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Purpose: We investigated the long-term prognosis of a cohort of children with nocturnal enuresis, and identified the prevalence of nocturia and persistent comorbid symptoms. Materials and Methods: A questionnaire was sent to 1,265 patients treated for nocturnal enuresis during childhood at our university hospital. We used a validated tool, the International Consultation on Incontinence Modular Questionnaire on overactive bladder and urinary incontinence, to evaluate the presence of current urological symptoms. Participants were also asked about treatment received for nocturnal enuresis, and their medical files were analyzed. Results: A total of 516 patients (41%) returned the questionnaire. Mean age was 17 years, and 64% of patients were male. Current urgency, daytime frequency and urinary incontinence were reported by 17%, 8% and 25% of patients, respectively. During the period of nocturnal enuresis up to 60% of patients had concomitant daytime symptoms. Nocturia was reported by 182 participants (35%). Males comprised 56% of patients (101) with nocturia and 69% of patients (230) without nocturia. Prevalence of current daytime symptoms and incontinence was higher in patients with nocturia (p <0.001). Those with nocturia were older at resolution of nocturnal enuresis (p <0.001) and suffered more nonmonosymptomatic nocturnal enuresis (p <0.014). Conclusions: About a third of patients experience nocturia, a fourth still report some kind of urinary incontinence, a fifth have regular urgency and a tenth have daytime frequency. Thus, resolution of nocturnal enuresis does not necessarily mean resolution of the underlying pathological condition. Some patients with nocturia who continue to suffer with bothersome symptoms might benefit from continuous treatment for the underlying condition. [Copyright &y& Elsevier]

Purpose: We examined the effects of doxazosin, finasteride and combined therapy in men with lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function, as assessed by the Brief Male Sexual Function Inventory during 4 years. Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in sexual function was a secondary outcome. We analyzed the records of 2,783 men enrolled in the study who completed the inventory at baseline and at least once during followup. Results: In men enrolled in MTOPS sexual function decreased with time. Men assigned to finasteride and combined therapy experienced overall statistically significant but slight worsening of ejaculatory function compared with men on placebo. Men assigned to combined therapy also experienced significant worsening in erectile function and sexual problem assessment. There was no significant difference in changes in any inventory domain in men assigned to doxazosin alone compared to placebo. Conclusions: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function. [Copyright &y& Elsevier]

Purpose: Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms associated with prostate cancer risk. Some of these genetic variants are also associated with serum prostate specific antigen levels and lower urinary tract symptoms, raising the question of whether they are truly prostate cancer biomarkers or simply lead to detection bias. Therefore, we determined whether single nucleotide polymorphisms associated with prostate cancer risk are more strongly associated with tumor or prostate volume. Materials and Methods: The genotypes of 38 validated prostate cancer risk single nucleotide polymorphisms were determined in 1,321 white men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship of single nucleotide polymorphism frequency with total prostate and tumor volumes. Results: On multivariate analysis 2 single nucleotide polymorphisms on chromosome 8q24, rs16901979 (A) and rs6983267 (G), were significantly associated with increased tumor volume (p = 0.01 and 0.02, respectively). In contrast, rs17632542 (T) near the PSA gene on 19q13 was associated with significantly lower tumor volume and rs10788160 (A) on 10q26 was associated with significantly larger prostate volume (p = 0.02 and 0.01, respectively). Conclusions: Analysis of 38 single nucleotide polymorphisms associated with prostate cancer risk revealed a significant association between several on chromosome 8q24 and increased tumor volume but not prostate volume. This suggests that they are bona fide markers of prostate cancer susceptibility and possibly more aggressive disease. Other prostate cancer risk alleles are associated with prostate specific antigen and increased prostate or decreased tumor volume, suggesting detection bias due to their phenotypic influence. [Copyright &y& Elsevier]

Purpose: We examine the association among depression, suicidal ideation and self-reported lower urinary tract symptoms using a large, cross-sectional, population based study. Materials and Methods: The study included 2,890 men from the 2005–2006 or 2007–2008 cycles of the NHANES (National Health and Nutrition Examination Survey) who were 40 years old or older. Men were asked if they experienced nocturia, urinary hesitancy and/or incomplete bladder emptying. The PHQ-9 (Patient Health Questionnaire-9) was used to determine the likelihood of clinical depression and suicidal ideation. Results: The prevalence of lower urinary tract symptoms was 33.7% and 10.3% for men reporting 1 and 2 or more symptoms, respectively. Moderate to severe depression (PHQ-9 score 10 or greater) and suicidal ideation were reported by 181 (6.3%) and 105 (3.6%) men, respectively. Men reporting moderate to severe depression (compared to those reporting minimal depression) had a higher odds of reporting lower urinary tract symptoms (adjusted odds ratio [AOR] 5.09, 95% CI 3.17–8.17 for PHQ-9 score 5 to 9 and AOR 7.62, 95% CI 3.90–14.87 for PHQ-9 score 10 or greater; p trend <0.0001). More lower urinary tract symptoms were associated with a significantly higher odds of moderate to severe depression (AOR 3.09, 95% CI 1.86–5.15 for 1 symptom and AOR 8.06, 95% CI 4.18–15.53 for 2 or more symptoms, p trend <0.0001) and a higher odds of suicidal ideation (AOR 1.70, 95% CI 0.85–3.42 and AOR 2.71, 95% CI 1.40–5.25, respectively, p trend = 0.004). Conclusions: A significant relationship was observed between lower urinary tract symptoms and depression/suicidal ideation. While the pathophysiology of the relationship and its significance in clinical practice remain unclear, clinicians may consider screening men with severe lower urinary tract symptoms for depression. [Copyright &y& Elsevier]

