研究者詳細 - 大家　基嗣

論文 - 大家　基嗣

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Clinical background analysis about transurethral electrocoagulation

Katsui Masahiro, Kikuchi Eiji, Yazawa Satoshi, Hagiwara Masayuki, Morita Shinya, Shinoda Kazunobu, Kosaka Takeo, Mizuno Ryuichi, Shinojima Toshiaki, Asanuma Hiroshi, Miyajima Akira, Oya Mototsugu

Japanese Journal of Urology 106 （ 4 ） 255 - 263 2015年10月

ISSN 0021-5287

(Purpose) Transurethral electrocoagulation (TUC) is a rare event but occurs in a constant manner with various causes or disorders and reduces patient quality of life. So far there have been no reports focusing on the details of TUC. We focused on the clinical background and related causes in cases of TUC in our institution. (Patients and methods) We identified 76 cases (65 patients) who underwent TUC at Keio University Hospital between April 2001 and March 2011. We focused on patient background, especially with respect to the primary disease, treatment modality, use of antiplatelet or anticoagulant agent, timing of TUC, type of electrosurgical device, and the incidence of transfusion. (Results) The primary disease for TUC included bladder tumor (BT) in 31 cases, benign prostate hyperplasia (BPH) in 13, prostate cancer (PCa) in 13, idiopathic bladder bleeding in 4, periarteritis nodosa in 3, uterine cervical cancer in 3, and others in 9. TUC after transurethral resection (TUR) was found in 38 cases, including transurethral resection of bladder tumor (TURBT) in 26 of 31 BT cases and transurethral resection of prostate (TURP) in 12 of 13 BPH cases. After TURBT, TUC was performed before removal of a urethral catheter in 7 cases, and after removal of a urethral catheter in 19 cases. With regard to TUC associated with TURP, the average estimated prostate volume in TUC cases before removal of the urethral catheter was 66.2 ml, which was significantly larger than that in TUC cases after removal of the urethral catheter (46.1 ml, p = 0.045). TUC after the radiation therapy was observed in 21 cases, and the average time from the radiation therapy to TUC was 3.4 years (7 months-10 years). (Conclusion) TUC was caused by multiple causes or disorders, and 75% of our TUC was associated with BT, BPH or PCa. TUC associated with TURBT frequently occurred within 1 week after TURBT but was still observed after 1 month following the operation. All TUC associated with TURP occurred within 3 weeks after operation. The average period from radiation therapy to TUC was 3.4 years (7 months-10 years) and TUC associated with radiation cystitis could occur beyond 5 years after radiation.

A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan

Akaza Hideyuki, Oya Mototsugu, Iijima Masafumi, Hyodo Ichinosuke, Gemma Akihiko, Itoh Hiroshi, Adachi Masatoshi, Okayama Yutaka, Sunaya Toshiyuki, Inuyama Lyo

Japanese Journal of Clinical Oncology 45 （ 10 ） 953 - 962 2015年10月

ISSN 0368-2811

Objective: Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. Methods: All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Results: Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis.

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Clinical background of patients with sperm in their urinary sediment

Tomita Masuomi, Kikuchi Eiji, Maeda Takahiro, Kabeya Yusuke, Katsuki Takeshi, Oikawa Yoichi, Kato Kiyoe, Ohashi Masakazu, Nakamura So, Oya Mototsugu, Shimada Akira

PLoS One 10 （ 9 ） 2015年09月

Introduction The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice. Aims The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples. Methods We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged ≥20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines. Main Outcomes In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%). Results Multivariate analysis demonstrated that younger age (

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Nicotine induces tumor growth and chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer

Yuge Kazuyuki, Kikuchi Eiji, Hagiwara Masayuki, Yasumizu Yota, Tanaka Nobuyuki, Kosaka Takeo, Miyajima Akira, Oya Mototsugu

