When Does Gastric Atrophy Develop in Japanese Children?

Background: Long-term Helicobacter pylori infection causes inflammatory sequelae such as atrophy and intestinal metaplasia in the stomach, which is thought to increase the risk of developing gastric malignancy. We previously reported that gastric atrophy can develop in Japanese children with H. pylori infection, predominantly in the antrum. However, detailed data about the age of children with atrophy are largely lacking.
Methods and results: In the present study, 131 children (79 boys) with H. pylori infection were re-analyzed for an association between age and the grade of gastric atrophy. The gastric antrum was histologically evaluated in all 131 patients and the corpus in 46 patients. Grade 2 and 3 antral atrophy was observed in 13 and one patients, respectively: the mean age was 12.1 years. Two patients (11 and 14 years old) had grade 2 corpus atrophy but no patients had grade 3. No significant difference was found in age among patients with grade 0, 1 and 2 or 3 atrophy in the antrum ( p =  .97) and in the corpus ( p =  .59). None of the patients with grade 2 or 3 atrophy had intestinal metaplasia either in the antrum or in the corpus.
Conclusions: The results of the present study require a careful interpretation because of the retrospective analysis. In high-risk countries of gastric cancer, however, eradicating H. pylori in childhood could prove more effective in preventing gastric atrophy, ultimately, the development of cancer.     

Effect of Helicobacter pylori infection and eradication on gastric epithelial cell proliferation and apoptosis.

OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.     

Histological Classif ication of Gastritis and Helicobacter pylori Infection: An Agreement at Last?

An international workshop has assessed and revised the Sydney System for the reporting of gastritis. Much of the original approach was retained including division into acute , chronic and special forms, and grading of chronic inflammation, polymorph activity, atrophy, intestinal metaplasia and H. pylori density into mild, moderate and marked categories. Visual analog scales have been introduced as a simple guide to grading. The four biopsy sites have been changed to optimize detection of H. pylori , and supplemented by a fifth biopsy from the incisura angularis, the site which is most likely to yield premalignant changes. Chronic gastritis is classified into non-atrophic and atrophic forms with the latter divided into autoimmune (diffuse corpus atrophy) and multifocal . Histological reporting of gastritis should take into account the topographical pattern ( antral or corpus predominant ), and the final diagnostic term should ideally combine morphology and etiology to maximize the clinical value of gastric biopsy diagnosis.     

No correlation of babA2 with vacA and cagA genotypes of Helicobacter pylori and grading of gastritis from peptic ulcer disease patients in Brazil

BACKGROUND: The babA2 gene, which encodes a blood-group antigen-binding adhesin that mediates attachment of Helicobacter pylori to human Lewis(b) antigens on gastric epithelial cells, has been associated with a higher risk of peptic ulcer and gastric cancer. The purpose of this study was to ascertain the frequency of babA2 genotype in H. pylori strains of patients with peptic ulcer and to correlate with other virulence factors. MATERIALS AND METHODS: vacA, cagA, and babA2 genotypes of H. pylori were determined by using polymerase chain reaction (PCR). DNA was extracted from positive urease test gastric samples of 150 patients with peptic ulcer. Antrum and corpus biopsies were taken for histologic examination according to the updated Sydney system classification. RESULTS: babA2 genotype was present in 104 (69.3%) and cagA in 113 (75.3%) gastric samples. No significant correlation was observed between babA2 and vacAs1 genotype or between babA2 and cagA status. The correlation of vacAs1 genotype with positive cagA was statistically significant ( p < .001). The babA2-positive strain was more frequently found from the gastric samples of men, than of women (p = .01). Strains harboring cagA, vacAs1, and babA2 genotypes had no association to the grading of gastritis, presence of glandular atrophy, or intestinal metaplasia. The simultaneous presence of cagA, vacAs1, and babA2 was found in 32.6% of the H. pylori strains. CONCLUSIONS: babA2 genotype is frequently found in H. pylori strains from peptic ulcer disease in Brazil, although it has no significant correlation to the worsening of the gastritis and to other virulence markers such as vacAs1 and cagA.     

