Toshihide Okada

Publications (29)94.39 Total impact

• Article: Can magnifying endoscopy with narrow band imaging be useful for low grade adenomas in preoperative biopsy specimens?

  Kazuhiro Miwa, Hisashi Doyama, Renma Ito, Hiroyoshi Nakanishi, Katsura Hirano, Satoko Inagaki, Kei Tominaga, Naohiro Yoshida, Kenichi Takemura, Shinya Yamada, Yoshibumi Kaneko, Kazuyoshi Katayanagi, Hiroshi Kurumaya, Toshihide Okada, Masakazu Yamagishi
  [show abstract] [hide abstract]
  ABSTRACT: In biopsy specimens with low grade adenomas, it is often difficult to identify the presence of high grade adenomas or early carcinomas and low grade adenomas preoperatively, and clear guidelines have not yet been defined for the applicability of endoscopic treatment to low grade adenomas identified in biopsy specimens. We aimed to clarify the usefulness of magnifying endoscopy with narrow band imaging (NBI) compared to conventional white light endoscopy for diagnosing actual high grade adenomas or early carcinomas with low grade adenomas, using the VS (microvascular pattern [V] and microsurface pattern [S]) classification for low grade adenomas in biopsy specimens. The study cohort consisted of 135 patients who were diagnosed with low grade adenomas in preoperative biopsy specimens and received endoscopic submucosal dissection. In the elevated type of lesion, magnifying endoscopy with NBI diagnosed high grade adenomas or early carcinomas at a higher sensitivity and specificity than conventional white light endoscopy (82.4 vs. 70.6%, P = 0.391, 97.3 vs. 54.7%, P < 0.0001). In the depressed macroscopic type of lesion, magnifying endoscopy with NBI also diagnosed high grade adenomas or early carcinomas at a higher sensitivity (95.5 vs. 68.2%, P = 0.0459) than conventional white light endoscopy. Although the specificity was high, at 100%, the difference when compared to conventional white light endoscopy was not significant (100 vs. 100%, P > 0.99). For low grade adenomas in biopsy specimens, it is vital to take sufficient consideration of endoscopic findings and not take action based only on the biopsy results. If a decision is made using the VS classification with magnifying endoscopy with NBI, actual high grade adenomas or early carcinomas can be differentiated from low grade adenomas so that endoscopic treatment can be performed more strictly.
  Gastric Cancer 03/2012; 15(2):170-8. · 2.42 Impact Factor
• Article: Hypomagnesemia associated with a proton pump inhibitor.

  Jun Matsuyama, Kunihiro Tsuji, Hisashi Doyama, Fae Kim, Yasuhito Takeda, Yosuke Kito, Renma Ito, Hiroyoshi Nakanishi, Tomoyuki Hayashi, Yohei Waseda, Shigetsugu Tsuji, Kenichi Takemura, Shinya Yamada, Toshihide Okada, Honin Kanaya
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  ABSTRACT: Severe hypomagnesemia is a serious clinical condition. Proton pump inhibitor (PPI) induced hypomagnesemia has been recognized since 2006. In March 2011 the U.S. Food and Drug Administration advised that long-term use of PPI can induce hypomagnesemia. We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. Blood analysis showed severe hypomagnesemia. He had been taking rabeprazole (10 mg/day) for 5 years. After stopping rabeprazole and correcting the electrolytes imbalances, his symptoms improved without recurrence.
  Internal Medicine 01/2012; 51(16):2231-4. · 0.94 Impact Factor
• Article: Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: insights from in vitro and in vivo experimental studies.

