Premalignant Gastric Lesions Research Articles

Helicobacter pylori Eradication and Gastric Cancer: When Is the Horse Out of the Barn?

Helicobacter pylori infection is a major risk factor for gastric cancer development. Therefore, H. pylori eradication may be an important approach in the prevention of gastric cancer. However, long-term data proving the efficacy of this approach are lacking. This report describes two patients who developed gastric cancer at, respectively, 4 and 14 years after H. pylori eradication therapy. These patients were included in a study cohort of H. pylori-infected subjects who received anti-H. pylori therapy during the early years of development of H. pylori eradication therapy and underwent strict endoscopic follow-up for several years. In both patients, gastric ulcer disease and premalignant gastric lesions, i.e., intestinal metaplasia at baseline and dysplasia during follow-up, were diagnosed before gastric cancer development. These case reports demonstrate that H. pylori eradication does not prevent gastric cancer development in all infected patients after long-term follow-up. In patients with premalignant gastric lesions, in particular in patients with a history of gastric ulcer disease, adequate endoscopic follow-up is essential for early detection of gastric neoplasia.

Narrow band imaging endoscopy for diagnosis of malignant and premalignant gastric lesions

Objective To evaluate the clinical value of narrow band imaging(NBI)for diagnosis of malignant and premalignant gastric lesions.Methods The gastric lesions,pits and microvascularity were observed using conventional endoscopy followed by narrow band imaging(NBI)and chromoendoscopy(0.2%indigo carmine)as well as magnifying endoscopy(×80)in 217 patients.The quality of images obtained by different endoscopies was evaluated and compared to pathologic interpretations. Results Of 217 patients,non-atrophic gastritis was found in 85 cases,chronic atrophic gastritis in 38 cases,mild dysplasia in 19 cases,moderate dysplasia in 9 cases,severe dysplasia in 4 cases,early gastric cancer in 5 cases,advanced gastric cancer in 20 cases and intestinal metaplasia in 91 cases.The NBI endoscopy was superior to conventional endoscopy and chromoendoscopy in finding gastric lesions(P=0.000).The gastric microvascularity was more clearly seen on images obtained by NBI combined with magnifying endoscopy in comparison with conventional endoscopy and chromoendoscopy(P=0.000).There were six patterns in description of gastric pits with NBI endoscopy.Type Ⅲ,Ⅳ or Ⅴ1 was usually found in chronic atrophic gastritis,type Ⅲ,Ⅳ,Ⅴ1 or Ⅴ2 in intestinal metaplasia,type V1 or Ⅳ in dysplasia and type Ⅵ in suspected malignant lesion.Conclusions NBl with magnifying endoscopy is helpful in improving the biopsy accuracy of malignant and dysplastic lesions and in detecting early gastric cancer. Key words: Stomach neoplasms; Gastroscopy; Diagnosis

M1988 Genetic and Epigenetic Alterations of Netrin Receptors in Gastric Cancer

Background: The recently proposed OLGA staging system (Gut 2007;56;631-636) is based on the extent and severity of atrophic gastritis (AG) and provides relevant clinical information regarding gastric cancer risk. However, AG is a difficult histopathological diagnosis of which the interobserver agreement is low. In contrast, intestinal metaplasia (IM) has better defined specific histopathological features and is associated with a much better interobserver agreement. The aim of this study was to evaluate interobserver agreement for AG, IM and dysplasia (DYS) and to assess whether a staging system based on IM instead of AG may be preferred to estimate gastric cancer risk. Methods: In a prospective multicenter study, patients with IM and DYS underwent surveillance endoscopy with extensive biopsy sampling. Three expert pathologists graded biopsy specimens according to the updated Sydney classification and the Vienna classification. Interobserver variation for these classifications was analysed by kappa (K) statistics. In the OLGA staging system AG was replaced by IM creating the IM staging system. Both classifications were evaluated for patient distribution and severe premalignant gastric lesions by stage. Results: In total, 125 patients (69 men and 56 women) with a mean (± SD) age of 61 ±11.7 years (range 23-81 years) were included in this study. DYS was diagnosed in 7 (6%) patients. For DYS interobserver variability was fair (K=0.4; low grade DYS K=0.2; and high gradeDYS K=0.5). The interobserver agreement was moderate for AG (K=0.6), whereas agreement was almost perfect for IM (K=0.9). Overall, 83 (66%) patients were classified in stage I-IV according to the OLGA staging system (stage I n=23; stage II n=29; stage III n=23; stage IV n=8) and 80 (64%) patients were classified in stage I-IV according to the IM staging system (stage I n=24; stage II n=25; stage III n=22; stage IV n=9). Of the dysplasia patients, 5 (71%) patients clustered in stage III-IV in the OLGA system, whereas 6 (86%) patients clustered in III-IV of the IM staging system. Conclusions: Replacement of AG by IM in the staging and grading of gastritis increases interobserver agreement considerably. Moreover, the correlation with the severity of gastritis remains at least as effective as the OLGA classification. Therefore, the intestinal metaplasia staging may be preferred over the OLGA system for the prediction of gastric cancer risk in patients with pre-malignant gastric lesions. Further research is needed to evaluate the use of this system for the selection of a small category of patients for more intense follow-up.

