Search

Background: Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori (H. pylori) infection, and thus cancer risk., Methods: Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person's gastric mucosa and those in an entirely healthy mucosa., Results: The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3). The average methylation levels of nine driver genes tended to increase according to the risk levels (P = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups., Conclusions: The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background and Study Aims: Helicobacter pylori (H. pylori) infection has been clearly shown to be a cause of gastric cancer, and the incidence of gastric cancer has been shown to decrease with eradication. However, few reports have described the utility of eradication therapy in elderly people. Thus, an investigation focusing on how much actual histological improvement is obtained with eradication therapy in elderly people was conducted., Patients and Methods: This was a retrospective study conducted using medical information of patients diagnosed with H. pylori-associated gastritis and who underwent eradication therapy. The histological improvement was assessed based on changes in the atrophy and intestinal metaplasia scores of the Updated Sydney system from before to after eradication. We investigated the rates of histological improvement in atrophy and intestinal metaplasia one year after and long term more than five years after H. pylori eradication in an elderly group and a younger group., Results: This study included 221 patients (elderly group 123, younger group 98). In histological atrophy, higher rates of improvement were seen in the corpus than in the antrum, and the rates of cure in the antrum were lower in elderly group than in younger group (p = 0.0282). With regard to intestinal metaplasia, the rates of improvement in the antrum were lower in elderly group than in younger. In long term observation, although the rates of cure in the antrum were lower in elderly, improvements were seen in atrophy scores in most of the patients and intestinal metaplasia scores in about half of patients., Conclusion: Though there is more obvious improvement in the gastric mucosa when H. pylori eradication therapy is performed at a young age, some mucosal improvement can be expected in about half of patients after eradication, even in elderly people., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background/aims: Although undifferentiated gastric cancer (UGC) diagnosed after Helicobacter pylori eradication (HPE) carries a poor prognosis, characteristics of post-HPE UGC have not been evaluated in detail because of its low incidence. Therefore, we compared the clinicopathologic characteristics of UGC and differentiated gastric cancers (DGC) diagnosed after successful HPE., Methods: GC lesions from patients who had successfully completed HPE and who had undergone upper gastrointestinal endoscopy between January 2004 and March 2016 were analyzed. Tumors were divided into DGC and UGC groups. Clinicopathologic factors of background and tumor characteristics were compared using univariate and multiple logistic analyses., Results: A total of 129 tumors from 115 patients were evaluated; 113 tumors were in the DGC group and 16 in the UGC group. Depressed-type tumors (P = 0.024) and sub-submucosal invasion (P<0.001) were significantly higher in the UGC group. The UGC group had larger tumor diameters (25.9±7.3 mm) than the DGC group (13.2±10.2 mm) (P<0.001). Multivariate analysis showed that female sex (odds ratio [OR] 3.24, 95%CI:1.02-10.37; P = 0.047) and absent follow-up (OR 4.99, 95%CI:1.60-15.57; P = 0.006) were significant independent risk factors for UGC. The DGC group showed a gradually decreasing temporal trend by trend test (P = 0.015), while the UGC group showed a relatively constant incidence over time, although the number of cases was small., Conclusion: UGC was diagnosed even after long time spans following HPE, although the number of cases was small. Female sex, and especially absent follow-up, were risks for post-HPE UGC, suggesting that diligent long-term follow-up after HPE is essential., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kodama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation., Methods: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2., Results: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments., Conclusions: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa., (© 2022. The Author(s).)

Background: Pancreatic acinar cell metaplasia (PACM) has been rarely reported in the gastric mucosa. In the present study, we aimed to elucidate the clinical and pathological characteristics of PACM associated with Helicobacter pylori (H. pylori)., Method: 5930 patients who underwent five- or two-point gastric biopsy according to the updated Sydney system (USS) by upper gastrointestinal endoscopy were enrolled. The patients were categorized into current H. pylori infection (CHI), post-H. pylori eradication (PHE), and non-H. pylori infection (NHI) groups according to the H. pylori infection status, and the frequency and location of PACM were compared. Additionally, a case-control study was performed to compare the USS scores between patients with CHI and PACM and those with CHI but not PACM., Result: The frequencies of PACM were 0.49% (10/2039), 0.75% (25/3332), and 0% (0/559) in the CHI, PHE, and NHI groups, respectively. PACM was found in the greater curvature of the antrum in 33 of the 35 patients with PACM. Among the patients with CHI, the inflammation scores in the greater curvature of the antrum and the greater curvature of the corpus were lower in patients with PACM than in those without PACM., Conclusion: Although rarely reported in the gastric mucosa, PACM was closely related to H. pylori infection, especially in the antrum, and was associated with relatively mild inflammation., (© 2022. The Author(s).)

