Robert M. Genta

Classification and grading of Gastritis: The updated Sydney system

The Sydney System for the classification of gastritis emphasized the importance of combining topographical, morphological, and etiological information into a schema that would help to generate reproducible and clinically useful diagnoses. To reappraise the Sydney System 4 years after its introduction, a group of gastrointestinal pathologists from various parts of the world met in Houston, Texas, in September 1994. The aims of the workshop were (a) to establish an agreed terminology of gastritis; (b) to identify, define, and attempt to resolve some of the problems associated with the Sydney System. This article introduces the Sydney System as it was revised at the Houston Gastritis Workshop and represents the consensus of the participants. Overall, the principles and grading of the Sydney System were only slightly modified, the grading being aided by the provision of a visual analogue scale. The terminology of the final classification has been improved to emphasize the distinction between the atrophic and nonatrophic stomach; the names used for each entity were selected because they are generally acceptable to both pathologists and gastroenterologists. In addition to the main categories and atrophic and nonatrophic gastritis, the special or distinctive forms are described and their respective diagnostic criteria are provided. The article includes practical guidelines for optimal biopsy sampling of the stomach, for the use of the visual analogue scales for grading the histopathologic features, and for the formulation of a comprehensive standardized diagnosis. A glossary of gastritis-related terms as used in this article is provided.

Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis

The histopathologic detection of Helicobacter pylori in gastric biopsy specimens is considered the gold standard for the diagnosis of H pylori infection. However, few studies have addressed the pathologists reliability to detect the organism and to assess the degree of the related inflammatory changes. The objectives of this study were to determine the degree of agreement among the findings of four gastrointestinal pathologists in the semiquantitative evaluation of H pylori infection and gastritis. Three slides from specified areas of the stomach of 99 patients with and without H pylori infection were stained with the triple stain, coded, and examined independently by four pathologists. For each specimen, a visual analogue scale graded from 0 (absent/normal) to 5 (maximal intensity) was used to score (1) H pylori (2) neutrophils, and (3) atrophy. Data were analyzed using kappa-statistics. The kappa-coefficient for the detection of H pylori (present vs absent) was approximately .9 (excellent); for the intensity of infection, it was considerably lower on the 6-point scale (approximately .61) and improved slightly on an amalgamated 4-point scale (approximately .71). The agreement on presence or absence of neutrophils was excellent (kappa = .8) in antral biopsies and good (kappa = .67) in corpus biopsies. The kappa for the semiquantitative scoring of neutrophils was poor on the 6-point scale (approximately .43) and fair on the amalgamated scale (approximately .54). The interobserver agreement was the poorest in the evaluation of atrophy (presence, absence, categories, or group categories) with kappa coefficients varying from .08 and .29. This group of pathologists had a high level of concordance on the diagnosis of H pylori infection in any particular patient and a high index in the assessment of the intensity of infection. The agreement was less in the semiquantitative evaluation of active inflammation. When the evaluation concerned a loosely defined feature, such as atrophy, there was essentially no agreement among the pathologists. This study suggests the need for further assessments of pathologists ability to provide reproducible diagnoses. These results also indicate that more stringent criteria for the diagnosis of soft histopathologic features (such as atrophy) are urgently needed.

Simultaneous visualization of Helicobacter pylori and gastric morphology: A new stain☆

Although the histopathologic patterns associated with Helicobacter pylori infection have been described, details of the interaction between bacteria, epithelial cells, and inflammatory cells remain elusive. One of the limiting factors has been the lack of a staining technique that allows the simultaneous visualization of H pylori and tissue morphology. By combining three commonly available stains (Steiner, hematoxylin-eosin, and alcian blue at pH 2.5) into a single procedure we have developed a stain that permits the optimal detection of H pylori in tissue sections while simultaneously allowing the histopathologic evaluation of all salient characteristics of the gastric mucosa. This procedure is inexpensive, as easy to perform as any silver stain, and provides consistent results. This stain is as sensitive as the Warthin-Starry stain for the detection of H pylori and significantly more sensitive than hematoxylin-eosin alone (> 99% v 85% when compared with the hematoxylin-eosin stain in a series of 332 positive biopsy specimens; > 99% v 61% in 49 biopsy specimens with rare bacteria). This stain is particularly useful for the visualization of small numbers of bacteria, such as in the evaluation of posttreatment gastric biopsy specimens, in specimens with abundant mucus or debris, and in specimens from the corpus, where H pylori usually does not elicit strong inflammatory responses and, therefore, pathologists index of suspicion tends to be low.

