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Purpose To assess the impact of previous transurethral surgery for benign prostate enlargement (BPE) and time interval between procedures on functional outcomes and health-related quality of life (HRQOL) after radical prostatectomy (RP). Methods A propensity score-matched patient cohort [n = 685, (513 without previous BPE surgery, 172 with BPE surgery)] was created and HRQOL was pre- and postoperatively assessed using validated questionnaires (EORTC QLQ-C30). Urinary continence was measured via ICIQ-SF questionnaire and pad usage. Multivariable analysis included binary logistic and Cox regression models (p Results Median follow-up was 18 months. There was no significant difference in recurrence-free survival in multivariate analysis (HR 0.66, 95%CI 0.40–1.07, p = 0.093). We observe higher mean ICIQ-SF scores (5.7 vs. 8.2, p p p p = 0.003). In multivariate analysis, continence recovery (OR 5.19, 95%CI 3.10–8.68, p p = 0.806) could be identified as independent predictors of good general HRQOL. There was no significant correlation between time interval between both surgeries and continence (p = 0.408), and HRQOL (p = 0.386) outcomes. Conclusions We observe favourable continence outcomes for patients without previous BPE surgery. Our results indicate that RP can be safely performed after transurethral BPE surgery, regardless of the time interval between both interventions.

To evaluate the diagnostic value of a high preoperative PSA level for the detection of incidental prostate cancer (iPCa) in LUTS patients with very large prostates (> 100 cc). We conducted a retrospective analysis of 1125 men treated for LUTS with holmium laser enucleation of the prostate (HoLEP). Patients were stratified according to a preoperative PSA level higher (high PSA; n = 365) or lower than 10 ng/ml (low PSA; n = 760). Preoperative and histopathological parameters were compared between both cohorts. Logistic regression models were used to identify independent predictors of iPCa. Demographic parameters were similar between both cohorts. The median PSA levels were 14.2 ng/ml (11.5–19.9) and 4 ng/ml (2.4–6.0). The prostate volume was significantly higher in the high PSA group (105 cc vs. 75 cc; p

Purpose Introduction of robot-assisted radical prostatectomy (RARP) has revolutionized the therapeutic landscape of organ-confined prostate cancer (PCa). However, comparative analyses focused on health-related quality of life (HRQOL) after RARP and open retropubic prostatectomy (ORP) are sparse. Methods In the current retrospective analysis,inclusion criteria encompassed PSA ≤ 10 ng/ml, ≤ pT2c, ISUP ≤ 3, age ≤ 65 years, and preoperative continence. A propensity score-matched patient cohort [n = 418 (ORP: 209, RARP: 209)] was created and HRQOL was prospectively assessed based on validated questionnaires (EORTC QLQ-C30) preoperatively, 3 months, 12 months, and 24 months postoperatively. Primary endpoint was good general HRQOL based on previously published cut-off values. Erectile function was measured via IIEF-5, urinary continence via ICIQ-SF questionnaire. Multivariable analysis included binary logistic regression models (p

To objectively quantify continence rates and to correlate continence outcomes with health-related quality of life (HRQOL) after radical cystectomy and orthotopic ileal neobladder (ONB). Questionnaires were sent to 244 patients who underwent radical cystectomy with ONB between 2004 and 2015, and information about the current continence status was retrieved. To objectify postoperative urine loss, daytime and nocturnal pad tests were performed. Continence was defined as need of up to one safety pad. HRQOL was assessed using EORTC QLQ-C30 scoring with global health status being the primary endpoint. Statistical analysis included Fisher’s test, Mann–Whitney U test, Pearson’s rank correlation, and binary regression models (p

Urolithiasis is a common diagnosis in urology. New technologies offer a variety of diagnostic and therapy and consequently display a financial burden on healthcare systems. Hence, clinical practice guidelines (CPG) are essential to implement evidence-based medicine and assure a standard of care considering limited resources. To date, there is no evidence of the use and adherence to CPG on urolithiasis. Therefore, we performed a cross-sectional study to analyze the use of CPG on urolithiasis. Data collection was carried out by a questionnaire given to 400 German urologists. The survey included use and adherence to guidelines, evaluation of the clinical situation, therapy spectrum, and workplace. In total, 150 (37%) questionnaires were received and included in our survey. Statistics were performed by SPSS using Chi-quadrat test/Fisher’s exact test. In our study, urologists were office based, hospital affiliated, non-academic, or academic centers in 53%, 32%, 16% and 5%, respectively. In 74% and 70%, urologists adhere to CPG in diagnostic and therapy. Interestingly, workplace and therapy spectrum determines the use of different CPG (p = 0.01; p = 0.022). Academic urologists were more likely to use international CPG of EAU (40%), while outpatient urologists significantly orientated on national CPG (46%). 86% of urologists with high volume of urolithiasis practice interventions in contrast to 53% in low volume (p = 0.001). More than 80% of urologists use short versions and app version of CPG. We firstly describe compliance and the use of CPG on urolithiasis. EAU and DGU present the most commonly used CPG. Short version and app version of CPG find frequent clinical utilization.

To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications. We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points. Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525–11.569; p = 0.006). A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.

To investigate the fragmentation capacity, clearance time, and drilling speed of combined ultrasonic with impact dual-energy and single energy ultrasonic lithotripter devices. Stone fragmentation and clearance tests were performed under direct view in an underwater layered hemisphere by four different operators using artificial stones (n = 10/operator). Time for complete clearance was measured. Drilling tests were performed using an underwater setup, consisting of a mounting rack for fixing the lithotripter handpiece with the probe in vertical position and in contact with the stone phantom placed on one side of a balance for defined and constant contact application pressure equivalent to 450 g load. Time until complete perforation or in case of no perforation, the penetration depth after 60 s into the stone sample was recorded. Four devices, one single energy device (SED), one dual-energy dual probe (DEDP), two dual-energy single probe (DESP-1, DESP-2), with different parameters were tested. Stone fragmentation and clearance speed were significantly faster for dual-energy device DESP-1 compared to all other devices (p

