Helicobacter Pylori-associated Chronic Gastritis Research Articles

Investigating the mechanism of Banxia Xiexin Decoction in treating Helicobacter pylori-associated chronic atrophic gastritis through network pharmacology and molecular docking

ObjectiveThe aim of this study was to investigate the mechanism of Banxia Xiexin Decoction in treating Helicobacter pylori (HP)-associated chronic atrophic gastritis (CAG) using network pharmacology methods. MethodsDifferential genes between HP-associated CAG and healthy individuals were screened from the Gene Expression Omnibus (GEO) database using high-throughput gene expression data. The compounds and targets of Banxia Xiexin Decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. ResultsThrough screening, 217 differentially expressed genes were obtained. Banxia Xiexin Decoction contained a total of 211 active components corresponding to 258 target genes. Nine key targets, including DPP4, SLC6A4, CYP3A4, HMOX1, MGAM, MTTP, APOB, UGT1A1, and CASP1, were identified. The enrichment analysis showed that Banxia Xiexin Decoction exerted its therapeutic effects on HP-associated CAG by participating in biological processes such as energy metabolism, oxidative reactions, cell apoptosis, anti-inflammatory response, and immune response, as well as regulating drug metabolism processes, heme and chlorophyll metabolism, steroid hormone biosynthesis, and retinol metabolism pathways. ConclusionThe main active components of Banxia Xiexin Decoction are quercetin, ellagic acid, and genistein, and it exerts its therapeutic effects on HP-associated chronic atrophic gastritis through a mechanism involving multiple components, targets, and pathways.

Helicobacter pylori-associated Chronic Atrophic Gastritis and Progression of Gastric Carcinogenesis.

Chronic inflammation due to a Helicobacter pylori (H. pylori) infection is a representative cause of gastric cancer that can promote gastric carcinogenesis by abnormally activating immune cells and increasing the inflammatory cytokines levels. H. pylori infections directly cause DNA double-strand breaks in gastric epithelial cells and genetic damage by increasing the enzymatic activity of cytidine deaminase. Eventually, gastric cancer is induced through dysplasia. Hypermethylation of tumor suppressor genes is an important cause of gastric cancer because of a H. pylori infection. In addition, the changes in gastric microbiota and the mucosal inflammatory changes associated with a co-infection with the Epstein-Barr virus are associated with gastric cancer development. DNA damage induced by H. pylori and the subsequent responses of gastric stem cells have implications for gastric carcinogenesis. Although the pathogenesis of H. pylori has been established, many uncertainties remain, requiring more study.

Concurrent Sarcina ventriculi infection in a patient with Helicobacter pylori-associated chronic gastritis: A case report

Concurrent Sarcina ventriculi infection in a patient with Helicobacter pylori-associated chronic gastritis: A case report

HISTOPATHOLOGICAL BASES OF ORGANIC DYSPEPSIA IN BENIN CITY – A HOSPITAL BASED STUDY OF 186 CASES

Dyspepsia is a symptom complex characterized by features which include epigastric pain or discomfort, belching, bloating and heart burn amongst others, and is one of the commonest indications for upper gastrointestinal endoscopy in Nigeria. The aim of this study was to determine the histopathological bases of organic dyspepsia in this environment. Upper gastrointestinal endoscopy specimens from 186 patients diagnosed with organic dyspepsia in our centre over the 6-month study period were the materials for the study. These were subjected to tissue processing and histopathological examination. The vast majority of the cases of organic dyspepsia had their histopathological bases in the stomach, mostly from various forms of chronic and reactive gastritis, with occasional cases of gastric mucosal ulcers and frank malignancies. Helicobacter pylori-associated chronic gastritis continues to underlie most organic causes of dyspepsia in our environment.

Effect of Helicobacter pylori-Associated Chronic Gastritis on Autonomous Activity and Sleep Quality in Mice.

