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[Ⅳ. Current Economic Issues in Treatment for Metastatic Renal Cell Carcinoma].

Mizuno R, Oya M

Gan to kagaku ryoho. Cancer & chemotherapy 46 （ 1 ） 50 - 53 2019年01月

研究論文（学術雑誌）, 共著, ISSN 0385-0684

Current economic issues in treatment for metastatic renal cell carcinoma

Mizuno R., Oya M.

Japanese Journal of Cancer and Chemotherapy （Japanese Journal of Cancer and Chemotherapy） 46 （ 1 ） 50 - 53 2019年01月

ISSN 03850684

VURおよびRN診断におけるカラードプラ法超音波検査を用いた尿管口jet角測定の有用性　尿路感染症患児への新たな診断アプローチ

松井善一, 浅沼宏, 佐藤裕之, 青木裕次郎, 水野隆一, 大家基嗣

日本逆流性腎症フォーラム記録集（日本逆流性腎症フォーラム） 26回 12 - 14 2019年01月

VURおよびRNの診断と治療方針決定には、排尿時膀胱造影(VCUG)と腎シンチグラフィが必要となるが、両検査とも極めて侵襲的であるため、非侵襲的な検査法の開発が待たれている。原発性VURの病因として、ureteric budの発生異常に伴い尿管口が外側偏位し、壁内尿管が短くなることでflap valve機構が機能しないために発生すると考えられている。この点に着目し、VURが高度なほど尿管口からの蠕動運動による尿噴出(尿管口jet)はより垂直方向になると想定し、尿管口jetの方向は超音波カラードプラ法で非侵襲的に検出可能と考え、尿管口から膀胱内への尿噴出角度(尿管口jet角)を測定する方法を考案した。その有用性について検討するため尿路感染症児125例に試行したところ、VCUG所見と強い相関が認められた。

CiNii Research

Suitable patients for single-port laparoscopic adrenalectomy : optimal cut-off value for body mass index

Matsumoto Kazuhiro, Takahashi Ryohei, Fukumoto Keishiro, Takeda Toshikazu, Kikuchi Eiji, Asanuma Hiroshi, Miyajima Akira, Nakagawa Ken, Oya Mototsugu

Japanese Journal of Endourology （日本泌尿器内視鏡学会） 32 （ 2 ） 221 - 224 2019年

ISSN 2186-1889

Introduction and Objective In this study, we clarified patients suitable for single-port laparoscopic adrenalectomy by focusing on the optimal cut-off values of the body mass index (BMI).Methods A retrospective study was conducted on 126 consecutive patients who underwent single-port adrenalectomy. We re-evaluated all medical records and surgical videos. The pneumoperitoneum time (PT) was employed as an objective index for the assessment of surgical difficulty.Results The total mean PT was 84 minutes. In 27 patients with a BMI less than 20 kg/m2, the mean PT was 71 minutes, whereas the mean PT was 104 minutes in 9 patients with a BMI exceeding 28 kg/m2.Conclusions Our results suggested that patients with a BMI less than 20 kg/m2 are suitable for novice surgeons. Conversely, even experienced surgeons should carefully consider performing single-port surgery on patients whose BMI exceeds 28 kg/m2.

成育医療における先天性腎尿路異常（CAKUT）の管理

浅沼宏, 大家基嗣

泌尿器外科 32 582 - 583 2019年

CiNii Research

Immunoglobulin G4-Related Disease Arising from the Bladder Wall.

