論文 - 大家　基嗣

特集 前立腺癌のバイオロジーと最新の治療-いま起こりつつあるパラダイムシフト 企画にあたって

大家 基嗣

臨床泌尿器科 （株式会社医学書院）  75 （ 5 ） 273 - 273 2021年04月

ISSN  0385-2393

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特集 前立腺癌のバイオロジーと最新の治療-いま起こりつつあるパラダイムシフト 〈注目トピックス〉 神経内分泌前立腺癌の治療

安水 洋太, 小坂 威雄, 大家 基嗣

臨床泌尿器科 （株式会社医学書院）  75 （ 5 ） 340 - 345 2021年04月

ISSN  0385-2393

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Utility of prophylactic antibiotics for preventing febrile neutropenia during cabazitaxel therapy for castration-resistant prostate cancer.

Watanabe K, Kosaka T, Hongo H, Oya M

Scientific reports （Scientific Reports）  11 （ 1 ） 8367 - 8367 2021年04月

研究論文（学術雑誌）, 共著,  ISSN  2045-2322

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The aim was to investigate the efficacy of prophylactic antibiotics for the prevention of febrile neutropenia (FN) during cabazitaxel therapy for castration-resistant prostate cancer (CRPC) with G-CSF. We retrospectively studied 443 cycles of cabazitaxel therapy given to 56 patients with CRPC at Keio University Hospital between May 2012 and August 2018. Statistical analysis was conducted to determine whether the combination of prophylactic G-CSF and antibiotics was more effective in preventing FN, compared with prophylactic G-CSF alone. Prophylactic PEG-G-CSF or G-CSF was administered in all 443 cycles. Only fluoroquinolones were used as prophylactic antibiotics and were administered in 328 cycles (74.0%). FN occurred in 5 cycles (1.1%). Prophylactic antibiotics were administered in 327 cycles (74.6%) in the FN-negative group and in only 1 cycle (20.0%) in the FN-positive group. Chi-square test indicated the incidence of FN was significantly lower in the group that received prophylactic antibiotics compared with the group that did not receive prophylactic antibiotics (P = 0.017). Compared with prophylactic G-CSF alone, prophylactic G-CSF and antibiotics significantly suppressed the occurrence of FN.

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A long-term survivor of metastatic neuroendocrine prostate cancer treated with multimodal therapy: genetic consideration from next-generation sequencing

Hongo Hiroshi, Kosaka Takeo, Nakatsuka Seishi, Oya Mototsugu

INTERNATIONAL CANCER CONFERENCE JOURNAL 10 （ 3 ） 174 - 180 2021年04月

ISSN  2192-3183

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Grading of Multifocal Prostate Cancer Cases in which the Largest Volume and the Highest Grade do Not Coincide within One Lesion.

Matsumoto K, Omura M, Takeda T, Kosaka T, Hashiguchi A, Takamatsu K, Yasumizu Y, Tanaka N, Morita S, Mizuno R, Asanuma H, Oya M

The Journal of urology （The Journal of urology）  206 （ 2 ） 101097JU0000000000001765 - 345 2021年04月

研究論文（学術雑誌）, 共著,  ISSN  0022-5347

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PURPOSE: In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years. RESULTS: Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively). CONCLUSIONS: Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

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増刊号特集 泌尿器科当直医マニュアル 企画にあたって

大家 基嗣

臨床泌尿器科 （株式会社医学書院）  75 （ 4 ） 7 - 7 2021年04月

ISSN  0385-2393

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特集 内科疾患の診断基準・病型分類・重症度 第3章　腎臓 腎細胞がん

水野 隆一, 大家 基嗣

内科 （南江堂）  127 （ 4 ） 643 - 646 2021年04月

ISSN  0022-1961

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Radiologic features of mixed epithelial and stromal tumors of the kidney: Hyperattenuating on unenhanced computed tomography and T2-hypointensity on magnetic resonance imaging

Suzuki Tatsuya, Akita Hirotaka, Arita Yuki, Tomiyama Akiko, Hashimoto Masahiro, Okuda Shigeo, Mikami Shuji, Mizuno Ryuichi, Oya Mototsugu, Jinzaki Masahiro

