Antimicrobial-resistant Helicobacter pylori in Japan: Report of nationwide surveillance for 2018-2020.

BACKGROUND: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria. METHOD: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX). RESULTS: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001). CONCLUSIONS: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.

Evaluation of screening tests for autoimmune gastritis in histopathologically confirmed Japanese patients, and re-evaluation of histopathological classification.

BACKGROUND: The aims of the present study are to evaluate non-invasive screening tests for autoimmune gastritis (AIG) and re-evaluate histopathological classification. METHODS: We screened candidates of AIG in JCHO Shiga Hospital between May 2012 and January 2020. The screening criteria were as follows: endoscopic O-p atrophy with Updated Kimura-Takemoto classification, 3 + pepsinogen (PG) test, low serum vitamin B12 or elevated serum gastrin with positive anti-parietal cell (PC) or intrinsic factor antibodies. We evaluated the screening criteria in the patients who were histopathologically confirmed as AIG, and re-evaluated histopathological staging in clinical aspects. RESULTS: Twenty-two of 28 (78.6%) patients who met the screening criteria were histopathologically confirmed as AIG. Common clinical findings in the AIG patients were 10 × or greater anti-PC antibody, elevated serum gastrin greater than 172 pg/mL and endoscopic atrophy O-1 or greater. The areas under the curve of PG I, PG II and PG I/II ratio were 0.81, 0.29 and 0.98, respectively. Among histopathologically confirmed AIG patients, 4 and 18 patients were histopathologically classified into florid and end stages, respectively, while no patients into early stage. We could not find a significant difference between florid and end stages in the screening items studied. CONCLUSIONS: Florid and end stages in histopathological classification are both advanced-stage AIG in clinical aspects. Our screening criteria without biopsy are applicable to screen clinically-advanced AIG with 78.6% positive predictive value. PG I and PG I/II ratio may be useful to screen AIG. However, we may need other criteria to screen early stage of AIG.

Incisura angularis belongs to fundic or transitional gland regions in Helicobacter pylori-naïve normal stomach: Sub-analysis of the prospective multi-center study.

OBJECTIVE: Incisura angularis is one of the important parts for evaluating mucosal atrophy and cancer risk. We determined the type of mucosa at incisura angularis in Helicobacter pylori-naïve normal stomach. METHODS: Subjects aged 40 years or older who underwent esophagogastroduodenoscopy for dyspepsia or a routine health checkup were recruited in 24 facilities between March 2008 and February 2009. Serum antibody to H. pylori was measured. Endoscopic atrophy was evaluated according to Updated Kimura-Takemoto classification. Five biopsy specimens were taken from the incisura angularis and greater and lesser curvatures of the antrum and corpus. These specimens were histologically classified as fundic, pyloric or transitional. H. pylori-naïve normal stomach was defined with the strictest criterion among various combinations of histological, endoscopic and serum findings. We determined histological type of mucosa at incisura angularis in H. pylori-naïve normal stomach. RESULTS: A total of 270 subjects (122 men, mean 64.6 yo) were analyzed. The strictest criterion consists of serum antibody ≤ 3.0 U/mL, endoscopic atrophy C-1 and histological grade 0 in all of the five items in Updated Sydney System. The numbers having fundic, transitional and pyloric mucosa at incisura angularis under the strictest criterion were 13 (50%), 13 (50%) and 0, respectively. The probability that the type of mucosa at incisura angularis would be pyloric was almost zero (97.5% confidence interval 0-0.132). CONCLUSIONS: Incisura angularis of the stomach may not belong to pyloric, but fundic or transitional mucosa in H. pylori-naïve normal stomach. UMIN000018218.

Characteristics of gastric cancer in negative test of serum anti-Helicobacter pylori antibody and pepsinogen test: a multicenter study.

BACKGROUND AND AIM: The serological risk prediction system combines the pepsinogen test and anti-Helicobacter pylori (H. pylori) antibody determination. In this system, chronic atrophic gastritis (CAG) is diagnosed using the pepsinogen test. Patients who are H. pylori negative and pepsinogen negative are classified into group A, are assumed to be H. pylori uninfected, and are at an extremely low risk for gastric cancer. However, gastric cancers are detected in this group. The aim of this study is to clarify the clinicopathological status of group A patients with gastric cancer. METHODS: A total of 109 gastric cancer patients classified as group A were enrolled in a multicenter study. Group A patients were divided into two subgroups: group AN (H. pylori uninfected) and group AP (H. pylori infected). They were compared to 183 H. pylori-infected gastric cancer patients who were not in group A. RESULTS: Of the 109 patients, only 7 were classified as group AN; the other 102 were classified as group AP. The clinicopathological features of group AP included older age, predominantly differentiated type cancer, endoscopically visualized CAG, and pepsinogen (PG) I/II ratio lower than that of group AN. In group AN, the depressed type was dominant, and the PG I/II ratio was higher than in those gastric cancer patients who were infected with H. pylori. CONCLUSION: Patients in group AP had CAG, and their gastric cancers were similar to those of H. pylori-eradicated patients. Concerning the recent ABC classification system, advanced decision criteria should be proposed to decrease the false-negative evaluation of gastric cancer risk.

