European Urology Supplements

Published by Elsevier
Online ISSN: 1569-9056
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Article
Percutaneous nephrolithotomy (PCNL) was mostly performed with fluoroscopy and/or ultrasonography. The safety and feasibility of PCNL performed totally under ultrasound are not clearly defined. Therefore, we introduce the 9-year experience of 8 025 ultrasound guided PCNL procedures from multiple centers in China performed by the same surgeon, to evaluate the feasibility and security of this technique. From September 2004 to August 2013, 8 025 cases, 4 398 males (54.8%) and 3 627 females (45.2%), whose age ranged from 6 months to 85 years old, with upper urinary tract stones, underwent PCNL in our center and the supported hospitals. Puncture site selection and channel dilation were all guided using only Doppler ultrasound. Single stones were treated in 1 356 cases, there were 2 817 cases of multi stones, and 3 852 cases of staghorn calculi. The pre- and post-operative imaging data, the intraoperative findings, operation time, perioperative complications, and related parameters were recorded. All procedures were successful. No patients died during the operation. Average operation time was 42 minutes (range 10 to 168 minutes), 4 cases converted to open surgery, and 2 patients lost the diseased kidney due to refractory bleeding in the early stage of the PCNL. Ninety-four (1.2%) patients received blood transfusions and 20 (0.25%) patients needed highly selective renal artery embolization. Fifteen (0.19%) patients had a pleural injury. 5 457 (68%) cases were completed by a single tract and 2 568 (32%) cases added more tracts. The mean stone size (longest diameter) was 2.8 cm (range 1.2 to 26.5 cm). The final stone-free rate was 85.5%. Residual stones occurred mainly in patients with renal dysfunction, medullary sponge kidney, and complete staghorn calculi with a slim calyceal neck. X-ray free Doppler ultrasound guided percutaneous nephrolithotomy is feasible and safe in a variety of cases of renal and/or upper ureteral stones. The probability of radiation hazard and adjacent organ injury is low. The morbidity from major complications was reduced remarkably after special training. It is worthy of wider use compared with fluoroscopy in patients with special kidneys (e.g. solitary kidney, spinal deformity, ectopic kidney) and in infants.
 
Effects of honokiol (100μM) on electric field stimulation-induced contractions of human prostate strips. Contractions were compared before and after application of solvent (dimethylsulfoxide, DMSO) (A) or honokiol (B) to prostate strips. Tensions are expressed as % of contraction induced by 80mM KCl. Data are mean±standard error of the mean from experiments with prostates from n=9 patients.
Effect of honokiol on WPMY-1 cells. Honokiol (100µM) was applied to cultured WPMY-1 cells for 24 hours. Shown are representative pictures after application of honokiol or from control samples without honokiol, from a series of 3 independent experiments with identical results.
Effects of honokiol (A) and magnolol (B) on noradrenaline- and phenylephrine-induced contractions of human prostate strips. Contractions were assessed after application of solvent (dimethylsulfoxide, DMSO), and honokiol (100μM) or magnolol (100μM). Tensions are expressed as % of contraction induced by 80mM KCl. Data are mean±standard error of the mean from experiments with prostates from n=10 patients for noradrenaline/honokiol, n=8 patients for phenylephrine/honokiol, n=6 patients for noradrenaline/magnolol, or n=5 patients for phenylephrine/magnolol. *P<0.05 for DMSO vs. honokiol.
Effects of magnolol on cell cycle of WPMY-1 cells. Magnolol (100μM) was applied to cultured WPMY-1 cells for 24 hours. (A) Proliferation was assessed by a 5-ethynyl-2′-deoxyuridine assay, where red-orange fluorescence of 5-carboxytetramethylrhodamine (5-TAMRA) in nuclei indicates proliferation. Counterstaining of all nuclei was performed with 4′,6-diamidino-2-phenylindole (DAPI). (B) mRNA expression of the proliferation marker, Ki-67, and of β-actin was assessed by quantitative reverse transcription-polymerase chain reaction. Content in magnolol samples was referred to control samples, which were set to 1. Shown are representative pictures (A) or mean±standard error of the mean (B) from series with 3 independent experiments.
Article
Purpose Smooth muscle contraction and prostate growth are important targets for medical therapy of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia. Honokiol and Magnolol are lignan constituents of Magnolia species, which are used in traditional Asian medicine. Here, we examined effects of honokiol and magnolol on contraction of human prostate tissue and on growth of stromal cells. Methods Prostate tissues were obtained from radical prostatectomy. Contraction of prostate strips was examined in organ bath studies. Effects in stromal cells were assessed in cultured immortalized human prostate stromal cells (WPMY-1). Ki-67 mRNA was assessed by reverse transcription-polymerase chain reaction, and proliferation by a fluorescence 5-ethynyl-2′-deoxyuridine assay. Results Honokiol (100μM) reduced noradrenaline-induced contractions, which was significant at 10 to 100μM noradrenaline. Honokiol reduced phenylephrine-induced contractions, which was significant at 3 to 100μM phenylephrine. Honokiol reduced electric field stimulation-induced contractions very slightly. In WPMY-1 cells, honokiol (24 hours) induced cell death. Magnolol (100μM) was without effects on contraction, and cellular viability. Conclusions Honokiol inhibits smooth muscle contraction in the human prostate, and induces cell death in cultured stromal cells. Because prostate smooth muscle tone and prostate growth may cause LUTS, it appears possible that honokiol improves voiding symptoms.
 
Conference Paper
To compare outcomes of open (O-), laparoscopic (L-) and robot-assisted laparoscopic (RAL-) radical prostatectomy (RP) performed by the same surgeon. From May 1999 to April 2012, 484 RPs were performed by a single surgeon. Patients' data including age, body-mass index, serum prostate specific antigen (PSA) level, Gleason score of prostate biopsy and prostatectomy specimen, preoperative prostate and specimen volumes, clinical and pathologic stages, operation time, estimated blood loss (EBL), catheterization time, blood transfusion rate were recorded. Prospectively collected data was evaluated retrospectively by statistical analyses. Of 484 radical prostatectomies, ORP (50), LRP (308) and RALRP (79) done by the same surgeon were included into study. Mean ages were 63.8, 62.7 and 60.3 years for ORP, LRP and RALRP respectively. Operation times for ORP, LRP and RALRP were 255, 208 and 242 minutes. EBL and hospitalization time were 602, 526, 234 mL, and 9.1, 3.2, 3.2 days for ORP, LRP and RALRP, respectively. While a significant advantage was found for EBL and complication rates in RALRP and for operation time in LRP, significant disadvantages were found in terms of catheterization time, hospitalization time, decrease in hemoglobin and blood transfusion in ORP. However, preoperative prostate volume and serum PSA level, oncologic outcomes and positive surgical margins were nearly similar in all operative techniques. Minimally invasive techniques such as LRP and RALRP are promising techniques with comparable outcomes with ORP. Shorter catheterization time, less blood loss and fewer complication rates can be provided by RALRP.
 
