Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Aspirin exposure and its association with metal stent patency in malignant distal biliary obstruction: a large international multicenter propensity score-matched study.

BACKGROUND AND AIMS: Stent dysfunction is common after ERCP with self-expandable metal stent (SEMS) insertion for malignant distal biliary obstruction (MDBO). Chronic aspirin (acetylsalicylic acid; ASA) exposure has been previously shown to potentially decrease this risk. We aim to further ascertain the protective effect of ASA and to identify other predictors of stent dysfunction. METHODS: This multicenter retrospective cohort study was conducted at 9 sites in Canada and 1 in the United States. Patients with MDBO who underwent ERCP with SEMS placement between January 2014 and December 2019 were included and divided into 2 cohorts: ASA exposed (ASA-E) and ASA unexposed (ASA-U). Propensity-score matching (PSM) was performed to limit selection bias. Matched variables were age, sex, tumor stage, and type of metal stent. The primary outcome was the hazard rate of stent dysfunction. A multivariable Cox proportional hazards model was used to identify independent predictors of stent dysfunction. RESULTS: Of 1396 patients assessed, after PSM 496 patients were analyzed (248 ASA-E and 248 ASA-U). ERCP with SEMS placement was associated with a high clinical success of 82.2% in ASA-E and 81.2% in ASA-U cohorts (P = .80). One hundred eighty-four patients had stent dysfunction with a mean stent patency time of 229.9 ± 306.2 days and 245.4 ± 241.4 days in ASA-E and ASA-U groups, respectively (P = .52). On multivariable analysis, ASA exposure did not protect against stent dysfunction (hazard ratio [HR], 1.25; 95% confidence interval [CI], .96-1.63). An etiology of pancreatic cancer (HR, 1.36; 95% CI, 1.15-1.61) predicted stent dysfunction, whereas cancer therapy was protective (HR, .73; 95% CI, .55-.96). Chronic ASA use was not associated with an increased risk for adverse events including bleeding, post-ERCP pancreatitis, and perforation. CONCLUSIONS: In this large, multicenter study using PSM, chronic exposure to ASA did not protect against stent dysfunction in MDBO. Instead, the analysis revealed that the etiology of pancreatic cancer was an independent predictor of stent dysfunction and cancer therapy was protective.

Self-propelling thrombin powder enables hemostasis with no observable recurrent bleeding or thrombosis over 3 days in a porcine model of upper GI bleeding.

BACKGROUND AND AIMS: Hemostatic powders used to manage upper GI bleeding continue to exhibit high recurrent bleeding rates. Previously, self-propelling thrombin powder (SPTP) sprayed endoscopically managed severe Forrest class 1A bleeding. Here, we evaluate SPTP in a 3-day recovery model of diffuse ulcerated bleeding. METHODS: Five anesthetized pigs underwent an endoscopic mucosal snare resection to trigger diffuse ulcer bleeding and were treated with SPTP. The time to hemostasis and the amount of powder delivered were measured. Pigs were recovered and monitored. RESULTS: Five pigs achieved hemostasis in 4.5 ± 1.2 minutes At 3 days after the procedure, the pigs were rescoped and showed no recurrent bleeding. Measured blood parameters were not significantly different from baseline. There were no signs of foreign bodies or thromboembolism during gross necropsy and histopathology of key organs. CONCLUSIONS: SPTP is a promising novel material that stopped diffuse ulcer bleeding in 5 pigs without recurrent bleeding or adverse local or systemic events.

Risk of lymph node metastasis in early gastric cancer for a Western population.

INTRODUCTION: Endoscopic resection (ER) of early gastric cancer (EGC) is increasingly used in Eastern countries due to their low rates of lymph node metastasis (LNM); however, there is a paucity of evidence in Western countries. We investigated LNM and its effect on overall survival (OS) in Western patients with EGC. METHODS: Patients diagnosed with T1 gastric cancer between 2000 and 2017 were retrospectively evaluated. Univariate Kaplan-Meier, multivariate logistic and Cox-regression models were used to assess the associations between clinical characteristics, LNM, and OS. RESULTS: Among 86 patients, median age was 68 years and 72% were male. Node positivity was 30%. Two percent of patients met the classical guidelines for ER and all were node-negative, while 16% met expanded criteria of which 14% were node-positive. T1b disease (odds ratio [OR] 41.2 [95% confidence interval [CI] 1.62-1048], p = 0.02) and lymphovascular/perineural invasion (OR 18.0 [95% CI 2.41-134], p = 0.01) were predictive of node positivity. The 5-year OS for node-negative and node-positive patients was 84% and 53% (p = 0.004), respectively. CONCLUSIONS: The risk of LNM in Western patients with EGC is higher; therefore, generalizability of the expanded criteria for ER should be interpreted with caution.

