Osamu Yokoyama

University of Fukui, Hukui, Fukui, Japan

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Publications (201)512.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Spontaneous hypertensive rats provide a genetic model for exploring the pathogenesis of urine storage dysfunction related to hypertension (HT). In humans, however, HT develops by both genetic and environmental factors including lifestyle factors such as a high-calorie diet, excessive salt intake and stress. We investigated the influence of salt-loading on bladder function and the underlying mechanisms of storage dysfunction related to HT. Main methods: Six-week-old male Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats were fed with a normal or high-salt diet for 12weeks. Micturition parameters were obtained from a metabolic cage. Whole bladders were excised from 18-week-old rats and distended in an organ bath. The releases of adenosine triphosphoric acid (ATP) and prostaglandin E2 (PGE2) from the distended bladder epithelia were measured. Changes in bladder blood flow (BBF) were determined with a laser-speckle-blood-flow imaging system. Key findings: An increase in mean blood pressure (BP) was noted only in DS rats after salt-loading. During the inactive (sleeping) period, voided volume per micturition gradually increased in DR rats fed a normal or high-salt diet and normal-diet DS rats, while it did not change in the DS rats fed a high-salt diet. Bladder distension significantly increased ATP and PGE2 release from the urothelium in DS rats fed a high-salt diet. BBF was significantly decreased in high-salt-diet DS rats. Significance: One mechanism behind the relationship between salt-sensitive HT and urine storage dysfunction may be an increase in ATP and PGE2 release from the urothelium via suppression of BBF.
    Life sciences 09/2015; 141. DOI:10.1016/j.lfs.2015.09.010 · 2.70 Impact Factor
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    ABSTRACT: It is widely accepted that sialyl Lewis X (sLeX) and sialyl Lewis A (sLeA, also known as CA 19-9) glycans expressed on cancer cells function in E-selectin-mediated metastasis. Recently, it was reported that 6-sulfo sLeX glycans detected by the MECA-79 monoclonal antibody are expressed in roughly a quarter of gastric adenocarcinoma cases, and that these cases show a poorer prognosis than MECA-79-negative cases do. The present study was undertaken to assess expression of 6-sulfo sLeX glycans in bladder urothelial carcinoma and evaluate potential clinical implications.
    Urologic Oncology 06/2015; 33(11). DOI:10.1016/j.urolonc.2015.05.026 · 2.77 Impact Factor
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    ABSTRACT: Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with BPH-LUTS, and to update the current understanding of the mechanism of action underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is highly expressed in the lower urinary tract and supporting vasculature, and that PDE5 inhibition potentially decreases smooth muscle cell proliferation in the prostate, relaxes smooth muscle in the prostate, bladder neck and supporting vasculature, increases blood perfusion to the lower urinary tract, and modulates bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind, randomized, placebo-controlled studies of tadalafil, including four Asian studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428 North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once-daily resulted in significant improvements in the change from baseline to endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and voiding subscores, and IPSS quality of life index compared with placebo. Tadalafil was well tolerated and had a favorable safety profile. These findings support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH-LUTS.
    Therapeutic Advances in Urology 06/2015; 7(5). DOI:10.1177/1756287215589238
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    The Journal of Urology 04/2015; 193(4):e129. DOI:10.1016/j.juro.2015.02.779 · 4.47 Impact Factor
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    The Journal of Urology 04/2015; 193(4):e79-e80. DOI:10.1016/j.juro.2015.02.284 · 4.47 Impact Factor
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    ABSTRACT: A 22-year-old man was admitted to our hospital complaining of a left cervical mass. Computed tomography (CT) showed multiple enlarged lymph nodes at the left cervical vein and para-aortic areas. Histological examination of a biopsy indicated an embryonal carcinoma. The levels of human β-chorionic gonadotropin (β-HCG) and lactic dehydrogenase (LDH) were both elevated. Ultrasonography revealed testicular calcification, but there were no findings on magnetic resonance imaging (MRI). The patient was diagnosed as having an extragonadal germ cell tumor. After four courses of chemotherapy with BEP protocol (bleomycin, etoposide and cisplatin), retroperineal lymph node dissection (RPLND) was performed and there was no involvement of the viable cells in the resected lymph nodes. Eight years after chemotherapy, he noticed an enlargement of his left scrotum without pain. β-HCG was again elevated. A unilateral high orchiectomy was performed, and histology revealed a seminoma. He was staged as pT1N0M0S0. Six months later he remains disease-free.
    Hinyokika kiyo. Acta urologica Japonica 04/2015; 61(4):173-6.
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    ABSTRACT: To investigate the efficacy of a once-daily oxybutynin patch for nocturia, and its influence on sleep quality in patients with overactive bladder. 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. 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). 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. © 2015 The Japanese Urological Association.
    International Journal of Urology 03/2015; 22(7). DOI:10.1111/iju.12755 · 2.41 Impact Factor