Many reports have shown that patients with Hp-associated chronic gastritis exhibit anxiety and poor sleep quality. However, less is known about the effects and specific manifestations of Hp-associated chronic gastritis on autonomous activity and sleep quality in animals. Here, we investigated the effect of Helicobacter pylori (Hp)-associated chronic gastritis on autonomous activity and sleep quality in mice. To do this, a Hp-associated chronic gastritis mouse model was first established, then analyzed for autonomous activity, relative to controls, for 15 min using an autonomous activity tester. Next, sleep quality of mice was detected by sodium pentobarbital-induced sleep experiment and results compared between groups. The results showed that male mice in the model group exhibited higher activity counts but lower forelimb lift counts, relative to those in the control group, although there were no significant differences (all p > .05). Conversely, female mice in the model group recorded lower activity counts, albeit at no significant difference (p > .05), and significantly lower counts of forelimb lift (p < .05), relative to those in the control group. Notably, male mice in the model group had longer sleep latency and shorter sleep duration than those in the control group, albeit at no significant differences (all p > .05). On the other hand, female mice in the model group recorded significantly longer sleep latency as well as shorter sleep duration compared to those in the control group (all p < .01). We conclude that Hp-associated chronic gastritis exerts certain effects on autonomous activity and sleep quality of mice in a gender-dependent manner. Notably, female mice with Hp-associated chronic gastritis had lower activity and forelimb lift counts, as well as prolonged sleep latency, and shortened sleep duration. These effects were all statistically significant except for activity counts.

Genetic differences between Helicobacter pylori strains isolated from patients with chronic mild and severe gastritis

Background. Helicobacter pylori-associated chronic gastritis (CG), being a very heterogeneous group, still does not have a divisin based on Helicobacter pylori (Hp) genotyping data, which could predict the clinical form of CG.The aim of the study is to search for the prevalence of the cagA gene or any allelic combination of the vacA gene, or stable combinations of cagA and any allelic combination of vacA genes in Hp isolates from patients with mild and severe CG, as well as patients with peptic ulcer disease (PUD).Methods. Hp isolates from gastrobiopsy specimens were genotyped for cagA and vacA allelic combinations (s1m1, s2m1, s1m2, s2m2). The difference in the occurrence of vacA allelic combinations was assessed by Mann–Whitney U test; the conjunction of cagA and vacA allelic combinations was assessed by the Spearman's rank correlation coefficient (rs).Results. The cagA gene was found in more than half of all cases, both in patients with ulcer and in patients with CG (mild and severe). The incidence of vacAs1m1 (the most virulent allelic combination) showed no significant differences in all forms of gastritis and in PUD; the correlation between cagA and vacAs1m1 was significant in all groups of patients, rs ranged from 0.57 to 0.72. In patients with mild CG, an abundance of non-virulent allelic combination vacAs2m2 was observed, which was significantly different from its occurrence both in patients with severe CG and in patients with ulcer; the joint occurrence of vacAs2m2 and cagA in patients with mild CG was chaotic (rs=-0.13; P=0.40).Conclusion. In mild CG, despite the absence of significant differences in cagA and vacAs1m1 (when compared with severe CG and ulcer disease), strains with a non-virulent allelic combination vacAs2m2 were significantly dominant; therefore, the detection of this particular allelic combination of vacA speaks in favor of a mild course of CG.

Benign effects of Helicobacter pylori in gastric mucosa among symptomatic Sudanese patients

