Papers - Oya, Mototsugu

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC.

Yoshihiko Tomita, Sei Naito, Naoto Sassa, Atsushi Takahashi, Tsunenori Kondo, Takuya Koie, Wataru Obara, Yasuyuki Kobayashi, Jun Teishima, Masayuki Takahashi, Hideyasu Matsuyama, Takeshi Ueda, Kenya Yamaguchi, Takeshi Kishida, Ryoichi Shiroki, Takashi Saika, Nobuo Shinohara, Mototsugu Oya, Hiro-Omi Kanayama

Clinical genitourinary cancer (CIG MEDIA GROUP, LP)  18 ( 4 ) e374 - e385 2020.08

Research paper (scientific journal), Joint Work,  ISSN  1558-7673

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PURPOSE: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. PATIENTS AND METHODS: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). RESULTS: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with < 5 metastatic sites). SO/SU was superior to SU/SO for patients without previous nephrectomy. CONCLUSIONS: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870).

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Umbilical closure using 2-octyl cyanoacrylate in transumbilical laparoscopic adrenalectomy: A randomized controlled trial.

Keishiro Fukumoto, Akira Miyajima, Kazuhiro Matsumoto, Hiroaki Kobayashi, Naoya Niwa, Hiroshi Hongo, Isao Kurihara, Eiji Kikuchi, Mototsugu Oya

International journal of urology : official journal of the Japanese Urological Association (WILEY)  27 ( 8 ) 670 - 675 2020.08

Research paper (scientific journal), Joint Work,  ISSN  0919-8172

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OBJECTIVES: To evaluate postoperative pain and esthetic outcomes in patients undergoing transumbilical laparoscopic adrenalectomy with wound closure using 2-octyl cyanoacrylate. METHODS: A total of 26 patients who underwent laparoscopic adrenalectomy with the transumbilical approach and agreed to participate in this study were included. Patients were randomly divided into two groups: the 2-octyl cyanoacrylate group (Glue group) or the non-use group (non-Glue group). A single surgeon (AM) carried out all procedures between 2014 and 2017. RESULTS: There were no significant differences in the clinical background of the Glue and non-Glue groups. The number of patients with moderate or high levels of pain in the resting/moving period on postoperative days 1, 2 and 3 was 6/10 (46%/77%), 6/9 (46%/69%) and 3/5 (23%/38%) in the non-Glue group, and 5/7 (38%/54%), 2/7 (15%/54%) and 1/3 (8%/23%) in the Glue group. These differences were not significant. In the subgroup analysis of patients aged <50 years, the numbers were 4/6 (57%/86%), 5/7 (71%/100%) and 3/5 (43%/71%) in the non-Glue group, and 3/4 (33%/44%), 1/4 (11%/44%) and 0/1 (0%/11%) in the Glue group in the resting/moving period. On postoperative days 2 and 3, these differences were significant (P = 0.035 and 0.037 in the resting period, and P = 0.017 and 0.013 in the moving period). CONCLUSIONS: 2-octyl cyanoacrylate can be used safely for laparoscopic adrenalectomy with the transumbilical approach, and might be useful for reducing postoperative pain in patients aged <50 years.

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PROGNOSTIC VALUE OF PD-L1 EXPRESSION ON TUMOR-INFILTRATING IMMUNE CELLS IN RENAL CELL CARCINOMA (ARCHERY STUDY)

Katsunori Tatsugami, Motohide Uemura, Noboru Nakaigawa, Naoto Sassa, Kenichi Harada, Toshinari Yamasaki, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Nobuaki Matsubara, Mototsugu Oya, Nobuo Shinohara, Hirotsugu Uemura, Toyonori Tsuzuki

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  80 ( 16 ) E1115 - E1115 2020.08

Joint Work,  ISSN  0008-5472

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IDENTIFICATION OF FOXO1 AS A TUMOR SUPPRESSOR MODULATED BY ANDROGEN RECEPTOR/ESTROGEN RECEPTOR-beta SIGNALS: IMPLICATIONS FOR BLADDER CANCER PROMOTION AND CHEMORESISTANCE

Hiroki Ide, Satoshi Inoue, Taichi Mizushima, Guiyang Jiang, Takuro Goto, Yujiro Nagata, Yuki Teramoto, Mototsugu Oya, George Netto, Hiroshi Miyamoto

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  80 ( 16 ) E230 - E230 2020.08

Joint Work,  ISSN  0008-5472

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Optimal treatment strategy for paratesticular liposarcoma: retrospective analysis of 265 reported cases.

