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Background: Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-based H pylori screening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations of H pylori infection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults., Methods: A case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30-79 years from ten areas in China (Qingdao, Haikou, Harbin, Suzhou, Liuzhou, Henan, Sichuan, Hunan, Gansu, and Zhejiang), and included 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants who were cancer-free and alive within the first two years since enrolment in 2004-08. H pylori biomarkers were measured in stored baseline plasma samples using a sensitive immunoblot assay (HelicoBlot 2.1), with adapted criteria to define H pylori seropositivity. Cox regression was used to estimate adjusted hazard ratios (HRs) for NCGC and CGC associated with H pylori infection. These values were used to estimate the number of gastric cancer cases attributable to H pylori infection in China., Findings: Of the 512 715 adults enrolled in the China Kadoorie Biobank between June, 2004, and July, 2008, 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants were selected for analysis. The seroprevalence of H pylori was 94·4% (95% CI 92·4-96·4) in NGCG, 92·2% (89·7-94·7) in CGC, and 75·6% (71·8-79·4) in subcohort participants. H pylori infection was associated with adjusted HRs of 5·94 (95% CI 3·25-10·86) for NCGC and 3·06 (1·54-6·10) for CGC. Among the seven individual infection biomarkers, cytotoxin-associated antigen had the highest HRs for both NCGC (HR 4·41, 95% CI 2·60-7·50) and CGC (2·94, 1·53-5·68). In this population, 78·5% of NCGC and 62·1% of CGC cases could be attributable to H pylori infection. H pylori infection accounted for an estimated 339 955 cases of gastric cancer in China in 2018., Interpretation: Among Chinese adults, H pylori infection is common and is the cause of large numbers of gastric cancer cases. Population-based mass screening and the eradication of H pylori should be considered to reduce the burden of gastric cancer in high-risk settings., Funding: Cancer Research UK, Wellcome Trust, UK Medical Research Council, British Heart Foundation, Kadoorie Charitable Foundation, National Key Research and Development Program of China, and National Natural Science Foundation of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to characterize alterations in mucosa-associated microbiota in different anatomical locations of the stomach during gastric cancer progression and to identify associations between Helicobacter pylori infection and gastric microbial changes in patients with gastric cancer., Methods: Twenty-five H. pylori negative subjects with chronic gastritis and thirty-four subjects with gastric cancer were recruited, including H. pylori negative and positive patients with tumors in the antrum and the corpus. Gastric mucosa-associated microbiota were determined by 16S ribosomal RNA gene sequencing using a 454 sequencing platform., Results: We found that individuals with chronic gastritis from three different anatomical sites exhibited different microbiota compositions, although the microbial alpha diversity, richness and beta diversity were similar. Compared to patients with chronic gastritis, the gastric microbiota compositions were significantly different at the order level in the antrum and the corpus of patients with gastric cancer, which was dependent on the H. pylori infection status. Microbial alpha diversity and species richness, however, were similar between chronic gastritis and gastric cancer cases and independent of H. pylori status. The microbial community structure in patients with gastric cancer was distinct from that in patients with chronic gastritis. In addition, we found that the presence of H. pylori markedly altered the structure in gastric corpus cancer, but only mildly affected the antrum., Conclusion: Our data revealed distinct niche-specific microbiota alterations during the progression from gastritis to gastric cancer. These alterations may reflect adaptions of the microbiota to the diverse specific environmental habitats in the stomach, and may play an important, as yet undetermined, role in gastric carcinogenesis.

Background and Aim: Nowadays, anti-inflammation treatment is a promising approach for preventing tumorigenesis, and human microflora is closely related to inflammation. This study aimed to investigate the gastric cardiac microbiome and identify inflammation-related microorganisms for gastric cardiac inflammation., Methods: We performed 16S rRNA sequencing on a total of 11 healthy individuals and 89 individuals with different degree of gastric cardiac inflammation. Immunohistochemistry was used for verifying candidate bacteria. Phylogenetic reconstruction of unobserved states (picrust) was used for predicting the pathways involved by cardiac microflora., Results: The resident phyla in normal were Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria, and the dominant genus in normal were Halomonas, shewanella, and Comamonas. In the progression of gastric cardiac inflammation, the diversity of cardiac microflora did not change (P > 0.05). However, the composition structure of cardiac microflora varied between healthy and inflamed tissues (P < 0.05). Meanwhile, there were 64 species parallel increased with inflammation degree, especially Helicobacter pylori, Lactobacillus spp. Additionally, inflammation-related species were detected (P < 0.05), including H. pylori, Acinetobacter ursingii, and Streptococcus agalactiae. Higher H. pylori colonization was positively related to the progression of cardiac inflammation (γ coefficient = 0.678, P < 0.001), and it also influenced the cardiac microbial community structure. Cardiac microflora also participated in DNA repair pathways and is affected by the relative abundance of H. pylori (P < 0.0001)., Conclusions: Cardiac microflora dysbiosis, especially the increasing of the relevant abundance of H. pylori, promotes the progression of cardiac inflammation., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Although the most extensive studies revealed the role of H. pylori VacA and CagA toxins in the development of gastric adenocarcinoma, the magnitude of this association and the correlations of vacA mosaicism and cagA status with cardia gastric adenocarcinoma (CGA) still remain controversial., Objective: We aimed to examine the linkage of H. pylori highly cytotoxic genotypes to CGA in Iranian populations as a model., Methods: A total of 601 Iranian patients were enrolled. Biopsies were cultured, genotyped, and anatomically and histologically classified., Results: The vacA c1 genotype, but not cagA status, showed a strong association with the risk of both CGA and non-cardia adenocarcinoma (NCGA), whether the controls were non-tumors, as those with either non-atrophic gastritis or peptic ulcerations, (the OR (95%CI) was 14.11 (4.91-40.52) and 9.59 (4.06-22.65), respectively) or those with NAG (the OR (95%CI) was 10.71 (3.49-32.82) and 8.11 (3.26-20.16), respectively). The vacA c1/cagA+ genotype was significantly associated with an increased risk of NCGA, whether the controls were non-tumors or those with NAG; the adjusted risk was 4.706 (1.41-15.67) and 4.85 (1.42-16.51), respectively., Conclusions: The H. pylori vacA c1 genotype, but not cagA status, might be the first important bacterial biomarker for predicting the cardia adenocarcinoma risk in male patients aged ⩾ 55 in Iran.

Little is known about the link between gastric microbiota and the epidemiology of gastric cancer. In order to determine the epidemiologic and clinical relevance of gastric microbiota, we used 16 S ribosomal RNA gene sequencing analysis to characterize the composition and structure of the gastric microbial community of 80 paired samples (non-malignant and matched tumor tissues) from gastric cardia adenocarcinoma (GCA) patients in Shanxi, China. We also used PICRUSt to predict microbial functional profiles. Compared to patients without family history of upper gastrointestinal (UGI) cancer in the non-malignant gastric tissue microbiota, patients with family history of UGI cancer had higher Helicobacter pylori (Hp) relative abundance (median: 0.83 vs. 0.38, p = 0.01) and lower alpha diversity (median observed species: 51 vs. 85, p = 0.01). Patients with higher (vs. lower) tumor grade had higher Hp relative abundance (0.73 vs. 0.18, p = 0.03), lower alpha diversity (observed species, 66 vs. 89, p = 0.01), altered beta diversity (weighted UniFrac, p = 0.002) and significant alterations in relative abundance of five KEGG functional modules in non-malignant gastric tissue microbiota. Patients without metastases had higher relative abundance of Lactobacillales than patients with metastases (0.05 vs. 0.01, p = 0.04) in non-malignant gastric tissue microbiota. These associations were observed in non-malignant tissues but not in tumor tissues. In conclusion, this study showed a link of gastric microbiota to a major gastric cancer risk factor and clinical features in GCA patients from Shanxi, China. Studies with both healthy controls and gastric cardia and noncardia cancer cases across different populations are needed to further examine the association between gastric cancer and the microbiota., (© 2017 UICC.)

Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: In the course of anastomotic insufficiency following resection of esophageal cancers the bacterial compound of the esophageal substance has a remarkable, presumable role in the outcome of complications., Aim: The purpose of this study is to compare the consequences of the anastomotic leak with the bacterial flora of patients' oral cavity., Method: In this prospective study a total of 131 patients were investigated directly before the surgical intervention taking a bacterial sample. Bacterial flora of patients' oral cavity was analysed; and the correlation between the consequences of the anastomotic leak and the content of the bacterial flora was examined., Results: Pathogenic bacteria in the oral microflora in 50 cases (38.2%) was found. Statistically significant, moderate correlation was found between the severity of the complication and the incidence of pathogenic bacteria (r s = 0.553; p≤0.05)., Conclusions: Pathogenic agent in the microbial flora might induce higher risk and more severe outcome in case of anastomotic leakage and it might be evaluated as a determinative factor. Consideration of the bacterial flora of the oral cavity requires more attention in the preoperative preparation than before and it demands the change of the current practice. Orv. Hetil., 2017, 158(1), 25-30.

Background: Gastric cardia cancer (GCC) is located in the distal stomach, and strongly correlates with atrophic gastritis and Helicobacter pylori (H.pylori) infection. Caudal-related homeobox transcription factor 2 (CDX2) is homeobox gene encoding an intestine-specific transcription factor usually expressed in the intestinal epithelium cells. However, in several recent published papers, CDX2 was found to be aberrantly expressed in gastric, thyroid and ovarian cancer., Results: Higher expression of CDX2 was found in GCC tissues in comparison with non-malignant cardia mucosa (p<0.05). Moreover, immunohistochemical analysis demonstrated that CDX2 expression correlated with lymphatic metastasis. In addition, we found that CDX2 expression progressively increased with the level of H. pylori infection (p<0.05), and also correlated with cell proliferation, based on Ki67 staining., Methods: To investigate the relationship between CDX2, cell proliferation and H. pylori infection, we detected CDX2, Ki62 and H.pylori expression in 83 non-malignant gastric cardia mucosacases and 60 GCC specimens in the Chaoshan area, a high-risk region for esophageal and gastric cardia cancer., Conclusion: These findings provide pathological evidence that H. pylori infectionis a driving force of gastric cardia carcinogenesis by upregulating CDX2 and inducing inflammation. These results provide new pathological evidence that H. pylori infection induces GCC tumorigenesis.

The reported associations with gastric adenocarcinoma and seropositivity to different Helicobacter pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between 15 different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric noncardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. Ninety-five percent of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, whereas two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be retested in other populations., (©2015 American Association for Cancer Research.)

Goals: To describe historical incidence trends of 2 subtypes of gastric cardia cancer., Background: The incidence of gastric cardia cancer has increased in western countries. Prior studies have treated cardia cancer as a single entity, but recent data suggest that there are 2 distinct subtypes: reflux-related and Helicobacter pylori-related., Study: We conducted a population-based study using Connecticut Tumor Registry data from 1955 to 2007. Age-adjusted incidence rates (per 100,000 person-years) were calculated for gastric cancer, as a whole and by anatomic subsite, and for esophageal adenocarcinoma. Cardia and noncardia cancer incidence rates were further adjusted to account for cases with unspecified subsite. Mathematical formulas were derived to calculate incidence rates for reflux-related and H. pylori-related cardia cancer., Results: The adjusted incidence of cardia cancer was 4.0 per 100,000 in 1955 to 1959, decreased to 2.4 per 100,000 in 1965 to 1969 before increasing to 3.4 per 100,000 by 2003 to 2007. The incidence of H. pylori-related cardia cancer decreased from 3.7 to 1.0 per 100,000 over the study period, whereas reflux-related cardia cancer increased progressively from 0.3 to 2.4 per 100,000. The curves for reflux-related cardia cancer and esophageal adenocarcinoma closely mirrored each other, and their combined incidence increased from 0.5 per 100,000 in 1955 to 1959 to 5.6 per 100,000 in 2003 to 2007., Conclusions: The incidence of reflux-related cardia cancer has steadily increased, whereas H. pylori-related cardia cancer has declined progressively since the mid-20th century. Trends in reflux-related cardia cancer and esophageal adenocarcinoma incidence are very similar, suggesting that these 2 cancers share a similar etiology and pathophysiological process.

Background: Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives (FDR) of gastric cancer (GC) patients following H. pylori eradication., Methods: Participants underwent endoscopy with antrum and corpus histological examinations. Subjects with pangastritis were randomly allocated to placebo or eradication therapy and followed over 4½ years. , Results: Among 989 evaluated FDR, we excluded 468 patients as follows: 108 had macroscopic lesions, 243 had no evidence of any H. pylori infection, and 117 were excluded for other reasons. The remaining subjects (n = 521) were allocated to therapy (group A, n = 261) or placebo (group B, n = 260) groups. Interim analysis of 403 subjects (201 placebo, 202 therapy) showed regression of atrophy (60 out of 97 in the antrum and 37 out of 104 in the corpus) in H.pylori-eradicated versus regression of atrophy (57 out of 184 in the antrum and 23 out of 173 in the corpus) in non-H.pylori-eradicated cases over 2½ years (P < 0.0001). No regression of intestinal metaplasia (IM) occurred in the antrum and corpus of treated subjects over 4½ years. However, progression of IM occurred in the antrum in 17 out of 90 patients in the non-H. pylori-eradicated versus 4 out of 68 H. pylori-eradicated subjects after 4½ years (P < 0.05)., Conclusion: Eradication of H. pylori is associated with regression of gastric atrophy but not IM, even in its early stages. Gastric atrophy and IM in the antrum have shown more rapid progression in cases not treated for H. pylori infection (over 4½ years follow-up) compared to H. pylori-eradicated cases.

