Randomised controlled, patient-blinded, multicentre, superiority trial to evaluate the efficacy of the line-attached sheath-type traction device for endoscopic submucosal dissection in patients with superficial gastric neoplasms.

INTRODUCTION: EndoTrac is a line-attached sheath-type traction device that enables us to control the direction and the force of traction during endoscopic submucosal dissection (ESD). The efficacy of EndoTrac for gastric ESD has not been fully verified. METHODS AND ANALYSIS: The G-Trac study is a multicentre (nine general hospitals and two university hospitals in Japan) collaborative trial assessing the efficacy of EndoTrac for gastric ESDs. Patients with superficial gastric neoplasms will be enrolled and randomly assigned to undergo either conventional ESD or EndoTrac ESD. Allocation will be stratified according to tumour location, operator experience and tumour diameter at an allocation rate of 1:1. The type of endoknife used will be confirmed before randomisation. The primary outcome, procedure time, will be compared between the groups in both intention-to-treat and per-protocol analyses using the Wilcoxon rank sum test. The efficacy-related, safety-related and device-related outcomes will be assessed in the secondary analysis. The planned sample size of the 142 patients in the two groups will enable us to detect a difference with a power of 80% by using the Wilcoxon rank sum test, assuming an effect size of 0.54, asymptotic relative efficiency of 0.864 and a two-sided type 1 error rate of 5%. ETHICS AND DISSEMINATION: This trial was approved by the certified review board of Kobe University (22 December 2022). The results from this trial will be disseminated through peer-review journals, presentations at national and international conferences, and data sharing with other researchers. TRIAL REGISTRATION NUMBER: jRCT1052220166.

Outcomes of endoscopic submucosal dissection for esophageal cancer with segmental absence of intestinal musculature.

BACKGROUND AND AIMS: Perforation during esophageal endoscopic submucosal dissection (ESD) typically results from electrical damage. However, there are cases in which perforation occurs because of segmental absence of intestinal musculature (SAIM) without iatrogenic muscular injury. We investigated the occurrence rate and clinical course of SAIM during esophageal ESD. METHODS: We conducted a retrospective review of esophageal ESDs performed between 2013 and 2019 at 10 centers in Japan. RESULTS: Five of 1708 (0.29%) patients received ESD for esophageal cancer and had SAIM. The median muscular defect size was 20 mm. All lesions were resected without discontinuation. After resection, 3 patients were closed with Endoloop. Four patients had mediastinal emphysema. All patients were managed conservatively. CONCLUSIONS: SAIM is a very rare condition that is usually only diagnosed during ESD. Physicians performing esophageal ESD should be aware of SAIM. When SAIM is detected, the ESD technique should be modified to prevent full-thickness perforation.

Assessment of predictive factors associated with the technical difficulty of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: Japanese multicenter retrospective study.

OBJECTIVES: Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) is performed for the treatment of lesions with varied backgrounds and factors. However, the predictive factors associated with the technical difficulty of ESD remain unknown in patients with varied lesions. Therefore, this study aimed to identify the predictive factors associated with the technical difficulty of ESD for ESCC using a retrospective cohort. METHODS: This multicenter, retrospective study was conducted in 10 hospitals in Japan. Consecutive patients who underwent esophageal ESD between January 2013 and December 2019 were enrolled. Lesions of subepithelial tumors, adenocarcinoma, and adenoma were excluded. Difficult lesions were defined as ESD requiring a long procedure time (≥120 min), perforation development, piecemeal resection, or discontinued ESD. In the present study, the clinical factors were assessed to identify the technical difficulty of ESD using univariate and multivariate analyses. RESULTS: Among 1708 lesions treated with esophageal ESD, eight subepithelial tumors, 44 adenocarcinomas, and two adenomas were excluded. Finally, 1505 patients with 1654 lesions were analyzed, and 217 patients with 217 lesions (13.1%) were classified as patients with difficult lesions. In multivariate analysis, the predictive factors associated with the technical difficulty of ESD were as follows: tumors with varices, tumors with diverticulum, antiplatelet use (discontinued), circumference of tumor (≥1/2), preoperative tumor size ≥30 mm, trainee, and nonhigh-volume center. CONCLUSION: This multicenter retrospective study identified the predictive factors associated with the technical difficulty of ESD for ESCC with varied backgrounds and factors.

