Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Development and validation of a practical clinical risk prediction model for post-endoscopic retrograde cholangiopancreatography pancreatitis.

Background: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) can lead to significant morbidity and mortality. We aimed to develop an accurate post-ERCP pancreatitis risk prediction model using easily obtainable variables. Methods: Using prospective multi-center ERCP data, we performed logistic regression using stepwise selection on several patient-, procedure-, and endoscopist-related factors that were determined a priori. The final model was based on a combination of the Bayesian information criterion and Akaike's information criterion performance, balancing the inclusion of clinically relevant variables and model parsimony. All available data were used for model development, with subsequent internal validation performed on bootstrapped data using 10-fold cross-validation. Results: Data from 3021 ERCPs were used to inform models. There were 151 cases of post-ERCP pancreatitis (5.0% incidence). Variables included in the final model included female sex, pancreatic duct cannulation, native papilla status, pre-cut sphincterotomy, increasing cannulation time, presence of biliary stricture, patient age, and placement of a pancreatic duct stent. The final model was discriminating, with a receiver operating characteristic curve statistic of 0.79, and well-calibrated, with a predicted risk-to-observed risk ratio of 1.003. Conclusions: We successfully developed and internally validated a promising post-ERCP pancreatitis clinical prediction model using easily obtainable variables that are known at baseline or observed during the ERCP procedure. The model achieved an area under the curve of 0.79. External validation is planned as additional data becomes available.

Post-ERCP cholecystitis: Incidence, characteristics, and outcomes from a prospective multicenter biliary endoscopy registry.

BACKGROUND AND AIMS: The incidence, risk factors, and outcomes of post-ERCP cholecystitis are poorly described. We aimed to describe cases of post-ERCP cholecystitis from a prospective multicenter registry with protocolized 30-day follow-up. METHODS: Patient- and procedure-related data from 7 centers were obtained. The primary outcome was post-ERCP cholecystitis, defined according to a Delphi-based criteria and causal attribution system. Risk factors and outcomes were described for all cases. RESULTS: Seventeen cases of post-ERCP cholecystitis were identified among 4428 patients with gallbladders undergoing ERCP between 2018 and 2023 (incidence, 0.38%; 95% confidence interval, 0.20-0.57). In ERCPs with covered metal stenting, 7 of 467 resulted in cholecystitis (incidence, 1.50%; 95% confidence interval, 0.40-2.60). Patients had symptoms at a median of 5 days (interquartile range, 5) after ERCP. Management strategies included cholecystectomy, percutaneous cholecystostomy, and endoscopic stent removal/exchange. CONCLUSIONS: Estimates of post-ERCP cholecystitis incidence can inform discussions around procedural risk.

Incidence and Predictors of Incidental Biochemical and Radiologic Pancreatic Alterations Following Uncomplicated ERCP.

BACKGROUND: Despite post-ERCP pancreatitis (PEP) being a major focus of outcomes research in endoscopic retrograde cholangiopancreatography (ERCP), little is known regarding the frequency with which asymptomatic biochemical and/or radiologic pancreatic alterations occur in patients following ERCP. METHODS: Adult inpatients undergoing ERCP were identified from a prospective ERCP registry. Patients with any abdominal pain, confirmed PEP, or pancreatitis or abnormal pancreatic enzymes preceding ERCP were excluded. Primary outcomes were asymptomatic lipase elevation on bloodwork within 24 h of ERCP or asymptomatic cross-sectional imaging findings consistent with acute pancreatitis in the absence of clinical PEP within 14 days. Multinomial logistic regression and multiple logistic regression were used to examine associations between exposures and lipase levels and between PEP or imaging findings, respectively. RESULTS: In total, 646 and 187 patients were analyzed as part of the biochemical and radiologic cohorts, respectively. A total of 26.0% of patients had asymptomatic elevations in lipase above the upper limit of normal (ULN) within 24 h, and 9.4% had elevations >3× ULN. A total of 20.9% of patients had incidental findings of enlargement, inflammation/edema/fat stranding, peri-pancreatic fluid collections, and/or necrosis on cross-sectional imaging within 14 days. Pancreatic contrast injection was associated with higher odds of asymptomatic lipasemia (adjusted odds ratio, AOR, 7.22; 95% confidence intervals, CI, 1.13 to 46.02), as was the use of the double-wire technique (AOR 15.74; 95% 1.15 to 214.74) and placement of a common bile duct stent (AOR 4.19; 95% CI 1.37 to 12.77). Over 10 cannulation attempts were associated with the presence of one or more radiologic finding(s) (AOR 33.95; 95% CI 1.64, to 704.13). CONCLUSIONS: Significant rates of incidental biochemical and/or radiologic pancreatic abnormalities are present following ERCP. Clinicians should be aware of our findings to minimize misclassification and better direct healthcare utilization.

