加賀 勘家

Abstract Background Quantitative and comprehensive visualization of urinary flow dynamics in the urethra is crucial for investigating patient‐specific mechanisms of lower urinary tract symptoms (LUTS). Although some methods can evaluate the global properties of the urethra, it is critical to assess the local information, such as the location of the responsible lesion and its interactions with urinary flow in relation to LUTS. This approach is vital for enhancing personalized and focal treatments. However, there is a lack of such diagnostic tools that can directly observe how the urethral shape and motion impact urinary flow in the urethra. Purpose This study aimed to develop a novel transrectal ultrasound imaging modality based on the contrast‐enhanced urodynamic vector projectile imaging (CE‐UroVPI) framework and validate its clinical applicability for visualizing time‐resolved flow dynamics in the urethra. Methods A new CE‐UroVPI system was developed using a research‐purpose ultrasound platform and a custom transrectal linear probe, and an imaging protocol for acquiring urodynamic echo data in male patients was designed. Thirty‐four male patients with LUTS participated in this study. CE‐UroVPI was performed to acquire ultrasound echo signals from the participant's urethra and urinary flow at various voiding phases (initiation, maintenance, and terminal). The ultrasound datasets were processed with custom software to visualize urinary flow dynamics and urethra tissue deformation. Results The transrectal CE‐UroVPI system successfully visualized the time‐resolved multidirectional urinary flow dynamics in the prostatic urethra during the initiation, maintenance, and terminal phases of voiding in 17 patients at a frame rate of 1250 fps. The maximum flow speed measured in this study was 2.5 m/s. In addition, when the urethra had an obstruction or an irregular partial deformation, the devised imaging modality visualized complex flow patterns, such as vortices and flow jets around the lesion. Conclusions Our study findings demonstrate that the transrectal CE‐UroVPI system developed in this study can effectively image fluid‐structural interactions in the urethra. This new diagnostic technology has the potential to facilitate quantitative and precise assessments of urethral voiding functions and aid in the improvement of focal and effective treatments for patients with LUTS.

BACKGROUND: The adipose stromal vascular fraction contains abundant mesenchymal stem cells and is utilized for cell therapy of male stress urinary incontinence. The purpose of this paper was to explore the effect of local transplantation of the stromal vascular fraction on improvement of damaged anal sphincter function. METHODS: A rat model of vaginal distension was used as a model of damaged anal sphincter function. The adipose stromal vascular fraction was separated from the inguinal fat of syngeneic green fluorescent protein transgenic rats and delivered into the internal anal sphincter of vaginal distension rats. The maximum resting pressure was evaluated during insertion and withdrawal of the catheter at 4 or 10 days after vaginal distension treatment to estimate anal sphincter function. Green fluorescent protein-transfected human-adipose-derived mesenchymal stem cells were transplanted into the internal anal sphincter of nude rats. Hematoxylin-eosin and Masson trichrome staining were performed to evaluate tissue damage and collagen synthesis. Transplanted cells were identified using a green fluorescent protein antibody and a human-specific antibody. Activation of the transplanted human-ADSC was evaluated by quantitative RT-PCR RESULTS: The mean maximum resting pressure (during catheter withdrawal) of vaginal distension rats was significantly lower than that of control rats, and stromal vascular fraction injection normalized it 4 days after treatment (control: 5.66 ± 0.98, vaginal distension: 4.04 ± 1.28, vaginal distension + stromal vascular fraction: 5.92 ± 1.28 [mmHg, control versus vaginal distension: P = .039; vaginal distension versus vaginal distension + stromal vascular fraction: P = .007]). Histological examination showed that vaginal distension disrupted the internal anal sphincter, and the transplanted syngeneic stromal vascular fraction survived for 10 days. Transplanted xenogeneic human-adipose-derived mesenchymal stem cells survived in the internal anal sphincter of nude rats for 4 and 10 days. Genes related to extracellular remodeling were up-regulated in the transplanted human-adipose-derived mesenchymal stem cells CONCLUSION: Syngeneic and heterotopic transplanted adipose-derived mesenchymal stem cells engrafted in the internal anal sphincter and ameliorated damaged anal sphincter function in a rat model of vaginal distension.