Prevalence of Helicobacter pylori infection by birth year and geographic area in Japan.

BACKGROUND: Helicobacter pylori (H. pylori)-related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults. MATERIALS AND METHODS: This cross-sectional study included 14,716 subjects aged 20 years or more who underwent a health checkup between May 1997 and March 2013 in seven geographic areas throughout Japan. Relevant information on the demographics and status of H. pylori infection was retrieved from the electronic database. The univariate log-binominal regression model was used to estimate the prevalence of H. pylori infection, taking birth year into consideration. The multivariate log-binominal regression model was used to compare the prevalence of H. pylori infection between seven geographic areas. RESULTS: The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Among seven geographic areas, Hokkaido showed the lowest prevalence (29.4%), while Yamagata Prefecture represented the highest (54.5%). The prevalence of H. pylori infection was highest in the 1940-1949 birth cohort and then decreased in the ensuing birth cohorts; the risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.84-0.87) for changes in the 10-year birth cohort. Individuals in Yamagata Prefecture had the highest RR of acquiring H. pylori infection in all three birth cohorts (RR = 1.53 for 1940, RR = 1.69 for 1950, and RR = 1.85 for 1960) when compared with those in Hokkaido. CONCLUSIONS: The prevalence of H. pylori infection increases with age and exhibits geographic variation in Japan. There has been a striking decrease in the prevalence of H. pylori infection, especially in younger Japanese populations.

Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation.

BACKGROUND: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. METHODS: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. RESULTS: Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. CONCLUSIONS: AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

Changes in endoscopic findings of gastritis after cure of H. pylori infection: multicenter prospective trial.

BACKGROUND AND AIM: Successful eradication of H. pylori changes pathological findings of gastritis dramatically. However, change of endoscopic mucosal findings is not fully understood. To clarify the short-term changes of endoscopic mucosal findings after cure of H. pylori infection, a multicenter prospective trial was conducted. METHODS: One hundred and forty-seven patients with H. pylori infection from 12 institutions were enrolled into this prospective cohort trial. Nineteen endoscopic findings using high-resolution white light electronic endoscopy were assessed before and 2-4 months after eradication treatment of H. pylori. H. pylori infection was diagnosed by pathology of three stomach sites using hematoxylin-eosin stain or H. pylori-specific immunostaining. Endoscopic features of the successful eradication group and the failed eradication group were compared. The change of severity of endoscopic features before and after H. pylori eradication were compared between successful eradication and failed eradication. RESULTS: One hundred and twenty-six patients were analyzed. Eradication rate was 81% (102/126). Non-transparency of gastric juice, diffuse redness of fundic mucosa, enlarged fold, spotty redness of fundic mucosa, flat erosion of stomach, and hemoglobin index of fundic mucosa were significantly different between the successful eradication group and the failed eradication group. Gastric flat erosion was of higher frequency in the successful eradication group. When eradication was successful, spotty redness of fundic gland improved significantly. CONCLUSION: Assessment of endoscopic findings of spotty redness after eradication treatment is useful in the diagnosis of H. pylori eradication.

Multiple-antibiotic-resistant Helicobacter pylori infection eradicated with a tailor-made quadruple therapy.

In 2008, a 44-year-old woman with mild epigastralgia diagnosed as having Helicobacter pylori-positive chronic gastritis without peptic ulcer underwent eradication therapy with lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) for 7 days, but it failed, so treatment with rabeprazole, AMPC, and metronidazole (MNZ) for another 7 days was given, but it also failed. She was then prescribed a modified, 14-day sequential therapy of LPZ and AMPC with an increased dose of CAM followed by MNZ supplement, but the infection was still not eradicated. The H. pylori was cultured and examined for antibiotic susceptibility with the agar dilution method and was found to be resistant to CAM, MNZ, and levofloxacin, and non-sensitive to AMPC, namely multiple-antibiotic-resistant, although sensitive to minocycline. The CYP2C19 genotype of the patient was an extensive metabolizer (G681A: G/A, G636A: G/G). In 2010, she gave informed consent for a 14-day, tailor-made, modified classical (or modified high-dose PPI + AMPC) quadruple therapy comprising 30 mg LPZ, 500 mg AMPC and 500 mg bismuth subnitrate, qid, and 100 mg minocycline, bid. Two months later, her urea breath test was negative. Histology and bacterial culture were still negative 1 year after the therapy. She did not have any adverse events during or after the novel therapy, nor did she feel any further epigastralgia.

