Takeshi Matsuhisa

Nippon Medical School, Edo, Tōkyō, Japan

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Publications (69)209.41 Total impact

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    ABSTRACT: Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg) + amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n = 242), 71.2%/72.9% (2002, n = 208), 67.8%/70.5% (2003, n = 183), 75.6%/84.6% (2004, n = 131), 56.4%/70.5% (2005, n = 114), 70.5%/75.8% (2006, n = 271), 67.4%/82.0% (2007,n = 135), 64.0%/76.3% (2008, n = 261), 60.5%/74.3% (2009, n = 329), and 66.5%/78.8% (2010, n = 370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
    Journal of Gastroenterology and Hepatology 12/2014; 29 Suppl 4:29-32. DOI:10.1111/jgh.12796 · 3.63 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):1148-1148. DOI:10.1158/1538-7445.AM2013-1148 · 9.28 Impact Factor
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    ABSTRACT: BACKGROUND: In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. MATERIALS AND METHODS: We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. RESULTS: We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. CONCLUSIONS: From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.
    Helicobacter 06/2013; DOI:10.1111/hel.12063 · 2.99 Impact Factor
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    ABSTRACT: AIM: To study gastric mucosal interleukine-8 (IL-8) mRNA expression, the cytotoxin-associated gene A (cagA) mutation, and serum pepsinogen (PG) I/II ratio related risk in Thai gastric cancer. METHODS: There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination, and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery. Tissue samples were taken by endoscopy with 3 points biopsies. The serum PG I, II, and Helicobacter pylori (H. pylori) immunoglobulin G (IgG) antibody for H. pylori were tested by enzyme-linked immunosorbent assay technique. The histopathology description of gastric cancer and non-cancer with H. pylori detection was defined with modified Sydney Score System. Gastric mucosal tissue H. pylori DNA was extracted and genotyped for cagA mutation. Tissue IL-8 and cyclooxygenase-2 (COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction. From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples, all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples. The multivariate analysis was used for the risk study. Correlation and standardized t-test were done for quantitative data, P value < 0.05 was considered as a statistically significant. RESULTS: There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA. The H. pylori infection prevalence in this study is reported by combined histopathology and H. pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity, respectively. The serum PG I/II ratio in gastric cancer is significantly lower than in the non-cancer group, P = 0.045. The serum PG I/II ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log10 ≥ 2 are significant cut off risk differences between Thai cancer and non-cancer, P = 0.03 and P < 0.001, respectively. There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer, P = 0.026. Serum PG I/II ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ > 100 or log10 > 2 are significantly difference between Thai cancer group when compared to non-cancer group, P = 0.013 and P < 0.001, respectively. In the correlation study, low PG I/II ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases. However, there is a trend, but not significant convert correlation between IL-8 mRNA expression level and low PG I/II ratio in Thai positive H. pylori infection. The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology. CONCLUSION:Predominant gastric mucosal IL-8 mRNA expression level, H. pylori infection, and low PG I/II ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.
    World Journal of Gastroenterology 05/2013; 19(19):2941-2949. DOI:10.3748/wjg.v19.i19.2941 · 2.43 Impact Factor
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    ABSTRACT: Background The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. Patients and Methods This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0-25%, group B: 26-50%, group C: 51-75%, and group D: 76-100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group. ResultsRegarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H.pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H.pylori infection, in group D. Conclusion High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia.
    Digestive Endoscopy 01/2013; 25(5). DOI:10.1111/den.12030 · 1.99 Impact Factor
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    Takeshi Matsuhisa, Hafeza Aftab
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    ABSTRACT: The prevalence of Helicobacter pylori (H. pylori) infection is high, but the incidence of gastric cancer is low in natives of Bangladesh. The gastric mucosa was observed in Bangladeshi patients to investigate the differences between Bangladeshis and Japanese. The study involved 418 Bangladeshi and 2356 Japanese patients with abdominal complaints who underwent endoscopy examinations and had no history of H. pylori eradication. The prevalence of H. pylori infection and the gastric mucosa in H. pylori-positive patients were compared between age-, gender-, and endoscopic diagnosis-matched Bangladeshi and Japanese subjects. The prevalence of H. pylori infection was higher in Bangladeshi than in Japanese subjects (60.2 and 45.1%, respectively). All the scores for chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia were significantly lower in H. pylori-positive Bangladeshis than in H. pylori-positive Japanese. The ratio of the corpus gastritis score (C) to the antrum gastritis score (A) (C/A ratio) was <1 (antrum-predominant gastritis) in all age groups of Bangladeshi subjects, whereas the C/A ratio changed from <1 to more than 1 (corpus-predominant gastritis) with aging in Japanese subjects. The scores for glandular atrophy and intestinal metaplasia in H. pylori-positive Bangladeshis were significantly lower than those in Japanese. All age groups of Bangladeshis had antrum-predominant gastritis, whereas corpus-predominant gastritis was more common than antrum-predominant gastritis in older Japanese age groups. These results may explain the low incidence of gastric cancer in Bangladeshis and the high incidence in Japanese.
