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ObjectiveTo date, several ultra-minimally-invasive surgical techniques are available for the treatment of male LUTS due to benign prostatic obstruction (BPO). Herein we report our preliminary experience with SoracteLite™ TPLA for the treatment of carefully selected patients with LUTS due to BPO.MethodsData from all consecutive patients undergoing TPLA at our institution between April 2021 and February 2022 were prospectively collected in a specific database. Data regarding functional and sexual outcomes evaluated by validated questionnaires and uroflowmetry were analyzed. All the procedure were performed in an outpatient setting, under local anesthesia and conscious sedation, using EchoLaser device, a multisource diode laser generator.ResultsOverall, 38 patients underwent TPLA at our institution during the study period. The median prostate volume was 46 ml (IQR 38-71). The median time to complete the procedure was 31 min (IQR 28-37). All patients but one were discharged within 8 hours of hospital stay. No perioperative Clavien-Dindo grade ≥2 complications were recorded. Median improvement in Qmax was 17%, 24% and 32% at 1 month, 3 months and last follow-up after surgery; as a result, the median postoperative IPSS at 1 month, 3 months and at last follow-up decreased by -14%, -36% and -35%, respectively. All patients preserved ejaculatory and sexual function. Two patients (5%), catheter carriers before the procedure, experienced acute urinary retention after TPLA treatment and required replacement of an indwelling catheter.ConclusionsTPLA can be a feasible, safe and effective ultra-minimally-invasive procedure for carefully selected patients with LUTS due to BPO.

Background Aim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive partial nephrectomy (MI-PN). Material and methods All consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score. Results 1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%); p = 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%); p = 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables), p Conclusions The results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP.

Simple Summary Urothelial bladder cancer (BC) is one of the most fatal cancers, with a dismal five-year survival rate of 5% in patients with metastatic disease. Clinically relevant benefits of immunotherapy in advanced or metastatic bladder cancer have led to Food and Drug Administration (FDA) approval of immune checkpoint inhibitors (ICIs) as second- or first-line therapy in patients unresponsive to or ineligible for standard treatment. The advantage of ICIs is being investigated in various stages of BC, either as monotherapy or in combination with other drugs. In this review we discuss the role of ICIs in BC, highlighting their current clinical application and outlining future therapeutic perspectives. Abstract Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.

Background: the aim of this study was to perform an Italian telematics survey analysis on the changes in couples’ sex lives during the coronavirus disease 2019 (COVID-19) lockdown. Methods: a multicenter cross sectional study was conducted on people sexually active and in stable relationships for at least 6 months. To evaluate male and female sexual dysfunctions, we used the international index of erectile function (IIEF-15) and the female sexual function index (FSFI), respectively, marital quality and stability were evaluated by the marital adjustment test (items 10–15), to evaluate the severity of anxiety symptoms, we used the Hamilton Anxiety Rating Scale. The effects of the quarantine on couples’ relationships was assessed with questions created in-house. Results: we included 2149 participants. The sex lives improved for 49% of participants, particularly those in cohabitation, for 29% it deteriorated, while for 22% of participants it did not change. Women who responded that their sex lives deteriorated had no sexual dysfunction, but they had anxiety, tension, fear, and insomnia. Contrarily, men who reported deteriorating sex lives had erectile dysfunctions and orgasmic disorders. In both genders, being unemployed or smart working, or having sons were risk factors for worsening the couples’ sex lives. Conclusion: this study should encourage evaluation of the long-term effects of COVID-19 on the sex lives of couples.

Background: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project). Methods: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared. Results: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6–8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74). Conclusion: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease.

