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Objective Mirabegron, a β 3 -adrenoceptor agonist, has been shown to be effective and safe in the treatment of overactive bladder (OAB). The aim of this study was to assess the efficacy and safety of mirabegron (50 mg) versus placebo in Taiwanese patients with OAB. Materials and patients This was a multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled trial conducted at 12 sites in Taiwan. Patients were randomized in a 1:1:1 ratio to receive placebo, mirabegron (50 mg), or tolterodine extended release (4 mg) orally once daily for 12 weeks. The primary efficacy end point was the change in the mean number of micturitions per 24 hours from baseline to the final visit. Secondary end points were volume voided, and the number of urgency, urinary incontinence, urge incontinence, and nocturia episodes per 24 hours; in addition, the King's Health Questionnaire (KHQ) was administered to assess effects on quality of life. Results A total of 218 patients were included in the full analysis set (68 in the placebo group; 76 in the mirabegron group; and 74 in the tolterodine group). The adjusted mean difference between the mirabegron and placebo groups for the change in mean number of micturitions per 24 hours was −1.42 ( p = 0.004). The adjusted mean difference between the mirabegron and placebo groups with regard to the change in volume voided per micturition was 16.7 mL ( p = 0.013). However, the mirabegron group did not show statistically significant superiority to the placebo group in the other efficacy variables. There was also no statistically significant difference between mirabegron and placebo in any KHQ domain score. The incidence of treatment-emergent adverse events in the mirabegron group was low and similar to that in the placebo group. Conclusion Mirabegron at a dose of 50 mg once daily for 12 weeks is superior to placebo in reducing the frequency of micturitions in Taiwanese patients with symptoms of OAB. No clinically relevant, serious adverse events were identified. [ABSTRACT FROM AUTHOR]

Summary Background We previously reported our initial experience with laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made single-port device and conventional straight laparoscopic instruments. Methods Between December 2010 and February 2012, LESS retroperitoneal partial adrenalectomies were performed in 11 patients. Six patients had aldosterone-producing adenomas (APAs) and five patients had nonfunctioning tumors. A single-port access was created with an Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) through an incision of 2–3 cm beneath the tip of the 12th rib. All procedures were performed with straight laparoscopic instruments. Results All LESS procedures were successfully completed without conversion to traditional laparoscopic conversion. The tumors ranged from 1 cm to 4.7 cm (mean, 2.3 cm). The operative time was 71–257 minutes (mean, 121 minutes). Most patients ( n = 8) had minimal blood loss; the other three patients had a blood loss of 150 mL, 100 mL, and 100 mL. The mean hospital stay was 3 days (range, 1–6 days). There were no perioperative or postoperative complications. Pathological examinations revealed negative surgical margins in all specimens. All patients with Conn's syndrome had an improvement in blood pressure and normalization of plasma renin activity and serum aldosterone levels; all patients were free of potassium supplementation. Conclusion Our results clearly demonstrate that LESS retroperitoneal partial adrenalectomy can be performed safely and effectively using a custom-made single-access platform and standard laparoscopic instruments. [ABSTRACT FROM AUTHOR]

Abstract: Background/purpose: To evaluate the efficacy of ketoconazole in castration-resistant prostate cancer. Materials and methods: We reviewed the medical records of consecutive patients with pathologically confirmed prostate cancer from May 2006 to December 2008. The inclusion criteria were: (1) receiving 200 or 400 mg ketoconazole three times daily and replacement doses of prednisolone; (2) antiandrogen withdrawal for at least 2 months before ketoconazole treatment; and (3) no prior cytotoxic agents or other CYP17 inhibitors. Treatment consisted of ketoconazole at 200 mg three times daily (Group A) and 400 mg three times daily (Group B). Patients'' characteristics, time to prostate-specific antigen (PSA) progression, duration of PSA response, and adverse events were evaluated. Results: Of the 37 patients in Group A, 14 (37.8%) experienced a PSA response. Of the seven patients in Group B, four (57.1%) experienced a PSA response. Median durations of time to progression in those who experienced a > 50% PSA decline were 7.5 and 11.5 months in Group A and Group B, respectively. Median duration of PSA response was 5.5 and 9.0 months in Group A and Group B, respectively. There was no difference in the PSA response or time to progression between the two groups. Orchiectomy had a borderline unfavorable effect on the PSA response rate (p = 0.067). Conclusion: The present study demonstrated that ketoconazole contributed to the PSA response in patients with castration-resistant prostate cancer. The efficacy and toxicity profiles were comparable to those in previous studies. Orchiectomy had a borderline unfavorable effect on PSA response rate. Further studies are required to confirm the efficacy of ketoconazole therapy in surgically castrated patients. [Copyright &y& Elsevier]

