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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

AlthoughHelicobacter pylorihas been regarded as a pathogen of gastric cancer, the mechanism by whichH. pyloriis involved in gastric carcinogenesis remains unknown. To clarify the role ofH. pyloriin carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and afterH. pylorieradication.Biopsy specimens were obtained from 31 patients withH. 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.Six months afterH. pylorieradication, 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 theH. pylori-infected group.A significant increase is shown in p53 and MDM2 expression inH. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication ofH. pyloridramatically reduced the p53 and MDM2 levels. Therefore,H. pyloriinfection may be associated with alteration of cell proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

In the seed production of several marine teleosts, large numbers of dead larvae are frequently observed on the water surface around the time of first feeding. We tried to prevent such “surface death” by the addition of chicken egg white (EW) into the rearing water. In the first experiment, larvae of striped bonito, Sarda orientalis, at the first feeding stage (2 and 3 days after hatching) were transferred to plastic beakers using a 5-ml pipette at a density of 10 larvae/l, in the absence or presence of EW (80 μl/l). No diet was supplied, the water was not renewed throughout the experiment, and dead larvae were removed daily. Numbers of surviving larvae of the EW-treated group were significantly higher than those of the control group. In particular, survival at the first observation (next day after transfer) was less than 30% in the control, while 100% in the EW-treated group. In a second experiment, mortality at 2 h after transfer was compared with special attention to the location of the dead larvae. Significantly (P<0.01) higher mortality was found in the control group, and more than 70% of the dead larvae were located on the water surface. Upward swimming toward the water surface was observed in both groups, but larvae “trapped” at the surface were only observed in the control group. In a third experiment, an oil film that was artificially created on the water surface prevented larval death after the transfer as well as the dissolved EW. Since the oil film is known to prevent “surface trap” of larvae and decrease “surface death” in a grouper, the addition of EW was considered to have a similar effect in reducing mortality. In a fourth experiment using 30-l tanks, survival of larval pez cochero, Dules auriga, was also higher in the presence of EW, especially during a period when dead larvae were frequently found on the water surface in the control. Thus, the addition of EW to the rearing water is suggested to prevent surface death in a variety of marine fish larvae, and the possibility of applying the method in practical rearing is discussed. [Copyright &y& Elsevier]

Striped bonito Sarda orientalis larvae and juveniles were reared in a laboratory from hatching to 14 days post hatching, and the development of their digestive system was investigated histologically. On day 2 (first feeding day), the larval-type digestive system was differentiated. On day 3, a blind sac with densely distributed gastric glands developed and pyloric ceca appeared, suggesting that the digestive system was attaining adult-type structure. The yolk was completely absorbed on day 4. Bonito larvae preyed on rotifers and/or Artemia nauplii on day 2, but almost the whole gut was occupied by fish larvae from day 4. In the striped bonito, the adult-type digestive system was established right after first feeding, and this precocious development was well synchronized with the appearance of piscivory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A 66-year-old man presented to our institution with a positive fecal occult blood test and lower abdominal pain. Although a tumor was found in the sigmoid colon, biopsy and imaging studies failed to enable the diagnosis of the cancer, and the patient underwent surgery for treatment and diagnosis. The tumor had two distinct areas with differing features shown both histopathologically and on imaging; it was thus diagnosed as a leiomyosarcoma of the sigmoid colon with a pleomorphic component. Here, we describe a rare case of leiomyosarcoma of the sigmoid colon with a pleomorphic component. There are no reports of leiomyosarcoma with pleomorphic components arising in the colon in the literature; thus, the recurrence and metastatic characteristics are unknown. Therefore, accumulating cases in the literature may provide valuable insights into diagnosing and treating these rare tumors. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about evaluation of the Helicobacter pyloristool antigen (HpSA) assay for diagnosing infection and confirming eradication after treatment.

