Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. METHODS: Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. RESULTS: Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). CONCLUSIONS: This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

Chronological Changes in Mucosal Deformity by Endoscopic Suturing after Gastric Endoscopic Submucosal Dissection: A Multicenter Retrospective Analysis.

INTRODUCTION: Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing. METHODS: Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated. RESULTS: A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively. DISCUSSION/CONCLUSION: The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

Prophylactic use of steroids for a mucosal defect with a circumference of less than three-fourths prevents both symptomatic and asymptomatic stricture after esophageal endoscopic submucosal dissection.

BACKGROUND: Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture. METHODS: In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR). RESULTS: In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred. CONCLUSION: Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.

Convolutional neural network-based system for endocytoscopic diagnosis of early gastric cancer.

BACKGROUND: Endocytoscopy (ECS) aids early gastric cancer (EGC) diagnosis by visualization of cells. However, it is difficult for non-experts to accurately diagnose EGC using ECS. In this study, we developed and evaluated a convolutional neural network (CNN)-based system for ECS-aided EGC diagnosis. METHODS: We constructed a CNN based on a residual neural network with a training dataset comprising 906 images from 61 EGC cases and 717 images from 65 noncancerous gastric mucosa (NGM) cases. To evaluate diagnostic ability, we used an independent test dataset comprising 313 images from 39 EGC cases and 235 images from 33 NGM cases. The test dataset was further evaluated by three endoscopists, and their findings were compared with CNN-based results. RESULTS: The trained CNN required 7.0 s to analyze the test dataset. The area under the curve of the total ECS images was 0.93. The CNN produced 18 false positives from 7 NGM lesions and 74 false negatives from 28 EGC lesions. In the per-image analysis, the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 83.2%, 76.4%, 92.3%, 93.0%, and 74.6%, respectively, with the CNN and 76.8%, 73.4%, 81.3%, 83.9%, and 69.6%, respectively, for the endoscopist-derived values. The CNN-based findings had significantly higher specificity than the findings determined by all endoscopists. In the per-lesion analysis, the accuracy, sensitivity, specificity, PPV, and NPV of the CNN-based findings were 86.1%, 82.1%, 90.9%, 91.4%, and 81.1%, respectively, and those of the results calculated by the endoscopists were 82.4%, 79.5%, 85.9%, 86.9%, and 78.0%, respectively. CONCLUSIONS: Compared with three endoscopists, our CNN for ECS demonstrated higher specificity for EGC diagnosis. Using the CNN in ECS-based EGC diagnosis may improve the diagnostic performance of endoscopists.

Prophylactic clip closure for mucosal defects is associated with reduced adverse events after colorectal endoscopic submucosal dissection: a propensity-score matching analysis.

BACKGROUND: It is unclear whether prophylactic endoscopic closure after colorectal endoscopic submucosal dissection (ESD) reduces the risk of postoperative adverse events due to variability in lesion characteristics. Therefore, we conducted a retrospective study using propensity score matching to evaluate the efficacy of prophylactic clip closure in preventing postoperative adverse events after colorectal ESD. METHODS: This single-center retrospective cohort study included 219 colorectal neoplasms which were removed by ESD. The patients were allocated into the closure and non-closure groups, which were compared before and after propensity-score matching. Post-ESD adverse events including major and minor bleeding and delayed perforation were compared between the two groups. RESULTS: In this present study, 97 and 122 lesions were allocated to the closure and non-closure groups, respectively, and propensity score matching created 61 matched pairs. The rate of adverse events was significantly lower in the closure group than in the non-closure group (8% vs. 28%, P = 0.008). Delayed perforation occurred in two patients in the non-closure group, whereas no patient in the closure group developed delayed perforation. In contrast, there were no significant differences in other postoperative events including the rate of abdominal pain; fever, white blood cell count, and C-reactive protein; and appetite loss between the two groups. CONCLUSIONS: Propensity score matching analysis demonstrated that prophylactic closure was associated with a significantly reduced rate of adverse events after colorectal ESD. When technically feasible, mucosal defect closure after colorectal ESD may result in a favorable postoperative course.

Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.

BACKGROUND: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. METHODS: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. RESULTS: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). CONCLUSIONS: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients.

