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Purposes: Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for the diagnosis and treatment of GC is crucial. Methods: A total of 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify the causal effect of blood plasma proteins on GC. Heterogeneity, pleiotropy, and directionality analyses were employed to evaluate proteins identified via two-sample MR. The robustness of results was further validated via colocalization. The drug targets of proteins were evaluated to reveal the compounds that can interfere with these proteins. Results: Ten proteins with potential causations in relation to GC were identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, and HCG22. Among these proteins, LY6D, SLURP1, and THSD1 were considered as the most reliable biomarkers of GC due to their significant H4 posterior probabilities in colocalization analysis and absence of pleiotropy. Compound 35, nitrosamide, and 0175029-0000 were potential drugs or small molecules targeting LY6D, SLURP1, and THSD1, respectively. Conclusion: This study identified several plasma proteins as potential biomarkers of GC and provided data support and new insights into the early diagnosis, intervention, and therapeutic targets of GC. [ABSTRACT FROM AUTHOR]

(1) Introduction: Toll-like receptors (TLRs) are key in immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In gastric cancer (GC), TLR2, TLR3, TLR4, and TLR9 are crucial for modulating immune response and tumor progression. (2) Objective: This study aimed to assess the percentage of dendritic cells and monocytes expressing TLR2, TLR3, TLR4, and TLR9, along with the concentration of their soluble forms in the serum of GC patients compared to healthy volunteers. Factors such as disease stage, tumor type, age, and gender were also analyzed. (3) Materials and Methods: Blood samples from newly diagnosed GC patients and healthy controls were immunophenotyped using flow cytometry to assess TLR expression on dendritic cell subpopulations and monocytes. Serum-soluble TLRs were measured by ELISA. Statistical analysis considered clinical variables such as tumor type, stage, age, and gender. (4) Results: TLR expression was significantly higher in GC patients, except for TLR3 on classical monocytes. Soluble forms of all TLRs were elevated in GC patients, with significant differences based on disease stage but not tumor type, except for serum TLR2, TLR4, and TLR9. (5) Conclusions: Elevated TLR expression and soluble TLR levels in GC patients suggest a role in tumor pathogenesis and progression, offering potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study's focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein–protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers. [ABSTRACT FROM AUTHOR]

Local immunotherapy represents a promising solution for preventing tumor recurrence and metastasis post tumor surgical resection by eliminating residue tumor cells as well as eliciting tumor‐specific immune responses. Minimally invasive surgery has become a mainstream surgical method worldwide due to its advantages of aesthetics and rapid postoperative recovery. Unfortunately, the currently reported local immunotherapy strategies are mostly designed to be used after open laparotomy, which go against the current surgical philosophy of minimally invasive therapy and is not suitable for clinical translation. Aiming at this problem, a minimally invasive injectable gel (MIGel) is herein reported loaded with immunotherapeutic agents for gastric and liver cancer postoperative treatment. The MIGel is formed by crosslinking between oxidized dextran (ODEX) and 4‐arm polyethylene glycol hydroxylamine (4‐arm PEG‐ONH2) through oxime bonds, which can be injected through a clinic‐used minimally invasive drainage tube and adhered tightly to the tissue. The loaded oxaliplatin (OxP) and resiquimod (R848) can be released constantly over two weeks and resulted in over 75% cure rate in orthotopic mouse gastric and liver cancer model. Collectively, a concept of minimally invasive local immunotherapy is proposed and MIGel is designed for local intraperitoneal cancer immunotherapy through minimally invasive surgery, with good clinical translation potential. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates, and it has a complex etiology and complex pathological features. Depending on the tumor type, gastric cancer can be classified as intestinal-type and diffuse-type gastric cancer, each with distinct pathogenic mechanisms and clinical presentations. In recent years, machine learning techniques have been widely applied in the medical field, offering new perspectives for the diagnosis, treatment, and prognosis of gastric cancer patients. Methods: This study recruited 2158 gastric cancer patients and constructed prognostic prediction models for both intestinal-type and diffuse-type gastric cancer. Clinical pathological data were collected from patients, and machine learning algorithms were used for feature selection and model construction. The performance of the models was validated with training and testing datasets. The Shapley additive explanations (SHAP) values were used to interpret the model predictions and identify the main factors that influence patient survival. Results: In the prognostic model for intestinal-type gastric cancer, the gradient boosting decision tree (GBDT) model demonstrated the best performance, with key features including pTNM, CA125, tumor size, CA199, and PALB. Similarly, in the prognostic model for diffuse-type gastric cancer, the GBDT model was utilized, with key features comprising pTNM, Borrmann type IV disease, lymphocyte (LYM), lactate dehydrogenase (LDH), potassium (K), perineural invasion (PNI), tumor size, and whole stomach location. Risk stratification analysis revealed that the prognosis of high-risk patients was significantly worse than that of low-risk patients. Conclusion: Machine learning shows great potential in predicting survival outcomes of gastric cancer patients, providing strong support for the development of personalized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is caused by different exogenous risk factors. Polymerase beta (POLB) is critical to repair oxidative and alkylating-induced DNA damage in genome maintenance. It is unknown whether overexpression of POLB genes in GC modulates tumor immunogenicity and plays a role in its prognostic value. Methods: RNA-Seq of GC data retrieved from TCGA and GEO database and patient survival were compared using Kaplan-Meier statistical test. The TIMER algorithm was used to calculate the abundance of tumor-infiltrating immune cells. Furthermore, ROC analysis was applied to evaluate the prognostic value of POLB overexpression. Results: Our data analysis of TCGA and GEO gastric cancer genomics datasets reveals that POLB overexpression is significantly associated with intestinal subtypes of stomach cancer. In addition, POLB overexpression is associated with low expression of innate immune signaling genes. In contrast, POLB-overexpressed tumor harbors high mutation frequency and MSI score. Furthermore, POLB-overexpressed tumor with high immune score exhibits a better prognosis. Interestingly, our ROC analysis results suggested that POLB overexpression has a potential for prognostic markers for stomach cancer. Conclusions: Our analysis suggests that aberrant POLB overexpression in stomach cancer impacts the diverse aspects of tumor immune microenvironment. In addition, POLB might be a potential prognosis marker and/or an attractive target for immune-based therapy in GC. However, our observation still requires further experimental-based scientific validation studies. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to evaluate the cytotoxic effects of enzymatically modified pectin products derived from grapefruit, jujube, and kumquat on the MKN‐45 gastric cancer cell line in vitro. FTIR analysis revealed that the spectra of the pectins produced were comparable to those of commercial pectin and included the characteristic peaks identified in the literature. The galacturonic acid content was measured as 612 mg/g in grapefruit pectin, 544 mg/g in jujube pectin, and 704 mg/g in kumquat pectin. DSC analysis indicated that all pectin samples and their modifications exhibited one endothermic peak and one exothermic peak. Cytotoxicity assessments revealed that the enzymatically modified grapefruit pectin demonstrated significant cytotoxic effects across all tested concentrations, with 0.075 mg/mL being the most effective. For kumquat pectin, all tested concentrations showed cytotoxic properties, with 0.3, 0.15, and 0.075 mg/mL being the most effective. In the case of jujube pectin, cytotoxic effects were observed at all concentrations except for 1.2 mg/mL. [ABSTRACT FROM AUTHOR]