Background/Purpose: To evaluate the long-term oncological outcomes of hand-assisted retroperitoneoscopic radical nephrectomy (HARRN) for treating clinically localized renal cell carcinoma. Methods: We retrospectively collected and analyzed the data and clinical outcomes of 46 patients who underwent HARRN and 50 patients who underwent conventional open radical nephrectomy (ORN) at our institution for clinical localized renal cell carcinoma (RCC). Results: The median follow-up period of the HARRN group was 56.5 months (range: 14.6–78.7 months); for the ORN group, the median follow-up period was 110.8 months (range: 15.5–123 months). Patient age, sex, body mass index, pathologic parameters, and classification based on the guidelines of the American Society of Anesthesiologists were not significantly different between the two groups. The HARRN group had a significantly longer operative time (218 minutes vs. 178 minutes, p = 0.003) and less blood loss (203 mL vs. 670 mL, p < 0.001). The complication rates of the ORN and HARRN groups were similar (8% and 4.3%, respectively, p = 0.46). No conversions to an open procedure or intraoperative mortality occurred in the HARRN group. The disease-free and disease-specific survival rates were comparable between the two groups. Conclusion: The results of our study indicate that HARRN is a feasible, minimally invasive treatment for managing clinically organ-confined RCC with a good long-term oncological outcome. [ABSTRACT FROM AUTHOR]

Purpose: We studied bladder motor dysfunction and searched for markers of neurogenic and myogenic alterations among fructose fed rats with or without abnormal voiding behavior. Materials and Methods: Female Wistar rats were fed with a fructose rich diet (60%) or a normal diet for 6 months. Based on cystometry and voiding behavior the fructose fed rats were divided into 3 groups, including a group with normal detrusor function with normal micturition frequency, a group with detrusor overactivity with increased micturition frequency and a group with acontractile detrusor with increased micturition frequency. Denuded bladder tissues were obtained to assess in vitro detrusor contractility, postsynaptic receptors, smoothelin, nitrosative products and the intrinsic pathway of apoptosis. Results: Fructose fed rats with abnormal voiding behavior had obvious neurogenic and myogenic alterations, including increased expression of postsynaptic receptors, dysregulation of smoothelin and decreased expression of Bcl-2 with a subsequent increase in apoptotic cells in the bladder stroma, causing decreased carbachol induced contractility. Rats with detrusor overactivity were also insulted by nitrosative stress associated with nitrotyrosine up-regulation in the bladder tissue. Up-regulation of M2 and M3-muscarinic receptors, and P2X1 receptors appeared to be generalized alterations of fructose fed rats and not exclusive to those with detrusor overactivity. Conclusions: Up-regulation of postsynaptic receptors and dysregulation of smoothelin contribute to overactive bladder symptoms in rats with metabolic syndrome. Nitrosative stress and decreased Bcl-2 expression lead to bladder muscle cell loss via the intrinsic pathway of apoptosis, which may further deteriorate bladder function. [ABSTRACT FROM AUTHOR]