Kufukihara R, Niwa N, Mizuno R, Ohara K, Mikami S, Kikuchi E, Oya M

Urologia internationalis （Urologia Internationalis） 103 （ 4 ） 1 - 3 2018年12月

研究論文（学術雑誌）, 共著, ISSN 0042-1138

© 2018 S. Karger AG, Basel. Copyright: All rights reserved Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease with multiorgan involvement. Although there were reports of IgG4-related kidney disease or prostatitis, this disease rarely presents in the bladder. In this report, we describe a case of IgG4-RD arising from bladder wall. This patient had a past history of autoimmune pancreatitis and presented with incidental bladder tumor. Magnetic resonance imaging showed low signal intensity tumor on T2-weighted image, and no invasion to the muscular layer. We performed transurethral resection. Pathological findings showed that there were chronic inflammatory changes infiltrates under the epithelium, and IgG4-positive plasma cells were scattered throughout the lesion. They met the pathological diagnostic criteria for IgG4-RD. We think this is the first case of IgG4-RD arising from and confined to the inside of the bladder wall.

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Is transperitoneal laparoscopic radical nephrectomy suitable for patients with a history of abdominal surgery?

Yanai Y, Takeda T, Miyajima A, Matsumoto K, Hagiwara M, Mizuno R, Kikuchi E, Asanuma H, Oya M

Asian journal of endoscopic surgery （Asian journal of endoscopic surgery） 12 （ 4 ） 429 - 433 2018年12月

研究論文（学術雑誌）, 共著, ISSN 1758-5902

© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd. INTRODUCTION: Laparoscopic radical nephrectomy is the gold standard for treatment of renal cell carcinoma. However, previous abdominal surgery is generally regarded as a contraindication to the laparoscopic approach because it causes intraperitoneal adhesions, which are thought to interfere with subsequent laparoscopic procedures inside the abdominal cavity. Few studies have examined the influence of prior surgery on laparoscopic nephrectomy. Therefore, the aim of this study was to evaluate the impact of previous laparotomy on laparoscopic nephrectomy. METHODS: The records of 251 consecutive patients who had undergone laparoscopic nephrectomy for renal cell carcinoma at our hospital between 2005 and 2015 were reviewed retrospectively. RESULTS: Of the 251 laparoscopic nephrectomy patients, 76 patients (30%) had undergone prior abdominal surgery (surgery group), whereas the remaining 175 patients (70%) had not previously had abdominal surgery (control group). There were no significant differences between the control group and the surgery group with regard to pneumoperitoneum time (143 vs 135 min, P = 0.241) or blood loss (39 vs 36 mL, P = 0.763). Next, we divided the patients into two cohorts based on surgeon experience: 98 patients had been treated by an expert (i.e. someone who performs more than 50 laparoscopic procedures per year) and 153 patients had been treated by a non-expert. There was no significant difference in pneumoperitoneum time between the control and surgery groups in each cohort (treated by experts, 108 vs 103 min; treated by non-experts: 162 vs 166 min). CONCLUSION: We conclude that laparoscopic nephrectomy may be feasible after previous abdominal surgery and could be one of the surgical options.

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No significant impact of patient age and prior treatment profile with docetaxel on the efficacy of cabazitaxel in patient with castration-resistant prostate cancer

Kosaka T., Hongo H., Watanabe K., Mizuno R., Kikuchi E., Oya M.

Cancer Chemotherapy and Pharmacology （Cancer Chemotherapy and Pharmacology） 82 （ 6 ） 1061 - 1066 2018年12月