Gastric cancer predominantly adenocarcinoma, accounts for over 85% of gastric cancer diagnoses. Current therapeutic options are limited, necessitating the discovery of novel drug targets and effective treatments. The Affymetrix gene expression microarray dataset (GSE64951) was retrieved from NCBI‐GEO data normalization and DEGs identification was done by using R‐Bioconductor package. Gene Ontology (GO) analysis of DEGs was performed using DAVID. The protein–protein interaction network was constructed by STRING database plugin in Cytoscape. Subclusters/modules of important interacting genes in main network were extracted by using MCODE. The hub genes from in the network were identified by using Cytohubba. The miRNet tool built a hub gene/mRNA‐miRNA network and Kaplan–Meier‐Plotter conducted survival analysis. AutoDock Vina and GROMACS MD simulations were used for docking and stability analysis of marine compounds against the 5CNN protein. Total 734 DEGs (507 up‐regulated and 228 down‐regulated) were identified. Differentially expressed genes (DEGs) were enriched in processes like cell–cell adhesion and ATP binding. Eight hub genes (EGFR, HSPA90AA1, MAPK1, HSPA4, PPP2CA, CDKN2A, CDC20, and ATM) were selected for further analysis. A total of 23 miRNAs associated with hub genes were identified, with 12 of them targeting PPP2CA. EGFR displayed the highest expression and hazard rate in survival analyses. The kinase domain of EGFR (PDBID: 5CNN) was chosen as the drug target. Adociaquinone A from Petrosia alfiani, docked with 5CNN, showed the lowest binding energy with stable interactions across a 50 ns MD simulation, highlighting its potential as a lead molecule against EGFR. This study has identified crucial DEGs and hub genes in gastric cancer, proposing novel therapeutic targets. Specifically, Adociaquinone A demonstrates promising potential as a bioactive drug against EGFR in gastric cancer, warranting further investigation. The predicted miRNA against the hub gene/proteins can also be used as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to elucidate the critical role of autophagy-related gene aggregation in gastric cancer tumor microenvironment cells and to investigate their major roles in cellular functions. In particular, the expression of these genes in tumor-associated fibroblast subtypes was scrutinized in an attempt to explain their cell-subpopulation-specific roles in cell–cell communication and regulation of cellular functions. Methods: In this study, single-cell RNA sequencing data were first analyzed in multiple steps, including data preprocessing, cell clustering, and cell classification. Cell subpopulations and gene expression patterns were identified and analyzed using unsupervised non-negative matrix factorization (NMF) techniques. The dynamic expression of autophagy-related gene aggregates in various cell types was deciphered by pseudotime trajectory analysis (PTA). Intercellular communication analysis was performed using the CellChat R software package, revealing the intricate communication patterns and exchange of key signaling molecules between cell subpopulations, and SCENIC analysis was used to identify gene regulatory networks and reveal the mechanisms behind cellular heterogeneity. Result: Cell subpopulations associated with pan-apoptosis were identified by NMF decomposition and SCENIC analysis. Cell–cell communication analysis revealed intricate communication patterns and exchange of key signaling molecules between cell subpopulations. Dynamic expression of autophagy-related genes aggregated in the pseudotemporal trajectory of STAD was observed by PTA. In the fibroblast subtype, different ligand-receptor interactions and their key roles in immunomodulation were observed. Conclusion: By deeply analyzing and comparing gene expression patterns within cellular subpopulations and intercellular communication, this study provides new insights into the role of pan-apoptosis-related genes in regulating immune responses and cellular functions in gastric cancer. These findings pave the way for further exploration of the role of these genes in tumorigenesis and immune regulation, as well as laying the foundation for potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case–control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67–0.90, P‐trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87–0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84–0.95). There was a significant interaction between folate intake and alcohol consumption (P‐interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85–1.56), and the OR100 μg/day = 1.02 (95% CI, 0.92–1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect. [ABSTRACT FROM AUTHOR]

More than 25 years ago, CDH1 pathogenic variants (PVs) were identified as the primary cause of hereditary diffuse gastric cancer (HDGC), an inherited cancer syndrome that increases the lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Since DGC is associated with a poor prognosis, a prophylactic total gastrectomy (PTG) is currently the gold standard for reducing the risk of DGC in CDH1 PV carriers. However, as germline genetic testing becomes more widespread, many CDH1 PV carriers have been identified, including in families with lower penetrance levels or without a history of gastric cancer (GC). When including these families, recent findings suggest that the cumulative lifetime risk of developing advanced DGC is much lower than previously thought and is now estimated to be 13–19%. This lower risk, combined with the fact that around one third of the CDH1 PV carriers decline PTG due to potential lifelong physical and psychological consequences, raises critical questions about the current uniformity in recommending PTG to all CDH1 PV carriers. As a result, there is a growing need to consider alternative strategies, such as endoscopic surveillance. However, despite the currently lower estimated risk of infiltrative (advanced) DGC, almost every PTG specimen shows the presence of small low-stage (pT1a) signet ring cell (SRC) lesions of which the behaviour is unpredictable but often are considered indolent or premalignant stages of DGC. Therefore, the primary goal of surveillance should be to identify atypical, deeper infiltrating lesions rather than every SRC lesion. Understanding the progression from indolent to more infiltrative lesions, and recognizing their endoscopic and histological features, is crucial in deciding the most suitable management option for each individual. [ABSTRACT FROM AUTHOR]

Lipid rafts are dynamic microdomains enriched with cholesterol and sphingolipids that play critical roles in cellular processes by organizing and concentrating specific proteins involved in signal transduction. The interplay between lipid rafts, raft-associated caveolae and the human epidermal growth factor receptors has significant implications in cancer biology, particularly in breast and gastric cancer therapy resistance. This review examines the structural and functional characteristics of lipid rafts, their involvement in EGFR and HER2 signaling, and the impact of lipid rafts/CXCL12/CXCR4/HER2 axis on bone metastasis. We also discuss the potential of targeting lipid rafts and caveolin-1 to enhance therapeutic strategies against HER2-positive cancers and the impact of co-localization of trastuzumab or antibody drug conjugates with caveolin-1 on therapy response. Emerging evidence suggests that disrupting lipid raft integrity or silencing caveolin-1, through several strategies including cholesterol-lowering molecules, can influence HER2 availability and internalization, enhancing anti-HER2 targeted therapy and offering a novel approach to counteract drug resistance and improve treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Integrin β5 (ITGB5) is a pivotal player in the pathogenesis of gastric cancer (GC). We aimed to explore the potential value of ITGB5 as a predictor of diagnosis and immunotherapy in gastric cancer. Methods: The expression of ITGB5 in GC was assessed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and verified through quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Kaplan-Meier curves were conducted to evaluate the prognostic significance. The immune cells infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS) were examined using CIBERSORT, TIMER, and TISIDB. In addition, colony formation, scratch assays, and transwell assays were employed to determine the impact on tumor progression and metastasis. CD276 expression was detected by western blotting following the knockdown of ITGB5. ELISA was utilized to measure serum ITGB5 levels. Results: The expression of ITGB5 in GC tissue surpassed that in normal tissue, it might contribute to GC pathogenesis through pathways including PI3K-AKT, ECM-receptor interaction, and TGF-beta. The elevated ITGB5 expression is associated with poor prognosis in GC patients. In addition, a strong positive association between ITGB5 overexpression and the infiltration levels of macrophages and monocytes, and it significantly influenced immune response. Moreover, lower expression of ITGB5 was associated with better immunotherapy efficacy. Subsequent investigation demonstrated that silencing of ITGB5 suppressed the proliferation and migration of GC cell lines in vitro. ITGB5 expression was positively correlated with CD276 expression and the knockdown of ITGB5 resulted a notable decrease CD276 expression. Futhermore, a significantly high level of serum ITGB5 was observed in GC patients. The combined assessment of ITGB5, CEA, and CA19-9 improved the diagnostic accuracy. Conclusions: ITGB5 potentially serve as both a diagnostic biomarker and therapeutic target in managing GC. [ABSTRACT FROM AUTHOR]

