The Japan Gastroenterological Endoscopy Society has prepared Guidelines for Endoscopic Practice in Nonvariceal Upper Gastrointestinal Bleeding as part of the initiative to develop evidence-based endoscopic practice guidelines. Hemorrhagic gastroduodenal (peptic) ulcers are the primary cause of nonvariceal upper gastrointestinal bleeding. With the advent of a super-aged society, the cases caused by Helicobacter pylori are on the decline, whereas those caused by drugs (e.g. aspirin) have been increasing. Endoscopic hemostasis is currently the first-line treatment for nonvariceal upper gastrointestinal bleeding, and various methods have been devised for this purpose. It is recommended to stabilize the vital signs of the patient before and after endoscopic hemostasis with appropriate management based on an assessment of the severity of illness, in addition to the administration of acid secretion inhibitors. These guidelines describe the evaluation and initial treatment of nonvariceal upper gastrointestinal bleeding, as well as the selection of endoscopic hemostasis for nonvariceal upper gastrointestinal bleeding and its management after endoscopic hemostasis. This is achieved by classifying nonvariceal upper gastrointestinal bleeding into two main categories, namely, peptic ulcer and other types of gastrointestinal bleeding. We prepared statements for any available literature with supporting evidence, including the levels of evidence and recommendations. New evidence has been pooled since the publication of the first edition in this area; however, the levels of evidence and recommendations mostly remain low.

Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract.

Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect.

Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h.

An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding.

This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations.

Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays.

The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.

To evaluate the risks of colorectal endoscopic submucosal dissection (ESD) in older adult patients, given the increasing number of ESD in an aging population.

We conducted a retrospective cohort study using the Japanese nationwide database from 2012 to 2023. Patients aged 60 years or older who underwent colorectal ESD were included. The primary outcome was overall adverse events (AEs), including in-hospital mortality, procedure-related perforation, abdominal surgery, aspiration pneumonia, and significant postoperative bleeding and thromboembolic events. We first examined the association between age and AEs using multivariable regression adjusting for patient characteristics. Next, to explore the factors associated with overall AEs in those aged 85 years or older, we fit a multivariable logistic regression.

The study included 143,925 cases. Age distribution was as follows: 60-64 (13.5%), 65-74 (44.9%), 75-84 (35.8%), and ≥85 (5.8%) years. The prevalence of overall AEs increased with age: 5.3% for ages 60-64 years, 7.9% for ages 85-89 years, and 9.2% for ages 90 years or older. Patients aged 85 years or older had a higher prevalence of overall AEs compared with patients aged 60-64 years, with an adjusted odds ratio of 1.19 (95% confidence interval: 1.07-1.33, P < 0.01) for those aged 85-89 years and an adjusted odds ratio of 1.45 (95% confidence interval: 1.16-1.80, P < 0.01) for those aged 90 years or older. Most AEs in patients aged 85 years or older were due to significant postoperative bleeding, with anticoagulant use and body mass index ≥30 identified as key risk factors.

The risks of AEs during colorectal ESD increase with age, particularly in patients aged 85 years or older.

 The effectiveness of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) is uncertain among patients on anticoagulants. We therefore aimed to assess this effectiveness using data from a large multicenter study.

 We used the ABCD-J study database to analyze delayed bleeding among 34 455 colorectal ESD cases from 47 Japanese institutions. Delayed bleeding rates among the no/partial and complete closure groups were compared in patients on direct oral anticoagulants (DOACs) or warfarin. Propensity score matching was used for baseline characteristics to reduce the effects of selection bias.

 Overall, data from 1478 patients on anticoagulants who underwent colorectal ESD were examined. After propensity score matching, the complete and no/partial closure groups were compared in 212 patients on DOACs and 82 on warfarin. The complete closure group showed a significantly lower delayed bleeding rate in patients receiving DOACs (10.8 % vs. 5.2 %, absolute risk reduction [ARR] 5.7 %, P = 0.048) and warfarin (17.1 % vs. 6.1 %, ARR 11.0 %, P = 0.049). Additionally, complete closure significantly reduced the risk of delayed bleeding among patients taking DOACs for right-sided lesions (ARR 6.7 %, P = 0.04), whereas no risk reduction was observed for left-sided (P > 0.99) or rectal (P = 0.50) lesions. A similar trend was observed among patients on warfarin.