研究論文（学術雑誌）, 共著, ISSN 03445704

© 2018, The Author(s). Background: The correlation of the oncological outcomes of docetaxel and cabazitaxel in Japanese metastatic castration-resistant prostate cancer (mCRPC) patients has not been unclear. Materials and methods: This study included a total of 47 consecutive Japanese mCRPC patients treated with cabazitaxel and assessed the prognostic significance of cabazitaxel, focusing on patient age and the correlation of efficacy between docetaxel and cabazitaxel. Results: Prostate-specific antigen (PSA) decline was observed in 27 patients (57.4%), including 19 (40.0%) achieving the response defined by PSA decline ≥ 30%. The median overall survival (OS) periods after the introduction of cabazitaxel was 16.1 months. Twenty (42.6%) were judged to have responded to cabazitaxel with a PSA decrease ≥ 30% from the baseline. A 30% PSA response to cabazitaxel was achieved in 4 (50.0%) patients with ≧ 75 years (n = 8) and 16 (41.0%) patients with less than 75 years (n = 39). There was no significant correlation between the PSA response and patients’ age (p = 0.707). A 30% PSA response to cabazitaxel was achieved in 13 (46.4%) and 7 (36.8%) patients with and without that to docetaxel, respectively. A 30% PSA response to cabazitaxel was achieved in 5 (16.6%) and 7 (41.2%) patients who had treated with less than 10 cycles docetaxel or 10 ≦ cycles, respectively. Univariate and multivariate analyses revealed that there were no significant correlation of patient age (p = 0.537), the response to prior docetaxel therapy (p = 0.339) or cycles of docetaxel therapy (p = 0.379) with shorter OS. Conclusion: These results indicate that the introduction of cabazitaxel for Japanese mCRPC patients could result in oncological outcomes without any association with patient’s age and the profiles of previous docetaxel therapy.

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Clinical evaluation of two consecutive UroVysion fluorescence in situ hybridization tests to detect intravesical recurrence of bladder cancer: a prospective blinded comparative study in Japan

Kojima T., Nishiyama H., Ozono S., Hinotsu S., Keino N., Yamaguchi A., Sakai H., Enomoto Y., Horie S., Fujimoto K., Matsuyama H., Okamura T., Kanimoto Y., Oya M., Nonomura N., Naito S., Akaza H.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 23 （ 6 ） 1140 - 1147 2018年12月

共著, ISSN 13419625

© 2018, Japan Society of Clinical Oncology. Background: We evaluated the use of UroVysion fluorescence in situ hybridization tests to detect the intravesical recurrence of bladder cancer during follow-up after a transurethral resection of bladder tumor (TURBT). Methods: In this prospective, blinded, comparative study, 486 patients treated by TURBT within the prior 2 years were registered at 12 centers. Urine cytology and UroVysion tests were performed once or twice at a central testing laboratory. For the patients with no suspicious findings of bladder cancer in the first analysis, the same examination set was repeated 3 months later as the second analysis. Totals of 468 and 399 patients were eligible for the first and second analyses, respectively. We determined the sensitivity and specificity of two consecutive UroVysion tests. Results: Bladder cancers were identified in 44 patients at the first analysis. The UroVysion test had 50.0% (95% CI 35.2–64.8%) sensitivity and 72.4% (68.3–76.8%). Urine cytology had 4.5% (0.0–10.7%) sensitivity and 99.8% (99.3–100.0%) specificity. The concordant rate of the first and second UroVysion test results was 72% (kappa coefficient 0.157). Interestingly, the patients with two consecutive positive UroVysion test results had the highest cancer detection rate (14.8%), which is greater than those of the patients with a positive result in either (7.2%) or neither (1.2%) of the two tests at the 3-month follow-up. Conclusions: The UroVysion test provided higher sensitivity than urine cytology to detect bladder cancer during post-TURBT follow-up. Two consecutive UroVysion tests might be a better indicator to predict intravesical recurrence.

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Single-cell RNA-seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63

Tanaka N., Katayama S., Reddy A., Nishimura K., Niwa N., Hongo H., Ogihara K., Kosaka T., Mizuno R., Kikuchi E., Mikami S., Miyakawa A., Arenas E., Kere J., Oya M., Uhlén P.

