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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. [ABSTRACT FROM AUTHOR]

Background: The burden of gastric cancer (GC) should be further clarified worldwide, and helped us to understand the current situation of GC. Methods: In the present study, we estimated disability-adjusted life-years (DALYs) and mortality rates attributable to several major GC risk factors, including smoking, dietary risk, and behavioral risk. In addition, we evaluated the incidence rate and trends of incidence-based mortality (IBM) due to GC in the United States (US) during 1992–2018. Results: Globally, GC incidences increased from 883,395 in 1990 to 1,269,805 in 2019 while GC-associated mortality increased from 788,316 in 1990 to 957,185 in 2019. In 2019, the age-standardized rate (ASR) of GC exhibited variations around the world, with Mongolia having the highest observed ASR (43.7 per 100,000), followed by Bolivia (34 per 100,000) and China (30.6 per 100,000). A negative association was found among estimated annual percentage change (EAPC) and ASR (age-standardized incidence rate (ASIR): r = − 0.28, p < 0.001; age-standardized death rate (ASDR): r = − 0.19, p = 0.005). There were 74,966 incidences of GC and 69,374 GC-related deaths recorded between 1992 and 2018. The significant decrease in GC incidences as well as decreasing trends in IBM of GC were first detected in 1994. The GC IBM significantly increased at a rate of 35%/y from 1992 to 1994 (95% CI 21.2% to 50.4%/y), and then begun to decrease at a rate of − 1.4%/y from 1994 to 2018 (95% CI − 1.6% to − 1.2%/y). Conclusion: These findings mirror the global disease burden of GC and are important for development of targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC), the fifth most common cancer globally, remains the leading cause of cancer deaths worldwide. Inflammationinduced tumorigenesis is the predominant process in GC development; therefore, systematic research in this area should improve understanding of the biological mechanisms that initiate GC development and promote cancer hallmarks. Here, we summarize biological knowledge regarding gastric inflammation-induced tumorigenesis, and characterize the multi-omics data and systems biology methods for investigating GC development. Of note, we highlight pioneering studies in multi-omics data and stateof-the-art network-based algorithms used for dissecting the features of gastric inflammation-induced tumorigenesis, and we propose translational applications in early GC warning biomarkers and precise treatment strategies. This review offers integrative insights for GC research, with the goal of paving the way to novel paradigms for GC precision oncology and prevention. [ABSTRACT FROM AUTHOR]

Background: Understanding the epidemiological patterns and futuristic trends in gastric cancer (GC) is crucial since the worldwide epidemiological status has altered significantly over time. GC is one of the most prevalent malignancies in terms of becoming an important cause of cancer-related deaths worldwide. However, recent years have seen a remarkable improvement in the study of microRNAs (miRNAs) controlling gene expression where miRNA aberrations have been linked to the development and incidence of GC. Methods: A considerate role of miRNAs in gastric carcinogenesis could deliver great perceptions toward understanding the physiology of tumor development. Therefore, this article reviews the epidemiology, risk factor, classification, and involvement of miRNAs in GC regulation and genes. During the process, more than 150 well-documented articles were reviewed, and collective data information was gathered through search databases such as the World Health Organization, National centre for biotechnology information (NCBI), and Google Scholar. Following this analysis, this review article comprises a number of miRNAs that are associated with types of tumor, stages of the tumor, GC prognosis, their effects on Helicobacter pylori-mediated infection, and potential applications in chemotherapy. Results: This review, thereby, supports a collective and comparative strategic role of miRNA, prominent attention of aberrantly expressed miRNAs, and their associated mechanism of cancer development that have been emphasized on exploiting new anticancer targets, thus effectuating the critical and comparative data for different subtypes, diagnosis, occurrence, and survival rate of GC among men and women. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals. Methods: We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity. Results: Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 − 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 − 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61–95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06–0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 − 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 − 1.78; I 2: 0.10%). Conclusions: H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications. [ABSTRACT FROM AUTHOR]

Objective: The development and advance of gastric cancer are inextricably linked to oxidative and antioxidant imbalance. Although immunotherapy has been shown to be clinically effective, the link between oxidative stress and gastric cancer patients treated with immune checkpoint inhibitor (ICIs) remains unknown. This study aims at looking into the prognostic value of oxidative stress scores in gastric cancer patients treated with ICIs. Methods: By taking the propagation to receiver operating characteristic (ROC) we got the best cut-off values, and divided 265 patients receiving ICIs and chemotherapy into high and low GC-Integrated Oxidative Stress Score (GIOSS) groups. We also used Kaplan-Meier and COX regression models to investigate the relationship between oxidative stress biomarkers and prognosis. Results: Through both univariate and multivariate analyses, it’s shown that GIOSS severs as an independent prognostic factor for progression-free survival (PFS) and Overall survival (OS). Based on GIOSS cutoff values, patients with high GIOSS levels, compared to those with low levels exhibited shorter PFS and OS, both in the high GIOSS group, which performed poorly in the ICIs subgroup and other subgroup analyses. Conclusion: GIOSS is a biomarker that responds to systemic oxidative stress in the body and can predict prognosis in patients with gastric cancer who are taking ICIs. Additionally, it might come to medical professionals’ aid in making more effective or more suitable treatment plans for gastric cancer. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common cancers, leading to the deaths of millions of people worldwide. Therefore, early detection and effective therapeutic strategies are of great value for decreasing the occurrence of advanced GC. The human microbiota is involved not only in the maintenance of physiological conditions, but also in human diseases such as obesity, diabetes, allergic and atopic diseases, and cancer. Currently, the composition of the bacteria in the host, their functions, and their influence on disease progression and treatment are being discussed. Previous studies on the gut microbiome have mostly focused on Helicobacter pylori (Hp) owing to its significant role in the development of GC. Nevertheless, the enrichment and diversity of other bacteria that can modulate the tumor microenvironment are involved in the progression of GC and the efficacy of immunotherapy. This review provides systematic insight into the components of the gut microbiota and their application in GC, including the specific bacteria of GC, their immunoregulatory effect, and their diagnostic value. Furthermore, we discuss the relationship between the metabolism of microbes and their potential applications, which may serve as a new approach for the diagnosis and treatment of GC. [ABSTRACT FROM AUTHOR]