Background/purpose: Various antimuscarinic agents have been developed for the treatment of overactive bladder (OAB). More data comparing these agents are still required. This study evaluated the efficacy and safety of solifenacin and tolterodine in Taiwanese patients with OAB symptoms.Methods: This was a prospective, randomized, open-label study. A total of 75 patients (25 men and 50 women) with OAB symptoms were randomized to treatment with solifenacin (n = 39) or tolterodine (n = 36). Efficacy and safety variables were assessed and compared with the baseline and between the two groups.Results: At week 12, solifenacin and tolterodine demonstrated equal efficacy in reducing the number of micturition (-2.56 ±3.31 vs. -2.44 ± 4.56, p = 0.58), urgency (-1.70 ± 3.07 vs. -1.15 ± 2.68, p =0.37) and incontinence (-2.79 ± 2.82 vs. -4.67 ± 9.29, p =0.28) episodes per 24 hours. There was no difference in improvement of the quality of life. The patient and physician assessments of treatment benefit were not statistically different for solifenacin and tolterodine (p = 0.23 and p = 0.52, respectively), with the majority showing benefits in both groups. The incidence of major adverse events, including dry mouth (18.0%vs. 8.3%, p = 0.31) and constipation (12.8%vs. 2.8%, p = 0.20) was not significantly different. Compared with baseline, the severity of dry mouth did not increase in either group.Conclusion: Both solifenacin and tolterodine are effective in treating key OAB symptoms, including urinary frequency, urgency and incontinence in the Taiwanese population. Both medications are comparably effective and safe, with the most common adverse effects being dry mouth and constipation. [ABSTRACT FROM AUTHOR]

Objective: We developed a novel ex vivo training model for advanced laparoscopic suturing techniques necessary in laparoscopic radical prostatectomy (LRP). Methods: An inanimate model was developed to approximate real-life conditions in laparoscopic urethrovesical anastomosis. A segment of porcine ovarian tube inserted through a hard piece of cardboard (urethral stump) in a small open box and a part of pig stomach with a 2-cm hole (bladder neck) were placed in a specially designed setup in a traditional pelvic trainer, while the trocars were arranged in the usual five-port style during an LRP. The trainees practised suturing the “bladder neck” to the “urethral stump” with intermittent or continuous sutures according to their preferences. Results: The setup successfully mimicked the spatial relationships of the organs to be anastomosed during live surgery. The directions of the trocars and the angles of the instrumentations in the training model also imitated those during LRP. After practising on our models, the surgeons spent significantly less time (65 ± 24 min vs. 36 ± 12 min, p = 0.035) performing actual urethrovesical anastomosis. Conclusion: This inanimate laparoscopic suturing training model for urethrovesical anastomosis is a novel, effective, convenient and economic training tool, especially for beginners of LRP. [ABSTRACT FROM AUTHOR]

Background/Purpose: This study examined the psychometric properties and clinical validity of the EORTC QLQ-PR25, a questionnaire for assessing the quality of life of patients with prostate cancer. Methods: The Taiwan Chinese version of the prostate cancer module (EORTC QLQ-PR25) and the core questionnaires (EORTC QLQ-C30) were administered to 81 patients with prostate cancer after they had been treated with surgery or hormone therapy or both. The QLQ-PR25 module assesses urinary symptoms, bowel symptoms, hormonal treatment-related symptoms, sexual activity and sexual functioning. Results: The questionnaires were well accepted by the patients and very few of the items had missing data. Only the urinary symptom scale showed satisfactory internal consistency. Scales were able to differentiate clinical groups of patients with corresponding symptoms, but the differences were smaller than that of major functioning scales in the core questionnaire. Conclusion: The Taiwan Chinese version of the EORTC QLQ-PR25 is acceptable in patients with prostate cancer in Taiwan, able to differentiate corresponding symptoms, but the scale structure needs further improvement. [ABSTRACT FROM AUTHOR]

