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To contrast opportunistic PCa screening, the European Union Council suggested extending screening programs to PCa by recommending the implementation of a stepwise approach in the EU Countries to evaluate the feasibility and effectiveness of an organized program based on PSA testing in combination with additional MRI as a follow-up test. The objective of this expert-based document is to propose an organized PCa screening program according to the EU Council recommendations. The Italian Society of Urology (SIU) developed a team of experts with the aim to report 1) the most recent epidemiologic data about incidence, prevalence, and mortality of PCa; 2) the most important risk factors to identify categories of men with an increased risk to eventually develop the disease; 3) the most relevant studies presenting data on population-based screening; and 4) the current recommendations of the leading International Guidelines. According to previous evidence, the Panel proposed some indications to develop a new organized PCa screening program for asymptomatic men with a life-expectancy of at least fifteen years. The SIU Panel strongly supports the implementation of a pilot, organized PCa screening program inviting asymptomatic men in the age range of 50-55 years. Invited men who are already performing opportunistic screening will be randomized to continue opportunistic screening or to cross into the organized protocol. Men with PSA level ≤3 ng/mL and familiarity for PCa received a DRE as well as all those with PSA levels >3 ng/mL. All other men with PSA levels greater than 3 ng/mL proceed to secondary testing represented by mpMRI. Men with Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3 and PSAD 0.15 ng/mL/cc or higher as well as those with PI-RADS 4-5 lesions proceed to targeted plus systematic prostate biopsy. The primary outcome of the proposed pilot PCa screening program will be the detection rate of clinically significant PCa defined as a tumor with a ISUP Grade Group ≥2. Main secondary outcomes will be the detection rate of aggressive PCa (ISUP Grade Group ≥4); the detection rate of insignificant PCa (ISUP Grade Group 1); the number of unnecessary prostate biopsy avoided, the metastasis-free survival, and the overall survival. Men will be invited over a one-year period. Preliminary analyses will be planned 2 and 5 years after the baseline enrollment. According to the recent EU Council recommendations on cancer screening, pilot studies evaluating the feasibility and effectiveness of PCa screening programs using PSA as the primary and mpMRI as the secondary screening test in selected cohorts of patients must be strongly promoted by scientific societies and supported by national governments.

Background: Voluntary PCa screening frequently results in excessive use of unnecessary diagnostic tests and an increasing risk of detection of indolent PCa and unaffordable costs for the various national health systems. In this scenario, the Italian Society of Urology (Società Italiana di Urologia, SIU) proposes an organized flow chart guiding physicians to improve early diagnosis of significant PCa avoiding unnecessary diagnostic tests and prostate biopsy., Methods: According to available evidence and international guidelines [i.e., European Association of Urology (EAU), American Association of Urology (AUA) and National Comprehensive Cancer Network (NCCN)] on PCa, a Panel of expert urologists selected by Italian Society of Urology (SIU, Società Italiana di Urologia) proposed some indications to develop a stepwise diagnostic pathway based on the diagnostic tests mainly used in the clinical practice. The final document was submitted to six expert urologists for external revision and approval. Moreover, the final document was shared with patient advocacy groups., Results: In voluntary men and symptomatic patients with elevated PSA value (>3 ng/mL), the Panel strongly discourage the use of antibiotic agents in absence of urinary tract infection confirmed by urine culture. DRE remains a key part of the urologic physical examination helping urologists to correctly interpret PSA elevation and prioritizing the execution of multiparametric Magnetic Resonance Imaging (mpMRI) in presence of suspicious PCa. Men with negative mpMRI and low clinical suspicion of PSA (PSA density < 0.20 ng/mL/cc, negative DRE findings, no family history) can be further monitored. Men with negative mpMRI and a higher risk of PCa (familial history, suspicious DRE, PSAD>0.20 ng/mL/cc or PSA>20 ng/mL) should be considered for systematic prostate biopsy. While PI-RADS 4-5 lesions represent a strong indication for prostate biopsy, PI-RADS 3 lesions should be further stratified according to PSAD values and prostate biopsy performed when PSAD is higher than 0.20. Accreditation, certification, and quality audits of radiologists and centers performing prostatic mpMRI should be strongly considered. The accessibility and/or the waiting list for MRI examinations should be also evaluated in the diagnostic pathway. The panel suggests performing transperineal or transrectal targeted plus systematic biopsies as standard of care., Conclusions: Scientific societies must support the use of shared diagnostic pathway with the aim to increase the early detection of significant PCa reducing a delayed diagnosis of advanced PCa. Moreover, a shared diagnostic pathway can reduce the incorrect use of antibiotic, the number of unnecessary laboratory and radiologic examinations as well as of prostate biopsies.