Background Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer. Materials and Methods This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening-to-treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty-five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting. Results There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first-line, second-line, and third-line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost-benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer. Conclusions This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients. Methods: This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors. Results: There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039–0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033–0.406, P < 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371–8.176, P = 0.008). The surgical approach was not a risk factor for any late complications. Conclusion: Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis. [ABSTRACT FROM AUTHOR]

Correa's cascade is a dynamic process in the development of intestinal‐type gastric cancer (GC), and its pathological features, gastric microbiota and interactions between microorganisms and their hosts vary at different developmental stages. The characteristics of cells, tissues and gastric microbiota before or after key therapeutic points are critical for monitoring malignant transformation and early tumour reversal. This review summarises the pathological features of gastric mucosa, characteristics of gastric microbiota, specific microbial markers, microbe‐microbe interactions and microbe‐host interactions at different stages in Correa's cascade. The markers related to each Correa's cascade point were analysed in detail. We attempted to identify key therapeutic points for early cancer reversal and provide a novel approach to reduce the incidence of GC and improve precise treatment. [ABSTRACT FROM AUTHOR]

Even though Helicobacter pylori infection was the most causative factor of gastric cancer, numerous in vivo studies failed to induce gastric cancer using H. pylori infection only. The utilization of established animal studies in cancer research is crucial as they aim to investigate the coincidental association between suspected oncogenes and pathogenesis as well as generate models for the development and testing of potential treatments. The methods to establish gastric cancer using infected animal models remain limited, diverse in methods, and showed different results. This study investigates the differences in animal models, which highlight different pathological results in gaster by literature research. Electronic databases searched were performed in PubMed, Science Direct, and Cochrane, without a period filter. A total of 135 articles were used in this study after a full‐text assessment was conducted. The most frequent animal models used for gastric cancer were Mice, while Mongolian gerbils and Transgenic mice were the most susceptible model for gastric cancer associated with H. pylori infection. Additionally, transgenic mice showed that the susceptibility to gastric cancer progression was due to genetic and epigenetic factors. These studies showed that in Mongolian gerbil models, H. pylori could function as a single agent to trigger stomach cancer. However, most gastric cancer susceptibilities were not solely relying on H. pylori infection, and numerous factors are involved in cancer progression. Further study using Mongolian gerbils and Transgenic mice is crucial to conduct and establish the best models for gastric cancer associated H. pylori. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori is an infection of concern for its chronic colonization leading to peptic ulcers and gastric cancer. In recent times, microRNAs have been extensively studied to understand their role in the pathogenesis of this bacteria in diverse contexts of gastric diseases. The current analysis reports the microRNA‐mRNA interactions that are associated with effective survival and virulence of this pathogen. Materials and Methods: We convened differentially regulated human microRNAs responsive to H. pylori infection (HP‐hDEmiRs) at different multiplicity of infection and time points in human gastric cell lines through retrospective data mining of experimental studies. In view of the molecular disparity of clinical samples and animal models, data from tissue, serum/plasma, urine, and ascites were excluded. Further, we utilized diverse bioinformatics approaches to retrieve experimentally validated, high‐confidence targets of the HP‐hDEmiRs to analyze the microRNA‐mRNA interactions that are relevant to H. pylori pathogenesis. Results: A total of 39 HP‐hDEmiRs that showed unidirectional expression of either overexpression or downregulation were identified to modulate 23 targets explicitly studied under this infection. We also identified 476 experimentally validated targets regulated by at least 4 of the HP‐hDEmiRs. In addition to the pathways prior‐associated with H. pylori infection, the microRNA‐mRNA interactome analysis identified several cellular processes and pathways highly associated with cell cycle, cell division, migration, and carcinogenesis. Conclusion: This study generated a platform to study the mechanisms utilized by this pathogen using microRNAs as surrogate. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer imposes a substantial global health burden despite its overall incidence decrease. A broad spectrum of inherited, environmental and infectious factors contributes to the development of gastric cancer. A profound understanding of the molecular underpinnings of gastric cancer has lagged compared to several other tumors with similar incidence and morbidity rates, owing to our limited knowledge of the role of carcinogens in this malignancy. The International Agency for Research on Cancer (IARC) has classified gastric carcinogenic agents into four groups based on scientific evidence from human and experimental animal studies. This review aims to explore the potential comprehensive molecular and biological impacts of carcinogens on gastric cancer development and their interactions and interferences with various cellular signaling pathways. Conclusions: In this review, we highlight recent clinical trial data reported in the literature dealing with different ways to target various carcinogens in gastric cancer. Moreover, we touch upon other multidisciplinary therapeutic approaches such as surgery, adjuvant and neoadjuvant chemotherapy. Rational clinical trials focusing on identifying suitable patient populations are imperative to the success of single-agent therapeutics. Novel insights regarding signaling pathways that regulate gastric cancer can potentially improve treatment responses to targeted therapy alone or in combination with other/conventional treatments. Preventive strategies such as control of H. pylori infection through eradication or immunization as well as dietary habit and lifestyle changes may reduce the incidence of this multifactorial disease, especially in high prevalence areas. Further in-depth understanding of the molecular mechanisms involved in the role of carcinogenic agents in gastric cancer development may offer valuable information and update state-of-the-art resources for physicians and researchers to explore novel ways to combat this disease, from bench to bedside. A schematic outlining of the interaction between gastric carcinogenic agents and intracellular pathways in gastric cancer H. pylori stimulates multiple intracellular pathways, including PI3K/AKT, NF-κB, Wnt, Shh, Ras/Raf, c-MET, and JAK/STAT, leading to epithelial cell proliferation and differentiation, apoptosis, survival, motility, and inflammatory cytokine release. EBV can stimulate intracellular pathways such as the PI3K/Akt, RAS/RAF, JAK/STAT, Notch, TGF-β, and NF-κB, leading to cell survival and motility, proliferation, invasion, metastasis, and the transcription of anti-apoptotic genes and pro-inflammatory cytokines. Nicotine and alcohol can lead to angiogenesis, metastasis, survival, proliferation, pro-inflammatory, migration, and chemotactic by stimulating various intracellular signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, ROS, and JAK/STAT. Processed meat contains numerous carcinogenic compounds that affect multiple intracellular pathways such as sGC/cGMP, p38 MAPK, ERK, and PI3K/AKT, leading to anti-apoptosis, angiogenesis, metastasis, inflammatory responses, proliferation, and invasion. Lead compounds may interact with multiple signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, DNA methylation-dependent, and epigenetic-dependent, leading to tumorigenesis, carcinogenesis, malignancy, angiogenesis, DNA hypermethylation, cell survival, and cell proliferation. Stimulating signaling pathways such as PI3K/Akt, RAS/RAF, JAK/STAT, WNT, TGF-β, EGF, FGFR2, and E-cadherin through UV ionizing radiation leads to cell survival, proliferation, and immortalization in gastric cancer. The consequence of PI3K/AKT, NF-κB, Ras/Raf, ROS, JAK/STAT, and WNT signaling stimulation by the carcinogenic component of Pickled vegetables and salted fish is the Warburg effect, tumorigenesis, angiogenesis, proliferation, inflammatory response, and migration. [ABSTRACT FROM AUTHOR]

