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Myxofibrosarcoma is common in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report herein a case of a 72-year-old male who presented with a 5-year history of right scrotal swelling and a month history of painful swelling in the scrotal area. Computed tomography scan revealed a scrotal tumor 5 cm in size and a tumor in the rectum. He subsequently underwent right high orchiectomy and rectal dissection with colostomy. The scrotal tumor was histopathologically diagnosed as a myxofibrosarcoma; the rectal tumor was a leiomyosarcoma. The patient underwent tumor resection for recurrence and left inguinal metastasis, but soon developed local recurrences and lymph node metastasis of the left iliac area. Chemotherapy with mesna, adriamycin, ifosfamide, and dacarbazine (MAID) resulted in partial remission. We report the rare case of myxofibrosarcoma in the spermatic cord for which chemotherapy with MAID was an effective treatment.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

Antimuscarinics improve detrusor overactivity. We evaluated the effects and action mechanisms of imidafenacin (Kyorin Pharmaceutical, Tokyo, Japan), a novel therapeutic agent for overactive bladder with antimuscarinic activity, on mediator release from urothelium and detrusor overactivity induced by cerebral infarction.Bladder hydrodistention was achieved by intravesical infusion of Krebs solution. Bladder adenosine triphosphate and prostaglandin E(2) were measured in the presence and absence of anticholinergics using luciferin-luciferase assay and enzyme-linked immunoassay, respectively. Cerebral infarction was induced in rats by occluding the left middle cerebral artery. The effects of intravenous imidafenacin on bladder function were examined using cystometry in rats with cerebral infarction and in those pretreated with resiniferatoxin.Increased intravesical adenosine triphosphate and prostaglandin E(2) were shown by induced distention of isolated rat bladders. Imidafenacin and darifenacin (Kemprotec, Middlesbrough, United Kingdom) significantly suppressed the increases in adenosine triphosphate and prostaglandin E(2). Decreased bladder capacity was observed in rats with cerebral infarction. Detrusor overactivity was suppressed with a minimum intravenous dose of 0.001 mg/kg imidafenacin. The effects of imidafenacin were not noted in rats pretreated with resiniferatoxin.Results support the hypothesis or suggest that imidafenacin improves cerebral infarction induced detrusor overactivity by suppressing peripheral C-fibers. This effect is thought to be associated with suppression of the release of adenosine triphosphate and prostaglandin E(2) from the urothelium.

Introduction. Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. Aim. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. Methods. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). Main Outcome Measure. The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Results. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Conclusions. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. Miwa Y, Nagase K, Oyama N, Akino H, and Yokoyama O. Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats. J Sex Med 2011;8:688–695.

Although invasive and expensive, the pressure-flow study is known as the reference standard for the diagnosis of bladder outlet obstruction. We investigated the usefulness of ultrasound-estimated bladder weight (UEBW) as a predictor of the need for surgery for benign prostatic hyperplasia (BPH).A total of 97 consecutive male patients50 years old with lower urinary tract symptoms (LUTS) were prospectively enrolled in this study. The surgery rate was correlated with the UEBW, the results of uroflowmetry, the postvoid residual urine volume, prostate volume, and International Prostate Symptom Score.Surgery for BPH was performed in 37 of the 97 patients studied. The surgery rate was associated with a high UEBW (or=35 g), severe LUTS (International Prostate Symptom Score ofor=20), a voided volume of100 mL at free uroflowmetry, and poor uroflow (maximal flow rate of10 mL/s). Multivariate analysis revealed that severe LUTS and a high UEBW were the risk factors for surgery for BPH.The results of our study have shown that the UEBW can be regarded as a useful parameter to identify patients with LUTS who are at risk of needing surgery for BPH.

