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Copyright of Turkish Journal of Surgery / Bilimsel Tip Yayinevi is the property of Bilimsel Tip Yayinevi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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: 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: 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]

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]

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]

Copyright of General Medicine & Health Sciences / Medycyna Ogólna i Nauki o Zdrowiu is the property of Witold Chodzki Institute of Rural Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

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]

Background: Gastric cancer (GC) is the third leading cause of cancer death, and most patients represent metastatic phenotype at the time of diagnosis. Urokinase plasminogen activator (uPA) system is well known for its critical roles in cancer cells invasion since uPA/uPA receptor (uPAR) overexpresses in several cancers. Subsequently, suppression of uPA/uPAR gene expression improves patients overall survival and prevents cancer progression.Objectives: The aim of the current study was to investigate possible effects of live Lactobacillus reuteri as a probiotic in inhibition of GC cells proliferation and invasion.Materials and Methods: Human gastric adenocarcinoma epithelial cell line (AGS) cells were treated with different ratios of live L. reuteri and were incubated for 24, 48, and 72 h. Viability of cancer cells was measured with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay, and the effects of L. reuteri on uPA/uPAR gene expression were assessed by real-time polymerase chain reaction.Results: Our results showed that L. reuteri inhibits cell proliferation significantly in dose-dependent manner. Expressions of uPA and uPAR were downregulated followed by co-incubation of AGS cells and live L. reuteri compared to untreated-based line level.Conclusion: This study provides strong support in the role of L. reuteri in suppression of GC cell invasion by downregulation of pathways which is involved in extracellular matrix degradation such as uPA and uPAR. [ABSTRACT FROM AUTHOR]

Background: A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. Methods: We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69 years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. Results: MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC ( n = 23) and in individuals for whom one parent and their sibling(s) had a history of GC ( n = 36) compared with those with no family history ( n = 3816) [30.4 % vs 11.6 %, OR 4.34, 95 % confidence interval (CI) 1.45-13.03 and 16.7 % vs 11.6 %, OR 2.26, 95 % CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1 %. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95 % CI 0.75-14.96 and OR 3.51, 95 % CI 1.35-9.15 respectively). Conclusions: MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends all countries consider screening for H. pylori to prevent gastric cancer. We therefore aimed to estimate the cost-effectiveness of a H. pylori serology-based screening program in New Zealand, a country that includes population groups with relatively high gastric cancer rates.Methods: A Markov model was developed using life-tables and morbidity data from a national burden of disease study. The modelled screening program reduced the incidence of non-cardia gastric cancer attributable to H. pylori, if infection was identified by serology screening, and for the population expected to be reached by the screening program. A health system perspective was taken and detailed individual-level costing data was used.Results: For adults aged 25-69 years old, nation-wide screening for H. pylori was found to have an incremental cost of US$196 million (95% uncertainty interval [95% UI]: $182-$211 million) with health gains of 14,200 QALYs (95% UI: 5,100-26,300). Cost per QALY gained was US$16,500 ($7,600-$38,400) in the total population and 17% (6%-29%) of future gastric cancer cases could be averted with lifetime follow-up. A targeted screening program for Māori only (indigenous population), was more cost-effective at US$8,000 ($3,800-$18,500) per QALY.Conclusions: This modeling study found that H. pylori screening was likely to be cost-effective in this high-income country, particularly for the indigenous population. While further research is needed to help clarify the precise benefits, costs and adverse effects of such screening programs, there seems a reasonable case for policy-makers to give pilot programs consideration, particularly for any population groups with relatively elevated rates of gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population. Methods: Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis. Results: For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05). Conclusion: Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastric intestinal metaplasia (IM) is an important risk factor for intestinal-type gastric carcinoma, and successful treatment critically depends on its timely detection. In order to guide appropriate endoscopic surveillance, objective knowledge on the anatomical predilection of intestinal metaplasia development is urgently needed. Materials and Methods: A total of 78,335 cases who underwent gastroduodenoscopy from 2008 to 2013 in Jiangsu and Anhui provinces in China, were studied. Demographic and clinical characteristics, as well as biopsy location and histological results, were analyzed. Results: This study revealed that intestinal metaplasia incidence was 28.5% in angulus, 20.24% in lesser curvature of the antrum, and 25.48% in corpus; and all these were significantly higher than those observed in other sites (P < 0.01). Histological grading of intestinal metaplasia in the lesser curvature of the antrum and angulus was generally worse than the grading observed in the greater curvature of the antrum. For Helicobacter pylori-positive patients, acute inflammation was more severe in the lesser curvature of the antrum compared with the greater curvature. In the H. Pylori-negative group, both acute and chronic inflammations were more severe in the lesser curvature of the antrum. Conclusions: The angulus, lesser curvature in the antrum, and corpus are most prone to the development of intestinal metaplasia. Inflammation is most severe in the lesser curvature of the antrum, which corresponds to a higher predilection to develop intestinal metaplasia at this site. The lesser curvature of the antrum and corpus require the most attention during endoscopic biopsy surveillance. [ABSTRACT FROM AUTHOR]