Visceral metastasis is widely considered a prognostic factor for overall survival of men with metastatic castration-sensitive prostate cancer (mCSPC) and has been historically managed with androgen deprivation therapy (ADT). More recently, this therapeutic scenario has been enriched by the possibility to integrate ADT with chemotherapy or novel androgen-signaling-targeted inhibitors. In order to define the effect of chemotherapy/androgen-signaling-targeted inhibitors plus ADT, we performed a pooled analysis on patients with mCSPC and visceral metastases, revealing that survival was significantly improved in patients without visceral metastasis (hazard ratio, 0.64; 95% confidence interval, 0.56-0.74; P .01) compared to men with visceral metastases (hazard ratio, 0.68; 95% confidence interval, 0.51-0.91; P .01). Although several limitations do not allow us to draw definitive conclusions, our analysis confirms the efficacy of chemotherapy/androgen-signaling-targeted inhibitors in combination with ADT in mCSPC with visceral metastases as well. In the absence of specific randomized controlled trials, symptoms, toxicity, cost, patient preference, and clinical experience should guide the decision to add chemotherapy or androgen receptor-targeted therapy to ADT in patients with visceral metastases from mCSPC.

Patients diagnosed with non-clear renal cell carcinoma have often been excluded from clinical trials due to the shortage of treatments available, the low incidence of tumours with non-clear histology, and the corresponding diversity of intrinsic molecular features. This approach led to a knowledge gap in finding the optimal treatment for patients diagnosed with non-clear cell renal carcinoma. Cabozantinib, a potent multiple tyrosine kinase receptor inhibitor, has been recently investigated in patients with non-clear cell histologies of renal cell cancer. In this review, we have summarized available data on the use of cabozantinib in non-clear renal cell carcinoma.

PURPOSE: to evaluate clinical predictors of positive surgical margins (PSMs) in a large multicenter prospective observational study and to develop a clinic nomogram to predict the likelihood of PSMs after partial nephrectomy (PN). MATERIALS AND METHODS: We prospectively evaluated 4308 patients who had surgical treatment for renal tumors between January 2013 and December 2016 at 26 urological Italian Centers (RECORd 2 project). Two multivariable logistic models were evaluated to predict the likelihood of PSMs. Center caseload was dichotomized using a visual assessment adjusted for several predictors of PSMs. A nomogram predicting PSMs was developed. RESULTS: Overall, 2076 patients treated with PN were evaluated. pT1a, pT1b, pT2 and pT3a were recorded in 68.7%, 22.6%, 2.1% and 6.6% of the patients, respectively. PSMs were recorded in 342 (16.5%) patients. From a null multivariable model against number of PN/year, 60 PN/year were identified as the best cut-off to define a high-volume centre. At multivariable analysis, clinical stage (cT1a vs. cT2 [OR 1.94]; p = 0.03), volume centre (≤60 PN/year) (OR 2.22; p

Introduction: Microchimerism (MC) is the presence of a small amount of foreign cells or DNA within a person’s circulation or tissues. It has been identified also in recipients of solid organ transplants where it seems to be critical for the development and maintenance of immunological tolerance. Nevertheless, natural and/or iatrogenic MC can be acquired prior to transplantation, through pregnancy and/or blood transfusion. Objective: The aim of this study was to detect the presence of MC in women after renal transplantation from male cadaveric donors and its relationship with graft outcomes. Methods: We studied by qPCR the presence of the DYS14 gene sequence of the Y chromosome in 12 females who received a kidney graft from a male donor before transplantation (T0), after 15 days (T1) and 1 year of transplantation (T2). We found the sequence in all recipients after renal transplantation. Results: All the women were negative for this sequence prior to transplantation (T0). Mean (SD) Y-related DNA quantity was 0.80 (0.69) ng/mL plasma and 0.15 (0.26) ng/mL plasma at T1 and T2, respectively. No acute rejection was observed, and mean (SD) estimated Cr clearance was 68.8 (16.9) mL/min within 1 year from transplantation. Conclusions: Presence of MC was associated with good kidney graft outcomes after 1 year of transplantation, but further studies will be needed to investigate the relationship between clinical outcomes and the development of MC in renal transplant recipient.