Molecular Cancer Therapeutics 14 （ 9 ） 2112 - 2120 2015年09月

ISSN 1535-7163

Continued smoking is highly associated with not only a higher incidence but also greater risk of tumor recurrence, progression, and acquired chemoresistance of urothelial carcinoma. We investigated whether nicotine affects urothelial carcinoma, and the detailed mechanism by which nicotine could induce tumor growth and any associated chemoresistance. Cell viability was evaluated in the human bladder cancer cell line T24 exposed to nicotine with or without cisplatin (CDDP) and NVP-BEZ235 as a PI3K/mTOR dual inhibitor by the WST-1 assay. Protein expression of the PI3K/Akt/mTOR pathway was investigated by Western blotting or immunohistochemical analysis. The influence of nicotine on tumor growth was also evaluated with or without CDDP and/or NVP-BEZ235 in a subcutaneous bladder tumor model. The result demonstrated that cell proliferation was increased in T24 cells after exposure to nicotine. Phospho-specific Akt (pAkt) and phospho-specific p70 S6 kinase (pS6) were significantly upregulated by nicotine exposure. Tumor growth in vivo was significantly induced by nicotine exposure in accordance with increased pS6 expression. Nicotine attenuated inhibition of T24 cell growth by CDDP and further upregulated pS6 expression in vitro and in vivo. NVP-BZE235 inhibited T24 cell proliferation and pAkt and pS6 expression induced after exposure to nicotine and/or CDDP. In conclusion, nicotine increases tumor growth and induces acquired chemoresistance through activation of the PI3K/Akt/mTOR pathway in bladder cancer.

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Clinical Background of Patients with Sperm in Their Urinary Sediment

大家基嗣

PLOS ONE 10 （ 9 ） 953 - 962 2015年09月

研究論文（学術雑誌）, ISSN 1932-6203

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Characterizing intermediate-risk non-muscle-invasive bladder cancer

Matsumoto Kazuhiro, Kikuchi Eiji, Yanai Yoshinori, Hayakawa Nozomi, Ito Yujiro, Maeda Takahiro, Nagata Hirohiko, Miyajima Akira, Oya Mototsugu

Urologic Oncology: Seminars and Original Investigations 2015年08月

ISSN 1078-1439

Purpose: Patients with intermediate-risk non-muscle-invasive bladder cancer have traditionally been defined as those not included in the low- or high-risk groups. Therefore, the intermediate-risk group consists of heterogeneous patients. Materials and methods: We reviewed 326 patients diagnosed with intermediate-risk tumors. We subclassified these patients into 3 groups according to their clinical courses. Group A included patients with initial and multiple low-grade tumors (N = 170). Group B consisted of patients with a low-grade tumor that recurred after a low-risk tumor (N = 97), and Group C consisted of patients with a low-grade tumor that recurred after a high-risk tumor (N = 59). Results: The 2-year recurrence-free survival rate was significantly lower in Group C (42%) than in Groups A (69%, P<0.01) and B (70%, P<0.01). Regarding progression-free survival, no significant differences were observed among the groups. In total, 167 patients received adjuvant bacillus Calmette-Guérin (BCG), and 39 received adjuvant chemotherapy instillations. In Groups A and B, there were no significant differences in efficiency against tumor recurrence between BCG and chemotherapy. In Group C, the 5-year recurrence-free survival rate was 65% in patients receiving BCG, which was significantly higher when compared with patients receiving chemotherapy (P = 0.01). Furthermore, Group C included 11 BCG refractory cases, 5 of whom later experienced stage progression during follow-up. Conclusion: Our subclassification analysis suggested that intermediate-risk tumors that recurred after a high-risk tumor (Group C) should be treated with adjuvant BCG therapy, owing to the high probability of subsequent recurrence. Furthermore, the definition of intermediate risk may include some BCG refractory cases.

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Impact of Combined Use of Blood-based Inflammatory Markers on Patients with Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Shirotake Suguru, Miyazaki Yasumasa, Kobayashi Hiroaki, Kaneko Gou, Hagiwara Masayuki, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Kosaka Takeo, Hara Satoshi, Nakagawa Ken, Jinzaki Masahiro, Oya Mototsugu

European Urology Focus 1 （ 1 ） 54 - 63 2015年08月

Background: Previous studies showed the prognostic impact of preoperative levels of neutrophil-to-lymphocyte ratio (NLR), plasma fibrinogen, and serum C-reactive protein (CRP) in surgically treated upper tract urothelial carcinoma; however, few papers have discussed the proper use of these indices. Objective: To investigate whether combinations of these three markers, as a cumulative marker score (CMS), improve the accuracy of prognostic models following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 394 patients from multiple institutions were included. Median follow-up was 30 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Associated outcomes were assessed using multivariate analysis. The CMS was defined as the number of elevated levels of preoperative NLR, plasma fibrinogen, and serum CRP. Results and limitations: Multivariate analyses revealed that an increasing CMS was independently associated with high rates of disease recurrence, cancer-specific mortality, and all-cause mortality following RNU. Addition of the CMS to a model that included standard clinicopathologic predictors significantly improved predictive accuracy by 2.7% for disease recurrence, 3.9% for cancer-specific mortality, and 4.0% for all-cause mortality, which were the highest among other prognostic models using each marker alone or combinations of two. The study is limited by its retrospective nature. Conclusions: Although the use of each inflammatory marker alone may be as predictive as clinicopathologic indices for prognosis, combinations like CMS can provide more accurate prognostic models following RNU. Patient summary: Elevation of blood-based inflammatory markers may be useful for predicting prognosis because of their low cost and accessibility. Among blood-based indices, we examined the efficacy of preoperative neutrophil-to-lymphocyte ratio, plasma fibrinogen, and serum C-reactive protein levels. Although use of each marker alone provides additional prognostic information, the combination of all three markers would be more predictive than any single marker or combinations of two.

