2021/04/20 更新

写真a

アカザワ コウヘイ
赤澤 宏平
AKAZAWA Kohei
所属
医歯学総合病院 医療情報部 教授
医歯学総合研究科 地域疾病制御医学専攻 教授
職名
教授
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外部リンク

学位

  • 博士(数理学) ( 1999年3月   九州大学 )

  • 博士(医学) ( 1993年7月   九州大学 )

研究分野

  • 情報通信 / 生命、健康、医療情報学

  • ライフサイエンス / 医療管理学、医療系社会学  / 医療経済

  • 情報通信 / 統計科学

経歴(researchmap)

  • 新潟大学   医歯学総合研究科 医科学専攻   教授

    2003年10月 - 現在

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  • 新潟大学   医歯学総合病院   教授

    2003年10月 - 現在

      詳細を見る

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻   教授

    2003年10月 - 現在

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経歴

  • 新潟大学   医歯学総合研究科 医科学専攻   教授

    2003年10月 - 現在

  • 新潟大学   医歯学総合病院   教授

    2003年10月 - 現在

  • 新潟大学   医歯学総合研究科 地域疾病制御医学専攻   教授

    2003年10月 - 現在

所属学協会

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論文

  • Surgical outcomes of elderly patients with Stage I gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. 査読

    Souya Nunobe, Ichiro Oda, Takashi Ishikawa, Kohei Akazawa, Hitoshi Katai, Yoh Isobe, Isao Miyashiro, Shunichi Tsujitani, Hiroyuki Ono, Satoshi Tanabe, Takeo Fukagawa, Satoshi Suzuki, Yoshihiro Kakeji

    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association23 ( 2 ) 328 - 338   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The proportion of elderly patients undergoing surgery for gastric cancer is increasing. However, limited number of therapeutic outcomes in the elderly has been reported. Here we examined the surgical results based on a nationwide survey of elderly patients who underwent surgery for Stage I gastric cancer. METHODS: Data from 68,353 Stage I patients who underwent gastrectomy between 2001 and 2007 were retrospectively collected. The accumulated data were reviewed and analyzed by the Japanese Gastric Cancer Association registration committee. We first classified the patients as those aged ≤ 74 years and ≥ 75 years. We further classified those patients aged ≥ 75 years into groups by 5-year increments to examine their short- and long-term postoperative outcomes. RESULTS: Patients aged ≥ 75 years accounted for 46.5%. The 30-day mortality rate was < 0.7% for any age group, but for those aged ≥ 75 years, the 60-day and 90-day mortality rates were 0.9-2.3% and 1.2-5.1%, respectively. An examination of long-term survival indicated that, as the class of age increased, the 5-year overall survival (OS) was 47.0-93.1% and disease-specific survival (DSS) was 91.4-98.2%, respectively. Although high DSS rates of ≥ 90% were found for all age groups, OS only accounted for ≤ 82% of patients aged ≥ 75 years. CONCLUSION: Among elderly patients with Stage I gastric cancer, deaths due to other diseases were frequently observed in the long term. Thus, for elderly patients, it may be appropriate to reconsider the treatment strategy with respect to the balance between the invasiveness of the treatment and the prognosis.

    DOI: 10.1007/s10120-019-01000-3

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  • Amyotrophic Lateral Sclerosis with Pallidonigroluysian Degeneration: A Clinicopathological Study. 査読 国際誌

    Junko Ito, Hiroshi Shimizu, Kentaro Ohta, Jiro Idezuka, Hajime Tanaka, Hiroshi Kondo, Takashi Nakajima, Hitoshi Takahashi, Kohei Akazawa, Osamu Onodera, Akiyoshi Kakita

    Annals of neurology87 ( 2 ) 302 - 312   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype. METHODS: From a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA-binding protein (TDP-43) inclusions, we selected those with PNLD and analyzed their clinicopathological features. RESULTS: Eleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP-43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneider's staging or Nishihira's typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP-43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP-43 aggregates from the cerebral cortex to the substantia nigra. INTERPRETATION: The PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP-43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302-312.

    DOI: 10.1002/ana.25652

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  • Risk Analysis for Chemotherapy-induced Nausea and Vomiting (CINV) in Patients Receiving FEC100 Treatment. 査読 国際誌

    Mitsuhiro Hayashi, Kyoko Nakazawa, Yoshie Hasegawa, Jun Horiguchi, Daishu Miura, Takashi Ishikawa, Shintaro Takao, Seung Jim Kim, Kazuhiko Yamagami, Masaru Miyashita, Muneharu Konishi, Yasushi Shigeoka, Masato Suzuki, Tetsuya Taguchi, Tomoyuki Kubota, Hirokazu Tanino, Kimito Yamada, Kazutaka Narui, Konomi Kimura, Kohei Akazawa, Norio Kohno

    Anticancer research39 ( 8 ) 4305 - 4314   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND/AIM: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. PATIENTS AND METHODS: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. RESULTS: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. CONCLUSION: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.

    DOI: 10.21873/anticanres.13596

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  • B-Mode Ultrasonography versus Contrast-Enhanced Ultrasonography for Surveillance of Hepatocellular Carcinoma: A Prospective Multicenter Randomized Controlled Trial. 査読

    Kudo M, Ueshima K, Osaki Y, Hirooka M, Imai Y, Aso K, Numata K, Kitano M, Kumada T, Izumi N, Sumino Y, Ogawa C, Akazawa K

    Liver cancer8 ( 4 ) 271 - 280   2019年7月

  • Hyperbilirubinemia predicts the infectious complications after esophagectomy for esophageal cancer. 査読

    Muneoka Y, Ichikawa H, Kosugi SI, Hanyu T, Ishikawa T, Kano Y, Shimada Y, Nagahashi M, Sakata J, Kobayashi T, Kameyama H, Akazawa K, Wakai T

    Annals of medicine and surgery (2012)39   16 - 21   2019年3月

  • Prevalence, significance and reversal of abnormal P-wave indices in hypertension: A review and meta-analysis. 査読

    Aizawa Y, Sato T, Akazawa K

    Journal of electrocardiology53   13 - 17   2019年3月

  • Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma. 査読 国際誌

    Hideaki Takahashi, Yuichiro Tada, Takashi Saotome, Kohei Akazawa, Hiroya Ojiri, Chihiro Fushimi, Tatsuo Masubuchi, Takashi Matsuki, Kaori Tani, Robert Y Osamura, Hideaki Hirai, Shuhei Yamada, Daisuke Kawakita, Kouki Miura, Shin-Etsu Kamata, Toshitaka Nagao

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology37 ( 2 ) 125 - 134   2019年1月

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    記述言語:英語  

    PURPOSE: Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease's rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2-positive SDC. PATIENTS AND METHODS: This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). RESULTS: Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. CONCLUSION: Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2-positive SDC, with a manageable toxicity profile.

    DOI: 10.1200/JCO.18.00545

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  • Urban-rural disparity in cervical cancer in China and feasible interventions for tackling the rural excess. 査読

    Wen X, Wen D, Yang Y, Chen Y, Akazawa K, Liu Y, Shan B

    Medicine98 ( 1 ) e13907   2019年1月

  • Professional oral care reduces carcinogenic acetaldehyde levels in mouth air of perioperative esophageal cancer patients: A prospective comparative study 査読

    Naoko Tanda, Jumpei Washio, Takashi Kamei, Kohei Akazawa, Nobuhiro Takahashi, Takeyoshi Koseki

    Tohoku Journal of Experimental Medicine249 ( 1 ) 75 - 83   2019年

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    掲載種別:研究論文(学術雑誌)  

    © 2019 Tohoku University Medical Press. Acetaldehyde is a potential carcinogen for esophageal cancer, and some oral microorganisms produce acetaldehyde from ethanol or glucose. In this prospective study, we examined the influence of professional oral care on acetaldehyde levels in mouth air of esophageal cancer patients. Acetaldehyde concentrations in mouth air and breath were measured by a portable gas chromatograph, and acetaldehyde production from oral microbiota was also evaluated. Samples were taken from 21 esophageal cancer patients (median age 68 years) and 20 age-matched healthy volunteers (control group) before and after oral care. Postoperative samples were also taken from 17 patients who had undergone surgery. All samples (mouth air, breath, and saliva) were collected 2 to 3 hours after lunch. Oral microbial samples were prepared from saliva. Genotype analysis of alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes revealed no significant differences in the genotypes between the two groups. In the control group, acetaldehyde levels in mouth air showed no significant changes after oral care, while the amount of microbial acetaldehyde production from ethanol was significantly decreased. By contrast, among the patients, acetaldehyde levels in mouth air were significantly decreased after oral care and after operation, while the amount of microbial acetaldehyde production from ethanol showed no significant changes. Moreover, microbial acetaldehyde production from glucose was significantly decreased after operation. Overall, oral health was poorer in the patient group. In conclusion, professional oral care for esophageal cancer patients is effective for reducing acetaldehyde levels in mouth air due to the reduction of microbial count.

    DOI: 10.1620/tjem.249.75

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  • Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma 査読

    Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida

    Scientific Reports8 ( 1 ) 1005   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

    DOI: 10.1038/s41598-017-18560-y

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  • Walking ability, anxiety and depression, significantly decrease EuroQol 5-Dimension 5-Level scores in older hemodialysis patients in Japan 査読

    Utako Shimizu, Hagiko Aoki, Momoe Sakagami, Kohei Akazawa

    Archives of Gerontology and Geriatrics78   96 - 100   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Ireland Ltd  

    Background: Hemodialysis patients in Japan are aging, but the influence of lifestyle factors on EuroQoL 5-Dimension 5-Level (EQ-5D-5 L) scores in older hemodialysis patients is unclear. This study aimed to measure health-related quality of life using the EQ-5D-5 L for older hemodialysis patients and to identify the lifestyle factors affecting EQ-5D-5 L scores in Japan. Methods: Outpatients aged 65 years or older who had been receiving maintenance hemodialysis for more than 5 years were selected to determine their EQ-5D-5 L scores. Multiple linear regression analysis was applied to identify items affecting the EQ-5D-5 L scores. Results: The response rate was 59.7% (748/1251), after excluding 9 patients who did not fulfill the participation criteria, and we analyzed data from 739 patients (462 men, 277 women) aged 72.9 ± 6.5 years (mean ± standard deviation) with a mean duration of hemodialysis of 15.1 ± 8.8 years. The mean EQ-5D-5 L score was 0.738 ± 0.207. Higher Hospital Anxiety and Depression Scale scores (regression coefficient, −0.467
    P &lt
    0.001), reduced walking ability (−0.201
    P &lt
    0.001), duration of hemodialysis (−0.175
    P &lt
    0.001), age (−0.143
    P &lt
    0.001), and subjective symptoms (−0.128
    P &lt
    0.001) showed significant negative correlations with the EQ-5D-5 L score. Conclusions: Reduced walking ability, and Anxiety and Depression, were associated with lower EQ-5D-5 L score and appeared to be important factors in decreasing health for older hemodialysis patients. These results suggest that patients’ families and dialysis facility staff should be trained in early detection of depression and that patients should maintain their walking ability by exercise therapy.

    DOI: 10.1016/j.archger.2018.06.006

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  • Association of socioeconomic factors and the risk for unintentional injuries among children in Japan: a cross-sectional study. 査読 国際誌

    Nobuhiro Sato, Yusuke Hagiwara, Junta Ishikawa, Kohei Akazawa

    BMJ open8 ( 8 ) e021621   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: While Japan has socioeconomic issues, such as income inequality, little is known about the association between socioeconomic factors and the risk of unintentional childhood injuries. The purpose of the study was to evaluate the influence of socioeconomic factors on the risk for unintentional injuries among preschool children in Japan. DESIGN: Cross-sectional study using data from a web-based questionnaire survey. SETTING: Japan (January 2015). PARTICIPANTS: 1000 households with preschool children under 6 years of age. OUTCOME MEASURES: Multivariate logistic regression was performed to analyse the influence of socioeconomic factors on the incidence of unintentional injuries. RESULTS: Overall, 976 households were eligible for the analysis, with 201 households reporting unintentional injuries. The incidence rates for unintentional injury were estimated to be constant across all strata constructed using combinations of socioeconomic factors. The multivariate logistic regression analysis showed no significant differences in socioeconomic factors between households that reported unintentional injuries and those that did not. CONCLUSION: The findings of our study demonstrated that unintentional injuries among preschool children occurred at approximately fixed rates, independent of socioeconomic factors. Accordingly, prevention strategies for unintentional injuries that concern socioeconomic disadvantages should be avoided in Japan.

    DOI: 10.1136/bmjopen-2018-021621

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  • Radiofrequency Ablation of Breast Cancer: A Retrospective Study. 査読

    Ito T, Oura S, Nagamine S, Takahashi M, Yamamoto N, Yamamichi N, Earashi M, Doihara H, Imoto S, Mitsuyama S, Akazawa K

    Clinical breast cancer18 ( 4 ) e495 - e500   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.clbc.2017.09.007

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  • Trabecular bone microstructure and mineral density in human residual ridge at various intervals over a long period after tooth extraction 査読

    Mikako Tanaka, Emi Yamashita-Mikami, Kohei Akazawa, Michiko Yoshizawa, Yoshiaki Arai, Sadakazu Ejiri

    Clinical Implant Dentistry and Related Research20 ( 3 ) 375 - 383   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Blackwell Publishing Ltd  

    Background: Long-term changes of trabecular microstructure in human tooth extraction socket have not been investigated. Purpose: To examine the trabecular microstructure of human residual ridges at various intervals following tooth extraction, and to determine whether bone remodeling activity can attain points of relative stability and when such points are reached. Materials and Methods: Forty-four bone biopsy specimens were obtained from lower molar or premolar regions of residual ridges. Postextraction times ranged from 1.6 to 360 months. Samples were analyzed using micro-computed tomography and three-dimensional bone morphometry with histological analyses. Trabecular bone parameters were plotted against postextraction times, and a stepwise piecewise linear regression analysis was performed to determine at which points of time these parameters either increased or decreased. Results: Using piecewise linear regression, “inflection points” were found in most trabecular bone parameters between 7 and 12 months postextraction. Among the residual ridge samples, woven trabecular structure became mature, consisting of thick lamellar trabeculae with sufficient bone density, under dynamic bone remodeling until the 7th to 12th month post-tooth extraction. After this period, the mature network structure remained stable with low remodeling activity. Conclusion: Bone remodeling of trabecular structure in human residual ridge after tooth extraction had a stabilization period.

    DOI: 10.1111/cid.12591

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  • Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung 査読

    Tatsuro Okamoto, Kazuki Takada, Seijiro Sato, Gouji Toyokawa, Tetsuzo Tagawa, Fumihiro Shoji, Ryota Nakanishi, Eiji Oki, Terumoto Koike, Masayuki Nagahashi, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kouhei Akazawa, Stephen Lyle, Kazuaki Takabe, Shujiro Okuda, Kenji Sugio, Toshifumi Wakai, Masanori Tsuchida, Yoshihiko Maehara

    Annals of Surgical Oncology25 ( 6 ) 1564 - 1571   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer New York LLC  

    Background: Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC. Methods: Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis. Results: TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B
    35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB
    p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively). Conclusions: The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.

    DOI: 10.1245/s10434-018-6401-1

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  • Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. 査読 国際誌

    Masatoshi Kudo, Kazuomi Ueshima, Osamu Yokosuka, Sadahisa Ogasawara, Shuntaro Obi, Namiki Izumi, Hiroshi Aikata, Hiroaki Nagano, Etsuro Hatano, Yutaka Sasaki, Keisuke Hino, Takashi Kumada, Kazuhide Yamamoto, Yasuharu Imai, Shouta Iwadou, Chikara Ogawa, Takuji Okusaka, Fumihiko Kanai, Kohei Akazawa, Ken-Ichi Yoshimura, Philip Johnson, Yasuaki Arai

    The lancet. Gastroenterology & hepatology3 ( 6 ) 424 - 432   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. METHODS: We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m2 on days 1 and 8 and fluorouracil 330 mg/m2 continuously on days 1-5 and 8-12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. FINDINGS: Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1-14·5] vs 11·5 months [8·2-14·8]; hazard ratio 1·009 [95% CI 0·743-1·371]; p=0·955). Grade 3-4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). INTERPRETATION: Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. FUNDING: Japanese Ministry of Health, Labour and Welfare.

    DOI: 10.1016/S2468-1253(18)30078-5

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  • The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: a report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society 査読

    Mitsuyoshi Namba, Toshio Iwakura, Rimei Nishimura, Kohei Akazawa, Munehide Matsuhisa, Yoshihito Atsumi, Jo Satoh, Toshimasa Yamauchi, on behalf of the Japan Diabetes Society (JDS) Committee for Surveys on Severe Hypoglycemia

    Diabetology International9 ( 2 ) 84 - 99   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 health-care facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these health-care facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a Web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480, and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively
    those with type 2 diabetes were shown to be significantly older [median (interquartile range), 77.0 (68.0–83.0)] than those with type 1 diabetes [54.0 (41.0–67.0)] (P &lt
     0.001)
    and the BMI was shown to be significantly higher for those with type 2 diabetes [22.0 (19.5–24.8) kg/m2] than for those with type 1 diabetes [21.3 (18.9–24.0) kg/m2] (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes [50.6 mL (31.8–71.1)/min/1.73 m2] than among those with type 1 diabetes [73.3 (53.5–91.1) mL/min/1.73 m2] (P &lt
     0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P &lt
     0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent, and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia, not only through education on hypoglycemia but also through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

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  • Prediction of pathological response to neoadjuvant chemotherapy in breast cancer patients by imaging 査読

    Hiroshi Kaise, Fumika Shimizu, Kohei Akazawa, Yoshie Hasegawa, Jun Horiguchi, Daishu Miura, Norio Kohno, Takashi Ishikawa

    Journal of Surgical Research225   175 - 180   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Academic Press Inc.  

    Background: Diagnostic imaging is important for predicting the pathological response to chemotherapy during neoadjuvant chemotherapy (NAC) and for considering the surgical management with appropriate resection after NAC. This study was performed to examine the accuracy of the present radiological imaging for predicting the pathological complete response (pCR). Methods: From 188 patients in our previous JONIE1 Study, a randomized controlled trial comparing chemotherapy with and without zoledronic acid for patients with human epidermal growth factor receptor 2-negative breast cancer, we evaluated 122 patients whose tumor size was examined by magnetic resonance imaging or ultrasound at three points: before NAC
    after administering fluorouracil, epirubicin, and cyclophosphamide
    and after NAC. The maximum tumor diameter was evaluated by magnetic resonance imaging or ultrasound. Tumor reduction ratios were calculated at the same three points. The association between the radiological clinical response and the pCR was examined. Results: Among the 122 patients evaluated, there were 98 and 24 patients with luminal (Lum) and triple-negative (TN) subtypes, respectively. There were no patients who showed tumor progression after treatment. The radiological size of the tumors was finally reduced by an average of 58.4%. Clinical complete response and pCR were achieved in 22 (18.0%) and 15 (12.3%) patients, respectively. In the overall population (n = 122), the accuracy, sensitivity, and specificity for predicting pCR were 86.1%, 88.8%, and 66.7%, respectively. The negative predictive value and false-negative rate were 45.5% and 11.2%, respectively. According to subtypes, the accuracies were 83.7% and 95.8% in Lum and TN, respectively. Negative predictive value and false-negative rate were markedly different between the Lum (29.4% and 13.5%) and TN subtypes (100% and 0%), respectively. Conclusions: This randomized clinical trial demonstrated that NAC was safe for operable breast cancer patients with appropriate radiological monitoring. Radiological evaluation after NAC may be a reliable method for predicting pathological response in the TN subtype, but not in the Lum subtype.

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  • Cost-effectiveness of combined serum anti-Helicobacter pylori IgG antibody and serum pepsinogen concentrations for screening for gastric cancer risk in Japan 査読

    Shota Saito, Motoi Azumi, Yusuke Muneoka, Katsuhiko Nishino, Takashi Ishikawa, Yuichi Sato, Shuji Terai, Kouhei Akazawa

    European Journal of Health Economics19 ( 4 ) 545 - 555   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Verlag  

    Background: A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this “ABC method” is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk. Methods: A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. Results: According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. Conclusions: A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

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  • The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: A report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society 査読

    Mitsuyoshi Namba, Toshio Iwakura, Rimei Nishimura, Kohei Akazawa, Munehide Matsuhisa, Yoshihito Atsumi, Jo Satoh, Toshimasa Yamauchi, the Japan Diabetes Society (JDS) Committee for Surveys on Severe Hypoglycemia

    Journal of Diabetes Investigation9 ( 3 ) 642 - 656   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Blackwell Publishing  

    Despite great strides in pharmacotherapy for diabetes, there is increasing concern over the risk of hypoglycemia in patients with diabetes receiving pharmacotherapy as they become increasingly older. This has prompted the Japan Diabetes Society (JDS) to initiate a survey on the current status of severe hypoglycemia in clinical settings. In July 2015, following approval from the JDS Scientific Survey/Research Ethics Committee, the JDS extended an invitation to executive educators, who represented a total of 631 healthcare facilities accredited by the JDS for diabetes education, to participate in the proposed survey. Of these, those who expressed their willingness to participate in the survey were sent an application form required for obtaining ethical approval at these healthcare facilities and were then asked, following approval, to enter relevant clinical data on an unlinked, anonymous basis in a web-based registry. The current survey was fully funded by the JDS Scientific Survey/Research Committee. A case registry (clinical case database) was launched after facility-specific information (healthcare facility database) was collected from all participating facilities and after informed consent was obtained from all participating patients. With severe hypoglycemia defined as the “presence of hypoglycemic symptoms requiring assistance from another person to treat and preferably venous plasma glucose levels at onset/diagnosis of disease or at presentation clearly less than 60 mg/dL (capillary whole blood glucose, less than 50 mg/dL)”, the current survey was conducted between April 1, 2014 and March 31, 2015, during which facility-specific information was collected from a total of 193 facilities with a total of 798 case reports collected from 113 facilities. Of the 193 respondent facilities, 149 reported having an emergency department as well, with the median number of patients who required emergency transportation services to reach these facilities totaling 4,962 annually, of which those with severe hypoglycemia accounted for 0.34% (17). The respondent facilities accommodated a total of 2,237 patients with severe hypoglycemia annually, with the number of patients thus accommodated being 6.5 patients per site. A total of 1,171 patients were admitted for severe hypoglycemia, with the number of patients thus admitted being 4.0 per site, who accounted for 52.3% of all patients visiting annually for severe hypoglycemia. A review of the 798 case reports collected during the survey revealed that 240, 480 and 78 patients had type 1 diabetes, type 2 diabetes, and other types of diabetes, respectively
    those with type 2 diabetes were shown to be significantly older (median [interquartile range], 77.0 [68.0–83.0]) than those with type 1 diabetes (54.0 [41.0–67.0]) (P &lt
     0.001)
    and the BMI was shown to be significantly higher for those with type 2 diabetes (22.0 [19.5–24.8] kg/m2) than for those with type 1 diabetes (21.3 [18.9–24.0] kg/m2) (P = 0.003). It was also found that the median estimated glomerular filtration rate (eGFR) was significantly lower among those with type 2 diabetes (50.6 mL [31.8–71.1]/min/1.73 m2) than among those with type 1 diabetes (73.3 [53.5–91.1] mL/min/1.73 m2) (P &lt
     0.001). Again, the median HbA1c value at onset of severe hypoglycemia was shown to be 7.0 (6.3–8.1)% among all patients examined, 7.5 (6.9–8.6)% among those with type 1 diabetes, and 6.8 (6.1–7.6)% among those with type 2 diabetes, with the HbA1c value at onset of hypoglycemia being significantly lower among those with type 2 diabetes (P &lt
     0.001). Antecedent symptoms of severe hypoglycemia were shown to be present, absent and unknown in 35.5, 35.6, and 28.9% of all patients, respectively, with the incidence of symptomatic hypoglycemia being significantly lower among those with type 1 diabetes (41.0%) than among those with type 2 diabetes (56.9%). The antidiabetic agents used in those with type 2 diabetes were insulin preparations (292 patients including 29 receiving concomitant sulfonylureas [SUs]) (60.8%), SUs (159 insulin-naïve patients) (33.1%), and no insulin preparations or SUs (29 patients) (6.0%). Of the 798 patients surveyed, 296 patients (37.2%) were shown to have required emergency transportation services for severe hypoglycemia before. Thus, the survey revealed, for the first time, the current status of treatment-related severe hypoglycemia in Japan and clearly highlights the acute need for implementing preventive measures against hypoglycemia not only through education on hypoglycemia but through optimization of antidiabetic therapy for those at high risk of severe hypoglycemia or those with a history of severe hypoglycemia.

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  • Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes. 査読 国際誌

    Michiko Imamura, Takashi Morimoto, Takashi Nomura, Shintaro Michishita, Arisa Nishimukai, Tomoko Higuchi, Yukie Fujimoto, Yoshimasa Miyagawa, Ayako Kira, Keiko Murase, Kazuhiro Araki, Yuichi Takatsuka, Koshi Oh, Yoshikazu Masai, Kouhei Akazawa, Yasuo Miyoshi

    World journal of surgical oncology16 ( 1 ) 26 - 26   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. METHODS: A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. RESULTS: The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). CONCLUSIONS: These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

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  • Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers 査読

    Takahiro Watanabe, Akira I. Hida, Natsuko Inoue, Michiko Imamura, Yukie Fujimoto, Kouhei Akazawa, Seiichi Hirota, Yasuo Miyoshi

    Breast Cancer Research and Treatment168 ( 1 ) 135 - 145   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer New York LLC  

    Purpose: The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2−) BC is still controversial. Methods: We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2− BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2− BCs. Results: A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2− BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2− cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2− BC (p = 0.034). Conclusion: Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2− BC.

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  • Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study) 査読

    Hideki Nakasone, Kiriko Terasako-Saito, Teiichi Hirano, Atsushi Wake, Seiichi Shimizu, Naoki Kurita, Etsuko Yamazaki, Kensuke Usuki, Kohei Akazawa, Junya Kanda, Koichiro Minauchi, Go Yamamoto, Shiori Tanimoto, Masaharu Kamoshita, Yasuhisa Yokoyama, Etsuo Miyaoka, Shuichi Ota, Shinichi Kako, Koji Izutsu, Yoshinobu Kanda

    Hematological Oncology36 ( 1 ) 202 - 209   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:John Wiley and Sons Ltd  

    Complete response (CR) after treatment for multiple myeloma is associated with superior progression-free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto-HCT) between 2010 and 2012. If patients did not achieve CR after auto-HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto-HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto-HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post-HCT VGPR and in 2 of 12 patients with post-HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto-HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post-HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.

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  • Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007) 査読

    Hitoshi Katai, Takashi Ishikawa, Kohei Akazawa, Yoh Isobe, Isao Miyashiro, Ichiro Oda, Shunichi Tsujitani, Hiroyuki Ono, Satoshi Tanabe, Takeo Fukagawa, Souya Nunobe, Yoshihiro Kakeji, Atsushi Nashimoto, Registration Committee of the Japanese Gastric Cancer Association

    Gastric Cancer21 ( 1 ) 144 - 154   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    Background: The aim of this retrospective study was to investigate the tumor characteristics, surgical details, and survival distribution of surgically resected cases of gastric cancer from the nationwide registry of the Japanese Gastric Cancer Association. Methods: Data from 118,367 patients with primary gastric carcinoma who underwent resection between 2001 and 2007 were included in the survival analyses. The 5-year survival rates were calculated for various subsets of prognostic factors. Results: The median age of the patients was 67 years. The proportions of patients with pathological stage (Japanese Gastric Cancer Association) IA, IB, II, IIIA, IIIB, and IV disease were 44.0%, 14.7%, 11.7%, 9.5%, 5.0%, and 12.4% respectively. The death rate within 30 days of operation was 0.5%. The 5-year overall survival rate in the 118,367 patients who were treated by resection was 71.1%. The 5-year overall survival rates of patients with pathological stage IA, IB, II, IIIA, IIIB, and IV disease were 91.5%, 83.6%, 70.6%, 53.6%, 34.8%, and 16.4% respectively. The 5-year disease-specific survival rates in the patients with pT1 (mucosa) disease after D1+ dissection of lymph node station no. 7 (D1 + α), D1+ dissection of lymph node station nos. 7, 8, and 9 (D1+ β), and D2 lymphadenectomy were 99.4%, 99.6%, and 99.1% respectively. The 5-year disease-specific survival rates in the patients with pT1 (submucosa) disease after D1 + α, D1 + β, and D2 lymphadenectomy were 97.3%, 98.1%, and 96.9% respectively. Conclusion: Detailed analyses of the data from more than 100,000 patients show the recent trends of the outcomes of gastric cancer treatment in Japan and provide baseline information for use by medical communities around world.