目的:バルサルバ負荷尿漏出時圧(Valsalva leak point pressure:VLPP)を含む腹圧下尿漏出時圧測定(abdominal leak point pressure:ALPP)は腹圧性尿失禁を捉える重要な測定法のひとつである.しかし,いまだ標準的な方法はないとされている.そこで,従来からの口頭指示によるバルサルバ負荷とシリンジを用いたバルサルバ負荷を行い,腹圧(膀胱内圧)および尿漏出検出に差異がみられるかどうか検討を行った.対象:2017年5月から2020年1月の期間に尿失禁の原因精査および骨盤臓器脱の手術前評価として尿流動態検査を施行した女性患者42名を対象とした.方法:同一患者において口頭指示による負荷とシリンジを用いた負荷を順に各1回行い,腹圧(膀胱内圧)の変化および尿漏出の有無について検討を行った.結果:シリンジを用いた負荷による腹圧(膀胱内圧)は矩形波様の上昇を示し,92.7±33.1cmH2Oであった.三角波様の上昇を示した口頭指示による腹圧(膀胱内圧)は58.2±21.7cmH2Oであり,シリンジを用いた負荷の方が有意に高く,尿漏出の検出率が2.5倍上昇していた.結論:シリンジを用いたバルサルバ負荷はより高く,そして長く腹圧を上昇させる可能性があり,腹圧下尿漏出時圧測定の検出率を向上させる優れた方法であると考えられた.(著者抄録)

OBJECTIVES: This study was carried out to identify biomarkers that distinguish Hunner-type interstitial cystitis from non-Hunner-type interstitial cystitis patients. METHODS: Total ribonucleic acid was purified from 212 punch biopsy specimens of 89 individuals who were diagnosed as interstitial cystitis/bladder pain syndrome. To examine the expression profile of patients' bladder specimens, 68 urothelial master transcription factors and nine known markers (E-cadherin, cytokeratins, uroplakins and sonic hedgehog) were selected. To classify the biopsy samples, principal component analysis was carried out. A decision tree algorithm was adopted to identify critical determinants, in which 102 and 116 bladder specimens were used for learning and validation, respectively. RESULTS: Principal component analysis segregated tissues from Hunner-type and non-Hunner-type interstitial cystitis specimens in principal component axes 2 and 4. Principal components 2 and 4 contained urothelial stem/progenitor transcription factors and cytokeratins, respectively. A decision tree identified KRT20, BATF and TP63 to classify non-Hunner-type and Hunner-type interstitial cystitis specimens. KRT20 was lower in tissues from Hunner-type compared with non-Hunner-type interstitial cystitis specimens (P < 0.001). TP63 was lower in Hunner's lesions compared with adjacent mucosa from Hunner-type interstitial cystitis patients (P < 0.001). Blinded validation using additional biopsy specimens verified that the decision tree showed fairly precise concordance with cystoscopic diagnosis. CONCLUSION: KRT20, BATF and TP63 were identified as biologically relevant biomarkers to classify tissues from interstitial cystitis/bladder pain syndrome specimens. The biologically explainable determinants could contribute to defining the elusive interstitial cystitis/bladder pain syndrome pathogenesis.