Effect of Disposable Elevator Cap Duodenoscopes on Persistent Microbial Contamination and Technical Performance of Endoscopic Retrograde Cholangiopancreatography: The ICECAP Randomized Clinical Trial.

Importance: Infection transmission following endoscopic retrograde cholangiopancreatography (ERCP) can occur due to persistent contamination of duodenoscopes despite high-level disinfection to completely eliminate microorganisms on the instrument. Objective: To determine (1) contamination rates after high-level disinfection and (2) technical performance of duodenoscopes with disposable elevator caps compared with those with standard designs. Design, Setting, and Participants: In this parallel-arm multicenter randomized clinical trial at 2 tertiary ERCP centers in Canada, all patients 18 years and older and undergoing ERCP for any indication were eligible. Intervention: The intervention was use of duodenoscopes with disposable elevator caps compared with duodenoscopes with a standard design. Main Outcomes and Measures: Coprimary outcomes were persistent microbial contamination of the duodenoscope elevator or channel, defined as growth of at least 10 colony-forming units of any organism or any growth of gram-negative bacteria following high-level disinfection (superiority outcome), and technical success of ERCP according to a priori criteria (noninferiority outcome with an a priori noninferiority margin of 7%), assessed by blinded reviewers. Results: From December 2019 to February 2022, 518 patients were enrolled (259 disposable elevator cap duodenoscopes, 259 standard duodenoscopes). Patients had a mean (SD) age of 60.7 (17.0) years and 258 (49.8%) were female. No significant differences were observed between study groups, including in ERCP difficulty. Persistent microbial contamination was detected in 11.2% (24 of 214) of standard duodenoscopes and 3.8% (8 of 208) of disposable elevator cap duodenoscopes (P = .004), corresponding to a relative risk of 0.34 (95% CI, 0.16-0.75) and number needed to treat of 13.6 (95% CI, 8.1-42.7) to avoid persistent contamination. Technical success using the disposable cap scope was noninferior to that of the standard scope (94.6% vs 90.7%, P = .13). There were no differences between study groups in adverse events and other secondary outcomes. Conclusions and Relevance: In this randomized clinical trial, disposable elevator cap duodenoscopes exhibited reduced contamination following high-level disinfection compared with standard scope designs, without affecting the technical performance and safety of ERCP. Trial Registration: ClinicalTrials.gov Identifier: NCT04040504.

Baseline Cannabinoid Use Is Associated with Increased Sedation Requirements for Outpatient Endoscopy.

Background and Aims: Given the underlying properties of cannabinoids, we aimed to assess associations between cannabinoid use and sedation requirements for esophagogastroduodenoscopy (EGD) and colonoscopy. Methods: A prospective cohort study was conducted at three endoscopy units. Adult outpatients undergoing EGD or colonoscopy with endoscopist-directed conscious sedation (EDCS) were given questionnaires on cannabinoid use and relevant parameters. Outcomes included intraprocedural midazolam, fentanyl, and diphenhydramine use, procedural tolerability, and adverse events. Multivariable logistic regression was performed to yield adjusted odds ratios (AORs) of outcomes. Results: A total of 419 patients were included. Baseline cannabinoid use was associated with high midazolam use, defined as ≥5 mg, during EGD (AOR 2.89, 95% confidence interval, CI: 1.19-7.50), but not during colonoscopy (AOR 0.89, 95% CI 0.41-1.91). Baseline cannabinoid use was associated with the administration of any diphenhydramine during EGD (AOR 3.04, 95% CI: 1.29-7.30) with a similar nonsignificant trend for colonoscopy (AOR 2.36, 95% CI: 0.81-7.04). Baseline cannabinoid use was associated with increased odds of requiring high total sedation, defined as any of midazolam ≥5 mg, fentanyl ≥100 mcg, or any diphenhydramine during EGD (AOR 3.72, 95% CI: 1.35-11.68). Cannabinoid use was not independently associated with fentanyl use, intraprocedural awareness, discomfort, or adverse events. Conclusions: Baseline cannabinoid use was associated with higher sedation use during endoscopy with EDCS, particularly with midazolam and diphenhydramine. Given increasingly widespread cannabinoid use, endoscopists should be equipped with optimal sedation strategies for this population. As part of the informed consent process, cannabis users should be counseled that they may require higher sedation doses to achieve the same effect.

