Lactate supports cell-autonomous ECM production to sustain metastatic behavior in prostate cancer.

Extracellular matrix (ECM) is a major component of the tumor environment, promoting the establishment of a pro-invasive behavior. Such environment is supported by both tumor- and stromal-derived metabolites, particularly lactate. In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) are major contributors of secreted lactate, able to impact on metabolic and transcriptional regulation in cancer cells. Here, we describe a mechanism by which CAF-secreted lactate promotes in PCa cells the expression of genes coding for the collagen family. Lactate-exploiting PCa cells rely on increased α-ketoglutarate (α-KG) which activates the α-KG-dependent collagen prolyl-4-hydroxylase (P4HA1) to support collagen hydroxylation. De novo synthetized collagen plays a signaling role by activating discoidin domain receptor 1 (DDR1), supporting stem-like and invasive features of PCa cells. Inhibition of lactate-induced collagen hydroxylation and DDR1 activation reduces the metastatic colonization of PCa cells. Overall, these results provide a new understanding of the link between collagen remodeling/signaling and the nutrient environment exploited by PCa.

Doppler-Derived Renal Functional Reserve in the Prediction of Postoperative Acute Kidney Injury in Patients Undergoing Robotic Surgery.

BACKGROUND: Postoperative acute kidney injury (PO-AKI) is a frequent complication after surgery. Various tools have been proposed to identify patients at high risk for AKI, including preoperative serum creatinine or estimated glomerular filtration rate (eGFR), urinary cell cycle arrest, and tubular damage biomarkers; however, none of these can appropriately assess AKI risk before surgery. Renal functional reserve (RFR) screened by the Doppler-derived intraparenchymal renal resistive index variation (IRRIV) test has been proposed to identify patients at risk for AKI before a kidney insult. IRRIV test has been developed in healthy individuals and previously investigated in cardiac surgery patients. This study aims to evaluate the value of the IRRIV test in identifying PO-AKI among patients undergoing robotic abdominal surgery in the Trendelenburg position for pelvic oncological disease. METHODS: We performed a prospective, double-blinded, observational study. Preoperative baseline renal function and RFR were assessed in 53 patients with baseline eGFR >60 mL/min/1.73 m2, undergoing robotic surgery in the Trendelenburg position for pelvic oncological disease. The capability of Doppler-derived RFR in predicting PO-AKI was investigated with the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Approximately 15.1% of patients developed AKI within the first 3 postoperative days. Thirty-one (58.5%) patients had a physiologic delta-RRI (ie, ≥0.05), while 22 (41.5%) patients did not. The ROC-AUC for PO-AKI was 0.85 (95% confidence interval [CI], 0.74-0.97; P = .007) for serum creatinine, 0.84 (95% CI, 0.71-0.96; P = .006) for eGFR, and 0.84 (95% CI, 0.78-0.91; P = .017) for delta-RRI. When combined with eGFR, the ROC-AUC for delta-RRI was 0.95 (95% CI, 0.9-1). CONCLUSIONS: Our findings show that the preoperative assessment of Doppler-derived RFR combined with baseline renal function improves the capability of identifying patients at high risk for PO-AKI with eGFR >60 mL/min/1.73 m2 after robotic abdominal surgery in Trendelenburg position for pelvic oncological disease.

Adjuvant Therapy for Renal Cell Carcinoma: Hype or Hope?

Renal cell carcinoma (RCC) is the third most common genitourinary cancer accounting for approximately 180,000 deaths worldwide in 2020. Although over two-thirds of patients initially present localized disease, up to 50% of them may progress to metastatic disease. Adjuvant therapy aims to reduce the recurrence risk and improve outcomes in several types of cancers but is currently an unmet need in RCC. The results achieved with tyrosine kinase inhibitors in metastatic RCC led to the evaluation of these target therapies in an early setting with conflicting results for disease-free survival and no overall survival (OS) benefit. Likewise, the results of immune checkpoint inhibitors (ICIs) in an adjuvant setting are conflicting. Available data did not show an improvement in OS with ICIs in the early phase, although a positive trend for pembrolizumab has been recorded, receiving the Food and Drug Administration's approval in this setting. However, the disappointing results of several ICIs and the heterogeneous pattern of RCC warrant biomarker identification and subgroup analyses to evaluate which patients could benefit from adjuvant therapy. In this review, we will discuss the rationale for adjuvant treatment in RCC, summarizing the results of the most important adjuvant therapy trials and current applications, to outline possible future directions.

