Gastric Cancer Research Articles

Map-Like Redness Development After Eradication Therapy for Helicobacter pylori Infection: Prospective Multicenter Observational Study.

Map-like redness, pathological intestinal metaplasia, is observed in one-fourth to one-third of patients 1 year after Helicobacter pylori eradication therapy, mainly in the corpus, and is a newly identified endoscopic risk factor for gastric cancer development after eradication. However, it is unclear whether intestinal metaplasia is present before eradication at the site where the map-like redness appears. We aimed to identify endoscopic findings that predict the occurrence of map-like redness before H. pylori eradication. As a prospective multicenter trial, the characteristics of patients in whom map-like redness developed after eradication, and the association between the endoscopic severity of gastritis and the development of map-like redness in patients who underwent endoscopy before and 1-year after eradication were investigated. The rate of map-like redness in all 93 patients 1-year postsuccessful eradication was 30.1% (95% confidence interval [CI]: 21.0-40.5). All patients with map-like redness were endoscopically observed to have intestinal metaplasia before eradication, in the site that subsequently developed map-like redness. Patients who developed map-like redness were older, had more severe intestinal metaplasia and nodularity and a higher total score on the Kyoto Classification of Gastritis both before and after eradication than patients who did not. On multivariate analysis, map-like redness was found to be associated with posttreatment intestinal metaplasia (odds ratio: 8.144; 95% CI: 2.811-23.592). In all patients who developed map-like redness after eradication, endoscopic intestinal metaplasia was observed at the site developed map-like redness before eradication therapy. Map-like redness was especially observed in patients with more severe intestinal metaplasia at 1-year after eradication. Such patients require increased attention at surveillance endoscopy, owing to generally having a higher risk of gastric cancer development. University Hospital Medical Information Network: UMIN000044707.

The RIP3 activator C8 regulates the autophagy flux mediated by p62 and promotes the immunogenic form of cell death in human gastric cancer cells

The RIP3 activator C8 regulates the autophagy flux mediated by p62 and promotes the immunogenic form of cell death in human gastric cancer cells

Utility of near-infrared fluorescent clip for the robot-assisted gastrectomy: Report of 2 cases (case series)

Introduction and importanceThe importance of preoperative tumor site marking has increased over the years, as the method of intraoperative primary lesion identification and determination of resection margins is one factor determining whether oncological safety and function-preserving gastrectomy are possible during surgery. We hypothesize that preoperative placement of the near-infrared fluorescent (NIRF) clip, ZEOCLIP FS, near the oral incision line of the gastric tumor will allow for Firefly recognition of the NIRF clip on da Vinci during surgery and easy determination of the tumor location and incision line. Hence, we report on two cases in which the procedure was performed. Case presentationCase 1: A 62-year-old woman was diagnosed with early gastric cancer of 35 mm in size located in the greater curvature of the gastric angle and underwent robot-assisted distal gastrectomy. NIRF clips were placed around the negative biopsy-confirmed area on the tumor's oral side by endoscopy on the day before surgery. The clips were identified intraoperatively in Firefly mode, and we performed gastrectomy without using an intraoperative endoscope. Case 2: A 60-year-old man was diagnosed with early gastric cancer 40 mm in size on the anterior wall of the gastric angle and underwent robot-assisted distal gastrectomy. Similarly, NIRF clips were placed around the site of negative biopsy confirmation the day before surgery. NIRF clips were identified, and we performed gastrectomy. Clinical discussionThe time taken to mark the gastric resection line after activating the Firefly imaging system was 120 and 154 s, respectively, and intraoperative endoscopy was not required. The advantage of our two-step method is that a surgeon can mark the clips the day before the surgery, even if they are not endoscopists. Increasing the recognition rate of fluorescent clips and preventing their remains are future issues. ConclusionBased on the results of the above two cases, ZEOCLIP FS is influential in determining the tumor's location and the resection line.

Nutritional status of early oral feeding for gastric cancer patients after laparoscopic total gastrectomy: a retrospective cohort study

Nutritional status of early oral feeding for gastric cancer patients after laparoscopic total gastrectomy: a retrospective cohort study

Efficacy of traditional Chinese medicine in the conservative management of complete small intestinal obstruction post-gastric cancer surgery: A case report

In this case report, we describe the successful treatment of a patient with complete small bowel obstruction following gastric cancer surgery, employing an integrated approach of traditional Chinese medicine and Western medicine. Initial treatment consisted of conventional biomedical interventions, including intestinal obstruction catheterization, but after 16 days without improvement, surgical intervention was recommended. The patient, however, refused surgery and opted for treatments based on traditional Chinese medicine. Comprehensive traditional Chinese medicine therapies such as acupuncture, moxibustion, flash cupping, oral administration of compound herbal formulas, and enemas using Chinese herbal medicine were implemented alongside modern medical care. The obstruction resolved, and the patient was discharged without requiring surgery. Follow-up revealed no recurrence of the condition. This case highlights the potential of integrating traditional Chinese medicine with Western medical practices in the conservative management of complete small bowel obstruction, offering a reference for clinical application.