To the Editor, The aim of this "position paper" is to describe the discipline of Pediatric Urology with its clinical and cultural competencies, represent the reasons for legitimizing its existence, and reinforce its importance in the "scenario" of the National Italian Healthcare System. The requisites and the educational requirements were defined by both the Italian Ministry of Health with the State-Regions Conference, and the European Union [...].

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.

Objective: Overweight and low physical activity (PA) increase the risk of prostatic enlargement and erectile dysfunction (ED). Less clear is the role of these factors at young age on the lifelong risk., Materials and Methods: During June 2018 the Italian Society of Urologists organized the month of Male Urologic Prevention "#Controllati". Men aged 18 years or more were invited to attend urologic centers for a visit and counselling about urologic/ andrologic conditions. Each participating man underwent a physical examination and was asked about urologic symptoms, sexual activity and possible related problems., Results: We analyzed data from 2786 men, aged 55.1 years (SD 10.9, range 19-97). A total of 710 (25.5%) subjects had a diagnosis of prostatic enlargement and 632 (22.7%) of DE. Overweight/obese men were at increased risk of prostatic enlargement and ED with corresponding odds ratio (0R) in comparison with normal or underweight men, being respectively 1.18 (95% Confidence Interval (CI) 1.00-1.44) and 1.69 (95% CI 1.39-2.05). The OR of prostatic enlargement in comparison with men reporting at age 25 a BMI < 25.0 was 1.22 (95% CI 1.01-1.51) for men with a BMI at 25 years of age ≥ 25; the corresponding OR value for ED was 1.17 (0.92- 1.48). Considering total PA at diagnosis, the OR of prostatic enlargement in comparison with no or low PA, was 0.69 (95%CI 0.55-0.86) for men reporting moderate PA and 0.75 (95%CI 0.58-0.98) for those reporting intense PA. When we considered PA at 25 years of age, the OR of subsequent diagnosis of prostatic enlargement, in comparison with men reporting no/low PA at 25 years of age was 0.81 (95%CI 0.63-1.04) for men reporting moderate PA and 0.70 (95%CI 0.52-0.99) for those reporting intense PA., Conclusions: These findings underline the utility of encouraging healthy lifestyle habits among young men in order to reduce the subsequent risk of prostatic enlargement and ED.

Objective: The risk factors for benign prostatic enlargement (BPE) are not well understood and particularly few data are available from Italian population., Materials and Methods: This was an observational cross sectional study aimed to examine the association between several risk factors and BPE. During the "#Controllati2017" initiative, men aged 18 years or more were invited to attend participating urologic centers for a free of charge visit for counseling about urologic or andrologic conditions. Each participating man underwent a physical examination including digital rectal examination (DRE). Further he was asked about his medical history, urologic symptoms, sexual activity and related problems. Diagnosis of BPE was made by the urologist after DRE., Results: Out of the 1902 [mean age 54 years (SD 12, range 18-92)] considered men, a total of 603 subjects (31.7%) had diagnosis of BPE. The diagnosis of BPE increased from 9.3% in men aged < = 50 years, to 34.1% in those aged 51-60 years and to 58.7% among men aged > 60 years. A history of hypertension, diabetes, heart diseases, hypercholesterolemia and hypertriglyceridemia were all significantly associated with an increased risk of BPE in the total series and, although not always in a statistically significant way, in strata of age. Physical activity (PA) was significantly associated with a decreased risk of BPE. We have further analyzed the risk of BPE in men with one or more of the identified risk factors (i.e. hypertension, diabetes, heart disease, hypercholesterolemia, hypertriglyceridemia and low PA): the risk of BPE increased with number of risk factors reported by the subjects. The estimated risk were higher among younger men., Conclusion: In our study a history of hypertension, diabetes, heart disease, hypercholesterolemia and hypertriglyceridemia increased the risk and physical activity lowered the risk of BPE. This risk profile was observed also in men aged < 50 years.

