A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis.

OBJECTIVE: To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). MATERIALS AND METHODS: Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O'Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. RESULTS: Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O'Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. CONCLUSIONS: Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

A minimum of 1-year follow-up for MiniArc single incision slings compared to Monarc transobturator slings: An analysis to evaluate durability of continence and medium-term outcomes.

AIMS: To compare efficacy and safety of two commercially available single incision slings (SIS) and trans-obturator vaginal tapes (TOT), namely MiniArc™ and Monarc™ slings, and report the results at 5-year follow-up. METHODS: A retrospective-observational study of prospectively collected data was conducted on 381 women with primary stress urinary incontinence (SUI) in a single tertiary referral center. Patients treated with MiniArc™ and Monarc™ were compared. Data regarding intraoperative and post-operative outcomes were collected and compared. Kaplan-Meier analyses assessed continence rate (CR), objective cure (OC) rate, de novo overactive bladder symptoms (OAB), surgical failure (SF), and erosion free rates at 1-, 3-, and 5-year follow-up. The log-rank test was used to compare efficacy and complication between patients stratified according to the type of surgery. RESULTS: Median follow-up was 60 months. Of 381 patients, 215 (56%) were treated with Monarc™ slings and 166 (44%) with MiniArc™. The two groups were homogeneous in terms of pre-operative characteristics. At 5-year follow-up, no difference was found in CR between Monarc™ and Miniarc™ patients (87% vs. 89%; P = 0.41). Monarc™ showed better OAB free rates (97% vs. 92%; P = 0.012). No significant differences have been found in terms of SF, erosion, and OC rates. These results are limited by their retrospective nature. CONCLUSIONS: We demonstrated that the short-term results of MiniArc™, are maintained over time, defining the comparability of the two slings at 5 years in terms of subjective and objective outcomes and complications. Neurourol. Urodynam. 36:803-807, 2017. © 2016 Wiley Periodicals, Inc.

Sexual and bladder comorbidity in women.

Sexual dysfunction in women is defined as disorders of sexual desire, arousal, orgasm, and/or sexual pain, which result in significant personal distress and may have a negative effect on a woman's health and an impact on her quality of life. A comprehensive understanding of the anatomic, neurobiologic, and psychologic mechanisms behind women's sexual function and dysfunction is of paramount importance. This chapter reviews the most frequent comorbid conditions related to urinary tract symptoms (thus including symptoms related to overactive bladder syndrome and urinary incontinence) and sexual dysfunction in women. Likewise, it considers the different disorders from the point of view of daily clinical practice.

Awareness and knowledge of human papillomavirus-related diseases are still dramatically insufficient in the era of high-coverage vaccination programs.

PURPOSE: Assess knowledge and awareness concerning human papillomavirus (HPV) infection, HPV-associated diseases, and the existence of a specific vaccine among non-HPV-screened Caucasian-European adults after the market introduction of HPV vaccines. METHODS: A cohort of 934 consecutive patients seeking their first medical help for uroandrologic purposes anonymously completed a 17-item questionnaire related to HPV. Data were compared with those of an age-comparable cohort of nurses (controls; n = 172). RESULTS: Knowledge and awareness of HPV infection were reported in 564 (51%) and 735 (66.5%) participants, respectively. Overall, 51.3% participants were informed that HPV is sexually transmitted, but most reported not being aware that HPV infection can be associated with anogenital warts (61.7%), female genitalia (46.6%), penile (58.5%), and oropharyngeal cancer (79.7%). Only 36.5% of the participants were informed regarding the existence of a specific vaccine. HPV knowledge was retrieved through the media and/or the Internet, at school, doctors, and relatives or friends in 395 (35.7%), 155 (14%), 97 (8.8%), and 88 (8.0%) participants, respectively. Multivariable analyses showed that female gender [odds ratio (OR) 3.08; p < 0.001; 95% confidence interval 2.18-4.35] and educational status [high school diploma versus primary-secondary (OR 1.61; p = 0.03; 1.04-2.51); university degree versus primary-secondary (OR 2.89; p < 0.001; 1.83-4.57)] were significantly associated with awareness of HPV. CONCLUSIONS: Only approximately half of the participants reported knowing what HPV infection is, even after the approval and market introduction of the HPV vaccine. Awareness about the existence and availability of a HPV vaccine was even lower.

Prevention and management of post prostatectomy erectile dysfunction.

