Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists.

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2-negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti-programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Long-term monitoring of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene.

The objective of this study was to clarify the long-term prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma with additional copies of MALT1. In this multicenter retrospective study, we enrolled 145 patients with gastric MALT lymphoma who underwent fluorescence in situ hybridization (FISH) analysis to detect t(11;18) translocation. The patient cohort was divided into three groups: Group A (n = 87), comprising individuals devoid of the t(11;18) translocation or extra MALT1 copies; Group B (n = 27), encompassing patients characterized by the presence of the t(11;18) translocation; and Group C (n = 31), including patients with extra MALT1 copies. The clinical outcomes in each cohort were collected. Over the course of a mean follow-up of 8.5 ± 4.2 years, one patient died of progressive MALT lymphoma, while 15 patients died due to etiologies unrelated to lymphoma. The progression or relapse of MALT lymphoma was observed in 11 patients: three in Group A, two in Group B, and six in Group C. In Groups A, B, and C, the 10-year overall survival rates were 82.5%, 93.8%, and 86.4%, respectively, and the 10-year event-free survival rates were 96.1%, 96.0%, and 82.9%, respectively. The event-free survival rate in Group C was significantly lower than that in Group A. However, no differences were observed in the 10-year event-free survival rates among individuals limited to stage I or II1 disease (equivalent to excluding patients with stage IV disease in this study, as there were no patients with stage II2), with rates of 98.6%, 95.8%, and 92.3% for Groups A, B, and C, respectively. In conclusion, the presence of extra copies of MALT1 was identified as an inferior prognostic determinant of event-free survival. Consequently, trisomy/tetrasomy 18 may serve as an indicator of progression and refractoriness to therapeutic intervention in patients with gastric MALT lymphoma, particularly stage IV gastric MALT lymphoma.

Evidence to Date on the Therapeutic Potential of Zolbetuximab in Advanced Gastroesophageal Adenocarcinoma.

Gastric adenocarcinoma (GAC) continues to be a prevalent worldwide malignancy and a leading cause of cancer death, and it is frequently cited as incurable. Targeted therapy in GAC has lagged behind other solid tumors. The human epidermal growth factor receptor-2 (HER-2) represented the single target in GACs for many years, seen in approximately 20% of patients with advanced GAC. Recent advances in management now include the addition of immunotherapy checkpoint inhibition to select front-line advanced GACs. Unfortunately, outcomes remain poor for most patients. We anticipate finding a key to future discoveries in GACs in next-generation sequencing and more targeted approaches. Claudin 18.2 (CLDN18.2) has emerged as a therapeutic target in GACs. CLDN18.2 is reportedly expressed in 14-87% of GACs, and CLDN18.2 is available for monoclonal antibody (mAb) binding as it is expressed on the outer cell membrane. Here, we review the exploration of CLDN18.2 as a target in GACs via the use of zolbetuximab (IMAB362). Zolbetuximab is now under priority FDA review for GACs, and we eagerly await the review outcome.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Computer-aided diagnosis in real-time endoscopy for all stages of gastric carcinogenesis: Development and validation study.

OBJECTIVE: Using endoscopic images, we have previously developed computer-aided diagnosis models to predict the histopathology of gastric neoplasms. However, no model that categorizes every stage of gastric carcinogenesis has been published. In this study, a deep-learning-based diagnosis model was developed and validated to automatically classify all stages of gastric carcinogenesis, including atrophy and intestinal metaplasia, in endoscopy images. DESIGN: A total of 18,701 endoscopic images were collected retrospectively and randomly divided into train, validation, and internal-test datasets in an 8:1:1 ratio. The primary outcome was lesion-classification accuracy in six categories: normal/atrophy/intestinal metaplasia/dysplasia/early /advanced gastric cancer. External-validation of performance in the established model used 1427 novel images from other institutions that were not used in training, validation, or internal-tests. RESULTS: The internal-test lesion-classification accuracy was 91.2% (95% confidence interval: 89.9%-92.5%). For performance validation, the established model achieved an accuracy of 82.3% (80.3%-84.3%). The external-test per-class receiver operating characteristic in the diagnosis of atrophy and intestinal metaplasia was 93.4 ± 0% and 91.3 ± 0%, respectively. CONCLUSIONS: The established model demonstrated high performance in the diagnosis of preneoplastic lesions (atrophy and intestinal metaplasia) as well as gastric neoplasms.