 Prophylactic complete clip closure after colorectal ESD significantly reduced the delayed bleeding rate in patients receiving DOACs or warfarin. It should be performed after ESD, particularly for right-sided lesions.

Development of a simple, optimized closure method for mucosal defects left by gastric endoscopic submucosal dissection (ESD) is warranted. Herein, we developed a novel and dedicated closure device called FLEXLOOP and aimed to assess feasibility and safety of the closure using FLEXLOOP following gastric ESD.

This multicenter, prospective, observational study enrolled patients clinically diagnosed with gastric neoplasms < 30 mm in size. Following gastric ESD, closure of the mucosal defect was performed using a FLEXLOOP with standard clips. The primary outcome was the complete closure rate. The secondary outcomes were procedure time, number of clips, sustained closure rate on second-look endoscopy on postoperative days (PODs) 5 to 7, and rate of post-ESD bleeding.

Overall, 35 patients were included in this study. The median specimen size was 32 mm. The mucosal defect was completely closed in 31 patients (89%; 95% confidence interval, 73%-99%) and incompletely closed in four patients (11%). Median closure time was 11 minutes and median number of clips was 10. Second-look endoscopy performed on PODs 5 to 7 demonstrated sustained, partially sustained, and unsustained closures in seven (20%), 22 (63%), and six patients (17%), respectively. Post-ESD bleeding and complications related to FLEXLOOP were not observed.

Closure using FLEXLOOP is feasible and safe. Our technique using this new device can be an attractive option for more easily closing mucosal defects. However, further clinical research is warranted to confirm that this technique can prevent delayed complications.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer. However, post-ESD bleeding presents significant risks. Closing mucosal defects after ESD may reduce the incidence of post-ESD bleeding. Currently, no optimal closure method exists. Therefore, we invented clip-line closure using the reopenable-clip over-the-line method (ROLM) and evaluated its efficacy in preventing post-ESD bleeding.

We retrospectively reviewed data from patients who underwent gastric ESD between January 2012 and March 2024. Patients were categorized into 2 groups: the nonclosure group (mucosal defect remained unclosed) and the ROLM group (defect was closed using ROLM). Baseline characteristics of patients, distribution of bleeding risk factors, and incidence and timing of post-ESD bleeding were compared between the groups. Propensity score matching was used to minimize potential bias.

After propensity score matching, 162 ESDs were performed for 168 lesions in the nonclosure group, whereas 160 ESDs were performed for 168 lesions in the ROLM group. The mean long diameter of the mucosal defects, procedure time for ROLM, and number of clips required for ROLM were 45.9 mm, 35.6 minutes, and 33.2, respectively. All mucosal defects resulting from the ESD were fully closed using ROLM. The post-ESD bleeding rate in the ROLM group was significantly lower (1.8%; 3 of 168 lesions) than in the nonclosure group (7.7%; 13 of 168 lesions; P = .02).

ROLM is feasible for mucosal defect closure after gastric ESD and effectively prevents post-ESD bleeding in high-risk patients, addressing a significant gap in existing methods.

Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs.

We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding.

The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran.

The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.

The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants.

This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%.

Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed.

Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants.

UMIN Clinical Trial Registry (UMIN000036734).

During intraoperative bleeding in endoscopic submucosal dissection (ESD), switching to spray coagulation may be beneficial compared with the continuous use of swift coagulation and can reduce the need for hemostatic forceps. We retrospectively assessed the effectiveness of spray modes on intraoperative bleeding during gastric ESD.

