BACKGROUND:Accurate prediction of lymph node metastasis (LNM) is crucial for treatment decisions in early gastric cancer (EGC). Current preoperative methods for LNM prediction are often insufficient. PATIENTS AND METHODS:This multicenter retrospective study enrolled 605 EGC patients who underwent endoscopic submucosal dissection (ESD) and/or surgery across five institutions between 2013 and 2023. We developed a deep learning model, LNMate, to predict LNM before ESD and evaluated its impact on endoscopists' diagnostic performance. We also conducted immunohistochemical (IHC) analysis on tissue samples from 32 patients. Additionally, we constructed a deep learning-based endoscopic nomogram (DLEN) to estimate LNM risk after ESD, validated through comparison with the eCura system. RESULTS:LNMate showed high predictive performance with area under the curves (AUCs) ranging from 0.843 (95% confidence interval [CI], 0.782-0.904) to 0.875 (95% CI, 0.814-0.936). With LNMate assistance, endoscopists improved diagnostic accuracy by 13.8%, particularly in specificity (mean increase of 0.17, P = 0.03). IHC analysis showed associations between CD8+ and CD20+ cell enrichment with non-LNM predictions, and CD68+ macrophage infiltration with LNM. The DLEN outperformed the eCura system (AUC, 0.91 [95% CI, 0.86-0.97] vs. 0.71 [95% CI, 0.58-0.83], P < 0.01), reducing oversurgery by 24.2%, with no false negatives. CONCLUSIONS:The deep learning-based intelligent system for the entire treatment process of EGC showed excellent performance in predicting LNM, offering valuable decision support for both endoscopists in pre-ESD treatment planning and surgeons in post-ESD surgical decision-making.

BACKGROUND: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. AIM:To determine risk factors for the metachronous occurrence of early gastric cancer (EGC) in elderly individuals. METHODS: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. RESULTS: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. CONCLUSION: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.

Background: Metachronous gastric cancer (MGC) has gained increasing attention due to the preservation of the stomach during endoscopic resection for early gastric cancer (EGC). Objectives: This study aims to investigate the risk factors associated with MGC in the postoperative surveillance of endoscopic submucosal dissection (ESD). Design: A retrospective case-control study. Methods: The retrospective study was conducted between January 1, 2014, and June 30, 2020, at the Affiliated Drum Tower Hospital of Nanjing University Medical School. Results: 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. Conclusion: 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.

Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. This retrospective, case–control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95

1Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China. Correspondence: Ying Lv, MD. E-mail: [email protected].

Background Endoscopic submucosal dissection (ESD) is commonly used to treat early gastric cancer (EGC). The effects of Helicobacter pylori (HP) infection on ESD and the potential benefits of preoperative eradication of HP are unclear. We aimed to study the impact of HP infection on bleeding and lesion detection during ESD in these patients. Methods A total of 634 consecutive patients who underwent ESD for EGC at our centre from January 2018 to January 2023 were enrolled retrospectively. Logistic regression was used to analyze intraoperative bleeding and lesion detection rate based on HP eradication status. The screened indicators were used to create a predictive model, and efficacy was assessed using the ROC curve. Results HP-positive patients had a higher intraoperative bleeding rate (28.8%) compared with Hp-negative patients (8.9%) (P<0.001). HP-positive patients also had longer procedure time (median: 58.5 vs 50.0 minutes, P<0.001) and postoperative hospital stay (median: 4.35 vs 4.07 days, P=0.036) compared to HP-negative patients. Multivariate analysis revealed that HP-positive (OR=4.84), multiple lesions (OR=1.81), specimen size > 40 mm (OR=3.67), and submucosal invasion (OR=2.27) were independent risk factors for intraoperative bleeding (IDDF2024-ABS-0046 Figure 1). The predictive model had an AUC of 0.807 (95%CI=0.761-0.852) with a sensitivity of 72.1% and a specificity of 75.9% (IDDF2024-ABS-0046 Figure 2). Eradicating HP also increased the rate of lesion detection independently (OR=2.82). Conclusions HP eradication before ESD in patients with EGC reduces intraoperative bleeding and improves lesion detection. It is very necessary to eradicate HP before ESD for patients with EGC.

