Oscar Gutierrez

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.

Helicobacter pylori outer membrane proteins and gastroduodenal disease

Background and aims: A number of Helicobacter pylori outer membrane proteins (OMPs) undergo phase variations. This study examined the relation between OMP phase variations and clinical outcome. Methods: Expression of H pylori BabA, BabB, SabA, and OipA proteins was determined by immunoblot. Multiple regression analysis was performed to determine the relation among OMP expression, clinical outcome, and mucosal histology. Results:H pylori were cultured from 200 patients (80 with gastritis, 80 with duodenal ulcer (DU), and 40 with gastric cancer). The most reliable results were obtained using cultures from single colonies of low passage number. Stability of expression with passage varied with OipA > BabA > BabB > SabA. OipA positive status was significantly associated with the presence of DU and gastric cancer, high H pylori density, and severe neutrophil infiltration. SabA positive status was associated with gastric cancer, intestinal metaplasia, and corpus atrophy, and negatively associated with DU and neutrophil infiltration. The Sydney system underestimated the prevalence of intestinal metaplasia/atrophy compared with systems using proximal and distal corpus biopsies. SabA expression dramatically decreased following exposure of H pylori to pH 5.0 for two hours. Conclusions: SabA expression frequently switched on or off, suggesting that SabA expression can rapidly respond to changing conditions in the stomach or in different regions of the stomach. SabA positive status was inversely related to the ability of the stomach to secrete acid, suggesting that its expression may be regulated by changes in acid secretion and/or in antigens expressed by the atrophic mucosa.

Helicobacter pylori in North and South America before Columbus

We present a molecular epidemiologic study, based on an analysis of vacA, cagA and cag right end junction genotypes from 1042 Helicobacter pylori isolates, suggesting that H. pylori was present in the New World before Columbus. Eight Native Colombian and Alaskan strains possessed novel vacA and/or cagA gene structures and were more closely related to East Asian than to non‐Asian H. pylori. Some Native Alaskan strains appear to have originated in Central Asia and to have arrived after strains found in South America suggesting that H. pylori crossed the Bering Strait from Asia to the New World at different times.

Discrimination between Cases of Duodenal Ulcer and Gastritis on the Basis of Putative Virulence Factors of Helicobacter pylori

ABSTRACT The BabA, cagA, and vacA statuses of 827 Helicobacter pylori isolates were used in logistic regression models to discriminate duodenal ulcer from gastritis. Only BabA was a candidate for a universal virulence factor, but the low c statistic value (0.581) indicates that none of these factors were helpful in predicting the clinical presentation.

Clinical presentation in relation to diversity within the Helicobacter pylori cag pathogenicity island

OBJECTIVE:This study investigated the genetic diversity of the cag pathogenicity island (PAI) in Helicobacter pylori (H. pylori) in relation to clinical outcome and interleukin (IL)-8 production.METHODS:Seven genes in the cag PAI (cagA, cagE, cagG, cagM, cagT, open reading frame 13 and 10) were examined by polymerase chain reaction and Southern blot hybridization using H. pylori from 120 patients with different presentations (duodenal ulcer, gastric cancer, gastritis alone). IL-8 production from AGS cells (gastric cancer cell line) cocultured with H. pylori was measured by ELISA.RESULTS:An intact cag PAI was present in 104 (87%) isolates, and five (4%) had deletions within the cag PAI; 11 (9%) lacked the entire cag PAI. Clinical isolates containing the complete cag PAI induced a greater secretion of IL-8 as compared with those without the cag PAI (3048 ± 263 vs 480 ± 28 pg/ml, p < 0.001). Deletion of only cagG reduced IL-8 secretion by two thirds. Deletions of more than one locus reduced IL-8 secretion to background. A similar proportion of H. pylori from patients with gastritis, duodenal ulcer, or gastric cancer had intact cag PAI (88%, 88%, and 85%, respectively). Although the presence of cagG was a better predictor of the presence of an intact cag PAI than cagA or cagE, the presence or absence of any of these genes had no association with clinical presentation.CONCLUSION:Although the cag PAI plays an important role in IL-8 production, clinical presentation cannot be predicted by the presence of an intact cag PAI or any of these seven cag PAI genes.

Marked Differences in the Frequency of Microsatellite Instability in Gastric Cancer From Different Countries

Objective:Previous studies have reported variable rates of microsatellite instability (MSI) in gastric cancer. We investigated the frequency of MSI in invasive gastric carcinoma of patients from three geographic regions.Methods:Genomic DNA from gastric cancer and nontumor tissue from 22 Korean, 20 Colombian, and 26 U.S. patients was amplified with five microsatellite markers.Results:MSI was more frequently seen in gastric cancer from Korea, affecting 50% of patients, in contrast with gastric cancers from the U.S. (7%) and Colombia (15%) (p= 0.003 and p= 0.03, respectively). MSI at one locus was significantly more frequent in gastric cancer from individuals >65 yr (p= 0.01). MSI was similarly associated with both diffuse and intestinal types of gastric cancer.Conclusion:MSI affects the two major histological types of gastric cancer, and was more frequent in gastric cancer from Korea than in the other countries, suggesting that the relative importance of different pathways of gastric carcinogenesis may vary in diverse regions of the world.