Use of topical mineral powder as monotherapy for treatment of active peptic ulcer bleeding.

BACKGROUND AND AIMS: The aim of this study was to evaluate the safety and effectiveness of Hemospray (Cook Medical, Winston-Salem, NC, USA), a hemostatic powder, as monotherapy for active peptic ulcer bleeding. METHODS: In this prospective, multicenter, single-arm study, patients with Forrest Ia or Ib peptic ulcers underwent endoscopic application of Hemospray as treatment of first intent. Effectiveness endpoints were successful hemostasis at the end of the index endoscopy, recurrent bleeding within 72 hours and from 72 hours to 30 days, adverse events requiring reintervention or resulting in morbidity or mortality, and 30-day mortality. RESULTS: Hemospray was successfully administered in 98.5% of patients (66/67). Hemostasis was achieved at the index endoscopy in 90.9% of patients (60/66) with Hemospray alone and in an additional 4 patients treated with additional modalities, yielding an overall hemostasis rate of 97.0% (64/66). Rebleeding occurred in 13.3% of patients (8/60), 5 within 72 hours and 3 between 72 hours and 30 days. Two cases of perforation and 2 patient deaths occurred during the study, but none of these cases or any other adverse events were attributed to the use of Hemospray. The rate of early rebleeding was significantly higher in patients with Forrest Ia ulcers compared with patients with Forrest Ib ulcers. Higher rates of early bleeding in patients with Forrest Ia ulcers is consistent with results from studies where Hemospray was used as rescue after failure of conventional methods. CONCLUSIONS: Hemospray is an effective initial treatment for patients with active peptic ulcer bleeding, but care should be taken to monitor for recurrent bleeding. (Clinical trial registration number: NCT01306864.).

Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard in the diagnosis of solid pancreatic lesions, in particular when combined with rapid onsite evaluation of cytopathology (ROSE). More recently, a fork-tip needle for core biopsy (FNB) has been shown to be associated with excellent diagnostic yield. EUS-FNB alone has however not been compared with EUS-FNA + ROSE in a large clinical trial. Our aim was to compare EUS-FNB alone to EUS-FNA + ROSE in solid pancreatic lesions. METHODS: A multicenter, non-inferiority, randomized controlled trial involving seven centers was performed. Solid pancreatic lesions referred for EUS were considered for inclusion. The primary end point was diagnostic accuracy. Secondary end points included sensitivity/specificity, mean number of needle passes, and cost. RESULTS: 235 patients were randomized: 115 EUS-FNB alone and 120 EUS-FNA + ROSE. Overall, 217 patients had malignant histology. The diagnostic accuracy for malignancy of EUS-FNB alone was non-inferior to EUS-FNA + ROSE at 92.2 % (95 %CI 86.6 %-96.9 %) and 93.3 % (95 %CI 88.8 %-97.9 %), respectively (P = 0.72). Diagnostic sensitivity for malignancy was 92.5 % (95 %CI 85.7 %-96.7 %) for EUS-FNB alone vs. 96.5 % (93.0 %-98.6 %) for EUS-FNA + ROSE (P = 0.46), while specificity was 100 % in both. Adequate histological yield was obtained in 87.5 % of the EUS-FNB samples. The mean (SD) number of needle passes and procedure time favored EUS-FNB alone (2.3 [0.6] passes vs. 3.0 [1.1] passes [P < 0.001]; and 19.3 [8.0] vs. 22.7 [10.8] minutes [P = 0.008]). EUS-FNB alone cost on average 45 US dollars more than EUS-FNA + ROSE. CONCLUSION: EUS-FNB alone is non-inferior to EUS-FNA + ROSE and is associated with fewer needle passes, shorter procedure time, and excellent histological yield at comparable cost.