Introduction:Infection with Helicobacter pylori is a worldwide problem. It plays an important role in gastric malignancies.The pathogenesis of gastric malignancies involves multistep progression changes in gastric mucosaand the Helicobacter pylori infections is the first step in most of cases.Aim:The aims of this study were to clarify the benign changes in gastric mucosa after Helicobacter pylori infection;to evaluate the endoscopic and histological patterns of infection and to correlate endoscopic findingwith histopathological parameters.Materials and Methods:A descriptive, retrospective study was done in Soba University Hospital between January 2009 - February2013. Paraffin-embedded blocks, Giemsa and Haematoxylin and Eosin-stained slides, were obtained from50 cases of Helicobacter pylori-associated chronic gastritis and examined under light microscopy. Theclinical information and endoscopy findings were obtained from the records. The data was analyzed usingStatistical Package for Social Sciences Software.Results:The most common affected age group was between 40-60 years. The prevalence of infection was equal inmales and females. The commonest endoscopic finding was inflammation of gastric mucosa. Most patientspresented with moderate degree of colonization; 62% of patients presented with a severe degree of chronicinflammation. There was a significant statistical correlation between the degree of Helicobacter pylori colonizationand the degree of chronic inflammation (p&lt;0.05). Most patients presented with severe degree ofactive gastritis. A significant correlation was found between the degree of chronic inflammation and degreeof activity. The prevalence of lymphoid follicles in a single biopsy specimen from antral mucosa was 36%.The dysplasia was seen in 12%; eosinophilia 8%; atrophy 8% and intestinal metaplasia in 6% of the cases.No significant correlation was found between the endoscopic findings and histological findings.Conclusion:Helicobacter pylori infection causes chronic active gastritis and it has a role in the development of lymphoidfollicles, intestinal metaplasia, atrophy and dysplasia.

Dependence of the state of the large intestine parietal microflora on the activity of Helicobacter pylori associated chronic gastritis

Introduction. The aim of the study was to detect the dependence of the composition of the parietal microflora of the colon on the activity of Helicobacter pylori-associated chronic gastritis and the degree of Helicobacter pylori contamination of the gastric mucosa. Materials and methods. The study was carried out on 50 patients aged 24 to 72 years, who were diagnosed with HP-associated chronic gastritis in the phase of exacerbation based on the results of FEGDS and histological examination of biopsies of the mucous membrane of the antrum of the stomach in combination with a rapid urease test. A series of dilutions 10¹-10⁹ was prepared from a homogenized biopsy specimen of the mucous membrane of the sigmoid colon in 0.1 ml of isotonic sodium chloride solution, and 0.1 ml of a solution of the corresponding dilution was inoculated onto the surface of the nutrient medium. The study of mucosal microflora was carried out by means of bacteriological examination of biopsies of the mucous membrane of the sigmoid and cecum. The degree of H. pylori contamination of the gastric mucosa was assessed in the course of histological examination by a semi-quantitative method: low degree of contamination — up to 20 microbial bodies, average — 20-50 microbial bodies, strong — over 50 microbial bodies in the field of view. Results. The study demonstrated that the indicators of the average concentrations of bifidobacteria, lactobacilli and typical strains of E. coli progressively decreased with the transition to a higher degree of HP infection. This tendency was maximum in relation to bifidobacteria — 6.1-1.57-1.09 x 10⁸ CFU/g, with a difference between the maximum (I degree) and minimum (III degree) 5.59 times. A similar relationship, but much less pronounced, was observed for Lactobacterium spp. and E. coli. As the severity of HP infiltration of the gastric mucosa increases, there is a decrease in the concentration of the above microorganisms in the parietal mucin - the correlation coefficient is r = -0.74. Discussion. Since the mucous microflora is more stable and functionally significant than the cavity microflora, the data obtained allow us to consider Helicobacter pylori as an etiological factor of colonic dysbiosis. Conclusion. The probability of excessive growth of conditionally pathogenic fraction of intestinal parietal microflora has a direct dependence on the severity of Helicobacter pylori infestation, being maximum at degree III contamination. Content of bifidobacteria, lactobacilli and typical E. coli strains in the intestinal biotope of the large intestine is inversely related to the degree of histological activity of HP-associated gastritis.

Interleukin-1β and Interleukin-1 receptor antagonist gene polymorphism in pediatric patients with Helicobacter pylori-associated chronic gastritis.