In the present prospective case series study, we investigated the lesion-detection ability of an AI-equipped colonoscopy as an addition to colonoscopy (CS) screening. Participants were 100 patients aged ≥20 years who had not undergone CS at the study site in the last 3 years and passed the exclusion criteria. CS procedures were conducted using conventional white light imaging and computer-aided detection (CADe). Adenoma detection rate (ADR; number of individuals with at least one adenoma detected) was compared between the conventional group and the CADe group. Of the 170 lesions identified, the ADR of the CADe group was significantly higher than the ADR of the conventional group (69% vs. 61%, p = 0.008). For the expert endoscopists, although ADR did not differ significantly, the mean number of detected adenomas per procedure (MAP) was significantly higher in the CADe group than in the conventional group (1.7 vs. 1.45, p = 0.034). For non-expert endoscopists, ADR and MAP were significantly higher in the CADe group than in the conventional group (ADR 69.5% vs. 56.6%, p = 0.016; MAP 1.66 vs. 1.11, p < 0.001). These results indicate that the CADe function in CS screening has a positive effect on adenoma detection, especially for non-experts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK‐1654, a half‐life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo‐controlled, single‐site, double‐blind trial of MK‐1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK‐1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK‐1654 was generally well‐tolerated in Japanese adults. There were no serious drug‐related adverse events (AEs) reported in any MK‐1654 recipient and no discontinuations due to any AEs in the study. The half‐life of MK‐1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose‐dependent manner among participants who received MK‐1654. These data support the development of MK‐1654 for use in Japanese infants. [ABSTRACT FROM AUTHOR]

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 H2 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. [ABSTRACT FROM AUTHOR]

Pseudo-nitzschia multiseries loses most of its ability to produce domoic acid when it is cultured axenically. However, domoic acid production recovers when bacteria from the original culture are reintroduced to axenic cultures, indicating a bacterial association with domoic acid production in this species. In order to determine the role of bacteria in domoic acid production, an axenic strain prepared from a nonaxenic strain of P. multiseries was inoculated into media in cellophane tubes, which were then placed in a bottle containing the original nonaxenic culture. Both strains showed characteristic domoic acid production similar to that previously observed. Domoic acid level in the cells of the axenic strain in the tubes was much smaller than that of the cells outside the tubes. These results show that direct contact between living bacteria and P. multiseries is necessary for producing high levels of domoic acid in P. multiseries. [ABSTRACT FROM AUTHOR]

A recent meta-analysis by Huang et al. clarified that Helicobacter pylori infection and nonsteroidal antiinflammatory drugs (NSAIDs) are important factors for peptic ulcer. The results showed that the risk for ulcer in NSAID(+)/ H. pylori(+) patients was 61.1 fold higher when compared with NSAID(−)/ H. pylori(−) patients. Some gastric ulcers detected in patients on NSAID therapy may actually be caused by H. pylori, but it is difficult to differentiate NSAID-induced gastric ulcer from H. pylori-induced gastric ulcer. Several studies have investigated the effects of H. pylori eradication on ulcer healing. One study reported that H. pylori eradication actually lowered the healing rate of gastric ulcers. Because there have been no studies finding that H. pylori eradication facilitates healing, H. pylori eradication is not recommended for NSAID users. Concerning the efficacy of H. pylori eradication in the prevention of NSAID-induced gastric ulcer, a meta-analysis concluded that among all patients on NSAID therapy, H. pylori eradication lowered the prevalence of ulcer, which was particularly marked in NSAID-naïve patients. When compared with those of proton pump inhibitors (PPIs), the preventative effects of H. pylori eradication were inferior. In Japan, national health insurance does not cover procedures that prevent or lower the risk for NSAID-induced ulcer. When administering NSAID to patients with risk factors, it is desirable to administer antiulcer agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori -infected stomachs of Mongolian gerbils for a long time. Materials and Methods. Five-week-old-male Mongolian gerbils were infected with H. pylori ATCC 43504 with cag A gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals. Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes. Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin-like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids. [ABSTRACT FROM AUTHOR]