Clinical outcomes of argon plasma coagulation for the treatment of gastric low grade dysplasia.

BACKGROUND & AIMS: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. METHODS: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. RESULTS: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01-1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm (p <0.004). CONCLUSIONS: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring.

Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial).

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

Differentiating gastric schwannoma from gastric stromal tumor (≤5 cm) by histogram analysis based on iodine-based material decomposition images: a preliminary study.

Objective: This study aims to investigate the value of histogram analysis based on iodine-based material decomposition (IMD) images obtained through dual-energy computed tomography (DECT) to differentiate gastric schwannoma (GS) from gastric stromal tumor (GST) (≤5 cm) preoperatively. Methods: From January 2015 to January 2023, 15 patients with GS and 30 patients with GST (≤5 cm) who underwent biphasic contrast-enhanced scans using DECT were enrolled in this study. For each tumor, we reconstructed IMD images at the arterial phase (AP) and venous phase (VP). Nine histogram parameters were automatically extracted and selected using MaZda software based on the IMD of AP and VP, respectively, including mean, 1st, 10th, 50th, 90th, and 99th percentile of the iodine concentration value (Perc.01, Perc.10, Perc.50, Perc.90, and Perc.99), variance, skewness, and kurtosis. The extracted IMD histogram parameters were compared using the Mann-Whitney U-test. The optimal IMD histogram parameters were selected using receiver operating characteristic (ROC) curves. Results: Among the IMD histogram parameters of AP, the mean, Perc.50, Perc.90, Perc.99, variance, and skewness of the GS group were lower than that of the GST group (all P < 0.05). Among the IMD histogram parameters of VP, Perc.90, Perc.99, and the variance of the GS group was lower than those of the GST group (all P < 0.05). The ROC analysis showed that Perc.99 (AP) generated the best diagnostic performance with the area under the curve, sensitivity, and specificity being 0.960, 86.67%, and 93.33%, respectively, when using 71.00 as the optimal threshold. Conclusion: Histogram analysis based on IMD images obtained through DECT holds promise as a valuable tool for the preoperative distinction between GS and GST (≤5 cm).

[Lactate promotes HMGB1 phosphorylation and release via Akt signaling pathway in gastric cancer cells HGC-27].