Safety and efficacy of endoscopic submucosal dissection for superficial esophageal cancer with esophageal varices.

BACKGROUND: Heavy drinking is associated with esophageal cancer and esophageal varices. However, there are limited reports of endoscopic resection for esophageal cancer with esophageal varices. In this multicenter study, we clarified the safety and efficacy of endoscopic submucosal dissection for superficial esophageal cancer with esophageal varices. METHODS: In this multicenter, retrospective, observational study, patients underwent esophageal endoscopic submucosal dissection at 10 referral centers in Japan from January 2013 to December 2019. We analyzed characteristics including backgrounds and varices, treatment outcomes, and adverse events in cases with esophageal varices. RESULTS: A total of 1708 patients were evaluated, 27 (1.6%) of whom had esophageal varices. In patients with esophageal varices, the en bloc resection rate and R0 resection rate were 100% and 77.8%, respectively. Patients with esophageal varices had longer procedure times than patients without esophageal varices (p = 0.015). There was no significant difference in adverse events. There was no significant difference in procedure time and number of adverse events between patients who underwent pretreatment and those who did not. There was no significant difference in these outcomes for patients with lesions on varices compared to those without. Child-Pugh classification and location of the lesions also did not affect these outcomes. CONCLUSIONS: Esophageal cancer with esophageal varices could be treated endoscopically safely and effectively.

Efficacy of lidocaine injection method for esophageal endoscopic submucosal dissection: single-center, double-blind, randomized controlled trial.

BACKGROUND: Intraoperative body movements are one of the causes of difficulty in performing esophageal endoscopic submucosal dissection (ESD) under conscious sedation. The use of local anesthetics as local injection materials during ESD may overcome this difficulty. We clinically evaluated the lidocaine injection method (LIM) in the submucosa during esophageal ESD. METHODS: This was a single-center, prospective, double-blind, randomized trial. Patients who underwent esophageal ESD under conscious sedation from June 2018 to May 2021 were included in this study. In the LIM group, lidocaine was used for submucosal injection during ESD; in the control group, ESD was performed without lidocaine. The primary outcome was the presence of body movements. RESULTS: Fifty patients were enrolled and randomized in a 1:1 ratio in two groups. The incidence of body movements was significantly lower in the LIM group (12% [3/25]) than in the control group (48% [12/25]; P = 0.01). The median additional dose of midazolam was 2 mg (interquartile range [IQR]: 0.5-4 mg) in the LIM group and 4 mg (IQR: 3-6 mg) in the control group, which was significantly lower in the LIM group (P < 0.01). The median visual analog scale score for endoscopist satisfaction was 7 (IQR: 5-8) in the LIM group and 5 (IQR: 4-6.5) in the control group, which was significantly higher in the LIM group. CONCLUSIONS: LIM during esophageal ESD reduced body movements while decreasing the level of sedation. Therefore, LIM during esophageal ESD is an option for maintaining good sedation (UMIN000032804).

Peroral endoscopic myotomy for advanced achalasia with megaesophagus.