Helicobacter pylori modulation of gastric acid

Helicobacter pylori plays major causative roles in peptic ulcer disease and gastric cancer. Elevated acid secretion in patients with duodenal ulcers (DUs) contributes to duodenal injury, and diminished acid secretion in patients with gastric cancer allows carcinogen-producing bacteria to colonize the stomach. Eradication of H. pylori normalizes acid secretion both in hyper-secreting DU patients and hypo-secreting relatives of gastric cancer patients. Therefore, we and others have asked how H. pylori causes these disparate changes in acid secretion. H. pylori gastritis more or less restricted to the gastric antrum in DU patients is associated with increased acid secretion. This is probably because gastritis increases release of the antral acid-stimulating hormone gastrin and diminished mucosal expression of the inhibitory peptide somatostatin. Bacterial products and inflammatory cytokines including TNFalpha may cause these changes in endocrine function. Gastritis involving the gastric corpus tends to diminish acid secretion, probably because bacterial products and cytokines including IL-1 inhibit parietal cells. Pharmacological inhibition of acid secretion increases corpus gastritis in H. pylori-infected subjects, so it is envisaged that gastric hypo-secretion of any cause might become self-perpetuating. H. pylori-associated mucosal atrophy will also contribute to acid hypo-secretion and is more likely in when the diet is high in salt or lacking in antioxidant vitamins. Data on gastric acid secretion in patients with esophagitis are limited but suggest that acid secretion is normal or slightly diminished. Nevertheless, H. pylori infection may be relevant to the management of esophagitis because: (i) H. pylori infection increases the pH-elevating effect of acid inhibiting drugs; (ii) proton pump inhibitors may increase the tendency of H. pylori to cause atrophic gastritis; and (iii) successful eradication of H. pylori is reported to increase the likelihood of esophagitis developing in patients who had DU disease. Points (ii) and (iii) remain controversial and more work is clearly required to elucidate the relationship between H. pylori, acid secretion, gastric mucosa atrophy and esophagitis.     

Inducible nitric oxide synthase expression before and after eradication of Helicobacter pylori in different forms of gastritis

An increased expression of inducible nitric oxide synthase (iNOS) has been observed in the inflamed human gastric mucosa as well as in some tumors. This observation suggests a pathobiological role of elevated NO production. The purpose of this study was to compare the immunohistochemical iNOS expression in the different kinds of gastritis before and after the eradication of Helicobacter pylori. We performed iNOS and H. pylori immunohistochemical staining and counted iNOS positive cells. We detected elevated expression of iNOS around sites infected with H. pylori. iNOS expression in chemical gastritis was strongly elevated in mucosal glands. After treatment, we found a significant difference in iNOS expression in patients with classical H. pylori-induced antrum predominant gastritis and in patients with active autoimmune gastritis. In the special case of progressed gastritis with intestinal metaplasia we found persistence of intestinal metaplasia, and we could not find a significant difference in the number of positive iNOS cells before and after treatment. The persistence of IM as a possibly precancerous lesion is probably at least in the antrum a source of continuous iNOS induction even after H. pylori eradication.     

Differential expression of laminin isoform (alpha2), integrins (alpha3beta1 and alpha6beta4) and cytokeratin 20 in H. pylori gastritis

The expression of laminin-1 chains (beta1 and gamma1), laminin-2 (merosin), integrin receptors to laminin (alpha3beta1 and alpha6beta4) and cytokeratin (CK20) were studied by immunohistochemical methods in gastric biopsies from antrum of 25 patients. H. pylori gastritis was found in 19 cases and intestinal metaplasia (IM) in four from these 19. Another 13 biopsies, all with IM were immunostained to laminin-2. Laminin-1 chains in normal and gastritis areas without IM were expressed as a strong, linear and continuous deposit in the basement membranes of the superficial and glandular epithelium. In metaplastic glands the reactivity to laminin-1 chains was decreased. Merosin was discontinuous when a moderate to accentuated H. pylori glandular colonization was present. Samples with IM were negative to laminin-2. The alpha3beta1 and alpha6beta4 integrins were negative only in IM gastric biopsies. The CK20 immunoreactivity was strong and homogeneous in the cells at the tip and the upper portion of foveolae in normal areas and in gastritis with IM the reactivity to CK 20 was heterogeneous. A differential expression of laminin isoforms is related to inflammation and subsequent IM caused by H. pylori. The alterations of alpha3beta1 and alpha6beta4 parallel both modifications in merosin and CK20 expression in H. pylori chronic gastritis.     