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    ABSTRACT: To clarify the possible interference of the 5α-reductase inhibitor dutasteride with α-adrenergic blockers, whose action is mainly mediated by α1A-adrenergic receptor. Male rats were divided into dutasteride and vehicle-treated groups. The drug treatment group was treated with oral dutasteride 0.5 mg/kg/d, and the control group received vehicle only for 2 months. After the 2-month treatment, the rats' ventral prostate weight changes and the testosterone and dihydrotestosterone levels in the serum were measured. In vitro organ-bath studies, real-time polymerase chain reaction, and tissue-segment binding were performed to determine the expression of α1A-adrenergic receptors and its mediated contractility. Dutasteride treatment significantly decreased the rats' ventral prostate weight, increased their testosterone levels, and decreased the dihydrotestosterone levels in their serum. There were no marked changes in the α1A-adrenergic receptor messenger ribonucleic acid expression, relative phenylephrine-induced contractility, or nerve-mediated contractility between the groups. Dutasteride treatment caused no marked changes in the relative binding capacity of α1A-adrenergic receptor, whereas it greatly decreased the total protein expression of this subtype and its mediated maximal contraction in the whole ventral prostate. These results suggest that dutasteride does not interfere with α-adrenergic blockers but otherwise has beneficial effects on their actions. Therefore, the long-term administration of the combination of dutasteride with an α-adrenergic blocker might be a better choice for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urology 03/2015; 85(3):704.e9-704.e14. DOI:10.1016/j.urology.2014.12.002 · 2.19 Impact Factor
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    ABSTRACT: Assess the efficacy and safety of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms by pooling data from three clinical studies. Data on 1199 Japanese, Korean, and Taiwanese men given tadalafil 5 mg (n = 601) or placebo (n = 598) were pooled from three double-blind, placebo-controlled, 12-week studies. Efficacy measures included International Prostate Symptom Score, and Patient and Clinician Global Impressions of Improvement. These measures were also assessed for patient subgroups (age categories, baseline disease severity and/or prostate volume, prior alpha-blocker treatment). Safety measures included adverse events, including those in selected body systems. Efficacy measure changes throughout treatment were assessed by mixed-effect model repeated-measures analysis; baseline to end-point changes for the total population and subgroups were evaluated by analysis of covariance. Tadalafil 5 mg led to significant improvement (vs placebo) in all International Prostate Symptom Scores at all time-points (week 4 P ≤ 0.013 for all measures; week 8 P ≤ 0.005, week 12 P < 0.001). End-point results for both global impressions scales also favored tadalafil (both P < 0.001 vs placebo). Tadalafil efficacy was similar between patient subgroups of varied disease severity (interaction P = 0.097), prior alpha-blocker use (P = 0.580), and prostate volume (P = 0.921). The drug was slightly less effective in older men (interaction P = 0.042). No unexpected adverse events were reported, and no meaningful adverse effects were observed in visual, auditory, or cardiovascular systems. Tadalafil 5 mg once-daily for 12 weeks is efficacious and safe in Asian men with lower urinary tract symptoms. Tadalafil is also effective in men of different ages, disease severity, prior alpha-blocker exposure, and prostate volumes. © 2015 The Japanese Urological Association.
    International Journal of Urology 02/2015; 22(4). DOI:10.1111/iju.12699 · 2.41 Impact Factor
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    ABSTRACT: Objective To examine the safety and efficacy of mirabegron as add-on therapy to solifenacin in patients with OAB.Patients and Methods This multicenter, open-label, Phase IV study enrolled patients ≥20 years old with OAB, as determined by an overactive bladder symptom score (OABSS) total score of ≥3 points and a Question 3 OABSS of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks.Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily), and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient's symptom improvement was not sufficient, he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns.Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram (ECG), QT corrected for heart rate using Fridericia's correction (QTcF) interval and post-void residual (PVR) volume.Efficacy endpoints were changes from baseline in OABSS total score, overactive bladder questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean number of urgency incontinence episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at week –2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at week 0, 8 and 16 (or at discontinuation), and patient micturition diaries at week 0, 4,8,12 and 16 (or at discontinuation).ResultsOverall incidence of drug-related TEAEs was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose.Changes in post-void residual volume, QTcF interval, pulse rate, and blood pressure were not considered to be clinically significant and there were no reports of urinary retention.Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg).Conclusions Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily.Significant improvements from baseline to EOT in OAB symptoms were observed with combination therapy with mirabegron and solifenacin.Add-on therapy with mirabgron and an antimuscarinic agent such as solifenacin may provide an attractive therapeutic option.
    BJU International 01/2015; 116(4). DOI:10.1111/bju.13068 · 3.53 Impact Factor
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    ABSTRACT: Purpose: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. Materials and methods: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. Results and limitations: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. Conclusions: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.
    World Journal of Urology 09/2014; 33(5). DOI:10.1007/s00345-014-1399-x · 2.67 Impact Factor
  • Tetsuyuki Kurokawa · Keiko Nagase · Xinmin Zha · Osamu Yokoyama ·

