You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD61)1 May 2024PD61-04 LONG-TERM ONCOLOGICAL OUTCOMES OF SURGICALLY MANAGED VERY HIGH-RISK PROSTATE CANCER PATIENTS ACCORDING TO THE STAMPEDE TRIAL DEFINITION: IMPLICATIONS FOR THE SELECTION OF CANDIDATES FOR CLINICAL TRIALS Antony Pellegrino, Simone Scuderi, Elio Mazzone, Armando Stabile, Leonardo Quarta, Alfonso Santangelo, Vito Cucchiara, Mattia Longoni, Pietro Scilipoti, Paolo Zaurito, Alice Mannazzu, Alessandro Viti, Francesco Barletta, Roberta Lucianò, Nazario Pio Tenace, Daniele Robesti, Riccardo Leni, Giorgio Gandaglia, Francesco Montorsi, and Alberto Briganti Antony PellegrinoAntony Pellegrino , Simone ScuderiSimone Scuderi , Elio MazzoneElio Mazzone , Armando StabileArmando Stabile , Leonardo QuartaLeonardo Quarta , Alfonso SantangeloAlfonso Santangelo , Vito CucchiaraVito Cucchiara , Mattia LongoniMattia Longoni , Pietro ScilipotiPietro Scilipoti , Paolo ZauritoPaolo Zaurito , Alice MannazzuAlice Mannazzu , Alessandro VitiAlessandro Viti , Francesco BarlettaFrancesco Barletta , Roberta LucianòRoberta Lucianò , Nazario Pio TenaceNazario Pio Tenace , Daniele RobestiDaniele Robesti , Riccardo LeniRiccardo Leni , Giorgio GandagliaGiorgio Gandaglia , Francesco MontorsiFrancesco Montorsi , and Alberto BrigantiAlberto Briganti View All Author Informationhttps://doi.org/10.1097/01.JU.0001009352.31737.3d.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In STAMPEDE trial, high-risk non-metastatic prostate cancer (PCa) men, treated with a radiotherapy (RT) plus androgen deprivation therapy (ADT) and eventual androgen receptor signaling inhibitors showed outstanding survival outcomes. However, a surgical arm (i.e., radical prostatectomy [RP] + extended lymph node dissection [ePLND]) was not included. METHODS: We relied on a cohort of 11,038 RP±ePLND treated patients at a single referral centre between 1986-2023. Among these, 558 very high-risk PCa patients according to STAMPEDE definition (node positive or node negative + ≥2 of the following: stage T3-T4, ISUP Grade Group 8–10, PSA≥40 ng/mL) were identified. Multimodal treatment (MMT) was defined as the use of any neoadjuvant or adjuvant treatment. Biochemical recurrence (BCR) was defined as 2 consecutive PSA≥0.2 ng/ml. High-grade (HG) complications were defined as Clavien-Dindo ≥2 within 90 days. Kaplan-Meier (KM) plots depicted BCR-free survival rates (FSR) after 5-year follow-up. Multivariable Cox regression (MCR) model assessed the predictors of BCR. Urinary continence (UC) and erectile function (EF) recovery were defined as the use of no pads over 24 hours and IIEF-EF score ≥21. RESULTS: Overall, 152 (27%) and 406 (73%) received surgery alone and MMT. Men who received surgery alone had more favorable pathology outcomes than MMT, with lower rates of pT≥3a (29 vs 71%), ISUP GG 4-5 (50 vs 61%) and lymph node invasion (19% vs 67%; all p<0.001). A total of 80 (14%) patients had HG complications, with no differences between groups (15 vs 12% for MMT vs surgery alone, p=0.2). Median follow-up for patients not experiencing BCR was 48 mo. A total of 275 men experienced BCR during the study period, of which 57 patients were treated with surgery alone. The 5-year BCR-FSRs were 49% (44-55%) for MMT vs 56% (47-66%, p=0.02) for surgery alone. At MCR, the strongest predictors of BCR were clinical stage T3-4 (HR 1.4, 95%CI 1.1–2.1, p=0.04) and biopsy ISUP GG 4-5 (HR 1.9, 95%CI 1.4–2.7, p<0.01) after accounting for clinical characteristics. MMT treated patients had similar rate of UC [308 (76%) vs 107 (70%)] and EF [44 (11%) vs 16 (11%), all p>0.1] recovery than surgery alone. CONCLUSIONS: A non-negligible number of very high-risk PCa patients treated with surgery alone have favorable pathological outcomes and are BCR-free after 5 years of follow-up. Randomized clinical trials are needed in this setting to identify very high-risk PCa men who can avoid MMT and can be cured with surgery alone. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1280 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Antony Pellegrino More articles by this author Simone Scuderi More articles by this author Elio Mazzone More articles by this author Armando Stabile More articles by this author Leonardo Quarta More articles by this author Alfonso Santangelo More articles by this author Vito Cucchiara More articles by this author Mattia Longoni More articles by this author Pietro Scilipoti More articles by this author Paolo Zaurito More articles by this author Alice Mannazzu More articles by this author Alessandro Viti More articles by this author Francesco Barletta More articles by this author Roberta Lucianò More articles by this author Nazario Pio Tenace More articles by this author Daniele Robesti More articles by this author Riccardo Leni More articles by this author Giorgio Gandaglia More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologySurgical Technology & Simulation: Training & Skills Assessment (MP73)1 May 2024MP73-11 TRAIN THE TRAINERS FOR THE DELIVERY OF PROFICIENCY BASED PROGRESSION TRAINING BY THE EUROPEAN ROBOTIC SURGICAL SECTION FELLOWSHIP CENTERS Nicola Frego, Marco Ticonosco, Silvia Rebuffo, Claudia Collà Ruvolo, Alessandro Pissavini, Gabriele Sorce, Mario Belmonte, Stefano Puliatti, Elio Mazzone, Alberto Breda, Henk Van der Poel, Christian Wagner Wagner, Alexandre Mottrie, and Anthony Gallagher Nicola FregoNicola Frego , Marco TiconoscoMarco Ticonosco , Silvia RebuffoSilvia Rebuffo , Claudia Collà RuvoloClaudia Collà Ruvolo , Alessandro PissaviniAlessandro Pissavini , Gabriele SorceGabriele Sorce , Mario BelmonteMario Belmonte , Stefano PuliattiStefano Puliatti , Elio MazzoneElio Mazzone , Alberto BredaAlberto Breda , Henk Van der PoelHenk Van der Poel , Christian Wagner WagnerChristian Wagner Wagner , Alexandre MottrieAlexandre Mottrie , and Anthony GallagherAnthony Gallagher View All Author Informationhttps://doi.org/10.1097/01.JU.0001009564.26544.1c.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Proficiency-based progression (PBP) training is a validated training method that yields superior surgical skills in comparison to the traditional training approach. The effectiveness of PBP surgical training however, relies on the quality of the trainers, and their implementation of metric-based, standardized, objective, and fair feedback to the trainee.We developed a "Train the Trainer" (TTT) course based on PBP methodology for the host centers of the European Robotic Urology Section (ERUS) for the robot-assisted radical prostatectomy (RARP) curriculum. METHODS: We invited trainers from the accredited ERUS host centers in ORSI Academy (Melle, Belgium) for a two-days training. The TTT course was scheduled as follow: 1)Pre-course e-learning modules about PBP methodology and video assessment of the procedure using binary performance metrics. 2)Two-days face-to-face course which included: hands-on-training and assessment session where TTT delegates will be coached and assessed on their ability to give explicit, constructive, formative feedback to trainees learning the tasks. 3) Autonomous evaluation of RARP according to the metrics (the inter-rater reliability (IRR) threshold was set >0.8). RESULTS: Overall, 17 trainers attended the course. Following the two-days course, the IRR threshold of 0.8 in the assessing of RARP procedure, based on the validated metrics, was achieved by 2 out of 17 trainers on the first attempt, 11 out of 17 after the second attempt, and 17 trainers on the third attempt. CONCLUSIONS: The TTT course is an important part of the training process. Periodic TTT courses are fundamentals to standardized the teaching process within an European structured robotic surgery curriculum. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1186 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Nicola Frego More articles by this author Marco Ticonosco More articles by this author Silvia Rebuffo More articles by this author Claudia Collà Ruvolo More articles by this author Alessandro Pissavini More articles by this author Gabriele Sorce More articles by this author Mario Belmonte More articles by this author Stefano Puliatti More articles by this author Elio Mazzone More articles by this author Alberto Breda More articles by this author Henk Van der Poel More articles by this author Christian Wagner Wagner More articles by this author Alexandre Mottrie More articles by this author Anthony Gallagher More articles by this author Expand All Advertisement PDF downloadLoading ...

Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4–5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2–5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). Overall, 12 vs 14 vs 6

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy IV (MP56)1 May 2024MP56-15 CLINICAL CHARACTERISTICS OF PATIENTS WITH RENAL CANCER DO IMPACT MORE THAN ISCHEMIA TIME ON POST-OPERATIVE RENAL FUNCTION Giuseppe Rosiello, Giacomo Musso, Chiara Re, Francesco Cei, Federico Belladelli, Francesco Trevisani, Daniele Cignoli, Giuseppe Basile, Lucia Salerno, Alessandro Bertini, Isaline Rowe, Annamaria Ferrara, Elio Mazzone, Giorgio Gandaglia, Roberto Bertini, Francesco Montorsi, Andrea Salonia, Alessandro Larcher, and Umberto Capitanio Giuseppe RosielloGiuseppe Rosiello , Giacomo MussoGiacomo Musso , Chiara ReChiara Re , Francesco CeiFrancesco Cei , Federico BelladelliFederico Belladelli , Francesco TrevisaniFrancesco Trevisani , Daniele CignoliDaniele Cignoli , Giuseppe BasileGiuseppe Basile , Lucia SalernoLucia Salerno , Alessandro BertiniAlessandro Bertini , Isaline RoweIsaline Rowe , Annamaria FerraraAnnamaria Ferrara , Elio MazzoneElio Mazzone , Giorgio GandagliaGiorgio Gandaglia , Roberto BertiniRoberto Bertini , Francesco MontorsiFrancesco Montorsi , Andrea SaloniaAndrea Salonia , Alessandro LarcherAlessandro Larcher , and Umberto CapitanioUmberto Capitanio View All Author Informationhttps://doi.org/10.1097/01.JU.0001008940.44711.d4.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of warm ischemia time (WIT) on renal function recovery after partial nephrectomy (PN) is still debated. We aimed at quantifying the weighted effect of ischemia time vs. preoperative clinical risk factors, namely hypertension, smoking status and diabetes. METHODS: Within a prospectively maintained database, we identified 1,100 patients treated with PN at a single European high-volume center (2000–2022). Only patients with estimated glomerular filtration rate (eGFR)>=60 mL/min/1.73 m3 were included. Acute kidney injury was defined according to the RIFLE criteria. Multivariable logistic regression analyses estimated the risk of AKI after surgery according to each preoperative clinical risk factor and their combinations. A local polynomial smoother weighted function was used to graphically explore the risk of AKI according to preoperative risk factors and WIT. Covariates were age at surgery, preoperative eGFR, Charlson Comorbidity Index, ischemia time, estimated blood loss, and surgical approach (open vs. robotic). RESULTS: Overall, 86 patients (7.8%) had diabetes, 397 (36%) hypertension and 415 (38%) were currently or former smoker. Median age at surgery was 59 [Interquartile range (IQR): 50-67] years. Median clinical tumor size was 3.1 (IQR: 2.5-4.1) cm. Overall, 480 (44%) vs. 273 (25%) vs. 43 (4%) had 1 vs. 2 vs. 3 preoperative risk factors. After adjusting for several confounders, presence of 1 [Odds ratio (OR): 1.34; p=0.01] vs. 2 (OR: 1.85; p<0.001) vs. 3 (OR: 2.35; p=0.02) risk factors was associated with a significantly increased risk of AKI. The impact of WIT on postoperative AKI differed accordingly with the number of preoperative risk factors (Figure 1). CONCLUSIONS: WIT in patients undergoing PN does not seem to have an impact on short-term kidney function, namely postoperative AKI, in absence of preoperative clinical risk factors. Conversely, the combination of risk factors increases the detrimental effect of WIT on renal function after surgery. Referral to nephrologist should be considered in presence of clinical risk factors, especially in complex cases, where a prolonged ischemia time is foreseen. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e932 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Giuseppe Rosiello More articles by this author Giacomo Musso More articles by this author Chiara Re More articles by this author Francesco Cei More articles by this author Federico Belladelli More articles by this author Francesco Trevisani More articles by this author Daniele Cignoli More articles by this author Giuseppe Basile More articles by this author Lucia Salerno More articles by this author Alessandro Bertini More articles by this author Isaline Rowe More articles by this author Annamaria Ferrara More articles by this author Elio Mazzone More articles by this author Giorgio Gandaglia More articles by this author Roberto Bertini