Objective: Prevention may improve the quality of life and sexual and reproductive health. To improve prevention require a comprehensive research approach that examines the frequency and risk factors for urologic conditions. In June 2016 the Italian Urologic Society coordinated a preventive initiative : the 1st Week of Male Urologic Prevention "#Controllati"., Material and Methods: During the 1st Week of Male Urologic Prevention "#Controllati", men aged 18 years or more were invited to attend participating urologic centers for a free of charge visit for counseling about urologic or andrologic conditions. Each participating man underwent a physical examination. Further he was asked about his a medical history and about his urologic symptoms, sexual activity and possible related problems., Results: Data were collected in 81 centers: 2380 men answered the questionnaire. A total of 1226 subjects participating in the study reported one or more urinary symptom [51.5% (IC 95% 48.9%-54.5%)]. The risk of any urinary symptoms increased with age: in comparison with men aged &lt; = 30 years or less the risk of any urinary symptoms was 2.31, 2.92, 5.12, 7.82 and 17.02 respectively in the class age 31-40, 41-50, 51-60, 61-70 and &gt; = 71. Overweight/obese men were at increased risk of any urinary symptoms [OR1.35 (95% CI 1.12-1.64)]. 27.2% (IC 95% overall 25.2% -29.3%) of the subjects had at least a sexual disorder (erectile dysfunction, premature ejaculation, hypoactive sexual desire). The erectile dysfunction and hypoactive sexual desire increased with age, but premature ejaculation tended to be higher among younger aged men aged 40 years or more. Current any urinary symptoms [OR 1.85 (CI 1.40-2.43)], hypertension [OR 1.66 (95% CI 1.21-2.26) and diabetes (OR 2.37 (95% CI 1.45-3.88)] increased the risk of erectile dysfunction., Conclusions: This large survey gives a picture of the burden of the more frequent urologic conditions offering useful information in order to focus preventive campaign.

This study aimed to determine the occurrence and grade of cystographically detected urinary leakage (UL) in a contemporary series of open retropubic radical prostatectomy (RP), whether patients' clinical variables predict occurrence of UL, and whether occurrence of UL correlates with patients' voiding outcomes in terms of urinary continence and anastomotic stricture (AS). Enrolled patients underwent cystography 7 days after retropubic RP; in case of UL, the catheter was left in situ and cystography repeated at 7 days intervals until demonstrating absence of UL. Leakage was classified as grade I = extraperitoneal leak <6 cm, grade II = extraperitoneal leak >6 cm, grade III = leak freely extending in the small pelvis. Voiding was evaluated at 3, 6, and 12 months after RP using the 24-hour pad test and uroflowmetry; in cases of maximum flow rate <10 mL/s, urethrocystoscopy was carried out to determine presence and location of an AS. The first postoperative cystogram showed UL in 52.6% of patients (grade I in 48.1%, grade II in 21.5%, and grade III in 30.4% of the cases). Multivariate analysis demonstrated that patients with UL had significantly greater prostate volume (64.5 vs 34.8 cc, P < 0.001), loss of serum hemoglobin (4.77 vs 4.19 g/dL, P < 0.001), lower postoperative serum total proteins (4.85 vs 5.4 g/dL, P < 0.001), and higher rate of AS (20.6% vs. 2.8%, p < 0.001) than those without UL. Continence rate at 3, 6, and 12 months postoperatively was 34.2%, 76%, and 90%, respectively, in patients with UL compared with 77.5%, 80.3%, and 93% in patients without UL; such difference was statistically significant (P < 0.001) only at 3 months follow-up. ROC curve analysis showed that prostate volume and postoperative serum total proteins had the best AUC (0.821 and 0.822, respectively) and when combined, their positive and negative predictive values for UL were 90% and 93%, respectively. In conclusion, half of the patients undergoing open retropubic RP may present, 7 days postoperatively, some degree of cystographically detected UL; prostate volume, loss of serum hemoglobin, and postoperative serum total proteins could be used to predict it. UL delayed return to urinary continence without affecting long-term results, but led to a significantly higher rate of AS.

Objective: Water source and cigarette smoking are related to clinical characteristics and pathology of superficial transitional cell carcinoma of the bladder., Methods: Tumor number, dimension, G-grade, T-stage, recurrences, cigarette smoking and water supply were recorded in patients harboring Ta-T1 G1-3 transitional cell carcinoma of the bladder., Results: Of 577 patients, 61% had multiple and 36% recurrent tumors. Two hundred and forty-one patients (42%) were current smokers and 188 (33%) were former smokers. Bottled water was the only drinkable source for 249 (45%) patients, municipal water supply for 177 (32%), artesian wells for 38 (7%), spring water for 7 (1%) and mixed source for 89 (16%). By adopting a cut-off of 30 years of smoking, patients affected by recurrent tumors varied from 22 to 43% (p = 0.0001). T1 tumors were more frequent in patients drinking nonbottled water (p = 0.03). Nonbottled supply was more frequent in never smokers (p = 0.015) and could represent a weak risk factor not detectable in smokers., Conclusions: Cigarette smoking correlates with the number of recurrences. T1 tumors were statistically more frequent in patients taking nonbottled drinking water. Chlorinated water supply was more frequent among patients who did not present cigarette smoking as a risk factor., (Copyright 2009 S. Karger AG, Basel.)