Background: Effectively diagnosing lymph node (LN) metastasis (LNM) is crucial in determining the condition of patients with gastric cancer (GC). The present study was devised to develop and validate a preoperative predictive model (PPM) capable of assessing the LNM status of individuals with GC. Methods: A retrospective analysis of consecutive GC patients from two centers was conducted over the period from January 2021 to December 2023. These patients were utilized to construct a 289-patient training cohort for identifying LNM-related risk factors and developing a PPM, as well as a 90-patient testing cohort used for PPM validation. Results: Of the GC patients included in the training cohort, 67 (23.2%) and 222 (76.8%) were respectively LNM negative and positive. Risk factors independently related to LNM status included cT3 invasion (P = 0.001), CT-reported LN (+) (P = 0.044), and CA199 value (P = 0.030). LNM risk scores were established with the following formula: score = -2.382 + 0.694×CT-reported LN status (+: 1; -: 0) +2.497×invasion depth (cT1: 0; cT2: 1; cT3: 2)+0.032×CA199 value. The area under the curve (AUC) values for PPM and CT-reported LN status were 0.753 and 0.609, respectively, with a significant difference between them (P < 0.001). When clinical data from the testing cohort was included in the PPM, the AUC values for the PPM and CT-reported LN status were 0.756 and 0.568 (P < 0.001). Conclusions: The established PPM may be an effective technique for predicting the LNM status of patients preoperatively. This model can better diagnose LNM than CT-reported LN status alone, this model is better able to diagnose LNM. [ABSTRACT FROM AUTHOR]

A 70-year-old woman underwent distal gastrectomy due to gastric adenocarcinoma in 2015. After 6 years, the follow-up CT revealed a suspicious mass in the right hilar of the lung mimicking mediastinal lymph nodes. Further dynamic PET/CT images showed a mass located in the right intermediate bronchus with increased FDG uptake and relatively high Ki value, which may imply the possibility of malignancy. However, the symmetrical mediastinal lymph nodes had intense FDG uptake but relatively low Ki value, suggesting benign lesions. The initial pathological result of the bronchoscopy biopsy was considered suspicious for metastatic gastric adenocarcinoma. However, it was then found consistent with middle-grade mucoepidermoid carcinoma, considered a second primary cancer without metastatic lymph nodes as confirmed by a surgical procedure (lower bilobectomy + hilar and mediastinal lymphadenectomy). 18F-FDG PET/CT has an important value in the follow-up of indeterminate findings for patients with a tumor history. Moreover, dynamic quantification parameters such as Ki may be additionally helpful in identifying malignancies in some equivocal situations. [ABSTRACT FROM AUTHOR]

Introduction: Almost all cases of malignant acanthosis nigricans with oral manifestations occurred in older age groups. Here, we report a case of malignant acanthosis nigricans in a young female presented with chief complaints of oral mucosal hyperplasia, who had previously been diagnosed with allergies. Case presentation: A 30-year-old female developed oral hyperplasia and rash following seafood consumption, with subsequent resolution of the rash but persistent oral lesions and the appearance of pigmentation on her hands, neck, and axillae. Clinical examination revealed papillomatosis, hyperemia, and velvety hyperplasia in the oral cavity. Biopsy results confirmed papillary hyperplasia. Despite the patient’s belief in good health, she was advised to undergo further systemic examinations. Elevated serum tumor markers and histologic analysis of an endoscopic biopsy confirmed gastric cancer with duodenal infiltration, leading to the diagnosis of malignant acanthosis nigricans. Unfortunately, the patient passed away due to heart failure during chemotherapy treatment. Conclusions: The majority of patients with malignant acanthosis nigricans present with oral lesions before the underlying malignancy is detected, emphasizing the importance of timely comprehensive systemic examination. Furthermore, our case suggests that age may not be a restrictive factor for the development of malignant acanthosis nigricans, and the presence of a rash can potentially obscure the cutaneous manifestations associated with this condition. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a prevalent form of malignancy among many common carcinoma cases globally. This study was designed to assess the anticancer potential of the crude ethanolic seed extract from Mucuna pruriens against the gastric cancer cell line (AGS). Various assays were employed to assess the anticancer properties, including examinations of cell viability, nuclear morphology, apoptosis using AO/EB staining, changes in mitochondrial membrane potential, lactate dehydrogenase activity, DNA fragmentation, and cell cycle arrest. Results: The crude extract exhibited significant anticancer activity against the human gastric cancer cell line (AGS), as determined by the MTT assay, with an inhibition concentration (IC50) of 600 µg/mL at 24 h. Distinct cellular and nuclear morphological changes were observed with different concentrations of crude ethanolic seed extract. The LDH release assay reveals cell death in AGS cells, as evidenced by a significant increase in the release of LDH enzyme. DNA fragmentation analysis and flow cytometry results indicate that the extract induces chromatin condensation, apoptotic cell death, and cell cycle arrest at the G0/G1 phase in the AGS cancer cell line. These results highlight the potential therapeutic advantages of Mucuna pruriens seed extract against gastric cancer cells. Conclusion: This study could pave the way for identifying diverse natural bioactive compounds sourced from Mucuna pruriens seed, leading to the development of novel drug with potential anticancer properties. [ABSTRACT FROM AUTHOR]