    The Journal of Urology 04/2014; 191(4):e43. DOI:10.1016/j.juro.2014.02.204 · 4.47 Impact Factor
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    ABSTRACT: Objective To investigate the efficacy of fesoterodine vs placebo on nocturia, sleep disturbance, and sleep-related quality of life (QoL) in patients with overactive bladder and nocturia. Methods This posthoc analysis used data from a 12-week, randomized, placebo-controlled trial of fesoterodine 4 and 8 mg per day in Asian adults reporting ≥8 micturitions and ≥1 urgency urinary incontinence episodes per 24 hours at baseline. Patients who reported ≥1 nocturnal micturition/24 h were included in this analysis. Efficacy variables included change from baseline to week 12/end of treatment in nocturnal micturitions/24 h, nocturnal voided volume/micturition, and hours of undisturbed sleep. Sleep-related QoL was assessed using King's Health Questionnaire Sleep/Energy domain. Treatment comparisons were made using analysis of covariance. Results Among 555 patients, reductions in nocturnal micturitions with fesoterodine 4 mg (−0.63) and 8 mg (−0.77) were numerically greater vs placebo (−0.56), but differences were not significant (P >.05). When patients with a nocturnal polyuria index >33% were excluded, the decrease in nocturnal micturitions was significantly greater with fesoterodine 8 mg vs placebo (−0.24; P = .031). Increases in nocturnal voided volume/micturition were significantly greater with fesoterodine 4 (38.07 mL; P = .013) and 8 mg (42.05 mL; P <.001) vs placebo (14.89 mL). Hours of undisturbed sleep was significantly longer with fesoterodine 4 mg vs placebo (80 vs 54 minutes; P = .032); improvement in King's Health Questionnaire Sleep/Energy scores was significantly greater with fesoterodine 4 (P = .034) and 8 mg (P = .019) vs placebo. Conclusion These results suggest that fesoterodine may reduce nocturnal micturitions and improve sleep quality and QoL in overactive bladder patients with nocturia.
    Urology 04/2014; 83(4). DOI:10.1016/j.urology.2013.12.008 · 2.19 Impact Factor
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    ABSTRACT: The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) is the standard questionnaire that determines the degree of symptoms and efficacy of treatment in patients with chronic prostatitis/chronic pelvic pain syndrome. Because there was no officially approved Japanese version of the NIH-CPSI, the Japanese Urological Association (JUA) formed a committee to develop one chaired by Dr. Masayuki Takeda, who also chairs the special field of voiding function and neurourology in the JUA. Consequently, the committee produced a Japanese version, referring to previous proposals and the Japanese version of the International Prostate Symptom Score. The committee strongly expects that the Japanese version of the NIH-CPSI will be taken full advantage of in future clinical research.
    Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 04/2014; 105(2):62-5. DOI:10.5980/jpnjurol.105.62