The regulatory role of tRNA-derived small RNAs in the prognosis of gastric cancer

The regulatory role of tRNA-derived small RNAs in the prognosis of gastric cancer

Stair climbing outperforms gait speed in predicting postoperative outcomes in patients undergoing radical gastrectomy for gastric cancer: a prospective study.

BackgroundStair climbing test (SCT) and gait speed test (GST) are two physical performance measures, both of which are associated with postoperative outcomes. However, few studies have compared these two tests for the prognostic value. MethodsA prospective study was conducted in patients undergoing radical gastrectomy for gastric cancer. Handgrip strength (HGS) test, 7-steps SCT and 6-meters GST were performed before surgery. Body compositions were analyzed using abdominal computed tomography (CT). Sarcopenia was diagnosed by low HGS plus either low muscle mass or quality. ResultsA total of 548 patients were included in this study. Time of GST and SCT were both significantly correlated with HGS, skeletal muscle index and skeletal muscle density, but not with subcutaneous or visceral fat area. Low SCT performance (SCT time ≥12.65s) was associated with higher incidence of postoperative complications and longer postoperative length of stay, whereas low GST performance (GST time ≥5.45s) did not. Low performance in SCT and GST were both associated with worse overall survival (OS) and disease-free survival (DFS) after surgery. Low SCT performance was an independent predictor for postoperative complications, OS, and DFS, whereas low GST performance was not significant in multivariate analyses adjusting for the same covariates. The combination of sarcopenia with low SCT performance showed higher accuracy in predicting postoperative complications and mortality compared with sarcopenia combined with low GST performance. ConclusionSCT outperformed GST in predicting outcomes after radical gastrectomy for gastric cancer, either as a singular indicator or in combination with sarcopenia assessments.

Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

The Long-Term Results of Proximal Gastrectomy for Proximal Gastric Cancer: A Propensity Score Matching Analysis Based on SEER Database.

Proximal gastrectomy (PG) is one of function-preserving gastrectomy (FPG). In this study, we compared the long-term results of proximal gastric cancer (PGC) patients undergoing proximal gastrectomy and total gastrectomy (TG). Patients diagnosed with PGC and receiving PG or TG between 2004 and 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was applied to minimize confounding factors. Kaplan-Meier analysis and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS) between the PG and TG groups. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS. A total of 3916 patients were recruited according to the inclusion and exclusion criteria, with 2614 undergoing PG and 1302 undergoing TG. After 1:1 PSM matching, 912 pairs of data were included for analysis. Before PSM matching, PG group tended to have better OS and CSS outcomes. However, after PSM matching, both surgical approaches showed similar long-term results. PG for PGC yields comparable long-term outcomes to TG and demonstrates safety in terms of oncologic outcomes.

Commentary on: MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application

Commentary on: MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application

Closure of gastric mucosal defects using the reopenable-clip over the line method to decrease the risk of bleeding after endoscopic submucosal dissection: a multicenter propensity score-matched case-control study (with video)

Background and AimsEndoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer. However, post-ESD bleeding presents significant risks. Closing mucosal defects following ESD may reduce the incidence of post-ESD bleeding. Currently, no optimal closure method exists. Therefore, we invented clip-line closure using the reopenable-clip over the line method (ROLM) and evaluated its efficacy in preventing post-ESD bleeding. MethodsWe retrospectively reviewed data from patients who underwent gastric ESD between January 2012–March 2024. Patients were categorized into two groups: the non-closure group (mucosal defect remained unclosed) and the ROLM group (defect was closed using ROLM). Baseline characteristics of patients, distribution of bleeding risk factors, and incidence and timing of post-ESD bleeding were compared between the groups. Propensity score matching was employed to minimize potential bias. ResultsFollowing propensity score-matching, 162 ESDs were performed for 168 lesions in the non-closure group, whereas 160 ESDs were performed for 168 lesions in the ROLM group. The mean long diameter of the mucosal defects, procedure time for ROLM, and number of clips required for ROLM were 45.9 mm, 35.6 min, and 33.2, respectively. All mucosal defects resulting from the ESD were fully closed using ROLM. The post-ESD bleeding rate in the ROLM group was significantly lower (1.8%, 3/168 lesions) than in the non-closure group (7.7%, 13/168 lesions, p = 0.02). ConclusionsROLM is feasible for mucosal defect closure following gastric ESD and effectively prevents post-ESD bleeding in high-risk patients, addressing a significant gap in existing methods.