The sentinel lymph node (SN) concept has a significant impact on cancer surgery. We aimed to examine which morphology of dendritic cells (DCs) and macrophages corresponds to “preconditioning” of the SN against cancer. Although macrophages are generally able to tolerate cancer metastasis, the CD169‐positive subtype is believed to be a limited exception. Immunohistochemical and morphometric analyses were performed to examine DC‐SIGN‐, CD68‐, and CD169‐positive cells in SNs and non‐SNs of 23 patients with gastric cancer with or without nodal metastasis. All patients survived for >5 years without recurrence. DCs were present in the subcapsular, paracortical, and medullary sinuses, the endothelia of which expressed DC‐SIGN and smooth muscle actin (SMA). In the non‐SNs of patients without metastasis, subcapsular DCs occupied a larger area than SNs, and this difference was statistically significant. Conversely, subcapsular DCs were likely to have migrated to the paracortical area of the SNs. DC clusters often overlapped with macrophage clusters; however, histiocytosis‐like clusters of CD169‐negative macrophages showed a smaller overlap. We found a significantly larger overlap between DC‐SIGN and CD169‐positive clusters in SNs than in non‐SNs; the larger overlap seemed to correspond to a higher cross‐presentation of cancer antigens between these cell populations. DC‐SIGN–CD169‐double positive cells might exist within this overlap. SNs in gastric cancers are usually preconditioned as a frontier of cancer immunity, but they may sometimes be suppressed earlier than non‐SNs. DC‐SIGN‐ and CD169‐positive cells appeared to decrease owing to a long lag time from the primary lesion occurrence and a short distance from the metastasis. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a malignant disease worldwide. Angiopoietin-like protein 4 (ANGPTL4) plays a role in pathophysiological processes, including metabolic reprogramming, angiogenesis, proliferation, and metastasis. Current evidence shows conflicting findings regarding the role of ANGPTL4 in the progression of GC. ANGPTL4 in GC was confirmed through bioinformatic analysis and immunofluorescence staining. The impact of ANGPTL4 was subsequently validated in GC cell lines using various assays, including 5-ethynyl-2-deoxyuridine (EdU), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow Cytometry (FCM), wound healing, transwell, tube formation, chorioallantoic membrane model, and nude mouse model assays. RNA-seq analysis, polymerase chain reaction (PCR), western blotting (WB), immunofluorescence (IF) and coimmunoprecipitation (co-IP) were conducted to determine the potential downstream mechanism of ANGPTL4. In SNU5 and MKN7 cells, ANGPTL4 was found to augment proliferation, migration, invasion, evasion of apoptosis, and angiogenesis. Conversely, in the AGS cell line, ANGPTL4 was observed to suppress these processes. Notably, the overexpression of ANGPTL4 in AGS cells led to the upregulation of LGALS7, which has emerged as a pivotal factor contributing to the manifestation of an anticancer phenotype induced by ANGPTL4. LGALS7, which is involved in the regulation of the hedgehog pathway and subsequent promotion of GC progression through various processes, such as proliferation, migration, apoptosis evasion, angiogenesis, and lymphangiogenesis, was found to contribute to the contradictory effects of ANGPTL4. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a prevalent malignant tumor and ranks as the second leading cause of death among cancer patients worldwide. Due to its hidden nature and difficulty in detection, GC has a high incidence and poor prognosis. Traditional treatment methods such as systemic chemotherapy, radiotherapy, and surgical resection are commonly used, but they often fail to achieve satisfactory curative effects, resulting in a very low 5-year survival rate for GC patients. Currently, targeted therapy and immunotherapy are prominent areas of research both domestically and internationally. These methods hold promise for the treatment of GC. This article focuses on the signaling pathways associated with the development of GC, as well as the recent advancements and applications of targeted therapy and immunotherapy. The aim is to provide fresh insights for the clinical treatment of GC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a common upper gastrointestinal tumor. However, the evaluation of prognosis and treatment response in patients with gastric cancer remains a challenge. Programmed cell death (PCD) is one of the important terminal paths for the cells of metazoans, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. The objective of this project is to investigate the predictive significance of cell death pathways and create prognostic signatures associated to cell death, with the purpose of forecasting prognosis and providing guidance for the treatment of gastric cancer. Methods: Gene transcription profiles and corresponding clinical data of gastric cancer patients were collected from The Cancer Genome Atlas (TCGA-STAD, n = 448) and the Gene Expression Comprehensive Database (GSE84437, n = 483). Thirteen types of cell death-related genes, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, cuprotosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, were analysed. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Patients were categorized into high and low-risk groups based on the median risk score for survival difference analysis. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Additionally, the response to immunotherapy in the high-risk and low-risk groups was calculated using the oncoPredict algorithm. Futhermore, the model genes were validated in the GEO validation set. Results: A total of 324 differential programmed cell death (PCD)-related genes were identified, and 65 were selected through single-factor Cox analysis. Six PCD-related genes were ultimately identified by Lasso regression to construct a prognostic risk score model. The log-rank test revealed that patients in the high-risk group had inferior survival time compared with those in the low-risk group. The area under the ROC curve (AUC) for the training group at years 1, 3, and 5 were 0.684, 0.713, 0.743, respectively, while the AUC for the validation cohort at years 1, 3, and 5 were 0.695, 0.704, and 0.707, respectively. Unsupervised clustering identified potential subtypes included in the model, and a survival difference was also observed between the two subgroups. Multifactor Cox results, combined with clinical information, demonstrated that the prognostic risk score can serve as an independent prognostic factor, irrespective of other clinical features. Conclusion: By comprehensively analyzing multiple cell death patterns, we have established a novel model that accurately forecasts the clinical prognosis and drug sensitivity of gastric cancer. It was found that all 12 representative drugs may not be suitable for patients in high-risk groups. [ABSTRACT FROM AUTHOR]

Background: Comprehensive treatment of gastric cancer (GC) is progressing, but the rapid proliferation and metastasis of GC remains a cause of high recurrence and mortality rates. In this study we investigated GC-associated circRNA tending to yield more insight into the mechanisms of gastric cancer development. Methods: We detected the expression levels of circTSN in GC tissues and cell lines using qRT-PCR. The circular structure of circTSN was confirmed by Sanger sequencing, agarose gel electrophoresis and RNase R. A series of cell functional experiments were employed to investigate the implication of circTSN aberrant expression on the proliferation and metastasis of GC cells. The predicted binding domain between circTSN and miR-1825 was analyzed by luciferase reporter gene analysis. Meanwhile, subcutaneous tumor xenografts in nude mice were used to validate the role of circTSN in vivo. Results: It was found that RNA levels of circTSN were significantly elevated in GC tissues and cell lines, which was also confirmed to contain a closed-loop structure. CCK8, clone formation, EdU, transwell and in vivo experiments indicated that the highly expressed circTSN was involved in the proliferation and metastasis process of GC. In addition, circTSN modulates the expression of SLC38A2 by sequence-specific binding to miR-1825. Conclusion: This study identified that circTSN, which is highly expressed in GC, was able to contribute to the proliferation and metastasis of GC cell through miR-1825/SLC38A2 axis and this might provide a new candidate target for the precision treatment of GC. [ABSTRACT FROM AUTHOR]

Using the modified discrete dipole approximation (DDA) method, the absorption spectrum of the multi-core-satellite structures (which are formed by connecting plasmonic nanoparticles by two probe molecules and one microRNA-21 molecule) was investigated. Two spherical and chain models were considered for the connection of the plasmonic nanoparticles. The results showed that using the chain connection model of nanoparticles leads to the formation of multiple absorption peaks, which we classified in the three wavelength regions, the short, the middle, and the long region. The three regions was 350 to 500 nm, 500 to 650 nm, and 650 to 800 nm for silver-based structures and 500 to 600 nm, 600 to 700 nm, and 700 to 800 nm for gold based structures. Due to the large number of peaks, the wavelength of the peak with the highest intensity was examined in each region. The superposition of spectra of the different structures can lead to the formation of broad peaks at longer wavelengths, which is in agreement with the previously published experimental results. [ABSTRACT FROM AUTHOR]

The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26–27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers. [ABSTRACT FROM AUTHOR]

