Non-cardia Gastric Cancer Research Articles

Developing a prognostic signature: identifying differentially expressed genes in cardia and non-cardia gastric cancer for immunity and therapeutic sensitivity analysis.

Gastric cancer (GC) can be anatomically categorized into two subtypes; that is, cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC), which have distinct molecular mechanisms and prognoses. At present, the majority of pharmacological interventions for GC adhere to non-specific treatment regimens. The stratification of GC based on molecular disparities between CGC and NCGC has important clinical guidance value and could help in the development of precision therapies tailored to individual patient needs. Nevertheless, research in this specialized field remains notably limited. This study aims to investigate the molecular differences between CGC and NCGC and to leverage these differences to develop a prognostic risk scoring model (PRSM). We used patient data from The Cancer Genome Atlas (TCGA) and performed a differentially expressed gene (DEG) analysis between CGC and NCGC. A PRSM was developed from the prognosis-associated DEGs identified through Cox regression analyses and was well validated using Gene Expression Omnibus (GEO) data. A total of 339 DEGs were identified between CGC and NCGC, and four prognosis-associated genes were used to construct the PRSM. Using the risk coefficients and expression levels of signature genes, a median risk score (RS) was calculated to classify patients into high- and low-risk groups. The high-risk group had a significantly worse prognosis than the low-risk group. An in-depth analysis revealed that TP53 mutations were more prevalent in the high-risk group, and MUC16 mutations were more prevalent in the low-risk group. A gene set enrichment analysis (GSEA) and the CIBERSORT algorithm were used to assess the differences in the significantly enriched pathways and immune microenvironment in the high- and low-risk groups, respectively. The inhibitory concentration (IC50) values of the chemotherapy drugs for GC also varied between the two groups. This study elucidated the unique molecular characteristics of GC subtypes based on the anatomical site and provided a preliminary contribution for the development of precision medicine for GC.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study

BackgroundThe Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce.MethodsWe compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison.ResultsA total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference.ConclusionsIncreased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

The clinical implications of staging laparoscopy in the diagnostic workup of gastric cancer patients: A population based study

BackgroundSince 2016, staging laparoscopy has been implemented in the diagnostic workup of patients with gastric cancer. Staging laparoscopy aims to detect incurable disease (peritoneal metastases and irresectable tumors) and to prevent futile laparotomies. MethodsIn this population-based nationwide study, we sought patient- and tumor characteristics associated with undergoing a staging laparoscopy. Additionally, we analyzed the prevalence of synchronous peritoneal metastases, the outcome of the staging laparoscopy and its clinical impact on treatment decisions. All patients diagnosed with non-cardia gastric cancer from the Netherlands Cancer Registry between 2016 and 2021 were included. ResultsAlongside tumor characteristics, patient characteristics such as younger age, absence of comorbidities and lower WHO performance status were associated with performing a staging laparoscopy. In the study period, an increase in the proportion of patients who underwent a staging laparoscopy was observed, from 19.6% in 2016 to 32.3% in 2021 (p-value<0.001). In the same period, the prevalence of synchronous peritoneal metastases increased from 25% to 31%. In 37.6% of the patients who had the outcome of their staging laparoscopy reported, had incurable disease diagnosed during staging laparoscopy. Significantly less of these patients were treated with triplet regimens as compared to patients with a negative staging laparoscopy (18.5 vs. 76.3%; p-value<0.001). ConclusionThe implementation of staging laparoscopy in gastric cancer patients paralleled the increase in diagnosis of incurable disease and a decrease in the application of triplet systemic therapies in these patients.

Racial, Ethnic, and Sex Differences in Incidence-Based Mortality of Aggregate Upper Gastrointestinal Cancers.

Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities. We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines. Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95). UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach.

