Endoscopic submucosal dissection (ESD) is a technique for removing dysplastic lesions in the gastrointestinal tract but carries risks like pain and perforation. Dexmedetomidine, an α2-receptor agonist, offers potential benefits as an adjunct sedative during ESD by providing anxiolysis and analgesia. This systematic review and meta-analysis assesses its efficacy and safety.

We searched databases including Embase, Medline/PubMed, Scopus, and Web of Science up to April 21, 2024, following PRISMA guidelines. Eligible studies used dexmedetomidine with other sedatives for ESD. We analyzed outcomes such as en-bloc and complete resection rates, sedation duration, and adverse events, using RevMan for meta-analysis with a random-effects model.

The initial search retrieved 216 studies and after screening, eight studies were included in the final analysis. Dexmedetomidine showed no significant difference in en-bloc or complete resection rates compared to controls. Sedation and procedure times were similar between the two groups as well. Dexmedetomidine significantly reduced restlessness (OR 0.15, 95% CI:0.07 to 0.29) and increased bradycardia (OR 7.15, 95% CI 3.17 to 16.11) compared to controls. Upon subgroup analysis, Dexmedetomidine plus Propofol, and Dexmedetomidine plus Midazolam, revealed the same findings regarding restlessness and bradycardia compared to controls which confirmed the adjunctive effects of Dexmedetomidine.

Dexmedetomidine as an adjunctive sedative appears safe and effective in ESD, reducing restlessness without significant adverse events. The risk of bradycardia is increased, which may be reflective of reduced physiological stress. Future studies should explore optimal dosing and compare Dexmedetomidine with other sedatives in diverse populations.

Metachronous gastric cancer (MGC) has gained increasing attention due to the preservation of the stomach during endoscopic resection for early gastric cancer (EGC).

This study aims to investigate the risk factors associated with MGC in the postoperative surveillance of endoscopic submucosal dissection (ESD).

A retrospective case-control study.

The retrospective study was conducted between January 1, 2014, and June 30, 2020, at the Affiliated Drum Tower Hospital of Nanjing University Medical School.

Several independent risk factors for developing MGC were identified as smoking history (hazard ratio (HR) 2.39, 95% confidence interval (CI) 1.25-4.58), metabolic dysfunction-associated steatotic liver disease (MASLD; HR 2.44, 95% CI 1.23-4.87), cerebrovascular disease (CD; HR 2.55, 95% CI 1.09-5.99), multiple lesions (HR 2.06, 95% CI 1.17-3.63), Helicobacter pylori infection status (eradicated vs negative: HR 1.42, 95% CI 0.60-3.39; persistent vs negative: HR 5.47, 95% CI 2.13-14.03), and atrophic gastritis (AG; moderate vs mild: HR 4.44, 95% CI 1.36-14.53; severe vs mild: HR 7.30, 95% CI 2.11-25.22). The established nomogram based on these risk factors demonstrated high accuracy both in the training and test sets, with concordance indexes of 0.787, 0.762, and 0.845 for the training set, and 0.764, 0.824, and 0.788 for the test set at 2, 3, and 5 years, respectively.

The risk factors for developing MGC after curative ESD for EGC were identified as smoking history, MASLD, CD, multiple lesions, H. pylori infection status, and AG. To reduce the risk of MGC, a healthy lifestyle, regular H. pylori testing, and annual endoscopic screening are recommended.

