Publications by authors named "Ettore De Berardinis"

67 Publications

Association of daily step count and serum testosterone among men in the United States.

Endocrine 2021 Feb 12. Epub 2021 Feb 12.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

Purpose: To describe the association between daily activity (i.e., daily step counts and accelerometer intensity measures) and serum TT levels in a representative sample of US adults aged 18 years or older.

Methods: A retrospective cohort study was carried out utilizing the NHANES (National Health and Nutrition Examination Survey) 2003-2004 cycle. Physical activity was measured with a waist-worn uniaxial accelerometer (AM-7164; ActiGraph) for up to 7 days using a standardized protocol. Using linear and multivariable logistic regression controlling for relevant social, demographic, lifestyle, and comorbidity characteristics, we assessed the association between daily step counts and TT.

Results: A total of 279 subjects with a median age 46 (IQR: 33-56) were included in the analysis. 23.3% of the cohort had a low serum TT level (TT < 350 ng/dl). Compared to men who took <4000 steps per day, men who took >4000 or >8000 steps/day had a lower odd of being hypogonadal (OR 0.14, 95% CI: 0.07-0.49 and 0.08, 95%CI: 0.02-0.44, respectively). While a threshold effect was noted on average, TT increased 7 ng/dL for each additional 1000 steps taken daily (β-estimate: 0.007, 95% CI: 0.002-0.013).

Conclusions: Patients with the lowest daily step counts had higher odds of being hypogonadal. The current work supports a possible association between daily steps, total testosterone, and hypogonadism for men in the US.
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http://dx.doi.org/10.1007/s12020-021-02631-2DOI Listing
February 2021

The Clinical Efficacy of Nitrofurantoin for Treating Uncomplicated Urinary Tract Infection in Adults: A Systematic Review of Randomized Control Trials.

Urol Int 2021 Feb 3:1-10. Epub 2021 Feb 3.

Department of Urology and Renal Transplantation, University of Foggia Policlinico Riuniti of Foggia, Foggia, Italy,

Objective: To provide an updated systematic review of randomized control trials (RCTs) to investigate the clinical and microbiological efficacy of nitrofurantoin compared to other antibiotics or placebo for treatment of uncomplicated urinary tract infections (uUTI). A secondary aim is to assess whether nitrofurantoin use is associated with increased side effects compared to other treatment regimens.

Summary: The review was performed according to PRISMA guidelines. We searched 4 databases for articles published from database inception to May 6, 2020: (1) PubMed electronic database of the National Library of Medicine, (2) Web of Science, (3) Embase, and (4) Cochrane Library. Nine RCTs were selected for the review. RCTs were a mixture of double-blind, single-blind, and open-label trials. The most common comparators were trimethoprim-sulfamethoxazole and fosfomycin tromethamine. Overall study quality was poor with a high risk of bias. The clinical cure rates in nitrofurantoin ranged from 51 to 94% depending on the length of follow-up, and bacteriological cure rates ranged from 61 to 92%. Overall the evidence suggests that nitrofurantoin is at least comparable with other uUTI treatments in terms of efficacy. Patients taking nitrofurantoin reported fewer side effects than other drugs and the most commonly reported were gastrointestinal and central nervous system symptoms. Key Messages: Evidence on the clinical and bacteriological efficacy of nitrofurantoin is sparse, with a lack of new data, and hampered by high risk of bias. Although no firm conclusions can be made on the current base of evidence, the studies generally suggest that nitrofurantoin is at least comparable to other common uUTI treatments in terms of clinical and bacteriological cure. More robust research with well-designed double-blinded RCTs is needed.
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http://dx.doi.org/10.1159/000512582DOI Listing
February 2021

Impact of uni- or multifocal perineural invasion in prostate cancer at radical prostatectomy.

Transl Androl Urol 2021 Jan;10(1):66-76

Department of Maternal-Infant and Urological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.

Background: Aim of this study was to correlate perineural invasion (PNI) with other clinical-pathological parameters in terms of prognostic indicators in prostate cancer (PC) cases at the time of radical prostatectomy (RP).

Methods: Prospective study of 288 consecutive PC cases undergoing RP. PNI determination was performed either in biopsy or in RP specimens classifying as uni- and multifocal PNI. The median follow-up time was 22 (range, 6-36) months.