Differences in cancer rates among adults born between 1920 and 1990 in the USA: an analysis of population-based cancer registry data

Trends in cancer incidence in recent birth cohorts largely reflect changes in exposures during early life and foreshadow the future disease burden. Herein, we examined cancer incidence and mortality trends, by birth cohort, for 34 types of cancer in the USA. In this analysis, we obtained incidence data for 34 types of cancer and mortality data for 25 types of cancer for individuals aged 25-84 years for the period Jan 1, 2000, to Dec 31, 2019 from the North American Association of Central Cancer Registries and the US National Center for Health Statistics, respectively. We calculated birth cohort-specific incidence rate ratios (IRRs) and mortality rate ratios (MRRs), adjusted for age and period effects, by nominal birth cohort, separated by 5 year intervals, from 1920 to 1990. We extracted data for 23 654 000 patients diagnosed with 34 types of cancer and 7 348 137 deaths from 25 cancers for the period Jan 1, 2000, to Dec 31, 2019. We found that IRRs increased with each successive birth cohort born since approximately 1920 for eight of 34 cancers (pcohort<0·050). Notably, the incidence rate was approximately two-to-three times higher in the 1990 birth cohort than in the 1955 birth cohort for small intestine (IRR 3·56 [95% CI 2·96-4·27]), kidney and renal pelvis (2·92 [2·50-3·42]), and pancreatic (2·61 [2·22-3·07]) cancers in both male and female individuals; and for liver and intrahepatic bile duct cancer in female individuals (2·05 [1·23-3·44]). Additionally, the IRRs increased in younger cohorts, after a decline in older birth cohorts, for nine of the remaining cancers (pcohort<0·050): oestrogen-receptor-positive breast cancer, uterine corpus cancer, colorectal cancer, non-cardia gastric cancer, gallbladder and other biliary cancer, ovarian cancer, testicular cancer, anal cancer in male individuals, and Kaposi sarcoma in male individuals. Across cancer types, the incidence rate in the 1990 birth cohort ranged from 12% (IRR1990 vs 1975 1·12 [95% CI 1·03-1·21] for ovarian cancer) to 169% (IRR1990 vs 1930 2·69 [2·34-3·08] for uterine corpus cancer) higher than the rate in the birth cohort with the lowest incidence rate. The MRRs increased in successively younger birth cohorts alongside IRRs for liver and intrahepatic bile duct cancer in female individuals, uterine corpus, gallbladder and other biliary, testicular, and colorectal cancers, while MRRs declined or stabilised in younger birth cohorts for most cancers types. 17 of 34 cancers had an increasing incidence in younger birth cohorts, including nine that previously had declining incidence in older birth cohorts. These findings add to growing evidence of increased cancer risk in younger generations, highlighting the need to identify and tackle underlying risk factors. American Cancer Society.

Does a High Ratio of Dietary Omega-6/Omega-3 Fatty Acids Increase the Risk of Helicobacter pylori Infection? A Case-Control Study.

Helicobacter pylori infection is the cause of 90% of non-cardia gastric cancer. Several dietary elements have been identified as possible contributors to H. pylori infection and its advancement through various pathways. Based on the anti-inflammatory and anti-microbial effects of a diet low in omega-6 and high in omega-3 polyunsaturated fatty acids (PUFAs), this study aimed to assess the ratio of dietary omega-6 to omega-3 PUFAs and the risk of developing H. pylori. The present case-control study was conducted on 150 cases with H. pylori infection and 302 controls. The omega-6 to omega-3 ratio was calculated using food intake information sourced from a validated food frequency questionnaire. Physical activity and demographic data were collected through a related questionnaire. The association between the odds of H. pylori infection and the omega-6 to omega-3 ratio was evaluated using logistic regression models. A p value < 0.05 was considered statistically significant. The findings revealed that individuals in the third tertile had significantly higher odds of H. pylori (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.30-3.40) in the crude model. Furthermore, even after adjusting the potential confounders including sex, age, body mass index, physical activity, energy intake, alcohol, and smoking status, this association remained significant (fully adjusted model: OR, 2.00; 95% CI, 1.17-3.34). Our study revealed a higher ratio of omega-6 to omega-3 was related to a higher likelihood of H. pylori infection. Therefore, it is advisable to maintain a balanced intake of PUFAs in the diet.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Pathogenesis and potential reversibility of intestinal metaplasia - a milestone in gastric carcinogenesis.

