San Raffaele Cimena, Italy
San Raffaele Cimena, Italy

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Umari P.,University of Trieste | Umari P.,Onze Lieve Vrouwziekenhuis Hospital | Fossati N.,Urological Research Institute | Fossati N.,Onze Lieve Vrouwziekenhuis Hospital | And 9 more authors.
Journal of Urology | Year: 2017

Purpose We report a comparative analysis of robotic assisted simple prostatectomy vs holmium laser enucleation of the prostate in patients who had benign prostatic hyperplasia with a large volume prostate (greater than 100 ml). Materials and Methods A total of 81 patients underwent robotic assisted simple prostatectomy and 45 underwent holmium laser enucleation of the prostate in a 7-year period. Patients were preoperatively assessed with transrectal ultrasound and uroflowmetry. Functional parameters were assessed postoperatively during followup. Perioperative outcomes included operative time, postoperative hemoglobin, catheterization time and hospitalization. Complications were reported according to the Clavien-Dindo classification. Results Compared to the holmium laser enucleation group, patients treated with prostatectomy were significantly younger (median age 69 vs 74 years, p = 0.032) and less healthy (Charlson comorbidity index 2 or greater in 62% vs 29%, p = 0.0003), and had a lower rate of suprapubic catheterization (23% vs 42%, p = 0.028) and a higher preoperative I-PSS (International Prostate Symptom Score) (25 vs 21, p = 0.049). Both groups showed an improvement in the maximum flow rate (15 vs 11 ml per second, p = 0.7), and a significant reduction in post-void residual urine (−73 vs −100 ml, p = 0.4) and I-PSS (−20 vs −18, p = 0.8). Median operative time (105 vs 105 minutes, p = 0.9) and postoperative hemoglobin (13.2 vs 13.8 gm/dl, p = 0.08) were similar for robotic assisted prostatectomy and holmium laser enucleation, respectively. Median catheterization time (3 vs 2 days, p = 0.005) and median hospitalization (4 vs 2 days, p = 0.0001) were slightly shorter in the holmium laser group. Complication rates were similar with no Clavien grade greater than 3 in either group. Conclusions Our results from a single center suggest comparable outcomes for robotic assisted simple prostatectomy and holmium laser enucleation of the prostate in patients with a large volume prostate. These findings require external validation at other high volume centers. © 2017 American Urological Association Education and Research, Inc.

News Article | April 18, 2017

My 'colleagues' and I at the fictitious Arthur Vandelay Urological Research Institute were surprised to find our bogus 'uromycitisis' case report swiftly accepted, with only minor revisions requested.

News Article | April 17, 2017

My “colleagues” and I at the fictitious Arthur Vandelay Urological Research Institute were surprised to find our bogus “uromycitisis” case report swiftly accepted, with only...

Loeb S.,New York University | Bruinsma S.M.,Erasmus Medical Center | Nicholson J.,New York University | Briganti A.,Urological Research Institute | And 6 more authors.
European Urology | Year: 2015

Context Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way. © 2014 European Association of Urology. All rights reserved.

Hannan J.L.,The James Buchanan Brady Urological Institute | Kutlu O.,Karadeniz Technical University | Stopak B.L.,The James Buchanan Brady Urological Institute | Liu X.,The James Buchanan Brady Urological Institute | And 5 more authors.
Journal of Sexual Medicine | Year: 2014

Introduction: Bilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases. Aims: This study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI-induced ED and penile fibrosis. Methods: Five groups of rats (8-10 weeks, n=10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor-β1 (TGF-β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α-SMA) antibodies. Main Outcome Measures: We measured ICP; HDAC3, HDAC4, fibronectin, and TGF-β1 protein expression; penile fibrosis; penile α-SMA content. Results: There was a voltage-dependent decline (P<0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P<0.05) 14 days after BCNI. There was a slight increase in TGF-β1 protein expression after BCNI. Histological analysis showed increased (P<0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P<0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α-SMA between all groups. Furthermore, VPA-treated BCNI rats had improved erectile responses to CNS (P<0.05). Conclusion: HDAC-induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post-radical prostatectomy. Hannan JL, Kutlu O, Stopak BL, Liu X, Castiglione F, Hedlund P, Burnett AL, and Bivalacqua TJ. Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve-injured rats. J Sex Med 2014;11:1442-1451. © 2014 International Society for Sexual Medicine.