OBJECTIVE: To examine the urodynamic effects of fesoterodine on neurogenic detrusor overactivity and/or low compliance bladder. METHODS: A total of 77 patients (52 men, 25 women; aged 61.6 ± 20.3 years) were given fesoterodine 4-8 mg/day and prospectively followed for 12 weeks. The primary end-point variable was change in the maximum cystometric capacity on urodynamic study. The secondary end-point was to assess the number of patients whose neurogenic detrusor overactivity disappeared, and the changes in the urodynamic parameters, lower urinary tract symptoms questionnaires and the 3-day frequency volume chart parameters after the treatment. RESULTS: A total of 13 patients (16.9%) withdrew because of adverse events (dry mouth or blurred vision), and four patients dropped out for unknown reasons. Finally, 60 patients completed the study. Bladder capacity at first desire to void, maximum cystometric capacity and bladder compliance increased by 29.2 mL, 79.9 mL and 22.2 mL/cm H2 O, respectively, showed statistical significance (P = 0.026, P < 0.001 and P < 0.001). Neurogenic detrusor overactivity disappeared in 12 of 51 patients (23.5%), and a significant increase was observed in bladder capacity at first involuntary contraction (P < 0.001), and a significant decrease was observed in maximum detrusor contraction (P < 0.001). In patients with low compliance bladder (with detrusor underactivity without neurogenic detrusor overactivity; n = 9), maximum cystometric capacity and bladder compliance increased significantly (P = 0.003 and P = 0.006, respectively). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire-Short Form, most items of King's Health Questionnaire, and the number of urgency episodes and leaks in a day decreased significantly after treatment. CONCLUSIONS: Fesoterodine seems to be a valid treatment option for neurogenic detrusor overactivity and/or low compliance bladder in neurogenic bladder patients.

AIM: To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH). METHODS: Male patients with lower urinary tract symptoms (50 to 89 years), with remaining OAB symptoms even after administering tadalafil for more than 8 weeks were randomly assigned to either tadalafil monotherapy group (5 mg/day) or tadalafil/mirabegron combination therapy group (5 mg/50 mg/day). The primary endpoint was change from baseline in total OAB symptom score (OABSS) at week 12. The secondary endpoints were changes in International Prostate Symptom Score (IPSS), NIH-chronic prostatitis symptom index (NIH-CPSI), and micturition chart parameters at weeks 4 and 12. RESULTS: A total of 176 patients were randomized to either monotherapy (87 patients) or combination therapy (89 patients). The baseline characteristics of patients in the two groups were similar. The total OABSS (95% confidence interval) of combination therapy was significantly decreased by 1.78 (1.05-2.50) points compared with that of monotherapy (P < .001). Changes from baseline in OABSS nighttime voiding score, urgency score, urgency incontinence score, IPSS storage subscores, NIH-CPSI total score, and numbers of voids, nighttime-voids, and urgency episodes/day in micturition chart were significantly reduced in combination therapy (all P < .001). Patient-reported outcome was significantly more satisfactory in combination therapy than in monotherapy (P < .001). One moderate adverse event (pain in hip joint) with hardly presumed causal relationship with therapy and seven mild adverse events were noted in monotherapy and combination therapy group, respectively. CONCLUSIONS: The effect of tadalafil/mirabegron combination therapy on relieving OAB symptoms appeared to be greater than that of tadalafil monotherapy and can be safely used.

OBJECTIVE: The aim of the present study was to evaluate the effect of magnetic stimulation on urodynamic stress incontinence refractory to pelvic floor muscle training in a randomized sham-controlled study. METHODS: Female patients with urodynamic stress incontinence who had not been cured by pelvic floor muscle training were randomly assigned at a ratio of 2 : 1 to either active treatment or sham treatment for 10 weeks. The randomization was made using magnetic cards for individuals indicating active or sham stimulation. The primary endpoint was changes in the number of incontinence episodes/week, with secondary endpoints of the degree of incontinence (in g/day; determined using the pad test), the total score on the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), the ICIQ quality of life (QOL) score, and the abdominal leak point pressure (ALPP) on urodynamic study. RESULTS: Although 39 patients were enrolled in the study, 9 dropped out, leaving a total patients for analysis (18 in the active treatment group, 12 in the sham treatment group). The number of incontinence episodes/week, the degree of incontinence, total ICIQ-SF score, ICIQ-QOL score, and ALPP were significantly improved after active treatment compared with baseline (all P < .05), but did not change significantly after sham treatment. There was a significant intergroup difference with regard to changes from baseline in the ICIQ-SF and ALPP in favor of the active treatment group (P < .05). There were no significant differences in any other parameters between the 2 groups. Treatment-related adverse events were not found in both groups. CONCLUSION: Magnetic stimulation was effective in treating urodynamic stress incontinence.