Introduction of robot-assisted radical prostatectomy (RARP) has revolutionized the therapeutic landscape of organ-confined prostate cancer (PCa). However, comparative analyses focused on health-related quality of life (HRQOL) after RARP and open retropubic prostatectomy (ORP) are sparse.In the current retrospective analysis, inclusion criteria encompassed PSA ≤ 10 ng/ml, ≤ pT2c, ISUP ≤ 3, age ≤ 65 years, and preoperative continence. A propensity score-matched patient cohort [n = 418 (ORP: 209, RARP: 209)] was created and HRQOL was prospectively assessed based on validated questionnaires (EORTC QLQ-C30) preoperatively, 3 months, 12 months, and 24 months postoperatively. Primary endpoint was good general HRQOL based on previously published cut-off values. Erectile function was measured via IIEF-5, urinary continence via ICIQ-SF questionnaire. Multivariable analysis included binary logistic regression models (p 0.05).Open retropubic prostatectomy and RARP cohorts were well balanced. General HRQOL was significantly higher for ORP compared to RARP after 3 months (70.1 vs. 61.6, p = 0.001), but not at the remaining follow-up time points. There were no significant differences for the remaining QLQ-C30 functioning and symptom scores. In multivariable analysis stratified for IIEF-5 and ICIQ-SF scores and surgeon experience, RARP could be confirmed as a marginally independent predictor for lower ratios of good general HRQOL after 3 months (OR 0.464, 95% CI 0.215-0.999; p = 0.050) without any differences at the remaining time points.The current study addresses various HRQOL outcomes over a postoperative period of up to 2 years in a homogenous propensity score-matched contemporary cohort. Marginally better general HRQOL outcomes could be detected for ORP compared to RARP 3 months postoperatively.

To assess the impact of previous transurethral surgery for benign prostate enlargement (BPE) and time interval between procedures on functional outcomes and health-related quality of life (HRQOL) after radical prostatectomy (RP). A propensity score-matched patient cohort [n = 685, (513 without previous BPE surgery, 172 with BPE surgery)] was created and HRQOL was pre- and postoperatively assessed using validated questionnaires (EORTC QLQ-C30). Urinary continence was measured via ICIQ-SF questionnaire and pad usage. Multivariable analysis included binary logistic and Cox regression models (p

To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p

The aim of the study was to compare single-dose ertapenem (ERT) with the 3-day regime of ciprofloxacin (CIP) for prophylaxis of possible infections following transrectal prostate biopsy.Data from a consecutive group of 542 patients from January 2012 to January 2017 were retrospectively analysed. As preinterventional prophylaxis patient group A (179) received 500 mg CIP twice a day for three days, beginning on the day before the biopsy (until June 2013); group B (363) received a single dose of ERT 60 min prior to intervention. The first follow-up examination for all patients was between post-intervention days 2 and 3. The second follow-up examination was between day 15 and 30 following biopsy. Urine was cultured in all cases and any adverse drug reactions (ADRs) related to the antibiotic treatment were noted. We also recorded all clinically relevant morbidities requiring intervention (ischuria, macrohaematuria, symptomatic urinary tract infections and urosepsis), as well as those not requiring active intervention (macrohaematuria, decreased urinary stream, pain, haemospermia). The main study criterion was the symptomatic urinary tract infection rate and ADRs.All 542 biopsied patients could be included in the study and the drop-out rate was zero. There were no significant differences between groups A and B with regards to complications not requiring intervention. There was, however, a significant reduction from 14.5% (group A) to 0.8% (group B) in infectious complications. This showed a significant correlation in favour of ERT (p 0.001). Furthermore, in the ERT group there was also a distinct and significant reduction (p 0.001) in the number of patients with bacteriuria (10e4 cfu per ml urine) without fever (0.5%) compared to the CIP group (12.3%).A single-dose of 1 g of intravenous ERT applied 1 h before a scheduled transrectal prostate biopsy is a safe option and provides effective protection against infection-related complications arising from surgery.

To analyse the impact of perioperative complications and complex treatment courses on postoperative health-related quality of life (HRQOL) after radical cystectomy (RC) and continent (ONB) or incontinent (IC) urinary diversion at multiple prospective time points. A total of 121 consecutive patients underwent RC with curative intent between 2013 and 2014. HRQOL was prospectively assessed preoperatively, after 3 and 12 months, using the QLQ-C30 questionnaire. The impact of complex perioperative treatment courses including cases requiring surgical re-interventions was retrospectively assessed using Martin criteria and the Clavien–Dindo scale. Urinary continence was determined using the validated ICIQ-SF questionnaire. Statistical analysis included Kruskal–Wallis ANOVA, Spearman’s rank correlation, and ordinal regression models (p

For the treatment of persistent post-prostatectomy incontinence (PPI), several surgical treatment options including male slings are available. In 2010, the second generation of the retrourethral male sling Advance, AdVanceXP, was introduced. Aim of the study was to examine in a prospective multicentre study the outcome of AdVanceXP in the treatment of PPI.Ninety-four patients were treated with AdVanceXP. Patients with nocturnal incontinence, previous incontinence surgery, with coaptive zone1 cm and irradiated patients were excluded. Measurements included: daily pad usage, 24-h pad weight test, post-operative pain in the visual analogue scale, International Quality of Life questionnaire, International Consultation on Incontinence Questionnaire short form, IEEF5 and Patient Global Impression of Improvement. Adverse events were recorded. All patients with no pads and 0-5 g in the 24-h pad test were defined as cured and those with a reduction in urine loss50 % as improved.Preoperatively, the median 24-h pad weight test was 274 g and daily pad usage was 3. At 1-year follow-up, 66.3 % of patients could be classified as cured and 25.3 % as improved. After 2 years, 73.1 % could be classified as cured and 19.6 % as improved. Urine loss decreased (p 0.001), and quality of life improved significantly (p 0.001). Mean PGI was 1.5 after 1 year and 1.4 after 2 years. Majority of complications were minor. No intraoperative complications and five serious post-operative events occurred (grade IIIB complications). No explantation was necessary.AdVanceXP, when correctly indicated, shows good effectiveness and low complication rates after up to 2 years.