[Gastric cancer screening in Japan, now and tomorrow].

The screening rate of gastric cancer in the population surveyed by Japanese government was 34.3% in 2010. The rates differed by medical insurance holders: 60-70% in the big-company insurances; 32% in the national government-assisted small-company insurances; 10% in the local government-assisted non-company individual insurances and the dependents of any insurance holders. The only method of gastric cancer mass screening that Japanese government approves now is sodium bicarbonate-barium X-ray examination. The rate diagnosed as gastric cancer in the system was 0.088% in 2009. A new strategy using serum tests for pepsinogens and Helicobacter pylori-antibody has been proposed. Test and eradication may be the best method for screening high-risk subjects and primary prevention of gastric cancer, and the subsequent cancer screening.

Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential.

BACKGROUND: Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown. METHODS: Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR. RESULTS: The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation. CONCLUSIONS: AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population.

BACKGROUND: Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (SLC6A4) polymorphism and FD was explored. METHODS: Subjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the SLC6A4 promoter polymorphism, 5-hydroxytryptamin transporter gene linked polymorphic region (5-HTTLPR), was then evaluated, and logistic regression analysis was used to test all variables. RESULTS: The 5-HTTLPR genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the 5-HTTLPR genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, P = 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, P = 0.009). CONCLUSION: The present results suggest that 5-HTTLPR L allele may influence the susceptibility to PDS.

Genetic factors for functional dyspepsia.

BACKGROUND: Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well established. Several reports indicate the associations between FD and gene polymorphisms, however the data are inconsistent. This review summarized the evidence of genetics in FD based on genetic epidemiology. RESULTS: Genetic association studies with FD symptom phenotype have limited for several candidate genes investigated. There have been no genome wide association studies in FD. G-protein beta3 (GNB3) subunit C825T was first reported as a candidate gene for FD susceptibility. However, the data are inconsistent in countries. Significant link between homozygous 825C allele of GNB3 protein and dyspepsia was reported from Germany and the USA. On the other hand, the association between T allele of GNB3 C825T polymorphism and dyspepsia was reported from Japan and Netherlands. Association of serotonin transporter promoter (SERT-P) gene polymorphism and FD was reported negatively from a USA community and Netherlands. However we found that SERT SL genotype was significantly associated with PDS. Involvement of IL-17F, migration inhibitory factor (MIF), catechol-o-methyltransferase (COMT) gene val158met, 779 TC of CCK-1 intron 1, cyclooxygenase-1 (COX-1), transient receptor potential cation channel, subfamily V, member 1 (TRPV1) 315C and regulated upon activation normal T cell expressed and secreted (RANTES) polymorphisms was reported in Japanese studies. CONCLUSIONS: Genetic factors are associated with the development of dyspeptic symptoms. Further studies are needed to confirm these data and to determine how genetic factors influence the clinical manifestation of FD patients.

Pyloric, pseudopyloric, and spasmolytic polypeptide-expressing metaplasias in autoimmune gastritis: a case series of 22 Japanese patients.

There are two types of pyloric gland-like metaplasia in the corpus of stomach: pyloric and pseudopyloric metaplasias. They show the same morphology as the original pyloric glands in H&E staining. Pseudopyloric metaplasia is positive for pepsinogen (PG) I immunohistochemically, whereas pyloric metaplasia is negative. Recently, spasmolytic polypeptide-expressing metaplasia (SPEM) is proposed for pyloric gland-like metaplasia mainly in animal experiments. SPEM expresses trefoil factor family 2 (TFF2) and is often considered synonymous with pseudopyloric metaplasia. We reviewed consecutive 22 Japanese patients with autoimmune gastritis (AIG) to investigate TFF2 expression in pyloric and pseudopyloric metaplasias by counting all pyloric gland-like glands in biopsy specimens taken from greater curvature of the middle corpus according to the Updated Sydney System. Pyloric metaplasia was seen in all the 22 cases, and pseudopyloric metaplasia was found in 15 cases. Of 1567 pyloric gland-like glands in all the cases, 1381 (88.1%) glands were pyloric metaplasia glands, and the remaining 186 (11.9%) glands were pseudopyloric metaplasia glands. TFF2 expression was observed in pyloric or pseudopyloric metaplasia glands in 20 cases. TFF2 expression was recognized in 409 of 1381 (26.9%) pyloric metaplasia glands and 27 of 186 (14.5%) pseudopyloric metaplasia glands (P<0.01, chi-square test). In conclusion, SPEM was not always the same as pseudopyloric metaplasia in human AIG, and the majority of metaplasia in AIG was not pseudopyloric but pyloric metaplasia.

