Can gastric cancer be prevented?

Gastric adenocarcinoma is the fourth most common malignancy worldwide and is globally the second leading cause of cancer-related deaths each year. Among the risk factors are genetic factors (genetic diffuse gastric cancer - E-cadherin mutation (CDH1), pro- and anti-inflammatory cytokine genes and innate immune response gene polymorphisms), environmental factors (infection with the bacterium Helicobacter pylori (H. pylori), Epstein-Barr virus, nutrition: nitroso compounds, salt and antioxidants intake) and other factors (pernicious anemia, gastric polyps, gastric surgery, reproductive hormones, smoking). The bacterium H. pylori has been found to be the major carcinogen in gastric cancer development. Approximately 65%-80% of non-cardia gastric adenocarcinoma is attributable to H. pylori infection. One percent of patients infected with H. pylori will develop gastric cancer. American and European guidelines on the management of H. pylori infection recommend H. pylori eradication in all patients with atrophy and/or intestinal metaplasia and in all first-degree relatives of gastric cancer patients. In the Asian Pacific Gastric Cancer Consensus, it was suggested for the first time that it is time for population-based screening and treatment of H. pylori infection in regions with gastric cancer incidence above 20/100000 per year. Population screen and treat of H. pylori infection should be recommended in regions with gastric cancer incidence above 20/100000 per year. This can be a good approach in H. pylori infected patients before they develop premalignant gastric lesions. In patients with intestinal metaplasia, atrophy or dysplasia, regular endoscopic and histological surveillance should be done.

Specific T cell responses to Helicobacter pylori predict successful eradication therapy.

OBJECTIVE: The aim of our prospective study was to test a specific T cell response to Helicobacter pylori before therapy and compare it to the success of H. pylori eradication 12 months later. METHODS: A total of 14 dyspeptic patients and 10 patients with previous H. pylori eradication failure were recruited into the study; before therapy their gastric samples for H. pylori cultivation and blood samples for dendritic cell cultivation were obtained. H. pylori antigens were produced to prime dendritic cells for stimulation of T lymphocyte response. RESULTS: The level of cytokine response by T cells was measured and results were compared with the success of H. pylori eradication one year later. There was a significantly increased response in expression of IFN-gamma and IL-4 molecules by DCs stimulated T cells in subjects that successfully eradicated H. pylori compared with those who failed to eradicate the infection. Our results support the hypothesis that successful H. pylori eradication requires established anti-H. pylori immune response besides antibiotic treatment. CONCLUSION: Effective IFN-gamma cytokine response to H. pylori antigens seems to be of particular importance. Immunisation could be therefore beneficial for H. pylori eradication, while immunodeficiency could cause the failure in H. pylori eradication.

Is a one-week course of triple anti-Helicobacter pylori therapy sufficient to control active duodenal ulcer?

BACKGROUND: Triple therapy currently forms the cornerstone of the treatment of patients with Helicobacter pylori-positive duodenal ulcer. AIM: To establish whether prolonged antisecretory therapy is necessary in patients with active duodenal ulcer. METHODS: A total of 77 patients with H. pylori-positive duodenal ulcer were included in a prospective, controlled, double-blind study. All patients received a 7-day treatment with omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1000 mg b.d. Patients in the omeprazole group underwent an additional 14-day therapy with omeprazole 20 mg; patients in placebo group received placebo. Endoscopy was performed upon inclusion in the study and after 3 and 8 weeks. RESULTS: Seventy-four patients were eligible for a per protocol analysis after 3 weeks, and 65 after 8 weeks. After 3 weeks, the healing rate was 89% in the omeprazole group and 81% in the placebo group (P=0.51). After 8 weeks, the ulcer healed in 97% of the patients in the total group (95% CI: 92.7-100%). H. pylori was eradicated in 88% of patients in the omeprazole group and in 91% in the placebo group (P=1.0). No statistically significant differences between the groups were found in ulcer-related symptoms or in ulcer healing. CONCLUSION: In patients with H. pylori-positive duodenal ulcer, a 7-day triple therapy alone is sufficient to control the disease.

Diminished Th1-type cytokine production in gastric mucosa T-lymphocytes after H. pylori eradication in duodenal ulcer patients.

Helicobacter pylori infects an estimated 50% of the world population, however only a small proportion of individuals develop clinical symptoms of gastritis, peptic ulceration or gastric cancer. The variations in disease presentation may be due to differences in bacterial virulence and/or immune response to the pathogen. In the previous study we reported an increased expression of the IL-2 receptor in duodenal ulcer (DU) patients infected with H. pylori. This study examined intracellular lymphokine production in gastric mucosa infiltrating T lymphocytes in DU patients before and after H. pylori eradication. T lymphocytes were isolated from gastric mucosa biopsies by using mechanical and enzymatic tissue desegregation. Ficoll-purified lymphocytes were incubated with monoclonal antibodies and analysed by using 3-colour flow cytometry analysis for intracellular interferon gamma (IFNgamma) and interleukin 4 (IL-4) expression in order to define Th1 and Th2 cell population. We demonstrated a significant decrease in the proportion of Th1 cells infiltrating gastric mucosa 6 and 12 months after H. pylori eradication. Our results suggest the importance of the local immune response in the development of H. pylori related gastritis.