BACKGROUND: The outcomes of peroral endoscopic myotomy for advanced achalasia are not well known. This study aimed to evaluate the outcomes of peroral endoscopic myotomy for achalasia with megaesophagus, which is one of the characteristics of advanced achalasia. METHODS: In total, 234 patients with achalasia who underwent peroral endoscopic myotomy in our hospital from April 2015 to March 2019 were included in this retrospective observational study. Megaesophagus was defined as a maximum esophageal diameter of 6 cm or more. Outcomes, including clinical success (Eckardt score ≤ 3 without retreatment) at the 1-year follow-up, technical success, and perioperative complications, were investigated and compared between patients with and without megaesophagus. RESULTS: Eleven patients (4.7%) were diagnosed with megaesophagus. The clinical success rate achieved was 63.6% in patients with megaesophagus, with a significant decrease in the Eckardt score (6 vs. 2, p = 0.003) and integrated relaxation pressure (28 mmHg vs. 9 mmHg, p = 0.028). The technical success rate was 100%. However, patients with megaesophagus had a significantly lower clinical success rate than those without megaesophagus (63.6% vs. 96.0%, p = 0.002). Furthermore, patients with megaesophagus had significantly higher rates of major adverse events than those without megaesophagus (18.2% vs. 2.7%, p = 0.048). CONCLUSIONS: Peroral endoscopic myotomy improved achalasia-related symptoms, and this was technically feasible in patients with megaesophagus. However, the clinical success rate was somewhat low, and the rate of major adverse events was high. Therefore, peroral endoscopic myotomy should be carefully performed for advanced achalasia with megaesophagus.

Development of a preoperative risk-scoring system for predicting poor responders to peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is an effective treatment for esophageal motility disorder. However, some people are poor responders who will probably need retreatments, such as endoscopic pneumatic dilation or re-POEM, and a scoring system for the prediction of poor responders preoperatively has not yet been established. We aimed to develop and validate a preoperative scoring system for predicting poor responders. METHODS: Overall, 244 patients who underwent POEM for esophageal motility disorders in our hospital from April 2015 to March 2019 were retrospectively included in this study. Poor responders were defined as patients with any of following: (1) Eckardt score ≥3 at 1-year follow-up, (2) endoscopic findings of food retention at 1-year follow-up, and (3) retreatments within 1 year after POEM. A risk-scoring system for poor responders was developed based on multiple logistic regression analysis, and its performance was internally validated using bootstrapping. RESULTS: Forty patients were diagnosed as poor responders at the 1-year follow-up. In the multivariate study, points for risk scores were assigned for 4 independent risk factors as follows: pretreatment Eckardt score (1-point increments), previous treatments (4 points), sigmoid-type esophagus (4 points), and esophageal dilation grade ≥II (4 points). The scoring system could predict an estimated risk for poor responders and provided satisfactory discrimination (area under the receiver operating characteristic curve, 0.78; 95% confidence interval, 0.68-0.88) and calibration (slope = 0.93; 95% confidence interval, 0.62-1.31). CONCLUSIONS: A validated risk-scoring system for predicting poor responders preoperatively was established; this system could be useful for selecting treatment strategies and postoperative surveillance.

Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is used for acid-related diseases. Occasionally, small white protrusions called "stardust" gastric mucosa have been detected in the stomachs of some patients taking vonoprazan. AIMS: To determine the incidence of, and risk factors for, stardust gastric mucosa potentially induced by vonoprazan METHODS: In this study, we enrolled 19 503 patients who underwent endoscopy at our hospital between 2016 and 2019. Using propensity score matching, we retrospectively compared patients who received and did not receive vonoprazan. The two groups were matched for age, sex, history of proton pump inhibitor use, and atrophic gastritis. RESULTS: After 1:1 propensity score matching, each group comprised 2516 patients. Stardust gastric mucosa was detected significantly more often in the stomachs of patients receiving vonoprazan than those who had not received vonoprazan (4.9% vs 0.2%, P < 0.001). Its location was 70.7% in the upper third of the stomach, 29.3% in the middle third and none in the lower third. Histologically, this lesion had a mucus pool within a dilated duct surrounded by flattened glandular epithelium. The cumulative incidence rate of stardust gastric mucosa at 1, 2 and 3 years was 4.6%, 16.5% and 26.2%, respectively. The factors independently associated with the presence of stardust gastric mucosa were >205 days of vonoprazan oral intake (odds ratio [OR]: 6.99, 95% confidence interval [CI]: 4.60-10.88) and female sex (OR: 1.75, 95% CI: 1.20-2.58). CONCLUSIONS: Stardust gastric mucosa appeared more frequently in the stomachs of patients taking vonoprazan.