Background: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation.Methods: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2.Results: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments.Conclusions: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess the latest prevalence and secular trend of Helicobacter pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan. Materials and Methods: Adults naive to H. pylori eradication received 13C‐urea breath test (13C‐UBT), H. pylori stool antigen test, and serology test during 2019–2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13C‐UBT for H. pylori screening. We also conducted a systematic review and meta‐analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age‐standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry. Results: A total of 1494 participants were enrolled, including 294 children or adolescents and 1200 adults. The overall prevalence of active H. pylori infection by 13C‐UBT was 26.6% (397/1494), which was 30.8% in adults and 9.5% in adolescents/children. The age‐standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta‐analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%–71%) in 1990–2000 to 28.2% (95% CI:21.8%–35.6%) in 2016–2020. The age‐standardized incidence and mortality of gastric cancer have also declined from 15.2 to 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019. Conclusions: The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age‐standardized incidence and mortality of gastric cancer in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer exhibits familial clustering, and gastric cancer familial relatives (GCF) tend to present with corpus-predominant gastritis and precancerous lesions as SPEM or IM after H. pylori infection. The study determined whether the children of gastric cancer patients (GCA) had genomic single nucleotide polymorphisms (SNPs) predisposed to the gastric precancerous lesions as spasmolytic polypeptide-expressing metaplasia (SPEM) or intestinal metaplasia (IM). Results: There were 389 family relatives of 193 non-cardiac GCA and 173 duodenal ulcer patients (DU), received blood sampling for DNA collection. The differences of the risk alleles of SNPs in the ITGA5, ITGB1, IL-10, COX-2, RUNX3, and TFF2 genes were compared between 195 children of GCA and 143 DU. The children of GCA had higher allele frequencies of ITGA5-1160 T-carrier (P = 0.006, OR[95% CI] = 2.2[1.2-4]), ITGB1-1949 A-carrier (P = 0.047; OR[95% CI] = 2.8[1.4-5.3]), ITGB1 + 31804 C-carrier (P = 0.013; OR[95% CI] = 4.7[1.7-13.0]), IL-10-592 AA (P = 0.014; OR [95% CI] = 2.3[1.4-4.0]) and COX-2-1195 G-carrier (P = 0.019; OR[95% CI] = 1.7[0.9-3.2]) than DU. The combined genotype with ITGA5-1160/ITGB1-1949/ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA was more prevalent in the children of GCA than in DU (P < 1×10-4), and predisposed with a 5.3-fold risk of getting SPEM in the H. pylori-infected children of GCA (P = 0.016). Such risk of getting SPEM increased to 112 folds, if combined with RUNX3 + 492/TFF2-308 as A-carrier/CC in this limited study scale (P = 1×10-4). Conclusions: The SNPs of ITGA5-1160/ITGB1-1949/ ITGB1 + 31804 as T/A/C carriers and COX-2-1195/IL-10-592 as G-carrier/AA, or more specific to combine RUNX3 + 492/TFF2-308 as A-carrier/CC shall be host factor predisposing to gastric cancer during H. pylori infection, and serve as marker to identify high-risk subjects for H. pylori eradication. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori as the causative agent of the most common chronic bacterial infectious disease in human still involves a range of clinical challenging complications. In this meantime, the survey of the interaction between H. pylori virulence genes expression and its consequences on gastric antral epithelial cells is Controversial. This study surveyed the correlations between H. pylori cag Pathogenicity Island and virulence factors genes with Fgf7 gene expression as an angiogenic factor in developing gastric cancer in gastric antral epithelial cells of patients with H. pylori infection. Method: Gastric antral biopsy samples collected from patients out of exclusion criteria, including consumption of tobacco, alchohol and anti-H. pylori drugs, were categorized into gastric cancer (case group n:53) and gastritis (control group n:50) with and without H. pylori infection to detect changes in cDNA of fgf7 in gastric antral epithelial cells by using Real Time RT PCR. Extracted total RNA from gastric antral biopsy samples was used to synthesize cDNA for real time PCR. Furthermore, the cDNA of H. pylori cag Pathogenicity Island and other virulence factors genes were detected by using specific designed primers and simple PCR. Results: Fgf7 gene expression revealed a significantly increase in gastric antral epithelial cells of gastric cancer and H. pylori-positive patients in contrast with gastritis and H. pylori-negative patients (p < 0.05). In the meanwhile, cag Pathogenicity Island and hopQ genotypes showed a positive correlation with Fgf7 gene expression (fold changes of cDNA) in gastric antral epithelial cells (p < 0.05). Conclusion: This study revealed an obvious correlation between Fgf7 gene expression in gastric antral epithelial cells of patients with H. pylori carcinogenic genotypes infection and some host factors including age. [ABSTRACT FROM AUTHOR]

