Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing upper gastrointestinal endoscopy: Phase III investigator-initiated clinical trial.

OBJECTIVES: To assess the effectiveness of remimazolam against normal saline (placebo) as a sedative agent for endoscopy in a multicenter, randomized, double-blind, investigator-initiated phase III controlled trial. METHODS: We included 48 Japanese patients undergoing upper gastrointestinal endoscopy. For the procedure, an initial remimazolam dose of 3 mg and additional doses of 1 mg were administered, as determined in the phase II clinical study. The primary study end-point was the successful sedation rate during gastrointestinal endoscopy, determined as a Modified Observer's Assessment of Alertness/Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per 6 min. RESULTS: The successful endoscopy sedation rates were 91.9% and 9.1% in the remimazolam and placebo groups, respectively (P < 0.01). The time from the end of endoscopy to arousal was 0.0 (0.0-0.0) min for both groups. The number of additional doses required to achieve sedation was lower in the remimazolam group than that in the placebo group (P < 0.01). CONCLUSIONS: Remimazolam demonstrated a significantly higher sedation effect during upper gastrointestinal endoscopy in Japanese patients with safe and fast recovery compared with placebo.

A single-center prospective study on pain alleviation during peroral upper endoscopy with an ultrathin endoscope.

BACKGROUND: The efficacy of transnasal endoscopy using an ultrathin endoscope has been reported in several studies. However, few studies regarding peroral endoscopy with ultrathin endoscopes with high resolution have been reported. This study investigates the pain alleviation of peroral endoscopy with an ultrathin endoscope. METHODS: Patients with a history of peroral endoscopy using a conventional, normal-diameter scope with no sedation who underwent peroral esophagogastroduodenoscopy (EGD) using a thin scope between April-July 2022 were included in this study. After the procedure, the patients completed a questionnaire evaluating pain during the examination and willingness to repeat the procedure. The physicians were surveyed regarding their level of satisfaction. The primary endpoint was patient satisfaction, which corresponded to the rate of patients who rated the thin endoscope as more comfortable or somewhat more comfortable than the previously-used, conventional endoscope. RESULTS: One hundred and forty-five patients were included in the analyses. Patient satisfaction was achieved in 86.2% (125/145) of patients. The median visual analog scale pain score was 3 (0-7) points in this study, which is significantly lower than the pain score after the previous endoscopy (5 (0-10) points; p < 0.001). In addition, 96% (24/25) of patients who underwent EGD by an expert and 95.8% (115/120) who underwent EGD by a non-expert were willing to repeat endoscopy using the thin scope (p = 0.69). CONCLUSION: Peroral endoscopy using a thin scope reduces patient pain regardless of the endoscopist's experience.

Randomized controlled trial comparing conventional and traction endoscopic submucosal dissection for early colon tumor (CONNECT-C trial).

OBJECTIVES: Endoscopic submucosal dissection (ESD) is a widely used treatment for early gastrointestinal cancer. However, colon ESD remains challenging. Previous studies on colon ESD using the traction method used a small sample, single-center design, providing insufficient evidence of this procedure's efficacy. We thus aimed to investigate the efficacy and safety of the traction method in colon ESD in this multicenter randomized trial. METHODS: We conducted a prospective, multicenter, randomized, two-arm controlled trial at 10 facilities in Japan. A 1:1 allocation was conducted for the conventional ESD (C-ESD) and traction ESD (T-ESD) groups. The primary end-point was ESD procedure time. RESULTS: We included 128 C-ESD and 123 T-ESD cases from April 2020 to August 2021. The median procedure times for C-ESD and T-ESD were 61 (40-100) and 53 (40-76) min (P = 0.18), respectively, and no significant differences were observed between the groups. Subgroup analysis showed that the median procedure times for patients with a lesion diameter of ≥30 mm in the C-ESD and T-ESD groups were 89 (57-80) and 69 (50-104) min (P = 0.05), respectively, and for nonexpert operators were 81 (62-120) and 64 (52-109) min (P = 0.07), respectively. CONCLUSIONS: The traction method did not contribute to a significantly shortened ESD procedure time. However, this method may be useful when the tumor diameter is large or if the procedure is conducted by nonexpert endoscopists.

The Ideal Helicobacter pylori Treatment for the Present and the Future.

