Updated on 2024/05/03

写真a

 
YAMANA Kazutoshi
 
Organization
University Medical and Dental Hospital Urology Lecturer
Title
Lecturer
External link

Degree

  • 博士（医学） ( 2005.9   新潟大学 )

Research History

  • Niigata University   University Medical and Dental Hospital Urology   Lecturer

    2022.4

  • Niigata University   University Medical and Dental Hospital Urology   Assistant Professor

    2015.8 - 2022.3

  • Niigata University   University Medical and Dental Hospital Urology   Specially Appointed Assistant Professor

    2015.6 - 2015.7

 

Papers

  • High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term androgen deprivation therapy for very high-risk prostate cancer. International journal

    Takashi Kasahara, Fumio Ishizaki, Akira Kazama, Eri Yuki, Kazutoshi Yamana, Ryo Maruyama, Tomoya Oshikane, Motoki Kaidu, Hidefumi Aoyama, Vladimir Bilim, Tsutomu Nishiyama, Yoshihiko Tomita

    International journal of urology : official journal of the Japanese Urological Association   27 ( 9 )   800 - 806   2020.9

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    OBJECTIVE: To estimate the outcomes of high-dose-rate brachytherapy combined with hypofractionated external beam radiotherapy in prostate cancer patients classified as very high risk by the National Comprehensive Cancer Network. METHODS: Between June 2009 and September 2015, 66 patients meeting the criteria for very high-risk disease received high-dose-rate brachytherapy (2 fractions of 9 Gy) as a boost of external beam radiotherapy (13 fractions of 3 Gy). Androgen deprivation therapy was administered for approximately 3 years. Biochemical failure was assessed using the Phoenix definition. RESULTS: The median follow-up period was 53 months from the completion of radiotherapy. The 5-year biochemical failure-free, distant metastasis-free, prostate cancer-specific and overall survival rates were 88.7, 89.2, 98.5 and 97.0%, respectively. The independent contribution of each component of the very high-risk criteria was assessed in multivariable models. Primary Gleason pattern 5 was associated with increased risks of biochemical failure (P = 0.017) and distant metastasis (P = 0.049), whereas clinical stage ≥T3b or >4 biopsy cores with Gleason score 8-10 had no significant impact on the two outcomes. Grade 3 genitourinary toxicities were observed in two (3.0%) patients, whereas no grade ≥3 gastrointestinal toxicities occurred. CONCLUSIONS: The present study shows that this multimodal approach provides potentially excellent cancer control and acceptable associated morbidity for very high-risk disease. Patients with primary Gleason pattern 5 are at a higher risk of poor outcomes, indicating the need for more aggressive approaches in these cases.

    DOI： 10.1111/iju.14305

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  • A multicenter retrospective study of nivolumab monotherapy in previously treated metastatic renal cell carcinoma patients: interim analysis of Japanese real-world data.

    Nobuyuki Hinata, Junji Yonese, Satoru Masui, Yasutomo Nakai, Suguru Shirotake, Katsunori Tatsugami, Teruo Inamoto, Masahiro Nozawa, Kosuke Ueda, Toru Etsunaga, Takahiro Osawa, Motohide Uemura, Go Kimura, Kazuyuki Numakura, Kazutoshi Yamana, Hideaki Miyake, Satoshi Fukasawa, Kenya Ochi, Hirokazu Kaneko, Hirotsugu Uemura

    International journal of clinical oncology   25 ( 8 )   1533 - 1542   2020.8

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    BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.

    DOI： 10.1007/s10147-020-01692-z

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  • Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride. International journal

    Kazutoshi Yamana, Fernand Labrie, Van Luu-The

    Hormone molecular biology and clinical investigation   2 ( 3 )   293 - 9   2010.8