  Yoshiaki Hayashi, Kenta Narumi, Shigetsugu Tsuji, Toshinari Tsubokawa, Masa-aki Nakaya, Tomohiko Wakayama, Masahiko Zuka, Tohru Ohshima, Masakazu Yamagishi, Toshihide Okada
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  ABSTRACT: Although adrenomedullin (AM) is known to ameliorate inflammatory processes, few data exist regarding the effect of AM on inflammatory colitis. Therefore, we examined the effect of AM on inflammatory response in vitro and in vivo colitis model. In mice experimental colitis induced by 3% dextran sulfate sodium (DSS) in drinking water for 7 days, AM with 225-900 μg/kg in 0.5 ml of saline or saline alone were given intraperitoneally once a day. In the in vitro experiment, we determined the cytokine response in THP-1 cell activated by lipopolysaccharide with or without AM of 10 nM. Additionally, we performed wound healing assay in Caco-2 cell interfered by DSS with or without AM of 100 nM. In the colitis model, AM significantly reduced the disease activity index, histological score, and local production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in accordance with reduction of serum amyloid A levels. Secretion of TNF-α in lipopolysaccharide-stimulated THP-1 cells was significantly reduced in the presence of AM. The distance of wound healing interfered by 0.25% DSS was significantly improved in the presence of AM of 100 nM. These results demonstrate that AM could ameliorate DSS-induced experimental colitis possibly through suppression of systemic and local production of cytokines such as TNF-α, associated with acceleration of ulcer reepithelialization and colon tissue regeneration.
  International Journal of Colorectal Disease 06/2011; 26(11):1453-62. · 2.38 Impact Factor
• Source

  Available from: Hiroaki Miyajima

  Article: Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders.

  Yoshibumi Kaneko, Hiroaki Miyajima, Alberto Piperno, Naohisa Tomosugi, Hisao Hayashi, Natsuko Morotomi, Ken-ichi Tsuchida, Takaaki Ikeda, Akihisa Ishikawa, Yusuke Ota, Shinya Wakusawa, Kentaro Yoshioka, Satoshi Kono, Sara Pelucchi, Ai Hattori, Yasuaki Tatsumi, Toshihide Okada, Masakazu Yamagishi
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  ABSTRACT: Iron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes. We measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography-tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis. One patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes. Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.
  Journal of Gastroenterology 11/2010; 45(11):1163-71. · 4.16 Impact Factor
• Article: High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease.

  Toshihide Okada, Yuta Shiono, Yoshibumi Kaneko, Kazuhiro Miwa, Kenkei Hasatani, Yoshiaki Hayashi, Hiroshi Mibayashi, Hiroyuki Aoyagi, Shigetsugu Tsuji, Masashi Yoshimitsu, Hisao Hayashi, Masakazu Yamagishi
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  ABSTRACT: Although many mutations of the Wilson's disease (WD) gene (ATP7B) have been reported, few data exist regarding the occurrence of fulminant hepatic failure (FHF). We sought to determine if genotypic assignment according to type of protein-product could be related to the prevalence of FHF among patients with WD. We performed gene analysis in Japanese patients with WD as well as genotype-phenotype analysis in 51 patients. We divided genotypes into two groups according to type of ATP7B product: truncated group [T] consisted of two truncated alleles including nonsense, insertion, deletion, or splice site mutation, and missense group [M] consisted of one or two missense alleles. We also divided phenotypes into two groups: [FHF] group and [non-FHF] group. We were able to determine genotype in 42 patients. Genotypically, 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [FHF] and 38 were [non-FHF]. All patients in [FHF] group belonged to [T] group. The prevalence of [FHF] in [T] group was 36.4% and was significantly higher than in [M] group (p < 0.003). These results demonstrated that genotypes for truncation of ATP7B are associated with high prevalence of FHF.
  Scandinavian journal of gastroenterology 10/2010; 45(10):1232-7. · 2.08 Impact Factor
• Article: Administration route-dependent induction of antitumor immunity by interferon-alpha gene transfer.

