論文 - 大家　基嗣

RISK FACTORS FOR HEMODYNAMIC INSTABILITY DURING LAPAROSCOPIC ADRENALECTOMY FOR PHEOCHROMOCYTOMA.

Toshikazu Takeda, Kimiharu Takamatsu, Yu Teranishi, Kyohei Hakozaki, Nobuyuki Tanaka, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikuchi, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E985 - E986 2019年04月

共著,  ISSN  0022-5347

PRETREATMENT NEUTROPHIL-TO-LYMPHOCYTE RATIO IS A NOVEL BIOMARKER FOR PREDICTING WORSE CLINICAL OUTCOME IN CHEMO-RESISTANT UROTHELIAL CARCINOMA PATIENTS TREATED WITH PEMBROLIZUMAB

Koichiro Ogihara, Eiji Kikuchi, Takashi Okabe, Seiya Hattori, Ryo Yamashita, Syunsuke Yoshimine, Suguru Shirotake, Kazuhiro Matsumoto, Ryuichi Mizuno, Satoshi Hara, Masafumi Oyama, Takeshi Masuda, Masashi Niwakawa, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E352 - E352 2019年04月

共著,  ISSN  0022-5347

OVERCOMING CABAZITAXEL RESISTANCE BY G2/M REGULATING GENES IN CASTRATION-RESISTANT PROSTATE CANCER

Hiroshi Hongo, Takeo Kosaka, Yoshinori Yanai, Yota Yasumizu, Yasumasa Miyazaki, Nobuyuki Tanaka, Kazuhiro Matsumoto, Ryuichi Mizuno, Eiji Kikuchi, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E1172 - E1173 2019年04月

共著,  ISSN  0022-5347

OPTIMAL SUBCLASSIFICATION SYSTEM FOR INTERMEDIATE-RISK NON-MUSCLE INVASIVE BLADDER CANCER

Kazuhiro Matsumoto, Eiji Kikuchi, Yoshinori Yanai, Nozomi Hayakawa, Naoya Niwa, Maeda Takahiro, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E315 - E315 2019年04月

共著,  ISSN  0022-5347

HIGH GAMMA-GLOBULIN LEVEL IS ASSOCIATED WITH ONCOLOGICAL OUTCOMES IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER

Naoya Niwa, Kazuhiro Matsumoto, Hiroki Ide, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E622 - E623 2019年04月

共著,  ISSN  0022-5347

COULD LAPAROSCOPIC SURGERY HAVE SAME LONG-TERM ONCOLOGICAL OUTCOMES AS OPEN RADICAL NEPHROURETERECTOMY IN T3N0M0 UPPER TRACT UROTHELIAL CARCINOMA? A MULTICENTER COHORT STUDY ADJUSTED BY PROPENSITY SCORE MATCHING

Keisuke Shigeta, Eiji Kikuchi, Takayuki Abe, Masayuki Hagiwara, Koichiro Ogihara, Toshikazu Takeda, Kazuhiro Matsumoto, Ryuichi Mizuno, Masahiro Jinzaki, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E716 - E716 2019年04月

共著,  ISSN  0022-5347

COULD A HISTORY OF NON-MUSCLE INVASIVE BLADDER CANCER HAVE A PROGNOSTIC ROLE IN CT2-4AN0M0 BLADDER CANCER PATIENTS TREATED WITH RADICAL CYSTECTOMY AND NEOADJUVANT CHEMOTHERAPY?

Emina Kayama, Eiji Kikuchi, Kyohei Hakozaki, Nobuyuki Tanaka, Gou Kaneko, Suguru Shirotake, Yasumasa Miyazaki, Shunsuke Yokomine, Maeda Takahiro, Kunimitsu Kanai, Masafumi Oyama, Yosuke Nakajima, Satoshi Hara, Tetsuo Monma, Mototsugu Oya

JOURNAL OF UROLOGY （LIPPINCOTT WILLIAMS & WILKINS）  201 （ 4 ） E360 - E360 2019年04月

共著,  ISSN  0022-5347

Is the occurrence of higher adverse effects associated with better oncological outcome in metastatic urothelial carcinoma patients treated with pembrolizumab?

Hayakawa Nozomi, Kikuchi Eiji, Ogihara Koichirou, Hattori Seiya, Yoshimine Shunsuke, Shirotake Suguru, Okabe Takashi, Yamashita Ryo, Oya Mototsugu

JOURNAL OF CLINICAL ONCOLOGY （AMER SOC CLINICAL ONCOLOGY）  37 （ 7 ）  2019年03月

共著,  ISSN  0732-183X

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The timing from perioperative chemotherapy and disease recurrence could have clinical impact on survival in bladder cancer patients treated with salvage chemotherapy.

