Articles

  • A β3 Agonist, Mirabegron for the Treatment of Overactive Bladder

    ABSTRACT

    Overactive bladder syndrome (OAB) has a negative impact on quality of life and social functioning. Although antimuscarinic drugs are the first line of treatment for OAB, adverse effects and the limitations of efficacy hinder their use.β-adrenoceptors are found in the bladder body and mediate relaxation to noradrenalin. Stimulation ofβ3-adrenoceptor subtypes has been shown to relax bladder smooth muscle in humans. Mirabegron, a novel selectiveβ3-adorenoceptor agonist, is in development for the treatment of OAB. Phase II placebo-controlled clinical trials showed that mirabegron significantly improved the majority of variables when administered to patients with OAB. Mirabegron is well tolerated with significant efficacy in reducing the number of incontinence episodes and the mean micturition frequency. Commonly reported adverse effects were gastrointestinal adverse events and headache. The lower propensity of dry mouth and constipation while taking mirabegron may make it an attractive drug candidate.


    Motoaki Saito, Fotios Dimitriadis, Fumiya Ohmasa, Seiya Inoue, Keisuke Satoh

    Submitted: Oct 10, 2011 Accepted for Publication: October 27, 2011


    KEYWORDS: Mirabegron; Adrenergic β3 receptor; Bladder; OAB (overactive bladder); LUTS (lower urinary tract symptoms)

    CORRESPONDENCE: Fotios Dimitriadis, MD, PhD, Division of Molecular Pharmacology, Tottori University School of Medicine, 86 Nishimachi, Yonago 683-8503, Japan ().

    CITATION: UroToday Int J. 2011 Dec;4(6):art 70. http://dx.doi.org/10.3834/uij.1944-5784.2011.12.03

    Acronyms and Abbreviations: ACh, acetylcholine; M1-4, muscarinic su types, 1-4 respectively; PLC, Phospholipase-C; IP3/DAG, Inositol 1,4,5 Trisphosphate/1,2-Diacylglycerol; NA, noradrenalin; AC, adenylyl cyclase; cATP, cyclic adenosine triphosphate

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    Published December 1, 2011
  • Androgen Insensitivity Syndrome: Case Report With Review of the Literature

    ABSTRACT

    Androgen insensitivity syndrome (AIS), also known as testicular feminization, encompasses a wide range of phenotypes that are caused by numerous different mutations in the androgen receptor gene. AIS is an X-linked recessive disorder that is classified as complete, partial, or mild based on the phenotypic presentation. The clinical findings include a female type of external genitalia, 46-XY karyotype, absence of Mullerian structures, presence of Wolffian structures to various degree, and normal to high testosterone and gonadotropin levels. The syndrome is illustrated by a 24-year-old phenotypic female who presented with an inability to conceive, normal-appearing external genitalia, an absent uterus and ovaries, and bilateral testes at the level of the internal inguinal ring. Management includes counseling, gonadectomy to prevent primary malignancy in undescended gonad, and hormone replacement. The karyotyping of family members is advocated because of known familial tendencies.

    KEYWORDS:Androgen insensitivity syndrome; Androgen receptor gene; Testicular feminization syndrome; Gonadectomy

    CORRESPONDENCE:Dr. Gajanan S. Bhat, Resident in Urology, Institute of Nephrourology, Victoria Hospital Campus, Fort Bangalore- 560 002, Karnataka, India ().

    CITATION:UroToday Int J. 2011 Jun;4(3):art33. doi:10.3834/uij.1944-5784.2011.06.04

    ABBREVIATIONS AND ACRONYMS: AIS, androgen insensitivity syndrome (CAIS, complete; MAIS, mild; PAIS, partial); AR, androgen receptor; LH, luteinizing hormone.