Results: At biopsy PNI was found in 34 (11.8%) cases and in 202 (70.1%) cases at the time of surgery. Among those identified at RP 133 (46.1%) and 69 (23.9%) cases had uni- and multi-PNI, respectively. Presence of PNI was significantly (P<0.05) correlated with unfavorable pathological parameters such higher stage and grade. The percentage of extracapsular extension in PNI negative RP specimens was 18.6% 60.4% of PNI positive specimens. However, the distribution of pathological staging and International Society of Urological Pathology (ISUP) grading did not vary according to whether PNI was uni- or multifocal. The risk of biochemical progression increased 2.3 times in PNI positive cases was significantly associated with the risk of biochemical progression (r=0.136; P=0.04). However, at multivariate analysis PNI was not significantly associated with biochemical progression [hazard ratio (HR): 1.87, 95% confidence interval (CI): 0.68-3.12; P=0.089]. Within patients with intermediate risk disease, multifocal PNI was able to predict cases with lower mean time to biochemical and progression free survival (chi-square 5.95; P=0.04).

Conclusions: PNI at biopsy is not a good predictor of the PNI incidence at the time of RP. PNI detection in surgical specimens may help stratify intermediate risk cases for the risk of biochemical progression.
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http://dx.doi.org/10.21037/tau-20-850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844528PMC
January 2021

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer.

BMC Cancer 2021 Jan 11;21(1):51. Epub 2021 Jan 11.

Department of Urology, Policlinico Abano Terme, Abano Terme, PD, Italy.

Background: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence.

Methods: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc).

Discussion: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique.

Trial Registration: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-020-07748-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802145PMC
January 2021

How Can the COVID-19 Pandemic Lead to Positive Changes in Urology Residency?

Front Surg 2020 24;7:563006. Epub 2020 Nov 24.

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

The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both "junior" and "senior" residents, and those working in any of three geographical areas created (Italian regions were clustered in three major zones according to the prevalence of COVID-19). A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having "senior" resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having "senior" resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having "senior" resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training.
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http://dx.doi.org/10.3389/fsurg.2020.563006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732553PMC
November 2020

Vesical Imaging-Reporting and Data System (VI-RADS) incorporated into bladder cancer clinical practice: what's the perspectives beyond diagnostic accuracy?

Transl Androl Urol 2020 Oct;9(5):2320-2322

Department of Radiological, Oncological and Anatomopathological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.

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http://dx.doi.org/10.21037/tau-2020-07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658160PMC
October 2020

Androgen-deprivation therapy and SARS-Cov-2 infection: the potential double-face role of testosterone.

Ther Adv Endocrinol Metab 2020 31;11:2042018820969019. Epub 2020 Oct 31.

Department of Maternal-Infant and Urological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.

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http://dx.doi.org/10.1177/2042018820969019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607784PMC
October 2020

Safety and Feasibility of Outpatient Surgery in Benign Prostatic Hyperplasia: a Systematic Review and Meta-analysis.

J Endourol 2020 Oct 21. Epub 2020 Oct 21.

Sapienza University of Rome, 9311, Department of Maternal-Infant and Urological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Lazio, Italy;

Purpose: Most of endourological procedures along the urinary tract have been widely practiced as outpatient operations, including surgery for BPH. This systematic review and meta-analysis was conducted to assess safety and feasibility of outpatient surgery for patients suffering from symptomatic BPH candidate for endoscopic disobstruction.

Materials And Methods: PubMed, Web of Science, Cochrane, and Embase were searched up until March 30, 2020. MINORS tool was utilized to assess the quality of included studies and a pooled measure of failure or event rate (FR, ER) estimate was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate contribution of moderators to heterogeneity.

Results: Twenty studies with a total of 1626 patients treated according to outpatient criteria for endoscopic BPH surgery were included. In total, 18 studies reporting data on immediate hospital readmission and/or inability to discharge after endoscopic procedure presented FR estimates ranging from 1.7% to 51.1%. Pooled FR estimate was 7.8% (95% confidence interval [CI]: 5.2%-10.3%); Heterogeneity: Q=76.85; d.f.=17, p<.001; I2= 75.12%. Subgroup analysis according to surgical technique revealed difference among the three approaches with pooled FR of 3% (95%CI: 1%-4.9%), 7.1% (95%CI: 3.9-10.4) and 11.8% (95%CI: 7-16.7%) for TURP, Green-light and HoLEP respectively (p<.001). At meta-regression analysis, none of the retrieved covariates were able to significantly influence the cumulative outcomes reported. ER for postoperative complications and early outpatient visit showed a pooled estimate of 18.6% (95%CI: 13.2%-23.9%) and 7.7% (95%CI: 4.3%-11%) respectively.