INTRODUCTION: Autologous transplantation of adipose stromal vascular fraction (SVF) is a cost-effective and technically accessible option for cell therapy. Clinical study of SVF transplantation for male stress urinary incontinence (SUI) is underway, but the effectiveness remains unknown for female SUI, majority of which is caused by childbirth trauma. METHODS: Vaginal Distension (VD) rats were generated as in vivo model for female SUI. To quantitate the severity of SUI, leak point pressure (LPP) was measured by placing a bladder catheter. There was a characteristic waveform of LPP with two-peaks, and we counted the second peak as an LPP value. Adipose SVF was separated from inguinal fat and delivered into external urethral sphincter (EUS) through transperineal injection. LPP was measured 7 or 14 days after SVF transplantation. Tissue damage and collagen synthesis around the EUS were visualized by Masson's trichrome and eosin staining. Antibody against α-smooth muscle actin (α-SMA) was used to stain smooth muscle or activated stromal cells. Donor SVF cells were distinguished from recipient EUS tissue by tracking with GFP transgene. RESULTS: VD procedure decreased the frequency at which the normal LPP waveform appeared and lowered the LPP value. SVF injection normalized the waveform as well as the level of LPP. VD disrupted histological structure of EUS and SVF failed to differentiate into striatal muscles. Instead, SVF increased α-SMA positive cells and collagen synthesis but the phenomena depended on VD stimulus. GFP tracking indicated that the transplanted SVF cells persisted for four weeks and synthesized α-SMA protein simultaneously. CONCLUSIONS: Autologous transplantation of adipose SVF displayed bulking effects through collagen synthesis. However, such heterotopic activation was dependent on tissue damage.

Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic inflammatory disease that affects the bladder. The symptoms of IC vary, including feeling an urgent need for immediate urination and of needing to urinate often, as well as bladder or pelvic pain. Despite its high incidence, no molecular diagnostic methods are available for IC, and the molecular pathogenesis is unknown. microRNAs (miRNA) can regulate expression of RNA transcripts in cells and aberrant expression of miRNAs is associated with several human diseases. Here, we investigated the molecular pathogenesis of IC based on miRNA expression signatures. RNA sequencing of miRNA levels in IC tissues and comparison with levels in normal bladder tissue and bladder cancer revealed dysregulated expression of 366 miRNAs (203 and 163 down- and upregulated miRNAs, respectively). In particular, miR-320 family miRNAs(miR-320a, miR-320b, miR-320c, miR-320d and miR-320e) had downregulated expression in IC tissues. Genome-wide gene expression analyses and in silico database analyses showed that three transcription factors, E2F-1, E2F-2 and TUB, are regulated by miR-320 family miRNAs. Immunostaining of IC tissues confirmed that these transcription factors are overexpressed in IC tissues. Novel approaches that identify aberrantly expressed miRNA regulatory networks in IC could provide new prognostic markers and therapeutic targets for this disease.

OBJECTIVES: To show the efficacy of propiverine hydrochloride in the management of symptoms of stress urinary incontinence in female patients with mixed-type urinary incontinence. METHODS: The study was carried out as a multicenter single-arm clinical trial at 64 institutions in Japan. The participants were female patients aged ≥20 years with mixed-type urinary incontinence. The frequency of stress urinary incontinence and urgency urinary incontinence was evaluated at baseline and 4, 8 and 12 weeks after treatment with propiverine hydrochloride. Subjective symptoms were evaluated using the Overactive Bladder Symptom Score and the International Consultation on Incontinence Questionnaire-Short Form. Functional urethral length and maximum urethral closing pressure were also measured at baseline and 12 weeks after treatment at the institutions where the urethral pressure profile was taken. RESULTS: In total, 49 mixed-type urinary incontinence patients were enrolled in the present study. The number of cases of urgency urinary incontinence was reduced time-dependently, which showed statistically significant differences between baseline and 4, 8 and 12 weeks after treatment. A similar statistically different reduction was also observed for stress urinary incontinence. The mean reduction rates of urgency urinary incontinence and stress urinary incontinence at 12 weeks after treatment were 63.9% and 44.3%, respectively. The total scores of International Consultation on Incontinence Questionnaire-Short Form and Overactive Bladder Symptom Score were gradually reduced, and the differences were statistically significant. Functional urethral length and maximum urethral closing pressure at 12 weeks after treatment did not show any statistical differences compared with those at baseline. CONCLUSIONS: Propiverine hydrochloride can be an effective therapeutic option for stress urinary incontinence in patients with mixed-type urinary incontinence.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.