The early detection accuracy of early gastric cancer (EGC) determines the choice of the optimal treatment strategy and the related medical expenses. We aimed to develop a simple, affordable, and time-saving diagnostic model using six machine learning (ML) algorithms for the diagnosis of EGC. It is based on the endoscopy-based Kyoto classification score obtained after the completion of endoscopy and other clinical features obtained after medical consultation. We retrospectively evaluated 1999 patients who underwent gastrointestinal endoscopy at the China Beijing Hospital. Of these, 203 subjects were diagnosed with EGC. The data were randomly divided into training and test sets (ratio 4:1). We constructed six ML models, and the developed models were evaluated on the testing set. This procedure was repeated five times. The Kolmogorov–Arnold Networks (KANs) model achieved the best performance (mean AUC value: 0.76; mean balanced accuracy: 70.96%; mean precision: 58.91%; mean recall: 70.96%; mean false positive rate: 26.11%; mean false negative rate: 31.96%; and mean F1 score value: 58.46). The endoscopy-based Kyoto classification score was the most important feature with the highest feature importance score. The results suggest that the KAN model, the optimal ML model in this study, has the potential to identify EGC patients, which may result in a reduction in both the time cost and medical expenses in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Migration–proliferation dichotomy (MPD) is a characteristic that has been observed in cancer cells growing in artificial culture media. The MPD principle states that when cells begin to grow in number (cell proliferation), their ability to migrate from one point to another (cell migration) is paused, and vice versa. This phenomenon has been used to study cancer advancement in cancer cells growing in culture, and is proposed to be responsible for the adverse therapeutic outcomes observed in patients with cancer. However, MPD has not been comprehensively investigated in cancer tissues obtained directly from patients. This study investigated MPD in stomach and bowel cancers using gene expression signatures of natural cancers. The overall findings confirm that cell proliferation and migration occur in the reverse direction in cancer cells, which is in keeping with the features that have long been observed in artificially grown cancer cells. These results also provide a basis for further investigation of MPD in natural cancers. The migration–proliferation dichotomy (MPD) has long been observed in cultured cancer cells. This phenomenon is not only relevant to tumour progression but may also have therapeutic significance in clinical cancer. However, MPD has rarely been investigated in primary cancer. This study aimed to either confirm or disprove the existence of MPD in primary cancer. Using primary gastric, colorectal and prostate cancer (GC, CRC and PCa) cohorts from the Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center, this study interrogated the MPD phenomenon by utilising RNA–Seq-based proliferation (CIN70 signature) and migration (epithelial-mesenchymal transition) indices, as well as gene set enrichment analyses (GSEA). Alternative hypothetical migration–proliferation models—The simultaneous migration–proliferation (SMP) and phenotype–refractory (PR) models—were compared to the MPD model by probing the migration–proliferation relationships within cancer stages and between early- and late-stage diseases using chi-square and independent T tests, z-score statistics and GSEA. The results revealed an inverse relationship between migration and proliferation signatures overall in the GC, CRC and PCa cohorts, as well as in early- and late-stage diseases. Additionally, a shift in proliferation- to migration dominance was observed from early- to late-stage diseases in the GC and CRC cohorts but not in the PCa cohorts, which showed enhanced proliferation dominance in metastatic tumours compared to primary cancers. The above features exhibited by the cancer cohorts are in keeping with the MPD model of the migration–proliferation relationship at the cellular level and exclude the SMP and PR migration–proliferation models. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Isolated gastric outlet obstruction secondary to breast carcinoma is a rare and often challenging diagnosis. Clinicians must be cognizant of this diagnosis even in cases where breast cancers have been in remission alongside more common causes of mechanical obstruction including pancreatic and gastric carcinomas and peptic ulcer disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: The incidence of gastric cancer is continuing to fall with the reduction exclusively affecting carcinoma arising in the body of the stomach and distal stomach. In contrast, the incidence in the proximal stomach, particularly the oesophago-gastric junction, appears to be increasing. Carcinoma of the distal stomach and body of the stomach is most common in low-socioeconomic groups, whereas the increase in proximal gastric cancer seems to affect principally higher socio-economic groups. This clinical study is undertaken to find the survival and prognostic factors in patients undergoing D1 resection and D2 resection. AIM AND OBJECTIVE: 1. To find out the survival rate of D1 and D2 resection. 2. To determine the operative morbidity in D1 and D2 resection. 3. To determine the operative mortality in D1 and D2 resection. 4. To study the possible prognostic factors of D1 and D2 resection. 5. To study relationship between age, sex, location of tumour, size, stage and survival rate in D1 and D2 resection. 6. To compare the data with other data found in the literatures PATIENTS AND METHODS: A total of 220 patients with histologically proven gastric adenocarcinoma were admitted to various surgical wards of M.K.C.G. Medical College and Hospital, Berhampur, Odisha during the study period (June 2022 - June 2024). Out of these 220 patients 130 patients were ineligible by staging laparotomy because of advanced disease and 90 patients were included randomly into the study group. All patients were admitted to the surgery indoor of M.K.C.G. Medical College Hospital. After a detail history, proper consent and thorough laboratory investigation, cardiological and pre-anaesthetic check-up as mentioned under CASE REPORT FORM (CRF) were operated. INCLUSION CRITERIA • Patients enrolled in the study were to have histologically proven admitted to Surgical wards of M.K.C.G. Medical College & Hospital, Berhampur, Odisha. • Who fell within the UICC TNM cancer stages I to III after laparoscopy. EXCLUSION CRITERIA • Young (< 20 years) patients • Co-existing cancer • Serious co-morbid cardiorespiratory disease • Distant metastasis • Previous gastric surgery • Patients not willing for the operation. RESULTS: Out of 45 patients undergoing D1 resection shows 25 patients (56%) had gastric cancer at antrum, 10 patients (22%) at cardiac, 8 patients (18%) at body and 2 patients (4%) at CMA. Out of 45 patients undergoing D2 resection shows 28 patients (62%) had gastric cancer at antrum, 8 patients (18%) at cardiac, 6 patients (13%) at body and 3 patients (7%) at CMA. There is not significant increase in the survival after D2 resection as compared to D1 resection (89% vs. 87%; x2 = 0.1036). The survival rate after D1 resection is better in lesion of size <2 cm and >5 cm but reverse in lesion of size 2-5 cm. There is not much difference between the mortality rate after D1 resection (11%) and D2 resection (13%) i.e. the mortality rate following D1 resection and D2 resection are similar (x2 = 0.1036; p = 0.05). CONCLUSION: The incidence of distal gastric is decreasing and proximal gastric cancer is increasing. This trend is not evident in the Asian population. Most patients present in late stage of disease in our study. The mortality rate following D1 resection and D2 resection are similar. Overall morbidity following D1 resection is less than D2 resection. There is no difference in survival rate between D1 and D2 resection. Extent of lymphadenectomy is controversy and need not always go for D2 resection. [ABSTRACT FROM AUTHOR]