Efficacy of Hemospray (TC-325) in the Treatment of Gastrointestinal Bleeding: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Hemospray (TC-325) is now approved for use in gastrointestinal bleeding. Data regarding their use pattern, efficacy, complications, and impact on clinical outcomes is limited. METHODS: Electronic search from relevant databases was conducted up to January 2019. Etiologies, therapy characteristics, hemostasis rates, rebleed rates, additional procedures, complications and mortality rates were extracted and pooled. RESULTS: Twenty-seven articles were included for analysis (n=1916). Pooled hemostasis was 94.5%. Pooled rebleed rate within 3 days was 9.9%, and within 30 days 17.6%. Pooled repeat Hemospray use was 13.6%. Radiology guided embolization was required with rate of 3.3% and surgery at rate of 4.7%. Rate of adverse events directly attributable to Hemospray was 0.7%. 30-day mortality was 11.8%. Comparison of conventional endoscopic therapy to Hemospray augmented therapy demonstrated that Hemospray therapy had increased immediate hemostasis [odds ratio (OR) 4.40]. There was no difference in rate of rebleeding at 8 days (OR 0.52) or overall mortality at 30 days (OR 0.53). Benign nonvariceal bleeds, malignant bleeds, and postprocedural bleeds had similar rates of hemostasis but rebleed rate at 30 days was less for postprocedural bleeding. CONCLUSIONS: The addition of Hemospray to conventional therapy appears to increase immediate hemostasis but does not decrease rebleeding or mortality. As such, the use of Hemospray will likely be limited to clinical situations requiring urgent, but temporary, hemostasis to bridge to more definitive therapy.

Colorectal Polyps in Childhood Cancer Survivors Treated with Radiation Therapy.

BACKGROUND: Cancer survivors treated with abdominal or pelvic radiation therapy (RT) for childhood cancer have an increased risk of colorectal cancer. However, clinical guidelines are inconsistent on recommendations regarding the early initiation of screening in these patients due to the lack of supporting evidence that these patients pass through a pre-invasive phase, in which adenomatous polyps can be detected and removed. AIMS: To determine the prevalence of adenomatous polyps in cancer survivors treated with RT for childhood cancer; the prevalence in average-risk patients aged 17-49; and the prevalence in average-risk patients aged 50-75. METHODS: We conducted a retrospective study comparing the prevalence of adenomatous polyps among three patient groups: childhood cancer survivors aged 17-49 with prior RT who underwent colonoscopy screening from 2006 to 2017; age- and gender-matched patients in the average-risk population; and average-risk patients aged 50-75. RESULTS: One hundred and forty-five patients were included in the study. The proportion of patients with adenomatous polyps in the cancer survivor group was significantly higher than that in the age- and gender-matched average-risk group (58.6 vs 17.2%, p = 0.00) and higher than the average-risk group aged 50-75 (58.6 vs 27.6%, p = 0.009). The prevalence of adenomas with high-risk features was higher in the survivor group compared to patients aged 50-75 (20.7 vs 3.5%, p = 0.015). CONCLUSIONS: Cancer survivors treated with RT for childhood cancer have a higher prevalence of adenomatous polyps compared to the average-risk population. These findings support the early initiation of colonoscopy screening 10 years after radiation therapy, even in patients who have received RT doses below 30 Gy.

IgG4-related disease and lymphocyte-variant hypereosinophilic syndrome: A comparative case series.