Gastric premalignant conditions (GPMC) are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. GPMC have an increased risk of progression to gastric adenocarcinoma. Gastric cancer (GC) in the United States represents an important cancer disparity because incidence rates are 2- to 13-fold greater in non-White individuals, particularly early-generation immigrants from regions of high GC incidence. The US 5-year survival rate for GC is 36%, which falls short of global standards and is driven by the fact that only a small percentage of GC in the US is diagnosed in the early, curable stage. This document represents the first iteration of American College of Gastroenterology guidelines on this topic and encompasses endoscopic surveillance for high-risk patients with GPMC, the performance of high-quality endoscopy and image-enhanced endoscopy for diagnosis and surveillance, GPMC histology criteria and reporting, endoscopic treatment of dysplasia, the role of Helicobacter pylori eradication, general risk reduction measures, and the management of autoimmune gastritis and gastric epithelial polyps. There is insufficient evidence to make a recommendation on upper endoscopic screening for GC/GPMC detection in US populations deemed high-risk for GC. Surveillance endoscopy is recommended for individuals at high risk for GPMC progression, as defined by endoscopic, histologic, and demographic factors, typically every 3 years, but an individualized interval may be warranted. H. pylori testing, treatment, and eradication confirmation are recommended in all individuals with GPMC. Extensive high-quality data from US populations regarding GPMC management are lacking, but continue to accrue, and the quality of evidence for the recommendations presented herein should be interpreted with this dynamic context in mind. The GPMC research and education agendas are broad and include high-quality prospective studies evaluating opportunistic endoscopic screening for GC/GPMC, refined delineation of what constitutes "high-risk" populations, development of novel biomarkers, alignment of best practices, implementation of training programs for improved GPMC/GC detection, and evaluation of the impact of these interventions on GC incidence and mortality in the US.

A significant association between increased age and an increased risk of metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) has previously been reported.

To determine risk factors for the metachronous occurrence of early gastric cancer (EGC) in elderly individuals.

This retrospective cohort study comprised 653 elderly patients (aged ≥ 65 years) who underwent curative ESD for EGC between January 2014 and June 2020 at Nanjing Drum Tower Hospital. Comprehensive analyses were conducted to compare lifestyle habits, comorbidities, and Helicobacter pylori (H. pylori) infections as potential indicators.

During a median follow-up of 38 months, 46 patients (7.0%, 20.46/1000 person-years) developed MGC in the elderly cohort. The cumulative incidences of MGC at 2, 3, and 5 years were 3.3%, 5.3%, and 11.5%, respectively. In multivariate Cox regression analyses, the independent risk factors for MGC included metabolic dysfunction-associated steatotic liver disease (MASLD) [hazard ratio (HR) = 2.44, 95% confidence interval (CI): 1.15-5.17], persistent H. pylori infection (HR = 10.38, 95%CI: 3.36-32.07), severe mucosal atrophy (HR = 2.71, 95%CI: 1.45-5.08), and pathological differentiation of EGC (well/moderately differentiated vs poorly differentiated: HR = 10.18, 95%CI: 1.30-79.65). Based on these risk factors, a risk stratification system was developed to categorize individuals into low (0-1 point), intermediate (2-3 points), and high (4-8 points) risk categories for MGC, with cumulative incidence rates of 12.3%, 21.6%, and 45%, respectively.

Among elderly individuals, MASLD, persistent H. pylori infection, severe mucosal atrophy, and well/moderately differentiated EGC were associated with an increased risk of MGC. Elderly patients are recommended to adopt healthy lifestyle practices, and undergo regular endoscopic screening and H. pylori testing after curative ESD for EGC.

In early gastric cancer, local recurrence develops after endoscopic resection by field cancerization. Understanding the nature of cancer-prone environments is important to establish effective strategies to prevent recurrence. We hypothesized that the molecular/immune profiles in non-tumor (cancer-prone) tissue differ according to the relative distance from the gastric tumor. For this purpose, we performed whole-exome and transcriptome sequencing of 16 early gastric cancer samples with paired non-tumor mucosa 1 cm (N1) and 3 cm (N3) away from the tumor. The whole exome sequencing revealed mutations in both the tumor and non-tumor mucosa. TTN was the most frequently altered gene in tumors (31 %) and was the second most frequently altered gene in N1 (25 %) samples; however, the mutation rate was significantly lower in N3 (12 %) samples (P = 0.0046). Moreover, the expression levels of TTN mRNA were higher in tumors than in the N1 and N3 samples and were significantly associated with TTN mutations (P = 0.04). TP53 mutations were mainly observed in tumors (50 %) and in 6.3 % of N1, with no mutation detected in N3 samples. Transcriptome sequencing revealed that the expression of the epithelial-mesenchymal transition signature, mesenchymal signature, and proliferation signature was increased in tumors, whereas programmed death-ligand 1 expression was decreased in the non-tumor mucosa. In the tumor, although the numbers of M0/M1 macrophages, neutrophils, and eosinophils increased, plasma cell numbers were markedly decreased compared to non-tumor mucosa. In conclusion, non-tumor mucosa at 1 cm and 3 cm from the tumor harbored different genomic, transcriptomic, and immune cell profiles. The non-tumor mucosa closer to the tumor (1 cm) exhibited similar genomic and transcriptomic features. These findings can offer clinical guidance for acquiring a safe horizontal margin in endoscopic resection for early gastric cancer.

