Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial.

OBJECTIVE: Hemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. METHODS: In this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. RESULTS: A total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. CONCLUSION: We failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01855841).

ERCP for the initial management of malignant biliary obstruction - real world data on 596 procedures.

AIMS: To evaluate outcomes of ERCP as first-line management in patients with malignant biliary obstruction (MBO) of all causes and stages, reflecting a real-life setting. METHODS: Retrospective observational study of patients with ERCP as the first-line management of MBO at Oslo University Hospital between 2015 and 2021. Primary outcome measure was a ≥ 50% decrease from the pre-procedural bilirubin within 30 days after ERCP. Secondary outcome measures were technical success of ERCP, complications and overall mortality. RESULTS: A total of 596 patients were included, median age 70 years. ASA score was ≥ III in 67% of patients. The most common cancers causing MBO were pancreatic cancer (52%), metastatic lesions (20%) and cholangiocarcinoma (16%). The primary outcome measure was achieved in 62% of patients. With endoscopic access, overall technical success was 80% with 85% for the distal extrahepatic group, 71% for the perihilar, 40% for the intrahepatic and 53% for multiple level MBOs. Reinterventions were performed in 27% of the patients. Complications occurred in 15% of the patients, including post-ERCP pancreatitis in 9%. Most complications were of minor/moderate severity (81%). Overall mortality was 33% within the first 90 days. Patients deceased by the end of the study period (83%) had median survival of 146 days (range 1-2,582 days). CONCLUSIONS: ERCP has a high rate of clinical effect and technical success in the management of both distal extrahepatic and perihilar MBO. Our data indicate that ERCP is a valid option in the first-line management of MBO.

The impact of COVID-19 on hospitalizations that underwent endoscopic retrograde cholangiopancreatography in the United States.

BACKGROUND/OBJECTIVES: COVID-19 impacts technical success of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we aimed to assess the influence of COVID-19 on hospitalizations that underwent ERCP. METHODS: We identified all adult COVID-19 and non-COVID-19 hospitalizations that underwent ERCP in the United States using the National Inpatient Sample for 2020. Hospitalization characteristics, clinical outcomes, and complications were compared between the two groups. RESULTS: In 2020, 2015 COVID-19 and 203,094 non-COVID-19 hospitalizations underwent ERCP. The COVID-19 cohort had a higher mean age (60.3 vs 55.6 years, p < 0.001) and a higher proportion of Blacks and Hispanics compared to the non-COVID-19 cohort. After adjusting for confounders, the COVID-19 cohort had higher all-cause inpatient mortality (4.77 vs 1.45%, aOR 4.09, 95% CI 2.50-6.69, p < 0.001), mean length of stay (LOS) [10.19 vs 5.94 days, mean difference: 3.88, 95% CI 2.68-5.07, p < 0.001] and mean total hospital charges (THC) [$152,933 vs $96,398, mean difference: 46,367, 95% CI 21,776-70,957, p < 0.001] compared to the non-COVID-19 cohort. Increasing age, higher Charlson Comorbidity Index, and post-ERCP pancreatitis were identified to be independent predictors of inpatient mortality for COVID-19 hospitalizations that underwent ERCP. Furthermore, the COVID-19 cohort had higher odds of developing post-ERCP pancreatitis (PEP) (11.55 vs 7.05%, aOR 1.64, 95% CI 1.19-2.25, p = 0.002) compared to the non-COVID-19 cohort, after adjusting for confounders. However, there was no statistical difference in the rates of bowel perforations and post-ERCP hemorrhage between the two groups. CONCLUSION: COVID-19 hospitalizations that underwent ERCP had higher inpatient mortality, mean LOS, mean THC, and odds of developing PEP compared to the non-COVID-19 cohort. CLINICAL TRIAL REGISTRATION: This study is not a part of a clinical trial.

Comparative Risks of Post-ERCP Adverse Events in Patients with Asymptomatic and Symptomatic Choledocholithiasis: A Systematic Review and Meta-Analysis.

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.

Prediction for post-ERCP pancreatitis in non-elderly patients with common bile duct stones: a cross-sectional study at a major Chinese tertiary hospital (2015-2023).