Radiology Case Reports （Radiology Case Reports）  16 （ 4 ） 858 - 862 2021年04月

研究論文（学術雑誌）, 共著

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© 2021 In the 2016 World Health Organization renal tumor classification, the mixed epithelial and stromal tumor family was introduced as a new entity. This family encompasses a spectrum of tumors, ranging from predominantly cystic tumors (adult cystic nephromas) to tumors that are variably solid (mixed epithelial and stromal tumors). The majority of previous studies incorporating “mixed epithelial and stromal tumor” in the titles were actually reports of imaging findings of adult cystic nephroma. Thus, the solid component of mixed epithelial and stromal tumors has not been well evaluated. In this study, we present 2 cases of mixed epithelial and stromal tumors, as defined by the 2016 World Health Organization classification, showing a predominantly solid component. The characteristic findings of the solid component of these tumors were T2-hypointensity on magnetic resonance imaging and hyperattenuation on unenhanced computed tomography. Angiomyolipoma with epithelial cysts and epithelioid angiomyolipoma should be considered in the differential diagnosis of mixed epithelial and stromal tumors.

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ASO Author Reflections: Previous History of Non-urothelial Malignancy May Provide Predictive Information of Worse Clinical Outcome for Initially Diagnosed Non-Muscle Invasive Bladder Cancer.

Kufukihara R, Kikuchi E, Ogihara K, Shigeta K, Oya M

Annals of surgical oncology （Annals of Surgical Oncology）  28 （ 9 ） 5360 - 5361 2021年03月

研究論文（学術雑誌）, 共著,  ISSN  1068-9265

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A first Japanese case of BRCA2 and RB1 co-loss organ-confined prostate cancer successfully treated by radical prostatectomy

Matsumoto Kazuhiro, Kosaka Takeo, Nakamura Kohei, Nishihara Hiroshi, Oya Mototsugu

INTERNATIONAL CANCER CONFERENCE JOURNAL 10 （ 3 ） 170 - 173 2021年03月

ISSN  2192-3183

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Role of Previous Malignancy History in Clinical Outcomes in Patients with Initially Diagnosed Non-Muscle Invasive Bladder Cancer.

Kufukihara R, Kikuchi E, Ogihara K, Shigeta K, Yanai Y, Takamatsu K, Ide H, Oyama M, Asakura H, Mizuno R, Oya M

Annals of surgical oncology （Annals of Surgical Oncology）  28 （ 9 ） 5349 - 5359 2021年03月

研究論文（学術雑誌）, 共著,  ISSN  1068-9265

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© 2021, Society of Surgical Oncology. Introduction: Our aim is to evaluate whether previous non-urothelial malignant history affects the clinical outcomes of patients with non-muscle invasive bladder cancer (NMIBC). Patients and Methods: We identified 1097 cases treated by transurethral resection of bladder tumors for initially diagnosed NMIBC at our four institutions between 1999 and 2017. We compared clinical characteristics and outcomes between NMIBC patients with and without previous non-urothelial malignant history and investigated whether smoking status and treatment modality for previous cancer affected NMIBC outcomes. Results: A total of 177 patients (16.1%) had previous non-urothelial malignant history (malignant history group). The 5-year recurrence-free survival rate and the 5-year progression-free survival rate in the malignant history group was 46.4% and 88.3%, respectively, which was significantly lower than that in the counterpart (60.2% p = 0.004, and 94.5% p = 0.002, respectively). A multivariate Cox regression analysis identified previous non-urothelial malignant history as an independent risk factor for tumor recurrence (p = 0.001) and stage progression (p = 0.003). In a subgroup of patients who were current smokers (N = 347), previous non-urothelial malignant history was associated with tumor recurrence and stage progression. In contrast, previous non-urothelial malignant history was not associated with tumor recurrence or stage progression in ex-smokers or non-smokers. In a subgroup analysis of NMIBC patients with previous prostate cancer history, those treated with androgen deprivation therapy had a significantly lower bladder tumor recurrence rate than their counterparts (p = 0.027). Conclusions: Previous history of non-urothelial malignancy may lead to worse clinical outcome in patients with NMIBC, particularly current smokers.