Different blood parameters have shown to be associated with patient’s oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35–97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan–Meier method, log-rank test, and Cox regression models. Median CRP level was 0.5 mg/dl (0.1–28.3), and median Hb level was 13.4 g/dl (6.7–17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p

To analyze the impact of surgeon's experience on surgical margin status, postoperative continence and operative time after radical prostatectomy (RP) in a surgeon who performed more than 2000 open RP.We retrospectively analyzed 2269 patients who underwent RP by one surgeon from April 2004 to June 2012. Multivariable logistic models were used to quantify the impact of surgeon's experience (measured by the number of prior performed RP) on surgical margin status, postoperative continence and operative time.Negative surgical margin rate was 86 % for patients with pT2 stage, and continence rate at 3 years after RP was 94 %. Patients with negative surgical margin had lower preoperative PSA level (p = 0.02), lower pT stage (p0.001) and lower Gleason score (p0.001). The influence of the experience of the surgeon was nonlinear, positive and highly significant up to 750 performed surgeries (75-90 % negative surgical margin) (p0.01). The probability of continence rises significantly with surgeon's experience (from 88-96 %) (p0.05). A reduction in operative time (90-65 min) per RP was observed up to 1000 RP.In the present study, we showed evidence that surgeon's experience has a strong positive impact on pathologic and functional outcomes as well as on operative time. While significant learning effects concerning positive surgical margin rate and preserved long-term continence were detectable during the first 750 and 300 procedures, respectively, improvement in operative time was detectable up to a threshold of almost 1000 RP and hence is relevant even for very high-volume surgeons.

Gleason score upgrading should be considered when indicating surgery in prostate cancer (PCa) patients. In elderly patients, definitive treatment of low-risk PCa must be weighed with the risks of overtreatment. Our aim was to evaluate rates of Gleason score upgrading in patients ≥75 years undergoing radical prostatectomy (RP) for localized PCa and to identify predictors associated with upgrading. 3296 patients undergoing RP were retrospectively evaluated and categorized into age groups

To evaluate the impact of the retrourethral transobturator sling (RTS) on pelvic floor muscle function (PFMF) and whether preoperative PFMF is associated with RTS outcome. Between May 2008 and December 2010, 59 consecutive men with postprostatectomy stress urinary incontinence (PSUI) underwent PFMF assessment before RTS and 6 months thereafter in a prospective cohort study. The assessments included demographic and clinical characteristics, and quality of life (QoL) questionnaires. PFMF was evaluated by digital rectal examination on the modified 6-point Oxford scale and by surface electromyography. The primary outcome measurement was success after RTS defined as PSUI cure with use of no or one dry “security” pad. For secondary outcome, PFMF, 1-h pad test, and impact of PSUI on QoL were evaluated. Uni- and multivariate analyses were performed. After 6-month follow-up, the cure, improvement (>50 % pad reduction) and failure rates were 50 % (29/58 patients), 24 % (14/58 patients) and 26 % (15/58 patients), respectively. Significant improvement of QoL, clinical and PFMF parameters occurred after RTS. On multivariate analysis, weak PFMF (OR 86.29) and greater muscle fatigue (OR 3.31) were significant independent predictors of RTS failure. The final model demonstrated good calibration (p = 0.882) and excellent discriminative ability (0.942, 95 % CI 0.883–1.0) to predict success after RTS. PFMF improved significantly after RTS procedure. Higher muscle fatigue and weak PFMF were independent predictors of RTS failure. Digital rectal evaluation of PFMF is a simple and reliable clinical tool, which can be used by urologists in daily routine to predict the RTS outcome.

To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21–82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

To report effect of different nerve sparing techniques (NS) during radical prostatectomy (RP) (intrafascial-RP vs. interfascial-RP) on post-RP incontinence outcomes (UI) in impotent/erectile dysfunction (ED) men.A total of 420 impotent/ED patients (International Index of Erectile Function-score15) with organ-confined prostate cancer were treated with bilateral-NS [intrafascial-RP (239) or interfascial-RP (181)] in our institution. Intrafascial-RP was indicated for biopsy Gleason score ≤6 and PSA ≤10 ng/ml while interfascial-RP for Gleason score ≤7 and higher serum PSA. Seventy-seven patients with bilateral non-NS-RP were taken for comparison. No patient received pre-/postoperative radiation/hormonal therapy or had prostatic enlargement surgery. UI was assessed 3, 12 and 36 months postoperatively by third party. Continence was defined as no pads/day, safety 1 pad/day as separate group, 1-2 pads/day as "mild-incontinence" and2 pads/day as "incontinence".All groups had comparable perioperative criteria without significant preoperative morbidities. International Prostate Symptom Score showed severe symptoms in 5 % of patients without correlation to UI. UI-recovery increased until 36 months. Full continence was reported from 56 versus 62 and 53 % patients after intrafascial-RP versus interfascial-RP and wide excision at 3 months, respectively (p = 0.521). Corresponding figures at 12 months were 70 versus 61 versus 51 % (p = 0.114) and at 36 months 85 versus 75 versus 65 % (p = 0.135), respectively. After 12 and 36 months, there was tendency to better UI-results in advantage of NS-technique; best results were achieved in intrafascial-RP group. UI-recovery was age-dependant. Advantage was found in NS-group compared with non-NS-group in older patients (70 years, p = 0.052).Impotent/ED patients have higher chances of recovering full continence after NS-RP. NS should be planned independently of preoperative potencystatus whenever technically and oncologically feasible. Age and lower urinary symptoms are not restrictions. Current data should be considered in preoperative patient counselling.

To examine the outcomes with the AdVance XP and AdVance slings in the management of post-prostatectomy incontinence (PPI).Eighty patients were treated with the AdVance resp. AdVance XP at one tertiary reference centre. The initial patients were implanted with the AdVance male sling with no associated surgery. Following the introduction of the AdVance XP sling, subsequent patients were implanted with the AdVance XP slings. Measurements included: daily pad usage, 24-h pad weight test, International Quality of Life Questionnaire, International Consultation on Incontinence Questionnaire Short Form and the Patient Global Impression of Improvement. Adverse events were recorded.Follow-up was available for 39 and 41 patients treated with the AdVance and AdVance XP slings, respectively. At a median follow-up of 24.7 months, 69.3 % of patients could be classified as cured or improved in the AdVance group and at a median follow-up of 11.9 months, 90.3 % of AdVance XP-treated patients. At 3-month follow-up, 96.8 and 97.3 % of patients could be classed as cured or improved in the AdVance and AdVance XP groups, respectively (not significant). There were no perioperative complications. Two AdVance and three AdVance XP serious post-operative complications were reported, which were resolved following treatment. QOL was improved in both treatment groups.Both the AdVance and the AdVance XP slings are effective and safe for the treatment of PPI.