  Kenta Narumi, Atsushi Kondoh, Takeshi Udagawa, Hidehiko Hara, Naoko Goto, Yoshinori Ikarashi, Shumpei Ohnami, Toshihide Okada, Masakazu Yamagishi, Teruhiko Yoshida, Kazunori Aoki
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  ABSTRACT: Type I interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis, and immunomodulation. We have demonstrated that intratumoral injection of an IFN-alpha-expressing adenovirus effectively induces cell death of cancer cells and elicits a systemic tumor-specific immunity in several animal models. On the other hand, reports demonstrated that an elevation of IFN in the serum following an intramuscular delivery of a vector is able to activate antitumor immunity. In this study, we compared the intratumoral and systemic routes of IFN gene transfer with regard to the effect and safety of the treatment. Intratumoral injection of an IFN-alpha adenovirus effectively activated tumor-responsive lymphocytes and caused tumor suppression not only in the gene-transduced tumors but also in distant tumors, which was more effective than the intravenous administration of the same vector. The expression of co-stimulatory molecules on CD11c(+) cells isolated from regional lymph nodes was enhanced by IFN gene transfer into the tumors. Systemic toxicity such as an elevation of hepatic enzymes was much lower in mice treated by intratumoral gene transfer than in those treated by systemic gene transfer. Our data suggest that the intratumoral route of the IFN vector is superior to intravenous administration, due to the effective induction of antitumor immunity and the lower toxicity.
  Cancer Science 07/2010; 101(7):1686-94. · 3.33 Impact Factor
• Source

  Available from: kanazawa-u.ac.jp

  Article: Current state of Wilson disease patients in central Japan.

  Yasuaki Tatsumi, Ai Hattori, Hisao Hayashi, Jiro Ikoma, Masahiko Kaito, Masami Imoto, Shinya Wakusawa, Motoyoshi Yano, Kazuhiko Hayashi, Yoshiaki Katano, Hidemi Goto, Toshihide Okada, Shuichi Kaneko
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  ABSTRACT: This study evaluated the current state of patients with Wilson disease in central Japan. Between 1999 and 2007, 30 patients were diagnosed as having Wilson disease with an International Diagnostic Score of 4 or more. The phenotypes, genotypes and post-diagnostic courses of these patients were analyzed. Twenty-six patients had ATP7B mutations responsible for Wilson disease. Four patients had a single mutant chromosome. There were 2 major mutations of 2333 G>T and 2871 delC (40%), and 6 novel mutations (13%) in our patients. The first clinical manifestation was the hepatic form in 22, neurological form in 5, and hemolysis in 3 patients. The hepatic form was diagnosed around the age of 13 years, followed by neurological complication with a time lag of 9 years. Thus, some patients, especially patients with the neurological form, did not undergo early diagnostic tests including ATP7B analysis. During the post-diagnosis period, 3 patients were hospitalized for recurrent liver disease, and 2 patients committed suicide. One female patient died from acute hepatic failure associated with encephalopathy after fertilization therapy, while 2 male patients recovered from encephalopathy-free, prolonged hepatic failure after noncompliance with drug therapy. The King's Scores for liver transplantation were below the cut-off in both cases. To minimize delayed diagnosis, ceruloplasmin determination and ATP7B analysis may be recommended to patients showing hepatic damage of unknown etiology. At gene diagnosis, appropriate management of patients including compliance education and emotional care to prevent suicide might be important.
  Internal Medicine 01/2010; 49(9):809-15. · 0.94 Impact Factor
• Article: Pseudolymphoma of the liver associated with primary biliary cirrhosis: a case report and review of literature.

  Toshihide Okada, Hiroshi Mibayashi, Kenkei Hasatani, Yoshiaki Hayashi, Shigetsugu Tsuji, Yoshibumi Kaneko, Masashi Yoshimitsu, Takashi Tani, Yoh Zen, Masakazu Yamagishi
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  ABSTRACT: We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis. One of the lesions was found incidentally during a medical examination, presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography (CT) after injection of contrast medium. Retrospectively, the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously. Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7. CT during arterial portography revealed two hypointense nodules. Findings with other imaging modalities such as ultrasonography, magnetic resonance imaging, and hepatic angiography were consistent with hepatocellular carcinoma. A right posterior segmentectomy was performed, and the lesions were microscopically diagnosed as pseudolymphoma. To the best of our knowledge, only 31 other cases of this disease have ever been reported, with a highly asymmetrical male:female ratio of 1:9.7. Although we could find only one case of transformation of hepatic pseudolymphoma into lymphoma in the liver, the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully.
  World Journal of Gastroenterology 09/2009; 15(36):4587-92. · 2.47 Impact Factor
• Article: Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia.