Non-cardia gastric cancer remains a major cause of cancer-related mortality worldwide, despite declining incidence rates in many industrialized countries. The development of intestinal-type gastric cancer occurs through a multistep process in which normal mucosa is sequentially transformed into hyperproliferative epithelium, followed by metaplastic processes leading to carcinogenesis. Chronic infection with Helicobacter pylori is the primary etiological agent that causes chronic inflammation of the gastric mucosa, induces atrophic gastritis, and can lead to intestinal metaplasia and dysplasia. Both intestinal metaplasia and dysplasia are precancerous lesions, in which gastric cancer is more likely to occur. Atrophic gastritis often improves after eradication of Helicobacter pylori; however, the occurrence of intestinal metaplasia has been traditionally regarded as "the point of no return" in the carcinogenesis sequence. Helicobacter pylori eradication heals non-atrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions. In this article, we discuss the pathogenesis, epigenomics, and reversibility of intestinal metaplasia and briefly touch upon potential treatment strategy. Gastric intestinal metaplasia no longer appears to be an irreversible precancerous lesion. However, there are still many controversies regarding the improvement of intestinal metaplasia after Helicobacter pylori eradication.

The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer

Objective To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. Methods One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. Results Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995–16.330, p < 0.001). Conclusions Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.

Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project

BackgroundPrevious studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC.MethodsFourteen case–control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose–response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials.ResultsIndividuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose–response analysis showed decreasing ORs of GC up to 150–200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0.ConclusionsThe findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Association Study between SNPs in MST1 and MST2 and H. pylori Infection as well as Noncardia Gastric Carcinogenesis

Introduction: Gastric cancer (GC) remains a global health challenge, and H. pylori infection is a main risk factor for noncardia GC. The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in mammalian sterile 20-like kinase 1 (MST1) and MST2, H. pylori (H. pylori) infection, and the risk of noncardia gastric cancer (GC). Methods: A case-control study was conducted using enzyme-linked immunosorbent assay (ELISA) and TaqMan method to detect the titer of anti-H. pylori antibody in normal human serum and genotype 9 SNPs of MST1 and MST2 genes among 808 samples. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and H. pylori infection, as well as the risk of noncardia gastric cancer in codominant, dominant, overdominant, recessive, and log-additive genetic models. Haplotypes were constructed using the Haploview 4.2 software. Results: The CC genotype of MST2 SNP rs10955176 was associated with a reduced risk of H. pylori infection compared to the TT + CT genotype. None of other SNPs were associated with H. pylori infection. The TT genotype of MST2 SNP rs7827435 was associated with a reduced risk of noncardia gastric cancer compared to the AA + AT genotype. None of the SNPs were associated with noncardia gastric cancer. There were no associations between haplotypes and H. pylori infection or the risk of noncardia gastric cancer. Conclusions: The CC genotype of rs10955176 and the TT genotype of rs7827435 may serve as protective factors against H. pylori infection and noncardia gastric cancer risk, respectively.

Li Fraumeni Syndrome predisposes to gastro-esophageal junction tumours

Li-Fraumeni Syndrome (LFS), caused by germline pathogenic variants in TP53, predisposes to a wide range of young-onset malignancies, particularly sarcoma, breast and brain cancer. More recently, an increased risk of gastric adenocarcinoma has been recognised, although uptake of surveillance upper endoscopy is unclear. Our retrospective review of 65 patients with LFS, of whom 53.8% had undergone endoscopy, identified four patients (6.2%) with gastro-esophageal junction (GEJ) adenocarcinomas. Two cases were found on asymptomatic screening and were early stage. No cases had family history of gastrointestinal malignancy. Reviewing genomic data from The Cancer Genome Atlas Program, 76.4% of sporadic esophageal adenocarcinomas harboured somatic TP53 pathogenic variants, compared with 39.9% of non-cardia gastric cancers. This similar pattern observed in germline and sporadic cases warrants further investigation. We propose that upper endoscopy be recommended to all patients with LFS, with a focus on appropriate surveillance of the GEJ.