Rei Kamitani, Kazuhiro Matsumoto, Toshikazu Takeda, Ryuichi Mizuno, Mototsugu Oya

International journal of clinical oncology (SPRINGER JAPAN KK)  25 ( 12 ) 2099 - 2106 2020.07

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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BACKGROUND: Liposarcoma is one of the most common subtypes of soft tissue sarcoma. Although the standard treatment for localized liposarcoma is surgical resection with negative margins, a treatment specific to paratesticular liposarcoma has yet to be quantitatively evaluated. METHODS: A systematic search of Medline, Web of Science, Embase, and Google was performed to find articles describing localized paratesticular liposarcoma published between 1979 and 2018 in English. The final cohort included 265 patients in 183 articles. The starting point was the time of surgical treatment, and the endpoint was the time of recurrence, including local recurrence, or distant metastasis. RESULTS: The median patient age was 62 years and the median tumor size was 9.5 cm. In total, 178 patients underwent high inguinal orchiectomy and 40 underwent simple tumorectomy. Based on the Kaplan-Meier curves, recurrence-free survival rates were significantly higher for those who underwent high inguinal orchiectomy than for those who underwent tumorectomy. Moreover, those with microscopic positive margins had a higher risk of recurrence than those with negative margins, but adjuvant radiation therapy after resection had no statistically significant effect on recurrence-free survival, even in subgroup analysis of patients with positive margins. Regarding the pathological subtypes, dedifferentiated, pleomorphic, and round-cell liposarcoma had a higher risk of recurrence than well-differentiated or myxoid liposarcoma. In the multivariate analysis, high inguinal orchiectomy greatly affected recurrence-free survival. The tumor size and histological subtype were independent risk factors for recurrence. CONCLUSION: Complete resection with high inguinal orchiectomy is the optimal treatment for paratesticular liposarcoma.

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Role of the MUC1-C oncoprotein in the acquisition of cisplatin resistance by urothelial carcinoma.

Keisuke Shigeta, Masanori Hasegawa, Eiji Kikuchi, Yota Yasumizu, Takeo Kosaka, Ryuichi Mizuno, Shuji Mikami, Akira Miyajima, Donald Kufe, Mototsugu Oya

Cancer science (WILEY)  111 ( 10 ) 3639 - 3652 2020.07

Research paper (scientific journal), Joint Work,  ISSN  1347-9032

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Mucin 1 C-terminal subunit (MUC1-C) has been introduced as a key regulator for acquiring drug resistance in various cancers, but the functional role of MUC1-C in urothelial carcinoma (UC) cells remains unknown. We aimed to elucidate the molecular mechanisms underlying the acquisition of cisplatin (CDDP) resistance through MUC1-C oncoprotein in UC cells. MUC1-C expression was examined immunohistochemically in tumor specimens of 159 UC patients who received CDDP-based perioperative chemotherapy. As a result, moderate to high MUC1-C expression was independently associated with poor survival in UC patients. Using human bladder cancer cell lines and CDDP-resistant (CR) cell lines, we compared the expression levels of MUC1-C, multiple drug resistance 1 (MDR1), the PI3K-AKT-mTOR pathway, and x-cystine/glutamate transporter (xCT) to elucidate the biological mechanisms contributing to the acquisition of chemoresistance. MUC1-C was strongly expressed in CR cell lines, followed with MDR1 expression via activation of the PI3K-AKT-mTOR pathway. MUC1-C also stabilized the expression of xCT, which enhanced antioxidant defenses by increasing intracellular glutathione (GSH) levels. MUC1 down-regulation showed MDR1 inhibition along with PI3K-AKT-mTOR pathway suppression. Moreover, it inhibited xCT stabilization and resulted in significant decreases in intracellular GSH levels and increased reactive oxygen species (ROS) generation. The MUC1-C inhibitor restored sensitivity to CDDP in CR cells and UC murine xenograft models. In conclusion, we found that MUC1-C plays a pivotal role in the acquisition of CDDP resistance in UC cells, and therefore the combined treatment of CDDP with a MUC1-C inhibitor may become a novel therapeutic option in CR UC patients.

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

Inamoto T., Azuma H., Tatsugami K., Oya M., Adachi M., Okayama Y., Sunaya T., Akaza H.

