Granulomatous gastritis associated with Campylobacter pylori

Three cases of granulomatous inflammation in gastric biopsies showing Campylobacter pylori infestation are described. This type of reaction to Campylobacter pylori has not previously been described, and occurred in 1.1% of gastric biopsies containing Campylobacter-like organisms (CLO), in this series of all gastric biopsies submitted for histological examination during one year. Two other cases each showed a mucosal granuloma: one was a patient with Crohn's disease and the other had foreign body giant cells in a biopsy of the edge of a healing gastric ulcer. Each of our three CLO-positive cases with granulomas showed scanty CLO's only. Thus, although granulomatous inflammation associated with CLO's is uncommon as a proportion of all CLO-positive gastric biopsies, these currently represent the commonest condition associated with granulomas in gastric biopsies, in our experience.     

Campylobacter pylori is associated with chronic gastritis but not with active peptic ulcer disease

Campylobacter pylori is supposed to be involved in the pathogenesis of gastroduodenal peptic ulcer diseases and chronic gastritis. In order to study whether the Campylobacter pylori in the stomach of peptic ulcer patients is related to ulcer itself or to a co-existing chronic gastritis, we examined the frequency of the bacteria in Giemsa stained histological sections of biopsy specimens from a series of patients with active peptic ulcer and from series of non-ulcer control subjects. We found no difference in the frequency of Campylobacter- positive cases between ulcer patients and non-ulcer controls when the comparison was done within the same category of chronic gastritis; e.g., within the category of chronic superficial gastritis 74% and 78% of cases showed the bacteria in antral biopsies from ulcer patients and from non-ulcer controls, respectively. In both ulcer patients and control subjects, in similar way in both antral and body mucosa, the Campylobacter pylori was strongly associated with chronic superficial gastritis but was more weakly associated with chronic atrophic gastritis, and the bacteria were only occasionally seen in normal mucosa. We conclude that Campylobacter pylori is associated with chronic gastritis in peptic ulcer patients but is not related to active ulcer.     

Immunocytochemical identification of Campylobacter pylori in gastritis and correlation with culture

Endoscopic biopsy specimens of antral mucosa from 25 patients presenting with gastric complaints were obtained for culture and histologic and immunocytochemical studies. The histopathologic study revealed chronic gastritis in 22 patients and borderline chronic gastritis in three patients. The unlabeled-antibody peroxidase-antiperoxidase (PAP) method was applied for the detection of Campylobacter pylori, and its results were compared with those obtained with the culture technique. Strongly positive immunoperoxidase staining was localized in spiral, curved bacteria that were present in the mucus layer adjacent to the gastric epithelial cell surface. The microorganisms were frequently congregated in clumps and were sectioned in several directions. The PAP stains were positive in 19 specimens (76%), and the cultures were positive in 20 (80%). All results negative by culture were also negative by PAP method. Compared with the cultures, the sensitivity and positive predictive value of the PAP method for identification of C pylori in antral mucosa obtained from endoscopic biopsy specimens were 95% and 100%, respectively.     

Helicobacter heilmannii gastritis: association with acid peptic diseases and comparison with Helicobacter pylori gastritis.

We analyzed 2 antral and 1 corpus full-thickness random endoscopic gastric mucosal samples obtained from 946 patients with duodenal ulcers (6077 biopsies) and from 281 patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (1794 biopsies). We stained tissue sections with hematoxylin and eosin and Warthin-Starry silver stain and immunostained them with polyclonal antibodies against Helicobacter pylori. Hematoxylin- and eosin-stained sections from 6 patients with Helicobacter heilmannii (18 biopsies) and 23 randomly selected patients with H. pylori (68 biopsies) were evaluated and semiquantitated for the presence of acute inflammation, chronic inflammation, glandular atrophy, intestinal metaplasia, H. pylori, H. heilmannii, lymphoid follicles, or vasodilatation. Additional specimens were obtained for H. pylori culture, a CLO test, and serologic examination. H. heilmannii was detected in 6 (0.49%) of 1227 patients (14 [0.18%] of 7871 biopsies). Of these, 4 (0.42%) of 946 were patients with duodenal ulcers (9 [0.15%] of 6077 biopsies), and 2 (0.71%) of 281 were patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (5 [0.28%] of 1794 biopsies). We found H. heilmannii with hematoxylin and eosin stain, Warthin-Starry stain, and immunoperoxidase stain for H. pylori. Culture for H. pylori was negative in the four patients with duodenal ulcers. The CLO and serologic tests were positive in three of five and five of five patients, respectively. Our results indicate that H. heilmannii, like H. pylori, is associated with peptic ulcer disease (both active and inactive gastritis) and that it preferentially colonizes the gastric antrum. The severity of the H. heilmannii-associated gastritis is less intense and lymphoid aggregates are less common than in H. pylori-associated gastritis. Morphologic detection seems to be the method of choice for detecting H. heilmanni. Immunoperoxidase stain specific for H. pylori also stains H. heilmannii, indicating cross-reacting antigenic epitopes between H. heilmannii and H. pylori.     