BACKGROUND: Post-ERCP pancreatitis is one of the most common adverse events in ERCP-related procedures. The purpose of this study is to construct an online model to predict the risk of post-ERCP pancreatitis in non-elderly patients with common bile duct stones through screening of relevant clinical parameters. METHODS: A total of 919 cases were selected from 7154 cases from a major Chinese tertiary hospital. Multivariable logistic regression model was fitted using the variables selected by the LASSO regression from 28 potential predictor variables. The internal and external validation was assessed by evaluating the receiver operating characteristic curve and the area under curve. Restricted cubic spline modelling was used to explore non-linear associations. The interactive Web application developed for risk prediction was built using the R "shiny" package. RESULTS: The incidence of post-ERCP pancreatitis was 5.22% (48/919) and significantly higher in non-elderly patients with female, high blood pressure, the history of pancreatitis, difficult intubation, endoscopic sphincterotomy, lower alkaline phosphatase and smaller diameter of common bile duct. The predictive performance in the test and external validation set was 0.915 (95% CI, 0.858-0.972) and 0.838 (95% CI, 0.689-0.986), respectively. The multivariate restricted cubic spline results showed that the incidence of pancreatitis was increased at 33-50 years old, neutrophil percentage > 58.90%, hemoglobin > 131 g/L, platelet < 203.04 or > 241.40 × 109/L, total bilirubin > 18.39 umol / L, aspartate amino transferase < 36.56 IU / L, alkaline phosphatase < 124.92 IU / L, Albumin < 42.21 g / L and common bile duct diameter between 7.25 and 10.02 mm. In addition, a web server was developed that supports query for immediate PEP risk. CONCLUSION: The visualized networked version of the above model is able to most accurately predict the risk of PEP in non-elderly patients with choledocholithiasis and allows clinicians to assess the risk of PEP in real time and provide preventive treatment measures as early as possible.

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OBJECTIVES: To investigate the application of endoscopic retrograde cholangiopancreatography (ERCP) in children and the risk factors for post-ERCP pancreatitis (PEP). METHODS: A retrospective analysis was conducted on the clinical data of 66 children, aged ≤16 years, who underwent ERCP for pancreaticobiliary diseases at the Gastrointestinal Endoscopy Center of the Second Affiliated Hospital of Kunming Medical University from September 2013 to September 2023. The incidence rate of PEP and the risk factors for the development of PEP were analyzed. RESULTS: A total of 78 ERCP procedures were performed on 66 children, with 5 diagnostic ERCPs, 69 therapeutic ERCPs, and 4 failed procedures. The success rate of ERCP operations was 95% (74/78). There were 17 cases of PEP in total, with an incidence rate of 22%. In the PEP group, the proportion of children with normal preoperative bilirubin and the proportion of guidewire insertion into the pancreatic duct during surgery were higher than in the non-PEP group (P<0.05). The multivariate logistic regression analysis showed that guidewire insertion into the pancreatic duct was an independent risk factor for PEP (P<0.05). CONCLUSIONS: With the increasing application of ERCP in children with pancreaticobiliary diseases, it is important to select an appropriate intubation technique during surgery to avoid blindly entering the guidewire into the pancreatic duct and reduce the occurrence of PEP.

A Prospective Cohort Study Evaluating PAN-PROMISE, a Patient-reported Outcome Measure to Detect Post-ERCP Morbidity.

