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GENOMIC LANDSCAPE AND MOLECULAR CHARACTERIZATION OF RENAL CELL CARCINOMA IN DIALYSIS PATIENTS

Ryohei Takahashi, Nobuyuki Tanaka, Fuyuki Miya, Takashi Kamatani, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Shuji Mikami, Kazuhiro Kakimi, Tatsuhiko Tsunoda, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E108 - E109 2020年04月

共著, ISSN 0022-5347

EVALUATING THE DIAGNOSTIC ACCURACY OF VESICAL IMAGING-REPORTING AND DATA SYSTEM FOR DETECTING MUSCLE-INVASIVE BLADDER CANCER IN REAL CLINICAL SETTING

Ryohei Kufukihara, Eiji Kikuchi, Keisuke Shigeta, Youta Yasumizu, Nobuyuki Tanaka, Toshikazu Takeda, Kazuhiro Matsumoto, Ryuichi Mizuno, Yuki Arita, Hirotaka Akita, Masahiro Jinzaki, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E524 - E524 2020年04月

共著, ISSN 0022-5347

DO ALL PATIENTS WHO HAVE PROSTATE CANCER WITH SEMINAL VESICLE INVASION HAVE POOR PROGNOSIS?

Yoshinori Yanai, Takeo Kosaka, Hiroshi Hongo, Yota Yasumizu, Nobuyuki Tanaka, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E948 - E948 2020年04月

共著, ISSN 0022-5347

DO ALL CASES OF MAGNETIC RESONANCE IMAGING NEGATIVE HAVE GOOD PROGNOSIS?

Yoshinori Yanai, Takeo Kosaka, Hiroshi Hongo, Yota Yasumizu, Nobuyuki Tanaka, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Ryuichi Mizuno, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E185 - E185 2020年04月

共著, ISSN 0022-5347

ARE SURVIVAL OUTCOMES AFTER NEOADJUVANT CHEMOTHERAPY SUPERIOR TO THOSE AFTER UPFRONT RADICAL NEPHROURETERECTOMY FOR NODE-POSITIVE UPPER TRACT UROTHELIAL CARCINOMA? RESULTS OF A MULTI-CENTER COHORT STUDY

Keisuke Shigeta, Kazuhiro Matsumoto, Nobuyuki Tanaka, Yota Yasumizu, Toshikazu Takeda, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Eiji Kikuchi, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E376 - E376 2020年04月

共著, ISSN 0022-5347

ANDROGEN DEPRIVATION THERAPY THROUGH THE PERI-RADIATION PERIOD REDUCES THE RISK OF BLADDER HEMORRHAGE IN PROSTATE CANCER PATIENTS UNDERGOING EXTERNAL BEAM RADIOTHERAPY

Yuto Baba, Hiroki Ide, Naoya Niwa, Junichi Fukuda, Hirohiko Nagata, Kazuhiro Matsumoto, Mototsugu Oya, Hiroshi Miyamoto

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E790 - E790 2020年04月

共著, ISSN 0022-5347

A SIMPLE/RAPID RNA IMAGING TECHNIQUE QHCR REVEALS MALIGNANCY ASSOCIATED WITH LONG NON-CODING RNA IN CLEAR CELL RENAL CELL CARCINOMA

Ryohei Kufukihara, Nobuyuki Tanaka, Youta Yasumizu, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS） 203 E113 - E113 2020年04月

共著, ISSN 0022-5347

Editorial Comment to Comparison of single- and multiple-dose cefazolin as prophylaxis for transurethral enucleation of prostate: A multicenter, prospective, randomized controlled trial by the Japanese Research Group for Urinary Tract Infection.

Yazawa S, Hasegawa N, Oya M

International journal of urology : official journal of the Japanese Urological Association （International Journal of Urology） 27 （ 3 ） 248 - 249 2020年03月

研究論文（学術雑誌）, 共著, ISSN 0919-8172

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Avelumab plus axitinib vs sunitinib for advanced renal cell carcinoma: Japanese subgroup analysis from JAVELIN Renal 101.

Uemura M, Tomita Y, Miyake H, Hatakeyama S, Kanayama HO, Numakura K, Takagi T, Kato T, Eto M, Obara W, Uemura H, Choueiri TK, Motzer RJ, Fujii Y, Kamei Y, Umeyama Y, di Pietro A, Oya M

Cancer science （Cancer Science） 111 （ 3 ） 907 - 923 2020年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1347-9032

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment-naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression-free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD-L1+ tumors (≥1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD-L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD-L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD-L1+ tumors and irrespective of PD-L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD-L1 expression. Common treatment-emergent adverse events (all grade; grade ≥3) in each arm were hand-foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment-naive Japanese patients with advanced RCC, which is consistent with results in the overall population.

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A case of inguinal cellular angiofibroma.