Background: Dyspepsia is one of the most common complaints in gastroenterology. While its etiology is usually benign, rare cases of malignancy have to be identified. Individualized risk stratification is essential for cost-effective management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia at the specialist level and provide a framework for rational workup and surveillance strategies. Summary: Causes of dyspepsia can be functional or organic, including gastritis, peptic ulcers, or malignancy. H. pylori gastritis represents a specific entity of dyspepsia and increases the risk of gastric cancer. H. pylori eradication can improve symptoms in a subset of patients and reduce gastric cancer risk. In young patients without alarm features, malignancy is rare, and noninvasive testing for H. pylori is appropriate. In elder patients and those with alarm features, high-quality endoscopy is the method of choice to rule out malignancy. Advanced corpus-predominant atrophic gastritis with or without intestinal metaplasia represent precancerous lesions. Key Messages: Symptom assessment requires to distinguish dyspepsia of functional or organic origin. Risk stratification in dyspeptic patients is based on age, alarm features, and H. pylori status. Noninvasive test-and-treat is recommended in patients with low gastric cancer risk, while endoscopy is recommended in individuals at increased risk. H. pylori infection should be eradicated in order to obtain a symptomatic benefit and reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic surveillance. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, several artificial intelligence (AI) systems are developed to assist in endoscopic assessment of (pre-)cancerous lesions of the gastrointestinal (GI) tract. In this review, we aimed to provide an overview of the possible indications of AI technology in upper GI endoscopy and hypothesize about potential challenges for its use in clinical practice. Summary: Application of AI in upper GI endoscopy has been investigated for several indications: (1) detection, characterization, and delineation of esophageal and gastric cancer (GC) and their premalignant conditions; (2) prediction of tumor invasion; and (3) detection of Helicobacter pylori. AI systems show promising results with an accuracy of up to 99% for the detection of superficial and advanced upper GI cancers. AI outperformed trainee and experienced endoscopists for the detection of esophageal lesions and atrophic gastritis. For GC, AI outperformed mid-level and trainee endoscopists but not expert endoscopists. Key Messages: Application of artificial intelligence (AI) in upper gastrointestinal endoscopy may improve early diagnosis of esophageal and gastric cancer and may enable endoscopists to better identify patients eligible for endoscopic resection. The benefit of AI on the quality of upper endoscopy still needs to be demonstrated, while prospective trials are needed to confirm accuracy and feasibility during real-time daily endoscopy. [ABSTRACT FROM AUTHOR]

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a reduced risk of gastrointestinal malignancies, which is thought to be mediated mainly through the inhibition of cyclooxygenases-2 (COX-2). Due to the severe side effects of aspirin/NSAIDs, selective COX-2 inhibitors may be a more ideal choice. The objective is to evaluate the association of selective COX-2 inhibitors with gastrointestinal (GI) malignancies and premalignant lesions. We searched for published manuscripts evaluating the association between COX-2 inhibitors and GI malignancies or precancerous lesion. Two investigators independently abstracted the data; then, we conducted the analysis by Review Manager V.5.0; evaluation of effectiveness was performed by an intention to treat (ITT) method. Selective COX-2 inhibitors had no beneficial effects on the progression or regression of esophageal and gastric dysplasia (OR = 1.06, 95% CI 0.63–1.78, P = 0.83 for regression of esophageal dysplasia; OR = 1.06, 95% CI 0.58–1.91, P = 0.86 for progression of esophageal dysplasia; OR = 1.95, 95%CI 0.92–4.17, P = 0.08 for regression of gastric dysplasia; and OR = 0.99, 95%CI 0.68–1.43, P = 0.94 for progression of gastric dysplasia). There is no protective effect on colorectal cancer (OR = 0.89, 95% CI 0.77–1.03, P = 0.11), and the use could not improve the effect of chemoradiation (OR = 1.20, 95% CI 0.46–3.19, P = 0.71). This pooled analysis indicates no meaningful association between selective COX-2 inhibitors and GI malignancies. [ABSTRACT FROM AUTHOR]

Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a well-known risk factor for a variety of gastrointestinal disorders (GID). Helicobacter pylori is associated with different GID, such as gastric cancer and chronic gastritis. In this study, we investigated the prevalence of dominant genotypes in H. pylori isolated from obese patients diagnosed with gastric ulcer, duodenal ulcer, and gastric cancer. Methods: A total of 222 H. pylori-positive samples were collected from patients with obesity. GID and gastric cancer were identified by endoscopy and histopathology, respectively. Three biopsy specimens from the gastric antrum were obtained from each patient for culture tests, histological examination, and identification of vacuolating cytotoxin A (vacA) (vacA s1, vacA s2, vacA m1, vacA m2, vacA s1m1 vacA s1m2, vacA s2m1, and vacA s2m2), cagA, cagE, iceA1, oipA, dupA, and babA2 using polymerase chain reaction. Results:vacA, cagE, cagA, iceA1, oipA, dupA, and babA2 genes were detected in 222 (100%), 171 (77%), 161 (72.5%), 77 (34.6%), 77 (34.6%), 137 (61%), and 69 (31%) patients with obesity, respectively. Our findings revealed that vacA, iceA1, oipA, and babA2 were significantly associated with a higher risk of GID, while cagE, cagA, and dupA indicated no correlation with the development of GID. Also, in the combination of s- and m-region genotypes, s1m2 (79%) was the most frequently identified genotype in patients with obesity. A significant association was also found between cagA and the presence of vacA genotypes (except for vacA m1 and babA2). Conclusions: This study indicated the high prevalence of different virulence genes in H. pylori isolated from obese patients and supported the significant role of H. pylori in the development of GID. [ABSTRACT FROM AUTHOR]