    DOI: 10.1007/s10120-017-0716-7

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  • A Hybrid Electronic Health Record System Integrating Electronic and Paper-based Records 査読

    Kenshi Terajima, Norito Negishi, Kouichi Maruyama, Hiroaki Hasegawa, Kouhei Akazawa

    European Journal for Biomedical Informatic14 ( 1 ) 58 - 66   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan 査読

    Shota Saito, Yusuke Muneoka, Takashi Ishikawa, Kouhei Akazawa

    Clinical Therapeutics39 ( 12 ) 2380 - 2388   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Excerpta Medica Inc.  

    Purpose The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. Methods We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (\1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of \12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Findings Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of \3,870,077, resulting in an incremental cost-effectiveness ratio of \43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was &gt
    \12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Implications Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed.

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  • Survival outcomes of neoadjuvant chemotherapy with zoledronic acid for HER2-negative breast cancer 査読

    Takashi Ishikawa, Kouhei Akazawa, Yoshie Hasegawa, Hirokazu Tanino, Jun Horiguchi, Daishu Miura, Mitsuhiro Hayashi, Norio Kohno

    JOURNAL OF SURGICAL RESEARCH220   46 - 51   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Background: A randomized phase 2 trial in women with HER2-negative breast cancer has shown that adding zoledronic acid (ZOL) to neoadjuvant chemotherapy (CT) has potential anticancer benefits in postmenopausal and triple-negative (TN) breast cancer patients. We report the data for the secondary end point of disease-free survival (DFS).
    Methods: Patients were randomly assigned to receive CT or CT + ZOL (CT-Z). All patients received four cycles of FEC100 followed by 12 cycles of paclitaxel weekly. ZOL (4 mg) was administered 3-4 times weekly for 7 wk to the CT-Z group patients. The primary end point was pathologic complete response (pCR). The secondary end points were the clinical response rates, rate of breast-conserving surgery, safety, and DFS.
    Results: Of the 188 patients enrolled, 95 were assigned to the CT group and 93 to the CT-Z group. DFS and overall survival were analyzed in 92 and 88 patients with the mean times of 5.15 y and 5.38 y, respectively. The 3-y DFS rate was 84.6% in the CT group and 90.8% in the CT-Z group (P = 0.188). The particular benefit from ZOL for the neoadjuvant CT seen as improvement of the pCR rate was indicated in the 3-y DFS period for TN cancer cases (CT versus CT-Z: 70.6% versus 94.1%) but not for postmenopausal cases.
    Conclusions: ZOL did not improve DFS when combined with CT. However, the improvement of the pCR rate translated to survival outcomes in TN breast cancer. The short-term application of ZOL may not be sufficient to improve the outcome in postmenopausal patients. (C) 2017 Elsevier Inc. All rights reserved.

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  • Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial (vol 47, pg 1060, 2017) 査読

    Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa

    SURGERY TODAY47 ( 12 ) 1539 - 1540   2017年12月

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    記述言語:英語   出版者・発行元:SPRINGER  

    In the original publication, the article category was published as "Review Article". The correct category should read as "Original Article".

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  • Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer 査読

    Yoshifumi Shimada, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yusuke Muneoka, Ryoma Yagi, Yosuke Tajima, Takuma Okamura, Masato Nakano, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Tetsu Hayashida, Hiromasa Takaishi, Yuko Kitagawa, Eiji Oki, Tsuyoshi Konishi, Fumio Ishida, Shin-ei Kudo, Jennifer E. Ring, Alexei Protopopov, Stephen Lyle, Yiwei Ling, Shujiro Okuda, Takashi Ishikawa, Kohei Akazawa, Kazuaki Takabe, Toshifumi Wakai

    ONCOTARGET8 ( 55 ) 93567 - 93579   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IMPACT JOURNALS LLC  

    Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.
    Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as "all wild-type", while remaining patients were defined as "mutant-type".
    Results: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were "all wild-type" compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and "mutant-type" RCRC showed significantly worse PFS compared with "all wild-type" LCRC (P = 0.004).
    Conclusions: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC.

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  • Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study 査読

    Nobutaka Kitamura, Kuniaki Seyama, Yoshikazu Inoue, Katsura Nagai, Masaru Suzuki, Hiroshi Moriyama, Toshinori Takada, Ryushi Tazawa, Toyohiro Hirai, Michiaki Mishima, Mie Hayashida, Masaki Hirose, Toru Arai, Chikatoshi Sugimoto, Noboru Hattori, Kentaro Watanabe, Tsutomu Tamada, Kohei Akazawa, Takahiro Tanaka, Koh Nakata

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY26 ( 10 ) 1182 - 1189   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    PurposeLymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.
    MethodsSubjects received sirolimus for 2years at doses adjusted to maintain a trough blood level of 5 to 15ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.
    ResultsThe most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (&lt;14.5g/dL) showed significantly higher incidence than those with high Hb (14.5g/dL, P&lt;.01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.
    ConclusionsBaseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

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  • Actionable gene-based classification toward precision medicine in gastric cancer 査読

    Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Takaaki Hanyu, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Jun Sakata, Hiroshi Yabusaki, Satoru Nakagawa, Nobuaki Sato, Yuki Hirata, Yuko Kitagawa, Toshiyuki Tanahashi, Kazuhiro Yoshida, Ryota Nakanishi, Eiji Oki, Dana Vuzman, Stephen Lyle, Kazuaki Takabe, Yiwei Ling, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai

    GENOME MEDICINE9 ( 1 ) 93   2017年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed.& para;& para;Methods: A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tum or tissues were obtained from surgical or biopsy specimens and were subjected, to DMA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired, with US Food and Drug Administration-approved targeted therapies, and the evaluation o f Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status.& para;& para;Results: Comprehensive genomic sequencing detected at least one alteration o f 435 cancer-related genes in 194 GCs (93.7%) and o f 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomicaliy stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated. phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six dusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM duster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC. with a remarkable response to anti-HER2 therapy in the ERBB2 duster.& para;& para;Conclusions: This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.

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  • Tumor size and proliferative marker geminin rather than Ki67 expression levels significantly associated with maximum uptake of F-18-deoxyglucose levels on positron emission tomography for breast cancers 査読

    Arisa Nishimukai, Natsuko Inoue, Ayako Kira, Masashi Takeda, Koji Morimoto, Kazuhiro Araki, Kazuhiro Kitajima, Takahiro Watanabe, Seiichi Hirota, Toyomasa Katagiri, Shoji Nakamori, Kouhei Akazawa, Yasuo Miyoshi

    PLOS ONE12 ( 9 ) e0184508   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    It has been well established that maximum standardized uptake value (SUVmax) for F-18-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p&lt;0.0001), but there was no significant association between pMAPK expression levels and SUVmax levels. Multivariable analysis showed that a high geminin level (odds ratio: 6.497, 95% confidence interval: 2.427-19.202, p = 0.0001) and large tumor size (6.438, 2.224-20.946, p = 0.0005) were significantly and independently associate d with SUVmax-high. Univariable but not multivariable analysis indicated that Ki67-high significantly correlated with SUVmax-high. Twenty of 23 (87.0%) breast cancers with tumor size &gt;2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers &lt;= 2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67-high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53.

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  • Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial 査読

    Yoshihiko Maehara, Ken Shirabe, Shunji Kohnoe, Yasunori Emi, Eiji Oki, Yoshihiro Kakeji, Hideo Baba, Masataka Ikeda, Michiya Kobayashi, Tadatoshi Takayama, Shoji Natsugoe, Masashi Haraguchi, Kazuhiro Yoshida, Masanori Terashima, Mitsuru Sasako, Hiroki Yamaue, Norihiro Kokudo, Katsuhiko Uesaka, Shinji Uemoto, Tomoo Kosuge, Yoshiki Sawa, Mitsuo Shimada, Yuichiro Doki, Masakazu Yamamoto, Akinobu Taketomi, Masahiro Takeuchi, Kouhei Akazawa, Takeharu Yamanaka, Mototsugu Shimokawa

    SURGERY TODAY47 ( 9 ) 1060 - 1071   2017年9月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Background The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI.
    Methods At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula.
    Results The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant.
    Conclusion The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.

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  • Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery 査読

    Masaki Sonoda, Hiroshi Masuda, Hiroshi Shirozu, Yosuke Ito, Kohei Akazawa, Eishi Asano, Shigeki Kameyama

    EPILEPSIA58 ( 9 ) 1556 - 1565   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Objective: To determine the predictors of cognitive function in patients with drugresistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT).
    Methods: We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as "high-functioning" (full-scale intelligence quotient [FSIQ] &gt;= 70; n = 48) and "low-functioning" group (FSIQ &lt;70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change.
    Results: Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p &lt; 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03).
    Significance: Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.

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  • Utility of comprehensive genomic sequencing for detecting HER2-positive colorectal cancer 査読

    Yoshifumi Shimada, Ryoma Yagi, Hitoshi Kameyama, Masayuki Nagahashi, Hiroshi Ichikawa, Yosuke Tajima, Takuma Okamura, Mae Nakano, Masato Nakano, Yo Sato, Takeaki Matsuzawa, Jun Sakata, Takashi Kobayashi, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii, Takashi Kawasaki, Kei-ichi Homma, Hiroshi Izutsu, Keisuke Kodama, Jennifer E. Ring, Alexei Protopopov, Stephen Lyle, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai

    HUMAN PATHOLOGY66   1 - 9   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    HER2-targeted therapy is considered effective for KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (CRC). In general, HER2 status is determined by the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Comprehensive genomic sequencing (CGS) enables the detection of gene mutations and copy number alterations including KRAS mutation and HER2 amplification; however, little is known about the utility of CGS for detecting HER2-positive CRC. To assess its utility, we retrospectively investigated 201 patients with stage I-IV CRC. The HER2 status of the primary site was assessed using IHC and FISH, and HER2 amplification of the primary site was also assessed using CGS, and the findings of these approaches were compared in each patient. CGS successfully detected alterations in 415 genes including KRAS codon 12/13 mutation and HER2 amplification. Fifty-nine (29%) patients had a KRAS codon 12/13 mutation. Ten (5%) patients were diagnosed as HER2 positive because of HER2 MC 3+, and the same 10 (5%) patients had HER2 amplification evaluated using CGS. The results of HER2 status and HER2 amplification were completely identical in all 201 patients (P &lt; .001). Nine of the 10 HER2-positive patients were KRAS 12/13 wild-type and were considered possible candidates for HER2-targeted therapy. CGS has the same utility as IHC and FISH for detecting HER2-positive patients who are candidates for HER2-targeted therapy, and facilitates precision medicine and tailor-made treatment. (C) 2017 The Authors. Published by Elsevier Inc.

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  • Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes 査読

    Kaori Tane, Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Kouhei Akazawa, Yasuo Miyoshi

    BREAST CANCER24 ( 4 ) 528 - 534   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs).
    For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline.
    Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2 % of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7 %, respectively. About 80 % of newly occurring symptoms were Grade 1, and less than 5 % were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5 %) during the first year and the mean time to onset was 5.6 months. Patients with vasomotor symptoms were significantly younger (mean 62.8 years, range 38-86 vs 64.7 years, range 37-84; p = 0.02), had higher body mass index (BMI) (23.4 kg/m(2), range 15.8-39.9 vs 22.4 kg/m(2), range 15.8-34.9; p = 0.01), had vasomotor symptoms sooner after menopause (12.4 years, range 0-51 vs 15.1 years, range 1-37; p = 0.002), and had more menopausal disorders during menopause (63.3 vs 36.7 %; p = 0.002). Multivariate analysis showed that BMI [odds ratio (OR) 1.09 per unit of increase, 95 % confidence interval (CI) 1.02-1.16; p = 0.009] and experiencing menopausal disorders (OR 2.11, 95 % CI 1.35-3.30; p = 0.001) were significantly associated with vasomotor symptoms.
    High BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.

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  • Heterogeneity in esophageal and gastric cardia precursor progression during six-year endoscopic surveillance after population-based screening in a Chinese high-risk region 査読

    Denggui Wen, Liwei Zhang, Xiaoling Wang, Xiaoduo Wen, Yi Yang, Yuetong Chen, Guiying Wang, Kohei Akazawa, Shijie Wang, Baoen Shan

    THORACIC CANCER8 ( 4 ) 328 - 336   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundThe study was conducted to examine esophageal and gastric cardia precursor progression.
    MethodsAfter population-based baseline screening, 145 precursor and 335 chronic inflammation cases were endoscopically surveyed for sixyears.
    ResultsSurveillance of interval and baseline diagnoses for 18 severe dysplasia (SD) cases later detected were: 13, 23, 39, and 44months since a diagnosis of chronic inflammation in four cases; 6, 6, 6, 11, 13, 16, 16, and 23months since mild dysplasia (mD) diagnoses in eight; and 6, 9, 10, 13, 18, and 48months since moderate dysplasia (MD) diagnoses in six. Rates for 11 carcinoma in situ (Cis) cases later detected were: 7 and 18months since basal cell hyperplasia (Bch) diagnoses in two; and 6, 6, 9, 13, 13, 18, 35, 44, and 50months since MD diagnoses in nine. In 10 cancer cases later detected, rates were: 6, 6, 7, 18, 19, 34, 36, and 48months since SD diagnoses in eight cases with submucosal carcinoma; 46months since MD diagnosis in a T2N0M0 carcinoma case; and 52months since Bch diagnosis in another T2N0M0 case.
    ConclusionEsophageal and gastric cardia precursors are heterogeneous. Male gender, advanced age, family history of upper gastrointestinal cancer, and multifocal dysplasia are significant independent predictors for progression, and Bch/mD, MD, and SD constitute three distinctive entities regarding the risk of cancer.

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  • Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer 査読

    Kohei Miyata, Fusanori Yotsumoto, Satoshi Fukagawa, Chihiro Kiyoshima, Nam Sung Ouk, Daichi Urushiyama, Tomohiro Ito, Takahiro Katsuda, Masamitsu Kurakazu, Ryota Araki, Ayako Sanui, Daisuke Miyahara, Masaharu Murata, Kyoko Shirota, Hiroshi Yagi, Tadao Takono, Kiyoko Kato, Nobuo Yaegashi, Kohei Akazawa, Masahide Kuroki, ShiN'Ichiro Yasunaga, Shingo Miyamoto

    ANTICANCER RESEARCH37 ( 7 ) 3955 - 3960   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Ovarian cancer is the most lethal malignancy among gynaecological cancers. Although many anticancer agents have been developed for the treatment of ovarian cancer, it continues to have an extremely poor prognosis. Heparin-binding epidermal growth factor-like grown factor (HB-EGF) has been reported to be a rational therapeutic target for ovarian cancer. Here, we evaluated the clinical significance of serum HB-EGF by examining the association between prognosis and serum HB-EGF levels in patients with primary ovarian cancer. We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease. In addition, serum HB-EGF levels increased as the cancer advanced. These data suggest that serum HB-EGF may be a target for the design of novel therapies for ovarian cancer.

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  • Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis 査読

    Harumi Gomi, Tadahiro Takada, Tsann-Long Hwang, Kohei Akazawa, Rintaro Mori, Itaru Endo, Fumihiko Miura, Seiki Kiriyama, Naohisa Matsunaga, Takao Itoi, Masamichi Yokoe, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 310 - 318   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundThe international practice guidelines for patients with acute cholangitis and cholecystitis were released in 2007 (TG07) and revised in 2013 (TG13). This study investigated updated epidemiology and outcomes among patients with acute cholangitis on a larger scale for the first time.
    MethodsThis is an international multi-center retrospective observational study in Japan and Taiwan. All consecutive patients older than 18years of age and given a clinical diagnosis of acute cholangitis by clinicians between 1 January 2011 and 31 December 2012 were enrolled. Those who met the diagnostic criteria of acute cholangitis by TG13 were statistically analyzed.
    ResultsA total of 7,294 patients were enrolled and 6,433 patients met the TG13 diagnostic criteria. The severity distribution was Grade I (37.5%), Grade II (36.2%), and Grade III (26.2%). The 30-day all-cause mortality was 2.4%, 4.7%, and 8.4% in Grade I, II, III severity, respectively (P&lt;0.001). The incidence of liver abscess and endocarditis as complications of acute cholangitis was 2.0% and 0.26%, respectively.
    ConclusionsThis is the first large scale study to investigate patients with acute cholangitis. This study provides the basis to define the best practices to manage patients with acute cholangitis in future studies.

    DOI: 10.1002/jhbp.452

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  • Descriptive review of acute cholecystitis: Japan-Taiwan collaborative epidemiological study 査読

    Masamichi Yokoe, Tadahiro Takada, Tsann-Long Hwang, Itaru Endo, Kohei Akazawa, Fumihiko Miura, Toshihiko Mayumi, Rintaro Mori, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Takao Itoi, Harumi Gomi, Seiki Kiriyama, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 319 - 328   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundSince the publication of the Tokyo Guidelines (TG13) for the management of acute cholecystitis (AC), multidirectional studies have been published. However, epidemiological research about AC with big data was not projected. The aim of this study was to reveal the actual clinical conditions of AC.
    MethodThe study was designed as an international multicenter retrospective study of AC in Japan and Taiwan from 2011 to 2013. The factors investigated comprised data related to demographic, history, physical examinations, laboratory and imaging findings. Based on these data, we investigated the various values of AC, and real situation with respect to severity and treatment.
    ResultsA total of 5,459 patients with AC were reviewed. Thirty-day mortality rate was 1.1%. Based on the diagnostic criteria, 4,088 patients had a definite diagnosis and 291 had a suspected diagnosis. According to the severity grading, 939 patients were classified as Grade III, 2,308 as Grade II, and 2,130 as Grade I. Cholecystectomy was performed in total of 4,266 patients and 2,765 patients had laparoscopic cholecystectomy. The main etiologies were gallbladder stones in 4,623 cases.
    ConclusionThis epidemiological study with large population will undoubtedly contribute to establish the best practice for managing AC worldwide.

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  • Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: an international multicenter observational study 査読

    Seiki Kiriyama, Tadahiro Takada, Tsann-Long Hwang, Kohei Akazawa, Fumihiko Miura, Harumi Gomi, Rintaro Mori, Itaru Endo, Takao Itoi, Masamichi Yokoe, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 329 - 337   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundThe Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study.
    MethodsWe reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated.
    ResultsA diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases.
    ConclusionBy using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

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  • Percutaneous and endoscopic gallbladder drainage for acute cholecystitis: international multicenter comparative study using propensity score-matched analysis 査読

    Takao Itoi, Tadahiro Takada, Tsann-Long Hwang, Itaru Endo, Kohei Akazawa, Fumihiko Miura, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Harumi Gomi, Masamichi Yokoe, Seiki Kiriyama, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 362 - 368   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundTokyo Guideline 2013 (TG13) proposed three drainage techniques for the treatment of acute cholecystitis. We evaluated the clinical efficacy and adverse events between percutaneous transhepatic intervention (PTGBI) including percutaneous transhepatic gallbladder drainage (PTGBD) and percutaneous transhepatic gallbladder aspiration (PTGBA) and endoscopic transpapillary gallbladder drainage (EGBD).
    MethodsA cohort study was performed using propensity score matching to reduce treatment selection bias. This involved the analysis of collected data for 1,764 patients who underwent PTGBI and EGBD.
    ResultsPropensity score matching extracted 330 pairs of patients. The difference in the clinical success rate within 3 days between PTGBI and EGBD were 62.5% and 69.8%, respectively (P = 0.085). The differences in the suboptimal clinical success rates within 7 days between PTGBI and EGBD were 87.6% and 89.2% (P = 0.579). The differences in the complication rate between PTGBI and EGBD were 4.8% and 8.2% (P = 0.083). The differences in the complication rate among PTGBD, PTGBA and EGBD were 5.6%, 1.6% and 8.2% (P = 0.11). Median required days of PTGBD (3.0 days) was significantly longer than those of PTGBA and EGBD (1.5 and 2.0 days, respectively) (P = 0.001).
    ConclusionThe current study showed the PTGBI showed similar clinical efficacy compared with EGBD without significant discrepancy of complication rate for the treatment of acute cholecystitis.

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  • Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan collaborative study for acute cholecystitis 査読

    Masamichi Yokoe, Tadahiro Takada, Tsann-Long Hwang, Itaru Endo, Kohei Akazawa, Fumihiko Miura, Toshihiko Mayumi, Rintaro Mori, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Takao Itoi, Harumi Gomi, Seiki Kiriyama, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 338 - 345   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundThe collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC.
    MethodThe study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis.
    ResultsAn investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P&lt;0.001). The greater the number of organ dysfunction, the higher the mortality rate (P&lt;0.001). However, the mortality rate varied depending on the number of organ dysfunction (3.1-25%). With respect to the surgical procedures, laparoscopic cholecystectomy was performed for Grade I patients (P&lt;0.001), and the higher the grade, the more likely open surgery would be selected (P&lt;0.001).
    ConclusionTG13 severity grading criteria for AC are providing great benefits in actual clinical settings. From this study, the position of each severity grade was obviously confirmed.

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  • Optimal treatment strategy for acute cholecystitis based on predictive factors: Japan-Taiwan multicenter cohort study 査読

    Itaru Endo, Tadahiro Takada, Tsann-Long Hwang, Kohei Akazawa, Rintaro Mori, Fumihiko Miura, Masamichi Yokoe, Takao Itoi, Harumi Gomi, Miin-Fu Chen, Yi-Yin Jan, Chen-Guo Ker, Hsiu-Po Wang, Seiki Kiriyama, Keita Wada, Hiroki Yamaue, Masaru Miyazaki, Masakazu Yamamoto

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES24 ( 6 ) 346 - 361   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    BackgroundAlthough early laparoscopic cholecystectomy is widely performed for acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill patients remains controversial. This study aims to determine the best practice for the patients presenting with acute cholecystitis focused on disease severity and comorbidities.
    MethodsAn international multicentric retrospective observational study was conducted over a 2-year period. Patients were divided into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy after gallbladder drainage; Group C: gallbladder drainage alone; and Group D: medical treatment alone.
    ResultsThe subjects of analyses were 5,329 patients. There were statistically significant differences in mortality rates between patients with Charlson comorbidity index (CCI) scores below and above 6 (P &lt; 0.001). The shortest operative time was observed in Group A patients who underwent surgery 0-3 days after admission (P &lt; 0.01). Multiple regression analysis revealed CCI and low body mass index &lt;20 as predictive factors of 30-day mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and respiratory dysfunction were predictive factors of 30-day mortality in Grade III patients. In Grade III patients without predictive factors, there were no difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%) in cases with at least one predictive factor.
    ConclusionEven patients with Grade III severity, primary cholecystectomy can be performed safely if they have no predictive factors of mortality. Gallbladder drainage may have a therapeutic role in subgroups with higher CCI or higher disease severity.

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  • Effects of an educational intervention on oral hygiene and self-care among people with mental illness in Japan: a longitudinal study 査読

    Hatsumi Yoshii, Nobutaka Kitamura, Kouhei Akazawa, Hidemitsu Saito

    BMC ORAL HEALTH17 ( 1 ) 81   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: The oral hygiene of patients with a mental illness is an important concern in psychiatric care, and it is necessary to increase the level of self-care among these patients. In this study, we administered an oral care questionnaire to people with mental illness in Japan and compared their answers before (baseline) and at 1 week and 1, 3 and 6 months after they participated in an educational program.
    Methods: The questionnaire was distributed to 390 patients. It included questions about age, education, income, between-meal snacks, number of teeth, frequency of tooth brushing, and other items. The educational program was developed for the purposes of improving self-care.
    Results: Before the program, the proportion of male patients who had had a mental illness for &gt;= 10 years was significantly higher among those patients who did not brush their teeth before bed. In addition, such patients did not have primary care dentists, and a significantly higher proportion of male patients, compared with female patients, did not undergo routine dental checkups more than once per year. The educational program resulted in an improvement in the use of fluoride toothpaste from baseline to 6 months after the intervention (p = 0.001). The daily use of interdental brushes or floss was significantly different 6 months after the intervention.
    Conclusions: Male and long-term inpatients need oral hygiene instructions. Our educational program showed the effects of using oral hygiene tools. Future studies should include a control group to measure the impact of the educational program.

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  • Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study 査読

    Motoi Azumi, Takeshi Suda, Shuji Terai, Kouhei Akazawa

    INTERNAL MEDICINE56 ( 9 ) 1001 - 1007   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables.
    Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score.
    Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74 +/- 0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54 +/- 0.03) and Japan Integrated Staging score (0.59 +/- 0.07).
    Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

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  • Analysis of Hospital Characteristics Affecting the Choice of Management Strategy Types: A Cross-Sectional Survey of Private Hospitals in Japan 査読

    Yuji Mitadera, Mayumi Watanabe, Nobuhiro Sato, Motoi Azumi, Kouhei Akazawa

    Health9 ( 11 ) 1494 - 1508   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/health.2017.911110

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  • Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis. 査読

    Takada T, Mikami A, Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Akasaka K, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Sugimoto C, Arai T, Hattori N, Watanabe K, Tamada T, Yoshizawa H, Akazawa K, Tanaka T, Yagi K, Young LR, McCormack FX, Nakata K

    Annals of the American Thoracic Society13 ( 11 ) 1912 - 1922   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1513/AnnalsATS.201605-335OC

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  • Nomogram for 5-year relapse-free survival of a patient with advanced gastric cancer after surgery 査読

    Yusuke Muneoka, Kohei Akazawa, Takashi Ishikawa, Hiroshi Ichikawa, Atsushi Nashimoto, Hiroshi Yabusaki, Norio Tanaka, Shin-ichi Kosugi, Toshifumi Wakai

    INTERNATIONAL JOURNAL OF SURGERY35   153 - 159   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Prognoses vary substantially among patients with advanced gastric cancer following curative surgery. The aim of the current study was to develop and verify the validity of a novel nomogram that predicts the probability of 5-year relapse-free survival (RFS) in patients who underwent curative resection for stage II/III gastric cancer.
    Materials and methods: A nomogram to predict 5-year RFS following surgical resection of gastric cancer was constructed based on the data of patients who underwent surgery for primary gastric carcinoma at three institutions in Japan in January 2001-December 2006. Multivariate analysis using a Cox proportional hazards regression model was performed, and the nomogram's predictive accuracy (discrimination) and the agreement between observed outcomes and predictions (calibration) were evaluated by internal validation.
    Results: Multivariate analyses revealed that age at operation, depth of tumor, tumor location, lymph node classification, and presence of combined resection were significant prognostic factors for RFS. In the internal validation, discrimination of the developed nomogram for 5-year RFS was superior to that of the American Joint Committee on Cancer TNM classification (concordance indices of 0.80 versus 0.67; P &lt; 0.001). Moreover, calibration appeared to be accurate. Based on these results, we have created free software to more easily predict 5-year RFS.
    Conclusion: We developed and validated a nomogram to predict 5-year RFS after curative surgery for stage II/III gastric cancer. This tool will be useful for the assessing a patient's individual recurrence risk when considering additional therapy in clinical practice. (C) 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

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  • Lobectomy and limited resection in small-sized peripheral non-small cell lung cancer 査読

    Terumoto Koike, Teruaki Koike, Seijiro Sato, Takehisa Hashimoto, Tadashi Aoki, Katsuo Yoshiya, Yasushi Yamato, Takehiro Watanabe, Kohei Akazawa, Shin-Ichi Toyabe, Masanori Tsuchida

    JOURNAL OF THORACIC DISEASE8 ( 11 ) 3265 - 3274   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PIONEER BIOSCIENCE PUBL CO  

    Background: Although lobectomy is the standard surgical procedure for non-small cell lung cancer (NSCLC), recent studies show favorable outcomes after limited resection in patients with small-sized peripheral tumors. We conducted a randomized controlled trial of such patients to estimate postoperative outcomes and pulmonary function following these surgical techniques.
    Methods: Between 2005 and 2008, eligible patients with tumors of 2 cm or less were randomly assigned 1: 1 to undergo lobectomy or limited resection; 32 and 33 NSCLC patients in each group, respectively, were analyzed. The primary end points were 5-year overall survival (OS) and disease-free survival (DFS), while the secondary end points were postoperative pulmonary function including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1).
    Results: The 5-year OS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.921). The 5-year DFS rates were 93.8% and 90.9% in the lobectomy and limited resection groups, respectively (P=0.714). These rates did not differ significantly between the two resection groups. The median postoperative/preoperative FVC ratios were 84.1% and 90.0% in the lobectomy and limited resection groups, respectively, while the median postoperative/preoperative FEV1 ratios were 81.9% and 89.1%, respectively. Both ratios were significantly higher in the limited resection group (P=0.032 and P=0.005 for FVC and FEV1 ratios, respectively).
    Conclusions: A similar outcome, with more preserved postoperative pulmonary function, was observed in patients who underwent limited resection compared to those who underwent lobectomy. Ongoing large-scale multi-institutional prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLCs will hopefully provide definitive information about intentional limited resection of small peripheral tumors.

