Kazunari Murakami

Oita University, Ōita, Oita, Japan

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Publications (143)527.92 Total impact

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    ABSTRACT: Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.
    No preview · Article · Dec 2015 · American Journal of Cancer Research
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    ABSTRACT: A 46-year-old woman was diagnosed with congenital hepatic fibrosis by histological examination of a liver biopsy specimen in 2001. She was routinely followed up with computed tomography (CT) examinations. She had some liver nodules,but these nodules did not enlarge. In August 2013, dynamic CT revealed a lesion with early arterial uptake in the right hepatic lobe. The nodule enlarged progressively. Histopathological examination of a tumor biopsy specimen revealed a well-differentiated hepatocellular carcinoma. The tumor was treated by chemolipoidolization and radiofrequency ablation therapy. The patient developed acute cholangitis 1 year later, and her liver function deteriorated rapidly. She died of hepatic failure at 47 years of age. After careful re-evaluation of histological findings and additional immunohistochemical study, the diagnosis was revised to be a FNH-like lesion of the progressive type.
    Preview · Article · Oct 2015 · Kanzo
  • Tadayoshi Okimoto · Masaaki Kodama · Kazunari Murakami
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    ABSTRACT: H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. In Japan, 12 months after treatment, gastric ulcers had recurred in 11.4% of those with successful H. pylori eradication and 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. About long-term study, 4 years after treatment, gastric ulcers had recurred in 9.3% of those with successful H. pylori eradication and duodenal ulcers recurrence was occurred in 6.2% of those. The annual recurrence rates of gastric, duodenal ulcer were 2.3% and 1.6%, respectively. However, in current Japan, the decrease of the primary eradication rate is reported by the increase of clarithromycin-resistant strains. The increase of metronidazole-resistant strains used for the second eradication is not recognized so far, but in future, increase is concerned about. Therefore, the making of the regimen of the third-line eradication therapy is needed now.
    No preview · Article · Jul 2015 · Nippon rinsho. Japanese journal of clinical medicine
  • Masaaki Kodama · Tadayoshi Okimoto · Kazunari Murakami

    No preview · Article · Jun 2015 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
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    ABSTRACT: Background and study aims: The relationship between endoscopic atrophy classification (EAC) and histological gastric atrophy and intestinal metaplasia (IM) was examined before and after Helicobacter pylori (H. pylori) eradication in order to evaluate the usefulness of EAC for detecting the risk of gastric cancer following eradication. Patients and methods: A total of 230 patients (137 males, 93 females; mean age: 58.0 ± 11.8 y) with successful eradication were enrolled. EAC score was defined as follows: C0(none): 0, C1: 1, C2: 2, C3: 3, O1: 4, O2: 5, and O3(severe): 6. Histological atrophy and IM score (0 to 3) from the antrum and the corpus were evaluated with updated Sydney system for histological atrophy and IM. Results: The mean EAC scores were 3.46 before eradication and 3.20 after eradication (P = 0.026). The mean atrophy scores before and after eradication were 1.45 and 0.92 at the antrum (P < 0.001) and 0.50 and 0.07 at the corpus (P < 0.001), respectively. The mean IM scores before and after eradication were 0.55 and 0.47 at the antrum (P = 0.154), and 0.09 and 0.05 at the corpus (P = 0.096), respectively. The histological atrophy scores showed significant improvement after eradication, while IM showed no significant change. The Mantel-Haenszel test for trend indicated there was a significant correlation between EAC and histological atrophy and IM, except antral atrophy after eradication. Conclusions: EAC exhibited a significant correlation between histological atrophy and IM, and represents a noninvasive classification method. EAC may be beneficial in evaluating the risk of gastric cancer after H. pylori eradication.
    Preview · Article · May 2015
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    ABSTRACT: Proton pump inhibitor (PPI) therapy, the first-line treatment for gastroesophageal reflux disease (GERD), is not always effective. This study aimed to examine the effect of pretreatment patient characteristics on response to PPI therapy. Japanese outpatients with symptomatic GERD scheduled to receive endoscopy and PPI therapy were enrolled in this multicenter prospective observational study. The patients' characteristics, including GERD and dyspeptic symptoms, anxiety, depression, and quality of life, were assessed using questionnaires before and 2 and 4 weeks after the start of PPI therapy. Factors affecting therapeutic response were examined by simple and multiple regression analyses using three patient-reported outcome measures as objective variables. Data from 182 patients were analyzed. In multiple regression analysis using the residual symptom rate as an objective variable, lower GERD symptom score (p < 0.05), absence of erosive esophagitis (p < 0.05), higher epigastric pain/burning symptom score (p < 0.05), and higher depression subscale score (p < 0.05) accompanied poorer therapeutic response. In analyses using the patient's impression of therapy, lower GERD symptom score (p < 0.05) and absence of erosive esophagitis (p < 0.05) accompanied poorer therapeutic response. In analyses using the relative GERD symptom intensity evaluated using a numeric rating scale, lower GERD symptom score (p < 0.05), higher epigastric pain/burning symptom score (p < 0.1), and lower body mass index (p < 0.05) accompanied poorer therapeutic response. Patients who complained of milder GERD symptoms before treatment were likely to have poorer response to PPI therapy. Association of absence of erosive esophagitis, severer epigastric pain/burning symptoms, lower body mass index, and severer depression with poorer therapeutic response was also suggested.
    No preview · Article · Apr 2015 · Journal of Gastroenterology
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    ABSTRACT: A 42-year-old woman underwent renal transplantation in 200X. After the transplant, she received tacrolimus as immunosuppressant therapy. Eleven years after the transplant, diffuse large B-cell lymphomas were detected in the duodenum and terminal ileum. Wireless capsule endoscopy (WCE) revealed multiple lymphoma lesions in the entire small intestine. The patient achieved complete response through the administration of R-CHOP therapy and discontinuation of immunosuppressant therapy. Post-transplant lymphoproliferative disorder (PTLD) is a rare complication and WCE may be useful for diagnosing PTLD of the small intestine.
    No preview · Article · Apr 2015 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology

  • No preview · Article · Apr 2015 · Gastroenterology
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    ABSTRACT: The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. Two hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals). Trial registration
    Full-text · Article · Jul 2014 · BMC Gastroenterology

  • No preview · Article · May 2014 · Gastroenterology

  • No preview · Article · May 2014 · Gastroenterology
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    ABSTRACT: The aim of this study was to investigate the efficacy of rikkunshito (RKT), a traditional Japanese medicine, combined with proton pump inhibitor (PPI) in patients with PPI-refractory non-erosive reflux disease (NERD). Patients with PPI-refractory NERD (n = 242) were randomly assigned to the RKT group [rabeprazole (10 mg/day) + RKT (7.5 g/t.i.d.) for 8 weeks] or the placebo group (rabeprazole + placebo). After the 4- and 8-week treatments, we assessed symptoms and quality of life (QOL) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG), Gastrointestinal Symptom Rating Scale (GSRS), and Short-Form Health Survey-8 (SF-8). There were no significant differences in FSSG and GSRS score improvement between these groups after the 4- and 8-week treatments. The mental component summary (MCS) scores of the SF-8 improved more in the RKT group (from 45.8 ± 8.1 to 48.5 ± 7.4) than in the placebo group (from 47.7 ± 7.1 to 48.4 ± 7.5) after the 4-week treatment (P < 0.05). The 8-week treatment with RKT was more effective for improvement of the degree of MCS score in patients with a low body mass index (<22) (P < 0.05) and significantly improved the acid-related dysmotility symptoms of FSSG in female and elderly patients (≥65 years). There were no significant differences in improvement of GERD symptoms in patients with PPI-refractory NERD between these groups. However, RKT may be useful for improving mental QOL in non-obese patients and acid-related dyspeptic symptoms, especially in women and the elderly.
    No preview · Article · Feb 2014 · Journal of Gastroenterology
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    ABSTRACT: Helicobacter pylori (H. pylori)-related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults. This cross-sectional study included 14,716 subjects aged 20 years or more who underwent a health checkup between May 1997 and March 2013 in seven geographic areas throughout Japan. Relevant information on the demographics and status of H. pylori infection was retrieved from the electronic database. The univariate log-binominal regression model was used to estimate the prevalence of H. pylori infection, taking birth year into consideration. The multivariate log-binominal regression model was used to compare the prevalence of H. pylori infection between seven geographic areas. The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Among seven geographic areas, Hokkaido showed the lowest prevalence (29.4%), while Yamagata Prefecture represented the highest (54.5%). The prevalence of H. pylori infection was highest in the 1940-1949 birth cohort and then decreased in the ensuing birth cohorts; the risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.84-0.87) for changes in the 10-year birth cohort. Individuals in Yamagata Prefecture had the highest RR of acquiring H. pylori infection in all three birth cohorts (RR = 1.53 for 1940, RR = 1.69 for 1950, and RR = 1.85 for 1960) when compared with those in Hokkaido. The prevalence of H. pylori infection increases with age and exhibits geographic variation in Japan. There has been a striking decrease in the prevalence of H. pylori infection, especially in younger Japanese populations.
    Full-text · Article · Feb 2014 · Helicobacter

