Prevention Of Gastric Cancer Research Articles

Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk.

Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.

Changes in Gastric Pathology after H. pylori Treatment in Community-Driven Research Aimed at Gastric Cancer Prevention.

Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008-2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.

Interleukin-33 as a Potential Therapeutic Target in Gastric Cancer Patients: Current Insights.

Gastric cancer is a significant global health problem as it is the fifth most prevalent cancer worldwide and the fourth leading cause of cancer-related mortality. While cytotoxic chemotherapy remains the primary treatment for advanced GC, response rates are limited. Recent progresses, focused on molecular signalling within gastric cancer, have ignited new hope for potential therapeutic targets that may improve survival and/or reduce the toxic effects of traditional therapies. Carcinomas are generally initiated when critical regulatory genes get mutated, but the progression to malignancy is usually supported by the non-neoplastic cells that create a conducive environment for transformation and progression to occur. Interleukin 33 (IL-33) functions as a dual activity cytokine as it is also a nuclear factor. IL-33 is usually present in the nuclei of the cells. Upon tissue damage, it is released into the extracellular space and binds to its receptor, suppression of tumorigenicity 2 (ST2) L, which is expressed on the membranes of the target cells. IL-33 signalling activates the T Helper 2 (Th2) immune response among other responses. Although the studies on the role of IL-33 in gastric cancer are still in the early stages, they have revealed potentially important (though sometimes conflicting) functions or roles in cancer development and progression. The pro-tumorigenic roles include induction and the recruitment of tumor-associated immune cells, promoting metaplasia progression, and inducing stem cell like and EMT properties in gastric cancer cells. Therapeutic interventions to disrupt these functions may provide a unique strategy for gastric cancer prevention and treatment. This review aims to provide a summary of the role of IL-33 in GC, state its multiple functions in relation to GC, and show potential avenues for promising therapeutic investigation.

Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case-control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism 'TC' genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35-.63), p<.001]. GC cases with dominant genetic model 'TC+CC' had a 47% reduced risk of GC [OR, 95%CI: .53 (.40-.71), p<.001]. Subgroup analyses revealed that the rs733618 'TC+CC' genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31-.58), p<.001], those aged ≤60 years old [OR, 95%CI: .27 (.18-.42), p<.001], non-drinkers [OR, 95%CI: .21 (.13-.33), p<.001], non-smokers [OR, 95%CI: .38 (.25-.57), p<.001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10-.26), p<.001]. Further multivariated analyses indicated that individuals with the 'TC+CC' rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29-.83), p=.032] and had no H. pylori infection [OR, 95%CI: .35 (.28-.76), p=.018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with 'TC' and 'TC+CC' genotypes (all p<.05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.

Effectiveness of eradication therapy for Hp infection of residents of Perm and the Perm region

Purpose: to evaluate the effectiveness of eradication therapy for Hp infection in Perm and the Perm region. Materials and methods: a retrospective analysis of 88 case histories of patients who underwent eradication of Hp infection was carried out at the Perm Medical Center (GASTROCENTER). Primary infection with H. pylori was confirmed by: serological blood test or determination of Hp antigen in feces, rapid urease test, and C13 urease breath test. Hp eradication therapy regimens, depending on the source of prescription, included standard triple therapy with the addition of bismuth preparations for a period of 14 days (main group) or 7-10-day triple therapy (control group). Results and discussion: the main indications for Hp eradication were: chronic gastritis and gastroesophageal reflux disease. In the main group, all patients received Hp eradication therapy with the inclusion of: esomeprazole (emanera) 40 mg, amoxicillin 1000 mg, clarithromycin (fromilid) 50 mg and bismuth tripotassium dicitrate (ulcavis) 240 mg twice a day for 14 days. The control group included patients who received Hp eradication schemes with various proton pump inhibitors, amoxicillin and clarithromycin or metronidazole or levofloxacin or even rifaximin for 7 or 10 days. Adverse events: abdominal pain and diarrhea occurred in both groups. Patients of the main group complained about bitterness in the mouth, where all patients received clarithromycin. Approximately the same small number of patients complained of nausea. With a differentiated assessment by groups, in the main group, Hp eradication was highly effective and reached 93%, while in the control group it was significantly lower and did not exceed 48% (p=0,00087) Conclusions: modern detection of Hp infection and its eradication is an effective approach to the prevention of atrophic gastritis, gastric cancer and peptic ulcer of the stomach and duodenum. The “gold” standard for diagnosing Hp infection is the 13C-urease breath test. For residents of Perm and the Perm Territory, it is recommended to use Hp eradication with the appointment of a 14-day regimen with the inclusion of esomeprazole (Emaner), clarithromycin (Fromilide), amoxicillin and bismuth tripotassium dicitrate (Ulkavis) as the first line of therapy.