    Helicobacter 10/2012; 17(5):398-403. DOI:10.1111/j.1523-5378.2012.00967.x · 2.99 Impact Factor
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    Takeshi Matsuhisa, Taku Tsukui
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    ABSTRACT: During endoscopic examinations we collected fluid in the stomach that included reflux fluid from the duodenum, and assessed the effect of quantitatively determined bile acids on glandular atrophy and intestinal metaplasia using biopsy specimens. A total of 294 outpatients were enrolled in this study. Total bile acid concentration was measured by an enzyme immunoassay. Glandular atrophy and intestinal metaplasia scores were graded according to the Updated Sydney System. An effect of refluxed bile acids on atrophy and intestinal metaplasia was shown in the high-concentration reflux group in comparison with the control group. However, when the odds ratios (ORs) were calculated according to whether Helicobacter pylori (H. pylori) infection was present, no significant associations were shown between reflux bile acids and atrophy in either the H. pylori-positive cases or -negative cases. The same was true for intestinal metaplasia in the H. pylori-positive cases, whereas intestinal metaplasia was more pronounced in the high-concentration reflux group in the H. pylori-negative cases (OR 2.4, 95%CI 1.1-5.6). We could not clarify the effect of the reflux of bile acids into the stomach in the progression of atrophy. High-concentration bile acids had an effect on the progression of intestinal metaplasia in the H. pylori-negative cases.
    Journal of Clinical Biochemistry and Nutrition 05/2012; 50(3):217-21. DOI:10.3164/jcbn.11-90 · 2.29 Impact Factor
  • Cancer Research 01/2011; 70(8 Supplement):3834-3834. DOI:10.1158/1538-7445.AM10-3834 · 9.28 Impact Factor
  • Takeshi Matsuhisa, Taku Tsukui
    Gastroenterology 01/2011; 140(5). DOI:10.1016/S0016-5085(11)63672-X · 13.93 Impact Factor
  • Takeshi Matsuhisa, Nobutaka Yamada, Hafeza Aftab
    Gastroenterology 01/2011; 140(5). DOI:10.1016/S0016-5085(11)63052-7 · 13.93 Impact Factor
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    ABSTRACT: 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. 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. Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh. 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.
    BMC Gastroenterology 09/2010; 10:114. DOI:10.1186/1471-230X-10-114 · 2.11 Impact Factor
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    ABSTRACT: The purpose of this paper is to investigate the relationship between clinical outcome and the intactness of cagPAI in Helicobacter pylori strains from Vietnam. The presence or absence of 30 cagPAI genes was investigated by polymerase chain reaction (PCR) and dot-blotting. H. pylori-induced interleukin-8 secretion and hummingbird phenotype, and H. pylori adhesion to gastric epithelial cells were examined. The serum concentration of pepsinogen 1, pepsinogen 2, and gastrin was also measured in all patients. cagPAI was present in all 103 Vietnamese H. pylori isolates, of which 91 had intact cagPAI and 12 contained only a part of cagPAI. Infection with the partial cagPAI strains was less likely to be associated with peptic ulcer and chronic gastric mucosal inflammation than infection with strains possessing intact cagPAI. The partial cagPAI strains lacked almost all ability to induce interleukin-8 secretion and the hummingbird phenotype in gastric cells. Their adhesion to epithelial cells was significantly decreased in comparison with intact cagPAI strains. Moreover, for the first time, we found an association between cagPAI status and the serum concentration of pepsinogens 1 and 2 in infected patients. H. pylori strains with internal deletion within cagPAI are less virulent and, thus, less likely to be associated with severe clinical outcomes.
    European Journal of Clinical Microbiology 04/2010; 29(6):651-60. DOI:10.1007/s10096-010-0909-z · 2.54 Impact Factor
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    ABSTRACT: The determination of the cagA genotype is generally based on sequencing the variable 3' region of the cagA gene. In a previous study, we successfully generated an anti-East Asian CagA-specific antibody (anti-EAS Ab) immunoreactive only with the East Asian CagA and not with the Western CagA. In a small number of Japanese patients, anti-EAS Ab appeared to be a useful tool for phenotyping CagA immunohistochemically. The present study was conducted to validate the anti-EAS Ab immunohistochemistry method in a larger number of patients from Vietnam and Thailand. A total of 385 Vietnamese and Thais were recruited. Helicobacter pylori status was determined by a combination of three methods, including culture, histology, and immunohistochemistry with anti-H. pylori antibody. The sensitivity, specificity, and accuracy of the anti-EAS Ab immunohistochemistry method for the diagnosis of CagA phenotype were calculated based on the results of the cagA sequencing as the gold standard. The sensitivity, specificity, and accuracy of our immunohistochemistry method were 96.7%, 97.9%, and 97.1%, respectively. Moreover, anti-EAS Ab was not cross-reactive with noninfected gastric mucosa. In conclusion, immunohistochemistry with anti-EAS Ab appears to be a good method for determination of CagA phenotype.