Background Pipeline is a compound comprising 5-9% of black pepper {Piper nigrum), which has a variety of biological roles related to anticancer activities. He licobacter pylori has been classified as a gastric carcinogen, because it causes gastritis and gastric cancer by injecting the virulent toxin CagA and translocating VacA. The present study investigated the inhibitory action of pipeline on H. pylori growth and adhesion. Methods Inhibition of H. pylori growth was determined by the broth macrodilution method, and adhesion to gastric adenocarcinoma cells validated by urease assay. Motility test was performed by motility agar and the expression of adhesion gene and flagellar gene in response to the pipeline treatment was assessed by RT-PCR and immunoblotting. Results Administrated pipeline suppressed the level of H. pylori adhesion to gastric adenocarcinoma cells in a dose dependent manner and the inhibition was statistically significant as determined by student's Mest. In addition, piperine treatment effects on the flagellar hook gene flgE and integral membrane component of the export apparatus gene flhA expression to be suppressed and piperine diminished the H. pylori motility. Conclusions flhA, encodes an integral membrane component of the export apparatus, which is also one of the regulatory protein in the class 2 genes expression and flgE is one of them that encodes hook part of the flagella. Suppression of both genes, leads to less motility results in the organism attracted less towards to the gastric epithelial cells might be the possible reason in the adhesion inhibition. To our knowledge, this is the first report published on the inhibitory effects of piperine against the adhesion of H. pylori to gastric adenocarcinoma cells. [ABSTRACT FROM AUTHOR]

Chemoresistance remains a major problem in the treatment of gastric cancer patients. Hence, novel pharmacological agents that can overcome drug resistance are urgently required. Whether simvastatin can sensitize the gastric cancer to the antitumor effects of capecitabine in vitro and in vivo was investigated. The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-κB activation by DNA binding assay, and protein expression by western blot analysis. The effect of simvastatin on the tumor growth in xenograft mouse model of human gastric cancer was also examined. Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-κB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. In a xenograft mouse model, we observed that the administration of simvastatin alone (5 mg/kg body weight, intraperitoneal thrice/week) significantly suppressed the growth of the tumor and this effect was further potentiated by capecitabine treatment. As compared to the vehicle control, simvastatin also suppressed the expression of NF-κB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-κB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. Key message: [ABSTRACT FROM AUTHOR]

Background Numerous proteins have been proposed as virulence factors for the gram negative gastric bacterium Helicobacter pylori but only for a few this has unequivocally been demonstrated. The aim of the current study was to evaluate the association of the putative virulence factors tnpA and tnpB (no cagA) with H. pylori associated gastroduodenal diseases. Methods A PCR based assay was used to determine the presence of the tnpA and tnpB genes, as well as of cagA, in 360H. pylori strains isolated from H. pylori infected patients. Results Of 360H. pylori culture positive patients (196 men, 164 women; average age 42.1 years (range 17-73), 95 had gastritis, 92 had gastric ulcers, 108 had duodenal ulcers, and 65 had gastric cancer. Using the gastritis group as a reference a significantly aberrant gene distribution was observed for the tnpA (Relative risk: 1.45; 95% CI 1.04-1.93), the cagA (Relative risk: 1.81; 95% CI 1.44-2.29), but not the tnpB gene in the gastric cancer group. Conclusion The increased incidence of the tnpA gene in gastric cancer patients suggests a role of the tnpA gene in the development of H. pylori induced gastric cancer. [ABSTRACT FROM AUTHOR]

Background/Aims: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis. Methods: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks. Results: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05). Conclusions: H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication. [ABSTRACT FROM AUTHOR]

CagL is a pilus protein of Helicobacter pylori that interacts with host cellular α5β1 integrins through its arginine-glycine-aspartate (RGD) motif, guiding proper positioning of the T4SS and translocation of CagA. Deletion or sequence variations of cagL significantly diminished the ability of H. pylori to induce secretion of IL-8 by the host cell. Therefore, this study was undertaken to investigate the association of cagL and its amino acid sequence polymorphisms with gastric cancer (GC), peptic ulcer disease (PUD), and non-ulcer dyspepsia (NUD) as there are no such studies from India. In total, 200 adult patients (NUD 120, PUD 30, GC 50) who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, and PCR. The collected isolates were screened for cagL genotype by PCR and assessed for amino acid sequence polymorphisms using sequence translation. The prevalence of H. pylori infection in study population was 52.5 %. Most of the isolates were cagL genopositive (86.6 %), and all had RGD motif in their amino acid sequences. D58 and K59 polymorphisms in cagL-genopositive strains were significantly higher in GC patients ( P < 0.05). Combined D58K59 polymorphism was associated with higher risk of GC (3.8-fold) when compared to NUD. In conclusion, H. pylori cagL amino acid polymorphisms such as D58K59 are correlated with a higher risk of GC in the Indian population. Further studies are required to know the exact role of particular cagL amino acid polymorphisms in the pathogenicity of H. pylori infection. [ABSTRACT FROM AUTHOR]

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV−/H. pylori−, neither HCMV+/H. pylori− nor HCMV+/H. pylori+ were associated with metastasis, but HCMV−/H. pylori+ co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation. [ABSTRACT FROM AUTHOR]