Objective: To investigate the molecular mechanism of how lactate induces high mobility group box 1 (HMGB1) release. Methods: Gastric cancer HGC-27 cells were divided into the control group and the lactate group (The cells were treated with lactate for 6 h). The level of HMGB1 in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA), the localization of HMGB1 was detected using laser confocal microscopy, and the nuclear translocation of HMGB1 was detected using the nucleoplasmic separation assay. The phosphorylation and acetylation levels of HMGB1 were determined by co-immunoprecipitation, and Western blot was used to measure the phosphorylation of Akt and protein kinase C (PKC). HGC-27 cells were first treated with lactate and LY294002, the inhibitor of Akt, and then the phosphorylation of HMGB1 and Akt was analyzed by co-immunoprecipitation and Western blot, respectively. The localization of HMGB1 in cells was detected by laser confocal microscopy. EdU and Transwell assays were used to detect the proliferation and migration abilities of HGC-27 cells, respectively. HGC-27 cells were then injected into the BALB/C null mice for subcutaneous tumor implantation. Mice in the lactate group were intraperitoneally injected with lactate (0.2 g/kg/2 d), while those in the control group were intraperitoneally injected with an equal amount of PBS for 20 consecutive days. ELISA was used to detect the HMGB1 levels in the blood samples taken from the medial canthus vein of the mice, while co-immunoprecipitation and Western blot were used to detect the phosphorylation of HMGB1 and Akt in tumor tissue proteins, respectively. Results: The release levels of HMGB1 in the lactate group were (2 995.00±660.91) pg/ml and (696.33±22.03) pg/ml, after lactate treatment for 6 h and 12 h, respectively, both higher than those in the control group (485.00±105.83) pg/ml (P<0.001 and P=0.028, respectively). After lactate treatment for 6 h, the relative expression of HMGB1 protein in the cytoplasm of HGC-27 cells was 1.13±0.09, higher than that of the control group (0.83±0.07, P=0.001), while the relative expression of HMGB1 in the nucleus was 0.79±0.06, lower than that of the control group (1.07±0.06, P=0.007). The phosphorylation level of HMGB1 reached 1.41±0.09, which was higher than that of the control group (0.97±0.10, P=0.031). The phosphorylation level of Akt was 11.16±0.06, higher than that of the control group (0.91±0.022, P=0.002). The phosphorylation level and nuclear translocation of HMGB1 induced by lactate decreased obviously after Akt inhibition; the proliferation and migration abilities induced by lactate were also obviously inhibited after Akt inhibition. In vivo, the HMGB1 level in the peripheral blood was (1 280.70±389.66) pg/ml in the lactate group, which was obviously higher than that in the control group (595.11±44.75) pg/ml (P=0.008), and the phosphorylation levels of HMGB1 and Akt in tumor tissues in the lactate group were obviously enhanced compared with the control group. Conclusion: Lactate induces HMGB1 release through enhancing HMGB1 phosphorylation via the Akt signaling pathway.

BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy.

BACKGROUND: Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations. METHODS: To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype. RESULTS: Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype. CONCLUSIONS: In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

Differential Diagnosis of Thickened Gastric Wall between Hypertrophic Gastritis and Borrmann Type 4 Advanced Gastric Cancer.

Background/Aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them. Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness. Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4. Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Texture and color enhancement imaging improves the visibility of gastric neoplasms: clinical trial with image catalogue assessment using conventional and newly developed endoscopes.

BACKGROUND: Texture and color enhancement imaging (TXI) enhances the changes in endoscopic features caused by gastric neoplasms, such as redness/whiteness and elevation/depression. This study aimed to demonstrate the effectiveness of TXI in improving the visibility of gastric neoplasms compared with white light imaging (WLI) using conventional (CE) and newly developed endoscopes (NE). METHODS: We recruited patients who were histologically diagnosed with gastric neoplasms; endoscopy was performed, and gastric neoplasms photographed using three imaging modalities, including WLI, TXI mode 1 (TXI-1) and TXI mode 2 (TXI-2). Two different endoscopes (CE and NE) were used for the same patients. Six endoscopists provided the visibility scale scores ranging from 1 (poor) to 4 (excellent) for gastric neoplasms. The primary outcome was the visibility scale scores based on each modality and endoscope. The secondary outcome was the identification of factors including H. pylori infection, atrophy, location, size, morphology, histological diagnosis and intestinal metaplasia that affect the differences in visibility scale scores between TXI-1/TXI-2 and WLI. RESULTS: Fifty-two gastric neoplasms were analyzed. The mean visibility scale scores with the NE were 2.79 ± 1.07, 3.23 ± 0.96 and 3.14 ± 0.92 for WLI, TXI-1 and TXI-2, respectively. The mean visibility scales with the CE were 2.53 ± 1.10, 3.04 ± 1.05 and 2.96 ± 1.92 for WLI, TXI-1 and TXI-2, respectively. For both endoscopes, significant differences were observed in visibility scale scores between WLI and TXI-1 (p < 0.001) and between WLI and TXI-2 (p < 0.001). The visibility scale scores of NE were superior to those of CE in all modalities. In the secondary outcome, there was no factor affected the differences of visibility scale scores between TXI-1/TXI-2 and WLI. CONCLUSIONS: This study demonstrated that TXI-1 and TXI-2 enhanced the visibility scale scores of gastric neoplasms compared with that of WLI. Moreover, newly developed endoscope has the potential to improve visibility compared to conventional endoscope. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN000042429, 16/11/2020).

