Erratum: Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

This corrects the article on p. 327 in vol. 24, PMID: 38960891.

Long-term Outcomes and Prognostic Factors of Gastric MALT Lymphoma.

PURPOSE: This study aimed to evaluate the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, including overall survival (OS), remission, and factors associated with an aggressive disease course. MATERIALS AND METHODS: Medical records of 153 patients diagnosed with gastric MALT lymphoma between 2013 and 2020 were retrospectively reviewed. Patients experiencing relapse, progression, high-grade transformation, or residual diseasewere included in the aggressive group and were compared with those in the indolent group. Additionally, the endoscopic findings of Helicobacter pylori-negative patients were reviewed. RESULTS: Patient characteristics were as follows: mean age (56.9±11.2 years), sex (male, 51.0%), H. pylori infection (positive, 79.7%), endoscopic location (distal, 89.5%), endoscopic feature (superficial, 89.5%), clinical stage (stage I, 92.8%), invasion depth by endoscopic ultrasound (mucosa, n=115, 75.7%), and bone marrow result (no involvement, n=77, 100.0%). The median follow-up period was 59 months (mean, 61; range, 36-124) and the continuous remission period (n=149) was 51 months (mean, 50; range, 3-112). The 5-year survival rate was 97.7% while the 5-year continuous remission was 88.3%. Factors associated with the patients in the aggressive group were old age, sex(male), and clinical stage II or higher. H. pylori-negative patients' endoscopy revealed a high incidence of atrophic gastritis in the antrum. CONCLUSIONS: The long-term prognosis of gastric MALT lymphoma appears indolent and is indicated by the 5-year OS and continuous remission rates. Aggressive disease courses are associated with old age, sex (male), and clinical stage II or higher, but are not related to OS.

Proteomic Heterogeneity of the Extracellular Matrix Identifies Histologic Subtype-Specific Fibroblast in Gastric Cancer.

Gastric cancer (GC) is a highly heterogeneous disease regarding histologic features, genotypes, and molecular phenotypes. Here, we investigate extracellular matrix (ECM)-centric analysis, examining its association with histologic subtypes and patient prognosis in human GC. We performed quantitative proteomic analysis of decellularized GC tissues that characterizes tumorous ECM, highlighting proteomic heterogeneity in ECM components. We identified 20 tumor-enriched proteins including four glycoproteins, serpin family H member 1 (SERPINH1), annexin family (ANXA3/4/5/13), S100A family (S100A6/8/9), MMP14, and other matrisome-associated proteins. In addition, histopathological characteristics of GC reveals differential expression in ECM composition, with the poorly cohesive carcinoma-not otherwise specified (PCC-NOS) subtype being distinctly demarcated from other histologic subtypes. Integrating ECM proteomics with single-cell RNA sequencing, we identified crucial molecular markers in the PCC-NOS-specific stroma. PCC-NOS-enriched matrisome proteins and gene expression signatures of adipogenic cancer-associated fibroblasts (CAFadi) are closely linked, both associated with adverse outcomes in GC. Using tumor microarray analysis, we confirmed the CAFadi surface marker, ATP binding cassette subfamily A member 8 (ABCA8), predominantly present in PCC-NOS tumors. Our ECM-focused analysis paves the way for studies to determine their utility as biomarkers for patient stratification, offering valuable insights for linking molecular and histologic features in GC.

Predictive biomarkers for metachronous gastric cancer development after endoscopic resection of early gastric cancer.

OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

PURPOSE: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. MATERIALS AND METHODS: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). RESULTS: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. CONCLUSIONS: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

Association of lifestyle modification with the development of cardiovascular disease in gastric cancer patients who underwent gastrectomy: A nationwide population-based study.

BACKGROUND: While cancer patients are at an increased risk of cardiovascular disease (CVD), the role of modifiable risk factors remains poorly understood. This study investigated whether lifestyle modifications affect CVD development in gastric cancer patients who undergo surgery. METHODS: Using data from the Korean National Health Insurance Service (NHIS), gastric cancer patients who underwent surgery from 2010 to 2017 were identified. Lifestyle behaviours, surveyed within 2 years before and after surgery were analysed. Incident CVD, defined as a composite of myocardial infarction and stroke, was compared among subgroups of lifestyle behaviour changes. RESULTS: Among 22,211 gastrectomy patients, 628 (2.8%) developed CVD (5.68/1000 person-years). Persistent smokers (HR: 1.72, 95% CI: 1.33-2.22) and new smokers (HR: 1.85, 95% CI: 1.04-3.30) faced higher CVD risks than non-smokers, with an especially pronounced risk in persistent-smoking females (HR: 3.89, 95% CI: 1.20-12.62). Smoking cessation showed no significant risk difference compared to non-smokers (HR: 1.16, 95% CI: 0.93-1.43). Female new drinkers had a higher CVD risk than non-drinking females (HR: 2.89, 95% CI: 1.06-7.88), while men did not show such association. Changes in physical activity, when compared to physical inactivity, were not associated with CVD risk. CONCLUSION: Gastric cancer patients who smoked after surgery were more likely to develop CVD irrespective of their prior smoking status, with a notable vulnerability in persistent female smokers. Smoking cessation could potentially mitigate CVD risk to levels observed in non-smokers. Alcohol intake should be avoided following surgery, especially for female gastric cancer patients.

