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Introduction Metastases from renal cell carcinoma develop in various organs. However, the breadth of discrepancy in response to immune checkpoint inhibitors across tumor sites within the same individual remains unclear. Patients and methods We reviewed 50 patients with metastatic renal cell carcinoma who had target lesions at multiple sites and received nivolumab monotherapy (n = 36) or nivolumab plus ipilimumab (n = 14). When the best overall response in tumor burden increased at one site but decreased at other sites, the response was defined as a dissociated response. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1, and patients who met the definition of dissociated response were categorized as dissociated response. The rate of dissociated response and prognosis were evaluated. Results Eight of 36 (22%) and 4 of 14 (29%) patients treated with nivolumab and nivolumab plus ipilimumab were categorized as having dissociated response, respectively. The median overall survival of the patients treated with nivolumab was 20.2 months for those with a partial response, 6.8 months for those with stable disease, and 13.2 months for those with progressive disease, while dissociated response was not reached. There was no significant difference in the median overall survival between patients categorized as having progressive disease and those with dissociates response (P = 0.224). Conclusion A certain proportion of patients with metastatic renal cell carcinoma show dissociated response when treated with immune checkpoint inhibitors. The prognosis of patients with dissociated response and progressive disease was not shown to be significantly different.

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Shingo Tamura,7 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab.Materials and Methods: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk.Results: There were no significant differences in the overall survival (OS) between the REC ≥ 4.8% and < 4.8% groups and the NER ≥ 13.7 and < 13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p< 0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥ 2 (P=0.003), albumin < 3.7 g/dl (p=0.002), LDH > 246 U/L (p=0.011), disease site ≥ 3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS.Conclusion: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.Keywords: urothelial carcinoma, pembrolizumab, eosinophil, neutrophil-to-eosinophil ratio

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Hiroki Kobayashi,1 Yamato Wada,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the eosinophil changes, efficacy and safety of pembrolizumab treatment in advanced urothelial carcinoma patients of older age and those with a poor performance status (PS).Materials and Methods: Consecutive patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy between January 2018 and June 2021 were retrospectively examined.Results: 105 patients (median age, 72 years), 71.4% of whom were men, were enrolled. Patients of ≥ 75 years of age were considered to be older patients (n=40), and patients with PS ≥ 2 were considered to have a poor PS (n=10). The objective response and disease control rates were 42.5% and 52.5%, respectively, in older patients and 0% and 10.0%, respectively, in patients with a poor PS. Overall survival (OS) in the older and younger groups did not differ to a statistically significant extent. However, a poor PS was significantly associated with poor survival. Safety analyses demonstrated no significant difference in the occurrence of any immune-related adverse events (irAEs), including grade ≥ 3, between the older and younger groups. However, a poor PS was significantly associated with the low occurrence of any irAEs. The change of the eosinophil count, the increase of the relative eosinophil count (REC) and the decrease of the neutrophil-to-eosinophil ratio (NER) did not differ to a statistically significant extent between the older and younger groups, but showed significant differences between the poor and good PS (PS 0– 1) groups.Conclusion: Pembrolizumab for advanced UC demonstrated similar changes in the eosinophil count, efficacy and toxicity in both older and younger patients. In patients with a poor PS, although toxicity was significantly lower, survival was significantly worse, and neither an increase in REC nor a decrease in NER were observed, but these values showed significant changes in patients with a good PS.Keywords: urothelial carcinoma, pembrolizumab, age, performance status, immune-related adverse events, relative eosinophil count, neutrophil-to-eosinophil ratio

Background/aim Nivolumab monotherapy for advanced/metastatic renal cell carcinoma (RCC) shows a survival benefit. The purpose of this study was to evaluate tumor responses to nivolumab in various metastatic and primary sites in patients with RCC. Patients and methods We retrospectively reviewed 68 patients who underwent nivolumab monotherapy after one or more regimens of targeted therapy for advanced/metastatic RCC. The site-specific response was evaluated and progression-free survival was estimated. Results The site-specific overall response rates (ORRs) were as follows: lung (36%), bone (5%), lymph node (33%), liver (50%), adrenal gland (29%), pancreas (33%), and brain (0%). The ORR of bone metastasis was significantly worse in comparison to lung and liver metastases (p=0.017, 0.008). The site-specific median progression-free survival times were as follows: lung (5.1 months), bone (not reached), lymph node (not reached), and liver (17.5 months). Conclusion Responses to nivolumab may vary depending on metastasized organs.

Radium-223 (Ra-223) dichloride is the bone-targeted radioligand therapy that prolongs overall survival (OS) in patients with bone-metastatic castration-resistant prostate cancer (CRPC). We aimed to evaluate the safety and effectiveness of this treatment in real-world practice.We included Japanese men treated with Ra-223 for bone-metastatic CRPC from 10 institutions, retrospectively. Primary endpoint was OS. Secondary endpoint was maximum decline of alkaline phosphatase (ALP), lactate dehydrogenase, and prostate-specific antigen values, the rate of adverse events, and time to pathological fracture after Ra-223 treatment. Exploratory endpoint was the associations between clinical parameters and OS.In total, 73 men with bone metastatic CRPC treated with Ra-223 were enrolled. The median OS was 20.9 months. ALP levels decreased significantly from pre-treatment (p = 0.03). Anemia occurred in three (4.1%) patients. Grade ≥ 3 non-pathological fractures occurred in four (5.5%) men. Nine (12.3%) patients presented pathological fracture; 7/30 (23.3%) were in men without concomitant use of a bone-modifying agent (BMA) while 2/43 (4.7%) were in patients with concomitant BMA (p = 0.03). The median OS in patients with ≥3 cycles treatment (27.2 months, p 0.001) or hemoglobin ≥12 g/dl (27.2 months, p = 0.001) or absence of bone pain (36.3 months, p = 0.004) was significantly longer compared to those who with ≤2 cycles or hemoglobin12 g/dl or presence of bone paint, respectively.This study has shown the outcomes of Ra-223 treatment in real-world practice, where the number of treatment cycles, baseline anemia and bone pain may be useful to predict OS in Ra-223 treatment.