Epstein Barr virus: A cellular hijacker in cancer.

Numerous studies have demonstrated the importance of the Epstein-Barr Virus (EBV), which was initially identified in 1964 while studying Burkitt's lymphoma, in the development of a number of cancers, including nasopharyngeal carcinoma, Hodgkin's lymphoma, Burkitt's lymphoma, and EBV-associated gastric carcinoma. Gammaherpesvirus EBV is extremely common; by adulthood, over 90 % of people worldwide have been infected. Usually, the virus causes a permanent latent infection in B cells, epithelial cells, and NK/T cells. It then contributes to oncogenesis by inhibiting apoptosis and promoting unchecked cell proliferation through its latent proteins, which include EBNA-1, LMP1, and LMP2A. Tumor progression further accelerated by EBV's capacity to transition between latent and lytic phases, especially in cases of nasopharyngeal carcinoma. Although our understanding of the molecular underpinnings of EBV has advanced, there are still difficulties in identifying latent infections and creating targeted therapeutics. To tackle EBV-associated malignancies, current research efforts are concentrated on developing vaccines, developing better diagnostic tools, and developing targeted treatments. In order to improve treatment approaches and lower the incidence of EBV-related cancers worldwide, more research into the relationship between EBV and immune evasion and cancer formation is necessary.

Methionine restriction promotes cisplatin sensitivity of gastric cancer resistant cells by down-regulating circ-CDK13 level

BackgroundMethionine restriction (MR) is a research direction in the treatment of gastric cancer (GC). The aim of this study was to investigate the molecular mechanism of MR on enhancing cisplatin (DDP) sensitivity of drug-resistant GC cells. MethodsTwenty pairs of GC tissues and adjacent normal gastric mucosa tissues were collected. DDP-resistant cell lines (KATO/DDP and MKN45/DDP), mouse model of GC and GC patient-derived organoid (PDO) models were established. Lentivirus-mediated METase overexpression was used for MR. Cell viability and apoptosis were detected by MTT assay and flow cytometry. Western blotting was used to detect multi-drug resistance-1 (MDR1), MDR-associated protein 1 (MRP1) eukaryotic initiation factor 4A-Ⅲ (EIF4A3), and METase protein expressions. The levels of circRNAs were detected by qRT-PCR. Tumor volume and weight were measured. The proliferation of tumor cells was detected by immunohistochemical staining. ResultsThe differentially expressed circRNAs of GC were screened in Gene Expression Omnibus database. MR in KATO/DDP and MKN45/DDP cells significantly down-regulated circ-CDK13 level. Overexpression of circ-CDK13 significantly inhibited apoptosis of sensitive cells (KATO III and MKN45). Interference with circ-CDK13 significantly promoted apoptosis of drug-resistant cells (KATO/DDP and MKN45/DDP). MR enhanced the DDP sensitivity of GC resistant cells, GC PDO and GC mice by down-regulating circ-CDK13. EIF4A3 binds to the downstream flanking sequence of circ-CDK13, and interference with EIF4A3 reduces circ-CDK13 levels, but does not affect CDK13. The expressions of circ-CDK13 and EIF4A3 in GC clinical samples were increased and positively correlated. Simultaneously overexpression of METase and EIF4A3 in resistant cells inhibited apoptosis, and further interference with circ-CDK13 reversed this effect. ConclusionMR inhibits circ-CDK13 level by down-regulating EIF4A3, thereby increasing the sensitivity of GC drug-resistant cells to DDP.

Gastric cancer and associated pathogens: is there any association in Moroccan region?