Background. p53 gene mutations are believed to play a critical role in the development of gastric carcinoma. We examined the relation between Helicobacter pylori infection and p53 gene mutations of the gastric mucosa in human and animal models. Methods. To detect the original p53 DNA sequences of the Japanese monkey and Mongolian gerbil, the p53 genes of these animals were amplified using the nested polymerase chain reaction method with primers for the human p53 gene. Direct DNA sequencing of exons 5, 6, 7, and S of the p53 genes was performed by the dyedeoxy terminator method for gastric mucosa of humans, the Japanese monkey, and the Mongolian gerbil. The expression of p53 was examined immunohistochemically in a Japanese monkey model. Results. Mutations of the p53 gene were identified in 52.4% of human H. pylori-positive mucosa and in 100% of monkey H. pylori-positive mucosa. However, no mutations of the p53 gene were found in the H. pylori-positive gastric mucosa of Mongolian gerbils. There were no mutations in H. pylori-negative gastritis mucosa of humans, monkeys, or Mongolian gerbils. Nuclear staining of p53 was seen in the glandular cells of the H. pylori-infected mucosa of Japanese monkeys, especially in the neck region of the glands. Conclusions. These findings demonstrate that the H. pylori infection can induce p53 point mutations in humans and the Japanese monkey and appear to be involved in the pathway leading to dysplasia or carcinoma. However, our direct DNA sequencing method showed no p53 mutations in the Mongolian gerbil model at present. Further studies with this model are needed. [ABSTRACT FROM AUTHOR]

Many studies have investigated the ability to identify species from environmental DNA (eDNA). However, even when individual species are identified, the accurate estimation of their abundances by traditional eDNA analyses has been still difficult. We previously developed a novel analytical method called HaCeD-Seq (Haplotype Count from eDNA), which focuses on the mitochondrial D-loop sequence. The D-loop is a rapidly evolving sequence and has been used to estimate the abundance of eel species in breeding water. In the current study, we have further improved this method by applying unique molecular identifier (UMI) tags, which eliminate the PCR and sequencing errors and extend the detection range by an order of magnitude. Based on this improved HaCeD-Seq pipeline, we computed the abundance of Pacific bluefin tuna (Thunnus orientalis) in aquarium tanks at the Tokyo Sea Life Park (Kasai, Tokyo, Japan). This tuna species is commercially important but is at high risk of resource depletion. With the developed UMI tag method, 90 out of 96 haplotypes (94%) were successfully detected from Pacific bluefin tuna eDNA. By contrast, only 29 out of 96 haplotypes (30%) were detected when UMI tags were not used. Our findings indicate the potential for conducting non-invasive fish stock surveys by sampling eDNA. [ABSTRACT FROM AUTHOR]

Background: We previously reported the development of pancreatic acinar cell metaplasia (PACM) in the glandular stomach of a duodenal contents reflux model (reflux model). Aims: We aimed to investigate the characteristics and histogenesis of PACM using a reflux model. Methods: A reflux model was created using 8-week-old male Wistar rats, which were killed up to 30 weeks postoperatively. Histological examination was performed to analyze the glandular stomach–jejunal anastomosis. Furthermore, electron microscopic images of PACM samples were compared with pancreatic and gastric glands removed from rats that had not undergone surgery. Immunostaining for α-amylase, HIK1083, TFF2, and Ki-67 was performed, and double fluorescent staining was carried out using antibodies against α-amylase and HIK1083, or α-amylase and TFF2. Results: In all reflux model rats, PACM was observed proximal to the glandular stomach–jejunal anastomosis, surrounded by pseudopyloric metaplasia. The number of chief cells was decreased in the deep part of the gland, where PACM occurred. Electron microscopy showed that PACM cells had greater numbers of rough endoplasmic reticulum tubules than chief cells, and exhibited pancreatic acinar cell morphology. Upon immunochemical staining, the regenerative foveolar epithelium and part of the pseudopyloric glands stained strongly positive for TFF2, whereas PACM cells were only weakly positive. Double fluorescent staining identified early lesions of PACM in the neck, which were double positive for α-amylase and TFF2, but negative for HIK1083. Conclusions: PACM could be induced by duodenal contents reflux. PACM originates from stem cells located in the neck of oxyntic glands during gastric mucosal regeneration. [ABSTRACT FROM AUTHOR]