Sexual dysfunction is common in patients with prostate cancer (PC) following radical prostatectomy (RP). Review the available literature concerning prevention and management strategies for post-RP erectile function (EF) impairment in terms of preoperative patient characteristics, intra and postoperative factors that may influence EF recovery, and postoperative treatments for erectile dysfunction (ED). A literature search was performed using Google and PubMed database for English-language original and review articles, either published or e-published up to July 2013. The literature still demonstrates a great inconsistency in the definition of what is considered normal EF both before and after RP. Thus, using validated psychometric instruments with recognized cut-offs for normalcy and severity during the pre- and post-operative evaluation should be routinely considered. Therefore, a comprehensive discussion with the patient about the true prevalence of postoperative ED, the concept of spontaneous or pharmacologically-assisted erections, and the difference between "back to baseline" EF and "erections adequate enough to have successful intercourse" clearly emerge as key issues in the eventual understanding of post-RP ED prevention and promotion of satisfactory EF recovery. Patient factors (including age, baseline EF, comorbid conditions status), cancer selection (non- vs. uni- vs. bilateral nerve-sparing), type of surgery (i.e., intra vs. inter vs. extrafascial surgeries), surgical techniques (i.e., open, laparoscopic and robotically-assisted RP), and surgeon factors (i.e., surgical volume and surgical skill) represent the key significant contributors to EF recovery. A number of preclinical and clinical data show that rehabilitation and treatment in due time are undoubtedly better than leaving the erectile tissue to its unassisted postoperative fate. The role of postoperative ED treatment for those patients who received a non-nerve-sparing RP was also extensively discussed. Optimal outcomes are achieved mainly by the careful choice of the correct patient for the correct type of surgery. Despite a plethora of potential rehabilitative approaches, they should be only considered as "strategies", since incontrovertible evidence of their effectiveness for improving natural EF recovery is limited. Conversely, numerous effective therapeutic options are available for treating post-RP ED.

One patient out of four with newly diagnosed erectile dysfunction is a young man--worrisome picture from the everyday clinical practice.

INTRODUCTION: Erectile dysfunction (ED) is a common complaint in men over 40 years of age, and prevalence rates increase throughout the aging period. Prevalence and risk factors of ED among young men have been scantly analyzed. AIM: Assessing sociodemographic and clinical characteristics of young men (defined as ≤ 40 years) seeking first medical help for new onset ED as their primary sexual disorder. METHODS: Complete sociodemographic and clinical data from 439 consecutive patients were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). MAIN OUTCOME MEASURE: Descriptive statistics tested sociodemographic and clinical differences between ED patients ≤ 40 years and >40 years. RESULTS: New onset ED as the primary disorder was found in 114 (26%) men ≤ 40 years (mean [standard deviation [SD]] age: 32.4 [6.0]; range: 17-40 years). Patients ≤ 40 years had a lower rate of comorbid conditions (CCI = 0 in 90.4% vs. 58.3%; χ(2) , 39.12; P < 0.001), a lower mean body mass index value (P = 0.005), and a higher mean circulating total testosterone level (P = 0.005) as compared with those >40 years. Younger ED patients more frequently showed habit of cigarette smoking and use of illicit drug, as compared with older men (all P ≤ 0.02). Premature ejaculation was more comorbid in younger men, whereas Peyronie's disease was prevalent in the older group (all P = 0.03). At IIEF, severe ED rates were found in 48.8% younger men and 40% older men, respectively (P > 0.05). Similarly, rates of mild, mild-to-moderate, and moderate ED were not significantly different between the two groups. CONCLUSIONS: This exploratory analysis showed that one in four patients seeking first medical help for new onset ED was younger than 40 years. Almost half of the young men suffered from severe ED, with comparable rates in older patients. Overall, younger men differed from older individuals in terms of both clinical and sociodemographic parameters.

Sperm banking is of key importance in patients with prostate cancer.

OBJECTIVE: To assess the need for sperm banking among patients with prostate cancer (PCa) who are candidates for radical prostatectomy (RP). DESIGN: Cross-sectional study. SETTING: Urologic department. PATIENT(S): Cohort of 510 Caucasian-European candidates for RP. INTERVENTION(S): A 10-item self-administered questionnaire to assess opinions on sperm banking before RP, to which descriptive statistics and logistic regression models were applied. MAIN OUTCOME MEASURE(S): PCa patients' wishes for preoperative sperm banking. RESULT(S): Data collection was completed for 495 patients (97.1%). Ninety-nine (20%) expressed a wish for preoperative sperm banking. Men who wanted to bank sperm were younger (mean 62.2 vs. 65.1 years), were more frequently childless (21.2% vs. 8.8%), and more frequently had a more intense desire for fatherhood (64.7% vs. 9.3%) than the patients not interested in banking sperm. Willingness to bank sperm was not affected by the patient's educational or relationship status. Moreover, the interest for sperm banking was maintained regardless of cost issues. Overall, 84% of the patients considered it necessary to have a dedicated service of preoperative sperm cryopreservation. CONCLUSION(S): One out of five PCa patients would bank sperm before RP. Most patients considered it necessary to establish a dedicated service for preoperative sperm cryopreservation, regardless of their own motivation to bank sperm.