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  • Therapeutic or spontaneous Helicobacter pylori eradication can obscure magnifying narrow-band imaging of gastric tumors. 査読

    Kobayashi M, Hashimoto S, Mizuno K, Takeuchi M, Sato Y, Watanabe G, Ajioka Y, Azumi M, Akazawa K, Terai S

    Endoscopy international open4 ( 6 ) E665 - 72   2016年6月

  • Hypothalamic hamartomas Response 査読

    Shigeki Kameyama, Hiroshi Shirozu, Hiroshi Masuda, Yosuke Ito, Masaki Sonoda, Kohei Akazawa

    JOURNAL OF NEUROSURGERY124 ( 5 ) 1502 - 1502   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    DOI: 10.3171/2015.4.JNS1582

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  • Mutation burden and microsatellite instability in colorectal cancer in Japan and US 査読

    Masayuki Nagahashi, Toshifumi Wakai, Yoshifumi Shimada, Hiroshi Ichikawa, Hitoshi Kameyama, Takashi Kobayashi, Masato Nakajima, Yusuke Muneoka, Kohei Akazawa, Kazuki Moro, Junko Tsuchida, Daiki Soma, Kizuki Yuza, Takuya Ando, Hiroshi Izutsu, Julie Tse, Shujiro Okuda, Kazuaki Takabe, Alexei Protopopov, Stephen Lyle

    JOURNAL OF CLINICAL ONCOLOGY34 ( 15 )   2016年5月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/JCO.2016.34.15_suppl.e15103

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  • Clinicopathological features in anterior visual pathway in neuromyelitis optica 査読

    Mariko Hokari, Akiko Yokoseki, Musashi Arakawa, Etsuji Saji, Kaori Yanagawa, Fumihiro Yanagimura, Yasuko Toyoshima, Kouichirou Okamoto, Satoshi Ueki, Tetsuhisa Hatase, Riuko Ohashi, Takeo Fukuchi, Kohei Akazawa, Mitsunori Yamada, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa, Izumi Kawachi

    ANNALS OF NEUROLOGY79 ( 4 ) 605 - 624   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    ObjectiveNeuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd.
    MethodsThirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
    ResultsThe AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Muller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON.
    InterpretationSevere and widespread neuroaxonal damage and unique dynamics of astrocytes/Muller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. Ann Neurol 2016;79:605-624

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  • Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers 査読

    Tomoko Yagi, Natsuko Inoue, Ayako Yanai, Keiko Murase, Michiko Imamura, Yoshimasa Miyagawa, Yukie Enomoto, Arisa Nishimukai, Yuichi Takatsuka, Seiichi Hirota, Kouhei Akazawa, Yasuo Miyoshi

    BREAST CANCER23 ( 2 ) 224 - 230   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Indication for chemotherapy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers is determined on the basis of Ki67 expression level. However, since Ki67-high cancers are not necessarily sensitive to chemotherapy, identification of such patients who do not need chemotherapy is an important issue.
    We used immunohistochemical staining to examine the expression levels of ER, progesterone receptor (PgR), Ki67, and geminin, a marker of S to G2/M phases, in 80 ER-positive/HER2-negative breast cancers. The labeling indices of Ki67 and geminin were determined and cutoff values were set at 15 and 6 %, respectively.
    Ki67 and geminin expression levels were significantly associated with nuclear grade. In the Ki67-low subset, 26 out of 28 (92.9 %) cancers were geminin low and in the Ki67-high subset, 31 out of 52 (59.6 %) were geminin high. Distant disease-free survival (DDFS) of the geminin-high subset was significantly poorer than that of the geminin-low subset (P = 0.009). In the Ki67-low subset, only one patient showed recurrence. Metastasis was detected in eight out of 31 (25.8 %) patients in the geminin-high group of the Ki67-high subset, but no recurrence was observed in the geminin-low group of the Ki67-high subset.
    Geminin-high breast cancers are significantly associated with worse prognosis. Since poorer prognosis was recognized only in the geminin-high group in Ki67-high cancers, we speculate that geminin may be useful for identifying patients in the Ki67-high subset who can avoid unnecessary chemotherapy.

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  • Microbiological and Clinical Effects of Sitafloxacin and Azithromycin in Periodontitis Patients Receiving Supportive Periodontal Therapy 査読

    Takako Nakajima, Takafumi Okui, Harue Ito, Mayuka Nakajima, Tomoyuki Honda, Yasuko Shimada, Koichi Tabeta, Kohei Akazawa, Kazuhisa Yamazaki

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY60 ( 3 ) 1779 - 1787   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate.

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  • Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma 査読

    Jun Sakata, Toshifumi Wakai, Yasunobu Matsuda, Taku Ohashi, Yuki Hirose, Hiroshi Ichikawa, Takashi Kobayashi, Masahiro Minagawa, Shin-ichi Kosugi, Yu Koyama, Kouhei Akazawa, Yoichi Ajioka

    ANNALS OF SURGICAL ONCOLOGY23 ( 1 ) 225 - 234   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma.
    A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model.
    Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or a parts per thousand yen2; P = 0.005) and the LNR (0, 0-5, or &gt; 5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes.
    The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

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  • Randomized Controlled Trial of Zoledronic Acid plus Chemotherapy versus Chemotherapy Alone as Neoadjuvant Treatment of HER2-Negative Primary Breast Cancer (JONIE Study) 査読

    Yoshie Hasegawa, Hirokazu Tanino, Jun Horiguchi, Daishu Miura, Takashi Ishikawa, Mitsuhiro Hayashi, Shintaro Takao, Seung Jin Kim, Kazuhiko Yamagami, Masaru Miyashita, Muneharu Konishi, Yasushi Shigeoka, Masato Suzuki, Tetsuya Taguchi, Tomoyuki Kubota, Kouhei Akazawa, Norio Kohno

    PLOS ONE10 ( 12 ) e0143643   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Purpose
    Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT).
    Methods
    Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)), followed by 12 cycles of paclitaxel at 80 mg/m(2) weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.
    Results
    This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and patients with triple-negative breast cancer. Further investigation is warranted.

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  • Effects of body mass index (BMI) on surgical outcomes: a nationwide survey using a Japanese web-based database 査読

    Motonari Ri, Hiroaki Miyata, Susumu Aikou, Yasuyuki Seto, Kohei Akazawa, Masahiro Takeuchi, Yoshiro Matsui, Hiroyuki Konno, Mitsukazu Gotoh, Masaki Mori, Noboru Motomura, Shinichi Takamoto, Yoshiki Sawa, Hiroyuki Kuwano, Norihiro Kokudo

    SURGERY TODAY45 ( 10 ) 1271 - 1279   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    To define the effects of body mass index (BMI) on operative outcomes for both gastroenterological and cardiovascular surgery, using the National Clinical Database (NCD) of the Japanese nationwide web-based database.
    The subjects of this study were 288,418 patients who underwent typical surgical procedures between January 2011 and December 2012. There were eight gastroenterological procedures, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy of &gt; 1 segment excluding the lateral segment, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis (n = 232,199); and five cardiovascular procedures, including aortic valve replacement, total arch replacement (TAR), descending thoracic aorta replacement (descending TAR), and on- or off-pump coronary artery bypass grafting (n = 56,219). The relationships of BMI with operation time and operative mortality for each procedure were investigated, using the NCD.
    Operation times were longer for patients with a higher BMI. When a BMI cut-off of 30 was used, the operation time for obese patients was significantly longer than that for non-obese patients, for all procedures except esophagectomy (P &lt; 0.01). The mortality rate based on BMI revealed a U-shaped distribution, with both underweight and obese patients having high mortality rates for almost all procedures.
    This Japanese nationwide study provides solid evidence to reinforce that both obesity and excessively low weight are factors that impact operative outcomes significantly.

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  • NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K⁺ transport that controls the electrochemical properties in the mammalian cochlea. 査読

    Yoshida T, Nin F, Ogata G, Uetsuka S, Kitahara T, Inohara H, Akazawa K, Komune S, Kurachi Y, Hibino H

    Pflugers Archiv : European journal of physiology467 ( 7 ) 1577 - 1589   2015年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00424-014-1597-9

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  • Gonadotropin-releasing hormone antagonist: A real advantage? 査読

    Takahiro Kimura, Hiroshi Sasaki, Kouhei Akazawa, Shin Egawa

    UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS33 ( 7 ) 322 - 328   2015年7月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE INC  

    Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist that is approved for the treatment of prostate cancer. GnRH antagonists bind directly to and block GnRH receptors, without causing the initial testosterone surge associated with GnRH agonists. A pivotal phase El study indicated that degarelix induced significantly faster reduction of testosterone and prostate-specific antigen level than GnRH agonist does. In addition, its 5-year extension trial suggested that patients could be safely switched from GnRH agonist to degarelix treatment with sustained efficacy, as measured by biochemical markers. Possible benefits of GnRH antagonists over agonists were suggested especially in patients with advanced prostate cancer with metastatic and symptomatic disease. Moreover, the recent reports including pooled data analyses on degarelix suggest improved disease control, quality of life, and lower urinary tract symptoms and decreased risk of cardiovascular diseases when compared with GnRH agonists. However, interpretation of these reports should be conducted cautiously because of the potential biases involved. This article critically reviews the results of the clinical trials and subsequent analyses and evaluates the points and counterpoints of the conclusions. (C) 2015 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.urolonc.2015.04.013

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  • Exploring biomarkers of response to zoledronic acid in breast cancer from clinical trial result of neoadjuvant chemotherapy with zoledronic acid: JONIE-1 study 査読

    Takafumi Sangai, Takashi Ishikawa, Norio Kohno, Daishu Miura, Eiichi Sato, Hiroshi Kaise, Masato Suzuki, Yoshie Hasegawa, Hirokazu Tanino, Jun Horiguchi, Kohei Akazawa

    CANCER RESEARCH75   2015年5月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.SABCS14-P6-01-02

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  • Dialysis Patients' Utilization of Health Care Services Covered by Long-Term Care Insurance in Japan 査読

    Utako Shimizu, Yuji Mitadera, Hagiko Aoki, Kouhei Akazawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE236 ( 1 ) 9 - 19   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TOHOKU UNIV MEDICAL PRESS  

    Hemodialysis patients in Japan are aging and thus more patients need support for attending hemodialysis facilities. This study aimed to clarify how dialysis patients utilize the services covered by Japan's public long-term care insurance (LTCI) system. This cross-sectional study was based on LTCI data of March 31, 2009, the latest available data provided by Niigata City, located on the northwest coast of Honshu. Among 30,349 LTCI users in Niigata City, there were 234 dialysis patients. To clarify the characteristics of the dialysis patients, we compared the utilization of LTCI services between the dialysis patients (234 users) and randomly selected 765 non-dialysis users. We also calculated the annual transportation service costs per patient for dialysis patients who continued home care (home care group) and those who switched to long-term hospital care at LTCI care levels 4 and 5 (hospital admission group). These care levels indicate difficulty in walking or maintaining a sitting posture without assistance. The dialysis group more frequently utilized home care and equipment services, such as renting or purchasing care-support products and support for home equipment repair, and utilized facility services and short-stay services (respite care) less frequently (both p &lt; 0.001). Cost per patient was higher in the home care group than in the hospital admission group, because the transportation services for dialysis patients at care levels 4 and 5 involve higher costs. These findings indicate that LTCI services usable for dialysis patients were limited. Therefore, instead of merely subsidizing transportation expenses, transportation services must be improved. (C) 2015 Tohoku University Medical Press

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  • Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials 査読

    Judith R. Kroep, Ayoub Charehbili, Rob E. Coleman, Rebecca L. Aft, Yoshie Hasegawa, Gerrit-Jan Liefers, Matthew C. Winter, Katherine N. Weilbaecher, Kohei Akazawa, Samantha Hinsley, Hein Putter, Hans W. R. Nortier, Norio Kohno

    CANCER RESEARCH75   2015年5月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    DOI: 10.1158/1538-7445.SABCS14-P3-11-04

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  • Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging 査読

    Tsutomu Kanefuji, Toru Takano, Takeshi Suda, Kouhei Akazawa, Takeshi Yokoo, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Hidefumi Aoyama, Minoru Nomoto, Shuji Terai

    WORLD JOURNAL OF GASTROENTEROLOGY21 ( 15 ) 4583 - 4591   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BAISHIDENG PUBLISHING GROUP INC  

    AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules (NHNs) with higher aggressiveness from less hazardous one.
    METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew that the patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, alpha-fetoprotein, des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations.
    RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm (interquartile range: 8-12 mm) grew or shrank by 68.5% (fifty nodules) or 20.5% (fifteen nodules), respectively, whereas hypervascularity developed in 38.4% (twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0% (eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-gamma- carboxy prothrombin, and -4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% +/- 5.7%, 83.8% +/- 13.6%, and 87.3% +/- 4.5% in the bootstrap samples.
    CONCLUSION: These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.

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  • Body Weight Reduction Results in Favorable Changes in Blood Pressure, Serum Lipids, and Blood Sugar in Middle-Aged Japanese Persons: A 5-Year Interval Observational Study of 26,824 Cases. 査読

    Mandai N, Akazawa K, Hara N, Ide Y, Ide K, Dazai U, Chishaki A, Chishaki H

    Global journal of health science7 ( 5 ) 159 - 70   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Statistical Properties and Power Analysis of Cox ’ s Proportional Hazards Model Regularized by Various Penalties for DNA Microarray Gene Expression Survival Data 査読

    Nobutaka Kitamura, Kouhei Akazawa, Kosuke Yoshihara

    Journal of Health & Medical Informatics6 ( 1 )   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4172/2157-7420.1000180

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  • Prognostic Significance of Initial Recurrence Site in Hematogenous Recurrence of Esophageal Squamous Cell Carcinoma 査読

    Hiroshi Ichikawa, Shin-ichi Kosugi, Tatsuo Kanda, Takashi Ishikawa, Kazuhito Yajima, Kohei Akazawa, Tsutomu Suzuki, Toshifumi Wakai

    HEPATO-GASTROENTEROLOGY61 ( 136 ) 2241 - 2246   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:H G E UPDATE MEDICAL PUBLISHING S A  

    Background/Aims: Hematogenous recurrences of esophageal squamous cell carcinoma (ESCC) have dismal prognoses, but prognostic heterogeneity exists in this disease. The objectives of this study were to clarify the prognosis in this disease with regard to the initial recurrence site and to define the prognostic factors. Methodology: We retrospectively reviewed the cases of 67 consecutive patients with hematogenous recurrence in major organs after esophagectomy for ESCC of the thoracic esophagus and the esophagogastric junction. We analyzed clinicopathological characteristics, survival probability and potential prognostic factors. Results: Lung, liver, bone, and multiple-organ metastases occurred in 24, 19, 14, and 10 patients, respectively. Twenty-seven patients simultaneously had locoregional recurrence (combined recurrence). Among all 67 patients, the median disease-free interval (DFI) was 9.7 months, and the median survival time after the initial recurrence was 4.9 months. The patients with initial lung metastasis had most favorable prognosis with the median survival time of 9.8 months. A multivariate analysis identified that initial recurrence site, DFI, combined recurrence, and anticancer therapy were independent prognostic factors. Conclusions: The initial recurrence site contributes to the prognostic heterogeneity of patients with hematogenous recurrence of ESCC. The prognostic factors identified in this study are useful to optimize the management of these patients.

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  • Reliability and validity of the workplace social distance scale. 査読

    Yoshii H, Mandai N, Saito H, Akazawa K

    Global journal of health science7 ( 3 ) 46 - 51   2014年10月

  • Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease 査読

    A. Miyashita, H. Hatsuta, M. Kikuchi, A. Nakaya, Y. Saito, T. Tsukie, N. Hara, S. Ogishima, N. Kitamura, K. Akazawa, A. Kakita, H. Takahashi, S. Murayama, Y. Ihara, T. Ikeuchi, R. Kuwano

    TRANSLATIONAL PSYCHIATRY4   e396   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimer's disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted whole-genome exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), I-II (N = 20), III-IV (N = 19) and V-VI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30), and in patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Protein-protein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.

    DOI: 10.1038/tp.2014.35

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  • Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer 査読

    S. Hirabayashi, S. Kosugi, Y. Isobe, A. Nashimoto, I. Oda, K. Hayashi, I. Miyashiro, S. Tsujitani, Y. Kodera, Y. Seto, H. Furukawa, H. Ono, S. Tanabe, M. Kaminishi, S. Nunobe, T. Fukagawa, R. Matsuo, T. Nagai, H. Katai, T. Wakai, K. Akazawa

    ANNALS OF ONCOLOGY25 ( 6 ) 1179 - 1184   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003).
    Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set.
    Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P &lt; 0.001). Moreover, calibration was accurate.
    We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

    DOI: 10.1093/annonc/mdu125

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  • Hypertrophic pachymeningitis: significance of myeloperoxidase anti-neutrophil cytoplasmic antibody 査読

    Akiko Yokoseki, Etsuji Saji, Musashi Arakawa, Takayuki Kosaka, Mariko Hokari, Yasuko Toyoshima, Kouichirou Okamoto, Shigeki Takeda, Kazuhiro Sanpei, Hirotoshi Kikuchi, Shunsei Hirohata, Kouhei Akazawa, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa, Izumi Kawachi

    BRAIN137   520 - 536   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    The aim of this study was to elucidate the characteristics, pathogenesis and treatment strategy of hypertrophic pachymeningitis that is associated with myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA). We retrospectively investigated clinical, radiological, immunological and pathological profiles of 36 patients with immune-mediated or idiopathic hypertrophic pachymeningitis, including 17 patients with myeloperoxidase-ANCA, four patients with proteinase 3-ANCA, six patients with other immune-mediated disorders, and nine patients with 'idiopathic' variety. Myeloperoxidase-ANCA-positive hypertrophic pachymeningitis was characterized by: (i) an elderly female predominance; (ii) 82% of patients diagnosed with granulomatosis with polyangiitis (previously known as Wegener's granulomatosis) according to Watts' algorithm; (iii) a high frequency of patients with lesions limited to the dura mater and upper airways, developing headaches, chronic sinusitis, otitis media or mastoiditis; (iv) a low frequency of patients with the 'classical or generalized form' of granulomatosis with polyangiitis involving the entire upper and lower airways and kidney, or progressing to generalized disease, in contrast to proteinase 3-ANCA-positive hypertrophic pachymeningitis; (v) less severe neurological damage according to the modified Rankin Scale and low disease activity according to the Birmingham Vasculitis Activity Score compared with proteinase 3-ANCA-positive hypertrophic pachymeningitis; (vi) increased levels of CXCL10, CXCL8 and interleukin 6 in cerebrospinal fluids, and increased numbers of T cells, neutrophils, eosinophils, plasma cells and monocytes/macrophages in autopsied or biopsied dura mater with pachymeningitis, suggesting T(H)1-predominant granulomatous lesions in hypertrophic pachymeningitis, as previously reported in pulmonary or renal lesions of granulomatosis with polyangiitis; and (vii) greater efficacy of combination therapy with prednisolone and cyclophosphamide compared with monotherapy with prednisolone. Proteinase 3-ANCA may be considered a marker for more severe neurological damage, higher disease activity and a higher frequency of the generalized form compared with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. However, categorization into 'granulomatosis with polyangiitis' according to Watts' algorithm and immunological or pathological features were common in both proteinase 3- and myeloperoxidase-ANCA-positive hypertrophic pachymeningitis. These data indicate that most patients with myeloperoxidase-ANCA-positive hypertrophic pachymeningitis should be categorized as having the central nervous system-limited form of ANCA-associated vasculitis, consistent with the concept of ophthalmic-, pulmonary- or renal-limited vasculitis.

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  • A phase II study of second-line S-1/CPT-11+bev for advanced colon cancer (NCCSG04): Subset analysis by K-ras, EGFR, UGT1A1, and previous bevacizumab. 査読

    Yasumasa Takii, Kouichi Furukawa, Satoshi Maruyama, Toshiyuki Yamazaki, Atsushi Nishimura, Mikako Kawahara, Takemi Tomiyama, Kohei Akazawa, Katsuyoshi Hatakeyama

    JOURNAL OF CLINICAL ONCOLOGY32 ( 3 )   2014年1月

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    記述言語:英語   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    DOI: 10.1200/jco.2014.32.3_suppl.564

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  • Characteristics linked to the reduction of stigma towards schizophrenia: a pre-and-post study of parents of adolescents attending an educational program 査読

    Ling Y, Watanabe M, Yoshii H, Akazawa K

    BMC Public Health14 ( 1 ) 258 - 258   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/1471-2458-14-258.

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  • Phase I/II trial of irinotecan and S-1 combination chemotherapy as a second-line treatment for advanced colorectal cancer 査読

    Yasumasa Takii, Toshiyuki Yamazaki, Takayuki Okada, Tatsuo Tani, Kazuhiro Funakoshi, Satoshi Maruyama, Jun Hasegawa, Kouhei Akazawa, Katsuyoshi Hatakeyama

    Chemotherapy59 ( 5 ) 338 - 343   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    Background: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC). Methods: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15. The irinotecan dose was then escalated to determine the maximum-tolerated dose and the recommended dose at a fixed dosage of S-1 (80 or 65 mg·m-2·day-1). The S-1 dose was reduced to 65 mg·m-2·day-1 when dose-limiting toxicities were observed at 80 mg·m-2· day-1 and the irinotecan dose was increased. Results: The recommended dose was 65 mg/m2 for S-1 and 75 mg/m2 for irinotecan. Twenty-one patients were treated at the recommended dose. The overall response rate was 28.6%. Conclusion: This modified IRIS regimen is considered effective with acceptable toxicities for advanced CRC resistant to treatment with 5-fluorouracil/leucovorin or uracil and tegafur/leucovorin. © 2014 S. Karger AG, Basel.

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  • Lack of genetic association between TREM2 and late-onset Alzheimer's disease in a Japanese population. 査読 国際誌

    Akinori Miyashita, Yanan Wen, Nobutaka Kitamura, Etsuro Matsubara, Takeshi Kawarabayashi, Mikio Shoji, Naoki Tomita, Katsutoshi Furukawa, Hiroyuki Arai, Takashi Asada, Yasuo Harigaya, Masaki Ikeda, Masakuni Amari, Haruo Hanyu, Susumu Higuchi, Masatoyo Nishizawa, Masaichi Suga, Yasuhiro Kawase, Hiroyasu Akatsu, Masaki Imagawa, Tsuyoshi Hamaguchi, Masahito Yamada, Takashi Morihara, Masatoshi Takeda, Takeo Takao, Kenji Nakata, Ken Sasaki, Ken Watanabe, Kenji Nakashima, Katsuya Urakami, Terumi Ooya, Mitsuo Takahashi, Takefumi Yuzuriha, Kayoko Serikawa, Seishi Yoshimoto, Ryuji Nakagawa, Yuko Saito, Hiroyuki Hatsuta, Shigeo Murayama, Akiyoshi Kakita, Hitoshi Takahashi, Haruyasu Yamaguchi, Kohei Akazawa, Ichiro Kanazawa, Yasuo Ihara, Takeshi Ikeuchi, Ryozo Kuwano

    Journal of Alzheimer's disease : JAD41 ( 4 ) 1031 - 8   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

    DOI: 10.3233/JAD-140225

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  • Simulation Program to Determine Sample Size and Power for a Multiple Logistic Regression Model with Unspecified Covariate Distributions 査読

    Naoko Kumagai, Kohei Akazawa, Hiromi Kataoka, Yutaka Hatakeyama, Yoshiyasu Okuhara

    Helth6 ( 21 ) 2973 - 2998   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/health.2014.621336

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  • Heavy alcohol intake is a risk factor for esophageal squamous cell carcinoma among middle-aged men: A case-control and simulation study. 査読

    Kumagai N, Wakai T, Akazawa K, Ling Y, Wang S, Shan B, Okuhara Y, Hatakeyama Y, Kataoka H

    Molecular and clinical oncology1 ( 5 ) 811 - 816   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/mco.2013.142

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  • Growth of Japanese breastfed infants compared to national references and World Health Organization growth standards 査読

    H. Tanaka, H. Ishii, T. Yamada, K. Akazawa, S. Nagata, Y. Yamashiro

    ACTA PAEDIATRICA102 ( 7 ) 739 - 743   2013年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim The aim of this study was to compare the growth of Japanese infants that were exclusively breastfed to those of national references and World Health Organization (WHO) standards.
    Methods Mothers, who delivered a normal term baby and had been exclusively breastfeeding for at least 4months, were enrolled. The lengths, body weights and head circumferences of 647 children, aged 0-24months, were obtained and compared to national references and WHO standards.
    Results Comparisons of the national references for both length and body weight indicated that breastfed infants were significantly shorter and lighter almost throughout the first 24months. Conversely, head circumferences of breastfed infants were significantly larger at 1 and 6months of age in boys and 6months in girls. Compared to WHO standards, similar trends to the comparisons with national references were found.
    Conclusion There were significant differences identified between the growth of breastfed infants and existing national references and WHO standards.

    DOI: 10.1111/apa.12262

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  • Randomized phase III clinical study comparing postoperative UFT/LV, UFT plus LV/UFT and UFT plus LV plus PSK/UFT plus PSK as adjuvant therapy for curatively resected stage III colorectal cancer HGCSG-CAD study 査読

    Shichinohe Toshiaki, Komatsu Yoshito, Akazawa Kohei, Yuki Satoshi, Fukushima Hiraku, Ohno Kouichi, Nakamura Fumitaka, Kusumi Takaya, Morita Takayuki, Senmaru Naoto, Kumagai Naoko, Hirano Satoshi

    JOURNAL OF CLINICAL ONCOLOGY31 ( 15 )   2013年5月

  • Suspected limited efficacy of γ-secretase modulators. 査読

    Kakuda N, Akazawa K, Hatsuta H, Murayama S, Ihara Y, Japanese Alzheimer's, Disease Neuroimaging Initiative

    Neurobiology of aging34 ( 4 ) 1101 - 1104   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.neurobiolaging.2012.08.017

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  • Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: A cost-effectiveness analysis 査読

    Shota Saito, Utako Shimizu, Zhang Nan, Nozomu Mandai, Junji Yokoyama, Kenshi Terajima, Kouhei Akazawa

    JOURNAL OF CROHNS & COLITIS7 ( 2 ) 167 - 174   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease.
    Aim: To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD.
    Methods: A decision analysis model is constructed to compare, over a time horizon of 1 year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-alpha therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results.
    Results: The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750.
    Conclusions: Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

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  • Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry 査読

    Atsushi Nashimoto, Kohei Akazawa, Yoh Isobe, Isao Miyashiro, Hitoshi Katai, Yasuhiro Kodera, Shunichi Tsujitani, Yasuyuki Seto, Hiroshi Furukawa, Ichiro Oda, Hiroyuki Ono, Satoshi Tanabe, Michio Kaminishi

    GASTRIC CANCER16 ( 1 ) 1 - 27   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Background The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008.
    Methods From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed.
    Results The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.
    Conclusions Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed.