Conclusions: Our analysis revealed how transurethral procedures for BPH on an outpatient setting are overall reliable and safe. Of note, there were significant outcome differences between groups with regard of type of surgical procedure, perioperative prostate volume and discharge protocol suggesting the need for further prospective analysis to better elucidate the best strategy in such outpatient conduct.
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http://dx.doi.org/10.1089/end.2020.0538DOI Listing
October 2020

Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection.

Cancers (Basel) 2020 Oct 15;12(10). Epub 2020 Oct 15.

Department of Radiological Sciences, Oncology and Pathology, "Sapienza"/Policlinico Umberto I, 00161 Rome, Italy.

The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen's Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78-0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader's experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; = 0.003 and 0.036, SE: 0.009; = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.
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http://dx.doi.org/10.3390/cancers12102994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602537PMC
October 2020

Increased Mortality Among Men Diagnosed With Impaired Fertility: Analysis of US Claims Data.

Urology 2021 Jan 2;147:143-149. Epub 2020 Oct 2.

Department of Urology, Stanford University School of Medicine, Stanford, CA; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA. Electronic address:

Objective: To determine whether male infertility or impaired spermatogenesis is associated with mortality.

Methods: The Optum de-identified Clinformatics Data Mart database was queried from 2003 to 2017. Infertile men were compared to subjects undergoing semen analysis (ie, infertility testing). Infertile men with oligozoospermia or azoospermia were included. Mortality was determined by data linkage to the Social Security Administration Death Master File. Results were adjusted for age, smoking, obesity, year of evaluation, and health care visits as well as for most prevalent comorbidities. We separately examined men with prevalent or incident cardiovascular disease and cancer diagnoses to determine associations with mortality.

Results: A total of 134,796 infertile men and 242,282 controls were followed for a mean of 3.6 and 3.1 years respectively. Overall, infertile men had a higher risk of death (Hazard Ratio [HR]= 1.42, 95% CI: 1.27-1.60) The diagnosis of azoospermia was associated with a significantly increased risk of death (HR= 2.01, 95% CI: 1.60-2.53) with a higher trend among men with oligospermia (HR: 1.17, 95% CI: 0.92-1.49) compared to controls. Subanalysis was done excluding prevalent cardiovascular and malignant disease (alone and combined) showing similar hazard ratios.

Conclusion: Male infertility is associated with a higher risk of mortality especially among azoospermic men. Prevalent disease (which is known to be higher among infertile men) did not explain the higher risk of death among infertile men. The implications for treatment and surveillance of infertile men require further study.
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http://dx.doi.org/10.1016/j.urology.2020.07.087DOI Listing
January 2021

Liquid Biopsy for Predicting Bacillus Calmette-Guérin Unresponsiveness in Non-muscle-invasive Bladder Cancer.

Eur Urol Oncol 2021 Feb 2;4(1):124-125. Epub 2020 Oct 2.

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.euo.2020.09.003DOI Listing
February 2021

Cribriform pattern does not have a significant impact in Gleason Score ≥7/ISUP Grade ≥2 prostate cancers submitted to radical prostatectomy.

Medicine (Baltimore) 2020 Sep;99(38):e22156

Department of Maternal-Infant and Urological Sciences.

Introduction: The aim of this study was to correlate cribriform pattern (CP) with other parameters in a large prospective series of Gleason score ≥7/ISUP grade ≥2 prostate cancer (PC) cases undergoing radical prostatectomy (RP).

Methods: This is a prospective single-center study on 210 consecutive patients. Gleason pattern 4 and individual tumor growth patterns determination were performed either in biopsy or in surgical specimens for all patients.

Results: At multiparametric magnetic resonance, a higher percentage of PI-RADS 5 was associated to CP (53.3% vs 17.7%, P = .038). CP was significantly and inversely (r = -0.261; P = .001) correlated with perineural invasion (PNI) but not with other pathological parameters. Kaplan-Meier analysis showed that mean biochemical (Bp) and radiological (Rp) progression-free survival were similar (Bp = χ 0.906; P = .341; Rp = χ 1.880; P = .170) independently to CP. In PNI positive cases, Bp-free survival was higher (χ = 3.617; P = .057) in cases without CP.