Helicobacter pylori, Epstein-Barr virus and human papillomavirus are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in Moroccan population. For this, a retrospective study has been conducted on participants attending the gastroenterology department of Hassan II University Hospital of Fez. A total of 279 participants were enrolled. H. pylori, EBV and HPV were detected and genotyped by PCR. In results, a significant association has been established between H. pylori, EBV and gastric cancer. 93.4% and 43.3% of gastric cancer cases are related to H. pylori and EBV respectively (p≤0.01). H. pylori-EBV co-infection is responsible of 31.6% of gastric cancer cases (p<0.01). Correlation between pathogens genotypes and gastric cancer shows 54.6% of GC EBV positives are carrying the 30 bp deletion in LMP1gene, while 16% of gastric cancers cases are carrying high-risk genotypes of HPV (p=0.21). The obtained results highlight the possible role of co-infection in gastric cancer development.

Helicobacter pylori a karcinom žaludku

Helicobacter pylori belongs to the most common bacterial infections worldwide; despite its decreasing prevalence during the past four decades (currently ~ 40–50%), it is more prevalent in developing countries compared to developed ones. Intensive research of chronic Helicobacter pylori infection clarified the pathogenesis of several gastric and extragastric diseases, including different cancers. This review pointed out the role of Helicobacter pylori in different gastric malignancies. Chronic Helicobacter pylori infection is an etiological factor in non-cardia gastric cancer and most cases of low-grade MALT lymphoma of the stomach. However, there is an inverse association of Helicobacter pylori infection with other gastric malignancies, like cardia gastric cancer or rare hereditary Gastric Adenocarcinoma and Proximal Polyposis of the Stomach syndrome (GAPPS). A crucial issue has not been definitely solved yet: whether early eradication of Helicobacter pylori could prevent sporadic gastric cancer in the future? There is moderate evidence that searching for and eradicating Helicobacter pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, although data cannot necessarily be extrapolated to European or US populations so far. Indication for the eradication of Helicobacter pylori must now be considered with caution, on an individual basis of personalized medicine.

A competing-risk nomogram for predicting gastric cancer-specific survival in patients over 70 years: A SEER-based study

BackgroundCancer-specific survival in older patients with gastric cancer is competitively affected by death from other causes. This study aimed to investigate cancer-specific survival and associated risk factors by competing-risk analysis in older patients with gastric cancer. MethodsThe data of this study are from the SEER database, using univariable and multivariable analysis of competitive risk model to weaken the impact of competitive events, explore the risk factors of cancer-specific survival, and developed a nomogram model. Then, the performance of the model is verified by C-index, ROC curve, calibration curve and DCA, and the new model is compared with the traditional TNM stage by NRI and IDI. ResultsOur study encompassed a total of 8183 patients, with 5731 in the training cohort and 2452 in the validation cohort. Univariable and multivariable analysis showed that age, years of diagnosis, race, site, SEER stage, TNM stage, surgery, radiation or chemotherapy, LNE, tumor grade and size are independent risk factors for cancer-specific survival in older patients with gastric cancer. Based on the risk factors, we developed a diagram model to predict cancer-specific survival. C-index, ROC curve, calibration curve and DCA also show good results. We compared the new model with the traditional TNM stage model, and the NRI and IDI showed the new model has been significantly improved. ConclusionThis study developed a nomogram to predict the cancer-specific survival of older patients with gastric cancer, which can accurately predict the prognosis and contribute to clinical treatment decision-making.

Tuning the peroxidase-mimic activity of CuX-trithiocyanuric acid complexes for colorimetric detection of gastric cancer-associated D-amino acids

A cascade colorimetric detection of salivary D-amino acids (DAAs) holds promise for the preliminary screening diagnosis of gastric cancer. Pursuing metal-organic complexes with high peroxidase-mimic (POD-mimic) activity is crucial to enhance diagnosis efficiency. In this work, we developed a straightforward strategy in a “one-pot” process to modulate the POD-mimic activity of CuX-trithiocyanuric acid (CuX-TTCA) complexes. By adjusting the molar ratios of CuX (Cl, Br, and I) and TTCA during synthesis to modify the coordination configuration of Cu(I) in CuX-TTCA, we easily tuned their POD-mimic activities. Among them, CuCl-TTCA-2 with a feeding molar ratio of 2:1 for CuCl:TTCA exhibited remarkable POD-mimic activity attributed to its exposed catalytic active sites and efficient mass transfer ability during catalysis. Long-lived 1O2 was identified as the primary reactive oxygen intermediate. A highly sensitive and selective cascade colorimetric detection platform was developed for two typical DAAs associated with gastric cancer, namely D-proline and D-alanine, achieving limit of detection values of 1.1 and 0.8 μM, respectively. As a proof-of-concept application, our cascade detection platform demonstrated excellent specificity in distinguishing saliva samples between gastric cancer patients and healthy individuals. The outstanding selectivity and reliable outcomes from DAAs assay make our detection platform highly promising for preliminary screening diagnosis of gastric cancer and patient self-detection applications. Our straightforward strategy for tuning POD-mimic activity provides an in-depth understanding on structure-activity relationship in nanozymes, offering valuable opportunities to advance enzyme-mimic optimization for other potential applications.