Apoptosis in Helicobacter pylori gastritis is related to cagA status

BACKGROUND: Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa. MATERIALS AND METHODS: We studied by immunohistochemistry (streptavidin-biotin method) pro-apoptotic (Bax and Bak) and antiapoptotic (Bcl-2 and Bcl-x) proteins expression, scored from 0 to 4, in gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males, 28 females, median age 40 years) and eight non-infected patients (6 males, median age 39.6 years). H. pylori and cagA status were determined by polymerase chain reaction. RESULTS: Apoptotic proteins were expressed in a granular pattern, in the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl-2 and Bcl-x in most cases and was significantly higher in patients infected by cagA-positive strains than in those infected by cagA-negative strains (p = .001). Bak expression was higher at the lesser curvature (antrum and incisura) than in the other regions (p = .002) and was correlated with atrophy. Anti-apoptotic proteins were significantly more expressed at the antral lesser curvature than in the other regions of the stomach (Bcl-2: p = .02; Bcl-x: p < .001). CONCLUSIONS: Infection with cagA-positive strains is significantly associated with overexpression of pro-apoptotic proteins in the gastric mucosa, mainly at the antral lesser curvature, which may have a role on atrophy development. Anti-apoptotic proteins were also overexpressed at the lesser curvature, which may occur to keep epithelial cell turnover or might be related to malignant transformation.     

Functional Role of Metaplastic Paneth Cell Defensins in Helicobacter pylori-Infected Stomach

Background and Aims:  Chronic gastritis is caused by Helicobacter pylori infection, and gastritis is classified as inflammation, atrophy, and intestinal metaplasia. Detailed pathologic studies have shown that H. pylori settles on the surface of gastric mucosa, and that it is eliminated from metaplastic mucosa. However, its mechanism of natural protection is not well known.
Methods:  Antimicrobial human enteric defensin expression was determined in the RNA and protein levels. Recombinant enteric defensins were produced with a bacterial expression system and their anti- H. pylori activities were assessed by bactericidal assay.
Results:  Human enteric defensin (HD)-5 and HD-6 were detected in Paneth cells, which are observed in the gastric metaplastic mucosa as well as small intestinal epithelia. HD-5 protein was coexpressed with trypsin, which is considered to be an activating enzyme of HD-5. Less H. pylori was observed in the intestinal metaplasia with HD-5 expressing Paneth cells. The recombinant defensins showed killing activity against H. pylori at a low concentration in vitro.
Conclusions:  The human defensins that are expressed in the metaplastic Paneth cells eliminate H. pylori . Metaplastic change may be a purposive development of the human stomach.     

Mucosal production of antigastric autoantibodies in Helicobacter pylori gastritis

Background. Apart form bacterial virulence factors of Helicobacter pylori , certain host factors influence the pathogenesis of H. pylori gastritis. In particular, antigastric autoantibodies that are detectable in the sera of a substantial proportion of H. pylori were shown to correlate with the development of gastric atrophy. The aim of this study was to analyze the possible antigastric autoimmune response in H. pylori gastritis at the site where the action is, i.e., in the gastric mucosa.
Material and Methods. Gastric biopsy specimens from antrum and corpus mucosa of 24 H. pylori –infected and of 33 noninfected patients were cultured for 3 days, and tissue culture supernatants were analyzed for the amount of locally produced IgA and IgG. Antigastric autoantibodies were screened in the sera and in the supernatants by means of immunohistochemistry.
Results. The infected patients had significantly higher concentrations of locally produced IgA, whereas the IgG concentrations were virtually the same in infected and noninfected patients. IgG or IgA antigastric autoantibodies, or both, were detectable only in the sera (38%) and supernatants (17%) of infected patients. Interestingly, the patient with the strongest local autoimmune response showed body-predominant H. pylori gastritis, with destruction of gastric glands and atrophy of the body mucosa.
Conclusions. These results demonstrate that antigastric autoimmune reactions are detectable at the site of the disease and might be relevant for the pathogenesis of gastric mucosa atrophy in H. pylori gastritis.     