Circulating sex steroids and prostate cancer: introducing the time-dependency theory.

PURPOSE: We sought whether serum total testosterone (tT), estradiol (E2), tT/E2 ratio, and sex hormone-binding globulin (SHBG) significantly fluctuate throughout time in men with prostate cancer (PCa). METHODS: Circulating hormones were measured in a cohort of 631 candidates for radical prostatectomy. Hormone levels were analyzed according to either patient age, stratified into quartiles, or body mass index (BMI). Linear regression analyses tested the association between sex steroids and continuously coded patient age and BMI values. RESULTS: No significant differences were found among age quartiles regarding serum tT levels and tT/E2 ratio. Conversely, E2 and SHBG levels significantly increased throughout time (all, p ≤ 0.001). Total T did not linearly change according to continuously coded patient age; in contrast, E2 and SHBG linearly increased (all, p ≤ 0.001), whereas tT/E2 decreased (p = 0.016) with aging. Rate of hypogonadism significantly increased with aging (p = 0.04). Total T, T/E2 ratio, and SHBG linearly decreased along with BMI increases (all p ≤ 0.02), whereas serum E2 did not significantly change. Rate of hypogonadism significantly increased with BMI increases (p < 0.001). CONCLUSIONS: In contrast with longitudinal studies in the general male population, these data indirectly suggest that serum tT levels could be stable over time in PCa patients. This finding led to formulation of a "time-dependency theory", which postulates that the endocrine biology of prostate tissue is dependent on the exposure time at a given concentration of sex steroid, which, in turn, fluctuates throughout the lifespan of the individual.

Inhibition of phosphodiesterase 4 enhances clitoral and vaginal blood flow responses to dorsal clitoral nerve stimulation or PGE1 in anesthetized female rats.

INTRODUCTION.: Cyclic adenosine 3'5' monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response. AIM.: The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat. METHODS.: Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated. MAIN OUTCOME MEASURE.: Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2 O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used. RESULTS.: Compared with control stimulations, rolipram (0.3 mg/kg) caused a twofold increase in peak blood flow (P < 0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (P < 0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (P < 0.05). Similar effects were noted for sildenafil (0.2 mg/kg) (P < 0.05). Inhibitory effects by L-NNA (60 mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P < 0.05). PGE1-induced (10 µg) blood flow responses were significantly higher (P < 0.05) in rats treated with rolipram than with sildenafil. CONCLUSIONS.: These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat.

Is erectile dysfunction a reliable indicator of general health status in men?

INTRODUCTION: Erectile dysfunction (ED) is a common risk factor in men and its incidence increases with age. Ageing and older men frequently have comorbidities such as cardiovascular diseases (CVD), diabetes mellitus (DM), hypertension, chronic obstructive pulmonary disease and dyslipidaemia; likewise, they concurrently refer to a clinician for impairments in sexual function, mostly for ED. The association of ED and other organic, multi-organic or even systemic diseases is widely described, with a specific emphasis on the fact that they often share common pathophysiological factors and mechanisms. Thus we reviewed previous reports assessing the role of ED as a sentinel marker of overall men's health. DISCUSSION: ED is considered an important sentinel marker for CVD. Numerous studies have highlighted the predictive role of ED for subsequent CV events in patients with a silent history of coronary artery disease. Indeed, ED might be considered as a clinical manifestation of a generalised vascular disease, and it should provoke clinicians to check for CVDs in those patients complaining of impaired erectile function. This concept appears to be even more important for men with DM, where ED has already been shown to have a significant predictive ability for major vascular complications. Moreover, data from large population-based studies showed that ED is a significant predictor of all-cause mortality, in addition to CV outcomes. The severity of erectile function is assessed with the International Index of Erectile Function-Erectile Function domain score, and this has emerged as a proxy for men's general health status, as assessed with the Charlson Comorbidity Index score. CONCLUSIONS: Patients complaining of ED should be evaluated with a comprehensive medical and sexual history, and a thorough physical examination, regardless of their age, considering ED as an opportunity to screen for the presence of health-threatening concomitant comorbidities.

Delay in seeking medical help in patients with new-onset erectile dysfunction remained high over and despite the PDE5 era--an ecological study.

