Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) 5 8.9, 95% confidence interval (CI) 5 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR 5 17.7, 95% CI 5 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR 5 69.7, 95% CI 5 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune responsebased high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.Despite worldwide declines in the incidence of gastric cancer and associated mortality over the past 50 years, this pathology remains one of the leading causes of cancer-related death in Eastern Asia, including Japan, South America and Eastern Europe.1-4 In Japan, more than 100,000 new cases of gastric cancer are diagnosed every year, and the Japanese Ministry of Health, Labor and Welfare reported that 50,136 deaths attributed to the cancer in 2010.5 Gastric cancer thus remains a major health problem in Japan. Development of gastric cancer represents a classical example of host-genetic and environmental interactions and is characterized by a multistep process of molecular and morphological events known as the gastritisatrophy-metaplasia-dysplasia-cancer sequence.6,7 Based on a large number of epidemiological and clinicopathological studies and also on animal experiments using Mongolian gerbils, this sequence, which predominantly leads to intestinal-type cancer, is considered to represent a major route of stomach carcinogenesis, particularly in areas of high cancer risk, such as Japan. Although other environmental and lifestyle factors together wi...

A longitudinal cohort study was conducted in Helicobactor pyloriinfected middle-aged Japanese males to evaluate the preventive effects of H. pylori eradication on the development of gastric cancer according to the extent of chronic atrophic gastritis (CAG). The extent of CAG was monitored by baseline serum pepsinogen (PG) levels. We followed 3,656 subjects with persistent H. pylori infection and 473 subjects with successful H. pylori eradication for cancer development for a mean (SD) of 9.3 (0.7) years. Groups with and without extensive CAG were categorized based on PG test-positive criteria to detect extensive CAG of PG I 70 ng/ml and PG I/II ratio 3.0. During the study period, 5 and 55 gastric cancers developed in H. pylori-eradicated and the noneradicated subjects, respectively, indicating no significant reduction in cancer incidence after H. pylori eradication. Among the noneradicated subjects, 1,329 were PG test-positive and 2,327 were PG test-negative. Gastric cancer was confirmed in 30 and 25 subjects, respectively. Among subjects whose infection was eradicated, 155 were PG test-positive and 318 were PG test-negative. Of these subjects, gastric cancer was confirmed in 3 and 2 subjects, respectively. Significant reduction in cancer incidence after eradication was observed only in PG test-negative subjects (p < 0.05; log-rank test). The results of this study strongly indicate that cancer development after eradication depends on the presence of extensive CAG before eradication and that H. pylori eradication is beneficial to most PG test-negative subjects with mild CAG as defined by the aforementioned criteria. ' 2009 UICC

This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the lowtiter subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.Gastric cancer is one of the leading causes of cancer-related deaths in Japan, with 50,017 deaths attributed to this cancer in 2009. 1 Helicobacter pylori infection is now widely accepted as playing a major role in the development of gastric cancer in areas showing high-risk for this cancer, including Japan. 2-5 H. pylori triggers chronic inflammation in the gastric mucosa, leading to a series of molecular and morphological events known as the atrophy-metaplasia-dysplasia-cancer sequence. [3][4][5] This carcinogenic sequence is considered to represent a major route of stomach carcinogenesis, and previous studies, including our own, have identified positive correlations between extent of chronic atrophic gastritis (CAG) and risk of gastric cancer. 6-13 Our longitudinal cohort study clearly indicated that progression of H. pylori-associated chronic gastritis increases cancer risk in a stepwise manner, and that patients with metaplastic gastritis, an end result of chronic H. pylori infection, show the highest annual cancer incidence rate of around 1% among asymptomatic middle-aged Japanese men. 11 Other

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.Helicobacter pylori infection induces chronic inflammation in the stomach mucosa of both humans and animals, and H. pylori-related chronic gastritis is deeply involved in the development of gastric neoplasms, such as adenoma or cancer. 1 H. pylori infection is now widely accepted as a major driving force in the progression of a series of carcinogenic cascades representing the gastritis-atrophy-metaplasia-dysplasia-cancer sequence.2 Our previous seroepidemiological study clearly demonstrated a positive correlation between progression of chronic gastritis and risk of gastric cancer. Subjects with extensive chronic atrophic gastritis (CAG), as determined by serum pepsinogen (PG) levels, showed an annual cancer incidence rate of 0.24%.

Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.