Introduction: Petersen’s hernia is a rare and serious complication that can occur after radical gastrectomy and digestive tract reconstruction for gastric cancer. This article summarises the symptoms, diagnosis and treatment of Petersen’s hernia after surgery for gastric cancer. Patients and Methods: A retrospective analysis was conducted on 11 male patients who were diagnosed with Petersen’s hernia and underwent surgical treatment at our hospital from January 2020 to December 2022. Their clinical manifestations, perioperative conditions and follow‑up after treatment were collected. Results: The median age was 58.5 years (range: 45–73), and the median time since gastrectomy was 24 months (range: 4–125). Open distal gastrectomy (45.5%) and open total gastrectomy (27.3%) were the most common procedures. Roux‑en‑Y (81.8%) was the predominant anastomosis method. All patients underwent emergency surgery within a median time of 30 h (range: 4–45). Intestine necrosis occurred in 36.4% of cases, with a perioperative death rate of 27.3%. Conclusion: Petersen’s hernia after gastric cancer surgery can quickly lead to necrotising intestinal obstruction and poor prognosis. Enhanced abdominal computed tomography should be performed as soon as possible, and early exploratory laparotomy should be done to avoid intestinal necrosis. Routine closure of the mesenteric defect after gastric cancer resection can prevent the occurrence of Petersen’s hernia. This article highlights the need for increased awareness and preventive measures to minimise the occurrence of Petersen’s hernia in gastric cancer patients. It emphasises the importance of early detection and appropriate management strategies for improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Actin-like protein 8 (ACTL8) significantly correlates with tumor growth and prognosis across various cancer types. Nevertheless, the potential relationship between ACTL8 and gastric cancer (GC) remains uncertain. Objective: This study aimed to elucidate the role of ACTL8 in human GC cells and to explore its mechanism. Methods: Bioinformatics analysis tools, such as GEPIA2, Kaplan–Meier, and STRING, were utilized for a comprehensive investigation of the characteristics and functional roles of ACTL8 in GC, including differential expression, prognostic value, and related signaling pathways. Subsequently, gene expression analyses, cell function assays, and signaling pathway experiments were conducted to verify key findings. Results: Bioinformatics analysis showed that ACTL8 was significantly elevated in GC and closely associated with poor prognosis. Gene expression experiments confirmed the bioinformatics results. Furthermore, ACTL8 knockdown markedly reduced GC cell proliferation and inhibited migration and invasion. Mechanistically, a significant increase in the phosphorylation levels of signaling proteins was observed in GC cells following ACTL8 overexpression, and PI3K/Akt/mTOR pathway inhibitors could reverse this effect. Conclusion: ACTL8 expression is significantly upregulated in GC cells and is closely correlated with poor patient prognosis. Further mechanistic studies revealed that ACTL8 may promote GC cell migration and proliferation through activation of the PI3K/Akt/mTOR signaling pathway. Consequently, ACTL8 emerges as a promising therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Objective: Exploring the clinical efficacy and safety of targeted therapy, immunotherapy combined with chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective analysis was performed on the medical records of 134 patients with advanced gastric cancer who visited Renmin Hospital, Hubei University of Medicine from January 2019 to December 2022. According to therapeutic regimens, enrolled patients were divided into the control group and the study group. Patients in the control group received chemotherapy intervention, while those in the study group were provided with a combined intervention of apatinib, PD-1 inhibitor and chemotherapy. We analyze the tumor control effect and incidence of adverse reactions in two groups of patients. Results: The disease control rate (DCR) of patients in the study group and the control group was 72.06% and 42.42%, with an overall response rate (ORR) of 8.82% and 4.55%, The differences are statistically significant(P<0.05). By the end of follow-up, the median progression-free survival (mPFS) and the median overall survival (mOS) of the control group patients were 3.0±0.266 and 5.0±0.224 months respectively; while the mPFS and mOS of the study group were 5.0±0.261 and 7.0±0.172 months respectively, the differences are statistically significant (P<0.05). However, there was no significant difference in adverse reactions between the two groups (P>0.05). Conclusion: The therapeutic regimen of apatinib, a PD-1 inhibitor combined with chemotherapy exhibits relatively high clinical efficacy and safety for the treatment of patients with advanced gastric cancer. It can be considered as an interventional option for this type of patient. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of refined nursing combined with Zhao’s thunder-fire moxibustion in treating patients with gastric cancer (GC) of spleen-Qi deficiency syndrome. Methods: This was a retrospective study. Ninety patients with GC of spleen-Qi deficiency syndrome admitted to Baoding Hospital of Traditional Chinese Medicine from February 2022 to March 2023 were randomly divided into the observation group and the control group. Patients in the control group were intervened with XELOX chemotherapeutic regimen + routine nursing. On this basis, patients in the observation group were additionally treated with refined nursing combined with Zhao’s thunder-fire moxibustion. Changes in Traditional Chinese Medicine (TCM) syndrome scores, KPS scores for physical status, and quality of life (QOL) scores were observed and compared between the two groups before and after treatment. Results: After treatment, the scores of anorexia, fatigue and weakness, postprandial abdominal bloating, loose stools, mental fatigue and laziness to speak decreased significantly in the two groups (P< 0.05), and each TCM syndrome score in the observation group was significantly lower than that in the control group (P< 0.05). After treatment, KPS and QOL scores in the observation group were significantly higher than those in the control group (P< 0.05). The overall nursing satisfaction was 93.3% (42/45) in the observation group, which was significantly higher than 71.1% (32/45) in the control group (P< 0.05). Conclusion: Refined nursing combined with Zhao’s thunder-fire moxibustion can alleviate the clinical symptoms of patients with GC of spleen-Qi deficiency syndrome, reduce chemotherapeutic-induced adverse reactions, with high clinical application value. [ABSTRACT FROM AUTHOR]

Objective: This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high‐risk individuals in China. Methods: From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high‐risk individuals for gastric cancer were screened. These identified high‐risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021. Results: The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person‐years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38–2.08], 1.52 (95%CI: 0.50–4.66), and 4.63 (95%CI: 1.98–10.82). When using the 40–54 age group as the reference, the HR for 55–69 age group was 3.49 (95%CI: 1.52–7.98). Conclusion: Among high‐risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to investigate the efficacy of behavioral activation (BA), a novel psychological intervention, in ameliorating psychological distress and anxiety symptoms among patients diagnosed with esophageal and gastric cancer, as well as the mediating role of self‐efficacy between BA and psychological distress. Methods: A total of 139 patients diagnosed with esophageal and gastric cancer were recruited in China from March 2023 to October 2023 and randomly assigned to either the BA plus care as usual group (BA+CAU group) or the care as usual group (CAU group). Pre‐ and post‐intervention questionnaires, including the Psychological Distress Thermometer (DT), Generalized anxiety disorder 7‐item (GAD‐7) Scale, General Self‐Efficacy Scale (GSES) and the activation subscale of Behavioral Activation for Depression Scale (BADS‐A), were administered. Results: Generalized estimating equation analyses revealed that, compared to usual care alone, combining BA with usual care significantly ameliorated psychological distress, anxiety as well as improved self‐efficacy and activation. The mediation analysis revealed that self‐efficacy served as a mediator in the relationship between activation and psychological distress. Conclusions: BA primarily based on telephone or WeChat can not only directly ameliorates psychological distress and anxiety symptoms in patients with esophageal cancer and gastric cancer but also indirectly alleviates psychological distress by enhancing self‐efficacy. The study also demonstrates the potential of BA in cancer patients, a skill that can be effectively acquired by primary care workers without specialized training and implemented more flexible. Trial Registration: NCT06348940 [ABSTRACT FROM AUTHOR]

Background: Gastric adenocarcinoma of the fundic gland type (GA‐FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features. Methods: We performed whole‐genome sequencing (WGS) in formalin‐fixed paraffin‐embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA‐FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA‐FG disease. Results: We characterized the genomic architecture of GA‐FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored "Kataegis." Distinct genomic alterations between GA‐FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non‐silent alterations of formerly well‐known drivers such as TP53, PIK3CA and KRAS were identified in GA‐FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA‐FG and conventional gastric cancer. Conclusion: Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA‐FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease. [ABSTRACT FROM AUTHOR]

The significance of HER-1 and CA 125 lies in their ability to guide cancer diagnosis, treatment, and monitoring, improving personalized care and enhancing prognostic accuracy. The utilization of HER-1 and CA 125 as screening biomarkers for the anticipation of early-stage cancer and monitoring cancer progression is expanding due to the invasive and costly nature of present techniques. In this study, a novel stochastic sensor was developed for the simultaneous determination of HER-1 and CA 125 in whole blood, saliva, and gastric tumor tissue samples using a fast, easy, inexpensive, and portable method. The stochastic sensor was prepared by electropolymerization of cysteine on the surface of the Au-TiO2@rGO/SPCE sensor. The Au-TiO2@rGO nanocomposite was synthesized using a simple chemical reduction process. The proposed sensor showed wide linear concentration ranges and very low limits of quantification (LOQ). The concentration ranges were from 3.9 × 10−14 to 3.9 × 10−8 µg mL−1, with a LOQ of 3.9 × 10−14 µg mL−1 for HER-1. For CA 125, the concentration ranges were from 8.3 × 10−14 to 8.3 × 10−10 U mL−1, with a LOQ of 8.3 × 10−14 U mL−1. Both biomarkers exhibit precise discrimination in different biological samples, with recoveries above 96.78% and RSD values below 0.04%. With a confidence level of 99%, the Student t-test revealed that there is no statistically significant difference between the outcomes obtained by using the poly-Cys/Au-TiO2@rGO/SPCE sensor for screening examinations of biological samples. This was determined because the results were not significantly different from one another. [ABSTRACT FROM AUTHOR]

