Asia-Pacific consensus guidelines on gastric cancer prevention.

BACKGROUND AND AIM: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. METHODS: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. RESULTS: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. CONCLUSION: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis.

AIM: To systematically evaluate the efficacy of H(2)-receptor antagonists (H(2)RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H(2)RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H(2)RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H(2)RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H(2)RAs of all doses across all grades of esophagitis, including patients refractory to H(2)RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H(2)RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H(2)RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.

Low-dose rabeprazole, amoxicillin and metronidazole triple therapy for the treatment of Helicobacter pylori infection in Chinese patients.

BACKGROUND: Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to be an effective second-line treatment of Helicobacter pylori infection. The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients. METHODS: Helicobacter pylori-positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications. side-effects of treatments were documented. RESULTS: A total of 120 patients were eligible for analysis. By intention-to-treat and per-protocol analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and 76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well-tolerated and compliance was >98% in both groups. CONCLUSIONS: Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.

Effects of primary metronidazole and clarithromycin resistance to Helicobacter pylori on omeprazole, metronidazole, and clarithromycin triple-therapy regimen in a region with high rates of metronidazole resistance.

The aim of this study was to investigate the effect of metronidazole resistance (MtzR) and clarithromycin resistance (ClaR) on the eradication rate for omeprazole, clarithromycin, and metronidazole triple-therapy regimen and on the development of posttherapy drug resistance in a region of high rates of MtzR. One hundred ninety-six Helicobacter pylori isolates were recovered from patients with duodenal ulcer, gastric ulcer, or nonulcer dyspepsia during upper endoscopy. The prevalences of MtzR, ClaR, and dual resistance were 37.8%, 13.8%, and 8.7%, respectively. The intention-to-treat eradication rates for metronidazole-susceptible (87.2% vs. 67.6%; P=.001) and clarithromycin-susceptible (86.4% vs. 40.7%; P<.001) strains were significantly higher than the rates for resistant strains. Multiple logistic regression analysis implicated younger age (<40 years old), MtzR, ClaR, and the diagnosis of nonulcer dyspepsia as independent factors that predicted treatment failure. The rates of posttreatment MtzR, ClaR, and dual resistance were 88%, 88%, and 75%, respectively. MtxR and ClaR significantly affected the success of eradication therapy. Posttreatment rates of resistance were high and were related to the presence of pretreatment antibiotic resistance.

Chemoprevention of gastric cancer: current status.

The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer.

Alternative and rescue treatment regimens for Helicobacter pylori eradication.

Eradication therapy has been incorporated into clinical practice. The regimens currently recommended for first-line treatment include a 2-week bismuth-based triple therapy (mainly in developing countries), a 1 - 2 week proton pump inhibitor (PPI)-based triple therapy and a 1-week ranitidine bismuth citrate (RBC)-based triple therapy. However, these regimens fail to eradicate Helicobacter pylori in up to 20% of patients due to poor compliance, inadequate treatment duration, smoking, old age and bacterial resistance to nitroimidazoles and/or macrolides in particular. Therefore, alternative regimens that avoid nitroimidazoles and/or macrolides or overcome bacterial resistance to these drugs, improve compliance, minimise side effects and/or reduce costs have been evaluated. One-week quadruple therapy, which adds a PPI or histamine receptor 2-blocker to bismuth-based triple therapy, usually achieves an eradication rate of 90% when used as an alternative first-line therapy but the efficacy decreases when used as a rescue therapy. Several new triple therapies that may be used as alternative and/or rescue therapies have been evaluated. Among these are furazolidone-based (furazolidone plus an antibiotic and a bismuth salt, a PPI or RBC), fluoroquinolone-based (levofloxacin or moxifloxacin plus an antibiotic and a PPI) and ecabet sodium-based (ecabet plus two antibiotics) triple therapies. Recently, rifabutin has been used in combination with a PPI and amoxycillin as a rescue therapy, with satisfactory eradication rates. In addition, a number of new antimicrobial agents are currently under investigation in in vitro studies but the clinical values of these agents needs to be confirmed.

Epidemiology of gastric cancer in relation to diet and Helicobacter pylori infection.

Gastric cancer is the second most common fatal malignancy in the world. In China, gastric cancer is now the second most common malignancy, while in Hong Kong, the mortality rate ranked fourth among all cancers in 1995. Dietary factors in gastric carcinogenesis came mostly from case-control studies. N-Nitroso compounds from dietary sources such as preserved, smoked and salted foods were found to be associated with gastric cancer. ß-Carotene, selenium and α-tocopherol have been shown in an intervention study to be favourable in the reduction of stomach cancer mortality. Fruits and vegetables showed the most consistent results of inverse association with gastric cancer. Dietary salt intake in preserved or salted foods is also shown to be associated with gastric cancer. Tea drinking, especially green tea, has a protective effect against gastric cancer as shown in some studies. Prospective case-control studies of the association between Helicobacter pylori infection and the subsequent development of gastric cancer showed that the odds ratio ranged from 2.8 to 6.0. However, results of similar case-control studies in countries with a high frequency of gastric cancer are controversial. Infection with H. pylori leads to changes in the vitamin C content of gastric juice, reactive oxygen metabolites, epithelial cell proliferation and apoptosis. Recently, CagA-positive strains were found to be associated with gastric cancer and also duodenal ulcers. The exact role of H. pylori in gastric carcinogenesis is still under investigation. Large-scale intervention studies are underway to examine dietary supplementation, H. pylori infection and gastric cancer. Helicobacter pylori eradication for gastric cancer prevention is being conducted in China and other parts of the world. In high-risk areas, for example in China, a combination approach including H. pylori eradication and dietary supplementation may be necessary.