Faculty Bibliography

Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated 'blindly' using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization

BACKGROUND: Helicobacter pylori carriage (i.e., persistent exposure to the organism without gastric epithelial cell invasion) is an established risk factor for noncardia gastric cancer. However, its association with the risk of cancer of the gastric cardia is controversial. Consequently, we designed this prospective, nested case-control study to further explore the subsite-specific gastric cancer risks associated with H. pylori seropositivity (a surrogate marker for persistent exposure). METHODS: A total of 99 patients with gastric cardia cancer, 82 patients with noncardia gastric cancer, and 192 cancer-free subjects were selected from among the participants (n = 29 584) of a nutrition intervention trial previously conducted in Linxian, China. H. pylori seropositivity was determined by assaying for the presence of H. pylori whole cell and CagA antibodies in baseline serum samples from all subjects. Seropositivity was defined as one or both serum assays being positive. Odds ratios (ORs) for subsite-specific gastric cancer were estimated by multivariate logistic regression analyses. All statistical comparisons were two-sided (alpha =.05). RESULTS: H. pylori seropositivity rates for subjects with gastric cardia cancer, noncardia gastric cancer, and gastric cardia and noncardia cancers combined were 70% (P =.02), 72% (P: =.01), and 71% (P =.003) compared with 56% for cancer-free control subjects. OR estimates for H. pylori seropositivity were 1.87 (95% confidence interval [CI] = 1.10 to 3.17) for gastric cardia cancer, 2.29 (95% CI = 1.26 to 4.14) for noncardia gastric cancer, and 2.04 (95% CI = 1.31 to 3.18) for gastric cardia and noncardia cancers combined. CONCLUSIONS: H. pylori seropositivity was associated with increased risks for both gastric cardia cancer and noncardia gastric cancer in this well-characterized cohort. Thus, H. pylori carriage may increase the risk of cancer throughout the stomach

Bacteriology laboratories are interested in culturing H. pylori for several reasons: (1) to investigate its growth requirements and metabolism; (2) for diagnostic purposes; (3) to establish the antibiotic susceptibility of isolates; (4) to identify potential virulence factors; and (5) to investigate microbial host-cell interactions. Despite the reasons listed, culture of H. pylori from gastric biopsy specimens is becoming less popular among clinical laboratories and physicians. The main reason is that it has become generally accepted that culture techniques are too demanding with many factors that must be controlled, in addition to simple and less expensive methods now available. Some of the disadvantages of culture include (1) special conditions for specimen transportation, (2) speed in processing of the sample to increase the probability of recovering the organism, (3) the use of expensive and complicated media with special conditions for maintenance, (4) the need for special incubation conditions, and (5) the length of time necessary to obtain a result for establishing treatment options in the patient. This article reviews aspects of H. pylori culture that could explain use being relegated to only a few clinical laboratories, some regional laboratories, and reference centers. There are several misconceptions in relation to culture techniques, such as transport and the processing of biopsy specimens. This article has mentioned simple and clear points that optimize the recovery rates of H. pylori by culture

The acquisition of iron is a necessity for bacterial growth in Helicobacterpylori, as it is for other organisms. In addition, iron is a critical factor for the virulence of this organism. Therefore, it is not surprising that H. pylori isolates have the potential to express at least three major iron acquisition mechanisms. The association of H. pylori infection with host iron deficiency might indicate that the iron-scavenging systems play a role in the virulence of H. pylori

BACKGROUND: Between 1976 and 1987, 35 cases of acute gastritis with hypochlorhydria (AGH) were seen in our research laboratory. The aims of this study were to determine the natural history of AGH and the role of Helicobacter pylori in its pathogenesis. METHODS: Archived serum and gastric biopsy samples obtained from AGH subjects were examined for evidence of H pylori colonisation. Twenty eight of 33 (85%) surviving AGH subjects returned a mean of 12 years after AGH for follow up studies, including determination of H pylori antibodies, basal and peak acid output, endoscopy, and gastric biopsies. A matched control group underwent the same studies. RESULTS: Archived material provided strong evidence of new H pylori acquisition in a total of 14 subjects within two months, in 18 within four months, and in 22 within 12 months of recognition of AGH. Prevalence of H pylori colonisation at follow up was 82% (23 of 28) in AGH subjects, significantly (p<0.05) higher than in matched controls (29%). Basal and peak acid output returned to pre-AGH levels in all but two subjects. CONCLUSIONS: One of several possible initial manifestations of H pylori acquisition in adults may be AGH. While H pylori colonisation usually persists, hypochlorhydria resolves in most subjects