Background: Glycosylation is a common post-translational modification, and it has been reported that alterations in the glycosylation patterns on cells are related to cell proliferation, differentiation, tissue adhesion, and carcinogenesis. This study aimed to investigate the relationship between Helicobacter pylori infection and gastric mucosal glycosylation using a lectin microarray system., Methods: Gastric mucosal samples were obtained from 10 Helicobacter pylori-non-infected patients, 10 H. pylori-infected patients, and 10 after H. pylori-eradicated patients who underwent gastric mucosal biopsy by endoscopy in our institute. The gastric gland cells which were isolated from formalin-fixed, paraffin-embedded gastric mucosal biopsy samples using laser capture microdissection were used for lectin microarray to obtain lectin-glycan interaction values., Results: Comparison of the lectin-glycan interaction values before and after eradication in the same patients showed significant increases for Ricinus communis agglutinin 120, Trichosanthes japonica agglutinin II, Euonymus europaeus lectin, jacalin, Amaranthus caudatus agglutinin, and Maclura pomifera agglutinin and significant decreases for Urtica dioica agglutinin, Lycopersicon esculentum lectin, Ulex europaeus agglutinin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I. Furthermore, jacalin and MPA in the gastric antrum were significantly decreased with H. pylori infection compared with the without infection group and improved to the levels seen without infection as a result of eradication. Lycopersicon esculentum lectin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I in the gastric body were significantly increased with H. pylori infection and improved to the level seen without infection as a result of eradication., Conclusion: H. pylori infection changes the lectin binding state which is related to various cancers on the gastric mucosal cell. Furthermore, those changes are reversible by H. pylori eradication.

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.

Background and Aim: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa., Methods: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system., Results: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints., Conclusions: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: To determine the application range of diagnostic kits utilizing anti-Helicobacter pylori antibody, we tested a newly developed latex aggregation turbidity assay (latex) and a conventional enzyme-linked immunosorbent assay (E-plate), both containing Japanese H. pylori protein lysates as antigens, using sera from seven Asian countries., Methods: Serum samples (1797) were obtained, and standard H. pylori infection status and atrophy status were determined by culture and histology (immunohistochemistry) using gastric biopsy samples from the same individuals. The two tests (enzyme-linked immunosorbent assay and latex) were applied, and receiver operating characteristics analysis was performed., Results: Area under the curve (AUC) from the receiver operating characteristic of E-plate and latex curves were almost the same and the highest in Vietnam. The latex AUC was slightly lower than the E-plate AUC in other countries, and the difference became statistically significant in Myanmar and then Bangladesh as the lowest. To consider past infection cases, atrophy was additionally evaluated. Most of the AUCs decreased using this atrophy-evaluated status; however, the difference between the two kits was not significant in each country, but the latex AUC was better using all samples. Practical cut-off values were 3.0 U/mL in the E-test and 3.5 U/mL in the latex test, to avoid missing gastric cancer patients to the greatest extent possible., Conclusions: The kits were applicable in all countries, but new kits using regional H. pylori strains are recommended for Myanmar and Bangladesh. Use of a cut-off value lower than the best cut-off value is essential for screening gastric cancer patients., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Pyloric metaplasia (PM) and pseudopyloric metaplasia (PPM) are metaplastic changes resulting in pyloric-type glands in the gastric oxyntic mucosa that mainly occur in chronic gastritis caused by Helicobacter pylori (H. pylori) infection. Focusing on PM and PPM, we classified the histological changes in gastric mucosa according to the Updated Sydney System, using 314 biopsy specimens of gastric greater curvature of the middle body before H. pylori eradication (HPE). Next, the numbers of PM and PPM glands were counted in 47 specimens, and subjects were followed up over 10 years after HPE. PPM was recognized jointly with inflammation, activity, atrophy, and intestinal metaplasia, but PM was recognized more frequently than PPM as atrophy and intestinal metaplasia progressed. Both PM and PPM regressed significantly within 6 years after HPE. Additionally, we demonstrated that PM and PPM are not always coincident with spasmolytic polypeptide-expressing metaplasia (SPEM). In conclusion, PM and PPM are considered different modulations of the same line of differentiation, which are both reversible, with PM potentially emerging from PPM upon progression.

Background: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H 2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H 2 S production., Materials and Methods: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H 2 S levels were measured by using HSip-1 fluorescent probe., Results: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H 2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H 2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H 2 S than ATCC 51932-inoculated cells., Conclusions: H pylori infection modulates endogenous H 2 S production in AGS cells, suggesting that H 2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy., (© 2020 John Wiley & Sons Ltd.)

Background: While all modalities used for diagnosis of Helicobacter pylori (H. pylori) have demonstrated sufficient sensitivity and specificity, each test has advantages and limitations. The serum test for anti-H. pylori antibody with the latex method is noninvasive, easy, and inexpensive; it is thus a useful tool for mass-screening for H. pylori. In this study, we evaluated the utility of a newly developed latex kit, in comparison with other serum diagnostic kits based on enzyme-linked immunosorbent assay (ELISA)., Methods: In total, 187 subjects (77: H. pylori-positive, 75: H. pylori-negative, 35: previous infection with H. pylori) seen at Oita University Hospital during the period from January 1988 to September 2014 were enrolled in the study. All subjects were evaluated with 4 types of serum H. pylori antibody kits. One modality was based on the use of latex (Denka Kit, Denka Seiken Co., Ltd., Tokyo, Japan). Three kits were based on the use of ELISA. The E-Plate II Eiken (Eiken Chemical Co., Ltd., Tokyo, Japan) is henceforth referred to as Kit A. The Premier H. pylori kit (Meridian Bioscience, Inc., USA) is referred to as Kit B. The Platelia H. pylori IgG (Bio-Rad, Marnes-la-Coquette, France) is referred to as Kit C., Results: Evaluation of 152 study participants, including some who were positive for H. pylori and some who were negative, sensitivity, specificity, and accuracy values were as follows: for the Denka kit, these values were, respec-tively, 92.2%, 93.3%, and 92.8%. For Kit A, these values were 88.3%, 100.0%, and 194.1%. For Kit B, these values were 98.7%, 76.0%, and 87.5%. For Kit C, these values were 98.7%, 80.0%, and 89.5%. The specificity of Kit A was > 90%. Sensitivity was > 90% for Kits B and C. For the Denka kit, both sensitivity and specificity were > 90%. Among the 35 subjects previously infected with H. pylori, the rate of positive diagnosis was 48.6% (17/35) with the Denka kit, 17.1% (6/35) with Kit A, 54.3% (19/35) with Kit B, and 54.3% (19/35) with Kit C. The rate of positive diagnosis was significantly higher with the Denka kit than with Kit A (p < 0.05)., Conclusions: An assay based on use of the latex method, H. pylori-latex Seiken, demonstrated satisfactory sensitivity and specificity for detecting serum levels of H. pylori antibody. The performance of this kit was equivalent to that of ELISA kits currently used for the same purpose. This kit is therefore considered to be extremely suitable for diagnosis of H. pylori and mass-screening of patients at high risk for gastric cancer.

