EUS-guided coil injection therapy in the management of gastric varices: the first U.S. multicenter experience (with video).

BACKGROUND AND AIMS: Despite the significant morbidity associated with gastric variceal bleeding, there is a paucity of high-quality data regarding optimal management. EUS-guided coil injection therapy (EUS-COIL) has recently emerged as a promising endoscopic modality for the treatment of gastric varices (GV), particularly compared with traditional direct endoscopic glue injection. Although there are data on the feasibility and safety of EUS-COIL in the management of GV, these have been limited to select centers with particular expertise. The aim of this study was to report the first U.S. multicenter experience of EUS-COIL for the management of GV. METHODS: This retrospective analysis included patients with bleeding GV or GV at risk of bleeding who underwent EUS-COIL at 10 U.S. tertiary care centers between 2018 and 2022. Baseline patient and procedure-related information was obtained. EUS-COIL entailed the injection of .018 inch or .035 inch hemostatic coils using a 22-gauge or 19-gauge FNA needle. Primary outcomes were technical success (defined as successful deployment of coil into varix under EUS guidance with diminution of Doppler flow), clinical success (defined as cessation of bleeding if present and/or absence of bleeding at 30 days' postintervention), and intraprocedural and postprocedural adverse events. RESULTS: A total of 106 patients were included (mean age 60.4 ± 12.8 years; 41.5% female). The most common etiology of GV was cirrhosis (71.7%), with alcohol being the most common cause (43.4%). Overall, 71.7% presented with acute GV bleeding requiring intensive care unit stay and/or blood transfusion. The most common GV encountered were isolated GV type 1 (60.4%). A mean of 3.8 ± 3 coils were injected with a total mean length of 44.7 ± 46.1 cm. Adjunctive glue or absorbable gelatin sponge was injected in 82% of patients. Technical success and clinical success were 100% and 88.7%, respectively. Intraprocedural adverse events (pulmonary embolism and GV bleeding from FNA needle access) occurred in 2 patients (1.8%), and postprocedural adverse events occurred in 5 (4.7%), of which 3 were mild. Recurrent bleeding was observed in 15 patients (14.1%) at a mean of 32 days. Eighty percent of patients with recurrent bleeding were successfully re-treated with repeat EUS-COIL. No significant differences were observed in outcomes between high-volume (>15 cases) and low-volume (<7 cases) centers. CONCLUSIONS: This U.S. multicenter experience on EUS-COIL for GV confirms high technical and clinical success with low adverse events. No significant differences were seen between high- and low-volume centers. Repeat EUS-COIL seems to be an effective rescue option for patients with recurrent bleeding GV. Further prospective studies should compare this modality versus other interventions commonly used for GV.

Index admission cholecystectomy for biliary acute pancreatitis or choledocholithiasis reduces 30-day readmission rates in children.

BACKGROUND: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not. METHODS: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission. RESULTS: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001). CONCLUSIONS: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy.

Index admission cholecystectomy for acute cholecystitis reduces 30-day readmission rates in pediatric patients.

BACKGROUND: Adult patients with cholecystitis who do not undergo cholecystectomy on index admission have worse outcomes, however, there is a paucity of data of the role of cholecystectomy during index hospitalization in the pediatric population. Our aim was to determine outcomes and readmission rates among pediatric patients with cholecystitis who underwent index cholecystectomy versus those who did not. METHODS: We performed a retrospective study of pediatric (< 18 years old) admitted with acute cholecystitis (AC) requiring hospitalization using the 2018 National Readmission Database (NRD). Exclusion criteria included age ≥ 18 years and death on index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmissions. RESULTS: We identified 550 unique index acute cholecystitis admissions. Mean age was 14.6 ± 3.0 years. Majority of patients were female (n = 372, 67.6%). Index cholecystectomy was performed in (n = 435, 79.1%) of cases. Thirty-day readmission rate was 2.8% in patients who underwent index cholecystectomy and 22.6% in those who did not (p < 0.001). On multivariable analysis, patients who did not undergo index cholecystectomy had higher odds of 30-day readmission than those who did not (OR 10.66, 95% CI 5.06-22.45, p < 0.001). Female patients also had higher odds of 30-day readmission compared to males (OR 3.37, 95% CI 1.31-8.69). CONCLUSIONS: Patients who did not undergo index cholecystectomy had over tenfold increase in odds of 30-day readmission. Further research is required to understand the barriers to index cholecystectomy despite society recommendations and clear clinical benefit.

Impact of Telemedicine on No-Show Rates in an Ambulatory Gastroenterology Practice.