Article
Background: Transrectal prostate needle biopsy (PNB) is a standard procedure for the diagnosis of prostate cancer. We recently found an increasing frequency of hospitalization with infectious complications associated with PNB over time. Objective: To perform an updated analysis of overall complication rates in a large screening population over the past 18 years and to examine possible predictors of complications on initial PNB. Design, setting and participants: From 1993-2011, 7216 men underwent initial lateralized sextant PNB in European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam. After 2 weeks a questionnaire was administered to 6962 men regarding PNB-related complications. Outcome Measurements & Statistical Analysis: Overall complication rates as well as specific complications (hematuria for >3 days, hematospermia, significant pain after biopsy, fever, and hospitalizations) were prospectively recorded. Multivariable logistic regression models were performed to assess the relationship between age, comorbidities, and prostate volume with specific complications. Results and limitations: A total of 4674 (67.1%) men reported any sequelae after initial PNB, with hematospermia as the most frequent (53.8%), followed by hematuria (24.3%). Significant pain (4.8%), fever (4.1%), and hospital admission (0.7%) were reported less frequently. Hematospermia was significantly more likely in younger men with fewer comorbidities and smaller prostate volume; whereas hematuria was significantly more frequent among men with increasing comorbidities and prostate volume. In addition, pain was inversely associated with age and was also reported less frequently during later years of biopsy. Limitations of our study include the use of sextant biopsies and a relatively healthy population, while strengths include the large sample size and data on patient-specific covariates. Conclusion: Many men experience minor complications after initial PNB, although the frequency of specific complications such as hematospermia and hematuria differed based upon factors such as prostate volume and comorbidities. Overall, these data are useful to counsel patients who are undergoing their first PNB on the frequency of complications in a screening population.
 
Article
Background Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone. Methods Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided. Results A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets. Conclusions The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management.
 
Potential effects on timing of radical cystectomy that were assessed in the study 
Article
The aim of the study was to assess the waiting time, from establishing the indications for radical cystectomy to surgery, in patients with urothelial carcinoma of the bladder at different Polish urological centres and to determine its influencing factors. Retrospective analysis of data was performed on all consecutive radical cystectomies, performed in 2008-2012, at 10 Polish urological centres. The waiting time of patients from establishing the indications for radical cystectomy to surgery, as well as factors potentially influencing this time, were assessed. University (3), provincial (3) and regional (4) hospitals were defined as the 3(rd), 2(nd) and 1(st) level referral hospitals, respectively. A total of 575 patients qualified for radical cystectomy due to muscle invasive urothelial carcinoma of the bladder (MIBC, 68% of cases) or failure of previous treatment of non-muscle invasive urothelial carcinoma of the bladder (NMIBC, 32%) were included in the analysis. The average time after the establishment of indications to surgery was 73.4 days, with a median of 56 days. In the case of 121 patients (22.1%), the waiting time exceeded 90 days. Significant differences in waiting time were found when the hospital referral levels were taken into consideration. In the 3(rd) level referral hospitals the median time for cystectomy was 61.5 days (p = 0.035), in the 2(nd) level referral hospitals - 45 days (p = 0.000) and, in the 1(st) level referral hospitals - 58 days (p = 0.051). The waiting time from establishing the indications for radical cystectomy to surgery for most cases in Poland does not exceed 90 days.
 
A) Comparison of progression-free survival (PFS) in patients with positive lymph nodes versus patients without positive lymph nodes (median 7.8 mo vs. 6.1 mo) without consideration of histologic subtype. Patients with lymph node metastases (LNM) had worse PFS (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.06-1.24; p = 0.001). (B) Comparison of PFS according to lymph node localization. Patients without LNM had the best PFS (8.8 mo), and patients with both supradiaphragmatic (SPD) and subdiaphragmatic (SBD) LNM localizations (SPD+/SBD+) had the worst PFS (5.5 mo). Patients with SBD LNM had significantly worse PFS compared to patients with no LNM (6.8 vs 8.8 mo; p = 0.003) and those with SPD LNM (6.8 vs 8.3 mo; p = 0.022). Any metastatic involvement of retroperitoneal lymph nodes, either alone (HR 1.25, 95% CI 1.08-1.45) or in combination with SPD+/ SBD+LNM (HR 1.50, 95% CI 1.24-1.74; p < 0.001) was associated with higher risk of progression. By contrast, SPD LNM alone was not a prognostic factor for progression (HR 1.03, 95% 0.895-1.18; p = 0.695). (C) PFS by lymph node localization in clear cell renal cell carcinoma (ccRCC; median PFS: no nodes, 9.9 mo; SPD LNM, 8.7 mo; SBD LNM, 8.0 mo; and both, 5.6 mo). Patients with SPD LNM (HR 1.09, 95% CI 0.94-1.25) and SBD LNM (HR 1.04, 95% CI 0.96-1.14) had similar PFS, and this was not significantly worse than the PFS of patients without LNM ( p = 0.265 and p = 0.333 for SPD and SBD LNM, respectively). 
-Multivariate analyses for association between lymph node metastases (LNM) and progression-free survival (PFS) in renal cell carcinoma
A) Patients with lymph node metastases (LNM) had a higher risk of death (median overall survival [OS] 23.9 mo, 95% confidence interval [CI] 21.6-26.3 mo) than those without LNM (median OS 16.0 mo, 95% CI 14.9-17.1; hazard ratio [HR] 1.41, 95% CI 1.28-1.54; p < 0.001). (B) A comparison without consideration of the histologic subtypes demonstrates that any lymph node involvement was associated with worse survival outcome compared to patients without LNM. Median survival times were 25.2 mo, 20.3 mo, 16.2 mo, and 11.5 mo in patients with no LNM and lymph node involvement in supradiaphragmatic (SPD), subdiaphragmatic (SBD), and both localizations (SPD+/SBD+), respectively. The HRs (95% CIs) for patients with SPD, SBD, and SPD+/SBD+ LNM were 1.24 (1.06-1.44), 1.45 (1.23-1.71), and 1.93 (1.60-2.33), respectively. (C) In clear cell renal cell carcinoma (ccRCC), patients with SPD and SBD LNM had similar median OS (SPD, 21.6 mo; SBD, 19.8 mo). However, both groups had a significantly higher risk of death (SPD: HR 1.24, 95% CI 1.05-1.47; SBD: HR 1.28, 95% CI 1.05-1.56) in comparison to those without lymph nodes. Patients with SPD+/SBD+ metastases had the worst OS (12.85 mo) and a twofold higher risk of death than patients without lymph node involvement (HR 2.04, 95% CI 1.682.48). (D) In non-clear cell RCC (nccRCC), median OS times according to lymph node localization were 15.8 mo for no lymph nodes, 16.1 mo for SPD LNM, 11.2 mo for SBD LNM, and 12.5 mo for SPD+/SBD+ LNM. There were no significant differences between the groups (log rank p = 0.444). 
-Multivariate Cox regression analysis of association between lymph node metastases (LNM) and overall survival (OS) in renal cell carcinoma
-General comparison of clinicopathologic features of patients with lymph node metastases (LNM) compared to those without LNM a
Conference Paper
It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients. To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT). Patients (n=2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype. Additional analyses (n=1536) were performed in subgroups of patients with supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) patients, respectively. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). All patients with LNM had worse PFS (p=0.001) and OS (p<0.001) compared to those without LNM. Compared to patients without LNM (PFS 8.8 mo; OS 25.1 mo), any SBD LNM involvement was associated with worse PFS (SBD, 6.8 mo; p=0.003; SPD+/SBD+, 5.5 mo; p<0.001) and OS (SBD, 16.2 mo; p<0.001; SPD+/SBD+, 11.5 mo; p<0.001). Both SBD and SPD+/SBD+ LNM were retained as independent prognostic factors in multivariate analyses (MVA) for PFS (p=0.006 and p=0.022, respectively) and OS (both p<0.001), while SPD LNM was not an independent risk factor. Likewise, in ccRCC, SBD LNM (19.8 mo) and SPD+/SBD+ LNM (12.85 mo) patients had the worst OS. SPD+/SBD+ LNM (p=0.006) and SBD LNM (p=0.028) were independent prognostic factors for OS in MVA, while SPD LNM was not significant (p=0.301). The study is limited by its retrospective design and the lack of pathologic evaluation of LNM in all cases. The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT. The presence of lymph node metastases below the diaphragm is associated with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
 