Purpose: Tadalafil significantly improves lower urinary tract symptoms suggestive of benign prostatic hyperplasia. We post hoc characterized changes in the maximum urinary flow rate using integrated data from 4 international, placebo controlled studies of tadalafil once daily for lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Materials and Methods: After a 4-week placebo lead-in period 1,500 men were randomized to tadalafil 5 mg or placebo for 12 weeks. Data were analyzed using ANCOVA. Maximum urinary flow rate values were rank transformed for analysis. Results: Baseline maximum urinary flow rate data were available on 1,371 men with a mean age of 63.1 years and end point data were available on 1,197. Tadalafil 5 mg significantly increased maximum urinary flow vs placebo (median 1.1 vs 0.4 ml per second, p = 0.003). At a baseline voided volume of 125 to less than 250 ml the median change in the maximum urinary flow rate was 0.9 and 1.2 ml per second (p = 0.142) in 731 patients, at a baseline of 250 to 450 ml the change was –0.3 and 0.7 ml per second (p = 0.011) in 428, and at a baseline of greater than 450 ml the change was –0.2 and 2.0 ml per second (p = 0.186) in 38 for placebo and tadalafil, respectively. The difference was 0.3, 1.0 and 2.2 ml per second, respectively. At a baseline maximum urinary flow rate of greater than 15 ml per second in 128 patients the median flow rate change was –2.1 and –0.8 ml per second (p = 0.246), at a maximum of 10 to 15 ml per second in 522 the change was 0.2 and 0.8 ml per second (p = 0.044), and at a maximum of less than 10 ml per second in 547 the change was 1.2 and 1.8 ml per second (p = 0.189) for placebo and tadalafil, respectively. Tadalafil improved I-PSS (International Prostate Symptom Score) voiding subscores significantly vs placebo across all baseline maximum urinary flow subgroups (each p <0.001). Conclusions: This integrated analysis revealed a small but statistically significant median maximum urinary flow rate improvement for tadalafil vs placebo. The numerical difference in the maximum urinary flow change from baseline between tadalafil and placebo increased with increased voided volume. [Copyright &y& Elsevier]

Purpose: We determined the fluctuation of nocturia in a 12-month period in men with lower urinary tract symptoms. Materials and Methods: Men with lower urinary tract symptoms were allocated to the placebo arm of the United States Department of Veterans Affairs Cooperative Studies Program Benign Prostatic Hyperplasia Study. Reported nocturia frequency using the American Urological Association Symptom Index was collected at 6 time points (2, 4, 13, 26, 39 and 52 weeks). Repeat measurements of nocturia during a 1-year period were analyzed using a generalized mixed linear model. Results: Of the 305 men allocated to the placebo group 256 participants (84%) gave answers for all 6 time points. In the entire sample the mean nocturia count did not significantly vary from baseline (week 2) after adjusting for covariates (p = 0.542). However, there was considerable fluctuation in nocturia during 1 year. Of the 93 men with 3 or 4 episodes at baseline 47% had improvement and 12% had worsening at 1 year. Of the 184 men who reported 2 or greater nocturia episodes at baseline 15% reported 0 or 1 at 52 weeks. Depending on the case definition during followup the probability of nocturia progression varied between 8% and 54% while nocturia regression varied between 2% and 33%. Conclusions: Using repeat questionnaire based assessments we observed considerable fluctuation in nocturia. However, overall there was no significant increase in prevalence in a 1-year period. These findings may be reassuring to providers and patients who elect to delay interventions for nocturia. [Copyright &y& Elsevier]

Purpose: Many conditions and characteristics are cross-sectionally associated with nocturia. However, to our knowledge longitudinal associations of frequency-volume chart based nocturia have not yet been studied. We identify (modifiable) determinants of nocturia in older men in a longitudinal setting. Materials and Methods: A longitudinal, community based study was conducted among 1,688 men age 50 to 78 years in Krimpen aan den IJssel, The Netherlands with planned followup rounds at 2, 4 and 6 years. Men without a history of radical prostatectomy, transurethral surgery, or bladder or prostate cancer were included in the study. Data were obtained using frequency-volume charts, from which the nocturnal voiding frequency, maximum voided volume and (nocturnal) urine production were determined. Nocturia was defined as a nocturnal voiding frequency of 2 or more episodes. Polyuria was defined as greater than 2,800 ml voided per 24 hours. For nocturnal polyuria we used the 2 definitions of 1) greater than 33% of 24-hour voided volume and 2) nocturnal urine production of greater than 90 ml per hour. Conditions and characteristics were determined via medical examinations and questionnaires. A generalized linear mixed effect model was used to determine factors longitudinally associated with nocturia. Results: Age (50 to 55 years vs greater than 60 years), maximum voided volume (greater than 300 ml vs less than 300 ml), 24-hour polyuria, nocturnal polyuria (both definitions) and lower urinary tract symptoms were all longitudinally associated with an increased prevalence of nocturia in older men. Conclusions: A smaller maximum voided volume, lower urinary tract symptoms, 24-hour polyuria and nocturnal polyuria are significant and potentially modifiable determinants of nocturia. The finding that both definitions for nocturnal polyuria are independent significant determinants may indicate a 2-step etiologic process for nocturnal polyuria. [Copyright &y& Elsevier]

Purpose: Medical treatment for men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia is 5α-reductase inhibitor monotherapy or coadministration with an α-blocker. We assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg during 26 weeks on lower urinary tract symptoms and sexual symptoms. Materials and Methods: In an international, randomized, double-blind, parallel study of men 45 years old or older who were 5α-reductase inhibitor naïve and had an I-PSS (International Prostate Symptom Score) of 13 or greater and prostate volume 30 ml or greater, 350 were treated with placebo/finasteride and 345 received tadalafil/finasteride for 26 weeks. Changes in lower urinary tract symptoms secondary to benign prostatic hyperplasia were assessed with the I-PSS, erectile dysfunction improvements were assessed with the IIEF-EF (International Index of Erectile Function-Erectile Function) in sexually active men and safety was assessed by evaluating adverse events. Results: Least squares mean changes from baseline in I-PSS after 4, 12 and 26 weeks of tadalafil/finasteride coadministration were −4.0, −5.2 and −5.5, respectively. Corresponding values for placebo/finasteride coadministration were −2.3, −3.8 and −4.5 (p ≤0.022 at all visits favoring tadalafil/finasteride coadministration). I-PSS subscores (storage and voiding) and quality of life index were also numerically improved with tadalafil/finasteride coadministration. Least squares mean changes from baseline in IIEF-EF with tadalafil/finasteride coadministration were 3.7 after 4 weeks, and 4.7 after 12 and 26 weeks. Corresponding values for placebo/finasteride coadministration were −1.1, 0.6 and −0.0 (p <0.001 at all visits favoring tadalafil/finasteride coadministration). Tadalafil/finasteride coadministration was well tolerated and most adverse events were mild/moderate. Conclusions: The coadministration of tadalafil/finasteride provides early improvement in lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement. Tadalafil/finasteride coadministration also improves erectile function in men who have comorbid erectile dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: We investigate the prevalence of lower urinary tract symptoms in a cohort of methamphetamine abusers, and assess the therapeutic efficacy of α-blockers and anticholinergics. Materials and Methods: From May 2011 to March 2013, 78 male methamphetamine abusers diagnosed with methamphetamine addiction were identified at the National Forensic Hospital, Korea. The I-PSS (International Prostate Symptom Score) with consultation was used to investigate the prevalence of lower urinary tract symptoms, defined as total I-PSS 8 or greater and quality of life index score of 2 or greater. These values for methamphetamine abusers were compared to those of 71 age matched controls. α-Blockers and anticholinergics were administered to methamphetamine abusers with lower urinary tract symptoms according to predominant voiding and storage symptoms based on voiding-to-storage subscore ratios. For methamphetamine abusers with no response, defined as a reduction of 4 or less in total I-PSS, an alternative drug or combination was administered. Efficacy was assessed based on a 4-week interval. Results: The median periods of methamphetamine abuse and abstinence were 18.1 years and 5.7 months, respectively. Methamphetamine abusers showed a higher prevalence of lower urinary tract symptoms compared to controls (77% vs 15%, p <0.001), with higher I-PSS and quality of life index score (13.3 vs 5.6 and 2.9 vs 0.9, respectively; p <0.001). Anticholinergics showed the greatest effect on I-PSS reduction with overall response rates for α-blockers, anticholinergics and combinations of 13%, 61% and 14%, respectively. Seven (12%) methamphetamine abusers did not respond to any therapy. Conclusions: Lower urinary tract symptoms were highly prevalent among methamphetamine abusers. Our results imply that pathological dopaminergic mechanisms have a role in methamphetamine associated lower urinary tract symptoms. Moreover, first line anticholinergics and prompt combination with α-blockers conferred the most therapeutic benefit to nonresponders. [Copyright &y& Elsevier]