Gastroesophageal reflux disease is associated with impaired epithelial barrier function and abnormal expression of proteins forming cell-cell contacts by tight junctions and desmosomes in distal esophageal squamous mucosa. Although gastroesophageal reflux disease and Helicobacter pylori are both associated with chronic inflammation of the adjacent cardia mucosa, it is not known whether these lead to derangements of the desmosomal complexes. Here, we assessed the expression of 4 proteins (plakoglobin and desmoglein 1, 2, and 3) forming epithelial desmosomal complexes by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in biopsies from 67 patients with gastroesophageal reflux disease and 23 gastroesophageal reflux disease-negative controls. Plakoglobin and desmoglein 2 were ubiquitously expressed in all samples, whereas desmoglein 1 and 3 were not expressed in cardia mucosa. Gastroesophageal reflux disease was specifically associated with elevated transcript levels of desmoglein 2 and plakoglobin. These were significantly increased from 2.0- to 2.7-fold in patients with gastroesophageal reflux disease compared with controls (P < .01), and significantly increased immunohistochemical scores for both proteins were observed (P < .05) as well. The combined presence of gastroesophageal reflux disease and Helicobacter pylori infection had no additional effect on desmosomal gene expression. Taken together, the up-regulation of plakoglobin and desmoglein 2 in cardia mucosa of patients with gastroesophageal reflux disease supports the concept that the "transition zone" between distal esophagus and proximal stomach is affected by gastroesophageal reflux disease as well, and architectural and molecular changes in the desmosomal compartment contribute to the pathogenesis of gastroesophageal reflux disease in the cardia mucosa., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: To explore the role of Helicobacter pylori (H pylori) infection on the risk of digestive tract cancers., Methods: In total, 199 oral squamous-cell carcinoma (SCC), 317 esophageal SCC, 196 gastric cardia and non-cardia adenocarcinoma and 240 colon adenocarcinoma patients were recruited for serum tests of H pylori infection. Two hospital- and one community-based control groups were used for the comparisons. H pylori seropositivity was determined by an enzyme linked immunosorbent assay method against H pylori IgG., Results: Presence of H pylori infection was significantly inversely associated with esophageal SCC [adjusted odds ratio (AOR): 0.315-0.472, all P-value < 0.05] but positively associated with gastric adenocarcinoma (both cardia and non-cardia) (AOR: 1.636-3.060, all P-value < 0.05) in comparison to the three control groups. Similar results were not found in cancers of the oral cavity and colon., Conclusion: Our findings support the finding that H pylori seropositivity is inversely associated with esophageal SCC risk, but increases the risk of gastric cardia adenocarcinoma.

Objective: The risk factors most strongly associated with gastric cancer are the gastric bacteria Helicobacter pylori and diet. Utilizing data from a case-control study among residents in Hawaii, we examined the association of diet, presence of H. pylori, and non-cardia gastric cancer risk., Methods: Serum taken at diagnosis for cases (n = 212) and at interview for controls (n = 336) was assayed for IgG antibodies to H. pylori group antigens and to a recombinant fragment of the cytotoxin-associated antigen A (CagA) protein, and subjects completed food frequency questionnaires. Risk measures were calculated using logistic regression. The likelihood ratio test was used to assess interactions., Results: Inverse associations were found between gastric cancer risk and increasing intake of several micronutrients and vegetables among all individuals. For H. pylori/CagA-positive subjects, significant trends were present for total, green, and yellow vegetables, while a significant trend was present only for yellow vegetables among H. pylori/CagA-negative individuals. For intestinal gastric cancer, there was a suggestion that intake of vegetables, especially cruciferous vegetables, had a stronger protective effect for the H. pylori/CagA-positive group., Conclusions: Diet may play a greater role in the etiology of non-cardia gastric cancer among individuals with evidence of H. pylori infection than among those without.

Background: Helicobacter pylori causes gastric inflammation. Despite the induction of H. pylori-specific B- and T cells, the immune response is not sufficient to clear the infection. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. FOXP3 was shown to be expressed in a subset of Treg cells known as 'naturally occurring Treg cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa., Materials and Methods: The study included 76 patients stratified according to the presence of H. pylori. Gene expression levels of FOXP3, transforming growth factor (TGF)-beta1, and interleukin-10 were analyzed by quantitative real-time polymerase chain reaction in biopsies from gastric antrum, corpus, and cardia. FOXP3 expression was also analyzed by immunohistochemistry. Differences in expression levels were analyzed by comprehensive statistical analyses and correlated with clinical and histomorphologic parameters., Results: H. pylori-positive patients revealed a 19- to 25-fold induction of FOXP3 transcript levels in antrum and cardia (p < .02). FOXP3 transcript levels correlated positively with inflammation (p < .04) and TGF-beta1 transcript levels (p < .001). Furthermore, a positive correlation between FOXP3(+) Treg cells and H. pylori colonization was demonstrated., Conclusion: This study demonstrates that H. pylori-induced gastritis is associated with a recruitment of naturally occurring FOXP3(+) Treg cells that correlates with the degree of bacterial colonization and mucosal TGF-beta1 expression. Together, these data support the hypothesis that naturally FOXP3(+) Treg cells play a role in the lifelong persistence of H. pylori infection in humans.

We have investigated the role of Helicobacter pylori infection and of other risk factors of gastritis and carditis in residents of a high-risk area for gastric cardia cancer. During a national population-based endoscopic survey, 508 randomly-selected participants aged > or =40 were enrolled. Mucosal biopsies were obtained from six standard sites. Polymorphonuclear (PMN) and mononuclear (MN) infiltration and combined inflammatory scores (CIS) for chronic gastritis and H.pylori were assessed. Relationships of H.pylori and reflux esophagitis with these variables were calculated for cardia and non-cardia subsites. Both PMN and MN infiltrations correlated strongly with H.pylori infection. For PMN the relationship was maximum for the antrum (odds ratio (OR) = 9.4 (5.2-17.1)) and minimum for the gastric body (OR = 1.7 (1.0-2.9)). There was a significant relationship between carditis and H.pylori (OR = 2.8 (1.7-4.9)). A similar relationship was obtained for MN infiltration. In 56% of subjects the mean MN score for the corpus was equal to or greater than that for the antrum. For 59% of subjects the MN score for the cardia was greater than or equal to the antral score. Use of logistic regression revealed that was the main risk factor for gastritis and carditis in all sites. There was an inverse relationship between reflux esophagitis and carditis. H.pylori is the main risk factor for gastritis for all sites of the stomach including the cardia; but this relationship is stronger for the antrum and cardia than for the body. Continuous cardia inflammation may contribute to the high incidence of gastric cardia cancer in this region.

Background: The role of H. pylori infection in GERD is highly controversial. Our aim was to investigate the relationship between reflux esophagitis and H. pylori infection in Jordanian subjects and to examine the gastric site for H. pylori that is most strongly associated with reflux esophagitis., Methods: During endoscopy two biopsies from the cardia and another two biopsies from the antrum were taken from 100 consecutive patients with reflux esophagitis (RE group) and from a sex- and age-matched group of 50 patients, who were referred to the endoscopy unit for evaluation of upper gastrointestinal symptoms and whose endoscopic findings were normal (control group). The biopsies were examined histologically for the presence of gastritis and H. pylori., Results: Antral histological gastritis, Barrett's esophagus and hiatus hernia were significantly more common in the RE group than in the control group. Out of the 100 patients, 68 (68%) in the RE group and 26 of 50 (52%) in the control group were found to have H. pylori infection. The presence of H. pylori in both antral and cardiac biopsies was significantly more frequent in patients of the RE group. Forty-four patients in the RE group had positive H. pylori in both antral and cardiac biopsies (44%), while only 12 out of 50 patients of the control group (24%) had positive H. pylori in both biopsies. In the control group the prevalence of H. pylori in the antrum was similar to that of patients of the RE group (52% vs. 59%), but colonization of H. pylori in the cardia was significantly much lower than that of the RE group (24% vs. 53%; P = 0.0007)., Conclusions: The increased prevalence of H. pylori colonization in the cardia is associated with reflux esophagitis and further controlled clinical study is required to show the impact of H. pylori eradication in patients with reflux esophagitis.