Inflammation in Urological Malignancies: The Silent Killer.

Several studies have investigated the role of inflammation in promoting tumorigenesis and cancer progression. Neoplastic as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to establish an inflammatory tumor microenvironment. The tumor-associated inflammatory tissue is highly plastic, capable of continuously modifying its phenotypic and functional characteristics. Accumulating evidence suggests that chronic inflammation plays a critical role in the development of urological cancers. Here, we review the origins of inflammation in urothelial, prostatic, renal, testicular, and penile cancers, focusing on the mechanisms that drive tumor initiation, growth, progression, and metastasis. We also discuss how tumor-associated inflammatory tissue may be a diagnostic marker of clinically significant tumor progression risk and the target for future anti-cancer therapies.

Gender and Advanced Urothelial Cancer: Outcome, Efficacy and Toxicity following Chemotherapy.

Background and Objectives: The incidence of urothelial cancer in males is higher than in females; however, females have a higher risk of recurrence and progression. The aim of our study was to report the effect of gender on the oncological outcome in advanced urothelial cancer. Materials and Methods: In our retrospective study, all patients had undergone primary surgical treatment for urothelial cancer and were affected by stage IV disease at the time of chemotherapy. Response to therapy and toxicity were evaluated. Subgroups were analyzed for tumour presentation, first- and second-line treatment response, progression-free survival (PFS) and overall survival (OS). Results. Seventy-five patients, 18 (24%) females and 57 (76%) males, were considered. Investigation into the distribution of individual characteristics according to gender revealed a significant difference only for smoking, with a prevalence of smokers in women (p = 0.029). At the end of follow-up, OS was higher in females (27.5% vs. 17.4%; p = 0.047). Smoking did not significantly influence OS (p = 0.055), while univariate Cox regression analysis confirmed that males had a higher risk of death (HR = 2.28, 95% CI 0.99-129 5.25), with borderline statistical significance (p = 0.053). Men showed higher PFS than women both after first-line (p = 0.051) and second-line chemotherapy (p = 0.018), with a lower risk of progression (HR = 0.29, 95% CI 0.10-0.86; p = 0.026). No differences were found between genders with regard to toxicity. Conclusions. In our series, PFS rates following first- and second-line therapies for advanced urothelial carcinoma confirmed that females have a greater risk of progression than males.

Quantitative Polymerase Chain Reaction Detection of Microchimerism in Female Transplant Renal Recipients.

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.

Association between metabolic syndrome and intravesical prostatic protrusion in patients with benign prostatic enlargement and lower urinary tract symptoms (MIPS Study).

OBJECTIVE: To investigate the association between metabolic syndrome (MetS) and morphological features of benign prostatic enlargement (BPE), including total prostate volume (TPV), transitional zone volume (TZV) and intravesical prostatic protrusion (IPP). PATIENTS AND METHODS: Between January 2015 and January 2017, 224 consecutive men aged >50 years presenting with lower urinary tract symptoms (LUTS) suggestive of BPE were recruited to this multicentre cross-sectional study. MetS was defined according to International Diabetes Federation criteria. Multivariate linear and logistic regression models were performed to verify factors associated with IPP, TZV and TPV. RESULTS: Patients with MetS were observed to have a significant increase in IPP (P < 0.01), TPV (P < 0.01) and TZV (P = 0.02). On linear regression analysis, adjusted for age and metabolic factors of MetS, we found that high-density lipoprotein (HDL) cholesterol was negatively associated with IPP (r = -0.17), TPV (r = -0.19) and TZV (r = -0.17), while hypertension was positively associated with IPP (r = 0.16), TPV (r = 0.19) and TZV (r = 0.16). On multivariate logistic regression analysis adjusted for age and factors of MetS, hypertension (categorical; odds ratio [OR] 2.95), HDL cholesterol (OR 0.94) and triglycerides (OR 1.01) were independent predictors of TPV ≥ 40 mL. We also found that HDL cholesterol (OR 0.86), hypertension (OR 2.0) and waist circumference (OR 1.09) were significantly associated with TZV ≥ 20 mL. On age-adjusted logistic regression analysis, MetS was significantly associated with IPP ≥ 10 mm (OR 34.0; P < 0.01), TZV ≥ 20 mL (OR 4.40; P < 0.01) and TPV ≥ 40 mL (OR 5.89; P = 0.03). CONCLUSION: We found an association between MetS and BPE, demonstrating a relationship with IPP.