BACKGROUND: Helicobacter pylori eradication treatments are widely performed to improve gastric mucosal inflammation, promote ulcer healing, and reduce the incidence of gastric cancer. However, there are several issues associated with H. pylori eradication treatment. First, various treatment regimens are currently used worldwide, and the standard treatment varies with region and country. Second, the antimicrobial resistance of H. pylori is increasing due to indiscriminate antibiotic use. Finally, gut microbiota dysbiosis is potentially induced by H. pylori treatment. SUMMARY: Based on current international guidelines and a network meta-analysis comparing the effects of various treatment regimens, nonbismuth quadruple therapies for 10-14 days and vonoprazan-based triple therapy for 7 days are the currently recommended H. pylori treatment regimens. These regimens show good eradication rates of approximately 90%, even in areas where antimicrobial-resistant strains are highly prevalent. However, these regimens still have inherent drawbacks that may promote further increases in antimicrobial resistance and induce gut microbiota dysbiosis because of the empiric use of multiple antibiotics. Key Message: The ideal concept for the present and future H. pylori eradication treatment involves "a simple, cost-effective strategy that fosters compliance without having a negative impact on the gut microbiota or contributing to future antimicrobial resistance." One interesting possibility that may fulfill this concept is a dual therapy involving vonoprazan and amoxicillin. This is the simplest treatment regimen that provides acceptable eradication rates, improves safety and tolerability, and minimizes the potential for increasing antimicrobial resistance or causing gut microbiota dysbiosis.

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.

Long term impact of vonoprazan-based Helicobacter pylori treatment on gut microbiota and its relation to post-treatment body weight changes.

BACKGROUND: Vonoprazan-based Helicobacter pylori (H. pylori) treatment is highly effective in eradicating the target bacteria; however, its post-1-year impact on gut microbiota is unknown. This study evaluated the impact of vonoprazan-based H. pylori therapy on gut microbiota 1-year post-therapy and investigated the relationship between body weight changes and post-therapy gut microbiota perturbations. MATERIALS AND METHODS: Between March and May 2019, 43 patients with H. pylori infections received either vonoprazan/amoxicillin (VA) or vonoprazan/amoxicillin/clarithromycin (VAC) therapy. Fecal samples were collected prior to treatment and 1 year after treatment. The alpha and beta diversities and the bacterial taxa composition ratios were determined using polymerase chain reaction amplification of the V3-V4 region of the 16S ribosomal RNA gene. The correlation between body weight changes and relative abundances of genera post-therapy was also analyzed. RESULTS: Among the 43 patients, 18 received VA therapy and 21 received VAC therapy. One year after treatment, the alpha diversity was significantly higher in both the treatment groups (p < .001, using observed operational taxonomic units and Chao1 index), and beta diversity was significantly different in both the groups (p = .001, using unweighted UniFrac distance) compared with baseline findings. Significant positive correlations were found between body weight changes and the relative abundances of Coprococcus spp. (p = .037) and Odoribacter spp. (p = .022) post-therapy. CONCLUSION: Vonoprazan-based H. pylori therapies are associated with long-term impacts on gut microbiota, including effects on bacterial species richness, and potentially affect metabolism by altering the microbiota. TRIAL REGISTRATION NUMBER: UMIN000040025.

Impact of body size on first-line Helicobacter pylori eradication success using vonoprazan and amoxicillin dual therapy.

BACKGROUND: As a first-line therapy for Helicobacter pylori, dual therapy with vonoprazan and amoxicillin (VA-dual) provides an eradication rate similar to that of vonoprazan-based triple therapy. As the factors associated with the eradication rate of H. pylori with VA-dual are unknown,we investigated them in this study. MATERIALS AND METHODS: Overall, 163 patients diagnosed with H. pylori infection received VA-dual (vonoprazan 20 mg twice daily and amoxicillin 750 mg twice daily for 7 d). The association between successful H. pylori eradication and the following patient clinical factors was analyzed: sex, age, height, weight, body surface area (BSA), body mass index (BMI), history of early gastric carcinoma and peptic ulcer, comorbidity of cirrhosis, alcohol consumption habit, smoking habit, common use of proton pump inhibitors, and concomitant use of drugs that are substratesof cytochrome P450 (CYP) 3A4. The association between post-eradication adverse events and clinical factors was analyzed retrospectively. RESULTS: Successful H. pylori eradication was associated with a lower BSA (eradication rate: 90.8% in patients with BSA <1.723 vs. 79.6% in those with BSA ≥1.723; p = 0.045). The incidence of adverse events was higher in women than in men (adverse events: 40.0% in women vs. 19.4% in men; p = 0.004). CONCLUSIONS: Successful H. pylori eradication with VA-dual was associated with the small body size of patients. This therapy may have to be adjusted per body size.

Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in patients with chronic constipation.

BACKGROUND: Chronic constipation is a significant factor in poor bowel preparation for colonoscopy. Macrogol 4000 plus electrolytes (Movicol, EA Pharma, Tokyo, Japan), containing polyethylene glycol (PEG) and electrolytes, have been used recently to treat patients with constipation. However, prospective studies on the use of macrogol 4000 for bowel cleansing for colonoscopy are lacking. This study aimed to investigate the efficacy and safety of macrogol 4000 in addition to PEG administered in patients with chronic constipation. METHODS: This single-center, single-arm prospective study enrolled patients with chronic constipation who were scheduled to undergo colonoscopy. The primary endpoint was the proportion of good bowel preparation assessed using the Boston bowel preparation scale (BBPS) (6 or more points). The secondary endpoints were the time from when pPEG (MoviPrep, EA Pharma, Tokyo, Japan) was taken until colonoscopy could be started, amount of PEG taken, number of defecations, whether additional PEG doses were taken, and adverse events. Endoscopy-related endpoints included cecal intubation rate, insertion time, observation time, adenoma detection rate (ADR), and polyp detection rate (PDR). The tolerability of PEG and macrogol 4000 was assessed using a questionnaire. RESULTS: Forty patients were included in the analysis. The median BBPS was 7 (range 3-9) and ≥ 6 points in 37 cases (92.5%). The median time until colonoscopy can be started was 210 min (90-360 min), the median volume of PEG taken was 1500 mL (1000-2000 mL), and the median number of defecations was 7 (3-20). No adverse events were observed. Fourteen patients required an additional dose of PEG. Cecal intubation was achieved in all cases, the median insertion time was 6.0 min (range 2.3-22 min), and the median observation time was 8.8 min (range 4.0-16.0 min). The ADR and PDR were 60.0% and 75.0%, respectively. A proportion of patients rated the tolerability of macrogol 4000 and PEG as 95.0% and 50.0%, respectively. CONCLUSIONS: Intake of macrogol 4000 in addition to PEG is effective and safe for colonoscopy in patients with chronic constipation. Clinical trial registration statement This study was registered in the UMIN-CTR database (UMIN-ID000038315).

Minimizing endoscopist facial exposure to droplets: Optimal patient-endoscopist distance and use of a barrier device.

BACKGROUND AND AIM: Minimizing endoscopist exposure to bodily fluids is important for reducing the risk of infection transmission. This study investigated the patient-endoscopist vertical distance necessary to minimize an endoscopist's facial exposure to a patient's visible droplets during upper gastrointestinal endoscopy and the ability of a new device to prevent droplets from reaching the endoscopist's face. METHODS: A model was developed to simulate a patient experiencing a forceful cough during an upper gastrointestinal endoscopy with a model endoscopist. Fluorescent dye was expelled from the model patient's mouth towards the model endoscopist during simulated coughs; dye adhesion to the model endoscopist's face was evaluated using ultraviolet light. The simulation was repeated with the model patient positioned 70-100 cm above the floor, with and without a barrier to shield the patient's face. The accuracy of the cough simulation model and the relationship between patient-endoscopist vertical distance and endoscopist's facial exposure were evaluated. RESULTS: The flow dynamics of the cough simulation model were similar to that of an actual human cough. There was a significant inverse correlation between the patient-endoscopist vertical distance and the model endoscopist's facial exposure, with positive exposures decreasing from 87% at 70 cm to 0% at 100 cm (P < 0.001). The barrier device prevented facial exposure to droplets at all distances. CONCLUSIONS: We found that positioning the patient at least 100 cm below the top of the endoscopist's head or using a barrier device minimized the endoscopist's facial exposure to visible droplets during upper gastrointestinal endoscopy.

Lower impact of vonoprazan-amoxicillin dual therapy on gut microbiota for Helicobacter pylori eradication.