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.

Background: Etiology of gastric cardia inflammation is still controversial., Aims: To evaluate the association between carditis and Helicobacter pylori infection and the correlation among inflammatory changes observed in biopsies taken from cardia, corpus, and antrum in a well-defined group of patients., Patients: The mean age of 45 dyspeptic patients was 10.4 years (range 5.1-17.0 years); gender F/M rate: 1.6/1., Methods: A total of 450 specimens from esophagus (2), cardia (2), corpus (3), and antrum (4) were collected for biopsy. The presence of H. pylori was assessed by histology and a rapid urease test. The types of glandular epithelium of cardia found in specimens were identified and both inflammatory changes and H. pylori density were graded., Results: Carditis was present in specimens of 30/45 (66.7%) of the patients. Presence of H. pylori in specimens was detected in the antrum (26/45; 57.8%), in the corpus (19/45; 42.2%), and in the cardia (14/45; 31.1%). There was a strong association between carditis and presence of H. pylori infection (OR=27.08) by multivariate analysis. The scores for inflammation and activity in the cardia, corpus and antrum have shown a relationship except for both cardia and antrum H. pylori density and corpus and cardia activity. The intensity of gastritis and degree of colonization with H. pylori were significantly higher in the antrum than in both the corpus and the cardia. Pangastritis was highly associated to H. pylori infection in 22/25 (88%) of the patients., Conclusions: 1. Carditis is associated to H. pylori infection in children with symptoms of dyspepsia; 2. The degrees of gastritis found at the cardia were correlated to those at the antrum and body except for both cardia and antrum H. pylori density and corpus and cardia activity.

Aim: To examine the relationship between H. pylori and gastro-oesophageal reflux disease (GORD) in Iran., Methods: In this study 51 GORD patients (referred to endoscopy at Taleghani hospital) were compared with 49 age-sex matched controls. Diagnosis of H. pylori was made by gastric mucosal biopsy and rapid urease test (positive if the result of one or both diagnostic methods was positive). Updated Sydney system was used to report histopathological changes., Results: The frequency of H. pylori infection based on rapid urease test and histology was 88.2% (45) in patients and 77.6% (38) in controls, which showed no significant difference. The frequency of H. pylori infection was significantly higher in the antrum than in the corpus and cardia. The mean activity, inflammation, and gastritis scores were also higher in the antrum of patients than in the antrum of controls. The mean scores were significantly higher in the corpus of controls than in the corpus of patients. Diffuse active gastritis was observed in a significantly larger number of controls, while the frequency of diffuse chronic gastritis was higher in patients. There was no significant difference in the frequency of other histological findings between patients and controls., Conclusion: H. pylori infection cannot prevent GORD in this region.

We attempted to clarify the pathogenesis of gastric inflammation in the cardia. Eighty Japanese participated in this study. Biopsy specimens of the gastric antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained, and histological gastritis was evaluated. Cardiac inflammation was also evaluated using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal reflux disease (GERD), and habitual smoking and assessed the relations between these factors and cardiac inflammation. The prevalence of H. pylori infection was statistically higher in patients with cardiac inflammation than in those without inflammation (P < 0.05). The relationship was also demonstrated by magnifying gastroscopy. Cardiac inflammation was linked to low acid output but not linked to the BA concentration or habitual smoking. Cardiac inflammation was more pronounced in patients without GERD. These results suggest that H. pylori is a major risk factor for cardiac inflammation in the Japanese.

Objective: To compare the Helicobacter pylori-associated pathology in gastric biopsies taken from patients living at sea level with those taken from patients living at high altitude., Methods and Results: We included 38 patients from a hospital in the Andean city of La Oroya, Peru, located at 3700 m in altitude, and 40 control patients taken from Comas Clinic located in the city of Lima at sea level. Fibrepanendoscopy and multiple biopsies were performed in all the patients followed by histopathological examination. In the antrum, patients from the Andean town had a higher prevalence of glandular lymphoid adherence lesions, active germinal centres, moderate to severe chronic atrophic gastritis, intestinal metaplasia and moderate to severe total deep gland loss, than did patients from the coastal town. Furthermore, the severity of the histological lesions seen in the gastric body and cardia was significantly greater in the high-altitude patients than in those from sea level., Conclusion: This study suggests that the severity of H. pylori-associated gastric lesions seen on histopathological examination is greater in patients living at high altitude, the cause of which is most probably multifactorial but nonetheless principally altitude related.

Previous studies have indicated that the gross anatomical structure of the stomach of the babirusa (Babyrousa babyrussa) differs markedly from that of all other pigs. This light and scanning electron microscopic study revealed a previously unknown, microscopic structure characterised by a 'honeycomb' pattern at the luminal surface of the tunica mucosa. The walls of the 'honeycomb' were about 0.20-0.25 mm high and appeared almost entirely composed of various types of bacteria. Underneath the bacteria the walls were formed by thin tubes composed of non-glandular squamous epithelial-like cells, extending from the tops of the ridges between each glandular pit. There is as yet no evidence of a comparable structure in the stomach of any other pig, or to our knowledge any other forestomach-fermenting mammal.

The relationship between Helicobacter pylori infection and gastroesophageal reflux disease (GERD) remains controversial. Over 20 studies presented at the 2003 Digestive Disease Week meeting examined the implications of H. pylori infection for GERD. Although the findings were not uniform, most of the studies presented indicated a negative association between the presence of H. pylori and the presence of GERD symptoms, signs, or complications. In addition, eradication of H. pylori infection was related to the emergence of GERD and its complications. However, most studies favored a role for H. pylori rather than GERD in the development of pathologic changes in the gastric cardia. Finally, a few studies suggested the intriguing possibility that the modulation of GERD by H. pylori could be through the effects of H. pylori eradication on weight gain.

At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor-alpha (TNF-alpha) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett's esophagus.

Background: Adenocarcinoma of the gastro-oesophageal junction is rapidly increasing in incidence and there is much interest in precursor lesions. The aetiology of inflammation of the gastric cardia (carditis) and the concept of the cardia as a native zone of mucinous gastric glands are disputed., Aims: To investigate the relationship between the type of cardiac mucosa and carditis with various histological and clinical parameters., Methods: Ninety-eight sets of gastric biopsies (cardia, corpus, incisura and antrum) were obtained prospectively in young patients (median age 40 years) who presented to the outpatient clinic with symptoms of gastro-oesophageal reflux (n = 25) or other upper gastrointestinal symptoms. Patients with neoplasia or Barrett's oesophagus were excluded. The presence (n = 19) or absence of oesophagitis at endoscopy was recorded. The degree of inflammation, Helicobacter pylori density, intestinal metaplasia and atrophy were scored according to the Sydney classification and the type of cardiac mucosa (oxyntic or mucinous) was noted., Results: We found that carditis and mucinous-type cardiac mucosa were strongly associated with H. pylori-related gastritis (P = 0.00019 and P = 0.006, respectively) but not with clinical or endoscopic gastro-oesophageal reflux. Mucinous mucosa in the cardia was only seen in 17% of biopsies., Conclusion: H. pylori-related gastritis is associated with mucinous-type cardiac mucosa as well as with carditis. The former strongly points to expansion of mucinous cardiac mucosa in H. pylori gastritis. This probably represents metaplasia of oxyntic to mucinous mucosa and raises the possibility of a role in carcinogenesis of the gastro-oesophageal junction.