Background: Studies suggest that telemedicine worsens health care disparities in certain groups, partly owing to a lack of access to appropriate technology or poor technological literacy. Our aim was to use clinic no-show data to determine the impact of telemedicine on patient access to care in the ambulatory gastroenterology setting. Methods: Single-center retrospective study of ambulatory in-person and telemedicine clinic appointments comparing the 15-month prepandemic (PP) with the first 15 months during the pandemic (DTP) using an administrative database. Statistical analysis was performed using univariate and multivariable logistic regression. Results: About 9,746 and 12,808 patient-encounters were scheduled PP and DTP respectively. The no-show rate decreased from 9.8% to 6.9% DTP (p < 0.001). The no-show rate decreased for Black (p = 0.02) and non-Hispanic White patients (p = 0.018). The no-show rate increased for LatinX (p < 0.001) and Asian (p = 0.007) patients. In multivariate analysis, older patients and patients identifying as Black, Asian, or LatinX all had higher odds of no-show DTP (p < 0.05 for all). Patients from high-income counties were 43% less likely to no-show than those in the lowest income counties. Conclusions: The transition to telemedicine improves health care access by decreasing the overall no-show rate. Some groups have been negatively affected, including the older, lower income, LatinX, and Asian populations. Future studies should aim to identify the risk factors within these populations that can be modified to increase health care participation, including targeted application of in-person visits, and improved technology to drive engagement.

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

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

Telecytology versus in-room cytopathologist for EUS-guided FNA or fine-needle biopsy sampling of solid pancreatic lesions.

BACKGROUND AND AIMS: Rapid on-site-evaluation (ROSE) with an in-room cytopathologist (ROSE-P) has been shown to improve the diagnostic yield of specimens obtained from patients undergoing EUS-guided FNA or fine-needle biopsy sampling (EUS-FNAB) of pancreatic lesions. Recently, there has been an increased interest and use of ROSE using telecytology (ROSE-T) to optimize clinical workflows and to address social distancing mandates created during the coronavirus disease 2019 pandemic. The purpose of this study was to compare diagnostic outcomes of ROSE-P and ROSE-T. METHODS: 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-FNAB were entered into a prospectively maintained database. Statistical analyses were performed using descriptive statistics and univariate analysis. RESULTS: 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 an increased use of 22-gauge needles (P = .006) and more needle passes (P < .001). No significant differences were found in age, gender, lesion size, needle type, procedure times, or adverse events between the 2 groups (P < .05 for all). More pancreatic tail lesions were sampled in the ROSE-P group (P < .001). CONCLUSIONS: ROSE-T 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.

Benefits of EUS-guided gastroenterostomy over surgical gastrojejunostomy in the palliation of malignant gastric outlet obstruction: a large multicenter experience.

BACKGROUND AND AIMS: Palliation of malignant gastric outlet obstruction (mGOO) allows resumption of peroral intake. Although surgical gastrojejunostomy (SGJ) provides durable relief, it may be associated with a higher morbidity, interfere with chemotherapy, and require an optimum nutritional status. EUS-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We aimed to conduct the largest comparative series to date between EUS-GE and SGJ for mGOO. METHODS: This multicenter retrospective study included consecutive patients undergoing SGJ or EUS-GE at 6 centers. Primary outcomes included time to resumption of oral intake, length of stay (LOS), and mortality. Secondary outcomes included technical and clinical success, reintervention rates, adverse events (AEs), and resumption of chemotherapy. RESULTS: A total of 310 patients were included (EUS-GE, n = 187; SGJ, n = 123). EUS-GE exhibited significantly lower time to resumption of oral intake (1.40 vs 4.06 days, P < .001), at lower albumin levels (2.95 vs 3.33 g/dL, P < .001), and a shorter LOS (5.31 vs 8.54 days, P < .001) compared with SGJ; there was no difference in mortality (48.1% vs 50.4%, P = .78). Technical (97.9% and 100%) and clinical (94.1% vs 94.3%) success was similar in the EUS-GE and SGJ groups, respectively. EUS-GE had lower rates of AEs (13.4% vs 33.3%, P < .001) but higher reintervention rates (15.5% vs 1.63%, P < .001). EUS-GE patients exhibited significantly lower interval time to resumption of chemotherapy (16.6 vs 37.8 days, P < .001). Outcomes between the EUS-GE and laparoscopic (n = 46) surgical approach showed that EUS-GE had shorter interval time to initiation/resumption of oral intake (3.49 vs 1.46 days, P < .001), decreased LOS (9 vs 5.31 days, P < .001), and a lower rate of AEs (11.9% vs 17.9%, P = .003). CONCLUSIONS: This is the largest study to date showing that EUS-GE can be performed among nutritionally deficient patients without affecting the technical and clinical success compared with SGJ. EUS-GE is associated with fewer AEs while allowing earlier resumption of diet and chemotherapy.

Over-the-Scope Clips Versus Standard Endoscopic Treatment for First Line Therapy of Non-variceal Upper Gastrointestinal Bleeding: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB. METHODS: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I2 statistic. RESULTS: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23). CONCLUSIONS: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB.