Circularity Is a Potential Noninvasive Diagnostic Indicator to Differentiate Gastric Submucosal Tumors.

BACKGROUND AND AIMS: Noninvasive, imaging diagnosis of gastrointestinal mesenchymal tumors (GIMTs) is still difficult. This study aimed to develop a novel diagnostic method of GIMTs via endoscopic ultrasonography (EUS) using circularity. METHODS: In a derivation series, we retrospectively collected 50 GIMTs 2-5 cm in diameter of two institutions. After selecting one EUS still image showing the maximal area per lesion, two endoscopists who were blind to the histological diagnosis assessed circularity, a surrogate indicator of roundness (range, 0-1; 1 = a true circle), with an image-analyzing software. Median circularity of three types of GIMT was compared, and the cutoff value to differentiate a group from other groups was presented by drawing a receiver operating characteristic curve. Subsequently, we assessed the diagnostic ability of circularity in 91 GIMTs which were retrospectively collected from the other two institutions by using the optimal cutoff value presented in the derivation series. RESULTS: The circularity in leiomyomas indicated 0.70 and was significantly lower than that of gastrointestinal stromal tumors (0.89), schwannomas (0.90), and their combined group. When leiomyomas were diagnosed as the circularity of <0.8305, which was presented as the optimal cutoff value, the diagnostic accuracy, sensitivity, and specificity in the validation series were 73.6%, 80.0%, and 72.4%, respectively. CONCLUSION: The data demonstrated that leiomyomas significantly exhibited more distortion than other GIMTs. That implies that the difference in shape, which is objectively determined as circularity, is useful to noninvasively discriminate leiomyomas from other GIMTs.

Bilateral Risk Assessments of Surgery and Nonsurgery Contribute to Providing Optimal Management in Early Gastric Cancers after Noncurative Endoscopic Submucosal Dissection: A Multicenter Retrospective Study of 485 Patients.

BACKGROUND AND AIMS: Surgery is recommended in early gastric cancer (EGC) after noncurative endoscopic submucosal dissection (ESD), although observation can be an alternative. We aimed to develop a tailor-made treatment strategy for noncurative EGCs by comparing the lymph node metastasis risk (LNMR) and the surgical risk. METHODS: We retrospectively identified 485 patients with differentiated-type, noncurative EGCs removed by ESD and classified them into two groups: a surgery-preferable group and an observation-preferable group, according to the clinical courses. Subsequently, LNMR and surgery-related death risk were assessed using a published scoring system and a risk calculator for gastrectomy, respectively. Finally, we investigated the optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to efficiently allocate these cases into either of two groups, surgery-preferable or observation-preferable. RESULTS: In 485 patients (surgery in 322, observation in 163), 57 and 428 patients were classified into the surgery-preferable group and the observation-preferable group, respectively. The optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to allocate the cases to the two preferable groups was 7.85 with the highest area under the curve (0.689). When cases with >7.85 LNMR over the surgery-related death risk were allocated into the surgery-preferable group and vice versa, the discriminability was 73.2%, which was sufficiently higher than that in the clinical decision (44.5%). CONCLUSION: Personalized comparison of LNMR and surgery-related death risk is helpful to provide a favorable treatment option for each patient with EGCs after noncurative ESD.

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software, SAMURAI model.

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.

Three-dimensional visualization improves the endoscopic diagnosis of superficial gastric neoplasia.

BACKGROUND: Three-dimensional (3D) technology has been used in many fields, including flexible endoscopy. We evaluated the usefulness of 3D visualization for endoscopically diagnosing superficial gastric neoplasia. METHODS: Twelve participants (4 novices, 4 trainees and 4 experts) evaluated two-dimensional (2D) and 3D endoscopic still images of 28 gastric neoplasias, obtained before ESD with white-light imaging (WLI) and narrow-band imaging (NBI). Assessments of the delineation accuracy of tumor extent and tumor morphology under 2D and 3D visualization were based on the histopathological diagnosis of ESD specimens. Participants answered visual analog scale (VAS) questionnaires (0-10, worst to best) concerning the (a) ease of recognition of lesion morphology, (b) lesion extent and (c) comprehensive endoscopic cognition under 2D and 3D visualization. The endpoints were the accuracy of tumor extent and morphology type and the degree of confidence in assessing (a)-(c). RESULTS: The delineation accuracy of lesion extent [mean (95% confidence interval)] with WLI under 3D visualization [60.2% (56.1-64.3%)] was significantly higher than that under 2D visualization [52.3% (48.2-56.4%)] (P < 0.001). The accuracy with NBI under 3D visualization [70.3% (66.8-73.7%)] was also significantly higher than that under 2D visualization [64.2% (60.7-67.4%)] (P < 0.001). The accuracy of the morphology type with NBI under 3D visualization was significantly higher than that under 2D visualization (P = 0.004). The VAS for all aspects of endoscopic recognition under 3D visualization was significantly better than that under 2D visualization (P < 0.01). CONCLUSIONS: Three-dimensional visualization can enhance the diagnostic quality for superficial gastric tumors.