Polyphenol intake and gastric cancer: A case-control study in the Brazilian Amazon region

BackgroundPolyphenol intake has been associated with a decreased risk of some types of cancer, including gastric cancer (GC). However, few studies address this topic in the Latin American population. In the present study, we evaluated the association between polyphenol intake and the risk of GC in the Brazilian Amazon region. MethodsA case-control study was conducted in Belém (Amazon region) from July 2017 to February 2021. A total of 193 GC cases and 194 controls of both sexes, between 18 and 75 years old, were included in the study. Dietary data were collected using a validated food-frequency questionnaire and polyphenol intake identified using the Phenol-Explorer database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI), with adjustement for potential confounders. ResultsCases and controls had similar total polyphenol intake (356.4 mg/1000 kcal/d and 331.1 mg/1000 kcal/d, respectively; p = 0.086). After adjusting for potential confounders, high consumption of flavan-3-ols (highest vs. lowest tertile: OR 0.41, 95% CI 0.18–0.94) and hydroxybenzoic acids (highest vs. lowest tertile: OR 0.24, 95% CI 0.10–0.56) was associated with a decreased risk of GC. The opposite was true regarding the intake of flavones (OR 2.46, 95% IC 1.17–5.18) and other polyphenols (OR 2.54, 95% IC 1.16–5.54). When stratifying according to anatomical topography, we observed that the intake of total flavonoids, flavan-3-ols, and flavanones reduced the risk of cardia GC while that of hydroxybenzoic acids reduced the risk of non-cardia GC. In addition, the intake of flavones and other polyphenols was associated with an increased risk of non-cardia GC. According to histologic subtypes, hydroxybenzoic acid intake was associated with a reduced risk of intestinal-type GC (OR 0.21, 95% IC 0.07–0.64), while flavone consumption was associated with an increased risk of diffuse-type GC (OR 2.59, 95% IC 1.05–6.42). ConclusionsOur findings suggest that in the Brazilian Amazon region the high intake of flavan-3-ols and hydroxybenzoic acids is associated with a reduced risk of GC, suggesting a potential beneficial role of these compounds against GC.

Risk Factors of Gastric Cancer and Lifestyle Modification for Prevention.

Gastric cancer has been consistently decreasing worldwide, whereas cardia gastric cancer is on the rise. This indicates that the exposure rates to epidemiological causes are changing. In this study, we aim to review the risk factors for gastric cancer with respect to cardia and non-cardia types. One of the most significant risk factors for gastric cancer is Helicobacter pylori infection. H. pylori infection is known as a risk factor for non-cardia gastric cancer, and there have been results indicating that H. pylori infection is not associated with cardia gastric cancer. However, in the East Asian region, there is epidemiological evidence suggesting that H. pylori infection might be a risk factor for cardia gastric cancer. Smoking and alcohol consumption are known risk factors for gastric cancer, regardless of anatomical location. Obesity is considered a factor in the development of cardia gastric cancer. However, further research is needed to understand the specific relationship with non-cardia gastric cancer. The consumption of high-salt and processed meat is more distinctly associated with non-cardia gastric cancer than in cardia gastric cancer. In addition to these factors, exposure to chemicals and radiation are considered risk factors for gastric cancer. Primary prevention of gastric cancer involves eliminating or avoiding risk factors such as H. pylori eradication and adopting a healthy lifestyle, including quitting smoking, reducing alcohol consumption, maintaining a healthy weight, and having a low-salt diet.