This study aimed to compare the safety and efficacy of three different laser prostate vaporization surgeries, which were photoselective vaporization of the prostate (PVP), diode laser vaporization (DVP), and thulium laser vaporization (ThuVAP), for the treatment of benign prostatic hyperplasia (BPH) in a randomized clinical trial.A total of 71 consecutive patients with BPH were included; 23 patients were treated with PVP, 23 with DVP, and 25 with ThuVAP. Patients were evaluated with disease-related symptomatic questionnaires, Quality of Life (QOL) Index, and maximum urinary flow rate (QIn all three groups, patients showed significant and comparable improvements in symptom scores, QOL Index, and QOur study demonstrated that these three types of laser surgeries are similar in terms of complications and outcomes, with excellent hemostasis and high patient satisfaction. It was suggested that sufficient tissue vaporization could be achieved using less energy through PVP surgery.

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Akihiro Miura,1 Hiroki Komori,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined.Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P< 0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥ 3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥ 3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥ 1 (P=0.024), albumin < 3.7 g/dl (P< 0.001), decreased REC (3 weeks later) (P< 0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS.Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.Keywords: urothelial carcinoma, pembrolizumab, immune-related adverse events, relative eosinophil count

OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

Background/aim The novel taxane cabazitaxel has been shown to exert excellent anticancer effects after androgen receptor axis-targeting (ARAT) agents in clinical data, but not in in vitro data. We investigated the clinical outcome of cabazitaxel chemotherapy after docetaxel according to use of ARAT agents. Patients and methods Prostate specific antigen (PSA) response, progression-free survival, and overall survival were compared between cases with and without prior use of ARAT agents in 74 Japanese patients with metastatic castration-resistant prostate cancer treated with cabazitaxel chemotherapy. Results Background characteristics were comparable between patients with and without prior use of ARAT agents. PSA response, progression-free survival, and overall survival in cabazitaxel chemotherapy were comparable between patients with and without prior use of ARAT agents. Conclusion No detrimental effects of prior ARAT agents on clinical outcome were observed for cabazitaxel chemotherapy in the post-docetaxel setting, suggesting that cabazitaxel can be expected to remain active even after ARAT agent therapy.

The Halabi model predicts the overall survival (OS) of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with second-line therapy after docetaxel. We aimed to validate this model externally with an independent cohort, outside the setting of a clinical trial.In a multi-institutional study, we included 66 patients treated with cabazitaxel after docetaxel for mCRPC. Patients were stratified according to the two- and three-risk groups of the Halabi nomogram. Kaplan-Meier and Cox proportional hazard analyses were performed to estimate survival and hazard ratios (HRs). The model performance was assessed using receiver operating characteristic curves, and the associated c-index (area under the curve [AUC]).The median OS in the two-risk groups was 5.06 months in the high-risk group (n=22) and 12.9 months in the low-risk group (n=44, p0.001). High-risk patients had an HR of 9.50 (95% confidence interval (CI) 4.12-21.6, p0.001) compared to low-risk patients. For the three-risk groups, the median OS was 6.44 months in the high-risk group (n=15), 5.75 months in the intermediate-risk group (n=11), and 13.7 months in the low-risk group (n=40, p=0.84). Compared to low-risk patients, intermediate-risk patients had an HR of 7.49 (95% CI 3.08-20.4, p0.001), and high-risk patients had an HR of 8.48 (95% CI, 3.39-21.7, p0.001). The AUC was 0.72 (95% CI 0.64-0.76) for the two-risk stratification. When comparing different risks, the AUCs were 0.48 (high vs intermediate), 0.66 (high vs low), and 0.65 (intermediate vs low).The two-risk stratification version but not the three-risk group analysis confirmed the ability of the model to predict survival. These results support the value of the Halabi nomogram in men receiving post-docetaxel second-line chemotherapy for mCRPC.

Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease.We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC.We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497).Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.

Background/aim Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. Patients and methods Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. Results Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). Conclusion A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.

Background/aim Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. Patients and methods This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. Results Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. Conclusion Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.

This study aimed to reveal the efficacy and safety profiles of 4-weekly cabazitaxel in patients with castration-resistant prostate cancer (CRPC). The study included 62 Japanese patients who were treated for CRPC with ≥ 2 courses of cabazitaxel between 2014 and 2017. The oncological outcomes and adverse events were compared between 16 (25.8%) and 46 (74.2%) men who were treated with standard 3-weekly and alternative 4-weekly regimens, respectively. The prostate-specific antigen (PSA) response was comparable between the 3-weekly and 4-weekly regimens (median [interquartile range]: − 9.9% [− 64.5 to 13.0%] and − 30.7% [− 52.8 to 10.9%], P = 0.89), respectively. For patients on the 4-weekly regimen, the risks of progression (hazard ratio [HR], 95% confidence interval [CI] 1.27, 0.71–2.43, P = 0.44), treatment failure (HR, 95% CI 0.84, 0.48–1.55, P = 0.57) and any-cause mortality (HR, 95% CI 1.09, 0.58–2.17, P = 0.79) were comparable to those for patients on the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. 3-weekly and 4-weekly regimens of cabazitaxel showed similar efficacy and safety profiles in a real-world clinical setting. These data suggest that a 4-weekly regimen may be acceptable for selected patients.