  Shoji Katsuda, Masa-Aki Kawashiri, Akihiro Inazu, Hayato Tada, Masayuki Tsuchida, Yoshibumi Kaneko, Tsuyoshi Nozue, Atsushi Nohara, Toshihide Okada, Junji Kobayashi, Ichiro Michishita, Hiroshi Mabuchi, Masakazu Yamagishi
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  ABSTRACT: Familial hypobetalipoproteinemia (FHBL) is a hereditary disorder characterized by decreased plasma concentrations of low-density lipoprotein cholesterol. The best-characterized causes of FHBL are apolipoprotein B (apoB) gene mutations, which produce truncated apoB proteins. Fatty liver is thought to be frequent in FHBL, owing to impaired secretion of very-low-density lipoprotein from the liver. Homozygotes for FHBL present with extremely low concentrations of plasma lipids, and may suffer from deficiencies of fat-soluble vitamins. The objectives of this study were to identify apoB-defective FHBL subjects and investigate fatty liver in Japanese population. We screened 14 hypocholesterolemic subjects for apoB gene mutations by PCR-SSCP and performed liver ultrasonography in a Japanese population. We identified an apoB-82 homozygote in one subject and an apoB-13.7 heterozygote in another subject. Four of 6 individuals with FHBL presented with fatty liver in those 2 FHBL families. Liver biopsy of the apoB-13.7 heterozygote, which had obesity and insulin resistance, showed severe fatty liver. The apoB-82 homozygote was asymptomatic with fat-soluble vitamin concentrations being normal, possibly due to spared secretion of apoB-48 from the intestine and increased plasma concentrations of high-density lipoprotein cholesterol. ApoB gene mutations might not be rare and that fatty liver might be frequent in Japanese FHBL.
  Clinica chimica acta; international journal of clinical chemistry 10/2008; 399(1-2):64-8. · 2.54 Impact Factor
• Article: [Significance of endoscopic transpapillary approach in diagnosis of intrabiliary growth type of hepatocellular carcinoma].

  Takahiro Zenda, Takeshi Sawada, Kei Tominaga, Keizou Taniguchi, Yasuo Takeshita, Toshihide Okada, Syuichi Kaneko, Hiroshi Minato
  Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 06/2008; 105(6):860-3.
• Article: [Diffuse large B-cell lymphoma initially manifested by massive ascites and a small gastric lesion, clinically mimicking primary effusion lymphoma (PEL) in the abdominal cavity: a case report and review of the literature on Japanese PEL patients].

  Takahiro Zenda, Kei Tominaga, Syuichi Choto, Toshihide Okada, Syuichi Kaneko, Hiroshi Minato
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  ABSTRACT: A 50-year-old man was admitted because of increasing massive ascites. While lymphoma cells (diffuse large B-cell lymphoma: DLBCL) were detected in the ascites, pleural effusion, cerebrospinal fluid and bone marrow, no tumor masses other than a submucosal lymphoma lesion in the stomach only 1 cm in diameter were identified. The patient was treated with chemotherapy including rituximab (R-CHOP-ESHAP) and injection of methotrexate and dexamethasone into the medullary cavity as well as radiation to the whole brain, and achieved complete remission 4 months later. The present case suggests that DLBCL can initially manifest as a form of effusion lymphoma with minimum solid tumor component. The distinctive clinical features of Japanese patients with primary effusion lymphoma are also reviewed.
  Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2008; 104(12):1772-80.
• Article: Genetic background of Japanese patients with adult-onset storage diseases in the liver.

