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BACKGROUND Several studies have examined the efficacy of gastric peroral endoscopic myotomy (G-POEM) for gastroparesis. AIM To evaluate the mid-term efficacy of G-POEM by meta-analysis of studies with a minimum 1 year of follow-up. METHODS We reviewed several databases from inception to 10 June 2021 to identify studies that evaluated the efficacy of G-POEM in refractory gastroparesis, and had at least 1 year of follow-up. Our outcomes of interest were clinical success at 1 year, adverse events, difference in mean pre- and 1 year post-procedure Gastroparesis Cardinal Symptom Index (GCSI) score, and difference in mean pre- and post-procedure EndoFLIP measurements. We analysed data using a random-effects model and assessed heterogeneity by I2 statistic. RESULTS We included 10 studies comprising 482 patients. Pooled rates (95% CI) of clinical success at 1 year and adverse events were 61% (49%, 71%) and 8% (6%, 11%), respectively. Mean GCSI at 1 year post-procedure was significantly lower than pre-procedure; mean difference (MD) (95% CI) -1.4 (-1.9, -0.9). Mean post-procedure distensibility index was significantly higher than pre-procedure in the clinical success group at 40 and 50 mL volume distension; standardised mean difference (95% CI) 0.82 (0.07, 1.64) and 0.91 (0.32, 1.49), respectively. In the clinical failure group, there was no significant difference between mean pre- and post-procedure EndoFLIP measurements. CONCLUSIONS G-POEM is associated with modest clinical success at 1 year. Additional studies with longer follow-up are required to evaluate its longer-term efficacy.

Background and Aims Gastric variceal bleeding (GVB) is associated with high morbidity and mortality. EUS-guided coil and cyanoacrylate (CYA) injection (EUS-CCI) has been shown to be an effective therapy in acute bleeding and secondary prophylaxis; however, there is a paucity of data on primary prophylaxis. Methods In this single-center observational study, adult patients with high-risk gastric varices (GV; size >10 mm or cherry red spot) without prior bleeding underwent EUS-CCI for the primary prophylaxis of GVB between June 2009 and December 2019. The primary outcome was post-treatment GVB. Results Eighty patients with a mean variceal size of 22.5 ± 9.4 mm and a mean length of follow-up of 3.0 ± 2.4 years were included. The etiology of portal hypertension was cirrhosis in 71 patients (88.7%) and noncirrhotic in 9 (11.3). The mean model for end-stage liver disease score was 12.3 ± 3.7 in patients with cirrhosis. The mean coil number was 1.5 (range, 1-3) and mean glue volume injected 2 mL (range, .5-5). Technical success was achieved in 100%, 96.7% had EUS confirmation of GV obliteration, and 67.7% were obliterated with 1 treatment session. Post-treatment GVB occurred in 2 patients (2.5%) and adverse events in 4 (4.9%). No deaths related to GVB occurred, and emergent transjugular intrahepatic shunts were not needed during the follow-up period. Conclusions In patients with high-risk GV, EUS-CCI for primary prophylaxis is highly effective at preventing GVB with a low rate of adverse events. Primary prophylaxis of high-risk GV with coil and CYA glue injection should be considered in centers with the appropriate expertise.

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.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 of7 at 7 days post-procedure. The McNemar test assessed discordance between PEP and elevated-PROM.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.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.gov number, NCT05310409.

Rapid On-Site-Evaluation (ROSE) with an in-room pathologist (ROSE-P) has been shown to improve the diagnostic yield of specimens obtained from patients undergoing Endoscopic Ultrasound fine needle aspiration or biopsy (EUS-FNAB) of pancreatic lesions. Recently, there has been an increased interest and utilization of Telecytology (ROSE-T) to optimize clinical workflows, and to address social distancing mandates created during the COVID-19 pandemic. The purpose of this study is to compare diagnostic outcomes of ROSE-P and ROSE-T.A single center cohort study of patients who underwent EUS-FNAB of solid pancreatic lesions with ROSE was conducted. The primary outcome was overall diagnostic yield of cancer. All patients who underwent EUS-FNA were entered into a prospectively maintained database. Statistical analyses were performed using descriptive statistics and univariate analysis.There were 165 patients in each arm. There was no difference in diagnostic yield between ROSE-P and ROSE-T (96.4% vs 94.5%, p=.428). ROSE-T was associated with increased use of 22-gauge needles (p=.006) and more needle passes (p.001). There was no significant difference in age, gender, lesion size, needle type, procedure times, or adverse events between the two groups (p.05 for all). There were more pancreatic tail lesions sampled in the ROSE-P group (p.001).Rapid on-site evaluation using Telecytology was not associated with any difference in final histologic diagnosis for EUS-FNAB of solid pancreatic masses. This has important implications for optimizing clinical workflows.