Objectives To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron. Methods During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions. Results Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores. Conclusions Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Nobuki Furubayashi,1 Takahito Negishi,1 Naotaka Sakamoto,2 Hozumi Shimokawa,3 Futoshi Morokuma,4 Yoohyun Song,5 Yoshifumi Hori,6 Toshihisa Tomoda,7 Noriaki Tokuda,4 Narihito Seki,5 Kentaro Kuroiwa,6 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 3Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Saga-ken Medical Centre Koseikan, Saga, Japan; 5Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 6Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 7Department of Urology, Oita Prefectural Hospital, Oita, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-Ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC).Materials and Methods: Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1.Results: We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9‑13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p< 0.001).Conclusion: Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.Keywords: urothelial carcinoma, platinum-based chemotherapy, pembrolizumab, organ-specific response rate, tumor microenvironment

Aim: To verify if the efficacy of the triple therapy with tamsulosin, dutasteride, and imidafenacin (TDI) is influenced by any background characteristics in patients with overactive bladder (OAB). Methods: A subanalysis of data from the DIrecT study was conducted. Superiority of TDI over tamsulosin and dutasteride in terms of efficacy based on the Overactive Bladder Symptom Score (OABSS), total International Prostate Symptom Score (IPSS), IPSS quality of life index, and postvoid residual (PVR) was evaluated in binary subgroups. Results: In the treatment groups, there was a significant interaction of total OABSS with testosterone level (≥4.8 vs. p = 0.043) and PVR (≥20 vs. p = 0.018). For the total IPSS, no significant interaction was found except for the IPSS QOL index. For the IPSS QOL index, a significant interaction was found with testosterone level (≥4.8 vs. p < 0.0001) as well as with total IPSS and total OABSS. For the PVR, no significant interaction was found except with total OABSS. Conclusions: Triple therapy with TDI is suggested to be a therapeutic option for benign prostatic hyperplasia in patients with residual OAB symptoms refractory to tamsulosin and in patients with various background characteristics regardless of severity of OAB symptoms. Trial Registry No. UMIN 000011980.

OBJECTIVES This study aimed to compare the safety and efficacy of laser vaporization with 532 nm GreenLight High Performance System (HPS) laser 120 W (PVP) and 980 nm diode laser 300 W (CVP) for the treatment of benign prostatic hyperplasia (BPH) in a prospective, single-center, randomized clinical trial. METHODS A total of 153 consecutive patients with symptomatic BPH were included; 79 patients were treated with PVP and 74 with CVP. Patients were assessed preoperatively and at 3, 6, and 12 months postoperatively using the International Prostate Symptom Score, quality of life index, peak urinary flow rate, and postvoid residual urine volume. All perioperative and postoperative complications were noted. RESULTS There were significant and comparable improvements in each of the outcome variables over a follow-up period of 12 months in both groups. The mean operation/vaporization duration (minutes) was comparable at 74/38 (PVP) and 76/34 (CVP), whereas the mean applied laser energy was significantly higher with CVP than with PVP at 260 vs 195 (kJ), respectively. The mean vaporization rate (mL/min) was not significantly different between the two groups (0.53 PVP vs 0.56 CVP). Immediately after surgery, the rate of recatheterization for urinary retention was significantly higher with CVP than with PVP (17.6% vs 6.8%; P

This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score [≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047], presence of pain [HR, 95% CI: 2.02 (1.14-3.58); P = 0.016], and lactate dehydrogenase (LDH) level [HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019] were significantly associated with PFS. Similarly, number of docetaxel cycles [HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057], performance status [≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001], and LDH level [HR, 95% CI: 2946 (50-420994); P = 0.0001] were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.

Objective The aim of this study was to examine the long-term efficacy of combination of tamsulosin 0.2 mg + dutasteride 0.5 mg + imidafenacin 0.2 mg (TDI) therapy compared with tamsulosin + dutasteride (TD) therapy for 52 weeks in benign prostatic hyperplasia (BPH) patients with a prostate volume (PV) ≥30 mL and remaining overactive bladder (OAB) symptoms after having received tamsulosin for ≥8 weeks. Previously, we reported that the improvement in OAB symptoms at 24 weeks was significantly greater in the TDI than TD group. Methods BPH patients with OAB symptoms after ≥8 weeks tamsulosin were randomly assigned to the TDI or TD group in a ratio of 1:1 ratio, and followed-up for 52 weeks. Changes in the OAB Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and post-void residual (PVR) were evaluated. Results In all, 163 patients were randomized, and 125 patients (76.7%) completed 52 weeks of treatment. At Week 52, there were significant decreases in the OABSS and IPSS storage subscore compared with baseline in the TDI versus TD group, but the change in the total IPSS did not differ significantly between the two groups. There was no change in PVR from Week 24 to Week 52 in either group. Conclusions For BPH patients with PVR ≥30 mL and remaining storage symptoms despite tamsulosin monotherapy, TDI treatment showed better results in terms of improved OAB symptoms than TD treatment up to 52 weeks.

Objectives To evaluate the efficacy and safety of a combination therapy with dutasteride and imidafenacin in patients with benign prostatic hyperplasia and persistent overactive bladder symptoms. Methods A total of 163 patients presenting an enlarged prostate (volume >30 mL) and persistent overactive bladder symptoms despite at least 8 weeks of tamsulosin were randomized to receive tamsulosin and dutasteride, or tamsulosin, dutasteride and imidafenacin at a 1:1 ratio. The primary end-point was the mean change from baseline to week 24 in total overactive bladder symptom score. Results The mean change in total overactive bladder symptom score from baseline at week 24 was −1.99 (95% confidence interval −2.57 to −1.41) in the tamsulosin and dutasteride group, and −3.12 (95% confidence interval −3.72 to −2.52) in the tamsulosin, dutasteride and imidafenacin group. The tamsulosin, dutasteride and imidafenacin group significantly improved total overactive bladder symptom score at week 24 as compared with the tamsulosin and dutasteride group; the mean difference was −1.18 (−2.02 to −0.34). The between-group difference was statistically significant as early as week 4. The total International Prostate Symptom Score, storage subscore, quality of life index, and benign prostatic hyperplasia impact index also significantly improved in the tamsulosin, dutasteride and imidafenacin group. Conclusions Tamsulosin, dutasteride and imidafenacin combination therapy improves overactive bladder symptoms and quality of life without causing serious adverse drug reactions in patients with enlarged prostate not responding to tamsulosin. This combination therapy seems to represent a promising therapeutic option in these patients.