Vonoprazan has been known to have a high Helicobacter pylori (H. pylori) eradication rate since its launch in 2015. Yet, the risk factors for eradication failure and development of post-eradication gastric cancer (GC) using VPZ regimen remain unclear.

This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using VPZ between February 2015 and June 2017 and were followed up for five years by the end of 2022. We examined several indicators of systemic immune, inflammatory, and nutritional status at the time of eradication to identify those indicators could predict eradication success, risk of post-eradication GC development, and long-term prognosis.

The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Multivariate analysis showed that only a high peripheral blood neutrophil-to-lymphocyte ratio (NLR) was significantly associated with eradication failure. The 5-year GC incidence rate was 1.67%, and all GCs were stage IA. The mean (standard deviation [SD]) time from eradication to diagnosis was 40.5 (6.1) months. Multivariate analysis showed that high NLR and history of GC and hypertension were significantly associated with GC development. Patients with elevated NLR post-eradication had a higher risk of newly developed GC. Twelve patients died during the study period, and a high NLR was associated with a significantly higher mortality rate.

NLR has the potential to be a biomarker that predicts the failure of eradication and development of post-eradication GC. High NLR was also associated with poor long-term prognosis after H. pylori eradication.

Endoscopic submucosal dissection (ESD) allows for curative en-bloc resection of dysplastic gastrointestinal (GI) tract lesions. However, it is associated with postoperative adverse events (AEs) such as pain, bleeding, and perforation. Dexmedetomidine, an α2-receptor agonist, has emerged as a promising adjunct sedative for ESD under moderate sedation, offering anxiolysis and analgesia. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety for use in ESD.

A comprehensive systematic search was conducted across multiple databases, including Embase, Medline, Scopus, and Web of Science. Studies that involved ESD utilizing dexmedetomidine as an adjunctive medication in combination with other sedatives, were included. Data extraction and risk of bias assessment were independently performed by two reviewers. Meta-analysis was carried out with RevMan using a random-effects model.

Eight studies were included in the final analysis. Dexmedetomidine showed no significant difference in en-bloc or complete resection rates compared to controls. Sedation and procedure times were similar between the two groups as well. Dexmedetomidine significantly reduced restlessness (OR 0.15, 95% CI:0.07 to 0.29) and increased bradycardia (OR 7.15, 95% CI 3.17 to 16.11) compared to controls. Upon subgroup analysis, Dexmedetomidine plus Propofol, and Dexmedetomidine plus Midazolam, revealed the same findings regarding restlessness and bradycardia compared to controls which confirmed the adjunctive effects of Dexmedetomidine.

Dexmedetomidine as an adjunctive sedative appears safe and effective in ESD, reducing restlessness without significant adverse events. The risk of bradycardia is increased, which may be reflective of reduced physiological stress. Future studies should explore optimal dosing and compare Dexmedetomidine with other sedatives in diverse populations.

Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H. pylori eradication.

Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50-59 years), group 3 (60-69 years), and group 4 (≥70 years).

All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12). After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57).

The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.

Endoscopic submucosal dissection (ESD) has become the treatment of choice for many superficial gastric neoplasms. Clinical outcomes are increasingly comparable between Japanese and Western series; however, data are lacking on the validity of risk stratification tools in Western cohorts. We aimed to evaluate clinical outcomes, explore risk stratification, and compare our data with published Western series.

We conducted a retrospective, observational cohort study in a single tertiary referral center over a 13-year period. Primary outcomes were rates of en bloc, complete (R0) and curative resection. Secondary outcomes included adverse events, recurrence, metachronous lesions, eCura grades, and ESGE criteria. A comparative analysis was performed with existing published series from Western centers.