Article
To compare the postoperative outcomes and complications of transobturator tape (TOT) procedure in women with mixed urinary incontinence (MUI) and stress urinary incontinence (SUI) in long term follow--up. 193 women who underwent TOT procedure were documented in the study. Patients were divided into two groups in terms of incontinence type. Group1 consists of patients with SUI and group 2 with MUI. All patients were evaluated with pelvic examination including cough stress test and international consultation on incontinence questionnaire--short form at 3 and 12 months and annually. Visual analog scale (VAS) was used to evaluate postoperative patient satisfaction. Two groups were retrospectively compared for postoperative complication, patient satisfaction, objective and subjective cure rates. 105 patients in group 1 and 67 patients in group 2 were documented in this study. There was no significant difference between the objective cure rates in two groups, however subjective cure and patients satisfaction rates were significantly higher in SUI group (p<0.05). Complications were reported according to the Clavien--Dindo classification with Gr I 8.3 %, Gr II 66,7 %, Gr IIIa 8.3 % and Gr IIIb 16,7 % and Gr I 16.7 %, Gr II 66,6 %, Gr IIIa 16,7 % and Gr IIIb 0 % in group 1 and group 2, respectively. It is not easy to identify an ideal treatment modality for women with MUI but TOT procedure seems to be effective and safe in the surgical treatment of MUI after 5 years follow--up.
 
Article
Robotic and laparoscopic surgical training is an integral part of resident education in urology, yet the effect of resident involvement on outcomes of minimally-invasive urologic procedures remains largely unknown. We assess the impact of resident participation on surgical outcomes using a large multi-institutional prospective database. Relying on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant User Files (2005-2011), we abstracted the 3 most frequently performed minimally-invasive urologic oncology procedures. These included radical prostatectomy, radical nephrectomy and partial nephrectomy. Multivariable logistic regression models were constructed to assess the impact of trainee involvement (PGY 1-2: junior, PGY 3-4: senior, PGY ≥5: chief) versus attending-only on operative time, length-of-stay, 30-day complication, reoperation and readmission rates. A total of 5459 minimally-invasive radical prostatectomies, 1740 minimally-invasive radical nephrectomies and 786 minimally-invasive partial nephrectomies were performed during the study period, for which data on resident surgeon involvement was available. In multivariable analyses, resident involvement was not associated with increased odds of overall complications, reoperation, or readmission rates for minimally-invasive prostatectomy, radical and partial nephrectomy. However, operative time was prolonged when residents were involved irrespective of the type of procedure. Length-of-stay was decreased with senior resident involvement in minimally-invasive partial nephrectomies (odds ratio [OR] 0.49, p = 0.04) and prostatectomies (OR 0.68, p = 0.01). The major limitations of this study include its retrospective observational design, inability to adjust for the case complexity and surgeon/hospital characteristics, and the lack of information regarding the minimally-invasive approach utilized (whether robotic or laparoscopic). Resident involvement is associated with increased operative time in minimally-invasive urologic oncology procedures. However, it does not adversely affect the complication, reoperation or readmission rates, as well as length-of-stay.
 
Article
ObjectivesThis report summarises major new findings in the field of prostate cancer (PCa) presented during the 2006 annual meetings of the European Association of Urology (EAU), American Urological Association (AUA), American Society of Clinical Oncology (ASCO), and the American Society for Therapeutic Radiology and Oncology (ASTRO).MethodsUrologic experts in the field of PCa selected relevant new findings that were discussed during a closed meeting in September 2006. The key points are communicated in this paper.ResultsThere was much discussion about the relevance of Prostate-Specific Antigen (PSA) screening. There seems to be no specific threshold for early detection of clinically relevant PCa. PSA doubling time and PSA velocity may be more reliable to predict the risk of disease progression in patients with PCa. The first randomised controlled trial showed a comparable survival rate and risk of disease progression for external-beam radiation therapy and radical prostatectomy in patients with clinically localised PCa. In patients with advanced PCa, intermittent hormone therapy does not increase the risk of disease progression compared to continuous hormone therapy, while it has less impact on patient's quality of life. Patients receiving hormone therapy may benefit from an annual single-dose injection of zoledronic acid for the prevention of bone complications. Besides PSA, testosterone levels should be monitored in patients on androgen-deprivation treatment.ConclusionsMany interesting data in the field of PCa have been presented at this year's uro-oncologic meetings, which will improve the management of patients with PCa.
 
Article
ContextA significant proportion of patients with prostate cancer (PCa) will experience clinical or biochemical failure after local treatment with radical prostatectomy (RP) or radiotherapy (RT). It is still a matter of debate whether hormone therapy (HT) in either a neoadjuvant or adjuvant setting can offer a survival benefit for these patients.ObjectiveThis review paper discusses how and when neoadjuvant and adjuvant HT could be applied for treatment of PCa. Furthermore, the paper outlines the optimal duration of adjuvant HT to RT for treatment of patients with high-grade localised or locally advanced PCa.Evidence acquisitionThis paper is based on a presentation given at a satellite symposium held at the European Association of Urology (EAU) 2008 annual congress in Milan, Italy. Data were retrieved from recent review articles, original articles, and abstracts on neoadjuvant or adjuvant HT in PCa.Evidence synthesisLuteinising hormone-releasing hormone agonists have become the standard of care in HT. Neoadjuvant androgen deprivation therapy (ADT) to RP seems to have potential to downstage PCa disease but does not offer a survival benefit over RP alone in patients with localised PCa. On the other hand, short-term neoadjuvant ADT to RT appears to improve treatment outcomes compared with RT alone in patients with locally advanced PCa but seems to be specifically indicated in patients with Gleason score 2–6. Adjuvant ADT with RT seems to offer a survival benefit over RT alone in high-risk localised and locally advanced PCa. Recent data indicate that 6-mo ADT is inferior in terms of survival to 3-yr adjuvant ADT after RT for patients with locally advanced PCa. The role of immediate ADT for men with node-positive PCa after RP should be further investigated.ConclusionsNeoadjuvant and adjuvant ADT to local treatment may be indicated in carefully selected patients with PCa.
 
Article
At present there are no effective treatment options for patients with hormone-refractory prostate cancer (HRPC) and current medical management is largely palliative. Therefore, there is a need for novel, non-cytotoxic treatment approaches in HRPC. Cancer development is a multistep process, involving initiation, proliferation, angiogenesis, invasion, and metastasis, each of which present potential targets for anticancer therapy. A number of agents exploiting each of these cellular targets are in clinical development and are reviewed in this article, particularly: inhibitors of the epidermal growth factor signalling cascade (e.g. cetuximab, trastuzumab, and ZD1839 [‘Iressa’]); endothelin-A receptor antagonists (e.g. atrasentan); and angiogenesis inhibitors (e.g. ZD6474 and PTK 787). Other potential approaches include novel uses of existing compounds, inhibition of invasion/metastasis, induction of apoptosis, and gene therapy. These novel approaches and agents have the potential to be used in sequence or combination with established therapies, but also in combination with other new treatments. New, targeted biological therapies should lead to many more therapeutic options and better outcomes for patients with prostate cancer, particularly those with HRPC.
 