A total of 316 bleeding events (156 in the Swift group and 160 in the Spray group) were consecutively recorded. In the Swift group, hemostasis was performed using the swift mode with a retracted tip of the needle-type knife, followed by the hemostatic forceps. In the Spray group, bleeding was treated in a stepwise manner: the swift mode, the spray mode, and the hemostatic forceps. All bleeding events were assigned to one of two groups by an endoscopist who retrospectively reviewed the videos. We compared the use of hemostatic forceps, the total hemostatic time, and the cumulative hemostasis rate between the two groups.The use of hemostatic forceps was significantly lower in the Spray group than in the Swift group (32.7% vs. 13.8%, P < 0.001). There was no significant difference in the total hemostatic time (Swift group, 20 s.; Spray group, 16 s.; P = 0.42), whereas the cumulative hemostasis rate with the knife was significantly higher in the Spray group (P = 0.007).

The results suggested that spray coagulation from the tip of the needle-type knife could reduce the use of hemostatic forceps. In gastric ESD, spray coagulation may facilitate the hemostasis of intraoperative bleeding.

Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable.

We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants.

Delayed bleeding occurred in 40 of 1,708 patients (2.3%). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used.

Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Sarcopenia has been reported to be associated with short-term outcomes after gastric endoscopic submucosal dissection (ESD). The "strength, assistance with walking, rising from a chair, climbing stairs, and falls" (SARC-F) questionnaire has been widely used as a screening tool for sarcopenia; however, SARC-F combined with body mass index and age (SARC-F+EBM) has recently been reported to be more useful than SARC-F alone. This study aimed to investigate the association between sarcopenia, measured using SARC-F+EBM, and short-term outcomes after gastric ESD.

Patients who underwent gastric ESD at our institution between May 2020 and June 2023 were included, and their medical records were reviewed retrospectively. A SARC-F+EBM score ≥ 12 indicated sarcopenia. We evaluated the incidence of adverse events and the length of hospital stay in the sarcopenia and non-sarcopenia groups.

Overall, 263 patients (64 and 199 in the sarcopenia and non-sarcopenia groups, respectively) were investigated. The incidence of adverse events with a Common Terminology Criteria for Adverse Events grade ≥ 3 was not significantly different between the sarcopenia and non-sarcopenia groups (6.2% vs. 8.5%, p = 0.791). The proportion of patients with an extended hospital stay (≥ 10 days) was significantly higher in the sarcopenia group than that in the non-sarcopenia group (12.5% [8/64] vs. 3.5% [7/199], p = 0.012). Multivariate analysis showed that sarcopenia and lesions that present technical difficulty in ESD were independent risk factors for extended hospital stays (≥ 10 days). Of the eight cases having extended hospital stays in the sarcopenia group, four were due to the management after gastric ESD, three were due to family circumstances, and one was due to decreased activities of daily living.

Sarcopenia is not a predictor of adverse events associated with gastric ESD. However, patients with sarcopenia may be hospitalized for longer owing to non-ESD-related factors.

The purpose of this study was to evaluate the feasibility of a simple method named aspiration and coagulation (AC) for reducing the risk of postoperative bleeding after gastric endoscopic submucosal dissection (ESD).

Data were retrospectively reviewed and collected from the medical records and endoscopic and pathologic reports about consecutive patients who underwent ESD for early gastric cancer or precancerous lesions or gastric submucosal lesions from January 2016 to December 2021 at the Seventh Medical Center of Chinese PLA General Hospital. Enrolled patients who underwent the AC method during ESD were included in the AC group, and the others were included in the control group. Propensity score (PS) matching (1:1 match) was used to compensate for the differences that might affect post-ESD bleeding. Massive hemorrhage and overall delayed bleeding events after gastric ESD were compared between the two groups.

Propensity score matching analysis created 242 matched pairs in the study. Characteristics of the subjects such as age and use of antithrombotic drugs were all similar between the two groups after PS matching. The rate of massive hemorrhage and overall delayed bleeding was both significantly lower in the AC group than in the control (0.4% vs. 3.3% for massive hemorrhage, P = 0.037, and 1.2% vs. 5.0% for overall delayed bleeding, P = 0.032), predominantly in mucosal lesions (0.6% vs. 4.4% for massive hemorrhage, P = 0.032, and 1.2% vs. 5.6% for overall delayed bleeding, P = 0.031).