  Hisao Hayashi, Shinya Wakusawa, Motoyoshi Yano, Toshihide Okada
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  ABSTRACT: In contrast to primary lysosomal diseases in young subjects, adult-onset liver storage disorders may be explained by non-lysosomal genetic defects. The aim of the present review is to summarize the genetic backgrounds of Japanese patients with hemochromatosis of unknown etiology, Wilson disease of primary copper toxicosis, and the black liver of Dubin-Johnson syndrome. Three patients with middle-age onset hemochromatosis were homozygous for mutations of HJV and two patients were homozygous for mutations of TFR2. Minor genes other than HJV and TFR2 might be involved in Japanese patients. Five of the six patients with Wilson disease were compound heterozygous, while the remaining patient was heterozygous for the mutation in ATP7B responsible for copper toxicosis. Involvement of MURR1 was not proved in the heterozygote of ATP7B. Because of ferroxidase deficiency,most patients had secondary lysosomes shared by cuprothioneins and iron complex. Six patients with Dubin-Johnson syndrome were homozygous or compound heterozygous for mutant MRP2. Despite complex metabolic disorders, the syndrome had a single genetic background. Thus, most patients with adult-onset lysosomal proliferation in the liver had genetic defects in non-lysosomal organelles, named the secondary lysosomal diseases. The proliferating lysosomes in these conditions seemed to be heterogeneous in their matrices.
  Hepatology Research 11/2007; 37(10):777-83. · 2.20 Impact Factor
• Article: Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia.

  Ayako Suzuki, Paul Angulo, Jennifer St Sauver, Ayako Muto, Toshihide Okada, Keith Lindor
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  ABSTRACT: The effect of light to moderate alcohol consumption on the liver is controversial. To determine the association between light to moderate alcohol consumption and frequency of hypertransaminasemia, a cross-sectional and a subsequent longitudinal cohort study were conducted using annual health checkup data at a Japanese workplace. We analyzed 1,177 male subjects (age 20-59) without HCV or HBV infection or other chronic liver diseases. To determine the association between alcohol consumption (none or minimal <70 g/wk, light > or =70 g and <140 g/wk, moderate > or =140 g and <280 g/wk, excessive > or =280 g/wk) and hypertransaminasemia, we performed multiple logistic regressions. We then followed 326 subjects without a history of fatty liver or hypertransaminasemia up to 5 years for incidental hypertransaminasemia and performed Cox proportional hazard regressions. Excess alcohol consumption was associated with increased odds of hypertransaminasemia (adjusted odds ratio [AOR]versus none or minimal consumption 1.4[1.1-1.93], P= 0.023). There was significant interaction between age group and alcohol consumption (P < 0.01). In the younger group, moderate consumption was associated with decreased odds (AOR 0.5 [0.3-0.9], P= 0.032), while in the older group, light consumption was associated with decreased odds (AOR 0.6 [0.4-1.0], P= 0.036) and excess consumption was associated with increased odds (AOR 1.6 [1.1-2.3], P= 0.014) of hypertransaminasemia. During follow-up, moderate consumption was associated with decreased incidence of hypertransaminasemia versus none or minimal consumption (adjusted hazard ratio 0.4 [0.1-0.9], P= 0.02). Light to moderate alcohol consumption may protect against the development of hypertransaminasemia among male subjects without other liver conditions. Further studies are required before recommending light to moderate alcohol consumption.
  The American Journal of Gastroenterology 09/2007; 102(9):1912-9. · 7.28 Impact Factor
• Article: Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon.