Helicobacter pylori Infection and Family History of Gastric Cancer Decrease Expression of FHIT Tumor Suppressor Gene in Gastric Mucosa of Dyspeptic Patients

Background:  The expression of a fragile histidine triad (FHIT) protein is lost in stomach tumors. The study aimed at determining whether FHIT expression is affected by Helicobacter pylori infection, strain virulence ( vacA and cagA genes) and histopathological changes in the gastric mucosa of patients with functional dyspepsia having first-degree relatives with gastric cancer.
Materials and Methods:  Eighty-eight never-smoking patients with functional dyspepsia were selected for the study, and 48 of them had first-degree relatives with gastric cancer. Bacterial DNA amplification was used to identify H. pylori colonization. The level of FHIT gene expression was determined by qRT-PCR (mRNA) and Western blot (FHIT protein) analyses.
Results:  For patients having first-degree relatives with gastric cancer FHIT expression was lower (mRNA by ca. 40–45% and protein by 30%) compared with the control patients ( p  < .05). H. pylori infection decreased the FHIT mRNA level by 10–35% and the protein level by 10–20%. Bacterial strain vacA (+) cagA (+) lowered FHIT mRNA by ca. 30–35% in the antrum samples of both groups and in corpus samples of patients with first-degree relatives with gastric cancer ( p  < .05). The FHIT mRNA level was twice as high in control H. pylori- negative patients with intestinal metaplasia, compared with those with non-atrophic gastritis.
Conclusions:  The decreased FHIT gene expression associated with hereditary factors and with H. pylori infection, especially with vacA (+) cagA (+)-positive strains, may be related to gastric carcinoma development.     

Benign epithelial gastric polyps--frequency,location, and age and sex distribution

Prospective investigation has been undertaken with the aim to study the frequency, location and age and sex distribution of various histological types of benign gastric epithelial polyps. Histological type--adenomatous, hyperplastic and fundic gland polyps--was diagnosed on the basis of at least three histological samples taken from the polyp. Biopsy samples were also taken from the antrum and the body of the stomach so that gastritis could be graded and classified, and the presence of H. pylori could be determined by histology. All 6,700 patients, who had undergone upper gastrointestinal endoscopy in a one-year period, participated in this study. Among them 42 benign gastric epithelial polyp were found in 31 patients: adenomatous gastric polyps in 7 patients, hyperplastic gastric polyp in 21 and fundic gland polyp in 3 patients. All patients with hyperplastic polyps had chronic active superficial gastritis, whereas most of the patients with adenomatous polyps had a chronic atrophic gastritis with high prevalence of intestinal metaplasia. Among 21 patients with hyperplastic gastric polyps, 16 (76%) patients were positive for H. pylori infection in contrast to only 2 patients (29%) with adenomatous gastric polyps and 1 patient (33%) with fundic gland polyp. Presented data indicates that hyperplastic gastric polyps are the most common and they are associated with the presence of chronic active superficial gastritis and concomitant H. pylori infection. Adenomatous polyps are rarer and they tend to be associated with chronic atrophic gastritis and intestinal metaplasia. Fundic gland polyp is the rarest type of gastric polyps.     

Helicobacter pylori CagA Status,Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer?

Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori‐cagA‐positive strains are associated with the highest risk of gastric cancer. Aims. To ascertain whether cagA‐positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori‐negative. Among the H. pylori‐positive patients, 34 were cagA‐positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8‐hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA‐positive infection significantly correlated with a higher prevalence of atrophic‐metaplastic lesions (p = 0.04). cagA‐positive patients had higher 8‐hydroxydeoxyguanosine levels than both cagA‐negative and H. pylori‐negative cases (p = 0.01). The 8‐hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA‐positive patients having 8OHdG levels above a cut‐off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. Conclusions. cagA‐positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer‐prone biological context.     

Factors that affect results of the 13C urea breath test in Japanese patients

Background. The ¹³C urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Our objective was to investigate the accuracy of the UBT in Japanese patients and the association of UBT values with histological findings.
Materials and Methods. A total of 169 consecutive patients were studied by endoscopy with histology, by serology with IgG antibody and test serum pepsinogen (PG), and by UBT. The association between UBT values and histological findings and the PG I / II ratio were analyzed in H. pylori –positive patients.
Results. Of 169 Japanese patients, 135 were H. pylori –positive on both histology and serology analysis, 27 were H. pylori –negative on both histology and serology analysis, and 7 patients showed differing results. Using a cutoff value of 2.5‰, test sensitivity was 100%, while specificity was 96%. Among the 135 H. pylori –positive patients, a significant relation was observed between UBT value and H. pylori colonization density of the corpus and antrum, neutrophil activity of the antrum, atrophy, and intestinal metaplasia of the corpus in the H. pylori –positive patients. Also, UBT values correlated with the PG I /II ratio. In multivariate analysis, the PG I /II ratio was the most important factor related to UBT values (odds ration [OR], 4.99; 95% confidence interval, 1.60–15.55).
Conclusions. The UBT is an accurate method for detecting H. pylori infection in the Japanese population, which shows a high prevalence of atrophic gastritis. Values are affected by H. pylori infection and by the severity of atrophic gastritis.     