Background: Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined., Methods: The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects., Results: For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%)., Conclusions: The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.

Background/aims: The rate of gastric cancer (GC) after Helicobacter pylori eradication has gradually increased; therefore, we investigate the clinicopathological features of GC following eradication in comparison with those of GC with H. pylori infection., Methods: This study included 50 subjects with GC after eradication (GCE) and 151 patients with GC with H. pylori infection (GCI). Clinicopathological factors were assessed. The manifestation of GC was further evaluated using immunohistochemical analysis and in situ hybridization., Results: Macroscopic analysis revealed a significantly higher ratio of depressed type /elevated type in the GCE compared with the GCI (30/19 vs. 61/77, p = 0.041). The gastric phenotype was more common in the GCE compared with the GCI, and the proportion of CDX2-positive cases was lower in the GCE (8 out of 18; 44.4%) compared with the GCI (18 out of 19; 94.7%; p = 0.00082). Ki-67 labeling index was significantly lower in the GCE (32.03 ± 22.15) compared with the GCI (79.20 ± 14.87, p < 0.0001). No patient in the GCE showed evidence of Epstein-Barr virus infection., Conclusion: The clinicopathological characteristics of GC following H. pylori eradication differ from those of GC in patients with H. pylori infection in terms of morphology, mucin phenotype, and proliferation rate., (© 2018 S. Karger AG, Basel.)

H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. In Japan, 12 months after treatment, gastric ulcers had recurred in 11.4% of those with successful H. pylori eradication and 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. About long-term study, 4 years after treatment, gastric ulcers had recurred in 9.3% of those with successful H. pylori eradication and duodenal ulcers recurrence was occurred in 6.2% of those. The annual recurrence rates of gastric, duodenal ulcer were 2.3% and 1.6%, respectively. However, in current Japan, the decrease of the primary eradication rate is reported by the increase of clarithromycin-resistant strains. The increase of metronidazole-resistant strains used for the second eradication is not recognized so far, but in future, increase is concerned about. Therefore, the making of the regimen of the third-line eradication therapy is needed now.

Background and Aim: Subjects infected with Helicobacter pylori containing cagA do not always induce serum CagA antibody. Our previous meta-analysis showed that serum CagA seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum CagA-positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti-CagA antibody titer and the levels of pepsinogen (PG), and histological score., Methods: Eighty-eight H. pylori-positive Japanese patients with gastritis were included. Serum CagA antibody titer, PG I, and PG II were evaluated by ELISA. Histological scores were evaluated according to Update Sydney System. CagA expression was examined by immunoblot., Results: Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA antibody titer was significantly correlated with PG I and PG II levels (P = 0.003 and 0.004, respectively). Serum CagA antibody titer was also significantly correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand, bacterial density was not related with CagA antibody titer. CagA expression level of the strains was irrespective of the status of PG and serum CagA antibody., Conclusions: Subjects with higher serum CagA antibody titer can be considered as high-risk population for the development of gastric cancer from the point of strong gastric inflammatory response even in Japan. Host recognition rather than bacterial colonization might be associated with the difference of serum CagA antibody titer., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objective: Although Helicobacter pylori (H. pylori) eradication has been shown to inhibit gastric cancer, it does not completely suppress it. Therefore, risk factors of gastric cancer development following H. pylori eradication were examined., Material and Methods: A total of 2355 patients (1501 males and 824 females) underwent successful eradication of H. pylori. Endoscopic atrophy, histological gastritis, atrophy, intestinal metaplasia (IM), and operative link for gastritis assessment (OLGA) staging were subsequently evaluated., Results: Following eradication, 33/2355 patients (25 males and 8 females) developed gastric cancer. Compared to a nongastric cancer group that was matched according to gender and age, the incidence of endoscopic atrophy (3.52 ± 1.45 vs. 4.85 ± 1.18, p < 0.001), histological atrophy at the greater curvature of the antrum (1.42 ± 0.80 vs. 1.95 ± 0.86, p = 0.0059), inflammation (2.05 ± 0.59 vs. 2.33 ± 0.66, p = 0.031), IM at the greater curvature of the corpus (0.06 ± 0.30 vs. 0.24 ± 0.54, p = 0.029), the ratio of OLGA-stage 0-II/III, IV (13/8 vs. 55/11, p = 0.038) were significantly higher for the gastric cancer group. Multivariate analysis also showed the highest odds ratio (6.26, 95% confidence interval or CI, 1.28-30.60, p = 0.023) for IM at the greater curvature of the corpus., Conclusions: Severe endoscopical atrophy, OLGA staging, histological atrophy at the antrum, inflammation, and particularly IM at the corpus, were identified as risk factors for gastric cancer development following H. pylori eradication. Therefore, eradication should be performed before these predictors develop.

