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.

Endoscopic Submucosal Dissection Versus Surgery or Endoscopic Mucosal Resection for Metachronous Early Gastric Cancer: a Meta-analysis.

BACKGROUND: Resection options for early gastric cancer (EGC) include endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and surgery. In patients with metachronous EGC following previous resection, the optimal resection technique is not well elucidated. We conducted a systematic review and meta-analysis of studies comparing ESD to EMR, or ESD to surgery, in patients with metachronous EGC. METHODS: We conducted an electronic search of studies reporting on outcomes and AEs following ESD versus either EMR or surgery for patients with metachronous EGC. Pooled odds ratios (OR) of included studies were obtained using DerSimonian and Laird random effects models. Funnel plots were produced and visually inspected for evidence of publication bias. The quality of the evidence was assessed using GRADE. RESULTS: A total of 9367 abstracts were screened and 10 observational studies were included. The odds of complete resection were higher amongst patients undergoing ESD compared to EMR (OR 5.88, 95% confidence intervals, CI, 1.79-19.35), whereas the odds of complete resection were no different between ESD and surgery (OR 0.57, 95% CI 0.04-8.24). There were no differences in the odds of local recurrence with ESD versus surgery (OR 5.01, 95% CI 0.86-29.13). Post-procedural bleeding did not differ significantly between ESD and EMR (OR 0.70, 95% CI 0.16-3.00). There was no evidence of publication bias. DISCUSSION: For metachronous EGC, ESD or surgery is preferred over EMR depending on local expertise and patient preferences, largely due to a higher risk of incomplete resection with EMR. REVIEW REGISTRATION: PROSPERO CRD42021270445.

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.

Clip closure to prevent adverse events after EMR of proximal large nonpedunculated colorectal polyps: meta-analysis of individual patient data from randomized controlled trials.

BACKGROUND AND AIMS: After EMR, prophylactic clipping is often performed to prevent clinically significant post-EMR bleeding (CSPEB) and other adverse events (AEs). Prior evidence syntheses have lacked sufficient power to assess clipping in relevant subgroups or in nonbleeding AEs. We performed a meta-analysis of individual patient data (IPD) from randomized trials assessing the efficacy of clipping to prevent AEs after EMR of proximal large nonpedunculated colorectal polyps (LNPCPs) ≥20 mm. METHODS: We searched EMBASE, MEDLINE, Cochrane Central Registry of Controlled Trials, and PubMed from inception to May 19, 2021. Two reviewers screened citations in duplicate. Corresponding authors of eligible studies were invited to contribute IPD. A random-effects 1-stage model was specified for estimating pooled effects, adjusting for patient sex and age and for lesion location and size, whereas a fixed-effects model was used for traditional meta-analyses. RESULTS: From 3145 citations, 4 trials were included, representing 1248 patients with proximal LNPCPs. The overall rate of CSPEB was 3.5% and 9.0% in clipped and unclipped patients, respectively. IPD were available for 1150 patients, in which prophylactic clipping prevented CSPEB with an odds ratio (OR) of .31 (95% confidence interval [CI], .17-.54). Clipping was not associated with perforation or abdominal pain, with ORs of .78 (95% CI, .17-3.54) and .67 (95% CI, .20-2.22), respectively. CONCLUSIONS: Prophylactic clipping is efficacious in preventing CSPEB after EMR of proximal LNPCPs. Therefore, clip closure should be considered a standard component of EMR of LNPCPs in the proximal colon.

Prophylactic clipping to prevent delayed colonic post-polypectomy bleeding: meta-analysis of randomized and observational studies.