Conclusions: In a homogeneous population excluding ISUP 1 cases, CP showed limited prognostic value. We first described an association with PNI and a prognostic value influenced by PNI status.
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http://dx.doi.org/10.1097/MD.0000000000022156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505347PMC
September 2020

Adding systematic biopsy to magnetic resonance ultrasound fusion targeted biopsy of the prostate in men with previous negative biopsy or enrolled in active surveillance programs: A prospective single center, randomized study.

Medicine (Baltimore) 2020 Sep;99(37):e22059

Department of Maternal-Child and Urological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome.

Magnetic resonance imaging (MRI) targeted biopsy (TBx) of the prostate demonstrated to improve detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy-naive patients achieving strong level of evidence. Nevertheless, the csPCa yield for TBx alone versus TBx plus systematic biopsy (SBx) after accounting for overlapping of SBx cores with TBx cores, in prior-negative or active surveillance (AS) patients has not been well established.The objective of the study was to investigate benefits in terms of detection rate and pathological stratification of prostate cancer (PCa) using contextual SBx during MRI-TBx.Patients previously submitted to negative-SBx (cohort A) and those enrolled in an AS program (cohort B) who showed at least 1 suspicious area with a PIRADSv2 score ≥ 3 were prospectively and randomly assigned to only TBx strategy versus TBx plus SBx strategy. SBx locations could not encompass the TBx sites, so that the results of each type of biopsy were independent and did not overlap.A total of 312 patients were included in the 2 cohorts (cohort A: 213 cases; cohort B: 99 cases). No significant differences were found in terms of overall PCa-DR (77.6% vs 69.6% respectively; P = .36) and csPCa-DR (48.2% vs 60.9 respectively; P = .12). The MRI-TBx alone cohort showed higher csPCa/PCa ratio (87.5% vs 62.2%; P = .03). The MRI-TBx plus SBx group subanalysis showed significantly higher csPCa-DR obtained at the MRI-TBx cores when compared with the SBx cores (43.7% vs 24.1%, respectively; P = .01). Independently to age, prostatic-specific antigen and prostate imaging-reporting and data system score, either in rebiopsy (OR 0.43, 0.21-0.97) or AS (OR 0.46, 0.32-0.89) setting, SBx cores were negatively associated with the csPCa-DR when combined to TBx cores.MRI-TBx should be considered the elective method to perform prostate biopsy in patients with previous negative SBx and those considered for an AS program. Adding SBx samples to MRI-TBx did not improve detection rate of csPCa.
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http://dx.doi.org/10.1097/MD.0000000000022059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489582PMC
September 2020

Preoperative detection of Vesical Imaging-Reporting and Data System (VI-RADS) score 5 reliably identifies extravesical extension of urothelial carcinoma of the urinary bladder and predicts significant delayed time to cystectomy: time to reconsider the need for primary deep transurethral resection of bladder tumour in cases of locally advanced disease?

BJU Int 2020 11 17;126(5):610-619. Epub 2020 Aug 17.

Department of Radiological Sciences, Oncology & Pathology, "Sapienza" University of Rome, Policlinico Umberto, Hospital, Rome, Italy.

Objectives: (I) To determine Vesical Imaging-Reporting and Data System (VI-RADS) score 5 accuracy in predicting locally advanced bladder cancer (BCa), so as to potentially identify those patients who could avoid the morbidity of deep transurethral resection of bladder tumour (TURBT) in favour of histological sampling-TUR prior to radical cystectomy (RC). (II) To explore the predictive value of VI-RADS score 5 on time-to-cystectomy (TTC) outcomes.

Patients And Methods: We retrospectively reviewed patients' ineligible or refusing cisplatin-based combination neoadjuvant chemotherapy who underwent multiparametric magnetic resonance imaging (mpMRI) of the bladder prior to staging TURBT followed by RC for muscle-invasive BCa. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for VI-RADS score 5 vs. score 2-4 cases to assess the accuracy of mpMRI for extravesical BCa detection (≥pT3). VI-RADS score performance was assessed by receiver operating characteristics curve analysis. A Κ statistic was calculated to estimate mpMRI and pathological diagnostic agreement. The risk of delayed TTC (i.e. time from initial BCa diagnosis of >3 months) was assessed using multivariable logistic regression model.