Totally 112 patients were included in the study cohort. 50.9% were male, 87.5% Caucasian, and median age was 75.5 years (IQR 14.3 years). Lesions were predominantly antral (36.6%) or body (35.7%); median size 20 mm (IQR 15 mm). Rates of en bloc, R0 resection, and curative resection were 96.4%, 89.3%, and 78.6% (identical between eCura and ESGE), respectively. Adverse events occurred in 5.8%, recurrence in 0%, and metachronous lesions in 9.9%. Our data compared favorably with a review existing Western series, which illustrates increasing adoption of ESD and stable outcomes over time.

ESD represents a safe and effective method of treatment for gastric neoplasia in the Western setting. This study highlights the potential for excellent outcomes in a single center with a heterogeneous patient cohort and supports the use of eCura in guiding post procedural management.

Postoperative pain is a common yet often underestimated complication following esophageal endoscopic submucosal dissection (ESD), with limited strategies for effective management. This prospective, double-blind, randomized controlled trial assessed the effects of adding dexmedetomidine (DEX) to the anesthesia regimen on postoperative pain and early recovery in patients undergoing esophageal ESD.

In total, 60 patients scheduled for elective esophageal ESD under general anesthesia were randomly assigned to the DEX or control group. The DEX group received an intravenous loading dose of DEX at 1 μg/kg for 10 min, followed by a continuous intravenous infusion of 0.6 µg/kg/h, which was stopped 30 min before the end of the procedure. The control group received normal saline as a placebo. The study's primary outcome was the incidence of moderate-to-severe postoperative pain. Secondary outcomes included postoperative pain scores, hemodynamic parameters, the occurrence of postoperative nausea and vomiting (PONV), patient satisfaction, and lengths of stay in the post-anesthesia care unit (PACU) and hospital.

The incidence of moderate-to-severe postoperative pain in the DEX group was significantly lower than that in the control group (absolute difference: -33.4%; OR: 0.250; 95% CI: 0.085-0.731, P = 0.01). Pain scores at 1 h postoperatively (0.5[2.0] vs 3.0[1.3], P = 0.003) were significantly lower in the DEX group. Additionally, morphine dosage in the PACU (0[0] vs 1.0[2.0] P = 0.004) was significantly reduced in the DEX group compared with the control group. In the DEX group, the incidence and severity of PONV were significantly decreased and the length of PACU stay was shorter than in the control group (P < 0.01). However, the rates of intraoperative hypotension, tachycardia, and bradycardia were similar between the two groups. Patient satisfaction and length of hospital stay were also comparable.

Adding DEX to the anesthesia regimen for esophageal ESD significantly attenuates postoperative pain and improves early recovery outcomes.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD.

This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports.

During a median follow-up period of 70.5 months (3-120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer.

Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD.

Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients.

This case-cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan-Meier and Cox proportional hazards model analyses.

MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03-5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07-8.95, p = 0.037).

This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care.

We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD).

From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis.

From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction.

Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.

Esophagogastroduodenoscopy (EGD) is a fundamental procedure for early detection of upper gastrointestinal (UGI) cancer. However, limited research has been conducted on the impact of sedation during EGD on the identification of precancerous lesions and early cancer (EC). This retrospective study aims to evaluate whether sedation during EGD can improve the detection rates of precancerous lesions and EC.

In this propensity score-matched retrospective study, we examined medical records from outpatients who underwent diagnostic EGD at a large tertiary center between January 2023 and December 2023. Data on endoscopic findings and histology biopsies were obtained from an endoscopy quality-control system. The primary objective was to compare the rates of detecting precancerous lesions and EC in patients who received sedation during EGD vs. those who did not receive sedation. Additionally, we aimed to identify factors influencing these detection rates using binary logistic regression analysis.

Following propensity score matching, a total of 17,862 patients who underwent diagnostic EGD with or without propofol sedation were identified. The group that received sedation exhibited a higher detection rate of precancerous lesions and EC in comparison to the non-sedated group (1.04 vs. 0.75%; p = 0.039). Additionally, within the sedated group, there was an increased likelihood of identifying precancerous lesions and EC specifically at the gastric antrum (0.60 vs. 0.32%, p = 0.006). Binary logistic regression analysis demonstrated that independent risk factors influencing the detection rates included age, gender, observation time, and number of biopsies conducted during the procedure.

