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Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial., Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894., Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients)., Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy., Funding: Steba Biotech., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time., Patients and Methods: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS., Results: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men., Conclusions: Results support prostate safety of TRT in newly diagnosed men with HG., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Androgen deprivation therapy is frequently used to treat patients with advanced prostate cancer. New therapies for metastatic castration-resistant prostate cancer have drawn increased attention to serum and intratumoral testosterone levels. The present review examines the role of testosterone in prostate cancer progression, discusses the nuances and potential pitfalls in measuring serum testosterone using available assays, and summarizes current data relevant to the arguments for and against achieving and maintaining the lowest possible testosterone levels during androgen deprivation therapy, including the adverse effects of such treatment. Incorporating this information, we have made recommendations incorporating testosterone evaluation and its effect on the clinical decision-making process., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Patients and physicians consider a rapid onset of action to be an important attribute of oral pharmacotherapy for erectile dysfunction., Aim: To investigate the time to onset of action of a new orodispersible tablet (ODT) formulation of vardenafil., Methods: A post hoc integrated analysis was performed on data from two 12-week, double-blind, multicenter, randomized, parallel-group, placebo-controlled phase III trials of 10 mg vardenafil ODT. Data for the vardenafil film-coated tablet were generated from a retrospective integrated analysis at week 12 of four double-blind, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-, 30-, and 60-minute increments, up to ≥6 hours after study medication intake) were determined for the period between dosing and start of sexual activity (with the intention of intercourse)., Main Outcome Measures: The total number of sexual intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates were calculated per time interval., Results: Within 15 minutes postdosing, mean per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo), with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by subjects taking vardenafil ODT (n = 89) or placebo (n = 62), respectively. At 16-30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean per-patient) and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with a corresponding 10.4% and 8.7% of all sexual activity attempts being made by subjects taking vardenafil ODT (n = 170) or placebo (n = 118). Comparable results were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding time intervals., Conclusions: Vardenafil ODT shows a rapid onset of action comparable with that of vardenafil film-coated tablet. In those men who begin sexual activity within 30 minutes after dosing, the majority of sexual attempts lead to successful intercourse., (© 2011 International Society for Sexual Medicine.)

Objectives: To determine the role of treatment-associated improvement in nocturia in health-related quality of life (HRQL) in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, and secondarily to confirm the role of nocturia in HRQL at baseline and to compare the effects of watchful waiting, transurethral microwave treatment (TUMT) and transurethral resection of the prostate (TURP) to those of α1-adrenoceptor antagonists (α-blockers) on nocturia., Patients and Methods: We retrospectively analysed using multiple regression a large single-centre database of patients receiving routine care for treatment-associated alterations of symptoms and HRQL (assessed at baseline, 2611 men) and 6-12 months after initiation of treatment (1258 men)., Results: Among the symptoms assessed using the International Prostate Symptom Score, nocturia (together with urgency and weak stream) had the strongest correlation with HRQL at baseline and after treatment. Watchful waiting, α-blockers, TUMT and TURP reduced nocturia episodes by a mean (sd) of 7 (53)%, 17 (40)%, 32 (47)% and 75 (23)%, respectively. The treatment-associated improvements in nocturia (together with those of weak stream) had the strongest association with those of HRQL., Conclusions: We conclude that among all LUTS assessed in the IPSS, nocturia has one of the strongest associations with HRQL, and that treatment-associated improvements in nocturia contribute considerably to overall improvements in HRQL., (© 2009 THE AUTHORS. JOURNAL COMPILATION © 2009 BJU INTERNATIONAL.)

Objective: To study the value of PSA velocity (PSAV) to predict benign prostatic hyperplasia (BPH) progression in patients managed with alpha(1)-blockers or watchful waiting (WW)., Methods: Nine hundred and forty two BPH patients treated with alpha(1)-blocker or WW were reviewed. PSAV was defined as: (PSA(t)-PSA(b))/(t/12); where PSA(t) = PSA at time of follow-up (t, in months), PSA(b) = PSA at baseline. PSA(t) was taken from the 1 year follow-up visit or, if not present, from the next available visit with a maximum of 24 months., Results: Five hundred and ninety five patients (234 alpha(1)-blocker, 361 WW) were included in the analyses. PSAV range was -5.24 to 43.06 ng/ml/year in alpha(1)-blocker patients and -6.11 to 19.55 ng/ml/year in WW patients (median: 0.01 ng/ml/year). PSAV was stratified into tertiles (Stable/Decrease/Increase). There were no significant differences in retreatment-free survival and the risk of BPH-related invasive therapy between the tertiles in both treatment groups., Conclusions: PSAV did not predict BPH progression in either alpha(1)-blocker treated patients or WW group.

