Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study.

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Bile reflux gastritis and intestinal metaplasia at the cardia.

BACKGROUND AND AIMS: Intestinal metaplasia (IM) at the cardia is likely to be a precursor of cardia cancer. Previous work has shown that it is associated with chronic inflammation attributable to either gastro-oesophageal reflux disease (GORD) or Helicobacter pylori infection. An alternative aetiological factor is bile reflux. Duodenogastric reflux brings about histological changes in the gastric mucosa that can be graded and used to calculate a bile reflux index (BRI). We used the BRI to assess whether reflux of bile plays a part in the development of cardia IM. METHODS: Histological changes in simultaneous gastric antrum and cardia biopsies from 267 dyspeptic patients were independently graded by two pathologists. The association between cardia IM and age, sex, clinical group, H pylori status, increased BRI (>14), and inflammation at the cardia were evaluated using logistic regression. RESULTS: A total of 226 patients had adequate cardia and antral biopsies; 149 had GORD and 77 had non-ulcer dyspepsia. Cardia IM was present in 66 (29%) patients, of whom 28 (42%) had complete IM. Increasing age, male sex, chronic inflammation, and a high BRI emerged as significant independent associations with cardia IM. Clinical group and H pylori status were not independent risk factors. CONCLUSIONS: Histological evidence of bile reflux into the stomach is associated with cardia IM. This could have an important bearing on carcinogenesis at this site.

Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux?

BACKGROUND: There is increasing evidence that reflux of bile plays a part in the pathogenesis of Barrett's oesophagus. Bile injury to the gastric mucosa results in a "chemical" gastritis in which oedema and intestinal metaplasia are prominent. AIM: To determine if patients with Barrett's oesophagus have more bile related changes in antral mucosa than patients with uncomplicated gastro-oesophageal reflux disease (GORD) or non-ulcer dyspepsia (NUD). PATIENTS AND METHODS: Patients were identified by a retrospective search of pathology records and those with a clinically confirmed diagnosis of either Barrett's oesophagus or reflux oesophagitis who had oesophageal and gastric biopsies taken at the same endoscopy and had no evidence of Helicobacter pylori infection entered the study. Control biopsies were taken from H pylori negative NUD patients. Antral biopsies were examined "blind" to clinical group and graded for a series of histological features from which the "reflux gastritis score" (RGS) and "bile reflux index" (BRI) could be calculated. The reproducibility of these histological scores was tested by a second pathologist. RESULTS: There were 100 patients with Barrett's, 61 with GORD, and 50 with NUD. The RGSs did not differ between groups. BRI values in the Barrett's group were significantly higher than those in GORD subjects (p=0.014) which in turn were higher than those in NUD patients (p=0.037). Similarly, the frequency of high BRI values (>14) was significantly greater in the Barrett's group (29/100; 29%) than in the GORD (9/61; 14.8%) or NUD (4/50; 8%) group. However, agreement on BRI values was "poor", indicating limited applicability of this approach. CONCLUSION: Patients with Barrett's oesophagus have more evidence of bile related gastritis than subjects with uncomplicated GORD or NUD. The presence of bile in the refluxate could be a factor in both the development of "specialised" intestinal metaplasia and malignancy in the oesophagus.

Randomised study of the efficacy of omeprazole and clarithromycin with either amoxycillin or metronidazole in the eradication of Helicobacter pylori in screened primary care patients.

BACKGROUND: Population Helicobacter pylori screening and treatment has been advocated as a means of reducing mortality from gastric cancer. The optimum Helicobacter pylori eradication therapy to use in this setting is uncertain. AIMS: To compare efficacy of seven days of omeprazole, clarithromycin and either metronidazole, or amoxycillin in Helicobacter pylori positive subjects detected by population screening. PATIENTS: Helicobacter pylori positive patients from the placebo group of a population screening and treatment trial were invited to take part in the investigation. METHODS: Patients were randomised to receive either omeprazole, clarithromycin and metronidazole or omeprazole, clarithromycin and amoxycillin, and Helicobacter pylori eradication was verified with a 13C-urea breath test at least four weeks after completion of therapy. RESULTS: A total of 221 patients took part in the study and 210 completed the protocol. Treatment was successful in 93/111 [84%) patients allocated to omeprazole, clarithromycin and metronidazole and in 96/110 (87%) allocated to omeprazole, clarithromycin and amoxycillin in an intention-to-treat analysis (p=0.46). Per protocol eradication rates were 93/107 (87%) in the metronidazole, and 96/103 (93%) amoxycillin group (p=0.129). CONCLUSIONS: There was no significant difference between the two regimens. The eradication rates achieved are comparable with previous studies in both dyspepsia and peptic ulcer patients.

The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen.

BACKGROUND: Current guidelines for Helicobacter pylori eradication recommend 7 days of a proton-pump inhibitor, clarithromycin (C), and either metronidazole (M) or amoxycillin (A). A shorter course would be cheaper and could be as effective. AIM: This study was designed to investigate the efficacy of three 5-day regimens based on lansoprazole (L). METHODS: 168 dyspepsia patients with H. pylori infection were randomized to receive a 5-day course of either LCM, LAC or CALM, and a 13C-urea breath test was performed after 4 weeks to assess eradication. RESULTS: 160 patients completed the study. Intention-to-treat eradication rates were as follows: LCM 81%, LAC 59%, CALM 88%. LCM and CALM gave significantly better eradication rates than LAC. There was no significant difference in adverse events across the three groups. Logistical regression analysis showed that the specific regimen used and the age of the patient were the only factors influencing eradication outcome. CONCLUSIONS: Five days of CALM yields acceptable eradication rates, and is cheaper than conventional 7-day proton pump inhibitor-triple therapy. It appears to offer good results in metronidazole-resistant strains of H. pylori. A randomized trial comparing 5-day CALM with conventional 7-day therapy is needed before this regimen can be recommended for routine use.