Objective: There is a continued need for biomarkers for patients with gastric cancer that can aid in diagnosis, treatment follow-up, and relapse detection. The objective of this study was to investigate the role of serum microRNA (miRNAs) in diagnosing gastric cancer and their relationship with prognostic factors that impact the choice of surgical approach. Methods: We compared the serum miRNA expression levels of 35 patients who underwent gastrectomy and D2 lymph node dissection for gastric adenocarcinoma between 2015-2018 with those of 33 controls. We also evaluated the relationship between serum miRNA expression levels and pathological prognostic factors. Results: The serum levels of miR-17-5p, miR-21-5p, miR-27a-3p, miR-146a-5p, miR-148a-3p, and miR-203a-3p were significantly higher in gastric cancer patients. In early gastric cancer patients, serum levels of miR-21-5p, miR-27a-3p, miR-106b-5p, miR-146a-5p, and miR-148a-3p levels were significantly higher. Furthermore, serum levels of miR-106b-5p and miR-146a-5p were associated with tumor localization [area under the curve (AUC): 0.773, 0.797; p=0.049, 0.036], while serum levels of miR-27a-3p and miR-148a-5p were associated with the T-stage of the tumor (AUC: 0.748, 0.729; p=0.036, 0.049). Conclusion: Serum levels of miR-17-5p, miR-21-5p, miR-27a-3p, and miR-203a-3p were found to be diagnostic biomarkers in gastric cancers. The expression levels of serum miR-106b-5p and miR-146a-5p were found to be related to tumor location, whereas the expression levels of serum miR-27a-3p and miR-148a-5p were found to be related to the T-stage of the tumor. These findings can impact the surgical approach for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Less than 25% of gastric cancers (GC) are discovered early, leading to limited treatment options and poor outcomes (27.8% mortality, 3.7% 5-year survival). Screening programs have improved cure rates, yet post-diagnosis treatment guidelines remain unclear (systemic chemotherapy versus surgery). The optimal type of palliative surgery (palliative gastrectomy (PG), surgical bypass (SB), endoscopic stenting (ES)) for long-term outcomes is also debated. Methods: A literature review was conducted using PubMed, MEDLINE, and EMBASE databases along with Google Scholar with the search terms "gastric cancer" and "palliative surgery" for studies post-1985. From the initial 1018 articles, multiple screenings narrowed it to 92 articles meeting criteria such as "metastatic, stage IV GC", and intervention (surgery or chemotherapy). Data regarding survival and other long-term outcomes were recorded. Results: Overall, there was significant variation between studies but there were similarities of the conclusions reached. ES provided quick symptom relief, while PG showed improved overall survival (OS) only with adjuvant chemotherapy in a selective population. PG had higher mortality rates compared to SB, with ES having a reported 0% mortality, but OS improved with chemotherapy across both SB and PG. Conclusions: Less frail patients may experience an improvement in OS with palliative resection under limited circumstances. However, operative intervention without systemic chemotherapy is unlikely to demonstrate a survival benefit. Further research is needed to explore any correlations. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI. METHODS: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%. RESULTS: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively. DISCUSSION: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection. [ABSTRACT FROM AUTHOR]

Background: The use of robotic surgery (RS) for gastric cancer (GC) has been rapidly increasing. However, the utility of RS for advanced GC (AGC), especially T3 or more AGC, is unclear. Methods: Ninety patients who underwent curative upfront minimally invasive surgery (MIS) (D2 lymph node dissection) for fStage II or III GC were enrolled in this study. Among these patients, 68 underwent MIS for T3 or more AGC. Thirty‐six patients underwent RS, and 32 patients underwent laparoscopic surgery (LS). The short‐term and long‐term surgical outcomes were compared between the two groups. Results: In the T3 or more AGC cohort, there were no significant intergroup differences in the operative time or blood loss volume. The number of retrieved lymph nodes tended to be higher in the RS than LS group (38.5 vs. 33.0, p =.11). The drain amylase content on postoperative day 1 was significantly lower in the RS than LS group (243.5 vs. 521.0 IU/L, p <.01). The morbidity rate (Clavien–Dindo grade ≥2) was similar between the groups. There were no significant differences between the LS and RS groups in the 3‐year overall survival rate (80.7% vs. 74.5%, respectively; p =.95) or 3‐year disease‐free survival rate (75.0% vs. 69.7%, respectively; p =.95). Conclusions: RS for primary T3 or more AGC was safe and contributed to similar short‐term and long‐term outcomes compared with LS. [ABSTRACT FROM AUTHOR]

Robotic surgery has been widely used in surgical gastric cancer treatments, including proximal gastrectomy. Single‐port robotic system is gaining more popularity in robotic surgery, but there has been no report on its application in robotic proximal gastrectomy with right‐sided overlap and single‐flap valvuloplasty (RPG‐ROSF). Here, we report an RPG‐ROSF using a novel single‐port robotic system in a 51‐year‐old male patient with an early‐stage gastroesophageal cancer detected by gastroscopy. It took 90 min for robotic setup, 143 min for dissection, and 161 min for digestive tract reconstruction. There was no complication during and after the surgery. The patient was discharged in 8 days postsurgery. The pathological staging of the adenocarcinoma was pT1aN0M0. This preliminary study demonstrated the feasibility and safety of a novel single‐port robot in RPG‐ROSF. [ABSTRACT FROM AUTHOR]

Background: As the incidence of obesity increases worldwide, laparoscopic gastrectomy (LG) in obese patients with gastric cancer is more common. It is unclear how visceral fat obesity (obesity disease [OD]) may influence short‐ and long‐term outcomes after LG. Methods: This study included 170 gastric cancer patients who underwent curative LG at Minoh City Hospital from 2008 to 2020. Patients were classified based on preoperative body mass index (BMI) and visceral fat area (VFA): normal (N; n = 95), visceral fat accumulation alone (VF; n = 35), obesity with visceral fat accumulation (OD; n = 35), and obesity alone (n = 5). Results: Compared with normal VFA, high preoperative VFA (≥100 cm2) was significantly associated with longer operation time, greater blood loss, more frequent postoperative complications, and longer hospital stay. Multivariate analysis revealed the following independent risk factors for postoperative intra‐abdominal infectious complications: Charlson Comorbidity Index ≥4 (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.2–8.5), dissected lymph node area (D2) (OR: 3.0, 95% CI: 1.2–7.1), and preoperative VFA (≥100 cm2) (OR: 3.7, 95% CI: 1.6–8.8). Intraoperative and postoperative courses were comparable between groups VF and OD. The 3‐year overall survival rate was significantly worse in group VF (73.2%) compared with groups OD (96.7%) and N (96.7%) (p <.0001). Recurrence‐free survival and cancer‐specific survival were comparable between groups VF, OD, and N. Conclusion: Visceral fat accumulation strongly predicted postoperative morbidity. Despite increased perioperative risk, OD did not negatively impact successful lymphadenectomy or survival following LG. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the short‐term outcomes of older adult patients with locally advanced gastric cancer who underwent open distal gastrectomy (ODG) with those who underwent laparoscopic distal gastrectomy (LDG) using propensity score matching analysis. Methods: Overall, 341 consecutive older adult patients aged 75 years with gastric cancer who underwent ODG or LDG between January 2013 and December 2020 were retrospectively assessed. Among them, 121 patients with locally advanced gastric cancer were included. To compare short‐term outcomes, a 1:1 propensity score matching analysis was performed. Results: After matching, 29 patients were included in both groups. Compared with the ODG group, the LDG group had a longer operative time (mean, 290 vs. 190 min; p <.0001) and lower estimated blood loss (mean, 39 vs. 223 mL; p <.0001). Overall postoperative complications of grade 2 and higher were observed in 2 (6.9%) and 12 (41%) patients in the LDG and ODG groups, respectively (p =.0046). Of these, the LDG group had a significantly lower incidence rate of infectious complications than the ODG group (3.4% vs. 27.6%; p =.025). Furthermore, in multivariate analysis, the laparoscopic approach was an independent protective factor against postoperative complications (p =.029). Conclusions: LDG is safe and feasible for locally advanced gastric cancer in patients aged ≥75 years. Moreover, it may be a promising alternative to ODG with better short‐term outcomes, including significantly lower incidence rates of postoperative complications. [ABSTRACT FROM AUTHOR]

