The phenotype of gastric mucosa coexisting with Barrett's oesophagus

BACKGROUND/AIMS: Barrett's oesophagus complicates the gastro-oesophageal acid reflux. Helicobacter pylori infection, particularly with cagA positive strains, induces inflammatory/atrophic lesions of the gastric mucosa, which may impair acid output. No systematic study has investigated the phenotype of the gastric mucosa coexisting with Barrett's oesophagus. This study was designed to identify the phenotype of gastric mucosa associated with Barrett's oesophagus. METHODS: In this retrospective case control study, the phenotype of the gastric mucosa was histologically characterised in 53 consecutive patients with Barrett's oesophagus and in 53 (sex and age matched) non-ulcer dyspeptic controls. Both patients and controls underwent extensive sampling of the gastric mucosa (two antral, one incisural, and two oxyntic biopsies). Intestinal metaplasia (IM) was categorised (type I, complete IM; types II and III, incomplete IM) by the high iron diamine stain; cagA status was ascertained by genotyping. RESULTS: Helicobacter pylori was present in 19 of the 53 patients with Barrett's oesophagus and in 30 of the 53 controls (p < 0.02); eight of the 19 patients with Barrett's oesophagus and 28 of the 35 controls harboured cagA positive H pylori (p < 0.03). The histological severity of non-atrophic gastritis detected in the controls was significantly higher than that detected in the patients with Barrett's oesophagus (p < 0.0001). Multifocal atrophic gastritis was present in 4% of the patients with Barrett's oesophagus and in 23% of controls (p < 0.01). The odds ratio for the association between multifocal atrophic gastritis and Barrett's oesophagus was 0.20 (95% confidence interval, 0.006 to 0.60). Gastric IM was detected in 13.2% of the patients with Barrett's oesophagus and in 30.1% of the controls (p < 0.03). Type III IM at the gastric mucosa was only detected among controls. CONCLUSIONS: Barrett's oesophagus is associated with a low prevalence of H pylori cagA positive infection and multifocal atrophic gastritis. This pathobiological pattern is considered to be associated with a low risk of distal gastric cancer.     

Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence

Polarized immune response to Helicobacter pylori and induction of chronic inflammation may increase the risk of gastric atrophy and adenocarcinoma. We studied the association of the response of IgG1 and IgG2 antibodies to H. pylori with grade of gastric chronic inflammation and atrophy in a population with a high prevalence of H. pylori, and compared these data with the data obtained from the study of gastric cancer patients, as well as with the data for CagA positivity. Altogether, 114 persons from two adult population samples from Estonia and 45 consecutive gastric cancer patients were studied. All patients were positive for the H. pylori antibody determined by ELISA. Adenocarcinoma was classified histologically according to the Laurén's system. The response of the IgG subclasses to H. pylori (acid glycine-extracted whole cell proteins) was determined by ELISA and the results were compared with the ELISA results for the recombinant fragment of the CagA protein. Helicobacter pylori IgG level was lower in atrophic gastritis compared with nonatrophic gastritis (chronic inflammation) (p=0.001). In the group of cancer patients, the response of IgG and IgG1 was lower compared with both gastritis groups (p=0.01 and p=0.0002 for IgG, and p=0.001 and p=0.0005 for IgG1). IgG2 was lower for gastric cancer localized in the corpus (p=0.03). In conclusion, atrophic gastritis and gastric cancer were associated with a significant decline in IgG and IgG1 response to H. pylori compared with nonatrophic gastritis. Higher value of CagA antibodies was seen in gastric cancer and in gastric atrophy compared with nonatrophic gastritis; in gastric cancer patients, IgG1 response to H. pylori was correlated with CagA status.     

Helicobacter pylori infection in patients with Barrett's oesophagus: a prospective immunohistochemical study.

The prevalence of Helicobacter pylori infection in patients with Barrett's oesophagus was studied prospectively. A sensitive immunohistochemical staining of H pylori was performed in oesophageal and gastric biopsies of 73 patients from a surveillance group with this condition. H pylori was detected in 11 cases of Barrett's mucosa (15%) and in 26 gastric mucosa specimens (35.6%). All cases positive in Barrett's mucosa were also positive in the stomach. In Barrett's oesophagus, H pylori was never found on specialised epithelium. The percentage of Barrett's mucosa showing inflammatory changes was similar in specimens with and without H pylori, both for chronic (81% v 79%) and acute (9% v 10%) infiltrates. These results indicate that H pylori infection does not play an aetiological role in Barrett's oesophagus and that colonisation of the metaplastic mucosa by this bacteria is related with the presence of gastric type mucosa in the oesophagus and of H pylori infection in the stomach.     