Topographic patterns of intestinal metaplasia and gastric cancer

OBJECTIVE:The role of intestinal metaplasia in gastric oncogenesis has been demonstrated by both cross-sectional and longitudinal studies. This study was designed to determine whether, in a population at high risk for gastric cancer, different topographical patterns and phenotypes of intestinal metaplasia were associated with different degrees of cancer risk.METHODS:A total of 68 Colombian patients with gastric cancer and 67 controls with nonulcer dyspepsia were studied by an extensive biopsy protocol. Intestinal metaplasia was assessed semiquantitatively by histology and was characterized histochemically. In both patients and controls, the Spearmans correlation test was applied to the test if the gastric distribution of metaplastic lesions resulted in specific topographical patterns associated with different risks for cancer.RESULTS:Four topographical patterns of intestinalization emerged: 1) “Focal,” in 14 cancer patients and 16 controls; 2) “Antrum-predominant,” in seven cancer patients and six controls; 3) “Magenstraße” (involving the lesser curvature from cardia to pylorus) in 25 cancer patients and four controls. This pattern was associated with higher cancer risk (OR = 5.7; 95% CI: 1.3–26) than were the two less extensive patterns; and 4) “Diffuse,” involving essentially the entire gastric mucosa with the exception of the fundus, was unique to 13 cancer patients. The OR for cancer was 12.2; 95% CI: 2.0–72.9. Incomplete-type metaplasia significantly correlated with the extent of total metaplasia and was also associated with greater cancer risk.CONCLUSIONS:In a population with high risk for gastric cancer, the extension of intestinal metaplasia correlates with the extent of its “incomplete” phenotype and is significantly associated with increased cancer risk. Both the extent and location of intestinal metaplasia along the lesser curvature (from the cardia to the prepyloric zones) identify patients with the highest cancer risk.

The gastric cardia in Helicobacter pylori infection

Helicobacter pylori gastritis is believed to be both more prevalent and more severe in the antrum than in the corpus. The mucosa of the cardia is architecturally similar to that of the antrum. This study was designed to test the hypothesis that intensity of H pylori infection and the associated inflammation are similar in the cardia and the antrum and are greater in these locations than in the corpus. A total of 445 gastric biopsy specimens were obtained from predetermined sites from 50 subjects (42 with demonstrated H pylori infection). Slides were stained with a combined stain to simultaneously visualize H pylori, mucosal morphology, and inflammatory infiltrate. Numbers of H pylori, inflammatory responses, and intestinal metaplasia were graded on a scale from 0 to 5. Helicobacter pylori was detected in the cardia of 40 of the 42 infected subjects (95%). Helicobacter pylori density was similar in the three gastric regions. The intensity of chronic active gastritis was similar in the antrum and the cardia, and was higher in these locations than in the corpus (P < .005). Lymphoid follicles were significantly less prevalent in the cardia and in the corpus than in the antrum (P < .05). Helicobacter pylori infection was as prevalent in the cardia as in the rest of the stomach and its density was similar in all sites of antrum, corpus, and cardia. The inflammatory responses characteristic of chronic active gastritis, except for lymphoid follicles, were similar in the antrum and the cardia and in both these locations were more intense than in the corpus. The significance of these findings is discussed with respect to the relationship between H pylori infection and the genesis of gastric adenocarcinoma and lymphoma.