The G-protein beta3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia.

BACKGROUND: Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein beta3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up. METHODS: Subjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables. RESULTS: The GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91). CONCLUSION: The homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.

Changes in the prevalence of Helicobacter pylori infection and gastrointestinal diseases in the past 17 years.

BACKGROUND AND AIMS: The aim of the study was to examine whether the change in the prevalence of Helicobacter pylori infection had influenced upper gastrointestinal diseases in a recent 17-year period. METHODS: The prevalence of H. pylori infection was examined by serum H. pylori antibody tests in the subjects undergoing annual health checks at the Social Insurance Shiga Hospital in 1998 and 2005 (142 and 242 subjects, respectively). The prevalence of H. pylori infection in 1988 was estimated by parallel translation from the prevalence in 1998. A total of 2833 records of endoscopy performed in 1988 and 2005 at Otsu Municipal Hospital were studied. The age-adjusted prevalence of peptic ulcer, gastric cancer and reflux esophagitis were compared between 1988 and 2005. RESULTS: The age-adjusted prevalence of H. pylori infection significantly decreased in 2005 compared with 1988 (70.5-52.7%). The endoscopic records of 937 and 1246 patients in 1988 and 2005, respectively, were included in the analysis. The age-adjusted prevalence of peptic ulcer significantly decreased 0.34-fold in both men and women in 2005 compared with 1988. The age-adjusted prevalence of gastric cancer significantly decreased 0.44-fold in men, but did not change in women (0.99-fold), and overall significantly decreased 0.56-fold. The age-adjusted prevalence of reflux esophagitis significantly increased 6.6-, 2.7- and 4.8-fold in men, women and total, respectively. The increase was dominant in men aged 30-69 years. CONCLUSION: Over the 17-year period, accompanying the decreasing prevalence of H. pylori infection, the age-adjusted prevalence of peptic ulcer and gastric cancer decreased, but that of reflux esophagitis increased.

Spectra of functional gastrointestinal disorders diagnosed by Rome III integrative questionnaire in a Japanese outpatient office and the impact of overlapping.

BACKGROUND AND AIMS: The aim of this study was to establish the spectra of functional gastrointestinal disorders (FGID) in a Japanese outpatient office in Rome III. METHODS: The Rome III Diagnostic Questionnaire for Adult Functional GI Disorders was translated into Japanese and an automated analyzing program was made according to the scoring algorithm of the questionnaire. Among 1378 patients who visited the outpatient office of the Social Insurance Shiga Hospital between May 2007 and April 2009, 112 serial patients who had symptoms possibly originating from the gastrointestinal (GI) tract, but did not have evidence of organic disease, were recruited. The subjects answered the questionnaire, and the answers were analyzed with the automatic analyzer. RESULTS: During the study period, 94 of the 112 patients were diagnosed as having active FGID. Non-overlapping FGID was diagnosed in 41 (43.6%) of those. Of the 41 non-overlapping FGID patients, the most frequent diagnosis was irritable bowel syndrome (IBS) in 13 patients. Including overlapping cases, 165 FGID were diagnosed in 94 patients. The most frequent diagnosis was IBS in 33 patients (35.1%), the second was functional dyspepsia (FD) in 29 (30.9%) and the third was functional constipation in 21 (22.3%). The most frequent FGID overlapping with IBS was FD (36.4%), and the most frequent FGID overlapping with FD was IBS (41.4%). Of the 29 FD patients, 20 (69.0%) had functional bowel disorders. CONCLUSION: The most frequent FGID was IBS in both overlapping and non-overlapping FGID patients. IBS and FD were the most frequent combinations in overlapping FGID. Most cases of FD are possibly parts of functional bowel disorders.

Methicillin resistant Staphylococcus aureus in a Japanese community hospital: 5-year experience.

