H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.

There are no established criteria to classify patients into high or low risk of progressing to gastric cancer (GC). The aim of the study was to identify predictors of GC occurrence among patients with gastric preneoplastic lesions. A prospective and retrospective follow-up study was carried out in a province in Spain with one of the highest risk of GC. The study included 478 patients who underwent gastric biopsy in 1988-1994 with diagnoses of normal mucosa, nonatrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG) and complete or incomplete intestinal metaplasia (IM) and who accepted to undergo a new biopsy during [2005][2006][2007] or had an event during follow up. Inter-and intra-observer variability of histological diagnosis was assessed. Analysis was done using Cox proportional hazards risk (HR) models. The mean age of the patients was 50 years, 47% were males and the mean follow-up time was 12.8 years. During follow-up, 23 GC (4.8%) were diagnosed (21 adenocarcinomas and 2 lymphomas) with an incidence of 3.77 per 1,000 person per year. The incidence rate of GC for those with incomplete IM was 16.5 per 1,000 person years. Out the 21 adenocarcinomas, 16 had an incomplete IM in the baseline diagnosis. Incomplete IM (HR 11.3; 95% CI 3.8-33.9) and a family history of GC (HR 6.1; 95% CI 1.7-22.4) were the strongest risk factors for gastric adenocarcinoma. Subtyping of IM and family history of GC may be useful for the identification of high-risk patients who need more intensive surveillance.Experimental and epidemiological evidence indicates that gastric cancer (GC) is the result of a long multistep and multifactorial process. 1 An inflammatory process in the antrum, usually associated with Helicobacter pylori (Hp) infection, is considered to be the cause of the initial lesion, which may progress toward a multifocal chronic atrophic gastritis in the corpus, intestinal metaplasia (IM), dysplasia and finally the invasive carcinoma. 2 This seems to be the sequence of the intestinal type of gastric adenocarcinoma, which is the predominant type of GC in many countries, and these lesions are considered as precursors of this type of cancer. IM is usually subclassified as ''complete'' (small intestinal type or Type I) or ''incomplete'' (colonic type or Types II and III), which is thought to be the most advanced stage of IM. 3 The diffuse type of GC, on the contrary, lacks well-defined precursors, although many studies have observed that it is also associated with intestinal metaplasia. 3 Symptoms are often absent or nonspecific in patients suffering this long multistep process, and, therefore, GC is usually diagnosed at an advanced stage when curative options are very limited. 4,5 Five-year relative survival rates of GC in European patients are very low (less than 23%) 6 ; therefore, better control of risk factors and identification of high-risk patients at an early stage of disease represent the most effective ways for reducing the burden of this tumor.The need to reevaluate premalignant gastric le...

We examined the variation with ionic strength (I, adjusted with KCl, KNO(3), KBr, NaCl or NaClO(4)) of the formal potential (E(const)) for glass electrodes exhibiting a Nernstian response (i.e. E(cell)=E(const)-slog[H(+)]). For this purpose, we investigated the different factors included in the formal potential, so we obtained reported values for the liquid junction potential as a function of ionic strength and determined the logarithm of the activity coefficient for the proton in various saline media, using Pitzer equations.

method design for H. pylori genotyping, sample typing, manuscript draft , and fi nal version: R.M. Ferreira and C. Figueiredo; gastroscopies: P. Alonso; statistical analyses: C. Bonet; pathology reviews: M.L. Pardo, J.M. Ruiz Liso, and J.M. Sanz-Anquela; result interpretation and fi nal approval of the manuscript: all authors.

In order to assess whether inherited genetic variability in the mucin genes associates with the evolution of gastric cancer precursor lesions (GCPLs), we genotyped 22 tagSNPs in MUC1, MUC6 and MUC2 genes of 387 patients with GCPLs that had been followed up for 12.8 years. According to the diagnosis at recruitment and at the end of follow-up, the lesions did not change in 43.1% of the patients, regressed in 28.7% and progressed in 28.2%. Three SNPs in the 3'-moiety of MUC2 were significantly associated with a decreased risk of progression of the lesions, whereas another four SNPs, located at the 5'-moiety, were found to be significantly associated either with increased [one single-nucleotide polymorphism (SNP)] or decreased (three SNPs) probability of regression. Stratified analysis indicated that significance was maintained only in those subjects positive for Helicobacter pylori infection and in those not consuming non-steroidal anti-inflammatory drugs, which were found protective against lesion progression. Haplotype analyses indicated the presence of two haplotypes, one in each moiety of the gene, that were significantly associated with decreased risk of progression of the lesions [odds ratio (OR) = 0.49 and 0.46; 95% confidence interval (CI) = 0.28-0.85 and 0.25-0.86, respectively]. The 5'-end haplotype was also associated with increased probability of regression (OR = 1.67; 95% CI = 1.02-2.73), altogether suggesting a protective role against progression of the precancerous lesions. No significant association was found with variants in MUC1 and MUC6 genes. These results indicate, for the first time, that genetic variability in MUC2 is associated with evolution of GCPLs, especially in H.pylori infected patients, suggesting a role of this secreted mucin in gastric carcinogenesis.