M1983 Grading and Staging Gastritis with the Olga System: Intestinal Metaplasia As a Reproducible Alternative

Background: The recently proposed OLGA staging system (Gut 2007;56;631-636) is based on the extent and severity of atrophic gastritis (AG) and provides relevant clinical information regarding gastric cancer risk. However, AG is a difficult histopathological diagnosis of which the interobserver agreement is low. In contrast, intestinal metaplasia (IM) has better defined specific histopathological features and is associated with a much better interobserver agreement. The aim of this study was to evaluate interobserver agreement for AG, IM and dysplasia (DYS) and to assess whether a staging system based on IM instead of AG may be preferred to estimate gastric cancer risk. Methods: In a prospective multicenter study, patients with IM and DYS underwent surveillance endoscopy with extensive biopsy sampling. Three expert pathologists graded biopsy specimens according to the updated Sydney classification and the Vienna classification. Interobserver variation for these classifications was analysed by kappa (K) statistics. In the OLGA staging system AG was replaced by IM creating the IM staging system. Both classifications were evaluated for patient distribution and severe premalignant gastric lesions by stage. Results: In total, 125 patients (69 men and 56 women) with a mean (± SD) age of 61 ±11.7 years (range 23-81 years) were included in this study. DYS was diagnosed in 7 (6%) patients. For DYS interobserver variability was fair (K=0.4; low grade DYS K=0.2; and high gradeDYS K=0.5). The interobserver agreement was moderate for AG (K=0.6), whereas agreement was almost perfect for IM (K=0.9). Overall, 83 (66%) patients were classified in stage I-IV according to the OLGA staging system (stage I n=23; stage II n=29; stage III n=23; stage IV n=8) and 80 (64%) patients were classified in stage I-IV according to the IM staging system (stage I n=24; stage II n=25; stage III n=22; stage IV n=9). Of the dysplasia patients, 5 (71%) patients clustered in stage III-IV in the OLGA system, whereas 6 (86%) patients clustered in III-IV of the IM staging system. Conclusions: Replacement of AG by IM in the staging and grading of gastritis increases interobserver agreement considerably. Moreover, the correlation with the severity of gastritis remains at least as effective as the OLGA classification. Therefore, the intestinal metaplasia staging may be preferred over the OLGA system for the prediction of gastric cancer risk in patients with pre-malignant gastric lesions. Further research is needed to evaluate the use of this system for the selection of a small category of patients for more intense follow-up.

Evaluación de la visualización por endoscopia en la identificación de lesiones gástricas premalignas en una población colombiana con prueba de referencia histopatológica

Aim To evaluate the performance of endoscopic visualization in the identification of premalignant gastric lesions, with histopathological examination of biopsy samples as a reference test, in Bucaramanga, Colombia. Location League for the Fight Against Cancer, Bucaramanga, Colombia. Design Diagnostic technology evaluation with cross-sectional sampling. Measurements We calculate the sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio (+), likelihood ratio (−), kappa index and the prevalence rate kappa. Results A total of 155 patients were studied, with a mean age of 45.43 (14.15) years and an approximate male:female ratio of 2:1. The endoscopic visualization had a sensitivity of 87.84%, a specificity of 55.56%, a positive predictive value of 64.36%, a negative predictive value of 83.33%, a likelihood ratio+of 1.98, a likelihood ratio−de 0.22 and a kappa index of 0.4272, in the identification of preneoplastic lesions of the stomach in a population with a disease prevalence of 47.74%. Conclusions The endoscopic visualization of the gastrointestinal mucosa, allows a moderate and fast identification of early preneoplastic lesions, providing an opportunity of its early histopathological diagnosis.

Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer

BackgroundPersistent colonization of the human stomach by Helicobacter pylori is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of H. pylori strains from patients with gastritis or duodenal ulcer disease have been analyzed. In this study, we analyzed the genome sequences of an H. pylori strain (98-10) isolated from a patient with gastric cancer and an H. pylori strain (B128) isolated from a patient with gastric ulcer disease.ResultsBased on multilocus sequence typing, strain 98-10 was most closely related to H. pylori strains of East Asian origin and strain B128 was most closely related to strains of European origin. Strain 98-10 contained multiple features characteristic of East Asian strains, including a type s1c vacA allele and a cagA allele encoding an EPIYA-D tyrosine phosphorylation motif. A core genome of 1237 genes was present in all five strains for which genome sequences were available. Among the 1237 core genes, a subset of alleles was highly divergent in the East Asian strain 98-10, encoding proteins that exhibited <90% amino acid sequence identity compared to corresponding proteins in the other four strains. Unique strain-specific genes were identified in each of the newly sequenced strains, and a set of strain-specific genes was shared among H. pylori strains associated with gastric cancer or premalignant gastric lesions.ConclusionThese data provide insight into the diversity that exists among H. pylori strains from diverse clinical and geographic origins. Highly divergent alleles and strain-specific genes identified in this study may represent useful biomarkers for analyzing geographic partitioning of H. pylori and for identifying strains capable of inducing malignant or premalignant gastric lesions.

Comparison of Chromoendoscopy and Conventional Endoscopy in the Detection of Premalignant Gastric Lesions

Diagnosis and localization of intestinal metaplasia and early gastric cancer is problematic because of the lack of any telltale gross endoscopic signs. To compare the efficacy of chromoendoscopy with conventional endoscopy for the detection of gastric premalignant lesions (intestinal metaplasia). Thirty-three patients in whom previous routine endoscopic biopsies showed intestinal metaplasia were enrolled in a prospective study. Each patient underwent a two-step endoscopy procedure: conventional endoscopy and chromoendoscopy using methylene blue. Biopsies were taken during each step and were studied by an expert pathologist. Presence of intestinal metaplasia was considered a positive result. Considering the presence of intestinal metaplasia anywhere in the stomach as a positive result, 13 patients were diagnosed with intestinal metaplasia using both endoscopic methods, while eight patients had positive results using chromoendoscopy without any metaplastic changes detected with the conventional method (P=0.003). One patient showed positive biopsies with the conventional method while the pathology report showed no positive biopsies using the chromoendoscopy method. The number of positive biopsies from the antrum, body and fundus were 18, 15 and seven, respectively, using chromoendoscopy, and 10, four and two, respectively, from the same sites using conventional endoscopy. The present study demonstrated that chromoendoscopy is superior to conventional endoscopy for the detection of metaplastic changes and its use can be suggested for the screening of early malignancies of the stomach.

Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer

Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.

The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

BackgroundOverall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints.MethodsProtein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation.ResultsBy significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated.ConclusionThis simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

P120 and Kaiso RegulateHelicobacter pylori-induced Expression of Matrix Metalloproteinase-7

Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Matrix metalloproteinase (MMP)-7, a member of a family of enzymes with tumor-initiating properties, is overexpressed in premalignant and malignant gastric lesions, and H. pylori cag(+) strains selectively increase MMP-7 protein levels in gastric epithelial cells in vitro and in vivo. We now report that H. pylori-mediated mmp-7 induction is transcriptionally regulated via aberrant activation of p120-catenin (p120), a component of adherens junctions. H. pylori increases mmp-7 mRNA levels in a cag- and p120-dependent manner and induces translocation of p120 to the nucleus in vitro and in a novel ex vivo gastric gland culture system. Nuclear translocation of p120 in response to H. pylori relieves Kaiso-mediated transcriptional repression of mmp-7, which is implicated in tumorigenesis. These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains.

This Month in Gastroenterology

This Month in Gastroenterology

W1881 The Yield of Endoscopic Surveillance of Pre-Malignant Gastric Lesions: Optimalization of Biopsy Strategies

W1881 The Yield of Endoscopic Surveillance of Pre-Malignant Gastric Lesions: Optimalization of Biopsy Strategies

Source of variation in the diagnosis of Helicobacter pylori-associated multifocal atrophic gastritis.