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Renin-angiotensin system blockade

Miyajima Akira, Kosaka Takeo, Kikuchi Eiji, Oya Mototsugu

International Journal of Urology 22 （ 8 ） 721 - 730 2015年08月

ISSN 0919-8172

Angiotensin II is a key biological peptide in the renin-angiotensin system that regulates blood pressure and renal hemodynamics, and extensive experimental studies have shown that angiotensin II promotes diverse fibrotic changes and induces neovascularization in several inflammatory diseases. It is known that angiotensin II can be controlled using renin-angiotensin system blockade when angiotensin II is the main factor inducing a particular disease, and renin-angiotensin system blockade has assumed a central role in the treatment of inflammatory nephritis, cardiovascular disorders and retinopathy. In contrast, renin-angiotensin system blockade was found to have not only these effects but also other functions, such as inhibition of cancer growth, angiogenesis and metastasis. Numerous studies have sought to elucidate the mechanisms and support these antitumor effects. However, a recent meta-analysis showed that renin-angiotensin system blockade use might in fact increase the incidence of cancer, so renin-angiotensin system blockade use has become somewhat controversial. Although the renin-angiotensin system has most certainly made great contributions to experimental models and clinical practice, some issues still need to be resolved. The present review discusses the contribution and controversy surrounding the renin-angiotensin system up to the present time.

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Efficacy of treatment with a GnRH antagonist in prostate cancer patients previously treated with a GnRH agonist

Ezaki Taisuke, Kosaka Takeo, Mizuno Ryuichi, Shinojima Toshiaki, Kikuchi Eiji, Miyajima Akira, Oya Mototsugu

CANCER CHEMOTHERAPY AND PHARMACOLOGY 76 （ 2 ） 301 - 306 2015年08月

研究論文（学術雑誌）, 共著, ISSN 0344-5704

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Comparison of continence outcomes of early catheter removal on postoperative day 2 and 4 after laparoscopic radical prostatectomy

Matsushima Masashi, Miyajima Akira, Hattori Seiya, Takeda Toshikazu, Mizuno Ryuichi, Kikuchi Eiji, Oya Mototsugu

BMC Urology 15 （ 1 ） 2015年07月

ISSN 1471-2490

Background: The optimal timing of catheter removal following laparoscopic radical prostatectomy (LRP) has not yet been determined. This prospective study was designed to compare the efficacy and safety of catheter removal on postoperative day (POD) 2 versus POD 4 after LRP and its impact on urinary continence outcomes. Methods: One hundred and thirteen patients underwent LRP and were prospectively randomized into two groups: group 1 (n = 57) had the urinary catheter removed on POD 2 while group 2 (n = 56) had the catheter removed on POD 4. The urine loss ratio (ULR) was defined as the weight of urine loss in the pad divided by the daily micturition volume. Continence was defined as a pad-free status. Results: No significant differences were observed in clinical features between groups 1 and 2. Acute urinary retention (AUR) after catheter removal occurred in 21 patients (18.6 %) (13 (22.8 %) in group 1 and 8 (14.3 %) in group 2 (p = 0.244). The first-day mean ULR values were 1.16 ± 4.95 in group 1 and 1.02 ± 3.27 in group 2 (p = 0.870). The last-day mean ULR values were 0.57 ± 1.60 in group 1 and 2.78 ± 15.49 in group 2 (p = 0.353). Continence rates at 3, 6, 9, and 12 months were 21.8, 41.1, 58.0, and 71.4 % in group 1 and 34.5, 66.0, 79.2, and 83.7 % in group 2 (p = 0.138, 0.009, 0.024, and 0.146, respectively). In AUR cases, continence rates at 3, 6, 9, and 12 months were 0, 23.1, 38.5, and 54.5 % in group 1 and 37.5, 75.0, 87.5, and 87.5 % in group 2 (p = 0.017, 0.020, 0.027, and 0.127, respectively). A multivariate analysis identified AUR after catheter removal on POD 2 as the only predictive factor for incontinence 6 and 9 months after LRP (p = 0.030 and 0.018, respectively). Conclusions: Our results demonstrated that early catheter removal on POD 2 after LRP may increase the risk of incontinence. Trial registration: The study was registered as Clinical trial: (UMIN000014944); registration date: 12 March 2012.

