Helicobacter heilmannii gastritis: a histological and immunohistochemical trait

AIM: Biopsies of the gastric antrum were reviewed over a period of 10 years to determine the prevalence of Helicobacter heilmannii in symptomatic subjects from this geographical area and to relate its presence to distinctive histopathological and immunohistochemical features. METHODS: Biopsies from 7926 symptomatic patients were reviewed. Ten serial sections were stained with haematoxylin and eosin for conventional histology. Another 10 sections were stained with the Gram method for spiral bacteria. When H heilmannii was suspected, 10 additional serial sections were stained with methylene blue to obtain homogeneous colouring. An equal number of sections from patients affected by isolated H heilmannii or H pylori gastritis were analysed by immunohistochemistry to evaluate lymphoid aggregate/mucosal lymphocyte clonality (CD20 and CD3) and tumour necrosis factor alpha (TNF-alpha) in stromal cells. RESULTS: The prevalence of H heilmannii was 0.1% (eight of 7926), whereas H pylori was present in 60.7% of patients (4813 of 7926). In two of the eight H heilmannii positive patients both helicobacters were found. In all subjects infected by H heilmannii only, distinctive histology (lymphocyte exudation into gastric foveolae) was seen. Lymphoid aggregates, chronic mucosal inflammation with patchy activity, and the absence of epithelial mucus depletion were regular features of H heilmannii gastritis. Immunohistochemistry did not reveal different lymphocyte clonal patterns between H pylori and H heilmannii gastritis: CD20 positive cells were predominant in the centre of aggregates and mucosal infiltrates, whereas CD3 positive cells were prevalent at the periphery of follicles. Only H pylori gastritis showed a significant increase in TNF-alpha positive stromal cells. CONCLUSION: These data suggest that an unusual lymphocyte reaction, with the tendency to invade the foveolar lumen, is a distinctive histopathological aspect of H heilmannii chronic gastritis, although further studies in a larger series are necessary to confirm this fact. Nevertheless, lymphocyte clones do not differ qualitatively from those found in H pylori infection. Moreover, compared with H heilmannii, H pylori provokes a more intense release of TNF-alpha, suggesting that different inflammatory responses exist to these two organisms.     

Helicobacter heilmannii infection: clinical, endoscopic and histopathological features in Japanese patients

Gastric biopsy materials of 4074 consecutive Japanese patients undergoing esophagogastroduodenoscopy were reviewed, along with those of 15 patients with Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa-associated lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection, the materials were examined by transmission electronmicroscopy. Urea breath test (three patients) and antibody test (five patients) were performed in patients with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive series. In chronic gastritis, the gastric mucosa was endoscopically normal (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed no epithelial change, mild mononuclear cell infiltration, and slight and focal neutrophil infiltration; Helicobacter heilmannii was positive with anti-H. pylori antibody, and was detected in the mucous gel layer and in foveolae. In MALT lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds without ulcers (two cases), with small ulcers (one case), or with multiple erosions (one case). Urea breath test and antibody test were both negative. Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter heilmannii infection is therefore uncommon in Japanese adults, but is associated with chronic gastritis and gastric MALT lymphoma.     

Evaluation of diagnostic methods for Helicobacter pylori gastritis

The authors evaluated the use of direct Gram-stained smears, 1- and 24-hour urease broth tests, histologic examination, and culture to detect Helicobacter pylori in 100 gastric biopsy specimens from 97 patients with epigastric symptoms. Twenty-six patients had positive cultures and 27 had H. pylori identifiable in hematoxylin and eosin-stained sections. The gastric biopsy specimens from the 29 patients with culture and/or histologic findings positive for H. pylori showed active gastritis in 27 cases (93%), compared with 26 cases (37%) without H. pylori (P less than 0.0001). Chronic gastritis was present in 25 cases (86%) with H. pylori and 40 cases (56%) without H. pylori (P less than 0.01). Twenty patients had positive Gram-stained smears. Fifteen patients had positive 1-hour urease tests, and 3 had delayed positive 24-hour urease tests. There were no false-positive Gram's stain results, three false-positive 24-hour urease tests, two false-negative histologic results, and three false-negative cultures (one inadvertently incubated anaerobically). The sensitivities of the methods were as follows: 62% for the 24-hour urease test, 69% for direct Gram's stain, 90% for culture, and 93% for histologic examination. The authors conclude that the urease test used in this study has low sensitivity and limited specificity; that the direct Gram-stained smear is a useful, highly specific, rapid screening test; and that the lengthier methods of culture and histologic examination have comparably high sensitivity for the definitive diagnosis of H. pylori gastritis.     

Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis.

We have observed expansions of intraepithelial lymphocytes in duodenal biopsies from patients with Helicobacter pylori gastritis. This study was undertaken to prospectively evaluate, unselected, paired gastric and duodenal biopsies from 50 patients with H. pylori gastritis and a comparison group of 30 patients with other types of gastritis (10 autoimmune and 20 reactive) to: (1) quantify duodenal intraepithelial lymphocytes, determine their distribution patterns, epithelial location, and phenotype, and (2) correlate the intraepithelial lymphocyte elevations with various features of gastric and duodenal pathology. Intraepithelial lymphocytes were analyzed with antibodies including CD3, CD8, and TIA-1. A stain for H. pylori was performed on all gastric and duodenal biopsies. Duodenal intraepithelial lymphocytes from patients with H. pylori gastritis (using CD3) ranged from 3 to 42 lymphocytes/100 epithelial cells (mean 18.5) compared to 3 to 18 lymphocytes/100 epithelial cells (mean 6.6) in the comparison group. Intraepithelial lymphocyte elevations were seen in 44% of the duodenal biopsies from patients with H. pylori gastritis (using CD3). Significant differences in the intraepithelial lymphocyte counts between patients with H. pylori gastritis and the comparison group were seen for all three T-cell antigens (P<0.001 for CD3 and CD8 and P<0.002 for TIA-1). Duodenal intraepithelial lymphocytes in the H. pylori+ cases had a latent cytotoxic phenotype, H. pylori was not visualized in any of the duodenal biopsies from patients with H. pylori gastritis, and no patient had clinical evidence of celiac disease. Our study highlights frequent duodenal intraepithelial lymphocytosis in individuals with H. pylori gastritis and the lymphocyte distribution patterns (and numbers) overlapped with those described for celiac disease patients. H. pylori gastritis must be considered as a possible explanation for duodenal intraepithelial lymphocytosis with normal villous architecture, especially when lymphocytosis is patchy, intraepithelial lymphocytes display a 'latent' cytotoxic phenotype, and the clinical findings and serologic profile does not fit celiac disease.     

High prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic Hispanics.

In this study, we estimated the prevalence of Helicobacter pylori infection and histologic gastritis in 58 asymptomatic Hispanic adult volunteers (mean age, 41 years; 59% male) by endoscopic biopsy of the upper gastrointestinal tract. Forty-six subjects (79%) were found to harbor H. pylori in gastric biopsies, and all had histologic gastritis. Four other subjects were found to have gastritis in the absence of H. pylori. Similar prevalences of H. pylori and gastritis were noted in all age groups and also in American-born and immigrant Hispanics. Biopsy data and serologic studies of H. pylori antibodies correlated well. We conclude that H. pylori infection is an almost universal finding in the gastric mucosa of asymptomatic adult Hispanics, regardless of age. The clinical significance of these findings is unknown, but we speculate that H. pylori and its associated gastritis could have a role in the high incidence of gastric carcinoma in Hispanic populations.     