Background: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2S), 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 H2S 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 H2S 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 H2S production, was the most frequently altered pathway. H pylori‐inoculated cells produced more endogenous H2S than control cells. Moreover, ATCC 43504‐inoculated cells produced less H2S than ATCC 51932‐inoculated cells. Conclusions: H pylori infection modulates endogenous H2S production in AGS cells, suggesting that H2S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy. [ABSTRACT FROM AUTHOR]

Objectives. Differentiating gastrointestinal stromal tumor (GIST) from other submucosal tumors (SMTs) is important in diagnosing SMT. GIST is an immunohistological diagnosis that cannot be made from images alone. Tissue sampling of tumor sites is thus becoming increasingly important. In this study, the utility and associated complications of mucosal cutting biopsy (MCB) for gastric SMTs were investigated. Methods. This was a case series study. The subjects were patients aged ≥20 years old in whom an SMT was seen on esophagogastroduodenography and who underwent MCB between January 2012 and December 2016. Patient information, endoscopy findings, gastric SMT size, pathological diagnosis, and other information were gathered from medical records. The SMT size was the maximum diameter that could be visualized on EUS. The pathological diagnosis was made with hematoxylin-eosin staining, with immunostaining added to diagnose GIST. The endpoint was the histopathological diagnostic yield. Risk assessment using the Miettinen classification and modified Fletcher classification was also done for GISTs treated with surgery. Results. The mean tumor diameter was 15.4 mm. The tumor diameter was ≥20 mm in seven patients and <20 mm in 23 patients. The tissue-acquiring rate was 93.3%. A histological diagnosis could not be made in two patients. The only complication was that bleeding required endoscopic hemostasis during the procedure in one patient, but no subsequent bleeding or no postoperative bleeding was seen. Conclusions. MCB is an appropriate and safe procedure in the diagnosis of gastric SMTs. Many hospitals will be able to perform MCB if they have the environment, including skills and equipment, to perform endoscopic submucosal dissection. [ABSTRACT FROM AUTHOR]

We aimed to determine the significance and usefulness of imaging characteristics of gubernaculum tracts (GT) for the diagnosis of odontogenic tumors or cysts. This was a retrospective analysis of relationships between odontogenic or non-odontogenic tumors or cysts and the GT that were visualized using multi-detector computed tomography (MDCT). The relationship between the size of a mass and expansion of the GT in all odontogenic tumors or cysts to which GTs were contiguous on MDCT, was statistically analyzed. Intact or expanded GTs were detected in MDCT images on the top of almost all odontogenic tumors or cysts, but not on non-odontogenic tumors or cysts. Characteristic image findings regarding the relationship between the GT and the odontogenic mass were detected for the respective odontogenic tumors or cysts in which the GTs were contiguous to the mass on MDCT. In ameloblastomas, expansion of the GTs significantly and very strongly correlated with tumor size (r = 0.741, p = 0.0001), but this correlation was very weak in dentigerous cysts (r = 0.167, p = 0.028) and there was no correlation between these parameters in odontogenic keratocysts (r = -0.089, p = 0.557). The imaging characteristics of GTs at the top of masses should be very useful for both the differential diagnosis of the pathological diagnosis of odontogenic masses and for differentiation between odontogenic and non-odontogenic masses. [ABSTRACT FROM AUTHOR]

Objectives. We aimed to determine whether linked color imaging (LCI), a new image-enhanced endoscopy that enhances subtle differences in mucosal colors, can distinguish the border of endoscopic mucosal atrophy. Methods. This study included 30 patients with atrophic gastritis. In endoscopy, we continuously took images in the same composition with both LCI and white light imaging (WLI). In each image, the color values of atrophic and nonatrophic mucosae were quantified using the International Commission on Illumination 1976 (L∗, a∗, b∗) color space. Color differences at the atrophic border, defined as Euclidean distances of color values between the atrophic and nonatrophic mucosae, were compared between WLI and LCI for the overall cohort and separately for patients with Helicobacter pylori infection status. Results. We found that the color difference became significantly higher with LCI than with WLI in the overall samples of 90 points in 30 patients. LCI was 14.79 ± 6.68, and WLI was 11.06 ± 5.44 (P<0.00001). LCI was also more effective in both of the Helicobacter pylori-infected group (P=0.00003) and the Helicobacter pylori-eradicated group (P=0.00002). Conclusions. LCI allows clear endoscopic visualization of the atrophic border under various conditions of gastritis, regardless of Helicobacter pylori infection status. [ABSTRACT FROM AUTHOR]