OBJECTIVES: To characterize interstitial cystitis pathology based on the expression profile of urothelial tissue-specific master transcription factors. METHODS: Bladder carcinoma cell lines derived from the urothelial stem cells (epithelial or mesenchymal) were used to identify candidate urothelial master transcription factors. Gene expression was measured with quantitative reverse transcription polymerase chain reaction. From the initial screening of 170 transcription factors (human homologs of Drosophila segmentation genes and known master transcription factors from a database), 28 transcription factors were selected. Subsequently, messenger ribonucleic acid from bladder biopsies of interstitial cystitis patients was purified, and gene expression levels of known urothelial marker genes and candidate master transcription factors were measured. Multivariate expression data were analyzed with spss software. RESULTS: Factor analysis decomposed the expression profile into four axes: principal axis 1 included retinoic acid receptors and 17 candidate master transcription factors. Principal axis 2 included KRT5 and five candidates. Principal axis 3 included transcription factor TP63 and two candidates. Principal axis 4 included SHH and two candidates. Principal component analysis segregated biopsies from Hunner's lesion in the principal component 1 (retinoic acid)/principal component 2 (SOX13)/principal component 3 (TP63) space. CONCLUSIONS: Urothelial master transcription factors could serve as novel diagnostic markers and potentially explain the molecular pathology of interstitial cystitis.

In a 68-year-old man on maintenance hemodialysis (HD), severe anemia was detected. Bone marrow biopsy was performed for investigation of pancytopenia and pathological examination revealed adenocarcinoma of the prostate. Prostate specific antigen (PSA) was 574 ng/mL. After androgen deprivation therapy was initiated, PSA decreased to 13.7 ng/mL. But subsequent elevation of PSA and pain due to bone metastases were recognized. Denosumab (120 mg) was administered. Although improvement of bone pain was observed, severe hypocalcemia occurred. Severe hypophosphatemia was subsequently detected. When we use denosumab in dialysis patients with advanced cancer, we should be careful of hypophosphatemia.

We report a rare case of extravasation of urine, which may be associated with bilateral complete ureteral duplication, vesicoureteral reflux (VUR), and benign prostatic hyperplasia (BPH). A 71-year-old male presented with a complaint of right abdominal pain. An extravasation of urine was noted, and was improved by indwelling urethral catheterization. Transurethral resection of the prostate and the endoscopic subureteral injection of dextanomer/hyaluronic acid were performed for the treatment of BPH and VUR, respectively. The post-surgery recovery was successful.

OBJECTIVES: To investigate the factors for continuation or withdrawal as an extension of a prospective study of silodosin monotherapy for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia for more than 6 years. METHODS: A total of 104 patients (age 71.5 ± 8.2 years) were enrolled in the present study. The mean prostate volume was 44.1 ± 23.9 mL. International Prostate Symptom Score, quality of life index, maximum flow rate, and postvoid residual urine volume were determined at baseline, and at 1, 3, 6 and 12-72 months after treatment. RESULTS: Adverse events were noted in 14 patients (13.5%), and the most frequent adverse event was ejaculatory dysfunction (5.8%). Withdrawal was noted in 78 patients, and 26 patients (25.0%) were still taking silodosin at 72 months (continuing group). The reasons for withdrawals were: unknown in 27 patients (26.0%), adverse events in nine patients (8.7%), unsatisfactory effects in 30 patients (28.8%) and satisfied with the current condition for six patients (5.8%). In 30 patients who withdrew because of unsatisfactory effects, surgery was carried out in 21 patients (surgery group). The baseline total International Prostate Symptom Score did not differ between the continuing group and the surgery group. However, patients with the continuing group had significantly smaller baseline prostate volume, and lower baseline quality of life index and prostate-specific antigen, than in the surgery group. The mean total International Prostate Symptom Score, quality of life index and maximum flow rate improved significantly at 1 month, and remained stable up to 72 months. CONCLUSIONS: The withdrawal rate was higher in patients with a larger prostate. The effects of silodosin for lower urinary tract symptoms was immediate and stable up to 72 months.