Methicillin resistant Staphylococcus aureus (MRSA) is exceptionally critical to infection treatment and control in the health-care setting. MRSA has been detected at high levels in Japan, and the frequency of MRSA infection must be ascertained to provide a baseline with which to assess various infection control efforts. We studied MRSA infection rate at a general hospital in Japan in all 65,135 inpatients of Sendai Kousei Hospital from January 2004 to December 2008. MRSA's prevalence among strains of S. aureus and the rate of MRSA detection were studied. Identification of MRSA infection is according to the laboratory-based ward liaison surveillance. The minimal inhibitory concentrations (MICs) of vancomycin, teicoplanin, and arbekacin for the various isolates were determined. During the period studied, there were 621 MRSA-positive patients. MRSA prevalence among strains of S. aureus was 45.5% (621/1,365). The rate of MRSA detection in inpatients was 0.953/100 inpatients. Of the 621 patients from whom MRSA was isolated, 51 (8.2%) had an MRSA infection (MRSA infection rate 0.078/100 inpatients). MRSA was often detected from the respiratory tract, but this seldom led to infection, since many of those affected were merely carriers. MICs against MRSA was 0.5-4 µg/ml for vancomycin, 0.5-16 µg/ml for teicoplanin, and 0.5 to >16 µg/ml for arbekacin, with no tendency for tolerance observed for these drugs. Findings suggest that whereas MRSA remains prevalent, there is a low incidence of infection in a general hospital in Japan.

A Rare Combination of Gastric Mucosa-associated Lymphoid Tissue Lymphoma, Autoimmune Gastritis, Thyroiditis, Hemolysis, and Systemic Lupus Erythematosus.

We herein report a case with the rare combination of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the stomach, autoimmune gastritis (AIG), autoimmune thyroiditis, autoimmune hemolytic anemia (AIHA), and systemic lupus erythematosus. A 68-year-old woman was diagnosed with gastric MALT lymphoma associated with Helicobacter pylori (H. pylori) infection and AIG. Complete remission of the MALT lymphoma was achieved by H. pylori eradication and radiotherapy. Three years after the diagnosis of MALT lymphoma, the patient developed AIHA and anti-nuclear and anti-Smith autoantibody-positive lupus serositis, which were successfully managed with prednisolone administration.

Stepwise diagnosis and treatment from uninvestigated dyspepsia to functional dyspepsia in clinical practice in Japan: proposal of a 4-step algorithm.

BACKGROUND/AIM: Management of dyspepsia may differ between countries. In Japan, Helicobacter pylori infection should be considered because of the high prevalence of the infection and the related diseases. I tried to propose an algorithm for stepwise diagnosis and treatment from uninvestigated dyspepsia to functional dyspepsia in clinical practice in Japan. METHODS: A proposal was made from my personal review of published studies. RESULTS: A 4-step algorithm was proposed. In the first step, organic, systemic or metabolic diseases are excluded and nonulcer dyspepsia (NUD) is diagnosed. The second step is to test and treat H. pylori infection for NUD patients. In the third step, proton pump inhibitor (PPI)-responsive NUD is discriminated by PPI. Nonresponsive patients in the third step are diagnosed as having PPI-resistant NUD. In the fourth step, functional dyspepsia is diagnosed with the Rome III questionnaire. In this algorithm, it is not necessary to do special function tests for functional gastrointestinal disorders. Treatment options are automatically restricted in each step. CONCLUSIONS: The proposed 4-step algorithm may be useful in clinical practice for the diagnosis from uninvestigated dyspepsia to functional dyspepsia in Japan. With this stepwise algorithm, treatment options are restricted in each step and the management of dyspepsia may be easier.

When does gastric atrophy develop in Japanese children?

BACKGROUND: Long-term Helicobacter pylori infection causes inflammatory sequelae such as atrophy and intestinal metaplasia in the stomach, which is thought to increase the risk of developing gastric malignancy. We previously reported that gastric atrophy can develop in Japanese children with H. pylori infection, predominantly in the antrum. However, detailed data about the age of children with atrophy are largely lacking. METHODS AND RESULTS: In the present study, 131 children (79 boys) with H. pylori infection were re-analyzed for an association between age and the grade of gastric atrophy. The gastric antrum was histologically evaluated in all 131 patients and the corpus in 46 patients. Grade 2 and 3 antral atrophy was observed in 13 and one patients, respectively: the mean age was 12.1 years. Two patients (11 and 14 years old) had grade 2 corpus atrophy but no patients had grade 3. No significant difference was found in age among patients with grade 0, 1 and 2 or 3 atrophy in the antrum (p = .97) and in the corpus (p = .59). None of the patients with grade 2 or 3 atrophy had intestinal metaplasia either in the antrum or in the corpus. CONCLUSIONS: The results of the present study require a careful interpretation because of the retrospective analysis. In high-risk countries of gastric cancer, however, eradicating H. pylori in childhood could prove more effective in preventing gastric atrophy, ultimately, the development of cancer.