OBJECTIVE To investigate the correlation of a history of lower urinary tract symptomatology during childhood with lower urinary tract dysfunction in young adult women. SUBJECTS AND METHODS This was a multicentre, prospective, case-control study conducted between April 2013 and November 2015. A total of 300 women, aged 18-40 years, participated. The case group comprised women attending urogynaecology clinics for various lower urinary tract complaints and the control group was recruited from a healthy population. Exclusion criteria were designed to avoid common causes of lower urinary tract dysfunction and symptoms and included diabetes mellitus, neurological disease and pelvic inflammatory disease. All women completed a self-administered 77-item questionnaire, exploring childhood urological and bowel history, as well as current urological, bowel and sexual symptoms. Statistical analysis was performed using chi-squared and Fisher's exact tests to compare categorical variables. Multivariate logistic regression models were fit for the prediction of the adult outcomes, incorporating as explanatory variables all those that showed a significant P value in bivariate analysis. P values < 0.05 were considered statistically significant. RESULTS Women with childhood urinary voiding and storage symptoms had a higher prevalence of these symptoms in adult life compared with women without such history. Women with urinary tract infections (UTIs) during childhood had a higher incidence of adult UTIs compared with women without this problem in childhood. CONCLUSIONS Lower urinary tract dysfunction in childhood seems to 'persist' in young adult life but the implications of this finding in clinical practice need to be defined in future studies.

Objectives To present our experience with a sigmoid orthotopic neobladder. Methods We retrospectively evaluated the functional and oncological outcomes of 160 patients who underwent orthotopic neobladder reconstruction using a detubularized 20–25-cm sigmoid segment at our institution. Each patient was evaluated every 3 months the first year, every 6 months for the next 4 years and annually thereafter. Urodynamic studies of all consenting patients were carried out after 6 months, and 2, 5 and 10 years. We carried out the log–rank test, and used Cox regression models and Kaplan–Meier survival analysis. The anova test was used to compare urodynamic findings over time. Results Mean follow up was 6.8 years (range 0.65–21.7 years). Overall survival was 58.1% at 5 years, and 47.1% at 10 years. Early complications occurred in 36 patients (22.6%); late complications in 40 (25%). Stage V chronic kidney disease developed in two patients (1.3%). Complete (daytime and night-time) continence, defined as no need for pads or condom devices, was achieved by 45% of patients at 5 years, daytime continence was achieved by just 36% of patients; both were unchanged at 10 years. A significant difference emerged in maximal neobladder capacity and post-void residual values between 6 months and 2 years, and between 2 and 5 years (P < 0.01 and P = 0.03, respectively). Conclusions Sigmoid neobladder continence and capacity significantly improve over the first 5 years, and they remain stable over the long term. Upper urinary tract function is not affected by endoluminal pressure, and the rate of metabolic imbalance is negligible.

Objectives To evaluate outcomes and quality of life in patients operated transvaginally with an original mesh shape for uterus-sparing prolapse surgery and to demonstrate the safety and efficacy of the technique. Study design We prospectively evaluated 66 postmenopausal patients (POP-Q Stage III: 32, IV: 34) operated between May 2008 and December 2013. We used wide weave polypropylene monofilament mesh that functions as a hammock anchored posteriorly to sacrospinous ligaments, its anterior wings exit the pelvis through the obturatory membrane. Follow-up was scheduled at 3-, 12- months and in May 2016. Prolapse-Quality of Life Questionnaire (P-QoL) was administered preoperatively, at 12 months and in May 2016. The chi square and Wilcoxon test were used for statistical analysis. Results Mean follow-up was 5.6 (SD: 1.6, Range: 1.1–8.1) years. The overall success rate (POP-Q ≤ 2) was 92.5% at 12 months and 84.4% at May 2016, these data remained stable over time (p > 0.05). Early complications occurred in 2 (3%) patients, late in 5 (7.8%) of which mesh extrusion in 4 (6.3%). Data from P-QoL showed significant improvement between preoperative and postoperative data (P 0.05). De-novo dyspareunia was 17.6% at 12 months and 10.3% at May 2016. Conclusions The low rate and grade of complications demonstrates the safety of the procedure, which offers stable anatomical correction with significant improvement in QoL.