Background/Aims. It is difficult to confirm the accurate cutoff value to diagnose Helicobacter pylori (Hp) infection using commercial serology kits. It is reported that there were many cases with present/past infection that even the serum Hp-IgG antibody (HpAb) titers were below the cutoff value (e.g., 10 U/mL for E-Plate®), suggesting that we might overlook many gastric cancer (GC). We investigated an association between gastric cancer risk and serum Helicobacter pylori antibody titers. Methods. We conducted a primary screening between 2014 and 2015. We performed gastroendoscopy if HpAb titers were ≥3.0 U/mL (i.e., more than measurable limit, E-Plate). These patients were divided into two groups: HpAb = 3.0–9.9 U/mL (“negative-high” group) and HpAb ≥ 10 U/mL; cutoff value (“over-10 U/mL” group). Hp infection status was investigated, and the number of GC patients was counted. Results. Among the 3321 subjects in the primary screening, 56.9% (1891/3321) showed HpAb titers ≥3.0 U/mL; 1314 patients underwent gastroendoscopy. Ten were GC. 421 patients were “negative-high” group; two were GC. After evaluating 381 patients for Hp infection, 22.6%/60.6% was with present/past infection among the “negative-high” group. Conclusion. We also found a correlation between HpAb titers and Hp infection status. “Negative-high” group has a risk of GC. [ABSTRACT FROM AUTHOR]

Electrochemical telomerase assay (ECTA) developed by our group was evaluated in an oral cancer screening using exfoliated oral cells and tissues obtained from patients of oral cancer, mucosa associated disease, or healthy volunteers. Telomerase activity from ECTA is correlated with hTERT mRNA expression level using a real-time PCR and was increasing in the following order: healthy volunteer group

Pufferfish accumulate tetrodotoxin (TTX) mainly in the liver and ovary. This study aims at investigating the effect of TTX accumulation in the liver of cultured specimens of torafugu Takifugu rubripes on the hepatic gene expression by microarray analysis on Day 5 after the intramuscular administration of 0.25 mg TTX/kg body weight into the caudal muscle. TTX was detected in the liver, skin and ovary in the TTX-administered individuals. The total amount of TTX accumulated in the body was 67 ± 8% of the administered dose on Day 5. Compared with the buffer-administered control group, a total of 59 genes were significantly upregulated more than two-fold in the TTX-administered group, including those encoding chymotrypsin-like elastase family member 2A, transmembrane protein 168 and Rho GTP-activating protein 29. In contrast, a total of 427 genes were downregulated by TTX administration, including those encoding elongation factor G2, R-spondin-3, nuclear receptor activator 2 and fatty acyl-CoA hydrolase precursor. In conclusion, our results demonstrate that the intramuscular administration of TTX changes the expression of hepatic genes involved in various signaling pathways. [ABSTRACT FROM AUTHOR]

Background and Aim Subjects infected with Helicobacter pylori containing cagA do not always induce serum Cag A antibody. Our previous meta-analysis showed that serum Cag A seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum Cag A-positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti- Cag A antibody titer and the levels of pepsinogen ( PG), and histological score. Methods Eighty-eight H. pylori-positive Japanese patients with gastritis were included. Serum Cag A antibody titer, PG I, and PG II were evaluated by ELISA. Histological scores were evaluated according to Update Sydney System. Cag A expression was examined by immunoblot. Results Seroprevalence of Cag A antibody was found in 75.0%. Interestingly, serum Cag A antibody titer was significantly correlated with PG I and PG II levels ( P = 0.003 and 0.004, respectively). Serum Cag A 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 Cag A antibody titer. Cag A expression level of the strains was irrespective of the status of PG and serum Cag A antibody. Conclusions Subjects with higher serum Cag A 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 Cag A antibody titer. [ABSTRACT FROM AUTHOR]