Using the Electronic Health Record to Develop a Gastric Cancer Risk Prediction Model

Background and aimsGastric cancer (GC) is a leading cause of cancer incidence and mortality globally. Population screening is limited by the low incidence and prevalence of GC in the United States. A risk prediction algorithm to identify high-risk patients allows for targeted GC screening. We aimed to determine the feasibility and performance of a logistic regression model based on electronic health records (EHR) to identify individuals at high risk for non-cardia gastric cancer (NCGC). MethodsWe included 614 patients who had a diagnosis of NCGC between ages 40-80 years and who were seen at our large tertiary medical center in multiple states between 2010 and 2021. Controls without a diagnosis of NCGC were randomly selected in a 1:10 ratio of cases to controls. Multiple imputation by chained equation for missing data followed by logistic regression on imputed datasets was used to estimate the probability of NCGC. Area under the curve (AUC) and the 0.632 estimator was used as the estimate for discrimination. ResultsThe 0.632 estimator value was 0.731, indicating robust model performance. Probability of NCGC was higher with increasing age (odds ratio [OR]=1.16, 95% confidence interval [CI]: 1.04 – 1.3), male sex (OR = 1.97; 95% CI: 1.64-2.36), Black (OR= 3.07; 95% CI: 2.46-3.83) or Asian race (OR=4.39; 95% CI: 2.60-7.42), tobacco use (OR=1.61; 95% CI: 1.34-1.94), anemia (OR=1.35; 95% CI: 1.09-1.68) and pernicious anemia (OR=6.12, 95% CI: 3.42-10.95). ConclusionWe demonstrate the feasibility and good performance of an EHR-based logistic regression model for estimating the probability of NCGC. Future studies will refine and validate this model, ultimately identifying a high-risk cohort who could be eligible for NCGC screening.

CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies.

Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region. Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders. Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73-91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67-90%) in H. pylori-infected gastritis, 86% (95%CI = 73-96%) in peptic ulcer disease, and 83% (95%CI = 51-100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15-5.55). Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease.

Survival Outcomes and Patterns of Care for Stage II or III Resected Gastric Cancer by Race and Ethnicity

Many multimodality treatment regimens exist for gastric adenocarcinoma, including neoadjuvant vs adjuvant chemotherapy, radiation, or both. Neoadjuvant therapy is recommended in the United States for patients with locally advanced gastric cancer; however, it is unknown whether the outcomes of neoadjuvant therapy are associated with race and ethnicity. To evaluate the differences in outcomes by race and ethnicity of patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy. This retrospective cohort study examined the National Cancer Database from the American College of Surgeons for patients with clinical stage II or III gastric adenocarcinoma, excluding gastric cardia tumors, undergoing surgical resection procedures from January 2006 to December 2019. Statistical analysis was performed from December 2021 to May 2023. Patients were stratified by race and ethnicity, and their outcomes were analyzed for those who received and did not receive neoadjuvant therapy. The Cox proportional hazard model was used to compare overall survival (OS) between racial and ethnic groups (Asian, Black, Hispanic, and White) overall and according to receipt of neoadjuvant therapy. Among those who received neoadjuvant therapy, proportional differences in pathological responses were calculated in each group. Among a total of 6938 patients in the cohort, 4266 (61.4%) were male; mean (SD) age was 65.9 (12.8) years; 1046 (15.8%) were Asian, 1606 (24.3%) were Black, 1175 (17.8%) were Hispanic, and 3540 (53.6%) were White. Compared with other races and ethnicities, the group of White patients had significantly more who were 65 years or older with more comorbidities. White patients underwent surgical resection procedures alone without neoadjuvant or adjuvant therapy more frequently than other races and ethnicities. Asian and Black patients had the highest proportion of being downstaged or achieving pathological complete response after neoadjuvant therapy. In multivariate models, perioperative chemotherapy was associated with improved OS (HR, 0.79 [95% CI, 0.69-0.90]), whereas number of positive lymph nodes and surgical margins were associated with the largest decreases in OS. Asian and Hispanic race and ethnicity were associated with significantly improved OS compared with Black and White races (eg, Asian patients: HR, 0.64 [95% CI, 0.58-0.72]; and Hispanic patients: HR, 0.77 [95% CI, 0.69-0.85]). Black race was associated with improved OS compared with White race when receiving neoadjuvant therapy (HR, 0.78 [95% CI, 0.67-0.90]). In this large nationwide cohort study of survival outcomes among patients with resected clinical stage II or III gastric cancer, there were significant differences in response to treatment and OS between different racial and ethnic groups.