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  • Cognitive Impairment and Cortical Degeneration in Neuromyelitis Optica 査読

    Etsuji Saji, Musashi Arakawa, Kaori Yanagawa, Yasuko Toyoshima, Akiko Yokoseki, Kouichirou Okamoto, Mika Otsuki, Kohei Akazawa, Akiyoshi Kakita, Hitoshi Takahashi, Masatoyo Nishizawa, Izumi Kawachi

    ANNALS OF NEUROLOGY73 ( 1 ) 65 - 76   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Objective: Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains.
    Methods: Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd.
    Results: In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessments showed neuronal loss in cortical layers II, III, and IV, with nonlytic reaction of aquaporin-4 (AQP4)-negative astrocytes in layer I, massive activated microglia in layer II, and meningeal inflammation in NMOsd brains. All NMO cases showed no evidence of cortical demyelination.
    Interpretation: We demonstrate cognitive impairment and substantial cortical neuronal loss with unique AQP4 dynamics in astrocytes in NMOsd. These data indicate pathological processes consisting not only of inflammatory demyelinating events characterized by pattern-specific loss of AQP4 immunoreactivity but also cortical neurodegeneration in NMOsd brains. ANN NEUROL 2013;73:65-76

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  • SORL1 is Genetically Associated with Neuropathologically Characterized Late-Onset Alzheimer's Disease 査読

    Yanan Wen, Akinori Miyashita, Nobutaka Kitamura, Tamao Tsukie, Yuko Saito, Hiroyuki Hatsuta, Shigeo Murayama, Akiyoshi Kakita, Hitoshi Takahashi, Hiroyasu Akatsu, Takayuki Yamamoto, Kenji Kosaka, Haruyasu Yamaguchi, Kohei Akazawa, Yasuo Ihara, Ryozo Kuwano

    JOURNAL OF ALZHEIMERS DISEASE35 ( 2 ) 387 - 394   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IOS PRESS  

    SORL1 was shown to be genetically associated with late-onset Alzheimer's disease (LOAD) in a large-scale genome-wide association study (GWAS) involving clinically verified subjects. Here, we attempted to replicate the association of SORL1 in Japanese neuropathologically characterized brain donor subjects (LOAD, 213; control, 370) through a single-nucleotide polymorphism (SNP)-based genetic study involving 19 SNPs: 11 SNPs were selected from the initial study reported by Rogaeva et al. (2007), and the other eight were from our GWAS. Among these SNPs, five exhibited a significant association with LOAD after multiple test correction (p &lt; 2.63E-03 [=0.05/19]), which was supported by means of multiple logistic regression analysis with adjustment for age, gender, and carrier status of the APOE epsilon 4 allele. Three of these SNPs (rs985421, rs12364988 [Rogaeva's SNP 7], and rs4598682) were encompassed by a 5' linkage disequilibrium (LD) region, and the remaining two (rs3781834 and rs3781836) by a 3' LD region. Strong LD among SNPs was observed within each LD region, implying that there are two genomic regions showing association with LOAD in SORL1. Case-control haplotype analysis demonstrated that some haplotypes are associated with LOAD in both LD regions. Our replication study strongly supports the preceding evidence that SORL1 is likely one of the genes associated with LOAD.

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  • The effects of application of an ancient type of acupuncture needle on increase in urination of hospitalized oldest-old people. 査読

    Watanabe M, Takano O, Tomiyama C, Guan J, Hou G, Mori H, Nishijo K, Abo T, Akazawa K

    Health5 ( 7 ) 1092 - 1098   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4236/health.2013.57147

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  • Factors Related to Postoperative Delirium in Patients with Lower Limb Ischaemia: A Prospective Cohort Study 査読

    Y. Sasajima, T. Sasajima, N. Azuma, K. Akazawa, Y. Saito, M. Inaba, H. Uchida

    EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY44 ( 4 ) 411 - 415   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO LTD  

    Objectives: To preoperatively determine candidates at definitive risk of postoperative delirium (POD), we identified relevant factors in patients with arteriosclerosis obliterans who underwent bypass surgery.
    Design: A prospective cohort study.
    Patients and methods: 299 patients (age &gt;= 60 years) who underwent bypasses in 1995-2006 were enrolled. Cognitive impairment was assessed by the Revised Hasegawa Dementia Scale, the Confusion Assessment Method was also used, and severity was graded as Grade I Ill (mild to severe) based on the Delirium Rating Scale. All patients were followed for 3 years.
    Results: POD occurred in 88 patients (29%), with a median age of 75 (10) years (IQR). Onset was 2 (1)days postoperatively, and a duration of 2 (2) days was observed. POD was hyperactive in 89% and was Grade II, and III in 11%, 68%, and 21% respectively. Multiple logistic regression analysis identified the following risk factors for POD: age &gt;= 72 years (&lt;0.0001), end-stage renal failure (0.001), multiple occlusive lesions (&lt;0.0001), cognitive impairment (0.003), and critical limb ischaemia (0.034). The 3-year survival rate was similar when comparing POD and non-POD patients (84% vs. 88%, NS).
    Conclusions: This study identified 5 risk factors for POD in patients undergoing bypasses for limb ischaemia. Long-term outcomes were similar when comparing the patients who experienced POD with those who did not. (C) 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.ejvs.2012.06.028

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  • Long-term chemotherapy may prolong survival in advanced non-small-cell lung cancer among responders to first-line chemotherapy 査読

    Tomonori Hirashima, Hidekazu Suzuki, Masashi Kobayashi, Youko Kondoh, Yoshie Tokuoka, Yuka Matsuura, Motohiro Tamiya, Naoko Morishita, Shinji Sasada, Norio Okamoto, Kohei Akazawa, Ichiro Kawase

    MEDICAL ONCOLOGY29 ( 3 ) 1629 - 1637   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    Survival in patientswith advanced non-small-cell lung cancer (NSCLC) has substantially improved. Long-term chemotherapy with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) and other agents has been associated with long survival. We retrospectively examined the associations between overall survival (OS) and clinical variables in patients with advanced NSCLC who received at least one dose or course of outpatient chemotherapy in our institution. Of 360 patients who received first-line chemotherapy between January 1, 2004 and December 31, 2007, 185 subsequently received additional outpatient chemotherapy and 175 underwent inpatient chemotherapy only. Of the 185 patients, 147 (79.5%), 96 (51.9%), and 60 (32.4%) received second-line, third-line, and fourth-line chemotherapy, respectively. Patients who received outpatient chemotherapy had significantly longer median OS (22.3 months) than did those undergoing inpatient chemotherapy only (7.6 months; P &lt; 0.0001). In univariate analysis of the 185 patients, sex, performance status (PS), smoking status, stage, best response to first-line chemotherapy, use of docetaxel, and EGFR-TKIs were significantly associated with OS (P values: 0.0019, 0.0066, 0.0001, 0.0231, 0.0011, 0.0250, and 0.0023, respectively). In multivariate analysis, PS, stage, best response to first-line chemotherapy, and use of docetaxel were significantly associated with OS (P values: 0.0272, 0.0030, 0.0022, and 0.0376, respectively). Survival was significantly longer among patients who responded to docetaxel and/or EGF-RTKIs. Long-term chemotherapy did not increase cumulative hospitalization. In patients with advanced NSCLC, an effective long-termchemotherapy regimen might prolong survival in responders to first-line chemotherapy.

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  • Effects of systemic sitafloxacin on periodontal infection control in elderly patients 査読

    Takako Nakajima, Takafumi Okui, Sayuri Miyauchi, Tomoyuki Honda, Yasuko Shimada, Harue Ito, Kohei Akazawa, Kazuhisa Yamazaki

    GERODONTOLOGY29 ( 2 ) E1024 - E1032   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Effects of systemic sitafloxacin on periodontal infection control in elderly patients
    Objective: To evaluate the microbiological and clinical effects of the systemic administration of sitafloxacin (STFX) on periodontal pockets in elderly patients receiving supportive periodontal therapy (SPT).
    Background: Periodontitis is a risk factor for atherosclerosis. Better periodontal health contributes to reduce atherosclerosis-related diseases in elderly population.
    Materials and methods: Forty-four patients undergoing SPT were randomly assigned to two groups: a test group took 100 mg/day of STFX for five consecutive days, or a control group received scaling and root planing (SRP) under local anaesthesia. Microbiological and clinical parameters were examined at baseline and at 1 and 3 months after therapy.
    Results: The presence of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia was significantly reduced at 1 month after treatment in both groups. The median reductions of the bacteria between the baseline and 1 month were 3.08 and 2.54% in the STFX- and SRP-treated groups, respectively. Both treatments significantly decreased the probing depth at 1 and 3 months compared to the baseline.
    Conclusion: The systemic administration of STFX is effective at improving periodontal health during SPT and could be an alternative to SRP for elderly patients who cannot undergo anaesthesia or are at risk of tissue injury.

    DOI: 10.1111/j.1741-2358.2011.00605.x

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  • Cost-effectiveness achieved through changing the composition of renal replacement therapy in Japan 査読

    Utako Shimizu, Shota Saito, Yiwei Lings, Noriaki Iino, Junichirou James Kazama, Kohei Akazawa

    Journal of Medical Economics15 ( 3 ) 444 - 453   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: The cost-effectiveness of renal replacement therapy (RRT) is affected by the composition of treatment. This study aimed to estimate the costs and outcomes associated with changing the composition of RRT modality over time. Methods: By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the four main treatments available for RRT in Japan. The model included direct health service costs and quality-adjusted life years (QALY). Sensitivity analyses were performed to assess the robustness of the results. Results: Over the 15-year period of the model, the current composition of RRT (i.e., the base composition of RRT) was $84,008/QALY. The most cost-effective treatment was when the likelihood of a living donor transplant was increased by 2.4-times ($70,581/QALY). Compared with the base composition of RRT, dominant treatments with respect to cost-effectiveness were when the likelihood of a deceased donor transplant was increased by 22-times and when the likelihood of a pre-emptive living donor transplant was increased by 2.4-times. Little difference was found between these two treatments. One-way sensitivity analysis did not change the cost effectiveness except for costs of chronic hemodialysis and a living donor transplant in subsequent years. Limitations: It is difficult to increase the rate of transplant overall in the shorter term nationally and internationally. Conclusions: Appropriate distribution of all transplant options and hemodialysis is necessary to achieve the most cost-effective solution. © 2012 Informa UK Ltd All rights reserved.

    DOI: 10.3111/13696998.2011.653512

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  • Altered γ-secretase activity in mild cognitive impairment and Alzheimer's disease. 査読

    Kakuda N, Shoji M, Arai H, Furukawa K, Ikeuchi T, Akazawa K, Takami M, Hatsuta H, Murayama S, Hashimoto Y, Miyajima M, Arai H, Nagashima Y, Yamaguchi H, Kuwano R, Nagaike K, Ihara Y, Japanese Alzheimer's, Disease Neuroimaging Initiative

    EMBO molecular medicine4 ( 4 ) 344 - 352   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway 査読

    Kosuke Yoshihara, Tatsuhiko Tsunoda, Daichi Shigemizu, Hiroyuki Fujiwara, Masayuki Hatae, Hisaya Fujiwara, Hideaki Masuzaki, Hidetaka Katabuchi, Yosuke Kawakami, Aikou Okamoto, Takayoshi Nogawa, Noriomi Matsumura, Yasuhiro Udagawa, Tsuyoshi Saito, Hiroaki Itamochi, Masashi Takano, Etsuko Miyagi, Tamotsu Sudo, Kimio Ushijima, Haruko Iwase, Hiroyuki Seki, Yasuhisa Terao, Takayuki Enomoto, Mikio Mikami, Kohei Akazawa, Hitoshi Tsuda, Takuya Moriya, Atsushi Tajima, Ituro Inoue, Kenichi Tanaka

    CLINICAL CANCER RESEARCH18 ( 5 ) 1374 - 1385   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Purpose: High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.
    Experimental Design: In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high-and low-risk ovarian cancer groups.
    Results: An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 x 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 x 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.
    Conclusions: This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients. Clin Cancer Res; 18(5); 1374-85. (C)2012 AACR.

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  • Association of Nitrogen Compounds in Drinking Water with Incidence of Esophageal Squamous Cell Carcinoma in Shexian, China 査読

    Nan Zhang, Cao Yu, Denggui Wen, Jun Chen, Yiwei Ling, Kenshi Terajima, Kohei Akazawa, Baoen Shan, Shijie Wang

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE226 ( 1 ) 11 - 17   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TOHOKU UNIV MEDICAL PRESS  

    The incidence of esophageal squamous cell carcinoma (ESCC), which is the eighth most common malignancy worldwide, is highest in China. The purpose of this study was to investigate the association between nitrogen compounds in drinking water with the incidence of ESCC by geographical spatial analysis. The incidence of ESCC is high in Shexian county, China, and environmental factors, particularly nitrogen-contaminated drinking water, are the main suspected risk factors. This study focuses on three nitrogen compounds in drinking water, namely, nitrates, nitrites, and ammonia, all of which are derived mainly from domestic garbage and agricultural fertilizer. The study surveyed 48 villages in the Shexian area with a total population of 54,716 (661 adults with ESCC and 54,055 non-cancer subjects). Hot-spot analysis was used to identify spatial clusters with a high incidence of ESCC and a high concentration of nitrogen compounds. Logistic regression analysis was used to detect risk factors for ESCC incidence. Most areas with high concentrations of nitrate nitrogen in drinking water had a high incidence of ESCC. Correlation analysis revealed a significant positive relationship between nitrate concentration and ESCC (P = 0.01). Logistic regression analysis also confirmed that nitrate nitrogen has a significantly higher odds ratio. The results indicate that nitrate nitrogen is associated with ESCC incidence in Shexian county. In conclusion, high concentrations of nitrate nitrogen in drinking water may be a significant risk factor for the incidence of ESCC.

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  • Study on levels of nitrate nitrogen, nitrite nitrogen and ammonia in drinking water in the high-incidence area of esophageal cancer. 査読

    Liang SY, Cao Y, Akazawa K, Chen ZF, Huang SB, Song GH, Li HG, Wang SJ

    Chinese Journal of Cancer Prevention and Treatment19 ( 9 ) 649 - 651+662   2012年

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  • Factors associated with an absence of effect of an education program for improving knowledge of schizophrenia. 査読

    Yoshii H, Watanabe Y, Kitamura H, Sakai Y, Akazawa K

    Global Journal of Health Science4 ( 4 ) 42 - 47   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Comparison of dynamic responses of cellular metabolites in Escherichia coli to pulse addition of substrates 査読

    Md. Aminul Hoque, Atefeh Taherian Fard, Mosfequr Rahman, Omar Alattas, Kohei Akazawa, Amir Feisal Merican

    BIOLOGIA66 ( 6 ) 954 - 966   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:VERSITA  

    We conducted an integrated study of cell growth parameters, product formation, and the dynamics of intracellular metabolite concentrations using Escherichia coli with genes knocked out in the glycolytic and oxidative pentose phosphate pathway (PPP) for glucose catabolism. We investigated the same characteristics in the wild-type strain, using acetate or pyruvate as the sole carbon source. Dramatic effects on growth parameters and extracellular and intracellular metabolite concentrations were observed after blocking either glycolytic breakdown of glucose by inactivation of phosphoglucose isomerase (disruption of pgi gene) or pentose phosphate breakdown of glucose by inactivation of glucose-6-phosphate dehydrogenase (disruption of zwf gene). Reducing power (NADPH) was mainly produced through PPP when the pgi gene was knocked out, while NADPH was produced through the tricarboxylic acid (TCA) cycle by isocitrate dehydrogenase or NADP-linked malic enzyme when the zwf gene was knocked out. As expected, when the pgi gene was knocked out, intracellular concentrations of PPP metabolites were high and glycolytic and concentrations of TCA cycle pathway metabolites were low. In the zwf gene knockout, concentrations of PPP metabolites were low and concentrations of intracellular glycolytic and TCA cycle metabolites were high.

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  • External Validation of the UCSF-CAPRA (University of California, San Francisco, Cancer of the Prostate Risk Assessment) in Japanese Patients Receiving Radical Prostatectomy 査読

    Fumio Ishizaki, Md. Aminul Hoque, Tsutomu Nishiyama, Takashi Kawasaki, Takashi Kasahara, Noboru Hara, Itsuhiro Takizawa, Toshihiro Saito, Yasuo Kitamura, Kohei Akazawa, Kota Takahashi

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY41 ( 11 ) 1259 - 1264   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Objective: In 2005, the University of California, San Francisco developed the Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score as a new risk stratification tool. The UCSF-CAPRA, which ranges from 0 to 10 points, consists of five clinical variables, prostate-specific antigen, Gleason score, T stage, percent of positive biopsies and age. The aim of this study was to validate the UCSF-CAPRA score for Japanese prostate cancer patients receiving radical prostatectomy using the contemporary Gleason grading.
    Methods: From 1999 to 2010, 211 men who underwent radical prostatectomy were used for validation. Biochemical progression-free survival was calculated using the Kaplan-Meier method and the UCSF-CAPRA and D&apos;Amico risk categories were compared using the log-rank method. The concordance index (c-index) for the UCSF-CAPRA and D&apos;Amico risk classification was calculated.
    Results: Using the UCSF-CAPRA score, 85 (40.3%), 106 (50.2%) and 20 (9.5%) subjects were stratified as 0-2 points (low risk), 3-5 points (intermediate risk) and 6-10 points (high risk). Using the D&apos;Amico risk criteria, 66 (31.3%), 89 (42.2%) and 56 (26.5%) were stratified as low-, intermediate- and high-risk groups, respectively. The Kaplan-Meier analysis showed that the UCSF-CAPRA divided the patients significantly into each risk category. There was no significant difference between low and intermediate in the D&apos;Amico risk classification. The c-index of the UCSF-CAPRA and D&apos;Amico classification was 0.755 and 0.713, respectively.
    Conclusion: The UCSF-CAPRA is an acceptable risk category tool comparable to that of the D&apos;Amico risk classification for Japanese prostate cancer patients receiving radical prostatectomy in the contemporary Gleason grading era.

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  • Gastric cancer treatment in Japan: 2008 annual report of the JGCA nationwide registry 査読

    Yoh Isobe, Atsushi Nashimoto, Kohei Akazawa, Ichiro Oda, Kenichi Hayashi, Isao Miyashiro, Hitoshi Katai, Shunichi Tsujitani, Yasuhiro Kodera, Yasuyuki Seto, Michio Kaminishi

    GASTRIC CANCER14 ( 4 ) 301 - 316   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registry in 2008. Approximately 50 data items, including surgical procedures, pathological diagnoses, and survival outcomes, for 12004 patients with primary gastric cancer treated in 2001 were collected retrospectively from 187 participating hospitals. Data were entered into the JGCA database according to the JGCA Classification of gastric carcinoma, 13th edition and the International Union Against Cancer (UICC) TNM Classification of malignant tumors, 5th edition by using an electronic data collecting system. Finally, data of 11261 patients with gastric resection were analyzed. The 5-year follow-up rate was 83.5%. The direct death rate was 0.6%. TNM 5-year survival rates (5YSRs)/JGCA 5YSRs were 91.8/91.9% for stage IA, 84.6/85.1% for stage IB, 70.5/73.1% for stage II, 46.6/51.0% for stage IIIA, 29.9/33.4% for stage IIIB, and 16.6/15.8% for stage IV. The proportion of patients more than 80 years old was 7.0%, and their 5YSR was 48.7%. Compared to the JGCA archived data, though the follow-up rate needs to be improved, these data suggest that the postoperative results of patients with primary gastric carcinoma have improved in those with advanced disease and in the aged population in Japan.

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  • Assessment of the Nodal Status in Ampullary Carcinoma: The Number of Positive Lymph Nodes Versus the Lymph Node Ratio 査読

    Jun Sakata, Yoshio Shirai, Toshifumi Wakai, Yoichi Ajioka, Kouhei Akazawa, Katsuyoshi Hatakeyama

    WORLD JOURNAL OF SURGERY35 ( 9 ) 2118 - 2124   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    This study was intended to compare the prognostic power of the number of positive lymph nodes with that of the lymph node ratio in patients with ampullary carcinoma.
    A retrospective analysis was conducted of the medical records of 71 consecutive patients with ampullary carcinoma who underwent pancreaticoduodenectomy with regional lymph node dissection. A total of 2151 lymph nodes were dissected (median: 28 nodes per patient) and examined histologically. Cutoff points were determined for both the number of positive nodes and the lymph node ratio using chi(2) scores calculated with the Cox proportional hazards regression model.
    Lymph node metastasis was found in 34 patients. The best cutoff point for the number of positive nodes was identified as three nodes, and that for the lymph node ratio was identified as 10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or a parts per thousand yen4; P &lt; 0.0001) and the lymph node ratio (0%, 0-10%, or &gt; 10%; P &lt; 0.0001) as significant prognostic factors. Multivariate analysis identified the number of positive nodes as an independent prognostic factor (P &lt; 0.001), whereas the lymph node ratio failed to remain as an independent variable. The cumulative 5-year survival rates were 85% for patients with 0 positive nodes, 63% for patients with 1-3 positive nodes, and 0% for patients with a parts per thousand yen4 positive nodes (P &lt; 0.0001).
    The number of positive lymph nodes better predicts the outcome after resection than the lymph node ratio in patients with ampullary carcinoma.

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  • Relationship between Heart Rate and Optimal Reconstruction Phase in Dual-source CT Coronary Angiography 査読

    Yosuke Horii, Norihiko Yoshimura, Yoshiro Hori, Toru Takano, Shoichi Inagawa, Kohei Akazawa, Hidefumi Aoyama

    ACADEMIC RADIOLOGY18 ( 6 ) 726 - 730   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Rationale and Objectives: To evaluate reconstruction image quality at the systolic and diastolic cardiac phases and determine the optimal phase for reconstruction according to heart rate when using dual-source computed tomography (CT) with 75 ms temporal resolution.
    Materials and Methods: We retrospectively reviewed the CT datasets of 35 patients with regular heartbeats who underwent coronary CT angiography. Images were reconstructed in 2% steps between 32 and 78% of the beat-to-beat interval. Two experienced radiologists determined the reconstruction interval with the fewest motion artifacts and the motion score of each vessel for the systolic and diastolic phases. Subgroup analysis was performed in patients having heart rates of &lt;70,70-80, and &gt;80 beats per minute (bpm).
    Results: In the subgroup with heart rates of &lt;70 bpm, the diastolic phase reconstruction image quality was significantly better than for the systolic phase (P &lt; .01). In the 70-80 bpm and &gt;80 bpm subgroups, no significant difference was observed. In the diastolic phase, the image quality of the &lt;70 bpm subgroup was significantly better than for the &gt;80 bpm subgroup (P &lt; .05). In all systolic phase subgroups and other diastolic phase subgroups, no significant difference was observed.
    Conclusions: Using a DSCT scanner with 75 ms temporal resolution, reconstruction at the diastolic phases should be used for patients with heart rates &lt;70 bpm. For heart rates &gt;70 bpm, larger studies are necessary to determine whether reconstruction at the systolic, diastolic, or both phases should be used.

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  • Alcohol Consumption as a Risk Factor for Esophageal Adenocarcinoma in North China 査読

    Jun Chen, Nan Zhang, Yiwei Ling, Toshifumi Wakai, Yutong He, Lizhen Wei, Shijie Wang, Kouhei Akazawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE224 ( 1 ) 21 - 27   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TOHOKU UNIV MEDICAL PRESS  

    The incidence of esophageal adenocarcinoma has been rising in many countries, while esophageal squamous cell carcinoma has remained stable or even declined in the same populations over the identical periods. These differences in trends indicate that these cancer subtypes may have a different etiology, which may be caused by lifestyle factors such as alcohol consumption and cigarette smoking. Therefore, a matched case-control study to clarify the risk factors of alcohol and tobacco intake on the development of esophageal adenocarcinoma was collected in Hebei Province of China. The life expectancy of the study area was around 70 years old. In the present study, 98 patients younger than 65 years who were diagnosed with esophageal adenocarcinoma and had initial surgeries (cases) were matched with 294 healthy adults (controls) at a ratio of 1:3 according to sex and age. We found the proportions of drinkers and smokers among cases were 48.0% and 60.2%, respectively, versus 21.2% and 43.5% among controls. Univariate conditional logistic regression analyses revealed that the odds ratios (ORs) showed a nearly monotonic increase for the duration of alcohol consumption and duration of tobacco smoking. Multivariate conditional logistic regression analysis indicated that only alcohol consumption was a significant risk factor for esophageal adenocarcinoma. Additional analysis of the combination of amount and duration of alcohol consumption indicated that heavy drinkers (&gt; 30 ml/day) had significantly higher ORs, irrespective of the duration of alcohol consumption. In conclusion, heavy alcohol consumption increases the risk for esophageal adenocarcinoma independent of the duration of such consumption.

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  • Effect of an education program on improving knowledge of schizophrenia among parents of junior and senior high school students in Japan 査読

    Hatsumi Yoshii, Yuichiro Watanabe, Hideaki Kitamura, Jun Chen, Kouhei Akazawa

    BMC PUBLIC HEALTH11   323   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Early detection and intervention in schizophrenia are important in improving quality of life after treatment and are major issues in psychiatric care. Therefore, it is necessary to increase knowledge of schizophrenia among the general public. Among parents of junior and senior high school students in Japan, we compared rates of correct answers for items on knowledge of schizophrenia and ability to discriminate this psychosis from other disorders on questionnaires given before and after viewing a web-based education program.
    Methods: Questionnaires were distributed to 2,690 parents. The program was developed to help parents obtain a basic understanding of schizophrenia and to emphasize the necessity of early detection.
    Results: Before the program, the rate of correct answers was 77% for items concerning basic knowledge of schizophrenia, 47% for "discrimination of schizophrenia symptoms," and 30% for "discrimination of prodromal symptoms." The program resulted in an improvement in basic knowledge of schizophrenia, discrimination of schizophrenia symptoms, and discrimination of prodromal symptoms (P &lt; 0.001 for all).
    Conclusions: Our web-based education program was useful in helping parents acquire a basic knowledge of schizophrenia and discriminate correctly the symptoms of schizophrenia.

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  • Associations of Age and Birth Cohort with Total and Specific IgE Antibody Levels 査読

    Kazuharu Tsukioka, Shin-Ichi Toyabe, Kohei Akazawa

    JOURNAL OF ASTHMA48 ( 3 ) 211 - 216   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    Background. Total and antigen-specific IgE levels vary greatly with age; however, it is unclear whether they are more closely related to patient age or birth cohort. Objective. To determine whether birth cohort or age was more strongly correlated with total and specific IgE levels. Methods. We retrospectively examined the medical records of 5136 asthma patients who were treated at the Niigata Allergic Disease Research Institute Outpatient Clinic during the period from 1997 to 2005. The subjects were divided into four birth cohorts based on their year of birth: the first cohort was born in 1935 or earlier, the second in 1936--1955, the third in 1956--1975, and the fourth in 1976 or later. Their total IgE level and mite-, cedar-, and Candida albicans (Candida)-specific IgE levels were measured using the CAP RAST fluoroenzyme immunoassay test. Results. Univariate analysis revealed that total IgE level and mite-, cedar-, and Candida-specific IgE levels significantly decreased (p &lt; .001) with advancing age. In addition, there were significantly higher IgE levels in later birth cohorts (p &lt; .01). On multivariate analysis, there were associations of total IgE level and mite- and cedar-specific IgE levels with both age and birth cohort. However, there was no significant association between Candida-specific IgE antibody level and either age or birth cohort. Conclusions. The associations of total and specific IgE levels with age and birth cohort were different. Thus, in comparing the results of IgE antibody testing done in different years, even for patients of the same age, the possibility of a birth cohort effect on IgE levels should be considered.&lt;/.