Introduction Coital urinary incontinence (CUI) is not much explored during clinical history, and this could lead to an underestimation of the problem. Aim To evaluate the prevalence and clinical risk factors of CUI in women with urinary incontinence (UI), and to measure the impact of CUI on women’s sexuality and quality of life. Methods This was a multicenter international study, conducted in Italy, Greece, the United States, and Egypt. Inclusion criteria were: sexually active women with UI and in a stable relationship for at least 6 months. Exclusion criteria were: age Main Outcome Measures To evaluate the CUI and its impact on sexual life we used the open questions on CUI as well as the International Consultation on Incontinence questionnaire and Patient Perception of Bladder Condition questionnaire. Results In this study 1,041 women (age 52.4 ± 10.7 years) were included. In all, 53.8% of women had CUI: 8% at penetration, 35% during intercourse, 9% at orgasm, and 48% during a combination of these. Women with CUI at penetration had a higher prevalence of SUI, women with CUI during intercourse had higher prevalence of MUI with predominant SUI, and women with CUI at orgasm had higher prevalence of UUI and MUI with predominant UUI component. Previous hysterectomy was a risk factor for CUI during any phase, while cesarean delivery was a protective factor. Previous failed anti-UI surgery was a risk factor for CUI during penetration and intercourse, and body mass index >25 kg/m2 was a risk factor for CUI at intercourse. According to International Consultation on Incontinence questionnaire scores, increased severity of UI positively correlated with CUI, and had a negative impact on the quality and frequency of sexual activity. Clinical Implications This study should encourage physicians to evaluate the CUI; in fact, it is an underestimated clinical problem, but with a negative impact on quality of life. Strengths & Limitations The strength of this study is the large number of women enrolled, while the limitation is its observational design. Conclusion CUI is a symptom that can affect sexual life and should be investigated during counseling in all patients who are referred to urogynecological centers.

There is evidence that an inflammatory microenvironment is associated with the development and progression of prostate cancer (PCa), although the determinants of intrinsic inflammation in PCa cells are not completely understood. Here we investigated whether expression of intrinsic microsomal PGE synthase-1 (mPGES-1) enhanced aggressiveness of PCa cells and might be critical for epidermal growth factor receptor (EGFR)-mediated tumour progression. In PCa, overexpression of EGFR promotes metastatic invasion and correlates with a high Gleason score, while prostaglandin E2 (PGE2) has been reported to modulate oncogenic EGFR-driven oncogenicity. Immunohistochemical studies revealed that mPGES-1 in human prostate tissues is correlated with EGFR expression in advanced tumours. In DU145 and PC-3 cell lines expressing mPGES-1 (mPGES-1SC cells), we demonstrate that silencing or ‘knock down’ of mPGES-1 (mPGES-1KD) or pharmacological inhibition by MF63 strongly attenuates overall oncogenic drive. Indeed, mPGES-1SC cells express stem-cell-like features (high CD44, β1-integrin, Nanog and Oct4 and low CD24 and α6-integrin) as well as mesenchymal transition markers (high vimentin, high fibronectin, low E-cadherin). They also show increased capacity to survive irrespective of anchorage condition, and overexpress EGFR compared to mPGES-1KD cells. mPGES-1 expression correlates with increased in vivo tumour growth and metastasis. Although EGFR inhibition reduces mPGES-1SC and mPGES-1KD cell xenograft tumour growth, we show that mPGES-1/PGE2 signalling sensitizes tumour cells to EGFR inhibitors. We propose mPGES-1 as a possible new marker of tumour aggressiveness in PCa.