Abstract: Pufferfish accumulate tetrodotoxin (TTX) at high levels in liver and ovary through the food chain. However, the mechanisms underlying TTX toxification in pufferfish have been poorly understood. In order to search gene candidates involved in TTX accumulation in the torafugu pufferfish Takifugu rubripes, a custom 4x44k oligonucleotide microarray slide was designed by the Agilent eArray program using oligonucleotide probes of 60 bp in length referring to 42,724 predicted transcripts in the publicly available Fugu genome database. DNA microarray analysis was performed with total RNA samples from the livers of two toxic wild specimens in comparison with those from a nontoxic wild specimen and two nontoxic cultured specimens. The mRNA levels of 1108 transcripts were more than 2-fold higher in the toxic specimens than in the nontoxic specimens. The levels of 613 transcripts were remarkably high, and 16 transcripts encoded by 9 genes were up-regulated more than 10-fold. These genes included those encoding forming structural filaments (keratins) and those related to vitamin D metabolism and immunity. It was also noted that the levels of the transcripts encoding serpin peptidase inhibitor clade C member 1, coagulation factor X precursor, complement C2, C3, C5, C8 precursors, and interleukin-6 receptor were high in the toxic liver samples. [Copyright &y& Elsevier]

Aim Non-steroidal anti-inflammatory drugs have the potential to injure the mucosa of the upper digestive tract and small bowel, whereas celecoxib (a selective cyclooxygenase-2 inhibitor) has less influence on the entire digestive tract mucosa. The present study was conducted to compare the extents of small bowel mucosal injury induced by celecoxib and loxoprofen (the most frequently used non-steroidal anti-inflammatory drugs in Japan). Methods Ten healthy adult males were given celecoxib (200 mg/day, Group C) and loxoprofen (180 mg/day, Group L) in a cross-over design for 14 days, and the influence of each drug on small bowel mucosa was evaluated by comparing pre- and post-treatment capsule endoscopy findings. We measured the percentage of patients with small bowel mucosal injury following administration of these drugs as primary endpoint. Additionally, mean number of small bowel mucosal injuries per subject was analyzed as secondary endpoint. Results The percentage of subjects experiencing small bowel mucosal injury as primary endpoint was 10% in Group C and 70% in Group L after treatment. This magnitude of the difference of between Group C and Group L was statistically significant ( P = 0.031). The number of small bowel mucosal injuries as secondary endpoint differed significantly between the two groups, and the influence of celecoxib on small bowel injury was less than that of loxoprofen. Conclusion These results indicate that celecoxib has less influence on small bowel mucosa than loxoprofen and can be used safely. [ABSTRACT FROM AUTHOR]

Aims. FSSG {frequency scale for the symptoms of gastroesophageal reflux disease (GERD)} was developed as a diagnostic tool for dysmotility and acid reflux symptoms. We first used FSSG to investigate the prevalence and risk factors for dysmotility and acid reflux symptoms and overlap of the two symptoms in a Japanese population. Methods. A cross-sectional survey was performed in Japanese underwent the routine medical examination. Dysmotility and acid reflux symptom were diagnosed by using FSSG. Subjects met both criteria were considered as overlap group. Results. Among 778 subjects, 395 persons were included in the final analyses. Dysmotility symptoms were found in 32.6% and acid reflux symptoms in 20.5%. Their overlap was found in 13.9% of all 395 subjects, which in 42.6% of dysmotility symptoms and 67.9% of acid reflux symptoms. Multiple logistic analysis showed that female gender was significantly associated with dysmotility symptoms compared with controls. Female gender, smoking, and hiatus hernia were significantly associated with overlap. Smoking was significantly associated with overlap compared with dysmotility symptoms alone and acid reflux symptoms alone. Conclusions. Overlap between dysmotility and acid reflux symptoms was common in Japan. Smoking was an independent risk factor for overlap among two symptoms. [ABSTRACT FROM AUTHOR]