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  • Phase II Trial of Preoperative Chemotherapy for Breast Cancer: Japan Breast Cancer Research Network (JBCRN)-02 Trial 査読

    S. Iwase, D. Yamamoto, Y. Kuroda, T. Kawaguchi, K. Kitamura, H. Odagiri, S. Teramoto, K. Akazawa, Y. Nagumo

    ANTICANCER RESEARCH31 ( 4 ) 1483 - 1487   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT INST ANTICANCER RESEARCH  

    Background: Neoadjuvant chemotherapy (NAC) is one of the main strategies for patients with locally advanced breast cancer. In our previous study, biological markers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2 were essential predictors of the effectiveness of NAC to help individualize treatment. This study examined the effect of NAC on the disease-free survival (DFS) of breast cancer patients. Furthermore, the study was expanded by adding Ki-67 as a biological marker, and examined the correlation between Ki-67 and the prognosis. Patients and Methods: Between September 2005 and September 2007, 43 patients with breast cancer received NAC and surgery. Four cycles of DC (doxorubicin: 60 mg/m(2), and cyclophosphamide: 500 mg/m2) were administered intravenously (i.v.) on day 1 every 21 days, followed by 12 cycles of paclitaxel i.v. (80 mg/m2) every 7 days, prior to surgery. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoint was DFS; the pCR rate was estimated for each groups stratified by the presence or absence of different factors (PcR, ER/PgR, and Ki-67). Results: The clinical response (cCR+cPR) rate was 81.0%, and the pCR rate was 25.6%. The pCR rate was 75, 50, 9 and 0% in HER2(+)/ER(-), HER2(+)/ER(+), HER2(-)/ER(-), and HER2(-)/ER(+) patients, respectively. The 4-year DFS rate was estimated at 78% for all patients. The HER2 status was an independent predictor of pathological complete response (pCR). The DFS rate of patients with lower Ki-67 values (&lt; 15%) was higher than that of patients with higher Ki-67 values (&gt;= 15%). The treatment-related adverse events were manageable: the majority were mild, but five patients experienced grade 3 (neutropenia and sensory neuropathy) adverse events. Conclusion: DC followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. HER2 overexpression may be a good predictive marker of pCR, and the Ki-67 value after NAC may be a prognostic factor for DFS.

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  • Intraepithelial ductal spread in colorectal carcinoma liver metastasis. 査読

    Wakai T, Korita PV, Ajioka Y, Inoue M, Takamura M, Akazawa K, Shirai Y, Hatakeyama K

    Hepato-gastroenterology58 ( 106 ) 583 - 8   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Kattan postoperative nomogram for renal cell carcinoma: Predictive accuracy in a Japanese population 査読

    Kazuya Suzuki, Tsutomu Nishiyama, Noboru Hara, Kohei Akazawa, Kota Takahashi

    INTERNATIONAL JOURNAL OF UROLOGY18 ( 3 ) 194 - 199   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Objectives:
    The aim of the current study was to establish the predictive accuracy of the Kattan postoperative nomogram for non-metastatic renal cell carcinoma (RCC) in a Japanese population.
    Methods:
    A total of 211 patients with stage T1-3N0M0 clear cell RCC who underwent radical nephrectomy or nephron-sparing surgery between 1991 and 2004 were included in this analysis. Median follow up was 81 months (range: 4-208). Univariate and multivariate analyses were performed, and the influence of age, sex, clinical presentation, T stage, histological tumor size, grade, and microvascular invasion on disease recurrence-free survival (RFS) was determined. For each patient, the prognostic score for 5-year RFS was calculated using the Kattan nomogram. The discriminating ability of this model was assessed by the concordance index, and bootstrapping was used to evaluate confidence intervals.
    Results:
    The 5-year RFS rate for all patients calculated using the Kaplan-Meier method was 80.6%. In multivariate analysis, the statistically significant prognostic factors for 5-year RFS were high-grade tumors (P = 0.019) and symptomatic disease (P = 0.017). The concordance index for RFS predicted by the Kattan nomogram was 0.735 (95% confidence interval: 0.734-0.736). There was a slight discrepancy between the RFS predicted by the Kattan nomogram and the likelihood of being recurrence-free at 5 years according to the Cox analysis in the current patient population.
    Conclusion:
    These findings suggest the necessity of constructing a more useful nomogram for predicting the prognosis of Japanese patients with non-metastatic RCC.

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  • Effect of an Education Program on Improving Help-Seeking among Parents of Junior and Senior High School Students in Japan. 査読

    Yoshii H, Watanabe Y, Kitamura H, Nan Z, Akazawa K

    Global Journal of Health Science4 ( 1 ) 33 - 41   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Clustering and geographic variation of upper gastrointestinal cancers in a high-risk region of esophageal cancer in northern China. 査読

    Zhang N, Wen D, Shan B, Wang S, Zhang L, Wei L, Zou W, Kitsu K, Akazawa K

    Asian Pacific journal of cancer prevention : APJCP12 ( 1 ) 193 - 8   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Stigma toward schizophrenia among parents of junior and senior high school students in Japan 査読

    Hatsumi Yoshii, Yuichiro Watanabe, Hideaki Kitamura, Zhang Nan, Kouhei Akazawa

    BMC Research Notes4   558   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Stigma toward schizophrenia is a substantial barrier to accessing care and adhering to treatment. Provisions to combat stigma are important, but in Japan and other developed countries there are few such provisions in place that target parents of adolescents. The attitudes of parents are important to address as first schizophrenic episodes typically occur in adolescence. In overall efforts to develop an education program and provisions against stigma, here we examined the relationship between stigma toward schizophrenia and demographic characteristics of parents of junior and senior high school students in Japan. The specific hypothesis tested was that contact and communication with a person with schizophrenia would be important to reducing stigma. A questionnaire inquiring about respondent characteristics and which included a survey on stigma toward schizophrenia was completed by 2690 parents. Results: The demographic characteristics significantly associated with the Devaluation- Discrimination Measure were family income, occupation, presence of a neighbor with schizophrenia, and participation in welfare activities for people with mental illness (p &lt
    0.05). The mean ±SD score was 32.74 ± 5.66 out of a maximum of 48 points on the Link Devaluation- Discrimination Measure. Conclusions: Stigma toward schizophrenia among parents of junior and senior high school students was in fact significantly stronger among members of the general public who had had contact with individuals with schizophrenia. In addition, stigma was associated with family income. © 2011 Yoshii et al
    licensee BioMed Central Ltd.

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  • Internal environment for growth of cancer cells in mice:hypothermia, anemia and lymphocytopenia. 査読

    Watanabe M, Matsumoto H, Tomiyama C, Akazawa K, Abo T

    Health3 ( 4 ) 238 - 244   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • [Relationship between asthma severity and age at onset in Japanese adults]. 査読

    Tsukioka K, Toyabe S, Akazawa K

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society48 ( 12 ) 898 - 905   2010年12月

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  • Effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the risk of esophageal cancer: A case-control study 査読

    Jun Chen, Nan Zhang, Toshifumi Wakai, Lizhen Wei, Yutong He, Naoko Kumagai, Keiko Kitsu, Shijie Wang, Kohei Akazawa

    EXPERIMENTAL AND THERAPEUTIC MEDICINE1 ( 6 ) 991 - 997   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The effects of alcohol consumption and tobacco smoking on the prevalence of esophageal cancer vary considerably by country, race and lifestyle. Few data exist on the effect of the interaction between the amount and duration of alcohol consumption and tobacco smoking on the incidence of esophageal cancer. In this case-control study, the cases included patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) younger than 60 years of age and recruited between January 1, 2002 and December 31, 2006. The controls had no abnormality during a medical checkup. A total of 835 pairs were created by pairing each case to a gender- and age-matched control. Conditional logistic regression analysis was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Univariate conditional logistic regression analyses revealed that the ORs according to both duration of alcohol consumption and tobacco smoking increased monotonically. Alcohol consumption and tobacco smoking may have a synergistic effect on the incidence of ESCC. Conditional logistic regression analysis using a forward stepwise selection procedure revealed that the incidence of ESCC was associated with the duration of tobacco smoking, the interaction between the amount and duration of alcohol consumption, and a family history of cancer. In particular, groups with a long duration of alcohol consumption and high alcohol intake had much higher ORs than those with short duration and low intake, which highlights the importance of the interaction between the amount and duration of alcohol intake. This study confirmed the significance of the interaction between alcohol consumption and tobacco smoking in esophageal cancer. This interaction between amount and duration is an accurate indicator for estimating the risk of esophageal cancer attributable to alcohol consumption and tobacco smoking. These findings suggest that decreasing the number of young and middle-aged drinkers and smokers will reduce the incidence of esophageal cancer.

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  • A stochastic model of neuronal growth cone guidance regulated by multiple sensors 査読

    Taichiro Kobayashi, Kenshi Terajima, Motohiro Nozumi, Michihiro Igarashi, Kouhei Akazawa

    JOURNAL OF THEORETICAL BIOLOGY266 ( 4 ) 712 - 722   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

    Neuronal growth cones migrate directionally under the control of axon guidance molecules, thereby forming synapses in the developing brain. The signal transduction system by which a growth cone detects surrounding guidance molecules, analyzes the detected signals, and then determines the overall behavior remains undetermined. In this study, we describe a novel stochastic model of this behavior that utilizes multiple sensors on filopodia to respond to guidance molecules. Overall growth cone behavior is determined by using only the concentration gradients of guidance molecules in the immediate vicinity of each sensor. The detected signal at each sensor, which is treated as a vector quantity, is sent to the growth cone center and then integrated to determine axonal growth in the next step by means of a simple vector operation. We compared the results of computer simulations of axonal growth with observations of actual axonal growth from co-culture experiments using olfactory bulb and septum. The probabilistic distributions of axonal growth generated by the computer simulation were consistent with those obtained from the culture experiments, indicating that our model accurately simulates growth cone behavior. We believe that this model will be useful for elucidating the as yet unknown mechanisms responsible for axonal growth in vivo. (c) 2010 Elsevier Ltd. All rights reserved.

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  • [The relationship between the duration and severity of asthma]. 査読

    Tsukioka K, Toyabe S, Akazawa K

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society48 ( 7 ) 475 - 481   2010年7月

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  • Single-Dose Intravenous Administration of Recombinant Human Erythropoietin Is a Promising Treatment for Patients With Acute Myocardial Infarction - Randomized Controlled Pilot Trial of EPO/AMI-1 Study 査読

    Takuya Ozawa, Ken Toba, Hiroshi Suzuki, Kiminori Kato, Yoshitaka Iso, Yasushi Akutsu, Youichi Kobayashi, Youichi Takeyama, Naohiko Kobayashi, Norihiko Yoshimura, Kohei Akazawa, Yoshifusa Aizawa

    CIRCULATION JOURNAL74 ( 7 ) 1415 - 1423   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE CIRCULATION SOC  

    Background: Erythropoietin (EPO) has been found to have anti-apoptotic and tissue protective effects on the myocardium. The aim of the present pilot study was to observe the safety and efficacy of EPO administration for patients with acute myocardial infarction (AMI).
    Methods and Results: Patients admitted with AMI had all undergone successful percutaneous coronary intervention (PCI). Patients were randomly assigned to 2 groups (control and EPO groups), and given 12,000 IU EPO iv or saline after PCI. The primary endpoints were the difference between the acute phase and chronic phase (6 months after the attack) regarding left ventricular function as measured on electrocardiogram-gated single-photon emission computed tomography. Thirty-six patients (control 16, EPO 20) were eligible for analysis. Left ventricular ejection fraction (LVEF) significantly increased in the EPO group (from 51.0 +/- 19.6% to 58.5 +/- 15.0%, P=0.0238), but not in the control group. Further analysis was separately undertaken in patients with occlusion in the left anterior descending artery (LAD) and others (non-LAD). LVEF was &lt;50% in most patients in the LAD subgroup, and LVEF significantly increased in the EPO group (37.5 +/- 13.0 to 52.7 +/- 15.8, P=0.0049), but not in the control group. EPO administration did not trigger any adverse clinical events.
    Conclusions: EPO administration is a promising treatment for AMI. (Circ J 2010; 74: 1415-1423)

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  • Single-Dose Intravenous Administration of Recombinant Human Erythropoietin Is a Promising Treatment for Patients With Acute Myocardial Infarction - Randomized Controlled Pilot Trial of EPO/AMI-1 Study 査読

    Takuya Ozawa, Ken Toba, Hiroshi Suzuki, Kiminori Kato, Yoshitaka Iso, Yasushi Akutsu, Youichi Kobayashi, Youichi Takeyama, Naohiko Kobayashi, Norihiko Yoshimura, Kohei Akazawa, Yoshifusa Aizawa

    CIRCULATION JOURNAL74 ( 7 ) 1415 - 1423   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE CIRCULATION SOC  

    Background: Erythropoietin (EPO) has been found to have anti-apoptotic and tissue protective effects on the myocardium. The aim of the present pilot study was to observe the safety and efficacy of EPO administration for patients with acute myocardial infarction (AMI).
    Methods and Results: Patients admitted with AMI had all undergone successful percutaneous coronary intervention (PCI). Patients were randomly assigned to 2 groups (control and EPO groups), and given 12,000 IU EPO iv or saline after PCI. The primary endpoints were the difference between the acute phase and chronic phase (6 months after the attack) regarding left ventricular function as measured on electrocardiogram-gated single-photon emission computed tomography. Thirty-six patients (control 16, EPO 20) were eligible for analysis. Left ventricular ejection fraction (LVEF) significantly increased in the EPO group (from 51.0 +/- 19.6% to 58.5 +/- 15.0%, P=0.0238), but not in the control group. Further analysis was separately undertaken in patients with occlusion in the left anterior descending artery (LAD) and others (non-LAD). LVEF was &lt;50% in most patients in the LAD subgroup, and LVEF significantly increased in the EPO group (37.5 +/- 13.0 to 52.7 +/- 15.8, P=0.0049), but not in the control group. EPO administration did not trigger any adverse clinical events.
    Conclusions: EPO administration is a promising treatment for AMI. (Circ J 2010; 74: 1415-1423)

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  • [Total and specific IgE levels in adolescents and adults with bronchial asthma]. 査読

    Tsukioka K, Toyabe S, Akazawa K

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society48 ( 6 ) 409 - 418   2010年6月

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  • Inhaled Granulocyte/Macrophage-Colony Stimulating Factor as Therapy for Pulmonary Alveolar Proteinosis 査読

    Ryushi Tazawa, Bruce C. Trapnell, Yoshikazu Inoue, Toru Arai, Toshinori Takada, Yasuyuki Nasuhara, Nobuyuki Hizawa, Yasunori Kasahara, Koichiro Tatsumi, Masayuki Hojo, Haruyuki Ishii, Masanori Yokoba, Naohiko Tanaka, Etsuro Yamaguchi, Ryosttke Eda, Yoshiko Tsuchihashi, Konosuke Morimoto, Masanori Akira, Masaki Terada, Junji Otsuka, Masahito Ebina, Chinatsu Kaneko, Toshihiro Nukiwa, Jeffery P. Krischer, Kohei Akazawa, Koh Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE181 ( 12 ) 1345 - 1354   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER THORACIC SOC  

    Rationale: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied.
    Objectives: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP.
    Methods: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O2) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 mu g Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 mu g Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk).
    Measurements and Main Results: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P &lt; 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year.
    Conclusions: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP.

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  • Risk factors for persistent and relapsed childhood-onset asthma 査読

    Kazuharu Tsukioka, Shin-Ichi Toyabe, Kouhei Akazawa

    Japanese Journal of Allergology59 ( 6 ) 699 - 705   2010年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Background: The aim of this study was to identify factors responsible for childhood-onset persistent asthma and childhood-onset asthma relapsing in adulthood. Methods: We compared a number of potential risk factors for asthma among 608 patients with childhood-onset persistent asthma (onset at 15 years of age or younger) and 286'patients with childhood-onset asthma (onset at 20 years or younger) that had relapsed "after a period of remission longer than 2 years. Results: Multiple linear regression analysis revealed that the factors associated with childhood-onset persistent asthma were a past or present history of allergic rhinitis (p = 0.001) and high serum total IgE concentration (≥300IU/ml
    p = 0.007). The factors associated, with relapse of childhood-onset asthma were female sex {p = 0.001), younger onset age (p = 0.036), and smoking (current or former: p&lt
    0.001). Conclusion: Our findings indicate that a past or present history of allergic rhinitis and high serum IgE level are significant risk factors for childhood-onset persistent asthma, and that female sex and a history of smoking are risk factors for relapse of childhood-onset asthma Fortunately, exposure to r tobacco smoke is a controllable risk factor. © 2010 Japanese Society of Allergology.

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  • [The age of onset of adult-onset asthma is increasing in Japanese women]. 査読

    Tsukioka K, Toyabe S, Kogusuri Y, Akazawa K

    Arerugi = [Allergy]58 ( 12 ) 1591 - 1601   2009年12月

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  • Single-dose Intravenous-administration of Recombinant Human Erythropoietin Considerably Improved Cardiac Function in Patients With Acute Myocardial Infarction: A Randomized Controlled Pilot Trial of EPO/AMI-I Study 査読

    Takuya Ozawa, Ken Toba, Kiminori Kato, Hiroshi Suzuki, Yoshitaka Iso, Naohiko Kobayashi, Yasushi Akutsu, Tsugumi Takayama, Takao Yanagawa, Norihiko Yoshimura, Youichi Kobayashi, Youichi Takeyama, Kohei Akazawa, Yoshifusa Aizawa

    CIRCULATION120 ( 18 ) S1173 - S1174   2009年11月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Estimating the case fatality rate using a constant cure-death hazard ratio 査読

    Zheng Chen, Kohei Akazawa, Tsuyoshi Nakamura

    LIFETIME DATA ANALYSIS15 ( 3 ) 316 - 329   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The case fatality rate is an important indicator of the severity of a disease, and unbiased and accurate estimates of it during an outbreak are important in the study of epidemic diseases, including severe acute respiratory syndrome (SARS). In this paper, estimation methods are developed using a constant cure-death hazard ratio. A semiparametric model is presented, in which the cure-death hazard ratio is a parameter of interest, and a profile likelihood-based technique is proposed for estimating the case fatality rate. An extensive simulation was carried out to investigate the performance of this technique for small and medium sample sizes, using both summary and individual data. The results show that the performance depends on the model validity but is not heavily dependent on the sample size. The method was applied to summary SARS data obtained from Hong Kong and Singapore.

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  • Predictors of microscopic portal vein invasion by hepatocellular carcinoma: Measurement of portal perfusion defect area ratio 査読

    Ken Shirabe, Kiyoshi Kajiyama, Tomoyuki Abe, Shigeru Sakamoto, Tatsuro Fukuya, Kohei Akazawa, Kazutoyo Morita, Yoshihiko Maehara

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY24 ( 8 ) 1431 - 1436   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Objective:
    Microscopic portal vein invasion (PVI) by cancer cells is a poor prognostic factor after hepatic resection for hepatocellular carcinoma (HCC). The aim of this study is to predict PVI preoperatively in patients with HCC.
    Methods:
    We studied 46 hepatectomized patients who had HCC without any portal venous invasion detected during preoperative radiographic evaluation. We defined the portal perfusion defect area ratio (PPDAR) as the following: the quotient of the maximal portal perfusion defect area, on computed tomography during arterio-portography (CTAP) is divided by the maximal tumor area on magnetic resonance imaging (MRI) or CT.
    Results:
    The median PPDAR was 1.3 (mean 1.4 +/- 1.1; ranged from 0.7 to 5.8). The incidence of PVI was 4.5% in patients with a PPDAR &lt; 1.3, 35.7% in those with a PPDAR of 1.3-1.6, 70% in those with a PPDAR &gt;= 1.6 (P = 0.0005). When analyzing the preoperative value of different cut-off points for the PPDAR, the lowest P-value by Fisher&apos;s exact test was achieved when the PPDAR threshold was 1.6 (P = 0.0012). The sensitivity was 58%, and specificity was 91% with this cut-off value. On univariate analyses, factors that significantly correlated with PVI were PPDAR (P = 0.0012), serum levels of des-gamma-carboxy prothrombin (P = 0.033), and tumor size (P = 0.0126). On multivariate analysis, PPDAR was the only significant independent predictor of PVI.
    Conclusion:
    Our study shows that PPDAR is a new concept, which is useful in predicting PVI and that a value &gt;= 1.6 is predictive of PVI.

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  • Tract-by-tract morphometric and diffusivity analyses in vivo of spinocerebellar degeneration 査読

    Kenshi Terajima, Hitoshi Matsuzawa, Takayoshi Shimohata, Kouhei Akazawa, Masatoyo Nishizawa, Tsutomu Nakada

    Journal of Neuroimaging19 ( 3 ) 220 - 226   2009年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND PURPOSE Three-dimensional anisotropy contrast (3DAC) based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) sequence on a 3.0T system is a new magnetic resonance imaging technique capable of providing images with significantly high anatomical resolution. The purpose of this study was to confirm whether this technique can characterize the degenerative processes in the brainstem of patients with spinocerebellar degeneration (SCD). METHODS 3DAC images of 13 patients with multiple system atrophy with predominant cerebellar symptoms (MSA-C) and seven International Cooperative Ataxia Rating Scale (ICARS) score-matched patients with Machado-Joseph disease (MJD) were created using a diffusion-weighted PROPELLER sequence on a 3.0T system. The section of the middle pons was chosen for morphometric and diffusivity analyses. RESULTS The above analyses showed that atrophy and increased diffusivity of the ventral portion of the pons indicated MSA-C, whereas atrophy and increased diffusivity of the pontine tegmentum indicated MJD. Furthermore, ICARS scores significantly correlated with both the severities of the pontine atrophy and the mean diffusivity values of the ventral pontocerebellar tracts. CONCLUSIONS This study demonstrated that 3DAC PROPELLER on a 3.0T system enables in vivo "tract by tract" quantitative analysis of pontine degeneration in SCD. J Neuroimaging 2009
    19:220-226. © 2008 by the American Society of Neuroimaging.

    DOI: 10.1111/j.1552-6569.2008.00273.x

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  • Serum hepcidin-20 is elevated during the acute phase of myocardial infarction. 査読

    Suzuki H, Toba K, Kato K, Ozawa T, Tomosugi N, Higuchi M, Kusuyama T, Iso Y, Kobayashi N, Yokoyama S, Fukuda N, Saitoh H, Akazawa K, Aizawa Y

    The Tohoku journal of experimental medicine218 ( 2 ) 93 - 8   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1620/tjem.218.93

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  • UNC5D, a dependence receptor for netrin-1, is down-regulated in unfavorable neuroblastomas 査読

    Yuyan Zhu, Yuanyuan Li, Miki Ohira, Atsuko Nakagawa, Kohei Akazawa, Meng Yu, Yohko Nakamura, Tadayuki Koda, Patrick Mehlen, Hirofumi Arakawa, Akira Nakagawara

    CANCER RESEARCH69   2009年5月

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    記述言語:英語   出版者・発行元:AMER ASSOC CANCER RESEARCH  

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  • GAB2 is not associated with late-onset Alzheimer&apos;s disease in Japanese 査読

    Akinori Miyashita, Hiroyuki Arai, Takashi Asada, Masaki Imagawa, Mikio Shoji, Susumu Higuchi, Katsuya Urakami, Shinichi Toyabe, Kohei Akazawa, Ichiro Kanazawa, Yasuo Ihara, Ryozo Kuwano

    EUROPEAN JOURNAL OF HUMAN GENETICS17 ( 5 ) 682 - 686   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    The epsilon 4 allele of the apolipoprotein E gene (APOE) is unequivocally recognized as a genetic risk factor for late-onset Alzheimer&apos;s disease (LOAD). Recently, single-nucleotide polymorphisms (SNPs) of the GRB2-associated binding protein 2 gene (GAB2) were shown to be associated with LOAD in Caucasians carrying the APOE-epsilon 4 allele through a genome-wide association study. Here, we attempted to replicate the finding by genotyping these SNPs in a large clinical cohort of Japanese. We observed no association of any of the SNPs with LOAD. GAB2 may not be a disease susceptibility gene for LOAD in Japanese.

    DOI: 10.1038/ejhg.2008.181

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  • Frontal White Matter Vulnerability to Carbon Monoxide Poisoning Demonstrated by Diffusion Tensor Imaging on 3.0T System 査読

    Kenshi Terajima, Hironaka Igarashi, Yuhei Takado, Koichiro Okamoto, Kohei Akazawa, Masatoyo Nishizawa, Tsutomu Nakada

    NEUROLOGY72 ( 11 ) A444 - A445   2009年3月

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    記述言語:英語   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Programs for calculating the statistical powers of detecting susceptibility genes in case-control studies based on multistage designs 査読

    Nobutaka Kitamura, Kouhei Akazawa, Akinori Miyashita, Ryozo Kuwano, Shin-ichi Toyabe, Junichiro Nakamura, Norihito Nakamura, Tatsuhiko Sato, M. Aminul Hoque

    BIOINFORMATICS25 ( 2 ) 272 - 273   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs.
    Results: We developed programs for a multistage case-control association study using R language. In our programs, input parameters include numbers of samples and candidate loci, genome-wide false positive rate and proportions of samples and loci to be selected at the k-th stage (k = 1,..., n). The programs output statistical powers, PPVs and numbers of typings in arbitrary n-stage designs. The programs can contribute to prior simulations under various conditions in planning a genome-wide association study.

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  • Influence on the suicide rate two years after a devastating disaster: A report from the 1995 Great Hanshin-Awaji Earthquake 査読

    Akihiro Nishio, Kouhei Akazawa, Futoshi Shibuya, Ryo Abe, Hideyuki Nushida, Yasuhiro Ueno, Akiyoshi Nishimura, Toshiki Shioiri

    PSYCHIATRY AND CLINICAL NEUROSCIENCES63 ( 2 ) 247 - 250   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    The relationship between suicide and disaster is an important problem but it&apos;s not clear. We conducted this study to determine whether a natural disaster affects suicide rates.
    We collected data on suicides during the 84 months before and the 60 months after the earthquake and compared the suicide rate in Kobe to that in Japan as a whole. We also examined what groups were significantly affected.
    Compared with Japan as a whole, the suicide rates in Kobe significantly decreased in the 2 years after the earthquake.
    An influence on suicide rate after the disaster clearly appeared in middle-aged men.

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  • Analysis of inhaled corticosteroid selection in patients with bronchial asthma using a questionnaire survey - Effects of age, gender, and disease severity 査読

    Kyuma Ota, Takashi Hasegawa, Toshiyuki Koya, Takuro Sakagami, Takashi Sekikawa, Shinichi Toyabe, Kohei Akazawa, Masaaki Arakawa, Fumitake Gejyo, Eiichi Suzuki

    Allergology International58 ( 3 ) 365 - 371   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Allergology  

    Background: Inhaled corticosteroid (ICS) has played an important role in the management of asthma. Although several kinds of ICSs are currently available, there is no established strategy for ICS selection. Methods: Using the data from the 2004 questionnaire surveys by the Niigata Asthma Treatment Study Group, we analyzed relationships between each patient and the ICS employed on the basis of patient background, asthma control and treatment, and indicated characteristics of ICS selection by the physician. Results: Of 2852 cases, 2279 (79.9%) were ICS users, and 1513 (66.4% of ICS users) were classified as being in the fluticasone propionate (FP) group, 438 (19.2%) in the budesonide (BUD) group, and 240 (10.5%) in the hydrofluoroalkane-beclometasone (HFA-BDP) group, indicating that FP was a standard ICS in this study. The mean age was significantly lower in the BUD group (52.3+/-18.2 years) and was significantly higher in the HFA-BDP group (59.9+/-17.0 years) than that in the FP group (55.8+/-16.6 yaers). The proportion of female patients was significantly higher not in the HFA-BDP (46.5%) but in the BUD group (59.0%) than in the FP group (51.1%). These results indicated that BUD was frequently prescribed to young female and HFA-BDP was employed in the elderly patients irrespective of gender compared with FP. Conclusions: Our study indicates that ICS selection is reasonably adapted to each patient's background at least in the surveyed area. We need to elucidate the characteristics of ICS selection further in the future as new ICS and devices are developed. ©2009 Japanese Society of Allergology.

