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This email contains the latest news and developments in urology and is sent to you from North Bristol NHS Trust Library & Information Service. Library & Information Service Latest News Bulletin - Urology Contact your local NBT library for: All enquiries Help with Athens Inter-library loans Full-text copies of any of the articles below Literature searches Information skills training Current awareness bulletins Your NBT libraries: Frenchay 0117 340 6570 [email protected] Southmead 0117 323 5333 [email protected] Primary Care Library (South Plaza) 0117 984 1675 [email protected] For more information on accessing electronic journals please go to http://library.nhs.uk/booksandjournals/journals/default.aspx or contact your NBT Library. 3.0 T multiparametric prostate MRI using pelvic phased-array coil: Utility for tumor detection prior to biopsy 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Andrew B. Rosenkrantz , Thais C. Mussi , Michael S. Borofsky , Stephen S. Scionti , Michael Grasso , Samir S. Taneja Objective To evaluate the role of multiparametric magnetic resonance imaging (MRI) performed in men without a biopsy-proven diagnosis of prostate cancer using follow-up biopsy as the reference standard. Materials and methods Forty-two patients without biopsy-proven cancer and who underwent MRI were included. In all patients, MRI was performed at 3T using a pelvic phased-array coil and included T2weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. Thirteen had undergone no previous biopsy, and 29 had undergone at least 1 previous negative biopsy. All patients underwent prostate biopsy following MRI. Two fellowship-trained radiologists in consensus reviewed all cases and categorized each lobe as positive or negative for tumor. These interpretations were correlated with findings on post-MRI biopsy. Results Follow-up biopsy was positive in 23 lobes in 15 patients (36% of study cohort). On a per-patient basis, MRI had a sensitivity of 100%, specificity of 74%, positive predictive value (PPV) of 68%, and negative predictive value (NPV) of 100%. On a per-lobe basis, MRI had a sensitivity of 65%, specificity of 84%, PPV of 60%, and NPV of 86%. There was a nearly significant association between Gleason score and tumor detection on MRI (P = 0.072). Conclusions In our sample, MRI had 100% sensitivity in predicting the presence of tumor on subsequent biopsy on a per-patient basis, suggesting a possible role for MRI in selecting patients with an elevated prostatic specific antigen (PSA) to undergo prostate biopsy. However, MRI had weaker specificity for prediction of a subsequent positive biopsy, as well as weaker sensitivity for tumor on a per-lobe basis, indicating that in patients with a positive MRI result, tissue sampling remains necessary for confirmation of the diagnosis as well as for treatment planning. A Hybrid Radioactive and Fluorescent Tracer for Sentinel Node Biopsy in Penile Carcinoma as a Potential Replacement for Blue Dye 27 Nov 2013 04:55 am Indocyanine green-99mTc-nanocolloid allows for both preoperative sentinel node (SN) imaging and imageguided SN biopsy in penile carcinoma patients. This hybrid approach combines the beneficial properties of both modalities and improves optical SN identification compared with blue dye. Background:Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer indocyanine green (ICG)-99mTc-nanocolloid was developed to combine the beneficial properties of both radio guidance and fluorescence imaging.Objective:To explore the added value of SN biopsy using ICG-99mTc-nanocolloid in patients with penile carcinoma.Design, setting, and participants:Sixty-five patients with penile squamous cell carcinoma were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed tomography (SPECT/CT) after peritumoural injection of ICG-99mTc-nanocolloid. During surgery, SNs were initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A portable gamma camera was used to confirm excision of all SNs.Surgical procedure:Patients underwent SN biopsy of the cN0 groin and treatment of the primary tumour.Outcome measurements and statistical analysis:The number and location of preoperatively identified SNs were documented. Intraoperative SN identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye. Statistical evaluation was performed using a two-sample test for equality of proportions with continuity correction.Results and limitations:Preoperative imaging after injection of ICG-99mTc-nanocolloid enabled SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs identified by preoperative mapping were localised using combined radio-guided, fluorescence-guided, and blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was stained by blue dye (p A Multinational, Multi-institutional Study Comparing Positive Surgical Margin Rates Among 22393 Open, Laparoscopic, and Robot-assisted Radical Prostatectomy Patients 25 Nov 2013 04:45 am Background:Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume.Objective:To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates.Design, setting, and participants:Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011.Outcome measurements and statistical analyses:The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort.Results and limitations:Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload.Conclusions:This multinational, multiinstitutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases.Patient summary:In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.In this multi-institutional, multinational study, positive surgical margin rates appear lower after minimally invasive radical prostatectomy than with the open approach. Case volume is likely to affect margin rates for laparoscopic and robotic techniques. A Plea for Higher-quality Data for GreenLight Laser Technology in the Context of Surgical Benign Prostatic Obstruction Trials: The GOLIATH Study—Fact or Fiction in the Era of Evidence-based Urology? 03 Dec 2013 04:45 am A cross-sectional investigation of fatigue in advanced renal cell carcinoma treatment: Results from the FAMOUS study 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): P.J. Goebell , A. Münch , L. Müller , H.J. Hurtz , M. Koska , S. Busies , N. Marschner Objective With an increasing choice of new treatment options, the management of side effects to maintain a chosen treatment if likely to be effective on the tumor remains important. The perception of side effects however varies between the physician and the patient, leading to possible wrong assumptions on tolerability that result in dose modifications, which may ultimately affect effectiveness. The aim was to assess fatigue in patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the physician to the one provided by their respective patient. In addition, we aimed to assess possible influences of fatigue on parameters of quality of life. Methods Patients receiving systemic treatment for advanced RCC and their physicians were questioned independently regarding incidence and severity of fatigue and its effect on quality of life. Results Both physicians and patients completed 98 matching questionnaires. Patients were treated with sunitinib, sorafenib, bevacizumab combined with interferon alpha, temsirolimus, everolimus, or interferon alpha alone. Incidence and severity of fatigue was differently assessed by patients and physicians, with fatigue being more severe when reported by the patient. The severity of fatigue increased with progressing treatment lines. Quality of life was significantly lower in patients experiencing fatigue compared with patients without fatigue. Emotional, functional, and physical well-being were all affected by fatigue, the latter being the most affected subscale. Social well-being was least affected. Conclusion Fatigue is a complex and cumulative condition of patients treated for advanced RCC, and it considerably affects patient's quality of life. As many of its underlying causes may be treated, the divergent perception of occurrence and severity of fatigue should be integrated in treatment concepts. The active role of the patient in helping to manage ailments through assessment should be implemented when optimizing treatment of RCC. Activated 5′flanking region of NANOGP8 in a self-renewal environment is associated with increased sphere formation and tumor growth of prostate cancer cells 07 Dec 2013 06:33 am INTRODUCTION NANOGP8 is a retrogene which encodes a full-length protein similar to the NANOG1 gene. The expression of NANOGP8 has been documented in several cancers and is related to cell proliferation and tumor development. However, the regulation of NANOGP8 expression has not been investigated. Therefore, the role of NANOGP8 in cell proliferation has not been completely understood. METHODS We evaluate the expression of NANOG1 and NANOGP8 in prostate cancer cell lines and primary cultures of prostate tissues. We investigate clonogenicity, sphere formation, and xenograft tumor growth of prostate cancer cells with an activated 5′flanking region of NANOGP8. We examine the role of NANOGP8 in cell cycle progression. RESULTS In the prostate cells the NANOG RNA was transcribed from NANOGP8 and not from NANOG1. Cells with the activated 5′flanking region of NANOGP8 exhibited enhanced clonogenicity, sphere formation, and xenograft tumor growth. The sphere culture and tumor initiation mouse mode promoted the activation of the 5′flanking region of NANOGP8. Forced expression of NANOGP8 increased the entry into the cell cycle. DISCUSSION In prostate cells NANOGP8 is a predominant molecule of NANOG. The activation of 5′flanking sequence of NANOGP8 could play a role in the regulation of the stem-like properties of cancer stem cells and prostate tumor initiation and development. The microenvironment favoring cancer stem cells could promote the activation of the 5′flanking region of NANOGP8. © 2013 Wiley Periodicals, Inc. Androgen Deprivation Therapy and Cardiovascular Harm: Are All Men Created Equal? 21 Nov 2013 05:05 am Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations 28 Nov 2013 04:35 am Context:The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size.Objective:To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective.Evidence acquisition:Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented.Evidence synthesis:A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods—based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure—and functional techniques including dynamic contrast-enhanced (DCE) CT, DCEmagnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies.Conclusions:Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques.Available evidence supports the use of functional imaging techniques to predict response to targeted therapy in renal cell carcinoma. Following further validation and standardisation, these techniques will ultimately allow tailoring of treatment to patients who are most likely to benefit from therapy. Beyond the androgen receptor: New approaches to treating metastatic prostate cancer. Report of the 2013 Prouts Neck Prostate Cancer Meeting 19 Nov 2013 06:24 am INTRODUCTION The Prouts Neck Meetings on Prostate Cancer began in 1985 through the efforts of the Organ Systems Branch of the National Cancer Institute to stimulate new research and focused around specific questions in prostate tumorigenesis and therapy. METHODS These meetings were think tanks, composed of around 75 individuals, and divided equally between young investigators and senior investigators. Over the years, many new concepts related to prostate cancer resulted from these meetings and the prostate cancer community has sorely missed them since the last one in 2007. RESULTS We report here the first of a new series of meetings. The 2013 meeting focused on defining how the field of treatment for metastatic prostate cancer needs to evolve to impact survival and was entitled: “Beyond AR: New Approaches to Treating Metastatic Prostate Cancer.” As castrate resistant prostate cancers escape second generation anti-androgen agents, three phenotypes/genotypes of CRPC appear to be increasing in prevalence and remain resistant to treatment: NeuroEndocrine Prostate Cancer, Persistent AR—Dependent Prostate Cancer, and Androgen Receptor Pathway Independent Prostate Cancer. DISCUSSION It is clear that new treatment paradigms need to be developed for this diverse group of diseases. The Prouts Neck 2013 Meeting on Prostate Cancer helped to frame the current state of the field and jumpstart ideas for new avenues of treatment. Prostate © 2013 Wiley Periodicals, Inc. Biomarkers of renal cell carcinoma 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Tin C. Ngo , Christopher G. Wood , Jose A. Karam The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease. Boldine induces cell cycle arrest and apoptosis in T24 human bladder cancer cell line via regulation of ERK, AKT, and GSK-3β 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Daniéli Gerhardt , Gabriela Bertola , Fabrícia Dietrich , Fabrício Figueiró , Alfeu Zanotto-Filho , José Cláudio Moreira Fonseca , Fernanda Bueno Morrone , Carlos Henrique Barrios , Ana Maria O. Battastini , Christianne G. Salbego Objective Bladder cancer is one of the most prevalent genitourinary malignancies. Despite active chemotherapy regimens, patients with bladder cancer suffer from a high rate of tumor recurrence. Thus, new approaches and agents to improve quality of life and survival still need to be developed. The objective of the present study was to evaluate the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on bladder cancer proliferation and cell death. Methods Sulforhodamine B assay, Tetrazolium reduction assay, Flow Cytometry Analysis, Ecto-5’-nucleotidase activity and Western blot assay were performed. Results The results showed that boldine was able to reduce cell viability and cell proliferation in T24 cells. In addition, boldine arrests the cell cycle at G2/M-phase and cause cell death by apoptosis. Boldine-induced inhibition of cell growth and cell cycle arrest appears to be linked to inactivation of extracellular signal–regulated kinase protein (ERK). Additionally, the efficacy of boldine in apoptosis-induced in T24 cells is correlated with modulation of AKT (inactivation) and glycogen synthase kinase-3β (GSK-3β) (activation) proteins. Conclusions The present findings may, in part, explain the therapeutic effects of boldine for treatment of urinary bladder cancer. Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Alexandr Poprach , Tomas Pavlik , Bohuslav Melichar , Katerina Kubackova , Zbynek Bortlicek , Marek Svoboda , Radek Lakomy , Rostislav Vyzula , Igor Kiss , Ladislav Dusek , Tomas Buchler Objectives The aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy. Materials and methods A national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib ( n = 181) or sorafenib ( n = 138) after progression on cytokine therapy were analyzed. Results Prognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients. Conclusion We demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible. Clinical prognostic factors associated with outcome in patients with renal cell cancer with prior tyrosine kinase inhibitors or immunotherapy treated with everolimus 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Robert J. Amato , Amber Flaherty , Yufeng Zhang , Fangqian Ouyang , Virginia Mohlere Background The mTOR inhibitor, everolimus, is approved for the treatment of metastatic renal cell carcinoma (RCC). However, prognostic models are needed to determine the patients who would most benefit from this therapy. We have developed a model based on clinical parameters and patient stratification into risk groups to predict patients with RCC who will derive the most benefit from treatment with everolimus. Methods We assessed retrospective data on 57 patients with RCC who received everolimus after previous treatment with immunotherapy or tyrosine kinase inhibitors to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). In the original phase II study, patients received 10 mg of everolimus daily without interruption and were assessed every other week for the first 8 weeks on therapy and every 4 weeks thereafter. Kaplan-Meier analysis was used to calculate OS and PFS. Univariate and multivariate analyses were constructed using the Cox proportional hazards model and a stepwise procedure to validate the data. Results We grouped patients according to risk: 0 prognostic factors indicated favorable risk, 1 to 2 factors intermediate risk, and≥3 factors poor risk. We found notable differences in median OS (29.6 mo for favorable risk, 14.3 mo for intermediate risk, and 7.2 mo for poor risk). Three risk factors (prior radiation treatment, no lung metastasis present at the start of treatment, and lymphocytes<25 cells/µl) in the multivariate analysis were found to be associated with PFS, and 4 risk factors were found to be associated with OS (bone metastasis at start of treatment, LDH>1.5×upper limit of normal, alkaline phosphatase>120 U/l, and lymphocytes<25 cells/µl). Conclusions Our prognostic model includes 3 readily available clinical parameters for PFS and 4 readily available clinical parameters for OS to help stratify patients into poor, intermediate, and favorable prognosis groups for the treatment of everolimus in clear cell RCC. These intriguing results warrant further study in a larger patient population to validate the findings. Cognitive problems in patients on androgen deprivation therapy: A qualitative pilot study 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Lisa M. Wu , Michael A. Diefenbach , Wayne A. Gordon , Joshua B. Cantor , Monique M. Cherrier Objectives Androgen deprivation therapy (ADT; also known as hormone therapy) is a well-established treatment for prostate cancer patients with rising prostate-specific antigen levels after localized treatment, and for those with metastatic disease. The neurological impact of ADT has been likened to that of aging and is therefore theorized to impair cognitive functioning in prostate cancer patients. We briefly summarize the research that has examined cognitive functioning of ADT patients primarily through neuropsychological assessment. A qualitative pilot study is presented with the aim of describing ADT patients' experiences of cognitive changes since starting ADT. Materials and methods Semistructured telephone interviews were undertaken with 11 community-dwelling prostate cancer patients undergoing ADT following definitive localized treatment. Participants were recruited via online prostate cancer support forums. Content analyses were conducted to establish relevant themes, which in this case were the cognitive domains of impairment. Results Eight of the 11 participants reported impairments in the domains of concentration, information processing, verbal fluency, visual information processing/visuospatial function, memory, and executive dysfunction. Neurobehavioral problems, including neurofatigue and apathy were also reported. Conclusions The interviews illustrate the potential negative effects of ADT on cognitive and neurobehavioral functions, and their impact on patients' work and in their daily lives. We describe how the field of cognitive rehabilitation offers promising tools to assist ADT patients with cognitive problems. Comparative Efficacy and Safety of Medical Treatments for the Management of Overactive Bladder: A Systematic Literature Review and Mixed Treatment Comparison 19 Nov 2013 04:45 am mg has efficacy similar to most antimuscarinics and is associated with a significantly lower probability of dry mouth. mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.Based on this systematic literature review and mixed treatment comparison, mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics.Conclusions:Mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg that was more efficacious than mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg versus antimuscarinics in patients with OAB.Evidence acquisition:A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision).Evidence synthesis:Overall, 44 RCTs involving 27 309 patients were included. The MTCs showed that mirabegron 50 Context:Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms.Objective:To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 Comparison of prostate volume measured by transrectal ultrasound and magnetic resonance imaging: Is transrectal ultrasound suitable to determine which patients should undergo active surveillance? 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Brian E. Weiss , Alan J. Wein , S. Bruce Malkowicz , Thomas J. Guzzo Objectives To compare prostate volume obtained by transrectal ultrasound (TRUS) and endorectal MRI (eMRI) to assess the reliability of TRUS in determining prostate-specific antigen (PSA) density. Materials and methods Data for 2,410 patients diagnosed with localized prostate cancer (CaP) and treated with radical retropubic prostatectomy (RRP) at the University of Pennsylvania Health System between 1991 and 2005 was reviewed. Of these patients, 756 had both a preoperative TRUS and eMRI of the prostate performed. Prostate size was estimated using the prolate ellipsoid formula (height × width × length × π/6); maximal height or antero-posterior (A-P) diameter was determined using a midsagittal view for TRUS and an axial view for eMRI. Pearson's correlation, linear regression, and paired t- test were performed to compare prostate volumes estimated via both imaging modalities. Results Average prostate size measured with TRUS and eMRI correlated significantly with one another ( R = 0.801; P < 0.0001), demonstrating a strong linear relationship (y = 0.891x + 2.622, R 2 = 0.642). Comparison of PSA density also demonstrated a strong linear relationship (y = 0.811x + 0.053, R 2 = 0.765). Average prostate volume differed by 1.7 ml (TRUS relative to eMRI), which was statistically significant based on a paired t -test ( P < 0.001). Upon stratification of patients into three groups based on average TRUS volume (≤30, >30–60, and >60 ml), significant correlation (0.318, 0.564, 0.650) and difference between volumes (−2.1, 4.0, 5.1 ml; P < 0.0001, P < 0.0001, P < 0.05 TRUS relative to eMRI) was maintained. Conclusions Prostate volume estimations with TRUS and eMRI are highly correlated. It is therefore, reasonable to conclude that in the hands of an experienced sonographer, TRUS is not only an efficient and economical examination, but also an accurate and reproducible modality to estimate prostate size. Contents 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Cutting for stone in augmented bladders: What is the risk of recurrence and is it impacted by treatment modality? - Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Introduction: Bladder stones are common after bladder augmentation, often resulting in numerous procedures for recurrence. We sought to determine whether surgical technique and stone fragmentation were significant predictors of bladder stone recurrence after augmentation. Materials and Methods: We conducted a retrospective review of 107 patients treated for first bladder stones at our institution. Patient demographics, details of surgeries, stone therapy and recurrence were reviewed. Kaplan-Meier survival and Cox proportional hazards analysis were used to determine predictors of time to first stone recurrence. Results: Of 107 patients, 55.1% were female and 79.4% had neuropathic bladder. Patients were augmented at a median 8.0 years old (range 2.4-22.8) and followed for a median 12.4 years (range 1.8-34). Segments used for augmentation included ileum (72.9%), sigmoid (16.8%), cecum/ileocecum (9.4%) and other (ureter, stomach/ileum) (1.8%). Bladder neck procedures were performed in 63.6%, catheterizable channels in 75.7%. First stone surgery occurred at a median 3.1 years post-augmentation (range 5 months21.8 years). Endoscopy was used in 66.4%, open cystolithotomy in 33.6%. Overall, 47.7% were fragmented. Bladder stones recurred in 47.7% patients (median recurrence time 9.5 years, range 3 months14.7 years). Recurrence risk was highest in the first 2 years (12.1% per patient per year, p=0.03). Recurrence risk did not change with technique (endoscopic vs. open) or fragmentation, even after controlling for surgical and clinical variables. Conclusions: Bladder stones recurred in almost half of patients at 9 years independent of treatment technique and patient characteristics. As a high-risk group, annual KUB films and RBUS are recommended. Defining prostate cancer risk before prostate biopsy 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Raj P. Pal , Neil U. Maitra , J. Kilian Mellon , Masood A. Khan Prostate cancer is the most commonly diagnosed cancer in men. At present, patients are selected for prostate biopsy on the basis of age, serum prostate specific antigen (PSA), and prostatic digital rectal examination (DRE) findings. However, due to limitations in the use of PSA and DRE, many patients undergo unnecessary prostate biopsy. A further problem arises as many patients are diagnosed and treated for indolent disease. This review of the literature highlights the strengths and weaknesses of existing methods of prebiopsy risk stratification and evaluates promising serum, urine, and radiologic prostate cancer biomarkers, which may improve risk stratification for prostate biopsy in the future. Differences in prostate cancer grade, stage, and location in radical prostatectomy specimens from United States and Japan 20 Nov 2013 01:10 pm BACKGROUND To compared prostate cancer at radical prostatectomy between men in the United States (US) and Japan in the modern era. METHODS Three hundred seventy consecutive totally embedded RP cases (159 US; 211 Japan) from 2010 to 2012 were reviewed. RESULTS US men were significantly younger (mean age 58.8 years) than Japanese men (mean age 64.6 years; P < 0.00001). Japanese patients presented with higher PSA levels (mean = 10.9 ng/ml) compared to US patients (mean = 5.8 ng/ml, P < 0.00001) and higher clinical stage (P = 0.003). Japanese tumors were: higher grade; larger; more advanced stage; with increased lymphovascular invasion; and more commonly TZ in location (P < 0.00001). In multivariate analysis, independent predictors of high tumor volume were PSA level, clinical stage, TZ location, Gleason grade, and country of origin (Japan). Independent predictors of TZ location were clinical stage, tumor volume, and country of origin (Japan). CONCLUSION A major factor for larger, higher grade and stage tumors in Japanese patients is the lower prevalence of screening for prostate cancer in Japan. Another contributing factor may be their TZ location, where they are not palpable until advanced and where they are difficult to sample on needle biopsy possibly leading to a delay in diagnosis. The finding of a difference in zonality of prostate cancer between US and Japanese cases is novel and may reflect differences in biology rather than different health care practice between the groups. If this data is confirmed, consideration should be given to TZ sampling as part of routine needle biopsies in Japanese men. Prostate © 2013 Wiley Periodicals, Inc. Do Erectile Dysfunction and Cardiovascular Disease Have the Same Mechanism? 