Sequence variations in a variety of pro- or anti-inflammatory cytokine genes have been found to influence successful aging and longevity. Because of the role played by the transforming growth factor beta1 (TGF-beta1) cytokine in inflammation and regulation of immune responses, the variability of the TGF-beta1 gene may affect longevity by playing a role in inflamm-aging. Two polymorphisms, G/A -800 and C/T -509, located in the 5' region, and two missense polymorphisms, T/C 869 and G/C 915 which change (Leu > Pro)10 and (Arg > Pro)25, respectively, located in the signal peptide, were analysed in 419 subjects from Northern and Central Italy, including 172 centenarians and 247 younger controls. In addition, the effects of the TGF-beta1 genetic variability on plasma levels of the biologically active form (naturally processed) of this cytokine were studied in 143 randomly selected subjects, including 73 centenarians. Significant differences were found at the +915 site as far as the C allele and GC genotype were concerned, both of them being lower in centenarians than in young controls (P=0.034 and 0.028, respectively), but none of the other tested genetic variants was significantly different between centenarians and controls. Moreover, a particular haplotype combination (G -800/C -509/C 869/C 915) was notably lower in centenarians than in younger individuals (P=0.007). Finally, active TGF-beta1 plasma levels were significantly increased in the elderly group, but no relationship with TGF-beta1 genotypes was observed. These results suggest that, at least in this population, the variability of the TGF-beta1 gene influences longevity and that the age-related increase in plasma levels of active TGF-beta1 seems not to be genetically regulated.

The human HRAS1 belongs to an evolutionarily-conserved family of genes which enrolls among its members the yeast RAS2, a gene which regulates stress response and longevity in the Saccharomyces cerevisiae. In this paper we report that the frequency of the a3 allele of HRAS1 3'variable number tandem repeat (HRAS1 3'VNTR) decreases in centenarians in respect to young people, and we estimate that during aging a3 carriers have a relative mortality risk of 1.126 (95% CI=1.044-1.213). We propose that the germ-line variability at the HRAS1 locus impacts on the individual's capacity to reach the extreme limits of human life-span. Furthermore, we provide suggestive evidence that a3 HRAS1 3'VNTR allele and inherited variants of the mitochondrial genome (mtDNA haplogroups) do not affect independently human longevity, thus recalling the nucleus-mitochondrion interaction which regulates stress response and life-span in the yeast.

Mitochondrial DNA (mtDNA) is characterized by high variability, maternal inheritance, and absence of recombination. Studies of human populations have revealed ancestral associated polymorphisms whose combination defines groups of mtDNA types (haplogroups) that are currently used to reconstruct human evolution lineages. We used such inherited mtDNA markers to compare mtDNA population pools between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (median age 38 years) carefully matched as to sex and geographic origin (northern and southern Italy). All nine haplogroups that are typical of Europeans were found in both samples, but male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity.

The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding the 3'APOB-VNTR alleles into three size-classes (small, S, 26-34 repeats; medium, M, 35-39 repeats; large, L, 41-55 repeats), an age-related convex trajectory of the frequency of SS homozygotes was found. The frequency of SS in the genotype pool increased from the group aged 10-19 years (3.06 +/- 1.74%) to that aged 40-49 years (8.51 +/- 4.07%). Then it declined reaching the minimum value in centenarians (1.58 +/- 0.90%). The observed trajectory is in agreement with that expected by assuming crossing of mortality curves relevant to subgroups of individuals having different genotypes.

Genotype and allele frequencies at seven Variable Number of Tandem Repeats (VNTR) loci currently used for forensic purposes have been estimated in a population sample from Calabria (south Italy). DNA target regions relevant to four microsatellites (THO.1; REN.4; D12S67; DYS19) and three minisatellites (D1S80; 3'APOB; TPO.10) were amplified by Polymerase Chain Reaction (PCR) and analysed by electrophoresis and ethidium bromide or silver staining. For all loci, the observed genotypes were found to be in agreement with those expected by the Hardy-Weinberg equilibrium. Data on allele frequencies were in line with those found in sample groups from northern or central Italy, tested for some of the above polymorphisms.