The Best Gastric Site for Obtaining a Positive Rapid Urease Test

Background Rapid urease tests (RUTs) provide a simple, sensitive method of detecting Helicobacter pylori infection.
Objectives. Our aim, therefore, was to determine whether the yield of detecting H. pylori infection by RUT varied depending on the site of gastric biopsy.
Materials and Methods. Gastric biopsies were obtained from 50 patients for RUT by use of hp fast (GI Supply, Camp Hill, PA). Biopsies were taken from the prepyloric greater curve antrum, from the gastric angle, and from the greater curve in mid-corpus. One biopsy specimen was placed in the RUT gel, and the biopsy from the adjacent mucosa was placed in formalin for subsequent histological evaluation by using the Genta stain. RUTs were examined and scored at intervals of 5, 10, 15, 30, and 45 minutes and after 1, 2, 4, and 24 hours.
Results. Fifty patients were entered in the test (150 RUTs), 32 having H. pylori infection. There were no false-positive RUTs (specificity, 100%). The gastric angle site was positive in 100%. The prepyloric site was positive in 87%, and the corpus site was positive in 84.4% ( p < .052 for angle or prepyloric antrum versus corpus). The most common pattern was for all to be positive (74%). The median time to positivity was similar with angle and prepyloric sites (37.5 and 60 minutes, respectively, p = not significant) and shorter than the corpus biopsy (180 minutes); ( p < .05 for angle or prepyloric antrum versus corpus).
Conclusion. The maximum probability for detecting H. pylori infection using a RUT is to obtain a biopsy from the gastric angle. To prevent missing a positive result when intestinal metaplasia is present, we recommend that (at a minimum) biopsies be taken from both the angle and the corpus.     

Seropositivity to Helicobacter pylori heat shock protein 60 is strongly associated with intensity of chronic inflammation, particularly in antrum mucosa: an extension of an 18-year follow-up study of chronic gastritis in Saaremaa, Estonia

Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 microg ml(-1) with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P=0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r=0.34; P=0.003; OR=5.97 (95% CI 1.21-29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa.     

Genetic factors in the development of gastric precancerous lesions--a role of Helicobacter pylori ?

Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric precancerous alterations. There is a well known predisposition to gastric cancer and the risk of developing it is greater in relatives of patients with familial cases of this malignancy. The aim of this study was to determine the prevalence of gastric precancerous lesions (atrophy and intestinal metaplasia) and their association with Hp infection in first-degree relatives in patients with noncardia gastric cancer. METHODS: Hp status and gastric histology assessed by upper gastrointestinal endoscopy, biopsies from the antral and body region, the rapid urease test and staining for Hp, inflammation, activity, atrophy and intestinal metaplasia (prevalence and grading) were studied in 108 first-degree relatives of patients with noncardia gastric cancer and compared with 73 controls with mild non-ulcer dyspepsia who had no cancer relatives and were examined in the same way. RESULTS: subjects with and without cancer relatives had a similar prevalence of Hp infection (49 vs. 47%). Endoscopy revealed a few asymptomatic duodenal ulcers and small hiatus hernias in Hp positive subjects of both groups. Hp positive relatives of gastric cancer had a markedly higher prevalence of atrophy than those with Hp negativity without cancer relatives (29 vs. 9%) and those with Hp negativity and cancer relatives (29 vs. 3%. Prevalence of intestinal metaplasia was also higher in those with Hp positivity and cancer relatives than in those without cancer relatives (15 vs. 5% and was not present in Hp negative subjects with cancer relatives. Inflammation and activity showed similar scores in subjects with and without cancer relatives with higher scores in both Hp positive groups. The prevalence of precancerous lesions in the relatives of gastric cancer was nearly always confined to those with Hp positivity. One year after eradication the prevalence of atrophy in cancer relatives decreased from 29 to 14%; prevalence of intestinal metaplasia remained without substantial changes. Scores for inflammation and activity were also lower after eradication. CONCLUSIONS: First-degree relatives of patients with gastric cancer have an increased prevalence of gastric precancerous abnormalities which are strongly confined to those with Hp infection. Eradication of Hp in these subjects with cancer relatives reduces the prevalence of precancerous lesions (atrophy) and grades of inflammation and activity. In view of these results, eradication of Hp should be offered to such subjects.     