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Axitinib dose titration

Rini Brian I., Melichar B., Fishman M. N., Oya M., Pithavala Y. K., Chen Y., Bair A. H., Grünwald V.

Annals of Oncology 26 （ 7 ） 1372 - 1377 2015年07月

ISSN 0923-7534

Background: In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients and methods: Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Results: Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Conclusions: Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor.

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Coincident detection of lung metastasis of prostate cancer and primary lung cancer

Muro Yusuke, Kosaka Takeo, Hato Tai, Mikami Shuji, Oya Mototsugu

Canadian Urological Association Journal 9 （ 7-8 ） E524 - E526 2015年07月

ISSN 1920-1214

We report an extremely rare case of 79-year-old man, who was discovered with coincidental lung metastasis of prostate cancer and primary lung cancer. The patient presented with low prostatespecific antigen and two lung lesions: one in the right lower lobe, and one in the right upper lobe, 3 years after he was treated with external beam radiotherapy for Gleason score 4+3=7, cT3aN0M0 prostate cancer. A computed tomography-guided needle biopsy of a nodule in the right lower lobe revealed suspicious metastasis of prostate cancer. Thoracoscopic excisions of both lesions were performed, and each lung lesion was diagnosed as being metastatic prostate cancer and primary lung cancer.

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Intravesical dual PI3K/mTOR complex 1/2 inhibitor NVP-BEZ235 therapy in an orthotopic bladder cancer model

Matsushima Masashi, Kikuchi Eiji, Matsumoto Kazuhiro, Hattori Seiya, Takeda Toshikazu, Kosaka Takeo, Miyajima Akira, Oya Mototsugu

INTERNATIONAL JOURNAL OF ONCOLOGY 47 （ 1 ） 377 - 383 2015年07月

研究論文（学術雑誌）, 共著, ISSN 1019-6439

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Activation of aryl hydrocarbon receptor promotes invasion of clear cell renal cell carcinoma and is associated with poor prognosis and cigarette smoke

Ishida Masaru, Mikami Shuji, Shinojima Toshiaki, Kosaka Takeo, Mizuno Ryuichi, Kikuchi Eiji, Miyajima Akira, Okada Yasunori, Oya Mototsugu

INTERNATIONAL JOURNAL OF CANCER 137 （ 2 ） 299 - 310 2015年07月

研究論文（学術雑誌）, 共著, ISSN 0020-7136

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Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer

Shigeta Keisuke, Kosaka Takeo, Yazawa Satoshi, Yasumizu Yota, Mizuno Ryuichi, Nagata Hirohiko, Shinoda Kazunobu, Morita Shinya, Miyajima Akira, Kikuchi Eiji, Nakagawa Ken, Hasegawa Shintaro, Oya Mototsugu

International Journal of Clinical Oncology 20 （ 3 ） 605 - 612 2015年06月

ISSN 1341-9625

Background: The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). Methods: We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm3 and defined FN as an ANC of <1000/mm3 with a body temperature of >38.3 °C. Results: The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6 % of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥75 years (p = 0.002), number of comorbidities ≥1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Conclusions: Patients aged ≥75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

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Follicle-stimulating hormone enhances recovery from low-dose doxorubicin-induced spermatogenic disorders in mice

大家基嗣

JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 32 （ 6 ） 917 - 923 2015年06月

研究論文（学術雑誌）, ISSN 1058-0468

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Comparison of genitourinary and gastrointestinal toxicity among four radiotherapy modalities for prostate cancer

Sutani Shinya, Ohashi Toshio, Sakayori Masanori, Kaneda Tomoya, Yamashita Shoji, Momma Tetsuo, Hanada Takashi, Shiraishi Yutaka, Fukada Junichi, Oya Mototsugu, Shigematsu Naoyuki