  • No preview · Article · Jan 2014 · Endoscopy
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    ABSTRACT: Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment have been produced by the Japan Gastroenterological Endoscopy Society in collaboration with the Japan Circulation Society, the Japanese Society of Neurology, the Japan Stroke Society, the Japanese Society on Thrombosis and Hemostasis and the Japan Diabetes Society. Previous guidelines from the Japan Gastroenterological Endoscopy Society have focused primarily on prevention of hemorrhage after gastroenterological endoscopy as a result of continuation ofantithrombotic therapy, without considering the associated risk of thrombosis. The new edition of the guidelines includes discussions of gastroenterological hemorrhage associated with continuation of antithrombotic therapy, as well as thromboembolism associated with withdrawal of antithrombotic therapy.
    Full-text · Article · Nov 2013 · Digestive Endoscopy
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    ABSTRACT: 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.
    No preview · Article · Sep 2013 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Subjects infected with H. pylori containing cagA do not always induce serum CagA antibody. Our previous meta-analysis showed that serum CagA seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum CagA positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti CagA antibody titer and the levels of pepsinogen, and histological score. Eighty-eight H. pylori positive Japanese patients with gastritis were included. Serum CagA antibody titer, pepsinogen (PG) I and PG II were evaluated by enzyme-linked immunosorbent assay. Histological scores were evaluated according to Update Sydney System. CagA expression was examined by immunoblot. Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA antibody titer was significantly correlated with PG I and PG II levels (P = 0.003 and 0.004, respectively). Serum CagA antibody titer was also significantly correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand, bacterial density was not related with CagA antibody titer. CagA expression level of the strains was irrespective of the status of PG and serum CagA antibody. Subjects with higher serum CagA antibody titer can be considered as high risk population for the development of gastric cancer from the point of strong gastric inflammatory response even in Japan. Host recognition rather than bacterial colonization might be associated with the difference of serum CagA antibody titer.
    Preview · Article · Aug 2013 · Journal of Gastroenterology and Hepatology
  • Masaaki Kodama · Kazunari Murakami · Tadayoshi Okimoto · Toshio Fujioka
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    ABSTRACT: Helicobacter pylori (H. pylori) is a major pathogen of chronic atrophic gastritis, intestinal metaplasia, and gastric cancer. Atrophic gastritis and intestinal metaplasia are recognized as precancerous lesion of gastric cancer. Many studies reported that H. pylori eradication had the preventive effect of gastric cancer. Moreover many studies mentioned the improvement of gastric atrophy and/or intestinal metaplasia. Two meta-analysis indicated the improvement of atrophic gastritis but not of intestinal metaplasia. In our study, intestinal metaplasia improved at lesser curvature of the corpus six years after eradication. H. pylori eradication has benefit for gastric cancer prevention provably due to improvement of the precancerous lesion such as atrophic gastritis and intestinal metaplasia. Especially, H. pylori eradication before the appearance of atrophy and intestinal metaplasia has been considered to be effective in inhibiting the development of gastric cancer. Therefore, improvement or elimination of chronic gastritis with H. pylori eradication might have possibility of gastric cancer inhibition.
    No preview · Article · Aug 2013 · Nippon rinsho. Japanese journal of clinical medicine
  • Hideki Ono · Takako Tasaki · Jin Tanahashi · Kazunari Murakami

    No preview · Article · Jun 2013 · Internal Medicine
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    ABSTRACT: Although the vast majority of depressed patients visit primary health care clinics, they often remain undiagnosed and untreated. Therefore, early detection in primary care settings is important. There is a high correlation between number of physical symptoms and the presence of depression, yet little has been reported regarding this relationship in Japanese primary care clinics. We examined number of physical symptoms and depression in a department of general medicine of a Japanese hospital. We included patients with unexplained symptoms after multiple tests to rule out organic diseases. Twenty-one common symptoms were assessed using a symptom checklist. Depression was diagnosed using the Patient Health Questionnaire-9, a self-administered questionnaire designed to diagnose depression. Among 386 patients, 105 (27.2%) (average age: 49.7 ± 20.9 years, 28 men and 77 women) met the criteria for depression. Among the 21 symptoms, 14 were significantly more frequent in patients with depression than in those without depression. When patients had neither general fatigue, nor sleep disturbance nor appetite loss, none met the criteria for depression. Number of symptoms was significantly higher in patients with compared with those without depression. The prevalence of depression increased with number of symptoms: 2% (2/100) for 0 or 1 symptom, 42.4% (42/99) for four to five symptoms and 68.7% (22/32) for more than nine symptoms. Japanese primary care physicians can often rule out depression when patients have neither general fatigue, nor sleep disturbance nor appetite loss. A diagnosis of depression should be considered in patients who report multiple physical symptoms.
    No preview · Article · Apr 2013 · The Tohoku Journal of Experimental Medicine