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    5α-Reductases are crucial enzymes involved in the biosynthesis of dihydrotestosterone, the most potent natural androgen. To date, three types of 5α-reductases, chronologically named types 1, 2 and 3 5α-reductases (SRD5a-1, 2 and 3) have been described. In the present paper, we characterized the activity and compared the mRNA expression levels of SRD5a-3 with those of SRD5a-1 and 2 in various human tissues, and determined its sensitivity to finasteride and dutasteride. We have established HEK-293 cell line that stably expressed SRD5a-3 for studying its activity and the inhibitory effect of finasteride, using [14C]labeled steroids. mRNA expression levels were quantified using real-time PCR in many male and female human tissues including the prostate, adipose tissue, mammary gland, as well as breast and prostate cancer cell lines. Incubation of HEK-SRD5a-3 cells with [14C]4-androstenedione and [14C]testosterone allowed us to show that SRD5a-3 can catalyze very efficiently both substrates 4-androstenedione and testosterone into 5α-androstanedione and dihydrotestosterone, respectively. We observed that the affinity of the enzyme for 4-androstenedione is higher than for testosterone. The activity of SRD5a-3 and SRD5a-2 are similarly sensitive to finasteride, whereas dutasteride is a much more potent inhibitor of SRD5a-3 than SRD5a-2. Tissue distribution analysis shows that SRD5a-3 mRNA expression levels are higher than those of SRD5a-1 and SRD5a-2 in 20 analyzed tissues. In particular, it is highly expressed in the skin, brain, mammary gland and breast cancer cell lines, thus suggesting that SRD5a-3 could play an important role in the production of androgens in these and other peripheral tissues.

    DOI： 10.1515/HMBCI.2010.035

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  • Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: Decreased expression of Fas is associated with disease progression

    K. Yamana, V. Bilim, N. Hara, T. Kasahara, T. Itoi, R. Maruyama, T. Nishiyama, K. Takahashi, Y. Tomita

    British Journal of Cancer   93 ( 5 )   544 - 551   2005.9

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    The death receptor Fas (Apo1/CD95) and Fas ligand (FasL) system is recognised as a major pathway for the induction of apoptosis in vivo, and antiapoptosis via its blockade plays a critical role in carcinogenesis and progression in several malignancies. However, the function of Fas-FasL system in urothelial cancer (UC) has not been elucidated. We therefore investigated the expression of Fas, FasL and Decoy receptor 3 for FasL (DcF3) in UC specimens and cell lines, and examined the cytotoxic effect of an anti-Fas-activating monoclonal antibody (mAb) in vitro. Immunohistochemical examinations of Fas-related molecules were performed on 123 UC and 30 normal urothelium surgical specimens. Normal urothelium showed Fas staining in the cell membrane and cytoplasm. In UC, less frequent Fas expression was significantly associated with a higher pathological grade (P < 0.0001), a more advanced stage (P = 0.023) and poorer prognosis (P = 0.010). Fas and the absence thereof were suggested to be crucial factors with which to select patients requiring more aggressive treatment. Moreover, low-dose anti-Fas-activating mAb sensitised resistant cells to adriamycin, and this synergistic effect could be applied in the development of new treatment strategy for UC patients with multidrug-resistant tumours. © 2005 Cancer Research.

    DOI： 10.1038/sj.bjc.6602732

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  • 進行性腎細胞癌に対するNivolumab単剤療法の有害事象と予後の検討

    晝間 楓, 村田 雅樹, 風間 明, 田崎 正行, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 53 )   104 - 104   2023.7

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  • 新潟大学医歯学総合病院における進行性腎細胞癌の一次治療成績

    田崎 正行, 風間 明, 山名 一寿, 丸山 亮, 石崎 文雄, 笠原 隆, 冨田 義彦

    腎癌研究会会報   ( 53 )   97 - 97   2023.7

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  • 腎癌に対するIO治療後の腫瘍切除術に関する検討

    田崎 正行, 大橋 瑠子, 風間 明, 晝間 楓, 石崎 文雄, 丸山 亮, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 53 )   47 - 47   2023.7

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  • 進行性腎細胞癌に対するNivolumab単剤療法の有害事象と予後の検討

    晝間 楓, 村田 雅樹, 風間 明, 田崎 正行, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 53 )   104 - 104   2023.7

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  • 腎癌に対するIO治療後の腫瘍切除術に関する検討

    田崎 正行, 大橋 瑠子, 風間 明, 晝間 楓, 石崎 文雄, 丸山 亮, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 53 )   47 - 47   2023.7

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  • 新潟大学におけるカボザンチニブ+ニボルマブ併用療法の使用経験

    晝間 楓, 田崎 正行, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 53 )   56 - 56   2023.7

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  • Real-world effectiveness of nivolumab and subsequent therapy in Japanese patients with metastatic renal cell carcinoma (POST-NIVO study): 36-month follow-up results of a clinical chart review. International journal

    Junji Yonese, Nobuyuki Hinata, Satoru Masui, Yasutomo Nakai, Suguru Shirotake, Ario Takeuchi, Teruo Inamoto, Masahiro Nozawa, Kosuke Ueda, Toru Etsunaga, Takahiro Osawa, Motohide Uemura, Go Kimura, Kazuyuki Numakura, Kazutoshi Yamana, Hideaki Miyake, Satoshi Fukasawa, Naoto Morishima, Hiroaki Ito, Hirotsugu Uemura

    International journal of urology : official journal of the Japanese Urological Association   2023.5

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    OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.