The severity of Helicobacter pylori infection is determined by the interplay between bacterial virulence, host genetic and environmental factors. This study aimed to identify interleukin-1 beta (IL-1β) and interleukin receptor antagonist (IL-1RN) gene polymorphisms and their associations with H. pylori infection, and severity of chronic gastritis in Egyptian children. A case control study was conducted on 100 children (50 H. pylori positive and 50 controls). Genotyping of IL-1β-31 gene was done by PCR-CTPP (confronting two-pair primers), of IL-1β-511 was performed using allele specific PCR, and investigation of the variable number tandem repeat polymorphism of the IL-1RN gene was done by PCR. The genotype C/T of IL1β-511 was the predominant genotype (36/50; 72%) among H. pylori positive cases (p ≤ 0.001). The presence of C/T genotype at position 511 of IL1β was associated with increased risk of infection with H. pylori (p ≤ 0.001, odds ratio = 6.612) and with more severe disease (p = 0.004, odds ratio = 8.333). No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases was found. Children who carry two polymorphisms are almost four times at risk for development of H. pylori infection (p = 0.026, odds ratio = 3.937). Polymorphism at position -511 of IL1β gene is associated with increased risk of H. pylori infection as well as of severe corpus gastric disease in Egyptian children. This population should be considered a high-risk group, which needs regular gastric endoscopic surveillance, and should be target for H. pylori eradication. Lay summaryThe genotype C/T of IL1β-511 gene was the predominant genotype (36/50; 72%) among H. pylori positive children. Polymorphism at position -511 of IL1β gene is associated with increased risk of Helicobacter pylori infection as well as of severe corpus gastric disease in Egyptian children. No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases in Egyptian children.

CORRECTION OF NITRIC OXIDE SYSTEM IN PATIENTS WITH HELICOBACTER PYLORI-ASSOCIATED CHRONIC GASTRITIS AND CONCOMITANT TYPE 2 DIABETES MELLITUS

The current data suggest that Helicobacter pylori infection and type 2 diabetes mellitus may affect the state of nitric oxide system, which significantly influences stomach functioning. The aim of the research was to study the state of nitric oxide system in patients with Helicobacter pylori-associated chronic gastritis and concomitant type 2 diabetes mellitus, and to investigate the potential of eupatilin in its correction. 172 patients with confirmed chronic gastritis were enrolled into the study. They were divided into 4 groups: І (n=71) included individuals with Helicobacter pylori-positive chronic gastritis and type 2 diabetes mellitus; ІІ (n=21) included patients with Helicobacter pylori-negative chronic gastritis and type 2 diabetes mellitus; ІІІ (n=48) included patients with Helicobacter pylori-positive chronic gastritis without type 2 diabetes mellitus; IV (n=32) was made up with individuals having Helicobacter pylori-negative chronic gastritis without type 2 diabetes mellitus. According to prescribed therapeutic schemes the patients of groups І and ІІІ were additionally subdivided into the following subgroups: groups I-A (n=35) and III-A (n=24) underwent anti-Helicobacter therapy, groups I-В (n=36) and III-B (n=24) were prescribed to receive anti-Helicobacter therapy and eupatilin. Anti-Helicobacter therapy included pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg bid for 10 days. The patients received Eupatilin as an active agent of Stilen preparation, which contains 0.48 – 1.44 mg of eupatilin, tid for 28 days. Nitrites content and activity of inducible and constitutional nitric oxide synthases were analyzed in blood serum before the treatment and on the 28th day after the therapy completed. The patients of group I before the treatment were found to have an increase of nitrites level in 1.4 times, inducible nitric oxide synthase in 1.5 times higher in comparison to the patients of group II. An activity of constitutional nitric oxide synthase in patients with chronic gastritis and type 2 diabetes mellitus was found to be decreased regardless the Helicobacter pylori-status in 2.3 and 2.7 times in comparison to the patients of groups III and IV respectively. Eupatilin prescription promoted Helicobacter therapy eradication and treatment outcomes through nitrites decrease in 1.5 times, reduction of inducible nitric oxide synthase activity in 1.2 times, and growth of constitutional nitric oxide synthase in1.2 times in patients of I-B group in comparison to group I-A. Combined anti-Helicobacter therapy with eupatilin promotes successful Helicobacter pylori eradication, which was 6.2% higher in patients of I-B group than in I-A group. Conclusions: Helicobacter pylori-associated chronic gastritis in patients with type 2 diabetes mellitus is followed by rise of nitrites, inducible nitric oxide synthase activity and simultaneous decline of constitutional nitric oxide synthase in blood serum. Eupatilin prescription as a component of integrated anti-Helicobacter therapy increases the efficacy of Helicobacter pylori eradication and improves the state of nitric oxide-system due to its anti-inflammatory, antioxidant and cytoprotective properties.