Purpose: We prospectively evaluated the association between adiposity and the risk of lower urinary tract symptoms incidence and progression in the Health Professionals Followup Study (HPFS). Materials and Methods: At baseline participants reported current height and weight, and weight at age 21 years. A year later they reported waist and hip circumferences, and every 2 years thereafter they reported weight. Participants periodically completed the International Prostate Symptom Score (I-PSS) and reported surgery or medication use for lower urinary tract symptoms. We used Cox proportional hazards regression to estimate the multivariable adjusted association between adiposity and lower urinary tract symptoms incidence and progression. The incidence analytical cohort of 18,055 men had no lower urinary tract symptoms at baseline. A total of 6,461 men entered the progression analytical cohort when they first experienced lower urinary tract symptoms. Results: The risk of lower urinary tract symptoms in 4,088 cases increased with increasing body mass index (35 kg/m2 or greater vs 23 to less than 25 HR 1.61, 95% CI 1.31–1.99), waist circumference (greater than 42 inches vs 33 or less HR 1.39, 95% CI 1.19–1.63) and weight gain since age 21 years (50 pounds or greater vs stable weight HR 1.31, 95% CI 1.17–1.46, each p trend <0.0001). The risk of lower urinary tract symptom progression in 1,691 cases increased with body mass index (35 kg/m2 or greater vs 23 to less than 25 HR 1.44, 95% CI 1.04–2.00, p trend <0.0001), weight gain since age 21 years (50 pounds or greater vs stable weight HR 1.35, 95% CI 1.14–1.60, p trend <0.0001) and waist circumference (greater than 42 inches vs 33 or less HR 1.32, 95% CI 0.95–1.85, p trend 0.005). Conclusions: Men with higher total and abdominal adiposity and those who gained weight were more likely to have lower urinary tract symptoms develop or progress. Our findings support the notion that obesity may be an important target for lower urinary tract symptom prevention and intervention. [Copyright &y& Elsevier]

Purpose: Urinary biomarkers were measured in women at baseline and 1 year after surgery for stress urinary incontinence, and associations with clinicodemographic covariates and outcomes were analyzed. Materials and Methods: Preoperative and postoperative urine specimens from 150 women were assayed for inflammatory biomarkers (tumor necrosis factor-α, interferon-γ, interleukin-1β, interleukin-6, interleukin-10, interleukin-12p70, interleukin-17 and nerve growth factor) and tissue remodeling biomarkers (collagenase activity, matrix metalloproteinases-1, 2, 9 and 13, and NTx [N-telopeptide cross-linked collagen], epidermal growth factor and heparin-binding epidermal growth factor-like growth factor). Paired t-tests were used to compare changes in biomarkers during 1 year (significance p <0.05). Linear regression models correlated baseline and changes in biomarker levels with covariates (significance p ≤0.001). Logistic regression models, controlling for age, were used to analyze associations of baseline and changes in biomarker levels with surgical failure (significance p <0.05). Results: During 1 year interleukin-12p70 decreased (mean ± SD 0.53 ± 1.4 to 0.28 ± 0.62 pg/mg creatinine, p = 0.04) and nerve growth factor increased (0.034 ± 0.046 to 0.044 ± 0.060 pg/ml/mOsm, p = 0.03). Baseline NTx level per mg creatinine was positively associated with age and postmenopausal status (p = 0.001), and negatively associated with current estrogen use (p = 0.0001). Baseline collagenase activity per mg creatinine was positively associated with age (p = 0.001). Epidermal growth factor per mOsm, NTx per mOsm and interferon-γ per mOsm were negatively correlated with age, current estrogen use and UDI (Urogenital Distress Inventory)-irritative subscale score, respectively (p ≤0.001). Subjects with lower baseline NTx per mg creatinine were less likely to experience surgical failure (OR 0.49, 95% CI 0.26–0.93, p = 0.03). Changes in biomarker levels were not associated with any covariates or surgical failure. Conclusions: Stress urinary incontinence surgery was significantly less likely to fail in women with lower baseline NTx levels. Studies are needed to validate NTx as a possible independent biomarker for stress urinary incontinence surgery outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Percutaneous tibial nerve stimulation is an effective second line therapy for lower urinary tract symptoms. Data on percutaneous tibial nerve stimulation maintenance treatment are scarce. In this study we evaluate its effectiveness and propose an algorithm of percutaneous tibial nerve stimulation maintenance treatment in patients with multiple sclerosis. Materials and Methods: In this prospective, multicenter, open label trial consecutive patients with multiple sclerosis and lower urinary tract symptoms unresponsive to medical therapy were treated with 12 weekly sessions of percutaneous tibial nerve stimulation. Responder patients (50% or greater improvement of lower urinary tract symptoms as measured by the patient perception of bladder condition questionnaire) entered a maintenance phase with individualized treatment frequency based on patient response. Lower urinary tract symptoms were assessed using a 3-day frequency volume chart, urodynamics and patient perception of bladder condition questionnaire. Treatment satisfaction was evaluated using a global response assessment scale and a treatment satisfaction visual analog scale. Results: A total of 83 patients were included in the study and 74 (89%) responded to initial treatment. Persistent efficacy occurred in all initial responders after a mean treatment of 24 months. The greatest frequency of maintenance percutaneous tibial nerve stimulation was every 2 weeks. Lower urinary tract symptoms and patient treatment satisfaction improved with time compared to initial treatment (p <0.05). Bladder diary parameters and voiding parameters improved compared to baseline (p <0.05). Conclusions: Prolonged percutaneous tibial nerve stimulation treatment leads to a persistent improvement of lower urinary tract symptoms in patients with multiple sclerosis. [Copyright &y& Elsevier]