Objectives To compare the efficacy and safety of silodosin versus tadalafil for treating lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Methods After informed consent, patients with LUTS/BPH were randomized in a 1:1 ratio to receive silodosin 8 mg/day or tadalafil 5 mg/day for 8 weeks (Period 1). Patients treated with tadalafil entered an exploratory phase and received silodosin or tadalafil for another 8 weeks. The primary efficacy endpoint was the change in the total International Prostate Symptom Score (IPSS) with Period 1 treatment. Results Both silodosin and tadalafil demonstrated statistically significant improvement in IPSS total symptom score, with a mean ± standard deviation change of −10.1 ± 6.4 (P < 0.0001) and −8.0 ± 6.3 (P < 0.0001), respectively. The former reduction was significantly greater than the latter (P = 0.0277). Adverse drug reactions occurred at a rate of 23.4% with silodosin and 8.4% with tadalafil. No serious adverse drug reactions were documented, suggesting that both drugs were well tolerated. Moreover, results of Period 2 showed that switching to silodosin from tadalafil achieved a faster onset of improvements in IPSS Quality of Life Index score and total Overactive Bladder Symptom Score. Conclusions Silodosin achieved significantly greater improvement than tadalafil, with a higher incidence of adverse drug reactions. The risk-benefit profiles obtained in this study will provide useful information for optimal pharmacological treatment of LUTS/BPH. Our results suggest that silodosin can be one of the first-line therapies for rapid and efficient relief in patients with LUTS/BPH.

This multi-institutional study aimed to investigate the efficacy and safety profiles of cabazitaxel after prior docetaxel chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 63 Japanese patients with CRPC who were treated with cabazitaxel from 2014 to 2017. The oncological outcomes and adverse events (AEs) were documented, and prognostic factors for oncological outcomes and predictive factors for AEs were analysed. PSA decline was observed in 68.3% of patients, including 25.4% who achieved a ≥ 50% decline. The median progression-free survival, treatment failure-free survival, and overall survival were 4.3, 4.1, and 9.0 months, respectively. More cycles of prior docetaxel therapy was identified as common favourable prognostic factors for progression-free survival, treatment failure-free survival, and overall survival. Severe neutropenia, febrile neutropenia, and severe non-haematological AEs were observed in 73.0%, 33.3%, and 23.8% of patients, respectively. However, > 10 cycles of docetaxel was not associated with increased incidence of AEs. In conclusion, cabazitaxel chemotherapy was still active in Japanese CRPC patients treated with > 10 cycles of docetaxel chemotherapy, with an acceptable risk of AE burden. Treatment with cabazitaxel after > 10 cycles of docetaxel may be an appropriate option when it can be administered.

Objectives To investigate the efficacy of a once-daily oxybutynin patch for nocturia, and its influence on sleep quality in patients with overactive bladder. Methods We carried out post-hoc analysis of a phase III, randomized, double-blind, comparative study in which an oxybutynin patch was administered once daily for 12 weeks to Japanese patients with overactive bladder. Patients with a baseline mean of one or more episodes of nocturia per night (data from voiding diaries) were analyzed. The mean number of micturitions, mean voided volume per micturition, mean first voided volume at night, mean sleep duration, and hours of undisturbed sleep were compared between the once-daily oxybutynin patch group and the placebo group. All parameters were expressed as the least squares mean values. Results The analysis included 576 patients. The number of nocturia episodes decreased by 0.66 in the oxybutynin patch group versus 0.51 in the placebo group (P = 0.0249). Also, the voided volume per nocturnal micturition and the first voided volume at night showed a significant increase in the oxybutynin patch group compared with the placebo group (P = 0.0073 and P = 0.0005, respectively). The hours of undisturbed sleep showed significant prolongation by 76.14 min in the oxybutynin patch group versus 56.07 min in the placebo group (P = 0.0257). Conclusions Oxybutynin patch treatment reduces the number of nocturia episodes and prolongs the hours of undisturbed sleep, thus improving sleep quality and sleep-related quality of life in patients with overactive bladder.

Objectives To compare the effect of treatment with silodosin 4 mg once daily versus that of silodosin 4 mg twice daily on storage symptoms in Japanese patients with benign prostatic hyperplasia. Methods A prospective, multicenter, 12-week, open-labeled study randomized a total of 268 men aged 50 years or older with benign prostatic hyperplasia and overactive bladder to silodosin 4 mg/day or 8 mg/day. Changes in the end-points of the average value of International Prostate Symptom Score, quality of life index in the International Prostate Symptom Score, Overactive Bladder Symptom Score and urodynamic parameters were evaluated. The change in the storage symptom subtotal score of the International Prostate Symptom Score was considered as the primary end-point. Results Silodosin 4 mg/day was not inferior to silodosin 8 mg/day in regard to the primary end-point. In contrast, the efficacy of treatment with silodosin 4 mg twice daily was greater than that of 4 mg once daily, based on both the quality of life index and the Overactive Bladder Symptom Score total score. There was a discrepancy between the scores evaluated using the International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires. Conclusions Silodosin 4 mg once daily is not inferior to silodosin 4 mg twice daily in regard to storage symptoms score evaluated by the International Prostate Symptom Score. In contrast, silodosin 4 mg twice daily is more effective on storage symptoms evaluated by the Overactive Bladder Symptom Score than silodosin 4 mg once daily.