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    Published June 15, 2011
  • Clean Intermittent Catheterization Following Urethral Stricture Surgery Using a Low Friction Catheter Versus Conventional Plastic Catheter: A Prospective, Randomized Trial

    ABSTRACT

    INTRODUCTION: The purpose of the study was to compare clean intermittent catheterization (CIC) after endoscopic urethrotomy for urethral stricture (US) using a low-friction hydrophilic catheter or standard Nelaton polyvinyl chloridePVC) catheter in a randomized study. Patient satisfaction, complications, and US recurrence were determined.

    METHODS: This was a prospective, randomized, parallel group, unicenter study conducted between August 2005 and February 2008. Patients had a unique US that was < 2 cm in length with low or moderate spongiofibrosis. A total of 62 male patients were randomized into 2 treatment groups using LoFric (Astra Tech; Molndal, Sweden) or standard plastic catheters. Catheters were inserted into the bladder via the urethra and immediately removed. The procedure was performed twice a month for 3 months and then monthly for 1 year. Follow-up lasted 24 months. Patient perception of ease, pain, and comfort of CIC was scored with a questionnaire; success rates and adverse events were documented.

    RESULTS: The median age at the time of treatment was 61.46 years (range, 21-86 years). The two groups were demographically comparable. The LoFric catheter was more comfortable (P = .02) with less pain at insertion (P = .002) than the conventional catheter. Patients were more satisfied with the hydrophilic catheter (P = .003). There were no significant differences in ratings of convenience. There were no significant group differences in complications. Within the first 2 years, 2 patients in the group using the LoFric catheter and 7 patients in the group using the conventional catheter developed urethral stricture. A life-table analysis did not show a significant group difference in the outcome (P = .15).

    CONCLUSIONS: CIC is a safe and efficient method of reducing the frequency of urethral stricture recurrence after internal urethrotomy. The Lofric catheter significantly increased the degree of comfort and satisfaction and decreased the feeling of pain when the catheter was removed or inserted, when compared with a conventional PVC catheter. Complication and recurrent rates were comparable between groups. Thus, low-friction catheters may prevent US recurrences with better quality of life.

    KEYWORDS: Urethral stricture; Internal urethrotomy; Clean intermittent catheterization; Hydrophilic-coated catheter.

    CORRESPONDENCE: Dr. Sataa Sallami, Department of Urology, La Rabta Hospital-University, Tunis 1007, Tunisia ().

    CITATION: Urotoday Int J. 2011 Feb;4(1):art7. doi:10.3834/uij.1944-5784.2011.04.07

    ABBREVIATIONS AND ACRONYMS: CIC, clean intermittent catheterization; PVC, polyvinyl chloride; US, urethral stricture.

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    Published December 22, 2010
  • Comparison of the Impact of Degarelix and Leuprolide on the Health-Related Quality of Life of Patients with Prostate Cancer: Results of a 12-Month Phase III Clinical Trial

    ABSTRACT

    Introduction: The objective of this study was to compare health-related quality of life (HRQoL) with degarelix (240 mg in month 1 and then 80 mg monthly, administered subcutaneously) or leuprolide (7.5 mg/month intramuscularly) in men with prostate cancer.

    Methods: HRQoL was assessed at baseline and throughout a 12-month randomized, open-label, parallel-group clinical trial using standard SF-12 and EORTC QLQ-C30 questionnaires. HRQoL outcomes were compared between treatments using trend, change score, and response analyses.

    Results: HRQoL data from 401 subjects were included in this analysis; 205 receiving degarelix 240/80 mg and 196 receiving leuprolide 7.5 mg. Over the 12-month treatment period, patients experienced worsening of most HRQoL domains except for bodily pain, general health (both SF-12), and diarrhea (QLQ-C30). No treatment group differences in HRQoL were noted at day 28 or 6 months. At 12 months, mean SF-12 scores for the mental component summary (p = 0.02) and mental health (p = 0.04) were significantly higher in degarelix- compared with leuprolide-treated patients. Treatment with leuprolide had a seemingly more favorable impact on insomnia (QLQ-C30; p = 0.04) and bodily pain (SF-12; p = 0.006) compared with degarelix. Patients with metastatic disease treated with degarelix reported significant improvements in the role-emotional domain (SF-12; p = 0.02), global health status (QLQ-C30; p = 0.04), and appetite loss (QLQ-C30; p = 0.02) at 12 months compared with leuprolide.