Chronic active gastritis after eradication of Campylobacter (now: Helicobacter) pylori. Results of a medium term follow-up study

11 patients with C.p.-associated chronic gastritis underwent a triple therapy with bismuth-subsalicylate, amoxicillin susp. and metronidazole. The C.p.-status and the inflammation parameters "polymorphonuclear leucocytes in the epithelium". "polymorphonuclear leucocytes in the lamina propria", "lympho-plasmacellular infiltrate in the lamina propria", "congestion and edema of the lamina propria" and "inflammatory alteration of the epithelium" were determined semi-quantitatively in semi-thin-sections by light microscopy in the same sections. The C.p.-status was verified further by means of the CLO-test and cultures. The biopsy probes were taken before treatment, immediately after treatment, 1 month following treatment and in differing time intervals up to 9 months following treatment. Eradication of C.p. could not be attained in 2 of the patients. Spherical forms and vibrioforms of C.p. exhibiting degenerative alterations could be demonstrated by electron microscopy. Throughout the study the inflammatory parameters "intraepithelial polymorphonuclear leucocytes", "polymorphonuclear leucocytes in the lamina propria", "inflammatory alterations of the epithelium" showed concordance in their reactions. They were closely correlated with the light microscopical demonstration of C.p.-organisms in the biopsy specimens. The regression of the lympho-plasmacellular infiltrate was still incomplete after 5 months of eradication. The time relationship between the end of treatment and complete remission differed. The results of our studies suggest that C.p. was the sole etiological factor for the development of chronic active gastritis in at least 4 of the 11 patients.     

Campylobacter like organisms and reflux gastritis.

A total of 98 patients, who had undergone gastric surgery (23), or who had peptic ulcers (56), or who had normal endoscopic findings (19) underwent gastric biopsy, together with measurement of pH and total bile acid concentration, in their fasting gastric juice. The biopsy specimens were stained by the Warthin-Starry method for Campylobacter like organisms and were also graded "blind," as described in the preceding paper, for the five features that we believe may constitute the histological picture of reflux gastritis. The individual grades were added together to give a composite "reflux score" (0-15) for each patient. We found a notable association between the absence of Campylobacter like organisms and previous surgery for peptic ulceration, high reflux scores (greater than 10), hypochlorhydria (pH greater than or equal to 4), and increased bile acid concentrations (greater than or equal to 1 mmol/l) in the stomach. These findings further support our contention that reflux gastritis represents a distinct histopathological entity causally related to the effects of enterogastric reflux on the gastric mucosa and suggest that there may be two major categories of chronic gastritis: chronic superficial, or atrophic gastritis related to Campylobacter like organisms and reflux gastritis. Our data also imply that patients with peptic ulceration may, after gastric surgery, revert from being positive for these organisms to being negative and may undergo a possible transition from Campylobacter related chronic gastritis to reflux gastritis.     

Campylobacter pylori and gastroduodenal disease.