20 Nov 2013 04:45 am Does genotyping of risk-associated single nucleotide polymorphisms improve patient selection for prostate biopsy when combined with a prostate cancer risk calculator? 22 Nov 2013 05:32 am BACKGROUND Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with higher risk of prostate cancer (PCa). This study aimed to evaluate whether published SNPs improve the performance of a clinical risk-calculator in predicting prostate biopsy result. METHODS Three hundred forty-six patients with a previous prostate biopsy (191 positive, 155 negative) were enrolled. After literature search, nine SNPs were selected for their statistically significant association with increased PCa risk. Allelic odds ratios were computed and a new logistic regression model was built integrating the clinical risk score (i.e., prior biopsy results, PSA level, prostate volume, transrectal ultrasound, and digital rectal examination) and a multilocus genetic risk score (MGRS). Areas under the receiver operating characteristic (ROC) curves (AUC) of the clinical score alone versus the integrated clinic-genetic model were compared. The added value of the MGRS was assessed using the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) statistics. RESULTS Predictive performance of the integrated clinico-genetic model (AUC = 0.781) was slightly higher than predictive performance of the clinical score alone (AUC = 0.770). The prediction of PCa was significantly improved with an IDI of 0.015 (P-value = 0.035) and a continuous NRI of 0.403 (P-value < 0.001). CONCLUSIONS The predictive performance of the clinical model was only slightly improved by adding MGRS questioning the real clinical added value with regards to the cost of genetic testing and performance of current inexpensive clinical risk-calculators. Prostate © 2013 Wiley Periodicals, Inc. Dual inhibition by S6K1 and Elf4E is essential for controlling cellular growth and invasion in bladder cancer☆,☆☆?> 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Jong Kyou Kwon , Soon-Ja Kim , Jung Hoon Kim , Kyung Mee Lee , In Ho Chang Purpose We investigated how dual inhibition of the molecular mechanism of mammalian target of rapamycin (mTOR) downstream of S6K1 and the eukaryotic initiation factor 4E (eIF4E) can lead to suppression of proliferation and progression of urothelial carcinoma. Materials and methods We characterized the molecular mechanism of the mTOR pathway in the T24 and 5637 urothelial carcinoma cell lines by interfering with different molecular components using rapamycin and short interfering (siRNA) technology (S6K1 or elF4E) and analyzed the effects on molecular activation status, cell growth, proliferation, and invasion. Results A high concentration of rapamycin (10 μM) blocked both S6K1 and elF4E phosphorylation and inhibited cell proliferation in T24 and 5637 cells. The inhibition of both S6K1 and elF4E phosphorylation by rapamycin reduced cell viability and proliferation more than transfection of siRNA against S6K1 or elF4E in 5637 and T24 cells. Cells silenced for S6K1 or elF4E expression exhibited significantly reduced cell migration and invasion compared with those of the control but inhibition of both S6K1 and elF4E phosphorylation by rapamycin reduced cell migration and invasion more than siRNA transfection against S6K1 or elF4E in 5637 and T24 cells. Conclusion These findings suggest that both the mTOR pathway downstream of eukaryotic initiation factor 4E and S6K1 can be successfully inhibited, therefore, the recurrence of bladder cancer can be prevented by high-dose rapamycin only, suggesting that 4E-BP1 might be still under mTORC1. Editorial Board 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Editorial Comment - Uncorrected Proof 06 Dec 2013 12:00 am The authors reviewed the risk factors associated with symptomatic VTE in a large population of patients who underwent RP plus pelvic lymph node dissection at a single institution during 23 years. They identified several factors associated with VTE on multivariate analysis, of which many were previously identified in other series. However, the association between VTE and nonO blood type (OR 1.87) is a novel and interesting finding that has not been previously studied in the RP population. Furthermore, a similar association between nonO blood type and VTE of similar magnitude (HR 1.85) was recently reported in the radical cystectomy population. The authors suggest that increased vWF in men with nonO blood type may increase the risk of thrombosis. Although studies have not shown benefit to routine heparin prophylaxis al after RP plus pelvic lymph node dissection (reference 24 in article), high risk populations such as men with nonO blood type may warrant special consideration. Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: A critical analysis of 1,994 patients 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Anirban P. Mitra , Eila C. Skinner , Anne K. Schuckman , David I. Quinn , Tanya B. Dorff , Siamak Daneshmand Objective The oncological basis behind the observation that females experience worse outcomes following radical cystectomy for urothelial carcinoma of the bladder (UCB) is unclear. This study was aimed at examining the sole effect of gender on postcystectomy UCB outcomes and identifying potential factors that may explain the poor prognosis in females using a balanced case-control approach. Materials and methods A review of 2,567 patients with UCB who underwent radical cystectomy identified 414 females (“cases”) who were matched 1:1 for demographic, tumor, and treatment characteristics with 414 male counterparts (“controls”). Cases were also compared with an independent male UCB cohort ( n = 1,166). Differences between females vs. matched control and independent male patients with UCB were analyzed. Recurrencefree survival, cancer-specific survival, and overall survival were compared by univariable and multivariable Cox regression models. Results Median follow-up for cases, controls, and independent control cohort was 12.2, 8.6, and 13.5 years, respectively. Females were matched to male controls for tumor and nodal stages ( P = 1.00), lymphovascular invasion and surgical margin status, age, prior intravesical treatment, and neoadjuvant and adjuvant chemotherapy administration ( P = 0.61–1.00). Cases were also balanced with controls for grade, p53 status, nodal yield, American Society of Anesthesiologists score, presence of hydronephrosis, and times to diagnosis and cystectomy ( P ≥0.14). When thus matched, outcomes between females and males were not different ( P ≥0.34). However, when compared with an independent unmatched male control cohort, females had significantly poorer outcomes ( P ≤0.006). In this comparison, females presented with higher tumor ( P <0.001) and nodal ( P = 0.049) stages and a lesser proportion received precystectomy intravesical therapy ( P = 0.032). Conclusions Females have similar UCB outcomes to males when matched for demographic, clinicopathologic, and management characteristics. However, they present with more advanced tumors, thus explaining the observation of poor outcomes. Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer 22 Nov 2013 04:45 am 0.406). There were no significant between-group differences in any erectile function subscale (p = min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow–mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p 25 per group) after RP. AT consisted of five walking sessions per week at 55–100% of peak oxygen uptake (VO2peak) for 30–60 = Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs . In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP.Trial registration:Clinicaltrials.gov identifier NCT00620932.This proof-of-concept trial demonstrated that aerobic training following a novel nonlinear prescription approach incorporating highintensity training is safe and feasible and improves cardiovascular function but not erectile dysfunction in men with localized prostate cancer in the acute period following radical prostatectomy. Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castrationresistant prostate cancer: Implications for prior therapy in clinical trials 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Gregory R. Pond , Andrew J. Armstrong , Matthew D. Galsky , Brian A. Wood , Lance Leopold , Guru Sonpavde Objectives Abiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients. Materials and methods A randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2 inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR), pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox proportional hazards regression models were used to estimate the effect of covariates on OS. Results Of 220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP-based therapy of KC-naive patients (18.3 months, 95% CI: 15.0, 24.5) and post-KC patients (17.0 months, 95% CI: 9.9, 20.4) was not statistically different ( P = 0.20). After controlling for prognostic classifications, analyses demonstrated consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33–1.46. Similar unfavorable trends were observed for ORR, PSA declines, and PFS. Conclusions In this hypothesis-generating analysis, patients treated with docetaxel-based chemotherapy following prior KC had numerically and consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of novel and emerging agents following AA, is of clinical importance, given its more potent androgen synthesis inhibition compared with KC. Drug development should take into account the potential impact of previous therapy. Epidemiological Studies Are Important to Trigger Health Care Decisions 29 Nov 2013 04:35 am Essential elements of personalized medicine 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Wylie Burke , Susan Brown Trinidad , Nancy A. Press Objectives Genomic information has been promoted as the basis for “personalized” health care. We considered the benefits provided by genomic testing in context of the concept of personalized medicine. Materials and Methods We evaluated current and potential uses of genomic testing in health care, using prostate cancer as an example, and considered their implications for individualizing or otherwise improving health care. Results and Conclusions Personalized medicine is most accurately seen as a comprehensive effort to tailor health care to the individual, spanning multiple dimensions. While genomic tests will offer many potential opportunities to improve the delivery of care, including the potential for genomic research to offer opportunities to improve prostate cancer screening and treatment, such advances do not in themselves constitute a paradigm shift in the delivery of health care. Rather, personalized medicine is based on a partnership between clinician and patient that utilizes shared decision making to determine the best health care options among the available choices, weighing the patient’s personal values and preferences together with clinical findings. This approach is particularly important for difficult clinical decisions involving uncertainty and trade-offs, such as those involved in prostate cancer screening and management. The delivery of personalized medicine also requires adequate health care access and assurance that basic health needs have been met. Substantial research investment will be needed to identify how genomic tests can contribute to this effort. European Association of Urology Guidelines on Priapism 16 Nov 2013 05:25 am Context:Priapism is defined as a penile erection that persists beyond or is unrelated to sexual interest or stimulation. It can be classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent or intermittent).Objective:To provide guidelines on the diagnosis and treatment of priapism.Evidence acquisition:Systematic literature search on the epidemiology, diagnosis, and treatment of priapism. Articles h unrelated to sexual stimulation. It is more common in patients with sickle cell disease. This article represents the shortened EAU priapism guidelines, based on a systematic literature review. Cases of priapism are classified into ischaemic (low flow), arterial (high flow), or stuttering (recurrent). Treatment for ischaemic priapism must be prompt in order to avoid the risk of permanent erectile dysfunction. This is not the case for arterial priapism.This paper summarises the first publication of the European Association of Urology guidelines on priapism. The guidelines aim to present the most recent scientific information and provide recommendations on diagnosis and treatment of the three forms of priapism: ischaemic, arterial, and stuttering. h, including decompression of the corpora cavernosa by aspiration and intracavernous injection of sympathomimetic drugs (e.g. phenylephrine). Surgical treatment is recommended for failed conservative management, although the best procedure is unclear. Immediate implantation of a prosthesis should be considered for long-lasting priapism. Arterial priapism is not an emergency. Selective embolization is the suggested treatment modality and has high success rates. Stuttering priapism is poorly understood and the main therapeutic goal is the