Purpose: The prevalence of lower urinary tract symptoms increases with age and impairs quality of life. Radical prostatectomy has been shown to relieve lower urinary tract symptoms at short-term followup but the long-term effect of radical prostatectomy on lower urinary tract symptoms is unclear. Materials and Methods: We performed a prospective cohort study of 1,788 men undergoing radical prostatectomy. The progression of scores from the self-administered AUASS (American Urological Association symptom score) preoperatively, and at 3, 6, 12, 24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for preoperative AUASS, age, prostate specific antigen, pathological Gleason score and stage, nerve sparing, race and marital status. This model was also applied to patients stratified by baseline clinically significant (AUASS greater than 7) and insignificant (AUASS 7 or less) lower urinary tract symptoms. Results: Men exhibited an immediate worsening of lower urinary tract symptoms that improved between 3 months and 2 years after radical prostatectomy. Overall the difference between mean AUASS at baseline and at 10 years was not statistically or clinically significant. Men with baseline clinically significant lower urinary tract symptoms experienced immediate improvements in lower urinary tract symptoms that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001). Men with baseline clinically insignificant lower urinary tract symptoms experienced a statistically significant but clinically insignificant increase in mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with clinically significant lower urinary tract symptoms decreased from baseline to 10 years after radical prostatectomy (p = 0.02). Conclusions: Radical prostatectomy is the only treatment for prostate cancer shown to improve and prevent the development of lower urinary tract symptoms at long-term followup. This previously unrecognized long-term benefit argues in favor of the prostate as the primary contributor to male lower urinary tract symptoms. [Copyright &y& Elsevier]

Purpose: Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction. Materials and Methods: Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. Results: A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of −2.3 (p <0.0001) in total I-PSS vs −2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r2 = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement. Conclusions: Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction. [Copyright &y& Elsevier]

Purpose: We determined the metabolic, lifestyle and physical factors associated with progression or improvement of storage and voiding lower urinary tract symptoms in a population based cohort of men. Materials and Methods: After the exclusion of men with prostate or bladder cancer and/or surgery from the study, progression and improvement of storage and voiding lower urinary tract symptoms was assessed using the AUA-SI (American Urological Association symptom index) in 780 men, age 35 to 80 years at baseline, who attended 5-year followup clinics. Results: Storage and voiding lower urinary tract symptoms progressed in 39.8% (308) and 32.3% (250) of men, and improved in 33.1% (256) and 23.4% (181), respectively. In final adjusted regression models greater bother and physical activity at baseline predicted improvement in storage and voiding lower urinary tract symptoms, while greater income, high-density lipoprotein cholesterol and lower triglycerides predicted improvement of storage lower urinary tract symptoms only. Being widowed, higher plasma estradiol and depression at baseline predicted the progression of storage and voiding lower urinary tract symptoms, while greater abdominal fat mass and obstructive sleep apnea risk predicted the progression of storage lower urinary tract symptoms only. Older age, lower high-density lipoprotein cholesterol, testosterone, income, previous benign prostatic hyperplasia and erectile dysfunction at baseline predicted the progression of voiding lower urinary tract symptoms only. The initiation or continued use of α-blockers or anticholinergics (storage lower urinary tract symptoms), and 5α-reductase inhibitors (voiding lower urinary tract symptoms), were associated with symptom improvement. Conclusions: Lower urinary tract symptoms may progress or remit. Even accounting for medication use, progression may be associated with modifiable disease, or metabolic or behavioral factors, which are also risk factors for type 2 diabetes and cardiovascular disease. These factors should be looked for and managed. [ABSTRACT FROM AUTHOR]

Purpose: We examined the association between military exposure and urinary incontinence in American men. Materials and Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 were merged to include 5,297 men 20 years old or older. The question, “Did you ever serve in the Armed Forces of the United States?” (yes/no) was used to assess military exposure. Urinary incontinence was categorized as any or moderate/severe urinary incontinence vs none. Because the impact of military exposure varied by age, multivariate logistic regression models were used to estimate the OR and 95% CI stratified by 3 age groups, including 55 or less, 56 to 69 and 70 years or greater. Analysis was adjusted for race/ethnicity, education, body mass index, self-reported health status, number of chronic conditions, depression and prostate conditions, the latter in men 40 years old or older. Results: Overall 23% of male respondents reported military exposure. Men with military exposure were more likely to report any urinary incontinence (18.6% vs 10.4%) and moderate/severe urinary incontinence (9.0% vs 3.1%, each p <0.001) than men without military exposure. After multivariate adjustment in men 55 years old or younger those with military exposure had 3 times greater odds of urinary incontinence (OR 3.28, 95% CI 1.38–7.77). Military exposure did not increase the odds of urinary incontinence in men 56 to 69 years old (OR 0.97, 95% CI 0.44–2.18), or 70 years old or older (OR 0.91, 95% CI 0.55–1.50). Conclusions: Prior military exposure was associated with moderate/severe urinary incontinence in American men 55 years old or younger even after controlling for known risk factors. Case finding is warranted for urinary incontinence in younger men with a history of military service. [Copyright &y& Elsevier]

Purpose: We report progression and regression of lower urinary tract symptoms in a population based cohort by race/ethnicity, gender, age and lower urinary tract symptom medication use. Materials and Methods: The BACH (Boston Area Community Health) Survey enrolled 5,502 participants 30 to 79 years old of black, Hispanic or white race/ethnicity. The 5-year followup interviews were completed by 1,610 men and 2,534 women for a conditional response rate of 80%. Population weighted estimates of lower urinary tract symptoms severity were assessed using the AUASI (American Urological Association symptom index) and analyzed using multivariate models. Results: Symptom progression (increase in AUASI score of 3 or more points) was reported by 21% to 33% of participants and regression (decrease 3 or greater) by 30% to 44% of participants, most commonly women and Hispanic participants. Age and higher body mass index were associated with progression (p <0.01), but not with regression. Lower urinary tract symptom medication use at baseline only was associated with improved symptoms scores 5 years later (multivariate adjusted OR 3.10, 95% CI 1.28–7.51, compared to nonusers), whereas using medication at baseline and followup was associated with similar rates of progression and regression as observed among participants not using lower urinary tract symptom medication at either point. Conclusions: Lower urinary tract symptoms persisted at followup for approximately half of the population experiencing symptoms at baseline, including many men and women using lower urinary tract symptom medications. However, overall lower urinary tract symptom medication use and surgical treatment appeared beneficial for symptom control at 5-year followup. Age and body mass index were associated with symptom worsening, and Hispanic ethnicity was associated with greater symptom fluctuation. Clinicians should consider the higher likelihood of lower urinary tract symptom progression for older or heavier patients, and monitor responsiveness to lower urinary tract symptom medication. [Copyright &y& Elsevier]