OBJECTIVE: To compare the clinical and laboratory features of IgG4-related disease (IgG4-RD) and lymphocyte-variant hypereosinophilic syndrome (L-HES), two rare diseases that often present with lymphadenopathy, gastrointestinal symptoms, eosinophilia, and elevated immunoglobulins/IgE. METHOD: Comparative case series of 31 patients with IgG4-RD and 13 patients with L-HES. RESULTS: Peripheral blood eosinophilia was present in eight of 31 patients with IgG4-RD compared to 13 of 13 patients with L-HES (median eosinophils 0.4 vs 7.0 giga/L, P=.001) and 12 of 20 patients with IgG4-RD had increased serum IgE compared to eight of 13 patients with L-HES, P=.930. Twenty-seven of 30 patients with IgG4-RD had elevated serum IgG4 compared to five of 12 patients with L-HES (median IgG4 9.6 g/L vs 0.80 g/L, P=.002). Flow cytometry demonstrated an aberrant T-cell phenotype in 7 of 23 patients with IgG4-RD and 13 of 13 patients with L-HES (P<.001). T-cell clonality by PCR was positive in 12 of 23 patients with IgG4-RD vs 10 of 13 patients with L-HES (P=.143). Patients in both groups received corticosteroids as first-line therapy. For refractory disease in IgG4-RD, rituximab was the most common steroid-sparing agent, whereas in L-HES, it was pegylated interferon-α-2a. CONCLUSION: The overlapping features of these two diseases with divergent treatment options demonstrate the importance of familiarity with both entities to optimize diagnosis and treatment.

Sensitivities of Biopsy Sites in the Endoscopic Evaluation of Graft-Versus-Host Disease: Retrospective Review from a Tertiary Center.

BACKGROUND: Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation that frequently affects the gastrointestinal (GI) tract. The best biopsy sites to establish the diagnosis have not been clearly established. AIMS: To determine the best sites for obtaining biopsies in evaluating GI GVHD. METHODS: All cases of biopsy-proven GI GVHD (GVHD+) were isolated from a pathology database over a 2-year period at a single tertiary center (n = 46). Demographic, clinical, and endoscopic data were extracted. For comparison, 46 consecutive GVHD-negative cases (GVHD-) were obtained. Sensitivities in diagnosing GVHD in the upper and lower GI tract were calculated. RESULTS: In the GVHD- group, they were commonly investigated with an esophagogastroduodenoscopy (EGD) (60 vs. 22 % in the GVHD+ group, p < 0.01), while a colonoscopy (CLN) was commonly performed in the GVHD+ group (33 vs. 12 %, p = 0.02). Among the GVHD + patients, for EGDs, the sensitivity was highest for duodenal biopsies at 89 %. For flexible sigmoidoscopies (FSs) and CLNs, the sensitivities among all sites were similar (85 % agreement, kappa 0.58, p = 0.01). There were no cases in which GVHD was diagnosed in the right side of the colon without a positive biopsy in the left side of the colon. CONCLUSIONS: In this cohort of GI GVHD patients, duodenum biopsies produced the highest yield in diagnosing GVHD when compared to other sites of the upper GI tract. Sensitivities were similar among all sites on lower endoscopies, suggesting that a FS is sufficient for diagnosing GVHD in suspected patients with diarrhea.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). This Guideline was also reviewed and endorsed by the Governing Board of the American Society for Gastrointestinal Endoscopy (ASGE). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 Prophylactic colonic stent placement is not recommended. Colonic stenting should be reserved for patients with clinical symptoms and imaging evidence of malignant large-bowel obstruction, without signs of perforation (strong recommendation, low quality evidence). 2 Colonic self-expandable metal stent (SEMS) placement as a bridge to elective surgery is not recommended as a standard treatment of symptomatic left-sided malignant colonic obstruction (strong recommendation, high quality evidence). 3 For patients with potentially curable but obstructing left-sided colonic cancer, stent placement may be considered as an alternative to emergency surgery in those who have an increased risk of postoperative mortality, I. e. American Society of Anesthesiologists (ASA) Physical Status ≥ III and/or age > 70 years (weak recommendation, low quality evidence). 4 SEMS placement is recommended as the preferred treatment for palliation of malignant colonic obstruction (strong recommendation, high quality evidence), except in patients treated or considered for treatment with antiangiogenic drugs (e. g. bevacizumab) (strong recommendation, low quality evidence).

Decision-Utility Analysis of Empiric Treatment Versus Test and Treat Strategies for Helicobacter pylori in Patients With Duodenal Ulcer.