Background/purpose: To better understand the result of radical cystectomy in the treatment of bladder cancer, we analyzed our data and reported the oncological outcomes and survival predictors.Methods: Patients underwent radical cystectomy for bladder transitional cell carcinoma between March 1995 and July 2007 were evaluated. The clinical course, pathological characteristics, and clinical outcomes were described and analyzed.Results: A total of 148 patients (98 men and 50 women) with a median age of 66.7 years (range: 23.8-83.3) were included in the study. Median follow-up was 64 months. The perioperative mortality was 2.7%. The 5-year recurrence-free survival (RFS) and overall survival (OS) for all 148 patients was 61% and 53%, respectively. The 5-year RFS and OS were 68% and 62% for pT2, 65% and 59% for pT3, 11% and 9% for pT4, and 37% and 31% for nodal-positive disease, respectively. The number of positive lymph nodes was significantly associated with survival: 5-year RFS and OS were 54% and 33%, for patients with only 1-3 positive lymph nodes, whereas, all patients with >or= 4 positive lymph nodes had recurrence. On multivariate analysis, age > 60 years, pT4 tumors, and lymph node involvement had a negative impact on survival.Conclusion: Radical cystectomy can be curative in a significant portion of patients with organ-confined (T2 or less) and extravesical (pT3) bladder cancer. Age > 60 years, pT4 tumors, and nodal metastases were associated with poor prognosis. Patients with limited lymph node involvement (1-3 nodes) can be cured by surgery alone, whereas a more extensive lymph node metastasis (>or= 4 nodes) eventually results in recurrence. Concomitant prostate cancer is of low grade and early stage, and is clinically insignificant. [ABSTRACT FROM AUTHOR]

Purpose: We compared clinicopathological characteristics and outcomes in patients with bladder cancer who were exposed to graded arsenic levels in drinking water. Materials and Methods: From 1993 through 2006, 977 patients with bladder cancer in Taiwan were studied retrospectively. Patients were from 3 areas, including the core zone (arsenic related blackfoot disease endemic area with a well water arsenic level of 350 to 1,100 ng/ml), zone 1 (a well water arsenic level of 350 ng/ml or greater but not a blackfoot disease endemic area) and zone 2 (a well water arsenic level of less than 350 ng/ml). Clinicopathological characteristics and survival outcome were compared among the groups. Results: Of these patients 81 (8.3%), 246 (25.2%) and 650 (66.5%) lived in the core zone, and zones 1 and 2, respectively. More high grade and high stage tumors were observed in core zone patients than in those in zones 1 and 2, including high grade in 48.7% vs 41.4% and 39.2% of patients, advanced disease in 39.5% vs 31.0% and 18.5% and nodal metastasis in 8.6% vs 3.3% and 3.4%, respectively. Median overall and cancer specific survival in core zone patients was significantly shorter than in patients in zones 1 and 2, including 69 vs 119 and 113-month overall survival and for the 75th percentile of cancer specific survival 34.5 vs 119 and 113 months, respectively. On multivariate analysis with adjustment for tumor grade and stage the zonal difference was not a significant factor for overall or cancer specific survival. Conclusions: Patients with arsenic related bladder cancer may have decreased overall and cancer specific survival because they have more unfavorable tumor phenotypes than patients in other areas in Taiwan. [Copyright &y& Elsevier]

Purpose: We studied urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in diabetic women. Materials and Methods: A total of 86 consecutive type 2 diabetic women with minimal confounders of voiding dysfunction followed at a diabetes clinic were prospectively enrolled and subjected to urodynamic studies. The sensory response of Aδ and C fibers of the bladder was measured by intravesical current perception threshold testing at frequencies of 250 and 5 Hz, respectively. Results: Of these 86 women 30 (34.9%) were classified as having detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred to as having bladder outlet obstruction and 33 (38.4%) showed normal detrusor function on urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation on cystometry and intravesical current perception threshold testing. The detrusor overactivity group showed impaired storage and emptying function but had no significant changes in intravesical current perception threshold values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in current perception threshold values was associated with a decrease in bladder voiding efficiency on 5 and 250 Hz current perception threshold testing. Conclusions: Our data provide the electrophysiological evidence that indicates an association between impaired Aδ as well as C fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Diabetes can affect the bladder presumably via peripheral pathogenetic mechanisms to induce detrusor overactivity with impaired contractility. [Copyright &y& Elsevier]