INTRODUCTION: It is common knowledge among researchers that erectile dysfunction (ED) is an important sentinel marker of cardiovascular and overall men's health. AIM: Determine whether the delay of time between ED onset and seeking medical help (DSH), considered as a proxy of awareness of the importance of ED for overall men's health, has shortened during the phosphodiesterase type 5 inhibitors (PDE5) era. METHODS: Complete data from 619 patients seeking first medical help for new-onset ED as their primary disorder between July 2000 and July 2010 were analyzed (i.e., DSH, ED severity as defined by the International Index of Erectile Function-erectile function [IIEF-EF] domain score, patient's awareness of any PDE5, and Charlson Comorbidity Index [CCI]). Analysis of variance tested DSH throughout the 10-year time frame. Cox regression models tested the association between predictors and DSH. MAIN OUTCOME MEASURES: Assess if DSH has shortened throughout PDE5 era. Evaluate potential predictors of DSH. RESULTS: Overall, mean DSH was 30.2 months (median 12.0; range 5-300 months). DSH shortened throughout the analyzed 10-year period (F = 1.918; P = 0.047), with a significant drop only from year 2009 (DSH up to year 2008 vs. from year 2009: 31.0 months [12.0] vs. 7.5 months [6.0], respectively; P < 0.001). Age, CCI, educational status, and ED severity did not significantly change over time. As a whole, 560 patients (90.5%) were aware of PDE5 at the time of their first office visit. PDE5 awareness emerged as an univarible and multivariable predictor of a shortened DSH. Conversely, DSH was not clearly associated with age, CCI, educational status, or ED severity. CONCLUSIONS: Delay in seeking medical help in new-onset ED patients remained high over the PDE5 era, with a significant drop only from the year 2009. PDE5 awareness emerged as an independent predictor of shortening of this delay.

Is erectile dysfunction a reliable proxy of general male health status? The case for the International Index of Erectile Function-Erectile Function domain.

INTRODUCTION: Erectile dysfunction (ED) has emerged progressively as a sentinel marker of cardiovascular disease (CVD). The correlation between ED and the burden arising from multiple comorbid conditions has been incompletely analyzed. AIM: Assess whether erectile function, defined with the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, is associated with health-significant comorbidities scored with the Charlson comorbidity index (CCI). METHODS: Clinical and hemodynamic variables of the last 140 consecutive patients who underwent penile color Doppler ultrasonography for new-onset ED were considered. Patients were assessed with a thorough medical and sexual history. Health-significant comorbidities were scored with the CCI. MAIN OUTCOME MEASURE: Descriptive statistics and either linear or logistic regression models tested the association among IIEF-EF, hemodynamic parameters, and CCI, which was included in the model both as continuous and categorized variable (0 vs. ≥1). RESULTS: Complete data were available for 138 patients (98.6%) (mean age 46.6 years [standard deviation 13.0]; range 21-75 years). CCI was 0, 1, and ≥2 in 94 (68.1%), 23 (16.7%), and 21 (15.25%) patients, respectively. Of all, 35 patients (79.5%) did not have a CVD comorbidity. Mean IIEF-EF was 13.7 (9.3). ED severity was no ED, mild, mild to moderate, moderate, and severe in 12 (9.1%), 28 (20.2%), 12 (9.1%), 23 (16.2%), and 63 (45.5%) patients, respectively. At multivariable linear regression analysis, CCI significantly worsened with increased age (ß=0.33; P=0.001) and decreased IIEF-EF values (ß=-0.25; P=0.01). At logistic regression analysis, age (odds ratio [OR]: 1.05; P=0.004) and IIEF-EF (OR: 0.95; P=0.04) emerged as significant predictors of categorized CCI. CONCLUSIONS: Severity of ED, as objectively interpreted with IIEF-EF, accounts for a higher CCI, which may be considered a reliable proxy of a lower general male health status regardless of the etiology of ED.

Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy.

PURPOSE: To assess the association between preoperative serum total testosterone (tT), 17ß-estradiol (E(2)), sex hormone-binding globulin (SHBG), and tT-E(2) ratio values with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network practice guidelines) at radical prostatectomy. EXPERIMENTAL DESIGN: Serum E(2), tT, and SHBG were dosed the day before surgery (7:00-11:00 am) in a cohort of 724 candidates to radical prostatectomy. Restricted cubic spline functions tested the association between predictors (i.e., model 1: age, body mass index, and serum tT, E(2), and SHBG levels; model 2: tT-E(2) values instead of tT and E(2) levels) and high-risk prostate cancer. RESULTS: Low-, intermediate-, or high-risk prostate cancer was found in 251 (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the high-risk class showed the lowest tT, E(2), and tT-E(2) ratio values (all P ≤ 0.02). At univariate analysis, only age, tT, E(2), and tT-E(2) ratio values were significantly associated with high-risk prostate cancer (all P ≤ 0.006). At multivariate analyses considering model 1 variables, age (P = 0.03), serum tT (all P < 0.001), and E(2) (all P ≤ 0.01) were associated with high-risk prostate cancer; only tT-E(2) ratios achieved independent predictor status for high-risk prostate cancer (all P < 0.001) when considering model 2. Both the lowest and the highest tT, E(2), and tT-E(2) values depicted a nonlinear U-shaped significant association with high-risk prostate cancer. CONCLUSIONS: These data showed that preoperative serum sex steroids are independent predictors of high-risk prostate cancer, depicting a nonlinear U-shaped association.