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

Abstract

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.

The Effects of Anti-inflammatory Drug Treatment in Gastric Cancer Prevention: an Update of a Meta-analysis

“…Forty-seven studies, comprising 2,345,540 patients and over 13,500 events reported the association between anti-inflammatory drug use and the risk of GC, met all of the selection criteria and were included in our meta-analysis (Figure 1) 10-15, 19, 21-29, 33-63. Of these enrolled articles, nine were RCT studies 12, 23, 27, 29, 38, 44, 48, 52, 61, fifteen were cohort studies 15, 24, 26, 28, 33-37, 45, 46, 58-60, 62, and the remaining twenty-three were case-control studies 10, 11, 13, 14, 21, 22, 24, 25, 39-43, 47, 49-51, 53, 54, 56, 57, 63. In our study, there were conducted, respectively, seventeen in North America 13-15, 21, 28, 35-37, 39, 43, 44, 47, 48, 53, 54, 57, 58, seventeen in Europe 11, 12, 27, 33, 34, 38, 40-42, 45, 46, 49, 50, 59, 60, 62, 63, eleven in Asia 22-26, 29, 51, 52, 61, and two in Australia 10, 56.…”

“…Twenty-two studies that were not adjusted for smoking, alcohol consumption, and BMI (body mass index) were omitted 10, 11, 19, 22, 28, 33, 34, 37, 39, 41, 44-46, 49, 52, 53, 56, 58-60, 62, 63. The remaining studies produced an RR of 0.74 (95% CI, 0.70-0.79), with substantial evidence of decreasing heterogeneity (P=0.043, I 2 = 37%).…”

“…For example, the largest scale study were generally enrolled twenty-one qualified studies range from1968 to 2003 and the summary RR was also with a high heterogeneity ( I 2 = 59.8%). In our study, we searched a multitude of online dataset and eventually forty-seven studies were included in our analysis, among of which nineteen new studies were never covered in the previous meta-analyses 19, 22-29, 38, 39, 44, 49-51, 53, 56, 58-60. Nevertheless, since the deficiency of randomized clinical trials, the strength of this study was impaired for drawbacks associated with an army of observational investigations.…”

Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process

“…In mice and Mongolian gerbils, high salt diet may exacerbate H. pylori -induced gastric cancer [46,50,51]. In mice, this occurs as increased proliferation and elongation of gastric pits, which may also provide more room for H. pylori to colonize [51].…”

“…Therefore, the presence of H. pylori may modify the effect of dietary salt intake on progression in the gastric precancerous process. To address these gaps, we analyzed data from a cohort study conducted in Colombia, South America [46] to estimate the effect of salt intake at baseline on future progression of gastric precancerous lesions in the entire cohort and within subgroups with and without H. pylori infection.…”