Our study demonstrated that the AC method effectively decreased delayed bleeding events after ESD.

The management of bleeding is an important aspect of endoscopic surgery to avoid excessive blood loss and minimize pain. In clinical settings, sprayable hemostatic particles are used for their easy delivery, adaptability to irregular shapes, and rapid hydration. However, conventional hemostatic particles present challenges associated with tissue adhesion. In a previous study, we reported tissue adhesive microparticles (C10-sa-MPs) derived from Alaska pollock gelatin modified with decyl groups (C10-sa-ApGltn) using secondary amines as linkages. The C10-sa-MPs adhere to soft tissues through a hydration mechanism. However, their application as a hemostatic agent was limited by their long hydration times, attributed to their high hydrophobicity. In this study, we present a new type microparticle, C10-am-MPs, synthesized by incorporating decanoyl group modifications into ApGltn (C10-am-ApGltn), using amide bonds as linkages. C10-am-MPs exhibited enhanced hydration characteristics compared to C10-sa-MPs, attributed to superior water absorption facilitated by amide bonds rather than secondary amines. Furthermore, C10-am-MPs demonstrated comparable tissue adhesion properties and underwater adhesion stability to C10-sa-MPs. Notably, C10-am-MPs exhibited accelerated blood coagulation in vitro compared to C10-sa-MPs. The application of C10-am-MPs in an in vivo rat liver hemorrhage model resulted in a hemostatic effect comparable to a commercially available hemostatic particle. These findings highlight the potential utility of C10-am-MPs as an effective hemostatic agent for endoscopic procedures and surgical interventions.

Gastric cancer is one of the most common malignant tumors in the digestive system in China. Few comprehensive practice guidelines for early gastric cancer in China are currently available. Therefore, we created the Chinese national clinical practice guideline for the prevention, diagnosis, and treatment of early gastric cancer.

This clinical practice guideline (CPG) was developed in accordance with the World Health Organization's recommended process and with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) in assessing evidence quality. We used the Evidence to Decision framework to formulate clinical recommendations to minimize bias and increase transparency in the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guidelines to ensure completeness and transparency of the CPG.

This CPG contains 40 recommendations regarding the prevention, screening, diagnosis, treatment, and follow-up of early gastric cancer based on available clinical studies and guidelines. We provide recommendations for the timing of Helicobacter pylori eradication, screening populations for early gastric cancer, indications for endoscopic resection and surgical gastrectomy, follow-up interval after treatment, and other recommendations.

This CPG can lead to optimum care for patients and populations by providing up-to-date medical information. We intend this CPG for widespread adoption to increase the standard of prevention, screening, diagnosis, treatment, and follow-up of early gastric cancer; thereby, contributing to improving national health care and patient quality of life.

Second-look endoscopy (SLE) to prevent recurrent bleeding in patients with peptic ulcer disease (PUD) and those undergoing endoscopic submucosal dissection (ESD) is routinely being performed. Conflicting evidence exists regarding efficacy, risk, benefit, and cost-effectiveness.

To identify the role and effectiveness of SLE in ESD and PUD, associated rebleeding and PUD-related outcomes like mortality, hospital length of stay, need for endoscopic or surgical intervention and blood transfusions.

A systematic review of literature databases PubMed, Cochrane, and Embase was conducted from inception to January 5, 2023. Randomized controlled trials that compared patients with SLE to those who did not have SLE or evaluated the role of prophylactic hemostasis during SLE compared to other conservative interventions were included. The study was conducted per PRISMA guidelines, and the protocol was registered in PROSPERO (ID CRD42023427555:). RevMan was used to perform meta-analysis, and Mantel-Haenszel Odds ratio (OR) were generated using random effect models.