Análise exploratória dos padrões alimentares de pacientes com adenocarcinoma gástrico: um estudo de caso-controle na Região Brasil Central / Exploratory analysis of dietary patterns of patients with gastric adenocarcinoma: a case-control study in central brazil

ABSTRACT Background: Diet is one of the most important modifiable risk factors for the incidence of gastric cancer. Objective: To carry out an exploratory analysis on the dietary patterns of individuals with gastric adenocarcinoma (AdG) in the Central Brazil region. Methods: This is a case-control study carried out from April 2019 to July 2022, in three reference centers for cancer treatment in Goiânia-GO. The cases were patients diagnosed with AdG, the control 1 dyspeptic patients submitted to upper digestive endoscopy and the control 2 patients without gastric complaints. In the three groups, patients aged 18 to 75 years and of both sexes were recruited. To assess food consumption, a Food Frequency Questionnaire validated for the Brazilian population was used. Dietary patterns were identified by Exploratory Factor Analysis (EFA), using principal component analysis as the extraction method, followed by Varimax rotation. Results: The commonality values in the EFA for the foods/food groups consumed by the cases and controls were above 0.30 for all variables. The variance explained by the model was 66.7% for cases, 60.3% for control 1 and 59.7% for control 2. Three eating patterns were identified in cases, control 1 and control 2 that explained 34, 87%, 35.41% and 33.25% respectively of the total variance. The first pattern ("healthy") was characterized by the consumption of vegetables, fruits, meat and cheese; the second ("unhealthy") for sausages, pizzas, snacks, ketchup, sweet drinks and instant noodles and the third ("prudent") rice, beans, meat and fried fish and pasta. Conclusion: This study identified three dietary patterns among patients with AdG and controls in the Central Brazil region. According to the identified patterns, it will be possible to establish a relationship between diet and other epidemiological measures aimed at the prevention of gastric cancer.

RESUMO Contexto: A dieta é um dos fatores de risco modificáveis mais importante para a incidência de câncer gástrico. Objetivo: Realizar uma análise exploratória sobre os padrões alimentares de indivíduos com adenocarcinoma gástrico (AdG) na região Brasil central. Métodos: Este é um estudo de caso-controle realizado no período de abril de 2019 a julho de 2022, em três centros de referência para o tratamento para câncer em Goiânia-GO. Os casos foram pacientes diagnosticados com AdG, o controle 1 pacientes dispépticos submetidos a endoscopia digestiva alta e o controle 2 pacientes sem queixas gástricas. Nos três grupos foram recrutados pacientes de 18 a 75 anos e de ambos os sexos. Para avaliar o consumo alimentar foi utilizado um Questionário de Frequência Alimentar validado para a população brasileira. Os padrões alimentares foram identificados por Análise Fatorial Exploratória (AFE), utilizando a análise de componentes principais como método de extração, seguida pela rotação Varimax. Resultados: Os valores de comunalidade na AFE para os alimentos/grupos alimentares consumidos pelos casos e controles ficaram acima de 0,30 para todas as variáveis. A variância explicada pelo modelo foi de 66,7%, para casos, 60,3% para o controle 1 e 59,7% para o controle 2. Foram identificados três padrões alimentares nos casos, controle 1 e controle 2 que explicaram 34,87%, 35,41% e 33,25% respectivamente da variância total. O primeiro padrão ("saudável") foi caracterizado pelo consumo de vegetais, frutas, carne e queijos; o segundo ("não saudável") por embutidos, pizzas, snacks, ketchup, bebidas doces e macarrão instantâneo e o terceiro ("prudente") arroz, feijão, carnes e peixes fritos e massas. Conclusão: Esse estudo identificou três padrões alimentares entre os pacientes com AdG e os controles na região Brasil central. De acordo com os padrões identificados, será possível estabelecer uma relação entre a dieta e outras medidas epidemiológicas destinadas à prevenção do câncer gástrico.

Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study.

PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.

Clinical Decision Support System for All Stages of Gastric Carcinogenesis in Real-Time Endoscopy: Model Establishment and Validation Study.

BACKGROUND: Our research group previously established a deep-learning-based clinical decision support system (CDSS) for real-time endoscopy-based detection and classification of gastric neoplasms. However, preneoplastic conditions, such as atrophy and intestinal metaplasia (IM) were not taken into account, and there is no established model that classifies all stages of gastric carcinogenesis. OBJECTIVE: This study aims to build and validate a CDSS for real-time endoscopy for all stages of gastric carcinogenesis, including atrophy and IM. METHODS: A total of 11,868 endoscopic images were used for training and internal testing. The primary outcomes were lesion classification accuracy (6 classes: advanced gastric cancer, early gastric cancer, dysplasia, atrophy, IM, and normal) and atrophy and IM lesion segmentation rates for the segmentation model. The following tests were carried out to validate the performance of lesion classification accuracy: (1) external testing using 1282 images from another institution and (2) evaluation of the classification accuracy of atrophy and IM in real-world procedures in a prospective manner. To estimate the clinical utility, 2 experienced endoscopists were invited to perform a blind test with the same data set. A CDSS was constructed by combining the established 6-class lesion classification model and the preneoplastic lesion segmentation model with the previously established lesion detection model. RESULTS: The overall lesion classification accuracy (95% CI) was 90.3% (89%-91.6%) in the internal test. For the performance validation, the CDSS achieved 85.3% (83.4%-97.2%) overall accuracy. The per-class external test accuracies for atrophy and IM were 95.3% (92.6%-98%) and 89.3% (85.4%-93.2%), respectively. CDSS-assisted endoscopy showed an accuracy of 92.1% (88.8%-95.4%) for atrophy and 95.5% (92%-99%) for IM in the real-world application of 522 consecutive screening endoscopies. There was no significant difference in the overall accuracy between the invited endoscopists and established CDSS in the prospective real-clinic evaluation (P=.23). The CDSS demonstrated a segmentation rate of 93.4% (95% CI 92.4%-94.4%) for atrophy or IM lesion segmentation in the internal testing. CONCLUSIONS: The CDSS achieved high performance in terms of computer-aided diagnosis of all stages of gastric carcinogenesis and demonstrated real-world application potential.

Impact of Autoimmune Gastritis on Occurrence of Metachronous Gastric Neoplasms after Endoscopic Resection for Gastric Neoplasms.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Autoimmune gastritis (AIG) is characterized by antibody production against the gastric parietal cells, reducing the number of functional parietal cells. It is also associated with an increased susceptibility to gastric neuroendocrine tumors and gastric cancer. Endoscopic resection (ER) is an effective treatment for early gastric cancer; however, metachronous gastric neoplasms (MGN) can develop. This study aimed to evaluate the clinical effect of AIG on the occurrence of MGN after ER for gastric neoplasms. We retrospectively analyzed patients who underwent ER for gastric neoplasms. Patients with multiple lesions, recurrent lesions, or a history of partial gastrectomy were excluded. The presence of AIG was determined using anti-parietal cell antibody (APCA) testing. Follow-up endoscopy and metachronous tumor occurrence rates were compared between the AIG and non-AIG groups. Of the 569 patients, 282 underwent APCA testing and 20 (7.1%) were diagnosed with AIG. The incidence of MGN was significantly higher in the AIG group than in the non-AIG group (45.0% vs. 18.3%); however, the MGN occurrence pattern was similar between the two groups. Multivariate analysis revealed that AIG (HR 3.32, 95% CI 1.55-7.10, p = 0.002) and a higher body mass index (HR 1.16, 95% CI 1.06-1.27, p = 0.002) were independent factors significantly associated with the occurrence of MGN. Patients with AIG have a higher risk of metachronous lesion occurrence after ER for gastric neoplasms. Positive results of APCA testing have independent clinical implications for predicting MGN. Proper monitoring and management are essential for early detection and treatment of recurrent lesions in patients with AIG.