A four-year follow-up of duodenal ulcer patients after Helicobacter pylori eradication.

BACKGROUND/AIMS: The aim of our study was to evaluate the clinical course of disease in 63 duodenal ulcer (DU) patients during a 4-year follow-up after Helicobacter pylori (H. pylori) eradication. METHODOLOGY: Upper gastrointestinal endoscopy and a clinical interview were performed before antimicrobial therapy, 2 months after, yearly and when symptoms recurred. Two antral and two corporal specimens were taken for histology, and one additional specimen from antrum was taken for rapid urease test at the first endoscopy and for culture at the following endoscopies. All patients received triple antimicrobial regimens based on colloidal bismuth subcitrate, amoxycillin and metronidazole for at least 2 weeks. Patients with a negative histology and culture 2 months after antimicrobial therapy were included in the study. RESULTS: After H. pylori eradication, ulcer recurrence dropped from 84.1% per year in the year before H. pylori eradication to a mean value of 5.2% per year during 2076 patient months (p<0.01). The increased incidence of gastroesophageal reflux disease (GERD) was found only in the first year of the follow-up period. The average percentage of anti-ulcer drug users per year was 30.8% because of GERD, reflux symptoms, ulcer recurrence or non-ulcer dyspepsia. Ulcers or acute erosions recurred in 9 H. pylori-negative patients; recurrences were attributable to non-steroidal anti-inflammatory drugs (NSAID) in 4 out of 9 cases (44.4%). CONCLUSIONS: H. pylori eradication changed the long-term course of DU disease.

Two- to four-year histological follow-up of gastric mucosa after Helicobacter pylori eradication.

In a 2- to 4-year prospective study, the reversibility of gastritis after Helicobacter pylori eradication was analysed. Sixty-three H. pylori-positive, chronic duodenal ulcer patients were studied after the successful eradication of bacteria in the period from 1990 to 1993. H. pylori eradication was obtained by triple antimicrobial regimens (colloidal bismuth subcitrate, amoxycillin, and metronidazole) applied for at least 14 days. The criteria for eradication were the absence of bacteria from two antral and two body of stomach biopsies stained with haematoxylin, eosin, and Warthin Starry, and a negative antral biopsy culture. The same diagnostic procedures were repeated, at regular follow-up endoscopies, each year for up to 4 years. Neutrophil-granulocyte infiltration of gastric mucosa disappeared in 2 months after bacterial eradication. Mononuclear cellular infiltration was disappearing with statistical significance up to the second year and normal mucosa was observed in the majority of patients in the fourth year of follow-up. Degeneratively changed lymphoid aggregates were also present in the fourth year in the antrum (12.5 per cent of patients) and in the body of stomach (14 per cent of patients). There was no significant change in antral intestinal metaplasia during the 4 years of follow-up. Antral atrophy declined significantly in the period from 1 to 3 years of follow-up. In conclusion, 3-4 years are needed for gastric mucosa to become normal after H. pylori eradication, although some residual lymphoid aggregates persist even after that period.

Interobserver agreement in the assessment of gastritis reversibility after Helicobacter pylori eradication.

AIM: Our aim was to determine interobserver agreement in the application of the Sydney system to assess reversibility of gastritis after Helicobacter pylori eradication. METHODS AND RESULTS: Forty-three patients with a Helicobacter pylori-positive duodenal ulcer disease were included in the study. All patients included had successful H. pylori eradication after different antimicrobial drug combinations. Biopsy samples were collected from antrum and body, according to the Sydney recommendations, before antimicrobial therapy, 2 months after and at yearly intervals during 2-4 years of follow up. Three pathologists, who were blind to clinical data, evaluated histological changes in 221 antral and 219 body specimens stained with haematoxylin and eosin and with Warthin Starry. The percentage of pairwise agreement, kappa and weighted kappa statistic were used. Agreement in recognizing the presence of H. pylori colonization of the gastric mucosa, activity of inflammation and intestinal metaplasia was over 90%. Agreement in recognizing chronic inflammation in the body and atrophy in the antrum was between 78 and 89% respectively. The kappa values were excellent (more than 0.75) for the grade of H. pylori in the body, good (between 0.50 and 0.75) for the grade of H. pylori in the antrum, grade of inflammatory activity and intestinal metaplasia in the antrum and moderate to good (0.38-0.53) for the grade of chronic inflammation. Kappa values were poor to good (from 0.17 to 0.57) only in evaluation of the grade of atrophy. CONCLUSION: Interobserver agreement in the application of the Sydney system to reversibility of gastritis after H. pylori was good. More strict criteria should be used for atrophy and to differentiate normal and mild chronic inflammation.

The comparison of two methods in the anthropological study of linguistic differentiation.

The paper presents the application of hidden Markov models (HMM) in the analysis of the linguistic microdifferentiation of 48 reproductively isolated populations in the Eastern Adriatic. The mathematical method is described in detail when applied for the recognition of the two main dialects (cakavian and stokavian) present in the investigated area, using two distinguished HMM. The resulting classification of villages is compared to those of the clustering methods applied previously for the same purpose.