Article
Antimuscarinic agents are the most commonly used treatments for overactive bladder (OAB) syndrome where they reduce urgency, frequency, and urge incontinence. Despite few studies investigating the effects of antimuscarinic agents on mixed urinary incontinence (MUI), awareness is increasing about their value as first-line treatments for patients with MUI (combination of OAB wet and stress urinary incontinence). Evidence suggests that they are as effective in patients with urgency-predominant MUI as they are in OAB, resulting in significant reductions in urgency episodes, urinary frequency, and incontinence.
 
Article
The rationale for locoregional staging lymphadenectomy in prostate and bladder cancer lies in the accurate diagnosis of occult micrometastases in order to stratify patients who might benefit from adjuvant therapeutic measures. In prostate cancer, extended pelvic lymphadenectomy including the lymphatic tissue along the common iliac region with the ureteral crossing as cranial margin, external and internal iliac region and the obturator fossa has been shown to significantly increase the yield of both total lymph nodes and lymph node metastases. The frequency of observed positive lymph nodes in clinically localized and locally advanced prostate cancer is significantly higher than predicted by nomograms such as Partin tables and CART analysis. Although there are no prospective randomized trials demonstrating a survival benefit associated with epLA, there might be an advantage for those with minimal lymph node involvement. Various studies have documented an equal risk of cancer associated mortality in patients with no or only 1–2 positive lymph nodes. Since the surgery associated morbidity of epLA is not increased as compared to standard lymphadenectomy, epLA should be favoured for all patients undergoing radical prostatectomy. For the future, ongoing prospective trials have to demonstrate a benefit in terms of biochemical free and cancer specific survival.
 
Article
ZD4054 is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of hormone-resistant prostate cancer (HRPC). ZD4054 binds specifically to the ETA receptor, with no detectable activity at the ETB receptor. In preclinical studies, ZD4054 inhibited endothelin (ET-1)-mediated changes in cellular invasiveness in vitro, and inhibited angiogenesis and growth of tumour xenografts in vivo. Consistent with its specific binding profile, ZD4054 inhibited ETA-receptor-mediated antiapoptotic events while allowing ETB-receptor-mediated proapoptotic signalling.
 
Article
Anti-inflammatory therapy is very commonly prescribed in men with chronic nonbacterial prostatitis, or chronic pelvic pain syndrome. This practice is based on clinical experience rather than clinical trial data. This paper reviews the evidence to support the use of anti-inflammatory therapy in chronic prostatitis, and presents some considerations for future research.
 
Conference Paper
This paper presents our work aimed at providing augmented reality (AR) guidance of robot-assisted laparoscopic surgery (RALP) using the da Vinci system. There is a good clinical case for guidance due to the significant rate of complications and steep learning curve for this procedure. Patients who were due to undergo robotic prostatectomy for organ-confined prostate cancer underwent preoperative 3T MRI scans of the pelvis. These were segmented and reconstructed to form 3D images of pelvic anatomy. The reconstructed image was successfully overlaid onto screenshots of the recorded surgery post-procedure. Surgeons who perform minimally-invasive prostatectomy took part in a user-needs analysis to determine the potential benefits of an image guidance system after viewing the overlaid images. All surgeons stated that the development would be useful at key stages of the surgery and could help to improve the learning curve of the procedure and improve functional and oncological outcomes. Establishing the clinical need in this way is a vital early step in development of an AR guidance system. We have also identified relevant anatomy from preoperative MRI. Further work will be aimed at automated registration to account for tissue deformation during the procedure, using a combination of transrectal ultrasound and stereoendoscopic video. KeywordsMRI scan prostate–image guidance–augmented reality–robot-assisted laparoscopic prostatectomy (RALP)
 
Article
ObjectivesThis paper reviews the latest technologic developments in the field of external-beam radiation therapy (RT) for prostate cancer (PCa) and their clinical applications in the postprostatectomy setting and in conjunction with hormonal manipulation.MethodsThis review is based on a presentation during the New Horizons in Urology 2007 meeting held in Monte Carlo, Monaco, and includes relevant data from recently published literature.ResultsModern computer imaging, for example, computer tomography or magnetic resonance imaging, allows three-dimensional treatment planning techniques and a better definition and delineation of the target (prostate with or without seminal vesicles) and of the organs at risk (rectum, bladder, and penile bulb). Intensity-modulated RT and image-guided RT approaches are now available for the RT of PCa. Several phase 3 randomized clinical trials have demonstrated that immediate adjuvant RT after radical prostatectomy (RP) for patients at high risk for local relapse is associated with improved biochemical-free survival and clinical progression-free survival, compared to salvage RT. Furthermore, for high-risk, locally advanced PCa, androgen-deprivation therapy (ADT) combined with RT has shown better overall survival, compared to RT alone and recent data have revealed that 3 yr of adjuvant ADT after RT is superior to 6 mo for this subgroup of patients.ConclusionsTechnologic progress has contributed to improved RT results in clinically localized and locally advanced PCa. Immediate, adjuvant RT should be considered for patients with high-risk pathologic features after RP. For patients with locally advanced PCa, ADT combined with RT yields better outcomes than RT alone.
 
– (a) Electron micrographs of untreated cocultured fibroblast cells. Micrograph A (T3888) shows characteristic elongated nuclei (N), high levels of Golgi apparatus (G), and cilia. Micrograph B (T86 400) shows a collagen fibril (F) produced by the cocultured fibroblast cells. (b) Electron micrographs of Serenoa repens extract (SrE)–treated (10 mg/ml) cocultured fibroblast cells. Micrograph A (T15 984) shows general disruption of the cell cytoplasm and accumulation of lipids (L) in the cell. Micrograph B shows damage to the Golgi apparatus (G) in a fibroblast cell treated with SrE [5].  
sual representation of the content of 14 brands of SrE, as determined by analysis [3]. FFA = free fatty acids.
Schematic diagram showing some of the Serenoa repens extract (SrE) targets at the level of the prostate cell. DHT = dihydrotestosterone; EGF = epidermal growth factor; FGF = fibroblast growth factor.
Article
ContextMedical therapies derived from natural sources have been used for centuries. Many are as effective as synthetic medications. The use of plant-derived medications for benign prostatic hyperplasia (BPH) is no exception. In particular, extracts of Serenoa repens (SrE), the fruit of the American dwarf palm, are widely available, and their use is rising throughout the world.ObjectiveThe underlying basis for SrE popularity stems from its safety and tolerability profile. However, despite its extensive use, its mechanism of action has not been definitely clarified. In this paper, we analyse the scientific basis for SrE efficacy in the treatment of BPH and explore the mechanisms by which its effects are induced.Evidence acquisitionThis literature review focuses on the actions of the lipidosterolic SrE on a host of targets. Several cellular and molecular techniques have been used to characterise the biologic pathways that may mediate these actions. Morphologic studies have been carried out to identify the changes of prostate ultrastructure and to determine modifications that may shed light on the mechanisms underlying SrE efficacy.Evidence synthesisSelectivity of the action of SrE for the prostate has been demonstrated. There are several morphologic changes, and these are accompanied by an increase in the apoptotic index of the gland, along with inhibition of the activity of the 5α-reductase isoenzymes. The drug also acts on a number of other biologic systems and shows a capacity to moderate the androgenic, apoptotic, and inflammatory pathways of the cell. These pathways have been implicated in the hyperplastic process.ConclusionsThe interaction between prostate cells and SrE is manifest at several levels of the gland's biological spectrum and results in antiandrogenic, anti-inflammatory, and proapoptotic effects. These effects may account for the beneficial response triggered in some patients with BPH treated with SrE.
 