Background: Nearly all Taiwanese H. pylori stains are cagA-genopositive and encode CagA protein. In this study, we evaluated whether different intensity of tyrosine phosphorylated-CagA (p-CagA) had an impact on the clinical diseases and histological outcomes in this area. Results: We enrolled 469 dyspeptic patients and prospectively obtained the gastric biopsy specimens and the H. pylori isolates. These patients were categorized according to the clinical diseases, such as duodenal ulcer, gastric ulcer, gastric cancer, and gastritis with or without intestinal metaplasia. Their gastric specimens were reviewed by the updated Sydney's system. Furthermore, a total of 146 patients were randomly selected from each clinical category for evaluation of their isolates' p-CagA intensity by in vitro AGS cells co-culture. The p-CagA was sparse in 30 (20.5%), weak in 59 (40.5%), and strong in 57 (39%) isolates. The isolates from the patients of gastric cancer or gastritis with intestinal metaplasia had stronger p-CagA intensity than those of gastritis without intestinal metaplasia (p ≤ 0.002). Moreover, the patients infected with isolates with strong or weak p-CagA intensity had a higher risk of gastric intestinal metaplasia (p < 0.05, odds ratio 3.09~15.26) than those infected with sparse p-CagA isolates. Conclusions: Infection with H. pylori stains with stronger p-CagA intensity may lead to an increased risk of gastric intestinal metaplasia and cancer. [ABSTRACT FROM AUTHOR]

Background: The purpose of the present study was to test whether host erythrocyte Lewis phenotypes correlated with the risk of gastric cancers. Because of the association of gastric cancer with familial clustering, cancer relatives were investigated as to whether they had unique distribution of Lewis phenotypes. Methods: The study prospectively enrolled 74 Helicobacter pylori-positive gastric cancer patients and 100 H. pylori-positive duodenal ulcer patients to serve as non-cancer controls after panendoscopy. In addition, 433 family members from the 74 index cancer and 100 non-cancer control patients were enrolled. All enrolled cases were checked for their H. pylori status and erythrocyte Lewis phenotypes, defined as Lea–b–, Lea–b+, Lea+b–, and Lea+b+ subtypes by the anti-Lea and anti-Leb monoclonal antibodies. Results: These H. pylori-infected patients with gastric cancer had a higher rate of Lea+b– phenotype and a lower rate of Lea–b+ phenotype than the non-cancer duodenal ulcer controls (20.3% vs 9%; 51.4% vs 72%, P < 0.05). Among these H. pylori-infected patients, the risk of the patients with Lea+b– phenotype having gastric cancer was 3.15-fold higher as compared with those with the Lea–b+ phenotype ( P = 0.02, 95% confidence interval: 1.26–7.87). The offspring and cousins of the cancer patients had a higher rate of Lea+b– phenotype as compared to either that of the spouses of cancer index patients or to that of the family members of the non-cancer control ( P < 0.05). Conclusion: Lea+b– phenotype of the H. pylori-infected host could be a risk factor (with familial clustering) for gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

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Background: Helicobacter pylori (H. pylori) is the causative agent of stomach diseases such as duodenal ulcer and gastric cancer, in this regard incomplete eradication of this bacterium has become to a serious concern. Probiotics are a group of the beneficial bacteria which increase the cure rate of H. pylori infections through various mechanisms such as competitive inhibition, co-aggregation ability, enhancing mucus production, production of bacteriocins, and modulating immune response.Result: In this study, according to the received articles, the anti-H. pylori activities of probiotics were reviewed. Based on studies, administration of standard antibiotic therapy combined with probiotics plays an important role in the effective treatment of H. pylori infection. According to the literature, Lactobacillus casei, Lactobacillus reuteri, Lactobacillus rhamnosus GG, and Saccharomyces boulardii can effectively eradicate H. pylori infection. Our results showed that in addition to decrease gastrointestinal symptoms, probiotics can reduce the side effects of antibiotics (especially diarrhea) by altering the intestinal microbiome.Conclusion: Nevertheless, antagonist activities of probiotics are H. pylori strain-specific. In general, these bacteria can be used for therapeutic purposes such as adjuvant therapy, drug-delivery system, as well as enhancing immune system against H. pylori infection. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) eradication reduces gastric cancer risk. Since 2013, a population‐wide H. pylori eradication strategy for patients with chronic gastritis has begun to prevent gastric cancer in Japan. The aim of this study was to evaluate the economic and health effects of H. pylori eradication strategy in national gastric cancer prevention program. Materials and Methods: We developed a cohort state‐transition model for H. pylori eradication and no eradication over a lifetime horizon from a healthcare payer perspective, and performed one‐way and probabilistic sensitivity analyses. We targeted a hypothetical cohort of H. pylori‐positive patients aged 20, 30, 40, 50, 60, 70, and 80. The main outcomes were costs, quality‐adjusted life‐years (QALYs), life expectancy life‐years (LYs), incremental cost‐effectiveness ratios, gastric cancer cases, and deaths from gastric cancer. Results: H. pylori eradication was more effective and cost‐saving for all age groups than no eradication. Sensitivity analyses showed strong robustness of the results. From 2013‐2019 for 8.50 million patients, H. pylori eradication saved US$3.75 billion, increased 11.11 million QALYs and 0.45 million LYs, and prevented 284,188 cases and 65,060 deaths. For 35.59 million patients without eradication, H. pylori eradication has the potential to save US$14.82 billion, increase 43.10 million QALYs and 1.66 million LYs, and prevent 1,084,532 cases and 250,256 deaths. Conclusions: National policy using population‐wide H. pylori eradication to prevent gastric cancer has significant cost savings and health impacts for young‐, middle‐, and old‐aged individuals in Japan. The findings strongly support the promotion of H. pylori eradication strategy for all age groups in high‐incidence countries. [ABSTRACT FROM AUTHOR]