Objective To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB). Patients and methods This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram. Results A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (-1.67 [2.212] vs -0.86 [2.354]; P Conclusions Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

To compare the efficacy and safety of silodosin versus tadalafil for treating lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH).After informed consent, patients with LUTS/BPH were randomized in a 1:1 ratio to receive silodosin 8 mg/day or tadalafil 5 mg/day for 8 weeks (Period 1). Patients treated with tadalafil entered an exploratory phase and received silodosin or tadalafil for another 8 weeks. The primary efficacy endpoint was the change in the total International Prostate Symptom Score (IPSS) with Period 1 treatment.Both silodosin and tadalafil demonstrated statistically significant improvement in IPSS total symptom score, with a mean ± standard deviation change of -10.1 ± 6.4 (P0.0001) and -8.0 ± 6.3 (P0.0001), respectively. The former reduction was significantly greater than the latter (P = 0.0277). Adverse drug reactions occurred at a rate of 23.4% with silodosin and 8.4% with tadalafil. No serious adverse drug reactions were documented, suggesting that both drugs were well tolerated. Moreover, results of Period 2 showed that switching to silodosin from tadalafil achieved a faster onset of improvements in IPSS Quality of Life Index score and total Overactive Bladder Symptom Score.Silodosin achieved significantly greater improvement than tadalafil, with a higher incidence of adverse drug reactions. The risk-benefit profiles obtained in this study will provide useful information for optimal pharmacological treatment of LUTS/BPH. Our results suggest that silodosin can be one of the first-line therapies for rapid and efficient relief in patients with LUTS/BPH.

Aims We investigated the relative important role of rho kinase (ROK) and protein kinase C (PKC) pathways in carbachol (CCh)-induced Ca2+ sensitization in α-toxin permeabilized Guinea pig detrusor smooth muscle (DSM) following bladder outlet obstruction (BOO). Methods Bladder outlet obstruction was created by placement of a silver jeweler's jump rings loosely round the urethro-vesical junction of Guinea pigs. Sham operated Guinea pig underwent a similar protocol without application of the ring and served as control. α-Toxin permeabilized DSM strips from control Guinea pigs and those subjected to 6–8 weeks of BOO were mounted horizontally for isometric force recording in 100 µl relaxing solution on perspex block. The effect of ROK inhibitor (Y-27632) and PKC inhibitor (GF-109203X) on CCh-induced Ca2+ sensitization was studied during sustained contraction. Permeabilized DSM strips were also stimulated by cumulative increase of Ca2+ concentration compared to that in control in the presence and in the absence of sensitization-induced PKC activator, phorbol 12,13-dibutyrate. Results Ca2+ sensitization-induced by CCh was greater in BOO compared to controls. This muscarinic agonist-induced Ca2+ sensitization was inhibited by Y-27632 or GF-109203X. The inhibitory effect of Y-27632 (5 µM) was greater while the inhibitory effect of GF-109203X (5 µM) was smaller in BOO compared to that in controls. Phorbol 12,13-dibutyrate (1 µM) markedly increased Ca2+ sensitivity in controls but not in BOO. Conclusions Our findings provide the first evidence that BOO enhances the ROK pathway and diminishes the PKC pathway in CCh-induced Ca2+ sensitization in contraction of permeabilized Guinea pig DSM and suggest that inhibitors of ROK might potentially relieve bladder dysfunction related to BOO. Neurourol. Urodynam. 31:593–599, 2012. © 2012 Wiley Periodicals, Inc.

Objectives: We report on our initial data from a prospective study to determine the efficacy of high-frequency magnetic stimulation on the sacral root (MSSR) for the intractable post-radical prostatectomy, stress urinary incontinence (SUI). Methods: A total of 14 men with persistent SUI after a radical prostatectomy underwent treatment once every 2 weeks over a 40-week period for a total of 20 sessions. The outcome was assessed by these variables at baseline, at immediately after the first session, and at immediately after the final (20th) session. Results: Mean leak episodes (per day) consistently decreased after the first to the final session (from 6.1 ± 2.9 to 3.5 ± 2.6, and to 3.0 ± 2.3, P < 0.01), and it remained to be decreased following 2 months after the final session. The mean pad weight (per h) also decreased after the treatment (but no statistically significant change compared to the pretreatment level). The cystometric bladder capacity at the first desire to void and the capacity at the strong desire to void increased significantly following the high-frequency MSSR (first desire to void: from 146 ± 43 to 182 ± 52 mL; strong desire to void: from 224 ± 69 to 258 ± 60 mL, P < 0.01). No obvious complication was observed in any patients during or after the treatment. Conclusion: This study provides the preliminary evidence that high-frequency MSSR may potentially afford a useful option with minimal invasiveness for the patients with obstinate SUI after a radical prostatectomy.

The Japanese Urological Association has developed Clinical Guidelines for Benign Prostatic Hyperplasia (BPH) for men with suspected BPH, which have been abridged and translated into English. This article is a shortened version of the English translation. The Guidelines were formulated on the basis of evidence retrieved from the PubMed database between 1995 and 2009, as well as other relevant sources. The target patients of these Guidelines are men with suspected BPH, and the target users are urologists. A mandatory assessment should include a medical history, a physical examination, the completion of symptom and quality of life questionnaires, urinalysis, prostate ultrasonography, measurement of serum prostate specific antigen and postvoid residual urine, and an uroflowmetry. Optional tests include a bladder diary, the measurement of serum creatinine, and upper urinary tract ultrasonography. Care should be taken to not overlook coexisting diseases such as an infection or malignancy that may obscure the diagnosis. Treatment should consist of conservative therapy or the use of medications such as α(1) -adrenoceptor antagonists, or both. The use of 5α-reductase inhibitors or anticholinergic agents should be considered in patients with an enlarged prostate (>30 mL) or overactive bladder symptoms (overactive bladder symptom score ≥ 6), respectively. Surgical intervention is indicated when non-surgical treatments fail to provide sufficient symptomatic relief and bladder outlet obstruction is highly suspected.