Cancer Medicine （Cancer Medicine） 7 （ 12 ） 6193 - 6204 2018年12月

研究論文（学術雑誌）, 共著, ISSN 2045-7634

© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Cancers acquire resistance to systemic treatment with platinum-based chemotherapy (eg, cisplatin [CDDP]) as a result of a dynamic intratumoral heterogeneity (ITH) and clonal repopulation. However, little is known about the influence of chemotherapy on ITH at the single-cell level. Here, mapping the transcriptome of cancers treated with CDDP by scRNA-seq, we uncovered a novel gene, COX7B, associated with platinum-resistance, and surrogate marker, CD63. Knockdown of COX7B in cancer cells decreased the sensitivity of CDDP whereas overexpression recovered the sensitivity of CDDP. Low COX7B levels correlated with higher mortality rates in patients with various types of cancer and were significantly associated with poor response to chemotherapy in urinary bladder cancer. Tumor samples from patients, who underwent CDDP therapy, showed decreased COX7B protein levels after the treatment. Analyzing scRNA-seq data from platinum-naïve cancer cells demonstrated a low-COX7B subclone that could be sorted out from bulk cancer cells by assaying CD63. This low-COX7B subclone behaved as cells with acquired platinum-resistance when challenged to CDDP. Our results offer a new transcriptome landscape of platinum-resistance that provides valuable insights into chemosensitivity and drug resistance in cancers, and we identify a novel platinum resistance gene, COX7B, and a surrogate marker, CD63.

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Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A Multi-Institutional Study in Japan

Ito K., Mikami S., Tatsugami K., Masumori N., Shinohara N., Kondo T., Nakanishi S., Nagashima Y., Eto M., Kamba T., Kuroda N., Tomita Y., Matsuyama H., Onishi T., Tsushima T., Nakazawa H., Oya M., Ozono S., Naito S., Asano T.

Clinical Genitourinary Cancer （Clinical Genitourinary Cancer） 16 （ 6 ） e1201 - e1214 2018年12月

研究論文（学術雑誌）, 共著, ISSN 15587673

© 2018 Elsevier Inc. Background: Standard treatments have not been established in metastatic papillary renal-cell carcinoma (PRCC). We aimed to investigate treatment outcomes in patients with mPRCC. Patients and Methods: This study included 51 patients who were diagnosed with PRCC at 14 institutions. Pathologic slides were reviewed by pathologists. The associations between clinical factors and overall survival (OS) were analyzed. Results: Final pathologic diagnoses could be determined in 50 patients. Thirty-five tumors were diagnosed as PRCC (type 2 PRCC, 91.4%), and 15 were diagnosed as other histologic types. Targeted therapies (TTs) were provided to 25 mPRCC patients. Patients treated with TT survived significantly longer than those treated before the era of TT (median OS, 22.5 vs. 6.3 months; P = .0035). Median OS of patients who experienced stable disease for ≥ 9 months using single TT was 43.1 months. Patients treated with a tyrosine kinase inhibitor (TKI) as first-line TT survived longer after TT initiation than those treated with an mTOR inhibitor (median, 22.4 vs. 11.7 months; P = .2684). Patients treated with TKIs in both first- and second-line settings had significantly better survival after TT initiation than those treated with a TKI in one therapy line and an mTOR inhibitor in the other (31.4 vs. 12.9 months, P = .0172). Patients treated with a TKI as second-line TT survived significantly longer after second-line TT initiation than did those treated with an mTOR inhibitor (16.2 vs. 7.4 months, P = .0016). Conclusion: Prognoses of patients with mPRCC were improved by TT, and TKIs appeared to be the treatment of choice in both the first- and second-line settings. We aimed to investigate treatment outcomes in patients with metastatic papillary renal-cell carcinoma. Patients treated with targeted therapy (TT) survived significantly longer than those treated before the era of TT. Patients treated with tyrosine kinase inhibitors (TKIs) in both first- and second-line settings had significantly better survival after initiation of TT than those treated with a TKI in one therapy line and an mTOR inhibitor in the other.

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Aldosterone and 18-Oxocortisol Coaccumulation in Aldosterone-Producing Lesions.