Aim: The purpose of this study was to determine the prevalence of intestinal metaplasia of the gastric cardia in Japanese patients with Helicobacter pylori infection., Methods: One hundred and fifty-seven patients with H. pylori infection participated in this study. Four biopsy specimens were taken from antrum, lesser and greater curvatures of stomach, and cardia for histological examination. The patients were divided into three groups: those < or = 39 years of age (group A), those 40-59 years old (group B), and those > or = 60 years of age (group C)., Results: The proportions of the patients with intestinal metaplasia of the gastric cardia in the three groups were 12, 39, and 65%, respectively. Their intestinal metaplasia of gastric cardia scores were 0.2, 0.54, and 0.81, respectively (significant difference among groups A, B, and C: p < 0.05), according to the updated Sydney classification., Conclusion: The prevalence of intestinal metaplasia of the gastric cardia and carditis in Japanese patients with H. pylori infection was similar to that of metaplasia of antrum and lesser curvature of the stomach., (Copyright 2004 S. Karger AG, Basel.)

Inflammation of the gastric cardia, which is the most proximal portion of the stomach, in most instances is the result of either gastroesophageal reflux disease or H. pylori infection. Histologic distinction between these two entities is important because the treatment, natural history, and risk of malignancy are different. Moreover, multilayered epithelium, a possible precursor to Barrett's esophagus, has only recently been described in the gastric cardia, and its relationship to gastroesophageal reflux disease is unknown. The aim of this study was to compare the histologic features of the gastric cardia and the prevalence of multilayered epithelium in patients with reflux versus H. pylori-associated carditis. Routinely processed hematoxylin and eosin-stained mucosal biopsies of the gastric cardia from 30 patients with reflux-associated carditis, 25 with H. pylori-associated carditis, and 30 control patients (no reflux, no H. pylori) were evaluated for a wide variety of histologic features such as goblet cell metaplasia, presence of multilayered epithelium, type of glandular epithelium (mucous, oxyntic, mixed mucous/oxyntic), pancreatic metaplasia, overall degree of inflammation, and the quantity of individual types of inflammatory cells. The clinical and histologic features were compared between the two study groups and controls. Clinically, the reflux carditis group (male/female ratio: 21/9, mean age 56 years) had a significantly higher male/female ratio (p <0.01) and a slightly higher mean age in comparison with the H. pylori group (male/female ratio: 9/16, mean age 50 years). Histologically, the reflux group had significantly less overall inflammation (p <0.05), with fewer plasma cells (p <0.04) and neutrophils (p <0.006), but a higher prevalence of multilayered epithelium [9 of 30 (30%) vs 1 of 25 (4%) in the H. pylori group, p = 0.01]. In the reflux carditis group, multilayered epithelium was significantly associated with neutrophilic inflammation (p <0.05), but not any other features of chronic carditis or with any of the specific epithelial cell types. The control group showed less inflammatory activity in comparison with the H. pylori group and a lower prevalence of multilayered epithelium and eosinophilic inflammation in comparison with the reflux group. The clinical and pathologic features of reflux carditis are distinct from H. pylori carditis and are characterized by less overall inflammation and fewer neutrophils and plasma cells. Multilayered epithelium not uncommonly occurs in the cardia of patients with gastroesophageal reflux disease but without Barrett's esophagus, further supporting our hypothesis that multilayered epithelium may represent an early precursor in the development of columnar metaplasia in Barrett's esophagus.

Background: The incidence of adenocarcinoma of the proximal stomach (cardia) is increasing. The pathophysiological processes underlying this trend are unclear. Normal cell turnover depends on cell proliferation being in balance with programmed cell death or apoptosis. It has been well documented that excessive proliferation potentiates the effects of any carcinogen that targets DNA. It is therefore accepted that excessive proliferation is a risk factor for subsequent neoplasia development., Aims: To compare apoptosis and proliferation in normal cardia tissue, carditis, and cardia intestinal metaplasia, and to determine the effect of Helicobacter pylori infection and gastro-oesophageal reflux disease., Methods: Biopsies from the cardia were obtained from consecutive dyspeptic patients and asymptomatic controls at the time of gastroscopy. Samples were assessed histologically and classified as normal, carditis, or cardia tissue with intestinal metaplasia. All samples were then examined, employing immunohistochemical techniques, for the presence of proliferating and apoptotic cells., Results: A total of 76 histological specimens were examined. There was a statistical significant difference in the proliferation index between controls and both carditis and cardia intestinal metaplasia, and also between carditis and cardia intestinal metaplasia. In contrast, there was a significant increase in the apoptotic index for carditis compared with controls, while that of intestinal metaplasia did not differ from controls. As a result, comparison of the apoptotic/proliferation ratios for each group revealed that, for both carditis and cardia intestinal metaplasia, the apoptotic index/proliferation index ratio is reduced significantly compared with controls, but as a result of different mechanisms., Conclusion: This study demonstrates that individuals with carditis and cardia intestinal metaplasia have alterations in epithelial cell kinetics. In particular, it shows that there is a persistent imbalance between proliferation and apoptosis, which may represent malignant potential.

Background: The etiopathogenesis of chronic inflammation at the gastric cardia is still debated. It is suggested that carditis may be a finding of gastro-oesophageal reflux disease (GORD) or it may occur as a result of the gastritis caused by Helicobacter pylori (H. pylori) infection., Aim: To examine morphological features of carditis, as well as the associations of carditis with Helicobacter pylori gastritis and oesophagitis as a marker of gastro-oesophageal reflux disease., Patients and Methods: Endoscopic biopsy specimens obtained systematically from oesophagus, cardia, corpus and antrum of 135 dyspeptic patients were retrospectively evaluated. In biopsies, we have searched for any correlations between clinical, endoscopic, and histological features., Results: Carditis was detected in 123 (91.1%) of the cases. The mean age of the carditis group was 47.9 years and the male-to-female ratio was 1.08:1. The relation of carditis with age and sex was not significant (p = 0.19 and p = 0.24, respectively). All cases of the carditis group had concomitant chronic gastritis. In these cases, chronic inflammation, degree of neutrophil-mediated activity and H. pylori colonisation were significantly correlated in cardia, corpus and antrum (p < 0.001). Intestinal metaplasia was observed in 14 cases (11.3%) and, was associated with H. pylori colonisation (p < 0.001). Microscopic oesophagitis detected in 37.7% cases also showed correlation with reflux symptoms and endoscopic oesophagitis but not carditis. When all cases with carditis were evaluated for H. pylori infection and oesophagitis, which are presumed risk factors for carditis, H. pylori infection appeared to be an independent risk factor for carditis (p = 0.012), while oesophagitis did not., Conclusions: This study suggests that carditis is commonly found in patients presenting with dyspepsia and the histological features of carditis were similar to those seen in H. pylori gastritis in antrum and corpus. In addition, our data have also shown that carditis was significantly associated with H. pylori infection but not with symptoms or signs of GORD.