Anesthesia assistance during EGD screening proved advantageous in detecting EC as well as precancerous lesions. It is crucial for endoscopists to consider these factors when performing EGD screening procedures.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus.

We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences.

The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively).

Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings.

A small portion of patients are diagnosed with early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at a young age. However, their clinical outcomes are rarely known.

We investigated to identify the feasibility and clinical outcomes of ESD for EGC focusing on young patients.

We analyzed the clinical characteristics and outscomes of patients who had undergone ESD for the treatment of EGC at < 50 years of age. We enrolled patients who had been diagnosed with EGC and had undergone ESD between 2006 and 2020. We divided them by age as follows: ≤ 50 and > 50 years into the young age (YA) and other age (OA) groups, respectively.

Altogether, 1681 patients underwent ESD for EGC (YA group: 124 [7.4%], OA group: 1557 [92.6%]). The YA group had less severe atrophy and more undifferentiated (37.1% vs. 13.9%, P < 0.001) and diffuse type (25% vs. 7.7%, P < 0.001) histology. The curative resection rate was not significantly different between the groups. However, among 1075 patients who had achieved curative resection and had been followed-up for > 12 months, the YA group had a lower incidence of MGN (5.2% vs. 17.5%, P = 0.004) and MGC (2.6% vs. 10.9%, P = 0.019) than those exhibited by the OA group. The YA group was a significant negative predictor of MGN (odds ratio [OR]: 2.983, 95% confidence interval [CI] 1.060-8.393, P = 0.038), and marginally negative predictor in MGC (OR: 3.909, 95% CI: 0.939-16.281, P = 0.061).

ESD is a favorable and effective therapeutic modality for EGC patients aged < 50 years, once curative resection is achieved.

We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization.

We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization.

Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region.

Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

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.

The increasing popularity of endoscopic submucosal dissection (ESD) as a treatment for early gastric cancer has highlighted the importance of quality assessment in achieving curative resections. This article emphasizes the significance of evaluating ESD quality, not only for curative cases but also for non-curative ones. Postoperative assessment relies on the endoscopic curability (eCura) classification, but management strategies for eCuraC-1 tumour with a positive horizontal margin are unclear. Current research primarily focuses on comparing additional surgical procedures in high-risk patients, while studies specifically targeting eCuraC-1 patients are limited. Exploring management strategies and follow-up outcomes for such cases could provide valuable insights. Furthermore, the application of molecular imaging using near-infrared fluorescent tracers holds promise for precise tumour diagnosis and navigation, potentially impacting the management of early-stage gastric cancer patients. Advancing research in these areas is essential for improving the overall efficacy of endoscopic techniques and refining treatment indications.

Japanese guidelines recommend posttreatment endoscopy once or twice a year after endoscopic submucosal dissection (ESD) for early gastric cancer. However, the impact of endoscopy intervals on metachronous gastric cancer (MGC) remains unclear, especially the difference between 1-year and half-a-year intervals. We aimed to investigate this difference.

This study retrospectively investigated 2429 patients who underwent gastric ESD between May 2001 and June 2019 at our hospital. Patients who developed MGC were classified based on those who underwent the previous endoscopy within at least 7 months (short-interval group) and within 8-13 months (regular-interval group). Propensity score matching (PSM) was used to adjust for possible confounders. The primary outcome was the proportion of MGC beyond curative ESD criteria established in the guidelines.

A total of 216 eligible patients developed MGC. The short- and regular-interval groups included 43 and 173 patients, respectively. Overall, no patients in the short-interval group had MGC beyond curative ESD criteria, while 27 patients in the regular-interval group did. The proportion of MGC beyond curative ESD criteria was significantly lower in the short-interval group than in the regular-interval group before (P = 0.003) and after (P = 0.028) PSM. Although not significant, the short-interval group tended to have a higher stomach preservation rate than the regular-interval group (P = 0.093).

Our study indicated a possible benefit of biannual surveillance endoscopy in the early post-ESD period.