    DOI： 10.1111/iju.15206

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  • 進行腎細胞癌に対するニボルマブおよびイピリムマブ併用療法の使用経験(Experience of treatment with nivolumab plus ipilimumab therapy(NIVO+IPI) for advanced renal cell carcinoma)

    晝間 楓, 村田 雅樹, 風間 明, 田崎 正行, 山名 一寿, 冨田 善彦

    日本泌尿器科学会総会   110回   PP67 - 05   2023.4

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  • Prognostic value of immune phenotype and PD-L1 status in recurrent or metastatic renal cell carcinoma: an exploratory analysis of the ARCHERY study Reviewed International journal

    Toyonori Tsuzuki, Chisato Ohe, Takahiro Osawa, Yosuke Yasuda, Toshiaki Tanaka, Satoshi Anai, Go Kimura, Kazutoshi Yamana, Shingo Hatakeyama, Takuya Yoshimoto, Yuki Nakagawa, Tamaki Fukuyama, Nobuaki Matsubara, Hirotsugu Uemura

    Pathology   55 ( 1 )   31 - 39   2022.9

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    Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis.

    DOI： 10.1016/j.pathol.2022.07.013

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  • 新潟大学医歯学総合病院における進行性腎細胞癌の一次治療成績

    田崎 正行, 風間 明, 山名 一寿, 丸山 亮, 石崎 文雄, 笠原 隆, 冨田 義彦

    腎癌研究会会報   ( 52 )   44 - 44   2022.7

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  • パゾパニブ投与中に間質性肺炎を発症した2症例と当院でのパゾパニブ使用症例の検討

    村田 雅樹, 晝間 楓, 池田 正博, 田崎 正行, 山名 一寿, 齋藤 和英, 冨田 善彦

    泌尿器外科   35 ( 臨増 )   814 - 814   2022.7

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  • 進行性腎細胞癌に対するNivolumab単剤療法の有害事象と予後の検討

    晝間 楓, 村田 雅樹, 風間 明, 田崎 正行, 山名 一寿, 冨田 善彦

    腎癌研究会会報   ( 52 )   51 - 51   2022.7

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  • 前立腺癌でのエンザルタミドによる全身倦怠感の検討

    丸山 亮, 山名 一寿, 石崎 文雄, 鈴木 一也, 笠原 隆, 片桐 明善, 米山 健志, 冨田 善彦

    日本泌尿器科学会総会   109回   PP58 - 08   2021.12

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  • ロボット支援下前立腺全摘術における鼠径ヘルニア予防

    丸山 亮, 笠原 隆, 石崎 文雄, 山名 一寿, 星井 達彦, 冨田 善彦

    日本泌尿器内視鏡学会総会   35回   P - 13   2021.11

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  • Subgroup analysis of the AFTER I-O study: a retrospective study on the efficacy and safety of subsequent molecular targeted therapy after immune-oncology therapy in Japanese patients with metastatic renal cell carcinoma

    Yoshihiko Tomita, Go Kimura, Satoshi Fukasawa, Kazuyuki Numakura, Yutaka Sugiyama, Kazutoshi Yamana, Sei Naito, Hirokazu Kaneko, Yohei Tajima, Mototsugu Oya

    Japanese Journal of Clinical Oncology   2021.8

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    <title>Abstract</title>
    <sec>
    <title>Background</title>
    We performed subgroup analyses of the AFTER I-O study to clarify the association of time-to-treatment failure (TTF) and discontinuation reason of prior immune-oncology (I-O) therapy, and molecular targeted therapy (TT) regimen with the outcomes of TT after I-O.


    </sec>
    <sec>
    <title>Methods</title>
    The data of Japanese metastatic renal cell carcinoma patients treated with TT after nivolumab (NIVO) (CheckMate 025) or NIVO + ipilimumab (IPI) (CheckMate 214) were retrospectively analyzed. The objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS) of TT after I-O were analyzed by subgroups: TTF (&amp;lt;6 or ≥6 months) and discontinuation reason of prior I-O (progression or adverse events), and TT regimen (sunitinib or axitinib). We also analyzed PFS2 of prior I-O and OS from first-line therapy.


