Francesco Montorsi

Università Vita-Salute San Raffaele, Milano, Lombardy, Italy

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Publications (804)4582.42 Total impact

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    ABSTRACT: Perioperative transfusions have been recently associated to poor outcomes as an indirect consequence of immune-hematological changes related to transfusion itself and blood type. We tested the role of blood transfusion on cancer-specific mortality (CSM) and overall mortality (OM), considering the effect of ABO system, Rh factor, and timing of transfusions.
    No preview · Article · Feb 2016
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    ABSTRACT: Introduction: To develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). Materials & methods: The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. Results: The 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6-87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8-10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0-91.7%). External validation of our nomogram showed a good PA at 83.2%. Conclusions: We developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment.
    No preview · Article · Feb 2016 · European journal of cancer (Oxford, England: 1990)
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    Giorgio Gandaglia · Alberto Briganti · Francesco Montorsi

    Preview · Article · Feb 2016 · European Urology
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    ABSTRACT: To address the thus far poorly investigated severity and duration of hematologic toxicity (HT) from whole-pelvis radiotherapy (WPRT) in a cohort of chemo-naïve patients treated with post-prostatectomy radiotherapy including WPRT with different IMRT techniques, doses and fractionations.
    No preview · Article · Jan 2016 · International journal of radiation oncology, biology, physics
  • Giorgio Gandaglia · Francesco Montorsi · Alberto Briganti