Backgrounds: The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan., Methods: Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX., Results: Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p < 0.05) and the LAL group (43.1 %; p < 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX., Conclusions: The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan.

Helicobacter pylori (H. pylori) is a major pathogen of chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Atrophic gastritis and intestinal metaplasia are recognized as precancerous lesion of gastric cancer. Many studies reported that H. pylori eradication had the preventive effect of gastric cancer. Moreover many studies mentioned the improvement of gastric atrophy and/or intestinal metaplasia. Two meta-analysis indicated the improvement of atrophic gastritis but not of intestinal metaplasia. In our study, intestinal metaplasia improved at lesser curvature of the corpus six years after eradication. H. pylori eradication has benefit for gastric cancer prevention provably due to improvement of the precancerous lesion such as atrophic gastritis and intestinal metaplasia. Especially, H. pylori eradication before the appearance of atrophy and intestinal metaplasia has been considered to be effective in inhibiting the development of gastric cancer. Therefore, improvement or elimination of chronic gastritis with H. pylori eradication might have possibility of gastric cancer inhibition.

Goals: To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy., Background: Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure., Study: The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses., Results: Among 142 strains, 44 (31.0%) were dupA positive. There was no association between dupA status and gastroduodenal diseases (P>0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4% vs. 35.7%, P=0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3% vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than dupA-negative H. pylori (P=0.04). In multivariate analysis adjusted for age, sex, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio=3.71; 95% confidence interval,1.07-12.83)., Conclusions: Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure.

Background: Atrophic gastritis and intestinal metaplasia (IM) are well known as precancerous lesions of gastric cancer. The present study evaluated the gastric mucosa for 10 years after H. pylori eradication at five points of the stomach as recommended by the updated Sydney system to clarify the relationship between H. pylori eradication and gastric cancer prevention., Methods: Among the comprised 373 patients, 323 were H. pylori-positive while 50 patients were H. pylori-negative. Patients with successful eradication underwent follow-up endoscopic examination every year. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system, and were evaluated for the degree of gastritis prospectively., Results: Two hundred ninety-four out of the 323 H. pylori-positive patients successfully achieved eradication. Of the 197 patients on whom five-point biopsy was performed, the courses of 30 patients were able to be observed every year for 10 years after successful eradication. Inflammation, activity, and atrophy score at all five points were significantly reduced half a year to 6 years after eradication. IM scores fluctuated intensely up and down during all observation periods; however, IM score of the lesser curvature of the corpus continued decreasing gradually and showed a significant decrease 6 years after (0.97 ± 0.09 to 0.42 ± 0.17, P < 0.05)., Conclusion: In 10 years after H. pylori eradication, atrophy at all sites and IM in the lesser curvature of the corpus gradually and significantly decreased. These results suggest that the improvement of gastric atrophy and IM might have association with the reduction of gastric cancer occurrence.

Aim: To investigate the effects of proton pump inhibitor (PPI) treatment on stool antigen test using the TestMate pylori enzyme immunoassay., Methods: This study assessed 28 patients [16 men and 12 women; mean age (63.1 ± 5.9) years; range, 25-84 years] who underwent stool antigen test and urea breath test (UBT) before and after PPI administration., Results: Using the UBT as the standard, the sensitivity, specificity and agreement of the stool antigen test in all 28 patients were 95.2%, 71.4%, and 89.3%, respectively, before PPI administration, and 88.9%, 90.9%, and 89.3%, respectively, after PPI treatment. Mean UBT values were 23.98% ± 5.33% before and 16.19% ± 4.75% after PPI treatment and, in 15 patients treated for ≥ 4 wk, were significantly lower after than before 4 wk of PPI treatment (12.58% ± 4.49% vs 24.53% ± 8.53%, P = 0.048). The mean optical density (A(450/630)) ratios on the stool antigen test were 1.16 ± 0.20 before and 1.17 ± 0.24 after PPI treatment (P = 0.989), and were 1.02 ± 0.26 and 0.69 ± 0.28, respectively, in the group treated for > 4 wk (P = 0.099)., Conclusion: The stool antigen test was equally sensitive to the UBT, making it a useful and reliable diagnostic method, even during PPI administration.

Background and Aim: Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication., Methods: We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5-13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2)., Results: Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05)., Conclusion: We were able to monitor the gastric mucosa for a mean of 8.6 years after H. pylori eradication, the longest period reported to date. Significant improvements in gastric atrophy and IM after H. pylori eradication may decrease the risk of gastric cancer., (Copyright © 2012 S. Karger AG, Basel.)