A total of twelve studies with 2687 patients were included in our systematic review and meta-analysis, of which 1074 patients underwent SLE after ESD and 1613 patients underwent SLE after PUD-related bleeding. In ESD, the rates of rebleeding were 7% in the SLE group compared to 4.4% in the non-SLE group with OR 1.65, 95% confidence intervals (CI) of 0.96 to 2.85; P = 0.07, whereas it was 11% in the SLE group compared to 13% in the non-SLE group with OR 0.8 95%CI: 0.50 to 1.29; P = 0.36. The mean difference in the blood transfusion rates in the SLE and no SLE group in PUD was OR 0.01, 95%CI: -0.22 to 0.25; P = 0.91. In SLE vs non-SLE groups with PUD, the OR for Endoscopic intervention was 0.29, 95%CI: 0.08 to 1.00; P = 0.05 while it was OR 2.03, 95%CI: 0.95 to 4.33; P = 0.07, for surgical intervention. The mean difference in the hospital length of stay was -3.57 d between the SLE and no SLE groups in PUD with 95%CI: -7.84 to 0.69; P = 0.10, denoting an average of approximately 3 fewer days of hospital stay among patients with PUD who underwent SLE. For mortality between SLE and non-SLE groups in PUD, the OR was 0.88, 95%CI: 0.45 to 1.72; P = 0.70.

SLE does not confer any benefit in preventing ESD and PUD-associated rebleeding. SLE also does not provide any significant improvement in mortality, need for interventions, or blood transfusions in PUD patients. SLE decreases the hospital length of stay on average by 3.5 d in PUD patients.

Minimally invasive surgery is a kind of surgical operation, which is performed by using professional surgical instruments and equipment to inactivate, resect, repair or reconstruct the pathological changes, deformities and wounds in human body through micro-trauma or micro-approach, in order to achieve the goal of treatment, its surgical effect is equivalent to the traditional open surgery, while avoiding the morbidity of conventional surgical wounds. In addition, it also has the advantages of less trauma, less blood loss during operation, less psychological burden and quick recovery on patients, and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients. Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer (EGC): endoscopic mucosal resection (EMR), underwater EMR (UEMR), endoscopic submucosal dissection (ESD), endoscopic full-thickness resection (EFTR), endoscopic submucosal excavation (ESE), submucosal tunnel endoscopic resection), laparoscopic and endoscopic cooperative surgery (LECS); Among them, EMR, EFTR and LECS technologies have a wide range of applications and different modifications have been derived from their respective surgical operations, such as band-assisted EMR (BA-EMR), conventional EMR (CEMR), over-the-scope clip-assisted EFTR, no-touch EFTR, the inverted LECS, closed LECS, and so on. These new and improved minimally invasive surgeries are more precise, specific and effective in treating different types of EGC.

Background and study aims While gastric endoscopic submucosal dissection (ESD) has become a treatment with fewer complications, delayed bleeding remains a challenge. Post-ESD coagulation (PEC) is performed to prevent delayed bleeding. Therefore, we developed an artificial intelligence (AI) to detect vessels that require PEC in real time. Materials and methods Training data were extracted from 153 gastric ESD videos with sufficient images taken with a second-look endoscopy (SLE) and annotated as follows: (1) vessels that showed bleeding during SLE without PEC; (2) vessels that did not bleed during SLE with PEC; and (3) vessels that did not bleed even without PEC. The training model was created using Google Cloud Vertex AI and a program was created to display the vessels requiring PEC in real time using a bounding box. The evaluation of this AI was verified with 12 unlearned test videos, including four cases that required additional coagulation during SLE. Results The results of the test video validation indicated that 109 vessels on the ulcer required cauterization. Of these, 80 vessels (73.4%) were correctly determined as not requiring additional treatment. However, 25 vessels (22.9%), which did not require PEC, were overestimated. In the four videos that required additional coagulation in SLE, AI was able to detect all bleeding vessels. Conclusions The effectiveness and safety of this endoscopic treatment-assisted AI system that identifies visible vessels requiring PEC should be confirmed in future studies.

