram (regardless of grade of filling) and patients without pancreatogram. (P < .001). However, there was no difference in the pancreatitis severity between groups 2 to 4 (patients with pancreatogram). Age (65 years vs >65 years), sex, and type of procedure performed (diagnostic and therapeutic) were not significantly different beyond the extent of pancreatic ductal opacification. Multivariate analysis showed that suspected sphincter of Oddi dysfunction with manometry and the extent of pancreatic duct opacification were independent predictors of post-ERCP pancreatitis., Conclusions: Less filling of the pancreatic ductal system was associated with less post-ERCP pancreatitis. Before performing endoscopic retrograde pancreatography, endoscopists should carefully evaluate whether any pancreatogram or what extent of pancreatogram is needed clinically. Greater use of noninvasive pancreatography and less use of endoscopic retrograde pancreatography should decrease post-ERCP pancreatitis.

Background: Our series of patients with idiopathic pancreatitis (IP) found a cystic fibrosis (CF) gene abnormality in 19% compared with 3.5% in patients without pancreatitis., Objective: The objective was to determine whether the CF gene predicts more severe ERP findings., Design: This was a retrospective case-control study., Setting and Patients: From July 1998 to August 2004, CF gene analysis was performed in 819 patients with IP via Genzyme Genetics. The panel tests for 70 to 87 alleles and has a detection rate of more than 90% of the cases. Sixty-nine patients (8.4%) who had at least one CF gene positive mutation were the study cohort. A total of 218 patients with IP and negative CF gene mutation were randomly selected from our database to be in the control group., Main Outcome Measurements: Pancreatograms were evaluated for chronic pancreatitis (CP) based on Cambridge criteria. The results of the gene analysis were not available at the time of pancreatogram interpretation., Results: Among patients positive for the CF gene, 42 (61%) were women. The mean age at intervention was 40 years (range 14-80 years), and 48 patients (70%) had cholecystectomy. Among patients who were negative for the CF gene, 147 (67%) were women. The mean age at intervention was 41 years (range 9-89 years), and 125 patients (57%) had cholecystectomy. Compared with controls, cases had higher incidence of CP (62% vs. 48%, p = 0.05), grade III CP (35% vs. 18%, p = 0.004), pseudocysts (12% vs. 4%, p = 0.036) and pancreatic strictures (20% vs. 8%, p = 0.008)., Limitations: The limitations of the study were (1) retrospective design and (2) the panel used tests only for 70 to 87 alleles (of approximately, 900 CF transmembrane conductance regulator genes known)., Conclusions: The mean age at intervention in both groups was similar. CP, grade III CP, pseudocysts, and pancreatic strictures were more common among patients who were CF gene positive.

Objectives: Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study., Methods: A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24-72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria., Results: Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), > or =2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis., Conclusion: This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.

Background: Pancreatitis is the most common major complication of ERCP. Efforts have been made to identify pharmacologic agents capable of reducing its incidence and severity. The aim of this trial was to determine whether prophylactic allopurinol, an inhibitor of oxygen-derived free radical production, would reduce the frequency and severity of post-ERCP pancreatitis. Methods A total of 701 patients were randomized to receive either allopurinol or placebo 4 hours and 1 hour before ERCP. A database was prospectively collected by a defined protocol on patients who underwent ERCP. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis., Results: The groups were similar with regard to patient demographics and to patient and procedure risk factors for pancreatitis. The overall incidence of pancreatitis was 12.55%. It occurred in 46 of 355 patients in the allopurinol group (12.96%) and in 42 of 346 patients in the control group (12.14%; p = 0.52). The pancreatitis was graded mild in 7.89%, moderate in 4.51%, and severe in 0.56% of the allopurinol group, and mild in 6.94%, moderate in 4.62%, and severe in 0.58% of the control group. There was no significant difference between the groups in the frequency or the severity of pancreatitis., Conclusions: Prophylactic oral allopurinol did not reduce the frequency or the severity of post-ERCP pancreatitis.