Sugiura Y, Takeo E, Shimma S, Yokota M, Higashi T, Seki T, Mizuno Y, Oya M, Kosaka T, Omura M, Nishikawa T, Suematsu M, Nishimoto K

Hypertension (Dallas, Tex. : 1979) （Hypertension） 72 （ 6 ） 1345 - 1354 2018年12月

研究論文（学術雑誌）, 共著, ISSN 0194-911X

© 2018 American Heart Association, Inc. Primary aldosteronism is a secondary hypertensive disease caused by autonomous aldosterone production that often caused by an aldosterone-producing adenoma (APA). Immunohistochemistry of aldosterone synthase (CYP11B2) shows the presence of aldosterone-producing cell clusters (APCCs) even in non-primary aldosteronism adult adrenal cortex. An APCC-like structure also exists as possible APCC-to-APA transitional lesions (a speculative designation) in primary aldosteronism adrenals. However, whether APCCs produce aldosterone or 18-oxocortisol, a potential serum marker of APA, remains unknown because of lack of technology to visualize adrenocorticosteroids on tissue sections. To address this obstacle, in this study, we used highly sensitive Fourier transform ion cyclotron resonance mass spectrometry to image various adrenocorticosteroids, including 18-oxocortisol, in adrenal tissue sections from 8 primary aldosteronism patients with APCC (cases 1-4), possible APCC-to-APA transitional lesions (case 5), and APA (cases 6-8). Further analyses by tandem mass spectrometry imaging allowed us to differentially visualize aldosterone from cortisone, which share identical mass-to-charge ratio value (m/z). In conclusion, these advanced imaging techniques revealed that aldosterone and 18-oxocortisol coaccumulated within CYP11B2-expressing lesions. These imaging outcomes along with a growing body of aldosterone research led us to build a progressive development hypothesis of an aldosterone-producing pathology in the adrenal glands.

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The therapeutic effect of sulfasalazine for metastatic urothelial carcinoma targeting to cancer stem cell

Ogihara Koichiro, Kikuchi Eiji, Takeda Toshikazu, Kosaka Takeo, Saya Hideyuki, Oya Mototsugu

CANCER SCIENCE （WILEY） 109 979 - 979 2018年12月

共著, ISSN 1349-7006

Roles of etoposide and cisplatin for CRPC in the post-cabazitaxel setting

Hongo Hiroshi, Kosaka Takeo, Kikuchi Eiji, Oya Mototsugu

CANCER SCIENCE （WILEY） 109 601 - 601 2018年12月

共著, ISSN 1349-7006

Risk stratification of castration-resistant prostate cancer patients treated with cabazitaxel.

Kosaka T, Hongo H, Mizuno R, Oya M

Molecular and clinical oncology （SPANDIDOS PUBL LTD） 9 （ 6 ） 683 - 688 2018年12月

研究論文（学術雑誌）, 共著, ISSN 2049-9450

Patient characteristics before administering the first cycle of cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) were collected to assess prognostic factors for overall survival (OS). Multivariate analysis revealed that prostate-specific antigen (PSA) ≥100 ng/ml prior to cabazitaxel treatment, visceral metastasis, and low absolute monocyte count were independent prognostic indicators for OS. The aim of the present study was to investigate prognostic biomarkers in patients treated with cabazitaxel among Japanese metastatic castration-resistant prostate cancer (mCRPC) patients. In this retrospective study, 45 patients with mCRPC treated with cabazitaxel were reviewed retrospectively. Clinicopathological factors and laboratory data before administering the first cycle of cabazitaxel were collected to assess the prognostic factors for overall survival (OS). Treatment was generally well tolerated, with a median of 5 cycles (range, 1-26). Median OS from the start of cabazitaxel treatment was 16.1 months (95% confidence interval 6.8-25.5). Univariate analysis revealed that poor performance status, visceral metastasis, hemoglobin <11 mg/dl, absolute monocyte count <400/µl, and prostate-specific antigen ≥100 ng/ml prior to cabazitaxel treatment (P=0.002) were significantly associated with shorter OS. Multivariate analysis revealed that PSA ≥100 ng/ml prior to cabazitaxel treatment, visceral metastasis, and absolute monocyte count <400/µl were independent prognostic indicators for OS. Based on the relative risk of death, patients with mCRPC before cabazitaxel therapy were divided into three risk groups: Low, intermediate, and high (P<0.001). In conclusion, the practical implications of our results may assist in tailoring the introduction of cabazitaxel.