Results: A total of 149 T2-T4a, cN0-M0 patients (VI-RADS score 5, n = 39 vs VI-RADS score 2-4, n = 110) were examined. VI-RADS score 5 demonstrated sensitivity, specificity, PPV and NPV, in detecting extravesical disease of 90.2% (95% confidence interval [CI] 84-94.3), 98.1% (95% CI 94-99.6), 94.9% (95% CI 89.6-97.6) and 96.4% (95% CI 91.6-98.6), respectively. The area under the curve was 94.2% (95% CI 88.7-99.7) and inter-reader agreement was excellent (Κ 0.89). The mean (SD) TTC was 4.2 (2.3) and 2.8 (1.1) months for score 5 vs 2-4, respectively (P < 0.001). VI-RADS score 5 was found to independently increase risk of delayed TTC (odds ratio 2.81, 95% CI 1.20-6.62).

Conclusion: The VI-RADS is valid and reliable in differentiating patients with extravesical disease from those with muscle-confined BCa before TURBT. Detection of VI-RADS score 5 was found to predict significant delay in TTC independently from other clinicopathological features. In the future, higher VI-RADS scores could potentially avoid the morbidity of extensive primary resections in favour of sampling-TUR for histology. Further prospective, larger, and multi-institutional trials are required to validate clinical applicability of our findings.
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http://dx.doi.org/10.1111/bju.15188DOI Listing
November 2020

Association between male infertility and male-specific malignancies: systematic review and meta-analysis of population-based retrospective cohort studies.

Fertil Steril 2020 Nov 22;114(5):984-996. Epub 2020 Jul 22.

Department of Urology, School of Medicine, Stanford University, Stanford, California; Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, California. Electronic address:

Objective: To investigate the current evidence that correlates impaired male fertility with the risk of developing male-related malignancies.

Design: Systematic review and meta-analysis of population-based retrospective cohort studies.

Setting: Not applicable.

Patient(s): Men diagnosed with impaired fertility status and subsequently observed to determine incidence risk in developing testicular cancer (TCa) or prostate cancer (PCa).

Intervention(s): Not applicable.

Main Outcome Measure(s): Pooled risk ratio (RR) differences among male factor infertility subjects compared with a fertile control population, and meta-regression analysis according to age at baseline, mean follow-up, range of study time, and year of publication.

Result(s): Six studies met the inclusion criteria and were critically examined. Four studies examined male infertility and TCa (n = 161,634; 174 TCa cases), and four examined infertility in relation to PCa (n = 183,950 men; 377 PCa cases) from 1963 to 2014. The pooled RR was 2.033 (95% confidence interval [CI], 1.66-2.48); heterogeneity: Q = 3.04 (degree of freedom [df] = 3); I = 1.55% for TCa and 1.68 (95% CI, 1.17-2.4); Q = 23.3(df = 3); I = 87.1% for PCa.

Conclusion(s): Male infertility was associated with a subsequent risk of both TCa and PCa. Although the clinical significance of these findings remains uncertain, future studies should evaluate the underlying mechanisms to determine whether testis and prostate screening practices should be altered in men with male infertility.

Clinical Trial Registration Number: PROSPERO 167277.
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http://dx.doi.org/10.1016/j.fertnstert.2020.04.042DOI Listing
November 2020

Prospective assessment of two-gene urinary test with multiparametric magnetic resonance imaging of the prostate for men undergoing primary prostate biopsy.

World J Urol 2020 Jul 17. Epub 2020 Jul 17.

Department of Urology, Sapienza Rome University, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy.

Purpose: To evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) in predicting prostate cancer (PCa) and clinically significant PCa (csPCa) on prostate biopsies among men scheduled for initial prostate biopsy.

Methods: In this single-center prospective study, 52 men scheduled for initial prostate biopsy, based on elevated total PSA level (> 3 ng/ml) or abnormal digital rectal examination, were consecutively included. All subjects underwent SelectMDx, PSA determination and mpMRI.

Results: SelectMDx score was positive in 94.1 and 100% of PCa and csPCa, respectively, and in only 8.6% of negative cases at biopsy. The probability for a csPCa at the SelectMDx score was significantly (p = 0.002) higher in csPCa (median value 52.0%) than in all PCa (median value 30.0%). SelectMDx showed slightly lower sensitivity (94.1 versus 100.0%) but higher specificity (91.4%) than total PSA (17.1%), and the same sensitivity but higher specificity than mpMRI (80.0%) in predicting PCa at biopsy. The association of SelectMDx plus mpMRI rather than PSA density (PSAD) plus mpMRI showed higher specificity (both 91.4%) compared to the association of PSA plus mpMRI (85.7%). In terms of csPCa predictive value, SelectMDx showed higher specificity (73.3%) than PSA (13.3%) and mpMRI (64.4%); as for the association of SelectMDx plus mpMRI (75.6%) versus PSA plus mpMRI (68.9%), the association of PSAD plus mpMRI showed the highest specificity (80.0%).