    Clinical and vaccine Immunology: CVI 09/2009; 16(11):1687-92. DOI:10.1128/CVI.00200-09 · 2.37 Impact Factor
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    ABSTRACT: The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects. The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh. Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.
    BMC Microbiology 09/2009; 9(1):175. DOI:10.1186/1471-2180-9-175 · 2.98 Impact Factor
  • Gastroenterology 05/2009; 136(5). DOI:10.1016/S0016-5085(09)62265-4 · 13.93 Impact Factor
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    ABSTRACT: This study attempted to assess the value of the RAPIRUN test for the diagnosis of Helicobacter pylori infection in the Vietnamese population. 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. The sensitivity, specificity, and accuracy of the RAPIRUN test in these Vietnamese patients were 79.5, 90.7, and 84.5%, respectively. 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.
    Digestive Diseases and Sciences 03/2009; 55(1):89-93. DOI:10.1007/s10620-009-0720-9 · 2.55 Impact Factor
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    ABSTRACT: Gallbladder stones are still a common pathology worldwide, and the number of patients diagnosed without any symptoms is increasing due to the use of ultrasound and imaging tools such as CT and MRI. The aim of this study was to identify gastroduodenal pathologies in patients with diagnosed asymptomatic gallbladder stones, since some cases of epigastric pain may have led to unnecessary cholecystectomies.
    2nd congress of APHPBA, Bangkok, Thailand; 01/2009
  • 01/2008; 73(2):66-70. DOI:10.11641/pde.73.2_66
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    ABSTRACT: The incidence and mortality from gastric cancer is high in Japanese but extremely low in Thailand. It is different among Asian countries. The aim of this study is to investigate the difference of peptic ulcer disease, glandular atrophy, intestinal metaplasia and topography of chronic active gastritis between the Nepalese and Japanese population. Nepalese patients were paired with Japanese patients by age, gender and endoscopic diagnosis in order to compare the prevalence of H. pylori infection (N=309) and the difference of H. pylori related peptic ulcer disease (N=48). Glandular atrophy and intestinal metaplasia scores were also compared between the Nepalese and Japanese population in H. pylori positive cases (N=152) and negative cases (N=145) using paired cases by age, gender and endoscopic diagnosis. Paired H. pylori-positive Nepalese and Japanese population were also used to compare the ratio of corpus gastritis to antrum gastritis (C/A ratio) (N=152). Among peptic ulcer diseases, gastric ulcer was frequent in Japanese and duodenal ulcer was frequent in Nepalese. The prevalence of H. pylori infection in the Nepalese and Japanese population were similar. Glandular atrophy and intestinal metaplasia scores in the H. pylori positive Japanese were significantly higher than those of Nepalese in all positions according to triple site biopsy. Furthermore, there were significant differences in glandular atrophy and intestinal metaplasia scores between in the H. pylori-negative Nepalese and Japanese population except intestinal metaplasia score in the greater curvature of the upper corpus. Japanese C/A ratio was significantly higher than that of Nepalese. Corpus predominant gastritis (C/A ratio>1.00) was characteristic in the elderly Japanese. Nepalese was antrum predominant (C/A ratio<1.00) in every age group. Gastric ulcer was a common disease in Japanese, in contrast duodenal ulcer was common in Nepalese. H. pylori infected Japanese patients showed severe atrophic and metaplastic gastritis in comparison with Nepalese. These results may be associated with the high incidence of gastric cancer in Japanese. Corpus predominant gastritis was found in the elderly Japanese and antrum predominant gastritis was found in every age Nepalese.
    Kathmandu University Medical Journal 07/2007; 5(3):295-301.
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    ABSTRACT: Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1beta-511 polymorphisms are suspected to be risk factors for gastric cancer. A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1beta-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups. The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10-4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4-6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50-0.81; P = 0.014). A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1beta-511 C/C genotype may be independent risk factors for gastric cancer in Thais.
    Journal of Gastroenterology 02/2007; 41(12):1169-77. DOI:10.1007/s00535-006-1951-6 · 4.02 Impact Factor

Publication Stats

439 Citations
209.41 Total Impact Points


  • 1997–2014
    • Nippon Medical School
      • • Nippon Medical School Hospital
      • • Department of Pathology
      Edo, Tōkyō, Japan
  • 2013
    • Chiang Mai University
      Amphoe Muang Chiang Mai, Chiang Mai, Thailand
  • 2004–2010
    • Tokyo Metropolitan Tama Medical Center
      Edo, Tōkyō, Japan
  • 2005
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China