Futterer J.J.,Radboud University Nijmegen | Briganti A.,Urological Research Institute | De Visschere P.,Ghent University | Emberton M.,University College London | And 6 more authors.
European Urology | Year: 2015

Context Detection of clinically significant prostate cancer (PCA) is a major challenge. It has been shown that multiparametric magnetic resonance imaging (mpMRI) facilitates localisation of PCA and can help in targeting prostate biopsy. Objective To systematically review the literature to determine the diagnostic accuracy of mpMRI in the detection of clinically significant PCA. Evidence acquisition The Pubmed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 1, 2000 to September 30, 2014, using the search criteria "prostate OR Pca OR PSA OR prostatic OR prostate cancer" AND "MR OR NMR OR NMRI OR MRI OR magnetic resonance OR ADC OR DWI OR DCE OR diffusion weighted OR dynamic contrast OR multiparametric OR MRSI OR MR spectroscopy". Two reviewers independently assessed 1729 records. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) 2 tool. Evidence synthesis Twelve articles were eventually selected. Patients had a median age of 62-65 yr (range 39-83 yr), a median prostate-specific antigen (PSA) level of 5.1-13.4 ng/ml (range 1.2-228 ng/ml), and Gleason score of 6-10. Various definitions of clinical significance were used, mainly based on maximum cancer core length and grade at biopsy, number of positive cores, and PSA. Detection of clinically significant PCA using mpMRI ranged from 44% to 87% in biopsy-naïve males and men with prior negative biopsies using prostate biopsy or definitive pathology of a radical prostatectomy specimen as the reference standard. The negative predictive value for exclusion of significant disease ranged from 63% to 98%. Conclusions mpMRI is able to detect significant PCA in biopsy-naïve males and men with prior negative biopsies. The negative predictive value of mpMRI is important to the clinician because mpMRI could be used to rule out significant disease. This may result in fewer or no systematic or targeted biopsies in patients with PSA suspicious for prostate cancer. Patient summary We reviewed the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (PCA). We conclude that mpMRI is able to detect significant PCA and may used to target prostate biopsies. © 2015 European Association of Urology.

Bourke L.,Sheffield Hallam University | Boorjian S.A.,Mayo Medical School | Briganti A.,Urological Research Institute | Klotz L.,Sunnybrook Health science Center | And 5 more authors.
European Urology | Year: 2015

Context Long-term survival following a diagnosis of cancer is improving in developed nations. However, living longer does not necessarily equate to living well. Objective To search systematically and synthesise narratively the evidence from randomised controlled trials (RCTs) of supportive interventions designed to improve prostate cancer (PCa)-specific quality of life (QoL). Evidence acquisition A systematic search of Medline and Embase was carried out from inception to July 2014 to identify interventions targeting PCa QoL outcomes. We did not include nonrandomised studies or trials of mixed cancer groups. In addition to database searches, citations from included papers were hand-searched for any potentially eligible trials. Evidence synthesis A total of 2654 PCa survivors from 20 eligible RCTs were identified from our database searches and reference checks. Disease-specific QoL was assessed most frequently by the Functional Assessment of Cancer Therapy-Prostate questionnaire. Included studies involved men across all stages of disease. Supportive interventions that featured individually tailored approaches and supportive interaction with dedicated staff produced the most convincing evidence of a benefit for PCa-specific QoL. Much of these data come from lifestyle interventions. Our review found little supportive evidence for simple literature provision (either in booklets or via online platforms) or cognitive behavioural approaches. Conclusions Physical and psychological health problems can have a serious negative impact on QoL in PCa survivors. Individually tailored supportive interventions such as exercise prescription/referral should be considered by multidisciplinary clinical teams where available. Cost-effectiveness data and an understanding of how to sustain benefits over the long term are important areas for future research. Patient summary This review of supportive interventions for improving quality of life in prostate cancer survivors found that supervised and individually tailored patient-centred interventions such as lifestyle programmes are of benefit. © 2015 European Association of Urology.