The Japanese Urological Association has developed Clinical Guidelines for Benign Prostatic Hyperplasia (BPH) for men with suspected BPH. This article is an English translation of the abridged version of the Guidelines. The Guidelines were formulated on the basis of evidence retrieved from the PubMed database between 1995 and 2009, as well as other relevant sources. The target patients of these Guidelines are men with suspected BPH, and the target users are urologists. A mandatory assessment should include a medical history, a physical examination, the completion of symptom and quality of life questionnaires, a urinalysis, a prostate ultrasonography, measurement of serum prostate specific antigen and postvoid residual urine, and uroflowmetry. Optional tests include keeping a bladder diary, the measurement of serum creatinine, and upper urinary tract ultrasonography. Care should be taken to not overlook coexisting diseases such as infections or malignancies that may obscure the diagnosis. Treatment should consist of conservative therapy or the use of medications such as α1-adrenoceptor antagonists, or both. The use of 5α-reductase inhibitors or anticholinergic agents should be considered in patients with an enlarged prostate (>30 mL) or overactive bladder symptoms (Overactive Bladder Symptom Score ≥6), respectively. Surgical intervention is indicated when non-surgical treatments fail to provide sufficient symptomatic relief, and when bladder outlet obstruction is highly suspected.

To clarify the properties of adenosine triphosphate sensitive K+ channel in human detrusor smooth muscle we examined the effect of the representative nicotinic acid derivatives β-nicotinamide adenine dinucleotide, cyclic adenosine diphosphate ribose and nicotinic acid adenine dinucleotide phosphate (Sigma-Aldrich®) on human detrusor adenosine triphosphate sensitive K+ channels.Patch clamp procedures were done in human detrusor cells. Reverse transcriptase and real-time polymerase chain reaction were performed to clarify the subunit components of adenosine triphosphate sensitive K+ channels.The K+ channel opener levcromakalim induced a long lasting outward current that was inhibited by glibenclamide (Sigma-Aldrich) under the whole cell configuration. The single channel study revealed that the unitary conductance of the adenosine triphosphate sensitive K+ channel in the human detrusor was 11 pS and nucleotide diphosphates increased its open probability. Applying β-nicotinamide adenine dinucleotide also activated the adenosine triphosphate sensitive K+ channel but applying cyclic adenosine diphosphate ribose or nicotinic acid adenine dinucleotide phosphate had little effect on channel activation. Molecular studies indicated that Kir6.1 and SUR2B were the predominant components of the adenosine triphosphate sensitive K+ channel in the human detrusor.To our knowledge we report the first single channel study of the adenosine triphosphate sensitive K+ channel in the human detrusor. The properties of this channel, ie unitary conductance, adenosine triphosphate sensitivity and diphosphate activation, were consistent with those of other smooth muscle organs. β-Nicotinamide adenine dinucleotide has the potency to activate adenosine triphosphate sensitive K+ channels in the human detrusor. This channel likely has some role during ischemic conditions as well as physiological muscle motion leading to the activation of cell metabolism.

To determine the influence of warm or cold ischemia on postoperative renal function, we conducted preoperative and postoperative analysis by renal scintigraphy of patients who were undergoing open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN).From May 2005 to February 2010, the preoperative and postoperative renal function was evaluated by 99mTc-mercaptoacetyltriglycine (MAG3) clearance in 37 patients who were treated with OPN (n=13) and LPN (n=24). LPN were achieved via retroperitoneal (RPLPN; n=12) or transperitoneal (TPLPN; n=12) routes. Renal cooling was performed after renal hilar clamping in OPN and RPLPN, but not TPLPN. Renal function was evaluated according to the ratio of affected to contralateral renal MAG3 clearance.Mean ischemic time was 29.5 minutes in OPN, 25.5 minutes in TPLPN, and 50 minutes in RPLPN (P0.01); median blood loss was 230 mL in OPN (P0.05), 110 mL in TPLPN, and 53 mL in RPLPN. There was no significant difference in postoperative total renal function between the groups. Although ischemic time in RPLPN was longer than in TPLPN, the postoperative recovery of affected renal function from 1 week to 3 months for RPLPN and OPN (cold ischemia) was significantly better than for TPLPN (P0.01).Cold ischemia has an advantage of postoperative recovery of affected renal function. If a patient has a risk of renal dysfunction, cold ischemia during renal hilar clamping is recommended to avoiding deterioration.

Objectives: Various types of minimally invasive surgical treatments, including transurethral resection of prostate (TURP), are being carried out in Japan for patients with benign prostatic hyperplasia (BPH). The aim of the present study was to elucidate the current status of perioperative care for these treatments by carrying out a nationwide survey. Methods: Assisted by the Japanese Endourology and ESWL Association, perioperative data from 157 institutions participating in this survey were collected and analyzed. Results: This survey included 3918 patients undergoing TURP, 242 TUR in saline (TURis), 638 holmium laser enucleation of the prostate (HoLEP), 90 holmium laser ablation (HoLAP) and 241 photoselective vaporization (PVP). Mean operative time was shorter in TURP (71 min) and longer in HoLEP (127). Although no transfusions were required in cases undergoing HoLAP or PVP, blood was frequently transfused in those undergoing TURis (25.6%), TURP (10.2%) and HoLEP (7.8%), and the difference was significant. During the hospital stay, the incidence of TUR-syndrome, postoperative bleeding requiring bladder irrigation, acute urinary retention/difficulty on micturition and pad use at discharge was highest in TURP (2.3%), TURis (7.9%), HoLAP (16.7%) and HoLEP (15.1%), respectively. Two patients undergoing TURP died (0.05%). The shortest mean postoperative hospital stay was for PVP (1.6 days, even if the readmission rate within 90 days was the highest in this same group; 6.2%). Perioperative care during hospital stay varied among the five types of procedures. Conclusions: This survey provides useful documentation on the current status of minimally invasive treatments for BPH in Japan. Complication rates for TURP are not significantly higher as compared with other procedures. Thus, TURP can still be considered as the gold standard for BPH treatment.