BACKGROUND & AIMS: The Cotton Consensus (CC) criteria for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) may not capture post-ERCP morbidity. PAN-PROMISE, a patient-reported outcome measure (PROM), was developed to quantify acute pancreatitis-related morbidity. This study aims to determine the value of PAN-PROMISE in independently defining ERCP-related morbidity. METHODS: We conducted a prospective cohort study of patients undergoing ERCP at 2 academic centers from September 2021 to August 2022. We administered PAN-PROMISE and assessed quality of life and work productivity at baseline, 48 to 72 hours, 7 days, and 30 days following ERCP. PEP was defined by a 3-physician committee using the CC criteria. We defined high morbidity following ERCP (elevated PROM) by an increase of PAN-PROMISE score of >7 at 7 days post-procedure. The McNemar test assessed discordance between PEP and elevated-PROM. RESULTS: A total of 679 patients were enrolled. Choledocholithiasis (30%) and malignant biliary obstruction (29%) were the main indications for ERCP. Thirty-two patients (4.7%) developed PEP. One hundred forty-seven patients (21.6%) had an elevated PROM, whereas only 20 of them (13.4%) had PEP by the CC criteria (P < .001 for discordance). An elevated PROM strongly correlated with lower physical quality of life and increased direct and indirect health care costs ($80 and $25 per point increase in PAN-PROMISE, respectively). Patients with pancreatic cancer (odds ratio, 4.52; 95% confidence interval, 1.68-10.74) and primary sclerosing cholangitis (odds ratio, 1.79; 95% confidence interval, 1.29-2.45) had the highest odds of elevated PROM. CONCLUSIONS: A substantial number of patients experience significant morbidity after ERCP despite not developing PEP or other adverse events. Future studies are needed to characterize better the reasons behind this increase in symptoms and potential interventions to reduce the symptom burden post-ERCP. CLINICALTRIALS: gov number, NCT05310409.

Preclinical safety evaluation of calcineurin inhibitors delivered through an intraductal route to prevent post-ERCP pancreatitis demonstrates endocrine and systemic safety.

OBJECTIVE: There is an urgent need for safe and targeted interventions to mitigate post-ERCP pancreatitis (PEP). Calcineurin inhibitors (CnIs) offer therapeutic promise as calcineurin signaling within acinar cells is a key initiating event in PEP. In previous proof-of-concept studies using experimental models, we showed that concurrent intra-pancreatic ductal administration of the CnIs, tacrolimus (Tac) or cyclosporine A (CsA) with the ERCP radiocontrast agent (RC) prevented PEP. To translate this finding clinically, we investigated potential toxic effects of intraductal delivery of a single-dose RC-CnI formulation on endocrine pancreas function and systemic toxicities in a preclinical PEP model. METHODS: C57BL/6J mice underwent ductal cannulation and received a single, intra-pancreatic ductal infusion of RC or RC with Tac or CsA (treatment groups) or underwent ductal cannulation without infusion ('sham' group). To assess endocrine function, intraperitoneal glucose tolerance test (IPGTT) was performed at two days before infusion and on day 2 and 14 post-surgery. To evaluate off-target tissue toxicities, renal and hepatic function-related parameters including blood urea nitrogen, plasma creatinine, potassium, aspartate aminotransferase, alanine aminotransferase, and total bilirubin were measured at the same time-points as IPGTT. Histological and biochemical indicators of pancreas injury and inflammation were also evaluated. RESULTS: No abnormalities in glucose metabolism, hepatic or renal function were observed on day 2 or 14 in mice administered with intraductal RC or RC with Tac or CsA. CONCLUSION: Intraductal delivery of RC-CnI formulation was safe and well-tolerated with no significant acute or subacute endocrine or systemic toxicities, underscoring its clinical utility to prevent PEP.

Rectal administration of tacrolimus protects against post-ERCP pancreatitis in mice.

OBJECTIVE: There is an unmet clinical need for effective, targeted interventions to prevent post-ERCP pancreatitis (PEP). We previously demonstrated that the serine-threonine phosphatase, calcineurin (Cn) is a critical mediator of PEP and that the FDA-approved calcineurin inhibitors, tacrolimus (Tac) or cyclosporine A, prevented PEP. Our recent observations in preclinical PEP models demonstrating that Cn deletion in both pancreatic and hematopoietic compartments is required for maximal pancreas protection, highlighted the need to target both systemic and pancreas-specific Cn signaling. We hypothesized that rectal administration of Tac would effectively mitigate PEP by ensuring systemic and pancreatic bioavailability of Tac. We have tested the efficacy of rectal Tac in a preclinical PEP model and in cerulein-induced experimental pancreatitis. METHODS: C57BL/6 mice underwent ductal cannulation with saline infusion to simulate pressure-induced PEP or were given seven, hourly, cerulein injections to induce pancreatitis. To test the efficacy of rectal Tac in pancreatitis prevention, a rectal Tac suppository (1 mg/kg) was administered 10 min prior to cannulation or first cerulein injection. Histological and biochemical indicators of pancreatitis were evaluated post-treatment. Pharmacokinetic parameters of Tac in the blood after rectal delivery compared to intravenous and intragastric administration was evaluated. RESULTS: Rectal Tac was effective in reducing pancreatic injury and inflammation in both PEP and cerulein models. Pharmacokinetic studies revealed that the rectal administration of Tac helped achieve optimal blood levels of Tac over an extended time compared to intravenous or intragastric delivery. CONCLUSION: Our results underscore the effectiveness and clinical utility of rectal Tac for PEP prophylaxis.

