Publications by authors named "Antonio Cioffi"

18 Publications

  • Page 1 of 1

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review.

Cancers (Basel) 2021 Mar 12;13(6). Epub 2021 Mar 12.

i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135 Porto, Portugal.

Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by germline mutations. Nevertheless, current genetic screening recommendations disregard an unbalanced worldwide distribution of variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.
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http://dx.doi.org/10.3390/cancers13061269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001745PMC
March 2021

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

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

Pathological findings at radical prostatectomy of biopsy naïve men diagnosed with MRI targeted biopsy alone without concomitant standard systematic sampling.

Urol Oncol 2020 12 26;38(12):929.e11-929.e19. Epub 2020 Jun 26.

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

Objectives: To test international society of urological pathology grade group (ISUP GG) concordance rates between multiparametric magnetic resonance imaging (mpMRI) targeted biopsies (TB) vs. standard systematic biopsies (SB) and radical prostatectomy (RP) specimens, in biopsy naïve patients.

Materials And Methods: This retrospective single center study included 80 vs. 500 biopsy naïve patients diagnosed with TB vs. SB and treated with RP between 2015 and 2018. First, we compared ISUP GG concordance rates and the percentages of undetected clinically significant prostate cancer (csPCa: ISUP GG  ≥ 3), between TB vs. SB and RP. Second, multivariable logistic regression models tested predictors of concordance rates before and after 1:3 propensity score (PS) matching. Third, among TB patients, univariable logistic regression models tested variables associated with ISUP GG concordance at RP.

Results: Overall, ISUP GG concordance rates were, respectively, 55 vs. 41.4% for TB vs. SB (P = 0.02). However, no differences in concordance rates were observed in patients with biopsy ISUP GG1 (31 vs. 33.9% for TB vs. SB; P = 0.8). Moreover, 15 vs. 18.8% csPCa were missed by TB vs. SB, respectively (P = 0.4). In multivariable logistic regression models, TB were associated with higher concordance rates before (odds ratio [OR]: 1.13; P = 0.04) and after 1:3 PS matching (OR: 1.15; P 0.03), compared to SB. In TB patients, age (OR: 0.98; P = 0.04), maximum cancer core involvement (MCCI; OR: 1.02; P = 0.02) and maximum cancer core length (MCCL; OR: 1.01; P = 0.07) were associated with ISUP GG concordance. Moreover, a trend for lower concordance rates was observed with higher PSA-D (OR: 0.77; P = 0.1). Finally, intermediate lesion location at mpMRI was associated with lowest concordance rates (44%).

Conclusion: In biopsy naïve patients treated with RP, TB achieved higher rates of ISUP GG concordance, but same percentages of csPCa missed, compared to SB. Moreover, only patients with ISUP GG ≥2, but not patients with ISUP GG1, exhibited higher concordance rates. Finally, age, MCCI, MCCL, PSA-D, and lesion location were associated with concordance between TB and RP.
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http://dx.doi.org/10.1016/j.urolonc.2020.05.027DOI Listing
December 2020

Systemic Inflammatory Markers and Oncologic Outcomes in Patients with High-risk Non-muscle-invasive Urothelial Bladder Cancer.

Eur Urol Oncol 2018 10 13;1(5):403-410. Epub 2018 Jul 13.

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

Background: Serum levels of neutrophils, platelets, and lymphocytes have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer (BC).

Objective: To evaluate the prognostic role of the combination of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) in patients with high-risk non-muscle-invasive urothelial BC (NIMBC).

Design, Setting, And Participants: A total of 1151 NMIBC patients who underwent first transurethral resection of the bladder tumor (TURBT) at 13 academic institutions between January 1, 2002 and December 31, 2012 were included in this analysis. The median follow-up was 48 mo.

Intervention: TURBT with intravesical chemotherapy or immunotherapy.

Outcome Measurements And Statistical Analysis: Multivariable Cox regression analysis was performed to identify factors predictive of recurrence, progression, cancer-specific mortality, and overall mortality. A systemic inflammatory marker (SIM) score was calculated based on cutoffs for NLR, PLR, and LMR.