Objectives: The aim of this study was to identify the urodynamic features of women with stress urinary incontinence (SUI) or with high-stage (stage 3 or greater) cystocele (HSC) as compared with symptom-free women. Methods: Fifty-six neurologically intact women with SUI and 47 women with HSC but without SUI were prospectively evaluated. All patients underwent full urodynamics, in addition to basic clinical evaluations. The urodynamic parameters of SUI and HSC were compared to the ones obtained from 78 urologically symptom-free normal women over the same period. Results: Patients with HSC, after correction of cystocele using a temporary vaginal pessary, had consistently lower maximum urinary flow rate with a lower detrusor pressure during micturition than the controls or those with SUI. On the other hand, patients with SUI had an equivalent to higher maximum urinary flow rate, normal detrusor contraction strength with a lower detrusor pressure during micturition than the controls. Both maximum Watts factor and bladder contractility index were significantly lower in the whole HSC cohort in comparison to the controls and patients with SUI. The urodynamic characteristics observed among the three groups were all maintained even after adjusting for age. Conclusions: Women with SUI demonstrate voiding with low-pressure, normal contraction strength with an equivalent to high urinary flow rate. Women with HSC demonstrate voiding with low pressures with weak contraction strengths and low urinary flow rates, suggesting a higher prevalence of detrusor underactivity. Chronically decreased or increased urethral resistance might alter voiding dynamics and performance.

Objectives To compare the Overactive Bladder Symptom Score (OABSS) and a bladder diary as a tool for assessing symptoms of overactive bladder (OAB). Methods Treatment-naive OAB patients received an antimuscarinic agent, solifenacin. At baseline and 12 weeks after treatment, patients completed a 3-day bladder diary and the OABSS. Relationships between the 2 methods were evaluated by comparison of changes after treatment, agreement between variables and correlation between changes. Results In total, 79 patients (42 male and 37 female, mean age 71.1 years) were included in the analysis. Statistically significant improvements were noted for all the OABSS and the corresponding diary variables. The effect size (ES) was largest for the OABSS urgency score (2.00), followed by the OABSS total score (1.54), and then by the diary urgency score (0.92). All of the ESs for the OABSS, except daytime frequency, were larger than those of the corresponding diary variables. The standard response means followed a similar pattern to the ESs. A fairly good agreement between OABSS items and the corresponding diary variables was found at baseline and 12 weeks (kappa coefficient, 0.33-0.80). High correlations (Spearman's rho, ≥ 0.5) between changes in OABSS items and the corresponding diary variables were found for urgency incontinence and night-time frequency. Conclusions The OABSS is highly sensitive to treatment-related changes of OAB symptoms. Because of its simplicity and dependability, the OABSS can be an alternative to a bladder diary for symptom and efficacy assessment in daily clinical practice.

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? α-blockers may have little effect in the facilitation of storage and emptying in patients with neurogenic lower urinary tract dysfunction (NLUTD). Naftopidil is a novel α-blocker, which is selective for the α1-D/A adrenoceptor. This study showed the first objective evidence for the effect of naftopidil in treatment of NLUTD patients by pressure-flow study. OBJECTIVES • To assess the effect of α1-D/A adrenoceptor antagonist naftopidil on patients with neurogenic lower urinary tract dysfunction (NLUTD) and voiding difficulty. • To explore the effectiveness of naftopidil in these patients by using urodynamic variables, including pressure flow study (PFS), and to find good and simple parameters (International Prostate Symptom Score (IPSS), Post-void residual urine (PVR), and uroflowmetry (UFM) parameters) as substitution of PFS for predicting the effect of naftopidil. PATIENTS AND METHODS • The main inclusion and exclusion criteria were, IPSS ≥8, voiding symptoms with IPSS ≥5, IPSS-quality of life (QOL) ≥2, PVR ≥50 mL, and without prostatic enlargement ≥20 mL. • After initial assessment, patients were stepwisely administered for 12 weeks with the following: placebo for 2 weeks, naftopidil 25 mg/day for 2 weeks, naftopidil 50 mg/day for 2 weeks, and naftopidil 75 mg/day for 6 weeks. At the end of both placebo and 6 weeks’ naftopidil 75 mg/day, their IPSS, UFM, PVR, and PFS were assessed. • A total of 82 Japanese patients (men 40, women 42) with lower urinary tract symptoms complicated by NLUTD, with a mean age of 63.9 years, were included from private or institutional clinics. • The lesions were spinal cord 42, and peripheral nervous system 40. The spinal cord lesions were all lumbar spine (injury or lumbar canal stenosis). RESULTS • In all patients, pressure at maximum urinary flow rate (PdetQmax) in PFS significantly decreased (P < 0.05), and maximum urinary flow rate in UFM significantly increased (P < 0.01). Analysis of data for men and for women also showed a significant decrease in PVR, %PVR, and total IPSS score. • The degree of improvement of voided volume, PVR (%), and IPSS in patients with PVR

