Tadalafil Improves Nocturia and Nocturia-Related Quality of Life in Patients with Benign Prostatic Hyperplasia (KYU-PRO Study).

INTRODUCTION: Tadalafil improves lower urinary tract symptoms (LUTS) including nocturia. However, the effect of tadalafil on the nocturia-related quality of life (QoL) is still unknown. OBJECTIVE: The effects of tadalafil on nocturia and nocturia-related QoL were evaluated prospectively in patients with benign prostatic hyperplasia (BPH) as a multicenter study. METHODS: Eligible men were ≥40 years with nocturia ≥2 and a prostate volume ≥20 mL. Patients were asked to complete a self-report questionnaire on the International Prostate Symptom Score (IPSS), the Nocturia Quality of Life questionnaire (N-QoL) and the International Index of Erectile Function 5 (IIEF5). Urinary frequency volume charts (FVCs) were also evaluated. These measures were evaluated at baseline, and after 4, 8, and 12 weeks of tadalafil administration (5 mg once daily). RESULTS: Thirty-one patients with a mean age of 74 years, a mean prostate volume of 31 mL, and a mean prostate-specific antigen level of 2.8 ng/mL were included. Treatment with tadalafil significantly improved their nocturia after 4 weeks, and these improvements were maintained for the 12-week treatment period. Total N-QoL score in new patients and several N-QoL items (inadequate sleep at night and overall bother) in all patients improved significantly after tadalafil treatment. FVCs revealed a significant improvement in the number of hours of undisturbed sleep (HUS) after treatment with tadalafil. No serious adverse events were observed. CONCLUSIONS: This study indicates that tadalafil 5 mg once daily improves nocturia, nocturia-related QoL, and HUS in BPH patients with nocturia. These results suggest that tadalafil can offer a clinically meaningful treatment option for BPH patients with nocturia.

Role of the serotonergic system in urethral continence reflexes during sneezing in rats.

To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT2C agonist) or LP44 (a 5-HT7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration. PCPA decreased A-URS by 35.1 cmH2O and UBP by 13.3 cmH2O compared with normal rats. In PCPA-administrated rats, CP-809101 increased A-URS by 24.1 cmH2O and UBP by 15.1 cmH2O, and LP44 also increased A-URS by 20.6 cmH2O and UBP by 11.4 cmH2O compared with rats treated with PCPA alone. SUI was observed with S-LPP of 40.1 cmH2O in PCPA-administrated rats, in which CP-809101 and LP44 increased S-LPP by 28.0 and 15.2 cmH2O, respectively, compared with rats treated with PCPA alone. The effects of CP-809101 and LP44 were antagonized by SB-242084 (a selective 5-HT2C antagonist) and SB-269970 (a selective 5-HT7 antagonist), respectively. These results indicate that activation of 5-HT receptors enhances the active urethral closure reflex during sneezing, at least in part via 5-HT2C and 5-HT7 receptors.

Tadalafil Improves Symptoms, Erectile Function and Quality of Life in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (KYU-PRO Study).

OBJECTIVES: Effect of tadalafil on lower urinary tract symptoms (LUTS), erectile function and quality of life (QoL) were prospectively evaluated in patients with benign prostatic hyperplasia (BPH) at multicenter. METHODS: Eligible men were ≥40 years who had no treatment with alpha-blocker for BPH, with total International Prostate Symptom Score (IPSS) ≥8, IPSS-QOL ≥2 and prostate volume ≥20 mL. Data were collected on age, body mass index (BMI), and prostate specific antigen (PSA). Patients were asked to complete a self-reported questionnaire regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), and Medical Outcome Study 8-Item Short-Form Health Survey (SF-8). These measures were assessed at baseline, 4-, 8-, 12-week of tadalafil treatment. In addition, uroflowmetry was also performed at baseline, and 12-week end point visit. RESULTS: Thirty five patients with mean age 67.3 years, mean BMI 23.6 kg/m2 , mean prostate volume 36 mL, and mean PSA 3.4 ng/mL were enrolled. Treatment with tadalafil significantly improved IPSS total score, IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS-QoL score after 4 weeks and these improvements were maintained for 12-week treatment period. IIEF5 score and general health in SF-8 are significantly improved with the treatment of tadalafil. However, maximum flow rate and postvoiding residual volume were not significantly changed. There were not any serious adverse events. CONCLUSIONS: These results indicate that tadalafil 5 mg once daily would be effective and well tolerated treatment in Japanese men with BPH-LUTS.

Laparoendoscopic single-site nephrectomy for hemodialysis patients with dialysis-related renal tumors.