This article analyses the literature regarding the value of computer-assisted systems in esogastroduodenoscopy-quality monitoring and the assessment of gastric lesions. Current data show promising results in upper-endoscopy quality control and a satisfactory detection accuracy of gastric premalignant and malignant lesions, similar or even exceeding that of experienced endoscopists. Moreover, artificial systems enable the decision for the best treatment strategies in gastric-cancer patient care, namely endoscopic vs surgical resection according to tumor depth. In so doing, unnecessary surgical interventions would be avoided whilst providing a better quality of life and prognosis for these patients. All these performance data have been revealed by numerous studies using different artificial intelligence (AI) algorithms in addition to white-light endoscopy or novel endoscopic techniques that are available in expert endoscopy centers. It is expected that ongoing clinical trials involving AI and the embedding of computer-assisted diagnosis systems into endoscopic devices will enable real-life implementation of AI endoscopic systems in the near future and at the same time will help to overcome the current limits of the computer-assisted systems leading to an improvement in performance. These benefits should lead to better diagnostic and treatment strategies for gastric-cancer patients. Furthermore, the incorporation of AI algorithms in endoscopic tools along with the development of large electronic databases containing endoscopic images might help in upper-endoscopy assistance and could be used for telemedicine purposes and second opinion for difficult cases. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods: This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined 'low risk' if they fulfilled requirements for discharge, and 'high risk' if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined 'low risk' with progression of disease during follow-up (FU) were considered 'misclassified' as low risk. Results: 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were 'misclassified', showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were 'misclassified'. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were 'misclassified'. Seven patients developed gastric cancer (GC) or dysplasia, four patients were 'misclassified' based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion: One-third of patients that would have been discharged from GC surveillance, appeared to be 'misclassified' as low risk. One additional endoscopy will reduce this risk by 70%. [ABSTRACT FROM AUTHOR]

The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first‐line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test‐and‐treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test‐and‐treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first‐line therapy against H. pylori‐associated diseases. The guidelines recommend against a "test‐and‐treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high‐risk population groups. What's new? H. pylori is a class 1 carcinogen. However, not all strains increase the risk of gastric cancer. In this study, the authors identified a number of SNPs in the cagA pathogenicity island of H. pylori that are associated with pre‐malignant lesions or gastric cancer. They then developed a scoring system based on these SNPs to quantify an individual patient's level of risk. These markers may enable risk stratification in a population, with the goal of targeting of H. pylori eradication to high‐risk groups. [ABSTRACT FROM AUTHOR]

Objective: This study aims to systematically review the application of artificial intelligence (AI) techniques in gastric cancer and to discuss the potential limitations and future directions of AI in gastric cancer. Methods: A systematic review was performed that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pubmed, EMBASE, the Web of Science, and the Cochrane Library were used to search for gastric cancer publications with an emphasis on AI that were published up to June 2020. The terms "artificial intelligence" and "gastric cancer" were used to search for the publications. Results: A total of 64 articles were included in this review. In gastric cancer, AI is mainly used for molecular bio-information analysis, endoscopic detection for Helicobacter pylori infection, chronic atrophic gastritis, early gastric cancer, invasion depth, and pathology recognition. AI may also be used to establish predictive models for evaluating lymph node metastasis, response to drug treatments, and prognosis. In addition, AI can be used for surgical training, skill assessment, and surgery guidance. Conclusions: In the foreseeable future, AI applications can play an important role in gastric cancer management in the era of precision medicine. [ABSTRACT FROM AUTHOR]

Programmed death-ligand 1 (PD-L1) and ICOS-L (also referred to as B7 homolog 1 and 2, respectively) modulate the immune inflammatory response. The aim of the present study was to examine the expression levels of these inflammatory mediators in two groups of patients with an Helicobacter pylori (H. pylori) infection; patients with and without gastric cancer. The association between bacterial virulence factors, CagA and VacA, was also examined, as well as their correlation with the inflammatory profile. Endoscopy analysis indicated that 18 patients suffered from cancer and 28 patients suffered from other gastric pathologies. PCR and reverse transcription-quantitative PCR were used to analyze gastric biopsies and determine the expression levels of the inflammatory modulators PD-L1 and ICOS-L, transcription factors, cytokines and other genes associated with inflammation and pathogenicity. All 46 patients were determined positive for markers of H. pylori. Patients with stomach cancer had lower levels of ICOS-L (P<0.05) and GATA3 (P<0.01), a negative correlation between CagA and IL-17 (P<0.05), a positive correlation between CagA and IL-10 (P<0.05), a negative correlation between vacA-m1 and retinoid orphan receptor γt (RORγt) (P<0.001), and a positive correlation between RORγt and ICOS-L (P<0.001). The reduced levels of ICOS-L and GATA3 along with the negative correlation between CagA and IL-17, and between vacA-m1 and RORγt were all associated with an increased risk of gastric cancer in the present cohort. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC).Methods: The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses.Results: The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival.Conclusions: CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is one of the most common bacteria in the stomach, colonizing about one-half of the population in the world, while most of them remain asymptomatic throughout their lives and gastric cancer (GC) occurs in only 1-2% of people. It seems that the final outcomes of Helicobacter pylori infection are dependent on bacterial virulence factors, host genetic characteristics, and the environmental conditions. In this study, we compared the expression of 20 known virulence factors associated with the development of GC in the isolated Helicobacter pylori strains from the Colombian patients belonging to the regions with low and high GC risks. Based on the results of the present study, it was found that the 20 studied virulence factors are closely related with each other and regulate their expressions through the required intermediates. We also showed that the Helicobacter pylori strains belonging to the region with high GC risk were more virulent and have developed into GC by destroying the intercellular bindings, cell skeletal dysregulation, and cell survival and proliferation stimulation, while the H. pylori strains in the region with low GC risk expressed virulence factors related to the chronic inflammation and apoptosis; adhesion factors were also different in both groups. [ABSTRACT FROM AUTHOR]

