Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

Development and Usability of an Endoscopist Report Card Assessing ERCP Quality.

BACKGROUND AND AIMS: Audit and feedback (A&F) for endoscopic retrograde cholangiopancreatography (ERCP) is relatively understudied despite the demonstrated effectiveness of A&F for endoscopic procedures such as colonoscopy. Endoscopist 'report cards' are one A&F tool. We aimed to develop an ERCP report card and assess its appropriateness, acceptability and feasibility through usability testing. METHODS: A prototype report card was designed using a combination of published quality indicators and established predictors of adverse events (AE). Exploratory analyses from a prospective multi-center registry were performed to further identify novel and/or understudied parameters for possible inclusion. Semi-structured interviews with ERCP endoscopists were conducted and framework analysis performed. Validated post-interview usability instruments were administered. Feedback was incorporated to create a final report card. RESULTS: The report card included domains of technical parameters, AE rates/prevention, and patient-reported experience measures (PREMs). Qualitative feedback was positive, with respondents agreeing with inclusion of relevant content in most domains. Post-interview instruments revealed adequate appropriateness and acceptability. PREMs were felt by respondents to be poorly actionable and were replaced with appropriateness of indication and fluoroscopy usage parameters in the final report card. Concerns were raised regarding the feasibility of implementation due to reliance on difficult-to-obtain granular intraprocedural data. CONCLUSIONS: We designed and tested an ERCP report card that has potential to be an effective A&F intervention for endoscopists in clinical practice. Though feasibility of data capture and implementation are currently limitations, advances in video recording and artificial intelligence technologies could accelerate widespread adoption of such a tool.

The Impact of Difficult Biliary Cannulation on Post-ERCP Pancreatitis: A Secondary Analysis of the Stent versus Indomethacin Trial Dataset.

BACKGROUND AND AIMS: Difficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors. METHODS: This was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk. RESULTS: In all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages. CONCLUSIONS: DBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages.

Survival analysis among unresectable pancreatic adenocarcinoma patients undergoing endoscopic or percutaneous interventions.

BACKGROUND AND AIMS: Most patients with pancreatic cancer are diagnosed at a late stage and are not candidates for surgical resection. Many have jaundice requiring biliary drainage, which can be accomplished using ERCP or percutaneous transhepatic biliary drainage (PTBD). To date, no studies have evaluated the impact of ERCP or PTBD on survival among patients with unresectable pancreatic cancer. The aims of our study were to compare overall survival between patients with unresectable pancreatic cancer receiving ERCP with those receiving PTBD, to compare overall survival between patients who received a biliary intervention (ERCP or PTBD) versus those who received no biliary intervention, and to compare secondary outcomes, such as length of hospital stay and costs, between ERCP and PTBD. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Patients with known pancreatic cancer were included if they had a pancreatic head mass and/or evidence of biliary obstruction. We used a time-varying Cox proportional hazards model to estimate overall survival of patients receiving ERCP versus PTBD and overall survival among patients who received a biliary intervention versus no biliary drainage. Secondary outcomes included length of hospital stay, costs, and admissions within 30 days. RESULTS: Of 14,808 patients with unresectable pancreatic cancer, 8898 patients (60.0%) underwent biliary drainage and 5910 patients (39.9%) received no biliary intervention. ERCP accounted for most biliary interventions (8271, 93.0%), whereas 623 patients (7.0%) underwent PTBD. In multivariable analysis, ERCP was associated with reduced mortality compared with PTBD (adjusted hazard ratio [aHR], .67; 95% confidence interval [CI], .60-.75). When ERCP or PTBD was compared with no biliary intervention, both procedures were associated with a survival benefit (aHR, .51 [95% CI, .49-.54] and .53 [95% CI, .48-.59], respectively). Compared with patients receiving PTBD, those who underwent ERCP had shorter mean length of hospital stay (7.0 ± 5.7 days vs 9.6 ± 6.6 days, respectively; P < .001) and lower hospital charges ($54,899.25 vs $75,246.00, P < .001) but no significant difference in hospitalization or 30-day readmissions. CONCLUSIONS: ERCP is associated with reduced mortality compared with PTBD in pancreatic cancer patients, highlighting the critical role of ERCP in the management of biliary obstruction from pancreatic cancer.