Introduction: Total resection of the gastric tube with lymphadenectomy for advanced gastric tube cancer is highly invasive and associated with severe complications. Other surgical option, partial gastrectomy or wedge resection, is insufficient if lymph node metastasis is suspected. Therefore, a technique balancing invasiveness and curability is required. Materials and Surgical Technique: First, we laparoscopically peeled off adhesions of the gastric tube, gastric mesentery (including the right gastroepiploic artery/vein), pericardial membrane, and aorta, up to the planned resection line. Subsequently, we cut the infrapyloric and right gastric arteries at their roots and dissected No. 5 and No. 6 lymph nodes. We taped and spared the right gastroepiploic artery and vein and dissected the tissues including No. 4d lymph nodes. Finally, the gastric tube was cut using a linear stapler, and the remaining gastric tube was anastomosed to the jejunum with a circular stapler. The mean operative time for the three cases treated using this intervention was 729 min. The patients were discharged on postoperative day 8 or 9 without any complications. They all remained alive and recurrence‐free. Discussion: This novel approach balances invasiveness and curability by leveraging the advantages of laparoscopy. The procedure was performed safely and reproducibly in three consecutive cases, providing another viable option for the treatment of gastric tube cancer. [ABSTRACT FROM AUTHOR]

Purpose: Ovarian metastasis of gastric cancer (GC), commonly referred to as Krukenberg tumors, leads to a poor prognosis. However, the cause of metastasis remains unknown. Here, we present an integrated single-cell RNA sequencing (scRNA-Seq) analysis of the immunological microenvironment of two paired clinical specimens with ovarian metastasis of GC. Methods: scRNA-Seq was performed to determine the immunological microenvironment in ovarian metastasis of gastric cancer. CellChat was employed to analyze cell-cell communications across different cell types. Functional enrichment analysis was done by enrichKEGG in clusterProfiler. GEPIA2 was used to assess the influence of certain genes and gene signatures on prognosis. Results: The ovarian metastasis tissues exhibit a heterogenous immunological microenvironment compared to the primary tumors. Exhaustion of T and B cells is observed in the ovarian metastasis tissues. Compared to the paired adjacent non-tumoral and primary tumors, the ratio of endothelial cells and fibroblasts is high in the ovarian metastasis tissues. Compared to primary ovarian cancers, we identify a specific group of tumor-associated fibroblasts with MFAP4 and CAPNS1 expression in the ovarian metastatic tissues of GC. We further define metastasis-related-endothelial and metastasis-related-fibroblast signatures and indicate that patients with these high signature scores have a poor prognosis. In addition, the ovarian metastasis tissue has a lower level of intercellular communications compared to the primary tumor. Conclusion: Our findings reveal the immunological microenvironment of ovarian metastasis of gastric cancer and will promote the discovery of new therapeutic strategies for ovarian metastasis in gastric cancer. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a malignant tumor with one of the lowest five-year survival rates. Traditional first-line treatment regimens, such as platinum drugs, have limited therapeutic efficacy in treating advanced GC and significant side effects, greatly reducing patient quality of life. In contrast, trastuzumab and other immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have demonstrated consistent and reliable efficacy in treating GC. Here, we discuss the intrinsic characteristics of GC from a molecular perspective and provide a comprehensive review of classification and treatment advances in the disease. Finally, we suggest several strategies based on the intrinsic molecular characteristics of GC to aid in overcoming clinical challenges in the development of precision medicine and improve patient prognosis. [ABSTRACT FROM AUTHOR]

Introduction Gastric cancer has become the third leading cause of cancer deaths globally. It accounts for 5.7% of cancer around the world, with a rate of mortality around 8.2%. Evaluation of human epidermal growth factor receptor 2 (HER2)/neu overexpression for targeted therapies is presently the mainstay of treatment in gastric cancer. High Ki-67 index expression in gastric cancer is an indicator of poor prognosis. Objectives To study the prevalence of HER2/neu expression and Ki-67 index in various types, sites, grade, and stage of gastric adenocarcinoma and to determine the correlation between HER2/neu expression and Ki-67 index. Materials and Methods This is a prospective study in a tertiary care hospital, Kolkata from January 2019 to June 2020. Gastrectomy and endoscopic biopsy of gastric adenocarcinoma were studied for histopathology and immunohistochemistry (HER2/neu and Ki-67 index). Statistical analysis used: SPSS (version 21.0, IBM, Chicago, Illinois, United States) for windows software. Results Among 54 cases, most of them were intestinal type, antral, moderately differentiated, stage III cases. HER2 expression and high Ki-67 index were observed in 28.0 and 40.75% cases, respectively. Statistically significant correlation was found in both HER2 expression and high Ki-67 index with location of the tumor and pathological nodal (pN) stage. A positive correlation was found between HER2/neu score and Ki-67 index (p=0.007) (correlation coefficient=0.4). Conclusion A positive correlation was found between HER2/neu positivity and high Ki-67 index, both were associated with higher pathological tumor stage and pN stage. So, advanced cases may be considered for targeted therapy using trastuzumab. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of gastric cancer (GC) play a vital role in improving efficacy, reducing mortality and prolonging patients' lives. Given the importance of early detection of gastric cancer, an electrochemical biosensor was developed for the ultrasensitive detection of miR-19b-3p by integrating MoS2-based nanozymes, hybridization chain reaction (HCR) with enzyme catalyzed reaction. The as-prepared MoS2-based nanocomposites were used as substrate materials to construct nanoprobes, which can simultaneously load probe DNA and HCR initiator for signal amplification. Moreover, the MoS2-based nanocomposites are also employed as nanozymes to amplify electrochemical response. The presence of miR-19b-3p induced the assembly of MoS2-based nanoprobes on the electrode surface, which can activate in-situ HCR reaction to load a large number of horseradish peroxidase (HRP) for signal amplification. Coupling with the co-catalytic ability of HRP and MoS2-based nanozymes, the designed electrochemical biosensor can detect as low as 0.7 aM miR-19b-3p. More importantly, this biosensor can efficiently analyze miR-19b-3p in clinical samples from healthy people and gastric cancer patients due to its excellent sensitivity and selectivity, suggesting that this biosensor has a potential application in early diagnosis of disease. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method.This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs.Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported.Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge. [ABSTRACT FROM AUTHOR]

Purpose: It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients. Methods: We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy. Results: Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094). Conclusions: Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis. [ABSTRACT FROM AUTHOR]