Background: Helicobacter hepaticus infection might be associated with liver and biliary tract diseases. To investigate its pathogenic role, the properties of anti- H. hepaticus serum antibody in patients with liver and diseases were elucidated. Methods: Serum samples were collected from 166 patients-69 with liver diseases, 38 with upper gastrointestinal diseases, 17 with lower gastrointestinal diseases, 26 with biliary tract diseases, and 16 with pancreas diseases; 30 control sera were obtained from 30 healthy blood donors. Serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) and western blot using the new monoclonal antibody HR II-51. Results: Anti- H. hepaticus serum antibody concentrations in patients with liver disease ( n = 69) were significantly increased compared with those in other disease groups ( p = 0.014 to <0.001). Particularly, liver cirrhosis ( n = 19) showed a significantly higher antibody level compared with other liver diseases ( n = 50, p = 0.005) and healthy donors ( n = 30, p = 0.0005), as well as a higher seroprevalence (68.4%) compared with other liver diseases ( p = 0.05) and healthy donors ( p = 0.004). Furthermore, the ELISA value in liver cirrhosis ( n = 19) was significantly higher than that in patients with hepatitis B virus (HBV)-and/or hepatitis C virus (HCV)-infected chronic hepatitis ( n = 15) (0.389 ± 0.084 vs. 0.350 ± 0.084, p = 0.029). However, there was no relationship between the total immunoglobulin concentration and the anti- H. hepaticus antibody level in each liver disease (Spearman's rank correlation coefficient [rs] < 0.225). Conclusions: H. hepaticus infection might play a role in the development of liver diseases; in particular, it might increase the risk of the development of HBV- and/or HCV-infected liver diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Nitzschia navis-varingica is a diatom that is known to produce significant levels of amnesic shellfish poisoning (ASP) toxins. A total of 33 N. navis-varingica strains were isolated from four brackish water localities in the Philippines and Indonesia, and cultured to characterize the toxins produced. The isolates were analyzed for domoic acid (DA) and isodomoic acids A (IA) and B (IB) by HPLC with fluorescence detection. Two toxin composition types were detected that have not been previously described: strains producing only IB and strains producing DA–IA–IB. These two types were isolated from two different localities. Eighteen strains were isolated from the Philippines (northern Luzon Island). Among them, 10 isolates from Alaminos produced only IB with an average toxin content of 3.05pgcell−1, seven isolates from Bulacan produced DA and IB with average toxin contents of 0.68pgcell−1 and 1.18pgcell−1, respectively. One isolate from Cavite produced DA, IA, and IB with a toxin content of 0.58, 0.20, and 0.92pgcell−1, respectively. Fifteen isolates from Indonesia (Bone, South Sulawesi) produced only DA (four isolates) or DA with trace amounts of IB (eleven isolates), with an average toxin content of 2.38pgcell−1 and 0.06pgcell−1, respectively. Sub-strains were established from strains producing either of the three toxin types: IB, DA–IA–IB, and DA-trace IB. Results showed that the toxin composition type was the same for parent and sub-strains, indicating that the toxin composition is a stable character for a strain. [Copyright &y& Elsevier]

Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic. [ABSTRACT FROM AUTHOR]

Objective. Stool antigen tests using monoclonal antibody are used to test the results of eradication therapy of Helicobacter pylori. A newly developed test using multiple monoclonal antibodies is considered to have higher sensitivity. The aim of this study was to examine whether monoclonal antibody-based stool antigen tests are equally applicable to determine the results of eradication therapy. Materials and methods. Stool specimens obtained from patients infected with H. pylori were diluted by human stool and tested by both Testmate pylori antigen enzyme immunoassay (TPAg EIA) and Premier Platinum HpSA PLUS (HpSA ELISA II). A total of 239 patients infected with H. pylori received eradication therapy and 5-8 weeks after finishing the treatment, stool samples were tested by TPAg EIA and HpSA ELISA II. On the same day of stool collection, all the patients received 13C-urea breath test (UBT). Results. After 5× dilution, optical density (OD) values of TPAg EIA were significantly reduced and three out of four stool specimens were tested negative after 10× dilution. By contrast, three specimens were tested positive even after 100× dilution by HpSA ELISA II. In the determination of eradication therapy, accordance between the two tests was 95.8%. Among 199 patients who tested negative by both stool antigen tests, 10 patients were positive by UBT. Overall accordance of TPAg EIA and HPSA ELISA II to UBT was 91.2% and 95.4%, respectively (NS). Conclusions. Although reduction of OD values was seen in TPAg EIA, it did not seem to cause false negative results in stool samples after eradication therapy. Both TPAg EIA and HpSA ELISA II were equally useful to determine the results of eradication therapy comparing with UBT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 noninfected 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. [ABSTRACT FROM AUTHOR]