Kamitani R, Matsumoto K, Fujiwara S, Akita H, Mikami S, Kameyama K, Jinzaki M, Oya M

IJU case reports 3 （ 2 ） 69 - 71 2020年03月

共著

Introduction: Cellular angiofibroma is a benign mesenchymal tumor that is rare and has a good prognosis. However, preoperative distinction of cellular angiofibroma from malignant tumors is difficult. Case presentation: A 77-year-old man complained of a left inguinal mass, which was a solid, painless, mobile tumor measuring approximately 40 mm and contacted with the left spermatic cord. Based on his age, the location and imaging findings, a preoperative diagnosis of myxoid liposarcoma was made. The patient underwent left high inguinal orchiectomy with complete resection of the tumor. Histologically and immunohistochemically, the tumor had no feature of malignancy. A postoperative diagnosis of cellular angiofibroma was made. The patient remains free of disease recurrence 12 months after surgery. Conclusion: Cellular angiofibroma is a benign but rare tumor, which is sometimes difficult to distinguish from malignant neoplasms. Further studies are needed to accurately preoperatively diagnose this tumor.

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Successful Treatment of End-stage Renal Disease in a Patient With Chronic Myeloid Leukemia by Kidney Transplantation and Tyrosine Kinase Inhibitors: A Case Report.

Shinoda K, Morita S, Tamaki S, Takahashi R, Kitaoka S, Asanuma H, Yoshida T, Okayama M, Kasahara H, Okamoto S, Oya M

Transplantation proceedings （Transplantation Proceedings） 52 （ 2 ） 604 - 607 2020年03月

研究論文（学術雑誌）, 共著, ISSN 0041-1345

© 2020 Elsevier Inc. Consensus regarding kidney transplantation feasibility in patients with chronic myeloid leukemia (CML) well controlled by tyrosine kinase inhibitors has not yet been achieved. Here, we report a patient with CML well controlled by tyrosine kinase inhibitors who developed end-stage renal disease during treatment and underwent kidney transplantation. CML activity has been carefully and successfully controlled for 4 years post-transplant. Very cautious dose adjustment and temporary cessation of nilotinib were required because kidney function fluctuated in reference to the doses of nilotinib.

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Physical Parameters, Use of Specific Medical Treatments, Nursing Levels, and Activities of Daily Living Are Potential Indicators for Forgoing Maintenance Hemodialysis

Yamaguchi, Nobuko ; Yoshida, Tadashi ; Oba, Miho ; Nakano, Reiko ; Saito, Miwa ; Hirokawa, Mihoko ; Shinmi, Tazuru ; Urasawa, Chisa ; Oya, Mototsugu

The Keio Journal of Medicine （The Keio Journal of Medicine） 69 （ 1 ） 16 - 25 2020年03月

共著, ISSN 0022-9717

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Author Correction: MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer.

Yasumizu Y, Rajabi H, Jin C, Hata T, Pitroda S, Long MD, Hagiwara M, Li W, Hu Q, Liu S, Yamashita N, Fushimi A, Kui L, Samur M, Yamamoto M, Zhang Y, Zhang N, Hong D, Maeda T, Kosaka T, Wong KK, Oya M, Kufe D

Nature communications （Nature Communications） 11 （ 1 ） 1095 - 1095 2020年02月

研究論文（学術雑誌）, 共著

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Treatment-free survival after discontinuation of immuno-checkpoint therapy, and outcome of subsequent molecular targeted therapy: Retrospective study of Japanese metastatic renal cell carcinoma patients (after I-O study)

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

JOURNAL OF CLINICAL ONCOLOGY （AMER SOC CLINICAL ONCOLOGY） 38 （ 6 ） 675 - 675 2020年02月

共著, ISSN 0732-183X

Extensive disease among potential candidates for hemi-ablative focal therapy for prostate cancer.

Takeda T, Tin AL, Corradi RB, Alvim R, Hashimoto T, Ito Y, Nguyen DP, Mamoor M, Robertson NL, Vargas HA, Benfante NE, Sjoberg DD, Eastham JA, Scardino PT, Fine SW, Oya M, Touijer KA

International journal of urology : official journal of the Japanese Urological Association （International Journal of Urology） 27 （ 2 ） 179 - 185 2020年02月

研究論文（学術雑誌）, 共著, ISSN 0919-8172

© 2019 The Japanese Urological Association Objective: To examine a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer and to determine the likelihood of residual extensive disease. Methods: We retrospectively analyzed data from 98 patients with unilateral prostate cancer on biopsy with detailed tumor maps from whole-mount slides and preoperative magnetic resonance imaging data. These patients met the focal therapy consensus meeting inclusion criteria (prostate-specific antigen <15 ng/mL, clinical stage T1c-T2a and Gleason score 3 + 3 or 3 + 4 on needle biopsy), and underwent radical prostatectomy between 2000 and 2014. Extensive disease was defined as having Gleason pattern 4/5 in bilateral lobes, any extraprostatic extension, seminal vesicle invasion or lymph node invasion. Both lobes of the prostate were scored on magnetic resonance imaging. Preoperative characteristics including biopsy and magnetic resonance imaging data were used to predict extensive disease. Results: Among our cohort of 98 patients, 40% (95% CI 30–50%) had extensive disease. A total of 33% (95% CI 24–43%) had Gleason pattern 4/5 in both lobes with a median Gleason pattern 4/5 tumor volume in the biopsy negative lobe of 0.06 cm3, 17 patients had pathological tumor stage ≥3 and one patient had lymph node invasion. Conclusions: An important number of patients meeting the focal therapy consensus meeting inclusion criteria can present extensive disease. Further studies using targeted biopsies might provide more accurate information about the selection of focal therapy candidates.