BACKGROUND AND AIMS: Delayed post-polypectomy bleeding (DPPB) is a commonly described adverse event following polypectomy. Prophylactic clipping may prevent DPPB in some patient subgroups. We performed a meta-analysis to assess both the efficacy and real-world effectiveness of prophylactic clipping. METHODS: We performed a database search through March 2020 for clinical trials or observational studies assessing prophylactic clipping and DPPB. Pooled risk ratios (RR) were calculated using random effects models. Subgroup, sensitivity, and meta-regression analyses were performed to elucidate clinical or methodological factors associated with effects on outcomes. RESULTS: A total of 2771 citations were screened, with 11 randomized controlled trials (RCTs) and 9 observational studies included, representing 24,670 colonoscopies. DPPB occurred in 2.0% of patients overall. The pooled RR of DPPB was 0.47 (95% CI 0.29-0.77) from RCTs enrolling only patients with polyps ≥ 20 mm. Remaining pooled RCT data did not demonstrate a benefit for clipping. The pooled RR of DPPB was 0.96 (95% CI 0.61-1.51) from observational studies including all polyp sizes. For patients with proximal polyps of any size, the RR was 0.73 (95% CI 0.33-1.62) from RCTs. Meta-regression confirmed that polyp size ≥ 20 mm significantly influenced the effect of clipping on DPPB. CONCLUSION: Pooled evidence demonstrates a benefit when clipping polyps measuring ≥ 20 mm, especially in the proximal colon. In lower-risk subgroups, prophylactic clipping likely results in little to no difference in DPPB.

Adverse events associated with endoscopic retrograde cholangiopancreatography: protocol for a systematic review and meta-analysis.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to diagnose and manage conditions of the biliary and pancreatic ducts. Though effective, it is associated with common adverse events (AEs). The purpose of this study is to systematically review ERCP AE rates and report up-to-date pooled estimates. METHODS AND ANALYSIS: A comprehensive electronic search will be conducted of relevant medical databases through 10 November 2020. A study team of eight data abstracters will independently determine study eligibility, assess quality and abstract data in parallel, with any two concordant entries constituting agreement and with discrepancies resolved by consensus. The primary outcome will be the pooled incidence of post-ERCP pancreatitis, with secondary outcomes including post-ERCP bleeding, cholangitis, perforation, cholecystitis, death and unplanned healthcare encounters. Secondary outcomes will also include rates of specific and overall AEs within clinically relevant subgroups determined a priori. DerSimonian and Laird random effects models will be used to perform meta-analyses of these outcomes. Sources of heterogeneity will be explored via meta-regression. Subgroup analyses based on median dates of data collection across studies will be performed to determine whether AE rates have changed over time. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as it is a planned meta-analysis of previously published data. Participant consent is similarly not required. Dissemination is planned via presentation at relevant conferences in addition to publication in peer-reviewed journals.PROSPERO registration numberCRD42020220221.

Darvadstrocel for the treatment of perianal fistulas in Crohn's disease.

INTRODUCTION: Perianal fistulizing Crohn's disease is associated with a poor quality of life and current medical and surgical treatment options are limited. Darvadstrocel, composed of mesenchymal stem (stromal) cells (MSC), has recently been approved by the European Medicines Agency (EMA) for the treatment for perianal disease. This drug profile educates the reader with this novel treatment approach. AREAS COVERED: A literature search was performed on PubMed with focus on perianal fistulizing Crohn's disease and mesenchymal stem (stromal) cells. This review summarizes evidence of the current standard of care and discusses the mechanism of action, manufacturing, and application and safety of darvadstrocel. EXPERT OPINION: Darvadstrocel is a safe and effective therapy for complex perianal fistulizing Crohn's disease.

Long-Term Effectiveness, Safety and Mortality Associated with the Use of TC-325 for Malignancy-Related Upper Gastrointestinal Bleeds: A Multicentre Retrospective Study.