Helicobacter pylori and Hetertopic Gastric Mucosa in the Upper Esophagus (the Inlet Patch)

OBJECTIVES:Helicobacter pylori (H. pylori) may colonize gastric mucosa wherever it is found in the GI tract. Heterotopic gastric mucosa in the upper esophagus (inlet patch) is a potential site for H. pylori infection and may provide a reservoir for oral-oral transmission or a niche where antibiotics might have difficulty reaching. The aim of this study was to analyze the intensity and distribution of H. pylori in the inlet patch.METHODS:Whenever a cervical inlet patch was observed, mucosal biopsy samples were taken to confirm the endoscopic diagnosis and to search for H. pylori and active inflammation. In addition, mucosal biopsy samples were also taken from the gastric mucosa. Formalin-fixed biopsy specimens were cut and stained with a new dual stain developed in our laboratory. The stain is a combination of periodic acid-Schiff and a silver stain that allows simultaneous visualization of H. pylori and gastric type epithelium. The density of H. pylori was scored using a visual analog scale of 0 to 5. The type of mucosa in the inlet patch was also recorded.RESULTS:The study included 48 patients; 37 had H. pylori gastritis and 27 of these (73%) had H. pylori identified on their heterotopic gastric mucosa. A higher density of H. pylori in the stomach was associated with a higher prevalence in the inlets. Active inflammation correlated with active infection in the inlet patch and the presence of antral type mucosa.CONCLUSION:H. pylori colonization of heterotopic gastric mucosa in the upper esophagus is common and is closely related to the H. pylori density in the stomach. The fact that H. pylori was not found in all cases suggests that another event such as reflux may be required for H. pylori to colonize heterotopic mucosa.

Comparison of Genotyping Helicobacter pylori Directly from Biopsy Specimens and Genotyping from Bacterial Cultures

ABSTRACT PCR for vacA and cagA genotypes of Helicobacter pylori using DNA isolated from infected gastric biopsy specimens was approximately equal to genotyping using bacterial DNA from cultures. Inconsistent results were associated with low H. pylori density in biopsies. A higher proportion of mixed infection was found when biopsies were used.

Geographic differences in the distribution of intestinal metaplasia in duodenal ulcer patients

OBJECTIVE:A strong correlation exists between atrophic gastritis and the intestinal type of gastric carcinoma. Duodenal ulcer disease characteristically has an antral predominant gastritis and a lower risk for gastric cancer. The aim of this study was to investigate the extent and distribution of intestinal metaplasia in duodenal ulcer in countries differing in gastric cancer incidence.METHODS:Topographically mapped gastric biopsy specimens (median 11) were obtained from patients with duodenal ulcer in four countries (Korea, Colombia, USA, and South Africa). Sections were stained with a triple stain and evaluated for Helicobacter pylori (H. pylori), active inflammation, and intestinal metaplasia.RESULTS:One hundred and sixty-five patients with duodenal ulcer were examined (29 from Korea, 52 from Colombia, 62 from the USA, and 22 from South Africa). The percentage of biopsies with intestinal metaplasia was significantly greater in Korean patients (86%) compared with that in other countries (50%) (p = 0.0004). Intestinal metaplasia was most prevalent in the antrum lesser curve and greater curve, and the body lesser curve. Intestinal metaplasia was present in the gastric corpus of 38% of duodenal ulcer patients from Korea compared with an average of 10% elsewhere (p = 0.018). No differences were observed in the density or distribution of H. pylori infection or in the degree of active gastritis between countries.CONCLUSIONS:Although antral predominant gastritis is the prevalent pattern of gastritis in duodenal ulcer, intestinal metaplasia in the gastric corpus may be found with geographic differences. These findings suggest that duodenal ulcer and gastric cancer are not mutually exclusive diseases but are rather ends of the spectrum of H. pylori infection.

Histological patterns of gastritis in H. pylori -infected individuals with a family history of gastric cancer

Abstract OBJECTIVE: Different types of chronic gastritis, including antral predominant, corpus predominant, and multifocal pangastritis, are associated with Helicobacter pylori infection. Specific patterns of H. pylori gastritis that might characterize individuals with family histories of noncardia gastric cancer (GC) were investigated. METHODS: Histopathological changes associated with H. pylori gastritis were assessed in 111 individuals with family histories of GC and in 77 without from a region with high prevalence of H. pylori infection and GC. Gastric biopsies were taken from 12 sites (antrum, five; corpus, six; and cardia, one). RESULTS: Individuals (age CONCLUSIONS: Pangastritis and high lymphoid follicle density associated with H. pylori infection were found in patients with family histories of GC. Because a family history of gastric carcinoma is associated with increased risk of gastric cancer development, characterization of histological patterns of gastritis may be applicable to gastric cancer screening and surveillance, especially in relatively young at-risk populations.