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Rare association of the anterior and posterior urethral valves.

Murakami T, Asanuma H, Shigeta K, Ezaki T, Oya M

Pediatrics international : official journal of the Japan Pediatric Society （Pediatrics International） 60 （ 12 ） 1090 - 1091 2018年12月

研究論文（学術雑誌）, 共著, ISSN 1328-8067

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MUC1C Oncoprotein Contributes to Acquiring Cisplatin and Gemcitabine Resistance in Urothelial Carcinoma Cells

Shigeta Keisuke, Kikuchi Eiji, Hasegawa Masanori, Ogihara Koichiro, Kosaka Takeo, Oya Mototsugu

CANCER SCIENCE （WILEY） 109 1192 - 1192 2018年12月

共著, ISSN 1349-7006

Evaluation of prostate-specific antigen density in the diagnosis of prostate cancer combined with magnetic resonance imaging before biopsy in men aged 70 years and older with elevated PSA.

Yanai Y, Kosaka T, Hongo H, Matsumoto K, Shinojima T, Kikuchi E, Miyajima A, Mizuno R, Mikami S, Jinzaki M, Oya M

Molecular and clinical oncology （SPANDIDOS PUBL LTD） 9 （ 6 ） 656 - 660 2018年12月

研究論文（学術雑誌）, 共著, ISSN 2049-9450

There is an increasing proportion of individuals aged 70 years and older, as well as an increasing life expectancy worldwide. The present study may guide the management of older patients with elevated prostate specific antigen (PSA). The medical records of 241 older men aged >70 years who underwent multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy (PBx) at our institution were reviewed retrospectively. Multiple variables were evaluated as predictors for the diagnosis of prostate cancer (PCa). The variables included serum PSA level, digital rectal examination, size of region of interest on mpMRI, prostate volume and PSA density. PCa was positive in 162 (67.2%). Prostate volume and PSA density were significant PCa predictors (P<0.001). In patients aged 70-75 and >75 years, PSA density was significantly higher in patients with PCa (0.21 ng/ml/cc, P=0.014 and 0.24 ng/ml/cc, P<0.001, respectively). Similarly, PSA density was significant higher in patients with significant PCa (0.24 ng/ml/cc, P=0.004 and 0.29 ng/ml/cc, P<0.001, respectively). The cut-off value of PSA density was calculated using receiver operating characteristic curves. Area under curve of PSA density was 0.698, and the best cut-off value was 0.20 ng/ml/cc. These results indicate that the combination of PSA density with mpMRI before PBx is a helpful method and can be a decision-making model for a selection of PBx.

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専門医のための泌尿器科基本手術腹腔鏡下膀胱憩室切除術

篠島利明, 松本一宏, 大家基嗣

臨床泌尿器科（株式会社医学書院） 72 （ 12 ） 1012 - 1017 2018年11月

ISSN 0385-2393

Retrocaval Ureter Manifested after Ureteral Reimplantation for Ipsilateral Vesicoureteral Reflux: A Case Report.

Katsui M, Asanuma H, Fukumoto K, Mizuno R, Oya M

Urology journal （Urology Journal） 15 （ 6 ） 397 - 399 2018年11月

研究論文（学術雑誌）, 共著, ISSN 1735-1308

© 2018 Urology and Nephrology Research Centre. We report a female patient diagnosed with retrocaval ureter (RCU) after ureteral reimplantation for vesicoureteral reflux (VUR). She was diagnosed as right grade IV VUR with breakthrough urinary tract infections, and underwent ureteral reimplantation with Cohen cross-trigonal technique. Thereafter, she developed severe right hydronephrosis associated with RCU, which was presumably due to caudal traction of right ureter at ureteral reimplantation. She underwent uretero-ureterostomy anterior to the inferior vena cava, and recovered well. Detailed evaluation for upper urinary tract is mandatory for high grade VUR, and Cohen technique should be avoided for VUR associated with RCU.

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