A new classification of periampullary diverticulum: cannulation of papilla on the inner margins of the diverticulum (Type IIa) is more challenging.

BACKGROUND: Periampullary diverticulum (PAD) may make the performance of endoscopic retrograde cholangiopancreatography (ERCP) in patients with choledocholithiasis more difficult and may increase complication rates. The present study evaluated the effects of PAD on first-time ERCP in patients with choledocholithiasis. METHODS: Outcomes were compared in patients with and without PAD and in those with four types of PAD: papilla located completely inside the diverticulum (type I), papilla located in the inner (type II a) and outer (type II b) margins of the diverticulum; and papilla located outside the diverticulum (type III). Parameters compared included cannulation time and rates of difficult cannulation, post-ERCP pancreatitis (PEP) and perforation. RESULTS: The median cannulation times in patients with types I, II a, II b, III PAD and in those without PAD were 2.0 min, 5.0 min, 0.67 min, 3.5 min, and 3.5 min, respectively, with difficult cannulation rates in these groups of 7.4%, 31.4%, 8.3%, 18.9%, and 23.2%, respectively. The rates of PEP in patients with and without PAD were 5.3% and 5.1%, respectively. Four patients with and one without PAD experienced perforation. CONCLUSIONS: The division of PAD into four types may be more appropriate than the traditional division into three types. Cannulation of type I and II b PAD was easier than cannulation of patients without PAD, whereas cannulation of type II a PAD was more challenging. PAD may not increase the rates of PEP.

A Risk Prediction Model for Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis After Stent Insertion for Malignant Biliary Obstruction: Development and Validation.

OBJECTIVES: Pancreatitis is the most common complication of post-endoscopic retrograde cholangiopancreatography (ERCP). There are currently no prediction models, particularly for post-ERCP pancreatitis (PEP) after biliary stent placement due to malignant biliary obstruction (MBO). To that end, we aim to develop and validate a predictive model for PEP. METHODS: We retrospectively analyzed the data of patients who underwent ERCP for biliary stent placement due to MBO at the Second Affiliated Hospital of Harbin Medical University from January 1, 2014 to August 31, 2021. The eligible patients were randomly allocated to the development and validation cohorts. A prediction model was built using the development cohort, and the model's effect was validated using a validation cohort. RESULTS: A total of 1524 patients were enrolled, including 1016 in the development cohort and 508 in the validation cohort, with an overall PEP rate of 7.1%. The model's predictors included acute pancreatitis history, the absence of pancreatic duct dilation, nonpancreatic cancer, difficult cannulation, and pancreatic injection. The area under the curve (AUC) in the development cohort was 0.810, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 1.53%, 9.12%, and 36.36%, respectively. Meanwhile, the AUC of the validation cohort was 0.781, and the incidence of PEP in the low-risk, medium-risk, and high-risk groups was 4.17%, 8.75%, and 41.67%, respectively. CONCLUSIONS: This study was the first to build and validate a risk prediction model, especially for PEP after biliary stent placement due to MBO. Moreover, this model might assist clinicians in identifying high-risk patients and help implement preventive measures in a more timely manner.