BACKGROUND AND STUDY AIMS: Malignant-related upper gastrointestinal bleeding (MRUGIB) is difficult to treat by conventional endoscopic methods. We sought to determine the efficacy, safety and mortality associated with the use of TC-325 for the treatment of MUGIB. PATIENTS AND METHODS: This is a multicentre, retrospective study at the University of Calgary and University of Ottawa performed between January 1, 2010, and July 30, 2016. TC-325 use was identified via staff polling, product order forms and endoscopic records review. Once identified, patient charts and online records were examined to identify MRUGIB cases and to assess our primary and secondary endpoints. OUTCOMES: The primary outcome was hemostasis at seven days. Secondary outcomes include immediate hemostasis, early hemostasis, hemostasis at 14 days, 30-day mortality, adverse events related to TC-325 therapy and the need for repeat endoscopic intervention, surgery or transarterial embolization. RESULTS: Twenty-five patients were identified. The median age was 62 years (interquartile range [IQR] 52.5-76), and most were male (64%). TC-325 was the primary treatment modality in 20 patients (80%). Hemostasis was 88%, 89%, 58% and 50% at 24 hours, 72 hours, 7 days and 14 days, respectively. Five patients underwent repeat endoscopy, two patients required surgical intervention, and transarterial embolization was not required. Twelve patients died by 30 days (48%). There were no complications directly attributed to the use of TC-325. CONCLUSIONS: TC-325 is effective for achieving and maintaining hemostasis in patients with malignancy-related upper gastrointestinal bleeding, and most patients do not require additional interventions. The 30-day mortality risk in this group of patients is high.

The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis.

BACKGROUND AND STUDY AIMS: It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. PATIENTS AND METHODS: We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. RESULTS: Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10-33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8-24%) after a CT scan was performed. LIMITATIONS: The majority of the included studies were retrospective. CONCLUSIONS: EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

Evolution of the Southampton Enhanced Recovery Programme for radical cystectomy and the aggregation of marginal gains.

OBJECTIVE: To describe and assess the evolution of an enhanced recovery programme (ERP) for open radical cystectomy. PATIENTS AND METHODS: We introduced a mentored ERP for radical cystectomy in January 2011. The programme underwent service evaluation and multiple changes in August 2012 that we define as marginal gains. We present a retrospective review of 133 consecutive patients undergoing open radical cystectomy, grouped according to the three stages of the ERP from October 2008 to April 2013: (1) non-ERP group (October 2008 to December 2010): n = 69; (2) ERP-1 group (January 2011 to July 2012): n = 37; and (3) ERP-2 group (August 2012 to April 2013): n = 27. Primary outcomes were length of hospital stay (LOS), readmission, morbidity at 90 days using the Clavien classification system and mortality. Secondary outcomes were time to flatus, ileus rates, re-operation rates and oncological outcomes. RESULTS: There were no differences in patient demographics among any of the groups for: age, gender, BMI, American Society of Anesthesiologists score and the use of neoadjuvant chemotherapy. There were no differences in readmission, morbidity and mortality rates. The overall 90-day mortality was six patients (4.5%). There were significant differences in ileus rates between the non-ERP, the ERP-1 and the ERP-2 groups: 44.9% (31 patients), 29.7% (11 patients) and 14.8% (four patients), respectively (P = 0.017). There was a significant difference in the presence of pathological lymphadenopathy in the ERP-2 group: non-ERP group, 10.1%; ERP-1 group, 16.2%; and ERP-2 group, 44.4%; P = 0.002. There was also a difference in the mean (sd) lymph node yield in ERP-2: non-ERP group, 8.4 (5.4) nodes; ERP-1, 8.2 (6.4) nodes; and ERP-2, 16.7 (5.4) nodes (P < 0.001). The median (range) LOS was 14 (7-91) days, 10 (6-55) days and 7 (3-99) days in the non-ERP, ERP-1 and ERP-2 groups, respectively (P < 0.001). CONCLUSIONS: Auditing an already successful ERP and implementing a number of marginal gains has led to a significant decrease in the median LOS for radical cystectomy. The LOS for open radical cystectomy at University Hospital Southampton has halved. In the second phase of our ERP, our median LOS is 7 days.