Background: This study aimed to assess the completion rate and postoperative bleeding incidence of endoscopic submucosal dissection (ESD) for gastric tumors under continuous antithrombotic therapy. Methods: A prospective observational study was conducted including 88 patients with 100 gastric lesions who underwent gastric endoscopic submucosal dissection (ESD) and received continuous antithrombotic therapy. Additionally, retrospective data on gastric ESD in 479 patients with 534 lesions who did not receive antithrombotic therapy were collected for comparison. Results: The en bloc resection rates (100% in the continuous antithrombotic therapy group vs. 100% in the non-antithrombotic therapy group) and complete resection rates (97.0% vs. 96.3%, respectively) were high and comparable between the groups. No significant differences were found in the specimen size or procedure time. Perforation rates were low (0% vs. 2.3%, respectively) and were not significantly different between the groups. However, postoperative bleeding occurred significantly more frequently in the continuous antithrombotic therapy group (10.2% vs. 4.2%, respectively) than in the non-antithrombotic therapy group. The subgroup analysis revealed a higher incidence of postoperative bleeding in patients receiving thienopyridine derivatives. Conclusions: Continuous administration of antithrombotic agents, especially thienopyridines, increased the risk of postprocedural hemorrhage following gastric ESD. These findings support the need for careful consideration of pharamcological management before ESD, aligning with the current guidelines.

Endoscopic treatment, particularly endoscopic submucosal dissection, has become the primary treatment for early gastric cancer. A comprehensive optical assessment, including white light endoscopy, image-enhanced endoscopy, and magnification, are the cornerstones for clinical staging and determining the resectability of lesions. This paper discusses factors that influence the indication for endoscopic resection and the likelihood of achieving a curative resection. Our review stresses the critical need for interpreting the histopathological report in accordance with clinical guidelines and the imperative of tailoring decisions based on the patients' and lesions' characteristics and preferences. Moreover, we offer guidance on managing complex scenarios, such as those involving non-curative resection. Finally, we identify future research avenues, including the role of artificial intelligence in estimating the depth of invasion and the urgent need to refine predictive scores for lymph node metastasis and metachronous lesions.

Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE.

From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed.

The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken-Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post-bleeding hospital stay was 10.0 ± 6.2 days. A brief meta-analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G-POEM was 0.4%.

Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions.

Gastric endoscopic submucosal dissection (ESD) is a curative treatment for gastric neoplasm. A scheduled second-look endoscopy could be performed to prevent delayed post-ESD bleeding. However, no studies on the efficacy of second-look endoscopy for the prevention of early delayed post-ESD bleeding have been conducted. So, the aim of this study was to be the first to investigate the efficacy of immediate second-look endoscopy for the prevention of post-ESD bleeding.

The 266 gastric ESD cases were included. Immediate second-look endoscopy was defined as repeated upper endoscopy soon after complete hemostasis of the ESD site and specimen fixation. Early and late delayed bleeding were classified as before or after 24 h after the ESD, respectively.

The 262 ESD cases were enrolled and divided into three groups: the immediate second-look (n = 79), scheduled second-look (n = 86), and no second-look (n = 97). Post-ESD bleeding occurred in 19 cases (7.3%). Of these, 13 (68.4%) were early delayed post-ESD bleeding. The immediate second-look endoscopy had a lower incidence of early delayed post-ESD bleeding compared to the groups without immediate second-look endoscopy, (3.8% vs. 0.8%, p = 0.009). In a multivariate analysis, immediate second-look endoscopy significantly reduced early delayed post-ESD bleeding (OR 0.39, p = 0.022). The resected specimen area ≥ 1,000 mm2 was an independent risk factor for early delayed post-ESD bleeding (OR 8.98, p = 0.010). However, the frequency of delayed post-ESD bleeding did not differ between the three groups.