IntroductionSolitary fibrous tumor (SFT) of the kidney represents a rare neoplasm, and its malignant potential seems to be scarce. Classically, a radical nephrectomy is regarded as the treatment of choice for this condition.Case ReportWe present the case of a 37-year-old male patient who underwent left robotic clampless partial nephrectomy of an SFT of the kidney. Our patient has been followed-up carefully, and at 15-month examination, he is free of recurrence. This is the second case of an SFT managed through a conservative approach.ConclusionsIn our opinion, according to tumor's dimensions, partial nephrectomy may be considered for treating small SFTs.

Serous borderline tumors are rare neoplasms. Herein we report our conservative approach, whose rationale is neoplasm low-malignant potential. Tumor was removed under general anesthesia, and frozen section ruled out a germinal malignancy or a stromal tumor such as rhabdomyosarcoma. Ultrasound evaluation was initially performed every 3 months during the first 2 years, every 6 months during the next 3 years, and annually thereafter. After 8 years, the patient has not experienced any relapse, either clinical or ultrasonographical. In our opinion, conservative approach, whose final decision relies on intraoperative frozen section, represents the best option and does not jeopardize long-term oncological outcome.

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 < = 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 > = 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.

After radical cystectomy or pathologies affecting the ureter(s), bowel segments can be employed to restore the natural urine flow or to create an external urinary diversion. Nevertheless, the interposition of bowel segments in the urinary tract is not devoid of complications. In fact, bowel's microstructure differs from the urothelium; specifically its mucosa is aimed at reabsorption, rather than storage. The aim of this paper is to revise the pathophysiology of complications related to bowel's mucosal properties. Those are: metabolic imbalance, malabsorption of vitamins, cholelitiasis, nephrolitiasis and infections. Their entity varies according to the segment used and to its length, which reflects the surface in contact with urine. Mostly, they occur on the long-term, but metabolic imbalances might occur soon after surgery as well.

Introduction Although several new measurements for female sexual dysfunction (FSD) have recently been developed, the Female Sexual Function Index (FSFI) remains the gold standard for screening and one of the most widely used questionnaires. The Italian translation of the FSFI has been used in several studies conducted in Italy, but a linguistic validation of the Italian version does not exist. Aim The aim of this study was to perform a linguistic validation of the Italian version of the FSFI. Methods A multicenter cross‐sectional study conducted in 14 urological and gynecological clinics, uniformly distributed over Italian territory. We performed all steps necessary to determine the reliability and the test–retest reliability of the Italian version of the FSFI. The study population was a convenience sample of 409 Italian women. Main Outcome Measures The reliability of the questionnaire was calculated using Cronbach's alpha, which was considered weak, moderate, or high if its value was found less than 0.6, between 0.6 and 0.8, or equal to or greater than 0.8, respectively. The test–retest reliability was assessed for all women in the sample by calculating Pearson's concordance correlation coefficient for each domain and for the total score, both at baseline and after 15 days (r range between −1.00 to +1.00, where +1.00 indicates the strongest positive association). Results Cronbach's alpha coefficents for total and domain score were sufficiently high, ranging from 0.92 to 0.97 for the total sample. The test–retest procedure revealed that the concordance correlation coefficient was very high both for FSFI‐I total score (Pearson's P = 0.93) and for each domain (Pearson's P always >0.92). Conclusion For the first time in the literature, our study has produced a validated and reliable Italian version of the FSFI questionnaire. Consequently, the Italian FSFI can be used as a reliable tool for preliminary screening for female sexual dysfunction for Italian women. Filocamo MT, Serati M, Li Marzi V, Costantini E, Milanesi M, Pietropaolo A, Polledro P, Gentile B, Maruccia S, Fornia S, Lauri I, Alei R, Arcangeli P, Sighinolfi MC, Manassero F, Andretta E, Palazzetti A, Bertelli E, Del Popolo G, and Villari D. The Female Sexual Function Index (FSFI): Linguistic validation of the Italian version. J Sex Med 2014;11:447–453.

We report a case of a 30 years old male affected by synchronous bilateral germ cell tumor with a history of unilateral cryptorchidism; the patient underwent surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac lymphnodes. Patients with synchronous tumors usually present with a higher stage disease in contrast to those with unilateral testicular carcinoma, yet the prognosis remains equally favorable.