Campylobacter pylori is a newly described, spiral-shaped, gram-negative bacillus that is oxidase positive, catalase positive, and urease positive and grows slowly in culture. Although observed in human tissue at the beginning of the century, it was not cultured until 1982. Because there are significant morphological and genetic differences between this organism and other species of Campylobacter, it will probably be reclassified in a new genus. Current information indicates that the organism primarily resides in the stomach tissue of humans and nonhuman primates and may occasionally spread to the esophagus or other parts of the alimentary tract under appropriate conditions. Significant evidence has accumulated in the last several years to show that it causes gastritis, and there is mounting evidence that it may participate in the development of duodenal ulcers. It may also be associated with gastric ulcers and nonulcer dyspepsia. It can be detected in patients by culture of biopsy specimens or histological staining of biopsy tissue. Indirect evidence for the presence of the organism can be obtained by detection of urease in a tissue biopsy specimen, by urea breath tests, or by detection of specific antibody. It may not be necessary to implement these procedures for routine use, however, until the role of the organism can be defined better. Ultimately, the discovery of this organism may lead to radical changes in the diagnosis and treatment of gastric disease.     

Rapidly decreased serum IgG to Campylobacter pylori following elimination of Campylobacter in histological chronic biopsy Campylobacter-positive gastritis

The anaerobic bacterium Campylobacter pylori (Cp) is thought to be associated with chronic gastritis. This paper presents clinical data underpinning this view. Five patients with histological chronic gastritis as determined by diagnostic endoscopy, which was associated with Cp as determined by positive biopsy cultures, all possessed statistically raised serum IgG ELISA titers to Cp during a longitudinal period of observation of 15 months. Treatment with the antibiotics amoxycillin (clamoxyl) or colloidal bismuth subcitrate (denol) eliminated Cp within one month. Associated with this, serum IgG ELISA titers were found to decrease sharply and rapidly. Tagamet and spiramycin had little effect. Although the data are preliminary, they support the assumed Cp involvement in chronic gastritis and suggest that specific serum IgG ELISA titers to Cp are useful parameters in monitoring disease status, exceeding bacteriological culture of biopsy specimens in speed and convenience.     

Sampling efficiency in the diagnosis of Helicobacter pylori infection and chronic active gastritis.

The methods and sampling procedures used in the diagnosis of Helicobacter pylori infection and chronic active gastritis were evaluated. Five biopsy specimens for bacteriological cultivation and three specimens for histological examination were obtained endoscopically from a defined area of the gastric antral mucosae of 83 patients. An increase in the number of biopsy specimens for cultivation from one to five revealed only one more H. pylori-infected patient. H. pylori was isolated from 31 of 83 patients. Three technically adequate samples for histological examination were obtained from each of 74 patients. Of these 74 patients, chronic active gastritis was diagnosed by demonstration of typical histological changes in all three specimens from each of 20 patients, in two of three specimens from each of 3 patients, and in one of three specimens from 1 patient. The results indicate that one biopsy specimen is sufficient for the isolation of H. pylori, whereas several specimens may be necessary for the histological diagnosis. Chronic active gastritis was found in four patients not infected with H. pylori; on the other hand, H. pylori was isolated from nine patients who showed no signs of chronic active gastritis in any of three samples.     

Treponema pallidum and Helicobacter pylori recovered in a case of chronic active gastritis.

A 49-year-old man complaining of epigastric pain underwent endoscopy, during which thickened stomach folds below the fundus were observed. Microscopic examination of gastric tissue biopsy specimens revealed chronic active gastritis. Dieterle stain revealed overwhelming numbers of "corkscrew-like" spirochetes. These were proved to be consistent with Treponema pallidum. A comprehensive study of the tissue revealed the added presence of Helicobacter pylori. This appears to be the first case report describing the involvement of H. pylori and T. pallidum together in a case of chronic active gastritis.     

Superficial gastritis and Campylobacter pylori in dyspeptic patients--a quantitative study using computer-linked image analysis

The purpose of this study was the quantitative assessment of mucosal inflammation and its relationship to Campylobacter pylori in gastric antral and body biopsies from patients with dyspepsia and controls. The study groups comprised patients with duodenal ulcer (DU; n = 20), duodenitis (DUN; n = 20), non-ulcer dyspepsia (NUD; n = 20). Using a semi-automatic, computer-linked image analyser (Kontron: MOP Videoplan), mucosal acute and chronic inflammatory cell densities were measured in defined gastric sites for each patient group and expressed as number per mm2 of lamina propria and number per mm length of epithelium. Measurements were also made on a group of asymptomatic controls (n = 9) who fulfilled strict exclusion criteria. All biopsies were analysed for the presence of Camplyobacter pylori (CP) with a Giemsa stain. Data between groups were compared using the Mann-Whitney U-test. In the antrum and body, the mononuclear cell count was significantly higher in lamina propria in DU patients than in DUN, NUD and controls. In the body, DU laminia propria mononuclear cell counts were higher than those of DUN and controls. Prevalence rates for CP for DU, DUN, and NUD were 94, 89, and 50 per cent for antral and 88, 83, and 56 per cent for body biopsies. Significant differences were present between CP-positive and negative subjects in the NUD group. Antral and body inflammation within these clinical groups shows a wide variation. Higher inflammatory cell counts in the DU group may reflect the prevalence of CP colonization.     