Radiotherapy and Oncology 2015年05月

ISSN 0167-8140

Purpose: To compare late genitourinary (GU) and gastrointestinal (GI) toxicity following different prostate cancer treatment modalities. Materials and methods: This study included 1084 consecutive prostate cancer patients treated with conventional radiotherapy, intensity-modulated radiotherapy (IMRT), permanent iodine-125 implantation (PI) alone, and PI combined with external beam radiotherapy (PI + EBRT). The effects of treatment- and patient-related factors on late grade. ≥. 2 (G2+) GU/GI toxicity risk were assessed. Results: The median follow-up was 43. months (range, 12-97. months). Compared to the PI + EBRT, there was significantly less G2+ GU toxicity in the conventional radiotherapy (hazard ratio [HR] = 0.39; 95% CI, 0.20-0.77) and the IMRT (HR = 0.45, 95% CI, 0.27-0.73). Compared to the PI + EBRT, there was significantly more G2+ GI toxicity in the IMRT (HR = 2.38; 95% CI, 1.16-4.87). In PI-related groups, prostate equivalent dose in 2. Gy fractions was a significant predictor of G2+ GU toxicity (p = 0.001), and the rectal volume receiving more than 100% of the prescribed dose was a significant predictor of G2+ GI toxicity (p = 0.001). Conclusion: The differences in the late G2+ GU/GI risk cannot be explained by the differences in treatment modalities themselves, but by the total radiation dose to the GU/GI tract, which had a causal role in the development of late G2+ GU/GI toxicity across all treatment modality groups.

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Solifenacin or Mirabegron Could Improve Persistent Overactive Bladder Symptoms After Dutasteride Treatment in Patients With Benign Prostatic Hyperplasia

Maeda Takahiro, Kikuchi Eiji, Hasegawa Masanori, Ishioka Katsura, Hagiwara Masayuki, Miyazaki Yasumasa, Shinojima Toshiaki, Miyajima Akira, Oya Mototsugu

Urology 85 （ 5 ） 1151 - 1155 2015年05月

ISSN 0090-4295

Objective To evaluate the clinical response and adverse events (AEs) of solifenacin (SOL) or mirabegron (MIR) in benign prostatic hyperplasia patients with persistent overactive bladder (OAB) symptoms after dutasteride (DUT) treatment. Methods Fifty cases with residual OAB symptom score (OABSS) ≥5 and OABSS Q3 ≥2 after at least 6 months treatment of DUT were included in this study. Patients were administered 5 mg/d of SOL (N = 25) or 50 mg/d of MIR (N = 25), and International Prostate Symptom Score (IPSS) and OABSS were prospectively collected at 4 and 12 weeks. The safety was evaluated by changes in postvoided residual urine volume and the incidence of AEs. Results After DUT administration, the mean prostate volume, IPSS, and OABSS were 39.0 mL, 17.6, and 8.1, respectively. SOL 5 mg significantly reduced the IPSS, OABSS, and OABSS Q3 at 4 and at 12 weeks (-3.1, -2.7, -1.3; P <.05); however, 4 patients could not continue the SOL treatment owing to AEs. All patients could continue the 12 weeks of MIR treatment, and MIR 50 mg reduced IPSS and OABSS at 4 weeks and reduced IPSS, OABSS, and the OABSS Q3 (-3.0, -2.5, -0.9; P <.05) at 12 weeks. Postvoided residual urine volume increased by ≥100 mL after treatment in 2 cases in the SOL group but not in any patient in the MIR group. Conclusion Additional SOL or MIR might result in amelioration of the persistent OAB symptom after DUT treatment in patients with an enlarged prostate.

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Evaluation of histopathological findings at the injection site following degarelix administration

Maeda Takahiro, Kosaka Takeo, Honda Aki, Okata Utako, Hayakawa Nozomi, Ito Yujiro, Nagata Hirohiko, Chen Ko Ron, Nakamura So, Oya Mototsugu

Supportive Care in Cancer 23 （ 5 ） 1377 - 1381 2015年05月

ISSN 0941-4355

Purpose: The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. Methods: This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. Results: The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. Conclusion: The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.

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Decision tree for the diagnosis of upper tract urothelial carcinoma: Can selective upper-tract urine cytology be omitted in diagnosis?

Hayakawa Nozomi, Kikuchi Eiji, Matshumoto Kazuhiro, Morita Shinya, Shinoda Kazunobu, Kosaka Takeo, Mizuno Ryuichi, Shinojima Toshiaki, Asanuma Hiroshi, Miyajima Akira, Oya Mototsugu

JOURNAL OF CLINICAL ONCOLOGY 33 （ 15 ） E304 - E305 2015年05月

研究論文（学術雑誌）, 共著, ISSN 0732-183X

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