Early data suggests that endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a safe and efficacious option for gastric outlet obstruction (GOO). However, there is a scarcity of data comparing outcomes with open gastrojejunostomy (OGJ). Single-center retrospective cohort study of adult patients hospitalized with GOO who underwent EUS-GE or OGJ between January 1, 2014 and February 28, 2020. Primary outcomes were technical and clinical success. Sixty-six patients were included of which 40 (60.0%) underwent EUS-GE and 26 (40.0%) underwent OGJ. Baseline characteristics were similar with respect to age (70.5 vs 69.7, p = 0.81), sex (42.5% vs 42.3% female, p = 0.99), median length of follow-up (98.0 vs 166.5 days, p = 0.8), prior failed intervention for GOO (22.5% vs 26.9%, p = 0.68), and the presence of altered anatomy (12.5% vs 30.8%, p = 0.07) between EUS-GE and OGJ, respectively. Technical success was achieved in 37 (92.5%) of EUS-GE and 26 (100%) of OGJ patients (p = 0.15). EUS-GE was associated with faster resumption of oral intake (1.3 vs 4.7 days, p

ERCP is the first line of treatment for malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. EUS-guided gallbladder drainage (EUS-GBD) has been suggested as a rescue treatment for patients who fail EUS-BD and ERCP. In this meta-analysis, we have evaluated the efficacy and safety of EUS-GBD as a rescue treatment of malignant biliary obstruction after failed ERCP and EUS-BD. We reviewed several databases from inception to August 27, 2021, to identify studies that evaluated the efficacy and/or safety of EUS-GBD as a rescue treatment in the management of malignant biliary obstruction after failed ERCP and EUS-BD. Our outcomes of interest were clinical success, adverse events, technical success, stent dysfunction requiring intervention, and difference in mean pre- and postprocedure bilirubin. We calculated pooled rates with 95% confidence intervals (CI) for categorical variables and standardized mean difference (SMD) with 95% CI for continuous variables. We analyzed data using a random-effects model. We included five studies with 104 patients. Pooled rates (95% CI) of clinical success and adverse events were 85% (76%, 91%) and 13% (7%, 21%). Pooled rate (95% CI) for stent dysfunction requiring intervention was 9% (4%, 21%). The postprocedure mean bilirubin was significantly lower compared to preprocedure bilirubin, SMD (95% CI): -1.12 (-1.62--0.61). EUS-GBD is a safe and effective option to achieve biliary drainage after unsuccessful ERCP and EUS-BD in patients with malignant biliary obstruction.

AIMS: Gastrointestinal endoscopic procedures are commonly performed outpatient procedures associated with adverse events that may lead to emergency department visits. Establishing risk factor for post-endoscopy emergency department visits may guide quality improvement efforts. MATERIALS AND METHODS: Matched case control study of patients over the age of 18 presenting to the emergency department of a safety-net hospital within two weeks of any outpatient endoscopic procedure between July 1, 2013 and December 31, 2014. Controls were matched to cases by age, sex, procedure type, date, and day of week procedure was performed. Univariable and multivariable analysis were performed to identify predictors of emergency visits after endoscopy. REULTS: We identified 143 cases from a total of 6,601 outpatient procedures during the study period. 64 (44.8%) of the visits were attributed to the procedure yielding a visit rate of 0.97%. Compared to controls, cases were more likely to have MediCal (Medicaid) insurance (75.7% vs 59.2%, p = 0.003), prior ED visits (2.5 vs 0.5, p < 0.001), multiple primary care visits (4.9 vs 3.3, p < 0.001), trainee involvement (62.9% vs 44.4%, p = 0.002), and speak English (67.1% vs 54.9%, p = 0.04). On multivariable analysis of cases with visits attributable to the procedure, antiplatelet/anticoagulant use (OR 2.81, CI 1.07-7.34, p = 0.04), MediCal insurance (OR 2.55, CI 1.02-6.40, p = 0.05), multiple ED visits per year (OR 3.31, CI 2.22-4.94, p < 0.001), number of endoscopic interventions (OR 1.22, CI 1.06-1.40, p = 0.006), and trainee involvement (OR 2.55, CI 1.09-5.97, p = 0.03) were all risk factors for post-procedure visits. CONCLUSION: In a safety-net system, medically complex patients, greater number of endoscopic interventions, and lower socioeconomic status may influence emergency department utilization after endoscopy. This information may inform future quality improvement efforts.