To investigate whether differences in the anatomy and dynamics of the pelvic floor (PF) in patients after radical prostatectomy (RP) depicted on magnetic resonance imaging (MRI) are associated with continence status. In the prospective designed study, 24 patients with post-prostatectomy stress urinary incontinence were enrolled. Additionally, 10 continent patients after RP were matched for age, body mass index and perioperative parameters. All patients underwent continence assessment and MRI (TrueFISP sequence; TR 4.57 ms; TE 2.29 ms; slice thickness 7 mm; FOV 270 mm) 12 months after RP. Images were analyzed for membranous urethra length (MUL), angle of the membranous urethra (AMU), severity of periurethral/urethral fibrosis, lifting of the levator ani muscle, lowering of the posterior bladder wall (BPW), bladder neck (BN) and external urinary sphincter (EUS), and symphyseal rotation of these structures during the Valsalva maneuver and voiding. Compared to continent controls, incontinent patients showed a significant wider AMU during voiding (p = 0.002) and more pronounced lowering of the BN and EUS (p

Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25 months; IQR: 19–30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. In 88 (16.0 %) and 100 (18.2 %) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0 %) patients, a single TURBT was performed prior to RC; in 194 patients (35.3 %), TURBT had been performed in a different center. CSM and OM rates at 3 years were 32 and 40 %, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

Nephroureterectomy with excision of a bladder cuff is the gold standard in the treatment of upper urinary tract carcinomas (UTUC). But especially for patients suffering from advanced tumor stages, life expectancy has not improved over the years with local recurrence or distant metastases being the main reasons for treatment failure. Chemotherapy in an adjuvant or neoadjuvant setting seems therefore to be a promising approach.The literature of the last 20 years was searched using Medline. Articles were chosen by using the given abstracts. Only articles written in English and not older than 20 years were considered.Most information concerning chemotherapy of urothelial carcinomas is gained from studies comprising patients suffering from lower urinary tract carcinomas. The combination of methotrexate, adriamycin, vinblastine and cisplatin as well as the combination of gemcitabine and cisplatin are the most used chemotherapy regimens in advanced UCC and have shown beneficial results. The summarized data of studies for UTUC contained no level one information. Down staging effects as well as prolongation of survival have been shown for some patients treated with neoadjuvant chemotherapy, but because of the small study groups and the retrospective design, no definite conclusions can be drawn from these results. In addition, there exists an uncertainty for preoperative staging. Results for adjuvant chemotherapy are lacking.No definite recommendations for peri-operative chemotherapy in UTUC can be derived from the current literature. Current therapy is largely based on extrapolation from the bladder cancer literature. Prospective studies dedicated to UTUC are needed.

To assess the power of multi-detector row computerized tomography (MDCT) in daily routine as a basic staging procedure for the decision on local treatment of patients with bladder cancer.We retrospectively analysed 276 patients who had undergone radical cystectomy between 2004 and 2008 and correlated the MDCT findings with pathological findings, number of removed lymph nodes and type of urinary diversion.Accuracy of MDCT in predicting pathological tumour stage was 49% (kappa coefficient, 0.23; P0.001). Overstaging occurred in 23.4%, and understaging occurred in 24.7%. Accuracy in predicting lymph node metastases was 54% (kappa coefficient, 0.04; P = 0.297). Overstaging and understaging occurred in 8.3 and 29.4%, respectively. Significantly more ileal conduits were performed in patients with high postoperative pathological tumour stages (P = 0.04) and positive lymph nodes (P = 0.013). In contrast, there was no correlation between preoperative CT tumour/nodal stage and the number of removed lymph nodes (P = 0.44 and P = 0.732, respectively), and between preoperative tumour stage and type of urinary diversion (P = 0.126).MDCT as a preoperative staging procedure has a low accuracy in predicting the correct tumour and nodal stage, and therefore, it has little impact on decision-making for local treatment of muscle-invasive bladder cancer during radical cystectomy.

Evaluation of clamp-off laser-assisted laparoscopic partial nephrectomy technique (LLPN) compared to the clamp-off laparoscopic (LPN) and open (OPN) techniques.Between September 2008 and July 2011, 36 patients suffering from small peripheral renal tumours (RT) underwent LLPN (n = 12), LPN (n = 12) and OPN (n = 12) in a prospective single-centre study. RT were excised with laser, Sonosurg or monopolar scissors during LLPN, LPN and OPN, respectively. Blood vessels are identified and sutured before opening them; alternatively, laser energy was used to coagulate them (LLPN). Early and late postoperative complications were assessed. Follow-up was done according to EAU-guidelines.Mean age was 64.9 years. Mean operative time was 135.8 min (100-180) versus 144.2 (85-255) versus 113.6 (50-170) for LLPN versus LPN versus OPN, respectively. Median estimated blood loss (EBL) was 170.8 ml (50-600) versus 245.2 (50-700) versus 425.8 (100-900) for LLPN versus LPN versus OPN, respectively. Tumours (19 right and 17 left) were located in upper (11), midparenchyma (13) and lower pole (12). Mean tumour size was 2.7 cm (1.2-5.5). There were no reported perioperative complications/conversions. There were no positive margins. Histological evaluations were not compromised in any LLPN-case. Compared to LPN, LLPN offered significant lower EBL, shorter operative time, otherwise, comparable results. Follow-up was uneventful without tumour recurrences.Current prospective comparative study shows that LLPN is a reproducible efficient alternative to LPN/OPN. Besides the absence of renal ischaemia, LLPN offered lower EBL, good haemostasis and minimal parenchyma damage. Surgical and oncological outcomes are comparable to LPN and OPN.

Small studies have suggested that older patients have worse outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We evaluated the association of patient age with clinical outcomes in a large multi-institutional RC series. Data were collected from 4,429 patients treated with RC and lymphadenectomy for UCB without neoadjuvant chemotherapy. Age at RC was analyzed both as a continuous and categorical variable. Higher age at RC, analyzed as a continuous or categorical variable, was associated with advanced pathologic stage (P

Alpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by β-arrestin-2, which may bind to receptors besides G proteins. Here, we investigated the expression and α1A-adrenoceptor binding of β-arrestin-2 in the human prostate.Human prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of β-arrestin-2 and α1A-adrenoceptors was studied by RT-PCR, Western blot analysis, and immunohistochemistry. The protein-protein interaction between α1A-adrenoceptors and β-arrestin-2 was investigated by coimmunoprecipitation.RT-PCR and Western blot analysis demonstrated the expression of β-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry demonstrated β-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that α1A-adrenoceptors in the human prostate may interact with β-arrestin-2. Thus, specific binding of β-arrestin-2 to α1A-adrenoceptors was significantly higher than background during α1A-adrenoceptor detection in β-arrestin-2 precipitates (P0.001) or during β-arrestin-2 detection in α1A-adrenoceptor precipitates (P0.005). This interaction may be located to prostate smooth muscle cells, as expression of the α1A-adrenoceptor was exclusively found in smooth muscle cells after immunohistochemical staining.With β-arrestin-2, we identified a new binding partner of the α1A-adrenoceptor in human prostate smooth muscle. Binding of β-arrestin-2 may be involved in posttranslational regulation of prostate α1A-adrenoceptors.