    Conclusions: After 12 months of treatment, the HRQoL of patients with advanced prostate cancer treated with the GnRH antagonist degarelix is similar to that of patients treated with leuprolide. The study also indicates benefits with degarelix treatment in the metastatic population.

    KEYWORDS: Degarelix; Gonadotropin-releasing hormone agonist; Gonadotropin-releasing hormone antagonist; Health-related quality of life; Leuprolide; Prostate

    CORRESPONDENCE: Bo-Eric Persson, MD, Director, Medical Sciences, Urology/Oncology Global Marketing, Ferring International Center SA, Chemin de la Vergognausaz 50, 1162 St-Prex, Switzerland ().

    CITATION: UroToday Int J. 2011 Dec;4(6):art 81. http://dx.doi.org/10.3834/uij.1944-5784.2011.12.14

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    Published December 1, 2011
  • Prostate Cancer Treated With Cryotherapy: A Subanalysis of Stratification by Risk Group, Race, Prostate Volume, and Neoadjuvant Hormone Therapy

    ABSTRACT

    INTRODUCTION: Prostate cryoablation was developed with the intent of maximizing effectiveness while minimizing the morbidity of treating clinically localized prostate cancer. Our focus was to determine Kaplan-Meier (KM) biochemical recurrence-free survival (BRFS) estimates and how they might be affected by neoadjuvant hormone therapy, race, D’Amico risk group, and prostate volume.

    METHODS: We retrospectively analyzed data from 190 patients receiving cryoablation for the primary treatment of T1 to T3 prostate cancer from 2003 to 2009. All patients underwent whole-gland prostate cryoablation by a single surgeon using the Cryocare CS System (HealthTronics; Austin, TX, USA). Patients received a prostate-specific antigen and digital rectal examination at 1, 3, 6, 9, 12, 18, 24, and 30 months after surgery. A PSA nadir of ≤ 0.1 ng/mL was used to define treatment success. KM BRFS curves were plotted overall and by subanalysis variable and compared using the log-rank test. Univariate Cox proportional hazard regression models were used to describe the effect of measured variables on risk of biochemical recurrence.

    RESULTS: The mean follow-up was 27 months. A total of 153 patients (81%) reached the treatment goal of PSA nadir ≤ 0.1 ng/mL. Using a nadir + 2 ng/mL failure definition, BRFS rates were 94% and 85% for 1 year and 3 years, respectively. High D’Amico risk significantly predicted biochemical recurrence (hazard ratio [HR] = 3.65; P = .045). African American men had a nonsignificant trend toward increased risk (HR= 1.91; P = .12). BRFS did not differ when comparing men who did or did not receive hormone therapy (log-rank test: P = .57) or men with prostate size < 40 g vs ≥ 40 g (P = .72). The majority of complications were minor, with a rate of 12%.

    CONCLUSIONS: Although neoadjuvant hormone therapy and prostate volume at the time of surgery were not statistically associated with BRFS, race approached significance and high D’Amico risk group was significant. Our short-term results justify the continuing use of cryosurgery for the management of localized prostate cancer.

    KEYWORDS: Cryotherapy; Neoadjuvant Hormone Therapy; Prostate; Prostate Cancer; Prostate Cryoablation

    CORRESPONDENCE: LCDR James C. Nederostek, MD, Department of Urology, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708, USA ().

    CITATION: Urotoday Int J. 2011 Aug;4(4):art48. doi:10.3834/uij.1944-5784.2011.08.04

    ABBREVIATIONS AND ACRONYMS: ASTRO, American Society for Therapeutic Radiology and Oncology; BRFS, biochemical recurrence-free survival; CT, computed tomography; KM, Kaplan-Meier; PSA, prostate-specific antigen; RTOG, Radiation Therapy Oncology Group.

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    Published August 31, 2011