Safety and efficacy of EUS-guided coil and glue injection for the primary prophylaxis of gastric variceal hemorrhage.

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.

Efficacy of empiric esophageal dilation in patients with non-obstructive dysphagia: systematic review and meta-analysis.

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.

Endoscopic ultrasound-guided gastroenterostomy versus open surgical gastrojejunostomy: clinical outcomes and cost effectiveness analysis.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Practice patterns of post-ERCP pancreatitis prophylaxis techniques in the United States: a survey of advanced endoscopists.

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.

Urgent colonoscopy in patients with lower GI bleeding: a systematic review and meta-analysis.

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.

Pharmacophore modeling of nilotinib as an inhibitor of ATP-binding cassette drug transporters and BCR-ABL kinase using a three-dimensional quantitative structure-activity relationship approach.

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.

Afferent Loop Syndrome as Second Presentation of Gastric Outlet Obstruction in Patient With Billroth II Anatomy.

Afferent loop syndrome can result from both benign and malignant strictures of the biliary limbs of patients with surgically altered anatomy. Afflicted patients accumulate intestinal and pancreaticobiliary secretions, which leads to bowel distention and pain. We describe the endoscopic management of a 52-year-old woman with a history of Billroth II gastrojejunostomy due to gastric cancer who developed malignant gastric outlet obstruction and subsequently malignant afferent loop syndrome, using lumen-apposing metal stents.

Current state of biliary cannulation techniques during endoscopic retrograde cholangiopancreatography (ERCP): International survey study.

Background and study aims Endoscopist techniques affect biliary cannulation success and the risk of adverse events during endoscopic retrograde cholangiopancreatography (ERCP). This survey study aims to understand the current practice of biliary cannulation techniques among endoscopists. Methods Practicing endoscopists were sent an anonymous 28-question electronic survey on biliary cannulation techniques and intraprocedural pancreatitis prophylactic strategies. Results The survey was completed by 692 endoscopists (6.2% females). A wire-guided cannulation technique (WGT) was the preferred initial biliary cannulation approach (95%). The preferred secondary approaches were a double-wire (DWT) (65.8%), precut needle-knife technique (NKT) (25.7%), transpancreatic sphincterotomy (5.9%) or other (2.6%). Overall, 18.1% of respondents were not comfortable with NKTs. In the setting of pancreatic duct (PD) access, 81.9% and 97% reported a threshold of three or more wire passes or contrast injections into the PD, respectively, before changing strategy, 34% reported placement of a prophylactic PD stent <50% of the time and 12.1% reported removal of the PD stent at the end of the procedure. Advanced endoscopy fellowship (AEF) training and high volume (>200 ERCPs per year) were associated with comfort with precut NKTs and likelihood of prophylactic PD stent ( P <0.001 for both). Conclusions A WGT technique followed by the DWT and NKT were the preferred biliary cannulation techniques; however, almost one-fifth of respondents were not comfortable with the NKT. There was considerable variability in secondary cannulation approaches, time spent attempting biliary cannulation and prophylactic PD stent placement, factors known to be associated with cannulation success and adverse outcomes.

Efficacy and safety of EUS-guided gallbladder drainage for rescue treatment of malignant biliary obstruction: A systematic review and meta-analysis.

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.

Efficacy and safety of EUS-guided biliary drainage for benign biliary obstruction - A systematic review and meta-analysis.

Background and Objectives: ERCP is the first line of treatment for benign and malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. Recently, several studies have evaluated the role of EUS-BD in the management of benign biliary obstruction. This meta-analysis evaluates the efficacy and safety of EUS-BD in the management of benign biliary obstruction. Methods: We reviewed several databases from inception to July 8, 2022, to identify studies evaluating the efficacy and safety of EUS-BD in the management of benign biliary obstruction. Our outcomes of interest were technical success, clinical success, and adverse events. Pooled rates with 95% confidence intervals (CIs) for all outcomes were calculated using a random effects model. Subgroup analyses were performed including patients with normal anatomy versus surgically altered anatomy (SAA). Heterogeneity was assessed by I2 statistic. Results: We included 14 studies with 329 patients. The pooled rate (95% CI) of technical success was 88% (83%, 92%). The pooled rate (95% CI) of technical success for patients with SAA and normal anatomy was 92% (85%, 96%) and 83% (75%, 89%), respectively. The pooled rates (95% CI) of clinical success and adverse events were 89% (83%, 93%) and 19% (13%, 26%), respectively. We found low heterogeneity in most of the analyses. Conclusions: EUS-BD is an effective and safe option in patients with benign biliary obstruction and should be considered after a failed attempt at ERCP or when ERCP is not technically possible.