Three-dimensional flexible endoscopy enables more accurate endoscopic recognition and endoscopic submucosal dissection marking for superficial gastric neoplasia: a pilot study to compare two- and three-dimensional imaging.

BACKGROUND: Three-dimensional (3D) visualization offers better depth recognition than two-dimensional (2D) imaging, thus helping to provide more useful information. We compared 3D and 2D endoscopy with regard to endoscopic recognition and endoscopic submucosal dissection (ESD) marking for superficial gastric neoplasia. METHODS: ESD marking was performed on half of a neoplasia margin under 2D observation and the on other half under 3D observation for 28 gastric lesions (26 early gastric cancers and 2 adenomas). The accuracy of ESD marking was evaluated based on the distance between the pathological and endoscopic neoplasia margins measured on histology sections of ESD specimens. The technical ease of ESD marking and endoscopic lesion recognition (lesion morphology, lesion extent, and comprehensive endoscopic cognition) were assessed using visual analog scale (VAS) questionnaires. RESULTS: The mean distance between the pathological and endoscopic margins under 3D observation (1.03 ± 0.80 mm) was significantly (p = 0.002) shorter than that under 2D observation (1.94 ± 1.96 mm). The VAS for technical ease of ESD marking under 3D observation was significantly better (p < 0.01) than that under 2D observation. The VAS for all aspects of endoscopic recognition under 3D observation was significantly better (p < 0.01) than under 2D observation. CONCLUSIONS: 3D flexible endoscopy achieved more accurate endoscopic recognition and ESD marking for superficial gastric neoplasia than a 2D approach in a clinical setting of ESD.

Usefulness of the flexible traction method in gastric endoscopic submucosal dissection: an in-vivo animal study.

BACKGROUND: An appropriate traction of the target lesion is a key for a safe and secure ESD procedure. We proposed the flexible traction method (F-trac) which provided an optimal traction using an endoscopic hand-suturing (EHS) and investigated the usefulness of this technique for gastric ESD in-vivo porcine model. METHODS: In the F-trac method, a lesion was suspended by pulling proximal side of endoscope which was connected to the contralateral side with a barbed suture using the EHS technique just before starting the submucosal dissection. A single endoscopist performed conventional ESD (C-ESD) and F-trac ESD alternately for a total of ten simulating lesions of 3 cm in diameter in a live porcine stomach. The pig was rotated so that each lesion was positioned in the direction of the gravity. The procedure time, technical accuracy, adverse events, and the number of additional injection to the submucosal layer during dissection were evaluated. RESULTS: The total ESD procedure time in the F-trac group was significantly shorter than in C-ESD group (19.0 min vs. 30.6 min, p = 0.039). There were no significant differences between both groups in muscular layer damage, sample damage, perforation, and intraoperative bleeding. The number of additional injection in the F-trac group was significantly fewer than that in C-ESD group (0 times vs. 4.4 times, p = 0.027). CONCLUSIONS: In gastric ESD, F-trac might be useful for shortening the total procedure time. This method can facilitate optimal traction without disturbing the endoscopic visualization and the movement of endoscope.

Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

BACKGROUND: The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. RESULTS: One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. CONCLUSION: On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE.

Correction: Potential for expanded application of endoscopic hand suturing: A pilot study of 15 cases.

[This corrects the article DOI: 10.1055/a-2284-9492.].