The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA.We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT.A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p0.0001) and at the multivariate analysis (p0.0001).Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

// Erika Terzuoli 1, * , Sandra Donnini 1, 2, * , Federica Finetti 1 , Gabriella Nesi 3 , Donata Villari 4 , Hiromi Hanaka 5 , Olof Radmark 5 , Antonio Giachetti 1 , Marina Ziche 1, 2 1 Department of Life Sciences, University of Siena, 53100, Siena, Italy 2 Istituto Toscano Tumori (ITT), 50136, Florence, Italy 3 Department of Surgery and Translational Medicine, University of Florence, 50136, Florence, Italy 4 Department of Clinical and Experimental Medicine, University of Florence, 50136, Florence, Italy 5 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77, Stockholm, Sweden * These authors contributed equally to this work Correspondence to: Marina Ziche, email: marina.ziche@unisi.it Keywords: miR-186, mPGES-1/PGE-2, VEGF, prostate cancer, tumor angiogenesis Received: January 12, 2016 Accepted: June 01, 2016 Published: June 14, 2016 ABSTRACT Prostaglandin E-2 (PGE-2) promotes tumor angiogenesis via paracrine secretion of pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Since miRNAs regulate several cell processes, including angiogenesis, we sought to determine whether they would influence PGE-2-induced VEGF. We compared DU145 and PC3 prostate cancer cells bearing the mPGES-1 enzyme (mPGES-1 +/+ ) and producing PGE-2, with those in which the enzyme was silenced or deleted (mPGES-1 -/- ). We demonstrated that mPGES-1/PGE-2 signaling decreased Dicer expression and miRNA biogenesis. Genome-wide sequencing of miRNAs revealed that miR-15a and miR-186, associated with expression of VEGF and hypoxia inducible factor-1α (HIF-1α), were down-regulated in mPGES-1 +/+ cells. As a consequence, mPGES-1 +/+ tumor cells expressed high levels of VEGF and HIF-1α, induced endothelial cells activation and formed highly vascularized tumors. Mir-186 mimic inhibited VEGF expression in mPGES-1 +/+ tumor xenografts and reduced tumor growth. In human prostate cancer specimens, mPGES-1 was over-expressed in tumors with high Gleason score, elevated expression of VEGF and HIF-1α, high microvessel density and decreased expression of Dicer, miR15a and miR-186. Thus, clear evidence for regulating miRNA processing and VEGF output by intrinsic PGE-2 production provides a means to distinguish between aggressive and indolent prostate tumors and suggests a potential target for controlling tumor progression.

Background To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine. Scope The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test. Procedures The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers. Results Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance. Conclusions The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis.

In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

In human cancers, carbonic anhydrase IX (CAIX) influences cell proliferation and tumor progression, maintaining intracellular and extracellular pH under hypoxic conditions. An alternative CAIX isoform, lacking of exons 8-9 (AS) and independent from the levels of hypoxia, was recently demonstrated in cancer cells. AS-CAIX competes with the full-length (FL) isoform in the regulation of the extracellular pH, mainly in a mild hypoxic status. In the present study, we evaluated mRNA expression of the 2 CAIX isoforms and their clinical relevance in bladder cancers and urine sediments.We measured mRNA expression of FL- and AS-CAIX isoforms in tumor tissues and benign mucosa from 45 patients with bladder transitional cell carcinoma. The expression of the 2 isoforms was also measured in urine sediment of 81 bladder cancer patients and 93 control subjects.Expression of FL-CAIX mRNA was lower than AS-CAIX in benign mucosa (P = 0.006) whereas in paired bladder cancers FL-CAIX mRNA was higher (P = 0.007). Consequently, the percentage of FL-CAIX in bladder cancers [median: 62.6%] was significantly higher than in benign mucosa [15.0%] (P0.0001). In the urinary sediments of bladder cancer patients FL-CAIX mRNA was significantly higher in comparison with normal controls (P = 0.003). FL-CAIX percentage appeared dramatically higher in urine sediments of bladder cancer patients [64.5%] in comparison with controls [7.5%] (P0.0001). In addition, FL-CAIX% was significantly different in sediments from pTa-pT1 and ≥ pT2 patients [51.5% and 91.7%, respectively] (P = 0.016). Stratification according tumor grade indicated that FL-CAIX% was significantly lower in G1 bladder cancers [33.3%] in comparison with G2-G3 [88.6%] (P = 0.005) The clinical sensitivity for FL-CAIX% in urine sediments was 0.93, with a 0.76 specificity. Using the same cut-off positive predictive value (PPV) was 0.78, whereas negative predictive value (NPV) was 0.93.Our results seem to indicate that in bladder cancers and related urine sediments, FL-CAIX is the prevalent and is the most accurate clinically relevant variant surrogate of hypoxic stress.