Kikuchi Eiji, Hayakawa Nozomi, Ogihara Koichirou, Omura Minami, Mizuno Ryuichi, Oya Mototsugu

JOURNAL OF CLINICAL ONCOLOGY （AMER SOC CLINICAL ONCOLOGY）  37 （ 7 ）  2019年03月

共著,  ISSN  0732-183X

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Real-world use of sorafenib for advanced renal cell carcinoma patients with cardiovascular disease: Nationwide survey in Japan.

Inamoto Teruo, Azuma Haruhito, Oya Mototsugu, Hamada Yoko, Akaza Hideyuki

JOURNAL OF CLINICAL ONCOLOGY 37 （ 7 ）  2019年03月

ISSN  0732-183X

PROPEL: A randomized, phase Ill trial evaluating the efficacy and safety of olaparib combined with abiraterone as first-line therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Clarke Noel W., Armstrong Andrew J., Thiery-Vuillemin Antoine, Oya Mototsugu, Ye Dingwei, Mateo Joaquin, Goessl Carsten Dietrich, Kang Jinyu, Liu Sherry, Saad Fred

JOURNAL OF CLINICAL ONCOLOGY （AMER SOC CLINICAL ONCOLOGY）  37 （ 7 ）  2019年03月

共著,  ISSN  0732-183X

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Editor's Note

Oya Mototsugu

WORLD JOURNAL OF UROLOGY （SPRINGER）  37 （ 3 ） 576 - 576 2019年03月

単著,  ISSN  0724-4983

「2017年度前立腺がん啓発週間」の活動実績報告

五十嵐 敦, 深貝 隆志, 山中 英壽, 木村 剛, 柏原 剛, 大家 基嗣, 門間 哲雄, 中島 洋介, 森山 正敏, 井上 啓史, 斉藤 史郎, 並木 幹生, 小路 直

日本腎泌尿器疾患予防医学研究会誌 （日本腎泌尿器疾患予防医学研究会）  27 （ 1 ） 28 - 30 2019年03月

ISSN  1347-5010

　概要を見る

「2017年度前立腺がん啓発週間」の活動実績について報告した。その結果、全国合計で公開講座には2360名の市民が参加し、918名の男性がPSAを測定した。うち149名(16.2%)がPSA 4.0ng/mlを超える異常値を示し、精査の必要性が受診者に連絡された。前年度の公開講座参加者、PSA検診参加者と比較すると、ともに増加傾向にあった。

Prediction of extraprostatic extension by MRI tumor contact length: difference between anterior and posterior prostate cancer.

Matsumoto K, Akita H, Narita K, Hashiguchi A, Takamatsu K, Takeda T, Kosaka T, Mizuno R, Kikuchi E, Oya M, Jinzaki M

Prostate cancer and prostatic diseases （Prostate Cancer and Prostatic Diseases）  22 （ 4 ） 539 - 545 2019年02月

研究論文（学術雑誌）, 共著,  ISSN  1365-7852

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© 2019, Springer Nature America, Inc. Background: Tumor contact length (TCL) is defined as the extent of contact between prostate cancer and the prostatic capsule, and its predictive value for microscopic extraprostatic extension (EPE) has been reported. However, the impact of the zonal origin (anterior or posterior tumor) of the tumor on the diagnosis of EPE is controversial. Methods: We retrospectively analyzed the records of 233 consecutive patients who underwent preoperative MRI and radical prostatectomy. We designated their tumors as anterior or posterior, and evaluated the correlation between the TCL measured by MRI and microscopic EPE in the radical prostatectomy specimen. Then, we created the predicted probability curves for EPE versus TCL for anterior and posterior prostate cancer. Results: There were 109 patients (47%) with an anterior tumor and 124 patients (53%) with a posterior tumor. Postoperative pathological analysis confirmed pT3 in 18 patients (17%) with an anterior tumor and in 53 patients (43%) with a posterior tumor. Multivariate analysis demonstrated that the zonal origin of the tumor was an independent predictive factor for EPE. We developed separate probability curves of EPE versus TCL for anterior and posterior prostate cancer, which revealed that anterior tumors were less likely to invade the extraprostatic tissues. Among patients whose TCL was 10–20 mm, 9/32 patients (28%) with an anterior tumor had EPE compared with 24/45 patients (53%) with a posterior tumor (p = 0.036). The decision curve of this EPE predictive model had high clinical efficacy. Conclusions: Our results indicate that anterior tumors have more favorable pathological characteristics than posterior tumors with the same TCL measured by MRI. We constructed two separate predicted probability curves for EPE after discriminating anterior and posterior tumors, which will be useful for decision making in clinical practice.