OBJECTIVES Despite the well-known association between lower urinary tract symptoms (LUTS) and male sexual dysfunction, few data are available that describe the relationship between LUTS and sex hormones. The aim of this study was to investigate a possible association between the severity of LUTS and the serum levels of sex hormones in men. METHODS A total of 182 randomly selected men attending our general urology clinic were recruited. All participants completed the International Prostate Symptom Score (IPSS), and their sera were evaluated for serum levels of prostate-specific antigen, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone, follicle-stimulating hormone, prolactin, and estradiol. Storage symptoms were evaluated by the sum of IPSS questions 2, 4, and 7. Voiding symptoms were evaluated by the sum of IPSS questions 3, 5, and 6. The relationship between the IPSSs and serum hormone levels was determined. RESULTS On univariate analysis, the total IPSS was significantly associated with age, DHEA-S, and free testosterone. Storage symptoms were significantly associated with age, DHEA-S, free testosterone, and prostate-specific antigen. Voiding symptoms were significantly associated with age and DHEA-S. On multivariate linear regression analysis, only age was significantly associated with LUTS. However, within the subgroup of men 65-82 years old, DHEA-S was significantly associated with the total IPSS and storage symptoms. CONCLUSIONS In our study, the severity of LUTS was not associated with serum levels of sex hormones in men. However, in older men, storage symptoms could be affected by the serum DHEA-S level.

Alpha(1)-blockers improve voiding symptoms by decreasing prostatic and urethral smooth muscle tone. However, to our knowledge the mechanism underlying improvements in storage symptoms is not known. Topical application of prostaglandin E(2) to the rat lower urinary tract stimulates the micturition reflex. Using an animal model we investigated whether the alpha(1)-blocker tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and, if so, the location of this effect.To induce desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was subcutaneously injected in female Sprague-Dawley rats 2 days before experiments. Simultaneous recordings of urethral pressure and rhythmic bladder pressure were made with the rats under urethane anesthesia. Prostaglandin E(2) (0.4 mg/ml) was continuously administered intravesically or intraurethrally to rats pretreated with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment (nonresiniferatoxin rats). We investigated the effects on the micturition reflex of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1 nmol) administration of tamsulosin.The bladder contraction interval was markedly decreased after intravesical or intraurethral administration of prostaglandin E(2) in nonresiniferatoxin rats but it was unchanged in resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of tamsulosin significantly increased the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2) but it had no effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2). Intrathecal administration of tamsulosin produced a slight and insignificant increase in the bladder contraction interval in nonresiniferatoxin rats receiving intraurethral prostaglandin E(2).These results suggest that prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves, thereby improving bladder storage function.

Aims α1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an α1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. Methods To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. Results Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. Conclusions These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc.

We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated.Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats.These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

Purpose: The purpose of this study was to investigate the prognostic value of measuring glucose metabolism of primary prostate cancer lesions, using 2-Deoxy-2-[F-18]Fluoro-D-Glucose positron emission tomography (FDG-PET). Procedures: Forty-two patients with prostate cancer were investigated with FDG-PET, and standardized uptake value (SUV) of the prostate was calculated. After PET study, radical prostatectomy was performed in 17 patients (RPT group), and endocrine therapy in 25 patients (ET group). Relapse-free survival curves were created by the Kaplan-Meier method. Results: In the RPT group, the patients with high SUV had a poorer prognosis compared to those with low SUV (P = 0.033). In the ET group, the patients with high SUV were likely to have a poorer prognosis with low significance at a level of P = 0.087. Conclusions: FDG-PET appeared to have a defined prognostic value for patients with prostate cancer undergoing radical prostatectomy, and more patients need to be studied for patients undergoing endocrine therapy. (Mol Imag Biol 2002;4:99–104)

Although sunitinib shows a high response rate in patients with untreated metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic effect. Therefore, it is crucial to distinguish the patients who respond to sunitinib from those who do not as early as possible after the administration of the therapy. We herein report a case of mRCC in which (11)C-acetate (AC) positron emission tomography (PET) showed an early therapeutic effect of sunitinib treatment 4 weeks after its administration.

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 125I 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.