Article
The management of symptomatic benign prostatic hyperplasia (BPH) has changed significantly over the last decade in response to the availability of new treatment options. Evidence from a large-scale, pan-European study has shown that assessment and treatment allocation for BPH varies significantly within Europe, reflecting local clinical practice preferences, and drug availability and pricing, rather than evidence-based clinical guidelines. There is now evidence from a wide range of epidemiologic and clinical studies to demonstrate that a proportion of men with BPH will have progression of their disease. Such men can be identified through prostate-specific antigen assessment. It has also become apparent that watchful waiting may not always be the optimal approach for all men with mild symptomatic BPH. Data from large-scale clinical studies have demonstrated that treatment with 5α-reductase (5-AR) inhibitors not only significantly ameliorates symptoms of BPH, but also, in contrast to α-blockers, reduces the long-term risks of acute urinary retention and BPH-related surgery. Knowledge of the clinical characteristics that may predict the progression of BPH may thus permit a proactive approach to the management of the disease, whereby men at risk of progression can be identified at an early stage and treated appropriately to reduce their risk of progression. However, it appears that 5-AR inhibitors are often under-prescribed in at-risk men in clinical practice. Therefore, there is a need for a change in clinical practice to reflect the level 1 evidence for 5-AR inhibitors in men with symptomatic BPH who are at risk of disease progression.
 
Article
Objectives: What should be done when a first set of prostate biopsies was negative is still a matter of debate.Methods: Literature on prostate re-biopsy was reviewed and a selection of articles made. Keywords used for the Medline search included: Prostate cancer, Biopsy, Diagnosis.Results: Several studies including data from the multicenter European Prostate Cancer Detection Study (EPCDS) have shown that at least 10% of patients with negative sextant biopsies had prostate cancer found on repeat biopsy. Re-biopsy can be performed 6 weeks after an intial set of biopsies without significant increase in pain or morbidity.Conclusions: The current review critically evaluated the indications, timing, number of cores and location of repeat biopsies focussing on the available literature.
 
Article
ObjectivesThe majority of patients with hormone-refractory prostate cancer (HRPC) develop bone metastases, which are also common in patients with other genitourinary malignancies. Bone metastases can lead to debilitating skeletal complications and reduced quality of life (QoL). Therefore, the goal of therapy for patients with malignant bone disease is preservation of functional independence and QoL by delaying onset of skeletal-related events (SREs) and by palliating bone pain. Bisphosphonates have become integral in achieving treatment goals for these patients.MethodsData from two phase 3, placebo-controlled trials in patients with malignant bone disease from HRPC or solid tumors including renal cell carcinoma (RCC) were reviewed to determine the efficacy of zoledronic acid in reducing the incidence and delaying the onset of SREs.ResultsIn patients with metastatic HRPC (n = 422), 4 mg zoledronic acid every 3 wk significantly reduced all types of SREs, delayed time to first SRE by >5 mo, and reduced ongoing risk of SREs by 36% compared with placebo. Moreover, zoledronic acid reduced the risk of experiencing a second SRE compared with placebo and appeared to be more beneficial in patients with no pain at baseline. In a separate trial in patients with solid tumors, zoledronic acid reduced the proportion of patients who experienced any SRE compared with placebo in the RCC subset (n = 46). Furthermore, zoledronic acid demonstrated trends for longer overall survival in these patient populations.ConclusionsZoledronic acid significantly delays the onset and reduces the incidence of SREs in patients with bone metastases secondary to HRPC and RCC.
 
Article
Infravesical obstruction impairs bladder function, and α1-adrenoceptor (AR) antagonists can relieve such dysfunction in part due to their moderate deobstructing effects. Moreover, α1-AR antagonists may also have beneficial effects on bladder function via mechanisms independent from those regulating bladder outlet resistance. Such beneficial effects have repeatedly been reported from various animal models of bladder outlet obstruction, and preliminary data indicate that this may perhaps also occur in lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) patients. The contribution of such effects on the bladder in the long-term treatment of LUTS/BPH remains to be assessed. The recently completed Medical Therapy Of Prostatic Symptoms (MTOPS) study has demonstrated that α1-AR antagonists have beneficial effects on the progression of LUTS/BPH which are quantitatively similar to but qualitatively different from those of 5α-reductase inhibition. Due to this differential mode of action, long-term combination treatment was significantly more effective than either treatment alone. Since combination therapy is at least associated with the side effects of both the α1-AR antagonist and 5α-reductase inhibitor, great care should be taken to identify patients at high risk in whom the benefits of combination treatment outweigh its risk. Use of an α1-AR antagonist with very high tolerability may facilitate the use of combination treatment.
 
Article
Despite being used extensively for the diagnosis and management of prostate cancer, prostate-specific antigen (PSA) testing remains controversial. Doubts have been raised over the continued use of PSA in the detection of clinically significant prostate cancer because many men now present with early-stage, small-volume tumours. This article examines the limitations of using a single PSA value in diagnosis and discusses alternative approaches to PSA testing, in particular PSA velocity and PSA doubling time, which are now emerging as valuable pretreatment disease predictors. A clinical scenario is also presented to illustrate the use of PSA kinetics in identifying candidates for biopsy.
 
Article
Prostate cancer is the second most commonly diagnosed cancer in men in the European Union (EU) and the third most common cause of cancer-related death in men in the Western world. In recent years, prostate-specific antigen (PSA) testing has become an indispensable tool in urological oncology. In addition to allowing risk stratification and prognosis determination, PSA testing also allows the earlier detection of hormone-refractory prostate cancer (HRPC). More patients, therefore, now present with potentially curative disease. For many men, however, disease prognosis is considerably poorer. Prostate cancer often progresses to HRPC with death from widespread metastases. Not only is it important to acknowledge the heterogeneity of patients with HRPC, and thus the need for individualised treatment, but it is also important to stratify patients according to their risk of disease recurrence, a process that can guide treatment decisions. Patients with HRPC present a treatment challenge. Until recently, once a patient started to fail to respond to androgen-deprivation therapy, the options were limited. Second- and third-line hormonal therapies represent the standard of care but are relatively ineffective. Patients with HRPC will therefore require multiple systemic therapies for their disease, ideally within the multidisciplinary team setting. Traditionally, HRPC was considered unresponsive to chemotherapy. This view may need to be refined in light of new data indicating that chemotherapy confers a survival advantage to these poor-prognosis patients.
 