Complication After Gastrectomy for Gastric Cancer According to Hospital Volume: Based on Korean Gastric Cancer Association-Led Nationwide Survey Data.

PURPOSE: This study aimed to analyze the incidence and risk factors of complications following gastric cancer surgery in Korea and to compare the correlation between hospital complications based on the annual number of gastrectomies performed. MATERIALS AND METHODS: A retrospective analysis was conducted using data from 12,244 patients from 64 Korean institutions. Complications were classified using the Clavien-Dindo classification (CDC). Univariate and multivariate analyses were performed to identify the risk factors for severe complications. RESULTS: Postoperative complications occurred in 14% of the patients, severe complications (CDC IIIa or higher) in 4.9%, and postoperative death in 0.2%. The study found that age, stage, American Society of Anesthesiologists (ASA) score, Eastern Cooperative Oncology Group (ECOG) score, hospital stay, approach methods, and extent of gastric resection showed statistically significant differences depending on hospital volumes (P<0.05). In the univariate analysis, patient age, comorbidity, ASA score, ECOG score, approach methods, extent of gastric resection, tumor-node-metastasis (TNM) stage, and hospital volume were significant risk factors for severe complications. However, only age, sex, ASA score, ECOG score, extent of gastric resection, and TNM stage were statistically significant in the multivariate analysis (P<0.05). Hospital volume was not a significant risk factor in the multivariate analysis (P=0.152). CONCLUSIONS: Hospital volume was not a significant risk factor for complications after gastric cancer surgery. The differences in the frequencies of complications based on hospital volumes may be attributed to larger hospitals treating patients with younger age, lower ASA scores, better general conditions, and earlier TNM stages.

Influence of the centralizing gastric cancer surgery on the health-related quality of life in Brazil.

Background: The assessment of health-related quality of life (QoL) has improved the treatment of gastric cancer. Aiming to compare the influence of skilled surgeons in general hospitals versus specialized hospitals in cancer in Brazil, this study evaluated the relationship between quality of life and types of hospitals (general or cancer) in treating patients with gastric adenocarcinoma operated by surgeons with specific training in Surgical Oncology. Methods: This was a cross-sectional study involving 104 patients. Inferential analyses were used to compare two Brazilian general hospitals and a cancer center, evaluating scores of the SF-36 and FACT-Ga QoL questionnaires (Kruskal-Wallis test, Mann-Whitney test); gender, smoking, and Helicobacter pylori tests status (Pearson's Chi-Square test); ethnicity, alcoholism, location of the tumor in the stomach, Lauren's histological types, and type of surgery (Fisher's exact test), number of lymph nodes resected by Surgical Oncologists [Analysis of Variance (ANOVA) with a Fixed Factor], and comparative survival analysis (Log-Rank test). Results: Patients treated at a cancer hospital had higher scores of the FACT-Ga (FACT-G total score, P=0.023; physical well-being, PWB, P=0.006; and functional well-being, FWB, P=0.011). The mean scores of the SF-36 questionnaire showed similar behavior but without reaching a significant difference. Patients operated by Surgical Oncologists at the cancer hospital had better scores in emotional well-being FACT-Ga domain (EWB, P=0.034 and P=0.047) compared to those operated by Surgical Oncologists in general hospitals. There was no significant difference in survival among the three hospitals (P=0.214). Conclusions: In this study, it was possible to suggest the relationship between QoL assessment scores with the centralization of care at specialized cancer hospital in the treatment of patients with gastric adenocarcinoma undergoing surgery with curative intent in Brazil.

[Clinical analysis of immunotherapy rechallenge in advanced gastric cancer].

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.