We report a rare case of a solitary adrenal metastasis from small cell carcinoma of the urinary bladder that was successfully treated with surgical resection. A 71-year-old man was suffering from bladder tamponade for hematuria. Computed tomography (CT) revealed a bladder tumor at the left wall. The patients underwent radical cystectomy. Histopathological results were obtained in small cell carcinoma of the bladder with muscle invasion. Thus, he received two courses of adjuvant etoposide and cisplatin chemotherapy, followed by the regimen for small cell lung cancer. Seven months after surgery, follow-up CT showed a gradually enlarged mass enhanced heterogeneously in the right adrenal gland. There was a solitary adrenal metastasis without any other metastasis; therefore, we performed right laparoscopic adrenalectomy. The patient has remained uneventful for four years after the adrenal gland surgery. For patients who have a solitary adrenal metastasis, adrenalectomy may provide a survival benefit.

Objectives. To compare the prognostic value of stereologically estimated volume-weighted mean nuclear volume (MNV) with other nuclear morphometric parameters using pretreatment needle-biopsy specimens of prostate cancer. Methods. The MNV, mean nuclear area, form factor, and coefficients of variation for nuclear area (VNA) and form factor were measured on pretreatment needle biopsy specimens from 66 patients with prostate cancer (clinical Stage B, n = 9; Stage C, n = 14; and Stage D, n = 43), all of whom underwent androgen deprivation therapy. The prognostic value of those morphometric parameters, as well as Gleason score and clinical stage, was examined in terms of cause-specific patient survival using univariate and multivariate analysis (Cox proportional hazard model). Results. Univariate analysis of the nuclear morphometric parameters revealed that MNV, mean nuclear area, VNA, coefficient of variation for form factor, and clinical stage were significant prognostic factors for cause-specific patient survival. However, when the patients with Stage D disease were selectively analyzed for survival, only the VNA was a significant prognostic parameter. Furthermore, the multivariate analysis, including the morphometric parameters, clinical stage, and Gleason score revealed that only VNA and clinical stage were independent variables. Conclusions. The present comparative study could not demonstrate any prognostic superiority of MNV over other nuclear morphometric parameters in patients with prostate cancer.

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Background: This study was conducted to determine if there are any specific histologic features that are associated with lymph node metastasis in renal cell carcinoma (RCC). Methods: TNM classification, histologic grade, mean nuclear volume, cell type, and histologic architecture of the tumors were evaluated in 66 patients who had undergone nephrectomy and lym-phadenectomy for RCC. In the 18 patients with positive lymph node metastasis, both primary lesions and metastatic lymph nodes were evaluated. Results: Lymph node status was correlated with primary tumor stage, venous involvement, and distant metastasis. The tumor grade was higher, and the mean nuclear volume was larger, in both primary and metastatic lesions of RCCs with lymph node metastasis than in tumors with no metastasis. In primary lesions of RCCs with lymph node metastasis, clear cell, alveolar, or cystic patterns were observed less frequently, and granular or spindle/pleomorphic cells and papillary or solid patterns, were observed more frequently, as compared to those lesions without metastasis. Comparison between primary and metastatic lesions in individual patients revealed no significant difference in grade or mean nuclear volume. The development of new cell types or histologic architectures, which was not noted in the primary lesions, was also a rare event in the metastatic lesions. Conclusion: Several characteristic histologic features, which may reflect the increased metastatic potential of the tumor, were observed in both primary and metastatic lesions in cases of RCC with lymph node metastasis. No substantial difference in histologic features was observed between the primary or metastatic lesions of individual patients.

BACKGROUND Although renal cell carcinoma (RCC) is often heterogeneous, the histological classification of RCC in Japanese Urological Association (JUA) is designed to select only the dominant histological components. We evaluated whether this system could provide an adequate information concerning the prognosis of the patients. METHODS Histological slides of 130 cases with RCC were microscopically evaluated. We classified these cases according to the JUA classification, and also checked the presence or absence of each histological components (3 cell types and 5 histological architectures) regardless of whether or not they were dominant. Univariate and multivariate analysis were then performed to determine the histological components which have prognostic impact on patient survival. RESULTS Multivariate analysis demonstrated that only spinde/pleomorphic cells and solid architecture were the significant prognostic parameters. The presence of these histological components was not correctly shown in the JUA classification. CONCLUSION The histological classification of RCC in JUA did not provide enough information about the presence of the important prognostic parameters. This system should be modified to describe all the histological components regardless of whether they are dominant or not.