Characteristics and Outcomes of ERCP at a Canadian Tertiary Centre: Initial Results from a Prospective High-Fidelity Biliary Endoscopy Registry.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure in the management of pancreatic and biliary disease. While its role is firmly established, further well-designed prospective ERCP research is required, as a large portion of previous work has employed retrospective or administrative methodologies, both prone to potential biases. The aim of the Calgary Registry for Advanced and Therapeutic Endoscopy (CReATE) is to be a high-fidelity prospective multicentre registry. METHODS: The study population consisted of consecutive adult ERCP patients from September 2018 to September 2019. Informed consent was acquired for each patient. All relevant preprocedural, procedural, peri-procedural and postprocedural data were captured in real time by a full-time third-party research assistant directly observing procedures. Outcomes were ascertained by comprehensive medical record review and patient phone interview 30 days after the index procedure. RESULTS: Five endoscopists performed 895 ERCP procedures, 90.1% of which were deemed successful. Suspected choledocholithiasis was the most common indication for ERCP, followed by suspected or confirmed stricture(s), at 61.0% and 29.5%, respectively. 61.0% of procedures were performed on ERCP-naive patients. Post-ERCP pancreatitis occurred following 4.9% of procedures, with clinically significant bleeding or perforation occurring following 1.8% and 0.1% of procedures, respectively. DISCUSSION: Through 12 months, CReATE captured 895 procedures prospectively, with each entry containing over 300 data fields. Active expansion to additional tertiary centres is underway, and this will enhance the existing data pool. CReATE has the potential to improve multiple facets of ERCP, including training, optimal procedural techniques, mitigation of adverse events and personalized patient care.

Development and validation of a patient-reported scale for tolerability of endoscopic procedures using conscious sedation.

BACKGROUND AND AIMS: Patient-reported experience measures (PREMs) assessing the tolerability of endoscopic procedures are scarce. In this study, we designed and validated a PREM to assess tolerability of endoscopy using conscious sedation. METHODS: The patient-reported scale for tolerability of endoscopic procedures (PRO-STEP) consists of questions within 2 domains and is administered to outpatients at discharge from the endoscopy unit. Domain 1 (intraprocedural) consists of 2 questions regarding discomfort/pain and awareness, whereas domain 2 (postprocedural) consists of 4 questions on pain, nausea, distention, and either throat or anal pain. All questions are scored on a Likert scale from 0 to 10. Cronbach's alpha was used to measure internal consistency of the questions. Multivariable logistic regression was performed to assess predictors of higher scores, reported using adjusted odds ratios and confidence intervals. RESULTS: Two hundred fifty-five patients (91 colonoscopy, 73 gastroscopy, and 91 ERCP) were included. Colonoscopy was the least tolerable procedure by recall, with mean intraprocedural awareness and discomfort scores of 5.1 ± 3.8, and 2.6 ± 2.7, respectively. Consistency between intraprocedural awareness and discomfort/pain yielded an acceptable Cronbach's alpha of .71 (95% confidence interval, .62-.78). Higher use of midazolam during colonoscopy was inversely associated with an intraprocedural awareness score of 7 or higher (per additional mg: adjusted odds ratio, .23; 95% confidence interval, .09-.54). CONCLUSIONS: PRO-STEP is a simple PREM that can be administered after multiple endoscopic procedures using conscious sedation. Future work should focus on its performance characteristics in adverse event prediction.