Racial Disparities and Trends in Pancreatic Cancer Incidence and Mortality in the United States.

BACKGROUND & AIMS: Pancreatic cancer is one of the few cancers in the United States that is increasing in incidence. Little is known about racial disparities in incidence and mortality. We characterized racial disparities in pancreatic cancer incidence and mortality in different locations, time periods, age groups, and disease stages. METHODS: We obtained data on the incidence of pancreatic cancer from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program of cancer registries from 2001 through 2015 on incidence, demographics, tumor characteristics, and population estimates for all 50 states and the District of Columbia. We obtained data on mortality from pancreatic cancer from the National Center for Health Statistics during the same time period. We plotted incidence rates by 10-year age group (30-39 years through 70-79 years and 80 years or older) separately for white and black patients. We calculated incidence and mortality rate ratios with 95% CIs for categories of age and race. To determine racial disparities, we calculated incidence rate ratios (IRR) for black vs white patients and mortality rate ratios by state. RESULTS: Disparities in pancreatic cancer incidence and mortality in black vs white patients decreased over 5-year time periods from 2001 through 2015. However, among all age groups, from 2001 through 2015, pancreatic cancer incidence and mortality were higher among blacks than whites (incidence, 24.7 vs 19.4 per 100,000; IRR, 1.28; 95% CI, 1.26-1.29; mortality, 23.3 vs 18.4 per 100,000; IRR, 1.27; 95% CI, 1.26-1.28). Black patients had a higher incidence of distant pancreatic cancer (IRR, 1.32; 95% CI, 1.31-1.34) and a lower incidence of local cancer. Incidence increased in whites and blacks of younger age groups and was most prominent among persons 30-39 years old. Incidence increased by 57% among younger whites (IRR, 1.70; 95% CI, 1.43-2.02) and by 44% among blacks (IRR, 1.47; 95% CI, 1.01-2.15) from 2001 through 2015. Mortality remained stable among blacks and slightly increased among whites during this time period. CONCLUSIONS: In the United States, there are racial disparities in pancreatic incidence and mortality that vary with location, patient age, and cancer stage. Further research is needed to identify factors associated with increasing incidence and persistence of racial disparities in pancreatic cancer.

Clinical and Economic Outcomes of Patients Undergoing Guideline-Directed Management of Pancreatic Cysts.

INTRODUCTION: Numerous guidelines exist for the management of pancreatic cysts. We sought to compare the guideline-directed management strategies for pancreatic cysts by comparing 2 approaches (2017 International Consensus Guidelines and 2015 American Gastroenterological Association Guidelines) that differ significantly in their thresholds for imaging, surveillance, and surgery. METHODS: We developed a Monte Carlo model to evaluate the outcomes for a cohort of 10,000 patients managed per each guideline. The primary outcome was mortality related to pancreatic cyst management. Secondary outcomes included all-cause mortality, missed cancers, number of surgeries, number of imaging studies, cumulative cost, and quality-adjusted life years. RESULTS: Deaths because of pancreatic cyst management and quality-adjusted life years were similar in both guidelines at a significantly higher cost of $3.6 million per additional cancer detected in the Consensus Guidelines. Deaths from "unrelated" causes (1,422) vastly outnumbered deaths related to pancreatic cysts (125). Secondary outcomes included more missed cancers in the American Gastroenterological Association guideline (71 vs 49), more surgeries and imaging studies in the Consensus guideline (711 vs 163; 116,997 vs 68,912), and higher cost in the Consensus guideline ($168.3 million vs $89.4 million). As the rate of malignant transformation increases, a more-intensive guideline resulted in fewer deaths related to pancreatic cyst management. DISCUSSION: Our study demonstrates trade-offs between more- and less-intensive management strategies for pancreatic cysts. Although deaths related to pancreatic cyst management were similar in each strategy, fewer missed cancers in the more-intensive surveillance strategy is offset by a greater number of surgical deaths and higher cost. In conclusion, our study identifies that if the rate malignant transformation of pancreatic cysts is low (0.12% annually), a less-intensive guideline will result in similar deaths to a more-intensive guideline at a much lower cost.