    DOI: 10.2332/allergolint.08-OA-0077

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  • Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation 査読

    Kiyohiro Ando, Miki Ohira, Toshinori Ozaki, Atsuko Nakagawa, Kohei Akazawa, Yusuke Suenaga, Yohko Nakamura, Tadayuki Koda, Takehiko Kamijo, Yoshinori Murakami, Akira Nakagawara

    INTERNATIONAL JOURNAL OF CANCER123 ( 9 ) 2087 - 2094   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Although it has been well documented that loss of human chromosome 11q is frequently observed in primary neuroblastomas, the smallest region of overlap (SRO) has not yet been precisely identified. Previously, we performed array-comparative genomic hybridization (array-CGH) analysis for 236 primary neuroblastomas to search for genomic aberrations with high-resolution. In our study, we have identified the SRO of deletion (10-Mb or less) at 11q23. Within this region, there exists a TSLC1/IGSF4/CADM1 gene (Tumor suppressor in lung cancer I/Immunoglobulin superfamily 4/Cell adhesion molecule 1), which has been identified as a putative tumor suppressor gene for lung and some other cancers. Consistent with previous observations, we have found that 35% of primary neuroblastomas harbor loss of heterozygosity (LOH) on TSLC1 locus. In contrast to other cancers, we could not detect the hypermethylation in its promoter region in primary neuroblastomas as well as neuroblastoma-derived cell lines. The clinicopathological analysis demonstrated that TSLC1 expression levels significantly correlate with stage, Shimada's pathological classification, MYCN amplification status, TrkA expression levels and DNA index in primary neuroblastomas. The immunohistochemical analysis showed that TSLC1 is remarkably reduced in unfavorable neuroblastomas. Furthermore, decreased expression levels of TSLC1 were significantly associated with a poor prognosis in 108 patients with neuroblastoma. Additionally, TSLC1 reduced cell proliferation in human neuroblastoma SH-SY5Y cells. Collectively, our present findings suggest that TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma. (c) 2008 Wiley-Liss, Inc.

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  • Factors impacting on psychological distress and recovery after the 2004 Niigata-Chuetsu earthquake, Japan: Community-based study 査読

    Hideki Kuwabara, Toshiki Shioiri, Shin-Ichi Toyabe, Tsuyoshi Kawamura, Masataka Koizumi, Miki Ito-Sawamura, Kouhei Akazawa, Toshiyuki Someya

    PSYCHIATRY AND CLINICAL NEUROSCIENCES62 ( 5 ) 503 - 507   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Aim: This study was undertaken 5 months after the 2004 Niigata-Chuetsu earthquake in Japan to assess factors that impacted on psychological distress and its recovery.
    Methods: Three thousand and twenty-six adult victims who lived in temporary shelter and in seriously damaged areas were evaluated by questionnaire. The questionnaire queried subject profile, degree of house damage, health status, and psychological distress using a 5-point scale before, immediately and 5 months after the earthquake.
    Results: Immediately after the earthquake, 59.3% of the subjects had psychological distress. At 5 months after the earthquake, however, this percentage decreased to 21.8%. The psychological distress immediately after the earthquake was significantly serious in victims who: (i) were female; (ii) felt stronger fear of the earthquake and the aftershocks; (iii) lived at home or office after the earthquake; and (iv) were injured due to the earthquake or suffered from sickness after the earthquake. In contrast, the factors impairing psychological recovery 5 months after the earthquake were as follows: (i) being with unfamiliar member(s) during the night after the earthquake; (ii) serious house damage; (iii) living in temporary shelter or at a relative&apos;s home after the earthquake; and (iv) physical illness after the earthquake.
    Conclusion: Despite differences between disasters, these results were consistent with those in some previous studies and may be useful for long-term mental care support.

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  • [Importance of clinical research design and statistical check point]. 査読

    Akazawa K

    Nihon Geka Gakkai zasshi109 Suppl 3   42 - 43   2008年9月

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  • Appraisal of 1 cm hepatectomy margins for intrahepatic micrometastases in patients with colorectal carcinoma liver metastasis 査読

    Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Vladimir A. Valera, Pavel V. Korita, Kouhei Akazawa, Yoichi Ajioka, Katsuyoshi Hatakeyama

    ANNALS OF SURGICAL ONCOLOGY15 ( 9 ) 2472 - 2481   2008年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Background: This study sought to clarify the distribution of intrahepatic micrometastases and elucidate an adequate hepatectomy margin for colorectal carcinoma liver metastases.
    Methods: Intrahepatic micrometastases in resected specimens from 90 patients who underwent hepatectomy for colorectal carcinoma liver metastases were examined retrospectively. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. Distances from these lesions to the hepatic tumor borders were measured histologically, and the density of intrahepatic micrometastases (number of lesions/mm(2)) calculated relative to the advancing tumor border in a zone &lt; 1 cm from the border (close) or &gt;= 1 cm away (distant). Median follow-up time was 127 months.
    Results: A total of 294 intrahepatic micrometastases were detected in 52 (58%) patients; 95% of these occurred in the close zone. The density of intrahepatic micrometastases was significantly higher in the close zone (mean 74.8 x 10(-4) lesions/mm(2)) than in the distant zone (mean 7.4 x 10(-4) lesions/mm(2); P &lt; 0.001). Hepatectomy margin status was positive by 0 cm in 10 patients or negative by &lt; 1 cm in 51, and by &gt;= 1 cm in 29 patients. The median survival times were 18, 33, and 89 months in patients with hepatectomy margins 0 cm, &lt; 1 cm, and &gt;= 1 cm, respectively. Hepatectomy margin status independently influenced survival (P &lt; 0.001) and disease-free survival (P &lt; 0.001).
    Conclusion: The currently recommended &gt;= 1 cm hepatectomy margin should remain the goal for resections of colorectal carcinoma liver metastases, based on the distribution of intrahepatic micrometastases and survival risk.

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  • Accuracy and efficiency of computer-aided nursing diagnosis. 査読

    Kurashima S, Kobayashi K, Toyabe S, Akazawa K

    International journal of nursing terminologies and classifications : the official journal of NANDA International19 ( 3 ) 95 - 101   2008年7月

  • Combined major hepatectomy and pancreaticoduodenectomy for locally advanced biliary carcinoma: Long-term results 査読

    Toshifumi Wakai, Yoshio Shirai, Yoshiaki Tsuchiya, Tatsuya Nomura, Kouhei Akazawa, Katsuyoshi Hatakeyama

    WORLD JOURNAL OF SURGERY32 ( 6 ) 1067 - 1076   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Background This study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure.
    Methods A retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (n = 17) or gallbladder carcinoma (n = 11). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pylorus-preserving pancreaticoduodenectomy. The median follow-up time was 169 months.
    Results Morbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (P = 0.0012). Residual tumor status was the only independent prognostic factor of significance (relative risk 4.65; P = 0.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor.
    Conclusions Combined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.

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  • Cost-effectiveness of the national screening program for hepatitis C virus in the general population and the high-risk groups 査読

    Junichiro Nakamura, Kenshi Terajima, Yutaka Aoyagi, Kouhei Akazawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE215 ( 1 ) 33 - 42   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TOHOKU UNIV MEDICAL PRESS  

    In Japan, the national screening for the hepatitis C virus (HCV) has been started for both the general population and the high-risk groups. Our cost-effectiveness analysis was based on the result of the screening program including 99,001 people among the general population and 42,538 people among the high risk group from 2003 to 2006. The screening was performed using the three steps of the semi-quantitative HCV antibody test, the HCV core antigen test and the HCV-PCR test. A Markov model for HCV infected patients was constructed to estimate the future clinical benefits and the lifetime cost and the cost-effectiveness analysis was performed considering the recent treatment with peginterferon plus ribavirin. In the cost-effectiveness analysis, the cohort, in which the screening was implemented (= screening strategy), was compared with the similar cohort without the screening (= no-screening strategy) in both the general population and the high-risk group, stratified by age. The infection rates of the general population and the high-risk group were 0.36% and 0.81%, respectively. The incremental cost-effectiveness ratio (ICER), a measure of cost-effectiveness, of the general population and the high-risk group was calculated to be from 848 to 4,825 and - 749 to 2,297 $/life expectancy gained, respectively. The treatment effectiveness, transition probabilities and the infection rate varied in the one-way sensitivity analyses, but the superiority of the screening strategy regarding the cost-effectiveness was unchanged. In conclusion, the screening strategy in both the general population and the high-risk group therefore appears to be more cost-effective than a no-screening strategy.

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  • Sample-size properties of a case-control association analysis of multistage SNP studies for identifying disease susceptibility genes 査読

    Nobutaka Kitamura, Kouhei Akazawa, Shin-ichi Toyabe, Akinori Miyashita, Ryozo Kuwano, Junichiro Nakamura

    JOURNAL OF HUMAN GENETICS53 ( 5 ) 390 - 400   2008年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    A two-stage association study is the most commonly used method to efficiently identify disease susceptibility genes. However, some recent single nucleotide polymorphism (SNP) studies recently utilized three-stage designs. The purpose of this study was to investigate the practical properties of statistical powers and positive predictive values (PPVs) of replication-based analysis (RBA) and the joint analysis (JA) in multistage designs. For this purpose, a program for multistage designs was developed to calculate these performance indicators under various conditions of the number of samples, alleles of candidates, alleles remaining in the final stage, and genotypings. The results showed that the powers and PPVs of RBA and JA in three-stage designs were higher than those in two-stage designs in the range of a smaller proportion of sample size than 0.5 at the first stage. This tendency was more remarkable in JA. In conclusion, researchers who perform SNP studies for identifying disease susceptibility genes need to take account of three-stage case-control association studies, corresponding to study conditions such as the total numbers of samples, alleles, and genotypings. Furthermore, the program developed in this study is useful for estimating powers and PPVs in planning multistage association studies.

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  • Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study. 査読

    Hiyama E, Iehara T, Sugimoto T, Fukuzawa M, Hayashi Y, Sasaki F, Sugiyama M, Kondo S, Yoneda A, Yamaoka H, Tajiri T, Akazawa K, Ohtaki M

    Lancet (London, England)371 ( 9619 ) 1173 - 80   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Prediction of Disease-associated Single Nucleotide Polymorphisms Using Virtual Genomes Constructed from a Public Haplotype Database 査読

    S. Toyabe, A. Miyashita, N. Kitamura, R. Kuwano, K. Akazowa

    METHODS OF INFORMATION IN MEDICINE47 ( 6 ) 522 - 528   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

    Objectives: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects.
    Methods. We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs.
    Results. We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs, We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved.
    Conclusions. Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

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  • Genetic association of CTNNA3 with late-onset Alzheimer's disease in females. 査読 国際誌

    Akinori Miyashita, Hiroyuki Arai, Takashi Asada, Masaki Imagawa, Etsuro Matsubara, Mikio Shoji, Susumu Higuchi, Katsuya Urakami, Akiyoshi Kakita, Hitoshi Takahashi, Shinichi Toyabe, Kohei Akazawa, Ichiro Kanazawa, Yasuo Ihara, Ryozo Kuwano

    Human molecular genetics16 ( 23 ) 2854 - 69   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Alzheimer's disease (AD), the most common form of dementia in the elderly, was found to exhibit a trend toward a higher risk in females than in males through epidemiological studies. Therefore, we hypothesized that gender-related genetic risks could exist. To reveal the ones for late-onset AD (LOAD), we extended our previous genetic work on chromosome 10q (genomic region, 60-107 Mb), and single nucleotide polymorphism (SNP)-based genetic association analyses were performed on the same chromosomal region, where the existence of genetic risk factors for plasma Abeta42 elevation in LOAD was implied on a linkage analysis. Two-step screening of 1140 SNPs was carried out using a total of 1408 subjects with the APOE-epsilon3*3 genotype: we first genotyped an exploratory sample set (LOAD, 363; control, 337), and then genotyped some associated SNPs in a validation sample set (LOAD, 336; control, 372). Seven SNPs, spanning about 38 kb, in intron 9 of CTNNA3 were found to show multiple-hit association with LOAD in females, and exhibited more significant association on Mantel-Haenszel test (allelic P-values(MH-F) = 0.000005945-0.0007658). Multiple logistic regression analysis of a total of 2762 subjects (LOAD, 1313; controls, 1449) demonstrated that one of the seven SNPs directly interacted with the female gender, but not with the male gender. Furthermore, we found that this SNP exhibited no interaction with the APOE-epsilon4 allele. Our data suggest that CTNNA3 may affect LOAD through a female-specific mechanism independent of the APOE-epsilon4 allele.

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  • Screening at 6 months of age reduced neuroblastoma incidence and mortality at elder age: Population based cohort study in Japan 査読

    Eiso Hiyama, Toru Sugimoto, Yutaka Hayashi, Masahiko Fukuzawa, Fumiaki Sasaki, Masahiko Sugiyama, Satoshi Kondo, Akihiro Yoneda, Tatsuro Tajiri, Hiroaki Yamaoka, Lehara Tomoko, Kohei Akazawa, Megu Ohtaki

    PEDIATRIC BLOOD & CANCER49 ( 4 ) 418 - 418   2007年10月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

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  • Comparison of the levels of accuracy of an artificial neural network model and a logistic regression model for the diagnosis of acute appendicitis 査読

    Shinya Sakai, Kuriko Kobayashi, Shin-ichi Toyabe, Nozomu Mandai, Tatsuo Kanda, Kohei Akazawa

    JOURNAL OF MEDICAL SYSTEMS31 ( 5 ) 357 - 364   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    An accurate diagnosis of acute appendicitis in the early stage is often difficult, and decision support tools to improve such a diagnosis might be required. This study compared the levels of accuracy of artificial neural network models and logistic regression models for the diagnosis of acute appendicitis. Data from 169 patients presenting with acute abdomen were used for the analyses. Nine variables were used for the evaluation of the accuracy of the two models. The constructed models were validated by the ".632+ bootstrap method". The levels of accuracy of the two models for diagnosis were compared by error rate and areas under receiver operating characteristic curves. The artificial neural network models provided more accurate results than did the logistic regression models for both indices, especially when categorical variables or normalized variables were used. The most accurate diagnosis was obtained by the artificial neural network model using normalized variables.

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  • The cost-effectiveness of the new protocol reflecting rapid virologic response to peginterferon alpha-2b and ribavirin for chronic hepatitis C 査読

    Junichiro Nakamura, Kuriko Kobayashi, Shin-ichi Toyabe, Yutaka Aoyagi, Kouhei Akazawa

    EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY19 ( 9 ) 733 - 739   2007年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Objective Recent studies have reported the effectiveness of shorter courses of treatment with peginterferon alpha-2b plus ribavirin for patients with chronic hepatitis C, who achieved a rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV-) RNA at week 4. The aim of this study was to evaluate the cost-effectiveness of the new protocol for treatment, from the perspective of RVR.
    Methods A cost-effectiveness analysis based on the rate of sustained virologic response was performed. A Markov cohort model of hepatitis C was constructed to demonstrate the clinical states on the basis of the assigned transition probabilities over 30 years. The treatment strategies were classified into five subgroups taking into consideration the viral genotypes, viral load, and RVR. The lifetime costs and quality-adjusted life years (QALYs) were compared between the new and standard protocols for treatment.
    Results Genotype 1-infected patients in the new protocol for treatment compared with the standard one could prolong OALYs by 0.33 and reduce lifetime cost by (sic) 5993. Genotype 2 or 3-infected patients in the new protocol for treatment compared with the standard one could prolong QALYs by 0.02 and reduce lifetime cost by (sic)2851.
    Conclusion Treatment strategies that consider viral load and RVR for patients with a low viral load infected with genotype 1 and those infected with genotype 2 or 3 are more cost-effective compared with the standard protocol for treatment.

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  • Mortality predictors after 10 years of dialysis: A prospective study of Japanese hemodialysis patients 査読

    Junya Ajiro, Bassam Alchi, Ichiei Narita, Kentaro Omori, Daisuke Kondo, Minoru Sakatsume, Junichiro J. Kazama, Kohei Akazawa, Fumitake Gejyo

    Clinical Journal of the American Society of Nephrology2 ( 4 ) 653 - 660   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD). Design, s etting, participants, and measurements: A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with &gt
    10 yr of prior HD at study enrollment (n = 391) and those with ≤10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately. Results: In patients with &gt
    10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with ≤10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD. Conclusions: Providing a dequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for &gt
    10 yr. Copyright © 2007 by the American Society of Nephrology.

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  • Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu earthquake in Japan: a community-based study 査読

    Shin-ichi Toyabe, Toshiki Shioiri, Kuriko Kobayashi, Hideki Kuwabara, Masataka Koizumi, Taro Endo, Miki Ito, Hiroko Honma, Noboru Fukushima, Toshiyuki Someya, Kouhei Akazawa

    BMC PUBLIC HEALTH7   175   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Factor structure of the 12-item General Health Questionnaire (GHQ- 12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.
    Methods: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.
    Results: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.
    Conclusion: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.

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  • Evaluation of magnetic resonance imaging-based prostate-specific antigen density of the prostate in the diagnosis of prostate cancer 査読

    Tatsuhiko Hoshii, Tsutomu Nishiyama, Shinichi Toyabe, Kohei Akazawa, Shuichi Komatsu, Masaaki Kaneko, Noboru Hara, Kota Takahashi

    INTERNATIONAL JOURNAL OF UROLOGY14 ( 4 ) 305 - 310   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Objectives: We evaluated prostate-specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS-based PSAD), magnetic resonance imaging (MRI; MRI-based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI-based PSATZD) in the diagnosis of prostate cancer (PCa).
    Methods: One hundred and twenty patients, who were suspected to have PCa based on PSA, ranged between 4.1 and 20.0 ng/mL were enrolled in this study.
    Results: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI by 11.4% in the patients with PSA levels ranging 4.1-20.0 ng/mL, 7.2% in those 4.1-10.0 ng/mL, and 15.7% in those 10.1-20.0 ng/mL, respectively. PSA levels were correlated with the prostatic volume estimated using TRUS and MRI, and TZ volume estimated using MRI in the patients without PCa; however, the level was not correlated with them in the patients with PCa. The area under the receiver operating characteristic curve of MRI-based PSAD was higher than that of TRUS-based PSAD; however, there was no statistical difference. Stepwise logistic regression analysis for the prediction of PCa by using PSA-related parameters confirmed that MRI-based PSATZD was the most significant predictor in patients with PSA levels in the range of 4.1-20.0 ng/mL (P &lt; 0.001), the range of 4.1-10.0 ng/mL (P=0.002), and the range of 10.1-20.0 ng/mL (P &lt; 0.001), respectively.
    Conclusions: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI. MRI-based PSATZD is the most significant predictor in the four parameters.

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  • Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma 査読

    Toshifumi Wakai, Yoshio Shirai, Jun Sakata, Kazuhiro Kaneko, Pauldion V. Cruz, Kouhei Akazawa, Katsuyoshi Hatakeyama

    ANNALS OF SURGICAL ONCOLOGY14 ( 4 ) 1356 - 1365   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Background: This study aimed to evaluate the effect of anatomic resection on long-term outcomes in patients with pathologic T1-T2 (pT1-T2) hepatocellular carcinoma.
    Methods: A retrospective analysis of 158 consecutive patients who underwent either anatomic (n = 95) or nonanatomic (n = 63) resection for pT1-T2 hepatocellular carcinoma was conducted. Anatomic resection was defined as the complete removal of at least one Couinaud segment containing the tumor; nonanatomic resection was defined as removal of the tumor plus a rim of nonneoplastic liver parenchyma. The median follow-up time was 83 months.
    Results: Patients who underwent anatomic resection were characterized by lower prevalence of cirrhosis (P = .015), more favorable hepatic function (P = .001), larger tumor size (P = .029), and higher prevalence of vascular invasion (P = .008) compared with patients who underwent nonanatomic resection. Anatomic resection provided better survival (median survival time, 122 months) than nonanatomic resection (median survival time, 76 months; P = .0358). Patients who underwent anatomic resection had better disease-free survival (P = .0121). Anatomic resection independently improved both survival (hazard ratio, .46; P = .003) and disease-free survival (hazard ratio, .55; P = .008). When stratified for pT classification, the effectiveness of anatomic resection remained only in patients with pT2 tumors in terms of survival (P = .0012) and disease-free survival (P = .0004).
    Conclusions: Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma, probably because of the clearance of venous tumor thrombi within the resected domain.

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  • Second-order interactions with the treatment groups in controlled clinical trials 査読

    Shyang-Yun Pamela K. Shiao, Chul W. Ahn, Kouhei Akazawa

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE86 ( 1 ) 10 - 16   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    The occurrence of significant second-order interactions for group characteristics was examined using real data in a randomized controlled trial (RCT). The interactions exist in all RCTs; they could be easily overlooked when using the simple randomization or stratification methods, but could become more obvious when minimization methods are used. Using real data from an RCT, the minimization method enabled balancing the distributions of the four selected stratified factors. Analyses for three-way second-order interactions including six additional potential confounding variables (for a total of 10 variables) presented 8 significant second-order interactions with the treatment groups. Interaction effects need to be evaluated when treatment effects are examined to maximize the power of the treatment effects in any RCTs. A stepwise regression method with piecewise linear functions would be useful to select the significant variables with interaction effects affecting the treatment outcomes in RCTs. Additional ways to handle interaction effects in RCTs are presented in this paper. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

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  • Parental mental health affects behavioral changes in children following a devastating disaster: a community survey after the 2004 Niigata-Chuetsu earthquake 査読

    Taro Endo, Toshiki Shioiri, Toshiyuki Someya, Shinichi Toyabe, Kohei Akazawa

    GENERAL HOSPITAL PSYCHIATRY29 ( 2 ) 175 - 176   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

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  • Mental development of infants with congenital hypothyroidism: A longitudinal study 査読

    Makiko Nakamizo, Shin-ichi Toyabe, Tadashi Asami, Kouhei Akazawa

    CLINICAL PEDIATRICS46 ( 1 ) 53 - 58   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS INC  

    The purpose of this study was to assess the relationship between the clinical findings before starting treatment and the development quotient in children treated for congenital hypothyroidism. Patients with congenital hypothroidism (n = 129) were divided into favorable and unfavorable groups according to intellectual performance. Children with congenital hypothyroidism generally have a similar intellectual outcome to that of healthy children. However, a low birth weight, the presence of complications, and a high serum thyroid-stimulating hormone value are the risk factors for unfavorable cases, who consistently have a development quotient score of less than 100.

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  • Accuracy in the diagnostic prediction of acute appendicitis based on the Bayesian network model 査読

    S. Sakai, K. Kobayashi, J. Nakamura, S. Toyabe, K. Akazawa

    METHODS OF INFORMATION IN MEDICINE46 ( 6 ) 723 - 726   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

    Objectives: The diagnosis of acute appendicitis is difficult, and a diagnostic error will often lead to either a perforation or the removal of a normal appendix. In this study, we constructed a Bayesian network model for the diagnosis of acute appendicitis and compared the diagnostic accuracy with other diagnostic models, such as the naive Bayes model, an artificial neural network model, and a logistic regression model.
    Methods: The data from 169 patients, who suffered from acute abdominal pain and who were suspected of having an acute appendicitis, were analyzed in this study. Nine variables were used for the evaluation of the accuracy of the four models for the diagnosis of an acute appendicitis. The naive Bayes model, the Bayesian network model, an artificial neural network model, and a logistic regression model were used in this study for the diagnosis of acute appendicitis. These four models were validated by using the ".632 + bootstrap method" for resampling. The levels of accuracy of the four models for diagnosis were compared by the error rates and by the areas under the receiver operating characteristic curves.
    Results: Through the course of illness, 50.9% (86 of 169) of the patients were diagnosed as having an acute appendicitis. The error rate was the lowest in the Bayesian network model, as compared with the other diagnostic models. The area under the receiver operating characteristic curve analysis also showed that the Bayesian network model provided the most reliable results.
    Conclusion: The Bayesian network model provided the most accurate results in comparison to other models for the diagnosis of acute appendicitis.

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  • Analysis of perimenstrual asthma based on questionnaire surveys in Japan 査読

    Kazuo Suzuki, Takashi Hasegawa, Takuro Sakagami, Toshiyuki Koya, Shinichi Toyabe, Kohei Akazawa, Masaaki Arakawa, Fumitake Gejyo, Eiichi Suzuki

    Allergology International56 ( 3 ) 249 - 255   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Allergology  

    Background: Perimenstrual asthma (PMA) has been documented in 30% to 40% of asthmatic women
    the characteristics of PMA have also been well described. However, there have been few epidemiological investigations of PMA in practice. In this study, we analyzed PMA based on a questionnaire survey carried out in Japan and compared the results with those of studies reported previously. Methods: For 8 weeks from September through October 2004, a questionnaire survey was administered to patients with bronchial asthma and their attending physicians. The questionnaire surveyed asthma control, asthma-related emergencies and satisfaction in daily life. The attending physicians were questioned about patient profiles and medications. All female patients who were menstruating during the survey period and who were known to have asthma exacerbation related to menstruation were allocated to the PMA group
    those who were not were allocated to the non-PMA group. Results: The rate of PMA in female patients who were menstruating during the survey period was 11.3% in this study. Characteristic features of the PMA group (n = 54) included more severe disease, worsened disease control and more aggressive patient management, including increased oral corticosteroid use compared with the non-PMA group. The rates of emergency episodes in the PMA group were higher than in the non-PMA group. There was a significant increase in aspirin intolerant asthma (AIA, 25.5%) in the PMA group compared with the non-PMA group (8.4%). Conclusions: Attention should be paid to the lack of knowledge regarding PMA in patients with asthma in actual clinical settings. The low rate of PMA reported in this study may be due to the study method using self-reports of PMA by patients without sufficient knowledge, and may not be an accurate representation of the actual incidence of the disease. The clinical similarity of PMA to AIA in this study may also provide a new insight into the mechanism of PMA. ©2007 Japanese Society of Allergology.

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  • Impaired psychological recovery in the elderly after the Niigata-Chuetsu Earthquake in Japan: a population-based study 査読

    Shin-ichi Toyabe, Toshiki Shioiri, Hideki Kuwabara, Taroh Endoh, Naohito Tanabe, Toshiyuki Someya, Kouhei Akazawa

    BMC PUBLIC HEALTH6   230   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P. M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly.
    Methods: Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale.
    Results: GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors ( social dysfunction and dysphoria) using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake.
    Conclusion: Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems.

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  • Differences in characteristics between suicide victims who left notes or not 査読

    Hideki Kuwabara, Toshiki Shioiri, Akiyoshi Nishimura, Ryo Abe, Hideyuki Nushida, Yasuhiro Ueno, Kohel Akazawa, Toshiyuki Someya

    JOURNAL OF AFFECTIVE DISORDERS94 ( 1-3 ) 145 - 149   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Background: Suicide notes (SN) are one of markers of the severity of a suicide attempt and are said to provide a valuable insight into the thinking of suicide victims before the fatal act [Shah, A., De, T., 1998. Suicide and the elderly. Int. J. Psychiat. Clin Pract. 2, 3-18]. To examine whether suicide victims who wrote notes (note writers: NW) differ from those who did not, we investigated the characteristics of a sample of more than 5000 Japanese suicides using multiple logistic regression analysis.
    Methods: For all suicide victims (5161 cases), we examined the following information: gender, age, suicide method, reason for suicide, marital status, residential status, history of psychiatric disorders, previous suicidal behavior, physical disease, and content of suicide notes.
    Results: Mean incidence of NW was 30.1% (male: 29.7%, female: 30.8%). NW in Japan had the following characteristics; higher proportion in female and living alone, suicide by more lethal methods such as carbon monoxide, hanging or sharp instruments. On the other hand, non-NW had tendencies to commit suicide for reasons of physical illness and psychiatric disorder, and/or history of previous psychiatric disorders.
    Limitations: This study is observational and discusses only completed, not attempted, suicide. Medical and psychiatric comorbidity are judged only by the history of diagnosis and the information about the problems in relationships is based not on valid criteria for inclusion.
    Conclusions: Although these findings show ethnic differences, it is possible that SN may be considered an indicator of a serious suicide attempt. Further studies of SN are needed to confirm this. (c) 2006 Elsevier B.V. All rights reserved.