    No preview · Article · Jan 2016 · International Journal of Urology
  • Eugenio Ventimiglia · Francesco Montorsi · Andrea Salonia
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    ABSTRACT: Purpose of review: The purpose of this review is to analyze the current literature concerning health status in the setting of male infertility, taking into account the potential contribution of each comorbidity. Recent findings: Latest findings, almost unanimously confirmed how infertile patients usually display a quite precarious health, because of the collection of coexistent diseases observed in these men. More precisely, relevant comorbidities might influence not only man's fertility but his life expectancy as well. Moreover, because of the increasing trend in delaying fatherhood observed in Western countries over time, age might somehow act as a possible detrimental factor. Overall, what emerges from these studies is a complex and worrisome scenario. Summary: General health status in the male reproductive setting is gaining increasing clinical attention and relevance. Infertile men appear to be rather unhealthy young men as compared with fertile ones. Therefore, uroandrologists are challenged with the compelling task of assessing the infertile man considering both his general and his reproductive health, since relevant comorbid conditions may influence not only his life expectancy, but his fertility as well.
    No preview · Article · Jan 2016 · Current opinion in urology
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    ABSTRACT: Objective: In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. Materials and methods: Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. Results: The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). Conclusions: Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.
    Full-text · Article · Dec 2015 · Urologic Oncology
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    ABSTRACT: Purpose: The purpose of this study is to review the current literature concerning the indication of pelvic lymph node dissection (PLND), its extent and complications in prostate cancer (PCa) staging, the available tools, and the future perspectives to assess the risk of lymph node invasion (LNI). Methods: A literature review was performed using the Medline, Embase, and Web of Science databases. The search strategy included the terms pelvic lymph nodes, PLND, radical prostatectomy, prostate cancer, lymph node invasion, biochemical recurrence, staging, sentinel lymph node dissection, imaging, and molecular markers. Results: PLND currently represents the gold standard for nodal staging in PCa patients. Available imaging techniques are characterized by poor accuracy in the prediction of LNI before surgery. On the contrary, an extended PLND (ePLND) would result into proper staging in the majority of the cases. Several models based on preoperative disease characteristics are available to assess the risk of LNI. Although ePLND is not associated with a substantial risk of severe complications, up to 10% of the men undergoing this procedure experience lymphoceles. Concerns over potential morbidity of ePLND led many authors to investigate the role of sentinel lymph node dissection in order to prevent unnecessary ePLND. Finally, the incorporation of novel biomarkers in currently available tools would improve our ability to identify men who should receive an ePLND. Conclusions: Nowadays, the most informative tools predicting LNI in PCa patients consist in preoperative clinical nomograms. Sentinel lymph node dissection still remains experimental and novel biomarkers are needed to identify patients at a higher risk of LNI.
    No preview · Article · Dec 2015 · Urologia
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    ABSTRACT: Background: Metastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits. Methods and results: The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. Conclusion: In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.
    No preview · Article · Dec 2015 · World Journal of Urology
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    ABSTRACT: Introduction: In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI). Methods: At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status. Results: Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9-4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1-1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI. Conclusions: Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.
    No preview · Article · Dec 2015 · World Journal of Urology
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    ABSTRACT: Many pathological changes in solid tumours are caused by the accumulation of genetic mutations and epigenetic molecular alterations. In addition, tumour progression is profoundly influenced by the environment surrounding the transformed cells. The interplay between tumour cells and their microenvironment has been recognized as one of the key determinants of cancer development and is being extensively investigated. Data suggest that both the extracellular matrix and the microbiota represent microenvironments that contribute to the onset and progression of tumours. Through the introduction of omics technologies and pyrosequencing analyses, a detailed investigation of these two microenvironments is now possible. In urological research, assessment of their dysregulation has become increasingly important to provide diagnostic, prognostic and predictive biomarkers for urothelial bladder cancer. Understanding the roles of the extracellular matrix and microbiota, two key components of the urothelial mucosa, in the sequelae of pathogenic events that occur in the development and progression of urothelial carcinomas will be important to overcome the shortcomings in current bladder cancer treatment strategies.
    Full-text · Article · Dec 2015 · Nature Reviews Urology
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    ABSTRACT: Introduction: Phosphodiesterase type 5 inhibitors (PDE5Is) are the leading drugs for the treatment of erectile dysfunction (ED), being recommended as a first line treatment by both the European and US urological guidelines. PDE5Is are highly effective as compared to placebo, well tolerated and have a very low, though not negligible, rate of severe treatment-related adverse events. Areas covered: This paper reviews the safety profile of currently available PDE5Is, comparing them in a broad spectrum ED population and outlining a number of real-life aspects of importance in the real-life everyday clinical setting. Expert opinion: Guidelines unanimously agree in considering PDE5Is as first line treatments for ED when well-tolerated and not contraindicated. Despite the fact that no high-grade evidence comparing the efficacy and the safety for PDE5Is is currently available, published data seem to suggest that there are no major differences in their safety profiles. Moreover, although oral PDE5Is were shown to cause more AEs than placebo, they were generally mild and well tolerated.
    No preview · Article · Dec 2015 · Expert Opinion on Drug Safety