BACKGROUND AND AIM: Helicobacter pylori eradication can disrupt the gut microbiome. Here, we investigated the short-term impact of minimum antibiotic treatment-a 7-day vonoprazan and low-dose amoxicillin regimen (VA-dual therapy)-on gut microbiota and compared it with that of vonoprazan-based triple therapy (VAC-triple therapy). METHODS: Fifty-nine patients with H. pylori infection were recruited (UMIN000034140) from March to May 2019 and randomly assigned to the VAC-triple therapy or VA-dual therapy groups, according to the first-line H. pylori treatment received. Fecal samples were collected before treatment initiation and 1 and 8 weeks after eradication therapy completion. The composition ratios of the bacterial taxa and the alpha and beta diversities were evaluated in both groups via polymerase chain reaction amplification of the V3-V4 region of the 16S rRNA gene and sequencing using the MiSeq system. RESULTS: Nineteen patients were assigned to the VA-dual group and 24 to the VAC-triple group. Compared with baseline, the alpha diversity reduced significantly 1 and 8 weeks after VAC-triple therapy. However, for VA-dual therapy, the alpha diversities at 1 and 8 weeks after the treatment did not change significantly compared with those at baseline. Additionally, the beta diversity differed significantly between baseline and 1 and 8 weeks after VAC-triple therapy. VAC-triple therapy led to significant alteration in the relative abundance of Actinobacteria at the phylum level and Collinsella, Blautia, and Streptococcus at the genus level. CONCLUSIONS: Compared with VAC-triple therapy, VA-dual therapy induced minimal changes in the diversity and relative abundance of gut microbiota.

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.

High Body Mass Index Is Correlated with the Success of Vonoprazan-Based Second-Line Therapy for Helicobacter Pylori Infection.

Eradication of Helicobacter pylori (Hp) is necessary for preventing peptic ulcers and stomach cancer. The potassium-competitive acid blocker vonoprazan is a gastric acid secretion inhibitor that improves the success rate of Hp eradication through its immediate and persistent inhibition of acid excretion. In Japan, first-line treatment involves a regimen in which vonoprazan is combined with amoxicillin and clarithromycin, while second-line treatment involves vonoprazan combined with amoxicillin and metronidazole. However, in contrast to the vonoprazan-based first-line therapy, no studies have investigated the factors influencing the success of vonoprazan-based second-line therapy. In this study, we therefore aimed to investigate factors related to the success of vonoprazan-based second-line therapy. We analyzed the association between the success of Hp eradication and patient factors including metronidazole/amoxicillin minimal inhibitory concentrations (MICs). MICs were measured using the Hp isolated from each patient. A receiver operating characteristic (ROC) analysis was conducted to examine continuous variables and eradication success. We reviewed the records of 33 patients (age: 34-79 years, male/female: 22/11, and body mass index (BMI): 16.1-28.8 kg/m2) who underwent vonoprazan-based second-line therapy after failure of first-line therapy at seven Japanese facilities between October 2018 and June 2019. The eradication success rate was 81.8% (27/33). ROC analysis revealed an area under the curve and BMI cutoff value of 0.796 and 23.8 kg/m2, respectively. The eradication success rate was higher in patients with high BMI than in those with low BMI (p = 0.007). Our findings indicate that higher BMI is correlated with the success of vonoprazan-based second-line therapy.

Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan.

OBJECTIVE: To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy. DESIGN: This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori-positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. RESULTS: Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups. CONCLUSION: The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance. TRIAL REGISTRATION NUMBER: UMIN000034140.

Efficacy of Full-Spectrum Endoscopy to Visualize the Major Duodenal Papilla in Patients with Familial Adenomatous Polyposis.

BACKGROUND AND AIMS: Duodenal cancer is one of the extracolonic malignancies with known mortality in familial adenomatous polyposis (FAP) patients. Visualization of the major duodenal papilla (MDP) with a standard esophagogastroduodenoscopy (EGD) is currently insufficient because of the limited field of view. Full-spectrum endoscopy (FUSE), utilizing double imagers located on the front and side of the endoscopic tip, provides a wider field of view up to 245 degrees. The aim of this study was to evaluate the efficacy of FUSE in visualizing MDP in patients with FAP. METHODS: This study was a single-center retrospective study including 49 FAP patients undergoing surveillance at our institution. EGD was performed by qualified endoscopists using FUSE, and visibility of the MDP was evaluated. All examinations were video-recorded, and the clips for individual patient were edited to forward view images alone (conventional group) and 2-view images of the duodenum (forward and side-view [FUSE group]). Three other qualified external endoscopists independently reviewed the videos and compared the visibility of MDP between the conventional and the FUSE groups. Primary endpoint was the rate of Type 1 visibility (whole area of the papilla) in off-site video reviews. We also assessed MDP visibility on-site as secondary endpoint. RESULTS: The rate of type 1 MDP visibility was significantly higher in the FUSE group than conventional group in both on-site (32.6/100%, p < 0.001) and off-site reviews (8.2, 16.3, 14.3/100, 98, and 100%, p < 0.001). CONCLUSIONS: FUSE is recommended in screening and surveillance EGD to better visualize MDP in FAP patients.