Article
ContextPatient involvement in the medical decision-making process has gained a good deal of importance during the last decades. It has become widely accepted that patient values and preferences should also be considered during treatment selection when reasonable alternatives are available.ObjectiveThis paper discusses the process of shared medical decision making and the importance of informing the patient and improving patient–physician communication concerning prostate cancer (PCa).Evidence acquisitionDuring a satellite symposium at the European Association of Urology (EAU) 2008 annual meeting, the issue of shared medical decision making in PCa was presented. This paper discusses the most important messages of this presentation, supported by recent findings in the literature.Evidence synthesisIn clinical situations where data do not clearly differentiate the treatment alternatives, patient involvement in the medical decision-making process becomes critical. Therefore, patient–physician communication should be emphasised, and physicians should take the time necessary to inform the patient about potential treatment options and their expected consequences. Increasing a patient’s ability to engage physicians in a dialogue and providing patients with balanced information will contribute to a well-considered decision, which in turn can minimise future regret. Misleading information on the Internet and poor literacy skills can hamper the decision-making process. Patients are often dissatisfied with inadequate time spent during physician visits and the not-uncommon perception that treatment choices the physician presents are more restricted than optimal.ConclusionsIn current clinical practice, the patient–physician dialogue should be enhanced, and patients’ preferences should be taken into consideration in the decision-making process. This will contribute to well-considered treatment decisions and improve patient satisfaction.
 
Article
Objective:Men with prostate cancer survive for many years after diagnosis and are at risk for clinically important skeletal complications throughout the course of their disease. This review discusses the effect of skeletal complications on quality of life and treatment options available to maintain bone health throughout the continuum of care for prostate cancer.Methods:Published studies were identified through MEDLINE searches, reviewing bibliographies of relevant articles, and reviewing abstracts from scientific meetings.Results:At the time of diagnosis, many men with prostate cancer are osteopenic or osteoporotic. Subsequent androgen ablation therapy increases bone loss and the risk of fracture. The development of bone metastases further increases the risk of skeletal complications, including pathologic fractures and bone pain requiring radiation therapy. Skeletal complications result in significant morbidity and reductions in the quality of life and survival of these patients. Pathologic fractures and radiation to bone (for palliation of pain) are associated with significant declines in physical functioning and emotional well-being. Fractures can also significantly reduce overall survival.Conclusions:Skeletal complications arising from bone metastases and bone loss can adversely affect quality of life. Therefore, bisphosphonates, which maintain bone health and reduce skeletal complications in men with prostate cancer, should improve the quality of life in these patients. Zoledronic acid is effective in preventing skeletal-related events in men with advanced prostate cancer.
 
Article
Keeping current with medical innovations is a challenge that all health care professionals are faced with. The closed expert meeting “New Horizons in Urology” (NHU), which takes place yearly, aims to give practising urologists an overview of new information and its potential implementation in clinical practice. The NHU2007 meeting was held in June in Monte Carlo, Monaco. The meeting focused on the multidisciplinary management of the prostate cancer (PCa) patient, which included the concept of modern androgen-deprivation therapy (ADT) for optimal control of testosterone as well as considerations about a new paradigm in clinical practice, integrative medicine. Furthermore, some pitfalls of pathological staging in PCa regarding core needle biopsies and radical prostatectomy specimens were highlighted. In addition, the technical advances of modern external beam radiation therapy (RT) as well as the clinical application of RT after radical prostatectomy and in combination with ADT were discussed.
 
Article
Background and objectiveThe gold standard for open radical nephroureterectomy is currently being challenged by minimally invasive procedures for upper tract tumour management. A nephron-sparing approach may be proposed in patients with an anatomic or functionally solitary kidney, bilateral disease, significant chronic renal insufficiency, or medical comorbidities in whom major surgical procedure would be poorly tolerated.Material, methods and resultsLocal recurrence has been observed in 65% of patients with endoscopically treated upper tract tumours, with an average time to recurrence of <10 mo. Adjuvant topical immunotherapy or chemotherapy agents have been reported in the literature for treatment and prophylaxis of transitional cell carcinoma. Two major techniques are usually recommended for the administration of mitomycin C (MMC) and bacillus Calmette-Guérin (BCG): perfusion through a percutaneous nephrostomy tube or by retrograde reflux from the bladder with an indwelling double-J stent in the Trendelenburg position. BCG therapy has been reported to provide cure in approximately 50% of renal units with carcinoma in situ; however, papillary and solid tumour recurrences of the urinary upper tract cannot be prevented with BCG therapy. Adjuvant therapy is considered safe, with no systemic side-effects resulting from perfusion with MMC as topical therapy following endoscopic resection of upper urinary tract carcinoma. In contrast, up to 25% of patients may have granulomatous involvement of the urinary tract after BCG administration.ConclusionThe efficacy and safety of this conservative approach warrants further evaluation, as long-term follow-up is necessary to confirm previously reported oncologic data. Moreover, adjuvant therapy may be proposed with the patient's consent, as it requires a strict ureteroscopic surveillance protocol.
 
Article
Prostate-specific antigen (PSA) testing advances the diagnosis of prostate cancer, shifting the stage at diagnosis towards localised disease. However, the widespread application of PSA testing is controversial, due to uncertainties over whether earlier diagnosis of prostate cancer improves the mortality associated with the disease. This article discusses the evidence on the relationship between PSA testing and prostate cancer mortality considering 5-year survival rates, data from randomised, controlled trials and epidemiological trends in disease mortality. Reported improvements in 5-year survival rates for prostate cancer are probably due to lead-time bias (screening leading to earlier diagnosis). Randomised studies evaluating PSA screening are ongoing and will not provide mortality results until the latter part of this decade. Epidemiological data reveal a decline in disease mortality in areas where PSA screening is routine, but the cause of this decline is likely to be multifactorial. In conclusion, an effect of PSA testing on the natural history of prostate cancer is not yet fact, as determined by a randomised controlled trial, but it is certainly more than fiction.
 
Article
Over the past few years, considerable advances in the understanding of the pathology and underlying molecular pathways in renal cell carcinoma (RCC) have been translated into the development of targeted therapeutics for this disease. Clear-cell RCC is characterised by the inactivation of the von Hippel-Lindau tumour suppressor gene, resulting in the dysregulation of hypoxia response genes, overproduction of vascular endothelial growth factor, which promotes tumour angiogenesis, proliferation, and metastasis. Novel multitarget tyrosine kinase and angiogenesis inhibitors have achieved a benefit in progression-free and overall survival in patients with advanced RCC in recent prospective randomised trials. This review will describe the most relevant clinical data with the new molecular-targeted agents in RCC and provide an overview of current indications for these compounds.
 
Article
Renal cell carcinoma (RCC) represents a chemotherapy- and radiation-resistant tumor with a generally poor prognosis and a 5-yr survival rate of patients of <10%. Although immunotherapy is an alternative intervention leading to clinical responses in a subset of patients with RCC, this tumor has developed different strategies to escape from immunosurveillance. This could be due to alterations in the tumor itself resulting in its impaired recognition by the immune system, by the tumor microenvironment, and by the dysfunction of immune cells of patients with RCC. This review summarizes the diverse immune escape mechanisms of RCC and discusses current and future strategies to circumvent these defects. This knowledge together with the identification of novel, more universal antigens will contribute to an improved design of RCC-specific immunotherapies.
 