Purpose: We studied the effects of long-term fructose feeding and metabolic perturbations on bladder function in rats. Materials and Methods: Female Wistar rats were fed a fructose enriched (60%) or control diet for 3 and 6 months. In vitro contractile responses to electrical field stimulation, KCl, carbachol and adenosine triphosphate, and in vivo cystometry were used to evaluate bladder function. Tissue staining and electron microscopy were also performed to evaluate the structural changes in rats subjected to metabolic syndrome. Biochemical and physiological data were compared between fructose fed rats and age matched controls. Results: All rats fed a fructose enriched diet for 3 months showed insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension. These fructose fed rats showed a decreased contractile response to high concentrations of KCl but not to other parameters tested compared to controls. Eight of the 12 rats (66.7%) showed abnormal cystometry, mainly by increased phasic contractions. In 6-month fructose fed rats contractile responses to electrical field stimulation, KCl and carbachol were decreased significantly. However, responsiveness to high concentrations of adenosine triphosphate was significantly increased. Morphological studies in fructose fed rats showed swollen mitochondria in bladder smooth muscle, increased leukocyte infiltration between interstitial tissue and neutrophil adhesion around the endothelium of vessels. Conclusions: Our data show that a significant proportion of fructose fed rats show time related alterations in bladder biochemical, morphological and functional properties. The proinflammation and myopathy of the bladder induced by metabolic perturbations have important roles in causing bladder dysfunction. [Copyright &y& Elsevier]

Abstract: Objective: We retrospectively reviewed the medical records of patients who underwent hand-assisted laparoscopic nephroureterectomy using a retroperitoneal or transperitoneal approach at National Taiwan University Hospital. Early postsurgical pain scores and the amount of morphine equivalents consumed were evaluated. Patients and Methods: From July 2001 to June 2005, a total of 96 patients who underwent hand-assisted laparoscopic nephroureterectomy and bladder cuff resection were retrospectively evaluated. Perioperative parameters, postoperative opioid dose, and daily pain score based on a 10-point visual analog scale (VAS) were recorded prior to discharge. Potential predictive factors included patient age, gender, body mass index, comorbid conditions, surgical time, patient controlled analgesia (PCA) use and surgical access. These were analyzed with regard to pain based on a daily VAS score and morphine dose (equivalents). Results: The daily VAS score decreased from 4.7 ± 1.5 on the day of surgery to 2.0 ± 0.7 on postoperative day (POD) 6. Only the operation time was associated with a high VAS score on POD1 (p < 0.01). On univariate analysis, a longer operation time (p = 0.04) and PCA use (p < 0.01) were associated with higher intake of morphine equivalents. Patients with end-stage renal disease (ESRD) required less morphine postoperatively (p = 0.02). On multivariate analysis, PCA use (p = 0.04), ESRD (p = 0.045), and operation time (p = 0.049) were independently associated with postoperative morphine dosage. Women had a trend of increased postoperative morphine use (p = 0.06) The postoperative daily VAS score and opioid dosage were comparable in patients receiving trans-and retroperitoneal access. Conclusion: Patients who had a longer operation had a significantly higher POD1 pain score. PCA use and prolonged operation time were predictive factors for a higher dosage of morphine. [Copyright &y& Elsevier]

Primary malignancies of female urethral diverticulum are rare. A well-documented female patient with primary clear cell carcinoma of the urethral diverticulum is presented here. A 65-year-old woman presented with frequency and voiding difficulty for 2 months. Physical examination showed a 4-cm mass protruding from anterior vaginal wall. Intravenous urography, magnetic resonance imaging, and cystoscopy showed a polypoid mass in urethral diverticulum. She then underwent anterior exenteration with ileal conduit diversion and urethrectomy. Pathology confirmed the diagnosis of clear cell adenocarcinoma with bladder neck invasion. She had no disease recurrence at 2-year follow-up. Careful clinical examination and image studies are helpful in making the preoperative diagnosis for the rare disease. Early radical surgery can achieve better survival. [ABSTRACT FROM AUTHOR]

Primary malignancies of female urethral diverticulum are rare. A well-documented female patient with primary clear cell carcinoma of the urethral diverticulum is presented here. A 65-year-old woman presented with frequency and voiding difficulty for 2 months. Physical examination showed a 4-cm mass protruding from anterior vaginal wall. Intravenous urography, magnetic resonance imaging, and cystoscopy showed a polypoid mass in urethral diverticulum. She then underwent anterior exenteration with ileal conduit diversion and urethrectomy. Pathology confirmed the diagnosis of clear cell adenocarcinoma with bladder neck invasion. She had no disease recurrence at 2-year follow-up. Careful clinical examination and image studies are helpful in making the preoperative diagnosis for the rare disease. Early radical surgery can achieve better survival. [ABSTRACT FROM AUTHOR]