Cytokeratin 7 and 20 expression in intestinal metaplasia of the distal oesophagus: relationship to gastro-oesophageal reflux disease

AIMS: Intestinal metaplasia and gastro-oesophageal reflux disease typify classical Barrett's oesophagus. Cytokeratin (CK) 7 and 20 phenotypes differentiate intestinal metaplasia in long segment Barrett's oesophagus from gastric intestinal metaplasia. This study examines the relationship between CK7/20 phenotypes and reflux disease in intestinal metaplasia of the distal oesophagus. METHODS AND RESULTS: Eighty patients with oesophageal pH studies included 30 with long segment Barrett's, 16 with short segment Barrett's and 34 with intestinal meatplasia of the gastro-oesophageal junction. Representative biopsy specimens were immunostained for CK7 and CK20. All 30 long segment patients demonstrated a Barrett's CK7/20 phenotype. All nine short segment patients with gastro-oesophageal reflux had a Barrett's CK7/20 phenotype, while four of seven short segment patients without reflux had a gastric CK7/20 phenotype (P = 0.019). Of 14 patients with intestinal metaplasia of the gastro-oesophageal junction and reflux, 10 (71%) had a Barrett's CK7/20 phenotype, compared with 11 (55%) of the 20 non-reflux patients. CONCLUSIONS: CK7/20 immunoreactivity for patients with intestinal metaplasia of the distal oesophagus without long segment Barrett's oesophagus suggests a heterogeneous group, with an association between Barrett's CK7/20 pattern and gastro-oesophageal reflux disease in both short segment Barrett's and intestinal metaplasia of the gastro-oesophageal junction.     

Role of corpus gastritis and cagA-positive Helicobacter pylori infection in reflux esophagitis

Considering that the role of Helicobacter pylori infection in gastroesophageal reflux and reflux esophagitis (GERD) is still controversial and that the role of virulence markers of the bacterium has not been evaluated in most studies of GERD, we investigated the association among H. pylori infection with cagA-positive and -negative strains, corpus gastritis, and GERD in a large group of patients by controlling for confounding factors. We studied prospectively 281 consecutive adult patients: 93 with GERD and 188 controls. H. pylori infection status was diagnosed by culture, by the preformed urease test, with a carbolfuchsin-stained smear, and by histology. The cagA status was determined by PCR of H. pylori isolates and gastric biopsy specimens. H. pylori infection was diagnosed in 191 (68.0%) of 281 patients. Among the 93 patients with GERD, 84 presented with mild or moderate esophagitis and 9 presented with severe esophagitis. In the multivariate analysis, the age of the patients and the degree of oxyntic gastritis were associated with GERD. Among the strains isolated from patients with GERD and from the control group, 24.4 and 66.9%, respectively, were positive for cagA (P < 0.001). Compared to infection with cagA-negative strains, infection with cagA-positive H. pylori strains was associated with a more intense gastritis in the corpus (P = 0.001). cagA status (odds ratio [OR] = 0.16, 95% confidence interval [CI] = 0.07 to 0.40), gastritis of the corpus (OR = 0.69, 95% CI = 0.48 to 0.99), and age (OR = 1.04, 95% CI = 1.01 to 1.07) were associated with GERD. In conclusion, the study provides evidence supporting the independent protective roles of cagA-positive H. pylori strains and the degree of corpus gastritis against GERD.     

Helicobacter pylori and gastroesophageal reflux disease

The latest accessible data indicate, that Helicobacter pylori (H.p.) infection, particularly by cagA-positive strains, protects against the development of gastroesophageal reflux disease (GERD) and its complications. Various epidemiological, pathophysiological and clinical studies demonstrate this protective effect, which is dependent on the extent of H.p. induced gastritis. Severe corpus gastritis may cause a profound reduction of acid secretion. In regard to acute or chronic PPI therapy of GERD the biological antisecretory effect of H.p. is of minor benefit. Development of atrophic gastritis in patients with GERD treated chronically with PPI is still uncertain. On account of the protective effect of H.p. against GERD, it is prudent to reserve H.p. eradication for the well-established indications.     