Efficacy and safety of three endoscopic techniques for small common bile duct stones (≤ 10 mm): a multicenter, retrospective, cohort study with propensity score matching.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a major option for common bile duct (CBD) stones. Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilatation (EPBD), and endoscopic sphincterotomy plus balloon dilatation (ESBD) are procedures for opening the bile duct orifice to extract CBD stones during ERCP. The optimal method for extracting small CBD stones (≤ 10 mm) has not yet been proposed. We aimed to compare the efficacy and safety of these three techniques in extracting small CBD stones. METHODS: ERCP for small stones was performed between January 2009 and November 2020 at three tertiary care centers. The incidence of post-ERCP pancreatitis (PEP) was compared among EST, EPBD, and ESBD groups. First and overall success rates of stone extraction, utilization rate of mechanical lithotripsy, and other ERCP complications such as bleeding, perforation, infection, and hyperamylasemia were compared. RESULTS: A total of 2181 patients were enrolled between January 2009 and November 2020. The proportion of young patients (≤ 45 years) in EPBD group was more than those in EST and ESBD group. Stone size in ESBD group was much larger than EST and EPBD group. After propensity score matching, the success rates of first and overall stone extraction in the three groups were high, and the rates of mechanical lithotripsy were low, with no significant difference. The PEP incidences showed no differences among the three groups. The incidence of bleeding complication in EST group was higher than that in EPBD group. No significant differences were observed in other complications between EPBD group and ESBD group. ESBD group had higher incidence of overall, infection, and hyperamylasemia complications than EST group. CONCLUSION: EPBD is equivalent to ESBD in stone removal efficiency and complication rate, but brings a lower bleeding risk than EST. Therefore, we recommend EPBD as the first choice for small CBD stones.

Postprocedure serum amylase or lipase levels predict postendoscopic retrograde cholangiopancreatography pancreatitis: Meta-analysis of diagnostic test accuracy studies and utility assessment.

OBJECTIVES: We aimed to clarify the clinical utility of measuring serum pancreatic enzymes after endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of predicting post-ERCP pancreatitis (PEP) by a meta-analysis of diagnostic test accuracy studies. METHODS: Studies on the prediction accuracy of PEP by serum amylase or lipase measured at 2, 3, and 4 h after ERCP were collected. A literature search was performed in PubMed and the Cochrane Library database for studies published between January 1980 and March 2023. The quality of individual studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Data were analyzed using Meta-DiSc 2.0 software. RESULTS: We searched the databases and identified 20 observational studies (12,313 participants). PEPs were defined according to criteria by Cotton or modified Cotton, revised Atlanta criteria, or the Japanese criteria. Meta-analysis of eight studies (4389 participants) showed a pooled sensitivity of 71.1% (95% confidence interval [CI] 56.1-82.5) and pooled specificity of 91.2% (95% CI 85.9-94.6) for the serum amylase cut-off value at 3 times the upper limit of normal (ULN). Another meta-analysis of five studies (1970 participants) showed a pooled sensitivity of 85.8% (95% CI 61.9-95.7) and pooled specificity of 85.3% (95% CI 81.9-88.1) for the serum lipase cut-off value at 3 times ULN. CONCLUSION: Despite a high risk of bias due to various reference standards, this updated meta-analysis and the utility assessment by a decision tree showed the utility of serum amylase or lipase levels more than 3 times ULN measured 2-4 h after ERCP for predicting PEP.

Efficacy of pancreatic duct stenting to prevent postendoscopic retrograde cholangiopancreatography pancreatitis after covered self-expandable metal stent deployment.

OBJECTIVES: Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation. METHODS: This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time. RESULTS: Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034). CONCLUSIONS: Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

Does patient's position count during Endoscopic Retrograde Cholangio-pancreatography? Left lateral decubitus versus prone position.

Objective: To compare the efficacy and safety of left lateral decubitus versus prone position during endoscopic retrograde cholangio-pancreaticography (ERCP). Methods: This prospective single-centre cohort study was carried out at Pak Emirates Military Hospital from January to June 2021. Patients requiring ERCP were subsequently allotted LL or PP group randomly (unequal randomization) except patients with recent abdominal surgery, in-dwelling catheters, raised intra-abdominal pressure, cervical spine abnormalities and limb contractures. Qualitative data was analysed using frequencies and chi square statistics whereas, quantitative data was analysed using mean±SD and student T or Mann Whitney U-test. Results: A total of 114 patients were enrolled according to the inclusion criteria with 62(54%) males and majority of the patients (42%) belonging to the age group 31-45 years. The most common ERCP indication was choledocholithiasis (36%). Technical success was achieved in 109(96%) patients with no statistically significant difference between the two groups. The total time of procedure, time for deep cannulation, time for acquiring therapeutic goal and ERCP complexity level were all similar between the two groups. The rate of inadvertent PD cannulation and PEP were relatively higher for the PP group but were statistically non-significant through univariate and logistic regression analyses and the only outcome measure that showed significance was multiple cannulations in the PP group. Conclusion: The study concludes that LL is non-inferior to PP and both positions have comparable outcomes with non-significant differences in terms of technical success rate, complications (specifically PEP), total procedure time, time required for deep cannulation and attainment of goal, ERCP complexity level and inadvertent PD cannulation.