The study aims to assess the usefulness of PET with C-acetate and F-FDG to differentiate renal cell carcinoma (RCC) from complicated renal cysts.Thirty-one patients were enrolled, 14 patients with complicated renal cysts (12 with Bosniak III and 2 with Bosniak IV) and 17 patients with 19 solid renal tumors. The patients underwent both C-acetate PET and FDG PET. Nephrectomy or partial nephrectomy was performed after the PET scans.In 29 patients, 32 renal lesions were diagnosed as RCC. Twenty-three of the 32 RCCs (72%) had positive C-acetate PET findings, whereas only 7 FDG PET studies were positive (22%). Considering the relationship between tumor size measured by macroscopic appearance of resected tumors and PET results, 22 of 25 (88%) tumors more than 1.5 cm showed positive C-acetate PET findings. In 12 patients with Bosniak III renal cysts, 10 renal lesions were diagnosed as RCC. In this subgroup, 5 of the 10 RCCs (50%) had positive C-acetate PET findings, whereas 2 RCCs (20%) had positive FDG PET findings. None of the cases with benign findings had positive C-acetate PET or FDG PET scans.C-acetate PET demonstrates a pronounced increase in tracer uptake in RCC, especially in renal tumors more than 1.5 cm, and displays a higher sensitivity than FDG PET. These preliminary data show that C-acetate may be a useful PET tracer to exclude RCC in complex renal cysts.

Background: Disease progression after Bacillus Calmette-Guerin (BCG) instillation therapy for bladder cancer is not rare. The purpose of this study was to evaluate the outcome of patients treated with BCG for superficial bladder cancer, focusing on the patients who developed invasive disease during follow-up. The possible mechanism and risk factors for early progression after BCG therapy are discussed. Methods: A total of 25 patients with superficial bladder cancer (pTa, pT1, and/or pTis) were treated with intravesical BCG instillation (80 mg in 80 mL saline) once a week for eight weeks. Four of the 25 patients received maintenance therapy with BCG (once a month for 3 to 10 months). Patients were followed every three months and underwent cystoscopy, biopsy, and urinary cytology at these intervals. Disease progression was defined as invasion to muscle or prostate, or development of metastatic disease. Clinicopathological features of the patients, especially those with progression, were analyzed. Results: Progression was observed in six of the 25 patients (including four of 19 patients with carcinoma in situ and two of five patients treated prophylactically with BCG). The average time to progression was 8.7 months. Four patients died of cancer despite intensive treatment. Two patients are alive: one without evidence of disease after cystectomy and the other with metastatic disease. Conclusions: Proper patient selection, careful follow-up, and immediate aggressive therapy in case of progression were considered to be important factors to obtain satisfactory results with BCG therapy for bladder cancer.

acetylcholine (Ach, 10 to 3 x 10M) were added with various concentrations into organ bath to induce isometric contraction of the isolated rat seminal vesicles. The dose response curve of the isolated rat seminal vesicles reacting to PE and Ach, the inhibitory dose response curve to the different adrenergic antagonists (prazosin for 1, WB-4101 for 1a, Chloroethylclonidine CEC for 1b), muscarinic antagonists (atropine for M, pirenzepine for M1, methoctramine for M2, and 4-DAMP for M3) and cross-over reaction were recorded. The twitch pattern of SVSM contraction was analyzed according to its phasic and tonic components. RESULTS: PE and Ach could both achieve good contraction of rat seminal vesicle. The IC50 of prazosin and WB-4101 were far greater than that of CEC. The IC50 of 4-DAMP was very close to atropine. PE and Ach could cause different patterns of SVSM twitch. PE induced SVSM contraction had more tonic components, but Ach induced SVSM contraction had more phasic components. CONCLUSIONS: The predominant subtypes of adrenergic and cholinergic receptors on rat seminal vesicle are £ 1a and M3 respectively. Different drugs also cause different pattern of SVSM twitch. In our speculation, sympathetic effect is more dominant during emission stage to squeeze seminal fluid out; however, parasympathetic effect is more dominant during ejection stage and provides an anti-reflux effect on ejaculatory duct. Further studies for realizing physiology of ejaculation are worthy.