Therapeutic strategies on treatment of T1G3 urothelial cancer of the urinary bladder are controversial. The objective of this study was to investigate the impact of photodynamic diagnosis (PDD) on the recurrence-free survival rate of patients with the initial diagnosis of T1G3 bladder cancer.Between 1995 and 2007, 153 patients were treated for T1G3 bladder cancer at our institution. In 77 patients, initial TUR-BT was performed under PDD condition at our hospital, and 76 patients underwent TUR-BT in a standard white light setting at other institutions. PDD was performed either using 5-aminolevulinate or hexaminolevulinate for induction of fluorescence. Average follow-up was 53.9 months. Fisher's exact test and Kaplan-Meier method were used to test data for significance.Of the 77 patients who were treated using PDD at initial TUR-BT, recurrence was observed in 23 (29.9%) cases, whereas 43 of 76 (56.6%) patients treated without PDD showed recurrence (P0.001). The detection rate of additional carcinoma in situ was 35.4% in the PDD group versus 21.8% in the white light group (P = 0.077). A limitation of the present study is the retrospective, monocentre setting, which is more likely to be biased.PDD during initial TUR-BT in T1G3 bladder cancer seems to reduce significantly the rate of recurrence in our study population. Therefore, PDD seems to be associated with superior initial tumour control and more effective tumour treatment even in patients with highly aggressive tumours like T1G3 bladder cancer.

The value of surgical resection of renal cell carcinoma (RCC) liver metastases still remains unclear.Of our study was to evaluate the efficacy of liver resection by comparing patients who could have undergone metastasectomy due to limited disease, but refused surgery.Eighty-eight patients were identified with liver metastases and indication of surgery between 1995 and 2006. In 68 patients, liver resection was performed, 20 patients denied surgery and served as comparison group. Patients were followed for survival.Median age was 58. Median amount of liver metastases was 2 (range 1-30). Median follow-up was 26 months (range 1-187). In both groups, 79% received systemic therapy. The 5-year overall survival rate (OSR-5) after metastasectomy was 62.2% +/- 11.4% (SEM) with a median survival (MS) of 142 (95% confidence interval (CI) 115-169) months. OSR-5 in the control group was 29.3% +/- 22.0% (SEM) with a MS of 27 (95% CI 16-38) months (P = 0.003). MS was 155 (95% CI 133-175) months with metachronous metastases compared to 29 (95% CI 25-33) months in the comparison group (P = 0.001). Low-grade primary RCC had a MS of 155 (95% CI 123-187) months compared to 29 (95% CI 8-50) months without resection (P = 0.0036). High-grade RCC as well as patients with synchronous metastases did not benefit from surgery.Liver metastasectomy is an independent valuable tool in the treatment of metastatic RCC and significantly prolongs patient's survival, even if further systemic treatment is necessary. With the evidence given, patients may benefit from liver metastasis resection if technically feasible.

the current status of MRI in active surveillance, particularly for predicting tumor stage and site. Here it becomes obvious that the diagnostic accuracy of dedicated centers is not reproduced by non-specialized radiologists. RenardPenna et al. [4] describe promising developments of imaging and molecular pathology in the stratification of patients with early prostate cancer. The second part of the manuscripts is dedicated to focal therapy of prostate cancer. Lebdai et al. [5] carefully describe a ‘standardized operating procedure’ (SOP) for vascular-targeted photodynamic therapy (VTP) followed by a pooled analysis of three phase 2 studies by Azzouzi et al. [6]. The histopathologic results of focal therapy and cryotherapy are summarized by Shah et al. [7], and oncological and functional outcomes of VTP are reviewed by Azzouzi et al. The feasibility of salvage surgery after VTP is described by Lebdai et al. [8]. Karl et al. [9] describe a carefully designed multicenter study on the PSA recurrence rate of men with pT2 prostate cancer and a positive surgical margin without any adjuvant therapy. Opportunistic PSA screening has resulted in increased numbers of patients with low and intermediate risk. This specifically dedicated issue of the World Journal of Urology draws the attention of the reader to the new management options for lowand intermediate-risk prostate cancer in the context of the two ‘new kids on the block,’ multiparametric MRI for diagnosis, and focal therapy for treatment. Van der Poel et al. [1] summarize the recent developments and their implications for the management of prostate cancer. Lellig et al. [2] and Billing et al. [3] examine

To analyze revision rates and risk factors for artificial urinary sphincter failure. Eighty-four patients underwent implantation of an artificial urinary sphincter in one reference center. Continence rates were defined by daily pad usage. Influence of predefined risk factors for device explantation, revision, differences in preoperative pad usage, and device survival was analyzed using Chi-squared test, Wilcoxon signed-rank test, and Kaplan–Meier analysis. A multivariate analysis was performed using a logistic regression model. A p value below 0.05 was considered statistically significant. After a mean follow-up of 39.7 months, the device was still in situ in 64 patients. In univariate analysis, perioperative need of anticoagulation led to a significant increase in urethral erosion (6 vs. 30 %; p = 0.002) and explantation rate (15 vs. 34 %; p = 0.047). Pelvic irradiation increased postoperative infection rates significantly (0 vs. 10 %; p = 0.018). Penoscrotal approach led to significant increase in urethral erosion rate (0 vs. 21 %; p = 0.015). Implantation of a double cuff led to a significant increase in explantation rate (58 vs. 24 %; p = 0.014), revision rate (75 vs. 38 %; p = 0.017), and infection rate (17 vs. 1 %; p = 0.008). When using cuff size of 3.5 cm, revision rate (20 vs. 50 %; p = 0.026) as well as incontinence rates (40 vs. 82 %; p = 0.014) was significantly lower. In multivariate analysis, only perioperative anticoagulation and double-cuff placement were independent predictors of artificial urinary sphincter failure. Our findings highlight the influence of perioperative anticoagulative therapy. In addition, the current study provides further evidence that double-cuff implantation should be performed only with caution during primary implantation.