Objectives.  To investigate feasibility and safety of implant-driven tibial nerve stimulation. Materials and Methods.  Eight patients with refractory overactive bladder were successfully treated with implanted percutaneous tibial nerve stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life questionnaires, and physical examination before implantation, and at 3, 6, and 12 months of follow-up. The primary objective was ≥ 50% reduction of the number of incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks test was used. Results.  At 3, 6 and 12 months, respectively five, six, and four patients met the primary objective. At 3- and 6-month follow-up, voiding and quality of life parameters had significantly (p < 0.05) improved. Urinary tract infection, temporarily walking difficulties, and spontaneous radiating sensations were reported as adverse events and no local infection, erosion, or dislocation. Conclusions.  Implant-driven tibial nerve stimulation seems to be feasible and safe.

Objective: To determine the effect of a pause in percutaneous tibial nerve stimulation (PTNS) in successfully treated patients with an overactive bladder (OAB), and the reproducibility of successful treatment when restored., Patients and Methods: Eleven patients (mean age 51 years) with refractory OAB (more than seven voids and/or three or more urge incontinence episodes per day) were successfully treated with PTNS, and then discontinued treatment. Patients completed bladder diaries and quality-of-life (QoL) questionnaires (Short Form-36 and I-QoL) before (T1) and after a 6-week pause (T2) of maintenance PTNS, and again after re-treatment (T3). The first objective was defined as a > or = 50% increase in the incontinence episodes and/or voiding frequency in the bladder diary after T2. The second objective was defined as > or = 50% fewer incontinence episodes and/or voiding frequency in bladder diary after T3., Results: At T2, seven of the 11 patients had a > or = 50% increase in incontinence episodes and/or voiding frequency in the bladder diary. The mean voided volume, nocturia, number of incontinence episodes and incontinence severity deteriorated significantly (P < 0.05). At T3, nine patients had > or = 50% fewer incontinence episodes and/or voiding frequency in the bladder diary. Nocturia, the number of incontinence episodes, incontinence severity, mean voided volume and quality of life improved significantly (P < 0.05)., Conclusions: Continuous therapy is necessary in patients with OAB treated successfully by PTNS. The efficacy of PTNS can be reproduced in patients formerly treated successfully.

Objective: To investigate the relationship between quality of life (QoL) and voiding variables in patients with lower urinary tract dysfunction treated with percutaneous tibial nerve stimulation (PTNS), as it is assumed that improvements in voiding will lead to a better QoL in such patients., Patients and Methods: The study included 30 patients with urge urinary incontinence who were treated with PTNS; 24-h bladder diaries and QoL questionnaires (Short Form, SF-36, and incontinence-specific QoL) were completed at baseline and after PTNS., Results: There was a significant correlation (P < 0.05) between the number of pads used and the SF-36 domains of physical and vitality, between the number of incontinence episodes and the SF-36 domains of physical and role physical, between nocturia and the SF-36 domains of general and mental health, between the mean voided volume and the SF-36 domains of role physical and final, and between the mean voided volume and the incontinence-specific QoL score., Conclusions: PTNS is useful for treating refractory urge incontinence and should at least be considered as a therapeutic alternative before resorting to aggressive surgery, as voiding and QoL variables significantly and quantifiably correlate in patients with refractory urge urinary incontinence who are treated with PTNS. Patients must have a reduction of >or = two pads/day before their QoL improves, and this might be the best definition of successful therapy for patients with urge urinary incontinence.