The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, carboplatin and gemcitabine in patients with advanced urothelial carcinoma, who have received prior cisplatin-based chemotherapy. Eligible patients had pathologically proven measurable metastatic urothelial carcinoma. Between April 2005 and May 2009, 8 patients with a mean age of 7 0 years were treated every 3 weeks with paclitaxel (200 mg/m² on day 1), carboplatin (AUC= 5/body on day 1) and gemcitabine (800 mg/m² on day 1 and 8). A total of 4 0 (median 4) cycles were administered. None of the 8 patients achieved a complete response(CR), but 3 patients (37. 5%) achieved a partial response (PR) and 3 were stable with the disease(SD). The median overall survival time and the median progression-free survival time were 8. 0 and 4. 5 months, respectively. Grade 4 hematological toxicities included neutropenia in 6 cycles (15. 0%), thrombocytopenia in 8 cycles (20. 0%) and anemia in 11 cycles (27. 5%). Three of the 8 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of paclitaxel, carboplatin and gemcitabine was effective, and an acceptable treatment for patients with advanced urothelial carcinoma who have received prior cisplatin-based chemotherapy.

A 58-year-old woman presented to our emergency room with cystitis-like symptoms and macroscopic hematuria. Her symptoms were improved by the administration of an antibiotic, but transabdominal ultrasonography revealed a mass in her pelvis. The pelvic magnetic resonance imaging (MRI) depicted a solid tumor in the retropubic space. The patient requested hasty surgical excision of the tumor, rather than the conservative treatment after the diagnosis by cytology and biopsy. The postoperative histopathological examination revealed nodular fasciitis. She has been followed up for 8 months without any evidence of local recurrence. Nodular fasciitis is a mesenchymal lesion of proliferated fibroblast and commonly occurs in the subcutaneous tissue of the extremities. Frequently, it resembles a sarcoma, but it is said to be a benign disorder. In the urological domain, 14 intravesical cases have been reported. To our knowledge, this is the first case of the nodular fasciitis arising in the pelvis. We report this case and discuss the literature.

In the present study, we used animal models to investigate whether the selective α(1A)-blocker silodosin exerts inhibitory effects on detrusor overactivity by modulating C-fiber afferent activity.To desensitize C-fiber afferents, 0.3 mg/kg of resiniferatoxin (RTX) was subcutaneously injected into some female Sprague-Dawley rats 2 days before creation of each model. (1) Left middle cerebral artery occlusion was performed to create a cerebral infarction (CI) model (CI rats). The effects of intravenous (i.v.) and intrathecal (i.t.) administrations of silodosin on cystometrography parameters were evaluated in conscious rats. (2) Rhythmic bladder pressure was recorded in rats under urethane anesthesia. Prostaglandin (PG) E(2) (0.4 mg/mL) was continuously administered intraurethrally, and the effects of intra-arterial (i.a.) silodosin on the micturition reflex (MR) were investigated.(1) Silodosin (i.v.) dose-dependently increased bladder capacity (BC) in CI rats without decreasing bladder contraction pressure, but had no effects on BC in RTX-CI rats. Silodosin (i.t.) markedly increased BC in CI rats, but not in RTX-CI rats. (2) After intraurethral administration of PGE(2), the bladder contraction interval (BCI) was markedly reduced in non-RTX rats, but unchanged in RTX rats. Silodosin (i.a.) significantly prolonged BCI in non-RTX rats receiving intraurethral PGE(2).These results suggest that the α(1A)-AR subtype activates C-fiber afferents, and that consequently α(1A)-blockade can improve bladder storage function.