Digestive Manifestations in Patients Hospitalized With Coronavirus Disease 2019.

BACKGROUND & AIMS: The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. METHODS: Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. RESULTS: A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76-1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80-2.12) were not associated independently with mechanical ventilation or death. CONCLUSIONS: Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

Morphology of the major papilla predicts ERCP procedural outcomes and adverse events.

BACKGROUND: The morphology of the major papilla affects the difficulty of endoscopic retrograde cholangiopancreatography (ERCP), but no associations with adverse events have previously been established. We aimed to assess whether papillary morphology predicts ERCP adverse events. METHODS: A retrospective analysis was performed of a prospective registry of patients undergoing ERCP for biliary indications. The primary outcome was post-ERCP pancreatitis (PEP), with secondary outcomes including other adverse events and procedural outcomes such as inadvertent pancreatic duct cannulation, cannulation time, and attempts. Papillae were classified as normal (Type I), small or flat (Type II), bulging (Type IIIa), pendulous (Type IIIb), creased (Type IV), or peri-diverticular (Type D). Outcomes were ascertained prospectively at 30 days from index procedures. RESULTS: A total of 637 patients with native papillae were included. Compared to Type I papillae, Type II and Type IIIb papillae were associated with PEP, with adjusted odds ratios (AOR) of 7.28 (95% confidence intervals, CI, 1.84-28.74) and 4.25 (95% CI 1.26-14.32), respectively. Type II and IIIb papillae were associated with significantly longer cannulation times by 5.37 (95% CI 2.39-8.35) and 4.01 (95% CI 1.72-6.30) minutes, respectively. Type IIIb papillae were associated with lower deep cannulation success (AOR 0.17, 95% CI 0.06-0.48). CONCLUSION: Papillary morphology is an important factor influencing both ERCP success and outcomes. Understanding this is key for managing intraprocedural approaches and minimizing adverse events. PROSPECTIVE REGISTRY REGISTRATION: Clinicaltrials.gov identifier NCT04259580.

Infection control in ERCP using a duodenoscope with a disposable cap (ICECAP): rationale for and design of a randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangio-pancreatography (ERCP) is commonly performed in the management of pancreatic and biliary disease. Duodenoscopes are specialized endoscopes used to perform ERCP, and inherent to their design, a high rate of persistent bacterial contamination exists even after automated reprocessing and disinfection. Consequently, in recent years, ERCP has been associated with infection transmission, leading to several fatal patient outbreaks. Due to increasing fears over widespread future duodenoscope-related outbreaks, regulatory bodies have called for alterations in the design of duodenoscopes. A duodenoscope has recently been developed that employs a disposable cap. This novel design theoretically eliminates the mechanism behind persistent bacterial contamination and infection transmission. However, there are no data demonstrating persistent bacterial contamination rates, technical success rates, or clinical outcomes associated with these duodenoscopes. METHODS: A parallel arm randomized controlled trial will be performed for which 520 patients will be recruited. The study population will consist of consecutive patients undergoing ERCP procedures for any indication at a high-volume tertiary care centre in Calgary, Alberta, Canada. Patients will be randomized to an intervention group, that will undergo ERCP with a novel duodenoscope with disposable cap, or to a control group who will undergo ERCP with a traditional duodenoscope. Co-primary outcomes will include persistent bacterial contamination rates (post automated reprocessing) and ERCP technical success rates. Secondary outcomes include clinical success rates, overall and specific early and late adverse event rates, 30-day mortality and healthcare utilization rates, procedure and reprocessing times, and ease of device use. DISCUSSION: The ICECAP trial will answer important questions regarding the use of a novel duodenoscope with disposable cap. Specifically, persistent bacterial contamination, technical performance, and relevant clinical outcomes will be assessed. Given the mortality and morbidity burden associated with ERCP-related infectious outbreaks, the results of this study have the capacity to be impactful at an international level. TRIAL REGISTRATION: This trial was registered on clinicaltrials.gov (NCT04040504) on July 31, 2019.