Early adenocarcinoma of the oesophagus and oesophageal cyst

Aims : An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. Methods and results : We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. Conclusions : As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

Reflux gastritis in gastroesophageal reflux disease: A histopathological study.

Increased intragastric alkaline reflux has been documented in patients with reflux esophagitis; however, the effect on gastric histology has not been investigated in this population. We examined gastric biopsies from 72 non-acid-suppressed patients with gastroesophageal reflux disease (GERD) for changes of reflux gastritis or other forms of gastritis. In the Helicobacter pylori-negative GERD patients (n = 52) using the Dixon scoring system for reflux gastritis with a threshold score of >/=11, reflux gastritis was found in 15% (three of 20) of GERD patients with erosions and in no GERD patients without erosions. When the reflux gastropathy threshold score was changed to more than 8, 90% (18 of 20) of GERD patients with erosions and 19% (six of 32) of GERD patients without erosions were classified as having reflux gastritis. Regardless of the reflux gastritis threshold used, only 14% (seven of 52) of the H pylori-negative GERD patients exhibited normal gastric histology. Inactive chronic gastritis or nonspecific reactive changes were histologic findings in those gastric biopsies not classified as reflux gastritis or normal. All H pylori-positive GERD patients (n = 20) had active chronic gastritis. We conclude that most GERD patients will exhibit some form of gastric pathology: either reflux gastritis, chronic gastritis, or nonspecific reactive changes, depending on what reflux threshold score is applied and the presence of H pylori. Studies to define the intragastric alkaline content in conjunction with gastric histopathology need to be performed to further define those reflux esophagitis patients with reflux gastritis.     

CagA antibodies in Japanese children with nodular gastritis or peptic ulcer disease

cagA(+) Helicobacter pylori strains have been linked to more severe gastric inflammation, peptic ulcer disease, and gastric cancer in adults, but there have been few studies of cagA in children. We examined the relationship between H. pylori cagA status and clinical status in Japanese children. Forty H. pylori-positive children were studied: 15 with nodular gastritis, 5 with gastric ulcers, and 20 with duodenal ulcers. H. pylori status was confirmed by biopsy-based tests and serum anti-H. pylori immunoglobulin G (IgG) antibody. As controls, 77 asymptomatic children with sera positive for anti-H. pylori IgG were enrolled. Levels of IgG antibodies to CagA in serum were measured by an antigen-specific enzyme-linked immunosorbent assay. In 16 patients with successful H. pylori eradication, posttreatment levels of CagA and H. pylori IgG antibodies also were studied. The CagA antibody seropositivities of asymptomatic controls (81.8%) and patients with nodular gastritis, gastric ulcers, and duodenal ulcers (80.0 to 95.0%) were not significantly different. Compared with pretreatment levels of CagA antibodies, posttreatment levels decreased progressively and significantly. We conclude that, as in Japanese adults, a high prevalence of cagA(+) H. pylori strains was found in Japanese children, and that there was no association with nodular gastritis or peptic ulcer disease. In the assessment of eradicative therapies, monitoring of serum anti-CagA antibodies does not appear to offer any direct benefit over monitoring of anti-H. pylori antibodies.     

Antimicrobial susceptibility testing of Helicobacter pylori to selected agents by agar dilution method in Shiraz-Iran

PURPOSE: To assess the pattern of antimicrobial susceptibility profile of Helicobacter pylori isolates from patients with gastritis, duodenal ulcer (DU) and gastroesophageal reflux disease (GERD) residing in Shiraz, Iran. METHODS: One hundred and six H. pylori isolates from patients with gastritis, DU and GERD undergoing endoscopy at our university hospitals and clinics were analysed for their antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin, co-amoxiclav, tetracycline, ciprofloxacin and furazolidone. The minimum inhibitory concentrations were determined by agar dilution method. RESULTS: Overall H. pylori resistance rate was 72.6% to metronidazole, 9.4% to clarithromycin and furazolidone, 20.8% to amoxicillin and 4.7% to tetracycline and ciprofloxacin. No resistance to co-amoxiclav was detected among H. pylori isolates. No significant differences between antimicrobial resistance and clinical outcome were detected. CONCLUSIONS: With regard to the increasing resistance of H. pylori isolates to various antibiotics, susceptibility testing of H. pylori isolates prior to the treatment of infection must be performed to achieve better eradication and to reduce the risk of selection of H. pylori resistant strains.     