The pathophysiology in the development of overactive bladder syndrome (OAB) possibly due to benign prostatic hyperplasia (BPH) has not fully been understood. The clinical study in male outpatients aged over 50 years with lower urinary tract symptoms showed that the frequency of urgency was significantly associated with aging, bladder outlet obstruction (BOO) and benign prostatic enlargement (BPE). From the results of the experiments we did using rats, the mechanisms underlying the development of OAB were suggested as follows. The functional impairment of acetylcholine neuron in the central nervous system is induced by aging and decreases the bladder capacity. Non-voiding contractions of the bladder may have some bearing on OAB associated with BOO. The C-fiber in the urethra may be involved in the generation of the detrusor overactivity associated with BPE. These results showed that the pathophysiology of OAB related to BPH is quite complex, suggesting that a multidisciplinary approach is necessary for the treatment.

Increase in bladder mucosal permeability can be reproduced by intravesical administration of protamine sulfate (PS); however, the influence of PS once administered into the bladder disappears within several days. We developed a chronic animal model of urothelial injury using PS. Insertion of a polyethylene catheter through the bladder dome was performed in female Wistar rats. The other end of the catheter was connected to an osmotic pump for continuous delivery of PS or vehicle for 2 wk. Urinary frequency (UF) and voided volume (VV) were measured in the metabolic cage. The fifth group of rats received a high dose of PS (10 mg/ml) for 2 wk and were followed for a further 2 wk without PS. The sixth group received a high dose of PS for 2 wk and loxoprofen (0.1 mg·kg−1·day−1) for 4 wk. UF was increased, and VV was reduced in rats treated with a high dose of PS but not changed in rats treated with a vehicle or a low dose of PS (1 mg/ml). UF was further increased in the fifth group, while unchanged in the sixth group. Histological sections in rats treated with a high dose of PS demonstrated a loss of the upper layer of urothelial cells and an increased number of mast cells. PGE2 level in the bladder was significantly elevated in the fifth group. These results indicate that chronic urotherial injury leads to an increase in UF and a decrease in VV. Increased PGE2 level in the bladder is likely to be associated with long-lasting storage dysfunction.

Muscarinic receptor antagonists are used clinically for their therapeutic peripheral effects on bladder function. However, these agents may also act on central muscarinic receptors, especially in individuals with compromised blood–brain barrier function. We compared the effects of atropine and tolterodine, agents that do and do not readily cross the blood–brain barrier, respectively, administered peripherally (intravenous [i.v.]) and centrally (intracerebroventricular [i.c.v.]) on cystometrography in conscious rats after cerebral infarction induced by middle cerebral artery occlusion or sham surgery. We hypothesized that tolterodine would produce greater improvement in bladder capacity and less impairment in bladder contractility and that the effects of both agents would be greater in rats with cerebral infarction and sham-operated rats after peripheral administration, but that tolterodine and atropine would exert similar effects after central administration. Bladder capacity was markedly reduced following cerebral infarction. Low-dose i.v. tolterodine (≤ 20 nmol/kg) significantly reversed this effect without altering residual volume or bladder contraction pressure. Low-dose i.v. atropine (2 nmol/kg) had no effect on bladder capacity but significantly decreased bladder contraction pressure. Higher doses of i.v. atropine (≥ 20 nmol/kg) significantly increased bladder capacity but also significantly increased residual volume and decreased bladder contraction pressure. Tolterodine was significantly more efficacious than atropine in increasing bladder capacity, whereas atropine produced significantly greater increases in residual volume and reductions in bladder contraction pressure; these treatment group differences were also observed in sham-operated animals. Tolterodine and atropine administered i.c.v. significantly increased bladder capacity following cerebral infarction or sham surgery; however, this was accompanied by significantly increased residual volume and decreased bladder contraction time. The decrease in bladder contraction time was significantly smaller after tolterodine vs atropine. Peripherally acting muscarinic receptor antagonists may be preferable to centrally acting agents for minimizing adverse events, such as incomplete bladder emptying, even in individuals with compromised blood–brain barrier function.