Impact of minimally invasive surgical procedures for Male Lower Urinary Tract Symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review.

BACKGROUND: Surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are affected by potentially bothersome side effects on sexual, and, above all, ejaculatory function. Several minimally invasive techniques have been proposed in the last years in order to overcome these consequences. Our aim is to summarize and evaluate the efficacy on LUTS relieve and the impact on sexual/ejaculatory function of Rezum, prostate artery embolization (PAE), implantation of a prostatic urethral lift (PUL) and the temporary implantable nitinol device (TIND). METHODS: A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to October 2022, according to the PRISMA guidelines (PROSPERO ID: CRD42023466515). Randomized controlled trials (RCTs), prospective studies and non-comparative or comparative studies assessing the impact on functional and ejaculatory function after minimally invasive surgical therapies for Male LUTS were evaluated. Risk of bias assessment was performed according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for comparative studies, and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. RESULTS: Overall, 47 studies were included (n = 4 for TIND; n = 9 for Rezum; n = 13 for PUL; n = 21 for PAE). Most studies relied on prospective patient cohorts and were rated as low risk of bias. Across studies assessing the efficacy of Rezum, a significant improvement in terms of IPSS (ranging from -47% to -56%) and Qmax (ranging from +39% to +87%) was reported. On the other hand, according to IIEF-5 score, Rezum had a minimal impact on sexual function (ranging from -1% to -3%). PUL showed a positive impact on IPSS (ranging from -35% to -58.2%) and Qmax (ranging from +49.9% to +114.7%) and sexual function. Finally, PAE showed encouraging functional results with IPSS score reducing from -12.8% to 63.3% and Qmax improving from +8% to 114.9% but the available evidence regarding the potential impact of PAE on sexual outcomes were limited. CONCLUSION: Rezum, PAE, PUL and TIND are safe and feasible techniques associated with a significant functional improvement. While available data suggest a minimal impact of Rezum and PUL on ejaculatory function, the evidence after PAE and TIND are still limited. Therefore, our review lays the foundation for further research aiming to identify the criteria to select best candidates for uMIST to tailor the management in light of specific patient- and disease- factors.

A Velocity-Based Approach to Noninvasive Methodology for Urodynamic Analysis.

PURPOSE: To date, invasive urodynamic investigations have been used to define most terms and conditions relating to lower urinary tract symptoms. This invasiveness is almost totally due to the urethral catheter. In order to remove this source of discomfort for patients, the present study investigated a noninvasive methodology able to provide diagnostic information on bladder outlet obstruction or detrusor underactivity without any contact with the human body. METHODS: The proposed approach is based on simultaneous measurements of flow rate and jet exit velocity. In particular, the jet exit kinetic energy appears to be strongly related to bladder pressure, providing useful information on the lower urinary tract functionality. We developed a new experimental apparatus to simulate the male lower urinary tract, thus allowing extensive laboratory activities. A large amount of data was collected regarding different functional statuses. RESULTS: Experimental results were compared successfully with data in the literature in terms of peak flow rate and jet exit velocity. A new diagram based on the kinetic energy of the exit jet is proposed herein. Using the same notation as a Schäfer diagram, it is possible to perform noninvasive urodynamic studies. CONCLUSION: A new noninvasive approach based on the measurement of jet exit kinetic energy has been proposed to replace current invasive urodynamic studies. A preliminary assessment of this approach was carried out in healthy men, with a specificity of 91.5%. An additional comparison using a small sample of available pressure-flow studies also confirmed the validity of the proposed approach.

The First Entirely 3D-Printed Training Model for Robot-assisted Kidney Transplantation: The RAKT Box.