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Pre-donation BMI and preserved kidney volume can predict the cohort with unfavorable renal functional compensation at 1-year after kidney donation.

Shinoda K, Morita S, Akita H, Tamaki S, Takahashi R, Kono H, Asanuma H, Kikuchi E, Jinzaki M, Nakagawa K, Oya M

BMC nephrology （BMC Nephrology）  20 （ 1 ） 46 - 46 2019年02月

研究論文（学術雑誌）, 共著,  ISSN  1471-2369

　概要を見る

© 2019 The Author(s). Background: The magnitude of renal function recovery after kidney donation differs in donors with a heterogeneous background. Preoperative assessment of candidates with potentially unfavorable renal functional compensation is critical when baseline kidney function is marginal. We explored the significance of preserved kidney volume (PKV) and known preoperative risk factors for the prediction of unfavorable renal function compensation. Methods: We enrolled 101 living donors for whom a 1-mm sliced enhanced computed tomography scan was performed preoperatively and clinical data could be collected up to 1 year after donation. The donors whose estimated glomerular filtration rate (eGFR) at 1 year after donation was 70% or higher of baseline eGFR were assigned to the "favorable renal compensation" group and the others to the "unfavorable renal compensation" group. Results: Age, sex, and preoperative serum uric acid level were not significant predictors for "unfavorable renal compensation." Multivariable logistic regression analysis revealed that body mass index (BMI) and body surface area (BSA)-adjusted PKV were independent preoperative risk factors for "unfavorable renal compensation" (adjusted odds ratio, 1.342 and 0.929, respectively). Hypertension and preoperative eGFR were not independent predictors when adjusted with BMI and BSA-adjusted PKV. Receiver operative characteristic analysis revealed that the predictive equation with the two independent predictors yielded a good accuracy to detect donor candidates with unfavorable renal functional compensation (area under the curve = 0.803), and the optimal cut-off values were identified as 23.4 kg/m 2 for BMI and 107.3 cm 3 /m 2 for BSA-adjusted PKV. Conclusions: BMI and BSA-adjusted PKV may be useful to select candidates with potentially unfavorable renal function compensation before kidney donation.

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BCG-induced cytokine release in bladder cancer cells is regulated by Ca²⁺ signaling.

Ibarra C, Karlsson M, Codeluppi S, Varas-Godoy M, Zhang S, Louhivuori L, Mangsbo S, Hosseini A, Soltani N, Kaba R, Kalle Lundgren T, Hosseini A, Tanaka N, Oya M, Wiklund P, Miyakawa A, Uhlén P

Molecular oncology （Molecular Oncology）  13 （ 2 ） 202 - 211 2019年02月

研究論文（学術雑誌）, 共著,  ISSN  1574-7891

　概要を見る

© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. Bacillus Calmette–Guérin (BCG) is widely used in the clinic to effectively treat superficial urinary bladder cancer. However, a significant proportion of patients who fail to respond to BCG risk cystectomy or death. Though more than 3 million cancer treatments with BCG occur annually, surprisingly little is known about the initial signaling cascades activated by BCG. Here, we report that BCG induces a rapid intracellular Ca 2+ (calcium ion) signal in bladder cancer cells that is essential for activating the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and for synthesizing and secreting proinflammatory cytokines, including interleukin 8 (IL-8). A similar Ca 2+ response was observed when cells were exposed to the supernatant of BCG. Studying cellular molecular mechanisms involved in the BCG signaling event, we found pivotal roles for phospholipase C and the Toll-like receptor 4. Further assessment revealed that this signaling pathway induces synthesis of IL-8, whereas exocytosis appeared to be controlled by global Ca 2+ signaling. These results shed new light on the molecular mechanisms underlying BCG treatment of bladder cancer, which can help in improving therapeutic efficacy and reducing adverse side effects.

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Mutation of GALNTL5 gene identified in patients diagnosed with asthenozoospermia.

Hagiuda J, Takasaki N, Oya M, Ishikawa H, Narimatsu H

Human fertility (Cambridge, England) （Human Fertility）  23 （ 4 ） 1 - 8 2019年01月

研究論文（学術雑誌）, 共著,  ISSN  1464-7273

　概要を見る

Asthenozoospermia is commonly observed in infertile men. However, very few causative gene mutations have been identified because an efficient detection method has not been established. We previously identified a patient with asthenozoospermia carrying a heterozygous point deletion in GALNTL5 by detecting an abnormal reduction in the abundance of GALNTL5 and other marker proteins. To identify other mutations in GALNTL5, we screened sperm samples from 208 infertile men mainly diagnosed with asthenozoospermia using the same method, and conducted next-generation sequencing. Consequently, another case of GALNTL5 mutation was detected only in sperm at a low frequency but not in the somatic blood cells of a patient diagnosed with asthenozoospermia. In this patient, sperm motility improved and the mutation disappeared at 2 years after the first observation. In this man, carrying a heterozygotic deficiency of GALNTL5, the swim-up method was useful to concentrate the spermatozoa without mutation. Intracytoplasmic sperm injection of the selected motile spermatozoa into oocytes of the patient's partner resulted in successful conception, and a female child was safely delivered. These results suggest the feasibility of our approach for the screening and treatment of asthenozoospermia associated with GALNTL5 mutation.