Introduction: Multiple sampling from different sites of the stomach as well as the number of fragments of gastric mucosa available for histopathologic evaluation are important sources of variation when classifying and grading chronic gastritis. Objective: To estimate the sensitivity of the number of fragments of gastric mucosa necessary to establish the diagnosis of atrophic gastritis with intestinal metaplasia, gastric dysplasia and H. pylori infection. In addition, this study will attempt to assess the intra-observer variability in the classification of these premalignant gastric lesions. Methods: This is a 6 year-cohort study, wherein 1958 gastric endoscopic procedures performed by two gastroenterologists were reviewed. Five gastric biopsy samples were obtained from the antrum, body and lesser curvature during each procedure. One pathologist was in charge of reviewing the five histopathology samples for each subject and providing a definitive diagnosis which was used as the gold standard. Each gastric mucosa sample reviewed led to an individual diagnosis for that sample which was compared with the gold standard. Intra-observer variability was assessed in 127 individuals who correspond to a random sample of 20% of the total endoscopic procedures performed during the 72 month-follow-up. Results: The sensitivity of the diagnosis of intestinal metaplasia (IM) and gastric dysplasia increased proportionally with the number of gastric mucosa samples reviewed. The lesser curvature of the stomach had the highest sensitivity for the diagnosis of IM and dysplasia, among all the stomach regions studied. Just one sample of gastric mucosa attained a sensitivity of 95.9% for the detection of H. pylori infection. The intra-observer agreement for the diagnosis of multifocal atrophic gastritis was 86.1% and the kappa value was 0.79 (95% CI 0.76-0.85). Alcohol-fixed biopsy specimens were inadequate to diagnose H. pylori infection and to assess dysplasia. Conclusion: The number of mucosa gastric fragments reviewed, the fixation method used, and the biopsy site are all important factors in order to ensure a correct classification of chronic gastritis.

External validation of a classification for methylene blue magnification chromoendoscopy in premalignant gastric lesions

Conventional endoscopy has low sensitivity, specificity, and interobserver agreement for the diagnosis of gastric atrophy, intestinal metaplasia, and dysplasia. Magnification chromoendoscopy (ME) may optimize the evaluation of premalignant gastric lesions. As part of a multicenter trial, we aimed at validating a previously proposed classification for gastric methylene blue ME at a different center. SETTING, PATIENTS, AND INTERVENTIONS: A sample of patients (n = 42) with previously diagnosed chronic atrophic gastritis with or without intestinal metaplasia underwent ME (Pentax EG-3430Z) with 1% methylene blue by 2 endoscopists. A simplified version of a previously published ME classification (group I, group II [further divided into subgroups IIE and IIF], and group III) was used for macroscopic lesions (n = 203) with Sydney-Houston and Vienna classifications being used for histologic analysis (n = 479 biopsy specimens). Excellent reproducibility (wK = 0.92 [95% CI, 0.88-0.96]) was observed for classification in groups and substantial reproducibility (wK = 0.78 [95% CI, 0.72-0.84]) was found for classification in subgroups. Global validity was 82% (range 78%-86%), showing no false negatives (sensitivity of 100% [1/1 biopsy]) and a very low rate of false positives (specificity 99% [297/299 biopsies]) for dysplasia detection. This classification for methylene blue ME was highly reproducible and valid for the diagnosis of premalignant gastric lesions when used in a center different from that involved in its conception. Despite requiring an unconventional endoscope and a longer procedure, these results could reinforce ME as a valuable technique in the surveillance of patients at risk for gastric cancer.

Gastric Cancer Risk in Patients With Premalignant Gastric Lesions: A Nationwide Cohort Study in the Netherlands

A cascade of precursor lesions (eg, atrophic gastritis, intestinal metaplasia, and dysplasia) precedes most gastric adenocarcinomas. Quantification of gastric cancer risk in patients with premalignant gastric lesions is unclear, however. Consequently, endoscopic surveillance is controversial, especially in Western populations. To analyze current surveillance practice and gastric cancer risk in patients with premalignant gastric lesions, all patients with a first diagnosis between 1991 and 2004 were identified in the Dutch nationwide histopathology registry (PALGA); follow-up data were evaluated until December 2005. In total, 22,365 (24%) patients were diagnosed with atrophic gastritis, 61,707 (67%) with intestinal metaplasia, 7616 (8%) with mild-to-moderate dysplasia, and 562 (0.6%) with severe dysplasia. Patients with a diagnosis of atrophic gastritis, intestinal metaplasia, or mild-to-moderate dysplasia received re-evaluation in 26%, 28%, and 38% of cases, respectively, compared with 61% after a diagnosis of severe dysplasia (P < .001). The annual incidence of gastric cancer was 0.1% for patients with atrophic gastritis, 0.25% for intestinal metaplasia, 0.6% for mild-to-moderate dysplasia, and 6% for severe dysplasia within 5 years after diagnosis. Risk factors for gastric cancer development were increasing severity of premalignant gastric lesions at initial diagnosis (eg, severe dysplasia, hazard ratio 40.14, 95% confidence interval 32.2-50.1), increased age (eg, 75-84 years, hazard ratio 3.75, 95% confidence interval 2.8-5.1), and male gender (hazard ratio 1.50, 95% CI 1.3-1.7). Patients with premalignant gastric lesions are at considerable risk of gastric cancer. As current surveillance of these patients is inconsistent with their cancer risk, development of guidelines is indicated.