Expert Review of Anticancer Therapy (Expert Review of Anticancer Therapy)  20 ( 7 ) 615 - 623 2020.07

ISSN  14737140

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© 2020 Informa UK Limited, trading as Taylor & Francis Group. Objectives: To assess whether the clinical outcome of advanced/metastatic renal cell carcinoma (mRCC) treated with sorafenib, in real-world conditions, differs in patients with cardiovascular disease (CVD). Methods: mRCC patients (n = 2256 before matching) were matched by propensity score into CVD (n = 560) and non-CVD groups (n = 560), followed by safety and effectiveness analyzes. Results: After matching, patients’ features used for matching were balanced between the CVD and non-CVD groups, except for age (p = 0.0049). Renal comorbidity occurred more frequently in the CVD group. Exposure to sorafenib and objective response rate (25.4% [CVD], 28.5% [non-CVD]) were comparable in both groups. Median progression-free survival (PFS; 7.1 months, 95% CI: 6.4–8.6 [CVD]; 6.7 months, 6.3–8.3 [non-CVD]), and hazard ratios for PFS (0.954, 0.821–1.108) and overall survival (0.889, 0.683–1.156), were similar in the matched population. The incidences of adverse drug reactions (ADR, ≥10%) were generally similar between groups, although hypertension (42.1% vs 34.5%), diarrhea (26.3% vs 19.6%), decreased appetite (11.3% vs 7.5%), and non-serious and serious renal failure/dysfunction (3.6% vs 1.4% and 1.8% vs 0.4%), occurred more frequently in the CVD group. Conclusion: This analyzes suggests that sorafenib has clinical benefit for mRCC patients regardless of baseline CVD. Serious ADRs increased for renal dysfunction. Clinical trial registration: www.clinicaltrials.gov identifier is NCT01411423.

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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, Tatsugami Katsunori, Oya Mototsugu, Adachi Masatoshi, Okayama Yutaka, Sunaya Toshiyuki, Akaza Hideyuki

EXPERT REVIEW OF ANTICANCER THERAPY 20 ( 7 ) 615 - 623 2020.07

ISSN  1473-7140

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External validation of the "optimal PSA follow-up schedule after radical prostatectomy" in a new cohort

Yoshinori Yanai, Kazuhiro Matsumoto, Takeo Kosaka, Toshikazu Takeda, Nobuyuki Tanaka, Shinya Morita, Ryuichi Mizuno, Toshiaki Shinojima, Hiroshi Asanuma, Mototsugu Oya

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY (SPRINGER JAPAN KK)  25 ( 7 ) 1393 - 1397 2020.07

Research paper (scientific journal), Joint Work,  ISSN  1341-9625

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Background Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the "optimal PSA follow-up schedule after RP". The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. Methods We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the "optimal PSA follow-up schedule" at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2-0.4 ng/ml. Results During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). Conclusion This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.

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TYPE OF PATIENTS IN WHOM BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY CAN BE OBSERVED WITHOUT SALVAGE THERAPY

Kazuhiro Matsumoto, Naoya Niwa, Masayuki Hagiwara, Takeo Kosaka, Nobuyuki Tanaka, Toshikazu Takeda, Shinya Morita, Ryuichi Mizuno, Toshiaki Shinojima, Satoshi Hara, Eiji Kikuchi, Hiroshi Asanuma, Mototsugu Oya

JOURNAL OF UROLOGY (LIPPINCOTT WILLIAMS & WILKINS)  38 ( 7 ) 1749 - 1756 2020.07

Research paper (scientific journal), Joint Work, Accepted,  ISSN  0724-4983

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PURPOSE: To examine the prognosis after BCR with and without salvage therapy, including radiation and/or androgen deprivation. METHODS: The study population consisted of 431 patients, all of whom underwent radical prostatectomy and developed BCR (PSA > 0.2 ng/mL). According to the two risk factors [Gleason score ≥ 8 and PSA-doubling time (DT) < 6 months], we divided the patients into two groups. The high/intermediate-risk group consisted of patients with both or one risk factor. On the other hand, patients with neither factor were in the low-risk group. We set the starting point at the timing of BCR, and the endpoints were development to castration-resistant prostate cancer (CRPC) and cancer-specific death. RESULTS: During the mean follow-up period of 8.3 years after BCR, CRPC was observed in 49 patients (11.4%), and 21 patients (4.9%) died due to prostate cancer. We first divided the 191 high/intermediate-risk patients according to the PSA level (PSA < 1.0 ng/mL, PSA 1.0-4.0, and PSA > 4.0 or no therapy) at the initiation of salvage therapy, including radiation and/or androgen deprivation. We found that delayed (PSA > 4.0 ng/mL) or no salvage therapy was significantly associated with CRPC and cancer-specific death. In the 240 low-risk patients, Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival or cancer-specific survival within 10 years from the timing of BCR. CONCLUSIONS: Observation after BCR without salvage therapy or delayed administration may be an option for low-risk patients with a Gleason score ≤ 7 and PSA-DT ≥ 6 months when their life expectancy is within 10 years.