Purpose: We assessed the value of baseline PVR as predictor of the need for invasive therapy during long-term followup of patients with clinical BPH treated initially with alpha1-blockers or WW., Materials and Methods: The records of a cohort of 942 patients with BPH treated with alpha(1)-blockers or WW were reviewed. Baseline I-PSS scores, PSA, prostate volume, uroflowmetry, pressure flow parameters and followup data were collected prospectively. Correlations between PVR and other baseline parameters were calculated. The 5-year cumulative risks of invasive therapy were calculated with the Kaplan-Meier method. After stratification of PVR by various cutoff levels (50, 100 and 300 ml), rate ratios between large and small PVRs were calculated using proportional hazards analyses., Results: PVR has weak (-0.2

Despite more than 30 years of clinical trials, investigations in prostate cancer have not succeeded in making advances comparable to those in other branches of research, such as breast cancer. Indeed, prostate cancer trials have repeatedly run into a series of "dead ends", as investigators face the problems of inadequate funding for research, treatments that result in only minimal improvements in survival, and lack of treatment options that have sufficient prospects for success. This article briefly reviews the strategies behind clinical investigations into prostate cancer over the last three decades, evaluates the pitfalls that have hindered research, and makes suggestions for the appropriate design of clinical trials that are safe and beneficial to patients while maintaining cost-effectiveness and accountability to patients and society.

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.

At present, the management of non-organ confined prostate cancer, whether it is a recurrence or metastasis, continues to evolve based on prostate cancer detection using prostate-specific antigen and the development of medications as alternatives for the classical orchiectomy, which induced irreversible implications for quality of life. Diethylstilbestrol therapy was associated with cardiovascular side-effects; GnRH agonists were able to create a castration level, but again considerable side-effects were described. Combination therapies using antiandrogens and GnRH agonists do not improve survival and have additional toxicity. GnRH antagonists, which also suppress FSH, represent the latest class of agents introduced for hormonal treatment, but phase III studies with survival data are not yet available. In spite of all these achievements, hormonal manipulation has resulted in only modest improvements during recent decades and new targets are needed to improve the clinical outcome. Selectively modifying the androgen receptor is currently one of the most promising developments.

Background and Purpose: Strictures of the vesicourethral anastomosis (VUA) following radical prostatectomy tend to recur. We used the holmium:YAG laser for treatment of recurrent stricture of the VUA. We evaluated the technique and its efficacy., Patients and Methods: In 10 patients, the Ho:YAG laser was used with a 365-mum fiber at a setting of 2 J and frequency 10 to 20 Hz, creating a deep incision of the scar tissue at the 6 o'clock position. This was followed by a vaporizing resection of the remaining scar tissue between 3 and 9 o'clock. We aimed to vaporize up to well-vascularized surrounding tissue. Retrospectively, the charts were reviewed for hospital stay, voiding complaints, recurrence of stenosis, complications, and flow rates. The mean follow-up was 18 months., Results: There were no operative complications. After removal of the catheter, all patients could void without difficulty. No re-treatment was needed for recurrent stenosis. Any existing irritative voiding complaints or incontinence did not change after treatment. In all patients, the flow pattern improved: the mean maximum flow rate increased, and the mean postvoiding residual volume decreased., Conclusion: The Ho:YAG laser seems to be a safe and effective treatment for first or recurrent strictures of the VUA after radical prostatectomy.

Objectives: To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice., Methods: Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy., Results: Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0., Conclusions: A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Objectives: To determine urodynamic changes and predictive factors in patients with voiding dysfunction who underwent 12 percutaneous tibial nerve stimulations., Methods: Thirty nine patients with chronic voiding dysfunction were enrolled in a prospective multicenter trial in the Netherlands (n = 19) and in Italy (n = 20). A 50% reduction in total catheterised volume per 24 hr was taken as a primary objective outcome measure. Patients' request for continuation of treatment was regarded as subjective success. Objective urodynamic parameters and bladder indices were determined. Odds ratios and their 95% confidence interval were computed as a measure for predictive power in order to reveal predictive factors (Pdet at Qmax, Qmax, BVE, and BCI)., Results: Primary outcome measure was obtained in 41%, an additional 26% reduced their 24 hr residuals with more than 25%. Fifty nine percent of patients chose to continue treatment. Detrusor pressure at maximal flow, cystometric residuals, and bladder indices improved significantly for all patients (P < 0.05). Patients with minor voiding dysfunction were more prone to notice success (Odds ratio: 0.73; 95% CI: 0.51-0.94)., Conclusions: PTNS is a young treatment modality, minimally invasive, and easily accessible. It might be an attractive first line option for patients with (minor) voiding dysfunction., (Copyright 2004 Wiley-Liss, Inc.)