Gastric Cancer Epidemiology: Current Trend and Future Direction

Gastric cancer (GC) is a significant global public health problem. It is the third leading cause of cancer-related mortality despite its decline in incidence since the past five decades. The incidence of GC varies between regions, and this heterogeneity is attributed to multi-factors, including infectious, environmental, and genetic traits. Most of the GC cases are linked to Helicobacter pylori (H. pylori) infection. Understanding the etiology, epidemiology, and risk factors of GC is necessary for the prevention and targeted treatment of the disease. In this study, we synthesized published studies, including data from the “International Agency for Research on Cancer GLOBOCAN” to narratively provide an updated overview of the recent global trends, etiology, known risk factors, pathogenesis, hallmarks, treatment, and prevention of GC. One area that significantly advanced GC research was understanding the mechanisms by which H. pylori colonizes humans and mediates physiological, microbiological, immune, and histologic features of the gut. However, there are still gaps present in understanding the molecular mechanisms underlying the initiation and progression of GC.

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45–70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

The expression and function of the B7 family in Helicobacter pylori infection and gastric carcinogenesis process.

The B7 protein family is one of the most important immune checkpoint proteins. Gastric cancer (GC) is the fourth most common cause of cancer-related mortality worldwide and shows a significant correlation with the B7 family in tumorigenesis and progression. Helicobacter pylori infection is the most important risk factor promoting the progression of gastric precancerous lesions and GC, which also affects the expression of B7 family members. We aimed to systematically summarize and review current studies on the expression and function of B7 family members during H. pylori infection in precancerous gastric lesions and GC. PubMed was searched for the relationship between B7 family, H. pylori and gastric carcinogenesis until April 5, 2023. Different permutation and combination of the search terms, including "H. pylori," "Helicobacter pylori," "B7," "gastric cancer," and "gastric precancerous lesions," all the different names of specific B7 molecules, and the names of signaling pathways were used. Literature related to our research topic was selected and summarized. The B7 family participates in gastric carcinogenesis through certain immune signaling pathways by binding to their receptors and exhibiting co-inhibitory or co-stimulatory effects. Targeting the B7 family members with mAbs may be a promising therapeutic strategy for treating gastric diseases. A thorough understanding of the role of B7 molecules during H. pylori infection and GC progression is helpful for the treatment and prevention of GC and the prediction of H. pylori infection outcomes, providing evidence for H. pylori eradication.

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer.

Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.

Bioinformatics and pathway enrichment analysis identified hub genes and potential biomarker for gastric cancer prognosis.

Gastric cancer is one of the most common cancers in the world. This study aimed to identify genes, biomarkers, and metabolic pathways affecting gastric cancer using bioinformatic analysis and meta-analysis. Datasets containing gene expression profiles of tumor lesions and adjacent non-tumor mucosa samples were downloaded. Common differentially expressed genes between data sets were selected to identify hub genes and further analysis. Gene Expression Profiling and Interactive Analyses (GEPIA) and the Kaplan-Meier method were used to further validate the expression level of genes and plot the overall survivalcurve, respectively. KEGG pathway analysis showed that the most important pathway was enriched in ECM-receptor interaction. Hub genes includingCOL1A2, FN1, BGN, THBS2, COL5A2, COL6A3, SPARC and COL12A1 wereidentified. The top interactive miRNAs including miR-29a-3p, miR-101-3p,miR-183-5p, and miR-15a-5p targeted the most hub genes. The survival chart showed an increase in mortality in patients with gastric cancer, which shows the importance of the role of these genes in the development of the disease and can be considered candidate genes in the prevention and early diagnosis of gastric cancer.