Pathogenesis of chronic inflammation at the gastric cardia is not yet clear. It is controversial whether cardiac-type mucosa is normal structure at the cardiac region. Therefore, we studied the existence of correlations between carditis, infection, and gastroesophageal reflux disease, and determined the prevalence of cardiac mucosa at the endoscopically defined cardiac region. Gastric biopsy specimens were analyzed from 27 patients with reflux esophagitis and 30 subjects without reflux esophagitis. Carditis was not associated with reflux esophagitis, but with infection. Moreover, the degree of gastritis and atrophy at the cardia were closely related to those of the antrum and body. Cardiac mucosa was not always present in the endoscopically defined cardiac region, and its prevalence was positively correlated with gastritis and atrophy grade of the cardia and age. In conclusion, -induced pangastritis may lead to the development of carditis, which is associated with occurrence of cardiac-type mucosa at the cardiac region.

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H. pylori, and Group A was not. Necropsy was performed on the pigs on postinfection Day 5, and biopsy specimens were taken from 16 sites of the stomach. H. pylori were recovered from 11 of 16 sites in Group B, 1 of 32 sites in Group C, and 13 of 16 sites in Group D. On the other hand, the degree of lymphocyte infiltration increased in the order of Group A < Group B < Group C < Group D. These observations suggest that magnesium ion in drinking water is essential for the colonization of H. pylori in the pig stomach. Possible mechanisms for the lymphocyte infiltration are discussed.

Objective: Specialized intestinal metaplasia (SIM) is often found at a normal-looking gastroesophageal junction on routine biopsy. The prevalence of SIM in Asian populations has not been recorded. Its significance is also unclear. The objective of the study was to document the prevalence of SIM at the gastroesophageal junction in a Chinese population undergoing endoscopy., Methods: Biopsies were taken at the gastroesophageal junction in 145 patients, both at the squamocolumnar junction and immediately below in the gastric cardia. Specimens were examined for the type of epithelium (squamous, cardiac, and fundic), the presence of SIM, and Helicobacter pylori (H. pylori)., Results: Of 145 patients who underwent endoscopy, 136 had a normal-looking gastroesophageal junction. Cardiac epithelium was found in 100 patients. Of these 100 patients, SIM was documented in 34% of patients and carditis in 20%. Patients with SIM were older compared with those without SIM (mean age 62 yr and 56 yr, p = 0.035). Carditis was more prevalent in patients with SIM. It was present in 11 out of 34 patients who had SIM (32.4%) compared with nine in 66 patients (13.6%) without SIM, p = 0.036. When carditis was found, H. pylori was present at the cardia in 40% of patients (eight of 20) compared with only 18% (14 of 80) in those without carditis, p = 0.039., Conclusions: SIM is prevalent at the gastroesophageal junction in Chinese patients undergoing endoscopy and is associated with carditis. Carditis in turn may be related to H. pylori infection.

Background: Recent epidemiological studies have reported a threefold increase in the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal junction (cardia). There are conflicting reports available implicating both gastro-oesophageal reflux disease and Helicobacter pylori infection in the aetiology of carditis and cardia intestinal metaplasia, despite strong evidence to show that these two conditions are, if anything, inversely related. We aimed to determine the prevalence of carditis and cardia intestinal metaplasia in dyspeptic subjects and also their association with H. pylori infection and gastro-oesophageal reflux disease., Method: Histological samples from the gastric cardia were obtained from dyspeptic subjects. H. pylori status was assessed based on histological, microbiological and rapid urease testing. Gastro-oesophageal disease was diagnosed on the basis of histological evidence and/or erosive oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia (CIM), when present, was subgrouped as complete or incomplete., Results: Overall, 276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150 (54%), respectively. H. pylori infection was strongly associated with carditis and CIM (P<0.001 and P<0.01). Older age and male gender were also associated with inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux was not associated with either entity., Conclusion: Carditis and CIM occur frequently. Both conditions are strongly associated with H. pylori infection, older age and male gender. There was no association with gastro-oesophageal reflux disease.

Objective: Although high prevalences of both chronic inflammation (carditis) and intestinal metaplasia at the gastric cardia have been reported, the pathogenesis is still unclear. This study assesses the role of Helicobacter pylori (H. pylori) infection and symptoms of gastroesophageal reflux disease (GERD) in these histological alterations., Methods: Consecutive patients who underwent upper endoscopy were enrolled in the study, irrespective of their symptoms. Patients previously treated for H. pylori infection and those using proton pump inhibitors were excluded. Two biopsies were performed in the antrum, two in the gastric body, and two at the gastric cardia. All biopsies were used to look for H. pylori and for histological assessment., Results: A total of 133 patients were enrolled. Carditis and intestinal metaplasia at the cardia were detected in 100 (75.2%) and in 18 (13.5%) patients, respectively. The H. pylori infection rate was significantly higher in patients with carditis than in those without it (87/100 vs 7/33; p < 0.0001), and was higher in those with intestinal metaplasia at the cardia than in those without it (17/94 vs 1/39; p = 0.03). Conversely, the prevalence of GERD symptoms was not significantly different between patients with and without carditis (34/100 vs 16/33; p = NS), and between those with and without intestinal metaplasia (5/50 vs 13/83; p = NS). Interestingly, the prevalence of both H. pylori (64/94 vs 39/94; p = 0.0005) and intestinal metaplasia (18/133 vs 4/133; p = 0.0042) in the gastric cardia was significantly higher than that in gastric body., Conclusion: According to our study data, the gastric cardia is frequently infected with H. pylori with consequent development of both carditis and intestinal metaplasia, whereas GERD does not seem to be involved in these histological changes.

Background/aims: Low local acid production is considered to be an important factor for Helicobacter pylori colonization. The increased bacterial density and inflammation are expected in cardiac mucosa because of low acid secretion. We aimed to investigate the bacterial density and the histologic pattern of gastritis in the cardia, and to compare with those of the antrum and corpus., Methodology: The biopsy specimens taken from the antrum, corpus and cardia in 97 patients during endoscopy were examined histopathologically., Results: The mean scores for bacterial density in the cardia, corpus and antrum were 1.32 +/- 0.35, 1.09 +/- 0.86, 1.42 +/- 0.97, respectively. Bacterial density of the cardia was significantly higher than that in corpus, but was similar to the antrum. The mean scores for the degree of gastritis in the cardia, corpus and antrum were 1.56 +/- 0.79, 1.64 +/- 0.75, 1.85 +/- 0.77, respectively. Gastritis was significantly more severe in the antrum than in the corpus and cardia. The activity scores of gastritis in the three regions were statistically similar., Conclusions: Although bacterial density in the cardiac mucosa were found to be high, the degree of gastritis was low.