    </sec>
    <sec>
    <title>Results</title>
    The ORR and median PFS of TT after NIVO and NIVO+IPI among the subgroups was 17–36% and 20–44%, and 7.1–11.6 months and 16.3-not reached (NR), respectively. The median OS of TT after NIVO was longer in patients with longer TTF of NIVO and treated with axitinib. Conversely, median OS of TT after NIVO+IPI was similar among subgroups. The median PFS2 of NIVO and NIVO+IPI was 36.7 and 32.0 months, respectively. The median OS from first-line therapy was 70.5 months for patients treated with NIVO and NR with NIVO+IPI. The safety profile of each TT after each I-O was similar to previous reports.


    </sec>
    <sec>
    <title>Conclusions</title>
    The efficacy of TT after NIVO or NIVO+IPI was favorable regardless of the TTF and discontinuation reason of prior I-O, and TT regimen.


    </sec>

    DOI： 10.1093/jjco/hyab114

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  • Efficacy and safety of subsequent molecular targeted therapy after immuno-checkpoint therapy, retrospective study of Japanese patients with metastatic renal cell carcinoma (AFTER I-O study). International journal

    Yoshihiko Tomita, Go Kimura, Satoshi Fukasawa, Kazuyuki Numakura, Yutaka Sugiyama, Kazutoshi Yamana, Sei Naito, Koki Kabu, Yohei Tajima, Mototsugu Oya

    Japanese journal of clinical oncology   51 ( 6 )   966 - 975   2021.2

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    OBJECTIVES: Guidelines for treatment of mRCC recommend nivolumab monotherapy (NIVO) for treated patients, and nivolumab plus ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor-risk mRCC patients. Although molecular-targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their efficacy and safety remain unclear. METHODS: Outcome of Japanese patients with mRCC who received TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator-assessed ORR of the first TT after either NIVO or NIVO+IPI. Secondary endpoints included TFS, PFS, OS and safety of TTs. RESULTS: Twenty six patients in CheckMate 025 and 19 patients in CheckMate 214 from 20 centers in Japan were analyzed. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most frequently treated regimen for both CheckMate 025 (54%) and CheckMate 214 (47%) patients. The ORRs of TT after NIVO and NIVO+IPI were 27 and 32% (all risks), and median PFSs were 8.9 and 16.3 months, respectively. During the treatment of first TT after either NIVO or NIVO+IPI, 98% of patients experienced treatment-related adverse events, including grade 3-4 events in 51% of patients, and no treatment-related deaths occurred. CONCLUSIONS: TTs have favorable antitumor activity in patients with mRCC after ICI, possibly via changing the mechanism of action. Safety signals of TTs after ICI were similar to previous reports. These results indicate that sequential TTs after ICI may contribute for long survival benefit.

    DOI： 10.1093/jjco/hyaa266

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  • 免疫チェックポイント阻害薬療法の中断後の無治療生存率とそれに続く分子標的療法の転帰 日本人の転移性腎細胞癌患者に関する後向き研究(AFTER I-O研究)(Treatment-free survival after discontinuation of immno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: retrospective study of Japanese metastatic renal cell carcinoma patients(AFTER I-O study))

    山名 一寿, 大家 基嗣, 木村 剛, 深沢 賢, 沼倉 一幸, 杉山 豊, 内藤 整, 加峰 弘毅, 田嶋 洋平, 冨田 善彦

    日本泌尿器科学会総会   108回   675 - 675   2020.12

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  • 進行性腎細胞癌へのニボルマブ・イピリムマブ併用療法後に生じた自己免疫性脳炎の1例

    小林 彩夏, 小出 眞悟, 佐治 越爾, 山名 一寿, 河内 泉, 富田 善彦, 小野寺 理

    神経免疫学   25 ( 1 )   131 - 131   2020.10

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  • Intraoperative intraocular pressure changes during robot-assisted radical prostatectomy: associations with perioperative and clinicopathological factors. International journal

    Yuko Shirono, Itsuhiro Takizawa, Takashi Kasahara, Ryo Maruyama, Kazutoshi Yamana, Toshiki Tanikawa, Noboru Hara, Yuta Sakaue, Tetsuya Togano, Tsutomu Nishiyama, Takeo Fukuchi, Yoshihiko Tomita