Background: Robot-assisted kidney transplantation (RAKT) is increasingly performed at selected referral institutions worldwide. However, simulation and proficiency-based progression training frameworks for RAKT are still lacking, making acquisition of the RAKT-specific skill set a critical unmet need for future RAKT surgeons. Objective: To develop and test the RAKT Box, the first entirely 3D-printed, perfused, hyperaccuracy simulator for vascular anastomoses during RAKT. Design setting and participants: The project was developed in a stepwise fashion by a multidisciplinary team including urologists and bioengineers via an iterative process over a 3-yr period (November 2019-November 2022) using an established methodology. The essential and time-sensitive steps of RAKT were selected by a team of RAKT experts and simulated using the RAKT Box according to the principles of the Vattituki-Medanta technique. The RAKT Box was tested in the operating theatre by an expert RAKT surgeon and independently by four trainees with heterogeneous expertise in robotic surgery and kidney transplantation. Surgical procedure: Simulation of RAKT. Measurements: Video recordings of the trainees' performance of vascular anastomoses using the RAKT Box were evaluated blind by a senior surgeon according to the Global Evaluative Assessment of Robotic Skills (GEARS) and Assessment of Robotic Console Skills (ARCS) tools. Results and limitations: All participants successfully completed the training session, confirming the technical reliability of the RAKT Box simulator. Tangible differences were observed among the trainees in both anastomosis time and performance metrics. Key limitations of the RAKT Box include lack of simulation of the ureterovesical anastomosis and the need for a robotic platform, specific training instruments, and disposable 3D-printed vessels. Conclusions: The RAKT Box is a reliable educational tool to train novice surgeons in the key steps of RAKT and may represent the first step toward the definition of a structured surgical curriculum in RAKT. Patient summary: We describe the first entirely 3D-printed simulator that allows surgeons to test the key steps of robot-assisted kidney transplantation (RAKT) in a training environment before performing the procedure in patients. The simulator, called the RAKT Box, has been successfully tested by an expert surgeon and four trainees. The results confirm its reliability and potential as an educational tool for training of future RAKT surgeons.

Transperineal Laser Ablation of the Prostate (TPLA) for Lower Urinary Tract Symptoms Due to Benign Prostatic Obstruction.

We aimed to review the current evidence on surgical and functional outcomes of Transperineal Laser Ablation for LUTS due to BPH. A comprehensive review of the English-language literature was performed using the MEDLINE and Web of Science databases until 1 August 2022, aiming to select studies evaluating TPLA for the treatment of LUTS due to BPH. Additional records were found from Google Scholar. Data were extracted and summarized in Tables. An appropriate form was used for qualitative data synthesis. Seven studies were included in the review, with all being single arm, non-comparative studies. In all studies, functional outcomes were evaluated with uroflowmetry parameters and validated questionnaires, showing a promising effectiveness at short- and mid-term follow-up. There is a lack of standardized pathways for preoperative assessment of patients suitable for TPLA, and even the technique itself has been reported with a few nuances. A good safety profile has been reported by all the authors. Although promising results have been reported by different groups, selection criteria for TPLA and few technical nuances regarding the procedure were found to be heterogeneous across the published series that should be standardized in the future. Further research is needed to confirm these findings.

Ureteral stent encrustation: evaluation of available scores as predictors of a complex surgery.

BACKGROUND: Stent encrustation is an uncommon event (13%) with a significant impact in patients' management. Aim of our study was to evaluate the available grading systems for encrusted stents. METHODS: A retrospective analysis of encrusted stents was performed in four Italian centers between 2006 and 2020. Encrusted stents were classified according to four classifications: the Forgotten Encrusted Calcificated (FECal) Score, the Kidney Ureter Bladder (KUB) Score, the Visual Grading for Ureteral Encrusted Stent Classification and the Encrustation Burden Score (EBS). Classifications were evaluated to predict complex surgery defined as: long operative time (>60 min), need of more than one surgery, and need of a percutaneous approach. The scores were compared with receiver operating characteristic (ROC) analysis as predictors of complex surgery. RESULTS: Seventy-seven patients were evaluated with a median age of 62 years (65/70). Overall FECal score >2 was present in 45/77 (58%) patients, median KUB score was 9 (6/14) and severe EBS was found in 47/77 (63%) patients. Patients were managed with cyst lithotripsy in 13/77 (17%), with ureteroscopy in 58/77 (75%) and with percutaneous nephrolithotomy (PCNL) in 6/77 (8%). Overall, 6/77 (8%) patients required a second intervention to remove the encrusted stent. All classifications predicted the need of complex surgery. On ROC analysis KUB score presented a better accuracy in predicting complex surgery compared to FECal, V-GUES and encrusted burden. CONCLUSIONS: KUB score, FECal score, V-GUES score, and encrustation burden accurately predict the need of a complex surgery. KUB showed to be superior to other classifications according to our results.

Emerging minimally invasive transurethral treatments for benign prostatic hyperplasia: a systematic review with meta-analysis of functional outcomes and description of complications.