The effect of scissor-type versus non-scissor-type knives on the technical outcomes in endoscopic submucosal dissection for superficial esophageal cancer: a multi-center retrospective study.

The Clutch Cutter was invented as a scissor-type knife for endoscopic submucosal dissection (ESD) of gastrointestinal neoplasms. ESD with the scissor-type knife (ESD-S) may be considered a technically easier procedure than ESD with non-scissor-type knives (ESD-NS). Therefore, this study aimed to compare the technical outcomes of ESD-S with those of ESD-NS for superficial esophageal cancer. This was a multicenter retrospective study. Patients with superficial esophageal cancer treated with ESD between October 2015 and March 2018 at three hospitals were retrospectively reviewed. The ESD-S group had 48 patients and the ESD-NS group had 114 patients. A propensity score matching analysis was performed to compensate for the confounding bias between both groups. Multivariate analyses and propensity score matching were used to adjust for age, sex, the tumor size, tumor location, tumor depth, degree of tumor circumference, operator level, usage of the traction method, and the sedation method. The primary outcome was the procedure time of the ESD. Secondary outcomes were the rate of en-bloc/complete resection and the rate of complications including perforation, delayed bleeding, and stricture. Propensity score matching analysis provided 36 matched pairs. Median procedure time in the ESD-S group was significantly shorter than that in the ESD-NS group (44.0 min vs. 66.5 min, P = 0.020). In addition, the treatment outcomes were similar in both groups (en-bloc resection: 100% vs. 97.2%, P = 1; complete resection: 88.9% vs. 86.1%, P = 1; curative resection: 80.6% vs. 77.8%, P = 1; perforation: 0% vs. 5.6%, P = 0.49; delayed bleeding: 0% in both groups; stricture: 2.8% vs. 8.3%, P = 0.61). ESD-S was associated with a shorter procedure time than ESD-NS, without an increase in the incidence of complications. Therefore, the scissor-type knife should be considered as an endo-knife for ESD of superficial esophageal cancers.

Ex vivo porcine model study on the treatment outcomes of scissor-type knife versus needle-type knife in endoscopic submucosal dissection performed by trainees.

BACKGROUND: Endoscopic submucosal dissection (ESD) for gastrointestinal neoplasms can be technically difficult for trainee endoscopists. Presently, there is no consensus for trainees to select the endo-knife type in ESD. Therefore, we conducted a comparison study of treatment outcomes between scissors-type and needle-type knives in ESD performed by trainees in an ex vivo porcine model. METHODS: This study was conducted on trainee endoscopists who participated in ESD hands-on seminars held in August 2018 and September 2019. A total of 22 trainees from 13 institutions were divided into two groups according to their endoscopic experience. Under expert supervision, each trainee performed two ESDs in porcine models, namely, scissor-type knife (ESD-S) and needle-type knife (ESD-N). The efficacy and safety, including the procedure time and rates of self-completion, en bloc resection, and complications, were compared between ESD-S and ESD-N. In subgroup analysis, we also investigated the predictors associated with the difficulty of ESD for trainees using multivariate logistic regression analysis. RESULTS: Eight trainees had an experience of over 1000 endoscopies (senior trainee: S-Trainee), whereas the others had an experience of less than 1000 endoscopies (junior trainee: J-Trainee). Among the S-Trainees, no significant differences were observed in any treatment outcome between ESD-S and ESD-N. Among the J-Trainees, the total procedure and mucosal incision times were significantly shorter in ESD-S than in ESD-N [total procedure time: 16.5 min (range 10.0-31.0) vs. 22.3 min (range 10.0-38.0), P = 0.018; circumferential incision time: 10.0 min (range 6-16) vs. 17.0 min (range 5.0-31.5); P = 0.019]. Regarding complications, muscular injury occurred in two patients during ESD-N performed by J-Trainees; however, no muscular injury occurred during ESD-S. In subgroup analysis, ESD-N was an independent predictive factor of difficult ESD (odds ratio 5.28, 95% confidence interval 1.25-22.30; P = 0.024). CONCLUSIONS: This study revealed that trainees, particularly those who have experienced less than 1000 endoscopies, should opt for the scissor-type knife to perform ESD.