    BMC urology   20 ( 1 )   26 - 26   2020.3

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    BACKGROUND: Steep Trendelenburg position (ST) during robot-assisted radical prostatectomy (RARP) poses a risk of increase in intraocular pressure (IOP) in men receiving robot-assisted radical prostatectomy (RARP). The aim of the study was to identify clinicopathological factors associated with increased IOP during RARP. METHODS: We prospectively studied 59 consecutive prostate cancer patients without glaucoma. IOP was measured at 6 predefined time points before, during and after the operation (T1 to T6). RESULTS: Compared with T1, IOP decreased after beginning of anesthesia(T2) (by - 6.5 mmHg, p < 0.05), and increased 1 h after induction of pneumoperitoneum in the steep Trendelenburg position (ST) (T3) (+ 7.3 mmHg, p < 0.05). IOP continued to increase until the end of ST (T4) (+ 10.2 mmHg, p < 0.05), and declined when the patient was returned to supine position under general anesthesia (T5) (T1: 20.0 and T5: 20.1 mmHg, p above 0.05). The console time affected the elevation of IOP in ST; IOP elevation during ST was more prominent in men with a console time of ≥4 h (n = 39) than in those with a console time of < 4 h (n = 19) (19.8 ± 6.3 and 15.4 ± 5.8 mmHg, respectively, p < 0.05). Of the 59 patients, 29 had a high baseline IOP (20.0 mmHg or higher), and their IOP elevated during ST was also reduced at T5 (T1: 22.6 and T5: 21.7 mmHg, p above 0.05). There were no postoperative ocular complications. CONCLUSIONS: Console time of < 4 h is important to prevent extreme elevation of IOP during RARP. Without long console time, RARP may be safely performed in those with relatively high baseline IOP.

    DOI： 10.1186/s12894-020-00595-5

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  • Free Tube Graft Urethroplasty for Repair of Hypospadias. International journal

    Kenji Obara, Tatsuhiko Hoshii, Sayaka Hoshino, Kazutoshi Yamana, Tsutomu Anraku, Ryo Maruyama, Hiroo Kuroki, Fumio Ishizaki, Hiroyuki Yamazaki, Yoshihiko Tomita

    Urologia internationalis   104 ( 5-6 )   386 - 390   2020

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    INTRODUCTION: We aimed to assess the outcome of free tube graft urethroplasty for single-stage repair of hypospadias with chordee in children. MATERIALS AND METHODS: We retrospectively evaluated a series of 56 patients (16 months to 9 years old, median 24 months) who underwent free graft urethroplasty for repair of hypospadias with chordee between May 2005 and November 2017. The median follow-up was 7 years (range 1-11). RESULTS: After releasing the chordee, the hypospadiac orifice was retracted to become penile in 32 patients (57%), penoscrotal in 18 patients (32%), and scrotal in 6 patients (11%). Single-stage repair was achieved without complications in 42 patients (75%). Of the remaining 14 patients with postoperative complications requiring surgical intervention, 2 had meatal stenosis, 9 had urethrocutaneous fistula, 1 had urethral diverticulum without meatal stenosis, and 1 had meatal regression. One patient who complained the urine stream went upwards in an arc underwent cutback meatoplasty to correct the stream. In all patients, a neomeatus with a vertically oriented slit-like appearance was eventually achieved at the tip of the glans. CONCLUSION: A free graft is an appropriate choice for repairing hypospadias with chordee. Our procedure achieved favorable functional and cosmetic outcomes with a low postoperative morbidity rate.

    DOI： 10.1159/000504146

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  • Solitary brain metastasis from prostate cancer after multi modality treatment: A case report. International journal

    Fumio Ishizaki, Ryo Maruyama, Kazutoshi Yamana, Takashi Kasahara, Tsutomu Nishiyama, Yoshihiko Tomita

    Urology case reports   24   100879 - 100879   2019.5

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    We herein report an unusual case of brain metastasis from prostate cancer during androgen deprivation therapy and post-docetaxel and definitive local therapy. The brain metastasis was surgically resected followed by Whole-brain radiation therapy. Postoperatively, his PSA again decreased to an undetectable level and remained undetectable with no evidence of new or recurrent disease.

