for the China Gastric Cancer Study Group T HE ASSOCIATION BETWEEN chronic Helicobacter pylori infection and development of gastric cancer is well established. [1][2][3][4] The International Agency for Research on Cancer has categorized H pylori as a group I carcinogen. 5 In Correa's model of gastric carcinogenesis, the gastric mucosa progresses through the stages of chronic active gastritis, glandular atrophy, intestinal metaplasia, and dysplasia before the development of gastric adenocarcinoma. 6-10 Two recent large-scale, prospective studies, 11,12 both in high-risk populations, have re-ported H pylori infection as a definite risk factor for the development of gastric cancer. In the first study, presence of H pylori at baseline was associated with an increased risk of progression to dyspla-Author Affiliations and Members of the China Gastric Cancer Study Group are listed at the end of this article.

The Asia-Pacific Consensus Conference was convened to review and synthesize the most current information on Helicobacter pylori management so as to update the previously published regional guidelines. The group recognized that in addition to long-established indications, such as peptic ulcer disease, early mucosa-associated lymphoid tissue (MALT) type lymphoma and family history of gastric cancer, H. pylori eradication was also indicated for H. pylori infected patients with functional dyspepsia, in those receiving long-term maintenance proton pump inhibitor (PPI) for gastroesophageal reflux disease, and in cases of unexplained iron deficiency anemia or idiopathic thrombocytopenic purpura. In addition, a population 'test and treat'strategy for H. pylori infection in communities with high incidence of gastric cancer was considered to be an effective strategy for gastric cancer prevention. It was recommended that H. pylori infection should be tested for and eradicated prior to long-term aspirin or non-steroidal anti-inflammatory drug therapy in patients at high risk for ulcers and ulcer-related complications. In Asia, the currently recommended first-line therapy for H. pylori infection is PPI-based triple therapy with amoxicillin/metronidazole and clarithromycin for 7 days, while bismuth-based quadruple therapy is an effective alternative. There appears to be an increasing rate of resistance to clarithromycin and metronidazole in parts of Asia, leading to reduced efficacy of PPI-based triple therapy. There are insufficient data to recommend sequential therapy as an alternative first-line therapy in Asia. Salvage therapies that can be used include: (i) standard triple therapy that has not been previously used; (ii) bismuth-based quadruple therapy; (iii) levofloxacin-based triple therapy; and (iv) rifabutin-based triple therapy. Both CYP2C19 genetic polymorphisms and cigarette smoking can influence future H. pylori eradication rates. Key wordshelicobacter pylori:diagnosis, helicobacter pylori:treatment and antimicrobial resistance, H. pylori and gastric cancer.

In patients who had ulcer complications related to the long-term use of low-dose aspirin, treatment with lansoprazole in addition to the eradication of H. pylori infection significantly reduced the rate of recurrence of ulcer complications.

DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.Helicobacter pylori is a microaerophilic bacterium with the extraordinary ability to establish infections in human stomachs that can last for years or decades, despite immune and inflammatory responses and normal turnover of the gastric epithelium and overlying mucin layer in which it resides. It is carried by more than half of all people worldwide and has attracted great attention as a major cause of peptic ulcer disease and an early risk factor for gastric cancer, one of the most frequently lethal of malignancies worldwide (for reviews see references 23, 48, and 60).

Background: E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer. Aims: This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer.Methods: E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry.Results: E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05).Conclusion: E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.

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. Firstline 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.

SUMMARYBackground: Population-based data on gastro-oesophageal reflux disease in Chinese are lacking. The prevalence, clinical spectrum and health care-seeking behaviour of subjects with gastro-oesophageal reflux disease were studied. Methods: Ethnic Chinese (3605) were invited to participate in a telephone survey using a validated gastro-oesophageal reflux disease questionnaire and the Hospital Anxiety and Depression Scale. Results: A total of 2209 subjects (58% female; mean age, 40.3 years) completed the interview. The annual, monthly and weekly prevalence rates of gastro-oesophageal reflux disease were 29.8%, 8.9% and 2.5%, respectively. Gastro-oesophageal reflux disease symptoms were associated with non-cardiac chest pain [odds ratio (OR), 2.3; 95% confidence interval (95% CI), 1.7-3.1], dyspepsia (OR, 1.9; 95% CI, 1.4-2.5), globus (OR,

Helicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz r strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz s H. pylori to Mtz r ; (ii) Mtz r mutant derivatives of a cultured Mtz s strain resulted from mutation in rdxA; and (iii) transformation of Mtz s strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 g/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz s , and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA ؉ cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.Helicobacter pylori is a gram-negative microaerophilic bacterium that chronically infects human gastric epithelial cell surfaces and the overlying gastric mucin, a niche that few if any other microbes can occupy. It is carried by more than half of all people worldwide and is an important human pathogen: a major cause of peptic ulcer disease, and a contributor to other illnesses, ranging from childhood malnutrition to gastric cancer, and to increased susceptibility to other food-and waterborne pathogens (7,8,32,38,47). There is great intrinsic and public health interest in fully elucidating H. pylori's metabolic pathways and how H. pylori maintains its redox balance during microaerobic growth. Such knowledge should help us to understand the extraordinary chronicity of H. pylori infection and factors that determine whether a given infection will be benign or virulent, elucidate mechanisms of drug susceptibility and resistance, and identify potential targets for new effective antimicrobial agents.Here we focus on mechanisms of susceptibility and resistance of H. pylori to metronidazole (Mtz), a synthetic nitroimidazole that is a key component of popular and affordable anti-H. pylori therapies worldwide and that is also widely used against various anaerobic and parasitic infections (13,36,45). Resistance to Mtz is common among H. pylori strains, with frequencies among clinical isolates ranging from 10 ...