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  • Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease 査読

    R Kuwano, A Miyashita, H Arai, T Asada, M Imagawa, M Shoji, S Higuchi, K Urakami, A Kakita, H Takahashi, T Tsukie, S Toyabe, K Akazawa, Kanazawa, I, Y Ihara

    HUMAN MOLECULAR GENETICS15 ( 13 ) 2170 - 2182   2006年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the epsilon 4 variant of APOE, because about half of AD patients have the APOE-epsilon 3*3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-epsilon 3*3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P &lt; 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P=0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P &lt; 0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-epsilon 3*3 genotype or lacking the epsilon 4 allele, and DNMBP may be one of the susceptibility genes for AD.

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  • Squamous cell carcinoma-antigen messenger RNA level in peripheral blood predicts recurrence after resection in patients with esophageal squamous cell carcinoma 査読

    H Honma, T Kanda, H Ito, T Wakai, S Nakagawa, M Ohashi, Y Koyama, VA Valera, K Akazawa, K Hatakeyama

    SURGERY139 ( 5 ) 678 - 685   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY, INC  

    Background. The aim of this study was to clarify whether preoperative squamous cell carcinoma-antigen messenger RNA (SCC-Ag mRNA) level in peripheral blood can be used to predict tumor recurrence after curative resection for esophageal squamous cell carcinoma.
    Methods. A prospective analysis was conducted for 46 consecutive patients who underwent curative esophagectomy and who had no residual tumor. The SCC-Ag mRNA level in the peripheral blood of each patient was measured preoperatively by using quantitative reverse transcriptase-polymerase chain reaction. Median follow-up period was 34 months.
    Results. Receiver operating characteristic analysis demonstrated that the optimal cutoff level of SCC-Ag mRNA was 40. Patients were divided into the high SCC-Ag mRNA level group (n = 14) and the low SCC-Ag mRNA level group (n = 32). The cumulative probabilities of tumor recurrence were higher in the high SCC-Ag mRNA level group (probability of recurrence was 71% at 2 years) than in the low group (22% at 2 years; P = .0005). SCC-Ag mRNA level (relative risk, 3.00; 95% confidence interval, 1.05-8.54; P = .040) was the strongest independent predictor of recurrence by multivariate analysis.
    Conclusions. Preoperative SCC-Ag mRNA levels in the peripheral blood are the best predictive factor for recurrence in patients with esophageal squamous cell carcinoma who undergo curative resection (R0).

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  • Seasonality in the incidence of biliary atresia in Japan. 査読

    Nakamizo M, Toyabe S, Kubota M, Komata O, Suzuki H, Akazawa K

    Acta paediatrica (Oslo, Norway : 1992)95 ( 4 ) 509 - 510   2006年4月

  • Development of a practical costing method for hospitals 査読

    P Cao, S Toyabe, K Akazawa

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE208 ( 3 ) 213 - 224   2006年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TOHOKU UNIV MEDICAL PRESS  

    To realize an effective cost control, a practical and accurate cost accounting system is indispensable in hospitals. In traditional cost accounting systems, the volume-based costing (VBC) is the most popular cost accounting method. In this method, the indirect costs are allocated to each cost object (services or units of a hospital) using a single indicator named a cost driver (e.g., Labor hours, revenues or the number of patients). However, this method often results in rough and inaccurate results. The activity based costing (ABC) method introduced in the mid 1990s can prove more accurate results. With the ABC method, all events or transactions that cause costs are recognized as "activities", and a specific cost driver is prepared for each activity. Finally, the costs of activities are allocated to cost objects by the corresponding cost driver. However, it is much more complex and costly than other traditional cost accounting methods because the data collection for cost drivers is not always easy. In this study, we developed a simplified ABC (S-ABC) costing method to reduce the workload of ABC costing by reducing the number of cost drivers used in the ABC method. Using the S-ABC method, we estimated the cost of the laboratory tests, and as a result, similarly accurate results were obtained with the ABC method (largest difference was 2.64%). Simultaneously, this new method reduces the seven cost drivers used in the ABC method to four. Moreover, we performed an evaluation using other sample data from physiological laboratory department to certify the effectiveness of this new method. In conclusion, the S-ABC method provides two advantages in comparison to the VBC and ABC methods: (1) it can obtain accurate results, and (2) it is simpler to perform. Once we reduce the number of cost drivers by applying the proposed S-ABC method to the data for the ABC method, we can easily perform the cost accounting using few cost drivers after the second round of costing.

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  • Risk factors for severe coronary artery disease - a case-control study of patients who have undergone coronary artery bypass grafting. 査読

    Kosuge K, Sasaki H, Ikarashi T, Toyabe S, Akazawa K, Kobayashi C, Abe E, Suzuki A, Saito H, Eguchi S, Otsuka H, Aizawa Y

    Journal of atherosclerosis and thrombosis13 ( 1 ) 62 - 7   2006年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5551/jat.13.62

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  • Referral from secondary care and to aftercare in a tertiary care university hospital in Japan 査読

    S Toyabe, A Kouhei

    BMC HEALTH SERVICES RESEARCH6   11   2006年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: In Japan, all citizens are covered by the national insurance system in which universal free access to healthcare services is promised to everybody. There are no general physicians or gatekeepers in the Japanese healthcare system.
    Methods: We studied the pattern of referral of inpatients from secondary care hospitals to a tertiary care university hospital and the reverse referral under the situations using a geographic information system (GIS), taking paediatric inpatients as an example.
    Results: The results showed that 61.2% of the patients were directly admitted to the hospital without referral from other hospitals or clinics and that 82.8% of the inpatients were referred to the outpatient department of the hospital to which they had been admitted. GIS analysis for the inpatients service area showed the hospital functions as both a secondary care hospital and tertiary care hospital. Patients who lived near the hospital tended to be admitted directly to the hospital, and patients who lived far from the hospital tended to utilize the hospital as a tertiary care provider. There were territorial disputes with other secondary care hospitals. To estimate spatial differences in referral to aftercare, we analyzed the spatial distribution of inpatients with focus on their length of hospital stay (LOS). GIS analysis revealed apparent foci of patients with long LOS and those with low LOS.
    Conclusion: These results suggest that the function of university hospital in Japan is unspecialized and that the referral route from the university hospital to aftercare is also unequipped.

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  • Profit and loss analysis for an intensive care unit (ICU) in Japan: a tool for strategic management 査読

    PY Cao, S Toyabe, T Abe, K Akazawa

    BMC HEALTH SERVICES RESEARCH6   1   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Accurate cost estimate and a profit and loss analysis are necessary for health care practice. We performed an actual financial analysis for an intensive care unit (ICU) of a university hospital in Japan, and tried to discuss the health care policy and resource allocation decisions that have an impact on critical intensive care.
    Methods: The costs were estimated by a department level activity based costing method, and the profit and loss analysis was based on a break-even point analysis. The data used included the monthly number of patients, the revenue, and the direct and indirect costs of the ICU in 2003.
    Results: The results of this analysis showed that the total costs of US$2,678,052 of the ICU were mainly incurred due to direct costs of 88.8%. On the other hand, the actual annual total patient days in the ICU were 1,549 which resulted in revenues of US$2,295,044. However, it was determined that the ICU required at least 1,986 patient days within one fiscal year based on a break-even point analysis. As a result, an annual deficit of US$383,008 has occurred in the ICU.
    Conclusion: These methods are useful for determining the profits or losses for the ICU practice, and how to evaluate and to improve it. In this study, the results indicate that most ICUs in Japanese hospitals may not be profitable at the present time. As a result, in order to increase the income to make up for this deficit, an increase of 437 patient days in the ICU in one fiscal year is needed, and the number of patients admitted to the ICU should thus be increased without increasing the number of beds or staff members. Increasing the number of patients referred from cooperating hospitals and clinics therefore appears to be the best strategy for achieving these goals.

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  • Comparison between compliance of fluticasone propionate Diskhaler and of fluticasone propionate Diskus in adult bronchial asthma patients 査読

    Takashi Hasegawa, Eiichi Suzuki, Katsuya Fujimori, Takuro Sakagami, Shinichi Toyabe, Kouhei Akazawa, Kenji Kawano, Michihiko Haraguchi, Joji Toyama, Masaaki Arakawa, Hiroshi Satoh, Fumitake Gejyo

    RESPIRATION73 ( 5 ) 680 - 684   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Background and Objectives: Because inhaled corticosteroids (ICS) play a central role in the management of asthma, new drug delivery systems for fluticasone propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few studies have focused on compliance with these drug delivery systems, which can influence drug efficacy. Hence, we compared compliance with FPdk versus that with FPdh. Methods: Data were obtained from a survey of pharmacists dispensing anti-asthmatic drugs to adult asthma patients who visited participating pharmacies between October 2002 and November 2003. Patients were limited to regular users of FPdh or FPdk whose medication and daily administration frequency of ICS were evaluated on the basis of pharmaceutical records. Data on asthma status and various other factors affecting ICS compliance were obtained by questionnaire. Results: Data were acquired on 337 patients. There were no significant differences in gender, age, and duration between the FPdk and FPdh groups. Although FPdk compliance was significantly higher than that of FPdh, conversely there was no significant difference in daily dose and administration frequency between the 2 groups. Furthermore, there was no significant difference in the rate of concomitant drug and in various influencing factors associated with drug compliance. Regarding compliance of concomitant drug, that of oral sustained-released theophylline was significantly lower in FPdk versus FPdh users. Conclusion: In the area of drug compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it is probably due to the characteristics of FPdk itself. Copyright (C) 2006 S. Karger AG, Basel.

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  • Development of a simulation program for estimating hospital incomes under the prospective payment system 査読

    T Abe, S Toyabe, PY Cao, S Kurashima, K Akazawa

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE80 ( 3 ) 271 - 276   2005年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    A prospective payment system based on diagnosis procedure combination (DPC/PPS) was introduced to acute care hospitals in Japan in April 2003. In order to increase hospital income, hospitals must shorten the average Length of stay (ALOS) and increase the number of patients. We constructed a simulation program for evaluating the relationships among ALOS, bed occupation rate (BOR) and hospital income of hospitals in which DPC/PPS has been introduced. This program can precisely evaluate the hospital income by regulating the ALOS and the number of patients for each DPC. By using this program, it is possible to predict the optimum ALOS and optimum number of inpatients for each DPC in order to increase hospital income. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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  • Development of a simulation program for estimating hospital incomes under the prospective payment system 査読

    T Abe, S Toyabe, PY Cao, S Kurashima, K Akazawa

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE80 ( 3 ) 271 - 276   2005年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    A prospective payment system based on diagnosis procedure combination (DPC/PPS) was introduced to acute care hospitals in Japan in April 2003. In order to increase hospital income, hospitals must shorten the average Length of stay (ALOS) and increase the number of patients. We constructed a simulation program for evaluating the relationships among ALOS, bed occupation rate (BOR) and hospital income of hospitals in which DPC/PPS has been introduced. This program can precisely evaluate the hospital income by regulating the ALOS and the number of patients for each DPC. By using this program, it is possible to predict the optimum ALOS and optimum number of inpatients for each DPC in order to increase hospital income. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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  • Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma. 査読

    Kaneko K, Shirai Y, Wakai T, Yokoyama N, Akazawa K, Hatakeyama K

    World journal of gastroenterology11 ( 37 ) 5888 - 92   2005年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3748/wjg.v11.i37.5888

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  • Serotonin-2A and 2C receptor gene polymorphisms in Japanese patients with obstructive sleep apnea. 査読

    Sakai K, Takada T, Nakayama H, Kubota Y, Nakamata M, Satoh M, Suzuki E, Akazawa K, Gejyo F

    Internal medicine (Tokyo, Japan)44 ( 9 ) 928 - 33   2005年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.44.928

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  • Facial axis angle as a risk factor for obstructive sleep apnea. 査読

    Kubota Y, Nakayama H, Takada T, Matsuyama N, Sakai K, Yoshizawa H, Nakamata M, Satoh M, Akazawa K, Suzuki E, Gejyo F

    Internal medicine (Tokyo, Japan)44 ( 8 ) 805 - 10   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma 査読

    K Hashimoto, Y Ikeda, D Korenaga, K Tanoue, M Hamatake, K Kawasaki, T Yamaoka, Y Iwatani, K Akazawa, K Takenaka

    CANCER103 ( 9 ) 1856 - 1864   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BACKGROUND. The authors evaluated the significance of the preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with hepatocellular carcinoma (HCC).
    METHODS. One hundred forty-one patients who underwent curative resection for HCC were reviewed retrospectively. Clinicopathologic variables were compared between patients with serum CRP levels &gt;= 1.0 mg/dL (n = 22 patients; the CRP-positive group) and patients with serum CRP levels &lt; 1.0 mg/dL (n = 119 patients; the CRP-negative group). Univariate and multivariate analyses were conducted to identify factors that affected survival and disease recurrence.
    RESULTS. There was a significant correlation between the preoperative serum CRP level and tumor size. Invasion to the portal vein in the CRP-positive group was significantly more frequent than that in the CRP-negative group. Even after they underwent curative resection, 75.3% of patients in the CRP-positive group experienced recurrence within 1 year. The overall survival and recurrence-free survival rates in the CRP-positive group were significantly lower compared with the rates in the CRP-negative group. On multivariate analysis, the preoperative serum CRP level was selected as one of the unfavorable indicators regarding survival and recurrence. When CRP levels, albumin levels, and platelet counts that were available before surgery were scored as a combined index, the total score demonstrated a good stratification value for survival after hepatic resection.
    CONCLUSIONS. The current results showed that the preoperative serum CRP level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC. The new CRP-based scoring system offers reliable information for predicting survival. (c) 2005 American Cancer Society.

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  • Incidence of note-leaving remains constant despite increasing suicide rates. 査読

    Shioiri T, Nishimura A, Akazawa K, Abe R, Nushida H, Ueno Y, Kojika-Maruyama M, Someya T

    Psychiatry and clinical neurosciences59 ( 2 ) 226 - 8   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: A pooled analysis of six randomized controlled trials 査読

    S Noguchi, H Koyama, J Uchino, R Abe, S Miura, K Sugimachi, K Akazawa, O Abe

    JOURNAL OF CLINICAL ONCOLOGY23 ( 10 ) 2172 - 2184   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC CLINICAL ONCOLOGY  

    Purpose This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients.
    Patients and Methods Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients).
    Results Overall survival was compared between the UFT group (including both the UFT group and the TAM plus OFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset.
    Conclusion Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer. (c) 2005 by American Society of Clinical Oncology.

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  • Jaundice at presentation heralds advanced disease and poor prognosis in patients with ampullary carcinoma 査読

    N Yokoyama, Y Shirai, T Wakai, S Nagakura, K Akazawa, K Hatakeyama

    WORLD JOURNAL OF SURGERY29 ( 4 ) 519 - 523   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Jaundice is a common manifestation of ampullary carcinoma. The aim of this study was to evaluate the correlation between jaundice at initial presentation and the degree of tumor spread and to determine the prognostic significance of jaundice in patients with ampullary carcinoma. Fifty-nine patients who had undergone curative resection for ampullary carcinoma were analyzed retrospectively. Jaundice was defined as a total bilirubin serum concentration of &gt;= 3 mg/dl. The median follow-up time was 106 months. Jaundice was noted at the time of initial presentation in 43 (73%) patients. Jaundice at presentation correlated with lymph node metastasis (p &lt; 0.0001), lymphatic vessel invasion (p &lt; 0.0001), invasion into the pancreas (p = 0.0007), and vascular invasion (p = 0.0487). Pancreatic invasion was absent in patients without jaundice. Superior mesenteric nodal involvement was more frequent in patients with jaundice (15143) than in those without (0/16) (p = 0.0062). The survival of patients with jaundice (median survival 48 months; cumulative 10-year survival rate 39%) was worse than for patients without jaundice (median survival time not available; cumulative 10-year survival rate 86%) (p = 0.0014). In conclusion, jaundice at presentation predicts advanced-stage ampullary carcinoma and a poor prognosis. Pancreatic invasion and superior mesenteric nodal involvement were not observed in non-jaundiced patients.

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  • Incidence and distribution of hybrid goblet cells in complete type intestinal metaplasia of the stomach 査読

    R Aihara, Y Ajioka, H Watanabe, H Shiroshita, K Akazawa, H Kuwano

    PATHOLOGY RESEARCH AND PRACTICE201 ( 1 ) 11 - 19   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:URBAN & FISCHER VERLAG  

    Previous reports suggest that hybrid goblet cells (HGCs) sharing both gastric and intestinal mucin phenotypes are rarely observed in complete intestinal metaplasia, (cIM) of the stomach. However, we have made a different observation. Thus, we compared the incidence and distribution of HGCs within the tubules of gastric cIM and the duodenum in order to define the significance of HGCs. Fifteen antral sections and 16 fundic sections from tissue with cIM and gastric cancer, as well as 19 sections from duodenal tissue with cancer of the Papilla of Vater, were stained for human gastric mucin (HGM), Con A, MUC2, CD10, and Ki-67. Multivariate analysis showed that antral location, a distance of 5 mm or less from the tumor margin, and the presence of underlying pyloric glands were significant predictive factors for tubules containing &gt; 50% HGCs as part of their goblet cell population. The incidence of tubules with HGCs differed significantly in tissue samples from the antrum, body and duodenum. HGCs did not stain for Ki-67 and were not surrounded by gastric foveolar-type epithelium within the tubules of cIM foci. These findings indicate that alterations in the proportion of HGCs may occur tinder some circumstances, and that HGCs are not precursors to gastric foveolar-type cells in the stomach and duodenum. (c) 2004 Elsevier GmbH. All rights reserved.

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  • Web-based delivery of medical multimedia contents using an MPEG-4 system 査読

    T Yamakawa, SI Toyabe, PY Cao, K Akazawa

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE75 ( 3 ) 259 - 264   2004年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Moving picture expert group compression standard version 4 (MPEG-4) is a standard for video coding aimed at multimedia applications. MPEG-4 was developed to enable high compression rate in a low bitrate transmission via the Internet or mobile telecommunications. Although these characteristics of MPEG-4 are suitable for tetemedicine, little is known about the possibility of using this technology in the field of telemedicine. We evaluated the quality of MPEG-4-encoded medical video streams and compared them with original analogue videos and audio-video-interleave (AVI) files. Although MPEG-4 video streams have the advantage of small file size, they were found to be inferior to original videos and AVI files in terms of smoothness of motion pictures, sharpness of images and clearness of sound. Illegibility of characters was a major probelem in MPEG-4 files. The score for total impression of MPEG-4 files was significantly lower than those for AVI files. The results of this study suggest that the quality of MPEG-4-encoded video streams is not adequate for telemedicine. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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  • Association of tumor necrosis factor receptor type 2+587 gene polymorphism with severe chronic periodontitis 査読

    Y Shimada, H Tai, M Endo, T Kobayashi, K Akazawa, K Yamazaki

    JOURNAL OF CLINICAL PERIODONTOLOGY31 ( 6 ) 463 - 469   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Background: Genetic polymorphisms for cytokines and their receptors have been proposed as potential markers for periodontal disease. Tumor necrosis factor receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and other diseases.
    Objectives: The aim of the present study is to evaluate whether TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP).
    Methods: One hundred and ninety-six unrelated subjects (age 40-65 years) with different levels of CP were identified according to established criteria, including measurements of probing pocket depth (PPD), clinical attachment level (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non-smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method.
    Results: The frequency and the positivity of the +587G allele were significantly higher in severe CP patients than in controls (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values of PPD, CAL, and BL were significantly higher in the +587G allele positive than in the negative subjects (p=0.035, 0.022, and 0.018, respectively).
    Conclusions: These findings suggest that the TNFR2(+587G) polymorphic allele could be associated with severe CP in Japanese.

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  • Economic slump and suicide method: preliminary study in Kobe. 査読

    Abe R, Shioiri T, Nishimura A, Nushida H, Ueno Y, Kojima M, Kitamura H, Akazawa K, Someya T

    Psychiatry and clinical neurosciences58 ( 2 ) 213 - 6   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1440-1819.2003.01219.x

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  • A method for displaying two images on a screen in distance medical education 査読

    A Motonaga, K Akazawa, S Takahashi, Y Yamamoto, H Tsukada, K Inagawa, T Yamakawa, M Hashiba

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE73 ( 3 ) 183 - 188   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    This article describes a method for simultaneously displaying several 'REALPLAYER' ages on a screen during an online multimedia presentation. Users with software and Web browsers can view images with synchronous audio on their personal computers via the Internet. Medical researchers and physicians often find it useful to compare images after treatment with those before treatment, by displaying several arranged images simultaneously. Medical care providers can browse this type of multimedia content in their offices and universities at their convenience. There presently exist two methods for creating multimedia content with voice and images using ReaLSystem technology. Electronic lectures of otorhinolaryngology explaining new surgical procedures for patients with chronic otitis media were created with this method and made available to otorhinotaryngologists through the Internet. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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  • Increased risk of cholelithiasis after esophagectomy 査読

    K Tsunoda, Y Shirai, T Wakai, N Yokoyama, K Akazawa, K Hatakeyama

    JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY11 ( 5 ) 319 - 323   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    Background/Purpose. Truncal vagotomy enhances gallstone formation. As esophagectomy involves truncal vagotomy, it was hypothesized that esophagectomy would increase the risk of cholelithiasis. This study was intended to test this hypothesis and to elucidate factors influencing the incidence of cholelithiasis after esophagectomy.
    Methods. The study was a retrospective analysis of 136 patients with esophageal carcinoma who had survived for 5 years or longer after esophagectomy. Eight patients (5.9%) had cholelithiasis before esophagectomy. Of the remaining 128 patients, 113 underwent abdominal ultrasonographic examination for cholelithiasis twice a year after esophagectomy; the median follow-up time was 89.5 months (range, 60-1.17 months).
    Results. Gallstones developed in 26 (23%) of the 113 patients undergoing regular ultrasonographic examination. The cumulative incidence of cholelithiasis reached a plateau of 34% at 10 years after esophagectomy. Reduction of body mass index after esophagectomy was the strongest independent predictor of gallstone formation after esophagectomy (P = 0.0001, log-rank test; P = 0.0003, Cox's proportional hazards model). The prevalence of cholelithiasis at 5 years after esophagectomy (18/113; 16%) was significantly higher than that before esophagectomy (8/136: 5.9%: P = 0.012, Fisher's exact test).
    Conclusions. Esophagectomy yields an increased risk of the development of cholelithiasis. Truncal vagotomy and postsuraical malnutrition may contribute to this increased gallstone formation after esophagectomy.

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  • Vascular endothelial growth factor-C and vascular endothelial growth factor-d messenger RNA expression in breast cancer: association with lymph node metastasis. 査読

    Koyama Y, Kaneko K, Akazawa K, Kanbayashi C, Kanda T, Hatakeyama K

    Clinical breast cancer4 ( 5 ) 354 - 60   2003年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Efficacy of fluticasone propionate compared with beclomethasone dipropionate in bronchial asthma: improvement in compliance and symptoms by fluticasone. 査読

    Suzuki T, Hasegawa T, Suzuki E, Sasahara K, Kawada T, Koya T, Akazawa K, Satoh H, Gejyo F

    Allergy and asthma proceedings24 ( 5 ) 347 - 51   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients 査読

    Narita, I, S Goto, N Saito, J Song, J Ajiro, F Sato, D Saga, D Kondo, K Akazawa, M Sakatsume, F Gejyo

    HYPERTENSION42 ( 3 ) 304 - 309   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    An interaction effect between the angiotensin-converting enzyme insertion/deletion ( ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi(2) = 6.062, P = 0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 ( P = 0.0016), but not for those with other ACE genotypes ( hazard ratio = 0.65, P = 0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.

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  • Pepstatin A induces extracellular acidification distinct from aspartic protease inhibition in microglial cell lines 査読

    M Okada, S Irie, M Sawada, R Urae, A Urae, N Iwata, N Ozaki, K Akazawa, H Nakanishi

    GLIA43 ( 2 ) 167 - 174   2003年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    The extrusion of protons is considered a very general parameter of the activation of many kinds of membrane or intracellular molecules, such as receptors, ion channels, and enzymes. We found that pepstatin A caused a reproducible, concentration-related increase in the extracellular acidification rate in two microglial cell lines, Ra2 and 6-3. Washing abolished pepstatin A-induced acidification immediately. However, pepstatin A did not cause the extracellular acidification in other cell types, such as CHO, C6 glioma, and NIH3T3 cells. These observations strongly suggest that pepstatin A interacts with certain membrane proteins specific to both Ra2 and 6-3 cells from outside. N-methylmaleimide and N,N-dicyclohexylcarbodiimide, inhibitors of H+-ATPase, were found to reduce pepstatin A-induced response strongly, while bafilomycin A1, a vacuolar H+-ATPase inhibitor, vanadate, a P-type H+-ATPase inhibitor, and NaN3, an F1 ATPase inhibitor, virtually did not. 5-(N-ethyl-N-isopropyl) amiloride, an inhibitor of Na+/H+ exchanger isoform 1, greatly enhanced pepstatin-induced response, while amiloride did not. Zn2+, a voltage-dependent proton channel blocker, did not affect pepstatin-induced response neither. Staurosporine, a nonspecific inhibitor of protein kinase C, inhibited pepstatin A-induced response, while chelerythrine, more selective inhibitor of protein kinase C, greatly enhanced it. H-7 and H-8 did not affected the response. These findings suggest that pepstatin A induces extracellular acidification in microglia cell lines, Ra2 and 6-3, through an N-methylmaleimide- and NN'-dicyclohexylearbodiimide-sensitive, but bafilomycin A1-insensitive, ATPase, which seems to be distinct from protein kinase C-dependent process. (C) 2003 Wiley-Liss, Inc.