Duodenal bulb biopsy findings for patients with non-ulcer dyspepsia with or without Campylobacter pylori gastritis

Duodenal bulb biopsy specimens from 85 patients with non-ulcer dyspepsia (30 of whom had normal stomachs and 52 of whom had Campylobacter pylori gastritis) were examined for the presence and amount of gastric surface epithelial metaplasia (using both the hematoxylin and eosin stain and the Alcian blue-periodic acid-Schiff method), acute inflammation, and C. pylori (using the Giemsa stain). Gastric metaplasia occurred in the duodenal bulb in 61% of patients with gastric C. pylori and in an identical percentage for those who lacked C. pylori gastritis. For patients with gastric metaplasia, foci of metaplastic cells were seen in 70% of their bulb biopsy fragments. The Alcian blue-periodic acid-Schiff stain was superior to the hematoxylin and eosin stain for detecting gastric metaplasia. Only one of 33 patients without gastric C. pylori had gastritis and duodenitis. Fourteen of 52 (27%) patients with C. pylori gastritis had duodenitis; C. pylori was seen in the duodenal biopsy specimens from 13 of these patients. The organisms were often few, requiring oil immersion microscopy for detection. Each patient with duodenitis had gastric metaplasia, but some of these metaplastic foci were not inflamed. When present in the duodenum of patients with C. pylori gastritis, gastric metaplasia, acute inflammation, and C. pylori are typically patchy. Hence, several biopsy fragments of the duodenal bulb would be required for studies designed to determine the effectiveness of compounds used to treat C. pylori duodenitis.     

Comparison of Helicobacter spp. in Cheetahs (Acinonyx jubatus) with and without gastritis

Chronic gastritis causes significant morbidity and mortality in captive cheetahs but is rare in wild cheetahs despite colonization by abundant spiral bacteria. This research aimed to identify the Helicobacter species that were associated with gastritis in captive cheetahs but are apparently commensal in wild cheetahs. Helicobacter species were characterized by PCR amplification and sequencing of the 16S rRNA, urease, and cagA genes and by transmission electron microscopy of frozen or formalin-fixed paraffin-embedded gastric samples from 33 cheetahs infected with Helicobacter organisms (10 wild without gastritis and 23 captive with gastritis). Samples were screened for mixed infections by denaturant gel gradient electrophoresis of the 16S rRNA gene and by transmission electron microscopy. There was no association between Helicobacter infection and the presence or severity of gastritis. Eight cheetahs had 16S rRNA sequences that were most similar (98 to 99%) to H. pylori. Twenty-five cheetahs had sequences that were most similar (97 to 99%) to "H. heilmannii" or H. felis. No cheetahs had mixed infections. The ultrastructural morphology of all bacteria was most consistent with "H. heilmannii," even when 16S rRNA sequences were H. pylori-like. The urease gene from H. pylori-like bacteria could not be amplified with primers for either "H. heilmannii" or H. pylori urease, suggesting that this bacteria is neither H. pylori nor "H. heilmannii." The cagA gene was not identified in any case. These findings question a direct role for Helicobacter infection in the pathogenesis of gastritis and support the premise that host factors account for the differences in disease between captive and wild cheetah populations.     

Chronic inactive gastritis and coccoid Helicobacter pylori in patients treated for gastroesophageal reflux disease or with H pylori eradication therapy

Gastric biopsy specimens from 105 consecutive adults with persistent dyspepsia who did not have changes due to esophageal reflux disease changes or gastric or duodenal ulcers at endoscopy were scored using the updated Sydney gastritis classification system. The medication history of proton pump inhibitors (PPIs) or Helicobacter pylori eradication therapy during the month before endoscopy was retrieved. Of the patients, 72 (68.6%) had chronic inactive gastritis, and 7 (6.7%) had antral-predominant, chronic mild active gastritis. H pylori infection was present in 36 patients (34.3%), of whom 29 had chronic inactive gastritis. Forty-six patients (43.8%) had a positive medication history, including 40 (56%) of 72 with chronic inactive gastritis. The most common morphologic feature associated with H pylori infection was moderate chronic inactive gastritis, which was found most often in patients who had received recent PPIs or H pylori eradication therapy. Pathologists should be aware of the extensive use of these medications, their association with chronic inactive gastritis, and rare H pylori thatfrequently are coccoid shaped. Modified Giemsa stain may not be the optimal method to detect H pylori in this group of patients.     