prevention of future episodes. This may be achieved pharmacologically, but data on efficacy are limited.Conclusions:These guidelines summarise current information on priapism. The extended version are available on the European Association of Urology Website (www.uroweb.org/guidelines/).Patient summary:Priapism is a persistent, often painful, penile erection lasting more than 4 with highest evidence available were selected to form the basis of these recommendations.Evidence synthesis:Ischaemic priapism is usually idiopathic and the most common form. Arterial priapism usually occurs after blunt perineal trauma. History is the mainstay of diagnosis and helps determine the pathogenesis. Laboratory testing is used to support clinical findings. Ischaemic priapism is an emergency condition. Intervention should start within 4–6 Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression 06 Dec 2013 12:54 am INTRODUCTION Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. METHODS In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. RESULTS Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13–2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01–2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. DISCUSSION Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. Prostate © 2013 Wiley Periodicals, Inc. Exercise as Treatment for Androgen Deprivation Therapy–Associated Physical Dysfunction: Ready for Prime Time? 30 Nov 2013 04:45 am Expression of molecular markers associated with the mammalian target of rapamycin pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following radical nephrectomy 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Masatomo Nishikawa , Hideaki Miyake , Ken-ichi Harada , Masato Fujisawa Objectives To evaluate the expression of multiple molecular markers involved in mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic significance of these markers following radical nephrectomy. Material and methods The expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic RCC by immunohistochemical staining. Results During the follow-up period of this series (median, 63.5 mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the Creactive protein level, pathological stage, and microvascular invasion, were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level, and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor (46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). Conclusions The combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC. Fluorescence-enhanced Robotic Radical Prostatectomy Using Real-time Lymphangiography and Tissue Marking with Percutaneous Injection of Unconjugated Indocyanine Green: The Initial Clinical Experience in 50 Patients 21 Nov 2013 05:05 am min postinjection and had 100% sensitivity, 75.4% specificity, 14.6% positive predictive value, and 100% negative predictive value for the detection of nodal metastasis.Conclusions:FERRP is safe, feasible, and allows for reliable prostate tissue marking and identification of sentinel lymphatic drainage in the majority of patients. ICG sentinel nodes are highly sensitive but relatively nonspecific for the detection of nodal metastasis.Percutaneous, robotic-guided injection of unconjugated indocyanine green is a simple and reproducible means of performing pelvic lymphangiography. The real-time technique is highly sensitive and avoids ionizing radiation or the need for adjunctive procedures. min postinjection. Sentinel nodes were identified in 76% of patients at a mean time of 30 mg/ml ICG solution were injected into each lobe of the prostate using a robotically guided percutaneous needle. After ICG was allowed to travel through the pelvic lymphatics, lymphadenectomy was performed from the endopelvic fascia to the aortic bifurcation.Outcome measurements and statistical analysis:Parameters describing the time course of tissue fluorescence and pelvic lymphangiography were systematically recorded. Lymphatic packets containing fluorescent nodes were considered sentinel.Results and limitations:Percutaneous, robotic-guided ICG injection proved superior to cystoscope or transrectal delivery. Tissue marking was achieved in all patients, positively identifying the prostate with uniform fluorescence relative to the obturator nerve, seminal vesicles, vas deferens, and neurovascular pedicles at a mean time of 10 ml of a 2.5 Background:Pilot studies have demonstrated the utility of indocyanine green (ICG) sentinel lymphadenectomy for prostate cancer. Prior work has used ICG with radiocontrast agents injected at a separate procedure and relied on assistantcontrolled fluorescence systems, making the technique costly and cumbersome.Objective:To describe the initial optimization and feasibility of fluorescence-enhanced robotic radical prostatectomy (FERRP) using real-time injection of ICG for tissue marking and identification of sentinel lymphatic drainage visualized by a fully integrated surgeon-controlled system.Design, setting, and participants:Patients with clinically localized prostate cancer at a tertiary referral center were offered FERRP. Ten patients participated in a pilot arm in which ICG dosing and injection technique were optimized. Fifty consecutive patients then underwent FERRP.Surgical procedure:After development of the space of Retzius, 0.4 Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients 05 Dec 2013 04:45 am 0.05).Conclusions:We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.We found female gender to be associated with a higher risk of cancer-specific mortality following radical cystectomy. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or lymphovascular invasion. 0.033) and had higher rates of pathologic stage T3/T4 disease (p = Background:The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.Objective:To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).Design, setting, and participants:Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.Outcome measurements and statistical analysis:Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancerspecific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).Results and limitations:Female patients were older at the time of RC (p Genetic analysis of the principal genes related to prostate cancer: A review 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Maria Jesus Alvarez-Cubero , Maria Saiz , Luis Javier Martinez-Gonzalez , Juan Carlos Alvarez , Jose Antonio Lorente , Jose Manuel Cozar Prostate cancer is one of the most common leading causes of cancer death in men. Attributable to many genetic linkage and genome-wide association studies (GWAS) around the world, several high-penetrance genetic variants have been identified. Many polymorphisms in genes, such as ELAC2 (locus HPC2), RNase L (locus hereditary prostate cancer 1 gene [HPC1]), and MSR1 have been recognized as important genetic factors that confer an increased risk of developing prostate cancer in many populations. A review of the literature was then performed analyzing the roles of these and other genes in prostate cancer. Our main challenge is optimizing the role of these genes in prostate cancer development, even trying to use these genes as general biomarkers. The principal aim of this review is to determine the most important variants in the principal genes related to prostate cancer and examine the differences among populations. The concept of individualized or personalized targeted cancer therapy has gained significant attention throughout oncology. In prostate cancer, the creation of a personalized panel of single-nucleotide polymorphisms (SNP) biomarkers may be important for the early and accurate detection of this cancer. As a result, the need for a good biomarker is required to detect prostate cancer earlier and to provide tools to follow patients during the early stages of the cancer. At present, prostate cancer continues to have an unclear etiology, which is a combination of genetic and numerous environmental factors. Among genetic factors, no variants of the RNase L, ELAC2, or MSR1 genes have been detected with similar expression patterns in different populations all around the world. Geographical and Temporal Trends in Bladder Cancer Occurrence: So What? 03 Dec 2013 04:45 am Health-related quality of life for men with prostate cancer—an evaluation of outcomes 12– 24 months after treatment 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Stephen A. Brassell , Sally I. Elsamanoudi , Jennifer Cullen , Molly E. Williams , David G. McLeod Objective To determine the health-related quality of life (HRQoL) impact of prostate cancer interventions at 2 years post-treatment, and between the 12- and 24-month interval, to better characterize this measure. Materials and methods Patients treated at the Center for Prostate Disease Research between June 2003 and February 2010 were offered enrollment into a HRQoL study that entailed a baseline evaluation before prostate biopsy and at 3, 6, 9, 12, 18, 24, and 30 months thereafter. The instruments used were the Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short-Form 36 (SF-36). A Student's t- test and ANOVA were used to examine the association between HRQoL scores, patient demographic, and disease features. Multivariable regression models were used to analyze change over time. Estimates of risk, corresponding confidence intervals, and P values are presented for these longitudinal findings. Results The study group was comprised of 595 patients. African Americans (AA) had slightly lower baseline raw scores in all EPIC and SF-36 HRQoL domains, but on bivariate analysis, there was no statistical difference in change of scores over time. Radical prostatectomy (RP) led to the greatest decline in urinary function. Bowel function significantly worsened with the addition of hormone therapy (HT) to external beam radiation therapy (EBRT). Sexual bother and function had a marked decline in all active treatment options. Despite these changes, there were no differences in overall satisfaction. SF-36 domains were not affected by RP, whereas EBRT and EBRT + HT had universal impact. For the 12- to 24-month interval, specifically, patients who underwent EBRT fared worse over this time period, showing continued worsening of urinary bother, hormonal function, physical role, physical component summary, and overall satisfaction. Patients who underwent RP did not show any further decline in the 12- to 24-month interval, but instead showed improvement. Conclusions Because of the protracted nature of recovery after surgery, delayed onset of effects from radiation, potential interval decline secondary to age-related symptoms, and longevity of patients with prostate cancer, determination of long-term HRQoL outcomes is integral. Counseling with regard to these outcomes should be balanced with oncologic expectations from treatment. Implications for human papillomavirus in penile cancer 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Amber Flaherty , Timothy Kim , Anna Giuliano , Anthony Magliocco , Tariq S. Hakky , Lance C. Pagliaro , Philippe E. Spiess Human papillomavirus infection (HPV) has been implicated in penile cancer, and although the annual incidence is estimated to be 1,570 in the United States, there are areas of the world in which the incidence is as much as 20-fold higher. Ample data in the literature support testing and vaccination against HPVrelated cervical cancer, but for men and penile cancer, these data are lacking. However, some preliminary data would suggest that HPV not only plays an important role in a significant subset of patients with penile cancer but also may be a target for penile cancer prevention as well via initiation of a vaccination program in high-risk male populations. Improving Outcome of Surgical Procedures Is Not Possible Without Adequate Quality Measurement 08 Dec 2013 05:05 am Outcome measurement allows for acknowledging differences in quality and must be used as a basis for quality assessment, regardless of what procedure is to be assessed and improved. As urologists, we should actively take the lead to guide this necessary and inevitable process. In-hospital death and hospital-acquired complications among patients undergoing partial cystectomy for bladder cancer in the United States 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Max Kates , Michael A. Gorin , Christopher M. Deibert , Phillip M. Pierorazio , Mark P. Schoenberg , James M. McKiernan , Trinity J. Bivalacqua Background Partial cystectomy (PC) is a therapeutic option for select patients with bladder cancer, but its associated perioperative risks and costs are unknown. We estimated annual rates of PC in a nationally representative sample of hospitals, and analyzed whether hospital volume affects postoperative outcomes and costs in patients undergoing PC. Methods From the Nationwide Inpatient Sample, we selected a weighted cohort of patients with bladder cancer who underwent PC between 2002 and 2008. Differences in length of stay, charges, and clinical outcomes were calculated based on operative volume, and univariate and multivariate regression models were fitted to predict in-hospital mortality (IHM) and hospital-acquired conditions. Results A total of 10,780 patients with bladder cancer who underwent PC were identified with an annual rate between 1457 and 1628 cases. IHM rates were 1.8%, constituting 195 patients (between 9 and 46 annually). A total of 417 patients (3.9%) experienced a “never event” complication, which Medicare no longer