Background: Further elucidation of the consequences of Helicobacter pylori infection on gastric mucosal inflammation and gastric secretory function would be facilitated by an animal model that is susceptible to infection with H. pylori, is broadly similar in gastric physiology and pathology to people, and is amenable to repeated non-invasive evaluation. The goal of this study was to examine the interrelationship of bacterial colonization, mucosal inflammation and gastric secretory function in cats with naturally acquired H. pylori infection., Materials and Methods: Twenty clinically healthy cats with naturally acquired H. pylori infection (cagA-, picB) and 19 Helicobacter-free cats were evaluated. Gastric colonization was determined by tissue urease activity, light microscopy, culture and PCR. The mucosal inflammatory response was evaluated by light microscopy, and by RT-PCR of the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-8 and TNF-alpha in gastric mucosa. Gastric secretory function was assessed by measuring pentagastrin-stimulated acid secretion, fasting plasma gastrin, and antral mucosal gastrin and somatostatin immunoreactivity., Results: H. pylori colonized the pylorus, fundus and cardia in similar density. Bacteria were observed free in the lumen of gastric glands and were also tightly adherent to epithelial cells where they were associated with microvillus effacement. Mononuclear inflammation, lymphoid follicle hyperplasia, atrophy and fibrosis were observed primarily in H. pylori-infected cats, with the pylorus most severely affected. Neutrophilic and eosinophilic infiltrates, epithelial dysplasia, and up-regulation of mucosal IL-1beta and IL-8 were observed solely in infected cats. Fasting plasma gastrin concentrations and pentagastrin-stimulated acid output were similar in both infected and uninfected cats. There was no relationship of bacterial colonization density or gastric inflammation to plasma gastrin concentrations or gastric acid output., Conclusions: The pattern of colonization and the mucosal inflammatory response in cats with naturally acquired H. pylori are broadly similar to those in infected people, particularly children, and non-human primates. The upregulation of IL-8 in infected cats was independent of cagA and picB. Our findings argue against a direct acid-suppressing effect of H. pylori on the gastric secretory-axis in chronically infected cats.

This series consists of 141 patients in whom cardiac mucosa (CM) was present in biopsy samples from the gastroesophageal junctional region. Inflammation of CM, irrespective of its exact anatomic location, was defined as carditis and classified as acute or chronic based on the number of inflammatory cells present. In all cases, CM showed significant chronic inflammation. One hundred and eleven (79%) of the 141 patients with carditis showed no evidence of gastritis in biopsy samples from the gastric antrum and body. Helicobacter pylori was present in 20 of 141 (14%) patients; of these, 17 had evidence of a pangastritis, with 15 of these patients also showing H. pylori in CM. Patients with severe chronic inflammation in CM had a significantly higher acid exposure of the lower esophagus as quantitated by a 24-hour pH test than those with mild chronic inflammation in CM. Acute inflammation was uncommon in CM; it was present in only 26 of 141 (18.4%) patients. There was no significant difference in acid exposure of the lower esophagus between patients with and without acute inflammation in CM. The presence of acute inflammation in CM was significantly associated with distal gastritis and H. pylori infection. Men with carditis had quantitatively higher acid exposure of the lower esophagus than did women with this disorder. This difference was greatest in men with severe inflammation in CM who had no evidence of distal gastritis. These findings provide evidence that chronic inflammation in CM is strongly associated with acid reflux and that H. pylori is not a significant etiologic factor in carditis. They also show that in patients with CM in whom H. pylori gastritis develops, the infection frequently spreads to involve CM, resulting in acute inflammation with neutrophils that is superimposed on the chronic inflammation already present.

Background: The role of Helicobacter pylori infection and/or gastro-oesophageal reflux disease in pathogenesis of intestinal metaplasia in gastric cardia is still unclear., Aims: To prospectively evaluate prevalence of inflammation and intestinal metaplasia of cardia in relationship to Helicobacter pylori infection in patients with gastro-oesophageal reflux disease and in healthy controls., Patients: A total of 122 consecutive patients with gastro-oesophageal reflux disease and 49 control subjects were included., Methods: During endoscopy, a total of six biopsies were taken from antrum, corpus and cardia. Helicobacter pylori infection was assessed by histology and rapid urease test. Degree of chronic gastritis, inflammatory activity and Helicobacter pylori colonization were scored from 0 to 3., Results: No difference in prevalence was observed between gastro-oesophageal reflux disease patients and controls as far as concerns Helicobacter pylori (41% vs 38%), inflammation of cardia (59.5% vs 70%) and intestinal metaplasia of cardia (18% vs 19%). Inflammation of cardia was significantly (p<0.001) associated with Helicobacter pylori irrespective of gastro-oesophageal reflux disease symptoms. Cardial intestinal metaplasia was more frequently (p=0.03) found in infected subjects ((27%) than in uncolonized subjects (13%). No relationship was observed between gastro-oesophageal reflux disease and carditis and cardial intestinal metaplasia. Cardial intestinal metaplasia was more frequently detected in association with carditis (26% vs 6%, p=0.001)., Conclusions: Inflammation and intestinal metaplasia of the gastric cardia are not markers of gastro-oesophageal reflux disease but are related to Helicobacter pylori.

Background: The mucosa distal to the endoscopic mucosal change zone can have easily diagnosed early alterations, in patients with chronic gastroesophageal reflux., Aim: To determine the type of mucosa existent in the zone distal to the squamous-columnar junction in patients with chronic gastroesophageal reflux without intestinal metaplasia., Patients and Methods: One hundred thirty four controls and 208 patients with chronic gastroesophageal reflux lasting two years were studied. Forty three of these patients had a normal endoscopy, 54 had an erosive esophagitis and 111 had a short columnar epithelium covering the distal esophagus, without intestinal metaplasia. In all subjects, four biopsies were obtained from a zone distal to the squamous-columnar junction and two from the distal gastric antrum., Results: In 59% of control subjects, fundic mucosa was present in the zone distal to the squamous-columnar junction. Cardial mucosa was present in the rest. In patient with chronic gastroesophageal reflux, cardial mucosa was predominant. Helicobacter pylorii infection decreased along with increasing extension of cardial mucosa covering the distal esophagus., Conclusions: In patients with chronic gastroesophageal reflux there is a metaplasia of fundic mucosa towards cardial mucosa. On the other hand, Helicobacter pylorii infection decreases gradually.

Background: The cause of inflammation in cardiac mucosa at the gastro-oesophageal junction (GOJ) is unclear, both gastro-oesophageal reflux disease (GORD) and Helicobacter pylori having been implicated., Aims: To describe patterns of gastritis in patients with symptomatic GORD., Methods: In 150 patients (126 normally located Z-line, 24 Barrett's oesophagus) with symptoms of GORD, biopsies were taken of the GOJ, corpus, and antrum. Inflammation was assessed using the updated Sydney System., Results: For the 126 patients with a normally located Z-line, biopsies of the GOJ revealed cardiac mucosa in 96, fundic mucosa in 29, and squamous mucosa in one. Inflammation in glandular mucosa at the GOJ was present in 99/125 specimens (79%), including 87/96 (91%) with cardiac mucosa and 12/29 (41%) with fundic mucosa. Inflammation in fundic mucosa was closely related to H pylori and active inflammation was only seen in its presence. Inflammation in cardiac mucosa was less closely linked to H pylori. When H pylori was present in cardiac mucosa (28/96, 29%) active inflammation was usually present (25/28, 89%). However, active inflammation was also found in 34/68 (50%) cardiac mucosa specimens without H pylori. Overall, 28/87 (32%) biopsies with carditis were colonised with H pylori and 59/87 (68%) were not. In H pylori colonised patients, inflammation was seen throughout the stomach, while in non-colonised patients, it was confined to cardiac mucosa., Conclusions: Patients with symptomatic GORD had a high prevalence of carditis. This was of two types, H pylori associated and unassociated. Except on Giemsa staining, the two were morphologically identical, suggesting mediation by a similar immunological mechanism.