Neuromodulation therapy incorporates electrical stimulation to target specific nerves that control lower urinary tract symptoms (LUTS). The objectives of this article are to review the mechanism of action, the type of neuromodulation, and the efficacy of neuromodulation mainly according to the results of randomized controlled trials. Neuromodulation includes pelvic floor electrical stimulation (ES) using vaginal, anal and surface electrodes, interferential therapy (IF), magnetic stimulation (MS), percutaneous tibial nerve stimulation, and sacral nerve stimulation (SNS). The former four stimulations are used for external periodic (short-term) stimulation, and SNS are used for internal, chronic (long-term) stimulation. All of these therapies have been reported to be effective for overactive bladder or urgency urinary incontinence. Pelvic floor ES, IF, and MS have also been reported to be effective for stress urinary incontinence. The mechanism of neuromodulation for overactive bladder has been reported to be the reflex inhibition of detrusor contraction by the activation of afferent fibers by three actions, i.e., the activation of hypogastric nerve, the direct inhibition of the pelvic nerve within the sacral cord and the supraspinal inhibition of the detrusor reflex. The mechanism of neuromodulation for stress incontinence is contraction of the pelvic floor muscles through an effect on the muscle fibers as well as through the stimulation of pudendal nerves. Overall, cure and improvement rates of these therapies for urinary incontinence are 30-50, and 60-90% respectively. MS has been considered to be a technique for stimulating nervous system noninvasively. SNS is indicated for patients with refractory overactive bladder and urinary retention.

The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (DO/BPH). Samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder), and those undergoing retropubic prostatectomy for BPH. All of the patients with DO/BPH had detrusor overactivity according to urodynamic studies. Detrusor muscle strips were mounted in 10-ml organ baths containing Krebs solution, and concentration-response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-DAMP, methoctramine, pirenzepine, tolterodine, solifenacin, trospium, propiverine, oxybutynin, and imidafenacin) or vehicle. All antagonists competitively antagonized concentration-response curves to carbachol with high affinities in normal bladder. The rank order of mean pA2 values was as follows: trospium (10.1) > 4-DAMP (9.87), imidafenacin (9.3) > solifenacin (8.8) > tolterodine (8.6) > oxybutynin (8.3) > propiverine (7.7) > pirenzepine (7.4) > methoctramine (6.6). The effects of these antimuscarinic antagonists did not change when tested with DO/BPH bladder, suggesting that each antimuscarinic antagonist has a similar effect in this condition. Schild plots showed a slope corresponding to unity, except for propiverine with DO/BPH detrusor. In conclusion, M3-receptors mainly mediate contractions in human bladder strips with normal state and DO/BPH.

OBJECTIVE: The outcome of trial of voiding without catheter in patients treated combination therapy with dutasteride and alpha1-adrenergic receptor blocker for acute urinary retention caused by benign prostatic hyperplasia was not reported. We evaluated the clinical efficacy of combination therapy with dutasteride in patients with unsuccessful trial without catheter after treatment with an alpha1-adrenergic receptor blocker monotherapy for acute urinary retention caused by benign prostatic hyperplasia. PATIENTS AND METHODS: Patients with acute urinary retention due to prostatic hyperplasia were catheterized and treated alpha1-adrenergic receptor blocker monotherapy. After two weeks later, patients were put on trial without catheter. 52 patients who were unsuccessful trial without catheter administered combination therapy with dutasteride and alpha1-adrenergic receptor blocker. We use criteria that voiding urine volume over 100 ml and post-void residual urine volume below 100 ml in deciding whether catheter should be removed. RESULTS: 33 (63.5%) men did not require re-catheterization within 7 months after combination therapy. The successful rate of Performance Status (PS) 0-1 group was significantly superior to that of PS 2-4 group. CONCLUSIONS: PS 0-1 men catheterized for AUR can void more successfully after catheter removal than PS 2-4 men if treated with combination therapy.