Citations

Objective CHAMPION‐NMOSD (NCT04201262) is a phase 3, open‐label, externally controlled interventional study evaluating the efficacy and safety of the terminal complement inhibitor ravulizumab in adult patients with anti–aquaporin‐4 antibody–positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). Ravulizumab binds the same complement component 5 epitope as the approved therapeutic eculizumab but has a longer half‐life, enabling an extended dosing interval (8 vs 2 weeks). Methods The availability of eculizumab precluded the use of a concurrent placebo control in CHAMPION‐NMOSD; consequently, the placebo group of the eculizumab phase 3 trial PREVENT (n = 47) was used as an external comparator. Patients received weight‐based intravenous ravulizumab on day 1 and maintenance doses on day 15, then once every 8 weeks. The primary endpoint was time to first adjudicated on‐trial relapse. Results The primary endpoint was met; no patients taking ravulizumab (n = 58) had an adjudicated relapse (during 84.0 patient‐years of treatment) versus 20 patients with adjudicated relapses in the placebo group of PREVENT (during 46.9 patient‐years; relapse risk reduction = 98.6%, 95% confidence interval = 89.7%–100.0%, p < 0.0001). Median (range) study period follow‐up time was 73.5 (11.0–117.7) weeks for ravulizumab. Most treatment‐emergent adverse events were mild/moderate; no deaths were reported. Two patients taking ravulizumab experienced meningococcal infections. Both recovered with no sequelae; one continued ravulizumab treatment. Interpretation Ravulizumab significantly reduced relapse risk in patients with AQP4+ NMOSD, with a safety profile consistent with those of eculizumab and ravulizumab across all approved indications. ANN NEUROL 2023;93:1053–1068

Abstract Background and study aims The risk of bleeding with endoscopic ultrasound-guided tissue acquisition (EUS-TA) in patients on uninterrupted antithrombotic agents is unknown. This study aimed to assess the safety of EUS-TA without discontinuing direct oral anticoagulants. Methods Twenty pigs were randomized (1:1) to oral apixaban or placebo. Treatment was administered for 3 days before and 3 days after EUS-TA of the pancreas. Primary endpoint was occurrence of clinically significant bleeding events (CSBEs), defined as a composite outcome of drop in hemoglobin ≥ 2 g/dL and evidence of intraprocedural or post-procedure bleeding. Secondary outcome was cytopathological adequacy of acquired specimens. Endoscopists and pathologists were blinded to the treatment arm. Results Total of 80 tissue samples were obtained. CSBE occurred in one animal with apixaban levels above the upper limit (P = 1). Intraprocedural bleeding occurred in five animals (25 %), four of which from the apixaban group. Hematoma at necropsy was found in 10 animals (50 %), six of which were on apixaban. Median drop in hemoglobin was similar in both groups. Adequacy of specimens for cytology and pathology evaluation was confirmed in 20 of 20 and 19 of 20 animals, respectively. Conclusions In this pilot preclinical trial, EUS-TA under apixaban showed a trend toward higher minor bleeding events but did not increase CSBE or prevent adequate cytopathological evaluation.

Abstract Background and study aims Gastric outlet obstruction (GOO) is traditionally managed with surgical gastroenterostomy (surgical-GE) and enteral stenting (ES). Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is now a third option. Large studies assessing their relative risks and benefits with adequate follow-up are lacking. We conducted a comparative analysis of patients who underwent EUS-GE, ES, or surgical-GE for GOO. Patients and methods In this retrospective comparative cohort study, consecutive patients presenting with GOO who underwent EUS-GE, ES, or surgical-GE at two academic institutions were reviewed and independently cross-edited to ensure accurate reporting. The primary outcome was need for reintervention. Secondary outcomes were technical and clinical success, length of hospital stay (LOS), and adverse events (AEs). Results A total of 436 patients (232 EUS-GE, 131 ES, 73 surgical-GE) were included. The median duration of follow-up of the entire cohort was 185.5 days (interquartile range 55.25–454.25 days). The rate of reintervention in the EUS-GE group was lower than in the ES and surgical-GE groups (0.9 %, 12.2 %, and 13.7 %, P < 0.0001). Technical success was achieved in 98.3 %, 99.2 %, and 100 % (P = 0.58), and clinical success was achieved in 98.3 %, 91.6 %, and 90.4 % (P < 0.0001) in the EUS-GE, ES, and surgical-GE groups, respectively. The EUS-GE group had a shorter LOS (2 days vs. 3 days vs. 5 days, P < 0.0001) and a lower AE rate than the ES and surgical-GE groups (8.6 % vs. 38.9 % vs. 27.4 %, P < 0.0001). Conclusion This large cohort study demonstrates the safety and palliation durability of EUS-GE as an alternative strategy for GOO palliation in select patients.

BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers. METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments. RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures. CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers. TRIAL REGISTRATION Not applicable. FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

Abstract Background and study aims Obtaining quality tissue during ERCP biliary stricture sampling is of paramount importance for a timely diagnosis. While single-operator cholangioscopy (SOC)-guided biopsies have been suggested to be the superior biliary tissue acquisition modality given direct tissue visualization, less is known about the specimen histological quality. We aimed to analyze the specimen quality of SOC biopsies and compare the new generation forceps with prior “legacy” forceps. Patients and methods Patients who underwent SOC from January 2017-August 2021 for biliary sampling were reviewed. In February 2020, the SOC-guided biopsy forceps were changed from legacy SpyBite to the SpyBite Max forceps (max). Specimens were assessed by blinded pathologists for crush artifact (none, mild, or severe) and gross size (greatest dimension in mm). Crush artifact and gross size were compared between the two groups. The diagnostic performance characteristics for cholangiocarcinoma (CCA), were assessed in an exploratory fashion. Results Eighty-one patients (max = 27, legacy = 54) with similar baseline characteristics were included in this study. On blinded pathological assessment, 58 % had crush artifact, without significant differences between the two groups (Max 63 % vs. Legacy 56 %; P = 0.64). A similar mean specimen size was found (max 3 mm vs. legacy 3.2 mm; P = 0.24). The overall prevalence of CCA was 40 %. The sensitivity, specificity, positive predictive value, and negative predictive value of the entire cohort using a combination of cytology, fluorescence in situ hybridization, and SOC-guided biopsies were 78.1 %, 91.8 %, 86.2 %, and 86.5 %, respectively. No difference between legacy or max groups was found. Conclusions A high rate of crush artifact was found in SOC-guided biopsy specimens. Further investigation regarding proper biopsy technique and handling is necessary to increase the diagnostic yield with SOC-guided biopsies.

Abstract Background and study aims Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) is an endoscopic procedure for treating gastric outlet obstruction (GOO). Limited data exist regarding the safety and efficacy of EUS-GJ in patients with malignant GOO with ascites. Thus, we aimed to study the outcomes and safety of EUS-GJ in GOO patients with vs. without ascites. Patients and methods This is a retrospective cohort study of patients with malignant GOO who underwent successful EUS-GJ at a tertiary care academic center. Primary outcomes included the efficacy and safety of EUS-GJ. Secondary outcomes included 30-day readmission, reintervention, and survival utilizing Kaplan-Meier analysis. Results A total of 55 patients (mean age of 67.0 ± 11.3 years, 40.0 % female) who underwent EUS-GJ, of whom 24 had ascites (small in 22, large in 2) were included. Clinical success was achieved in 91.7 % and 93.5 % (P = 1.00) of patients with and without ascites, respectively. A higher rate of adverse events (AEs) was noted in patients with ascites but this was not statistically significant (37.5 % vs. 19.4 %, P = 0.13). Four patients in the ascites group (16.6 %) developed clinical evidence of peritonitis or sepsis post-EUS-GJ. Eight patients with ascites developed worsening ascites within a month of EUS-GJ. In contrast, only one patient without ascites developed evidence of new ascites. The median survival of patients was not significantly different between the two groups (patients with ascites: 129 days vs. patients without ascites: 180 days, (P = 0.12). Conclusions The efficacy EUS-GJ in the presence of ascites is promising; however, the safety profile remains concerning given the high rate of AEs, specifically peritonitis and sepsis.