  • The Journal of Urology 04/2014; 191(4):e6. DOI:10.1016/j.juro.2014.02.112 · 4.47 Impact Factor
  • Ryusei Yokokawa · Hironobu Akino · Keiko Nagase · Osamu Yokoyama ·

    The Journal of Urology 04/2014; 191(4):e48. DOI:10.1016/j.juro.2014.02.214 · 4.47 Impact Factor

  • The Journal of Urology 04/2014; 191(4):e309. DOI:10.1016/j.juro.2014.02.754 · 4.47 Impact Factor
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    ABSTRACT: Purpose. To assess changes in lower urinary tract symptoms (LUTS) within 1 year after brachytherapy in patients receiving alpha 1-adrenoceptor antagonists. Methods. We retrospectively evaluated 116 patients who underwent (125)I prostate brachytherapy in our institute. Seventy-one patients were treated with a combination of external beam radiation therapy and brachytherapy. Alpha 1-adrenoceptor antagonists were prescribed to all patients after brachytherapy. International Prostate Symptom Score (IPSS) forms and postvoid residual urine volume were recorded at all follow-up visits. Results. Forty-nine patients were given tamsulosin hydrochloride, 32 were given silodosin hydrochloride, and 35 were given naftopidil for up to 6 months after seed implantation. Patients given tamsulosin or naftopidil tended to show a higher peak IPSS and slower recovery to baseline values than those given silodosin. The patients given naftopidil showed an insufficient recovery in storage symptoms in naftopidil group in comparison with tamsulosin group at 3 months and with silodosin group at 6 and 9 months. Conclusions. In the management of LUT after brachytherapy, silodosin may provide a more favorable improvement. Silodosin and tamsulosin may have an advantage in improving not only voiding but also storage lower urinary tract symptoms after brachytherapy.
    03/2014; 2014(2):140654. DOI:10.1155/2014/140654
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    ABSTRACT: To gain further evidence on the efficacy, safety and tolerability of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Japanese and Korean men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia were randomized to once-daily tadalafil 5 mg (n = 306) or placebo (n = 304) for 12 weeks. A significantly greater improvement (P < 0.001) in total International Prostate Symptom Score for the change from baseline (week 0) to study end-point (week 12) was observed for tadalafil (-6.0) versus placebo (-4.5). Significantly greater improvements (P < 0.01) in total International Prostate Symptom Score for the change from baseline to weeks 4 and 8 were observed for tadalafil versus placebo. Significantly greater improvements (P < 0.05) in International Prostate Symptom Score voiding and storage subscores, and International Prostate Symptom Score Quality of Life Index were observed for the change from baseline to end-point for tadalafil versus placebo. Significantly greater improvements (P < 0.001) in urinary symptoms were observed for tadalafil versus placebo for both Patient and Clinician Global Impressions of Improvement. No new safety concerns were identified. These findings confirm the efficacy and safety profile of tadalafil 5 mg once-daily in Asian men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.
    International Journal of Urology 02/2014; 21(7). DOI:10.1111/iju.12410 · 2.41 Impact Factor

Publication Stats

2k Citations
512.13 Total Impact Points


  • 2004-2015
    • University of Fukui
      • Division of Urology
      Hukui, Fukui, Japan
  • 2011
    • Nagoya City University
      Nagoya, Aichi, Japan
  • 2010
    • Shinshu University
      Shonai, Nagano, Japan
  • 2003-2006
    • Fukui University
      Hukui, Fukui, Japan
    • Fukui General Hospital
      Hukui, Fukui, Japan
  • 1988-2006
    • Kanazawa University
      • • Department of Urology
      • • School of Medicine
      Kanazawa, Ishikawa, Japan
  • 1999-2005
    • Kanazawa Medical University
      • Department of Urology
      Kanazawa, Ishikawa, Japan
  • 1999-2002
    • University of Pittsburgh
      • • School of Medicine
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States