PURPOSE: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors. MATERIAL AND METHODS: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n = 8) or conventional laparoendoscopic nephrectomy (C-N; n = 8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups. RESULTS: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0 ± 26.7 min versus 188.6 ± 36.4 min; p = .025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4 ± 14.4 ml versus 65.6 ± 45.2 ml; p = .047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group. CONCLUSIONS: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.

Effects of multiple simulated birth traumas on urethral continence function in rats.

Multiple vaginal parities have been reported to be an important risk factor for stress urinary incontinence (SUI). Simulated birth trauma with single vaginal distention (VD) has been used to induce the SUI condition in animals; however, the effect of multiple simulated birth traumas on the urethral continence function has not been well characterized. Therefore, we examined the effects of multiple VDs on urethral functions in vivo and the changes in gene expressions of several molecules in the urethra using female SD rats, which were divided into three groups; sham, VD-1 (single VD), and VD-3 groups (3 times of VDs every 2 wk). Two weeks after the final VD, leak point pressure (LPP) and urethral responses during sneezing were evaluated. Also, changes in mRNA levels of urethral molecules were quantified with RT-PCR.　The VD-1 group did not show any change in LPP with only a tendency of decrease in amplitudes of the urethral responses during sneezing (A-URS); however, the VD-3 group showed a significant decrease in LPP and urethral responses such as baseline urethral pressure and A-URS accompanied with SUI episodes during sneezing. Nicotinic receptor subtypes and transforming growth factor (TGF)-ß1 were significantly increased in both VD-1 and VD-3 groups while TNF receptor (TNFR)-1, IL-6, collagens, and matrix metalloproteinases-9 were significantly increased only in the VD-3 group.　These data indicate that rats with multiple simulated birth traumas exhibit profound impairment of the urethral continence function and that these functional changes are associated with those in cytokines, extracellular matrix molecules, and nicotinic receptor subtypes in the urethra.

Tumor necrosis factor-alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter.

OBJECTIVES: To examine the inhibitory effects of tumor necrosis factor-α on myogenic differentiation of human urethral rhabdosphincter cells. METHODS: A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin-dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human rhabdosphincter cells were induced for myogenic differentiation with recombinant human tumor necrosis factor-α and/or the tumor necrosis factor-α antagonist etanercept at different concentrations, and activation of signaling pathways was monitored. RESULTS: Human rhabdosphincter cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor-α treatment reduced the myosin heavy chain expression in a concentration-dependent manner, etanercept inhibited this suppression. Tumor necrosis factor-α suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and myosin heavy chain expression in a concentration-dependent manner. CONCLUSIONS: Tumor necrosis factor-α inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Inhibition of tumor necrosis factor-α might be a useful strategy to treat stress urinary incontinence.

Patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical laparoendoscopic single-site adrenalectomy.

INTRODUCTION: Laparoendoscopic single-site surgery is a recently innovated urologic surgical procedure. Transumbilical laparoendoscopic single-site adrenalectomy (LESS-A) is technically safe and feasible in patients with benign adrenal tumors. To improve patient counseling and informed consent, we evaluated patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical LESS-A. METHODS: We reviewed 24 patients who underwent transumbilical LESS-A and assessed their operative and esthetic outcomes and incisional pain. Incisional pain was evaluated using a 10-point visual analog scale, and the body image and cosmetic satisfaction were measured using a questionnaire that included a body image scale (range, 5-20 points) and a cosmetic scale (range, 3-24 points). RESULTS: Pure LESS-A was performed on 10 patients using a multichannel port; an additional 5-mm trocar was used in two obese patients. Supplementary to the single-incision approach, one or two 3-mm ports were used in 12 patients. The mean operative time was 203 min; the mean blood loss was 41 mL. The mean pain visual analog scale scores on postoperative days 1, 3, and 7 were 3.5, 2.2 (P = 0.012), and 1.5 points (P = 0.018), respectively. The mean body image scale and cosmetic scale scores indicating wound satisfaction 1 month after the surgery were 20 and 22 points, respectively. Although one patient had liver injury during surgery, the postoperative course during the 3-month follow-up was uneventful. CONCLUSION: Transumbilical LESS-A confers less postoperative pain and better cosmetic satisfaction than conventional laparoscopic adrenalectomy. Therefore, this procedure could potentially become a standard treatment option for benign adrenal tumors.

Pfannenstiel laparoendoscopic reduced-port radical nephrectomy.