The lymph nodes and bones are the most common sites of metastases in advanced prostate cancer. However, an unusual clinical presentation or one that mimics another entity may make diagnosis difficult. We report a male patient with metastatic prostate cancer who presented with a primarily localized buccal tumor. Prostatic origin was highly suspected only after positive results of prostate-specific antigen staining from biopsy pathology. We share our clinical experience and review the literature. [ABSTRACT FROM AUTHOR]

Metastatic hepatocellular carcinoma (HCC) to the urinary bladder is very rare. We present the case of a 58-year-old female patient who was diagnosed to have both HCC and cervical cancer. She developed hemorrhagic cystitis 2 years after radiation therapy for cervical cancer. During endoscopic electrocauterization for hemorrhagic cystitis, three small reddish tumors measuring less than 1 cm in diameter and with a raspberry-like appearance were found. Transurethral bladder tumor resection was performed. Pathology confirmed metastatic HCC to the bladder. Due to the similar appearance, these tumors are liable to be misinterpreted as engorged vessels secondary to irradiation if biopsies are not taken. Differential diagnosis by pathology is mandatory for such patients. [Copyright &y& Elsevier]

UPEC can internalize clonally in prostate to form biofilm-like intracellular bacterial communities (IBCs) for recurrent or chronic infection. We previously indicated that the exposure of prostate cells to testosterone could suppress UPEC invasion and their persistent survival within cells by effectively inhibiting the JAK/STAT1 signaling pathway. However, the regulatory mechanism by which testosterone affects UPEC-induced prostatitis via STAT3, another latent transcription factor signaling pathway is still unclear. The present study aimed to clarify the role of STAT3 in the process of UPEC-induced inflammation and colonization in prostate epithelial cells. The effects of testosterone-mediated inhibition were compared between the prostatitis by different UPEC strains (CFT073 and J96) through the specific GFP-UPEC-infected prostate cell model. Fluorescence microscopy was used for UPEC IBCs detection and quantifying, and Flow cytometry, RT-PCR and western blotting were used for analyzing related gene and protein expressions. Pretreatment of JAK and STAT3 inhibitors were also applied to verify the regulation of transduction pathway in testosterone-mediated anti-UPEC infection. This study revealed that testosterone effectively suppresses UPEC infection and IBC formation in prostate cells through the JAK/STAT3 pathway. The results show that CFT073 and J96 UPEC infection rates and colony numbers were dose-dependently reduced in RWPE-1 cells pretreated with 5 and 20 μg/mL testosterone at 0 and 24 h post-infection. Further, testosterone reduced the amounts of UPEC infecting and surviving within the prostate cells, as well as suppressed the size of IBCs formed. We demonstrated that pretreating testosterone effectively inhibited UPEC infection along with dose-dependent suppression of STAT3 and the phosphorylated-STAT3 expression in prostate cells, especially in 24 h J96 UPEC infected groups. The STAT inhibitor, SOCS3 also up-regulated at the same time. In addition, we pretreated the JAK1 or STAT3 inhibitor with testosterone to block the signaling transduction before CFT073 and J96 UPEC infection, and found the significant restoring in both the sizes of IBCs and bacterial numbers in RWPE-1 cells. Therefore, our results suggest that the suppression of STAT3 by testosterone treatment attenuate UPEC growing within IBCs and interfere with their infection to prostate cells. Overall, our study demonstrates that testosterone suppresses the initial infection of prostate epithelial cells by UPEC and reduces the survival of UPEC within IBCs after infection. These results indicate a critical role for STAT3 in facilitating UPEC infection and persistence, and its participation in driving testosterone-suppressive responses in prostate epithelial cells. In conclusion, this study suggests that testosterone may be beneficial in treating clinically recurrent UPEC infections and, thus, the persistent recurrence of prostatic inflammation. [ABSTRACT FROM AUTHOR]