Background Endoscopic submucosal dissection (ESD) is commonly used to treat early gastric cancer (EGC). The effects of Helicobacter pylori (HP) infection on ESD and the potential benefits of preoperative eradication of HP remain unclear. The study aims to evaluate the impact of HP infection on bleeding and lesion detection during ESD in patients with EGC. Methods We retrospectively analyzed 634 consecutive patients who underwent ESD for EGC at our center between January 2018 and January 2023. Logistic regression was used to assess the impact of HP infection status on intraoperative bleeding and lesion detection rates. We developed a predictive model based on selected indicators and evaluated its performance using the ROC curve. Results HP-positive patients experienced a higher rate of intraoperative bleeding (28.8%) compared with HP-negative patients (8.9%) (P < 0.001). HP-positive patients also had longer procedure time (median: 58.5 vs. 50.0 min, P < 0.001) and postoperative hospital stays (median: 4.35 vs. 4.07 days, P = 0.036). Multivariate analysis identified HP-positive (OR = 4.84), multiple lesions (OR = 1.81), specimen size > 40 mm (OR = 3.67), and submucosal invasion (OR = 2.27) as independent risk factors for intraoperative bleeding. The predictive model achieved an AUC of 0.807 (95%CI 0.761-0.852), with a sensitivity of 72.1% and specificity of 75.9%. Preoperative HP eradication was associated with an increased rate of lesion detection (OR = 2.82). Conclusions Eradicating HP before ESD in patients with EGC reduces intraoperative bleeding and improves lesion detection. Preoperative HP eradication is therefore recommended in patients with EGC.

BACKGROUND:Ferroptosis is an important iron-dependent form of cell death in hepatocellular carcinoma (HCC). Sorafenib, a potent ferroptosis inducer, is used to treat advanced HCC but its efficacy is limited by the development of drug resistance.METHODS:The effects of DUXAP8 expression on HCC progression were evaluated by TCGA database, Kaplan-Meier analysis, and in situ hybridization analysis. Sorafenib resistant HCC cell lines were modeled in vitro to study the regulation of DUXAP8 on ferroptosis in HCC induced by sorafenib. We used RNA pull-down, immunofluorescence assays, acyl-biotinyl exchange assay and mass spectrometry analysis to assess the molecular mechanism of ferroptosis regulation by DUXAP8. Syngeneic subcutaneous and orthotopic CDX models were used to assess whether DUXAP8 inhibition improves HCC in vivo.RESULTS:LncRNA DUXAP8, which is highly expressed in liver cancer and associated with poor prognosis, contributes to sorafenib resistance through suppression of ferroptosis. In vitro tests revealed that DUXAP8 reduced the sensitivity of HCC to sorafenib-induced ferroptosis by acting on SLC7A11, a subunit of the amino acid antiporter system xc-. DUXAP8 facilitates SLC7A11 palmitoylation and impedes its lysosomal degradation, thereby enhancing SLC7A11 action and suppressing ferroptosis. RNA pull-down and immunofluorescence assays confirmed that DUXAP8 decreased membrane translocation and promoted sorting of de-palmitoylated SLC7A11 to lysosomes by binding of DUXAP8 to SLC7A11. In addition, mass spectrometric analysis found that the Cys414 residue of SLC7A11 might be the predominant mutant site responsible for molecular masking of SLC7A11 lysosomal sorting. Further, the antitumor effect of DUXAP8 knockdown was verified in orthotopic and subcutaneous CDX models.CONCLUSIONS:Our findings suggest that a novel translational strategy combining sorafenib with DUXAP8 silencing to overcome drug resistance may improve treatment efficacy in patients with advanced HCC.

[This corrects the article on p. 546 in vol. 9, PMID: 30949409.].

INTRODUCTION: A modified cap-assisted endoscopic mucosal resection (mEMR-C), introduced in this study, was a novel variation of the standard EMR. We aimed to compare the outcomes of mEMR-C and endoscopic submucosal dissection (ESD) for the treatment of small (≤20 mm) intraluminal gastric gastrointestinal stromal tumors (gGISTs). METHODS: This retrospective study included 43 patients who underwent mEMR-C and 156 patients who received ESD at Nanjing Drum Tower Hospital. Baseline characteristics, adverse events, and clinical outcomes were compared between the 2 groups. Univariate and multivariable analyses were conducted to adjust for confounders. After propensity score matching using sex, year, location, and tumor size, outcomes were compared with 41 patients in each group. RESULTS: A total of 199 patients underwent endoscopic resection and the en bloc resection rate was 100%. The complete resection rate was comparable in both groups ( P = 1.000). Approximately 9.5% of all patients had a positive margin. There was no significant difference in positive margin for patients undergoing mEMR-C or ESD (9.3% vs 9.6%, P = 1.000). No difference in adverse events in both groups ( P = 0.724). The mEMR-C was associated with shorter operation time and lower cost than the ESD. Recurrence was reported in 2 patients at 1 and 5 years after ESD during a median follow-up of 62 months. No metastasis and disease-related death were identified in both groups. Propensity score matching analysis revealed similar results. DISCUSSION: The mEMR-C was found to be the preferable technique for small (≤20 mm) intraluminal gGISTs with shorter operation time and lower cost as compared with ESD.