Conclusion: Our results of SelectMDx can be confirmed as significant but their impact on clinical practice together with a cost-effectiveness evaluation should be investigated in a larger prospective multicenter analysis.
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http://dx.doi.org/10.1007/s00345-020-03359-wDOI Listing
July 2020

Clinical correlation among male infertility and overall male health: A systematic review of the literature.

Investig Clin Urol 2020 07 8;61(4):355-371. Epub 2020 Jun 8.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

Purpose: Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature.

Materials And Methods: A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality.

Results: In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016.

Conclusions: A man's fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health.
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http://dx.doi.org/10.4111/icu.2020.61.4.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329649PMC
July 2020

Prognostic performance of magnetic resonance imaging-guided biopsy in defining prostate cancer anterior lesions.

World J Urol 2020 Jul 3. Epub 2020 Jul 3.

Department of Urology, Sapienza Rome University Policlinico Umberto I, P.le Aldo Moro, 5, Rome, Italy.

Purpose: Diagnosis of anterior prostate cancer (PCa) can be quite challenging, often leading to delay in treatment. mpMRI-guided biopsy (GB) has been introduced aiming to increase the number of diagnoses of clinically significant PCa with fewer cores. The aim of our study is to compare pathological findings of prostate biopsy, In-bore or Fusion technique, with histopathological evaluation of radical prostatectomy.

Methods: We prospectively collected data from 90 consecutive patients who underwent either In-bore or Fusion biopsy following the detection of an index suspicious lesion at mpMRI in the anterior part of the prostatic gland. Bioptical pathological findings were compared with pathological findings reported after robot-assisted radical prostatectomy.

Results: Patients who underwent In-bore GB had a higher rate of previous negative prostate biopsies (19% vs 44%, p = 0.02). Median number of bioptic cores taken (13 vs 2) and number of positive cores (3 vs 2) were significantly superior in the Fusion group compared to the In-bore group (p < 0.001 and p = 0.002, respectively), whilst clinical International Society of Urological Pathology (ISUP) grade was homogeneous within groups. The concordance between anterior lesions detected at biopsy and those reported in the histopathological finding of radical prostatectomy was very high, without statistically significant difference between groups.

Conclusion: Both Fusion and In-bore GB are accurate in detecting anterior PCa, with enhanced precision detecting clinically significant tumours, as evidenced by pathologic examinations which confirmed the presence of index anterior PCa in > 50% of patients overall. Additional sextant biopsy is still required, especially among biopsy-näive patients, to avoid missing clinically significant PCa.
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http://dx.doi.org/10.1007/s00345-020-03335-4DOI Listing
July 2020

Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study.

Diagn Cytopathol 2020 Nov 20;48(11):1034-1040. Epub 2020 Jun 20.

Department of Urology, Sapienza Rome University, Rome, Italy.

Background: To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa).

Methods: We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided mid-stream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation.

Results: Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high-grade (HG) and 21 (56.8%) low-grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False-positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false-negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC.

Conclusion: In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different.
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http://dx.doi.org/10.1002/dc.24530DOI Listing
November 2020

SARS-CoV-2 Infection and High-Risk Non-Muscle-Invasive Bladder Cancer: Are There Any Common Features?

Urol Int 2020 9;104(7-8):510-522. Epub 2020 Jun 9.

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

Background: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death.

Summary: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. Key Messages: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field.
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http://dx.doi.org/10.1159/000509065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316644PMC
August 2020

Surgical blood loss during holmium laser enucleation of the prostate (HoLEP) is not affected by short-term pretreatment with dutasteride: a double-blind placebo-controlled trial on prostate vascularity.

Aging (Albany NY) 2020 03 11;12(5):4337-4347. Epub 2020 Mar 11.

Department of Urology, Policlinico Abano Terme, Abano Terme (PD), Italy.