Clinical outcomes of ablation of gastric dysplasia with argon plasma coagulation.

BACKGROUND: Although several small cohort studies have shown the utility of argon plasma coagulation (APC) in the treatment of gastric dysplasia, its clinical significance has not been established. This study aims to assess the efficacy of APC as a first line treatment for gastric dysplasia, and identify risk factors for residual dysplasia. METHODS: A total of 179 cases of gastric dysplasia were treated with APC and have been followed-up with upper endoscopy within 1 year. The overall incidence and the characteristics of lesions with residual dysplasia in follow-up endoscopy were analyzed by logistic regression. RESULTS: Among 179 lesions treated with APC, 171 (95.5%) lesions have achieved complete ablation in the follow-up endoscopy. Additional APC was applied for residual dysplasia, achieving complete ablation in 97.77% (175/179). The upper third location of the gastric dysplasia was significantly associated with residual dysplasia, while tumor size, horizontal location, macroscopic morphology and grade of dysplasia showed no significant associations with residual dysplasia following the initial APC. CONCLUSIONS: APC with meticulous follow-up can be recommended as a first line treatment in patients with gastric dysplasia.

An artificial intelligence system for comprehensive pathologic outcome prediction in early gastric cancer through endoscopic image analysis (with video).

BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.

Long-term Outcomes of Patients With Early Gastric Cancer Who Had Lateral Resection Margin-Positive Tumors Based on Pathology Following Endoscopic Submucosal Dissection.

PURPOSE: Long-term outcomes of patients with positive lateral margins (pLMs) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study aimed to evaluate the remnant cancer and survival rates of patients with pLMs compared with those who underwent curative resection. MATERIALS AND METHODS: A retrospective analysis was performed on consecutive patients with pLMs as the only non-curative factor of expanded indication who underwent ESD for EGC with a follow-up duration of 5 years or more. The rates of remnant cancer, recurrence, and survival were analyzed and compared to those of control patients who underwent curative resection by propensity score matching. RESULTS: Among 3,515 patients treated with ESD between 2005 and 2018, 123 non-curative EGCs were retrospectively analyzed. A total of 108 patients were followed up without endoscopic or surgical resection for 8.2 years. The control group was matched in a 1:1 ratio with patients with EGC who underwent curative resection after ESD. The observation group with pLMs had a higher incidence of remnant cancer (25.9%; 28/108) compared to that in the curative resection group (0/108; P=0.000). The remaining tumors were treated with surgical or endoscopic resection, and no additional recurrences were observed. The overall survival analysis demonstrated no significant difference between the observation and curative resection groups (P=0.577). CONCLUSIONS: No difference was observed in the overall survival rate between observation and curative resection groups. Therefore, observation may be a possible option for incomplete ESD with pLMs if continuous follow-up is performed.

Risk Assessment of Metachronous Gastric Neoplasm after Endoscopic Resection for Early Gastric Cancer According to Age at Helicobacter pylori Eradication.

Background/Aims: 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. Methods: 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). Results: 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). Conclusions: 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.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Risk of gastric cancer in relation with serum cholesterol profiles: A nationwide population-based cohort study.