Rapid and easy detection of Helicobacter pylori by in situ hybridization

Various in situ hybridization (ISH) methods have been used to identify Helicobacter pylori, a causative organism responsible for chronic gastritis and peptic ulcer disease, but they were hard to perform and time consuming. To detect H. pylori in a rapid and easily reproducible way, we developed synthetic biotinylated oligonucleotide probes which complement rRNA of H. pylori. Formalin-fixed and paraffin-embedded tissues from 50 gastric biopsy specimens were examined. Using a serologic test and histochemical stain (Warthin-Starry silver stain and/or Giemsa stain) as a standard, 40 of them were confirmed to be H. pylori-positive. Our ISH was quickly carried out within one hr and results were compared with those obtained from immunohistochemical stain. The ISH produced a positive reaction in 38 of 40 cases (95%). All H. pylori-negative cases failed to demonstrate a positive signal. The ISH has a sensitivity comparable to those of conventional histochemical and immunohistochemical stain, and has high specificity. In conclusion, ISH with a biotinylated oligonucleotide probe provides a useful diagnostic method for detecting H. pylori effectively in routinely processed tissue sections.     

Differing degree and distribution of gastritis in Helicobacter pylori-associated diseases

Infection with Helicobacter pylori (H. pylori) causes gastritis, and may be associated with gastric and duodenal ulcers and also with such malignant diseases as MALT lymphoma and gastric carcinoma. In order to determine whether there are differences in the degree and distribution of gastritis, each patient with H. pylori gastritis only (n = 50) was matched for sex and age with four patients, one each with H. pylori-associated duodenal ulcer, gastric ulcer, gastric carcinoma or MALT lymphoma. From each patient, two biopsies were taken from the antrum and two from the corpus for histopathological examination of H. pylori gastritis. The median summed gastritis score decreases in the following order: antrum: gastric ulcer > duodenal ulcer > gastritis alone > carcinoma > MALT lymphoma, and corpus: gastric ulcer > carcinoma > MALT lymphoma > gastritis alone and duodenal ulcer. We conclude that the degree and distribution of H. pylori gastritis differs significantly among H. pylori-associated diseases. These differences may explain some of the underlying pathomechanisms associated with H. pylori infection.     

Helicobacter heilmannii-associated gastritis: clinicopathologic findings and comparison with Helicobacter pylori-associated gastritis

The aims of this study were to evaluate the clinicopathologic features of Helicobacter heilmannii-associated gastritis and to compare H. heilmannii-associated gastritis with H. pylori-associated gastritis. We reviewed 5,985 consecutive gastric biopsy specimens. All cases of chronic gastritis with Helicobacter infection were evaluated with the Updated Sydney System, and the grades of all gastritis variables were compared between H. heilmannii-associated gastritis and H. pylori-associated gastritis groups. There were 10 cases of H. heilmannii-associated gastritis (0.17%) and 3,285 cases of H. pylori-associated gastritis (54.9%). The organisms were superficially located within the mucous layer without adhesion to epithelial cells. Interestingly, in one case many intracytoplasmic H. heilmannii organisms were observed in parietal cells with cell damage. A case of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma concomitant with H. heilmannii infection was detected. Compared to H. pylori-associated gastritis, H. heilmannii-associated gastritis showed less severe neutrophilic activity (p<0.0001), mononuclear cell infiltration (p=0.0029), and endoscopic findings of chronic gastritis devoid of erosion or ulcer (p=0.0309). In conclusion, we present the detailed clinicopathologic findings of H. heilmanniiassociated gastritis compared to H. pylori-associated gastritis. H. heilmannii-associated gastritis is uncommon and milder than H. pylori-associated gastritis, however it may be noteworthy with respect to the development of MALT lymphoma.     