Antimuscarinic drugs increase bladder capacity without prominent side effects such as urinary retention even when administered to patients with mild to moderate bladder outlet obstruction. Some mechanisms might exist in the urethra to compensate for the emptying function of the detrusor after the administration of antimuscarinic drugs. We investigated the influence of the antimuscarinic drug propiverine (Taiho Pharmaceutical, Tokyo, Japan) on urethral function.Urethral pressure and rhythmic bladder pressure were simultaneously monitored in urethane anesthetized female Sprague-Dawley rats. Prostaglandin E(2) was continuously administered intravesically or intraurethrally to induce detrusor overactivity. To eliminate the influence of bladder activity and monitor urethral baseline pressure isovolumetric pressure of the urethra was then recorded after cystectomy and ligation of the external urethral meatus. Furthermore, in vitro contractile responses of the urethral circular smooth muscle to field stimulation were examined in the presence of propiverine, tamsulosin (Taiho Pharmaceutical), verapamil, omega-conotoxin and atropine (Sigma).Intravesical or intraurethral administration of prostaglandin E(2) significantly decreased the bladder contraction interval by 10.7% and 36.0%, respectively. Intra-arterial administration of 2 x 10(2) nM/kg propiverine significantly increased the bladder contraction interval in rats receiving intraurethral prostaglandin E(2) by 81.8% but it had no marked effect on rats receiving intravesical prostaglandin E(2). Significant decreases in urethral baseline pressure were found after propiverine administration. Field stimulation induced contraction was inhibited by propiverine and verapamil but not by tamsulosin, omega-conotoxin or atropine.These results suggest that the inhibitory effects of propiverine are more prominent in rats with detrusor overactivity induced by intraurethral prostaglandin E(2) than by intravesical prostaglandin E(2). Propiverine may compensate for detrusor function by decreasing urethral resistance in the voiding phase.

Introduction Partial androgen deficiency of the aging male (PADAM) is defined as a biochemical syndrome associated with advancing age that is characterized by a deficiency in serum androgen levels. The Aging Males’ Symptoms (AMS) Scale was developed to evaluate PADAM‐related symptoms and is currently used worldwide; however, it has been reported that PADAM‐related symptoms evaluated by this scale are not related to serum testosterone levels. In addition to testosterone, the levels of other hormones also decrease with age; therefore, multihormone alterations may influence PADAM‐related symptoms. Aim To investigate the relationship between PADAM‐related symptoms evaluated by the AMS Scale and serum levels of testosterone, estradiol (E2), luteinizing hormone (LH), follicle‐stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEA‐S), and growth hormone (GH) in men. Methods A total of 141 ambulatory men were recruited after excluding men with endocrine and other related diseases. All participants completed the AMS questionnaire and an analysis of serum levels of total and free testosterone (TT and FT), E2, LH, FSH, DHEA‐S, and GH. Main Outcome Measure The relationship between AMS scores (total and subscores) and serum hormone levels was determined. Results There were significant negative correlations between age and serum FT and DHEA‐S levels, as well as positive correlations between age and serum LH and FSH levels, but no correlation between age and AMS scores. None of the three AMS domain scale scores and total scores significantly correlated with serum levels of TT, FT, E2, LH, FSH, DHEA‐S, or GH. Conclusions The results of the present study suggest that PADAM‐related symptoms as evaluated by the AMS Scale are not significantly related to serum levels of TT, FT, E2, LH, FSH, DHEA‐S, or GH. Because many factors related to aging are thought to contribute to the occurrence of PADAM‐related symptoms, the AMS Scale may not be able to predict serum hormone levels. Miwa Y, Kaneda T, and Yokoyama O. Correlation between the Aging Males’ Symptoms Scale and sex steroids, gonadotropins, dehydroepiandrosterone sulfate, and growth hormone levels in ambulatory men. J Sex Med 2006;3:723–726.