Five α-reductase inhibitors (5ARIs) are able to reduce prostate volume and are a useful treatment for reducing perioperative bleeding during prostate surgery. Holmium laser enucleation of the prostate (HoLEP) is an effective surgical technique for the definitive cure of benign prostate enlargement.We investigated whether pretreatment with dutasteride before HoLEP could reduce intraoperative bleeding. A total of 402 patients were included in this double-blind placebo-controlled trial to receive daily 0.5 mg of dutasteride or placebo over 8 weeks before HoLEP. Vascular endothelial growth factor (VEGF) and microvascular density (MVD) were evaluated. Analysis was also stratified according to prostate volume (<70 mL vs ≥70 mL).Hemoglobin and hematocrit values before and after surgery were not statistically different between the two groups. MVD and VEGF index in smaller prostates were 23.35±1.96 and 4.06±0.76 in the treatment group and 19.04±0.96 and 2.55±0.55 in placebo (p<0.05); in patients with larger prostates MVD and VEGF were 26.83±2.812 and 8.54±1.18 in the treatment group and 20.76±0.79 and 3.21±0.54 in placebo (p<0.05).Vascularization of the prostate was affected by 5ARIs therapy. HoLEP is less burdened in perioperative bleeding and for this reason we did not find any difference in hemoglobin/hematocrit values pre- and post- surgery.
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http://dx.doi.org/10.18632/aging.102883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093193PMC
March 2020

Body mass index and age correlate with antioxidant supplementation effects on sperm quality: Post hoc analyses from a double-blind placebo-controlled trial.

Andrologia 2020 Apr 4;52(3):e13523. Epub 2020 Feb 4.

Department of Urology, Sapienza Rome University, Rome, Italy.

Spermatozoa are vulnerable to lack of energy and oxidative stress as a result of elevated levels of reactive oxygen species. Therefore, it is essential that appropriate nutrients are available during maturation. This randomised, double-blind, placebo-controlled trial investigated the effect of 6-month supplementation with carnitines and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. Semen analyses were done at the beginning and end of the treatment. In addition to main analyses, post hoc analyses for age and body mass index (BMI) were carried out. Results were interpreted by dividing the population into two age and BMI classes. In 94 patients who completed the study, all sperm parameters increased in supplemented patients compared to the placebo group. A significant (p = .0272) difference in supplementation efficacy was observed for total motility on patients with varicocele and BMI < 25. In the same group, also the progressive motility was significantly superior (p = .0159). For Responder analysis, total motility results were confirmed in both the cited group (p = .0066) and in the varicocele group with BMI < 25 and age < 35 (p = .0078). This study suggests that supplementation is more effective in subjects with varicocele younger than 35 years with BMI < 25.
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http://dx.doi.org/10.1111/and.13523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065376PMC
April 2020

Efficacy and safety of Finasteride (5 alpha-reductase inhibitor) monotherapy in patients with benign prostatic hyperplasia: A critical review of the literature.

Arch Ital Urol Androl 2020 Jan 13;91(4):205-210. Epub 2020 Jan 13.

Department of Maternal-Child and Urological Sciences, Sapienza Rome University, Policlinico Umberto I Hospital, Rome.

Background: Combination therapy with 5 alpha-reductase inhibitor (5-ARI) and alpha-blocker can be considered as a gold standard intervention for medical management of lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH). On the other hand, 5-ARI monotherapy and in particular Finasteride alone is currently getting focus of attention especially due to lack of systematic reviews investigating efficacy outcomes and/or adverse events associated.

Objectives: Aim of the present critical review was to analyze current knowledge of clinical efficacy and incidence of adverse events associated with 5-ARI treatment for LUTS/BPH.

Materials And Methods: A systematic review of clinical trials of the literature of the past 20 years was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 8821 patients were included in this study and inclusion criteria for studies selection were: data from randomized clinical trials (RCTs) focusing their attention on the clinical role of Finasteride monotherapy for symptomatic BPH. Parameters of research included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), postvoid residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs).

Results: Overall 12 original articles were included and critically evaluated. Sample sizes of patient actively treated with finasteride varied from 13 to 1524 cases analyzed in a single study. Follow-up after treatments ranged from 3 to 54 months. The effect of finasteride in reducing prostate volume (PV) was moderate (standardized mean difference (SMD) effect between 0.5 to 0.8 for all trials evaluable) while the effect on IPSS score and Qmax was considered significant (SMD in the 0.2 to 0.5 variation range). No severe AEs and/or psychiatric disorders were retrieved among the studies. Sexual health dysfunctions were significantly influenced by finasteride therapy when compared with placebo treated patients.

