An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

First dose-ranging study of remimazolam in Japanese patients undergoing gastrointestinal endoscopy: Phase II investigator-initiated clinical trial.

OBJECTIVES: Remimazolam, an ultra-short-acting benzodiazepine, has been used for procedural sedation in the United States. We conducted an investigator-initiated clinical trial to determine the appropriate dose of remimazolam required for sedation during gastrointestinal endoscopy in Japanese subjects. METHODS: In this single-center, open-label, uncontrolled, phase II trial, a three-stage cohort investigated the appropriate initial and additional doses of remimazolam required for gastrointestinal endoscopy. This study was designed with advice from the Pharmaceuticals and Medical Devices Agency. The initial and additional doses were 2 mg and 1 mg/dose, 3 mg and 1 mg/dose, and 5 mg and 2 mg/dose in cohorts 1, 2, and 3, respectively. Each cohort included 10 cases of upper gastrointestinal endoscopy and colonoscopy. The primary end-point was the success rate of sedation during gastrointestinal endoscopy. RESULTS: Sedation was successful in all gastrointestinal endoscopies in cohorts 1 and 2. In cohort 1, sedation was achieved in five (25.0%) and 10 (50.0%) participants with the initial dose and total dose (initial dose + additional dose ≤ the initial dose of the next cohort), respectively, before endoscopy. In cohort 2, sedation was achieved in 11 (55.0%) and 18 (90.0%) participants with the initial dose and total dose, respectively, before endoscopy. No patient in either cohort lost consciousness or required flumazenil or manual ventilation. CONCLUSION: Initial and additional doses of 3 mg and 1 mg/dose of remimazolam, respectively, were shown to be effective and safe for sedation during gastrointestinal endoscopy in Japanese patients.

Self-Completion Method of Endoscopic Submucosal Dissection Using Endosaber without Any Other Device or Assistance: An ex vivo Porcine Model Study.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard treatment for tumors of the gastrointestinal tract. We developed a self-completion method of ESD using Endosaber to eliminate the need for an additional device or human assistance during the procedure. The aim of this study was to evaluate the technical feasibility and outcomes of this method in an ex vivo porcine training model. METHODS: This was a pilot study, and the procedures were performed by 4 experts. Mock lesions measuring 15 mm in diameter were prepared at the posterior wall in the middle or lower esophagus obtained from domestic pigs. Each operator performed ESD on the mock lesions in 3 models. The primary outcome was ESD completion rate using the self-completion method. The secondary outcomes were procedure time, en bloc resection rate, perforation rate, and number of injections during the procedure. RESULTS: All 12 ESDs were completed using the self-completion method. The median procedure time (interquartile range) was 483.5 (399-619.3) s (median incision time: 240.4 [168.3-332.5] s; median dissection time: 222 [182.8-257] s). En bloc resection rate was 100%. No perforation was noted during any of the procedures. The median number of injections was 10.5 (9-14.3). The procedure time decreased significantly with increase in experience (p = 0.020). CONCLUSIONS: The self-completion ESD method using one Endosaber without any assistance achieved a 100% en bloc resection rate without any perforation. The need for an additional device or assistance was successfully eliminated. This method may prove to be a simple and cost-effective ESD procedure for lesions in humans.

Efficacy of traction, using a clip-with-thread, for esophageal endoscopic submucosal dissection for esophageal lesions with fibrosis in an ex vivo pig training model.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) of recurrent esophageal carcinoma is technically difficult to perform due to submucosal fibrosis that develops after definitive chemoradiation therapy. Therefore, our aim was to evaluate the usefulness of clip-with-thread traction for ESD of esophageal lesions with submucosal fibrosis. MATERIALS AND METHODS: Four endoscopists excised 16 lesions by ESD in an ex vivo pig training model. Mock lesions (30 mm in diameter) were created, including a 10-mm area of submucosal fibrosis in the center of each lesion. Each endoscopist performed two ESDs with traction (ESD-T) and two without traction (ESD-N). The primary outcome was the time required for submucosal dissection. Secondary outcomes were the rate of en bloc (complete) resection and perforation during the procedure, and the total amount of solution injected. RESULTS: All esophageal ESDs were completed. The median dissection time was significantly shorter for the ESD-T group (median 12.5 min, interquartile range 10.2-14.5) when comparing to the ESD-N group (median 18.0 min, interquartile range 14.6-19.2) (P=0.040). The en bloc resection rate was 100% in both groups, with a rate of complete resection of 87.5% and a rate of perforation of 37.5% for both groups. The median amount of solution injected was not significantly different between the ESD-T (18.0 ml) and ESD-N (20.5 ml) groups (P=0.526). CONCLUSION: Clip-with-thread traction improved the performance of ESD for lesions with submucosal fibrosis. However, the method might not reduce the risk of perforation, which remains an important clinical issue to resolve.

Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms.

AIM: To compare the outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms using Clutch Cutter (ESD-C) or other knives (ESD-O). METHODS: This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer (scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding. RESULTS: A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C (median; 49 min) than for ESD-O (median; 88.5 min) (P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate (100% in both groups), complete resection rate (100% in both groups), curative resection rate (86.4% vs 88.6%, P = 0.730), delayed bleeding (2.3% vs 6.8%, P = 0.62) and perforation (0% in both groups). CONCLUSION: ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.