The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity.Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON.Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P0.05). In decerebrated rats, low dose of DON did not change micturition parameters.These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

Objectives. To perform pelvic venoablation with ethanol injection into the deep dorsal vein for the treatment of 10 patients with venogenic erectile dysfunction. This procedure was easily performed without any selective embolization technique. The efficacy and safety of this technique are discussed. Methods. A total of 10 patients with veno-occlusive dysfunction, severe enough to make vaginal insertion impossible, underwent pelvic venoablation with ethanol. The mean patient age was 67.1 years. Under spinal anesthesia, after the venous leaks were identified by cavernosography, a 20-gauge flexible needle was inserted into the deep dorsal vein. The pelvic venogram obtained with deep dorsal venography was included in what was revealed by the venogram obtained with cavernosography. A mixture of absolute ethanol and contrast medium (4:1) was used as a sclerosing agent. Under fluoroscopic control, the sclerosing agents were injected into the deep dorsal vein through a flexible needle. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. Results. The follow-up ranged from 25 to 37 months (mean 32.3). At the short-term follow-up visit (less than 6 months), 7 patients (70%) reported erections sufficient for vaginal insertion; at the long-term follow-up visit, 5 men (50%) reported sustained, sufficient potency and 5 (50%) reported persistent erectile dysfunction. No serious complications occurred. Conclusions. Our pelvic venoablation technique using ethanol was effective, minimally invasive, and cost-effective.

Objectives. To compare nuclear morphometric values and Gleason scores between biopsy and radical prostatectomy specimens in patients with clinically localized prostate cancer. Methods. The mean nuclear area (MNA), volume-weighted mean nuclear volume (MNV), and form factor (FF) were measured on the 18-gauge needle biopsy and radical prostatectomy specimens of 25 patients with clinically localized prostate cancer. The correlation between biopsy and surgical specimens was investigated for MNA, MNV, FF, and Gleason scores. Results. The average values for the MNA, MNV, and FF of the biopsy specimens (36.2 μm 2 , 366 μm 3 , and 0.86, respectively) were significantly smaller than those of the prostatectomy specimens (51.4 μm 2 , 646 μm 3 , and 0.91) by Student’s paired t test. The Pearson correlation of morphometric parameters between the biopsy and surgical specimens was significant only for FF. A comparison of histologic grading between the biopsy and surgical specimens revealed identical Gleason scores in 32% and identical grades (on a three-grade system) in 68% of all the cases. Conclusions. Discrepant nuclear morphometric results were observed between biopsy and surgical specimens of localized prostate cancer. The reason for such differing results is unclear but may be caused by artifacts associated with tissue sampling and processing. It is recommended that data obtained by biopsy should be considered separately from that obtained from surgical specimens.

differential gel electrophoresis followed by MS to identify proteins) to compare expression of genes and proteins between bladders of STZinduced diabetic rat and age matched non-diabetic controls. Oxidative damage of proteins was assessed by detection of carbonylation of proteins using OxyBlot and changes in ubiquitination and autophagy were determined using antibodies against -ubiquitin and LC3. RESULTS: Pathway analysis of genomics and proteomics data showed that targets involved in production of reactive oxygen species (ROS) are statistically enriched in the diabetic bladder compared to control (p = 1.27E-10 and p = 1.37E-03 for genomics and proteomics, respectively). In addition, OxyBlot analysis demonstrated that in the bladder of STZ-diabetic animals oxidatively damaged proteins were increased compared to non-diabetic controls. In addition major pathways degrading oxidatively damaged proteins (protein ubiquitinationproteasome and lysosomal pathways) were changed in the bladder of STZ-treated animals. The ubiquitinated proteins and short LC3 (a marker for lysosomal autophagy) decreased in the diabetic bladders compared to control, consistent with the proteomic and genomic data. CONCLUSIONS: Overall, these results suggest there are changes in the oxidative stress status in the diabetic bladder, accompanied with changes in pathways leading to degradation of oxidatively damaged proteins. These changes may contribute to the development of diabetic pathology and therefore represent targets for treatment strategies.