Objectives Urinary hypermethylation of BCL2, hTERT, and DAPK promoters has been previously demonstrated as an accurate biomarker for the detection of urothelial carcinoma of the bladder (UCB) in patients undergoing radical cystectomy. In the present study, we investigated with a validation intent the frequency and levels of methylation of the same 3 genes in tumor tissue and urine sediment of patients undergoing transurethral resection (TUR) for non-muscle-invasive (NMI) UCB. Materials and methods A total of 108 consecutive patients with NMI UCB and 105 controls with no genitourinary malignancies were enrolled in this prospective study conducted in 2 tertiary referral academic urological departments with an advanced molecular laboratory. The frequency and levels of methylated BCL2, hTERT, and DAPK promoters were evaluated with quantitative methylation-specific real-time polymerase chain reaction in DNA extracted from tumor tissue and paired normal bladder mucosa retrieved at the time of TUR in patients, and from urine in patients and controls. Results In tumor tissue, at least 1 gene was hypermethylated in 91% patients (BCL2 in 62%, hTERT in 53%, DAPK in 48%). Methylation of hTERT was significantly correlated with tumor grade ( P = 0.026). In urine sediment sensitivity and specificity were 76% and 98%, respectively, using BCL2 and hTERT. The number of methylated genes was highly correlated with tumor grade ( P = 0.005). Methylated BCL2 and hTERT in urine sediment were highly correlated with those of the corresponding bladder tumor qualitatively ( P P = 0.005). Methylation levels of BCL2 and hTERT were variably associated with tumor grade and stage, but were significantly correlated with patient age ( P = 0.004 and P = 0.027, respectively). Conclusions These findings suggest that quantitative methylation analysis of BCL2 and hTERT, but not DAPK, in urine sediment may be a useful tool in the diagnosis of NMI UCB, deserving future applicability studies.

The aim of this study was to review the treatment, toxicity, and outcomes in patients with stage I seminoma after orchidectomy.A retrospective chart review of all patients with stage I seminoma referred for initial treatment during the last 49 years was performed. Initial treatment approaches, toxicity, and outcomes were analyzed.A total of 320 patients were seen between 1960 and 2009. Median age at diagnosis was 37 years (range: 20-72), with a median follow-up of 22.7 years (range: 1-48). All patients but 12 were treated with adjuvant radiotherapy. Acute toxicity was mainly gastrointestinal, with 7.6% classified as grade 2. The 10-year disease-specific survival and relapse-free survival were 97.7 and 97.6%, respectively. 8 patients (2.7%) developed a relapse and were managed with chemotherapy. 10 patients died, 6 of the disease and 4 from other causes (disease-free at time of death).In the management of stage I seminoma, 3 treatment options are available; currently in the European Consensus, surveillance is the first choice, considering the overall comparable outcome and the low acute and late toxicity. Adjuvant radiotherapy and adjuvant chemotherapy should be considered as alternative options only if the patient declines the surveillance strategy.