The use of CNFA lectin in the diagnosis of precancerous changes in the gastric mucosa in patients with Helicobacter pylori-associated chronic gastritis

The use of CNFA lectin in the diagnosis of precancerous changes in the gastric mucosa in patients with Helicobacter pylori-associated chronic gastritis

Altered regulation of Ure A and β-catenin gene expression levels in Helicobacter pylori-associated chronic gastritis

Altered regulation of Ure A and β-catenin gene expression levels in Helicobacter pylori-associated chronic gastritis

E‐Poster Presentations – A2) Gastric and Duodenal

E‐Poster Presentations – A2) Gastric and Duodenal

Erratum to: Braf, Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer.

We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p < 0.001 as well as in patients with age above 50 years with a p value = 0.008. By applying logistic regression analysis it was reported that the H. pylori qPCR is a significant predictor to the adenocarcinoma with OR = 1.025 (95 % CI: 1. 002–1.048), with sensitivity of 90 % and specificity of 100 %. Adenocarcinoma patients had a significantly higher mean age and levels of H. Pylori, Braf, K-ras, methylated MGMT and methylated MLH1 than those of gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis. Conclusion: H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.

Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

Braf, Kras and Helicobacter pylori epigenetic changes-associated chronic gastritis in Egyptian patients with and without gastric cancer.

We aimed to study MLH1 and MGMT methylation status in Helicobacter pylori-associated chronic gastritis in Egyptian patients with and without gastric cancer. 39 patients were included in our study. They were divided into 2 groups; patients without (group I) and with gastric adenocarcinoma (group II). Patients were subjected to clinical examination, abdominal ultrasound and upper endoscopy for gastric biopsy. Biopsies were subjected to urease test, histological examination, and DNA purification. H. pylori, Braf, Kras, MLH1 and MGMT methylation were assessed by quantitative PCR. DNA sequencing was performed to assess Braf and Kras genes mutation. qPCR of H. pylori was significantly higher in patients with adenocarcinoma (group II) than those without adenocarcinoma (group I); with a p<0.001 as well as in patients with age above 50years with a p value=0.008. By applying logistic regression analysis it was reported that the H. pylori qPCR is a significant predictor to the adenocarcinoma with OR=1.025 (95% CI: 1. 002-1.048), with sensitivity of 90% and specificity of 100%. Adenocarcinoma patients had a significantly higher mean age and levels of H. Pylori, Braf, K-ras, methylated MGMT and methylated MLH1 than those of gastritis patients. DNA sequence analysis of Braf (codon 12) and Kras (codon 600) had genes mutation in gastric adenocarcinoma versus chronic gastritis. H. pylori may cause epigenetic changes predisposing the patients to cancer stomach. Estimation of H. pylori by qPCR can be a good predictor to adenocarcinoma. Braf and Kras genes mutation were reveled in gastritis and adenocarcinoma patients.

High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing

Gastric cancers are the most frequent gastric malignancy and usually arise in the sequence of Helicobacter pylori-associated chronic gastritis. CpG methylation is a central mechanism of epigenetic gene regulation affecting cancer-related genes, and occurs early in gastric carcinogenesis. DNA samples from non-metaplastic gastric mucosa with variable levels of gastritis (non-metaplastic mucosa), intestinal metaplasia, or gastric cancer were screened with methylation arrays for CpG methylation of cancer-related genes and 30 gene targets were further characterized by high-definition bisulfite next-generation sequencing. In addition, data from The Cancer Genome Atlas were analyzed for correlation of methylation with gene expression. Overall, 13 genes had significantly increased CpG methylation in gastric cancer vs non-metaplastic mucosa (BRINP1, CDH11, CHFR, EPHA5, EPHA7, FGF2, FLI1, GALR1, HS3ST2, PDGFRA, SEZ6L, SGCE, and SNRPN). Further, most of these genes had corresponding reduced expression levels in gastric cancer compared with intestinal metaplasia, including novel hypermethylated genes in gastric cancer (FLI1, GALR1, SGCE, and SNRPN), suggesting that they may regulate neoplastic transformation from non-malignant intestinal metaplasia to cancer. Our data suggest a tumor-suppressor role for FLI1 in gastric cancer, consistent with recently reported data in breast cancer. For the genes with strongest methylation/expression correlation, namely FLI1, the expression was lowest in microsatellite-unstable tumors compared with other gastric cancer molecular subtypes. Importantly, reduced expression of hypermethylated BRINP1 and SGCE was significantly associated with favorable survival in gastric cancer. In summary, we report novel methylation gene targets that may have functional roles in discrete stages of gastric carcinogenesis and may serve as biomarkers for diagnosis and prognosis of gastric cancer.

