Anti-inflammatory and tissue-protectant drug effects: results from a randomized placebo-controlled trial of gastritis patients at high risk for gastric cancer.

BACKGROUND: The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt. METHODS: We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo. RESULTS: Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation. CONCLUSION: The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.

Nutritional factors and Helicobacter pylori infection in Colombian children.

BACKGROUND: Helicobacter pylori infection occurs most frequently in impoverished populations; however, little is known about specific determinants of susceptibility. This report describes the relationship between H. pylori infection and nutritional indicators among children from a rural village in the Colombian Andes, where a prevalence of 69% was observed in children from 2 to 9 years old. METHODS: In a cross-sectional study of 684 children, comprising 92% of the 2- to 9-year-old population of Aldana, Colombia, information was obtained on dietary factors by questionnaire, height and weight by direct measurement, and H. pylori status using the carbon-13 urea breath test. Multivariate logistic regression was used to estimate relative risks for nutritional indicators. RESULTS: The infection was least frequent among children who are several servings of fruits and vegetables daily, drank two or more cups of milk daily, and were in the upper quintile of height for their age. The odds of infection increased 19-fold (95% confidence interval, 4.0-91.9) among children who consumed less than two daily servings of fruits and vegetables compared with the modal intake of three to five daily servings. Children whose daily vitamin C intake from fruits and vegetables was less than 40 mg had greatly increased odds of infection (odds ratio, 7.2; 95% confidence interval, 1.5-34.1) compared to the modal intake of 80-119 mg; for beta-carotene, the odds ratio was 3.1 (95% confidence interval, 1.2-7.9) for intakes of less than 300 IU per day, compared with the modal daily intake of 900 IU or more. CONCLUSIONS: The results of this population-based study suggest that nutritional factors may play a role in determining susceptibility to H. pylori infection.

Gastric precancerous process in a high risk population: cross-sectional studies.

The gastric precancerous process is evaluated in 1788 participants in a gastroscopy survey in the population of Nariño, Colombia, which has one of the highest gastric cancer incidence rates on record. A detailed histological classification is used, and a hierarchical distribution of lesions is described with the main stages being gland neck hyperplasia, atrophy (gland loss), intestinal metaplasia and dysplasia. Acute inflammation was not found to be a specific stage in the sequence but rather a common finding in all stages of the precancerous spectrum. Indices of disease progression for the different steps are calculated and found to increase with gastric pH and nitrate and nitrite content of the gastric juice. The effects of high pH and nitrite content are intimately correlated. Relative risks of specific lesions, namely, hyperplasia, atrophy, metaplasia, and dysplasia, increase linearly with higher pH, nitrate, and nitrite values in the gastric juice. The severity of atrophy correlates with the prevalence of metaplasia, suggesting a sequential relationship between the described stages, a finding supported by all parameters examined. The model of progression described may serve as a basis for comparisons with populations at different levels of gastric cancer risk but it fails to provide information concerning the time required for each change, which should be provided by follow-up (cohort) studies.

Gastric precancerous process in a high risk population: cohort follow-up.

In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Columbia, have been followed from 3-16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.

Genetic etiology of gastric carcinoma: I. Chronic atrophic gastritis.

Scientific evidence has accumulated to show that chronic atrophic gastritis (CAG) is a precursor of gastric carcinoma, especially its intestinal histologic type; thus the etiology of CAG is of interest. Data on 110 families (557 individuals) collected as part of a large cohort from the Narino region of Colombia, South America, are analyzed to determine the familiality of CAG as a risk factor, and the possible involvement of a major gene in its etiology. We found that age and having an affected mother are important risk factors. In the sample, 45% are affected; 56% of individuals above 30 are affected, whereas only 28% of those 30 and under are affected; 48% of those with affected mothers are affected, but only 7% of those with unaffected mothers are affected. A positive spouse association was confounded with age. Sex and an affected father are not significant risk factors. The genetic (segregation) analysis showed Mendelian transmission of a recessive autosomal gene with penetrance dependent on age and mother's CAG status. Homozygous recessives account for an estimated 61% of the sampled population and have penetrance reaching 72% at age 30 if the mother is affected, and 41% if the mother is not affected. Carriers and non-carriers, who make up an estimated 39% of the sampled population, have an appreciable estimated risk after age 50. The environment, particularly diet, as the sole determinant of CAG needs reevaluation; some combined action of genes and environment seems more plausible.

The impact of vaginal cytology on cervical cancer risks in Cali, Colombia.

The role of vaginal cytology screening in preventing invasive carcinoma of the cervix was investigated in Cali, Colombia. The history of previous participation in screening programs was obtained from 204 patients with invasive carcinoma and from 2 sets of age-matched controls: one from the same health center and one for the same neighborhood of the patient. Our results show that the risk of developing invasive carcinoma is at least 10 times greater in non-screened than in screened women.