INTRODUCTION: Several minimally invasive surgical procedures have been proposed as alternative therapies for benign prostatic hyperplasia (BPH). The present systematic review aimed to describe the functional outcomes and complications of emerging minimally invasive transurethral treatments for BPH. EVIDENCE ACQUISITION: A comprehensive bibliographic search on the Medline and Cochrane Library databases was conducted. No chronological restriction was applied. Retrospective and prospective primary studies were included. A meta-analysis of IPSS, IPSS-QoL, Qmax, and PVR was performed. Data on adverse events were presented narratively. EVIDENCE SYNTHESIS: A total of 18 studies were included. Thirteen papers were eligible for the meta-analysis. iTIND (Medi-Tate Ltd., Or-Akiva, Israel), Rezum (Rezum System, Boston Scientific, Marlborough, MA), and Aquablation (AquaBeam System, PROCEPT BioRobotics Inc., Redwood City, CA, USA) were associated with a significant improvement in IPSS (P<0.001), IPSS-QoL (P<0.001), and Qmax (P<0.001) compared to baseline. A significant reduction of PVR from baseline was found with Rezum (P<0.001) and Aquablation (P<0.001) but not iTIND (P=0.22). A significant difference in IPSS, IPSS-QoL, and Qmax was shown in favor of Aquablation compared to Rezum and iTIND (P<0.001). Rezum and iTIND were mainly associated with mild to moderate adverse effects. Hematuria or bleeding was reported in all studies regarding Aquablation (0.8-26%), the need for transfusion or intervention for bleeding varied between 1.8% and 9%. CONCLUSIONS: Aquablation, Rezum, and iTIND significantly improve urinary functional outcomes compared to baseline; however, Aquablation would seem to lead to better functional results compared to the other procedures. Rezum and iTIND appear to have an excellent safety profile, while Aquablation would seem to expose patients to a non-negligible risk of bleeding.

Contemporary techniques and outcomes of surgery for locally advanced renal cell carcinoma with focus on inferior vena cava thrombectomy: The value of a multidisciplinary team.

Objective: To report the outcomes of surgery for a contemporary series of patients with locally advanced non-metastatic renal cell carcinoma (RCC) treated at a referral academic centre, focusing on technical nuances and on the value of a multidisciplinary team. Methods: We queried our prospective institutional database to identify patients undergoing surgical treatment for locally advanced (cT3-T4 N0-1 M0) renal masses suspected of RCC at our centre between January 2017 and December 2020. Results: Overall, 32 patients were included in the analytic cohort. Of these, 12 (37.5%) tumours were staged as cT3a, 8 (25.0%) as cT3b, 5 (15.6%) as cT3c, and 7 (21.9%) as cT4; 6 (18.8%) patients had preoperative evidence of lymph node involvement. Nine (28.1%) patients underwent nephron-sparing surgery while 23 (71.9%) received radical nephrectomy. A template-based lymphadenectomy was performed in 12 cases, with evidence of disease in 3 (25.0%) at definitive histopathological analysis. Four cases of RCC with level IV inferior vena cava thrombosis were successfully treated using liver transplant techniques without the need for extracorporeal circulation. While intraoperative complications were recorded in 3 (9.4%) patients, no postoperative major complications (Clavien-Dindo ≥3) were observed. At histopathological analysis, 2 (6.2%) patients who underwent partial nephrectomy harboured oncocytoma, while the most common malignant histotype was clear cell RCC (62.5%), with a median Leibovich score of 6 (interquartile range 5-7). Conclusion: Locally advanced RCC is a complex and heterogenous disease posing several challenges to surgical teams. Our experience confirms that provided careful patient selection, surgery in experienced hands can achieve favourable perioperative, oncological, and functional outcomes.

Lactate Rewires Lipid Metabolism and Sustains a Metabolic-Epigenetic Axis in Prostate Cancer.