Association of Campylobacter pylori on the gastric mucosa with antral gastritis in children

We investigated the presence of Campylobacter pylori colonization of the gastric mucosa and of histologic evidence of gastritis in a prospective study of 71 consecutive children undergoing upper gastrointestinal tract endoscopy and gastric biopsies because of gastrointestinal symptoms. Two tissue samples from the gastric antrum were obtained from 67 of the 71 children (mean age [+/- SD], 11.4 +/- 3.8 years). One sample was evaluated for evidence of gastritis and stained with silver to detect organisms morphologically resembling campylobacter. The second sample was cultured for C. pylori, and a portion was used to perform a urease-screening test for the presence of C. pylori. Antral gastritis was diagnosed histologically in 18 of 67 patients. C. pylori was identified by both culture and silver staining on the antral mucosa in 7 of 10 patients with unexplained gastritis (primary gastritis) but in none of 8 patients with gastritis associated with an identifiable underlying cause (secondary gastritis). C. pylori was not identified in any of the 49 cases with normal histologic features. The urease-screening test was positive in only three of six patients with a positive culture for C. pylori. Duodenal ulcers were diagnosed by endoscopy in five patients. Each of the five had C. pylori on the antral mucosa, but organisms were not identified on the duodenal mucosa. We conclude that the presence of C. pylori on the antral mucosa is specifically associated with primary antral gastritis and may also be associated with primary duodenal ulceration.     

Helicobacter (Campylobacter) pylori in the etiology and pathogenesis of gastritis and peptic ulcer

Current information on the role of Helicobacter pylori (HP) in the stomach and duodenum pathology is presented. HP is always found in active chronic gastritis and duodenal ulcer. HP damage to gastric superficial epithelium may result in the accelerated proliferation and incomplete differentiation of epithelium, this being a basis of chronic gastritis morphogenesis. Factors of aggression such as HCl hypersecretion provoke a stomach metaplasia of the duodenal mucosa. HP damage to such areas combined with the factors of aggression result in the transition of a preulcer state into ulcer.     

Hemagglutination activity of Campylobacter pylori.

Forty-five strains of Campylobacter pylori isolated from gastric biopsy specimens showed distinct hemagglutination activity. The activity was partially decreased by treatment with heat, trypsin, or an alkylating agent and was inhibited by porcine gastric mucin but not by various compounds, including D-mannose.     

Campylobacter pyloridis, gastritis, and peptic ulceration.

Campylobacter pyloridis is a spiral bacterium which was seen by histopathologists several years before it was cultured in 1982 in Perth, Western Australia. It has unique cellular fatty acids, predominantly tetradecanoic acid and cis-11, 12 methylene octadecanoic acid. It also has a unique ultrastructure which is different from that of other campylobacters. C pyloridis possesses a powerful urease enzyme and produces large amounts of extracellular catalase. Both these features may be important virulence factors, allowing it to occupy a protected niche in the stomach below the mucus layer but above the gastric mucosa. Specific lesions are found in the gastric mucosa, and ultrastructural studies show the presence of adherence pedestals identical with those found with enteropathogenic Escherichia coli of the intestine. Histological examination of gastric biopsy tissue has shown that C pyloridis is strongly associated with active chronic gastritis, when polymorphonuclear leucocytes are present, and is not found on normal mucosa except when a biopsy specimen from elsewhere in the stomach shows active chronic gastritis. When patients with symptoms caused by gastritis are identified dual antibacterial treatment, combining the action of bismuth in the stomach with a systemic antibiotic, can eradicate C pyloridis, with remission of symptoms and restoration of normal epithelial morphology. Most peptic ulcers relapse after modern acid reducing treatment, and antibacterial treatment may be beneficial in preventing relapse.