Immediate second-look endoscopy after gastric ESD may prevent early delayed post-ESD bleeding under certain circumstances.

This study aimed to determine long-term outcomes of gastric endoscopic submucosal dissection (ESD) in Western settings based on the latest Japanese indication criteria, and to examine predictors of outcomes and complications.

Data were collected from consecutive patients undergoing gastric ESD at four participating centers from 2009 to 2021. Retrospective analysis using logistic regression and survival analysis was performed.

415 patients were included (mean age 71.7 years; 56.4 % male). Absolute indication criteria (2018 guideline) were met in 75.3 % of patients. Median follow-up was 52 months. Post-resection histology was adenocarcinoma, high grade dysplasia, and low grade dysplasia in 49.9 %, 22.7 %, and 17.1 %, respectively. Perforation, early and delayed bleeding occurred in 2.4 %, 4.3 %, and 3.4 %, respectively. Rates of en bloc and R0 resection, and recurrence on first endoscopic follow-up were 94.7 %, 83.4 %, and 2.7 %, respectively. Relative indication (2018 guideline) for ESD was associated with R1 outcome (P = 0.02). Distal location (P = 0.002) and increased procedure time (P = 0.04) were associated with bleeding, and scarring (P = 0.009) and increased procedure duration (P = 0.003) were associated with perforation. Recurrence-free survival at 2 and 5 years was 94 % and 83 %, respectively.

This is the largest Western multicenter cohort and suggests that gastric ESD is safe and effective in the Western setting. A quarter of patients fell outside the new absolute indications for ESD, suggesting that Western practice involves more advanced lesions. We identified the predictors of complications, which should help to inform future Western practice and research.

This study aimed to evaluate whether the use of antiplatelet agents increases the risk of bleeding after gastric endoscopic submucosal dissection (ESD) and to determine the appropriate time to discontinue antiplatelet agents to minimize complications.

This retrospective observational study utilized a collected dataset of patients who underwent ESD for gastric adenoma and cancer between January 2010 and December 2020. Patients were classified into three groups according to antiplatelet agent use and discontinuation status. We investigated the risk of post-ESD bleeding with different interruption times and antiplatelet agent types.

Of 1879 patients, 1389 were non-users, 190 were in the continuous group, and 203 were in the interrupted group. The rates of overall and delayed bleeding were significantly higher in patients who continued or were interrupted within three days before ESD than in the non-users and interrupted group (6.3% vs. 1.2%, p < 0.001, 6.3% vs. 2.5%, p = 0.01, respectively). Significant differences in delayed bleeding between the continuous and interrupted groups decreased with longer cessation periods. In multivariate analysis, continuous antiplatelet agents were still the strongest risk factor for bleeding (OR 2.81, 95% CI 1.14-6.90). Lower third location and longer procedure times were also independent risk factors for post-ESD bleeding (OR 2.75; 95% CI 1.08-6.97; OR 1.02; 95% CI 1.01-1.02).

Continuous antiplatelet agent use increases the risk of delayed bleeding after gastric ESD. Therefore, the optimal timing of interruption, rather than the type of antiplatelet agent, should be considered to avoid an additional risk of bleeding and thromboembolism.

Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection.

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of  > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.

In July 2017, supplementary guidelines on anticoagulants, including direct oral anticoagulants, were published in Japan. We investigated the changes in endoscopic submucosal dissection (ESD) of gastric mucosal lesions after the publication of the supplement, examined the risk factors, and developed a predictive model for post-ESD bleeding.

We included 2272 gastric ESD cases from our hospital between May 2003 and June 2021 and classified them into two groups: 1789 cases before and 483 after the publication of the supplementary guidelines. A predictive model for post-ESD bleeding was developed using the pre-publication cohort data.

The proportion of patients receiving warfarin decreased (5.0% vs. 1.4%) and those receiving direct oral anticoagulants increased (1.2% vs. 6.8%) after the publication of the supplementary guidelines. Post-ESD bleeding occurred in 61 patients, but there was no significant difference in the bleeding rate between the groups (50 [2.8%] vs. 11 [2.3%] patients, respectively). Five risk factors (number of antithrombotic agents, dialysis, heparin replacement, resection specimen size, and procedure time) were identified for model development. The C-statistic for the model and post-publication cohorts were 0.83 and 0.72, respectively. In the model, each risk factor for postoperative bleeding was scored, and the risk was classified into three levels according to the total score. Bleeding rates at low, intermediate, and high risks were 1.6%, 10.3%, and 38.9%, respectively.

Despite changes in patient characteristics and clinical practice regarding ESD before and after the publication of the supplementary guidelines, we could still develop a simple and useful predictive model.

This retrospective study aimed to evaluate the effect and safety of endoscopic submucosal dissection (ESD) for large laterally spreading lesions located in the descending duodenum based on multi-center experiences.

This multicentric retrospective study included 3 hospitals in China. Fifty-one patients with laterally spreading lesions of the duodenum who underwent ESD between February 2019 and December 2020 were enrolled. The en bloc resection rates, en bloc R0 resection rates, complication rates, and local recurrence after ESD were evaluated.

Of the 51 patients, the median age was 62 years old (ranging from 37 to 76 years old); among them, 29 were male and 22 were female. The average lesion size was 2.3 cm (ranging from 1.5 to 4.0 cm). All 51 lesions achieved en bloc R0 resection successfully, with the procedure time ranging from 20 to 117 min (median: 45.5 min). The hospital length of stay ranged from 4 to 90 days (median: 8.0 d). Two patients experienced delayed bleeding 3 days after ESD and 2 other patients were diagnosed with delayed perforation. Tumor residual and local recurrence did not occur during a short follow-up period.

ESD for laterally spreading lesions of the descending duodenum is feasible.

The risk-benefit profile of submucosal endoscopic procedures is generally favorable but there exist unique considerations regarding the recognition, treatment, and prevention of submucosal endoscopic complications. Bleeding during the procedure can be managed with knife electrocautery, tamponade by injection of additional submucosal agent, or hemostatic forceps, depending on the location and degree of bleeding. Delayed bleeding should be managed with repeat endoscopy. Potential means to reduce the risk of delayed bleeding include anticipatory coagulation of visible vessels in the dissection ulcer base, applied hemostatic chemicals, snares, clips, and sheets of cultured cells.

Prophylactic coagulation after gastric endoscopic submucosal dissection (ESD) decreases the rate of delayed bleeding; however, it cannot prevent bleeding completely, and delayed bleeding may occur from non-exposed vessels that were not detected immediately after ESD or where prophylactic coagulation was inadequate. Doppler monitoring systems which can evaluate vascular flow have been recently introduced in the endoscopic field. We developed the Doppler probe method (DOP) using the novel system and conducted a comparative study.

Data were retrospectively collected at a tertiary hospital between January 2017 and May 2021. Patients who underwent DOP were matched to those who did not (no-DOP, 1:3 ratio). After successful ESD, DOP was performed, and coagulation was additionally performed as necessary. The primary outcome was the rate of 30-day delayed bleeding.

Fifty DOP patients were matched to 151 no-DOP patients. Although the differences were not statistically significant, the DOP group had lower rates of delayed bleeding (2.0% vs. 8.6%, P = 0.11; risk differences, 6.6%; 95% confidence interval [CI] 1.2-12.1%), readmission due to bleeding (0% vs. 2.7%), and blood transfusion (2.0% vs. 3.3%) compared to the no-DOP group. In the whole study population (n = 245), the log-rank test revealed that DOP was correlated to a lower incidence of delayed bleeding (P = 0.036). The Cox regression model revealed a marginally significant effect on delayed bleeding (hazard ratio = 0.17, 95% CI 0.022-1.26, P = 0.082). No procedure-related adverse events were observed.

DOP is safe and may reduce delayed bleeding; however, further prospective studies are required to validate our findings.

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.

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.

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).

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.

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.