  Isao Yoshida, Ayako Suzuki, Marc Vallée, Yutaka Matano, Takaharu Masunaga, Takahiro Zenda, Kimihide Shinozaki, Toshihide Okada
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  ABSTRACT: Obesity and diabetes mellitus are associated with an increased incidence of proximal colon cancer. Colonic adenoma that has been reported to be associated with elevated serum insulin levels and subsets of hyperplastic polyps might serve as a precursor of colon cancer. In this study, we sought to determine segment-specific associations between serum insulin levels and the prevalence of adenoma and hyperplastic polyps in the proximal and distal colon. We studied 343 consecutive patients who underwent colonoscopy in our hospital. All medical information, including fasting serum insulin, was obtained at colonoscopy. We performed multinomial logistic regression models by using the outcome categories of none (reference), proximal-only, distal-only, and both-segment lesions for the presence of adenoma/hyperplastic polyp with serum insulin, age, gender, lifestyle characteristics, and the presence of other types of lesions as predictors. Odds ratios (ORs) and 95% confidence intervals (CIs) are provided for a 5-muU/mL increase in serum insulin. Overall, serum insulin levels were significantly associated with adenoma (OR, 1.5; 95% CI, 1.1-2.0; P = .005) and borderline associated with hyperplastic polyps (OR, 1.3; 95% CI, 1.0-1.7; P = .075). In multinomial logistic regression models, elevated serum insulin levels were significantly associated with proximal-only adenoma (OR, 1.8; 95% CI, 1.2-2.5; P = .002), both-side hyperplastic polyp (OR, 1.7; 95% CI, 1.1-2.5; P = .015), and proximal-only hyperplastic polyp (OR, 1.5; 95% CI, 1.0-2.1; P = .048) and borderline associated with distal-only adenoma (OR, 1.5; 95% CI, 1.0-2.1; P =.059) but not with distal-only hyperplastic polyp. Serum insulin levels directly correlate with the presence of adenoma and hyperplastic polyps in the proximal colon and might also less strongly correlate with the presence of distal adenoma.
  Clinical Gastroenterology and Hepatology 11/2006; 4(10):1225-31. · 5.63 Impact Factor
• Article: Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

  Ayako Suzuki, Keith Lindor, Jenny St Saver, James Lymp, Flavia Mendes, Ayako Muto, Toshihide Okada, Paul Angulo
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  ABSTRACT: The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. We analyzed annual health checkup data from 1546 employees. Of 469 subjects with elevated ALT, we selected 348 male subjects by excluding those who had other causes of liver disease. They were followed for one year to assess the association of change in lifestyle with change in serum ALT. The 136 subjects who had ALT normalization were followed for two years to assess the association between lifestyle management and persistently normal ALT. In adjusted analysis, weight loss and regular exercise were significantly associated with improvement in serum ALT and increased the odds of ALT normalization, while starting smoking was significantly associated with deterioration in serum ALT. Subjects achieving > or = 5% weight reduction showed improvement in serum ALT. Reduction in alcohol consumption was not associated with changes in serum ALT. Maintaining reduced weight (<5% gain) was significantly associated with persistently normal ALT. Reducing weight by at least 5% with subsequent weight control and exercising regularly may be beneficial in treating NAFLD.
  Journal of Hepatology 01/2006; 43(6):1060-6. · 9.26 Impact Factor
• Article: Two male patients with Wilson's disease treated using trientine and iron reduction therapy.

  Hisao Hayashi, Toshio Ueno, Motoyoshi Yano, Toshihide Okada, Hiroshi Mabuchi
  Journal of Gastroenterology and Hepatology 11/2005; 20(10):1627-8. · 2.87 Impact Factor
• Article: Small follicular lymphoma arising near the ampulla of vater

  Takahiro Zenda, Takaharu Masunaga, Bungo Fuwa, Toshihide Okada, Yasuo Ontachi, Yukio Kondo, Shinji Nakao, Hiroshi Minato
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  ABSTRACT: A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.
  International Journal of Gastrointestinal Cancer 09/2005; 36(2):113-119.
• Article: Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.

  Yutaka Matano, Toshihide Okada, Ayako Suzuki, Takashi Yoneda, Yoshiyun Takeda, Hiroshi Mabuchi
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  ABSTRACT: Acromegalics have been reported to be at an increased risk of colorectal neoplasm. However, the magnitude of the risk is still controversial and the mechanism has not been fully investigated. In this study, we attempted to determine the magnitude of the association between acromegaly and colorectal lesions after taking into account age, gender, smoking status, and treatment status. In addition, we assessed the relationship between colorectal lesions and serum growth hormone (GH) levels in acromegalics. We conducted a case-control study by using 19 consecutive untreated patients (male:female = 11:8) who were newly diagnosed with acromegaly between 1990 and 2000. All patients underwent colonoscopy and received a histological diagnosis of colorectal lesions. Prevalence of hyperplastic polyp, adenoma, and carcinoma were compared with the prevalence in 76 controls matched for gender, age, and smoking status. Serum GH levels were compared between acromegalic patients with and without each type of colorectal lesion. The prevalence of hyperplastic polyp, adenoma, and carcinoma were significantly higher in the acromegalic patients compared to the controls (p < 0.05, odds ratios; 8.3, 4.2, and 9.8, respectively). In acromegalics, the presence of hyperplastic polyps and carcinomas were significantly associated with higher serum GH levels after adjusting for the other lesions and age (p < 0.05). After controlling for age, gender, smoking status, and treatment status, acromegaly was associated with significantly higher prevalence of colorectal hyperplastic polyp, adenoma, and carcinoma. High serum GH levels may be associated with the presence of hyperplastic polyp and carcinoma.
  The American Journal of Gastroenterology 05/2005; 100(5):1154-60. · 7.28 Impact Factor
• Source