Objective: The clinical significance of chronic inflammation at the gastroesophageal junction (carditis) is unknown: it may be associated with Helicobacter pylori (H. pylori) gastritis or with gastroesophageal reflux disease (GERD). We aimed to examine the association between carditis and H. pylori gastritis and endoscopic erosive esophagitis., Methods: One thousand and fifty-three patients undergoing gastroscopy were enrolled in the study. Biopsy specimens were obtained from gastric antrum and corpus, immediately distal to normal-appearing squamocolumnar junction and distal esophagus., Results: Chronic inflammation at the gastroesophageal junctional mucosa (carditis) was detected in 790 (75%) of 1053 patients. The male:female ratio of the carditis group was 1:1.5 and of the noncarditis group 1:1.6 (p = 0.6). The mean age of the carditis group was 58.7 yr (95% confidence interval [CI], 57.6-59.9) and of the noncarditis group, 52.6 yr (95% CI, 50.7-54.6, p < 0.001). Of the carditis group (N = 790), 549 (69%) had chronic gastritis (70% H. pylori positive) and 241 (31%) had normal gastric histology. In multivariate analyses, the only risk factor for carditis in subjects with chronic gastritis was H. pylori infection (odds ratio [OR], 2.9; 95% CI, 1.6-5.0), whereas the independent risk factor for carditis in subjects with histologically normal stomach was endoscopic erosive esophagitis (OR, 1.8; 95% CI, 1.1-3.1). The prevalence of complete intestinal metaplasia (IM) in the gastric cardia mucosa was 7% in the noncarditis group, 19% (p < 0.001) in the carditis group with chronic gastritis, and 10% (p = 0.3) in the carditis group with normal stomach. The respective prevalences of incomplete IM were 3%, 12% (p < 0.001), and 12% (p < 0.001). Among carditis patients with normal stomach histologically (N = 241), those with complete and/or incomplete IM (N = 49) were older than those with carditis only (63.6 yr [95% CI, 59.9-67.2] vs 51.4 yr [95% CI, 48.9-53.9]; p < 0.001)., Conclusions: Two dissimilar types of chronic inflammation of the gastric cardia mucosa seem to occur, one existing in conjunction with chronic H. pylori gastritis and the other with normal stomach and erosive GERD. Most cases of chronic gastric cardia inflammation and intestinal metaplasia are detected in patients with chronic H. pylori gastritis.

Gastric cardia inflammation and intestinal metaplasia are the subjects of recent investigation. Some authors have found associations with gastroesophageal reflux disease, whereas others have identified relationships with Helicobacter pylori (HP). We studied 150 consecutive patients who underwent upper endoscopy, had normal gastroesophageal anatomy, and had biopsies of the antrum, cardia, and lower esophagus, to evaluate relationships between reflux esophagitis, cardia inflammation, intestinal metaplasia, and HP gastritis. Forty-two patients had HP infection. Cardia inflammation was significantly related to esophageal squamous inflammation in the non-HP-infected patient group and to antral inflammation and cardia HP infection in the HP-infected patient group. The differences between the patient groups was most apparent in the patients with moderate or marked inflammation. Twenty-seven percent of patients had cardia intestinal metaplasia that was related to cardia inflammation. Cardia inflammation and intestinal metaplasia probably have multiple causes. Pathologists should refrain from applying the term Barrett's esophagus for biopsies procured from the cardia that show intestinal metaplasia in patients with a normal squamocolumnar junction.

The incidence rates of gastric cardia and esophageal adenocarcinomas are increasing, but data suggest that carriage of cagA(+) Helicobacter pylori strains may protect against development of Barrett's esophagus and esophageal adenocarcinoma. Our aims were to examine the relationship between pre-malignant and malignant lesions in the gastric cardia and serum antibodies to H. pylori antigens in patients with and without complications of Barrett's esophagus. The prevalence of carditis was 40% in controls compared with 13% in patients with complicated or uncomplicated Barrett's esophagus and cardia adenocarcinoma (p < 0.001). Cardia intestinal metaplasia (IM) and atrophy were present and concordant in 28% of controls but less frequent in patients with Barrett's alone or with dysplasia/adenocarcinoma (0% for each, p < 0.001). Carriage of cagA(+) strains was present in 34% of patients with carditis and significantly associated with increased frequency and severity of cardia inflammation, IM, and atrophy but not with adenocarcinoma. IgA and HspA seropositivity were significantly increased in H. pylori-colonized patients with carditis compared to persons with normal cardia histology (p

Background: Earlier studies identified a pylorocardial expansion of chronic gastritis. We investigated the age-dependent changes in grading and topography of Helicobacter pylori gastritis., Methods: Antral, corpus, and cardial biopsy specimens from 216 H. pylori-positive patients with no peptic ulcer disease (PUD), malignancy, or Barrett's oesophagus were evaluated with haematoxylin and eosin and modified Giemsa. The patients were separated into four equal-sized age groups (1, < 46 years; II, 46-56 years; III, 57-68 years; IV, > 69 years). Sydney-system gradings of bacterial density and activity and degree of gastritis were used to calculate gastritis sum scores for age- and biopsy site-dependent comparisons. The prevalence of intestinal metaplasia (IM) and atrophy was also compared., Results: Mean antral sum scores decreased slightly in group IV but were higher than those in the corpus or cardia in all groups (P < 0.05 each). In the corpus mean scores increased in groups II-IV versus group I (P < 0.05 each), and aging was associated with a significant increase in bacterial density and active inflammation. The cardia scores remained virtually constant in all groups and exceeded significantly that in the corpus in group I. IM and atrophy increased with age, occurring more frequently and earlier in the antrum and cardia than in the corpus., Conclusions: Progression of gastritis with age involves the corpus but not the cardia. Antral inflammation decreases slightly in patients of advanced age.

Unlabelled: Helicobacter pylori is the most frequent cause of antral gastritis type B. Little is known about the affection of the gastric cardia by inflammation associated with H. pylori infection., Objective: Assess the status of morphological changes of the cardia in the presence of H. pylori infection in patients with non-ulcer dyspesia., Methods and Patients: 251 consecutive dyspeptic patients with H.pylori infection were subjected to endoscopic examination of the upper part of the gastrointestinal tract. Six biopsies were taken (2 antrum, 2, corpus, 2 cardia) for histological (HaE) and microscopic (Giemsa) status, scored according to the Sydney classification., Results: Chronic inflammation and its activity reached similar values in the antrum and cardia, the difference was not statistically significant (p>0.05). The findings of H.pylori and intestinal metaplasia (IM) were higher in the antrum than in the cardia (p<0.05) similarly as atrophy and hyperplasia of lymphatic tissue (p<0.01). Significantly higher values were recorded in chronic inflammation, its activity and number of HP in the antrum (p<0.001). The same applies to atrophy, IM, lymphoid follicles (p<0.01), dysplasia and hyperplasia of lymphatic tissue (p<0.05). Conversely chronic inflammation, activity and HP in the cardia were significantly higher than in the corpus (p<0.001), similarly IM and lymphoid follicles (p<0.01), atrophy and dysplasia (p<0.05)., Conclusion: The incidence of carditis and antral gastritis associated with H.pylori infection was equally expressed and reached a higher score than corporal gastritis. Inflammatory infiltration of the cardia may play a crucial role in the pathogenesis of non-ulcer dyspepsia.