Introduction: Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk. Experimental Design: Gastric mucosae were collected from 154 healthy volunteers (56 H. pylori negative and 98 H. pylori positive) and 72 cases with differentiated-type gastric cancers (29 H. pylori negative and 43 H. pylori positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated. Results: Among healthy volunteers, methylation levels of all the eight regions were 5.4-to 303-fold higher in H. pylori positives than in H. pylori negatives (P < 0.0001). Methylation levels of the LOX, HAND1, andTHBD promoter CGIs and p41ARC exonic CGI were as high as 7.4% or more in H. pylori^positive individuals. Among H. pylori^negative individuals, methylation levels of all the eight regions were 2.2-to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (P V 0.01). Among H. pylori^positive individuals, methylation levels were highly variable, and that of only HAND1 was significantly increased in gastric cancer cases (1.4-fold, P = 0.02). Conclusions: It was indicated that H. pylori infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in H. pylori^negative individuals.Gastric cancer is one of the most common malignancies worldwide and remains a leading cause of cancer death in Asia and some European countries (1). To reduce its mortality, early detection by endoscopy and curative resection are important (2). However, considering the potential risk and costs of early detection by endoscopic examination, implementation reflecting an individual's risk for developing a gastric cancer would be ideal. Also, endoscopic mucosal resection, which conserves the noncancerous gastric mucosae, is becoming popular, and the problem of metachronous gastric cancer recurrence is being recognized (3). Again, if the future risk of developing metachronous cancers in a specific case can be estimated, the information will be useful in the decision on either surgical resection or endoscopic mucosal resection for the case.The major etiologic risk factor for gastric cancers is Helicobacter pylori infection, which increases gastric cancer risk 2.2-to 21-fold (4 -6). In an animal model with Mongolian gerbil chronic infection with H. pylori rarely induces gastric cancers by itself, but markedly enhances their incidences after initiation with a mutagen, such as N-methyl-N-nitrosourea (7). Thi...

Colorectal endoscopic submucosal dissection (ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection (EMR) guidelines using evidence-based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas.

In response to the rapid and wide acceptance and use of endoscopic treatments for early gastric cancer, the Japan Gastroenterological Endoscopy Society (JGES), in collaboration with the Japanese Gastric Cancer Association (JGCA), has produced ‘Guidelines for ESD and EMR for Early Gastric Cancer’, as a set of basic guidelines in accordance with the principles of evidence‐based medicine. These Guidelines cover the present state of knowledge and are divided into the following seven categories: Indications, Preoperative diagnosis, Techniques, Evaluation of curability, Complications, Long‐term postoperative surveillance, and Histology. Twenty‐three statements were finally accepted as guidelines, and the majority of these were obtained from descriptive studies with lower evidence levels. A number of statements had to be created by consensus (the lowest evidence level), as evidence levels remain low for many specific areas in this field.

Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment have been produced by the Japan Gastroenterological Endoscopy Society in collaboration with the Japan Circulation Society, the Japanese Society of Neurology, the Japan Stroke Society, the Japanese Society on Thrombosis and Hemostasis and the Japan Diabetes Society. Previous guidelines from the Japan Gastroenterological Endoscopy Society have focused primarily on prevention of hemorrhage after gastroenterological endoscopy as a result of continuation ofantithrombotic therapy, without considering the associated risk of thrombosis. The new edition of the guidelines includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with withdrawal of antithrombotic therapy.

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4,655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100,000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. Despite a worldwide decline in incidence, gastric cancer remains one of the leading causes of cancer-related death in Japan. [1][2][3][4] There is a marked geographic variability in the gastric cancer incidence rate; the cancer is most common in China and Japan, and one of the lowest rates is in the United States. [1][2][3][4] Many epidemiologic studies have shown that the risk of gastric cancer is strongly associated with environmental factors, such as salt, nitrates and low intake of fresh fruits and vegetables. 1,4 -8 Recent studies have indicated that Helicobacter pylori infection is also a major risk factor for the development of gastric cancer. 9 -18 The prevalence of H. pylori infection is markedly higher in Japan than in other industrialized countries, although the reasons are not fully understood. 19 -21 The observed geographic variability in gastric cancer appears to be explained by a synergistic interaction between H. pylori infection and other environmental factors.The H. pylori bacterium colonizes the stomach mucosa and triggers a series of inflammatory reactions. It is considered an important cause of chronic atrophic gastritis (CAG), 19 -23 as shown in rodent models. 24 -26 CAG is considered the first step of a sequence of mucosal changes in the stomach leading to cancer. The current model for stomach carcinogenesis begins with gastritis, proceeds to CAG, then to intestinal metaplasia, dysplasia and, finally, carcinoma. 1,27 This hypothesis is supported by a considerable number of clinicopathological and epidemiological studies in countries with a high incidence of gastric cancer. However, longitudinal cohort studies that report an association of CAG with gastric cancer and a relation between the progression of CAG and the development of gastric cancer are limited. 28 -30 In addition, the role of H. pylori infection in the above-mentioned process of stomach carcinogenesis remains unclear. To investigate these problems relating to gastric cancer development, we established a cohort of male factory workers that we followed prospectively for 8 years.CAG in a high-risk population, such as Japanese subjects, usually begins at the gastric antrum and extends proximally towards the cardia. [31][32][33] As a result, gastric secretory function diminishes as the area of functional fundic gland mucosa gets smaller. 34 CAG is a histopathological diagnosis. It is difficult, howe...

Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

No abstract

The contribution of the aryl hydrocarbon receptor (AhR) in induction of a battery of xenobiotic-metabolizing enzymes has been studied extensively. However, no direct proof has been obtained that it plays a role in modulating carcinogenesis. To address the question of whether AhR is required for tumor induction, we have investigated the response of AhR-deficient mice to benzo