  Available from: haematologica.it

  Article: Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis.

  Chizu Koyama, Shinya Wakusawa, Hisao Hayashi, Rie Suzuki, Motoyoshi Yano, Kentaro Yoshioka, Mitsuo Kozuru, Yoshihiro Takayamam, Toshihide Okada, Hiroshi Mabuchi
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  ABSTRACT: The low prevalence of the C282Y mutation of the HFE gene in Japan means that the genetic background of hemochromatosis in Japanese patients remains unclear. In a previous report, we showed that 3 patients from one family had an AVAQ 594-597 deletion of the transferrin receptor (TfR2) gene. This suggests that the TfR2 gene is involved in hemochromatosis in Japanese patients. Nine patients clinically diagnosed with hemochromatosis were included in the study. DNA was extracted from whole blood samples collected with informed consent. The HFE and TfR2 genes were analyzed by sequencing the coding region and splicing sites. There were no mutations in the HFE gene. In the TfR2 gene, 2 novel mutations, 1469T->G (L490R) and 1665delC (V561X), were found in 2 patients. A known variation, 714C-> (I238M), was also found in the patient with L490R. The patient homozygous for both L490R and I238M presented with a mild manifestation of hemochromatosis at the age of 41 years. His liver was cirrhotic with parenchymal iron deposits and the result of a glucose tolerance test was compatible with diabetes mellitus. The patient homozygous for V561X had severe iron overload with the triad of cirrhosis, diabetes mellitus and skin pigmentation at the age of 58 years. Taken together with the previous report, 5 of our 12 patients with hemochromatosis manifesting in middle age had mutations in the TfR2 gene. Thus, TfR2 plays a role in the pathogenesis of hemochromatosis in Japan.
  Haematologica 04/2005; 90(3):302-7. · 6.42 Impact Factor
• Article: Primary minute invasive de novo colonic adenocarcinoma appearing as submucosal tumor.

  Takahiro Zenda, Takaharu Masunaga, Kimihide Shinozaki, Atsushi Hashiba, Bungo Fuwa, Toshihide Okada, Toshinari Minamoto, Hiroshi Minato
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  ABSTRACT: A 4 mm white-yellow submucosal tumor-like lesion was detected in the sigmoid colon of an asymptomatic 52-yr-old Japanese man. Because the lesion was unexpectedly suspicious for adenocarcinoma by pathological examination of the biopsy specimen, it was treated by endoscopic mucosal resection. The specimen obtained demonstrated well-differentiated adenocarcinoma without any adenomatous element, and was located principally in the submucosal layer with a maximum depth of 1600 mum from the muscularis mucosae. The cancer exposed to the luminal surface was pathologically concluded to be diminutive. Intriguingly, aggregation of lymphocytes was found beneath the mucosal layer, which might have compromised the integrity of the muscularis mucosae. Because of deep submucosal infiltration and the latent aggressive nature of de novo cancer, the patient underwent an additional partial sigmoidcolectomy, which demonstrated no residual cancer and no regional lymph node metastasis. The lesion in this patient exhibited a previously undescribed appearance of de novo colon cancer as submucosal tumor in an early phase of growth.
  International Journal of Gastrointestinal Cancer 02/2005; 36(3):177-81.