Article
ContextIndications, current endoscopic management, adjuvant therapies, and follow-up regimens in renal conservational management of upper urinary tract transitional cell carcinoma (UUTT) are described.ObjectiveThis short review emphasises contemporary endoscopic diagnostic and therapeutic ablative options and includes information about adjuvant therapies and surveillance protocols in patients with low- or intermediate-risk UUTT selected for renal conservation.Evidence acquisitionEvidence was acquired from a review of the recent published literature over the past 15 yr, with key articles selected from expert centres.Evidence synthesisKey points from cited articles were summarised in the review and blended with new material based on emerging techniques and technology along with expert experience.ConclusionsThe major findings of this review suggest that when optimally performed using a meticulous technique with appropriate equipment both for diagnosis and treatment in expert centres, safe renal conservation is possible in a defined UUTT population, even when a normal contralateral kidney is present. A strong case can be made for challenging the age-old paradigm that nephroureterectomy should be uniformly applied as the first-line treatment for all patients with suspicious filling defects in the upper urinary tract or proven clinically localised UUTT, provided there is no high grade-stage, or an imperative for renal preservation.
 
Article
This is a special edition publication examining the merits and disadvantages of focal therapy to treat prostate cancer. Although several publications have already dealt with this topic, outlining the benefits of several novel techniques to treat prostate cancer, in this paper we focus on the argument from the “con” perspective and outline the rationale for why focal therapy as an approach to treat prostate cancer with current technologies is suboptimal. We provide the basis for this reasoning, discussing four focal treatment modalities; namely, high-intensity focused ultrasound, cryotherapy, radio frequency ablation, and photodynamic therapy. Given that none of the focal treatment options is without potential morbidity or mortality, that current technological limitations prevent complete mapping of the prostate and subsequent identification and treatment of all lesions, and that there is still significant potential for residual disease after focal treatment, we feel that a subset of men with favourable disease parameters who do not want definitive treatment may be better suited to undergo the less morbid treatment option, active surveillance.
 
Article
The classic paradigm of obstructive benign prostate hyperplasia (BPH) causing lower urinary tract symptoms (LUTS; BPH/LUTS) has been replaced by the notion that not only the prostate but also the bladder contributes to symptoms.The severity of bladder outlet obstruction is closely related to the development of detrusor dysfunction associated with similar symptoms. Several explanations have been set forth to explain the onset of detrusor overactivity, including increase in sympathetic stimulation, supersensitivity to acetylcholine, local changes producing segmental contractions, and increase in nerve growth factor.Metabolic syndrome, defined as abdominal obesity associated with hyperinsulinemia, insulin resistance, and two additional cardiovascular risk factors, is associated with urologic disorders such as hypotestosteronemia and erectile dysfunction. A growing body of evidence suggests that it is also associated with BPH and LUTS.These new concepts should be used to design novel treatments for BPH/LUTS.
 
Article
Nocturia is one of the most bothersome complaints in men with lower urinary tract symptoms suggestive ofbenign prostatic obstruction (LUTS/BPO). Storage symptoms such as nocturia interfere considerably with the patient's performance of daily activities and quality of life. So far little attention has been paid as to why nocturia is such a trouble for men with LUTS/BPO and their partners. It is increasingly believed that disturbed sleep due to frequent awakenings at night resulting in reduced daytime energy and alertness is the underlying cause of the interference with daily-life activities and the reduced quality of life. It seems that in particular awakening during deep sleep, i.e. during the first third of the night, results in increased sleep inertia (i.e. performance impairment immediately after awakening) and reduced daytime performance. It has been shown that the prevalence of frequent night-time voiding interfering with sleep and leading to poor sleep, feeling tired during the day and poor health increases with the number of nocturnal voids. Disturbed sleep not only leads to reduced productivity and increase in the number of sick days, but nocturia and disturbed sleep can also have serious health consequences with a dramatic impact on patients, their family and society. Sleep deprivation has a detrimental effect on somatic and mental health, and is implicated in accidents and even increased mortality. Therefore, it is important to know how LUTS/BPO treatment improves nocturia, reduces disturbed sleep and improves the overall quality of life of patients. Preliminary data suggest that LUTS/BPO therapy reduces nocturia and that a reduction in the number of nocturnal voids during treatment for nocturnal polyuria improves the hours of undisturbed sleep in the first third of the night, when deep sleep predominates. However, further research is required to more precisely assess the impact of LUTS/BPO treatment on nocturia, disturbed sleep and quality of life. The Nocturia Quality of Life (N-QOL) questionnaire which is adopted in the International Consultation on Incontinence modular questionnaire may be a useful tool for this.
 
Article
IntroductionWe present our series of laparoscopic radical cystectomies. The program was started when our department had a previous experience of nearly 500 laparoscopic radical prostatectomies, which allowed this series to be performed with virtually no learning curve.MethodsFrom January 2005 to May 2006, we performed 35 laparoscopic radical cystectomies in 8 women and 27 men. Because of the high rate of ureterointestinal stenosis detected in the first 26 cases (19.2%, 5 of 26), we changed from open to laparoscopic urinary diversion. With this change, the rate has currently decreased to 14.2% (5 of 35).ResultsMean surgical time was 5.59 h for open urinary diversion and 9.42 h for pure laparoscopic surgery, with a mean blood loss of 488.57 ml and a mean hospital stay of 14.11 d. The mean number of nodes at lymphadenectomy was 13.5 (range: 5–24) and 37.1% of patients had lymph node involvement.ConclusionsRadical cystectomy is one of the most aggressive urologic surgeries, but numerous publications have shown that it can benefit from the advantages of laparoscopy. The question of whether open or laparoscopic methods are preferable for urinary diversion remains a subject of debate.
 
Article
Patients with neurogenic detrusor overactivity (NDO) usually have other disorders or disabilities, in addition to bladder dysfunction, that require treatment. A number of different medical specialists are, therefore, involved in the management of an individual patient and may well be working towards different treatment goals. This, together with the possible impact on NDO of treatments for other disabilities and vice versa, means that a global approach to management of a given patient is needed to ensure that patients receive the best possible treatment for all their conditions. This is particularly true for treatments that are used for multiple indications in the same patient, such as botulinum toxin, which has been used for many years as an effective treatment for dystonia and spasticity, and has more recently shown promise in the treatment of NDO and idiopathic detrusor overactivity. The appropriate choice of total dose and staging of dosing is required to maximise safety and efficacy in both indications. Development of multidisciplinary treatment algorithms for the various types of NDO patients could help to promote a global approach to the management of these individuals and to optimise their care.
 
Article
As first-line treatment for erectile dysfunction (ED), phosphodiesterase type 5 (PDE5) inhibitors are highly effective and well tolerated, making it possible for the majority of men with ED to experience better sex in terms of the restoration or improvement of erection rigidity and durability. Better erectile function can also improve the quality of the couple's relationship and the sexual satisfaction of female partners, yet a high proportion of men discontinue treatment even though the use of a PDE5 inhibitor has restored erection rigidity and durability. In the past, research focused on the influence of the drug regimen and side-effects on noncompliance and premature discontinuation. However, it is apparent that health professionals must also provide pretreatment education on the impact of drug therapy on the broader sexual experience for men and their partners, rather than limiting themselves to a discussion of erectile function alone. This education should be further reinforced through adequate and timely follow-up to optimise treatment outcome. In addition, any ED treatment plan must consider the context of a man's relationship with his partner, since a partner's encouragement is often crucial in motivating a man to continue with treatment. The partner's motivation to maintain or return to sexual intimacy, her satisfaction with sex, and his perception of that satisfaction are central to the restoration of a satisfactory sexual experience. These beneficial outcomes can best be achieved by adopting a holistic approach that recognises the complexities of ED, and the importance of the partner's central role in the success of treatment and the experience of better sex.
 