SPP1+ macrophages and FAP+ fibroblasts promote the progression of pMMR gastric cancer

Immunotherapy has become a primary and secondary treatment for gastric cancer (GC) patients with mismatch repair deficiency (dMMR), and is used in both perioperative and advanced stages. The tumor immune microenvironment (TiME) is crucial for immunotherapy efficacy, yet the impact of MMR status on TiME remains understudied. We employed single-cell RNA sequencing (scRNA-seq) to analyze 33 fresh tissue samples from 25 patients, which included 10 normal tissues, 6 dMMR tumor tissues, and 17 pMMR tumor tissues, aiming to characterize the cellular and molecular components of the TiME. The proficient mismatch repair (pMMR) group displayed a significantly higher prevalence of a specific GC cell type, termed GC2, characterized by increased hypoxia, epithelial-mesenchymal transition (EMT), and angiogenic activities compared to the dMMR group. GC2 cells overexpressed BEX3 and GPC3, and they significantly correlated with poorer survival. The pMMR group also showed increased infiltration of SPP1 + macrophages and FAP + fibroblasts, exhibiting strong hypoxic and pro-angiogenic features. Furthermore, a higher proportion of E2 endothelial cells, involved in extracellular matrix (ECM) remodeling and showing heightened VEGF pathway, HIF pathway, and angiogenesis activity, were identified in pMMR patients. Intercellular communication analyses revealed that GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells interact through VEGF, SPP1, and MIF signals, forming a TiME characterized by hypoxia, pro-angiogenesis, and ECM remodeling. This study uncovered TiME heterogeneity among GC patients with different MMR states, highlighting that the pMMR TiME is distinguished by hypoxia, pro-angiogenesis, and ECM remodeling, driven by the presence of GC2 cells, SPP1 + macrophages, FAP + fibroblasts, and E2 endothelial cells. These findings are pivotal for developing targeted immunotherapies for GC patients with pMMR.

Precision Medicine for Gastric Cancer: Current State of Organoid Drug Testing

Gastric cancer (GC) presents a significant health challenge and ranks as the fifth most common cancer in the world. Unfortunately, most patients with GC exhaust standard care treatment options due to late diagnosis and tumour heterogeneity that leads to drug resistance, resulting in poor survival outcomes. Potentially, this situation can be improved by personalising treatment choice. Organoids are an emerging cell model system that recapitulates tumour heterogeneity and drug responses. Coupled with genomic analysis, organoid culture can be used to guide personalised medicine. The GC organoid field, however, lacks standardised methodologies for assessing organoid drug sensitivities. Comparing results across different GC organoid studies and correlating organoid drug responses with patient outcomes is challenging. Hence, we aim to summarise the methodologies used in GC organoid drug testing and correlation with clinical outcomes and discuss design considerations and limitations to enhance the robustness of such studies in the future.

Construction and Validation of a Prognostic Prediction Model for Gastric Mucinous Adenocarcinoma Based on the SEER Database

This study focused on the development and validation of a prognostic model to predict overall survival (OS) in patients with gastric mucinous adenocarcinoma (GMA), utilizing data from the SEER database. A cohort of 537 GMA patients was analyzed to identify factors affecting survival, using both univariate and multivariate Cox regression analyses on demographic and clinicopathological variables. The analysis led to the creation of a nomogram model. Findings revealed that TNM staging and the administration of radiotherapy or chemotherapy were significant factors impacting survival outcomes. Specifically, patients at stages T4, N3, and M1 faced a notably higher mortality risk, while those who received radiotherapy and chemotherapy experienced a significant reduction in mortality risk. The model's performance, as indicated by C-indices of 0.73 in the training set and 0.66 in the validation set, suggests robust predictive capability. The area under the curve (AUC) analysis confirmed high accuracy in predicting 1-year, 3-year, and 5-year survival rates, and calibration curves displayed strong agreement between predicted and actual outcomes. Decision curve analysis (DCA) demonstrated that the model exhibited significant clinical utility across various thresholds. Overall, this study presents a reliable prognostic tool for individualized risk stratification and clinical treatment in GMA patients. Future work should focus on enhancing the model by incorporating molecular biological data to increase its predictive accuracy and applicability.