OBJECTIVES: The optimal strategy of Helicobacter pylori eradication in patients with duodenal ulcer is unclear. In this study, we aimed to compare the utility and the ulcer recurrence rate using the empiric treatment versus the test and treat strategies in patients with uncomplicated duodenal ulcer. METHODS: A decision-utility analysis was performed using a decision tree. The empiric treatment strategy was compared with the test and treat strategy. The probabilities of recurrent ulcers were determined and utilities of the 2 strategies were compared using the quality-adjusted life-year (QALY). Sensitivity analysis was performed to evaluate for model robustness. RESULTS: The probability of recurrent ulcer with the empiric strategy was 10.5%. The probabilities of recurrent ulcer with the test and treat strategy were 12.6%, 14.7%, 16.8%, and 17.9% based on 95%, 90%, 85%, and 80% sensitivity for histopathology, respectively. At the 95% estimate for the sensitivity of histopathology, the empiric strategy was associated with greater QALY compared with the test and treat strategy, 0.9875 versus 0.9853. The empiric treatment strategy was associated with greater QALY at extreme values for the estimates in our model. CONCLUSIONS: The empiric treatment strategy is associated with 2.1% to 7.4% lower recurrence rate for a range of test sensitivity between 95% and 80%, and results in greater QALY compared with the test and treat strategy.

Symptom Burden and Time from Symptom Onset to Cancer Diagnosis in Patients with Early-Onset Colorectal Cancer: A Multicenter Retrospective Analysis.

Background: The incidence of colorectal cancer (CRC) is decreasing in individuals >50 years due to organised screening but has increased for younger individuals. We characterized symptoms and their timing before diagnosis in young individuals. Methods: We identified all patients diagnosed with CRC between 1990-2017 in British Columbia, Canada. Individuals <50 years (n = 2544, EoCRC) and a matched cohort >50 (n = 2570, LoCRC) underwent chart review to identify CRC related symptoms at diagnosis and determine time from symptom onset to diagnosis. Results: Across all stages of CRC, EoCRC presented with significantly more symptoms than LoCRC (Stage 1 mean ± SD: 1.3 ± 0.9 vs. 0.7 ± 0.9, p = 0.0008; Stage 4: 3.3 ± 1.5 vs. 2.3 ± 1.7, p < 0.0001). Greater symptom burden at diagnosis was associated with worse survival in both EoCRC (p < 0.0001) and LoCRC (p < 0.0001). When controlling for cancer stage, both age (HR 0.87, 95% CI 0.8-1.0, p = 0.008) and increasing symptom number were independently associated with worse survival in multivariate models. Conclusions: Patients with EoCRC present with a greater number of symptoms of longer duration than LoCRC; however, time from patient reported symptom onset was not associated with worse outcomes.

Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation.

BACKGROUND: Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT. METHODS: This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed. RESULTS: A total of 362 patients underwent liver transplantation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9, P=0.38). CONCLUSIONS: Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.

Association of Reducing the Recommended Colorectal Cancer Screening Age With Cancer Incidence, Mortality, and Costs in Canada Using OncoSim.

Importance: Recent US guideline updates have advocated for colorectal cancer (CRC) screening to begin at age 45 years in average-risk adults, whereas Canadian screening programs continue to begin screening at age 50 years. Similarities in early-onset CRC rates in Canada and the US warrant discussion of earlier screening in Canada, but there is a lack of Canadian-specific modeling data to inform this. Objective: To estimate the association of a lowered initiation age for CRC screening by biennial fecal immunochemical test (FIT) with CRC incidence, mortality, and health care system costs in Canada. Design, Setting, and Participants/Exposures: This economic evaluation computational study used microsimulation modeling via the OncoSim platform. Main Outcomes and Measures: Modeled rates of CRC incidence, mortality, and health care costs in Canadian dollars. Results: This analysis included 4 birth cohorts (1973-1977, 1978-1982, 1983-1987, and 1988-1992) representative of the Canadian population accounting for previously documented effects of increasing CRC incidence in younger birth cohorts. Screening initiation at age 45 years resulted in a net 12 188 fewer CRC cases, 5261 fewer CRC deaths, and an added 92 112 quality-adjusted life-years (QALYs) to the cohort population over a 40-year period relative to screening from age 50 years. Screening initiation at age 40 years yielded 18 135 fewer CRC cases, 7988 fewer CRC deaths, and 150 373 QALYs. The cost per QALY decreased with younger birth cohorts to a cost of $762 per QALY when Canadians born in 1988 to 1992 began screening at age 45 years or $2622 per QALY with screening initiation at age 40 years. Although costs associated with screening and resulting therapeutic interventions increased with earlier screening, the overall health care system cost of managing CRC decreased. Conclusions and Relevance: This economic evaluation study using microsimulation modeling found that earlier screening may reduce CRC disease burden and add life-years to the Canadian population at a modest cost. Guideline changes suggesting earlier CRC screening in Canada may be justified, but evaluation of the resulting effects on colonoscopy capacity is necessary.