Metastatic breast carcinoma uncovered in an otherwise unremarkable “random colon biopsy”

Breast cancer is one of the most devastating cancers afflicting women, being a main cause of cancer related death. Approximately 50% of these patients have developed regional or distant metastases at the time of diagnosis; hence, an early diagnosis and surgery with indicated neoadjuvant therapy are crucial in eradicating this disease and improving patient survival. A significant percentage of patients, even after initial satisfactory tumor removal, still face the threat of metastatic diseases which could plague a wide spectrum of body sites such as bones, lungs, central nervous system, liver and gastrointestinal tract (mostly upper gastrointestinal locations). Colonic and anorectal involvement by metastatic breast cancer has been less frequently reported in disseminated diseases. Typically, metastatic disease presents as a mass, enteric stenosis, or obstruction. Rare cases, however, may not form an endoscopically or radiologically recognizable lesion, and thus could be overlooked. Here we report a unique case of random colon biopsies in a patient presenting with epigastric pain, whose stomach biopsy showed Helicobacter pylori-associated chronic active gastritis. No colonoscopic lesion was present; however, microscopic examination of the “random biopsy” revealed scattered single and small clusters of tumor cells involving the lamina propria of the colonic mucosa, morphologically and immunophenotypically consistent with metastatic disease from breast carcinoma. The clinical presentation and histopathology of the case were reviewed and compared with limited cases reported in the literature. We conclude that high levels of suspicion and alertness are essential to identify occult microscopic gastrointestinal metastatic breast cancer in the absence of a grossly appreciable lesion.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Elevated risk of recurrent colorectal neoplasia with Helicobacter pylori-associated chronic atrophic gastritis: A follow-up study of patients with endoscopically resected colorectal neoplasia

In a previous population-based case-control study, we demonstrated an elevated risk of colorectal neoplasia with Helicobacter pylori (H. pylori) infection. The present study investigated the effects of H. pylori-associated chronic gastritis on the development of colorectal neoplasia by analyzing the recurrence of colorectal neoplasia subsequent to endoscopic resection. Ninety-nine patients who had undergone endoscopic resection of colorectal neoplasia were monitored under colonoscopy, and the recurrence of colorectal neoplasia was prospectively investigated. The stage of H. pylori-associated chronic gastritis in each subject was evaluated using a combination of two serum tests: H. pylori antibody and pepsinogen. In the present cohort, colorectal neoplasia recurred at a rate of 15,296/100,000 person-years during the study period. After adjusting for the confounding factors, chronic atrophic gastritis (CAG) was identified as an independent risk factor [adjusted hazard ratio (HR), 2.72; 95% confidence interval, 1.33-5.57], while H. pylori-infected non-atrophic gastritis was not identified as an independent risk factor for recurrent colorectal neoplasia. Colorectal neoplasia recurred earlier and was significantly more frequent in patients with CAG (22,573/100,000 person-years) compared to patients without CAG (11,089/100,000 person-years; P=0.029, log-rank test). Patients with more extensive CAG showed a higher risk of recurrence. These results demonstrated a significant elevation of the risk of recurrent colorectal neoplasia with the establishment and progression of CAG, indicating the involvement of H. pylori infection in the development of colorectal neoplasia. The two serum tests were useful clinical markers for noninvasively evaluating the risk of each individual for recurrent colorectal neoplasia subsequent to endoscopic resection.