BACKGROUND AND AIMS Empiric esophageal dilation is frequently performed for non-obstructive dysphagia. Studies evaluating its efficacy have reported conflicting results. In this meta-analysis, we have evaluated the efficacy of esophageal dilation in the management of non-obstructive dysphagia. METHODS We reviewed several databases from inception to 26 May 2021 to identify randomized controlled trials (RCTs) and observational studies that evaluated the role of empiric esophageal dilation for non-obstructive dysphagia. Our outcomes of interest were clinical success (improvement in dysphagia after dilation) and difference in post-operative dysphagia score between groups. For categorical variables, we calculated pooled odds ratios (OR) with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effects model. We used GRADE framework to ascertain the quality of evidence. RESULTS We included 4 studies (3 RCTs and one observational) with 243 patients; there were 133 treated with empiric dilation and 110 controls. We found no significant difference in clinical success (OR (95% CI) 1.91 (0.89, 4.08)) or post-procedure dysphagia score between groups (SMD (95% CI) 0.38 (-0.37, 1.14)). Our findings remained consistent on subgroup analysis including RCTs only. Quality of evidence ranged from low to very low based on GRADE framework. CONCLUSIONS Our meta-analysis does not support the use of empiric esophageal dilation in patients with non-obstructive dysphagia. More studies are required to confirm these findings.

Early data suggests that endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a safe and efficacious option for gastric outlet obstruction (GOO). However, there is a scarcity of data comparing outcomes with open gastrojejunostomy (OGJ).Single-center retrospective cohort study of adult patients hospitalized with GOO who underwent EUS-GE or OGJ between January 1, 2014 and February 28, 2020. Primary outcomes were technical and clinical success.Sixty-six patients were included of which 40 (60.0%) underwent EUS-GE and 26 (40.0%) underwent OGJ. Baseline characteristics were similar with respect to age (70.5 vs 69.7, p = 0.81), sex (42.5% vs 42.3% female, p = 0.99), median length of follow-up (98.0 vs 166.5 days, p = 0.8), prior failed intervention for GOO (22.5% vs 26.9%, p = 0.68), and the presence of altered anatomy (12.5% vs 30.8%, p = 0.07) between EUS-GE and OGJ, respectively. Technical success was achieved in 37 (92.5%) of EUS-GE and 26 (100%) of OGJ patients (p = 0.15). EUS-GE was associated with faster resumption of oral intake (1.3 vs 4.7 days, p 0.001) and shorter length of stay (5 vs 14.5 days, p 0.001). There were no significant differences in symptom recurrence (17.5% vs 19.2%, HR 1.85, CI 0.52-6.65, p = 0.34), reintervention (20% vs 11.5%, HR 0.82, CI 0.22-3.15, p = 0.78), death within 30 days (12.5% vs 3.8%, HR 0.80, CI 0.09-6.85, p = 0.84), or 30-day readmission (17.5% vs 24.1%, HR 1.69, CI 0.53-5.41, p = 0.37) between EUS-GE and OGJ, respectively. EUS-GE patients initiated chemotherapy sooner (17.7 vs 31.3 days, p = 0.033) and had lower overall costs as compared to OGJ ($49,387 vs $124,192, p 0.001).There were no significant differences in technical or clinical success, symptom recurrence, reintervention, 30-day readmission, or 30-day mortality between EUS-GE and OGJ. EUS-GE patients experienced shorter delays to resumption of oral intake and chemotherapy, had shorter lengths of stay, and reduced hospital costs. Further prospective comparative studies are warranted to verify our results.

Epiphrenic (pulsion) esophageal diverticula can occur in the setting of underlying esophageal motility disorders such as achalasia and present a unique management challenge to the gastroenterologist. Asymptomatic diverticula do not require treatment, but symptomatic diverticula require therapy targeted to the underlying esophageal motility disorder, or else the diverticula will recur. Generally, laparoscopic or combined laparoscopic/thoracoscopic myotomy, diverticulectomy, and anterior fundoplication are required. However, therapeutic options for epiphrenic diverticula are evolving as peroral endoscopic myotomy (POEM) becomes more commonplace. We review two cases of achalasia complicated by epiphrenic diverticula at our institution. In the first case, type II achalasia was identified and the patient underwent laparoscopic myotomy. In the second case, type III achalasia was present and the patient underwent successful POEM. We discuss the presentation, pathophysiology, and management of epiphrenic diverticula as well as the expanding role for POEM in diverticula.

Background and Aims The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs. Methods An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs. Results Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP. Conclusions Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice.

Bronchogenic cysts belong in the category of foregut duplication cysts, along with esophageal and neuroenteric duplication cysts. They are often found incidentally on cross-sectional imaging. Although they are benign, patients often undergo surgical resection because of diagnostic uncertainties. We report the first case of bronchogenic cyst diagnosed with the microforceps, after previous nondiagnostic fine-needle aspirations, thus allowing the patient to avoid surgery.

Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with minimal interactions with ABC drug transporters. Three-dimensional pharmacophore modeling and quantitative structure-activity relationship (QSAR) studies were carried out on a series of nilotinib analogues to identify chemical features that contribute to inhibitory activity of nilotinib against BCR-ABL kinase activity, P-gp, and ABCG2. Twenty-five derivatives of nilotinib were synthesized and were then tested to measure their activity to inhibit BCR-ABL kinase and to inhibit the function of ABC drug transporters. A set of in vitro experiments including kinase activity and cell-based transport assays and photolabeling of P-gp and ABCG2 with a transport substrate, [(125)I]-iodoarylazido-prazosin (IAAP), were carried out in isolated membranes to evaluate the potency of the derivatives to inhibit the function of ABC drug transporters and BCR-ABL kinase. Sixteen, fourteen, and ten compounds were selected as QSAR data sets, respectively, to generate PHASE v3.1 pharmacophore models for BCR-ABL kinase, ABCG2, and P-gp inhibitors. The IC50 values of these derivatives against P-gp, ABCG2, or BCR-ABL kinase were used to generate pharmacophore features required for optimal interactions with these targets. A seven-point pharmacophore (AADDRRR) for BCR-ABL kinase inhibitory activity, a six-point pharmacophore (ADHRRR) for ABCG2 inhibitory activity, and a seven-point pharmacophore (AADDRRR) for P-gp inhibitory activity were generated. The derived models clearly demonstrate high predictive power for test sets of BCR-ABL, ABCG2, and P-gp inhibitors. In aggregate, these results should aid in the development of specific inhibitors of BCR-ABL kinase that exhibit no or minimal interaction with ABC drug transporters.

ATP-binding cassette (ABC) drug transporters ABCB1 [P-glycoprotein (Pgp)] and ABCG2 are expressed in many tissues including those of the intestines, the liver, the kidney and the brain and are known to influence the pharmacokinetics and toxicity of therapeutic drugs. In vitro studies involving their functional characteristics provide important information that allows improvements in drug delivery or drug design. In this study, we report use of the BacMam (baculovirus-based expression in mammalian cells) expression system to express and characterize the function of Pgp and ABCG2 in mammalian cell lines. BacMam-Pgp and BacMam-ABCG2 baculovirus-transduced cell lines showed similar cell surface expression (as detected by monoclonal antibodies with an external epitope) and transport function of these transporters compared to drug-resistant cell lines that overexpress the two transporters. Transient expression of Pgp was maintained in HeLa cells for up to 72 h after transduction (48 h after removal of the BacMam virus). These BacMam-baculovirus-transduced mammalian cells expressing Pgp or ABCG2 were used for assessing the functional activity of these transporters. Crude membranes isolated from these cells were further used to study the activity of these transporters by biochemical techniques such as photo-cross-linking with transport substrate and adenosine triphosphatase assays. In addition, we show that the BacMam expression system can be exploited to coexpress both Pgp and ABCG2 in mammalian cells to determine their contribution to the transport of a common anticancer drug substrate. Collectively, these data demonstrate that the BacMam-baculovirus-based expression system can be used to simultaneously study the transport function and biochemical properties of ABC transporters.

Background and Aims Lower GI bleeding (LGIB) is a common cause of morbidity and mortality. Colonoscopy is indicated in all hospitalized patients with LGIB, yet the time frame for performing colonoscopy remains unclear. Prior studies of outcomes in urgent versus elective colonoscopy have yielded conflicting results and were often underpowered. Our study objective was to compare several outcomes between urgent and elective colonoscopy in patients hospitalized for LGIB. Methods Systematic review and meta-analysis were performed on studies that compared urgent and elective colonoscopy in patients with LGIB. Pooled rates were calculated for specific outcomes, and rate ratios were determined for selected comparison groups. Results Twelve studies met inclusion criteria, with a total sample size of 10,172 patients in the urgent colonoscopy arm and 14,224 patients in the elective colonoscopy arm. Urgent colonoscopy was associated with increased use of endoscopic therapeutic intervention (RR, 1.70; 95% CI, 1.08-2.67). There were no significant differences in bleeding source localization (RR, 1.08; 95% CI, .92-1.25), adverse event rates (RR, 1.05; 95% CI, .65-1.71), rebleeding rates (RR, 1.14; 95% CI, .74-1.78), transfusion requirement (RR, 1.02; 95% CI, .73-1.41), or mortality (RR, 1.17; 95% CI, .45-3.02). Conclusions Urgent colonoscopy appears to be safe and well tolerated, but there is no clear evidence that it alters important clinical outcomes.