Comparison of the safety and efficacy of peroral endoscopic myotomy between octogenarians and non-octogenarians.

OBJECTIVES: This study compared the safety and efficacy of peroral endoscopic myotomy for esophageal motility disorders between octogenarians and non-octogenarians. METHODS: This retrospective observational study recruited 321 patients (28 octogenarians and 293 non-octogenarians) who underwent peroral endoscopic myotomy from two institutions. Clinical success (postoperative Eckardt score ≤ 3), technical success (completion of gastric and esophageal myotomy), and perioperative adverse events were compared between octogenarians and non-octogenarians. Perioperative adverse events were classified into major and minor adverse events based on the International Peroral Endoscopic Myotomy Survey criteria and were subdivided into technical and non-technical adverse events according to the presence of a direct causal relationship with the procedure. RESULTS: There were no significant differences in the rates of clinical success 1 year after treatment (100% vs. 97.3%, P = 0.64) and technical success (100% vs. 99.7%, P = 0.91) between octogenarians and non-octogenarians. Octogenarians had a higher incidence of perioperative adverse events (28.6% vs. 10.2%, P = 0.00097), particularly major adverse events (25.0% vs. 3.0%, P < 0.0001). There were no significant differences in the incidence of minor adverse events (7.1% vs. 7.9%, P = 0.67). Although there was no difference in the incidence of technical adverse events (10.7% vs. 9.2%, P = 0.74), octogenarians had a significantly higher incidence of non-technical adverse events (17.9% vs. 1.0%, P = 0.0002). CONCLUSIONS: There were no significant differences in short-term clinical success and technical success between octogenarians and non-octogenarians. However, octogenarians showed a significantly higher incidence of perioperative adverse events, particularly in major adverse events and non-technical adverse events. Peroral endoscopic myotomy for octogenarians should be carefully applied.

Endoscopic submucosal dissection involving the anal canal presents a risk factor for postoperative stricture.

BACKGROUND: Although postoperative strictures after endoscopic submucosal dissection (ESD) in the rectum are relatively rare, some rectal lesions require resection involving the anal canal, which is a narrow tract comprising squamous epithelium. To the best of our knowledge, no studies have investigated narrow anal canals when evaluating post-ESD strictures. This study aimed to evaluate the impact of resections involving the anal canal on postoperative stricture development. METHODS: Between April 2005 and October 2017, 707 rectal lesions were treated with ESD. We retrospectively investigated 102 lesions that required ≥ 75% circumferential resection. Risk factors for post-ESD stricture and, among patients with strictures, obstructive symptoms, and number of dilation therapies required were investigated. RESULTS: Post-ESD stricture occurred in 18 of 102 patients (17.6%). In the multivariate analysis, circumferential resection ≥ 90% and ESD involving the anal canal (ESD-IAC) were risk factors for postoperative strictures (P ≤ 0.0001 and 0.0115, respectively). Among the patients with strictures, obstructive symptoms were significantly related to anal strictures compared to rectal strictures (100% vs. 27.2%, P = 0.0041). Furthermore, the number of dilation therapies required was significantly greater among patients with anal strictures compared to those with rectal strictures (6.5 times vs. 2.7 times, P = 0.0263). CONCLUSION: Not only circumferential resection ≥ 90% but also ESD-IAC was a significant risk factor for the stricture after rectal ESD. Furthermore, anal strictures were associated with a significantly higher frequency of obstructive symptoms and larger number of required dilation therapies than were rectal strictures.

Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis.