reimburses. The mean annual hospital volume of patients who died was 1.7 cases/y compared with 2.4 cases/y among those without fatal complications. No cases of IHM were identified among hospitals performing at least 5 partial cystectomies/y. In a multivariate regression model increased hospital volume was independently associated with decreased mortality (odds ratio = 0.70, 95% confidence interval; 0.60– 0.80). Conclusions Approximately 1 in 25 patients undergoing PC experience a hospital-acquired complication, and nearly 1 in 50 die as a result of the operation. For each additional case a hospital performs annually, the risk of IHM decreases by 30%. Indications for and anatomical extent of pelvic lymph node dissection for prostate cancer: Practice patterns of uro-oncologists in North America 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Karim A. Touijer , Youness Ahallal , Bertrand D. Guillonneau Purpose To investigate the prevailing practice of uro-oncologists regarding the indications for and extent of pelvic lymph node dissection (PLND) for prostate cancer. Materials and methods A 9-question survey was sent as a hyperlink by electronic mail to all members of the Society of Urologic Oncology. Participants were asked about their surgical volume, indications for PLND, which nodal packets are dissected as delineated on anatomical schema, and type of surgical approach. Results Of 340 members, 183 urologists (58%) completed the survey. Of these, 43% were ≥10 years out of fellowship and 62% performed >50 radical prostatectomies per year. Of the surveyed surgeons, 45% performed PLND on all patients undergoing radical prostatectomy. The remainder used various risk-stratification schemas. A total of 32 different indications for PLND were reported, the most common being “intermediate risk” according to the American Urological Association's risk classification. As to extent of PLND, 15% perform a PLND limited to the external iliac, while 30% include the external iliac, obturator fossa, and hypogastric lymph nodes. Among surgeons using both open and robotic approaches, 19% reported that the indication for and extent of lymphadenectomy performed differ based on the surgical approach used. Conclusions The results of this survey provide insight into the practice patterns of uro-oncologists regarding PLND and highlight the lack of uniformity in determining when and how a PLND should be performed. Collaborative efforts are needed to develop guidelines on this issue and are a necessary step toward standardization of reporting the outcomes of surgical clinical trials. Kenneth Hubert Slatter 05 Dec 2013 04:22 pm Kenneth Hubert Slatter was the first consultant neurologist to be appointed in Liverpool at Walton Hospital in 1960. He was born in Droylsden near Manchester, but his father, a bank manager, died... Long-term oncological outcomes of men undergoing radical prostatectomy with preoperative prostate-specific antigen <2.5 ng/ml and 2.5–4 ng/ml 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Peter Qi , Matvey Tsivian , Michael R. Abern , Lionel L. Bañez , Ping Tang , Judd W. Moul , Thomas J. Polascik Objectives Prostate-specific antigen (PSA) screening has increased the detection of small, organ-confined tumors, and studies suggest that these patients may have favorable outcomes following radical prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with low PSA (≤4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of patients undergoing RP with preoperative PSA <2.5 and 2.5–4 ng/ml compared with PSA 4.1–10 ng/ml. Materials and methods Data were analyzed from 3,621 men who underwent RP between 1988 and 2010 at our institution. Patients were stratified into 3 PSA groups: <2.5 ng/ml ( n = 280), 2.5–4 ng/ml ( n = 563), and 4.1–10 ng/ml ( n = 2,778). Patient and disease characteristics were compared. Overall, biochemical disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups. Multivariable analyses were conducted using proportional hazards model. Results Compared with the 4.1– 10 ng/ml PSA group, Gleason score >7, extracapsular extension, and non-organ-confined disease were less common in patients with PSA ≤4 ng/ml (all P < 0.001). The incidence of organ-confined disease was similar between the PSA < 2.5 and 2.5–4 ng/ml groups while perineural invasion ( P = 0.050) and Gleason score ≥7 ( P = 0.026) were more common in the 2.5–4 ng/ml PSA group. Estimated 10-year overall and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower in PSA 4.1–10 group ( P < 0.001). bDFS was not statistically different between PSA <2.5 and 2.5–4 groups ( P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1–10, 2.5–4, and <2.5, respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were associated with overall survival. Conclusions Long-term oncological outcomes (overall, bDFS, PCa-specific survivals) of patients presenting with low PSA (≤4 ng/ml) were excellent in this study. Compared with PSA 4.1–10 ng/ml, patients presenting with PSA ≤4 ng/ml had better bDFS outcomes. However, there was no difference in long-term outcomes between PSA <2.5 and 2.5–4 ng/ml. Low Androgen-Induced Penile Mal-development Involves Altered Gene Expression for Biomarkers for Smooth Muscle Differentiation and a Key Enzyme Regulating Cavernous Smooth Muscle Cell Tone - Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Purpose:: To determine effects of low androgens in the neonatal period on biomarkers for smooth muscle cell differentiation, Myh11 and Acta2, and Pde5A expression in the penis. Materials and Methods:: One-day-old pups were treated daily with gonadotropin releasing hormone antagonist antide (GnRH-A), with or without dihydrotestosterone (DHT), for 1-6 days. Tissues were collected at age day 7 and adulthood (120-day-old). Penises were examined using quantitative RT-PCR (Q-RT-PCR), Western blot, and immunohistochemistry. Testes were assayed for intra-testicular testosterone and steroidogenic enzymes (Cyp17ą1, StAR). Results:: GnRH-A exposure suppressed the neonatal testicular testosterone surge by 7080%. Q-RT-PCR data revealed 80-90% reductions in Cyp17ą1 and StAR protein and 40-60% reductions in Myh11 and ACTA2, as a result of GnRH-A exposure, compared to controls. DHT co-administration mitigated the above decreases. Western blot analyses confirmed Myh11 decrease at the protein level. Immunohistochemistry of Acta2 confirmed cavernous smooth muscle (CSM) cell loss at the tissue level. Additionally, GnRH-A exposure decreased Pde5a expression, and DHT co-administration mitigated the decrease. Comparison of data between two parts of the penis body, corpora cavernosa (CC) and corpus spongiosum (CS), showed that GnRH-A-induced decreases in Myh11, Acta2, and Pde5a expression occurred only in CC, implying the latter as the target site for a low androgen action. Conclusion:: Low androgens in the neonatal period, as evidenced by GnRH-A-induced suppression of the neonatal testosterone surge and reduced steroidogenesis, altered gene expression of biomarkers for smooth muscle cell differentiation, leading to loss of CSM cells and, consequently, penile mal-development. Low flows after Tubularized Incised Plate (TIP) urethroplasty: increased fibrogenesis, elastin fibers loss or none of the above? - Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Introduction:: Low flows rates are common after TIP urethroplasty but their etiology remains unclear and may related to low urethral compliance, maybe due to abnormal collagen concentrations and/or less elastic fibers in the healed urethral plate. We also hypothesized that inserting a preputial mucosal graft over the dorsal raw area after the midline incision (TIPG) may avoid scarring and improve urethral compliance. Methods:: Adult rabbits were submitted to TIP and TIPG operations according to a previously described protocol. Tissular concentrations of collagens I/III/IV/VI/VIII/XIII were measured. Histomorphometry was used to quantify elastic fibers in the urethra. TIP, TIPG and normal rabbits’ urethras (controls) were compared. Results:: The mRNA concentrations for collagens I, II and XIII were similar between controls and operated rabbits. The proportions between collagen I and III were, respectively, 1.05, 1.21 and 0.87, in controls, TIP and TIPG animals. mRNA concentrations for collagen IV and for collagens VI/VIII tended to be higher and lower, respectively, in the operated urethras, despite showing statistical significance only for collagen VIII in TIPG animals versus controls (p=0.02). The operated animals did not show a lower number of elastic fibers in the urethral tissues, as compared to controls. Conclusion:: Elastic fiber number and distribution was similar between TIP and controls, suggesting that lower concentrations of elastic fibers are not the explanation for low urethral compliances after TIP. The raw area determined by the dorsal urethral incision regenerated after TIP, while cicatrization with fibrosis occurred in correspondence to the grafted areas after TIPG surgery. Masthead 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Might Men Diagnosed with Metastatic Prostate Cancer Benefit from Definitive Treatment of the Primary Tumor? A SEER-Based Study 20 Nov 2013 04:45 am Definitive treatment of the primary tumor, either through surgery or radiation therapy, suggests a survival benefit in men diagnosed with metastatic prostate cancer. These results, using a large population-based cancer database, should serve as a foundation for future prospective trials. 129). The 5-yr OS and predicted DSS were each significantly higher in patients undergoing RP (67.4% and 75.8%, respectively) or BT (52.6 and 61.3%, respectively) compared with NSR patients (22.5% and 48.7%, respectively) (p = 245), and BT (n = 7811), RP (n = Background:Few data exist regarding the impact on survival of definitive treatment of the prostate in men diagnosed with metastatic prostate cancer (mPCa).Objective:To evaluate the survival of men diagnosed with mPCa based on definitive treatment of the prostate.Design, setting, and participants:Men with documented stage IV (M1a–c) PCa at diagnosis identified using Surveillance Epidemiology and End Results (SEER) (2004–2010) and divided based on definitive treatment of the prostate (radical prostatectomy [RP] or brachytherapy [BT]) or no surgery or radiation therapy (NSR).Outcome measurements and statistical analysis:Kaplan-Meier methods were used to calculate overall survival (OS). Multivariable competing risks regression analysis was used to calculate diseasespecific survival (DSS) probability and identify factors associated with cause-specific mortality (CSM).Results and limitations:A total of 8185 patients were identified: NSR (n Mixed High and Low Grade Bladder Tumors- Are They Clinically High or Low Grade Tumors? - Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Purpose: The pathological grade of bladder cancer has an immense impact on patient management and prognosis. While most bladder tumors show pure high or low grade patterns, some tumors show a mixed pattern. We aimed to explore the incidence and the clinical significance of this phenomenon. Materials and Methods: Between June 1998 and December 2008, 642 patients (mean age of 67.5 years) underwent transurethral resection of non-muscle invasive bladder tumors, including 156, and 454 patients with low grade (LG) and high grade (HG), respectively. In 32 patients (5%), mixed grade (MG) tumors were found defined as LG tumors with ≤10% HG component. All patients were followed for a median period of 60 months post-operatively. Results: The mean age, the proportion of men and the proportions of stages Ta/T1 of patients with MG tumors were all in the middle between the HG and LG groups. The 5-year recurrence-free survival was similar for all tumor types (56.9%, 63.8%, 66.4% for HG, LG and MG respectively, p=0.252). The 5-year progression-free survival was significantly lower (p<0.0001) in patients with HG (73.9%), but similar for patients with LG and MG tumors (99% and 96.9%, p=0.167). Similarly, disease specific survival was significantly worse for patients with HG tumor (p<0.0001), but similar for patients with LG and MG (p=0.679). Conclusions: MG tumors are found in about 5% of the non-muscle invasive tumors. They represent a group of patients with unique clinical features. The clinical course of patients with MG tumors parallels that of patients with LG tumors. Moniliformediquinone induces in vitro and in vivo antitumor activity through glutathioneinvolved DNA damage response and mitochondrial stress in human hormone-refractory prostate cancers - Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Purpose:: Hormone-refractory metastatic prostate cancer (HRMPC) is a major obstacle in clinical treatment. Discovery and development of anti-HRMPC are the key focus in this study. Materials and methods:: Several pharmacological and biochemical assays were used to characterize the apoptotic signaling pathways of moniliformediquinone in HRMPC. Results:: Moniliformediquinone, a natural product, induced cell-cycle arrest at S-phase and subsequent apoptosis in both PC-3 and DU-145, two HRMPC cell lines. Further examination showed that moniliformediquinone induced DNA damage response associated with the activation of Chk1, Chk2, c-Jun and JNK. The activation of mitochondrial apoptosis pathways also occurred, including loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-9 and caspase-3. Both N-acetyl cysteine (NAC, an antioxidant and a