The role of eradication of Helicobacter pylori infection in the prevention of gastric cancer (based on the Maastricht-VI consensus report)

The article discusses the statements of the section of the consensus meeting “Maastricht-VI” (2021), dedicated to the role of H.pylori infection eradication in prevention of the development of gastric cancer. Experts have confi rmed that this infection is currently the main etiological factor of gastric cancer. Its eradication leads to regression of atrophic changes in the gastric mucosa and reduces the risk of development of gastric cancer. This makes it necessary to implement the population program “test and treat” for the purpose of cancer prevention and to include it among the priorities of healthcare.

Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)-NF-кB axis.

Spasmolytic polypeptide-expressing metaplasia (SPEM), as a pre-neoplastic precursor of intestinal metaplasia (IM), plays critical roles in the development of chronic atrophic gastritis (CAG) and gastric cancer (GC). However, the pathogenetic targets responsible for the SPEM pathogenesis remain poorly understood. Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), an essential subunit of the mitochondrial respiratory chain complex I, was progressively lost along with malignant transformation of human CAG, little is known about the potential link between GRIM-19 loss and CAG pathogenesis. Here, we show that lower GRIM-19 is associated with higher NF-кB RelA/p65 and NLR family pyrin domain-containing 3 (NLRP3) levels in CAG lesions. Functionally, GRIM-19 deficiency fails to drive direct differentiation of human GES-1cells into IM or SPEM-like cell lineages in vitro, whereas parietal cells (PCs)-specific GRIM-19 knockout disturbs gastric glandular differentiation and promotes spontaneous gastritis and SPEM pathogenesis without intestinal characteristics in mice. Mechanistically, GRIM-19 loss causes chronic mucosal injury and aberrant NRF2 (Nuclear factor erythroid 2-related factor 2)- HO-1 (Heme oxygenase-1) activation via reactive oxygen species (ROS)-mediated oxidative stress, resulting in aberrant NF-кB activation by inducing p65 nuclear translocation via an IKK/IкB partner, while NRF2-HO-1 activation contributes to GRIM-19 loss-driven NF-кB activation via a positive feedback NRF2-HO-1 loop. Furthermore, GRIM-19 loss did not cause obvious PCs loss but triggers NLRP3 inflammasome activation in PCs via a ROS-NRF2-HO-1-NF-кB axis, leading to NLRP3-dependent IL-33 expression, a key mediator for SPEM formation. Moreover, intraperitoneal administration of NLRP3 inhibitor MCC950 drastically attenuates GRIM-19 loss-driven gastritis and SPEM in vivo. Our study suggests that mitochondrial GRIM-19 maybe a potential pathogenetic target for the SPEM pathogenesis, and its deficiency promotes SPEM through NLRP3/IL-33 pathway via a ROS-NRF2-HO-1-NF-кB axis. This finding not only provides a causal link between GRIM-19 loss and SPEM pathogenesis, but offers potential therapeutic strategies for the early prevention of intestinal GC.

N6-methyladenosine modification of CENPF mRNA facilitates gastric cancer metastasis via regulating FAK nuclear export.