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    ABSTRACT: Context: The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective: To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition: We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis: The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions: An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life-and the ability of testosterone therapy to mitigate these effects-has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency. Patient summary: In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.
    No preview · Article · Dec 2015 · European Urology
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    ABSTRACT: Background: A complete biochemical response (BR) immediately after surgery could be considered an indicator of optimal cancer control after radical prostatectomy (RP). Objective: To evaluate the prognostic value of early postoperative prostate-specific antigen (PSA) levels after RP in patients with lymph node invasion (LNI). Design, setting, and participants: The study included 319 prostate cancer patients with LNI who were treated with RP and extended pelvic lymph node dissection (ePLND) at a single institution between 1998 and 2013. All men had complete clinical, pathologic, and follow-up data, including PSA value at 6 wk after surgery. Patients were divided into two groups according to PSA value at 6 wk after surgery: complete BR (PSA <0.1 ng/ml) and PSA persistence (PSA ≥0.1 ng/ml). Outcome measurements and statistical analysis: Kaplan-Meier analyses were used to assess 8-yr clinical recurrence (CR) and cancer-specific mortality (CSM) rates according to PSA persistence after RP. Multivariable Cox regression analysis was used to test the association between PSA persistence and CR. Covariates consisted of pathologic Gleason score (≤7 vs ≥8), number of positive nodes, surgical margins status (negative vs positive), and adjuvant therapies (none vs androgen deprivation therapy (ADT) vs adjuvant radiotherapy plus ADT). When we performed multivariable analyses assessing the association between PSA persistence and CSM pathologic Gleason score represented the only covariate due to the low number of events (n=13). Results and limitations: Overall, 83 patients (26%) had PSA persistence. Men with PSA persistence had higher 8-yr CR and CSM rates than those with complete BR (69% vs 12% and 16% vs 4.2%, respectively; all p≤0.002). This was confirmed in multivariable analyses, where PSA persistence at 6 wk after surgery was an independent predictor of both CR (hazard ratio [HR]: 8.3; 95% confidence interval [CI], 4.73-14.7; p≤0.001) and CSM (HR: 2.16; 95% CI, 1.63-2.86; p≤0.001). Pathologic stage lower than pT3a, biopsy and pathologic Gleason score ≥8, positive surgical margins, and three or more positive lymph nodes were significantly associated with PSA persistence (all p≤0.04). Our study is limited by its retrospective design. Conclusions: Early BR can be achieved in approximately 75% of men with LNI submitted to RP and ePLND. PSA assessment early after surgery has an important prognostic role in the prediction of CR and CSM in node-positive patients. A risk stratification of these patients based on PSA persistence could guide physicians to properly select patients who may benefit the most from timely multimodal treatments. Patient summary: The risk of clinical recurrence and cancer-specific mortality is heterogeneous in patients with prostate cancer with lymph node invasion. Node-positive patients with complete biochemical response early after surgery share more favorable oncologic outcomes than those with PSA persistence. These results are important to plan the optimal postoperative patient management.
    No preview · Article · Dec 2015 · European Urology
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    ABSTRACT: A non-negligible proportion of prostate cancer (PCa) patients undergoing radical prostatectomy (RP) harbors aggressive disease. These individuals are at higher risk of experiencing recurrence after surgery. Results from prospective, randomized trials support the efficacy of adjuvant radiotherapy (aRT) on cancer control in selected patients with adverse disease features at RP. However, only one of these randomized trials found a significant benefit of aRT on survival. Although such a level of evidence is not currently available for salvage RT, retrospective studies demonstrated that this approach leads to excellent outcomes if administered at the earliest sign of PSA recurrence. Prognostic models might help clinicians in identifying patients who would benefit the most from adjuvant and/or salvage RT. This individualized approach would allow sparing the risk of short- and long-term toxicity in a substantial proportion of patients. Nonetheless, results from randomized trials are still awaited to compare the efficacy of (early) salvage and aRT.
    No preview · Article · Dec 2015 · Current Oncology Reports
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    ABSTRACT: Purpose: To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Material and methods: Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Results: Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20Gy) and smaller receiving 40-50Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p⩽0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. Conclusions: Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT.
    No preview · Article · Dec 2015 · Radiotherapy and Oncology
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    ABSTRACT: Introduction: Previous studies showed high hospital readmission rates after radical cystectomy (RC) for bladder cancer (BCa), however at the time results of a European series analyzing this event were still missing. Patients and methods: Overall, 1090 consecutive BCa patients treated with RC at a single center between January 2002 and August 2012 were identified. Logistic regression analyses were used to test the association between covariates and 30-day readmission in the overall population and after stratifying according age at the time of surgery. Results: Mean length of stay (LOS) was 19 days (median, 16 days), and the overall 30-day readmission rate was 12.2%. The most frequent reasons for readmission at 30 days were ileus (n = 15; 11.3%), lymphoceles (n = 11; 8.3%), wound infection (n = 10; 7.5%), and fever (n = 12; 9.0%). In multivariable logistic regression analysis, age (odds ratio [OR], 1.02; P = .04) and LOS (OR, 0.94; P < .01) were associated with 30-day readmission. However, when analyzed according age at the time of surgery, a beneficial effect from a longer LOS was observed only in patients older than 70 years (P < .003). Conclusion: In the first European series on the effect of 30-day readmission, our data showed that even with a relative high mean LOS, 30-day readmission remained an ineradicable factor. Of note, older patients and shorter LOS were associated with an increased risk of readmission at 30 days, however, an increase of LOS to prevent readmission seemed effective only in patients older than 70 years.
    No preview · Article · Dec 2015 · Clinical Genitourinary Cancer