Pancreas divisum (PD), the most common congenital variant of pancreatic duct anatomy, occurs when the ductal systems of the ventral and dorsal pancreatic ducts fail to fuse during the second month of gestation. With non-union of the ducts, the major portion of the pancreatic exocrine secretion enters the duodenum by way of the dorsal duct and minor papilla. It has been generally accepted that a relative obstruction to pancreatic exocrine secretory flow through the minor duct and minor papilla could result in pancreatitis in small numbers of patients with PD. The debate whether PD causes pancreatitis continues, although most authorities agree that PD is a definite cause in a subgroup of patients. Most patients with PD and well-documented acute recurrent pancreatitis have responded favorably to surgical sphincteroplasty of the minor papilla. Endoscopic retrograde cholangiopancreatography (ERCP) is the most common procedure for diagnosis PD in patients who have pancreatobiliary symptoms. MRCP is being increasingly used to establish the diagnosis and secretin stimulation can improve ductal images greatly. Endoscopic management of symptomatic patients with PD is evolving. Only a limited number of series are available, using endoscopic pancreatic stent placement, minor papilla endoscopic papillotomy, or both to decompress the dorsal duct in an effort to restore pancreatic exocrine secretory flow. Even with relatively small numbers of patients and a near absence of controlled, randomized trials, it appears that the patients most likely to benefit, as with surgery, are those with well-documented ARP rather than pain alone or chronic pancreatitis. Overall we recommend that pancreatic stenting and pancreatic sphincterotomy should be done only in large centers with experience in therapeutic ERCP. Further randomized trials would be of interest.

Background & Aims: Pancreatic stenting is an effective method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in high-risk patients. This retrospective study evaluated the impact of modified stent characteristics on the rate of post-ERCP pancreatitis, spontaneous stent dislodgment, and stent-related sequelae., Methods: A total of 2283 patients underwent 2447 ERCPs over a 6-year period with placement of 3-4F diameter, unflanged pancreatic stents. The indication for stenting was pancreatitis prophylaxis predominantly in suspected sphincter of Oddi dysfunction (SOD), pancreas divisum therapy, and precut sphincterotomy. An abdominal radiograph was obtained 10-14 days later to assess spontaneous stent passage. Post-ERCP pancreatitis was defined according to established criteria. A total of 479 patients underwent repeat ERCPs after an initial ERCP with pancreatic stent placement. The prestenting pancreatogram was then compared with follow-up studies., Results: The pancreatitis rate with 3F, 4F, 5F, and 6F stents was 7.5%, 10.6%, 9.8%, and 14.6%, respectively (3F vs. 4F, 5F, 6F: P = 0.047). Spontaneous stent dislodgment was 86%, 73%, 67%, and 65%, respectively (3F vs. 4F, 5F, 6F: P < 0.0001). The frequency of ductal changes was 24% in patients with 3-4F stents compared with 80% with 5-6F stents. Ductal perforation from the stents occurred in 3 patients (0.1%)., Conclusions: Small diameter (3-4F), unflanged pancreatic stents are more effective than the traditionally used stents (5-6F) in preventing post-ERCP pancreatitis. Stent-induced ductal changes and the need for endoscopic removal are also significantly less with 3-4F stents. The 3F stent appears to be superior in all aspects studied. Additional studies are needed to define the ideal method to eliminate post-ERCP pancreatitis.