Expression of RASSF1A and CyclinD1 in gastric cancer and premalignant lesion and its significance

Expression of RASSF1A and CyclinD1 in gastric cancer and premalignant lesion and its significance

Argon plasma coagulation under magnifying chromoendoscopy for gastric premalignant lesions: an analysis of 90 cases

Argon plasma coagulation under magnifying chromoendoscopy for gastric premalignant lesions: an analysis of 90 cases

Vitamin C supplementation does not protect L-gulono-gamma-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy.

In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo(tm1Umc/mmcd) (gulo(-/-)) mice lacking L-gulono-gamma-lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori-infected gulo(-/-) mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo(-/-) mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo(-/-) mice supplemented with high vitamin C, but lesions were less severe in gulo(-/-) mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo(-/-) mice supplemented with low vitamin C correlated with reduced Th1-associated IgG2c, gastric IFN-gamma and TNF-alpha mRNA and higher H. pylori colonization levels. These results in the H. pylori-infected gulo(-/-) mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo(-/-) mice from H. pylori-induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo(-/-) mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response.

Review article: Helicobacter pylori eradication for the prevention of gastric cancer

Gastric cancer is the fourth most common cancer and second leading cause of cancer-related death worldwide. A clear association between Helicobacter pylori infection and gastric cancer was established years ago. H. pylori eradication may be an effective approach to decrease morbidity and mortality of gastric cancer. To discuss current evidence of H. pylori eradication for prevention of gastric cancer. Recent studies have shown that the association between H. pylori and gastric cancer has probably been underestimated. This may have resulted from negative H. pylori status in subjects after loss of colonisation in the presence of atrophic gastritis and intestinal metaplasia, prior to development of gastric cancer. The recognition of the central role of H. pylori in carcinogenesis has increased expectations of gastric cancer prevention by H. pylori eradication. A primary preventive effect of eradication in subjects with H. pylori-induced gastritis has been demonstrated. However, a secondary preventive effect in patients with pre-malignant gastric lesions is still controversial, especially in patients with intestinal metaplasia and dysplasia. At this moment, H. pylori eradication seems indicated at the earliest stage of gastric carcinogenesis. This treatment policy requires confirmation; results of ongoing randomised controlled trials are therefore eagerly awaited.

Serum Pepsinogen Levels,Helicobacter pyloriCagA Status, and Cytokine Gene Polymorphisms Associated with Gastric Premalignant Lesions in Costa Rica

The detection of gastric premalignant lesions, atrophic gastritis, corpus atrophic gastritis, and intestinal metaplasia, using several potential markers was examined in Costa Rica. Depending on the lesion investigated, from a total of 223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG) and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human genomic DNAs were used for the genotyping of interleukin (IL)-1beta (-511 and +3954), IL-10 (-1082 and -592), and IL-1RN intron 2 by PCR and RFLP. Multivariate analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG levels (L-PG; PG I < or = 70 microg/L + PG I/II < or = 3), very low PG levels (VL-PG; PG I < or = 30 microg/L + PG I/II < or = 2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1beta +3954T-carrier and IL-1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for corpus atrophic gastritis detection, was the single marker with the highest combination of test characteristics, sensitivity (77.4%), specificity (80.7%), positive predictive value (39.3%), negative predictive value (95.7%), and seropositivity rate (27.4%), expected to improve after periodic measurements. Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and positive predictive value (62.2%), with similar sensitivity (74.2%) and negative predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with periodic measurements of serum PG, alone or in combination with CagA-ab status, to identify high gastric cancer risk, seems to be the method best suited for mass screening in Costa Rica.