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  • Low-Dose-Rate and High-Dose-Rate Brachytherapy for Localized Prostate Cancer in ABO-Incompatible Renal Transplant Recipients. International journal

    M Tasaki, T Kasahara, M Kaidu, G Kawaguchi, N Hara, K Yamana, R Maruyama, I Takizawa, F Ishizaki, K Saito, Y Nakagawa, M Ikeda, H Umezu, T Nishiyama, H Aoyama, Y Tomita

    Transplantation proceedings   51 ( 3 )   774 - 778   2019.4

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    BACKGROUND: Brachytherapy is one of the standard treatments for localized prostate cancer (CaP). However, the feasibility of brachytherapy for renal transplant recipients (RTRs) is still uncertain. MATERIALS AND METHODS: Between August 2007 and March 2018, all patients who had undergone low-dose-rate (LDR) brachytherapy or high-dose-rate (HDR) brachytherapy for clinically localized CaP at our institution were retrospectively identified (n = 394). Of these patients, 3 had a history of renal transplantation. We reviewed all available clinical data retrospectively. RESULTS: All of the RTRs received ABO-incompatible renal grafts from their spouses and had stable renal graft function before the diagnosis of CaP. The median age at diagnosis of CaP was 65 years (range, 60-67 years). The median time between transplantation and brachytherapy was 7 years (range, 4-10 years). In all of the patients, clinical stage was cT1cN0M0. Two patients received 125I LDR-brachytherapy (dose, 145 Gy) and 1 patient was treated by 192Ir HDR brachytherapy (dose, 19 Gy in 2 fractions) combined with external beam radiation therapy of 39 Gy in 13 fractions. The median follow-up period after brachytherapy was 44 months (range, 34-50 months). During the follow-up period, none of the patients developed disease progression including biochemical recurrence or clinically significant adverse events associated with radiation therapy. CONCLUSIONS: LDR brachytherapy and HDR brachytherapy are safe and technically feasible in RTRs with CaP, and oncological outcomes in RTRs do not appear to be inferior to those of patients who did not receive renal transplant.

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  • Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan. International journal

    Kenichi Harada, Masahiro Nozawa, Motohide Uemura, Katsunori Tatsugami, Takahiro Osawa, Kazutoshi Yamana, Go Kimura, Masato Fujisawa, Norio Nonomura, Masatoshi Eto, Nobuo Shinohara, Yoshihiko Tomita, Yukihiro Kondo, Kenya Ochi, Yoshio Anazawa, Hirotsugu Uemura

    International journal of urology : official journal of the Japanese Urological Association   26 ( 2 )   202 - 210   2019.2

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    OBJECTIVES: To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. METHODS: A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. RESULTS: Of 277 eligible patients, 266, 170 and 77 received first-, second- and third-line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first-line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second-line treatment, tyrosine kinase inhibitor-tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor-mammalian target of rapamycin inhibitor (14.1%) and cytokine-tyrosine kinase inhibitor (14.1%). With a median follow-up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first-line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first-line tyrosine kinase inhibitors for ≥6 months. CONCLUSIONS: The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real-world setting in Japan. Tyrosine kinase inhibitor-tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first-line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options.

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  • Ulcerative interstitial cystitis in an adolescent successfully treated with complete transurethral ulcer resection: A case report. International journal

    Eri Yuki, Kenji Obara, Hiroo Kuroki, Hiroyuki Yamazaki, Kazutoshi Yamana, Akira Tadokoro, Kaede Hiruma, Yoshihiko Tomita

    IJU case reports   2 ( 1 )   51 - 53   2019.1

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    Introduction: Interstitial cystitis is difficult to treat and may affect adolescents. Case presentation: A 15-year-old girl presented with severe pain upon terminal micturition that persisted for approximately 2 hours. The pain had been present for more than 1 month. Cystoscopy revealed severe erosion throughout the trigone. Transurethral fulguration did not improve her symptoms. However, complete electric resection of the ulcer markedly reduced the symptom. After complete resection, pain on urination disappeared and she has had no pain without medication for 15 months. Conclusion: Complete resection not fulguration of the ulcer is effective for interstitial cystitis in adolescent female patients.

    DOI： 10.1002/iju5.12038

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  • Congenital Scaphoid Megalourethra: A Case Report. International journal

    Kenji Obara, Hiroyuki Yamazaki, Kazutoshi Yamana, Hiroo Kuroki, Yoshihiko Tomita

    Urology case reports   14   3 - 4   2017.9

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    A congenital megalourethra is an enlargement of the pendulous urethra without evidence of distal obstruction. A 1-month-old boy presented to us with complaint of weak stream, ballooning of the penis before and during voiding and post voiding dribbling, since birth. Physical examination and cystourethroscope confirmed the diagnosis of congenital scaphoid megalourethra. He underwent reduction urethroplasty. During postoperative follow up, he had normal looking penis with good urinary stream.