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT).

BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting. METHOD: Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established CV disease and taking chronic prescribed nsNSAIDs, were randomized to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalization for non-fatal myocardial infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR). RESULTS: In total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than expected developed an on-treatment (OT) primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient-years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence interval, 0.81-1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were 1.14 per 100 patient-years with celecoxib and 1.10 per 100 patient-years with nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81-1.33; P = 0.75). Pre-specified non-inferiority was achieved in the ITT analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was two primary events per 1000 patient-years exposure. There were only 15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100 patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More gastrointestinal serious adverse reactions and haematological adverse reactions were reported on nsNSAIDs than celecoxib, but more patients withdrew from celecoxib than nsNSAIDs (50.9% patients vs. 30.2%; P < 0.0001). INTERPRETATION: In subjects 60 years and over, free from CV disease and taking prescribed chronic nsNSAIDs, CV events were infrequent and similar on celecoxib and nsNSAIDs. There was no advantage of a strategy of switching prescribed nsNSAIDs to prescribed celecoxib. This study excluded an increased risk of the primary endpoint of more than two events per 1000 patient-years associated with switching to prescribed celecoxib. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT00447759; Unique identifier: NCT00447759.

Specialist Endoscopists Are Associated with a Decreased Risk of Incomplete Polyp Resection During Endoscopic Mucosal Resection in the Colon.

BACKGROUND: Endoscopic experience is known to correlate with outcomes of endoscopic mucosal resection (EMR), particularly complete resection of the polyp tissue. Whether specialist endoscopists can protect against incomplete polypectomy in the setting of known risk factors for incomplete resection (IR) is unknown. AIMS: We aimed to characterize how specialist endoscopists may help to mitigate the risk of IR of large sessile polyps. METHODS: This is a retrospective cohort study of patients who underwent EMR at the University of Michigan from January 1, 2006, to November 15, 2015. The primary outcome was endoscopist-reported polyp tissue remaining at the end of the initial EMR attempt. Specialist endoscopists were defined as endoscopists who receive tertiary referrals for difficult colonoscopy cases and completed at least 20 EMR colonic polyp resections over the study period. RESULTS: A total of 257 patients with 269 polyps were included in the study. IR occurred in 40 (16%) cases. IR was associated with polyp size ≥ 40 mm [adjusted odds ratio (aOR) 3.31, 95% confidence interval (CI) 1.38-7.93], flat/laterally spreading polyps (aOR 2.61, 95% CI 1.24-5.48), and difficulty lifting the polyp (aOR 11.0, 95% CI 2.66-45.3). A specialist endoscopist performing the initial EMR was protective against IR, even in the setting of risk factors for IR (aOR 0.13, 95% CI 0.04-0.41). CONCLUSIONS: IR is associated with polyp size ≥ 40 mm, flat and/or laterally spreading polyps, and difficulty lifting the polyp. A specialist endoscopist initiating the EMR was protective of IR.

EUS Needle Identification Comparison and Evaluation study (with videos).

BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.

NSAID-induced Gastrointestinal Injury: A Focused Update for Clinicians.

Gastroenterologists care for users of nonsteroidal anti-inflammatory drugs (NSAIDs) when the vast population exposed to the medication class experiences a relatively uncommon serious gastrointestinal (GI) side effect. As serious adverse cardiovascular (CV) effects of these drugs have also been recognized, there remains continued confusion about the best treatment for patients who benefit from NSAID therapy and are at risk for GI and CV adverse events. Recognition of those patients at risk and strategies to reduce the adverse side effects of NSAIDs continues to provide an opportunity to improve patient outcomes. This review discusses the injury induced by these agents throughout the GI tract as well as strategies to prevent acute injury and reduce the development of serious adverse events. NSAID medication selection as well as GI cotherapy should balance individual patients' GI and CV risks.

Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers.

Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for ≥3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers.

A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.

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.).

Evaluation of Pharmacologic Prevention of Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review.

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.

Variation in Aptitude of Trainees in Endoscopic Ultrasonography, Based on Cumulative Sum Analysis.

BACKGROUND & AIMS: Studies have reported substantial variation in the competency of advanced endoscopy trainees, indicating a need for more supervised training in endoscopic ultrasound (EUS). We used a standardized, validated, data collection tool to evaluate learning curves and measure competency in EUS among trainees at multiple centers. METHODS: In a prospective study performed at 15 centers, 17 trainees with no prior EUS experience were evaluated by experienced attending endosonographers at the 25th and then every 10th upper EUS examination, over a 12-month training period. A standardized data collection form was used (using a 5-point scoring system) to grade the EUS examination. Cumulative sum analysis was applied to produce a learning curve for each trainee; it tracked the overall performance based on median scores at different stations and also at each station. Competency was defined by a median score of 1, with acceptable and unacceptable failure rates of 10% and 20%, respectively. RESULTS: Twelve trainees were included in the final analysis. Each of the trainees performed 265 to 540 EUS examinations (total, 4257 examinations). There was a large amount of variation in their learning curves: 2 trainees crossed the threshold for acceptable performance (at cases 225 and 245), 2 trainees had a trend toward acceptable performance (after 289 and 355 cases) but required continued observation, and 8 trainees needed additional training and observation. Similar results were observed at individual stations. CONCLUSIONS: A specific case load does not ensure competency in EUS; 225 cases should be considered the minimum caseload for training because we found that no trainee achieved competency before this point. Ongoing training should be provided for trainees until competency is confirmed using objective measures.

The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement.

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.

Predicting the likelihood of a persistent bile duct stone in patients with suspected choledocholithiasis: accuracy of existing guidelines and the impact of laboratory trends.

BACKGROUND: Existing guidelines aim to stratify the likelihood of choledocholithiasis to guide the use of ERCP versus a lower-risk diagnostic study such as EUS, MRCP, or intraoperative cholangiography. OBJECTIVE: To assess the performance of existing guidelines in predicting choledocholithiasis and to determine whether trends in laboratory parameters improve diagnostic accuracy. DESIGN: Retrospective cohort study. SETTING: Tertiary-care hospital. PATIENTS: Hospitalized patients presenting with suspected choledocholithiasis over a 6-year period. INTERVENTIONS: Assessment of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, its component variables, and laboratory trends in predicting choledocholithiasis. MAIN OUTCOME MEASUREMENTS: The presence of choledocholithiasis confirmed by EUS, MRCP, or ERCP. RESULTS: A total of 179 (35.9%) of the 498 eligible patients met ASGE high-probability criteria for choledocholithiasis on initial presentation. Of those, 99 patients (56.3%) had a stone/sludge on subsequent confirmatory test. Of patients not meeting high-probability criteria on presentation, 111 (34.8%) had a stone/sludge. The overall accuracy of the guidelines in detecting choledocholithiasis was 62.1% (47.4% sensitivity, 73% specificity) based on data available at presentation. The accuracy was unchanged when incorporating the second set of liver chemistries obtained after admission (63.2%), suggesting that laboratory trends do not improve performance. LIMITATIONS: Retrospective study, inconsistent timing of the second set of biochemical markers. CONCLUSION: In our cohort of patients, existing choledocholithiasis guidelines lacked diagnostic accuracy, likely resulting in overuse of ERCP. Incorporation of laboratory trends did not improve performance. Additional research focused on risk stratification is necessary to meet the goal of eliminating unnecessary diagnostic ERCP.