INTRODUCTION: We previously reported cases of laparoendoscopic single-site nephrectomy performed through an umbilical or pararectal incision. To improve cosmesis and operability, we performed three Pfannenstiel laparoendoscopic reduced-port nephrectomies. MATERIALS AND SURGICAL TECHNIQUE: In the first case, a GelPOINT access was placed through a 2-cm umbilical incision, and two additional 3-mm trocars were inserted. The specimen was extracted through a 4-cm Pfannenstiel incision. In the second and third cases, a GelPOINT access was placed through a 5-cm Pfannenstiel incision, and two additional 3-mm trocars were inserted. The specimens were extracted without additional skin incisions. In all cases, the endoscope and vessel-sealing device were inserted through the GelPOINT access. We used 3-mm scissors, dissecting forceps, and bipolar forceps. DISCUSSION: The operating time and estimated blood loss were 228, 280, and 155 min and 10, 410, and 5 mL, respectively. There were no intraoperative or postoperative complications. The 3-mm forceps showed similar efficacy as the conventional 5-mm forceps. Therefore, a Pfannenstiel reduced-port nephrectomy using 3-mm working trocars is a safe and feasible procedure with good cosmesis.

IGF-1 as an Important Endogenous Growth Factor for Recovery from Impaired Urethral Continence Function in Rats with Simulated Childbirth Injury.

PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 µg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.

[MASSIVE HEMORRHAGE FROM THE FISTULA FORMATION BETWEEN CUTANEOUS URETEROSTOMY AND INFERIOR EPIGASTRIC ARTERY: A CASE REPORT].

A 87-year-old man received radical nephroureterectomy for right renal pelvic cancer in 2009 and left cutaneous ureterostomy after radical cystectomy for bladder cancer in 2013. He visited the hospital for exchanging a 7 or 8 Fr single-J catheter every 2 to 4 weeks. Eleven months after the 2nd operation, massive bleeding from the stoma occurred when ureteral catheter was exchanged. Contrast-enhanced computed tomography showed that left inferior epigastric artery was located close to left ureter. Angiography of the left inferior epigastric artery didn't show an obvious fistula, but revealed the stoma was surrounded by ramified new blood vessels from left inferior epigastric artery. We suspected a rupture of the vessels and performed embolization for the branch of inferior epigastric artery to left ureter. This embolization made it possible for the bleeding to be controlled. Massive bleeding from the branch of inferior epigastric artery is very rare, and we report the case and review the literature.

Rapidly progressive primitive neuroectodermal tumor of the prostate: A case report and review of the literature.

The present study reports a rare case of primitive neuroectodermal tumor (PNET) of the prostate. A 23-year-old male presented to Oita Medical Center (Oita, Japan) with the complaint of dysuria and anal pain. A large mass in the prostate and a number of swollen lymph nodes in the pelvic region were identified by a computed tomography scan and magnetic resonance imaging. The patient was, thus, admitted to Oita University Hospital (Yufu, Japan), where a biopsy of the prostate gland was performed. Histological analysis revealed small round cells that were positive for MIC-2 expression and fluorescent in situ hybridization analysis detected a translocation involving Ewing sarcoma breakpoint region 1 at chromosome 22q12. Thus, a diagnosis of PNET of the prostate was established. Systemic chemotherapy was the selected treatment, however, a poor response was obtained. The patient succumbed approximately four months after the initial onset of symptoms. PNET of the prostate has been reported in eight cases worldwide; in comparison, the present case exhibited the most unsatisfactory outcome.

A case of urethral duplication arising from the posterior urethra to the scrotum with urinary stone in a 6-year-old male.

Urethral duplication is a rare congenital anomaly. We report a 6-year-old male with type IIA2 (Y-type) using Effmann's classification. The accessory urethra, in which a urinary stone existed, arose from the posterior urethra to the scrotum. Because of recurrent urinary tract infection and urinary discharge from the accessory urethra, surgical removal of the accessory urethra through a scrotal incision was performed. At 7-month postoperative follow-up the patient was completely free from urinary incontinence and urinary tract infection.

Life-threatening rupture of an external iliac artery pseudoaneurysm caused by necrotizing fasciitis following laparoscopic radical cystectomy: a case report.

BACKGROUND: Pseudoaneurysms are caused by trauma, tumors, infections, vasculitis, atherosclerosis and iatrogenic complications. In this paper, we report about a patient with rupture of an external iliac artery pseudoaneurysm, which lead to hemorrhagic shock, after undergoing laparoscopic radical cystectomy and extended pelvic lymphadenectomy. CASE PRESENTATION: The patient was a 68-year-old Japanese male diagnosed with invasive bladder cancer. Laparoscopic radical cystectomy and extended pelvic lymphadenectomy were performed. On postoperative day 12, he developed a high fever and an acute inflammatory response with redness and swelling in the right inguinal region. He was diagnosed with necrotizing fasciitis and underwent debridement. On postoperative day 42, a sudden hemorrhage developed from the open wound in the right inguinal region. He was diagnosed with external iliac artery pseudoaneurysm rupture by computed tomography. CONCLUSION: These complications occur extremely rarely after cystectomy with pelvic lymphadenectomy. There are no reports to date on these complications following laparoscopic cystectomy with pelvic lymphadenectomy.

Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer.

Heat shock proteins (HSPs), which are molecular chaperones that stabilize numerous vital proteins, may be attractive targets for cancer therapy. The aim of the present study was to investigate the possible anticancer effect of single or dual targeting of HSP90 and HSP70 and the combination treatment with HSP inhibitors and chemotherapeutic agents in bladder cancer cells. The expression of HSP90 and the anticancer effect of the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) coupled with cisplatin, docetaxel, or gemcitabine were examined using immunohistochemistry, quantitative real-time PCR, cell growth, flow cytometry, immunoblots and caspase-3/7 assays. The expression of HSP70 under HSP90 inhibition and the additive effect of HSP70 inhibitor pifithrin-µ (PFT-µ) were examined by the same assays and transmission electron microscopy. HSP90 was highly expressed in bladder cancer tissues and cell lines. 17-AAG enhanced the antiproliferative and apoptotic effects of each chemotherapeutic agent. 17-AAG also suppressed Akt activity but induced the upregulation of HSP70. PFT-µ enhanced the effect of 17-AAG or chemotherapeutic agents; the triple combination of 17-AAG, PFT-µ and a chemotherapeutic agent showed the most significant anticancer effect on the T24 cell line. The combination of 17-AAG and PFT-µ markedly suppressed Akt and Bad activities. With HSP90 suppression, HSP70 overexpression possibly contributes to the avoidance of cell death and HSP70 may be a key molecule for overcoming resistance to the HSP90 inhibitor. The dual targeting of these two chaperones and the combination with conventional anticancer drugs could be a promising therapeutic option for patients with advanced bladder cancer.

Therapeutic effects of IGF-1 on stress urinary incontinence in rats with simulated childbirth trauma.

PURPOSE: We examined the effect of IGF-1 in a rat model of stress urinary incontinence induced by simulated childbirth trauma. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. Four, 7, 14 and 28 days after distension we performed functional assessment by measuring leak point pressure, urethral baseline pressure and the urethral response during a passive increment in intravesical pressure. The expression of IGF-1 and IGF1R mRNA and protein in damaged tissues was examined by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Thereafter hrIGF-1 (50 and 150 µg/kg per day) was continuously delivered from 1 day before distension using subcutaneous osmotic pumps. Four and 7 days after distension the effect of hrIGF-1 treatment was examined by functional analysis of leak point pressure, urethral baseline pressure and the urethral response as well as Western blot and histological analysis. RESULTS: After 4 and 7 days rats with vaginal distension had significantly decreased leak point pressure, urethral baseline pressure and urethral responses. IGF-1 and IGF1R mRNA and protein levels were significantly increased in urethral and pudendal nerves 4 and 7 days after distension. IGF-1 treated groups showed significant improvement in leak point pressure, urethral baseline pressure and urethral responses 4 and 7 days after distension. Moreover, IGF-1 treatment increased Akt phosphorylation and induced cellular proliferation and antiapoptotic effects in the urethra. CONCLUSIONS: IGF-1 treatment accelerated recovery from stress urinary incontinence induced by simulated childbirth trauma in association with activation of the Akt signal transduction pathway in rats. This suggests that IGF-1 has therapeutic potential for stress urinary incontinence in women.

Inhibitory role of the spinal cholinergic system in the control of urethral continence reflex during sneezing in rats.

AIMS: The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats. METHODS: Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined. RESULTS: Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist). CONCLUSIONS: These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing.

Regenerative medicine as a new therapeutic strategy for lower urinary tract dysfunction.

The use of regenerative medicine for the treatment of organic and functional disorders intractable to conventional treatment has increased worldwide. This innovative medical field might particularly hold promise for the treatment of life-threatening diseases or healing of irreplaceable organs, such as the heart, liver and brain. Dysfunction of the urogenital tract and associated organs other than the kidney might not have immediate life-threatening implications; furthermore, the effectiveness of alternative therapy, such as enterocystoplasty for bladder cancer, has been shown. Therefore, most physicians or scientists do not give much importance to these disorders. However, urological disease has increased in developed societies in recent years. Furthermore, medical costs have also escalated. Disorders of the lower urinary tract, such as urinary disturbance or incontinence, can lead to other complications, impairing quality of life and ultimately increasing short- and long-term medical expenses. Regenerative medicine might hold potential solutions to these problems. Recent advances in urogenital regenerative medicine are reviewed in the present article, with particular reference to lower urinary tract reconstruction. The potential of regenerative medicine for the treatment of intractable lower urinary tract dysfunction compared with conventional treatment is also discussed.

Myostatin inhibits proliferation of human urethral rhabdosphincter satellite cells.

OBJECTIVES: Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. METHODS: Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. RESULTS: Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. CONCLUSIONS: Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.