慢性胃炎组织病理特征和Hp感染与炎症程度的关系研究

目的:探讨慢性胃炎组织病理特征和Hp感染与慢性炎症程度的关系。方法:抽选我院2010年1月至2016年2月行胃镜检查诊断为慢性胃炎的467例患儿,作胃窦黏膜病理组织学检查,并检测有无HP感染,分析HP感染与慢性胃炎病理特征、慢性炎症程度之间的关系。结果:在病理检查中,轻度、中度、重度炎症反应患儿HP感染率(7.7%、41.2%、51.1%)依次升高,且差异具有统计学意义(P0.05),有炎症活动度患儿的HP阳性率76.3%明显高于无炎症活动度患儿23.7%(P0.05)。随着肠化分级加重、淋巴滤泡形成、萎缩程度分级升高等病理变化,Hp阳性率明显升高(P0.05)。轻度、中度、重度炎症三组淋巴滤泡形成、肠化生和胃萎缩发生率明显呈递增趋势,Hp阳性率明显呈递增趋势,比较差异显著(P0.05)。结论:Hp是慢性胃炎发病的重要影响因素,与患儿胃窦黏膜炎症程度、活动性、淋巴滤泡形成、肠化分级以及黏膜萎缩萎等病理变化密切相关。     

Use of Comet assay to assess DNA damage in patients infected by Helicobacter pylori: comparisons between visual and image analyses

Studies of DNA damage in gastric epithelial cells of Helicobacter pylori (H. pylori)-infected patients are conflicting, possibly due to different methods used for scoring DNA damage by Comet assay. Therefore, we compared the sensitivity of visual microscopic analysis (arbitrary units-scores and comets%) and image analysis system (tail moment), in the gastric epithelial cells from the antrum and corpus of 122 H. pylori-infected and 32 non-infected patients. The feasibility of cryopreserved peripheral blood lymphocytes and whole-blood cells for DNA damage biomonitoring was also investigated. In the antrum, the levels of DNA damage were significantly higher in H. pylori-infected patients with gastritis than in non-infected patients with normal mucosa, when evaluated by image analysis system, arbitrary units and comets%. In the corpus, the comets% was not sufficiently sensitive to detect the difference between H. pylori-infected patients with gastritis and non-infected patients with normal mucosa. The image analysis system was sensitive enough to detect differences between non-infected patients and H. pylori-infected patients with mild gastritis and between infected patients with moderate and severe gastritis, in both antrum and corpus, while arbitrary units and comets% were unable to detect these differences. In cryopreserved peripheral blood lymphocytes, the levels of DNA damage (tail moment) were significantly higher in H. pylori-infected patients with moderate and severe gastritis than in non-infected patients. Overall, our results indicate that the image analysis system is more sensitive and adequate to measure the levels of DNA damage in gastric epithelial cells than the other methods assayed.     

Molecular assessment of c-H-ras p21 expression in Helicobacter pylori-mediated gastric carcinogenesis

Helicobacter pylori (H. pylori) infection plays a significant role in causing gastric cancer; the exact molecular mechanisms of gastric carcinogenesis have not yet been fully determined. Therefore, this study was planned to examine the role of c-H-ras p21 expression in H. pylori infection at different stages of disease progression from precursor lesions to gastric carcinoma. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status have been analysed. The expression of c-H-ras p21 was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of c-H-ras p21 was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of c-H-ras p21 mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia, and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of c-H-ras p21 in the similar way. Overexpression of c-H-ras p21 might be due to H-ras mutation at codon 12 of ras gene family in H. pylori infection. The rate of expression of ras p21 was higher in the H. pylori-infected precursor lesions, chronic gastritis 49/56 (87.5%), intestinal metaplasia 16/17 (94%), and dysplasia 9/11(82%) whereas in the case of H. pylori negative cases these groups, show 12.5, 5.9, and 18.2%, respectively. The data suggested that H. pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis.