Publications by authors named "Gabriele Cozzi"

59 Publications

Assessment of PSIM (Prostatic Systemic Inflammatory Markers) Score in Predicting Pathologic Features at Robotic Radical Prostatectomy in Patients with Low-Risk Prostate Cancer Who Met the Inclusion Criteria for Active Surveillance.

Diagnostics (Basel) 2021 Feb 20;11(2). Epub 2021 Feb 20.

Department of Urology, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

Background: circulating levels of lymphocytes, platelets and neutrophils have been identified as factors related to unfavorable clinical outcome for many solid tumors. The aim of this cohort study is to evaluate and validate the use of the Prostatic Systemic Inflammatory Markers (PSIM) score in predicting and improving the detection of clinically significant prostate cancer (csPCa) in men undergoing robotic radical prostatectomy for low-risk prostate cancer who met the inclusion criteria for active surveillance.

Methods: we reviewed the medical records of 260 patients who fulfilled the inclusion criteria for active surveillance. We performed a head-to-head comparison between the histological findings of specimens after radical prostatectomy (RP) and prostate biopsies. The PSIM score was calculated on the basis of positivity according to cutoffs (neutrophil-to-lymphocyte ratio (NLR) 2.0, platelets-to-lymphocyte ratio (PLR) 118 and monocyte-to-lymphocyte-ratio (MLR) 5.0), with 1 point assigned for each value exceeding the specified threshold and then summed, yielding a final score ranging from 0 to 3.

Results: median NLR was 2.07, median PLR was 114.83, median MLR was 3.69.

Conclusion: we found a significantly increase in the rate of pathological International Society of Urological Pathology (ISUP) ≥ 2 with the increase of PSIM. At the multivariate logistic regression analysis adjusted for age, prostate specific antigen (PSA), PSA density, prostate volume and PSIM, the latter was found the sole independent prognostic variable influencing probability of adverse pathology.
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http://dx.doi.org/10.3390/diagnostics11020355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924196PMC
February 2021

MRI-targeted or systematic random biopsies for prostate cancer diagnosis in biopsy naïve patients: follow-up of a PRECISION trial-like retrospective cohort.

Prostate Cancer Prostatic Dis 2020 Sep 28. Epub 2020 Sep 28.

Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy.

Background: To test clinically significant prostate cancer (csPCa) rates during follow-up in biopsy naïve patients that underwent two different diagnostic pathways: (1) SB GROUP (n = 354): systematic random biopsies (SB) vs. (2) TB GROUP (n = 264): multiparametric magnetic resonance imaging (mpMRI) and only targeted biopsies (TB) of PI-RADS ≥ 3 lesions. Patients with PI-RADS ≤ 2 score avoided prostate biopsies.

Methods: Retrospective single centre study of 618 biopsy naive patients (2015-2018). Two different definitions of csPCa were used: (1) csPCa ISUP GG ≥ 2 (ISUP grade group [GG] ≥ 2) and (2) csPCa ISUP GG ≥ 3. Kaplan-Meier plots and univariable Cox regression models tested rates over time of csPCa ISUP GG ≥ 2 and caPCa ISUP GG ≥ 3 in SB GROUP vs. TB GROUP.

Results: At initial biopsy, TB achieved higher rates of csPCa ISUP GG ≥ 2 (35.3 vs. 18.9%; p < 0.001) and csPCa ISUP GG ≥ 3 (12.6 vs. 6.2%; p = 0.04), relative to SB. After a median time follow-up of 36 months, the rates of csPCa ISUP GG ≥ 2 (6.1 vs. 4.4%; p = 0.6) and csPCa ISUP GG ≥ 3 (3.3 vs. 1.1%; p = 0.2) were similar in SB GROUP vs. TB GROUP. Moreover, in TB GROUP patients that avoided prostate biopsies because of negative baseline mpMRI (n = 145), only 4.1% exhibited csPCa ISUP GG ≥ 2 during follow-up. Moreover, none of these patients (PI-RADS ≤ 2) had csPCa ISUP GG ≥ 3.

Conclusions: In biopsy naïve setting, a diagnostic pathway including pre-biopsy mpMRI and TB of only PCa suspicious lesions is not associated with higher rates of csPCa during follow-up, relative to a diagnostic pathway of SB. Moreover, patients with negative baseline mpMRI could safely avoid prostate biopsies and could be followed with repeated PSA testing, since only a small proportion of them would harbor csPCa.
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http://dx.doi.org/10.1038/s41391-020-00290-4DOI Listing
September 2020

Robot-Assisted Radical Cystectomy for Nonmetastatic Urothelial Carcinoma of Urinary Bladder: A Comparison Between Intracorporeal Versus Extracorporeal Orthotopic Ileal Neobladder.

J Endourol 2021 Feb 30;35(2):151-158. Epub 2020 Oct 30.

Department of Urology, European Institute of Oncology (IEO) IRCCS, Milan, Italy.

To compare surgical, oncologic, functional outcomes and complication rate between intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) orthotopic ileal neobladder of robot-assisted radical cystectomy (RARC) in patients with nonmetastatic bladder carcinoma (BC). From 2014 to 2019, we prospectively collected and retrospectively analyzed 101 patients with nonmetastatic BC treated with RARC and ortothopic neobladder. Chi-squared test estimated differences in proportions of functional and oncologic outcomes. Multivariable logistic regression models (MLRMs) focused on overall, early (<30 days from discharge), and late complication rate (>30 days from discharge) in ICNB ECNB. Of all patients, 57 (56.4%) ICNB and 44 (43.6%) ECNB patients were identified. At least one complication occurred in 75.4% 72.7% in ICNB ECNB, respectively ( = 0.9). In MLRMs, focusing on complication rate, there was no statistically significant difference between ICNB ECNB for overall ( = 0.8), early ( = 0.6), and late complications ( = 0.8). No statistically significant differences were recorded for tumor relapse rate, cancer-specific and other cause mortality. No positive surgical margins were recorded in both groups. Daytime and nighttime continence recovery were 89.4% 87.1% ( = 1.0) and 63.8% 51.6% ( = 1.0) for ICNB ECNB. Potency recovery was 59.1% 54.3% ( = 0.5) for ICNB ECNB. No statistically significant differences in complication rate (overall, early, or late) were identified, when ICNB and ECNB were compared. Similarly, no statistically significant difference was found in oncologic and functional outcomes.
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http://dx.doi.org/10.1089/end.2020.0622DOI Listing
February 2021

Clinical evaluation and disease management of PI-RADS 3 lesions. Analysis from a single tertiary high-volume center.

Scand J Urol 2020 Aug 10:1-5. Epub 2020 Aug 10.

Division of Urology, European Institute of Oncology, IRCCS, Milan, Italy.

Objective: To evaluate the clinical and pathological implications of Prostate Cancer (PCa) patients with a Prostate Imaging - Reporting and Data System (PI-RADS) 3 lesion at multi parametric magnetic resonance imaging (mpMRI).

Methods: We included 356 patients with a PI-RADS score 3 lesion at mpMRI who underwent prostate biopsy for a suspect of PCa at a single tertiary high-volume centre between 2013 and 2016. We developed Uni- (UVA) and multi variable (MVA) logistic regression analyses assessing the predictors of three endpoints: 1) diagnosis of PCa, 2) active surveillance (AS) criteria and 3) clinically significant (CS) PCa at final pathology.

Results: PCa was diagnosed in 285 patients (80%), out of these 154 (56%) were eligible for AS according to Prostate Cancer Research International Active Surveillance (PRIAS) criteria. Over the 228 (64%) patients who underwent surgery, 93 (40.8%) had a CS disease at final pathology. Hundred and ninety-three (84.6%) had a pT2 disease and 35 (15.4%) had a pT3 disease. The size of the main lesion, age, PSA and prostate volume efficiently predicted PCa at MVA (all  < 0.05). None of our predictors were significantly associated with AS characteristics. Over those patients who underwent surgery, the biopsy Gleason Score ( = 0.007) efficiently predicted a CS PCa at final pathology.

Conclusions: mpMRI-detected PI-RADS 3 lesions should be sent to a prostate biopsy if other clinical parameters suggest the presence of a PCa. In case of diagnosis of a PCa, patients should undergo confirmatory biopsy before being included in AS protocols to avoid underestimation of a CS disease.
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http://dx.doi.org/10.1080/21681805.2020.1798503DOI Listing
August 2020

When to stay and when to leave? Proximate causes of dispersal in an endangered social carnivore.

J Anim Ecol 2020 10 10;89(10):2356-2366. Epub 2020 Aug 10.

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zürich, Switzerland.

Reliable estimates of birth, death, emigration and immigration rates are fundamental to understanding and predicting the dynamics of wild populations and, consequently, inform appropriate management actions. However, when individuals disappear from a focal population, inference on their fate is often challenging. Here we used 30 years of individual-based mark-recapture data from a population of free-ranging African wild dogs Lycaon pictus in Botswana and a suite of individual, social and environmental predictors to investigate factors affecting the decision to emigrate from the pack. We subsequently used this information to assign an emigration probability to those individuals that were no longer sighted within their pack (i.e. missing individuals). Natal dispersal (i.e. emigration from the natal pack) showed seasonal patterns with female dispersal peaking prior to the mating season and male dispersal peaking at the beginning of the wet season. For both sexes, natal dispersal rate increased in the absence of unrelated individuals of the opposite sex in the pack. Male natal dispersal decreased with increasing number of pups in the pack and increased in larger packs. Female natal dispersal decreased with increasing number of pups in larger packs, but increased with increasing number of pups in smaller packs. Individuals of both sexes were less likely to exhibit secondary dispersal (i.e. emigration from a pack other than the natal pack) if they were dominant and if many pups were present in the pack. Our models predicted that 18% and 25% of missing females and males, respectively, had likely dispersed from the natal pack, rather than having died. A misclassification of this order of magnitude between dispersal and mortality can have far-reaching consequences in the evaluation and prediction of population dynamics and persistence, and potentially mislead conservation actions. Our study showed that the decision to disperse is context-dependent and that the effect of individual, social and environmental predictors differs between males and females and between natal and secondary dispersal related to different direct and indirect fitness consequences. Furthermore, we demonstrated how a thorough understanding of the proximate causes of dispersal can be used to assign a dispersal probability to missing individuals. Knowledge of causes of dispersal can then be used within an integrated framework to more reliably estimate mortality rates.
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http://dx.doi.org/10.1111/1365-2656.13300DOI Listing
October 2020

Insertion of a testicular prosthesis at the time of radical orchiectomy for testicular cancer is safe in patients who will subsequently undergo chemotherapy or radiotherapy.

Andrologia 2020 Jul 30;52(6):e13613. Epub 2020 Apr 30.

Division of Urology, European Institute of Oncology, IRCCS, Milan, Italy.

We aimed to assess the incidence of prosthesis-related complications in patients who received a testicular prosthesis at the time of radical orchiectomy for testicular cancer and were then treated with chemotherapy (ChT) or radiotherapy (RT). We reviewed the records of the patients who underwent radical orchiectomy at our Institute since 1999; we also retrieved data from patients who underwent surgery elsewhere and then received ChT or RT at our Institution since 1999. We used the chi-square test to evaluate differences in the incidence of prosthesis-related complications between the groups. We retrieved the records of 587 patients; 393 had a testicular prosthesis implanted. Median follow-up was 57.7 months. One hundred thirty-eight patients (35.11%) received ChT, 129 RT (38.82%) and 10 (2.55%) both ChT and RT; of them, 6 (4.34%), 8 (6.20%) and 0 reported problems respectively. Seven (6.03%) of the 116 patients (29.52%) who had no further treatment had complications. The incidence of complications was not significantly different between patients who had no further treatment versus patients who underwent ChT (p = .75) or RT (p = .83). Testicular prosthesis insertion at the time of radical orchiectomy is safe even in patients subsequently undergoing ChT or RT.
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http://dx.doi.org/10.1111/and.13613DOI Listing
July 2020

Robot-assisted inguinal lymphadenectomy: preliminary experience and perioperative outcomes from an Italian referral center.

Ther Adv Urol 2020 Jan-Dec;12:1756287220913386. Epub 2020 Apr 1.

Division of Urology, Istituto Europeo di Oncologia, IRCCS, Milan, Italy.

Background: Inguinal lymphadenectomy remains the gold standard for the treatment of inguinal lymph node metastases from penile carcinoma, melanoma, Merkel cell carcinoma, and squamous cell carcinoma (SCC). This procedure is associated with significant complications. In order to reduce morbidity, minimally invasive approaches have been described. We report our preliminary experience with robot-assisted inguinal lymphadenectomies (RAIL).

Methods: RAIL was performed according to the Sotelo technique. When indicated, a robot-assisted pelvic lymphadenectomy (RAPLND) was performed. We recorded age, sex, comorbidities, baseline oncologic diagnosis, operative time, hospital stay, lymph node yield, complications, time to drain removal, and oncologic outcomes.

Results: From December 2016 to February 2019, 13 patients underwent RAIL. Median age was 65 years (range: 31-85 years). Primary malignancy was melanoma in five patients, Merkel cell carcinoma in four, dermal duct tumor in one, penile cancer in two, and SCC in one. RAIL was monolateral in 12 cases and bilateral in 1 case. A total of 10 monolateral RAPLNDs were performed; median operative time was 279 min (range: 169-320). Median lymph nodes yield was 11 (range: 2-24) for monolateral RAIL and 9 for monolateral RAPLND (range 2-24). Median hospital stay was 4 days (range: 2-5). No procedure was converted to open. Median follow up was 16 months (range: 5-31). Five Clavien-Dindo grade I complications were recorded. Median time to drain removal was 32.5 days (range 7-65). Three recurrences and two cancer-related deaths were recorded.

Conclusions: RAIL is feasible and associated with a short hospital stay, with little incidence of perioperative complications.
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http://dx.doi.org/10.1177/1756287220913386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132788PMC
April 2020

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

BJU Int 2020 07 1;126(1):104-113. Epub 2020 Apr 1.

Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy.

Objectives: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification.

Patients And Methods: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used.

Results: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%).

Conclusion: The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.
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http://dx.doi.org/10.1111/bju.15048DOI Listing
July 2020

Behavioural compass: animal behaviour recognition using magnetometers.

Mov Ecol 2019 27;7:28. Epub 2019 Aug 27.

1School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Background: Animal-borne data loggers today often house several sensors recording simultaneously at high frequency. This offers opportunities to gain fine-scale insights into behaviour from individual-sensor as well as integrated multi-sensor data. In the context of behaviour recognition, even though accelerometers have been used extensively, magnetometers have recently been shown to detect specific behaviours that accelerometers miss. The prevalent constraint of limited training data necessitates the importance of identifying behaviours with high robustness to data from new individuals, and may require fusing data from both these sensors. However, no study yet has developed an end-to-end approach to recognise common animal behaviours such as foraging, locomotion, and resting from magnetometer data in a common classification framework capable of accommodating and comparing data from both sensors.

Methods: We address this by first leveraging magnetometers' similarity to accelerometers to develop biomechanical descriptors of movement: we use the static component given by sensor tilt with respect to Earth's local magnetic field to estimate posture, and the dynamic component given by change in sensor tilt with time to characterise movement intensity and periodicity. We use these descriptors within an existing hybrid scheme that combines biomechanics and machine learning to recognise behaviour. We showcase the utility of our method on triaxial magnetometer data collected on ten wild Kalahari meerkats (), with annotated video recordings of each individual serving as groundtruth. Finally, we compare our results with accelerometer-based behaviour recognition.

Results: The overall recognition accuracy of > 94% obtained with magnetometer data was found to be comparable to that achieved using accelerometer data. Interestingly, higher robustness to inter-individual variability in dynamic behaviour was achieved with the magnetometer, while the accelerometer was better at estimating posture.

Conclusions: Magnetometers were found to accurately identify common behaviours, and were particularly robust to dynamic behaviour recognition. The use of biomechanical considerations to summarise magnetometer data makes the hybrid scheme capable of accommodating data from either or both sensors within the same framework according to each sensor's strengths. This provides future studies with a method to assess the added benefit of using magnetometers for behaviour recognition.
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http://dx.doi.org/10.1186/s40462-019-0172-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712732PMC
August 2019

Sexual function recovery after robot-assisted radical prostatectomy: Outcomes from an Italian referral centre and predicting nomogram.

Andrologia 2019 Nov 18;51(10):e13385. Epub 2019 Aug 18.

Division of Urology, European Institute of Oncology, IRCCS, Milan, Italy.

Aims of this study were to assess sexual recovery after robotic-assisted radical prostatectomy (RARP) and to build a nomogram predicting 1-year sexual function. From May 2015 to July 2016, all patients eligible for RARP at our institution were invited to enter the study. The Expanded Prostate cancer Index Composite (EPIC) questionnaire was administered pre-operatively, then at 45 days, and at 3, 6, 9, and 12 months post-operatively. According to sexual function scores, patients were divided into four classes. Multivariate analysis was used to investigate the influence of patient- and disease-related features on sexual recovery. A total of 643 patients were included. Age was associated with baseline potency (p < .0001). Bioptic Gleason score (GS; p = .0002), American Society of Anesthesiologists (ASA) score ( = .002ASA Physical Status Classification System ) and Charlson Comorbidity Index (CCI; p = .02) were negatively associated with potency. Baseline sexual function was associated with potency recovery. A nomogram resulted from fitting a proportional odds logistic model for ordinal outcomes, with 1-year sexual function as a dependent variable and baseline sexual potency, age, body mass index (BMI), clinical stage, biopsy GS, initial prostate-specific antigen (iPSA), ASA score, and CCI as predictors. After further validation, this nomogram could be a useful tool for the pre-operative counselling.
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http://dx.doi.org/10.1111/and.13385DOI Listing
November 2019

Confirmatory multiparametric magnetic resonance imaging at recruitment confers prolonged stay in active surveillance and decreases the rate of upgrading at follow-up.

Prostate Cancer Prostatic Dis 2020 03 27;23(1):94-101. Epub 2019 Jun 27.

Department of Urology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, Milan, Italy.

Background: To understand the value of multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies at recruitment on active surveillance (AS) outcomes.

Materials And Methods: This retrospective single-center study enrolled two cohorts of 206 and 310 patients in AS. The latter group was submitted to mpMRI and targeted biopsies at recruitment. Kaplan-meier curves quantified progression-free survival (PFS) and Bioptic-PFS (B-PFS: no upgrading or >3 positive cores) in the two cohorts. Cox-regression analyses tested independent predictors of PFS and B-PFS. In patients submitted to radical prostatectomy (RP) after AS, significant cancer (csPCa) was defined as: GS ≥ 4 + 3 and/or pT ≥ 3a and/or pN+ . Logistic-regression analyses predicted csPCa at RP.

Results And Limitations: Median time follow-up and median time of persistence in AS were 46 (24-70) and 36 (23-58) months, respectively. Patients submitted to mpMRI at AS begin, showed greater PFS at 1- (98% vs. 91%), 3- (80% vs. 57%), and 5-years (70% vs. 35%) follow-up, respectively (all p < 0.01). At Cox-regression analysis only confirmatory mpMRI± targeted biopsy (HR: 0.3; 95% CI 0.2-0.5; p < 0.01) at AS begin was an independent predictor of PFS. Globally, 50 (16%) vs. 128 (62%) and 26 (8.5%) vs. 64 (31%) [all p < 0.01] men in the two groups experienced any-cause and bioptic AS discontinuation, respectively. Patients submitted to confirmatory mpMRI experienced greater 1-(98% vs. 93%), 3-(90% vs. 75%), and 5-years (83% vs. 56%) B-PFS, respectively (all p < 0.01). At Cox-regression analysis, mpMRI±-targeted biopsy at AS begin was associated with B-PFS (HR: 0.3; 95% CI 0.2-0.6; p < 0.01). No differences were recorded in csPCa rates between the two groups (22% vs. 28%; p = 0.47). Limitations of the study are the single-center retrospective nature and the absence of long-term follow-up.

Conclusions: Confirmatory mpMRI±-targeted biopsies are associated with higher PFS and B-PFS during AS. However, a non-negligible percentage of patients experience csPCa after switching to active treatment.
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http://dx.doi.org/10.1038/s41391-019-0160-3DOI Listing
March 2020

Cost of dispersal in a social mammal: body mass loss and increased stress.

Proc Biol Sci 2019 02;286(1896):20190033

1 Department of Evolutionary Biology and Environmental Studies, University of Zurich , Winterthurerstrasse 190, 8057 Zurich , Switzerland.

Dispersal is a key process influencing the dynamics of socially and spatially structured populations. Dispersal success is determined by the state of individuals at emigration and the costs incurred after emigration. However, quantification of such costs is often difficult, due to logistical constraints of following wide-ranging individuals. We investigated the effects of dispersal on individual body mass and stress hormone levels in a cooperative breeder, the meerkat ( Suricata suricatta). We measured body mass and faecal glucocorticoid metabolite (fGCM) concentrations from 95 dispersing females in 65 coalitions through the entire dispersal process. Females that successfully settled lost body mass, while females that did not settle but returned to their natal group after a short period of time did not. Furthermore, dispersing females had higher fGCM levels than resident females, and this was especially pronounced during the later stages of dispersal. By adding information on the transient stage of dispersal and by comparing dispersers that successfully settled to dispersers that returned to their natal group, we expand on previous studies focusing on the earlier stages of dispersal. We propose that body mass and stress hormone levels are good indicators to investigate dispersal costs, as these traits often play an important role in mediating the effects of the environment on other life-history events and individual fitness.
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http://dx.doi.org/10.1098/rspb.2019.0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408599PMC
February 2019

Predicting trajectories of recovery in prostate cancer patients undergone Robot-Assisted Radical Prostatectomy (RARP).

PLoS One 2019 4;14(4):e0214682. Epub 2019 Apr 4.

Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

Objective: To identify trends of patients' urinary and sexual dysfunctions from a clinical and psychological perspective and understand whether sociodemographic and medical predictors could differentiate among patients following different one-year longitudinal trajectories.

Methods: An Italian sample of 478 prostate cancer patients undergone Robot-Assisted Radical Prostatectomy completed the EPIC-26 survey between July 2015 and July 2016 at the pre-hospitalization (T0), 45 days (T1) and 3 (T2), 6 (T3), 9 (T4), and 12 months (T5) after surgery. Sociodemographic and clinical characteristics (age, BMI, diabetes, nerve-sparing procedure) were also collected. Latent Class Growth Analysis was conducted separately for sexual dysfunction and urinary incontinence EPIC-26 subscales. The association between membership in the two longitudinal trajectories of urinary and sexual dysfunctions was assessed by considering Chi-square test and its related contingency table.

Results: People who have a high level of urinary incontinence at T1 are likely to have a worse recovery. Age, BMI and pre-surgical continence may affect the level of incontinence at T1 and the recovery trajectories. Patients with low and moderate sexual problems at T1 can face a moderate linear recovery, while people with high level of impotence immediately after surgery may take a longer period to solve sexual dysfunctions. Age and the pre-surgical sexual condition may impact the recovery. Finally, a great proportion of patients reported both steady problems in sexual function and constant high levels of urinary incontinence over time.

Conclusions: This study highlights different categories of patients at risk who may be important to know in order to develop personalized medical pathways and predictive models in a value-based healthcare.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214682PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448842PMC
January 2020

Life history responses of meerkats to seasonal changes in extreme environments.

Science 2019 Feb;363(6427):631-635

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich 8057, Switzerland.

Species in extreme habitats increasingly face changes in seasonal climate, but the demographic mechanisms through which these changes affect population persistence remain unknown. We investigated how changes in seasonal rainfall and temperature influence vital rates and viability of an arid environment specialist, the Kalahari meerkat, through effects on body mass. We show that climate change-induced reduction in adult mass in the prebreeding season would decrease fecundity during the breeding season and increase extinction risk, particularly at low population densities. In contrast, a warmer nonbreeding season resulting in increased mass and survival would buffer negative effects of reduced rainfall during the breeding season, ensuring persistence. Because most ecosystems undergo seasonal climate variations, a full understanding of species vulnerability to global change relies on linking seasonal trait and population dynamics.
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http://dx.doi.org/10.1126/science.aau5905DOI Listing
February 2019

Neutrophil, Platelets, and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk Prostate Cancer Patients.

Urol Int 2019 8;102(1):43-50. Epub 2018 Nov 8.

Division of Urology, European Institute of Oncology, Milan, Italy.

Background: Several biochemical and clinical markers have been proposed for selecting patients for active surveillance (AS). However, some of these are expensive and not easily accessible. Moreover, currently about 30% of patients on AS harbor aggressive disease. Hence, there is an urgent need for other tools to accurately identify patients with low-risk prostate cancer (PCa).

Patients: We retrospectively reviewed the medical records of 260 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/mL, 2 or fewer cores involved with cancer, Gleason score (GS) ≤6 grade, and prostate-specific antigen density < 0.2 ng/mL/cc.

Methods: Univariate and multivariate analyses were performed to evaluate the association of patient and tumor characteristics with reclassification, defined as upstaged (pathological stage >pT2) and upgraded (GS ≥7) disease. A base model (age, prostate-specific antigen, prostate volume, and clinical stage) was compared with models considering neutrophil to lymphocyte ratio (NLR) or platelets to lymphocyte ratio (PLR), monocyte to lymphocyte (MLR), and eosinophil to lymphocyte ratio (ELR). OR and 95% CI were calculated. Finally, a decision curve analysis was performed.

Results: Univariate and multivariate analyses showed that NLR, PLR, and ELR upgrading were significantly associated with upgrading (ORs ranging from 2.13 to 4.13), but not with upstaging except for MLR in multivariate analysis, showing a protective effect.

Conclusion: Our results showed that NLR, PLR, and ELR are predictors of Gleason upgrading. Therefore, these inexpensive and easily available tests might be useful in the assessment of low-risk PCa, when considering patients for AS.
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http://dx.doi.org/10.1159/000494259DOI Listing
March 2019

Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT).

Br J Radiol 2019 Feb 9;92(1094):20180494. Epub 2018 Nov 9.

1 Division of Radiation Oncology, European Institute of Oncology IRCCS , Milan , Italy.

Objective:: To evaluate high-precision external beam reirradiation (re-EBRT) for local relapse of prostate cancer (PCa) after radiotherapy.

Methods:: This retrospective study included patients with biochemical failure and evidence of isolated local recurrence of PCa after radical/salvage EBRT or brachytherapy that received salvage stereotactic body radiation therapy (SBRT, re-EBRT). Biopsy was not mandatory if all diagnostic elements were univocal (prostate specific antigen evolution, choline-positron emission tomography or magnetic resonance imaging). Salvage SBRT (re-EBRT) was delivered with image-guided radiation therapy (RapidArc®, VERO® and CyberKnife®).

Results:: Data of 64 patients were included, median age at salvage SBRT was 73.2 years, median pre-salvage SBRT prostate specific antigen was 3.89  ng ml . Median total dose was 30  Gy in five fractions, biologically effective dose (BED) of 150  Gy. One acute G3 genitourinary event and one late G3 genitourinary event were observed. No G ≥ 3 bowel toxicity was registered. At the median follow-up of 26.1 months, tumor progression was observed in 41 patients (64%). 18 patients (28%) experienced local relapse. 2-year local control, biochemical and clinical relapse free survival rates were 75, 40 and 53%, respectively. With BED ≥130  Gy 1-year biochemical and clinical progression-free survival rate were 85 and 90%, respectively.

Conclusions:: Salvage SBRT (re-EBRT) for isolated local PCa recurrence is a safe, feasible and noninvasive salvage treatment. Further investigation is warranted to define the optimal patient selection, dose and volume parameters.

Advances In Knowledge:: Salvage SBRT reirradiation for the locally recurrent PCa offer a satisfactory tumor control and excellent toxicity profile, if BED ≥130 Gy is administered.
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http://dx.doi.org/10.1259/bjr.20180494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404844PMC
February 2019

Long-term oncologic and functional outcomes after robot-assisted partial nephrectomy in elderly patients.

Minerva Urol Nefrol 2019 Feb 19;71(1):31-37. Epub 2018 Sep 19.

Department of Urology, European Institute of Oncology, Milan, Italy.

Background: The aim of this study was to assess the long-term oncologic and functional outcomes in elderly patients having undergone robot-assisted partial nephrectomy (RAPN) for renal cancer (RC).

Methods: Sixty-one patients out of 323 who underwent RAPN for localized RC between July 2009 and March 2016 in our high-volume robotic surgery center (>800 procedures/year), had 70 years or more. Inclusion criteria of the study were age ≥70 years; pathological confirmed RCC and ASA Score ≤3. All patients were stratified according to PADUA classification system in three groups: <7 points, 8-9 points, >10 points. Trifecta was defined as a warm ischemia time (WIT) less then 25 min, negative surgical margins and no perioperative complications.

Results: A total of 52 patients were included; median follow-up was 47 months. Median age was 74 yrs. (IQR 72-76.5). Complication rate was 15.4%. Trifecta failure was associated to PADUA Score (P=0.02), and tumor diameter (P=0.04). Renal function was altered in 10 (19.2%) patients before surgery and at last follow-up in 11 (21.1%) patients (CKD stage>2) The DFS, OS and CSS were 89.33%, 90.06% and 94.4%, respectively.

Conclusions: In a high-volume center, robot-assisted approach is feasible and safe in surgical fit elderly patients with good long-term oncologic outcomes.
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http://dx.doi.org/10.23736/S0393-2249.18.03006-0DOI Listing
February 2019

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer.

World J Urol 2019 Mar 10;37(3):507-514. Epub 2018 Jul 10.

Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.

Purpose: The body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC).

Methods: A total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression.

Results: After re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9.

Conclusions: The BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.
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http://dx.doi.org/10.1007/s00345-018-2397-1DOI Listing
March 2019

Density-dependent dispersal strategies in a cooperative breeder.

Ecology 2018 09 27;99(9):1932-1941. Epub 2018 Jul 27.

Department of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, Zurich, CH-8057, Switzerland.

Dispersal is a key ecological process that influences the dynamics of spatially and socially structured populations and consists of three stages-emigration, transience, and settlement-and each stage is influenced by different social, individual, and environmental factors. Despite our appreciation of the complexity of the process, we lack a firm empirical understanding of the mechanisms underlying the different stages. Here, using data from 65 GPS-collared dispersing female coalitions of the cooperatively breeding meerkat (Suricata suricatta), we present a comprehensive analysis of the effects of population density, mate availability, dispersing coalition size, and individual factors on each of the three stages of dispersal in a wild population. We expected a positive effect of density on dispersal due to increased kin competition at high densities. We further anticipated positive effects of mate availability, coalition size, and body condition on dispersal success. We observed increasing daily emigration and settlement probabilities at high population densities. In addition, we found that emigration and settlement probabilities also increased at low densities and were lowest at medium densities. Daily emigration and settlement probabilities increased with increasing female coalition size and in the presence of unrelated males. Furthermore, the time individuals spent in the transient stage increased with population density, whereas coalition size and presence of unrelated males decreased dispersal distance. The observed nonlinear relationship between dispersal and population density is likely due to limited benefits of cooperation at low population densities and increased kin competition at high densities. Our study provides empirical validation for the theoretical predictions that population density is an important factor driving the evolution of delayed dispersal and philopatry in cooperative breeders.
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http://dx.doi.org/10.1002/ecy.2433DOI Listing
September 2018

Multiparametric Magnetic-Resonance to Confirm Eligibility to an Active Surveillance Program for Low-Risk Prostate Cancer: Intermediate Time Results of a Third Referral High Volume Centre Active Surveillance Protocol.

Urol Int 2018 7;101(1):56-64. Epub 2018 May 7.

Department of Urology, Istituto Europeo di Oncologia (IEO), Milan, Italy.

Background: To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification.

Materials: From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP.

Results: PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively.

Conclusions: MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions.
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http://dx.doi.org/10.1159/000488772DOI Listing
January 2019

Meta-analysis of studies comparing oncologic outcomes of radical prostatectomy and brachytherapy for localized prostate cancer.

Ther Adv Urol 2017 Nov 9;9(11):241-250. Epub 2017 Oct 9.

Division of Urology, European Institute of Oncology, Milan, Italy Università Degli Studi Di Milano, Milan, Italy.

Background: The aim of this study was to compare oncologic outcomes of radical prostatectomy (RP) with brachytherapy (BT).

Methods: A literature review was conducted according to the 'Preferred reporting items for systematic reviews and meta-analyses' (PRISMA) statement. We included studies reporting comparative oncologic outcomes of RP BT for localized prostate cancer (PCa). From each comparative study, we extracted the study design, the number and features of the included patients, and the oncologic outcomes expressed as all-cause mortality (ACM), PCa-specific mortality (PCSM) or, when the former were unavailable, as biochemical recurrence (BCR). All of the data retrieved from the selected studies were recorded in an electronic database. Cumulative analysis was conducted using the Review Manager version 5.3 software, designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). Statistical heterogeneity was tested using the Chi-square test.

Results: Our cumulative analysis did not show any significant difference in terms of BCR, ACM or PCSM rates between the RP and BT cohorts. Only three studies reported risk-stratified outcomes of intermediate- and high-risk patients, which are the most prone to treatment failure.

Conclusions: our analysis suggested that RP and BT may have similar oncologic outcomes. However, the analysis included a limited number of studies, and most of them were retrospective, making it impossible to derive any definitive conclusion, especially for intermediate- and high-risk patients. In this scenario, appropriate urologic counseling remains of utmost importance.
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http://dx.doi.org/10.1177/1756287217731449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896855PMC
November 2017

Socially informed dispersal in a territorial cooperative breeder.

J Anim Ecol 2018 05 12;87(3):838-849. Epub 2018 Feb 12.

Department of Evolutionary Biology and Environmental Studies, Zurich University, Zürich, Switzerland.

Dispersal is a key process governing the dynamics of socially and spatially structured populations and involves three distinct stages: emigration, transience and settlement. At each stage, individuals have to make movement decisions, which are influenced by social, environmental and individual factors. Yet, a comprehensive understanding of the drivers that influence such decisions is still lacking, particularly for the transient stage during which free-living individuals are inherently difficult to follow. Social circumstances such as the likelihood of encountering conspecifics can be expected to strongly affects decision-making during dispersal, particularly in territorial species where encounters with resident conspecifics are antagonistic. Here, we analysed the movement trajectories of 47 dispersing coalitions of Kalahari meerkats Suricata suricatta through a landscape occupied by constantly monitored resident groups, while simultaneously taking into account environmental and individual characteristics. We used GPS locations collected on resident groups to create a georeferenced social landscape representing the likelihood of encountering resident groups. We used a step-selection function to infer the effect of social, environmental and individual covariates on habitat selection during dispersal. Finally, we created a temporal mismatch between the social landscape and the dispersal event of interest to identify the temporal scale at which dispersers perceive the social landscape. Including information about the social landscape considerably improved our representation of the dispersal trajectory compared to analyses that only accounted for environmental variables. The latter were only marginally selected or avoided by dispersers. Before leaving their natal territory, dispersers selected areas frequently used by their natal group. In contrast, after leaving their natal territory, they selectively used areas where they were less likely to encounter unrelated groups. This pattern was particularly marked in larger dispersing coalitions and when unrelated males were part of the dispersing coalition. Our results suggest that, in socially and spatially structured species, dispersers gather and process social information during dispersal, and that reducing risk of aggression from unrelated resident groups outweighs benefits derived from conspecific attraction. Finally, our work underlines the intimate link between the social structure of a population and dispersal, which affect each other reciprocally.
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http://dx.doi.org/10.1111/1365-2656.12795DOI Listing
May 2018

Robot-assisted Partial Nephrectomy: 5-yr Oncological Outcomes at a Single European Tertiary Cancer Center.

Eur Urol Focus 2019 Jul 27;5(4):636-641. Epub 2017 Oct 27.

Division of Urology, European Institute of Oncology, Milan, Italy; University of Milan, Milan, Italy.

Background: Nowadays, there is a debate about which surgical treatment should be best for clinical T1 renal tumors. If the oncological outcomes are considered, there are many open and laparoscopic series published. As far as robotic series are concerned, only a few of them report 5-yr oncological outcomes.

Objective: The aim of this study was to analyze robot-assisted partial nephrectomy (RAPN) midterm oncological outcomes achieved in a tertiary robotic reference center.

Design, Setting, And Participants: Between April 2009 and September 2013, 123 consecutive patients with clinical T1-stage renal masses underwent RAPN in our tertiary cancer center. Inclusion criteria were as follows: pathologically confirmed renal cell carcinomas (RCCs) and follow-up for >12 mo. Eighteen patients were excluded due to follow-up of <12 mo and 15 due to benign final pathology. Median follow-up was 59 mo (interquartile range 44-73 mo). Patients were followed according to guideline recommendations and institutional protocol.

Outcome Measurements And Statistical Analysis: Outcomes were measured by time to disease progression, overall survival, or time to cancer-specific death. Kaplan-Meier method was used to estimate survival; log-rank tests were applied for pair-wise comparison of survival.

Results And Limitations: From the 90 patients included, 66 (73.3%) had T1a, 12 (13.3%) T1b, three (3.3%) T2a, and nine (10%) T3a tumors. Predominant histological type was clear cell carcinoma: 67 (74.5%). Fuhrmann grade 1 and 2 was found in 73.3% of all malignant tumors. Two patients (2.2%) had positive surgical margins, and complication rate was 17.8%. Relapse rate was 7.7%, including two cases (2.2%) of local recurrences and five (5.5%) distant metastasis. Five-year disease-free survival was 90.9%, 5-yr cancer-specific survival was 97.5%, and 5-yr overall survival was 95.1%.

Conclusions: Midterm oncological outcomes after RAPN for localized RCCs (predominantly T1a tumors of low anatomic complexity) were shown to be good, adding significant evidence to support the oncological efficacy and safety of RAPN for the treatment of this type of tumors.

Patient Summary: Robot-assisted partial nephrectomy seems to be the most promising minimally invasive approach in the treatment of renal masses suitable for organ-sparing surgery as midterm (5 yr) oncological outcomes are excellent.
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http://dx.doi.org/10.1016/j.euf.2017.10.005DOI Listing
July 2019

Outcomes of robot-assisted simple enucleation of renal masses: A single European center experience.

Medicine (Baltimore) 2017 May;96(18):e6771

Division of Urology, European Institute of Oncology, Milan, Italy Department of Urology, University of Medicine and Pharmacy 'Iuliu Hatieganu' Cluj-Napoca Department of Cell and Molecular Biology, University of Medicine and Pharmacy, Targu Mures, Romania Department of Laboratory and Pathology, European Institute of Oncology, Milan, Italy University of Milan, Milan Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.

The aim of this study was to assess the ability of pre-and intraoperative parameters, to predict the risk of perioperative complications after robot-assisted laparoscopic simple enucleation (RASE) of renal masses, and to evaluate the rate of trifecta achievement of this approach stratifying the cohort according to the use of ischemia during the enucleation.From April 2009 to June 2016, 129 patients underwent RASE at our Institution. We stratified the procedures in 2 groups: clamping and clamp-less RASE. After RASE, all specimens were retrospectively reviewed to assess the surface-intermediate-base (SIB) scoring system. Patients were followed-up according to the European Association of Urology guidelines recommendations. All pre-, intra-, and postoperative outcomes were prospectively collected in a customized database and retrospectively analyzed.A total of 112 (86.8%) patients underwent a pure RASE and 17 (13.2%) had a hybrid according to SIB classification system. The mean age was 61.17 years. In 21 patients (16.3%), complications occurred, 13 (61.9%) were Clavien 1 and 2, while 8 were Clavien 3a and b complications. Statistical significant association with complications was found in patients with American Society of Anestesiology (ASA) score 3 (44.5%, P = .04), longer mean operative time (OT) 195 versus 161.36 minutes (P =.03), mean postoperative hemoglobin (Hb) 10.1 versus 11.8 (P <.001), and mean ΔHb 3.59 versus 2.18 (P <.001). In multivariate logistic regression, only longer OT and ΔHb were statistical significant predictive factors for complications. In sub-group analysis, clamp-less RASE was safe in terms of complications (14.1%), positive surgical margins (1.3%), and mid-term local recurrence (1.3%). Although in this approach there is higher EBL (P = .01), this had no impact on ΔHb (P = .28). A clamp-less approach was associated with a higher rate of SIB 0 (71.8% vs 51%, P = .02), higher trifecta achievement (84.6% vs 62.7%, P = .004), and better impact on serum creatinine (mean 0.83 vs 0.91, P = .01).RASE of renal tumors is a safe technique with very good postoperative outcomes. Complication rate is low and associated with ASA score >3, longer OT, and ΔHb. RASE is suitable for the clamp-less approach, which allows to perform easier the pure enucleation (SIB 0) and to obtain higher rates of trifecta outcomes.
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http://dx.doi.org/10.1097/MD.0000000000006771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419918PMC
May 2017

Reliability of Frozen Section Examination in a Large Cohort of Testicular Masses: What Did We Learn?

Clin Genitourin Cancer 2017 08 1;15(4):e689-e696. Epub 2017 Feb 1.

Division of Urology, European Institute of Oncology, Milan, Italy; University of Milan, Milan, Italy.

Background: Frozen section examination (FSE) for testicular masses is gaining popularity because of the possibility of performing testis-sparing surgery (TSS) on the basis of the FSE results. The aim of our study was to investigate the reliability of FSE in the diagnosis of testicular masses.

Patients And Methods: From 1999 to 2016, 144 of 692 patients who underwent surgery in our tertiary center for testicular masses had FSE. The indications for FSE were: masses < 1 cm, nonpalpable, multiple, or with unusual presentation. Mean follow-up for patients was 25.5 months. The algorithm of surgery determined by FSE was: orchiectomy if malignant or nonconclusive pathology; TSS if benign or nontumor pathology. FSE data were analyzed retrospectively. Specificity and sensitivity of the method was calculated for benign, malignant, seminoma, and nonseminoma tumors.

Results: Intraoperative FSE was conducted on 21% of candidates for surgery on testicular masses. The sensitivity and specificity of FSE were 93% and 98%, respectively, for malignant tumors, and 90% and 99%, respectively, for benign tumors. The κ agreement coefficient between FSE and final histopathology was statistically significant (0.76). TSS was performed in 57 (40%) patients, including 6 of 23 monorchid patients.