This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes.

The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG.

The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258).

The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups.

The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

To externally validate the robustness of the FAMISH predicting score designed to estimate the risk of metachronous gastric lesions (MGLs) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).

This multicenter, retrospective study included 618 patients with EGC who underwent curative ESD at two tertiary referral teaching hospitals between January 2014 and December 2019. FAMISH score was a composite indicator of age, sex, family history, corpus intestinal metaplasia, synchronous lesions, and H. pylori infection. Discrimination, calibration, and risk stratification of these scores were assessed. Associations between MGL characteristics and FAMISH scores were also explored.

After a median follow-up period of 60 months, 83 of 618 patients (13.4%) developed MGL. The discrimination ability according to the area under the curve was 0.708 (95% CI, 0.645-0.772) for predicting the 5-year MGL. The calibration results showed good consistency between the predicted and actual MGL (Hosmer-Lemeshow, P  > 0.05). In terms of risk stratification, the 5-year MGL rates were 4.1% (95% CI, 1.6%-6.5%), 10.8% (95% CI, 7.2%-14.3%), and 32.1% (95% CI, 20.9%-41.7%) in the low-, intermediate-, and high-risk groups, respectively ( P  < 0.001). For patients with MGL, the curative resection rate of ESD was significantly higher in the low- and intermediate-risk groups than in the high-risk group (100% vs. 80%, P  = 0.037).

The FAMISH predicting score was externally validated and can be generalized to an independent patient population. This adjuvant tool can assist in individual clinical decision-making.

Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia.

Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated.

Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008).

Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.

Surveillance after gastric endoscopic submucosal dissection (ESD) is recommended for all patients owing to the persistent risk of metachronous gastric lesions (MGLs). We developed and validated a prediction score to estimate MGL risk after ESD for early neoplastic gastric lesions, to define an individualized and cost-saving approach.

Clinical predictors and a risk score were derived from meta-analysis data. A retrospective, single-center, cohort study including patients with ≥ 3 years of standardized surveillance after ESD was conducted for score validation. Predictive accuracy of the score by the area under the receiver operating characteristic curve (AUC) was assessed and cumulative probabilities of MGL were estimated.

The risk score (0-9 points) included six clinical predictors (scored 0-3): positive family history of gastric cancer, older age, male sex, corpus intestinal metaplasia, synchronous gastric lesions, and persistent Helicobacter pylori infection (FAMISH). The study population included 263 patients. The MGL rate was 16 %. The score diagnostic accuracy for predicting MGL at 3 years' follow-up, measured by the AUC, was 0.704 (95 %CI 0.603-0.806). At 3 years and a cutoff < 2, the score achieved maximal sensitivity and negative predictive value; 15 % of patients could be assigned to a low-risk group, in which the progression to MGL was significantly lower than for the high-risk group (P = 0.04).

The FAMISH score might be a useful tool to accurately identify patients with low-to-intermediate risk for MGL at 3 years of follow-up who could have surveillance intervals extended to reduce the burden of care.

Endoscopic mucosal resection is an innovative method for treating early gastric cancer and has been widely used in clinical practice.

To analyze the factors associated with the development of heterochronic gastric cancer in patients with early gastric cancer who had undergone endoscopic mucosal dissection (EMD).

A cohort of patients with early gastric cancer treated using EMD was retrospectively analyzed, and patients who developed heterochronic gastric cancer after the surgery were compared with those who did not. The effects of patient age, sex, tumor size, pathological type, and surgical technique on the development of heterochronic gastric cancer were assessed using statistical analysis.

Of the 300 patients with early gastric cancer, 150 patients developed heterochronic gastric cancer after EMD. Statistical analysis revealed that patient age (P value = XX), sex (P value = XX), tumor size (P value = XX), pathological type (P value = XX), and surgical technique (P value = XX) were significantly associated with the occurrence of heterochronic gastric cancer.

Age, sex, tumor size, pathological type, and surgical technique are key factors influencing the occurrence of heterochronic gastric cancer after EMD in patients with early gastric cancer. To address these factors, postoperative follow-up and management should be strengthened to improve the prognosis and survival rate of patients.