To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy.A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests.With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study.Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

Female sexual dysfunction (FSD) is considered a common medical problem estimated to affect millions of women in the westernized countries. FSD has been classified into four different categories including sexual arousal disorder (FSAD), sexual desire disorder (HSDD), orgasmic disorder and sexual pain disorder. The focus of this article is the potential role of pharmacological compounds currently under development, in the treatment of sexual arousal and orgasmic disorders in order to enhance the sexual response in adult females. While a number of potential therapeutic options are available to date, not one of the pharmacological treatment regimens has been yet considered the Gold standard in the management of symptoms of FSD. This article reviews the rationale and potential benefits of using distinct drug formulations in the treatment of FSD.

The aim of the current study was to determine in retrospect how many of a group of patients who underwent radical prostatectomy were correctly classified with an insignificant prostate carcinoma by means of preoperative diagnostics. Furthermore, we are aiming at finding preoperative parameters which predict an insignificant prostate carcinoma with higher accuracy. The current inclusion parameters of AS will be verified with regard to their reliability, and we will discuss the possibility of improving their prediction accuracy.We examined the data of 308 consecutive patients who were diagnosed with a clinically insignificant prostate carcinoma and therefore would be suited for AS, but opted for a radical prostatectomy. According to the literature(1), the following inclusion criteria were chosen for our evaluation: a proven prostate carcinoma, detected by either ultrasonically guided transrectal core needle biopsy (cT1c) with at least six obtained samples and with a maximum of two positive samples on one side and a less than a 50 % tumor rate per sample, or a 5 % or lower tumor rate found in the tissue obtained by transurethral prostate resection (cT1a). The PSA value in all cases was below 10 ng/ml and the Gleason Score ≤6. The probability of a preoperative "undergrading" or "understaging" was determined as a function of preoperative parameters like Gleason Score, PSA value, the number of collected samples and positive samples obtained by core needle biopsy, prostate volume, and PSA density. Based on the available preoperative data, we developed and tested several regression models for the identification of independent factors for upgrading and upstaging.Within the examined patient population, 232 of 308 patients (75 %) were, according to their final prostate histology, diagnosed with a stage ≥pT2b prostate carcinoma. Eight percentage of the patients who had undergone surgery had a stage ≥pT3a carcinoma, and 118 of 308 (38 %) had a Gleason Score of 6 or higher. Positive lymph nodes and an infiltration of the seminal vesicle each occurred in 1 % of the cases. Histopathologic positive margins of resection existed in 33 of 308 patients (11 %). Independent factors for upgrading and upstaging a prostate volume of50 ml and a preoperative Gleason Score of ≤6 were identified.The presented results show that the current inclusion criteria for AS are insufficient. For many patients, the beginning of the necessary therapy is delayed. According to our data, the prostate volume, the preoperative Gleason Score, and the number of positive samples obtained by transrectal core needle biopsy have the highest predictive power with regard to aggressiveness and expansion of the tumor. Despite the consideration of all these preoperative parameters, the differentiation of the prostate carcinomas was underrated in a third of all cases. The expansion of the tumor within the prostate was underrated even in three fourths of the cases.

Low-risk prostate cancer is found in about half of newly diagnosed men subjected to PSA screening.To define the role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers, an invited international panel of practicing physicians in the field of localized prostate cancer discussed the available literature in three consecutive meetings to come to a broad interpretation of the available data.The panel ("new prostate cancer management group," npm) agreed on the following observations. In most men with a low-volume Gleason 6 tumor, initial conservative management is appropriate. In men with a larger unifocal Gleason score 6 or 3 + 4 lesion, focal therapy, although still considered an investigational approach, appears to be a suitable option in early non-randomized comparison studies. Furthermore, in patients with multifocal small satellite Gleason 6 lesions in the presence of a larger index lesion, focal therapy of the index lesion is an option. For patients with high-grade, large-volume disease, or in young men with evidence of high-volume multifocal low-grade prostate cancer, whole-gland treatment should be considered.Active surveillance is a preferred and safe option for low-risk prostate cancer. Focal therapy is still under investigation, but the available phase II data are promising. Clinical benefits must be shown in prospective trials. With improved imaging, focal therapy may be an option for patients not choosing active surveillance with low-risk disease, progression upon active surveillance or intermediate-risk cancers with a localizable lesion.

To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. After a median follow-up of 25 months (interquartile range 19–29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p

Introduction Vascular-targeted photodynamic therapy with TOOKAD® Soluble is an innovative focal therapy procedure assessed in localized prostate cancer treatment. Materials and methods This mini-invasive technique destroys targeted tissues using a photosensitizer [TOOKAD® Soluble (WST11), STEBA Biotech] activated by laser light in the presence of oxygen. Its application for prostate cancer requires intravenous infusion of TOOKAD® Soluble and the illumination of the targeted area by transperineal optical fibers inserted under trans-rectal ultrasound guidance under general anesthesia. Conclusion Based on the experience gained through hundreds of procedures, we describe here the standardized technique of vascular-targeted photodynamic therapy with TOOKAD® Soluble defined during the phase II and III trials.