Purpose: We evaluate the bidirectional association between urological symptoms (urinary incontinence, lower urinary tract symptoms and nocturia) and sleep related variables. Materials and Methods: Data were obtained from a prospective cohort study of 1,610 men and 2,535 women who completed baseline (2002 to 2005) and followup (2006 to 2010) phases of the BACH (Boston Area Community Health) Survey, a population based random sample survey. Sleep restriction (5 hours or less per night), restless sleep, sleep medication use and urological symptoms were assessed by self-report. Urinary incontinence was defined as weekly leakage or moderate/severe leakage, lower urinary tract symptoms (overall, obstructive, irritative) were defined by the AUA-SI (American Urological Association symptom index) and nocturia was defined as urinary frequency 2 or more times per night. Results: At the 5-year followup 10.0%, 8.5% and 16.0% of subjects newly reported lower urinary tract symptoms, urinary incontinence and nocturia, respectively, and 24.2%, 13.3% and 11.6% newly reported poor sleep quality, sleep restriction and use of sleep medication, respectively. Controlling for confounders, the odds of urological symptoms developing were consistently increased for subjects who reported poor sleep quality and sleep restriction at baseline, but only baseline nocturia was positively associated with incident sleep related problems at followup. Body mass index, a potential mediator, reduced selected associations between sleep and incident urinary incontinence and irritative symptoms, but C-reactive protein did not. Conclusions: These data suggest that self-reported sleep related problems and urological symptoms are linked bidirectionally, and that body mass index may be a factor in the relationship between sleep and the development of urological symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Accurate urine assays for bladder cancer detection would benefit patients and health care systems. Through extensive genomic and proteomic profiling of urine components we previously identified a panel of 8 biomarkers that can facilitate the detection of bladder cancer in voided urine samples. In this study we confirmed this diagnostic molecular signature in a diverse multicenter cohort. Materials and Methods: We performed a case-control, phase II study in which we analyzed voided urine from 102 subjects with bladder cancer and 206 with varying urological disorders. The urinary concentration of 8 biomarkers (IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE) was assessed by enzyme-linked immunosorbent assay. Diagnostic performance of the panel of tested biomarkers was evaluated using ROCs and descriptive statistical values, eg sensitivity and specificity. Results: Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84–0.93), and 74% sensitivity and 90% specificity. In contrast, the sensitivity of voided urine cytology and the UroVysion® cytogenetic test in this cohort was 39% and 54%, respectively. Study limitations include analysis performed on banked urine samples and the lack of voided urine cytology and cytogenetic test data on controls. Conclusions: The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays. [ABSTRACT FROM AUTHOR]

Purpose: An epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidated Materials and Methods: We enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors. Results: Age, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p <0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy = 0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3. Conclusions: Risk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups. [Copyright &y& Elsevier]

Purpose: We report the first multicenter randomized blinded trial of the prostatic urethral lift for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Materials and Methods: Men at least 50 years old with AUASI (American Urological Association Symptom Index) 13 or greater, a maximum flow rate 12 ml per second or less and a prostate 30 to 80 cc were randomized 2:1 between prostatic urethral lift and sham. In the prostatic urethral lift group small permanent implants are placed within the prostate to retract encroaching lobes and open the prostatic urethra. Sham entailed rigid cystoscopy with sounds mimicking the prostatic urethral lift. The primary end point was comparison of AUASI reduction at 3 months. The prostatic urethral lift arm subjects were followed to 1 year and assessed for lower urinary tract symptoms, peak urinary flow rate, quality of life and sexual function. Results: A total of 206 men were randomized (prostatic urethral lift 140 vs sham 66). The prostatic urethral lift and sham AUASI was reduced by 11.1 ± 7.67 and 5.9 ± 7.66, respectively (p = 0.003), thus meeting the primary end point. Prostatic urethral lift subjects experienced AUASI reduction from 22.1 baseline to 18.0, 11.0 and 11.1 at 2 weeks, 3 months and 12 months, respectively, p <0.001. Peak urinary flow rate increased 4.4 ml per second at 3 months and was sustained at 4.0 ml per second at 12 months, p <0.001. Adverse events were typically mild and transient. There was no occurrence of de novo ejaculatory or erectile dysfunction. Conclusions: The prostatic urethral lift, reliably performed with the patient under local anesthesia, provides rapid and sustained improvement in symptoms and flow, while preserving sexual function. [ABSTRACT FROM AUTHOR]

Purpose: We performed a meta-analysis to compare treatment with α-blockers and anticholinergics (ie combination therapy) to α-blocker monotherapy to clarify the efficacy and safety of this treatment approach among men with storage urinary symptoms related to benign prostatic hyperplasia. Materials and Methods: We searched for trials of men with benign prostatic hyperplasia/lower urinary tract symptoms that were randomized to combination treatment or α-blockers alone. We pooled data from 7 placebo controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (storage subscores) and urinary frequency. We also assessed post-void residual volume, maximal flow rate and the incidence of urinary retention. Data were pooled using random effects models for continuous outcomes and the Peto method to generate odds ratios for acute urinary retention. Results: Combination therapy had a significantly greater reduction in International Prostate Symptom Score storage subscores (Δ −0.73, 95% CI −1.09 – −0.37) and voiding frequency (Δ −0.69 voids, 95% CI −0.97 – −0.41). There was also a greater reduction in maximal urinary flow rate (Δ −0.59 ml per second, 95% CI −1.04 – −0.14) and increase in post-void residual urine volume (Δ 11.60 ml, 95% CI 8.50–14.70) with combination therapy. The number needed to treat with combination therapy to cause 1 acute urinary retention episode was 101 (95% CI 60–267). Conclusions: Combination treatment with α-blockers and anticholinergics significantly improved storage voiding parameters compared to men treated with α-blocker therapy alone. This treatment approach is safe with a minimal risk of increased post-void residual urine volume, decreased maximal urinary flow rate or acute urinary retention. [ABSTRACT FROM AUTHOR]

Purpose: Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. Materials and Methods: An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Results: Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. Conclusions: We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