Cross-Reactivity of Anti-CagA Antibodies With Vascular Wall Antigens Possible Pathogenic Link Between Helicobacter pylori Infection and Atherosclerosis

Background—Helicobacter pylori-CagA positive strains have been shown to be associated with atherosclerosis. However, the pathogenesis is still undetermined. The aim of this study was to determine whether anti-CagA antibodies cross-react with antigens of normal and atherosclerotic arteries. Methods and Results—Eight umbilical cord sections, 14 atherosclerotic artery sections, and 10 gastrointestinal tract sections were examined by immunohistochemistry using polyclonal anti-CagA antibodies. Five atherosclerotic and 3 normal artery samples were also lysed in ice-cold lysis buffer containing protease inhibitors and were immunoprecipitated using the same antibodies. Anti-CagA antibodies reacted with cytoplasm and nuclei of smooth muscle cells in umbilical cord and atherosclerotic vessel sections, cytoplasm of fibroblasts-like cells in intimal atherosclerotic plaques, and the cell membranes of endothelial cells. Anti-CagA antibodies also specifically immunoprecipitated 2 high molecular weight antigens of 160 and 180 kDa from both normal and atherosclerotic artery lysates. Conclusions—Anti-CagA antibodies cross-react with antigens of both normal and atherosclerotic blood vessels. We speculate that the binding of anti-CagA antibodies to those antigens in injured arteries could influence the progression of atherosclerosis in CagA-positive H pylori-infected patients.

Mast cell involvement in gastritis with or without Helicobacter pylori infection

BACKGROUND & AIMSnMast cells are initiators and regulators of inflammation, but their role in the human stomach remains unclear. Therefore, the extent and distribution of mast cell involvement in gastritis with or without Helicobacter pylori infection was investigated.nnnMETHODSnMapped biopsy specimens from 17 H. pylori-positive and 20 H. pylori-negative subjects were examined. Sections were assessed for infection and inflammation and stained with anti-human mast cell tryptase to count mucosal and epithelial mast cells. Density of mast cells in different gastric compartments, their response to infection treatment, and their relationship with other inflammatory cells were evaluated. Mast cell degranulation was evaluated by electron microscopy.nnnRESULTSnMast cell density was significantly greater in the mucosa with gastritis, with or without H. pylori infection, than in the mucosa of noninfected normal subjects. In the antrum, density was much greater in H. pylori-infected peptic ulcer subjects than in the other gastritis groups. It also correlated significantly with the intensity of inflammation. Mast cell degranulation was demonstrated by electron microscopy in H. pylori-infected mucosa. Mast cell density in ulcer patients decreased significantly after cure of H. pylori infection.nnnCONCLUSIONSnMast cells may be important effector cells in the pathogenesis of gastritis, especially in H. pylori-associated peptic ulcer.

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.

Metronidazole, omeprazole and clarithromycin: An effective combination therapy for Helicobacter pylori infection

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multidrug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole.

Recognizing atrophy: Another step toward a classification of gastritis

The Sydney System is a novel classification of gastritis that attempts to incorporate etiologic, topographic, and morphologic criteria into a clinically relevant scheme. In September of 1994, a group of 20 gastric pathologists from various parts of the world gathered in Houston, Texas, U.S.A., to reappraise the Sydney System 4 years after its introduction and to attempt to reach a broad consensus on gastritis. One of the most controversial issues at the Houston Workshop was the concept of atrophy. Several factors converge to foment confusion and disagreement. Normal is imprecisely defined; the loss of glands occurs with distinct patterns and has different functional significance in antrum and corpus; inflammatory infiltrate and lymphoid follicles in the lamina propria may alter the architecture of the gastric mucosa, particularly in the antrum, making loss especially arduous to discern from mere displacement; the relationship between atrophy and intestinal metaplasia remains incompletely understood; and finally, and perhaps most important, the topographic patterns of distribution and the genesis and evolution of atrophic gastritis have been among the most divisive predicaments in the tumultuous arena of gastritis. This article explores some of the difficulties surrounding the concept of atrophy, summarizes the resolutions made at the Houston Workshop, and presents a novel approach to the histopathologic evaluation of atrophic gastritis.