Obesity is a known risk factor for gastric cancer. However, the relationship between serum lipids and gastric cancer risk has not been fully established. We investigated the relationship between serum cholesterol levels and gastric cancer risk using a nationwide population cohort. Adults who received health care screening in 2009 from the Korean National Health Insurance Service were enrolled. Gastric cancer risk in relation to quartiles of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were compared according to sex, using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Among 9690,168 subjects enrolled, 92,403 gastric cancer cases were diagnosed. Higher HDL-C levels were associated with lower gastric cancer risk in the total population, men, and women (aHR [for the highest quartile] = 0.98 [0.96-0.99, P < .0001], aHR = 0.98 [0.96-1.004, P = .0004], and aHR = 0.91 [0.88-0.94, P < .0001], respectively). HDL-C showed consistent trends regardless of age or statin use. Higher LDL-C levels were also associated with lower gastric cancer risk in the total population (aHR = 0.92 [0.91-0.94], P < .0001) and men (aHR = 0.94 [0.91-0.96], P < .0001), but not in women (P = .4073). A subgroup analysis of LDL-C showed significant interactions with age and statin use (Pinteraction < .0001 and Pinteraction = .0497, respectively). The risk of gastric cancer was higher in subjects with elevated LDL-C levels in the younger group (age < 55, HR [for the highest quartile] = 1.02 [0.99-1.04] in the total population; HR = 1.03 [1.003-1.06] in men), the risk was lower in subjects with elevated LDL-C in the elderly (age ≥ 55, HR = 0.93 [0.91-0.95] in the total population; HR = 0.94 [0.92-0.96] in men). Elevated TC was associated with lower gastric cancer risk in the total population (aHR = 0.95 [0.94-0.97], P < .0001), but not in each sex separately (P = .3922 in men; P = .1046 in women). Overall, higher HDL-C levels may play a protective role in gastric cancer pathogenesis. The association between LDL-C/TC and gastric cancer seems to vary according to sex, age, and statin use. Especially in young males under age 55, high LDL-C and TC levels were associated with higher risk of gastric cancer.

Optimal treatment duration of bismuth-containing quadruple therapy in Helicobacter pylori infection: A retrospective study.

The use of bismuth-containing quadruple therapy (BQT) in Helicobacter pylori eradication has been increasing. Although the recommended treatment length for BQT is 14 days, longer durations may be associated with higher rates of adverse events. The aim of this study was to evaluate the optimal duration of BQT by comparing eradication rates and adverse events among 7, 10, and 14-day regimens. A total of 328 patients treated with BQT at Seoul National University Hospital from January 2010 to May 2022 were retrospectively evaluated. The eradication rates of different treatment groups were compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Baseline characteristics of the enrolled patients and adverse events were also analyzed. A total of 74, 177, and 77 patients were included in the 7-, 10-, and 14-day groups, respectively. Forty-one patients were lost during the follow-up. The eradication rates were 71.6%, 84.2%, and 80.5% (P = .106) by ITT, and 84.1%, 94.9%, and 92.5% (P = .028) by PP analysis in the 7-, 10-, and 14-day groups, respectively. The 10-day regimen showed significantly higher eradication rates than the 7-day regimen in both ITT (P = .024) and PP (P = .018) analyses. However, there were no significant differences in eradication rates between the 10- and 14-day groups in either ITT (P = .667) or PP (P = .537) analysis. Adverse event incidence was comparable among the groups (P = .835). Treatment with BQT for 10 days was as effective as 14 days without increasing the adverse events.

Decision to perform additional surgery after non-curative endoscopic submucosal dissection for gastric cancer based on the risk of lymph node metastasis: a long-term follow-up study.

BACKGROUND: Radical surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may be excessive, since only 5-10% of patients have lymph node metastasis (LNM). This study investigated the suitability of the eCura system for determining the need for radical surgery after non-curative ESD. METHODS: We retrospectively investigated 343 patients who underwent non-curative ESD for EGC from 2006 to 2021 at a tertiary hospital in Korea. These patients were divided into surgery (n = 191) and observation (n = 152) groups based on whether they underwent additional surgery post-ESD. Each group was further classified into low-risk (eCura score 0-1), intermediate-risk (eCura score 2-4) and high-risk (eCura score 5-7). All patients were regularly followed-up at least annually after the initial treatment. The cumulative overall and recurrence-free survival rates were calculated for each category and compared between the surgery and observation groups. RESULTS: No significant differences in overall survival were found between the surgery and observation groups in low-risk (p = 0.168) and intermediate-risk patients (p = 0.306); however, high-risk patients had better 5-year overall survival rate in the surgery group than in the follow-up group (95.2% vs. 71.4%, p < 0.001). The 5-year recurrence-free survival rate was higher in the surgery group than in the observation group for low-risk (100% vs. 84.3%; p = 0.034), intermediate-risk (96.1% vs. 88.4%; p = 0.081) and high-risk patients (100% vs. 83.3%; p = 0.023). CONCLUSIONS: Follow-up without additional surgery after non-curative ESD can be a reasonable option for low-risk and even intermediate-risk patients according to the eCura system. However, surgery is warranted for eCura high-risk patients.