Purpose: Testosterone replacement therapy is commonly used to treat men with hypogonadism. However, there has been caution in using testosterone replacement therapy in men with moderate to severe lower urinary tract symptoms for fear of worsening the symptoms. In this study we examine the effect of testosterone replacement therapy on lower urinary tract symptoms in hypogonadal men. Materials and Methods: We retrospectively reviewed our outpatient database and identified patients with a diagnosis of hypogonadism who received testosterone replacement therapy from 2002 to 2012. Lower urinary tract symptoms were assessed using the AUASI (American Urological Association symptom index) before and after testosterone replacement therapy. Testosterone and prostate specific antigen were also continuously measured, and all patients were closely monitored for side effects of testosterone replacement therapy. Patients who had progression of lower urinary tract symptoms to the point of requiring surgery were included in the study. Results: We identified 120 hypogonadal men who received testosterone replacement therapy, the majority of whom had topical therapy or a combination of topical and pellet based therapy (57.5% and 20.8%, respectively). Mean baseline AUASI (±SD) was 10.8 (±7.8) and mean duration of testosterone replacement therapy was 692 days (±773). Mean change in AUASI was -1.07 (±6.06). Mean baseline prostate specific antigen was 1.6 ng/dl (±1.9) and mean change in prostate specific antigen was 0.44 (±2.2). Of the patients 8.1% had a baseline prostate specific antigen greater than 4.0 ng/dl, and these patients had greater improvement in AUASI than those with a baseline prostate specific antigen less than 4.0 ng/dl (-1.9 vs -1.0, p not significant). Overall 45.8% of patients had a less than 3-point change in AUASI in either direction. Of the 120 patients 38 (31.7%) had improvement in AUASI 3 or more points while 27 (22.5%) had worsening of AUASI 3 or more points. Patients with an improved AUASI had a mean prostate specific antigen change of 0.3 (±3.4), while those who had worsening of AUASI had a mean prostate specific antigen change of 0.7 (±2.2) (p not significant). Approximately 9 of 120 (7.5%) of these men initiated new medications for lower urinary tract symptoms during the course of the study. There was no significant change in AUASI compared to patients without any use of lower urinary tract symptoms medications. In addition, 4 (3.3%) patients had progression of lower urinary tract symptoms and required transurethral resection of the prostate. Conclusions: We demonstrate that initiating testosterone replacement therapy in hypogonadal men involves a low risk of worsening lower urinary tract symptoms. In fact, many men experience symptom improvement while changes in prostate specific antigen appear minor. Future research should focus on larger patient population studies to further examine this relationship. [ABSTRACT FROM AUTHOR]

Purpose: Due to varying clinical definitions of lower urinary tract symptoms, it has been difficult to determine comparable prevalence and incidence rates of lower urinary tract symptoms and their treatment modalities. We assessed the incidence of emergency department visits in men with lower urinary tract symptoms who presented to emergency departments in the United States and factors associated with an increased likelihood of hospitalization. Materials and Methods: Emergency department visits from 2006 to 2009 associated with a primary diagnosis of lower urinary tract symptoms using established criteria were abstracted from the Nationwide Emergency Department Sample. Age adjusted incidence rates of emergency department visits and charges were calculated. We performed multivariable analysis to examine patient and hospital characteristics of those hospitalized and those with benign prostatic hyperplasia related adverse events. Results: A weighted estimate of 1,178,423 emergency department visits for lower urinary tract symptoms was recorded with a national incidence of 197.6/100,000 males per year. A total of 112,288 visits (9.5%) resulted in hospitalization. Adverse events were identified in 734,269 patients (62.3%). The most common adverse events were catheterization in 44.6% of cases, infection in 17.4%, hematuria in 9.6%, bladder stones in 1.7%, hydronephrosis in 1.2% and acute renal failure in 0.1%. On multivariable analysis independent predictors of hospital admission included comorbidities, socioeconomic status, hospital characteristics and adverse events such as sepsis, acute renal failure and hydronephrosis. Independent predictors of adverse events included patient age, year of visit, socioeconomic status, hospital characteristics and concomitant neurological disease. In 2009 total emergency department charges for lower urinary tract symptoms were $494,981,922. Conclusions: The number of men with lower urinary tract symptoms who visit the emergency department has remained stable, while emergency department charges have increased by 40%. The rate of adverse events increased during the study period. These findings might suggest over reliance on medical and conservative therapy in the contemporary era. [Copyright &y& Elsevier]

Purpose: Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. Materials and Methods: We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Results: Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. Conclusions: As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. [Copyright &y& Elsevier]

Purpose: Phosphodiesterase type 5 inhibitors were recently introduced as a new treatment option for men with lower urinary tract symptoms. Safety and clinical effectiveness are well documented but the mode of action is still unclear. We determined and compared the expression of phosphodiesterase type 5 in the spinal cord of normal (sham operated) rats and rats with partial urethral obstruction induced bladder overactivity. We also assessed the urodynamic effects of intravenously and intrathecally administered sildenafil in the rats to determine whether phosphodiesterase type 5 inhibitors exert effects on the sacral spinal cord. Materials and Methods: A total of 65 male Sprague-Dawley® rats were used for molecular/morphological and functional experiments. Bladder overactivity was induced via surgical partial urethral obstruction in 39 of 65 rats. Spinal phosphodiesterase type 5 expression was assessed by histology and polymerase chain reaction. The effects of sildenafil administered intravenously or intrathecally were studied urodynamically. Results: Phosphodiesterase type 5 was expressed in various regions of the lumbosacral spinal cord, including the sacral regions of micturition control. Expression was similar in normal rats and rats with partial urethral obstruction/bladder overactivity. In normal rats intravenous and intrathecal sildenafil had no urodynamic effect. When administered intravenously and intrathecally to rats with partial urethral obstruction/bladder overactivity, sildenafil decreased micturition frequency and bladder pressure. Doses tested intrathecally had no effect when given intravenously. Conclusions: Phosphodiesterase type 5 is expressed in the rat spinal cord. Intravenous sildenafil may exert part of its urodynamic effect in rats with partial urethral obstruction/bladder overactivity via an effect on the sacral spinal cord. [ABSTRACT FROM AUTHOR]