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

Inamoto T, Azuma H, Tatsugami K, Oya M, Adachi M, Okayama Y, Sunaya T, Akaza H

Expert review of anticancer therapy 20 ( 7 ) 615 - 623 2020.07

ISSN  1473-7140

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Myasthenia gravis with myositis induced by pembrolizumab therapy in a patient with metastatic urothelial carcinoma.

Nozomi Hayakawa, Eiji Kikuchi, Shigeaki Suzuki, Mototsugu Oya

International cancer conference journal (SPRINGER INTERNATIONAL PUBLISHING AG)  9 ( 3 ) 123 - 126 2020.07

Research paper (scientific journal), Joint Work,  ISSN  2192-3183

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Pembrolizumab is a long-awaited drug for the treatment of metastatic urothelial carcinoma. It is an immune checkpoint inhibitor, which has been shown to trigger new autoimmune disorders. We report a case of pembrolizumab-induced myasthenia gravis that occurred in an 84-year-old Japanese female with metastatic urothelial carcinoma in multiple organs. She developed right ptosis 3 days after the second pembrolizumab treatment. Although prednisolone was administered, her symptoms did not change and dysphagia appeared. She needed the steroid pulse therapy for treatment eventually. On the other hand, 9 weeks after the first pembrolizumab treatment, reductions in the sizes of liver and adrenal metastases was observed. However, unfortunately, the severe immune-related adverse events did not allow her to continue the administration of pembrolizumab for the treatment of multiple metastatic urothelial carcinoma. To our knowledge, this is the first case of myasthenia gravis associated with pembrolizumab treatment against metastatic urothelial carcinoma. In this case, a relationship between immune-related adverse events associated with myasthenia gravis and tumor responses to pembrolizumab was suspected, because marked reductions in the sizes of some metastatic lesions were observed after the administration of only two courses of pembrolizumab.

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特集 小児泌尿器科オープンサージャリー-見て学ぶプロフェッショナルの技〈特別付録Web動画〉 〈泌尿器科医として習得したい手術〉 急性陰囊症-どんな場合に手術が必要か?　どのような手術をすべきか?

浅沼 宏, 高橋 遼平, 大家 基嗣

臨床泌尿器科 (株式会社医学書院)  74 ( 7 ) 472 - 477 2020.06

ISSN  0385-2393

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Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma.

Kimiharu Takamatsu, Toshikazu Takeda, Seiya Hattori, Nobuyuki Tanaka, Shinya Morita, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikuchi, Hiroshi Asanuma, Isao Kurihara, Hiroshi Itoh, Mototsugu Oya

Clinical endocrinology (WILEY)  92 ( 6 ) 503 - 508 2020.06

Research paper (scientific journal), Joint Work,  ISSN  0300-0664

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CONTEXT: The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. OBJECTIVE: To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. DESIGN AND PATIENTS: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). RESULTS: PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P < .001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, P < .001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P < .001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. CONCLUSION: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.

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Safety and efficacy of plasma exchange via direct femoral vein puncture in autoimmune blistering diseases.

Tadashi Yoshida, Hitoshi Minakuchi, Ryohei Takahashi, Shinya Morita, Mototsugu Oya

Journal of clinical apheresis (WILEY)  35 ( 3 ) 172 - 177 2020.06

Research paper (scientific journal), Joint Work,  ISSN  0733-2459

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Plasma exchange (PE) is performed for patients with autoimmune blistering diseases by using multiple vascular access routes. We retrospectively examined the safety and the efficacy of PE using direct femoral vein puncture (FVP) technique, by comparing with that using double-lumen catheter (DLC). The troubles related to vascular route, such as catheter occlusion, insufficient blood flow and hematoma, were not different between the FVP group (4.6%) and the DLC group (6.7%), whereas access-related infections occurred more frequently in the DLC group (6.7%) than the FVP group (0.4%). Regarding the efficacy, the removal rate of autoantibodies in PE using the FVP technique was similar or lower, as compared with that using the DLC. These results suggest that PE with the FVP technique is able to be performed safely in patients with autoimmune blistering diseases, although the removal of autoantibodies is not superior to that using the DLC.

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The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients.

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

Urologic oncology (ELSEVIER SCIENCE INC)  38 ( 6 ) 602.e1 - 602.e10 2020.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1078-1439

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PURPOSE: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. METHODS: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. RESULTS: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). CONCLUSIONS: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

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The efficacy of the TachoSil binding suturing technique in laparoscopic partial nephrectomy to prevent the development of pseudoaneurysm.