Background: A strict correlation between Helicobacter pylori eradication and an increase in platelet count has previously been reported in patients with chronic idiopathic thrombocytopenic purpura (ITP). To clarify the pathogenesis of H. pylori-induced ITP and the factors predicting the platelet response to H. pylori eradication therapy, we evaluated the markers of atrophic gastritis in ITP patients., Methods: The study population comprised 31 H. pylori-infected patients with chronic ITP. After undergoing upper gastrointestinal endoscopy and gastric biopsy, all patients received H. pylori eradication therapy. The effect of H. pylori eradication on the platelet count was evaluated for up to 6-54 months after the therapy. The degree of endoscopic gastric atrophy, histological parameters in the gastric mucosa, and serum pepsinogen (PG) levels were compared between platelet responders and nonresponders to the therapy., Results: H. pylori was successfully eradicated in all patients and a platelet response was seen in 18 (58%) of these patients. The serum pepsinogen (PG) I/II ratio at pretreatment was significantly lower in responders than in nonresponders. The degree of endoscopic gastric atrophy was significantly more severe in responders than in nonresponders. Furthermore, the levels of histological parameters of activity, inflammation, and atrophy in the gastric corpus, but not in the gastric antrum, were significantly more severe in responders than in nonresponders,., Conclusion: The development of corpus atrophic gastritis may be a suitable condition for inducing thrombocytopenia. Evaluation of the serum, endoscopic, and histological markers of atrophic gastritis may assist in selecting patients with ITP who are more likely to respond to H. pylori eradication therapy.

Although two studies have indicated a possible link between Alzheimer's disease (AD) and Helicobacter pylori (H. pylori) infection, these were reported from Europe, where the prevalence of H. pylori infection is not very high. In this study, the prevalence of H. pylori infection was examined in AD patients in Japan, where there is a high prevalence of H. pylori. Consecutive patients referred to the Memory and Dementia Outpatient Clinic from August 2002 to March 2009 were studied. H. pylori infection status was determined by measuring urinary levels of anti-H. pylori antibody (RAPIRUN(®)). Multiple stepwise logistic regression analyses were used to examine the associations of AD with the main predictor variables. Of the 917 patients who visited the clinic, 385 were diagnosed as having AD. Ninety-seven patients did not have dementia and were considered controls. On univariate analysis, average age and the proportion of males were significantly higher in AD patients than in controls. There was no difference in the prevalence of H. pylori infection between patients with AD and controls (62.0% vs. 59.7%, p = 0.67, crude odds ratio (OR), 1.10). Multiple logistic regression analysis showed that older age and male sex, but not H. pylori status, were significantly associated with AD (p < 0.001, p = 0.01, p = 0.83, respectively). The prevalence of H. pylori infection did not differ between AD patients and controls among Japanese subjects. The high prevalence of H. pylori in controls may contribute to the discrepancy with previous reports.

Background and Aims: Recently, we successfully produced an anti-East-Asian-type CagA-specific antibody called α-EAS Ab, which is specifically immunoreactive only with East-Asian-type CagA but not Western-type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with α-EAS Ab in Japan., Methods: There were 254 H. pylori-positive patients enrolled in this study. α-EAS Ab was used to determine the CagA phenotype instead of cagA sequencing, and, moreover, the histological findings and endoscopic gastric mucosal condition were evaluated according to the updated Sydney System and the Kimura-Takemoto classification system, respectively., Results: A total of 224 (88.2%) of the patients were immunoreactive for α-EAS Ab. The remaining 30 (11.8%) were negative for α-EAS Ab, suggesting that they were infected with either Western-type CagA or CagA-negative strains (i.e. non-East-Asian-type CagA strains). The grades of activity of gastritis, mucosal atrophy and intestinal metaplasia according to the updated Sydney System were significantly higher in patients infected with East-Asian-type CagA strains than those infected with non-East-Asian-type CagA strains. The grade of endoscopic gastric mucosal atrophy evaluated using the Kimura-Takemoto classification system was similar. All 28 strains isolated from patients with gastric cancer possessed the East-Asian-type CagA., Conclusions:   Infection with East-Asian-type CagA H. pylori was more closely associated with gastric mucosal atrophy and gastric cancer than infection with non-East-Asian-type CagA H. pylori. The efficiency of immunohistochemical analysis for CagA should be equivalent to that of cagA sequencing., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Objective: Helicobacter pylori eradication therapy alone cannot heal gastric ulcers in Japanese patients. Irsogladine has previously been shown to accelerate the healing of gastric ulcers after H. pylori eradication therapy. And we previously reported that histamine H(2) receptor antagonists inhibit gastric ulcer relapse after H. pylori eradication therapy. We therefore compared the efficacy of irsogladine with famotidine as appropriate treatments for ulcers after eradication therapy., Methods: Gastric ulcer patients with H. pylori infection (n = 119) were randomized to treatment with irsogladine 4 mg/day (n = 60) or famotidine 40 mg/day (n = 59) following 1-week H. pylori eradication therapy. After treatment, assessments of gastric ulcer healing were performed., Results: The ulcer healing rates in patients receiving irsogladine and famotidine were 85.2% (46/54) and 79.6% (43/54), respectively, and were not significantly different (p = 0.4484). In the famotidine group, the healing rate was significantly lower in patients who drink alcohol than in those who do not (60.0% vs. 91.2%; p = 0.0119). However, in the irsogladine group the healing rate did not differ between patients who drink alcohol and those who do not. Furthermore, the healing rate in smokers was significantly higher in the irsogladine group (88.0%) than in the famotidine group (59.1%) (p = 0.0233)., Conclusions: Irsogladine and famotidine are both acceptable in treatment after H. pylori eradication therapy in gastric ulcer patients. Findings also suggest that irsogladine is more beneficial than famotidine in patients who drink alcohol and smoke.