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  • 5 alpha- ANDROSTANE-3 alpha 17 beta-DIOL WILL BE A POTENTIAL PRECURSOR OF THE MOST ACTIVE ANDROGEN 5 alpha- DIHYDROTESTOSTERONE IN PROSTATE CANCER

    Tsutomu Nishiyama, Fumio Ishizaki, Itsuhiro Takizawa, Kazutoshi Yamana, Noboru Hara, Kota Takahashi

    JOURNAL OF UROLOGY   185 ( 4 )   E116 - E116   2011.4

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    DOI： 10.1016/j.juro.2011.02.378

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  • EXPRESSION FEATURES OF ANDROGEN-METABOLIC GENES INVOLVING INTRACRINE PRODUCTION OF ANDROGENS IN THE PROSTATE CANCER CELLS

    Tsutomu Nishiyama, Noboru Hara, Kazutoshi Yamana, Kazuya Suzuki, Tatsuhiko Hoshii, Itsuhiro Takizawa, Kota Takahashi

    JOURNAL OF UROLOGY   181 ( 4 )   94 - 94   2009.4

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    DOI： 10.1016/S0022-5347(09)60268-8

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  • High incidence of GalNAc disialosyl lactotetraosylceramide in metastatic renal cell carcinoma Reviewed

    Ryo Maruyama, Seiichi Saito, Vladimir Bilim, Noboru Hara, Toshiyuki Itoi, Kazutoshi Yamana, Tsutomu Nishiyama, Yoichi Arai, Kota Takahashi, Yoshihiko Tomita

    ANTICANCER RESEARCH   27 ( 6C )   4345 - 4350   2007.11

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    Background: In renal cell carcinoma (RCC), glycosphingolipids monosialosyl globopentaosylceramide (MSGb5) and GalNAc disialosyl lactotetraosylceramide (GalNAcDSLc4) were shown to be predictors of metastasis. Here we extended the research using a larger cohort of patients with a longer follow-up period, and reevaluate their relationship to malignant potential, metastasis and prognosis in patients with RCC. Patients and Methods: MSGb5 and GalNAcDSLc4 were examined in 114 primary RCCs by immunohistochemical method on ctyostat sections. Results: GalNAcDSLc4 was detected in 13.2% of RCCs and was associated with a significantly higher incidence of metastasis at the time of primary visit (60.0% vs. 31.3%, p=0.0419) as well as de novo metastasis during follow-up (33.3% vs. 14.7%), and a shorter survival (p=0.0399). MSGb5 was detected in 51.8% of tumors and was not related to clinocopathological characteristics or survival. Conclusion: RCC patients with tumors positive for GalNAcDSLc4 are at higher risk of metastasis at the time of diagnosis and during follow-up.

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  • Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

    K. Suzuki, T. Nishiyama, N. Hara, K. Yamana, K. Takahashi, F. Labrie

    Prostate Cancer and Prostatic Diseases   10 ( 3 )   301 - 306   2007.9

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    The metabolic pathways of androgens and processes by which androgens induce re-growth after androgen deprivation therapy in prostate cancer have not been fully elucidated. In this study, finasteride decreased PSA secretion in medium containing testosterone, androstenedione, androstenediol and dehydroepiandrosterone, whereas dihydrotestosterone (DHT)- and hydroxy-flutamide-induced PSA production was not inhibited by finasteride in LNCaP-FGC cells. The present data show that adrenal androgen precursors do not directly interact with androgen receptors (ARs) but are converted to DHT via the intraprostatic metabolic pathways, resulting in the induction of LNCaP activity. This is the first report confirming this mechanism experimentally and also suggest the use of combined therapies that target ARs and prevent the formation of DHT within prostate cancer cells to achieve optimal therapeutic efficacy.

    DOI： 10.1038/sj.pcan.4500956

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  • Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

    R. Maruyama, K. Yamana, T. Itoi, N. Hara, V. Bilim, T. Nishiyama, K. Takahashi, Y. Tomita

    British Journal of Cancer   95 ( 9 )   1244 - 1249   2006.11

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    Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P = 0.006). Progressive disease correlated with higher PI in the primary lesion (P = 0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC + PD patients, 40.6% were positive for Bcl-2 (P = 0.0373). Patients in whom the primary tumours were both Bcl-2- and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P = 0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy. © 2006 Cancer Research UK.