Results And Limitations: The 48-mo recurrence-free survival was 80.8%, 47.35%, 20.67%, and 17.06% for patients with an SIM score of 0, 1, 2, and 3, respectively (p<0.01, log-rank test) while the corresponding 48-mo progression free-survival was 92.0%, 75.67%, 72.85%, and 63.1% (p<0.01, log-rank test). SIM scores of 1, 2, and 3 were associated with recurrence (hazard ratio [HR] 3.73, 7.06, and 7.88) and progression (HR 3.15, 4.41, and 5.83). Limitations include the lack of external validation and comparison to other clinical risk models.

Conclusions: Patients with high-grade T1 stage NMIBC with high SIM scores have worse oncologic outcomes in terms of recurrence and progression. Further studies should be conducted to stratify patients according to SIM scores to identify individuals who might benefit from early cystectomy.

Patient Summary: In this study, we defined a risk score (the SIM score) based on the measurement of routine systemic inflammatory markers. This score can identify patients with high-grade bladder cancer not invading the muscular layer who are more likely to suffer from tumor recurrence and progression. Therefore, the score could be used to select patients who might benefit from early bladder removal.
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http://dx.doi.org/10.1016/j.euo.2018.06.006DOI Listing
October 2018

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

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

Comparison of 10-year overall survival between patients with G1 and G2 grade Ta bladder tumors.

Medicine (Baltimore) 2018 Apr;97(16):e0522

Department of Cell and Molecular Biology Department of Urology, University of Medicine and Pharmacy, Tirgu Mures, Romania Department of Urology, University of Pécs, Pécs, Hungary Department of Epidemiology, University of Medicine and Pharmacy, Tirgu Mures, Romania Division of Urology, European Institute of Oncology, Milan, Italy Department of Urology, Medical University of Vienna, Vienna, Austria Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari Department of Urology, Sapienza University of Rome, Rome, Italy Department of Histology, University of Medicine and Pharmacy, Tirgu Mures, Romania.

To compare long-term overall survival (OS) in patients with G1 and G2 grade Ta bladder cancer after transurethral resection of bladder tumors (TURBTs). Secondary aim was to investigate clinical and pathologic prognostic factors for OS of Ta patients, except G3/high grade (HG).A total of 243 patients, retrospectively selected, with Ta nonmuscle invasive bladder cancer (NMIBC) underwent TURBT between January 2006 and December 2008 (median follow-up 109 months). Inclusion criteria were: Ta at first manifestation, G1 or G2 grade with no associated carcinoma in situ (CIS). Seventy-nine patients were excluded due to concomitant CIS (1), G3/HG tumors (47), and lost to follow-up (31). Ethical approval was obtained from the Ethical Committee of the Mures County Hospital. Statistical analysis was performed using STATA 11.0.Following inclusion criteria, 164 patients with primary G1 or G2 Ta tumors, were enrolled. Recurrence was observed in 26 (15.8%) and progression in 5 (3%) patients. Ten-year survival in G1 patients was 67.8% (CI 54.3-78.1) and in G2 patients 59% (CI 49-67.3) (P = .31). Univariable and multivariable logistic regression analysis underlined that advanced age at diagnosis (hazard ratio [HR] 1.10) and no Bacillus Calmette-Guerin (BCG) treatment (HR 0.24 and 0.29) were independent predictors for death at 10 years after diagnosis.Long-term analysis confirms that patients with well differentiated (G1) and moderately well differentiated (G2) Ta tumors have similar OS. A longer OS was even reported in those who underwent BCG adjuvant therapy.
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http://dx.doi.org/10.1097/MD.0000000000010522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916673PMC
April 2018

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

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

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

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

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience.

Medicine (Baltimore) 2015 Oct;94(42):e1861

From the Division of Urology, European Institute of Oncology, Milan, Italy (MF, OD, DB, AC, DVM, GM, AB); Department of Urology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania (OD); Genitourinary Cancer Section, Medical Oncology Division, University Federico II, Napoli, Italy (CB, GD, SD); Division of Urology, University "Federico II", Naples, Italy (MC, VM); Department of Public Health, University "Federico II", Naples, Italy (DB); Urology Institute, University Hospitals, Cleveland, OH, USA (RA); Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy (MC); Department of Urology, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy (MB); Division of Urology, University "La Sapienza", Rome, Italy (ED, GMB, RG); Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy (GL, PD); Division of Urology, IRCCS Fondazione G. Pascale, Napoli, Italy (SP); Department of Urology, Tor Vergata University of Rome, Rome, Italy (PB, LC, RH); Institute of Genetics and Biophysics, National Research Council (CNR), Naples, Italy (MO, AC); Department of Urology, University of Salerno, Salerno, Italy (VA); Department of Urology, Magna Graecia University, Catanzaro, Italy (RD, FC); Department of Surgical, Oncological and Stomatological Sciences, Institute of Urology, University of Palermo, Palermo, Italy (VS); Urologic Oncology, Division of Hematology and Oncology, Department of Medicine, University of Alabama, Birmingham, AL, USA (GS); Department of Translational Medical Sciences, University "Federico II", Naples, Italy (DT).

Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients.A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3-60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%).In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31-1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86-3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS.In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.
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http://dx.doi.org/10.1097/MD.0000000000001861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620818PMC
October 2015

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging.

PLoS One 2015 7;10(10):e0139696. Epub 2015 Oct 7.

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

Purpose: The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.

Methods: A total of 223 patients who fulfilled the criteria for "Prostate Cancer Research International: Active Surveillance", were included. Mp-1.5 Tesla MRI examination staging with endorectal coil was performed at least 6-8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥ 0.5 ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score.

Results: Multivariate analysis demonstrated the association of PIRADS score with upgrading (P < 0.0001), ECE (P < 0.0001), unfavorable prognosis (P < 0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.

Conclusions: mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596627PMC
June 2016

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance.

Urol Oncol 2015 May 16;33(5):201.e1-8. Epub 2015 Mar 16.

Division of Urology, European Institute of Oncology, Milan, Italy. Electronic address:

Background: Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol.

Methods: We assessed 311 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 ≤ 6 grade, and prostate-specific antigen density < 0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage > pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded.

Results: We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001).

Conclusions: BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects.
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http://dx.doi.org/10.1016/j.urolonc.2015.02.004DOI Listing
May 2015

Upgrading and upstaging in prostate cancer: From prostate biopsy to radical prostatectomy.

Mol Clin Oncol 2014 Nov 5;2(6):1145-1149. Epub 2014 Aug 5.

Department of Surgery, Urology Clinic, A.O.U.I. Verona, I-37134 Verona, Italy.

Prostate cancer (CaP) is the most common malignancy in men and the second cause of cancer-related mortality after lung cancer. Several studies have evaluated the correlation between bioptic and pathological Gleason score (GS), documenting a correlation ranging between 30 and 60%. The aim of this study was the evaluation of the association between bioptic and pathological GS in a series of patients undergoing prostate needle biopsy and subsequent radical prostatectomy. We also aimed to evaluate the possible prognostic factors of upgrading and upstaging. We prospectively collected and retrospectively reviewed data from 300 consecutive patients who underwent radical retropubic or robot-assisted prostatectomy at our Institution. Patients who underwent prostate needle biopsy, transrectal or transperineal, with a minimum of 5 samples, were included in this study. Upgrading and downgrading were defined as increase or decrease, respectively, from one prognostic grade group to another, similar to up- or downstaging. The mean age of the patients was 62.97 years and the mean prostate-spesific antigen (PSA) level was 7.83 ng/ml. A total of 51.3% of the population underwent a transperineal prostate biopsy. The most frequently represented bioptic GS was 3+3 (64.0%) followed by 3+4=7 (15.6%); the most frequent pathological Gleason score was 3+4 (44.3%), followed by 3+3 (31.0%). With reagard to the bioptic GS 4-5-6 group, approximately half of the specimens (46.7%) were subsequently upgraded to GS 3+4, and 5.3% to 4+3. With regards to the bioptic GS 3+4 group, 57.4% was confirmed in the surgical specimen. In the 4+3 group, 23.5% of the cases was downgraded to 3+4 and 35.3% was confirmed. With regards to stage, ~39.7% of the patients received an upstaging on the pathological specimen. We evaluated the correlations between preoperative serum PSA level, prostate volume, digital rectal examination and biopsy type and none of the variables considered exhibited a correlation with any upgrading (P>0.05). Moreover, we evaluated the correlations between the aforementioned variables and upstaging and, at the multivariate analysis, only a serum PSA <4 ng/ml was found to be an independent variable predictive of upstaging (P=0.017). Therefore, new tools are required to predict upgrading and upstaging of our patients, in order to ensure better counseling for optimal treatment planning.
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http://dx.doi.org/10.3892/mco.2014.370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4179778PMC
November 2014