Objectives: It has been well established that male erectile dysfunction is frequently associated with vascular diseases. The normal function of cavernous arteries is considered a prerequisite to maintain sufficient blood flow to the trabecular spaces in order to enable penile erection. Contractility of cavernous arteries is regulated by the peripheral autonomic nervous system and endogenous factors released from the endothelial cell layer. A significant increase of blood flow in the central cavernous arteries is the initial event leading to penile tumescence and rigidity. Besides the significance of the nitric oxide/cyclic guanosine monophosphate (cGMP)-mediated mechanisms, the cyclic AMP (cAMP) signalling pathway is also involved in the regulation of tone of the erectile tissue, and interactions between cGMP- and cAMP-mediated mechanisms have been demonstrated. The aim of the present study was to investigate by means of immunohistochemistry the presence of the phosphodiesterase (PDE) isoenzymes 3, 4 (cAMP-specific PDEs) and 5 (cGMP-specific PDE) in thin sections of human central cavernous arteries (HCA) and their functional significance in the mechanism of vessel tone regulation. Methods: Functional experiments were performed using circular segments of HCA and strip preparations of the human corpus cavernosum (HCC). Relaxant effects induced by the cumulative addition of the PDE inhibitors milrinone (PDE3 inhibitor), rolipram (PDE4 inhibitor) and sildenafil (PDE5 inhibitor; 0.01, 0.1, 1 and 10 M) were studied in preparations of HCA and HCC challenged by 1 M norepinephrine (NE). Moreover, immunohistochemistry was carried out in order to evaluate the expression of PDE3, PDE4 and PDE5 in thin sections of HCA. Results: Milrinone, rolipram and sildenafil dose-dependently reversed the NE-induced tension of the isolated vascular segments and HCC strips with sildenafil being the most effective drug. Neither rolipram nor milrinone reached an EC50 value. Abundant immunoreactivities specific for PDE3, PDE4 and PDE5 were observed in the entire smooth musculature of the wall of HCA and resistance arteries. In addition, immunoreactivity for PDE4 was also detected in the cytoplasm of endothelial cells lining the cavernous arteries. Conclusions: The cGMP-dependent relaxation of cavernous arteries is not only dependent on the normal function of the peripheral autonomic nervous system but also on the functional integrity of the vascular endothelium. The expression of the cGMP-specific PDE5 and the ability of the PDE5 inhibitor sildenafil to reverse the adrenergic tension of isolated segments of HCA underline the important role of the NO/cGMP pathway in the control of smooth muscle tone of human trabecular smooth musculature and penile cavernous arteries. Our results also suggest a significance of the cAMP-dependent signaling mechanisms in the regulation of tension of central HCAs. The present findings are also in support of the hypothesis of interactions between the cGMP- and cAMP-mediated signaling pathways in HCAs. Further investigations are indicated in order to outline potential differences between central HCAs and helicine resistance arteries. This may help to understand better the relations between structural and functional changes in the penile erectile tissue in patients with cardiovascular diseases and endothelial dysfunction.

Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

Metastatic renal cell carcinoma has a poor prognosis. Conventional therapies such as chemotherapy, radiation or hormonal treatment have hardly any effect on the progression of this disease. As renal cell carcinoma seems to be an immunogenic tumor, several immunotherapeutic approaches with different response rates have been developed since the early 1990s. We present an overview of various immunotherapeutic approaches such as cytokine-based regimes, with and without different cytotoxic chemotherapy, of metastatic renal cell carcinoma. In addition, local therapies (e.g. inhalation of interleukin-2) are reviewed.

Nitric oxide (NO)/cyclic GMP (cGMP)-mediated mechanisms have a pivotal function in reducing the tone of the penile smooth musculature during normal erectile responses. The cyclic AMP (cAMP) signaling pathway is also involved in the adjustment of smooth muscle contractility, and suggestions for interactions between cGMP- and cAMP-mediated mechanisms have been presented. Using activators of the cGMP- or the cAMP-pathway, as well as inhibitors of protein kinase A (PKA; cAMP-dependent kinase) and protein kinase G (PKG; cGMP-dependent kinase), the present study was undertaken to further delineate the functional relation between these pathways in the penis. In addition, the distribution of PKA and some cAMP-binding phosphodiesterases (cAMP-PDEs) were investigated in human erectile tissue. Functional experiments were performed on isolated human corpus cavernosum (HCC). The effects of an inhibitor of the PKA, Rp-8CPT-cAMPS (10 microM), or the PKG, Rp-8-pCPT-cGMPS (10 microM), on relaxation induced by the cumulative administration of sodium nitroprusside (SNP), forskolin, sildenafil or tadalafil (IC351) were studied in preparations of HCC precontracted with 1 microM norepinephrine (NE). Using immunohistochemical procedures, the presence of immunoreactivity for cAMP-PDEs PDE3, PDE4, and PDE4A, as well as for PKA was investigated in specimens of HCC from which preparations were also used in the functional experiments. Forskolin, SNP, sildenafil, and IC 351 dose-dependently reversed NE-induced tension of isolated HCC preparations. The relaxing effects of SNP were significantly attenuated by Rp-8-pCPT-cGMPS, but not by Rp-8CPT-cAMPS. In contrast, relaxation induced by forskolin, sildenafil and tadalafil were significantly reversed by both Rp-8-pCPT-cGMPS and Rp-8CPT-cAMPS. Abundant immunoreactivity for PDE3 and PKA was observed in the corpus cavernosum smooth muscle cells. Immunoreactivity for PDE4 was also detected in the smooth musculature and in the cytoplasm of endothelial cells lining the cavernous sinusoids, as well as in nerve fibres interspersing the trabecular stroma. The present results support the hypothesis of interactions between cGMP- and cAMP-mediated signals in the HCC, and suggest that the effects of inhibitors of PDE5 on isolated erectile tissue may also partly or indirectly include actions of the cAMP second messenger system. The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP-inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. This will in turn lead to increasing levels of cAMP, facilitating the interaction of cAMP with the PKA. The immunoreactivity specific for PDE3, PDE4, PDE4A and PKA registered in HCC section is also in support of an important role for the cAMP/PKA-system for penile smooth muscle function.

To evaluate the staging accuracy of preoperative multiparametric MRI (mp-MRI), its influence on the technique of radical retropubic prostatectomy (RRP), and its value for daily clinical practice. A total of 106 patients underwent RRP (January 2011–June 2012) and had preoperative MRI staging data available for review. Staging results acquired by mp-MRI were correlated to both biopsy and histopathology results. Surgical reports were reviewed for intraoperative aspect of tumor extension, technique of RRP (nerve sparing or extended), and extent of lymphadenectomy. The accuracy of diagnosing extracapsular extension (ECE) was 72.2 %, with an overall sensitivity and specificity of 30.0 and 93.3 %, respectively. The negative predictive value was 72.7 %. The sensitivity and specificity to diagnose positive seminal vesical invasion (SVI) were 63.6 and 92.9 %, respectively. Neither higher field force nor the use of an endorectal coil could enhance the accuracy of mp-MRI. In case of awareness of an existing MRI, there was a significantly higher percentage of nerve protection (left: 93 %; right: 89 % vs. left 75 %; right: 75 %). The higher percentage of nerve sparing surgery did not result in a higher level of positive resection margins. In routine clinical practice, mp-MRI at non-academic centers has very limited clinical value in predicting ECE and SVI. Our data support the current recommendations against the widespread preoperative use of mp-MRI because it is not adding reliable predictive information on the extent of prostate cancer.

Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders. We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis. The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size. Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction.