    DOI: 10.1002/glia.10237

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  • An integrated medical image database and retrieval system using a web application server 査読

    PY Cao, M Hashiba, K Akazawa, T Yamakawa, T Matsuto

    INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS71 ( 1 ) 51 - 55   2003年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We developed an Integrated Medical Image Database and Retrieval System (INIS) for easy access by medical staff. The INIS mainly consisted of four parts: specific servers to save medical images from mutti-vendor modalities of CT, MRI, CR, ECG and endoscopy; an integrated image database (DB) server to save various kinds of images in a DICOM format; a Web application server to connect clients to, the integrated image DB and the Web browser terminals connected to an HIS system. The INIS provided a common screen design to retrieve CT, MRI, CR,endoscopic and ECG images, and radiological reports, which would allow doctors to retrieve radiological images and corresponding reports, or ECG images of a patient simultaineously on a screen. Doctors working in internal medicine on average accessed information 492 times a month. Doctors working in cardiological and gastroenterological accessed information 308 times a month. Using the INIS, medical staff could browse all or parts of a patient's medical images and reports. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/S1386-5056(03)00088-1

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  • Gastrointestinal cancer and herpes zoster in adults. 査読

    Yamamoto M, Mine H, Akazawa K, Maehara Y, Sugimachi K

    Hepato-gastroenterology50 ( 52 ) 1043 - 6   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Delivery of medical multimedia contents through the TCP/IP network using RealSystem 査読

    Suzuki, I, K Yamada, T Yamakawa, M Hashiba, K Akazawa

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE70 ( 3 ) 253 - 258   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We developed a low cost, user-friendly multimedia delivery system, to provide medical lectures saved as multimedia contents to persons engaged in medicine. This system was created using the RealSystem package with the TCP/IP network. Users can review lectures and medical meeting presentations with video and audio through the Internet, whenever convenient. Each medical source of video and slide has been clearly displayed on a screen. Members of medical associations or medical students can easily review the most interesting parts of these files. This system is being used efficiently in distance learning and aids the diffusion of the latest information and technology to busy physicians and medical students. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0169-2607(02)00012-3

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  • Immunohistochemically detected micrometastasis in lymph nodes from superficial esophageal squamous cell carcinoma 査読

    T Tanabe, T Nishimaki, H Watanabe, Y Ajioka, K Akazawa, S Komukai, K Hatakeyama

    JOURNAL OF SURGICAL ONCOLOGY82 ( 3 ) 153 - 159   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Background and Objectives: This study was conducted to determine the incidence and clarify the patterns of nodal micrometastasis, to elucidate the histopathologic parameters of tumor extension correlating with micrometastasis, and to evaluate whether nodal micrometastasis has clinical significance in patients with superficial esophageal cancer.
    Methods: Lymph nodes resected from 78 patients with superficial esophageal squamous cell carcinoma were examined immunohistochemically using the monoclonal antibody cocktail AE1/AE3 to define histologically undetectable micrometastasis. Clinical records and pathologic features of all cases were reviewed.
    Results: Of the 78 patients, 34 had neither micro- nor overt disease in the lymph nodes, 12 had nodal micrometastasis only, and 32 had histologically overt metastasis. Nodal micrometastasis was found in carcinomas reaching the muscularis mucosae or deeper tissues of the esophagus. Multivariate analysis showed that intraesophageal multicentric cancer and venous invasion had significant correlation with nodal micrometastasis (P = 0.005 and 0.017, respectively). However, no clinical impact of nodal micrometastasis could be detected regarding patient outcome.
    Conclusions: Nodal micrometastasis is not rare in patients with superficial esophageal cancer, but it does not appear to have clinical significance in these patients. Nodal Micrometastasis correlates with intraesophageal multicentric cancer and venous invasion. (C) 2003 Wiley-Liss, Inc.

    DOI: 10.1002/jso.10207

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  • Attitude control using CMAC for electric wheelchairs equipped with hydraulic cylinder 査読

    S Fujisawa, K Akazawa, R Kurozumi, K Kawada, T Yamamoto, H Uenaka

    2003 IEEE INTERNATIONAL SYMPOSIUM ON COMPUTATIONAL INTELLIGENCE IN ROBOTICS AND AUTOMATION, VOLS I-III, PROCEEDINGS   1312 - 1316   2003年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:IEEE  

    We developed a posture control system for an electric wheelchair equipped with active suspension, using CMAC which is a neural network type of control. Testing of the posture control of the wheelchair, which considers a learning result as an output to the target value inputted on-line using the learning function of CMAC (Cerebellar Model Arithmetic Controller), was performed. In this paper, testing of the learning control which holds the posture horizontally both by the simulation and in the experiment by the system, is performed, and the validity of CMAC is verified.

    DOI: 10.1109/CIRA.2003.1222186

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  • A(-20)C polymorphism of the angiotensinogen gene and progression of IgA nephropathy. 査読

    Goto S, Narita I, Saito N, Watanabe Y, Yamazaki H, Sakatsume M, Shimada H, Nishi S, Ueno M, Akazawa K, Arakawa M, Gejyo F

    Kidney international62 ( 3 ) 980 - 5   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1046/j.1523-1755.2002.00517.x

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  • Therapeutic value of lymph node dissection and the clinical outcome for patients with gastric cancer 査読

    Y Maehara, Y Kakeji, T Koga, Y Emi, H Baba, K Akazawa, K Sugimachi

    SURGERY131 ( 1 ) S85 - S91   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY, INC  

    Background. While the incidence of gamic cancer differs greatly between Japan and other countries, both diagnostic and treatment modalities for patients with gastric cancer have improved in Japan. What follows is an overview of the effects of lymph node dissection for such patients.
    Methods. We analyzed data on 2152 Japanese men and women with gastric cancer who underwent surgical resection from 1965 to 1995 at Kyushu University in Fukuoka, Japan. We focused on time trends of surgical management, including lymph node dissection and postoperative outcome.
    Results. In all cases of gastric cancer, the rate of early gastric cancer increased from 18% in the first 6-year period to 57% in the last 5-year period. Extensive lymph node dissections (D2 and D3) were performed more frequently in recent years. Due to early identification of the cancer and upgraded perioperative care, both postoperative morbidity and mortality rates 30 days after surgery have decreased greatly, even in aged patients.
    Conclusions. Early tumor detection, standardized surgical treatment, including routine lymph node dissection, and improved perioperative management have led to increased survival time among patients with this malignancy.

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  • An easily customized, random allocation system using the minimization method for multi-Institutional clinical trials 査読

    Y Kenjo, Y Antoku, K Akazawa, E Hanada, N Kinukawa, Y Nose

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE62 ( 1 ) 45 - 49   2000年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    In a randomized clinical trial, random allocation of patients to treatment groups should be done to balance in the distribution of prognostic factors. Random allocation in a multi-institutional randomized clinical trial is conducted by a coordinating center, independent of the medical institution the attending doctor uses for his/her practice. This study provides a sophisticated system for doing an exact random allocation of patients to treatment groups. The minimization method proposed by Pocock was applied to this system to balance the distribution of prognostic factors between two treatment groups, even when the number of registered patients is relatively small (S.J. Pocock, Allocation of patients to treatment in clinical trial, Biometrics 35 (1979) 183-197). Furthermore, Zelen's method is used to balance the number of patients allocated to the two groups within each institution (M. Zelen, The randomization and stratification of patients to clinical trials, J. Chron. Dis. 27 (1974) 365-375.). This system was created by the 'PERL' language for writing common gateway interface (CGI) script, and can therefore, be easily extended to include data entry function by attending doctors as well as the random allocation function. This system is being used effectively in thirteen multi-institutional randomized clinical trials for stomach, colon-rectum and breast cancers in Japan. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

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  • A statistical model that takes into account patient heterogeneity in decision making 査読

    K Akazawa, T Nakamura, Y Nose

    MEDINFO '98 - 9TH WORLD CONGRESS ON MEDICAL INFORMATICS, PTS 1 AND 252   525 - 528   1998年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:I O S PRESS  

    Statistical evaluation of clinical treatments or preventive medicine has profoundly contributed to decision making in medical fields such as with the acceptance of new treatment methods and health promotion policies. It is crucial in such decision making to find a correct statistical model to heat a surprisingly large variety of patients, or a heterogeneous group of patients, even with the same diagnosis. In diseases such as cancer, cardiovascular disease or diabetes, patients are often followed up to certain endpoints and these data are frequently analyzed by logrank tests or Cox-models to evaluate treatment effects. Although these methods have been widely accepted and extensively studied we are sometimes faced with problems in applying these methods when the heterogeneity of patients is large and a lot of prognostic factors affecting the endpoints have to be considered. Based on the results of the analyses of survival data from more than 6,000 gastric cancer patients, if is revealed that the stratified logrank test may suffer serious power loss, even though primary prognostic factors are used as stratified factors. A so-called 'piecewise linear Cox regression method' for properly heating the heterogeneity of patients is introduced and extensively studied. This method is shown to be appropriate for patient groups with a high degree of heterogeneity such as the gastric cancer patients. The same method is, in principle, applicable to patients of other diseases, too, using statistical software such as SAS, BMDP and etc.

    DOI: 10.3233/978-1-60750-896-0-525

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  • A NOTE ON THE CORRECTED SCORE FUNCTION ADJUSTING FOR MISCLASSIFICATION 査読

    Kouhei Akazawa, Naoko Kinukawa, Tsuyoshi Nakamura

    OURNAL OF THE JAPAN STATISTICAL SOCIETY28 ( 1 ) 115 - 123   1998年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.14490/jjss1995.28.115

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  • Power of logrank test and Cox regression model in clinical trials with heterogeneous samples. 査読

    Akazawa K, Nakamura T, Palesch Y

    Statistics in Medicine16 ( 5 ) 583 - 97   1997年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/(SICI)1097-0258(19970315)16:5<583::AID-SIM433>3.0.CO;2-Z

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  • Measures of explained variation for a regression model used in survival analysis 査読

    Kouhei Akazawa

    Journal of Medical Systems21 ( 4 ) 229 - 238   1997年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This paper describes a measure of explained variation (MEV) of survival times for a given regression model used in survival analysis. It quantifies the predictive power of a set of prognostic factors in the model, and therefore provides useful information for more precise prediction of patient prognosis, and for designing randomized clinical trials with the capability of determining treatment effects. The MEV defined in this article is asymptotically derived from the squared product-moment correlation
    it can be interpreted as an adaptation of the multiple correlation coefficient for the normal linear model to the Survival time regression model. Monte-Carlo simulations are performed to investigate the statistical behavior of the proposed MEV. The MEV is applied to estimate the predictive power of several sets of prognostic factors for gastric cancer in Japan using data from a large clinical trial.

    DOI: 10.1023/A:1022884504683

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  • COMPUTER-PROGRAM FOR THE PROPORTIONAL HAZARDS MEASUREMENT ERROR MODEL 査読

    T NAKAMURA, K AKAZAWA

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE45 ( 3 ) 203 - 212   1994年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI PUBL IRELAND LTD  

    The Cox-regression analysis based on the partial likelihood assumes that the covariates, or independent variables, are exactly measured without error. if the covariates are subject to measurement error and the error-prone observed values are used in the analysis by simply ignoring the measurement error, the results are generally biased and misleading; the bias does not diminish as the sample size is increased. The objective of the paper is to briefly describe a method searching for asymptotically unbiased estimates of the parameters correcting for the measurement error in the Cox-regression model and to present a FORTRAN program to perform the correction method; asymptotic standard errors of the corrected estimates are also obtained, The measurement error distribution, that is the conditional distribution of the observed values given the true value, must be specified. An advantage of the method described is that it does not require any assumption on the distribution of the true values; in other words, I, values are treated as unknown fixed constants. It can accommodate tied failure times unless ties are very frequent, and any censorship or loss to follow-up are allowed as long as they are 'independent of survival',

    DOI: 10.1016/0169-2607(94)90204-6

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  • CORRECTED LIKELIHOOD FOR PROPORTIONAL HAZARDS MEASUREMENT ERROR MODEL AND ITS APPLICATION 査読

    T NAKAMURA, K AKAZAWA

    ENVIRONMENTAL HEALTH PERSPECTIVES102 ( 8 ) 21 - 24   1994年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATL INST ENVIRON HEALTH SCI  

    Consider the case where the exact values of covariates in the proportional hazards model may not be observed but instead, only surrogates for them involving measurement errors are available. The maximum likelihood estimate based on the partial likelihood with the true covariate replaced by the observed surrogate is even asymptotically biased and may cause seriously misleading results in covariance analysis based on the partial likelihood. These facts are illustrated by Monte Carlo simulation. A correction to partial likelihood proposed by the first author is studied to gain insight into its merits and limitations in practical applications. The results indicate that when the ''effective magnitude oi the measurement error'' as defined in this article is smell, which is indeed the case for most applications, the method will be useful. Some other correction methods for the measurement error in censored survival models are also reviewed and discussed.

    DOI: 10.1289/ehp.94102s821

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  • SIMULATION PROGRAM FOR ESTIMATING STATISTICAL POWER OF COX PROPORTIONAL HAZARDS MODEL ASSUMING NO SPECIFIC DISTRIBUTION FOR THE SURVIVAL-TIME 査読

    K AKAZAWA, T NAKAMURA, S MORIGUCHI, M SHIMADA, Y NOSE

    COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE35 ( 3 ) 203 - 212   1991年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Small sample properties of the maximum partial likelihood estimates for Cox's proportional hazards model depend on the sample size, the true values of regression coefficients, covariate structure, censoring pattern and possibly baseline hazard functions. Therefore, it would be difficult to construct a formula or table to calculate the exact power of a statistical test for the treatment effect in any specific clinical trial. The simulation program, written in SAS/IML, described in this paper uses Monte-Carlo methods to provide estimates of the exact power for Cox's proportional hazards model. For illustrative purposes, the program was applied to real data obtained from a clinical trial performed in Japan. Since the program does not assume any specific function for the baseline hazard, it is, in principle, applicable to any censored survival data as long as they follow Cox's proportional hazards model.

    DOI: 10.1016/0169-2607(91)90122-A

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  • CHEMOSENSITIVITY DIFFERENCES BETWEEN PRIMARY AND METASTATIC LESIONS OF CLINICAL GASTRIC-CANCER 査読

    H KUSUMOTO, Y MAEHARA, T KUSUMOTO, H ANAI, K AKAZAWA, K SUGIMACHI

    EUROPEAN JOURNAL OF SURGICAL ONCOLOGY14 ( 6 ) 685 - 689   1988年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO  

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  • EXCISED HUMAN NEOPLASTIC TISSUES ARE MORE SENSITIVE TO HEAT THAN THE ADJACENT NORMAL-TISSUES 査読

    Y MAEHARA, T KUSUMOTO, H KUSUMOTO, H ANAI, K AKAZAWA, K SUGIMACHI

    EUROPEAN SURGICAL RESEARCH20 ( 4 ) 254 - 259   1988年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    DOI: 10.1159/000128770

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  • Long-term survival in Japanese patients with far advanced cartinoma of the stomach. 査読

    Korenaga D, Tsujitani S, Haraguchi M, Okamura T, Tamada R, Sugimachi K, Akazawa K, Nose Y

    World Journal of Surgery12   236 - 240   1988年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/BF01658063}

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  • 黄体化ホルモン放出ホルモン誘導体(LHRH-a)による骨量低下の臨床的検討 -前立腺癌治療による骨粗鬆症誘発の危険-. 査読

    鈴木康之, 相川健, 大石幸彦, 山崎春城, 大西哲郎, 鈴木正泰, 小針俊彦, 遠藤勝久, 簗田周一, 加藤伸樹, 吉野恭正, 和田鉄郎, 上田正山, 高坂哲, 赤澤宏平

    日本泌尿器科学会雑誌 1988; 89(12): 961-966.89 ( 12 ) 961 - 966   1988年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.5980/jpnjurol1989.89.961

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  • 臨床検査の夜間申込システム. 査読

    野瀬善明, 渡辺義明, 横田将生, 赤澤宏平, 中村元臣, 長嶺光隆, 大河内一雄

    医療情報学8 ( 2 ) 107 - 116   1988年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Prediction of the prognosis of liver cirrhosis in Japanese using cox's proportional hazard model 査読

    Yuji Tsuji, Shunichi Koga, Hiroshi Ibayashi, Yoshiaki Nose, Kouhei Akazawa

    Gastroenterologia Japonica22 ( 5 ) 599 - 606   1987年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer-Verlag  

    Data on 155 patients with liver cirrhosis were analyzed, using Cox's proportional hazard model. Twenty variables were screened, using a multiple linear regression analysis in a stepwise manner and 6 were considered to reflect the prognosis of cirrhotics. Three of the 6 variables were significantly prognostic, i.e. ascites, atrophy of the right lobe of the liver seen on liver scintigram and the concentration of serum albumin. The prognostic index (PI) for each patient was calculated by adding all the products of scores of these three variables with the corresponding coefficient: PI=0.895 X ascites (absent=0, present=l) + 0.983 X atrophy of right lobe of the liver on the liver scintigram (absent=0, present=l) + (-0.561) X serum albumin (g/dl). According to the PI, the subjects were separated into three groups
    group 1: PI&lt
    -1.9, group 2: -1.9≦PK-0.6, group 3: PI≧0.6. The global 5 and 10-year survival rates of each group were 80% and 65% in group 1, 50% and 30% in group 2 and 12% and 0% in group 3, respectively. Four of the 14 deaths in group 1,8 of 47 in groups 2 and 10 of 24 in group 3 were caused by hepatocellular carcinoma. Our observations suggest that advanced stage cases of cirrhosis are at a high risk concerning development of hepatocellular carcinoma. © 1987 The Japanese Society of Gastroenterobgy.

    DOI: 10.1007/BF02776720

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  • CLINICAL-FEATURES OF INTRACTABLE EPILEPSY IN JAPANESE-CHILDREN 査読

    T KUROKAWA, K AKAZAWA, S TOMITA, KITAMOTO, I, Y MAEDA, K SAKAMOTO, Y NOSE

    JAPANESE JOURNAL OF PSYCHIATRY AND NEUROLOGY41 ( 3 ) 347 - 354   1987年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FOLIA PUBL SOC  

    DOI: 10.1111/j.1440-1819.1987.tb01694.x

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  • AN ELECTROCARDIOGRAM DATABASE INCORPORATED INTO THE HOSPITAL INFORMATION-SYSTEM 査読

    Y NOSE, K AKAZAWA, M YOKOTA, Y WATANABE, M NAKAMURA

    MEDICAL INFORMATICS12 ( 1 ) 1 - 9   1987年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    DOI: 10.3109/14639238709010035

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  • 病歴データベースを使った癌登録の自動化とその応用. 査読

    野瀬善明, 赤澤宏平, 渡辺義明, 横田将生, 中村元臣, 岡村精一, 前原喜彦, 杉町圭蔵

    医療情報学7 ( 3 ) 277 - 286   1987年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 病歴サマリー自動作成による外来診療支援. 査読

    野瀬善明, 渡辺義明, 横田将生, 赤澤宏平, 中村元臣

    医療情報学7 ( 4 ) 411 - 418   1987年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 研究と診療の支援を目的とした病歴オンライン検索システム. 査読

    野瀬善明, 渡辺義明, 横田将生, 赤澤宏平, 中村元臣

    医療情報学7 ( 4 ) 419 - 431   1987年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • AN ONLINE SYSTEM FOR ELECTROCARDIOGRAM INTERPRETATION USING THE BONNER PROGRAM 査読

    Y NOSE, K AKAZAWA, Y WATANABE, M YOKOTA, M NAKAMURA

    MEDICAL INFORMATICS11 ( 4 ) 359 - 368   1986年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    DOI: 10.3109/14639238608997659

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  • A PATIENT FOLLOW-UP SYSTEM FOR STOMACH-CANCER 査読

    M YOKOTA, Y NOSE, Y WATANABE, T INOUE, K AKAZAWA, M NAKAMURA

    MEDICAL INFORMATICS11 ( 3 ) 249 - 258   1986年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

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▶ 全件表示

書籍等出版物

  • 敗血症の診断/治療の実状と 病態・メカニズムをふまえた開発戦略

    早川 峰司, 赤澤 宏平( 担当: 共著)

    技術情報協会  2013年  ( ISBN:9784861044892

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    記述言語:日本語 著書種別:学術書

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  • 成功・失敗の傾向、各疾患の特徴からつかむ臨床試験計画とデザインの設定

    青山 朋樹, 赤澤 宏平( 担当: 共著)

    技術情報協会  2012年  ( ISBN:9784861044458

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    記述言語:日本語 著書種別:学術書

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  • 医学統計学の事典

    丹後 俊郎, 小西 貞則, 赤澤 宏平, 北村 信隆( 担当: 分担執筆)

    朝倉書店  2010年7月  ( ISBN:9784254121766

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    記述言語:日本語 著書種別:学術書

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  • サバイバルデータの解析―生存時間とイベントヒストリデータ

    赤澤 宏平, 柳川 尭( 担当: 共著)

    近代科学社  2010年7月  ( ISBN:9784764903906

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    記述言語:日本語 著書種別:学術書

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  • バイオ統計の基礎―医薬統計入門

    柳川 堯, 荒木 由布子( 担当: 編集)

    近代科学社  2010年2月  ( ISBN:9784764903876

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    記述言語:日本語 著書種別:学術書

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  • Telemedicine and Distance Education in the Medical Field in Japan.

    Akazawa K, Toyabe S, Sakata N, Murase S, Iguchi S, Kaidu M( 担当: 共著)

    Nova Science Publishers,Inc  2007年12月 

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    記述言語:英語 著書種別:学術書

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  • 医療情報(医療情報システム編) 第8章 医療支援のためのデータ分析・評価

    赤澤宏平, 岡田美保子, 河林徹郎, 近藤博史, 鳥谷部真一, 長澤亨, 宮本正喜( 担当: 共著 ,  範囲: p.260-284)

    篠原出版新社  2006年12月 

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    記述言語:日本語

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  • IT革命と新潟県 -新潟のITは今どうなっているのか-

    仙石正和, 中野雅至( 担当: 単著 ,  範囲: 55-68)

    野島出版  2003年12月 

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    記述言語:日本語

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  • 統計科学の最前線

    柳川堯, 藤井良宣, 赤澤宏平, 森川俊彦, 菊池泰樹, 安楽和夫, 垣内逸郎, 岩佐学, 笛田薫( 担当: 共著)

    九州大学出版会  2003年12月 

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    記述言語:日本語

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  • 医学大辞典.医療統計学の用語解説

    伊藤正男, 井村裕夫, 高久史麿( 担当: 共著)

    医学書院  2003年12月 

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    記述言語:日本語

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  • <ブックレット新潟大学17> 最新医療のはなし

    赤澤宏平, 岡本浩一郎, 尾崎利郎( 担当: 共著 ,  範囲: 61-69)

    新潟日報事業社  2003年12月 

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    記述言語:日本語

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  • 日本人のピークフロー値《改訂版》

    月岡 一治, 赤澤宏平( 担当: 共著)

    協和企画  2002年12月 

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    記述言語:日本語

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  • Statistics for the Envirinment 4

    Nakamura T, Akazawa K, Kinukawa N, Nose Y( 担当: 共著 ,  範囲: 281-289)

    Wiley  1999年12月 

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    記述言語:英語

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▶ 全件表示

MISC

  • 病院の経営改善に電子カルテはいかに効果的か

    赤澤宏平

    新医療32 ( 7 ) 48 - 50   2005年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:(株)エムイー振興協会  

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  • 医療統計手法の開発と統計解析の実践について.

    赤澤宏平, 池田充, 本多正幸, 中野正孝

    医療情報学23 ( 3 ) 193 - 198   2003年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:日本医療情報学会  

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  • 遺伝子解析の匿名化とその情報管理

    赤澤宏平

    医療情報学in press   2003年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:日本医療情報学会  

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  • 大学病院における診療情報管理と電子カルテ導入による医療の変革

    赤澤宏平, 羽柴正夫, 曹 鵬宇, 山川智子

    法とコンピュータ20   39 - 45   2002年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:法とコンピュータ学会  

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  • EBMのインパクト

    赤澤宏平

    新潟医学会雑誌116 ( 5 ) 209 - 218   2002年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:新潟医学会  

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  • 生存時間データの解析

    赤澤宏平

    医療情報学20 ( 6 ) 451 - 461   2001年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:日本医療情報学会  

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  • 医療統計学を用いた新しい治療効果判定法の開発.

    赤澤宏平

    新潟医学会雑誌114 ( 5 ) 179 - 185   2000年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:新潟医学会  

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  • 統計的方法の10年と求められている新手法.

    中村剛, 赤澤宏平

    医療情報学13 ( 2 ) 82 - 83   1993年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:日本医療情報学会  

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  • Covariate measurement errors in censored survival data.

    Nakamura T, Akazawa K

    Japanese Journal of Biometrics13   47 - 63   1992年12月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(学術雑誌)   出版者・発行元:日本計量生物学会  

    DOI: 10.5691/jjb.13.47

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産業財産権

  • 画像処理法、画像処理装置および画像処理プログラムを記録した記録媒体

    松戸 隆之, 赤澤 宏平

     詳細を見る

    出願番号:特願2006-550645  出願日:2005年12月

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共同研究・競争的資金等の研究

  • 臨床試験で競合リスクに相関がある場合の新たな治療効果判定方法の開発

    2016年04月 - 現在

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    赤澤 宏平

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    担当区分:研究代表者  資金種別:競争的資金

    臨床試験の評価尺度として、Time-to-Event データ(ある時点から注目するイベントが発生するまでの時間)がしばしば用いられる。また、Time-to-Event データの統計解析では、追跡不能または研究終了によるイベント発生の観察不能の打ち切り例を含む。本研究の目的は、以下の実用上の問題点を生存時間解析の統計理論とモンテカルロ・シミュレーションにより解決することである。
    (1)特定の死因の症例をイベント発生例、他の死因の症例を打ち切り例とした競合リスクが存在する場合でのログランク検定の性能(サイズ(第Ⅰ種の過誤の大きさ)、検出力など)の評価
    (2)主要評価尺度として、複数のイベントのどれかが発生すればイベントありとする複合エンドポイントの場合のログランク検定、比例ハザードモデル解析の問題点の洗い出しとその解決策
    (3)主要評価尺度を無再発期間、副次評価尺度を生存期間に設定した場合、無再発期間が真の評価尺度である生存期間の代理評価尺度に

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  • 大規模疫学調査に基づく中国の食道癌発症リスクの同定と発症低減策の費用対効果の 分析

    2016年04月 - 現在

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    赤澤 宏平

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    担当区分:研究代表者  資金種別:競争的資金

    食道癌、特に腺癌の罹患率は多くの国で増加の一途をたどっている。たとえば、米国では2010年の罹患率は1975年のそれに比べて6倍高くなった。食道癌の原因究明と発症予防策の検討は国際的にも喫緊の課題である。そこで、本研究では次の2点を目的とした疫学研究を行う。
    1.中国河北省の食道癌多発地域とそれ以外の地域において、環境要因、後天的要因の大規模疫学データを収集し、食道癌発症に強く関与する確証的なリスク因子を同定する。
    2.発癌物質の除去や生活習慣の改善コストと癌発症リスクの低減効果とを考慮した費用対効果分析を行い、中国のみならず国際的な食道癌発症予防策を考える際の科学的根拠とする。
    本研究は、これまでの食道癌疫学研究の中でも最大規模の症例集積を行うこと、新しいリスク因子の発見が期待できること、新知見のリスク因子から費用対効果分析を行い予防効果の定量的な評価ができること、などが研究の特徴である。

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  • 遺伝子発現データに基づく予後予測モデル構築の統計理論の開発と実データによる検証

    2012年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業  挑戦的萌芽研究

    赤澤宏平

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    担当区分:研究代表者  資金種別:競争的資金

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  • 食道がん発症リスク因子を確証的に同定するための中国疫学調査の実施

    2010年04月 - 2013年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    赤澤宏平

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    担当区分:研究代表者  資金種別:競争的資金

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  • ゲノムワイド疾患関連遺伝子同定のための遺伝統計学手法の開発

    2009年09月 - 2011年09月

    科学研究費助成事業  特別研究員推奨費

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    資金種別:競争的資金

    ゲノムワイド疾患関連遺伝子同定のための遺伝統計学手法の開発

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  • 疾患関連遺伝子発見のための症例対照研究における統計学的問題とその解決策の検討

    2007年04月 - 2009年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

      詳細を見る

    資金種別:競争的資金

    疾患関連遺伝子発見のための症例対照研究における統計学的問題とその解決策の検討

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  • 診察情報の利用に関する研究(フェーズ2)

    2006年04月 - 2006年09月

    株式会社エヌ・ティ・ティ・データ  共同研究 

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    資金種別:競争的資金

    配分額:4000000円

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  • 診察情報の利用に関する研究

    2005年09月 - 2006年03月

    株式会社エヌ・ティ・ティ・データ  共同研究 

      詳細を見る

    資金種別:競争的資金

    配分額:8250000円

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  • 診療情報の利用に関する研究

    2005年 - 現在

    株式会社NTT データ  共同研究 

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    資金種別:競争的資金

    大学病院における診療情報を統合・分析し、各大学病院及び研究機関にて活用し「患者へのより良い医療サービスの提供」という社会的価値の提供につながるモデルが検証されている中で、その実現に向けた情報コンテンツのあり方とその有効性評価を行う事が目的で
    ある。

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  • 診療コストを算定するための新しい計算方法の開発と病院データに基づく妥当性の検証

    2004年04月 - 2006年03月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    資金種別:競争的資金

    配分額:7600000円 ( 直接経費:7600000円 )

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  • パナルジン新規投与患者における臨床検査実施率調査

    2001年04月 - 2002年03月

    第一製薬(株)  受託研究 

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    資金種別:競争的資金

    配分額:2988505円

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