Luteinizing hormone-releasing hormone (LHRH) agonist therapy to induce medical castration has become the most common form of hormonal therapy for advanced and metastatic prostate cancer. When treatment is started, LHRH agonists initially stimulate the release of LH, causing a surge in serum testosterone that can precipitate a "flare" phenomenon or worsening of disease, particularly in patients with bone metastatic disease. Gonadotropin-releasing hormone (GnRH) receptor antagonism represents a newer approach to medical castration. Abarelix is a pure GnRH receptor antagonist that is devoid of any LHRH agonist activity. Results from 1 phase II and 3 phase III clinical trials demonstrate that abarelix produces medical castration more quickly and without causing testosterone surge, as compared with LHRH agonists with or without a nonsteroidal antagonist. The safety profile in terms of adverse events is comparable between the 2 types of treatment, but the lack of testosterone surge with abarelix might confer a safety advantage by abolishing the risk of a disease flare.

Objectives: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH)., Methods: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values., Results: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml., Conclusions: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.

Objective: To compare the costs and outcome of high-energy transurethral microwave thermotherapy of the prostate (HE-TUMT) with transurethral resection of the prostate (TURP), as the former is considered to be the best minimally invasive method for managing lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH)., Patients and Methods: Between January 1996 and March 1997, 144 patients were randomized to treatment with HE-TUMT (78) using the Prostatron device and Prostasoft 2.5 software (EDAP Technomed, Lyon, France), or TURP (66). At baseline and during the annual follow-up, patients were evaluated by the International Prostate Symptom Score and uroflowmetry (maximum flow rate and postvoid residual volume). Kaplan-Meier survival analyses were used to calculate the cumulative risk of re-treatment. A cost-consequences analysis was performed based on the prospective measurement of healthcare use, with costs expressed as Netherland guilders (NLG)., Results: During a 3-year follow-up period, the mean (95% confidence interval) risk of re-treatment was 22.9 (12.5-33.2)% and 13.2 (4.5-21.9)% for HE-TUMT and TURP, respectively (P = 0.215). The mean direct cost of treatment was 3450 (3444-3456) and 6560 (5992-7128) NLG for HE-TUMT and TURP, respectively. The mean total (including re-treatments), discounted (4%) 3-year cost for the HE-TUMT and TURP group was 5300 (4692-5908) and 7800 (7118-8482) NLG, respectively., Conclusions: In this prospective randomized trial, HE-TUMT and TURP had a comparable 3-year risk of re-treatment. Healthcare expenditure on HE-TUMT, mainly because it is an outpatient treatment, was significantly lower than for TURP.

The treatment of hormone resistant prostate cancer) with epirubicin 25 mg/m(2)(Epi25) on a weekly intravenous regimen may be better in terms of health related quality of life (HRQOL) than with 100 mg/m(2)(Epi100) on a 4-weekly regimen. A total of 79 patients who filled out the EORTC-QLQ-C30 questionnaire for the assessment of HRQOL could be evaluated. Compared with the baseline, no changes in HRQOL function scales or significant changes in the following HRQOL symptom scales were found. The Epi25 group reported less pain during the first 3 months and the Epi100 group more dyspnoea after 4 weeks and less pain and less insomnia but more loss of appetite after 8 weeks. In both groups, toxicity was comparable, except for World Health Organisation grade II-III alopecia occurring in 82% in the Epi100 versus 31% in the Epi25 group. There were no significant differences between groups in response rates and survival. In this study, HRQOL was not improved which is in line with other studies using only epirubicine. Epirubicin as single agent therapy should not be used in future treatment of patients with HRPC.