Several studies have reported the metachronous gastric cancers (MGCs) with possible lymph node metastasis (LNM) after endoscopic submucosal dissection (ESD) and Helicobacter pylori (H. pylori) eradication in which a curative ESD had not been achieved. There have been no published reports of evaluations of the features of patients with MGC with possible LNM after ESD and H. pylori eradication.

We identified 264 patients with 369 MGCs after H. pylori eradication among the 4354 patients with 5059 early gastric cancers (EGCs) who underwent ESD between 1999 and 2017 and divided them into two groups: patients with MGCs with possible LNM (Group I) and patients with MGCs undergone curative ESD (Group II). We retrospectively compared the features of patients with MGCs and patients with EGCs at index ESD in the two groups.

Group I consisted of 20 patients with 21 MGCs, and Group II consisted of 244 patients with 348 MGCs. Group I lesions were significantly more common in the posterior wall than in the lesser curvature (odds ratio [OR] = 3.97; 95% confidence intervals [CI] 1.20-13.10). Development of Group I was significantly more common in patients with a body mass index (BMI) < 19.0 kg/m2 than in patients with a BMI ≥ 19.0 kg/m2 at index ESD (OR = 4.44; 95% CI 1.30-15.20).

During surveillance endoscopy after gastric ESD and H. pylori eradication, the posterior wall should be carefully examined to detect MGCs early. Lower BMI may be associated with the development of MGCs with possible LNM.

Post-operative pain of endoscopic submucosal dissection (ESD) is always be overlooked and undertreated by endoscopists. However, the incidence of moderate to severe pain after ESD is as high as 44.9% to 62.8%, which can greatly affect the patient's recovery, reduce their satisfaction, and extend their hospital stay. Transcutaneous electrical acupoint stimulation (TEAS) have been shown to reduce postoperative pain and enhance gastrointestinal (GI) function recovery in patients undergoing abdomen surgery. However, there is no evidence regarding on the effect of TEAS on post-operative pain and complications in patients undergoing ESD. Therefore, we aim to investigate whether perioperative TEAS treatment is superior to the sham acupuncture in terms of post-ESD pain and GI function recovery.

This study is a prospective, randomized controlled trail, which is single-blinded and in single center. A total of 120 patients undergoing elective gastric and esophageal ESD surgery in Beijing Friendship Hospital, Capital Medical University, will be involved in this study. These individuals will be stratified according to the type of ESD surgery (i.e. gastric or esophageal procedure) and be randomly divided into two groups. L14, PC6, ST36 and ST37 will be stimulated at the TEAS treatment group, and the control group will receive simulation at four sham acupoints. The primary outcome is post-EDS VAS score at the time of entering PACU, 10 min, 20 min, 30 min, 1 h, 2 h, 4 h, 6 h, 18 h, 24 h, 48 h after the surgery. The secondary outcomes include the anesthesia-associated parameters, sedation score, nausea and vomiting score, shivering score, recovery of gastrointestinal function, satisfaction of patients to anesthesia, incidence of postoperative complications, QLQ-C30 life quality scale, and the economic indicators.

The results of this study will confirm that continuous preventive application of TEAS can alleviate the postoperative pain among patients with gastric and esophageal ESD surgery and accelerate the recovery of post-ESD gastrointestinal function.

Chinese Clinical Trial Registry, ID: ChiCTR2100052837, registered on November 6, 2021. http://www.chictr.org.cn/showproj.aspx?proj=135892 .

The documented variation in gastric cancer (GC) detection among endoscopists has often been dismissed as a coincidental artefact of the low incidence of gastric neoplasms; it is not considered associated with differences in physicians' performance of the esophagogastroduodenoscopy procedure. This study is to confirm whether significant variations among endoscopists in early GC detection suggest the individual performance of the upper endoscopy.

A retrospective observational study at a single centre in Japan assessed the results of 218 early GCs detected during 25 688 routine esophagogastroduodenoscopies by 12 endoscopists. The main outcome was the rate of early GC detection for each endoscopist under the same circumstances. Other measures included the major diameters and locations of the lesions, Helicobacter pylori infection status, and baseline patient characteristics that could affect the prevalence of GC.