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Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up.

Tomita Y, Kondo T, Kimura G, Inoue T, Wakumoto Y, Yao M, Sugiyama T, Oya M, Fujii Y, Obara W, Motzer RJ, Uemura H

Japanese journal of clinical oncology （Japanese Journal of Clinical Oncology） 50 （ 1 ） 12 - 19 2020年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0368-2811

© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Background: Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. Methods: CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-To-Treat (ITT) patients and safety (ITT patients). Results: Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Conclusions: Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.

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MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer.

Nature communications （Nature Communications） 11 （ 1 ） 338 - 338 2020年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2041-1723

© 2020, The Author(s). Neuroendocrine prostate cancer (NEPC) is an aggressive malignancy with no effective targeted therapies. The oncogenic MUC1-C protein is overexpressed in castration-resistant prostate cancer (CRPC) and NEPC, but its specific role is unknown. Here, we demonstrate that upregulation of MUC1-C in androgen-dependent PC cells suppresses androgen receptor (AR) axis signaling and induces the neural BRN2 transcription factor. MUC1-C activates a MYC→BRN2 pathway in association with induction of MYCN, EZH2 and NE differentiation markers (ASCL1, AURKA and SYP) linked to NEPC progression. Moreover, MUC1-C suppresses the p53 pathway, induces the Yamanaka pluripotency factors (OCT4, SOX2, KLF4 and MYC) and drives stemness. Targeting MUC1-C decreases PC self-renewal capacity and tumorigenicity, suggesting a potential therapeutic approach for CRPC and NEPC. In PC tissues, MUC1 expression associates with suppression of AR signaling and increases in BRN2 expression and NEPC score. These results highlight MUC1-C as a master effector of lineage plasticity driving progression to NEPC.

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Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report.

Hongo H, Kosaka T, Aimono E, Nishihara H, Oya M

Diagnostic pathology （Diagnostic Pathology） 15 （ 1 ） 5 - 5 2020年01月

研究論文（学術雑誌）, 共著, 査読有り

© 2020 The Author(s). Background: Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment. Case presentation: A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castration-resistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefore, we sequentially performed docetaxel therapy followed by cabazitaxel. After the third cycle of cabazitaxel, his prostate-specific antigen level was stable at < 10 ng/mL, and no radiological progression was detected. The patient's formalin-fixed paraffin-embedded tumor biopsy specimen underwent multiple-gene testing by next-generation sequencing, which identified a FANCA homodeletion. No significant germline mutation was observed. Conclusions: We describe a case of aggressive, castration-resistant prostate cancer with FANCA homodeletion. Genomic analysis of prostate cancer tissue can be useful to determine optimal treatment of such cancers.

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Acute scrotum in children: Surgical indication and procedures

Asanuma H., Takahashi R., Oya M.

Japanese Journal of Clinical Urology （Japanese Journal of Clinical Urology） 74 （ 7 ） 472 - 477 2020年

ISSN 03852393

腎移植におけるエベロリムス併用ステロイド早期離脱プロトコールの検討

香野日高, 中川健, 環聡, 坂巻裕介, 谷川実央, 高橋遼平, 森田伸也, 伊藤祐二郎, 萩生田純, 大家基嗣

移植（一般社団法人日本移植学会） 55 （ 0 ） 358_2 - 358_2 2020年

ISSN 0578-7947

<p>我々はCNI、MMF、MP、BXLに加えてEVRを術後約2週間で導入しMPを2-3ヶ月で中止するプロトコールを用いている。CNIはトラフで術後1年ではCsAは50ng/ml、FKでは5ng/mlを目標としている。長期の成績を予測するために腎機能、拒絶反応、脈波伝導速度（PWV）、病理組織等について検討した。対象は2012年以降に当院および慶應義塾大学病院にて施行した生体腎移植症例76例(平均48.5歳)である。術後1年のsCrは1.41±0.58mg/dl、術後5年は1.49±0.79mg/dlであった。BPARはABO適合移植では11.5%(6/52例)、ABO不適合移植では33.3%(8/24例)であったが8例中7例がEVR開始前の術後早期の発症であった。ステロイドは68例(89.5％)、術後平均4.0ヶ月で中止できた。中止できなかった8例は全てARによりステロイド継続を余儀なくされた症例であった。baPWV値は、術前は1660±376cm/s、術後1年は1465±308cm/sであり、有意に低下していた（p<0.05）。1年後の病理組織において1時間生検と比較した非増悪が、cvスコアで59例(77.6%)、aahスコアで63例(82.9%)であった。EVRを使用しMPを早期に中止しCNIを減量することで、術後良好な経過が得られた。</p>

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