Background The clinicopathological features and endoscopic characteristics under magnifying endoscopy with narrow band imaging (ME-NBI) between early-stage gastric-type differentiated adenocarcinoma (GDA) and intestinal-type differentiated adenocarcinoma (IDA) remain controversial. Methods Early gastric adenocarcinomas that underwent endoscopic submucosal dissection (ESD) in Nanjing Drum Tower Hospital between August 2017 and August 2021 were included in the present study. GDA cases and IDA cases were selected based on morphology and immunohistochemistry staining of CD10, MUC2, MUC5AC, and MUC6. Clinicopathological data and endoscopic findings in ME-NBI were compared between GDAs and IDAs. Results The mucin phenotypes of 657 gastric cancers were gastric ( n = 307), intestinal ( n = 109), mixed ( n = 181) and unclassified ( n = 60). No significant difference was observed in terms of gender, age, tumor size, gross type, tumor location, background mucosa, lymphatic invasion, and vascular invasion between patients with GDA and IDA. GDA cases were associated with deeper invasion than IDA cases ( p = 0.007). In ME-NBI, GDAs were more likely to exhibit an intralobular loop patten, whereas IDAs were more likely to exhibit a fine network pattern. In addition, the proportion of none-curative resection in GDAs was significantly higher than that in IDAs ( p = 0.007). Conclusion The mucin phenotype of differentiated early gastric adenocarcinoma has clinical significance. GDA was associated with less endoscopically resectability than IDA.

Objective:To compare the histopathological features and treatment efficacy of different methods for metachronous early gastric cancer (MEGC) in the remnant stomach.Methods:A total of 66 patients [38 endoscopic submucosal dissection (ESD) and 28 gastrectomy] with MEGC in the remnant stomach from January 2014 to December 2020 in Drum Tower Hospital were divided into the ESD group and the gastrectomy group. The baseline characteristics, histopathological features, treatment efficacy, and cost differences of the two groups were analyzed.Results:The MEGC in the remnant stomach mostly occurred in elderly male patients, with the mean age of 69.7±8.5 years. The mean interval of the occurrence of MEGC in the remnant stomach was 6 years. As for the tumor location, the gastric body (31.6%) was the main location in the ESD group and gastric cardia (53.6%) in the gastrectomy group with significant difference ( χ2=11.07, P=0.026). The mean operation time, hospital stay, postoperative fasting time, and total treatment cost were 80.0 min, 6.0 d, 1.5 d, ￥19 436 in the ESD group and 215.0 min, 19.0 d, 6.5 d, and ￥68 665 in the gastrectomy group, respectively, with significant differences between the two groups ( P<0.05). The overall survival rate during follow-up was 76.3% in the ESD group and 71.4% in the gastrectomy group with no significant difference between the two groups ( χ2=0.736, P=0.778). In terms of postoperative complications, the incidences of bleeding and infection were 7.9% and 5.3% in the ESD group, and those of obstruction and infection were both 14.3% in the gastrectomy group. There was significant difference in the incidences of postoperative obstruction between the two groups ( P<0.05). Conclusion:ESD is safe and effective for MEGC in the remnant stomach and is better than gastrectomy in terms of the treatment cost and operation time, but the long-term efficacy still needs to be validated by large-scale prospective studies.

Perforation is a common complication during endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) associated with secondary infections, sepsis, hospitalization time and cost. However, the risk factors of perforation remain controversial. This study aimed to investigate the risk factors for perforation during ER of gGISTs. This retrospective case–control study included consecutive patients with gGISTs who underwent ER between June 2009 and November 2021 at the Nanjing Drum Tower Hospital. Univariate and multivariate analyses were performed to investigate the risk factors for perforation. Sensitivity analyses with propensity scoring (PS) were performed to evaluate the stability of the independent effects. In total, 422 patients with gGISTs were included. The following factors were associated with perforation during ER: in the non-intraluminal growth patterns (all confounders adjusted odds ratio [aOR]: 5.39, 95