The early GC detection rates exhibited wide variation among endoscopists (0.09%-2.87%) despite performing routine esophagogastroduodenoscopies in a population with a similar background. Endoscopists were assigned to a low-detection group (n=6; detection rate: 0.47% (range: 0.09%-0.55%)) and a high-detection group (n=5; detection rate: 0.83% (range: 0.63%-1.12%)), with the single highest detector analysed separately due to his distinct detection rate (2.87%). Endoscopists in the high-detection group had better detection rates for minute (major diameter ≤5 mm) and small (major diameter 6-10 mm) GCs than the low-detection group (0.19%/0.23% vs 0.085%/0.098%). These differences were significant (p<0.01), although there were no significant differences in detection of larger tumours (major diameter ≥11 mm; 0.40% vs 0.28%; p=0.13). The tumour location and H. pylori status were similar in the low-detection group, high-detection group and for the highest detector.

Significant variation in the detection of hard-to-find, smaller GCs may reflect individual performance of the examination.

The objective of this study was to clarify characteristics of metachronous endoscopic curability C2 (eCura C2) cancer during post-endoscopic submucosal dissection (ESD) follow-up.

Of 4,355 gastric lesions treated by ESD at our hospital during 2005-2021, 657 were metachronous. After excluding lesions found ≥2 years since the prior examination or in the gastric remnant, the remaining 515 were analyzed. Study 1: We compared 35 eCura C2 cancers and 480 eCura A-C1 cancers. Study 2: Endoscopic findings of the 35 lesions were examined to determine why they had been missed.

Mean tumor size was larger (34.0 mm vs. 12.1 mm, p < 0.01) and the proportions of mixed-type and poorly differentiated cancers were higher (highly:mixed:poorly, 34.3:57.1:8.6 vs. 94.2:5.0:0.8, p < 0.01) in the eCura C2 group. Study 2: At the prior examination, 4 lesions were noticed but considered benign, 2 lacked sufficient imaging, 19 were detectable on imaging but missed, and 10 were not detectable on imaging. Over half the lesions that were detectable but missed at the prior examination were in the lesser curvature, many being type IIa-IIb lesions with color similar to the background mucosa. All lesions not detectable on imaging at the prior examination were mixed-type or poorly differentiated type.

Metachronous cancer detected as eCura C2 cancers was significantly larger, and a significantly higher proportion was mixed-type or poorly differentiated cancers, compared with eCura A-C1 cancers. Possible reasons why these lesions were missed include rapid progression of mixed-type and poorly differentiated cancers, and poor recognition that lesions showing only slight color changes may be present at the lesser curvature.

Although proximal gastrectomy (PG) with the double-flap technique (DFT) is a function-preserving surgery that prevents esophagogastric reflux, there is a risk of developing metachronous remnant gastric cancer (MRGC). Moreover, details of MRGC and appropriate postoperative follow-up after PG with DFT are unclear.

We reviewed the medical records of 471 patients who underwent PG with DFT for cancer in a preceding, multicenter, retrospective study (rD-FLAP Study). We investigated the incidence of MRGC, frequency of follow-up endoscopy, and eradication of Helicobacter pylori (H. pylori) infection.

MRGC was diagnosed in 42 (8.9%) of the 471 patients, and 56 lesions of MRGC were observed. The cumulative 5- and 10-year incidence rates were 5.7 and 11.4%, respectively. There was no clinicopathological difference at the time of primary PG between patients with and without MRGC. Curative resection for MRGC was performed for 49 (88%) lesions. All patients with a 1-year, follow-up, endoscopy interval were diagnosed with early-stage MRGC, and none of them died due to MRGC. Overall and disease-specific survival rates did not significantly differ between patients with and without MRGC. The incidence rate of MRGC in the eradicated group after PG was 10.8% and that in the uneradicated group was 19.6%, which was significantly higher than that in patients without H. pylori infection at primary PG (7.6%) (p = 0.049).

The incidence rate of MRGC after PG with DFT was 8.9%. Early detection of MRGC with annual endoscopy provides survival benefits. Eradicating H. pylori infection can reduce the incidence of MRGC.