  • No preview · Article · Dec 2015 · European Urology
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    ABSTRACT: The transient receptor potential (TRP) melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity (BO) is available. This study characterizes a new TRPM8-selective antagonist (DFL23448) and evaluates it in cold-induced behavioral tests and on bladder function and experimental BO in vivo in rats. DFL23448 displayed IC50 values of 10 and 21nM in hTRPM8 HEK-293 cells activated by Cooling Agent 10 or cold, but had limited activity (IC50 > 10μM) at TRPV1, TRPA1, TRPV4, or at various G-protein-coupled receptors. In rats, DFL23448 had a half-life of 37 minutes (intravenous; i.v.) or 4.9 hours (oral). DLF23448 (10mg/kg, i.v) reduced icilin-induced wet-dog shakes in rats. Intravesical (i.ves.) DFL23448 (10mg/L) but not vehicle increased micturition intervals (MI), micturition volumes (MV) and bladder capacity (BC). During BO by i.ves. PGE2, vehicle controls exhibited reductions of MI, MV and BC by 37-39%, whereas the same parameters only decreased by 12-15% (p<0.05-0.01 vs. vehicle) in DFL23448-treated rats. In vehicle-treated rats but not in DFL23448-treated rats, i.ves. PGE2 increased bladder pressures. Intravenous DFL23448 at 10mg/kg, but not 1mg/kg DFL23448 or vehicle, increased MI, MV, and BC. During BO by i.ves. PGE2, MI, MV, and BC decreased in vehicle- and in DFL23448 1mg/kg-treated rats, but not in DFL23448 10mg/kg-treated rats. Bladder pressures increased less in rats treated with DFL23448 10mg/kg than in vehicle- or DFL23448 1mg/kg- treated rats. DFL23448 (10mg/kg, i.v.), but not vehicle, prevented cold-stress BO. Our results support a role for bladder TRPM8-mediated signals in experimental BO.
    No preview · Article · Nov 2015 · Journal of Pharmacology and Experimental Therapeutics
  • Giorgio Gandaglia · Alberto Briganti · Andrea Salonia · Francesco Montorsi

    No preview · Article · Nov 2015 · European Urology

Publication Stats

12k Citations
4,582.42 Total Impact Points

Institutions

  • 2001-2016
    • Università Vita-Salute San Raffaele
      • Faculty of Psychology
      Milano, Lombardy, Italy
  • 2015
    • Elsevier B.V.
      Philadelphia, Pennsylvania, United States
  • 1994-2015
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2014
    • University of Rhode Island
      Кингстон, Rhode Island, United States
    • Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
      Reggio nell'Emilia, Emilia-Romagna, Italy
  • 1994-2014
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      • Dipartimento di Urologia
      Milano, Lombardy, Italy
  • 1989-2014
    • University of Milan
      • Department of Biology and Genetics for Medical Sciences
      Milano, Lombardy, Italy
  • 2013
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
  • 2012
    • Cornell University
      Итак, New York, United States
  • 2011-2012
    • Università Telematica San Raffaele
      Milano, Lombardy, Italy
  • 2010
    • Research Triangle Park Laboratories, Inc.
      Raleigh, North Carolina, United States
  • 2008
    • Keio University
      Edo, Tōkyō, Japan
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 1997
    • Prostate Cancer Research Institute
      Los Ángeles, California, United States