The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA).Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52 ± 0.38 fmol/ml vs. 0.48 ± 0.46 fmol/ml, respectively; detumescence: 0.53 ± 0.33 fmol/ml vs. 0.27 ± 0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males.Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.

Based on the increasing knowledge of intracellular signal propagation in cavernous smooth muscle tone regulation, which is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have recently been introduced in the treatment of erectile dysfunction. The first promising clinical data on the use of the orally active PDE5 inhibitor Sildenafil in the treatment of erectile dysfunction were accompanied by boosting research activities on cavernous intracellular signal transduction and phosphodiesterase characterization with the aid of molecular biology and protein chemistry. The presence of mRNA transcripts specific for 14 different human phosphodiesterase isoenzymes and isoforms in human cavernous tissue was shown by RT-PCR: Three isogenes of PDEI, PDE2A and 10A, which hydrolyse cAMP as well as cGMP, the cAMP-specific PDE3A, four isogenes of PDE4, PDE7A and PDE8A, as well as cGMP-specific PDEs PDE5A and PDE9A. Using anion exchange chromatography, the activities of PDE isoenzymes 2, 3, 4, and 5 were detected in cytosolic supernatants of human cavernous smooth muscle. To date, the efficacy and safety of several next generation PDE5 inhibitors for use in the treatment of male erectile dysfunction are under evaluation in vitro and in vivo. Further research will possibly allow identification of diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.

The balance between contractant and relaxant factors controls the smooth muscle of the corpus cavernosum and determines the functional state of the penis (detumescence and flaccidity versus tumescence and erection). Noradrenaline contracts both the corpus cavernosum and penile vessels, mainly via stimulation of alpha(1)-adrenoceptors. Recent investigations have demonstrated the presence of several subtypes of alpha 1-adrenoceptors (alpha(1A), alpha(1B), and alpha(1D)) in the human corpus cavernosum and also that the noradrenaline-induced contraction in this tissue is probably mediated by two or, possibly, three receptor subtypes. Even if much of the available in vitro information suggests that endothelins (ETs) may be of importance for mechanisms of detumescence and flaccidity, the role of the peptides in the control of penile smooth-muscle tone in vivo is unclear, as is the question as to whether they can contribute to erectile dysfunction. For further evaluation of the clinical importance of ETs in penile physiology and pathophysiology, clinical studies on ET-receptor antagonists would be of interest. Neurogenic nitric oxide (NO) has been considered the most important factor for relaxation of penile vessels and the corpus cavernosum, but recent studies in mice lacking neurogenic NO synthase (NOS) have shown these animals to have normal erections. This focuses interest on the role of endothelial NOS and on other agents released from nerves or endothelium. For the time being the most effective means of inducing penile erection in men involves the intracavernous administration of prostaglandin E1 (PGE1). PGE1 may act partly by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP). Recent results obtained with the adenylate cyclase stimulator forskolin suggest that penile smooth-muscle relaxation leading to penile erection can be achieved through the cAMP pathway. Thus, transmitters and agents acting through this second-messenger system may significantly contribute to relaxation of penile smooth muscle and to erection.

Knowledge of intracellular signal propagation in smooth-muscle tone regulation is of major importance to the understanding of both the physiology of erection and the pathophysiology of erectile dysfunction and the development of new and selective pharmacological agents in the treatment of erectile dysfunction. Cavernous smooth-muscle tone depends heavily on the amount of intracellular free Ca2+. In the resting state the sarcoplasmic free Ca2+ amounts to about 120-270 nM, whereas in the extracellular fluid the Ca2+ level is in the range of 1.5-2 mM. Electromechanical and pharmacomechanical coupling induces an increase in the levels of free sarcoplasmic Ca2+ by a factor of 2-3 to 550-700 nM that triggers myosin phosphorylation and subsequent smooth muscle contraction. In this case, modulation of membrane-bound ion channels and regulation of the intracellular second-messenger system are attractive and feasible targets for pharmacological intervention. Besides the amount of free sarcoplasmic Ca2+, smooth-muscle tone is also modulated by the regulation of Ca2+ sensitivity ("Ca-sensitization") and Ca(2+)-independent contraction processes.

We prospectively evaluated changes in morphology and dynamics of the male pelvic floor on magnetic resonance imaging (MRI) associated with retrourethral transobturator sling (RTS) placement. Twenty-six men with post-prostatectomy incontinence consecutively underwent functional cine-MRI before and 12 months after RTS. The membranous urethra length (MUL) and severity of periurethral/urethral fibrosis were assessed on static MRI. A lowering of the posterior bladder wall (BPW), the bladder neck (BN), the external urinary sphincter (EUS) and symphysial rotation of these structures were analysed on dynamic MR images. The success rate was defined as cure (0–1 dry ‘security’ pad) or improvement (pad reduction ≥50 %). The success rate was 77 % (20/26 patients). The mean follow-up was 20.4 months. The MUL significantly increased post-operatively (p

To assess the impact of detailed clinical and histopathological criteria on gender-dependent cancer-specific survival (CSS) in a large consecutive series of patients following radical cystectomy (RCE) for muscle-invasive bladder cancer (MIBC).Between 1992 and 2007, 388 men and 133 women (25.5%) underwent RCE for MIBC. A prospectively maintained database was analysed retrospectively. Uni- and multivariable Cox-regression analyses calculated the impact of detailed clinical and histopathological criteria on CSS. Median follow-up was 59 months (2-162).Among clinical and histopathological parameters, only type of urinary diversion differed between men and women. In univariable analysis, CSS did not differ between genders. In multivariable Cox-regression analysis, advanced pT-stage (HR = 2.12; P0.001), lymphovascular invasion (LVI) (HR = 3.47; P0.001), time interval between diagnosis of MIBC and RCE exceeding 90 days (HR = 2.07; P0.001) and female gender (HR = 1.35; P = 0.048) were related to reduced CSS. In separate multivariable Cox-models for time period of surgery between 1992 an 1999 (HR = 1.52; P = 0.050), age ≤55 years (HR = 3.00; P = 0.022), presence of LVI (HR = 1.45; P = 0.031) and female gender were associated with independent reduced CSS.Established clinical and histopathological parameters do not differ significantly between both genders in the present series. Reduced CSS in women is present in historic cohorts possibly suggesting improvement in management over the last years. In particular, female gender has a significant negative impact on CSS in patients younger of age and with positive LVI status possibly suggesting different clinical phenotypes.