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Cranial nerve palsy caused by metastasis to the skull base in patients with castration-resistant prostate cancer: Three case reports.

Yasumizu Y, Kosaka T, Hongo H, Mizuno R, Oya M

IJU case reports 4 （ 2 ） 108 - 111 2021年03月

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Introduction: Skull base metastasis of prostate cancer associated with cranial nerve palsy is rare. We observed three patients with aggressive prostate cancer who experienced cranial nerve palsy. Case presentation: Case 1 was a 53-year-old patient who was treated with carboplatin and etoposide. He noticed sensory abnormalities on his left mouth edge. Head magnetic resonance imaging revealed skull base metastasis. Case 2 was a 50-year-old patient who received docetaxel. This patient exhibited ptosis of the left eye. Skull base metastasis was detected by magnetic resonance imaging. External beam radiation therapy was performed. Case 3 was a 64-year-old patient who was treated with docetaxel. He experienced ptosis of the right eye and diplopia. He was also treated with external beam radiation therapy. Conclusion: External beam radiation therapy exhibited some efficacy against the symptoms, but skull base metastasis of treatment-resistant prostate cancer has poor prognosis. Three patients died within 3 months after symptoms occurred with or without external beam radiation therapy.

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The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma.

Shigeta K, Matsumoto K, Ogihara K, Murakami T, Anno T, Umeda K, Izawa M, Baba Y, Sanjo T, Shojo K, Tanaka N, Takeda T, Kosaka T, Mizuno R, Mikami S, Kikuchi E, Oya M

Cancer science （WILEY）  112 （ 3 ） 1084 - 1094 2021年03月

研究論文（学術雑誌）, 共著,  ISSN  1347-9032

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© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.

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Frequent azoospermia in patients with testicular germ cell cancer and a history of cryptorchidism: a report of nine cases and review of the literature.

Hagiuda J, Nakagawa K, Oya M

Systems biology in reproductive medicine （TAYLOR & FRANCIS INC）  67 （ 3 ） 1 - 4 2021年02月

研究論文（学術雑誌）, 共著,  ISSN  1939-6368

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© 2021 Informa UK Limited, trading as Taylor & Francis Group. This study analyzed semen parameters in patients with testicular germ cell cancer and a history of cryptorchidism. Among testicular cancer patients referred for sperm cryopreservation, the semen of 9 patients with a history of cryptorchidism, including three cases of bilateral cryptorchidism and one case of cryptorchidism with bilateral metachronous tumor, was analyzed. Eight patients underwent orchidopexy during childhood. The tumor was observed on the contralateral side of the undescended testis, except in the bilateral metachronous tumor and cryptorchidism cases. Five patients, including the one who developed a metachronous testicular tumor on the undescended testis, showed azoospermia even though in three of them, semen was collected before undergoing orchiectomy. Clinical urologists should recognize that spermatogenesis is severely impaired in these patients and consider cryopreservation before orchiectomy or onco-TESE.

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Efficacy of avelumab plus axitinib (A plus Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

Tomita Yoshihiko, Motzer Robert J., Choueiri Toni K., Rini Brian I., Miyake Hideaki, Oya Mototsugu, Albiges Laurence, Fujii Yosuke, Umeyama Yoshiko, Wang Jing, Di Pietro Alessandra, Schmidinger Manuela

JOURNAL OF CLINICAL ONCOLOGY 39 （ 6 ）  2021年02月

ISSN  0732-183X

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Landscape of genomic alterations of circulating tumor DNA in advanced genitourinary cancer patients: SCRUM-Japan MONSTAR SCREEN Project.