Background: H. pylori CagL-Y58/E59 increase gastric cancer risk by stronger binding with integrin to faciliate type IV secretory system (T4SS). H. pylori can secrete high temperature requirement A (HtrA) to mediate E-Cadherin cleavage for gastric epithelial junction disruption, so H. pylori CagL can adhere to integrin located on basolateral side of epithelium. The study test whether H. pylori HtrA amino acid polymorphisms can increase gastric cancer risk synergistically with CagL-Y58/E59. Methods: One-hundred and sixty-four H. pylori-positive patients, including 71 with non-ulcer dyspepsia (NUD), 63 with peptic ulcers (PU), and 30 with gastric cancers (GC), were enrolled to receive upper gastrointestinal endoscopy to obtain gastric biopsies for H. pylori culture and histology by the updated Sydney system. Each isolate was screened for htrA & cagL genotype by polymerase chain reaction and HtrA & CagL-Y58/E59 amino acid sequence polymorphisms by sequencing. Results: The prevalence rates of htrA & cagL gene were both 100%. The HtrA amino acid sequence polymorphisms were not different between NUD and PU. The H. pylori isolates of GC had higher rates of HtrA residue 171 as leucine than those of NUD (73.3% vs. 50.7%, P = 0.036, OR[95%CI] = 2.7[1.1–6.8]). The risk of the H. pylori-infected subjects to get gastric cancer was increased up to 15.4-fold, if the infected isolates had presence of both HtrA-L171 and CagL-Y58/E59 (P < 0.001). Conclusions: The H. pylori isolates of gastric cancer subjects had a higher rate of HtrA-L171. H. pylori isolates with presence of both HtrA-171 & CagL-Y58/E59 can synergistically increase the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship between these parameters and the main clinical morphological characteristics of the disease was analyzed. Plasma levels of the proteins were measured using standard direct ELISA kits. The level of MMP-7 in patients with gastric cancer was significantly higher than in the control group (medians 2.7 and 1.2 ng/ml, respectively; p<0.01), but only in 51% patients this parameter surpassed the upper threshold normal value (2.35 ng/ml; 95% percentile of control). The level of MMP-9 in gastric cancer patients was lower than in control group by 1.6 times (medians 167 and 267 ng/ml, respectively; p<0.01). Plasma levels of MMP-2 and TIMP-2 in patients with gastric cancer and healthy subjects were similar. No appreciable associations of plasma matrixins and TIMP-2 with the main clinical morphological characteristics of the disease were detected. The patients were followed up for 8 to 85 months (median 70.8 months). Low level of MMP-2 and high level of MMP-7 in the plasma proved to be unfavorable prognostic factors for overall survival. At MMP-2<268 ng/ml, the 5-year overall survival was 32% vs. 60% for patients with the marker level higher than this threshold value (p=0.016). The differences in overall survival in relation to their MMP-7 levels for 5-year observation did not surpass 16% (39% at marker level >2.7 ng/ml and 55% at lower level; p=0.048). Plasma levels of MMP-2 and TIMP-2 were not significantly associated with overall survival. Multivariate analysis showed that only T index (p=0.034) and plasma MMP-7 level (p=0.007) were essential for overall survival. The increase in plasma or serum MMP-7 levels is a universal phenomenon in tumors of different histogenesis, which precluded the use of this parameter as a specific diagnostic marker of gastric cancer. At the same time, it could be useful for monitoring the treatment efficiency and detection of relapses. In addition, high plasma level of MMP-7 remained an independent factor of unfavorable prognosis for overall survival of patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is a gram-negative microaerophilic bacterium that has been introduced as a cause of mucosal inflammation and gastric cancer. The most important pathogenic factors are VacA and CagA, which are associated with increased disease severity in clinical strains. Autophagy is a protected lysosomal degradation pathway degrading cytoplasmic content and is important in host cell defense, survival, differentiation and development. It can have a tumor suppressor activity or cancer progression and plays an important role in host safety and homeostatic. H. pylori can affect host pathogenic pathway through VacA and CagA virulence factors and carcinogenesis. Increasing autophagy in tumor cells prevents the accumulation of non-functional mitochondria that can disrupt tumorigenicity. The ability of H. pylori to manipulate host pathogenesis pathway is considered as one of the important aspects of its pathogenesis. Several studies have shown that infection with H. pylori causes autophagy in both gastric epithelial cells and phagocytes. In the epithelial cells of the stomach, VacA is a necessary factor in autophagy. While CagA is a negative regulator of the phenomenon, the elimination of this gene from H. pylori has increased autophagy and the production of inflammatory cytokines is reduced. [ABSTRACT FROM AUTHOR]

Traditionally, the stomach was believed to be a sterile organ unsuitable for microbiota growth. However, the discovery of H. pylori subverted this conception. With the development of molecular techniques, an abundance of microbiota of great diversity was found in the stomach. In addition, various lines of evidence suggest that the gastric microbiota plays a critical role in the development and progression of the gastric disease.The gastrointestinal microbiome plays an important role in various physiologic and pathologic processes. [ABSTRACT FROM AUTHOR]