Since the first report of the potential role of Helicobacter pylori as cause of disease of the upper intestinal tract of humans, a major controversial has developed. First, the role of H. pylori as the etiological agent of duodenal and gastric ulcer has been questioned. Second, the possibility of H. pylori as a major risk factor in the development of distal gastric cancer has not been fully accepted. It is interesting that at the time when the etiological role of H. pylori is almost universally accepted, series of publications have suggested that the elimination of H. pylori from asymptomatic individuals might represent a risk for the development of other upper gastrointestinal diseases such as GERD and cancer of the esophagus. The main goal of this revision is to describe the virulence factors associated with H. pylori as well as its interaction with the human host, to establish whether H. pylori should be considered a true pathogen or only a commensal

OBJECTIVE: Helicobacter pylori (H. pylori) colonization is associated with chronic gastritis, peptic ulcer disease, and adenocarcinoma of the distal stomach. However, the role of H. pylori strain variation in complicated gastroesophageal reflux disease, especially Barrett's esophagus, is unknown. Therefore, the aim of this study was to evaluate the prevalence of colonization by cagA+ and cagA- H. pylori strains in the spectrum of gastroesophageal reflux disease, including Barrett's esophagus. METHODS: A total of 251 patients undergoing endoscopy were categorized into four groups: controls, patients with gastroesophageal reflux disease alone, and patients with short- and long-segment Barrett's esophagus. All patients underwent upper endoscopies with biopsies and serum collections. H. pylori and degree of mucosal inflammation in gastric biopsies were assessed and serological assessment made for H. pylori and cagA status. RESULTS: The overall prevalence of H. pylori colonization in the study population was 35% (95% confidence interval = 29.5-41.4%) which did not differ significantly among the groups. However, colonization by cagA+ H. pylori strains was significantly more prevalent among controls (11/25; 44%) and patients with gastroesophageal reflux disease (13/36; 36%) than in patients with short-segment (2/10; 20%) or long-segment Barrett's esophagus (0/18; 0%). Patients with Barrett's esophagus were less likely to be colonized by cagA+ H. pylori strains than reflux patients without Barrett's esophagus (odds ratio = 0.27, 95% confidence interval = 0.11-0.67, p = 0.004). CONCLUSIONS: Colonization by cagA+ H. pylori strains may be protective against the formation of short- and long-segment Barrett's esophagus and its malignant complications

Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA(+). As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8+/-3.5 versus 10.1+/-4.3 ng/mg of biopsy protein; P<0.001) and IL-6 levels (2.8+/-0.3 versus 0.26+/-0.2 ng/mg of protein; P<0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P<0.005) and neutrophil infiltration (P<0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P<0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P<0.005) and with IgG responses to whole-cell antigens (P<0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r = 0.75, P<0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts

Across populations of children, Helicobacter pylori prevalence ranges from under 10% to over 80%. Low prevalence occurs in the U.S., Canada, and northern and western Europe; high prevalence occurs in India, Africa, Latin America, and eastern Europe. Risk factors include socioeconomic status, household crowding, ethnicity, migration from high prevalence regions, and infection status of family members. H. pylori infection is not associated with specific symptoms in children; however, it is consistently associated with antral gastritis, although its clinical significance is unclear. Duodenal ulcers associated with H. pylori are seldom seen in children under 10 years of age. H. pylori-infected children demonstrate a chronic, macrophagic, and monocytic inflammatory cell infiltrate and a lack of neutrophils, as compared with the response observed in adults. The effect of H. pylori infection on acid secretion in children remains poorly defined. The events that occur during H. pylori colonization in children should be studied more thoroughly and should include urease activity, motility, chemotaxis, adherence, and downregulation of the host response. The importance of virulence determinants described as relevant for disease during H. pylori infection has not been extensively studied in children. Highly sensitive and specific methods for the detection of H. pylori in children are needed, especially in younger pediatric populations in which colonization is in its early phases. Criteria for the use of eradication treatment in H. pylori-infected children need to be established. Multicenter pediatric studies should focus on the identification of risk factors, which can be used as prognostic indicators for the development of gastroduodenal disease later in life