Does early application of needle-knife sphincterotomy (NKS) in patients with difficult biliary cannulation increase the risk of postERCP pancreatitis? A single centre study.

Objective: To determine that early needle-knife sphincterotomy does not increase post-ERCP pancreatitis in patients with difficult biliary cannulation as compared to standard cannulation. Method: This prospective single-centre cohort study was carried out at Pak Emirates Military Hospital from January 2021 to June 2021. Patients requiring ERCP were enrolled in the study (according to inclusion and exclusion criteria) and were subsequently allotted different groups according to the technique used for deep biliary cannulation. Qualitative data was analysed using frequencies and chi square statistics whereas, quantitative data was analysed using mean±SD and one way ANOVA test. Result: The cohort included 114 patients with 52.6% male patients and predominance of relatively younger age group (31-45 years). The most common indication for ERCP was choledocholithiasis (36%) with an overall technical success rate of 96%. Deep cannulation was achieved either through standard cannulation (56%), double guidewire and/or pancreatic stent assisted (10.5%), use of early Needle-Knife Sphincterotomy (19%), NKS as a last resort (3.5%) or Transpancreatic Stenting and/or combined sphincterotomy (6%). Pancreatitis as a complication occurred in 4(3.5%) patients, bleeding in 2(1.8%), on-table desaturation in 2(1.8%) and perforation in 1(0.9%) patient. The occurrence of pancreatitis was only related significantly to inadvertent PD cannulation through univariate and logistic regression analysis whereas, multiple cannulations (>5), gender, age, classification of papilla and the use of early NKS had no impact on pancreatitis or the occurrence of other complications. Conclusion: NKS is an effective and safe modality for deep biliary cannulation and achieving technical success where cannulation is deemed difficult and does not increase the risk of PEP if done by experienced endoscopists in high volume centres.

A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States.

BACKGROUND & AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common adverse event after endoscopic retrograde cholangiopancreatography, and is responsible for substantial morbidity and health care expenditures of at least $200 million. Therapies for PEP prevention include pancreatic stent placement (PSP), rectal indomethacin, sublingual nitrates, and aggressive lactated Ringer's hydration. Our objective was to determine which PEP prophylactic strategies are cost effective. METHODS: We developed 2 separate decision trees to evaluate PEP prophylactic strategies. The first, in high-risk patients, compared rectal indomethacin, PSP, PSP with indomethacin, sublingual nitrates, aggressive hydration with lactated Ringer's, and no prophylaxis. The second, in average-risk patients, compared rectal indomethacin, sublingual nitrates, aggressive hydration, and no prophylaxis. We used incidence rates, transition probabilities, and costs from publications and public data sources. Outcome measures were reported as incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life years (QALYs). RESULTS: Compared with no prophylaxis, all strategies were cost effective at a WTP of $100,000 in preventing PEP in high-risk patients. When directly compared with each other, rectal indomethacin was the cost-effective strategy in high-risk patients ($31,589/QALYs). In average-risk patients, indomethacin and sublingual nitrates were cost effective at a WTP of $100,000/QALYs compared with no prophylaxis. When directly compared with each other, rectal indomethacin was the cost-effective strategy ($53,016/QALYs). CONCLUSIONS: Rectal indomethacin was the cost-effective strategy for preventing PEP in both average-risk and high-risk patients undergoing endoscopic retrograde cholangiopancreatography. All strategies were cost effective when compared with no prophylaxis in high-risk patients, whereas all strategies except for aggressive hydration with lactated Ringer's were cost effective in average-risk patients. Further studies are needed to improve the utilization of PEP prevention strategies.

ERCP in patients with prior sphincterotomy has a 50% lower rate of post-ERCP pancreatitis and fewer unplanned hospital admissions.