Preface: We are heartily grateful for the warm support of all of the people concerned, including the moderators and panelists of both societies for giving us the opportunity to hold the 5th American Urological Association/Japanese Urological Association (AUA/JUA) International Affiliate Society Meeting, held once again at the 105th Annual Meeting of the American Urological Association (29 May–3 June 2010, San Francisco, California, USA). The year of 2010 is a memorable one, being the start of reciprocal collaborations between the AUA and the JUA. The JUA, in collaboration with the AUA, is promoting an academic exchange program whereby outstanding and promising Japanese and American junior faculty members will be given the opportunity to work in the USA and Japan for 1 month. The program not only allows the sharing of knowledge and experience, but also is designed to foster a closer alliance between the AUA and JUA, and assists in identifying future leaders within both organizations. The AUA and JUA will have an exhibit booth at each other's annual meeting, promoting our new joint activities. Both the JUA and AUA will organize educational courses in Hawaii in 2011. With all of these activities, the JUA hopes it will provide greater opportunities for young Japanese urologists to participate in educational projects in the USA. We would like to thank Professor Anton J. Bueschen, President of AUA, Professor Robert C Flanigan, Secretary General of AUA and the staff of the AUA and JUA for supporting our program. At the same time, we need the support of all the members and their valuable suggestions. We look forward to further participation of AUA members to this meeting. Seiji Naito md, President of JUA Shin Egawa md, Chairman of the International Committee of JUA

Many advanced cancers receive cisplatin-based chemotherapy. However, cisplatin resistance is a major obstacle for cancer chemotherapy. Foxo3a is a member of the Foxo transcription factor family, which modulates the expression of genes involved in DNA damage repair, apoptosis, and other cellular processes. In this study, we found that cisplatin-resistant cells were more sensitive to the anticancer agent mithramycin than their parental cells, and had a decreased level of Foxo3a expression. Foxo3a knockdown increased cell proliferation and resistance to cisplatin. On the other hand, mithramycin stimulated Foxo3a expression through reactive oxygen species production and sensitized cells to cisplatin, which was abolished by Foxo3a knockdown, while the acetylation status of Foxo3a was decreased in response to cisplatin treatment and was lower in cisplatin-resistant cells. Knockdown of Foxo3a-associated acetyltransferase p300 promoted cancer-cell growth and cisplatin resistance. In addition, non-acetylation-mimicking Foxo3a overexpression decreased cancer cell growth and sensitized cells to cisplatin less than wild-type Foxo3a overexpression. The current work may contribute to the evaluation of the therapeutic potential of inducing the Foxo3a pathway and acetylating the Foxo3a transcription factor, and lead to the reevaluation of cancer treatments based on mithramycin. (Cancer Sci 2010; 101: 1177–1185)

Twist1 has been proposed to have oncogenic properties. Although Twist1 was reported to interact with p300/CBP-associated factor (PCAF) and to inhibit the functions of PCAF, it remains unclear how PCAF affects the functions of Twist1, cell growth, invasive ability, and cellular sensitivity to anticancer agents. We found that PCAF, Twist1, and Y-box binding protein-1 (YB-1) expressions were elevated in cisplatin- and doxorubicin-resistant cancer cells. Luciferase reporter assays revealed that PCAF manipulation modulated YB-1 transcription in a Twist1-dependent manner. In addition, PCAF regulated the Twist1 intracellular localization and the Twist1 transcriptional activity through its acetylation function to the Twist1. Suppression of PCAF expression reduced YB-1 expression in human urothelial cancer KK47 cells. As a result, the cell growth and invasive ability of KK47 cells was retarded by PCAF knockdown, and PCAF knockdown rendered KK47 cells sensitive to cisplatin and doxorubicin, but not to 5-fluorouracil. The present data suggest that Twist1 and YB-1 as well as PCAF may be promising molecular therapeutic targets.

There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was found to be an AR cofactor. PGC-1α interacted with the N-terminal domain of AR, was involved in the N- and C-terminal interaction of AR, and enhanced the DNA-binding ability of AR to androgen-responsive elements in the prostate-specific antigen enhancer and promoter regions to increase the transcription of AR target genes. Silencing of PGC-1α suppressed cell growth of AR-expressing prostate cancer (PCa) cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, PGC-1α knock-down also suppressed cell growth in the castration-resistant LNCaP-derivatives. These findings indicate that PGC-1α is involved in the proliferation of AR-expressing PCa cells by acting as an AR coactivator. Modulation of PGC-1α expression or function may offer a useful strategy for developing novel therapeutics for PCa, including CRPC, which depends on AR signaling by overexpressing AR and its coactivators.

Aims To investigate the association of both the urodynamic profiles and patterns of detrusor overactivity (DO) with the severity of the symptoms related to overactive bladder (OAB) in men with benign prostatic enlargement (BPE) associated with DO. Methods A total of 777 men with symptomatic BPE who had undergone transurethral resection of the prostate (TURP) were retrospectively analyzed. All 231 cases of the 317 cases associated with DO were enrolled into the final analysis. The severity of the preoperative symptoms related to OAB were graded based on the International Prostate Symptoms Score (IPSS). The correlation between DO profiles and the severity of OAB related symptoms were analysed using Spearman's correlation test while the association of the DO patterns with the severity of symptoms related OAB were analysed using the Mann Whitney test. Values of P less than 0.05 were considered to be statistically significant. Results A significant negative correlation was found between the severity of nocturia symptoms and bladder filling volume at the beginning of the first DO. The severity of nocturia symptoms, the amplitude of DO pressure and DOtime were significantly increased with increasing age. The severity of nocturia symptom was significantly higher in single DO in comparison to that in multiple DO. Conclusions The significant association of the severity of nocturia symptoms with bladder filling volume at the beginning of the first DO, age and the number of DO pattern was established. The amplitude and duration of DO may affect the severity of the symptoms. Neurourol. Urodynam. 28:953–958, 2009. © 2009 Wiley-Liss, Inc.

Objectives: To identify the efficacy and safety of photoselective vaporization of the prostate (PVP) in relation to the prostate size in subjects with benign prostatic enlargement. Methods: The prospective study included 102 Japanese patients who underwent PVP. The efficacy and morbidity following PVP were compared in groups classified according to the baseline prostate size: prostates