Conclusion: FSE correlates well with final histopathological diagnosis of testicular masses. Thus, it reliably identifies patients who might benefit from TSS. FSE should be considered always in small, nonpalpable, multiple, or uncommonly presenting masses in solitary testis or both testes.
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http://dx.doi.org/10.1016/j.clgc.2017.01.012DOI Listing
August 2017

Cell-cycle Progression-score Might Improve the Current Risk Assessment in Newly Diagnosed Prostate Cancer Patients.

Urology 2017 Apr 25;102:73-78. Epub 2016 Nov 25.

Department of Surgical Sciences, Urology, University of Turin, Turin, Italy. Electronic address:

Objective: To assess whether cell-cycle progression (CCP)-score (Prolaris) can improve the current risk assessment in newly diagnosed prostate cancer (PCa) patients. CCP-score is a well-validated prognostic assay predictive of PCa death, biochemical recurrence, and progression.

Methods: We evaluated CCP-score at biopsy in 52 patients newly diagnosed with PCa who underwent radical prostatectomy. CCP-score was calculated as average RNA expression of 31 CCP genes, normalized to 15 housekeeping genes. The predictive ability of CCP-score was assessed in univariate and multivariate analyses, and compared to that of Ki-67 levels and traditional clinical variables including prostate-specific antigen, Gleason score, stage, and percentage of positive cores at biopsy.

Results: In spite of an overall good accuracy in attributing the correct risk class, 7 high-risk and 13 intermediate-risk patients were misclassified by the Prolaris test. On analysis of variance, mean CCP-score significantly differed across different risk classes based on pathologic results (-1.2 in low risk, -0.444 in intermediate risk, 0.208 in high risk). CCP-score was a significant predictor of high-risk PCa both on univariate and multivariate analyses, after adjusting for clinical variables. Combining CCP-score and the European Association of Urology clinical risk assessment improved the accuracy of risk attribution by around 10%, up to 87.8%. CCP-score was a significant predictor of biochemical recurrence, but only on univariate analysis.

Conclusion: The CCP-score might provide important new information to risk assessment of newly diagnosed PCa in addition to traditional clinical variables. A correct risk attribution is essential to tailor the best treatment for each patient.
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http://dx.doi.org/10.1016/j.urology.2016.11.038DOI Listing
April 2017

Virtue male sling for post-prostatectomy stress incontinence: a prospective evaluation and mid-term outcomes.

BJU Int 2017 03 1;119(3):482-488. Epub 2016 Nov 1.

Department of Urology, European Institute of Oncology, Milan, Italy.

Objective: To evaluate the efficacy and safety of the Virtue male sling (Coloplast, Humlebaek, Denmark) in a cohort of patients affected by post-prostatectomy stress urinary incontinence (SUI).

Methods: All 29 consecutive patients treated with a Virtue male sling at our Institution between July 2012 and October 2013 were included in the present prospective, non-randomized study. Patients were evaluated preoperatively and at 1, 3, 6, 12, 24 and 36 months after surgery using a 24-h pad weight test, the International Consultation on Incontinence short-form questionnaire (ICIQ-SF), Urinary Symptom Profile (USP) questionnaire, a bladder diary, uroflowmetry and the Patient Global Impression of Improvement (PGI-I) and Patient Global Impression of Severity questionnaires.

Results: The mean patient age was 65.5 years. A total of 72.4% of patients had preoperative mild incontinence (1-2 pads/day), while nine patients used 3-5 pads/day. There were a total of 17 complications, which occurred in 29 patients (58.6%); all were Clavien-Dindo grade I. At 12-month follow-up patients showed a significant improvement in 24-h pad test (128.6 vs 2.5 g), number of pads per day (2 vs 0), ICIQ-SF score (14.3 vs 0.9) and USP score for SUI (4 vs 0), and outcomes remained stable at 36 months. At last follow-up, the median score on the PGI-I questionnaire was 1 (very much better).

Conclusion: The Virtue male sling is an effective treatment option for low to moderate post-prostatectomy incontinence.
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http://dx.doi.org/10.1111/bju.13672DOI Listing
March 2017

Serosurvey for Selected Viral Pathogens among Sympatric Species of the African Large Predator Guild in Northern Botswana.

J Wildl Dis 2017 01 20;53(1):170-175. Epub 2016 Oct 20.

4 Botswana Predator Conservation Trust, Private Bag 13, Maun, Botswana.

The recent increase in the creation of transboundary protected areas and wildlife corridors between them lends importance to information on pathogen prevalence and transmission among wildlife species that will become connected. One such initiative is the Kavango Zambezi Transfrontier Conservation Area of which Botswana's Okavango Delta constitutes a major contribution for wildlife and ecosystems. Between 2008 and 2011, we collected serum samples from 14 lions ( Panthera leo ), four leopards ( Panthera pardus ), 19 spotted hyenas ( Crocuta crocuta ), and six cheetahs ( Acinonyx jubatus ) in the Okavango. Samples were tested for antibodies against canine distemper virus (CDV), feline panleukopenia virus, enteric coronavirus, feline calicivirus, feline herpesvirus (FHV-1), and feline immunodeficiency virus (FIV). Evidence of exposure to all of these pathogens was found, to varying degrees, in at least one of the species sampled. High antibody prevalence (>90%) was only found to FHV-1 and FIV in lions. Only hyenas (26%, 5/19) were positive for CDV antibody. Except for one case, all individuals displayed physical conditions consistent with normal health for ≥12 mo following sampling. Our results emphasize the need for a comprehensive, multispecies approach to disease monitoring and the development of coordinated management strategies for subpopulations likely to be connected in transboundary initiatives.
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http://dx.doi.org/10.7589/2015-11-302DOI Listing
January 2017

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy.

Medicine (Baltimore) 2016 Oct;95(40):e4519

Division of Urology Division of Radiology Division of Pathology, European Institute of Oncology Università degli Studi di Milano, Milan, Italy Department of Urology "Iuliu Hatieganu," University of Medicine and Pharmacy, Cluj-Napoca, Romania.

To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage
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http://dx.doi.org/10.1097/MD.0000000000004519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059027PMC
October 2016