Keisuke Shigeta, Kazuhiro Matsumoto, Takayuki Abe, Akari Komatsuda, Toshikazu Takeda, Ryuichi Mizuno, Eiji Kikuchi, Hiroshi Asanuma, Yuki Arita, Hirotaka Akita, Masahiro Jinzaki, Akira Miyajima, Mototsugu Oya

Asian journal of surgery (ELSEVIER SINGAPORE PTE LTD)  43 ( 6 ) 668 - 675 2020.06

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1015-9584

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OBJECTIVE: Our specific aim was to introduce the TachoSil binding suturing technique for renal cell carcinoma (RCC) patients when closing the parenchymal defect after tumor excision during laparoscopic partial nephrectomy (LPN), which is a novel technique for reducing the risk of developing subsequent pseudoaneurysm (PA). METHODS: We identified 113 pT1aN0M0 RCC patients who underwent LPN at our institution. Eighty-one (72%) patients underwent the suturing procedure without binding TachoSil, whereas 32 (28%) patients underwent renorraphy with the renal defect closed together with TachoSil. The vascular complications were evaluated by computed tomography or magnetic resonance imaging with enhanced contrast material at the first visit after LPN. We conducted Fischer's exact test to determine risk factors for transcatheter arterial embolization (TAE). RESULTS: The median age was 55 (36-86) years old and the median follow-up time was 65 (12-147) months. In the overall population, there were 11 (11%) patients who underwent TAE because they developed PA. All 11 patients exhibited the imaging findings of PA, and were all from the conventional suturing group. In contrast, no patients for whom the TachoSil binding method was used had any significant findings on imaging (14% vs. 0%). Based on the analysis to determine risk factors for TAE due to PA development, the TachoSil binding suturing technique was one of the significant indicators for reducing the risk of developing PA. CONCLUSIONS: Our study demonstrated that the TachoSil binding suturing technique might reduce the development of PA after LPN. Prospective randomized study and comparison to the standard 2 or 3-layer renorrhaphy is needed to prove its actual value.

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進行性前立腺がんにおける薬剤耐性遺伝子発現ネットワークを標的とした新規リプログラミング療法

小坂 威雄, 本郷 周, 三上 修治, 大家 基嗣

臨床薬理の進歩 ((公財)臨床薬理研究振興財団)   ( 41 ) 81 - 87 2020.06

ISSN  0914-4366

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難治性遺伝子ネットワークを標的とした再プログラム化戦略に基づく、革新的新規治療のための新規薬剤のスクリーニングおよび分子基盤の確立と応用を目指した。まず、コネクティビティマップ解析により約70種類の既存薬を含めた小分子化合物を同定した。これらの化合物は、理論的に、再発・転移遺伝子発現プロファイルを限局がん、初発の遺伝子プロファイルへとリプログラミングし得る候補薬剤として同定された。これら同定された薬剤のうち、臨床で既に使用されている薬剤を中心にリストアップし、in vitroで投与した。高転移能を有するヒト去勢抵抗性前立腺がん(CRPC)細胞であるDU145に対してDER35が濃度依存性に、細胞増殖を有意に抑制した。次に、オス去勢ヌードマウスにDU145を皮下に接種し、皮下腫瘍モデルを作製し、DER35を経口投与して薬剤感受性をin vivoで検討した。皮下腫瘍が150〜200mm3、増大したところでマウスを2群に分け、Control(n=10)、およびDER35 12.5mg/kg/day投与群(17日間連続経口投与、n=10)とした。DER35投与群では、腫瘍の増殖が有意に抑制された。

Pembrolizumab投与後に重症筋無力症を来たした1例

早川 望, 菊地 栄次, 鈴木 重明, 大家 基嗣

泌尿器科紀要 (泌尿器科紀要刊行会)  66 ( 6 ) 190 - 190 2020.06

Joint Work,  ISSN  0018-1994

A pooled analysis of the efficacy and safety of cabozantinib post immunotherapy in patients with advanced renal cell carcinoma.

Mototsugu Oya, Satoshi Tamada, Katsunori Tatsugami, Noboru Nakaigawa, Takahiro Osawa, Hiro-Omi Kanayama, Chihiro Kondoh, Naoto Sassa, Kazuo Nishimura, Masahiro Nozawa, Naoya Masumori, Yasuhide Miyoshi, Akiko Kimura, Shingo Kuroda, Robert J. Motzer, Toni K. Choueiri, Yoshihiko Tomita

JOURNAL OF CLINICAL ONCOLOGY (LIPPINCOTT WILLIAMS & WILKINS)  38 ( 15 )  2020.05

Joint Work,  ISSN  0732-183X