Purpose: Bladder outlet obstruction often presents as storage and voiding symptoms. We investigated urodynamic parameters in men with lower urinary tract symptoms and bladder outlet obstruction treated with the β3 agonist mirabegron, a new therapy for overactive bladder symptoms. Materials and Methods: A total of 200 men 45 years old or older with lower urinary tract symptoms and bladder outlet obstruction were randomized to receive once daily mirabegron 50 mg (70) or 100 mg (65), or placebo (65) for 12 weeks. The primary urodynamic parameters assessed were change from baseline to end of treatment in maximum urinary flow and detrusor pressure at maximum urinary flow (noninferiority margins –3 ml per second and 15 cm H2O, respectively). We evaluated adverse events and vital signs. Results: Treatment with mirabegron 50 and 100 mg was noninferior to placebo based on the lower and upper limits of the 95% CI, respectively, for maximum urinary flow and detrusor pressure at maximum urinary flow. The adjusted mean difference vs placebo was 0.40 (95% CI –0.63, 1.42) and 0.62 ml per second (95% CI –0.43, 1.68) for maximum urinary flow, and –5.94 (95% CI –13.98, 2.09) and –1.39 cm H2O (95% CI –9.73, 6.96), respectively, for detrusor pressure at maximum urinary flow. The incidence of adverse events was similar for mirabegron and placebo. Conclusions: Mirabegron did not adversely affect voiding urodynamics (maximum urinary flow and detrusor pressure at maximum urinary flow) compared with placebo after 12 weeks of treatment. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the effectiveness of photodynamic therapy using Radachlorin® in patients with high grade, nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy who refused radical cystectomy. Materials and Methods: Between July 2009 and December 2011 photodynamic therapy was performed in 22 men and 12 women. Radachlorin (0.5 to 0.6 mg/kg) was injected intravenously 2 to 3 hours before photodynamic therapy. After complete transurethral resection, a diffuser using a 22Fr cystoscope was placed in the bladder for irradiation with a 662 nm laser. Output beam power was adjusted to 1.8 W and the light dose was 15 J/cm2. Photodynamic therapy was performed for 16 to 30 minutes. Recurrence after photodynamic therapy was followed by regular cystoscopy at 1, 2 and 3 months, and at 3-month intervals thereafter for up to 2.8 years. Efficacy was assessed by cystoscopy, cytology and histology, and defined as the number of patients who were tumor free after initial photodynamic therapy. Results: Mean ± SD patient age was 62.94 ± 8.71 years. Average followup was 26.74 ± 6.34 months (median 28.12). As the primary efficacy outcome, the recurrence-free rate was 90.9% at 12 months, 64.4% at 24 months and 60.1% at 30 months. As the secondary efficacy outcome, there was no statistical difference in mass size, carcinoma in situ, number of previous bacillus Calmette-Guérin administrations, number of transurethral bladder resections or tumor multiplicity on Kaplan-Meier analysis (each p >0.05). No evidence of severe adverse effects was detected after photodynamic therapy. Conclusions: Photodynamic therapy with Radachlorin is a safe, effective treatment for nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy in select patients. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the effects of the selective α1A-adrenoceptor antagonist silodosin on bladder blood flow and bladder function in a rat model of atherosclerosis induced chronic bladder ischemia without bladder outlet obstruction. Materials and Methods: The chronic bladder ischemia model was prepared by creating balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, chronic bladder ischemia rats received silodosin subcutaneously at a rate of 0.1 or 0.3 mg/kg per day, or vehicle for 8 weeks. All groups received a 2% cholesterol diet throughout the experiment. For each α1-adrenoceptor subtype mRNA expression in bladder microvessels was examined by in situ hybridization. Bladder blood flow was measured using a laser speckle blood flow imager. Malondialdehyde in bladder tissue and 8-hydroxy-2′-deoxyguanosine in urine were measured as markers of oxidative stress. A metabolic cage study and cystometry were performed in conscious rats. Results: The expression of all α1-adrenoceptor subtype mRNA was observed in rat bladder microvessels. Silodosin abrogated the decreased bladder blood flow in the empty bladder and during bladder distention that were evident in rats with chronic bladder ischemia. Levels of oxidative stress markers in these rats were significantly decreased by silodosin administration. Silodosin ameliorated bladder dysfunction in rats with chronic bladder ischemia in the metabolic cage study and on cystometry. Conclusions: Results suggest that in ischemic conditions α1-adrenoceptor antagonists such as silodosin may improve bladder function by restoring bladder blood flow. [ABSTRACT FROM AUTHOR]

Purpose: It is recognized that there is a strong association between bladder and bowel dysfunction. We determined the association of constipation and/or encopresis with specific lower urinary tract conditions. Materials and Methods: We reviewed our database of children with lower urinary tract dysfunction and divided cases into 3 categories of bowel dysfunction (constipation, encopresis and constipation plus encopresis) and 4 lower urinary tract conditions (dysfunctional voiding, idiopathic detrusor overactivity disorder, detrusor underutilization disorder and primary bladder neck dysfunction). Associations between bowel dysfunction types and each lower urinary tract condition were determined. Results: Of 163 males and 205 females with a mean age of 8.5 years constipation was the most common bowel dysfunction (27%). Although encopresis is generally thought to reflect underlying constipation, only half of children with encopresis in this series had constipation. Dysfunctional voiding was associated with the highest incidence of bowel dysfunction. All but 1 patient with encopresis had associated urgency and detrusor overactivity, and the encopresis resolved in 75% of patients after initiation of anticholinergic therapy. Constipation was significantly more common in girls (27%) than in boys (11%, p <0.01), while encopresis was more common in boys (9%) than in girls (3%, p = 0.02), likely reflecting the higher incidence of dysfunctional voiding in girls and idiopathic detrusor overactivity disorder in boys. Conclusions: Active bowel dysfunction was seen in half of the children with a lower urinary tract condition. Constipation was more common in patients with dysfunctional voiding, while encopresis was significantly increased in those with idiopathic detrusor overactivity disorder and in those with dysfunctional voiding, severe urgency and detrusor overactivity. Anticholinergics, despite their constipating effect, given for treatment of detrusor overactivity resolved encopresis in most children with this bowel dysfunction. [Copyright &y& Elsevier]

Purpose: We determined flow rates and generated flow rate-voided volume nomograms based on healthy children 5 to 15 years old voiding spontaneously in their natural environment. Materials and Methods: A total of 824 healthy school children of both genders were enrolled. A single uroflow record from each child was evaluated. A total of 103 children with a voided volume of less than 50 ml and/or a staccato/interrupted uroflow pattern were excluded, and 721 records were analyzed. Data were evaluated using several mathematical formulas and goodness of fit was determined. Linear regression analysis was used to generate nomograms. Results: Flow rates and voided volumes increased with increasing age, with the effect being more pronounced in girls. No significant difference was noted in uroflow rates from 5 to 10 years, but significant differences (p <0.001) started appearing at 11 to 15 years. Also no significant difference was noted in uroflow rates among children 11 to 15 years. Therefore, 2 age groups were designated, with group 1 consisting of patients 5 to 10 years old and group 2 consisting of patients 11 to 15 years old. There were 222 boys and 122 girls in group 1 and 240 boys and 137 girls in group 2. In group 1 the maximum and average ± SD flow rates were 15.26 ± 4.54 ml per second and 7.68 ± 3.26 ml per second, respectively, for boys and 17.98 ± 6.06 ml per second and 9.19 ± 4.23 ml per second, respectively, for girls. In group 2 these rates were 22.50 ± 7.24 ml per second and 10.78 ± 4.03 ml per second, respectively, for boys and 27.16 ± 9.37 ml per second and 13.48 ± 5.21 ml per second, respectively, for girls. Conclusions: This large study, which expands the scant existing literature on uroflow parameters in healthy children, will hopefully promote wider application of uroflowmetry testing in the pediatric population. [ABSTRACT FROM AUTHOR]