The gastric cardia in gastro-oesophageal disease

BACKGROUND: There have been conflicting reports concerning the use of cardia biopsies in screening patients for gastro-oesophageal disease. AIM: To define the histopathological changes in the gastric cardia of patients with and without gastro-oesophageal disease. METHODS: Topographically mapped gastric biopsy specimens were obtained from patients with gastro-oesophageal disease and from controls. Biopsies were scored on a visual analogue scale of 0 to 5 for Helicobacter pylori, intestinal metaplasia, pancreatic metaplasia, foveolar hyperplasia, and active inflammation. The presence or absence of cardiac glands was recorded. RESULTS: Sixty-five patients with gastro-oesophageal disease and 71 controls were examined. Intestinal metaplasia was present in cardia biopsies of 10 patients with gastro-oesophageal disease and 11 controls. Only two patients with gastro-oesophageal disease and intestinal metaplasia in the cardia had no evidence of exposure to H pylori. Intestinal metaplasia was not found in the cardia of those with long segment Barrett's oesophagus. Carditis was strongly associated with active H pylori infection (p = 0.000) and resolved after treatment of the infection. A negative association was present between gastro-oesophageal disease and the presence of cardiac glands in cardiac biopsies (p = 0.003). Pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastro-oesophageal disease. CONCLUSION: Intestinal metaplasia in the cardia is uncommon in gastro-oesophageal disease in the absence of H pylori infection. With chronic H pylori infection the junction between the cardia and corpus expands in a cardia-corpal direction.     

Prevalence of serum antibodies to Helicobacter pylori VacA and CagA and gastric diseases in Chile

The objective of this study was to evaluate the prevalence of antibodies to Helicobacter pylori CagA and VacA proteins and correlate this prevalence with gastric diseases in colonised Chileans. The study was performed in 418 adults colonised with H. pylori: 316 with gastroduodenal pathology (152 duodenal ulcer, 14 gastric cancer and 150 gastritis patients) and 102 asymptomatic subjects. Serum IgG antibodies to H. pylori were determined by enzyme immunoassay (EIA). Antibodies to VacA and CagA proteins were detected by Western blotting. In a subgroup of the patients, the vacuolating activity was determined by HeLa cell assay and the CagA product was confirmed by PCR assay. IgG antibodies to both VacA and CagA proteins of H. pylori were found in 270 (85%) of 316 colonised gastric patients and in 72 (71%) of 102 asymptomatic subjects. Colonisation with virulent strains was significantly higher among duodenal ulcer and gastric cancer patients than in gastritis patients or asymptomatic subjects. Infections with VacA+/ CagA+ H. pylori strains is common in Chile but, in contrast to some Asian countries, this phenotype was more prevalent in isolates from patients with more severe gastric pathologies.     

Bile reflux and intestinal metaplasia in gastric mucosa.

AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis.     

Human defensin 5 expression in intestinal metaplasia of the upper gastrointestinal tract

BACKGROUND: Upper gastrointestinal tract intestinal metaplasia (IM) is termed Barrett's oesophagus (BO) or gastric intestinal metaplasia (GIM), depending on its location. BO and GIM are associated with chemical exposure resulting from gastro-oesophageal reflux and chronic Helicobacter pylori infection, respectively. Paneth cells (PCs), characterised by cytoplasmic eosinophilic granules, are found in a subset of IM at these sites, but histology may not accurately detect them. AIM: To determine human defensin 5 (HD5; an antimicrobial peptide produced by PCs) expression in BO and GIM, and to investigate its association with H pylori infection. METHODS: Endoscopic biopsies from 33 patients with BO and 51 with GIM, and control tissues, were examined by routine histology and for H pylori infection and HD5 mRNA and protein expression. RESULTS: In normal tissues, HD5 expression was specific for PCs in the small intestine. Five patients with BE and 42 with GIM expressed HD5, but few HD5 expressing cells in IM had the characteristic histological features of PCs. Most HD5 positive specimens were H pylori infected and most HD5 negative specimens were not infected. CONCLUSIONS: HD5 immunohistochemistry was often positive in IM when PCs were absent by conventional histology. Thus, HD5 immunohistochemistry may be superior to histology for identifying metaplastic PCs and distinguishing GIM from BO. The higher frequency of HD5 expression in GIM than in BO is associated with a higher frequency of H pylori infection, suggesting that in IM PCs may form part of the mucosal antibacterial response.     

Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion

BACKGROUND/AIMS: Interleukin 10 (IL-10) is a counter-inflammatory peptide implicated in the downregulation of human intestinal immune responses. Enhanced secretion of IL-10 has been documented in gastric biopsy organ culture in Helicobacter pylori infection. This study aimed to define the cellular origins of IL-10 in H pylori associated gastritis, and to determine the effects of endogenous IL-10 on proinflammatory cytokine secretion in vitro. METHODS: Endoscopic biopsies were obtained from the gastric antrum at endoscopy from patients with dyspepsia. Two pairs of antral biopsies were cultured in vitro for 24 hours, one pair in the presence of neutralising anti-IL-10 monoclonal antibody, the other pair as controls. The cytokine content of culture supernatants (tumour necrosis factor alpha (TNF-alpha), IL-6, and IL-8) was determined by enzyme linked immunosorbent assay and corrected for biopsy weight. Helicobacter pylori status was established by histology and biopsy urease test, and histopathology graded by the Sydney system. In a subgroup of patients, western blotting was used to establish CagA serological status. Immunohistochemistry for IL-10 was performed on formalin fixed tissues using a combination of microwave antigen retrieval and the indirect avidin-biotin technique. Immunoreactivity was scored semiquantitatively. RESULTS: In vitro culture was performed in 41 patients: 31 with H pylori positive chronic gastritis and 10 H pylori negative. In vitro secretion of TNF-alpha, IL-6, and IL-8 for "control" biopsies was significantly higher in H pylori positive versus negative samples, with values of TNF-alpha and IL-6 correlating with the degree of active and chronic inflammation and being higher in CagA seropositive cases. No evidence for enhanced cytokine secretion was seen in biopsies cocultured in the presence of anti-IL-10 monoclonal antibody. Immunohistochemistry was performed in 29 patients, of whom 13 were H pylori positive. IL-10 immunoreactivity was observed in the surface epithelium in all H pylori positive cases and in 13 of 16 negative cases, especially in areas of surface epithelial degeneration. Lamina propria mononuclear cells (LPMNCs) were positively stained in all H pylori positive cases and in 12 of 16 negative cases, with a significantly greater proportion of positive LPMNCs in the positive group. CONCLUSIONS: This study localised IL-10 protein to the gastric epithelium and LPMNCs. In vitro proinflammatory cytokine secretion was increased in H pylori infection (especially CagA positive infection), but blocking endogenous IL-10 secretion did not significantly increase cytokine secretion. IL-10 is implicated in H pylori infection and might "damp down" local inflammation. The role of gastric IL-10 secretion in determining the clinicopathological outcome of infection merits further study.     

Cell cycle regulation in patients with intestinal metaplasia at the gastro-oesophageal junction.

BACKGROUND/AIMS: The incidence of oesophageal adenocarcinoma is increasing rapidly and this may be related to the presence of intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ). Recent studies have distinguished two subtypes of IM at the GOJ: short segment Barrett's oesophagus (SSBO) and IM at a normal squamo-columnar junction (IMNSCJ). Because abnormal expression of cell cycle regulators is common in cancer and precancerous states, cell cycle regulation was studied in patients with IM at the GOJ. METHODS: Biopsy samples and resected materials were identified from patients with SSBO (10), IMNSCJ (14), a normal SCJ with (14) and without (12) inflammation, conventional Barrett's oesophagus (BO) (12), and oesophageal adenocarcinoma (12). Sections were stained with antibodies to p21, p27, p53, Ki67, cyclin D1, and c-erbB2 and were assessed independently by two observers, using predetermined criteria. RESULTS: Patients with oesophageal adenocarcinoma showed high expression of c-erbB2, p53, p27, and Ki67. Patients with BO showed expression of c-erbB2 but little expression of other markers. Greatly increased expression of cyclin D1 was seen in patients with IMNSCJ. The expression of all other markers was similar in patients with IMNSCJ and those with SSBO. Cyclin D1 and c-erbB-2 were coexpressed in patients with SSBO and IMNSCJ, and their expression was associated with the presence of p53 and p21. CONCLUSIONS: Although the proposed aetiologies of SSBO (gastro-oesophageal reflux) and IMNSCJ (Helicobacter pylori infection) differ, the cell cycle response is similar and both may have malignant potential.     

Atrophic gastritis in young children and adolescents

BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.     

Serum CagA antibodies in asymptomatic subjects and patients with peptic ulcer: lack of correlation of IgG antibody in patients with peptic ulcer or asymptomatic Helicobacter pylori gastritis.