glutathione precursor) and trolox (an antioxidant) completely abolished moniliformediquinone-induced generation of reactive oxygen species; however, NAC but not trolox blocked moniliformediquinone-mediated apoptosis and related signaling cascades. Further identification showed that moniliformediquinone, by itself, did not conjugate glutathione but significantly decreased the levels of cellular glutathione. The in vivo study also showed that moniliformediquinone completely inhibited tumor growth with no weight loss. Conclusions:: The data suggest that moniliformediquinone is a potential anticancer agent against HRMPC through the decrease of cellular glutathione levels, leading to DNA damage response and an arrest of cell cycle at S phase. The mitochondrial stress also occurs to moniliformediquinone action through loss of mitochondrial membrane potential and cytochrome c release, which in turn induce the activation of caspase cascades and apoptotic cell death. Morbidity and costs of salvage vs. primary radical prostatectomy in older men 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Sandip M. Prasad , Xiangmei Gu , Keith J. Kowalczyk , Stuart R. Lipsitz , Paul L. Nguyen , Jim C. Hu Objectives Salvage radical prostatectomy (RP) is performed with curative intent following post-radiotherapy recurrence for prostate cancer. While single-center salvage RP outcomes appear promising, little is known about outcomes in the community setting in elderly men. We sought to evaluate utilization, outcomes, and costs of salvage RP vs. primary RP in older men. Materials and methods Surveillance, Epidemiology and End Results-Medicare linked data from 1992 to 2007 was used to identify 18,317 men aged 65 years or older who underwent RP from 2002 to 2007. Propensity score analyses were used to compare outcomes and costs for primary vs. salvage RP. Results Salvage RP was rare, accounting for 0.5% of RP. Men undergoing salvage vs. primary RP were older, white, and less likely to undergo CT, bone scan and prostate biopsy preoperatively ( P < 0.05 for all). In adjusted analyses, salvage vs. primary RP was associated with increased 30-day complications (60.1% vs. 22.7%, P < 0.01), lengths of stay (mean 7 vs. 3 days, P < 0.01), and hospital readmissions within 30 days (30.4% vs. 5.7%, P < 0.01). The odds of death within 90 days were higher for salvage vs. primary RP (OR 26.7, 95% CI 12.9–55.1, P < 0.01). The median expenditure for salvage RP within 6 months postoperatively was almost twice that for primary RP (US$30,881 vs. US$12,431, P < 0.01). Conclusions Metastatic workup was performed less frequently before salvage vs. primary RP, and morbidity and mortality for salvage RP was high relative to primary RP. Given the morbidity and high cost of salvage RP, guidelines for patient selection and selective referral may optimize outcomes, especially in older men. Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer11Funding: This work was supported by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283) presented to Dr. Hu. 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Keith J. Kowalczyk , Xiangmei Gu , Paul L. Nguyen , Stuart R. Lipsitz , Quoc-Dien Trinh , John H. Lynch , Sean P. Collins , Jim C. Hu Objectives Although post–radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART. Materials and methods From the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4–12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer–specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease. Results When compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042). Conclusion Initiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing. Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Ryan P. Dorin , Gary Lieskovsky , Adrian S. Fairey , Jie Cai , Siamak Daneshmand Objectives To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. Materials and methods A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). Results Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only ( n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age ( P = 0.003), total number of lymph nodes identified ( P = 0.040), and total number of positive lymph nodes identified ( P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS ( P = 0.05). Conclusions The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone. Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: Correlation with dynamic microbubble ultrasound data and review of the literature 09 Dec 2013 01:56 am Publication date: Available online 7 December 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Georg A. Bjarnason , Bishoy Khalil , John M. Hudson , Ross Williams , Laurent M. Milot , Mostafa Atri , Alex Kiss , Peter N. Burns Background Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50 mg given for 28 days with a 14-day break (50 mg, 28/14). Methods A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade 2. DSM-1 was 50 mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50 mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5 mg with individualized 7-day breaks. DSM-4 was 25 mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables. Results Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9– 11.9 mo) and overall survival (OS) (23.4–24.5 mo) that was significantly better than the PFS (5.3 mo; P <0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50 mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy. Conclusions Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing. Overactive Bladder and Mental Health Symptoms in Recently Deployed Women Veterans Accepted Manuscript 06 Dec 2013 12:00 am Abstract: Purpose: Our objectives were to estimate the prevalence of current overactive bladder (OAB) symptoms in recently-deployed women veterans, and to determine if OAB symptoms were associated with problems commonly reported after deployment, including mental health symptoms and prior sexual assault. Materials and Methods: Baseline data were analyzed from a nationwide cohort study of urogenital symptoms in women veterans. Women returning from Iraq or Afghanistan deployment in the prior two years and ending military service were eligible. Self-reported data were collected by computer-assisted telephone interview. OAB and mental health conditions were identified using standardized definitions and validated urinary and mental health instruments. Associations between OAB and depression, post-traumatic stress disorder (PTSD), anxiety and sexual assault were assessed in separate logistic regression models using propensity scores to adjust for confounding. Results: The 1702 participants had mean (SD) age of 31.1 (8.4) years and were racially/ethnically diverse. Three hundred seventy-five (22%, 95% CI (20.1%, 24.1%)) reported OAB. Mental health outcomes included PTSD (19%), anxiety (21%), depression (10%), and prior sexual assault (27%); all were associated with OAB (adjusted OR [95% CI] = 2.7 [2.0, 3.6], 2.7 [2.0, 3.5], 2.5 [1.5, 4.3], and 1.4 [1.1, 1.9] respectively). Conclusions: OAB symptoms occurred in 22% of recentlydeployed women veterans and were associated with self-reported mental health symptoms and traumatic events, including prior sexual assault. Screening and evaluation for bothersome urinary symptoms and mental health problems in women veterans presenting for primary and urologic care after deployment appears warranted. PCA3 sensitivity and specificity for prostate cancer detection in patients with abnormal PSA and/or suspicious digital rectal examination. First Latin American experience 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Christian G. Ramos , Raul Valdevenito , Ivonne Vergara , Patricio Anabalon , Catherine Sanchez , Juan Fulla Introduction Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations. Objectives Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy. Materials and methods Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome. Results The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%. Conclusions This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies. Pathologic T0 Following Radical Cystectomy with or without Neoadjuvant Chemotherapy: A Useful Surrogate - Accepted Manuscript 02 Dec 2013 12:00 am Abstract: Purpose:: Several large randomized controlled trials have provided evidence that neoadjuvant chemotherapy (NC) improves outcomes in patients with muscle-invasive urothelial bladder cancer (MIBC) who undergo radical cystectomy (RC). We sought to analyze the study design, methods and observations in these trials to identify patient subgroups that appeared most likely to benefit and discover distinguishing features from those groups that did not obtain improved outcomes. Materials and Methods:: We analyzed the initial and updated methods and results of the four main prospective trials of NC (SWOG, MRC, and Nordic I and II) and subsequent meta-analyses that have been the basis for advocating the use of NC in all patients with MIBC who undergo RC. Results:: The group that demonstrated the greatest apparent benefit were those patients who were free of cancer at the time of RC (pT0). These patients had markedly improved overall and disease-specific survivals compared to those with residual disease. However, these improvements occurred regardless of whether downstaging from MIBC to pT0 was seen with transurethral resection (TUR) alone (control group) or with TUR+NC. Thus, the major benefit from NC appeared to be the greater number of patients achieving pT0 in the chemotherapy group. In focusing on this, we explored limitations in these studies which may have influenced these outcomes. We also considered the potential for overtreatment of patients not likely to benefit from chemotherapy regimens. Finally, we employed risk stratification techniques to offer a decision tree model in the selection of patients for NC that conceivably could maximize oncologic outcomes and minimize overtreatment. Conclusions:: In the four main NC trials and their subsequent meta-analyses, pT0 patients in each group experienced similar survival, far exceeding those in both groups that did not achieve pT0 status. The benefit from NC appeared to be the larger number of patients than in the TUR-only group that were downstaged to pT0, suggesting that variables other than NC may have influenced outcomes. Therefore, employing strategies to selectively administer NC to certain at-risk patients has the potential to maintain improved bladder cancer outcomes while reducing overtreatment and its associated toxicities. Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal cell carcinoma after tumor enucleation 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Andrea Minervini , Maria Rosaria Raspollini , Agostino Tuccio , Claudio Di Cristofano , Giampaolo Siena , Matteo Salvi , Gianni Vittori , Arcangelo Sebastianelli , Alberto Lapini , Sergio Serni , Marco Carini Objective To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically intracapsular renal cell carcinomas (RCCs). Methods and materials PC status was analyzed in 304 consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were evaluated. Mean (median, range) follow-up was 49 months (46, 25–69). Local recurrence rate, progressionfree survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. Results Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC−), 34.9% had capsular penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side (PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC−, PCK, and PCF were 97.5%, 96.7%, and 77.1%, respectively ( P <0.0001). The multivariate Cox model showed PCF to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a significant increased risk in developing recurrence. Conclusions Tumor enucleation is an oncologically safe nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the risk of recurrence. Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: A functional and MR imaging pilot study 25 Nov 2013 10:13 am BACKGROUND Obesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear. Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients. METHODS Adipose tissues were collected from PCa patients undergoing surgical prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant tissue culture secretions were used in proliferation assays on PCa and endothelial cells. RESULTS PPA secretions obtained from obese patients were significantly more pro-proliferative in both PCa and endothelial cells as compared to PPA obtained from lean or overweight men and SQA tissues. Consistent with this, PPA microvessel density was increased, and the T2 relaxation time was decreased, compared to SQA tissues, and we observed a modest, inverse correlation between the T2 and tumor stage. Moreover, the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest, inverse correlation with Gleason score. CONCLUSIONS These pilot data show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that MR technology may be useful in further elucidating the relationship between obesity and PCa progression. Prostate © 2013 Wiley Periodicals, Inc. Pirin down-regulates the EAF2/U19 protein and alleviates its growth inhibition in prostate cancer cells 23 Nov 2013 03:30 am BACKGROUND The tumor suppressor ELL associated factor 2 (EAF2/U19) has been reported to induce apoptosis of LNCaP cells and suppress AT6.1 xenograft prostate tumor growth. EAF2/U19 expression level is down-regulated in advanced human prostate cancer. EAF2/U19 is also a putative transcription factor with a transactivation domain and capability of sequence-specific DNA binding. Identification of binding partners and regulators of EAF2/U19 is essential to understand its function in regulating apoptosis/survival of prostate cancer cells. METHODS Through a yeast two-hybrid screening system, we identified Pirin as a binding partner of EAF2. We further determined the interaction between epitope-tagged EAF2/U19 and Pirin by co-immunoprecipitation in mammalian cells. The effect of Pirin on EAF2/U19 inhibition of LNCaP growth was assayed by colony formation. RESULTS Pirin co-immunoprecipitated with EAF2/U19 and the overexpressed Pirin decreased the expression level of EAF2/U19 protein in prostate cancer cell lines LNCaP and PC3. Furthermore, overexpression of EAF2/U19 suppressed LNCaP colony formation, and coexpression of Pirin significantly blocked the growth inhibition induced by EAF2/U19 overexpression. CONCLUSION Pirin is a newly identified binding partner of EAF2/U19 capable of down-regulating EAF2/U19 protein and alleviating its inhibition of prostate cancer cell survival/proliferation. Pirin may play an important role involved in EAF2/U19 function as an androgen-responsive gene and tumor repressor. Prostate © 2013 Wiley Periodicals, Inc. Practice patterns and resource utilization for infants with bladder exstrophy: a national perspective - Accepted Manuscript 02 Dec 2013 12:00 am Abstract: Purpose:: Substantial variability exists in bladder exstrophy (BE) care, and little is known about costs associated with BE. We aim to define the care patterns and first-year cost for BE patients at select free-standing children’s hospitals in the United States. Materials and Methods:: The Pediatric Health Information System (PHIS) database was used to identify BE patients born between 1/99 and 12/10 whose primary closure occurred in the first 120 days of life (DOL). Demographic, surgical, postoperative, and cost data for all encounters were assessed. A multivariable linear regression was used to examine the association between patient, surgeon, and hospital characteristics and costs. Results:: Of the 381 patients who underwent primary closure within the first 120 DOL, 279 (73%) had this done within 3 DOL. 119 (31%) patients received pelvic osteotomies, including 51/279 (18%) of those closed within DOL 3, 38/67 (56%) of those closed between DOL 4-30 and 30/35 (86%) of those closed between DOL 31-120 (p=0.0017). The median inflation-adjusted first-year cost (US$) per patient was $66,577 [IQR: 45,335-102,398]. The presence of non-renal comorbidity and primary closure after 30 DOL were associated with 24% and 53% increased first-year costs, respectively. Increasing post-closure length of stay (LOS) was associated with increased costs. Conclusions:: At select freestanding U.S. children’s hospitals, the majority of bladder closures occur within the first 3 DOL. Most, but not all, patients closed after the neonatal period underwent osteotomy. The presence of non-renal comorbidity and increasing postoperative LOS were associated with increased costs. Precision medicine for metastatic renal cell carcinoma11Disclosures: Guru Sonpavde, MD: Research support from Novartis, Pfizer, and speaker or advisory board for Novartis, Pfizer, and GSK. Toni K. Choueiri, MD: Research support from Pfizer. Advisory board: Pfizer, Novartis, Aveo, GSK, Bayer/Onyx, and Genentech. No speakers bureau. 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Guru Sonpavde , Toni K. Choueiri Objectives This review provides a broad overview of emerging data that provide hope that rational precision medicine for metastatic renal cell carcinoma (RCC) may be possible. Methods PubMed and major conferences were searched for studies reporting potential predictive biomarkers for the therapy of metastatic RCC. Results The availability of multiple new agents for the therapy of advanced RCC poses new challenges in terms of optimal selection of patients for the appropriate drug. Prognostic stratification based on routine histopathologic, clinical and laboratory factors have been utilized to broadly select individuals based, i.e. high-dose interleukin (IL)-2 or vascular endothelial growth factor (VEGF) inhibitors for good and intermediate risk patients and temsirolimus for poor risk patients. While multiple candidate predictive molecular biomarkers suggest that rational selection of patients for high-dose interleukin (IL)-2, and VEGF and mammalian target of rapamycin (mTOR) inhibitors may be possible, none have been validated for use in the clinic. Tumor heterogeneity and standardization of tissue collection and analysis are massive challenges that need to be addressed. Predictive molecules derived from tumor tissue, plasma and host tissue may all be predictive for therapeutic benefit. Moreover, gene expression may be modulated by multiple factors including epigenetics, transcription factors and post-transcriptional and post-translational modifications. Indeed, study of the interaction of molecular factors from all of these sources with environmental and clinical factors may be necessary to develop a unified profile composed of a panel of factors predictive of benefit from specific agents (i.e. sustained response, limited toxicity and overall a positive benefit/risk ratio). Conclusions Conducting clinical trials with 1) prospective incorporation of promising candidate predictive molecular biomarkers, 2) novel biomarkers endpoints, and 3) mandatory biopsies of metastatic sites at different time points on therapy, are potential important steps in developing the concept of “the right medication for the right patient”. Preoperative estimated glomerular filtration rate predicts overall mortality in patients undergoing radical prostatectomy 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Matthew K. Tollefson , Stephen A. Boorjian , Matthew T. Gettman , Laureano J. Rangel , Eric J. Bergstralh , R. Jeffrey Karnes Background Assessment of overall health is a critical component in the evaluation of patients presenting with clinically localized prostate cancer. Estimated glomerular filtration rate (eGFR) has been associated with increased risk of cardiovascular and overall mortality. Therefore, the objective of our study was to evaluate the impact of baseline renal function on oncologic outcomes and overall survival following radical prostatectomy. Materials and methods We identified 10,099 patients who underwent radical prostatectomy at our institution from 1990 to 2004 with a preoperative serum creatinine available for analysis. eGFR was calculated by the chronic kidney disease-epidemiology formula (CKD-EPI) and reported as ml/min per 1.73 m2. Patients were then classified according to their eGFR: <30, 30–59, 60–89, 90–119, and 120–150 ml/min/1.73 m2. Multivariate Cox proportional hazard regression models were used to analyze the impact of eGFR on postoperative outcomes. Results At the time of surgery, 25 patients (0.1%) had an eGFR <30 ml/min/1.73 m2, 2,398 (23.7%) between 30 and 60, 7,097 (70.3%) between 60 and 90, and 605 (6.0%) patients had an eGFR >90. eGFR was not associated with oncologic outcomes, including biochemical recurrence, systemic progression or cancer-specific survival ( P > 0.05 for all). However, eGFR was strongly associated with all-cause mortality and non-prostate cancer death. On multivariate analysis, after controlling for age, BMI, prostate-specific antigen doubling time (PSA), Gleason score, and clinical stage, eGFR remains a statistically significant predictor of all-cause mortality. Conclusions Assessment of eGFR is an important metric in the overall evaluation of patient health and should be considered in combination with patient age and other medical comorbidities when selecting the initial treatment of prostate cancer. While prostate cancer-specific outcomes do not appear to be impacted by renal function, overall survival is decreased in those with lower and higher than normal eGFR. Presence of positive surgical margin in patients with organ-confined prostate cancer equals to extracapsular extension negative surgical margin. A plea for TNM staging system reclassification 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Firas Abdollah , Maxine Sun , Nazareno Suardi , Andrea Gallina , Umberto Capitanio , Marco Bianchi , Manuela Tutolo , Nicola Fossati , Fabio Castiglione , Massimo Freschi , Pierre Karakiewicz , Patrizio Rigatti , Francesco Montorsi , Alberto Briganti Background To test the hypothesis that patients with pT2 and positive surgical margins (SM) have a similar biochemical-recurrence (BCR) risk to patients with pT3a, and negative SM. Moreover, we examined the effect of incorporating positive SM as a higher stage on the discrimination accuracy of the current TNM staging system. Materials and methods We evaluated 1,503 prostate cancer patients treated with radical prostatectomy, between 1998 and 2010. Only individuals with pT2N0 or pT3aN0, without neoadjuvant and/or adjuvant therapy, were included. Cox regression analyses tested the relationship between SM status (negative [R0] vs. positive [R1]) and BCR rate, after stratification according to T stage. Predictive accuracy of the current T stage and of a novel T stage, which consider positive SM as a higher stage, was quantified with Harrell's concordance index. Results Positive SM rate was 20.3%. The 5-year BCR rates were 96%, 82%, 78%, and 62% for patients with, respectively, pT2R0, pT2R1, pT3aR0, and pT3a1 (all P ≤ 0.03). In multivariable analyses, the BCR rate was 3.6-, 2.5-, and 6.0-fold higher (all P < 0.001) in patients with, respectively, pT2R1, pT3aR0, and pT3aR1 stage relative to patients with pT2R0 stage. The maximum univariable (14.1%) and multivariable (6.9%) discrimination accuracy gains were observed, when tumor stage was stratified into pT2R0 vs. pT2R1/pT3R0 vs. pT3R1. Conclusions The presence of positive SM at radical prostatectomy (RP) specimen substantially increases the BCR risk. Patients with pT2R1 have similar BCR risk to patients with pT3aR0. Considering these patients as 1 category substantially improves the discrimination accuracy of the current TNM staging system. Primary spermatic cord tumors: Disease characteristics, prognostic factors, and treatment outcomes 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Dayron Rodríguez , Glen W. Barrisford , Alejandro Sanchez , Mark A. Preston , Evgeniy I. Kreydin , Aria F. Olumi Introduction Experience with management of spermatic cord tumors (SCTs) is uncommon. We utilized a large population-based cancer registry to characterize the demographic, pathological, treatment characteristics, and outcomes of SCTs. Material and methods The Surveillance, Epidemiology, and End Results database (1973–2007) was queried. Results From the database, 362 patients were identified with SCT. The annual incidence of SCT was 0.3 cases per million and did not change over time. The most common histologic types were liposarcoma (46%), leiomyosarcoma (20%), histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was (26.3 y), whereas for other SCTs, it was (64.7 y) ( P <0.001). On multivariate analysis, a worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or histiocytoma cell histology. Conclusion We describe the largest cohort of SCT studied to date. Liposarcoma was most common, while leiomyosarcoma and histiocytoma histologic subtypes were observed to be the most aggressive. Multivariate analysis revealed that tumor grade, stage, histologic type, and lymph node involvement were independently predictive of prognosis. Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7 prostate cancer treated with radical prostatectomy 09 Dec 2013 01:56 am Publication date: November 2013 Source:Urologic Oncology: Seminars and Original Investigations, Volume 31, Issue 8 Author(s): Hideaki Miyake , Mototsugu Muramaki , Junya Furukawa , Hirokazu Tanaka , Taka-aki Inoue , Masato Fujisawa Objectives To evaluate the significance of the primary Gleason pattern in patients with Gleason score (GS) 7 prostate cancer treated with radical prostatectomy. Materials and methods This study included 959 consecutive Japanese men who underwent radical prostatectomy without neoadjuvant therapies and were subsequently diagnosed as having GS 7 prostate cancer based on the modified International Society of Urological Pathology (ISUP) 2005 Gleason grading system. Results Of these 959 patients, 666 (69.4%) and 293 (30.6%) had GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic invasion, microvenous invasion, and perineural invasion between these 2 groups. During the mean observation of 48.9 months, biochemical recurrence occurred in 211 patients (22.0%), and there was a significant difference in the biochemical recurrence-free survival between patients with GS 3+4 tumors and those with GS 4+3 tumors. Of several factors examined, biochemical recurrence-free survival was significantly associated with the PSA level, biopsy Gleason score, capsular penetration, seminal vesicle invasion, surgical margin status, lymphatic invasion, microvenous invasion, perineural invasion, and primary Gleason pattern, among which the PSA level, capsular penetration, seminal vesicle invasion, and surgical margin status, but not primary Gleason pattern, appeared to be independent predictors of biochemical recurrence. Conclusions Despite the lack of an independent significance, primary Gleason pattern based on the modified ISUP 2005 Gleason grading system is shown to be significantly associated with the biochemical outcome of Japanese men with GS 7 prostate cancer. Prostate angiogenesis in development and inflammation 30 Nov 2013 02:39 pm BACKGROUND Prostatic inflammation is an important factor in development and progression of BPH/LUTS. This study was performed to characterize the normal development and vascular anatomy of the mouse prostate and then examine, for the first time, the effects of prostatic inflammation on the prostate vasculature. METHODS Adult mice were perfused with India ink to visualize the prostatic vascular anatomy. Immunostaining was performed on the E16.5 UGS and the P5, P20, and adult prostate to characterize vascular development. Uropathogenic E. coli 1677 was instilled transurethrally into adult male mice to induce prostate inflammation. RT-PCR and BrdU labeling was performed to assay anigogenic factor expression and endothelial proliferation, respectively. RESULTS An artery on the ventral surface of the bladder trifurcates near the bladder neck to supply the prostate lobes and seminal vesicle. Development of the prostatic vascular system is associated with endothelial proliferation and robust expression of proangiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, and Figf. Bacterial-induced prostatic inflammation induced endothelial cell proliferation and increased vascular density but surprisingly decreased pro-angiogenic factor expression. CONCLUSIONS The striking decrease in pro-angiogenic factor mRNA expression associated with endothelial proliferation and increased vascular density during inflammation suggests that endothelial response to injury is not a recapitulation of normal development and may be initiated and regulated by different regulatory mechanisms. Prostate © 2013 Wiley Periodicals, Inc. Prostate-specific antigen growth rate constant after first-line cytotoxic chemotherapy in metastatic castration-resistant prostate cancer: A monoinstitutional experience 09 Dec 2013 01:56 am Publication date: Available online 13 November 2013 Source:Urologic Oncology: Seminars and Original Investigations Author(s): Giuseppe Colloca , Antonella Venturino , Gianfranco Addamo , Riccardo Ratti , Zaira Coccorullo , Graziano Caltabiano , Giorgio Viale , Domenico Guarneri Objective Validation in clinical practice, after first-line chemotherapy (CT) of metastatic castration-resistant prostate cancer (PC), of prostate-specific antigen growth rate constant logarithm (PSA-G), calculated by a formula developed by Stein et al. in comparison with PSA decrease (PSA-D), calculated as recommended by PCWG2. Patients and methods This study is a retrospective monoinstitutional assessment of PSA-G and PSA-D after 12 weeks from the beginning of first-line cytotoxic CT in 49 patients with metastatic castration-resistant PC treated from 2006 to 2011, and whose pre-CT PSA and post-CT PSA determinations have been measured at specific time points. The 12-week PSA was measured at 80 to 91 days from the beginning of CT. Results PSA-G exhibited a significant correlation with overall survival by Mann-Whitney U test and by linear regression, whereas PSA-D did only at the first test. After multivariate analysis, PSA-G was the only posttreatment measure to predict overall survival. Conclusion PSA-G appears a reliable surrogate end point after first-line cytotoxic CT outside of clinical trials. A cutoff value of PSA-G post-CT higher than−2.4 could be considered suggestive for moving to another treatment. Re: Aflibercept versus Placebo in Combination with Docetaxel and Prednisone for Treatment of Men with Metastatic Castration-Resistant Prostate Cancer (VENICE): A Phase 3, Double-Blind Randomised Trial - Uncorrected Proof 04 Dec 2013 12:00 am I. F. Tannock, K. Fizazi, S. Ivanov, C. T. Karlsson, A. Fléchon, I. Skoneczna, F. Orlandi, G. Gravis, V. Matveev, S. Bavbek, T. Gil, L. Viana, O. Arén, O. Karyakin, T. Elliott, A. Birtle, E. Magherini, L. Hatteville, D. Petrylak, B. Tombal and M. Rosenthal; VENICE Investigators Re: Age-Related Prevalence of Low Testosterone in Men with Spinal Cord Injury Uncorrected Proof 04 Dec 2013 12:00 am W. A. Bauman, M. F. Fountaine and A. M. Spungen James J. Peters VA Medical Center, Bronx, New York Re: Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer - Uncorrected Proof 04 Dec 2013 12:00 am C. Parker, S. Nilsson, D. Heinrich, S. I. Helle, J. M. O’Sullivan, S. D. Fosså, A. Chodacki, P. Wiechno, J. Logue, M. Seke, A. Widmark, D. C. Johannessen, P. Hoskin, D. Bottomley, N. D. James, A. Solberg, I. Syndikus, J. Kliment, S. Wedel, S. Boehmer, M. Dall’Oglio, L. Franzén, R. Coleman, N. J. Vogelzang, C. G. O’Bryan-Tear, K. Staudacher, J. Garcia-Vargas, M. Shan, Ø. S. Bruland and O. Sartor; ALSYMPCA Investigators Re: American Geriatrics Society Identifies Five Things that Healthcare Providers and Patients Should Question - Uncorrected Proof 02 Dec 2013 12:00 am AGS Choosing Wisely Workgroup American Geriatrics Society, New York, New York Re: Autonomic Nervous Control of the Urinary Bladder - Uncorrected Proof 04 Dec 2013 12:00 am P. Ochodnicky, B. Uvelius, K. E. Andersson and M. C. Michel Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Re: Clomiphene Citrate in the Management of Male Infertility - Uncorrected Proof 02 Dec 2013 12:00 am L. W. Roth, A. R. Ryan and R. B. Meacham Department of Obstetrics and Gynecology, University of Colorado at Denver School of Medicine, Aurora, Colorado Re: Coenzyme Q10 and Male Infertility: A Meta-Analysis - Uncorrected Proof 02 Dec 2013 12:00 am R. Lafuente, M. González-Comadrán, I. Solà, G. López, M. Brassesco, R. Carreras and M. A. Checa Andrology Laboratory, Centro de Infertilidad y Reproducción Humana, Clínica Corachan, Asociación Nacional de Clínicas de Reproducción Asistida, Barcelona, Spain Re: Determinants of Testosterone Recovery after Bariatric Surgery: Is it Only a Matter of Reduction of Body Mass Index? - Uncorrected Proof 02 Dec 2013 12:00 am M. Luconi, J. Samavat, G. Seghieri, G. Iannuzzi, M. Lucchese, C. Rotella, G. Forti, M. Maggi and E. Mannucci Department of Clinical Physiopathology, Endocrinology Unit, University of Florence, Florence, Italy Re: Docetaxel and Atrasentan versus Docetaxel and Placebo for Men with Advanced Castration-Resistant Prostate Cancer (SWOG S0421): A Randomised Phase 3 Trial Uncorrected Proof 02 Dec 2013 12:00 am D. I. Quinn, C. M. Tangen, M. Hussain, P. N. Lara, Jr., A. Goldkorn, C. M. Moinpour, M. G. Garzotto, P. C. Mack, M. A. Carducci, J. P. Monk, P. W. Twardowski, P. J. Van Veldhuizen, N. Agarwal, C. S. Higano, N. J. Vogelzang and I. M. Thompson, Jr. Re: Effects of PRM Rehabilitation on PFM Function and Morphology in Older Women Uncorrected Proof 02 Dec 2013 12:00 am S. J. Madill, S. Pontbriand-Drolet, A. Tang and C. Dumoulin School of Physical Therapy, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Re: High-Intensity Diode Laser in Combination with Bipolar Transurethral Resection of the Prostate: A New Strategy for the Treatment of Large Prostate (>80 ml) - Uncorrected Proof 02 Dec 2013 12:00 am C. H. Chen, P. H. Chiang, W. C. Lee, Y. C. Chuang, C. H. Kang, C. C. Hsu, W. C. Lee, Y. T. Chen and Y. T. Cheng Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Re: Improving BPH Symptoms and Sexual Dysfunctions with a Saw Palmetto Preparation? Results from a Pilot Trial - Uncorrected Proof 02 Dec 2013 12:00 am A. Suter, R. Saller, E. Riedi and M. Heinrich Medical Department, A. Vogel Bioforce AG, Roggwil, Switzerland Re: Increased Intra-Abdominal Fat Predicts Perioperative Complications Following Minimally Invasive Partial Nephrectomy - Uncorrected Proof 02 Dec 2013 12:00 am M. A. Gorin, J. K. Mullins, P. M. Pierorazio, G. Jayram and M. E. Allaf James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland Re: Increases in Consumer Cost Sharing Redirect Patient Volumes and Reduce Hospital Prices for Orthopedic Surgery - Uncorrected Proof 02 Dec 2013 12:00 am J. C. Robinson and T. T. Brown Berkeley Center for Health Technology, School of Public Health, University of California, Berkeley, California Re: Inhibition of Bladder Overactivity by a Combination of Tibial Neuromodulation and Tramadol Treatment in Cats - Uncorrected Proof 02 Dec 2013 12:00 am F. Zhang, A. D. Mally, P. D. Ogagan, B. Shen, J. Wang, J. R. Roppolo, W. C. de Groat and C. Tai Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania Re: Inhibitors of 5α-Reductase-Related Side Effects in Patients Seeking Medical Care for Sexual Dysfunction - Uncorrected Proof 02 Dec 2013 12:00 am G. Corona, G. Rastrelli, E. Maseroli, G. Balercia, A. Sforza, G. Forti, E. Mannucci and M. Maggi Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy Re: Inhibitory Control Task is Decreased in Vascular Incontinence Patients - Uncorrected Proof 02 Dec 2013 12:00 am H. Haruta, R. Sakakibara, T. Ogata, J. Panicker, C. J. Fowler, F. Tateno, M. Kishi, Y. Tsuyusaki, T. Uchiyama and T. Yamamoto Departments of Neurology and Internal Medicine, Sakura Medical Center, Sakura, Japan Re: Intravesical Bacille Calmette-Guérin (BCG) in Immunologically Compromised Patients with Bladder Cancer - Uncorrected Proof 02 Dec 2013 12:00 am H. W. Herr and G. Dalbagni Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York Re: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, et al. Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity. Eur Urol 2013;64:372–8 30 Nov 2013 04:45 am Re: Loss of β1-Integrin from Urothelium Results in Overactive Bladder and Incontinence in Mice: A Mechanosensory Rather than Structural Phenotype - Uncorrected Proof 04 Dec 2013 12:00 am K. Kanasaki, W. Yu, M. von Bodungen, J. D. Larigakis, M. Kanasaki, F. Ayala de la Pena, R. Kalluri and W. G. Hill Division of Matrix Biology, Beth Israel Deaconess Medical Center, Boston, Massachusetts Re: Management and Outcomes of Penile Fracture: 10 Years' Experience from a Tertiary Care Center - Uncorrected Proof 02 Dec 2013 12:00 am A. Ozorak, M. B. Hoşcan, T. Oksay, A. Güzel and A. Koşar Department of Urology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey Re: Novel Anti-Biofilm Mechanism for Wireless Capsule Endoscopy in the Urinary Tract: Preliminary Study in a Sheep Model - Uncorrected Proof 02 Dec 2013 12:00 am A. Neheman, C. Schulman and O. Yossepowitch Urology Department, Meir Medical Center, Kfar-Saba, Israel Re: Novel Tumor Subgroups of Urothelial Carcinoma of the Bladder Defined by Integrated Genomic Analysis - Uncorrected Proof 04 Dec 2013 12:00 am C. D. Hurst, F. M. Platt, C. F. Taylor and M. A. Knowles Cancer Research UK Centre, Leeds Institute of Molecular Medicine, St. James’s University Hospital, Leeds, United Kingdom Re: PS3-36: Testosterone Replacement Therapy Patterns for Aging Males in a Managed Care Setting - Uncorrected Proof 04 Dec 2013 12:00 am J. An, T. C. Cheetham and S. Van Den Eeden Kaiser Permanente Southern California, Pasadena, California Re: Pathological Response to Neoadjuvant Chemotherapy for Muscle-Invasive Micropapillary Bladder Cancer - Uncorrected Proof 04 Dec 2013 12:00 am J. J. Meeks, J. M. Taylor, K. Matsushita, H. W. Herr, S. M. Donat, B. H. Bochner and G. Dalbagni Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, New York Re: Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial Uncorrected Proof 04 Dec 2013 12:00 am T. M. Brasky, A. K. Darke, X. Song, C. M. Tangen, P. J. Goodman, I. M. Thompson, F. L. Meyskens, Jr., G. E. Goodman, L. M. Minasian, H. L. Parnes, E. A. Klein and A. R. Kristal Re: Randomised, Multicentre, Placebo-Controlled, Double-Blind Crossover Study Investigating the Effect of Solifenacin and Oxybutynin in Elderly People with Mild Cognitive Impairment: The SENIOR Study - Uncorrected Proof 04 Dec 2013 12:00 am A. Wagg, M. Dale, R. Tretter, B. Stow and G. Compion University of Alberta, Edmonton, Alberta, Canada Re: Solifenacin plus Tamsulosin Combination Treatment in Men with Lower Urinary Tract Symptoms and Bladder Outlet Obstruction: A Randomized Controlled Trial - Uncorrected Proof 02 Dec 2013 12:00 am S. A. Kaplan, W. He, W. D. Koltun, J. Cummings, T. Schneider and A. Fakhoury Weill Medical College of Cornell University, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York Re: Sperm Banking is of Key Importance in Patients with Prostate Cancer - Uncorrected Proof 02 Dec 2013 12:00 am A. Salonia, P. Capogrosso, F. Castiglione, A. Russo, A. Gallina, M. Ferrari, M. C. Clementi, G. Castagna, A. Briganti, F. Cantiello, R. Damiano and F. Montorsi Department of Urology, University Vita--Salute San Raffaele, Milan, Italy Re: Testosterone Therapy during Exercise Rehabilitation in Male Patients with Chronic Heart Failure Who Have Low Testosterone Status: A Double-Blind Randomized Controlled Feasibility Study - Uncorrected Proof 02 Dec 2013 12:00 am M. Stout, G. A. Tew, H. Doll, I. Zwierska, N. Woodroofe, K. S. Channer and J. M. Saxton Department of Cardiology, University Hospital of South Manchester, Wythenshawe, Manchester, United Kingdom Re: The Association between Urinary and Fecal Incontinence and Social Isolation in Older Women - Uncorrected Proof 02 Dec 2013 12:00 am S. O. Yip, M. A, Dick, A. M. McPencow, D. K. Martin, M. M. Ciarleglio and E. A. Erekson Section of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut Talk to us about our bulletins! We'd love to hear what you think of this bulletin. Is it too vague? Too specific? Spot on? Is it doing the job or missing the mark? Is there a resource we've missed out? Do you need a bulletin on a different topic? Please let us know (contact details above) so that we can provide you with a better service! 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