Purpose: We present 5 years of outcome data on metallic ureteral stents in a cohort of patients treated for chronic ureteral obstruction. Materials and Methods: We retrospectively identified and analyzed the records of all patients in whom a Resonance® Metallic Ureteral Stent was placed between early 2007 and late 2011 at our institution. We performed a descriptive analysis of key outcomes, including the failure and death rates, and stenting duration, defined as the time from initial stent placement to last stent failure or patient death. We also performed a secondary comparative analysis of patients with a benign vs malignant etiology of obstruction. Results: A total of 139 metallic stents were placed in 47 patients, including 27 (57%) with malignant and 20 (43%) with a benign etiology. Of the patients 15 (32%) had bilateral obstruction. Maximum followup was 59 months (mean 20, median 13, IQR 4–31). Stent failure occurred in 13 patients (28%), including 4 in the benign and 9 in the malignant group (p = 0.35). The median duration of stenting for benign and malignant obstruction was 22 (IQR 9–39) vs 7 months (IQR 3–25) (p = 0.106). Stenting duration was equivalent when controlling for the higher death rate in the malignant group. Conclusions: Resonance metallic stents are an adequate management strategy for benign and malignant ureteral obstruction. A subset of patients in each group continued to do well at more than a 3-year overall duration of stenting. Failure rates were similar for benign and malignant etiologies. [ABSTRACT FROM AUTHOR]

Purpose: Mammals urinate less frequently during the sleep period than the awake period. This is modulated by a triad of factors, including decreased arousal in the brain, a decreased urine production rate in the kidneys and increased functional bladder capacity during sleep. The circadian clock is genetic transcription-translation feedback machinery. It exists in most organs and cells, termed the peripheral clock, which is orchestrated by the central clock in the suprachiasmatic nucleus of the brain. We discuss the linkage between the day and night change in micturition frequency and the genetic rhythm maintained by the circadian clock system, focusing on the brain, kidney and bladder. Material and Methods: We performed an inclusive review of the literature on the diurnal change in micturition frequency, urine volume, functional bladder capacity and urodynamics in humans and rodents, relating this to recent basic biological findings about the circadian clock. Results: In humans various behavioral studies demonstrated a diurnal functional change in the kidney and bladder. Conversely, patients with nocturnal enuresis and nocturia showed impairment in this triad of factors. Rats and mice, which are nocturnal animals, also have a micturition frequency rhythm that is decreased during the day, which is the sleep phase for them. Mice with a genetically defective circadian clock system show impaired physiological rhythms in the triad of factors. The existence of the circadian clock has been proven in the brain, kidney and bladder, in which thousands of circadian oscillating genes exist. In the kidney they include genes involved in the regulation of water and major electrolytes. In the bladder they include connexin 43, a gene associated with the regulation of bladder capacity. Conclusions: Recent progress in molecular biology about the circadian clock provides an opportunity to investigate the genetic basis of the micturition rhythm or impairment of the rhythm in nocturnal enuresis and nocturia. If this approach is to be translated clinically, a strategy is to analyze and treat the triad of micturition factors as separate parts of 1 problem. The other way could be to cope with this triad of problems simultaneously, if possible, by treating the circadian physiological rhythm itself. The discoveries reviewed point toward further investigation of the micturition rhythm by basic and translational chronobiology. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effects of doxazosin, finasteride and combination therapy among men with benign prostatic hyperplasia on quality of life assessed with MOS-SF-36 (Medical Outcomes Study Short-Form 36) and 2 disease specific instruments (BII, benign prostatic hyperplasia Impact Index and I-PSS-QoL, International Prostate Symptom Score-QoL) during 4 years. Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in quality of life was a secondary outcome. A total of 2,872 men enrolled in the MTOPS study who had 3 baseline quality of life measures and at least 1 followup measure by any of the quality of life instruments were analyzed. Results: Compared with men assigned to placebo, men assigned to doxazosin and combination experienced a statistically significant improvement in the BII at year 4. Men assigned to each of the drug groups also experienced a significant improvement in the I-PSS-QoL compared with those assigned to placebo. Considering longitudinal changes during 4 years, a significant improvement in BII and I-PSS-QoL scores was observed in men assigned to the drug groups compared with those assigned to placebo. However, there were no significant differences for the MOS-SF-36 subscales and summary scores when drug groups were compared with the placebo group. Conclusions: The quality of life of men treated with doxazosin, finasteride, and the drugs combined generally improved when assessed with the BII and the I-PSS-QoL compared with those treated with placebo. Quality of life did not show improvement when measured by the MOS-SF-36. [Copyright &y& Elsevier]

Purpose: Alpha-blockers improve lower urinary tract symptoms associated with benign prostatic obstruction. Nocturia, a storage symptom, is a common complaint in men. However, it does not fully respond to α-blocker therapy, likely due to its multifactorial pathophysiology. We evaluated the efficacy and safety of desmopressin as add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms. Materials and Methods: Eligible patients were men 50 years old or older with lower urinary tract symptoms and persistent nocturia despite α-blocker treatment for a minimum of 4 weeks. The optimum dose of oral desmopressin was determined during a 4-week dose titration period and this dose was maintained for 24 weeks. Flow volume charts, International Prostate Symptom Score total and subscores, uroflowmetry and post-void residual urine volume were assessed. Results: A total of 216 patients were enrolled in the study. Of these patients there were 158 (76%) with nocturnal polyuria, 15 (7.2%) with decreased nocturnal bladder capacity and 35 (16.8%) with nocturia due to both causes. The number of nocturnal voids significantly decreased from a baseline mean of 7.0 to 5.7 episodes for 3 days at the 24-week visit. The average International Prostate Symptom Score total and subscore significantly decreased by 4 weeks and were maintained at 24 weeks. In patients younger than 65 years, International Prostate Symptom Score voiding subscores were significantly improved at 24 weeks compared to those age 65 years or older. Conclusions: Desmopressin add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms improved voiding symptoms as well as nocturia, storage symptoms. [Copyright &y& Elsevier]

Purpose: We present a consensus view of members of the International Children's Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms. Materials and Methods: Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary. Results: Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined. Conclusions: The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings. [Copyright &y& Elsevier]