AIM/BACKGROUND: Several studies have suggested that Helicobacter pylori which express CagA may be more virulent than those that do not, but limited populations have been studied to date. The aim of this study was to confirm and extend the association of CagA positive H pylori strains in a different geographical area and to a large, well defined patient population. METHOD: A validated ELISA for serum IgG to CagA was used to investigate the prevalence of CagA seropositivity in 100 patients with peptic ulcer compared with 77 with H pylori infection without ulcer disease in a North American population. The extent of antral and corpus inflammation and H pylori density in relation to CagA seropositivity in 40 subjects with H pylori infection were assessed semiquanitatively. All studies were carried out in a coded and blinded manner. RESULTS: The prevalence of serum IgG CagA antibodies was higher in H pylori infected patients with ulcer (59%) compared with healthy H pylori infected volunteers (44%), but the difference was not significant. In contrast, the titre of serum IgG anti-CagA antibodies was higher among the seropositive subjects without ulcer disease, but again the difference was not significant. Comparison of histological features between asymptomatic individuals with H pylori infection in relation to CagA IgG antibody status revealed no differences in infiltration with acute inflammatory cells, H pylori density, or gastritis index. There was no relation evident between the degree of polymorphonuclear cell infiltration and the serum IgG antibody titre to CagA. Mononuclear cell infiltration in the antrum, but not the corpus, was greater in those with CagA IgG compared with those without (median score 5 v 3). CONCLUSIONS: A right association between the presence or titre of serum IgG to CagA and peptic ulcer disease, greater H pylori density or infiltration of the mucosa with acute inflammatory cells could not confirmed in a North American population. Perhaps geographical differences in the prevalence of circulating H pylori strains are responsible for the discrepant results reported.     

Pathology of the gastric antrum and body associated with Helicobacter pylori infection in non-ulcerous patients: is the bacterium a promoter of intestinal metaplasia?

A series of 115 consecutive, non-ulcerous, dyspeptic patients were examined for Helicobacter pylori (H. pylori) colonization in the gastric antral and/or body mucosa using Giemsa staining. Findings were correlated with the presence and degree of activity of superficial gastritis, deep gastritis, atrophic gastritis and with the presence of intestinal metaplasia. The prevalence of H. pylori positivity was 61.7%. In 59 of the 71 positive patients (83%), H. pylori was detected in the antrum or in both the antral and oxyntic mucosa. In the remaining 12 positive patients, H. pylori was detected only in the oxyntic mucosa and in all these cases, the antrum showed intestinal metaplasia associated with atrophic gastritis (25%). In both antral and oxyntic mucosa, the activity of the gastritis was significantly correlated with H. pylori colonization. Linear logistic regression analysis showed that in patients with intestinal metaplasia the presence of H. pylori infection was significant in predicting the presence of more extensive intestinal metaplasia after adjusting for age. The prevalence of intestinal metaplasia types II and III was 65.5% in the H. pylori positive and 25% in the H. pylori negative patients. The antral mucosa is thought to be the elective site for H. pylori related histological lesions. At a later stage, H. pylori can be detected only in the oxyntic area while the antral mucosa shows extensive metaplastic or atrophic lesions. We would suggest that H. pylori plays a promotional role in the morphogenesis of intestinal metaplasia.     

Eradication therapy of Helicobacter pylori infection

Helicobacter pylori(H. pylori) infection is recognized to be a pathogen of various gastro-duodenal diseases. Eradication therapy of H. pylori reduces the recurrence of gastro-duodenal ulcer, and improves gastritis histologically. Recently, proton pump inhibitor(PPI) based triple therapy, that combining PPI, clarithromycin, amoxicillin is widely accepted throughout the world, and shows high eradication rate which ranged about 80-90%. In Japan, one week triple therapy is recommended for the treatment of gastro-duodenal ulcer, though it is expected the improvement of recurrent peptic ulcer. In the present studies, the rate of clarithromycin resistant strains has been increased gradually, and this fact may lead to the development of failure of PPI based triple therapy. Another problem is suggested by several studies that gastro-esophageal reflux disease(GERD) may increase after successful eradication of H. pylori. Reflux esophagitis and Barrett's esophagus are recognized as precancerous lesion of esophageal adenocarcinoma, but the association of newly occurrence of GERD after H. pylori eradication and increase of esophageal adenocarcinoma is not clear. Merits and demerits of H. pylori eradication need to be observed carefully over a long term.