N6-methyladenosine (m6 A) modification is the most common modification that occurs in eukaryotes. Although substantial effort has been made in the prevention and treatment of gastric cancer (GC) in recent years, the prognosis of GC patients remains unsatisfactory. The regulatory mechanism between m6 A modification and GC development needs to be elucidated. In this study, we examined m6 A modification and the downstream mechanism in GC. Dot blotting assays, The Cancer Genome Atlas analysis, and quantitative real-time PCR (qRT-PCR) were used to measure the m6 A levels in GC tissues. Methylated RNA-immunoprecipitation sequencing and RNA sequencing were performed to identify the targets of m6 A modification. Western blotting, Transwell, wound healing, and angiogenesis assays were conducted to examine the role of centromere protein F (CENPF) in GC in vitro. Xenograft, immunohistochemistry, and in vivo metastasis experiments were conducted to examine the role of CENPF in GC in vivo. Methylated RNA-immunoprecipitation-qPCR, RNA immunoprecipitation-qPCR and RNA pulldown assays were used to verify the m6 A modification sites of CENPF. Gain/loss-of-function and rescue experiments were conducted to determine the relationship between CENPF and the mitogen-activated protein kinase (MAPK) signaling pathway in GC cells. Coimmunoprecipitation, mass spectrometry, qRT-PCR, and immunofluorescence assays were performed to explore the proteins that interact with CENPF and elucidate the regulatory mechanisms between them. CENPF was upregulated in GC and facilitated the metastasis of GC both in vitro and in vivo. Mechanistically, increased m6 A modification of CENPF was mediated by methyltransferase 3, and this modified molecule could be recognized by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), thereby promoting its mRNA stability. In addition, the metastatic phenotype of CENPF was dependent on the MAPK signaling pathway. Furthermore, CENPF could bind to FAK and promote its localization in the cytoplasm. Moreover, we discovered that high expression of CENPF was related to lymphatic invasion and overall survival in GC patients. Our findings revealed that increased m6 A modification of CENPF facilitates the metastasis and angiogenesis of GC through the CENPF/FAK/MAPK and epithelial-mesenchymal transition axis. CENPF expression was correlated with the clinical features of GC patients; therefore, CENPF may serve as a prognostic marker of GC.

An increasing trend of gastric cancer deaths and inadequate preventive measures in elderly adults.

Japan became the world's first country to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system in February 2013. Thereafter, H. pylori eradication dramatically increased and gastric cancer deaths began to decrease in Japan. However, the details of gastric cancer deaths and its prevention in the very elderly have not been fully elucidated. We analyzed the temporal trend of gastric cancer deaths referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan-2021" and assessed the numbers of H. pylori test and gastric cancer screening using a national database and a report of cancer screening in Shimane Prefecture, respectively. Although gastric cancer deaths in total population have clearly decreased since 2013, those in people aged 80 years and older are still increasing. People aged 80 years and older represent 9% of the total population and accounted for half of all gastric cancer deaths in 2020. The numbers of H. pylori eradication and gastric cancer screening in people aged 80 years and older were 25% and 25% of those in other generations, respectively. In spite of a dramatic increase in H. pylori eradication and a clear decrease in gastric cancer deaths in Japan, gastric cancer deaths in people aged 80 years and older are increasing. This might be due to fewer H. pylori eradication in the elderly than in other generations, indicating the difficulty of gastric cancer prevention in the very elderly.

The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori.

Helicobacter pylori-induced chronic gastritis represents a well-established risk factor for gastric cancer (GC). However, the mechanism by which chronic inflammation caused by H. pylori induces the development of GC is unclear. H. pylori can influence host cell signalling pathways to induce gastric disease development and mediate cancer promotion and progression. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play a key role in the gastrointestinal innate immune response, and their signalling has been implicated in the pathogenesis of an increasing number of inflammation-associated cancers. The core adapter myeloid differentiation factor-88 (MyD88) is shared by most TLRs and functions primarily in H. pylori-triggered innate immune signalling. MyD88 is envisioned as a potential target for the regulation of immune responses and is involved in the regulation of tumourigenesis in a variety of cancer models. In recent years, the TLR/MyD88 signalling pathway has received increasing attention for its role in regulating innate and adaptive immune responses, inducing inflammatory activation and promoting tumour formation. In addition, TLR/MyD88 signalling can manipulate the expression of infiltrating immune cells and various cytokines in the tumour microenvironment (TME). In this review, we discuss the pathogenetic regulatory mechanisms of the TLR/MyD88 signalling cascade pathway and its downstream molecules in H. pylori infection-induced-associated GC. The focus is to elucidate the immunomolecular mechanisms of pathogen recognition and innate immune system activation of H. pylori in the TME of inflammation-associated GC. Ultimately, this study will provide insight into the mechanism of H. pylori-induced chronic inflammation-induced GC development and provide thoughts for GC prevention and treatment strategies.

Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United States

High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population. We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios. Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years. In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication.

Maastricht VI/Florence Consensus for the treatment of Helicobacter pylori infection: updated recommendations for cancer prevention opportunities

For many decades, one of the most relevant issues remains the effectiveness of treatment of diseases associated with Helicobacter pylori (H. pylori) infection, the main goal of which is the prevention of gastric cancer (GC). The basic principles of diagnosis and treatment of helicobacter infection from the standpoint of evidence‑based medicine formulated in the Maastricht Consensus series. The data is constantly updated and refined by experts based on dynamic research. The new Maastricht VI/Florence Consensus clarified a number of provisions that were previously under discussion. One of the main provisions is that infection with H. pylori always causes gastritis regardless of symptoms or complications. Helicobacter gastritis must be excluded before establishing a clinical diagnosis of functional dyspepsia. About 90% of stomach cancer cases are associated with H. pylori. It is the the main etiological factor of gastric adenocarcinoma, including proximal gastric cancer. Eradication of H. pylori provides an opportunity for cancer prevention at any age in adults, but its effectiveness decreases with age. Therefore, carrying out the timely and effective eradication allows preventing negative consequences in H. pylori — infected patients. In the modern algorithm of eradication therapy in accordance with the Maastricht VI/Florence consensus, preference has been given to quadruple therapy with the use of bismuth drugs. The value of triple therapy with clarithromycin has decreased. There is a rapid increase in the resistance of H. pylori to fluoroquinolones. Bismuth‑containing quadruple therapy with amoxicillin and tetracycline and triple therapy with rifabutin are among the final eradication protocols. Research is underway on new candidate molecules for inclusion in antihelicobacter therapy regimens. Further research will need to optimize new opportunities to improve eradication efficiency, particularly in non‑Asian populations. We hope that the publication of this important international consensus document will allow practicing doctors to use the knowledge of modern gastroenterology and increase the percentage of effective cancer prevention in Ukraine.&#x0D;

PDCD4 and CDX-2 as immunohistochemical markers of gastric mucosa atrophy in chronic gastritis

Introduction Diagnosis of the gastric mucosa atrophy represents an important problem, the solution of which depends on the possibility of secondary prevention of gastric cancer. A possible way of solution is the use of immunohistochemical markers - proteins associated with cellular remodeling of gastric mucosa, PDCD4 and CDX2.The aim of the work is to evaluate the possibility of using immunohistochemical markers PDCD4 and CDX-2 to diagnose atrophy of the gastric mucosa in chronic gastritis and increase the informative value of biopsy examination.Materials and method The object of the study was 155 cases of biopsy examination of the gastric mucosa of patients with chronic gastritis (5 fragments per case − 775 biopsy specimens). A comparative semi-quantitative assessment of immunohistochemical expression of CDX2, PDCD4 at different stages of chronic gastritis was performed. Spearman correlation coefficient was used to assess correlation relationship.Results There were no statistically significant differences in the level of PDCD4 in studied samples depending on the stage of chronic gastritis, p=0.06. Statistically significant increase of CDX2sum index in progressing stage of chronic atrophic gastritis (p=0.005), demonstrated a pronounced positive correlation r=0.70 (p&lt;0.01).Discussion According to the results obtained, it is shown that the decline in PDCD4 protein does not occur with the progression of atrophy severity. Complementary use of immunohistochemical marker CDX2 is able to give an idea of the presence and severity of both metaplastic and absolute atrophic changes in the gastric mucosa.Conclusion Equally high level of PDCD4 protein index in the gastric mucosa at different stages of chronic gastritis excludes the possibility of its use as an immunohistochemical marker of atrophy. Semi-quantitative immunohistochemical index of CDX2 protein can be used as an additional marker in decision support system for assessment of atrophic changes in gastric mucosa.

Gastric microbiota: an emerging player in gastric cancer.