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Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study.

Tomita Y, Uemura H, Oya M, Shinohara N, Habuchi T, Fujii Y, Kamei Y, Umeyama Y, Bair AH, Rini BI

BMC cancer （BMC Cancer）  19 （ 1 ） 17 - 17 2019年01月

研究論文（学術雑誌）, 共著,  ISSN  1471-2407

　概要を見る

© 2019 The Author(s). Background: A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration. Methods: Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus < 24 months, and compared their baseline characteristics with Fisher's exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model. Results: Overall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS ≥24 months versus 20 (38%) with OS < 24 months. Patients with OS ≥24 vs. < 24 months, respectively, had significantly fewer metastatic sites (≤2 metastases: 52% vs. 10%; ≥3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., ≥ lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil (≤ upper limit of normal, 97% vs. 75%) and platelet (≤ upper limit of normal, 82% vs. 50%) levels at baseline and ≥ 1 year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that ≥1 year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration. Conclusions: The current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration.

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Impact of inflammatory marker levels one month after the first-line targeted therapy initiation on progression-free survival prediction in patients with metastatic clear cell renal cell carcinoma.

Ito K, Masunaga A, Tanaka N, Mizuno R, Shirotake S, Yasumizu Y, Ito Y, Miyazaki Y, Hagiwara M, Kanao K, Mikami S, Momma T, Masuda T, Nakagawa K, Oyama M, Asano T, Oya M

Japanese journal of clinical oncology （Japanese Journal of Clinical Oncology）  49 （ 1 ） 69 - 76 2019年01月

研究論文（学術雑誌）, 共著,  ISSN  0368-2811

　概要を見る

© The Author(s) 2018. Published by Oxford University Press. All rights reserved. Objectives: Progression-free survival of first-line targeted therapy greatly influences the survival of patients with metastatic renal cell carcinoma. We evaluated whether post-treatment inflammatory markers and lactate dehydrogenase levels had impacts on progression-free survival prediction in addition to those of conventional predictors. Methods: Two hundred and fifteen patients whose tumors were clear cell type and in whom first-line targeted therapies could be continued for >1 month were evaluated. Pretreatment clinical factors, pathological factors and laboratory data 1 month after targeted therapy initiation—including inflammatory markers (neutrophil count, neutrophil-to-lymphocyte ratio and C-reactive protein) and lactate dehydrogenase—were reviewed. To identify progression-free survival predictors, multivariate analyses were done. Results: The 1-year progression-free survival rate was 47%. Female gender, Karnofsky performance status <80%, time from diagnosis to systemic treatment <12 months, pretreatment C-reactive protein >3.0 mg/dl and post-treatment neutrophil-to-lymphocyte ratio >3.0 were independent predictors for progression-free survival. In contrast, neither C-reactive protein increase nor neutrophil-to-lymphocyte ratio increase after targeted therapy initiation were independent predictors. Pretreatment lactate dehydrogenase, post-treatment lactate dehydrogenase and lactate dehydrogenase decline were not independent predictors. When all patients were stratified by these independent factors into three groups (0 risk vs. 1 or 2 risks vs. 3 or more risks), there were significant differences in progression-free survival rates between the groups (P < 0.0001). Furthermore, there were also significant differences in overall survival rates between the groups (P < 0.0001). Conclusions: Integration of post-treatment neutrophil-to-lymphocyte ratio value with pretreatment factors may lead to the establishment of effective predictive model for disease progression in patients with metastatic clear cell renal cell carcinoma who received first-line targeted therapies.

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Prospective clinical trial of 12-fraction carbon-ion radiotherapy for primary renal cell carcinoma.

Kasuya G, Tsuji H, Nomiya T, Makishima H, Haruyama Y, Kobashi G, Hayashi K, Ebner DK, Omatsu T, Kishimoto R, Yasuda S, Igarashi T, Oya M, Akakura K, Suzuki H, Ichikawa T, Shimazaki J, Kamada T, Working Group for Genitourinary Tumors.

Oncotarget （Oncotarget）  10 （ 1 ） 76 - 81 2019年01月

研究論文（学術雑誌）, 共著

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Copyright: Kasuya et al. The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.

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