Objectives: To evaluate the effect of stimulation of the posterior tibial nerve in the treatment of voiding dysfunction., Methods: Thirty-nine patients with chronic voiding dysfunction necessitating clean intermittent catheterization were enrolled in a prospective multicenter trial in the Netherlands (n = 19) and Italy (n = 20). They underwent 12 weekly sessions of posterior tibial nerve stimulation. Frequency/volume charts, an incontinence quality-of-life instrument, and the MOS 36-item Short-Form Health Survey were completed at 0 and 12 weeks. Subjective success was defined by the patient's positive response resulting in a request to continue treatment. Efficacy was based on analysis of the frequency/volume charts comparing the baseline values with the data at 12 weeks. A reduction of 50% or more in total catheterized volume was considered as an objective success (primary outcome measurement)., Results: Of the 39 patients, 23 (59%) chose to continue treatment. The frequency/volume charts showed a 50% decrease in total catheterized volume in 16 (41%) of 39 patients. Additionally, 10 patients (26%) noted a reduction of 25% to 50% in their total catheterized volume. For all patients, the total catheterized volume decreased by a mean of -228 mL (range -49 to -528). The incontinence quality-of-life instrument and Short-Form Health Survey parameters improved significantly., Conclusions: Percutaneous stimulation of the posterior tibial nerve seems to be an effective, minimally invasive option worth trying in patients with idiopathic voiding dysfunction. Improvement was seen in objective micturition parameters, as well as in subjective quality-of-life data.

Purpose: Neuromodulative therapies have been used with moderate success in patients with chronic pelvic pain. Intermittent Percutaneous Tibial Nerve Stimulation (PTNS) is a new, minimally invasive treatment option, which has shown to significantly decrease accompanying pain complaints in patients with lower urinary tract dysfunction, such as urge incontinence or urgency/frequency. In our study, we evaluate the objective results of PTNS in patients with chronic pelvic pain as their main complaint., Materials and Methods: In a prospective multicentre trial PTNS was evaluated in 33 patients with chronic pelvic pain. Effects were recorded by Visual Analogue Scale (VAS) for pain diaries, the McGill pain questionnaire and the SF-36 general quality of life questionnaire at baseline and after 12 weeks of treatment. Subjective (patients' request to continue chronic treatment to keep the obtained success) and objective responses (decrease in mean VAS >50% and VAS <3 after treatment) were evaluated., Results: A subjective response was seen in 42% of all patients. In seven patients (21%) mean VAS decreased >50%, in six cases (18%) the decrease was >25%. After 12 weeks of treatment, seven patients (21%) ended up with a mean VAS <3. In all patients quality of life (SF-36) significantly improved, as did the total pain rate intensity (McGill)., Conclusions: Despite very modest overall success rates and the need for placebo-controlled studies, PTNS may have a place in the treatment of patients with chronic pelvic pain who have already tried many other therapies and are left with no further option.

Aims: The objective of this study was to evaluate the effect of posterior tibial nerve stimulation (PTNS) for treatment of urge incontinence., Methods: In a prospective multicentre study, 35 patients with complaints of urge incontinence underwent 12 weekly sessions of PTNS at one of five sites in the Netherlands and one site in Italy. Frequency/volume charts and I-QoL and SF-36 questionnaires were completed at 0 and 12 weeks. Success was analysed by using subjective and objective criteria. Overall subjective success was defined as the willingness to continue treatment, whereas objective success was defined as a significant decrease (to<50%) in total number of leakage episodes., Results: Twenty-two patients (63%) reported a subjective success. Twenty-four patients (70%) showed a 50% or greater reduction in total number of leakage episodes. Sixteen (46%) of these-patients were completely cured (i.e., no leakage episodes) after 12 sessions. Quality of life parameters improved significantly., Conclusions: We conclude that posterior tibial nerve stimulation is an effective, minimally invasive option for treatment of patients with complaints of urge incontinence, as improvement was seen in subjective as well as objective parameters., (Copyright 2003 Wiley-Liss, Inc.)

Aim: The aim of this study was to evaluate urodynamic changes after percutaneous tibial nerve stimulation (PTNS) for the treatment of complaints related to overactive bladder syndrome and to search for urodynamic-based predictive factors., Methods: Ninety consecutive patients with symptoms related to overactive bladder syndrome were enrolled in this study. Patients underwent 12 PTNS sessions. For evaluating objective success, the primary outcome measure was a reduction in number of urinary leakage episodes of 50% or more per 24 hours. Patients' request for continuation of therapy was considered subjective success. This study focussed on urodynamic features at baseline and on changes found after 12 PTNS treatments., Results: The objective success rate was 56% (leakages/24 hours). Subjective success rate was 64%. Frequency/volume chart data and quality of life scores improved significantly (P < 0.01). Pre- and posturodynamic data were available from 46 participants. Detrusor instabilities (DI) could be abolished in a few cases only. Increments in cystometric bladder capacity and in volume at DI were significant (P = 0.043 and 0.012, respectively). Subjects without detrusor instabilities at baseline were 1.7 times more prone to respond to PTNS (odds ratio, 1.75; 95% confidence interval [CI], 0.67-4.6). The more the bladder overactivity was pronounced, the less these patients were found to respond to PTNS, the area under the receiver operating curve was 0.644 (95% CI, 0.48-0.804)., Conclusion: PTNS could not abolish DI. PTNS increased cystometric capacity and delayed the onset of DI. Cystometry seemed useful to select good candidates: patients without DI or with late DI onset proved to be the best candidates for PTNS., (Copyright 2003 Wiley-Liss, Inc.)