Gallina A.,Urological Research Institute
Prostate Cancer and Prostatic Diseases | Year: 2016

Background:Erectile dysfunction (ED) represents one of the most common long-term side effects in prostate cancer (PCa) patients treated with bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to assess the influence of non-surgically related causes of ED in patients treated with BNSRP.Methods:Overall, 716 patients treated with BNSRP were retrospectively identified. All patients had complete data on erectile function (EF) assessed by the Index of Erectile Function-EF domain (IIEF-EF) and depressive status assessed by the Center for Epidemiologic Studies-Depression (CES-D) questionnaire. EF recovery was defined as an IIEF-EF of ⩾22. Kaplan–Meier analyses assessed the impact of preoperative IIEF-EF, depression and adjuvant radiotherapy (aRT) on the time to EF recovery. Multivariable Cox regression models were used to test the impact of aRT on EF recovery after accounting for depression and baseline IIEF-EF.Results:Median follow-up was 48 months. Patients with a preoperative IIEF-EF of ⩾22 had substantially higher EF recovery rates compared with those with a lower IIEF-EF (P<0.001). Patients with a CES-D of <16 had significantly higher EF recovery rates compared to those with depression (60.8 vs 49.2%; P=0.03). Patients receiving postoperative aRT had lower rates of EF compared with their counterparts left untreated after surgery (40.7 vs 59.8%; P<0.001). These results were confirmed in multivariable analyses, where preoperative IIEF-EF (P<0.001), depression (P=0.04) and aRT (P=0.03) were confirmed as significant predictors of EF recovery.Conclusions:Preoperative functional status and depression should be considered when counseling PCa patients regarding the long-term side effects of BNSRP. Moreover, the administration of aRT has a detrimental effect on the probability of recovering EF after BNSRP. This should be taken into account when balancing the potential benefits and side effects of multimodal therapies in PCa patients.Prostate Cancer and Prostatic Diseases advance online publication, 9 February 2016; doi:10.1038/pcan.2016.1. © 2016 Macmillan Publishers Limited

Gallina A.,Urological Research Institute | Bianchi M.,Urological Research Institute | Gandaglia G.,Urological Research Institute | Cucchiara V.,Urological Research Institute | And 3 more authors.
European Urology | Year: 2015

A recent study reported a detrimental effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa). We tested the association between PDE5-I use, PDE5-I therapy scheme, number of PDE5-I pills taken, and BCR in 2579 patients treated with bilateral nerve-sparing RP for PCa between 2004 and 2013 at a single center. Patients were categorized according to PDE5-I use within 2 yr after surgery as on demand, rehabilitation schedule (daily PDE5-I use for at least 3 mo), and no PDE5-I use. Multivariable (MVA) Cox regression models tested the association between PDE5-I and BCR. The same analyses were repeated using the number of PDE5-I pills taken by each patient. Overall, 674 patients (26.1%) received PDE5-Is. At MVA analysis, PDE5-I use, type of administration schedule, and number of PDE5-I pills were not significantly associated with higher risk of BCR (all p ≥ 0.2) after accounting for multiple confounders including time from RP to PDE5-I use. While awaiting further studies, patients should not be denied PDE5-I treatment after RP. Patient summary Among patients treated with radical prostatectomy, phosphodiesterase type 5 inhibitor use was not associated with an increased risk of biochemical recurrence, regardless of the therapeutic regimen used. © 2015 European Association of Urology.

Abrate A.,Urological Research Institute
European journal of cancer (Oxford, England : 1990) | Year: 2014

Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase::uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

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