Gastric cancer (GC) is a common cancer worldwide with a high mortality rate. Many microbial factors influence GC, of which the most widely accepted one is Helicobacter pylori (H. pylori) infection. H. pylori causes inflammation, immune reactions and activation of multiple signaling pathways, leading to acid deficiency, epithelial atrophy, dysplasia and ultimately GC. It has been proved that complex microbial populations exist in the human stomach. H. pylori can affect the abundance and diversity of other bacteria. The interactions among gastric microbiota are collectively implicated in the onset of GC. Certain intervention strategies may regulate gastric homeostasis and mitigate gastric disorders. Probiotics, dietary fiber, and microbiota transplantation can potentially restore healthy microbiota. In this review, we elucidate the specific role of the gastric microbiota in GC and hope these data can facilitate the development of effective prevention and therapeutic approaches for GC.

Abstract 5890: Distinct differences in microbial enrichment and diversity identified between gastric and gastroesophageal junction adenocarcinoma

Abstract Objective: The microbiome is associated with the pathogenesis and progression of disease in gastric cancer (GC). Eradication of Helicobacter pylori has reduced overall GC incidence, however, gastroesophageal cancer (GEJC) continues to increase. While there are oncologic differences between GEJC and GC, distinctions based on microbial profiles are unknown. In this study, we characterize differences in the microbial profiles of GEJC and GC. Methods: 562 patients with microsatellite stable GC (n=303) and GEJC (n=259) who had an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay on the primary tumor were included in the study. A validated microbiome bioinformatics pipeline that is generalizable across multiple next generation sequencing platforms was utilized to compare microbial enrichment and alpha diversity between GC and GEJC, defined by type 1-3 Siewert classification. Results: Over 20 unique microbial species were enriched in GC when compared to GEJC, including Helicobacter and Lymphocryptovirus (Table 1). Prevotella had increased incidence in GEJC (OR:1.57,95%CI:1.02,2.41). Siewert type 2 and 3 GEJC had a significantly lower alpha diversity compared to GC. There was no significant difference in alpha diversity between GC and Siewert type 1 GEJC. Conclusion: There are distinct differences in microbial enrichment and alpha diversity between GEJC and GC. Helicobacter and Lymphocryptovirus, the genus family for Epstein Bar Virus, were noted to have the highest odds ratios in the GC group. Our findings showing the reduced incidence of microbes in GEJC which are the current targets of GC screening, prevention, and therapy, have implications in evaluating optimal preventative and treatment strategies in GEJC. Table 1. Microbes with enrichment in gastric cancer (GC) when compared to gastroesophageal cancer (GEJC) Microbes OR (95% Confidence Interval) p-value Helicobacter 85.40 (5.191, 1404.81) 0.002 Lymphocryptovirus 6.83 (2.3120,.17) 0.001 Pelagibacterium 6.01 (1.71, 21.06) 0.005 Gluconacetobacter 5.14 (1.70, 15.53) 0.004 Myxococcus 5.14 (1.70, 15.53) 0.004 Kribbella 4.48 (1.46, 13.74) 0.009 Celeribacter 3.46 (1.43, 8.37) 0.006 Halomonas 3.46 (1.43, 8.37) 0.006 Nakamurella 3.35 (1.46, 7.71) 0.004 Nitrobacter 2.91 (1.40, 6.05) 0.004 Pseudogulbenkiania 2.80 (1.30, 6.03) 0.009 Mycobacteroides 2.78 (1.33, 5.81) 0.006 Polaromonas 2.70 (1.49, 4.90) 0.001 Meiothermus 2.54 (1.41, 4.57) 0.002 Sphingopyxis 2.44 (1.33, 4.46) 0.004 Mesorhizobium 2.38 (1.32, 4.30) 0.004 Staphylococcus 2.23 (1.37, 3.62) 0.001 Thermus 2.13 (1.22, 3.70) 0.008 Mycolicibacterium 1.99 (1.29, 3.07) 0.002 Mycobacterium 1.95 (1.23, 3.08) 0.005 Lactobacillus 1.94 (1.17, 3.22) 0.01 Citation Format: Miseker Abate, Harrison Drebin, Shoji Shimada, Santosh Vardhana, Smita Sihag, Vivian E. Strong, Chad Vanderbilt. Distinct differences in microbial enrichment and diversity identified between gastric and gastroesophageal junction adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5890.