Dendritic cells (DC) have been recognized as the most potent antigen presenting cells (APC) of the immune system. We performed a phase 1 study in twelve patients with metastatic renal cell carcinoma (RCC) using autologous immature DC loaded with autologous tumorlysate (TuLy) as a vaccine based on our earlier in vitro observations that such DC can activate tumor-specific cytotoxic T-lymphocytes. The treatment was combined with low-dose interleukin (IL)-2, as this has shown benefit in DC-based therapies. Patients received three intradermal vaccinations at two weekly intervals, and, after each vaccination, IL-2 was administered for 5 consecutive days. In six patients, keyhole-limpet hemocyanin (KLH) was added to the DC culture for immunologic monitoring purposes. In general, DC phenotype was CD14(low), CD86(high), CD40(high), CD80(low), and CD83(low). We noticed that the number of CD14+ cultured DC increased during treatment. Nevertheless, ovalbumin uptake remained high, underlining that these cells were still functional immature DC. The vaccine was able to elicit cellular anti-KLH responses, emphasizing the ability of the injected DC to mount an immunologic response. However, proliferative responses against TuLy were not detected, and humoral responses against TuLy or KLH were absent. Objective clinical responses were not observed, but extended stable disease was noted. The absence of cellular, humoral, or clinical antitumor responses suggests that the vaccination strategy with immature DC has little benefit for patients with advanced RCC. Nevertheless, this study shows the feasibility of a completely autologous DC and tissue culture methodology for the generation of TuLy pulsed DC.

Purpose of Review: In the present review we outline the use of different staging methods and highlight future possibilities in the management of testicular germ cell cancer., Recent Findings: The 5-year survival for testicular cancer has improved dramatically over the past 30 years, with cure rates approaching 95%. This success is attributed to the appropriate integration of effective treatments and staging modalities. Staging currently represents the cornerstone on which treatment is based. Because most patients will be cured, attention has shifted toward reducing morbidity of treatment while maintaining high cure rates. This implies that staging must be accurate before any change to the treatment regimen can be instituted., Summary: Effective management of testicular germ cell cancer continues to pose a major challenge. Early and accurate diagnosis is very important because it will influence the choice of treatment and thus may impact on prognosis.

Objective: To present the long-term results of ileum interposition in the ureter for uni- or bilateral ureteral obstruction., Patients and Methods: Between 1981 and 2000, a total of 22 patients received an ileal segment interposition as a substitution for the ureter, of whom 18 were available for analysis. The mean age was 54 years (range 29-73). Patients were followed for a mean period of 65 months (range 2-196). Assessment included clinical examination, serum creatinine levels, renal ultrasonography, intravenous pyelography and isotopic renography. In eight patients, the ileal-ureteral substitution was the first reconstructive procedure. The other patients underwent up to four previous reconstructions of different types. Fourteen patients were treated for unilateral ureteral obstruction, four of whom had a functional or anatomical solitary kidney, the other four patients had bilateral obstruction., Results: In 16 patients renal function improved after ileal-ureteral substitution. One patient underwent a nephrectomy because of a decreased renal function due to an obstruction at the level of the uretero-ileal anastomosis. One patient had a nephrectomy because of recurrent macroscopic hematuria caused by multiple arterio-venous malformations. Overall, 15 patients (83%) had a good functioning kidney after a mean period of 65 months. In three patients an early reintervention was necessary because of bleeding, small bowel obstruction and urinary leakage from a pyelo-ileal anastomosis. Six patients required a reintervention in the long-term: two had a nephrectomy, three had a re-anastomosis between the renal pelvis and the proximal ileal segment, while the sixth patient underwent a PNL for a kidney stone. Recurrent urinary tract infections were seen in six patients, of whom three had to undergo a reintervention. Metabolic acidosis was detected in two patients and was treated with sodium bicarbonate substitution., Conclusion: Ileal-ureteral substitution is a valuable procedure with good long-term results and an acceptable rate of secondary interventions in patients for whom other alternatives are not feasible.