Nodular gastritis and pathologic findings in children and young adults with Helicobacter pylori infection

PURPOSE: The aim of this study was to investigate the pathologic characteristics of nodular gastritis in children and young adults infected with Helicobacter pylori (H. pylori). MATERIALS AND METHODS: A total of 328 patients were enrolled in this study, and the diagnosis of H. pylori infection was done with gastroduodenal endoscopy concomitant with a CLO(TM) test and pathologic analysis of the biopsy specimens. Diagnoses of normal, superficial gastritis, nodular gastritis, and peptic ulcer disease were made from the gastroduodenal endoscopic findings. The density of H. pylori organisms in the gastric mucosa was rated as normal, mild, moderate, or marked. The pathologic findings of nodular gastritis were based on the histopathologic findings of inflammation, immune activity, glandular atrophy and intestinal metaplasia. Each of these findings was scored as either normal (0), mild (1), moderate (2), or marked (3) according to the updated Sydney system and using visual analog scales. The gastritis score was the sum of the four histopathologic scores. RESULTS: In this study, nodular gastritis (50.6%) was most common, and mild density (51.5%) H. pylori infection was also common upon microscopic examination. Intestinal metaplasia occurred in 9 patients (2.7%). CONCLUSION: Logistic regression revealed a significant increase in the incidence of nodular gastritis with gastritis score (p=0.008), but not an association with sex, age, or H. pylori density. Gastritis score was the only significant factor influencing the occurrence of nodular gastritis. Intestinal metaplasia, which was originally thought to be a pre-malignant lesion, occurred in 2.7% of the patients with H. pylori infection.     

Endoscopic biopsy pathology of Helicobacter pylori gastritis. Comparison of bacterial detection by immunohistochemistry and Genta stain.

OBJECTIVES: To describe the endoscopic biopsy pathology of Helicobacter pylori gastritis, compare bacterial detection by immunohistochemistry using a specific antibody with the Genta stain, and to compare the relative costs of the 2 techniques. DESIGN: One hundred cases of gastritis identified as positive for H pylori by Genta stain and 100 cases considered negative by the same technique were stained using an anti-H pylori-specific polyclonal antibody. Laboratory reagent and labor costs for the 2 methods were compared. RESULTS: Chronic active gastritis with lymphoid follicles was significantly associated with H pylori infection (P <.0001). The immunohistochemical method had a sensitivity of 97% and a specificity of 98% compared with the Genta stain, with strong agreement for grading density of organisms (kappa = 0.85; P <.001). Reagent costs were similar for both methods, but immunohistochemistry using an autoimmunostainer required less dedicated technical time and hence was less expensive than the Genta stain. CONCLUSIONS: Immunohistochemistry using a specific antibody is an accurate and cost-effective method for H pylori detection in gastric biopsies.     

Helicobacter pylori infection and the development of gastric cancer

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.     

Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.     

Helicobacter (Campylobacter) pylori in gastric brushing cytology.

Helicobacter (formerly Campylobacter) pylori is frequently associated with chronic gastritis and peptic ulcer and has been implicated as an etiologic agent. Identification of H. pylori is important for specific treatment with antibiotics and bismuth compounds. We studied 27 patients who presented with symptoms of gastritis or peptic ulcer on whom paired gastric biopsies and gastric brushings for cytology had been performed. Biopsies were stained with H & E and Warthin-Starry or Giemsa for H. pylori. Previously, Papanicolaou-stained brushings were restained with Giemsa and reviewed blindly by two cytologists. Cytologic examination revealed the characteristic 1-3 mu curved or spiral gram-negative bacilli embedded in mucus in 12 of 27 (44%) of cases. Biopsies showed H. pylori in 13 of 27 (48%) of cases. Cytology and histology were concordant in 22 of 27 (81%) of cases. Three cases were positive on biopsy, negative on cytology; two of these were unsatisfactory cytology specimens. Two cases were positive on cytology, negative on biopsy, apparently sampling artifacts. Papanicolaou-stained slides were scored for several morphologic parameters; numbers of acute and chronic inflammatory cells and degree of cytologic atypia. None of these were predictive of the presence of H. pylori. We conclude that Giemsa-stained gastric brushings are a useful complement to gastric biopsies in establishing the diagnosis of H. pylori.     