Matsubara Nobuaki, Kato Taigo, Fujisawa Takao, Shiota Masaki, Eto Masatoshi, Osawa Takahiro, Abe Takashige, Shinohara Nobuo, Yasumizu Yota, Tanaka Nobuyuki, Oya Mototsugu, Nishimoto Koshiro, Horasawa Satoshi, Kuramoto Naomi, Nakamura Yoshiaki, Taniguchi Hiroya, Yoshino Takayuki, Nonomura Norio

JOURNAL OF CLINICAL ONCOLOGY 39 （ 6 ）  2021年02月

ISSN  0732-183X

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Enzalutamide plus androgen deprivation therapy (ADT) versus flutamide plus ADT in men with castration-resistant prostate cancer (CRPC): AFTERCAB

Uemura Hiroji, Kobayashi Kazuki, Yokomizo Akira, Hinotsu Shiro, Horie Shigeo, Kakehi Yoshiyuki, Naito Seiji, Nonomura Norio, Ogawa Osamu, Oya Mototsugu, Suzuki Kazuhiro, Saito Atsushi, Uno Satoshi, Akaza Hideyuki

JOURNAL OF CLINICAL ONCOLOGY 39 （ 6 ）  2021年02月

ISSN  0732-183X

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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).

Tomita Y, Kimura G, Fukasawa S, Numakura K, Sugiyama Y, Yamana K, Naito S, Kabu K, Tajima Y, Oya M

Japanese journal of clinical oncology （Japanese journal of clinical oncology）  51 （ 6 ） 966 - 975 2021年02月

研究論文（学術雑誌）, 共著,  ISSN  0368-2811

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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.

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Site-specific differences in survival among upper and lower tract urothelial carcinoma patients treated with radical surgery.

Anno T, Kikuchi E, Shigeta K, Ogihara K, Watanabe K, Yanai Y, Takamatsu K, Hasegawa S, Masuda T, Oyama M, Mizuno R, Oya M

Japanese journal of clinical oncology （Japanese journal of clinical oncology）  51 （ 6 ） 984 - 991 2021年02月

研究論文（学術雑誌）, 共著,  ISSN  0368-2811

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BACKGROUND: It currently remains unclear whether the location of primary tumours affects the clinical outcomes of patients with locally advanced urothelial carcinoma in the urinary tract. The aim of the present study was to compare prognostic differences between bladder urothelial carcinoma and upper tract urothelial carcinoma, particularly pT3 or higher tumours. METHODS: In total, 307 patients with pT3 or higher urothelial carcinoma without distant metastasis who underwent radical cystectomy for bladder urothelial carcinoma (N = 127, 41.4%) or radical nephroureterectomy for upper tract urothelial carcinoma (N = 180, 58.6%) at Keio University Hospital and three affiliated hospitals between 1994 and 2017 were enrolled. Oncological outcomes were compared between bladder urothelial carcinoma and upper tract urothelial carcinoma using Cox regression analysis. RESULTS: Significantly higher rates of male patients, smokers, neoadjuvant chemotherapy, lymph node involvement and lymphovascular invasion were observed in the bladder urothelial carcinoma group. The incidence of regional lymph node or local recurrence was higher in patients with bladder urothelial carcinoma than in those with upper tract urothelial carcinoma, while that of lung metastasis was lower. In all patients, bladder urothelial carcinoma was independently associated with disease recurrence (hazard ratio (HR) 1.504, P = 0.035) in addition to neoadjuvant chemotherapy and lymphovascular invasion. Bladder urothelial carcinoma was also independently associated with cancer death (HR = 1.998, P = 0.002) as well as lymphovascular invasion. Following the exclusion of patients who received neoadjuvant chemotherapy, bladder urothelial carcinoma remained an independent risk factor for disease recurrence and cancer death (HR = 1.702, P = 0.010 and HR = 1.888, P = 0.013, respectively). CONCLUSIONS: Bladder urothelial carcinoma may follow worse prognosis compared to upper tract urothelial carcinoma, particularly that with a high pathological stage.

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In silico screening for identification of novel drugs for overcoming taxane-resistant prostate cancer

Hongo Hiroshi, Kosaka Takeo, Miyazaki Yasumasa, Tanaka Nobuyuki, Oya Mototsugu

CANCER SCIENCE （(一社)日本癌学会）  112   916 - 916 2021年02月

共著,  ISSN  1347-9032