Background: Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP. There have been continuing efforts to identify a pharmacologic agent capable of reducing the frequency and severity of this complication. On the basis of several case reports, experimental data, and knowledge of their mechanism of action, corticosteroids might be effective in this regard. The aim of this randomized, double-blind, controlled trial was to determine whether prophylactic, orally administered corticosteroid reduces the frequency and/or severity of post-ERCP pancreatitis., Methods: A total of 1115 patients were randomized to receive either prednisone (40 mg) or a placebo orally 15 hours and 3 hours before ERCP. A 160 variable database was prospectively collected according to a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis., Results: The overall frequency of pancreatitis was 15.07%. It occurred in 92 of 555 patients in the corticosteroid group (16.6%), and in 76 of 560 patients in the control group (13.6%; p = 0.19). The pancreatitis was mild in 10.04%, moderate in 4.04%, and severe in 0.99%. There was no difference between the groups with regard to the severity of pancreatitis. Moreover, the groups were similar with regard to age, gender, body mass index, frequency of prior pancreatitis, type of procedure performed (diagnostic or therapeutic), difficulty of cannulation, frequency of pre-cut sphincterotomy, pancreatic sphincterotomy, sphincter of Oddi dysfunction, sphincter of Oddi manometry, pancreatic acinarization, chronic pancreatitis, number of pancreatic duct injections, and bile duct diameter., Conclusion: Prophylactic orally administered corticosteroid did not reduce the frequency or severity of post-ERCP pancreatitis.

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression. [Display omitted] Analysis of serum immune markers in a large cohort of pancreatitis allowed the identification of distinct immune markers that could serve as potential biomarkers providing mechanistic insights into pancreatitis progression. [ABSTRACT FROM AUTHOR]

Purpose: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study. Methods: This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI). Results: There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p < 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p < 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76). Conclusion: Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study. Methods: The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0–6) based on their clinical history, MRCP, and CT findings. Results: The mean pancreas-to-spleen T1 score was 1.30 in participants with chronic abdominal pain, 1.22 in those with acute or recurrent acute pancreatitis, and 1.03 in definite CP. After adjusting for covariates, we observed a linear, progressive decline in the pancreas-to-spleen T1 score with increasing MSCP from 0 to 6. The mean pancreas-to-spleen T1 scores were 1.34 (MSCP 0), 1.27 (MSCP 1), 1.21 (MSCP 2), 1.16 (MSCP 3), 1.18 (MSCP 4), 1.12 (MSCP 5), and 1.05 (MSCP 6) (p < 0.0001). The pancreas-to-liver and pancreas-to-muscle T1 scores showed less linear trends and wider confidence intervals. Conclusion: The T1 score calculated by SIR of the pancreas-to-spleen shows a negative linear correlation with the progression of chronic pancreatitis. It holds promise as a practical imaging biomarker in evaluating disease severity in clinical research and practice. [ABSTRACT FROM AUTHOR]

Objective: Biliary stricture in necrotizing pancreatitis (NP) has not been systematically categorized; therefore, we sought to define the incidence and natural history of biliary stricture caused by NP. Summary of Background Data: Benign biliary stricture occurs secondary to bile duct injury, anastomotic narrowing, or chronic inflammation and fibrosis. The profound locoregional inflammatory response of NP creates challenging biliary strictures. Methods: NP patients treated between 2005 and 2019 were reviewed. Biliary stricture was identified on cholangiography as narrowing of the extrahepatic biliary tree to <75% of the diameter of the unaffected duct. Biliary stricture risk factors and outcomes were evaluated. Results: Among 743 NP patients, 64 died, 13 were lost to follow-up; therefore, a total of 666 patients were included in the final cohort. Biliary stricture developed in 108 (16%) patients. Mean follow up was 3.5 ± 3.3 years. Median time from NP onset to biliary stricture diagnosis was 4.2 months (interquartile range, 1.8 to 10.9). Presentation was commonly clinical or biochemical jaundice, n = 30 (28%) each. Risk factors for stricture development were splanchnic vein thrombosis and pancreatic head parenchymal necrosis. Median time to stricture resolution was 6.0 months after onset (2.8 to 9.8). A mean of 3.3 ± 2.3 procedures were performed. Surgical intervention was required in 22 (20%) patients. Endoscopic treatment failed in 17% (17/99) of patients and was not associated with stricture length. Operative treatment of biliary stricture was more likely in patients with infected necrosis or NP disease duration ≥6 months. Conclusion: Biliary stricture occurs frequently after NP and is associated with splanchnic vein thrombosis and pancreatic head necrosis. Surgical correction was performed in 20%. [ABSTRACT FROM AUTHOR]