Article
The perception of lifelong premature ejaculation (PE) has evolved from that of a relatively obscure complaint to one of a relatively common syndrome with a neurobiological component. During the last century, four historical periods, each about 30 yr in duration, can be distinguished. In these periods PE was regarded according to the major prevailing viewpoint of mental disorders, that is, from phenomenological, psychoanalytic, behavioral, and neurobiological points of view. Although the influences of these different periods on the medical approach to PE are still present today, recent scientific evidence suggests that lifelong PE is related to an imbalance in central serotonin neurotransmission. A basic premise for further research remains an evidence-based definition of PE. Such an evidence-based definition is essential to ensure accurate and reproducible clinical outcomes.
 
Article
The investigation of the etiology and treatment of premature ejaculation (PE), a common and significant problem for men and their partners, has been limited by the lack of defined outcomes and differences in clinical trial designs. Currently, no medication has been approved for the treatment for PE worldwide. Recognition of serotonin as a key mediator in ejaculatory signaling has raised interest in the utility of pharmacologic intervention for treating PE. Selective serotonin reuptake inhibitors (SSRIs) have been used off-label for PE, with varied results. However, treatment with currently available SSRIs typically requires chronic dosing that increases drug accumulation and the attendant risk of adverse events. Dapoxetine is an SSRI with a short half-life (1.2 h), developed specifically for the treatment of men with PE. This agent has a unique pharmacokinetic profile characterized by rapid absorption and elimination. Dapoxetine is metabolized by multiple pathways, and no clinically relevant drug–drug interactions have been identified. Furthermore, dapoxetine pharmacokinetics do not appear to be affected by food, age, alcohol, or phosphodiesterase type 5 (PDE5) inhibitors to a relevant degree. In two placebo-controlled phase 3 trials involving >2600 men with PE, dapoxetine 60 mg given as needed over 12 wk significantly prolonged the stopwatch-assessed intravaginal ejaculatory latency time (IELT) from 0.91 min at baseline to 3.32 min (p < 0.0001), increased control over ejaculation, and increased sexual satisfaction for men and their partners compared with placebo (both p < 0.0001). These results suggest that dapoxetine may meet the medical need for on-demand therapy for PE.
 
Article
ObjectivesThis review paper discusses the importance of optimal testosterone control in prostate cancer (PCa) and the advantages of the luteinising hormone-releasing hormone (LHRH) agonist Eligard® in this respect.MethodsDuring an expert meeting in Marbella, Spain, in October 2006, PCa experts discussed optimal testosterone control and the role of Eligard. An interactive voting on these topics was held among the delegates. This paper reports on this meeting.ResultsLHRH agonists should suppress testosterone levels to an extent equivalent to surgical castration. A significant proportion of patients on conventional LHRH agonists do not achieve surgical castration levels. In addition, a significant percentage of patients experience hormonal escape during treatment. Eligard uses a modern delivery system and offers 1-, 3- and 6-mo depot formulations. The Eligard 1-mo, 3-mo, and 6-mo formulations achieve testosterone levels ≤20 ng/dl in up to 98% of patients. Injection-related and breakthrough testosterone escapes seldom occur. Eligard 6-mo formulation (45 mg; Eligard 6) is the first LHRH agonist able to extend treatment for 6 mo. Eligard 6 allows flexible monitoring of patients because the need for visits solely to administer injections is removed. In addition, reducing the number of injections may help reduce psychological burden in patients who then are less often reminded of their condition.ConclusionsEligard provides optimal testosterone control in PCa patients, that is, achieves castration testosterone levels and is associated with a very low percentage of hormonal escapes. Eligard 6 offers flexibility in follow-up of patients and may help reduce emotional distress.
 
Article
ObjectivesLaparoscopy has become an alternative procedure for various retroperitoneal conditions. It is not easy to learn, and special caution should be taken during its practice because of the presence of large vessels in the surgical field. We report here our 22-mo initial experience with retroperitoneal laparoscopic surgery.Material and methodsThe analysed period covers June 2004 to April 2006 (i.e., 22 mo) during which time 128 laparoscopic retroperitoneal surgical procedures were performed. Seventy-eight laparoscopic nephrectomies (43 radical, 16 simple, 14 nephroureterectomies, and 5 in living donors) were performed during this time period. Other types of retroperitoneal laparoscopic surgery were carried out in 50 cases: 10 pyeloplasties, 10 adrenalectomies, 10 partial nephrectomies, 9 retroperitoneal biopsies, 6 stone removals, and 5 cyst marsupialisations.ResultsMean hospital stay was 3.5 d (range: 2–9) for the laparoscopic nephrectomies and 3.3 d (range: 1–7) for the other retroperitoneal laparoscopic surgeries.The conversion rate to open surgery was 1.5% (2 of 128).ConclusionsLearning about renal laparoscopic surgery should be gradual and guided by common sense. The approach to retroperitoneal pathology is technically complex and dangerous because of the presence of the great vessels. The learning curve is long and the potential complications are severe.
 
Article
This review of the recent international literature updates the knowledge about the diagnostic procedures used in prostate-specific antigen (PSA) progression following radical treatments of clinically localized prostate cancer. Prostate-specific antigen (PSA) progression in these patients is a common problem facing both the patient and the urologist. Not all patients with relapsing disease have an equal risk of morbidity and death due to prostate cancer.After surgery, biochemical failure can be defined as persisting detectable levels of PSA after radical prostatectomy or a PSA rise after a period of normalization. On the other hand, definitions of PSA progression after radiation therapy vary and no clear consensus can be found.Predictors of progression are precised leading to a better patient selection, based on currently available tables and nomograms. Indeed, identification of high risk patients may allow a more appropriate treatment decision.After radical treatment, the analysis of time to recurrence, PSA doubling time, PSA kinetics combined to modern imaging techniques may allow a better identification of the recurrence site. Thus, an optimal treatment strategy such as local irradiation, salvage surgery, hormone therapy or combinations for which indications and results are provided may be envisaged. Alternative options such as cryotherapy still need further investigation.
 
Article
Testosterone substitution is reported to produce a wide range of benefits for men with hypogonadism that include improvements in muscle mass, body composition, mood, bone density, libido, and cognition. Understanding the actions of exogenous testosterone on the prostate gland is important since testosterone is the major regulator of growth and function of this organ. To date, clinical studies of the effects of testosterone substitution on prostate health suggest that testosterone substitution does not exacerbate lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH), although it may increase prostate volume. The greatest concern associated with testosterone substitution is the possibility of increased risk of prostate cancer. The relationship between prostate cancer and testosterone is not completely understood. While there is currently no compelling evidence that the use of testosterone substitution in men with hypogonadism increases the risk of prostate cancer, close monitoring of the levels of testosterone and prostate-specific antigen (PSA) along with regular digital rectal examination (DRE) are advised to detect early signs of prostate cancer in subjects receiving long-term testosterone substitution. This review considers the physiological and pharmacological actions of testosterone on the prostate gland, and the risks of BPH and prostate cancer in ageing males receiving testosterone substitution for the treatment of hypogonadism.
 
Top-cited authors
Alexandre Zlotta
  • University of Toronto
Richard Sylvester
  • European Organisation for Research and Treatment of Cancer
Maurizio Brausi
  • Azienda Unità Sanitaria Locale Modena
Chris H Bangma
  • Erasmus MC
Theodorus Van der Kwast
  • University Health Network