Cost-effective analysis of preliminary single-operator cholangioscopy for management of difficult biliary stones.

Background and study aims Single-operator peroral cholangioscopy (SOC) is a therapeutic modality for difficult biliary stone disease. Given its high success rate and increasing availability, analysis of the economic impact of early SOC utilization is critical for clinical decision-making. Our aim is to compare the cost-effectiveness of different first and second-line endoscopic modalities for difficult-to-treat choledocholithiasis. Patients and methods A decision-tree model with a 1-year time horizon and a hypothetical cohort of 200 patients was used to analyze the cost-effectiveness of SOC for first, second and third-line intervention in presumed difficult biliary stones. We adopted the perspective of a Canadian tertiary hospital, omitting recurrence rates associated with endoscopic retrograde cholangiopancreatography (ERCP). Effectiveness estimates were obtained from updated meta-analyses. One-way sensitivity analyses and probabilistic sensitivity analyses were also performed to assess how changes in key parameters affected model conclusions. Results First- and second-line SOC achieved comparable clinical efficacy from 96.3 % to 97. 6 % stone clearance. The least expensive strategy is third-line SOC (SOC-3: $800,936). Performing SOC during the second ERCP was marginally more expensive (SOC-2: $ 816,584) but 9 % more effective. The strategy of first-line SOC incurred the highest hospital expenditures (SOC-1: $ 851,457) but decreased total procedures performed by 16.9 % when compared with SOC-2. Sensitivity analysis was robust in showing SOC-2 as the most optimal approach. Conclusions Second-line SOC was superior to first and third-line SOC for treatment of difficult biliary stones. When based on meta-analysis of non-heterogeneous trials, SOC-2 is more cost-effective and cost-efficient. Our study warrants a larger pragmatic effectiveness trial.

Living on the EDGE: Canadian Experience With EUS-directed Transgastric ERCP (EDGE) in Patients With Roux-en-Y Gastric Bypass Anatomy.

Introduction: Roux-en-Y gastric bypass (RYGB) surgery imposes anatomic barriers to endoscopic retrograde cholangiopancreatography (ERCP). Potential options for biliary access in these patients include laparoscopic-assisted ERCP or balloon enteroscopy. However, these approaches require specialized equipment and/or operating room personnel and are associated with high rates of failure and adverse events compared to conventional ERCP. A recently described technique, EDGE, is an endoscopic approach which involves accessing the excluded stomach to facilitate ERCP. Objective: The objective of this study is to describe the results of EDGE procedures performed in Canada. Methods: Data were collected from patient cases who had undergone an EDGE procedure across centers in Canada. All patients had a history of RYGB bariatric surgery. In each procedure, a 20-mm diameter lumen-apposing metal stent (LAMS) was deployed under EUS guidance to allow access from the gastric remnant/proximal jejunum to the excluded stomach. Subsequently, during a separate procedure, a duodenoscope was passed through the LAMS to perform ERCP. Following ERCP, the LAMS was replaced with a pigtail stent or APC was used to facilitate closure of the gastro-jejunal/gastro-gastric fistula. Results: The indication for EDGE in the seven included cases was for the treatment of choledocholithiasis (six) or gallstone pancreatitis (one). The technical success rate of the EDGE procedure in these cases was 100%. Clinical success, defined by normalization of bilirubin and symptomatic relief, was observed in all cases. There were no adverse events reported. Conclusion: The results of this series support EDGE as a safe and minimally invasive approach to biliary access and therapy in patients with previous RYGB surgery.