OBJECTIVES: ERCP is essential in managing pancreaticobiliary disease, with well-documented complications. Rates of clinically significant complications are about 10%, approximately half of which is related to post-ERCP pancreatitis (PEP). We aimed to quantify the effect of previous sphincterotomy on post-endoiscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). MATERIALS AND METHODS: Data were collated from a contemporaneously collected database of 2876 consecutive ERCP procedures of a single operator in a tertiary referral centre. Analysis was conducted using R software, and logistic regression models. RESULTS: Of 2876 procedures (mean age 63 years, 56% female), 120 (4.2%) developed PEP and 268 (9.3%) had prolonged/unplanned hospital admission. Univariate analysis showed patients with previous sphincterotomy 28/1054 (2.7%) had decreased risk of PEP compared with those without sphincterotomy 92/1822 (5.0%) (OR 0.52, p = .0021). This difference was not evident when multivariate analysis for age, sex and indication was undertaken due to a particularly low risk of PEP in stent change patients (1.4%), which were disproportionately represented in the previous sphincterotomy group. The rate of prolonged/unplanned hospital admission was recorded for a total of 2876 patients, occurring in 184/1802 (10.1%) in the native ampulla group, versus 84/1045 (8.0%) in the previous sphincterotomy group. CONCLUSIONS: The risk of PEP is halved by prior sphincterotomy. The presence of a biliary stent conferred an even lower risk of PEP (1.4%), but those without an in situ stent at the time of ERCP had a similar risk of PEP (4.6%) of prolonged/unplanned hospitalisation to those with a native ampulla.

The effect of nafamostat mesilate infusion after ERCP for post-ERCP pancreatitis.

BACKGROUND: Nafamostat mesilate decreases the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, no studies have administered nafamostat mesilate after ERCP. So we investigated if the infusion of nafamostat mesilate after ERCP can affect the post-ERCP pancreatitis (PEP) in high-risk patients. METHODS: In a tertiary hospital, 350 high-risk patients of PEP were reviewed retrospectively. Among them, 201 patients received nafamostat mesilate after ERCP. Patient-related and procedure-related risk factors for PEP were collected. We performed a propensity score matching to adjust for the significant different baseline characteristics. The incidence and severity of PEP were evaluated according to the infusion of nafamostat mesilate. The risk factors of PEP were also analyzed by multivariate logistic regression. RESULTS: The baseline characteristics were not different after the matching. The PEP rate (17.4% vs. 10.3%, P = 0.141) was insignificant. Among the PEP patients, mild PEP was significantly higher in the nafamostat mesilate group (85.7% vs. 45.5%, P = 0.021). Only one patient in the nafamostat mesilate group developed severe PEP. Although young age (odds ratio [OR] 3.60, 95% CI 1.09-11.85, P = 0.035) was a risk factor, nafamostat mesilate (odds ratio [OR] 0.30, 95% CI 0.09-0.98, P = 0.047) was a protective factor for moderate to severe PEP. CONCLUSIONS: The administration of nafamostat mesilate after ERCP in high-risk patients was not effective in preventing PEP, but may attenuate the severity of PEP.

Effect of ice water injection toward the duodenal papilla for preventing post-ERCP pancreatitis: study protocol for a multicenter, single-blinded, randomized controlled trial (EUTOPIA study).

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential procedure in the diagnosis and treatment of biliopancreatic diseases. The most common adverse event of ERCP is post-ERCP pancreatitis (PEP), which can sometimes be severe. Our previous study suggested that injecting ice water at the end of ERCP suppressed PEP, and we decided to investigate this effect in a multicenter randomized controlled trial. METHODS: This study is being conducted at eight hospitals in Japan starting in April 2022. Patients undergoing ERCP will be randomized to ice water group and control group. In the ice water group, 250 ml of ice water is injected toward the papilla at the end of ERCP. The next morning, a physical examination and blood tests are performed to evaluate for the development of pancreatitis. The goal is to have 440 cases in each group. DISCUSSION: The main cause of PEP is thought to be papilla edema. Cooling the papilla, as everyone naturally does at the time of a burn, is expected to prevent its inflammation and edema. Various methods to suppress PEP have been reported, but so far none of them are reliable. The method we have devised is very simple, easy, and safe. We hope that our study will change the world's ERCP common practice. TRIAL REGISTRATION: UMIN000047528. Registered 20 April 2022, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053209.