Purpose: We assessed the prognostic value of baseline prostate specific antigen (PSA) for outcome after high energy transurethral thermotherapy in patients with lower urinary tract symptoms., Material and Methods: Data were collected prospectively in 404 consecutive patients treated with high energy transurethral thermotherapy with the Prostatron device (EDAP-Technomed, Lyon, France). Patients were followed a minimum of 1 year. At baseline certain criteria were assessed, including pretreatment PSA, uroflowmetry, ultrasound measurement of prostatic volume, voided and post-void residual urine volume, and International Prostate Symptom Score (I-PSS) and quality of life scores. Outcome assessment included I-PSS, quality of life score and uroflowmetry of peak urine flow. Linear regression analyses were performed to correlate baseline PSA with improved clinical parameters at 12 months of followup. Logistic regression analyses and receiver operating characteristics curves characterized the ability of baseline PSA to discriminate patients with a more or less favorable outcome., Results: An evident linear association was identified for prostate size at baseline and PSA. After 1 year 36 patients were treated again due to transurethral thermotherapy failure and 16 had died, which was not related to lower urinary tract symptoms or treatment for lower urinary tract symptoms. To include re-treated patients in the analyses we considered that their I-PSS, quality of life and peak urine flow values at 1 year were unchanged compared with baseline. Of the 388 evaluable patients an improvement of 50% or more in I-PSS, quality of life and peak urine flow was observed in 57%, 62% and 44%, respectively. Absolute mean changes at 1 year were -9.7, -2 and 5.2 ml. per second for I-PSS, quality of life and peak urine flow, respectively. Neither linear nor logistic regression analysis showed any clinically relevant correlation between baseline PSA and changes in I-PSS (r = -0.004), quality of life (r = -0.135) or peak urine flow (r = 0.105) at 1 year. Receiver operating characteristics curves failed to distinguish more or less favorable outcomes in all evaluated parameters., Conclusions: Pretreatment PSA cannot predict the clinical outcome after high energy transurethral thermotherapy.

Guidelines within the healthcare system aim to rationalize the diagnosis, treatment and follow-up of a particular disease and can be applicable on an international scale or may be country specific. Specialists, who determine the clinical evidence for individual practices, prepare these guidelines, and the strength of these recommendations depends on available evidence. The assessment of patients includes a minimal number of non-invasive tests. Only in cases of abnormalities are additional (more invasive) tests recommended. Treatment decisions should be evidence-based but, despite guidelines, the choice of treatment is often highly dependent on the personal preference of the urologist. Patients' awareness of different treatment options and their involvement in choosing a treatment is also increasing. Economical aspects are becoming more and more important in making healthcare decisions. Data on durability of treatments, however, are limited and deserve special attention in order to provide the most cost-effective care for different patient groups.

Purpose: Recently, intermittent percutaneous posterior tibial nerve stimulation was introduced as a treatment modality filling the gap between conservative and surgical therapies in patients with certain types of lower urinary tract dysfunction., Materials and Methods: In a prospective multicenter trial posterior tibial nerve stimulation was evaluated in 37 patients who presented with symptoms of bladder overactivity, that is the urgency and frequency syndrome and/or urge incontinence, and 12 with nonobstructive urinary retention. Results were recorded in voiding diaries and on quality of life questionnaires before and after treatment. Patients were classified as responders, including those in whom therapy was successful and chose to continue treatment after the initial 12 weeks, and nonresponders, those who chose to stop treatment., Results: Overall, a positive response was seen in 60% of all patients. In patients with bladder overactivity a statistically significant decrease was observed in leakage episodes, number of pads used, voiding frequency and nocturia, and an equal increase in mean and smallest volume voided. Improvements were also seen in nonobstructive urinary retention, including number of catheterizations, total and mean volume catheterized, and total and mean volume voided. Disease specific quality of life and some domains of general quality of life improved, especially of bladder overactivity. Only mild side effects were observed., Conclusions: Posterior tibial nerve stimulation is a minimally invasive and successful treatment option for patients with certain types of lower urinary tract dysfunction.