Virulence factors of H. pylori, such as outer inflammatory protein A (oipA), are closely involved in the development of gastric diseases such as chronic gastritis and gastric cancer. The functional status of oipA is regulated by a repair mechanism based on CT dinucleotide repeats that influence the reading frame, thus granting the gene a functional or nonfunctional status; in other words, the functional status of the oipA gene seems to be associated with the development of gastric diseases. This study sought to detect the presence of the oipA gene and to determine its functional status in patients with gastric diseases. We analyzed 516 biopsy samples (101 with normal gastric tissue, 365 with chronic gastritis, and 50 with gastric cancer). The presence of oipA was determined by PCR, and the gene status was determined using sequencing reactions. The oipA gene was found to be associated with the development of chronic gastritis, and the "on" status of the gene was the most frequent in patients with gastric cancer who were from Western countries. The CT repeats revealed geographic characteristics, but it is the functional status of the oipA gene that seems to be involved in the development of gastric diseases and in the development of gastric cancer in particular. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer is one of the top causes of cancer-related death worldwide. How to eliminate gastric cancer is an urgent public-health issue. Areas covered: In this review, we present up-to-date results of studies on gastric cancer prevention through the eradication of Helicobacter pylori and discuss strategies and obstacles for the implementation of population-wide screening and treatment of this pathogen to prevent gastric cancer. Expert commentary: Gastric cancer is an inflammation-associated cancer with multistep carcinogenesis. The process consists of H. pylori infection, ongoing inflammation, development of metaplastic epithelia and genetic instability eventuating in gastric cancer. H. pylori infection is critical for development of the disease and studies have consistently shown that H. pylori eradication results in a reduction in (a) gastric mucosal inflammation, (b) progression of histologic damage, (c) risk of peptic ulcers and ulcer recurrence, and (d) risk of gastric cancer. Compared with a large number of clinical trials evaluating chemopreventive approaches, studies of population-wide screening, and eradication of H. pylori have only recently begun and only in high-risk populations. To eliminate gastric cancer requires information on how to implement an effective program for screening and treatment of H. pylori taking into consideration the other health priorities in any specific population. [ABSTRACT FROM AUTHOR]

Gastric cancer is the third leading cause of cancer death worldwide. Gastric cancer screening using upper gastrointestinal series, endoscopy and serological testing has been performed in population-based (employee-based and community-based) and opportunistic cancer screening in Japan. There were 45 531 gastric cancer deaths in 2016, with the low screening and detection rates. Helicobacter pylori (H. pylori) screening followed by eradication treatment is recommended in high-risk population settings to reduce gastric cancer incidence. The aim of this study was to evaluate the cost-effectiveness of H. pylori screening followed by eradication treatment for a high-risk population in the occupational health setting. Decision trees and Markov models were developed for two strategies; H. pylori antibody test (HPA) screening and no screening. Targeted populations were hypothetical cohorts of employees aged 20, 30, 40, 50 and 60 years using a company health payer perspective on a lifetime horizon. Per-person costs and effectiveness (quality-adjusted life-years) were calculated and compared. HPA screening yielded greater benefits at the lower cost than no screening. One-way and probabilistic sensitivity analyses using Monte-Carlo simulation showed strong robustness of the results. H. pylori screening followed by eradication treatment is recommended to prevent gastric cancer for employees in Japan, on the basis of cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: The risk of gastric carcinoma (GC) varies around the world and between females and males. We aimed to compare the risk of GC among immigrants to Ontario, Canada, to the risk of GC in its general population.Methods: This was a retrospective population-based matched cohort study from 1991 to 2014. We identified immigrants who were first eligible for the Ontario Health Insurance Plan at age 40 years or older, and matched 5 controls by year of birth and sex. We calculated crude rates and relative rates of GC stratified by sex. We modeled GC hazard using multivariable Cox proportional hazards regression, where a time-varying coefficient was incorporated to examine changes in the association of immigrant status with GC hazard over time.Results: Among females, 415 GC cases were identified among 209,843 immigrants and 1872 among 1,049,215 controls. Among males, 596 GC cases were identified among 191,792 immigrants and 2998 among 958,960 controls. Comparing immigrants from East Asia and Pacific with the controls, the crude relative rate of GC was 1.54 for females and 1.32 for males. The adjusted hazard ratio (HR) for GC among female immigrants was 1.29 [95% confidence interval (CI) 1.12, 1.48] within 10 years and 1.19 (1.01, 1.40) beyond 10 years; for males, the HR was 1.17 (1.04, 1.31) within 10 years and 1.00 (0.87, 1.15) beyond 10 years.Conclusion: The risk of GC among immigrants is elevated. Although high-risk immigrant populations in Ontario have been identified, further knowledge is required before a program of GC prevention that is targeted to them can be planned. [ABSTRACT FROM AUTHOR]

Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways. [ABSTRACT FROM AUTHOR]

Background: An increased prevalence of gastric premalignant abnormalities was reported among relatives of gastric cancer (GC) patients, with rather unexplored clinical significance.Methods: In Swedish computerized pathology registers, we identified, as 'index' persons, 232 681 patients who were born after 1931 and underwent endoscopic examination with stomach biopsy between 1979 and 2014. Through linkage with the Multi-Generation Register, we compiled a cohort consisting of 903 337 first-degree relatives of these biopsied patients. The relatives were grouped according to their 'family histories', defined as the first gastric mucosal diagnosis of the index person or GC family history known before that. Standardized incidence ratios (SIRs) provided comparisons with the matched general population. For internal comparisons with relatives with 'normal/minor changes' mucosal family history, hazard ratios (HRs) were derived from adjusted Cox regression modelling.Results: During follow-up, 1302 relatives developed GC. Crude incidence rates of non-cardia GC were 7.7 × 10-5 year-1 for the 'normal/minor changes' family history group (SIR = 1.0), 11.2 to 12.6 × 10-5 year-1 for precancerous changes groups (atrophic gastritis/intestinal metaplasia/dysplasia, SIR = 1.5 to 1.6), and 18.4 × 10-5 year-1 for those with a family history of GC (SIR = 2.3). HRs derived from Cox models corroborated the family history-related risk pattern, with the most conspicuous trend observed among siblings-a family history of any precancerous changes and GC was associated with, respectively, a 2.5-fold and a 3.8-fold increment in non-cardia GC hazard, compared with siblings of index persons with 'normal/minor mucosal changes'.Conclusions: The precancerous mucosal abnormalities recorded in a person's first-degree relatives may improve GC risk stratification for this person. [ABSTRACT FROM AUTHOR]

Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies. [ABSTRACT FROM AUTHOR]

Background: Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. Methods: A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. Results: The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11-4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15-0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus. Conclusions: Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection. [ABSTRACT FROM AUTHOR]