Background: ODK-0702 is a stick-type urinary Helicobacter pylori (H. pylori) antibodies detection kit, developed to improve the original housing type urinary H. pylori antibodies detection kit "RAPIRUN H. pylori Antibody". This stick-type kit is designed for the efficient daily medical practice at hospital or clinic, public or school health checkup, to detect H. pylori infection. The aim of this study was to evaluate the performance and correlation of this kit with the original kit and the ELISA kit., Methods: Control kits were "RAPIRUN H. pylori Antibody" (Kit A) and "URINELISA H. pylori Antibody" (Kit B). Urine samples were obtained from 249 subjects scheduled for upper endoscopy, 99 subjects suspected of having upper gastrointestinal disease, and 150 subjects receiving health checkups. Rates of agreement in results between ODK-0702 and the control kits were investigated., Results: High agreement rates of 98.4% (245/249) and 88.8% (221/249) were found between ODK-0702 and the kits, Kit A and B, respectively. In patients, the agreement rates of ODK-0702 as compared to Kit A and B were 99.0% (98/99) and 88.9% (88/99), respectively. In control subjects, the agreement rates of ODK-0702 as compared to Kit A and B were 98.0% (147/150) and 88.7% (133/150), respectively., Conclusions: ODK-0702 enabled rapid testing within 15 minutes and showed equivalent performance as control kits, being clinically very useful in the diagnosis of H. pylori infection.

Background: The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail., Methods: Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing., Results: Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh., Conclusions: H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

Purpose: This study attempted to assess the value of the RAPIRUN test for the diagnosis of Helicobacter pylori infection in the Vietnamese population., Methods: We recruited 148 Vietnamese patients undergoing upper gastrointestinal endoscopy during which five gastric biopsies were taken; blood and urine samples were collected from each patient. Helicobacter pylori infection status was determined by a combination of three different methods, including culture, immunohistochemistry, and serum ELISA. RAPIRUN tests were performed using urine samples., Results: The sensitivity, specificity, and accuracy of the RAPIRUN test in these Vietnamese patients were 79.5, 90.7, and 84.5%, respectively., Conclusions: The RAPIRUN test is useful for the diagnosis of H. pylori infection in the Vietnamese population, showing high specificity, acceptable sensitivity, non-invasiveness, convenience, and rapidity.

The determination of the cagA genotype is generally based on sequencing the variable 3' region of the cagA gene. In a previous study, we successfully generated an anti-East Asian CagA-specific antibody (anti-EAS Ab) immunoreactive only with the East Asian CagA and not with the Western CagA. In a small number of Japanese patients, anti-EAS Ab appeared to be a useful tool for phenotyping CagA immunohistochemically. The present study was conducted to validate the anti-EAS Ab immunohistochemistry method in a larger number of patients from Vietnam and Thailand. A total of 385 Vietnamese and Thais were recruited. Helicobacter pylori status was determined by a combination of three methods, including culture, histology, and immunohistochemistry with anti-H. pylori antibody. The sensitivity, specificity, and accuracy of the anti-EAS Ab immunohistochemistry method for the diagnosis of CagA phenotype were calculated based on the results of the cagA sequencing as the gold standard. The sensitivity, specificity, and accuracy of our immunohistochemistry method were 96.7%, 97.9%, and 97.1%, respectively. Moreover, anti-EAS Ab was not cross-reactive with noninfected gastric mucosa. In conclusion, immunohistochemistry with anti-EAS Ab appears to be a good method for determination of CagA phenotype.

Background: The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects., Results: The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh., Conclusion: Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.

Sitafloxacin showed MICs of less than or equal to 0.5 microg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin.

The (13)C-urea breath test (UBT) is widely used to examine the results of eradication therapy for Helicobacter pylori. We examined whether a stool antigen test can be used as efficiently as UBT. (i) Ninety-four patients infected with H. pylori underwent eradication therapy. Six or eight weeks after the completion of treatment, the results were evaluated by UBT and a stool antigen test (TPAg). In 77 out of 78 patients who had negative UBT results, the TPAg results were also negative. Among the 16 UBT-positive patients, 12 were also positive by TPAg. Agreement of UBT and TPAg was 94.7%. (ii) Twenty-two patients with peptic ulcers in the active stage also received eradication therapy followed by proton pump inhibitor (PPI) administration. TPAg and UBT were performed to examine the results of eradication therapy at the end of PPI administration and at least 7 days after its discontinuation. Of the 22 patients taking PPIs, TPAg evaluated the results of eradication therapy accurately in 21 patients. TPAg appears to be an accurate test for evaluating the results of H. pylori eradication therapy, and to be as efficient as (13)C-UBT. Use of the stool antigen test should be considered as an alternative, particularly in patients who have to take PPIs in order to avoid the risk of peptic ulcers.

Purpose: The 2005 ACG guidelines for the management of dyspepsia recommend eradication and proton pump inhibitors for patients who are H. pylori-positive and-negative, respectively. To establish Japanese guidelines for dyspepsia, we evaluated H. pylori status and endoscopic findings among outpatients with dyspepsia., Methods: The status of H. pylori in dyspeptic patients was determined by measuring urinary levels of anti-H. pylori antibody (RAPIRAN). We then compared the endoscopic findings between H. pylori-positive and -negative patients., Results: The prevalence of H. pylori among 258 dyspeptic patients was 47.8%, and increased with age (11.1% at age 10-19 years; >50% at age >50 years). The prevalence of H. pylori in each age-group tended to be lower among male than female dyspeptic patients. Endoscopy (n = 138) showed that H. pylori-negative patients rarely had peptic ulcers or gastric cancer, and 84.7% had no endoscopic findings, which was significantly higher when compared to H. pylori-positive patients (67.3%) (p = 0.029)., Conclusions: Over half of the dyspeptic Japanese patients examined were negative for H. pylori. Patients who are H. pylori-positive should undergo endoscopy to rule out gastric malignancy, peptic ulcers and other diseases.