Background and Aims: To investigate the utility of a new method of carrying out esophageal manometry using a narrow gauge manometry catheter via a transnasal endoscope. Methods: The Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a GERD-specific questionnaire, was given to 45 subjects. Subjects underwent transnasal endoscopy with three dry and three wet (3 mL water) swallows. Direct observations of the primary peristaltic wave and peristaltic pressure measurement were conducted simultaneously. Results: Endoscopic observation of lower esophageal motility associated with swallowing revealed dilatation of the esophageal lumen after swallowing, followed by contraction in association with the primary peristaltic wave. The peristaltic pressure was significantly lower with increased FSSG scores for dry swallows ( r = −0.347, P = 0.0212), but no significant correlation was seen for wet swallows. Conclusions: The significant negative correlation between reflux symptoms and peristaltic pressure in dry swallows was thought to be that reduced pressure immediately rostral to the lower esophageal sphincter leads to decreased clearance following gastric acid reflux, playing a large part in the onset of symptoms. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Previously we reported that a significant level of domoic acid, a causative toxin for amnesic shellfish poisoning, was detected in bivalves belonging to a genus Spondylus from various tropical Asian countries. These findings indicate that causative plankton species for domoic acid widely distribute in these areas. In the present study, we monitored seasonal change of domoic acid level of Spondylus versicolor in association with that of plankton samples in Nha Phu Bay, Khanh Hoa, Vietnam from December 2004 to October 2005. The toxicity of S. versicolor showed distinct seasonal variation. During the period when domoic acid level of S. versicolor was increasing, a significant level of domoic acid was detected in the plankton samples, showing the correlation between these two parameters. These findings show that plankton causative for domoic acid occurred in the bay, and S. versicolor accumulate domoic acid during a bloom of the toxic plankton by food web transfer. [ABSTRACT FROM AUTHOR]

Domoic acid was found in bivalves belonging to the genus Spondylus collected randomly from the Philippines, Vietnam, Thailand and Ishigaki Island, Japan. This is the first report of domoic acid accumulating in bivalves from tropical waters. Large differences in domoic acid levels were observed among the Spondylus specimens collected from different areas. The Spondylus specimens from the Philippines and Vietnam showed higher levels of domoic acid whereas the level in Spondylus spp. from Thailand and Japan was low. The highest level of domoic acid—more than four times the safe consumption level of 20 μg/g whole tissue—was found in a specimen from the Philippines. On the other hand, bivalves other than Spondylus collected from the same area at the same time in the Philippines showed very low levels of domoic acid, showing that bivalves belonging to the genus Spondylus accumulate specifically high levels of domoic acid. These results suggest the wide distribution of causative phytoplankton in tropical waters. [ABSTRACT FROM AUTHOR]

Tetrodotoxin (TTX) was detected by HPLC and LC-MS/MS in specimens of the horseshoe crab Carcinoscorpius rotundicauda collected from Tan Hai village, Vung Tau province, Vietnam, where cases of poisoning due to the consumption of horseshoe crab have frequently been reported. The soft tissue from 10 out of the 12 specimens analyzed showed considerable levels of TTX, making them unsafe for human consumption (81.2 ± 50.3 MU/g). Paralytic shellfish poisoning (PSP) toxins were also detected in all of the specimens, but the levels were low. These findings show that the frequency of occurrence of C. rotundicauda specimens with a high level of TTX is significantly high, and that the TTX is responsible for the food poisonings caused by the consumption of C. rotundicauda in this area. [ABSTRACT FROM AUTHOR]

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 (α-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 α-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 α-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. [ABSTRACT FROM AUTHOR]