Conclusions: Although significant clinical benefits of finasteride monotherapy were demonstrated, the effective size of the available reports included in the analysis is limited. Additional head-to-head studies would be needed to re-evaluate clinical efficacy and safety of 5-ARI in combination or not with alpha blockers.
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http://dx.doi.org/10.4081/aiua.2019.4.205DOI Listing
January 2020

Prospective Assessment of Vesical Imaging Reporting and Data System (VI-RADS) and Its Clinical Impact on the Management of High-risk Non-muscle-invasive Bladder Cancer Patients Candidate for Repeated Transurethral Resection.

Eur Urol 2020 01 5;77(1):101-109. Epub 2019 Nov 5.

Department of Radiological, Oncological and Anatomopathological Sciences, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy. Electronic address:

Background: Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended in most of high-risk non-muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient's stratification for such recommendation exist.

Objective: To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT.

Design, Setting, And Participants: Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes.

Intervention: Multiparametric MRI of the bladder before TURBT.

Outcome Measurements And Statistical Analysis: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability.

Results And Limitations: A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval [CI]: 82.2-97.3), 91.1% (95% CI: 85.8-94.9), 77.5% (95% CI: 65.8-86.7), and 97.1% (95% CI: 93.3-99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91-0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1-96.8), 93.6% (95% CI: 86.6-97.6), 74.5% (95% CI: 52.4-90.1), and 96.6% (95% CI: 90.5-99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87-0.97).

Conclusions: VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT.

Patient Summary: We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non-muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site.
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http://dx.doi.org/10.1016/j.eururo.2019.09.029DOI Listing
January 2020

A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility.

Asian J Androl 2020 Jul-Aug;22(4):360-367

Department of Urology, Stanford University, School of Medicine, Stanford, CA 94305, USA.

Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.
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http://dx.doi.org/10.4103/aja.aja_101_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406101PMC
October 2019

Syndromic infertility.

Acta Biomed 2019 09 30;90(10-S):75-82. Epub 2019 Sep 30.

MAGI's Lab, Rovereto (TN), Italy.

Infertility due to genetic mutations that cause other defects, besides infertility, is defined as syndromic. Here we describe three of these disorders for which we perform genetic tests. 1) Hypopituitarism is an endocrine syndrome characterized by reduced or absent secretion of one or more anterior pituitary hormones with consequent dysfunction of the corresponding peripheral glands. Deficiencies in all the hormones is defined as pan-hypopituitarism, lack of two or more hormones is called partial hypopituitarism, whereas absence of a single hormone is defined as selective hypopituitarism. Pan-hypopituitarism is the rarest condition, whereas the other two are more frequent. Several forms exist: congenital, acquired, organic and functional. 2) The correct functioning of the hypothalamic-pituitary-gonadal axis is fundamental for sexual differentiation and development during fetal life and puberty and for normal gonad function. Alteration of the hypothalamic-pituitary system can determine a condition called hypogonadotropic hypogonadism, characterized by normal/low serum levels of the hormones FSH and LH. 3) Primary ciliary dyskinesia is frequently associated with infertility in males because it impairs sperm motility (asthenozoospermia). Primary ciliary dyskinesia is a group of genetically and phenotypically heterogeneous disorders that show morpho-structural alterations of the cilia. Adult women with primary ciliary dyskinesia can be subfertile and have an increased probability of extra-uterine pregnancies. This is due to delayed transport of the oocyte through the uterine tubes.
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http://dx.doi.org/10.23750/abm.v90i10-S.8764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233644PMC
September 2019

Non-syndromic monogenic male infertility.

Acta Biomed 2019 09 30;90(10-S):62-67. Epub 2019 Sep 30.

MAGI's Lab, Rovereto (TN), Italy.

Infertility is a widespread clinical problem affecting 8-12% of couples worldwide. Of these, about 30% are diagnosed with idiopathic infertility since no causative factor is found. Overall 40-50% of cases are due to male reproductive defects. Numerical or structural chromosome abnormalities have long been associated with male infertility. Monogenic mutations have only recently been addressed in the pathogenesis of this condition. Mutations of specific genes involved in meiosis, mitosis or spermiohistogenesis result in spermatogenic failure, leading to the following anomalies: insufficient (oligozoospermia) or no (azoospermia) sperm production, limited progressive and/or total sperm motility (asthenozoospermia), altered sperm morphology (teratozoospermia), or combinations thereof. Androgen insensitivity, causing hormonal and sexual impairment in males with normal karyotype, also affects male fertility. The genetic causes of non-syndromic monogenic of male infertility are summarized in this article and a gene panel is proposed.
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http://dx.doi.org/10.23750/abm.v90i10-S.8762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233647PMC
September 2019

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