The guidelines on the management of Helicobacter pylori were updated at the European Helicobacter study group third Maastricht consensus conference in March 2005. Especially, this conference emphasis on the management of non ulcer dyspepsia, GERD, and the patients who use non steroidal anti-inflammatory drug. Eradication of H. pylori is recommended in patients with peptic ulcer, low grade MALT lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura and first degree relatives of patients with gastric cancer. H. pylori eradication is less effective than proton pomp inhibitor(PPI) treatment in preventing ulcer recurrence in long term NSAIDs users. This meeting also emphasized on the relationship between H. pylori and gastric cancer. The guideline concluded that H. pylori eradication has the potential to reduce the risk of gastric cancer development. Japanese guideline in 2003 does not mention the effect of eradication for prevention of gastric cancer. The H. pylori eradication and new strategy should be desirable for global strategy of gastric cancer prevention.

The cytotoxin-associated antigen A (CagA) of Helicobacter pylori prevalent in East Asian countries, where the mortality rate due to gastric cancer is high, has been reported to be structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. Based on the structural features of the EPIYA motifs located at the carboxyl terminal of the protein, CagA was subdivided into two types: East Asian CagA and Western CagA. A recent study suggested that immunohistochemistry with anti-East Asian-specific antibody (alpha-EAS Ab), which was specifically immunoreactive with East Asian CagA but not with Western CagA, may be useful for diagnosis of the cagA genotype. To further evaluate the value of this diagnostic method in terms of sensitivity, specificity, and accuracy, 143 gastric biopsy specimens with alpha-EAS Ab were analyzed on immunohistochemistry and compared with the sequencing of the cagA gene. It was found that diagnosis of the cagA genotype of H. pylori on immunohistochemistry using the alpha-EAS Ab was highly sensitive (sensitivity 93.2%) and specific (specificity 72.7%), suggesting that immunohistochemical diagnosis of the cagA genotype is useful for diagnosis of the cagA genotype.

Goals: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin., Background: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs., Methods: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days., Results: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05)., Conclusions: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.

Cytotoxin-associated antigen A (CagA) protein produced by Helicobacter pylori is proposed to be associated with the pathogenesis of gastric cancer as well as gastritis and gastroduodenal ulcer. It has been reported that the CagA of H. pylori widespread in East Asian countries, where the mortality rate due to gastric cancer is high, is structurally different from that in Western countries, where the gastric cancer mortality rate is relatively low. In this study, we generated an antibody, East Asian CagA-specific antibody (alpha-EAS Ab), which is specifically immunoreactive with East Asian CagA but not with Western CagA. The CagA was immunohistochemically detected at the surface of the gastric mucosa. Interestingly, positive immunoreactivity was also detected in the nucleus and cytoplasm of the infected gastric epithelium, suggesting that CagA may play some pathogenic role in both the nucleus and cytoplasm. Immunohistochemistry of 47 gastric biopsy specimens detected East Asian CagA-positive H. pylori in 43 cases. In 46 of the 47 cases examined, the data obtained by immunohistochemistry were completely consistent with those obtained by sequencing of the cagA gene of the isolated strain, suggesting that our immunohistochemical method is reliable and useful for diagnosis of the cagA genotype.

Aim: To investigate the mutation of p53 immunohistochemically in non-tumorous gastric mucosa with H pylori infection before and after H pylori eradication therapy., Methods: 53 subjects (36 male, 17 female, mean age +/- SEM, 57.1 +/- 12.1) undergoing endoscopic examination were included in this study. 42 of 53 patients were H pylori-positive, and 11 were H pylori-negative. All H pylori-positive patients had successful eradication therapy. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system. Immunohistochemical studies were performed by using primary antibodies against p53 (DO-7 and PAb240)., Results: p53 (DO-7 and PAb240) immunoreactivity was shown in the neck region of the gastric pits, however, quite a few cells were found to be immunopositive for p53 (PAb240) in the H pylori-infected gastric mucosa. The proportion of patients immunopositive for p53 (PAb240) was significantly reduced 6 mo after eradication [28/42 (66.7%) to 6/42 (14.3%)] (P < 0.05), while the biopsies taken from H pylori-negative patients showed no immunoreactivity for p53 (PAb240). p53 (PAb240)-positive patients were divided into two groups by the number of positive cells detected: one with more than six positive cells per 10 gastric pits (group A, n = 12), and the other with less than five positive cells per 10 gastric pits (group B, n = 30). Atrophy scores in group A were significant higher than those in group B at the greater curvature of the antrum (group A: 2.00 +/- 0.14 vs group B: 1.40 +/- 0.15, P = 0.012), the lesser curvature of the corpus (group A: 2.00 +/- 0.21 vs group B: 1.07 +/- 0.23, P = 0.017), and the greater curvature of the corpus (group A: 1.20 +/- 0.30 vs group B: 0.47 +/- 0.21, P = 0.031). Group A showed significant higher intestinal metaplasia scores than group B only at the lesser curvature of the antrum (group A: 2.10 +/- 0.41 vs group B: 1.12 +/- 0.29, P = 0.035)., Conclusion: H pylori-associated chronic gastritis expressed the mutant-type p53, which was significantly associated with more severe atrophic and metaplastic changes. H pylori eradication led to a significant reduction in the expression of the mutant-type p53. It is considered that H pylori-infected chronic gastritis is associated with a genetic instability that leads to gastric carcinogenesis, and H pylori eradication may prevent gastric cancer.