Potential for expanded application of endoscopic hand suturing: A pilot study of 15 cases.

Endoscopic hand suturing (EHS) was first developed to firmly close a mucosal defect following endoscopic submucosal dissection and has the potential for expanded applications. This study aimed to investigate the feasibility and safety of EHS in various clinical settings. In this single-center pilot study, 15 patients who had diseases with potential indications for EHS were prospectively recruited. Technical success, clinical success after the procedure, and severe EHS-related adverse events (AEs) were evaluated. EHS was applied for defect closure after gastric subepithelial lesion removal under laparoscopic observation (n = 9), defect closure after rectal endoscopic full-thickness resection (EFTR) (n = 2), defect closure after thoracoscopy-assisted esophageal EFTR (n = 1), mucosal closure for gastric ulcer bleeding (n = 1), mucosal closure after peroral endoscopic myotomy (POEM) (n = 1), and postoperative anastomotic leak (n = 1). EHS was completed without severe AEs and the clinical courses were also favorable in 13 patients (87%). The median suturing time was 61 minutes. In patients with POEM and anastomotic leak, EHS was discontinued because of the narrow lumen. In conclusion, EHS appears feasible and safe in situations.

Tumor size discrepancy between endoscopic and pathological evaluations in colorectal endoscopic submucosal dissection.

BACKGROUND: Tumor size impacts the technical difficulty and histological curability of colorectal endoscopic submucosal dissection (ESD); however, the preoperative evaluation of tumor size is often different from histological assessment. Analyzing influential factors on failure to obtain an accurate tumor size evaluation could help prepare optimal conditions for safer and more reliable ESD. AIM: To investigate the tumor size discrepancy between endoscopic and pathological evaluations and the influencing factors. METHODS: This was a retrospective study conducted at a single institution. A total of 377 lesions removed by colorectal ESD at our hospital between April 2018 and March 2022 were collected. We first assessed the difference in size with an absolute percentage of the scaling discrepancy. Subsequently, we compared the clinicopathological characteristics of the correct scaling group (> -33% and < 33%) with that of the incorrect scaling group (< -33% or > 33%), which was further subdivided into the underscaling group (-33% or less of the discrepancy) and overscaling group (33% or more of the discrepancy), respectively. As secondary outcome measures, parameters on size estimation were compared between the underscaling and correct scaling groups, as well as between the overscaling and correct scaling groups. Finally, multivariate analysis was performed in terms of the following relevant parameters on size estimation: Pathological size, location, and possible influential factors (P < 0.1) in the univariate analysis. RESULTS: The mean of absolute percentage in the scaling discordance was 21%, and 91 lesions were considered to be incorrectly estimated in size. The incorrect scaling was significantly remarkable in larger lesions (40 mm vs 28 mm; P < 0.001) and less experience (P < 0.001), and these two factors were influential on the underscaling (75 lesions; P < 0.001). Conversely, compared with the correct scaling group, 16 lesions in the overscaling group were significantly small (20 mm vs 28 mm; P < 0.001), and the small lesion size was influential on the overscaling (P = 0.002). CONCLUSION: Lesions indicated for colorectal ESD tended to be underestimated in large tumors, but overestimated in small ones. This discrepancy appears worth understanding for optimal procedural preparation.

A successful treatment case of refractory hemorrhagic ulcer with eosinophilic gastritis by endoscopic hand suturing.

A 78-year-old man was admitted to our hospital with a tarry stool. Esophagogastroduodenoscopy identified tiny oozing on the greater curvature at the antrum. Despite repeated endoscopic hemostasis by coagulation and clipping, rebleeding occurred. On the third rebleeding, we performed endoscopic hand suturing to completely close the ulcer surface. Biopsy showing massive infiltration of eosinophils at the ulcer edge indicated eosinophilic gastritis. After the endoscopic closure by endoscopic hand suturing, the patient had no symptoms of bleeding thereafter and was discharged 19 days after the procedure by taking oral prednisolone. The patient remained well and was continuously treated with a small dose of steroids in outpatient. This is the first case report of the successful application of endoscopic hand suturing to a refractory hemorrhagic ulcer. Further accumulation of clinical experiences is desired to confirm the usefulness of this technique for the prevention of refractory ulcer bleeding.