    DOI： 10.1038/sj.bjc.6603359

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  • Role of connective tissue growth factor in fibronectin synthesis in cultured human prostate stromal cells. International journal

    Kazuya Suzuki, Kenji Obara, Kazuhiro Kobayashi, Kazutoshi Yamana, Vladimir Bilim, Toshiyuki Itoi, Kota Takahashi

    Urology   67 ( 3 )   647 - 53   2006.3

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    OBJECTIVES: To clarify the correlation of connective tissue growth factor (CTGF) expression and fibronectin (FN) synthesis after transforming growth factor-beta-1 (TGF-beta1) stimulation in human prostate stromal cells. METHODS: Primary cultures of human prostate stromal cells were established from nine normal prostates by the explant method. The gene and protein expressions of CTGF and FN after TGF-beta1 treatment were examined. We also investigated the effect of CTGF blockade on TGF-beta1-induced FN synthesis by CTGF antisense oligodeoxynucleotide treatment. RESULTS: CTGF expression was detected in all nine prostate stromal cells by reverse transcriptase-polymerase chain reaction and immunoblotting. In prostatic tissues, CTGF expression was observed more strongly in epithelial cells than in the stromal area by immunohistochemistry. The upregulation of both CTGF and FN protein by TGF-beta1 treatment was demonstrated in a dose-dependent manner. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated FN synthesis. CONCLUSIONS: CTGF plays a crucial role in extracellular matrix production as a TGF-beta1 downstream mediator in human prostate stromal cells, suggesting that CTGF blockade is likely to be a therapeutic target against benign prostatic hyperplasia.

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  • Stepping-stones to the further advancement of androgen-deprivation therapy for prostate cancer. International journal

    Tsutomu Nishiyama, Kazuya Suzuki, Kazutoshi Yamana, Etsuko Tonegawa, Koichi Wako, Kota Takahashi

    Expert review of anticancer therapy   6 ( 2 )   259 - 68   2006.2

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    Androgen-deprivation therapy has remained the critical therapeutic option for patients with advanced prostate cancer for over 60 years. Patients with poorly differentiated prostate cancer have low dihydrotestosterone levels in the prostate. After androgen-deprivation therapy, dihydrotestosterone levels in the prostate remain at approximately 25% of the level measured before therapy. The addition of a nonsteroidal anti-androgen to luteinizing hormone-releasing hormone analog or surgical castration significantly reduces the risk of all causes of death by 8%, which translates into a small, but significant, improvement in the 5-year survival of 2.9% over castration alone. The biologically aggressive prostate cancer cells may have an androgen receptor with heightened sensitivity to low dihydrotestosterone levels from the early stage of androgen-dependent disease. It is necessary to consider the androgen environment and the status of the androgen receptor in the prostate in order to improve the clinical efficacy of androgen-deprivation therapy and the quality of life of patients.

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  • Impact of frequent Bcl-2 expression on better prognosis in renal cell carcinoma patients

    T. Itoi, K. Yamana, V. Bilim, K. Takahashi, F. Tomita

    British Journal of Cancer   90 ( 1 )   200 - 205   2004.1

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    Previously, we reported that Bcl-2 was frequently expressed in renal cell carcinoma (RCC) specimens, but p53 mutation was a rare event. However, it was unclear whether Bcl-2 positivity was associated with the clinicopathological characteristics and prognosis in RCC. Therefore, we investigated the expression of Bcl-2 protein and its roles in 101 RCC specimens. In addition, the proliferation index (PI), apoptotic index (AI), caspase-3 and p53 expression were examined. The immunohistochemical method was applied for Bcl-2, caspase-3 and p53 protein expression. To investigate the proliferation activity and apoptosis of tumour cells, PI and AI were calculated based on Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL)-positive cells, respectively. Bcl-2 expression was detected in 72 out of 101 (71.3%) specimens. Bcl-2 positivity was inversely correlated with PI (P<0.0001) and AI (P = 0.0074). Furthermore, Bcl-2 positivity was significantly correlated with better survival (P = 0.0014), and was associated with lower stage (P = 0.0301) and grade (P = 0.0020). In RCC, frequent Bcl-2 expression was correlated with favourable character without higher PI and AI. Thus, Bcl-2 expression might be applied as a novel predictor of better prognosis in RCC patients. © 2004 Cancer Research UK.

    DOI： 10.1038/sj.bjc.6601454

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