INTRODUCTION: Elobixibat is a new laxative, but its efficacy and adverse events (AEs) are insufficiently examined compared with those of other laxatives. Hence, by propensity score (PS) matching, we compared the effects and AEs between elobixibat and lubiprostone. METHODS: We retrospectively analyzed 1,887 Japanese patients with chronic constipation (CC) treated at our hospital between October 2013 and April 2020. Enrolled patients were divided into three treatment groups, namely, elobixibat (10 mg daily) (E10 group, n = 293), lubiprostone (24 µg daily) (L24 group, n = 772), and lubiprostone (48 µg daily) (L48 group, n = 822), as their first treatment. We then investigated the changes on the weekly average number of spontaneous bowel movements, stool consistency scores (SCSs), and AEs starting from the baseline until the end of the 2-week treatment. To adjust for patients' background, we performed one-to-one nearest neighbor matching without replacement between elobixibat- and lubiprostone-treated patients according to the individual estimated PSs. RESULTS: After treatment, for SCSs, both the L24 and L48 groups significantly improved compared with the E10 group (p < 0.05), but their stools were soft (Bristol Stool Form Scale: 4.8). Notably, the E10 group had less frequent AEs than the L24 group (26 [9.0%] vs. 43 [14.8%], p = 0.03). Particularly, nausea was significantly less in the E10 group than that in the L48 group (2 [0.7%] vs. 7 [2.4%], p = 0.01). CONCLUSION: Elobixibat is a beneficial drug for patients with mildly symptomatic CC and is safe to use, given its few AEs.

Successful treatment of an esophageal perforation that occurred during endoscopic submucosal dissection for esophageal cancer using polyglycolic acid sheets and fibrin glue.

A 74-year-old female, who was diagnosed with superficial esophageal cancer, underwent endoscopic submucosal dissection (ESD) at another hospital, but a perforation occurred during the procedure. The perforation was closed with endoscopic clips, and the ESD was halted. The patient was referred to our hospital, and ESD was retried. There was severe fibrosis around the lesion, and injections into the submucosal layer were difficult. In addition, it was not possible to identify the submucosal layer, and making an oral-side incision caused a large perforation along the incision line. As continuing the submucosal dissection with an endoknife was considered difficult, the lesion was finally resected with hybrid ESD using a snare. The perforation was closed using polyglycolic acid (PGA) sheets and fibrin glue. Endoscopy performed 6 days later showed that the defect had been closed, and no contrast leakage was detected. Follow-up endoscopy conducted 3 months after the ESD showed ulcer healing at the dissection site and scar formation, but no residual tumor or esophageal stricture was noted. Our experience suggests that the use of PGA sheets with fibrin glue is a feasible, safe, and effective way of treating large esophageal perforations during ESD.

A novel ability of endocytoscopy to diagnose histological grade of differentiation in T1 colorectal carcinomas.

BACKGROUND AND STUDY AIMS: Endocytoscopic images closely resemble histopathology. We assessed whether endocytoscopy could be used to determine T1 colorectal cancer histological grade. PATIENTS AND METHODS: Endocytoscopic images of 161 lesions were divided into three types: tubular gland lumens, unclear gland lumens, and fused gland formations on endocytoscopy (FGFE). We retrospectively compared endocytoscopic findings with histological grade in the resected specimen superficial layer, and examined the incidence of risk factors for lymph node metastasis. RESULTS: Of the 118 eligible lesions, the sensitivity, specificity, accuracy, negative predictive value, and positive likelihood ratio of tubular or unclear gland lumens to identify well-differentiated adenocarcinomas were 91.0 %, 93.1 %, 91.5 %, 77.1 %, and 13.20, respectively. To identify moderately differentiated adenocarcinomas for FGFE, these values were 93.1 %, 91.0 %, 91.5 %, 97.6 %, and 10.36, respectively. In the 35 lesions with FGFE, the rates of massive invasion, lymphovascular infiltration, and tumor budding were 97.1 %, 60.0 %, and 37.1 %, respectively. CONCLUSIONS: Endocytoscopy could be used to diagnose T1 colorectal cancer histological grade, and FGFE was a marker for recommending surgery.