More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Alessandro Larcher More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP05)1 May 2024MP05-20 WHOLE EXOME SEQUENCING ANALYSIS IN LOW-RISK PROSTATE CANCER PATIENTS WITH KNOWN FAMILY HISTORY. IMPLICATION FOR ACTIVE SURVEILLANCE Vito Cucchiara, Giorgio Gandaglia, Armando Stabile, Elio Mazzone, Riccardo Leni, Pietro Scilipoti, Mattia Longoni, Alessandro Viti, Alfonso Santangelo, Francesco Montorsi, and Alberto Briganti Vito CucchiaraVito Cucchiara , Giorgio GandagliaGiorgio Gandaglia , Armando StabileArmando Stabile , Elio MazzoneElio Mazzone , Riccardo LeniRiccardo Leni , Pietro ScilipotiPietro Scilipoti , Mattia LongoniMattia Longoni , Alessandro VitiAlessandro Viti , Alfonso SantangeloAlfonso Santangelo , Francesco MontorsiFrancesco Montorsi , and Alberto BrigantiAlberto Briganti View All Author Informationhttps://doi.org/10.1097/01.JU.0001008740.27639.cc.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Germline mutations have been suggested to identify active surveillance (AS) patients at higher risk of disease reclassification and progression. However, only a minority of men is eligible for testing and a restricted set of genes associated with the risk of prostate cancer (PCa) are typically assessed according to international clinical guidelines. Our study aims to determine the prevalence of pathogenic germline mutations related to cancer by utilizing whole exome sequencing (WES) analysis in patients affected by localized disease with a positive family history. METHODS: A total of 47 men who had been diagnosed with low-risk PCa (Grade Group 1, PSA<10 ng/ml, T1c) and underwent WES according to the treating physicians' preference between March 2021 and May 2023 have been identified. A user-friendly self-test kit to collect saliva and blood samples has been used. Whole exome sequencing (WES), with an average sequencing depth of 100x, was conducted using DNA obtained from either saliva or blood samples. All patients had a positive family history of PCa, breast, or ovarian cancer in a first-degree relative, regardless of the age of diagnosis or specific disease characteristics. Sequencing was completed using the NovaSeq 6000 instrument (Illumina). The Nextera DNA Flex (Illumina) library was used during sequencing. RESULTS: Within our cohort of 47 patients, cancer-related germline pathogenic mutations were identified in 10 individuals (21%). We identified deleterious variants in several key genes, shedding light on the genetic landscape of these patients: BRCA1, PALB2, BARD1, KMT2C, CHD2, MAP3K1, CDKN2A, MSH5, FANCL, and MUTYH. Of note, only 3 patients (6.3%) had pathological mutations in genes which should be tested according to NCCN guidelines. In our cohort, patients with germline mutations had lower PSA values (5.78 vs 6.82 ng/ml, p=0.041), similar clinical T stage (cT1 90% vs 82%) and similar age (67.4 vs 68.2 years) compared to their counterparts without germline mutations. Furthermore, patients with germline mutations demonstrated a higher risk of disease progression, as evidenced by a reclassification rate of 50% at the 3-year follow-up, whereas their counterparts without germline mutations had a reclassification rate of 38% (p=0.046). CONCLUSIONS: The rate of significant germline mutations in localized PCa patients with a family history of neoplasm can be as high as 21%. However, when restricting our analysis to genes suggested by international guidelines, the detection rate remains notable at 6.3%. These men have an increased risk of reclassification and consequently require more rigorous follow-up. However, since the rate of reclassification of men with germline mutations was 50% at 3-year some of these patients can still might be safely managed with AS. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e50 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Vito Cucchiara More articles by this author Giorgio Gandaglia More articles by this author Armando Stabile More articles by this author Elio Mazzone More articles by this author Riccardo Leni More articles by this author Pietro Scilipoti More articles by this author Mattia Longoni More articles by this author Alessandro Viti More articles by this author Alfonso Santangelo More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (PD57)1 May 2024PD57-10 AGE-DEPENDENT EFFECT OF EARLY SALVAGE RADIOTHERAPY FOR BIOCHEMICAL RECURRENCE IN PROSTATE CANCER PATIENTS TREATED WITH RADICAL PROSTATECTOMY Antony Pellegrino, Francesco Barletta, Giorgio Gandaglia, Simone Scuderi, Pietro Scilipoti, Mattia Longoni, Armando Stabile, Donato Cannoletta, Leonardo Quarta, Elio Mazzone, Alfonso Santangelo, Paolo Zaurito, Alessandro Viti, Riccardo Leni, Giuseppe Ottone Cirulli, Vito Cucchiara, Daniele Robesti, Francesco Montorsi, and Alberto Briganti Antony PellegrinoAntony Pellegrino , Francesco BarlettaFrancesco Barletta , Giorgio GandagliaGiorgio Gandaglia , Simone ScuderiSimone Scuderi , Pietro ScilipotiPietro Scilipoti , Mattia LongoniMattia Longoni , Armando StabileArmando Stabile , Donato CannolettaDonato Cannoletta , Leonardo QuartaLeonardo Quarta , Elio MazzoneElio Mazzone , Alfonso SantangeloAlfonso Santangelo , Paolo ZauritoPaolo Zaurito , Alessandro VitiAlessandro Viti , Riccardo LeniRiccardo Leni , Giuseppe Ottone CirulliGiuseppe Ottone Cirulli , Vito CucchiaraVito Cucchiara , Daniele RobestiDaniele Robesti , Francesco MontorsiFrancesco Montorsi , and Alberto BrigantiAlberto Briganti View All Author Informationhttps://doi.org/10.1097/01.JU.0001008808.16085.aa.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Guidelines recommend early salvage radiotherapy (eSRT) for prostate cancer (PCa) patients who experience biochemical recurrence (BCR) after radical prostatectomy (RP). However, considering the natural history of treated PCa, it might be argued that older patients derive a lower benefit from additional treatment after RP compared to their younger counterparts. Our study aims to investigate the influence of age on the impact of eSRT in patients with BCR. METHODS: Overall, 794 PCa patients experiencing BCR after RP without adjuvant therapies at a single center from 1990 to 2023 were included. BCR was defined as 2 consecutive PSA ≥0.2 after RP. We focused on men treated with eSRT at PSA values ≤0.5. Kaplan-Meier (KM) plots depicted time to clinical recurrence (CR) at radiological imaging. In multivariable Cox-regression (MCR) models adjustment variables consisted of pT stage (pT2-3a vs pT3b-4), pN stage (pN0/x vs pN1), ISUP grade group (1-3 vs 4-5), age at eSRT, eSRT and salvage androgen deprivation therapy use. The relationship between age at eSRT and eSRT was explored using LOWESS function. RESULTS: Median age at eSRT was 70 years (65-75). A total of 510 (64%) patients received eSRT for BCR. In KM plots 10-yr CR-free rates according to eSRT vs no eSRT were 80 vs 63%. In MCR models, both eSRT (HR 0.6, 95%CI 0.4-0.9, p=0.005) and age at eSRT (HR 0.95, 95%CI 0.92-0.98, p=0.001) were predictors of CR. At interaction analysis, eSRT effect varied according to age at eSRT (p=0.04). Lowess plot showed a non-linear correlation between eSRT and age at eSRT, where a significant decrease in eSRT protective effect could be observed at approximately 75 years. After stratification according to age at eSRT (<75 vs ≥75 years), eSRT confirmed its independent predictor status (HR 0.6, 95%CI 0.4-0.8, p=0.01) in the younger patients group (n=589; 74%). Conversely, in older patients (n=205; 26%) eSRT failed to achieve independent predictor status for lower CSM (HR 0.9, 95%CI 0.4-1.6, p=0.7). CONCLUSIONS: The protective effect of eSRT is inversely associated with age at eSRT and not all patients older than 75 would benefit from eSRT in terms of cancer control. These men could be initially observed to reduce the risk of overtreatment and treatment-related side effects. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1212 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Antony Pellegrino More articles by this author Francesco Barletta More articles by this author Giorgio Gandaglia More articles by this author Simone Scuderi More articles by this author Pietro Scilipoti More articles by this author Mattia Longoni More articles by this author Armando Stabile More articles by this author Donato Cannoletta More articles by this author Leonardo Quarta More articles by this author Elio Mazzone More articles by this author Alfonso Santangelo More articles by this author Paolo Zaurito More articles by this author Alessandro Viti More articles by this author Riccardo Leni More articles by this author Giuseppe Ottone Cirulli More articles by this author Vito Cucchiara More articles by this author Daniele Robesti More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...