Biennial Endoscopic Surveillance of Gastrointestinal Metaplasia and Its Subtypes Reduces Gastric Cancer Mortality and Is Cost-Effective in a Markov State Transition Model.

Gastric cancer in the United States has a low survival rate mainly because of the late stage of diagnosis. Furthermore, there are no well-established guidelines concerning screening and surveillance even for higher risk patients such as those with nondysplastic noncardia gastrointestinal metaplasia (GIM), and thus they are not routinely performed. This study was designed to provide new evidence-based data that can be used to support the implementation of biennial surveillance guidelines in individuals with nondysplastic noncardia GIM. This practice can help detect early malignant lesions, thereby decreasing morbidity and mortality. We evaluated the cost-effectiveness of surveillance endoscopies for noncardia gastric cancer in populations with two different pathological diagnoses: mixed GIM and incomplete GIM (iGIM). Markov state transition models were developed using a cohort simulation of 1000 hypothetical patients. Analysis was conducted for both mixed and iGIM. Quality-adjusted life-years and transition probabilities were derived from the published medical literature. Costs associated with endoscopy, cancer care, and surgery were based on Medicare reimbursement. A willingness-to-pay threshold of $100,000 per quality-adjusted life-year was used to determine cost-effectiveness. Our study determined that it is significantly cost-effective to perform biennial endoscopy surveillance in patients who have been incidentally found to have noncardia mixed GIM, with a cost savings of $5783.84 per person, and in those with iGIM, with a cost savings of $8093.08 per person. Biennial endoscopy surveillance should be considered in all individuals found to have mixed or incomplete noncardia GIM on endoscopy. Furthermore, screening specifically for iGIM after differentiating between the two groups can lead to further cost savings. As such, we recommend that pathologists routinely differentiate between the two and recommend robust routine surveillance of iGIM.

Identifying the optimal treatment strategy in patients with resectable non-cardia gastric cancer.

Multimodal treatment strategy including perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) has been accepted as the standard of care in gastric cancer (GC). The ideal sequence and type of therapy remain undetermined. The National Cancer Database was examined from 2006 to 2016 to identify patients with resectable non-cardia gastric cancer. Patient outcomes were compared based on the receipt of PEC, POCR, and POC. This comparison was repeated in a sub-group of patients who received optimal treatment. Optimal treatment was defined as initial chemotherapy within 45days of diagnosis, resection within 45days of diagnosis, negative margins, adjuvant chemotherapy within 90days of resection and standard radiation dose (45Gy). Kaplan-Meier test, log-rank test, and multivariable analysis (MVA) were performed. We identified 9589 patients. Median survival was greater in the PEC group followed by POCR and POC (60.6, 42.3, and 31.2months, respectively). On MVA, factors associated with worse overall survival included age above median (≥ 63years), Charlson-Deyo score of ≥ 1, non-academic/research program, poorly differentiated/undifferentiated grade, positive margins, and positive lymph nodes. Both PEC and POCR were associated with improved survival when compared to POC (HR 0.78 and 0.79; p < 0.001). When compared with PEC, no significant difference was noted with POCR (HR 1.01; p = 0.987). These results were maintained in optimally treated cohort (n = 3418). In patients with resectable non-cardia gastric cancer, both perioperative chemotherapy and postoperative chemoradiation therapy were associated with improved survival when compared to postoperative chemotherapy. No difference was noted between perioperative chemotherapy and postoperative chemoradiation therapy. These results were maintained in the optimally treated cohort.

Impact of Helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors

BackgroundGut microbiota composition can influence cancer immunotherapy response. Recent evidence suggests Helicobacter pylori infection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of...