Objective: Increased microvessel density (MVD) of prostate cancer seems to be associated with poor prognosis and higher stage. Assessment of MVD using noninvasive methods could be of use in the work-up of patients with prostate cancer. The aim of the present study was to correlate three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) findings with MVD characteristics of radical prostatectomy specimens., Methods: Seven patients with biopsy-proven prostate cancer had 3D-CE-PDU investigations 2-3 weeks after prostate biopsies were taken and prior to radical prostatectomy. The investigations were performed using Levovist contrast agent (Schering AG, Berlin, Germany) in combination with a Voluson 530D ultrasound scanner (Kretz AG, Zipf, Austria). The 7 patients were selected because of lateralization of the contrast enhancement. Histology slides were made of the side with 'contrast enhancement' and of the contralateral 'unenhanced' side and stained according to the catalyzed reporter deposition (CARD) amplification procedure, and MVD parameters were obtained., Results: In all patients the MVD count of the 'enhanced' side was higher than the MVD count of the 'unenhanced' side, averaging 1.93 times higher. On histology all enhanced lesions proved to contain prostate cancer tissue (average maximum diameter 25 mm (range 17-31)). Two patients had a small bilateral tumor lesion (4 and 5 mm respectively) and in total 5 patients had even smaller satellite lesions (1-2 mm). The smaller lesions were not identified using 3D-CE-PDU., Conclusions: The present study shows that 3D power Doppler contrast ultrasonography is a minimally invasive imaging modality, which has the potential to visualize lesions with increased MVD. This property of 3D-CE-PDU could be used in the detection of prostate cancer.

Cystoscopy is currently considered the gold standard for the detection of bladder tumors. The role of urine cytology in the initial detection and follow-up of patients is under discussion. New elaborative and rapid assays are available that may circumvent the low sensitivity and poor reproducibility of urine cytology. The methods that have been tested extensively are the nuclear matrix protein (NMP22) assay, the BTA stat assay, and the BTA TRAK enzyme-linked immunosorbent assay. Both outperform cytology in the detection of low-grade lesions. The specificity of both assays, however, lags behind that of cytology. The data from retrospective analyses are insufficient to justify clinical integration, and the need to replace cystoscopy with these novel assays remains to be proven.

Purpose: We evaluate the durable effect of high-energy transurethral microwave thermotherapy and transurethral prostatic resection for treatment of patients with lower urinary tract symptoms suggestive of bladder outflow obstruction., Materials and Methods: Between January 1996 and March 1997, 155 patients with lower urinary tract symptoms suggestive of bladder outflow obstruction were randomized to receive transurethral microwave thermotherapy (Prostatron*; device and commercial software) (82) or undergo transurethral prostatic resection (73). Initial patient evaluation was performed according to international standards. Patients were followed annually with the International Prostate Symptom Score (I-PSS) and uroflowmetry (maximum flow rate). The Kaplan-Meier survival analysis was used to calculate the cumulative risk of re-treatment, adjusted for loss to followup., Results: A total of 78 patients received transurethral microwave thermotherapy and 66 underwent transurethral prostatic resection. Median followup was 33 months. In the thermotherapy group mean maximum urinary flow rate improved from 9.2 ml. per second at baseline to 15.1, 14.5 and 11.9 ml. per second at 1, 2 and 3 years, and mean I-PSS decreased from 20 to 8, 9, and 12, respectively. In the resection group the corresponding numbers for maximum urinary flow rate were 7.8, 24.5, 23.0 and 24.7 ml. per second at 1, 2 and 3 years, and for I-PSS were 20, 3, 4 and 3, respectively. At 36 months, 14 patients in the thermotherapy and 8 from the resection groups underwent re-treatment, and the cumulative risk was 19.8% (95% confidence interval 10.4% to 29.3%) and 12.9% (4.5% to 21.3%), respectively (p = 0.28)., Conclusions: Transurethral microwave thermotherapy and transurethral prostatic resection achieve durable improvement in patients with lower urinary tract symptoms suggestive of bladder outflow obstruction, while the magnitude of improvement is higher with resection. The repeat thermotherapy is based on failure of therapy whereas repeat resection is based on complications of therapy.