In the years that followed the issuance in 2000 of the Guidelines for the Management of Helicobacter pylori Infection in Japan by the Japanese Society for Helicobacter Research (JSHR), a number of major issues arose, including the emergence of H. pylori strains resistant to clarithromycin as part of primary eradication therapy, and this led to the Guidelines being revised by the JSHR in 2003. While the JSHR aimed in the 2000 Guidelines to prepare clinicians for the task ahead in view of H. pylori eradication therapy becoming available, the JSHR went a step further in the 2003 Guidelines to include more evidence-based recommendations to address clinical and institutional challenges and issues of interest in the management of H. pylori infection in Japan. Thus, a number of diseases were upgraded to either class A or B indications for H. pylori eradication, including mucosa-associated lymphoid tissue lymphoma (class A), and after endoscopic mucosal resection for early gastric cancer, atrophic gastritis, and gastric hyperplastic polyp (all class B), with further diseases such as extragastric disease also included as class C indications requiring further examination. Concern was expressed over reliance on a single diagnostic test for H. pylori infection, which is in place due to institutional constraints. Metronidazole was also recommended for use in the place of clarithromycin as part of a second-line eradication regimen in light of increasing clarithromycin resistance, although metronidazole remains to be approved for health insurance coverage. Finally, areas requiring further clinical research and endeavors, including establishment of second-line eradication therapy, were also proposed in the 2003 Guidelines to point the way for the future.

Background: Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor., Materials and Methods: Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second-line therapy including metronidazole: a 7-day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7-day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin., Results: Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains were found. The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively., Conclusions: Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health-care costs is also anticipated.

Purpose: This study examined the possible relationship between peptic ulcer recurrence and the presence or absence of maintenance therapy with an H(2)-receptor antagonist performed until evaluation of Helicobacter pylori eradication., Methods: The subjects were 483 patients with peptic ulcer (281 gastric ulcer and 202 duodenal ulcer) who were diagnosed as H. pylori positive. After receiving eradication therapy for H. pylori, patients were allocated at random to one of three different maintenance therapies: control group (no maintenance therapy), H(2)-receptor antagonist half-dose group, and H(2)-receptor antagonist full-dose group. The maintenance therapy was performed for 4 weeks until evaluation of H. pylori eradication., Results: Among the 25 patients with a recurrent ulcer, 18 patients (72%) had a recurrence at the time of or before evaluation of H. pylori eradication. In the control group, the rate of ulcer recurrence occurring before evaluation of H. pylori eradication was 10.5% (14/133). This rate was significantly higher than those in the H(2)-receptor antagonist half-dose group (2.9%, 4/136) and the full-dose group (0%, 0/135)., Conclusion: The results of this study suggest that maintenance therapy with an H(2)-receptor antagonist performed after eradication therapy until evaluation of H. pylori eradication is likely to greatly reduce the ulcer recurrence rate without affecting evaluation of H. pylori eradication.

There appears to be the strong association between Helicobacter pylori (H pylori) and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between H pylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pylori-associated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bone-marrow derived stem cells (BMDC) as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.

Background: Widespread use of eradication therapy for Helicobacter pylori has increased the prevalence of clarithromycin-resistant strains. The purpose of the present paper was to measure the in vitro antibacterial activity of minocycline against H. pylori, and study the effectiveness of minocycline-based first- and second-line eradication therapies., Methods: For first-line therapy, 79 patients were randomly assigned to the treatment with rabeprazole, amoxicillin, and clarithromycin or with rabeprazole, amoxicillin, and minocycline. For second-line therapy, 88 patients were tested for sensitivity to metronidazole: 67 patients with metronidazole-sensitive strains received a 7-day course of rabeprazole, minocycline, and metronidazole; the remaining 21 patients were given a 7-day course of rabeprazole, minocycline, and faropenem., Results: There was virtually no resistance to minocycline among the strains tested. The eradication rate of H. pylori infection in first-line therapy was significantly lower for minocycline-containing regimen (38.5%, 15/39) than for clarithromycin-containing regimen (82.5%, 33/40; P < 0.01). For second-line therapy, a high eradication rate against metronidazole-sensitive strains was obtained with rabeprazole, minocycline and metronidazole (85%, 57/67)., Conclusions: A combination of rabeprazole, minocycline, and metronidazole is safe and effective for second-line therapy of H. pylori infection. Because this regimen can be administered to patients with penicillin allergy and patients who suffer adverse reactions to amoxicillin, such as diarrhea and other digestive symptoms, it should be considered useful for second- and third-line eradication therapy.

Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (H pylori), several animal models with H pylori infection have been developed to confirm the association between H pylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53 mutation after long-term infection of H pylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methyl-N-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine. The histopathological changes of these animal models after H pylori inoculation are closely similar to those in human beings with H pylori infection. Eradication therapy attenuated the development of gastric cancer in H pylori-infected Mongolian gerbil. Although several features of animal models differ from those seen in human beings, these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of H pylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.

Background: Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication., Methods: Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2., Results: Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group., Conclusion: A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.