Association of Helicobacter pylori with gastritis and peptic ulcer diseases

The occurrence of Helicobacter pylori(H.pylori) and its relationship with gastric mucosa were studied by light and electron microscopy and culture of biopsy specimens from gastric mucosa of 160 patients with upper gastrointestinal symptoms. H. pylori were present in 96.6% of patients with active chronic gastritis, 100% of patients with duodenal ulcer and 76.9% of patients with gastric ulcer, while present in only 6.3% of individuals with histologically normal gastric mucosa. The bacteria colonized the antral mucosa more frequently than the body or than the duodenal cap mucosa. The bacteria were rarely seen in the intestinalized epithelium per se, but there was no significant difference in prevalence of H. pylori between gastritis with intestinal metaplasia and gastritis without intestinal metaplasia. H. pylori could be seen in close association with the surface of gastric epithelial cells below the mucus layer without evidence of intracellular parasitism, All of the strains tested were susceptible to penicillin, erythromycin, and most of them susceptible to tinidazole and bismuth salts. It is concluded that H. pylori are highly associated with gastritis and peptic ulcer diseases and its prevalence rates in patients with those diseases is higher than in developed countries. This strong association of H. pylori infection with gastritis and peptic ulcer diseases suggest a possible etiologic role for the bacterium in those diseases.     

Mast cells in Helicobacter pylori associated antral gastritis

Mast cells are known to be effector cells in various inflammatory reactions, but their role in gastritis is unclear. The present study was undertaken to investigate the extent of mast cell involvement in antral gastritis with and without Helicobacter pylori (H. pylori) infection and thus evaluate the possible role of mast cells in the pathogenesis of H. pylori-associated gastritis. Antral mucosal biopsies were taken from 212 subjects with symptoms suggestive of acid peptic disease. Sections were assessed for inflammation. Modified Giemsa stain was used to detect H. pylori infection and 1% toluidine blue to count mast cells. Mast cell counts were significantly higher in the antral mucosa even in H. pylori-negative gastritis (68.4 +/- 6.7/mm2), as compared to normal non-inflamed mucosa (45.7 +/- 5.8/mm2) (P < 0.05). However, with H. pylori infection, the mucosal mast cell count were markedly increased (123.8 +/- 4.7/mm2) as compared to normal mucosa (P < 0.01). and H. pylori-negative gastritis (P < 0.01) this increase was noticed uniformly in patients with H. pylori-positivity, irrespective of the presence or absence of a peptic ulcer. After cure of H. pylori infection, the mast cell density decreased significantly (44.9 +/- 4.6/mm2) to reach levels that were similar to those in normal mucosa. There was a positive correlation between the antral mucosal mast cell density and polymorphonuclear and mononuclear cell infiltration (rs = 0.61). H. pylori infection, and 0.73 respy. It was concluded that could be responsible for increasing the mast cell density in the gastric antrum. Probably by inducing castain mucosal cytokine.     

Acute inflammation of the proliferative zone of gastric mucosa in Helicobacter pylori gastritis.

The neutrophilic infiltration has been regarded to represent the activity of Helicobacter pylori gastritis. It may involve the epithelium and/or lamina propria. The incidence and degree of the two types of infiltration do not correlate with each other frequently. We correlated the two types of neutrophilic infiltration with H. pylori infection and other pathologic parameters respectively in 300 randomly selected gastric biopsies as well as serial biopsies from a separate group of 95 patients who were treated for H. pylori infection. The "random biopsies" had chronic gastritis of various degrees, and the organisms were identified in 239 cases (79.7%); in the "treated group," the organisms disappeared completely in 62 cases (65.3%). Characteristically, the intraepithelial neutrophilic infiltration was predominantly localized to the proliferative zone of the gastric mucosa (zone 2) where the density of H. pylori was considerably lower than the surface epithelium. In the "random biopsies," both acute epithelial and interstitial neutrophilic infiltration correlated significantly (p < 0.01) with the H. pylori infection. In the "treated group," however, only acute epithelial inflammation correlated significantly (p < 0.01) with the eradication of infection while acute interstitial inflammation did not. Acute epithelial inflammation was no less frequently present in advanced chronic gastritis than in early chronic gastritis. Acute epithelial inflammation of the proliferative zone is a characteristic pathologic finding of H. pylori gastritis, and appears to be directly associated with the pathogenesis of H. pylori gastritis and its progression.     

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.