Lactate is an abundant oncometabolite in the tumor environment. In prostate cancer, cancer-associated fibroblasts (CAF) are major contributors of secreted lactate, which can be taken up by cancer cells to sustain mitochondrial metabolism. However, how lactate impacts transcriptional regulation in tumors has yet to be fully elucidated. Here, we describe a mechanism by which CAF-secreted lactate is able to increase the expression of genes involved in lipid metabolism in prostate cancer cells. This regulation enhanced intracellular lipid accumulation in lipid droplets (LD) and provided acetyl moieties for histone acetylation, establishing a regulatory loop between metabolites and epigenetic modification. Inhibition of this loop by targeting the bromodomain and extraterminal protein family of histone acetylation readers suppressed the expression of perilipin 2 (PLIN2), a crucial component of LDs, disrupting lactate-dependent lipid metabolic rewiring. Inhibition of this CAF-induced metabolic-epigenetic regulatory loop in vivo reduced growth and metastasis of prostate cancer cells, demonstrating its translational relevance as a therapeutic target in prostate cancer. Clinically, PLIN2 expression was elevated in tumors with a higher Gleason grade and in castration-resistant prostate cancer compared with primary prostate cancer. Overall, these findings show that lactate has both a metabolic and an epigenetic role in promoting prostate cancer progression. SIGNIFICANCE: This work shows that stromal-derived lactate induces accumulation of lipid droplets, stimulates epigenetic rewiring, and fosters metastatic potential in prostate cancer.

Therapy-Induced Stromal Senescence Promoting Aggressiveness of Prostate and Ovarian Cancer.

Cancer progression is supported by the cross-talk between tumor cells and the surrounding stroma. In this context, senescent cells in the tumor microenvironment contribute to the development of a pro-inflammatory milieu and the acquisition of aggressive traits by cancer cells. Anticancer treatments induce cellular senescence (therapy-induced senescence, TIS) in both tumor and non-cancerous cells, contributing to many detrimental side effects of therapies. Thus, we focused on the effects of chemotherapy on the stromal compartment of prostate and ovarian cancer. We demonstrated that anticancer chemotherapeutics, regardless of their specific mechanism of action, promote a senescent phenotype in stromal fibroblasts, resulting in metabolic alterations and secretion of paracrine factors, sustaining the invasive and clonogenic potential of both prostate and ovarian cancer cells. The clearance of senescent stromal cells, through senolytic drug treatment, reverts the malignant phenotype of tumor cells. The clinical relevance of TIS was validated in ovarian and prostate cancer patients, highlighting increased accumulation of lipofuscin aggregates, a marker of the senescent phenotype, in the stromal compartment of tissues from chemotherapy-treated patients. These data provide new insights into the potential efficacy of combining traditional anticancer strategies with innovative senotherapy to potentiate anticancer treatments and overcome the adverse effects of chemotherapy.

Translation and validation of the Italian version of the user version of the Mobile Application Rating Scale (uMARS).

BACKGROUND: Health sciences are steadily developing apps to help people to adopt correct lifestyles and to help physicians to monitor patients with chronic diseases. However, a properly validated tool that can evaluate patients' perception of apps is still lacking in many languages. In English, a validated questionnaire, called User Version of the Mobile Application Rating Scale (uMARS), is currently available. We translated the uMARS into Italian and validated our version. METHODS: The uMARS questionnaire was translated from English to Italian by an official translator, and then administered to 100 smartphone users in order to evaluate the same app at times 1 and 2 (after 2 weeks). Paired t-test, Pearson Correlation Coefficient, Intraclass Correlation Coefficient (ICCs) and Cronbach's Alpha were used to evaluate the reliability and validity of the Italian uMARS. RESULTS: We recruited 100 subjects, 52 males (52%) and 48 females (48%), with a mean age of 22.8 (SD: 3.4). All subjects answered all questions both at time 1 and at time 2. Paired t-test showed no statistically significant difference in each answer or group of answers between times 1 and 2 (P > 0.05). Cronbach's alpha was 0.945, as all subjects answered all questions. Each question was further assessed through the Pearson correlation coefficient, which demonstrated high reliability, with significant P (< 0.05) and Pearson Coefficients higher than 0.7. Similarly, ICCs were always higher than 0.750. CONCLUSIONS: Our results validated the Italian version of uMARS, which may become a reliable and useful tool for evaluating health apps.

Proctored Step by Step Training Program for GreenLight Laser Anatomic Photovaporization of the Prostate: A Single Surgeon's Experience.

Objectives: To evaluate the feasibility and safety of a proctored step-by-step training program for GreenLight laser anatomic photovaporization (aPVP) of the prostate. Methods: Data from patients undergoing aPVP between January 2019 and December 2020 operated by a single surgeon following a dedicated step-by-step proctored program were prospectively collected. The procedure was divided into five modular steps of increasing complexity. Preoperative patients' data as well as total operative time, energy delivered on the prostate and postoperative data, were recorded. Then, we assessed how the overall amount of energy delivered and the operative times varied during the training program. Surgical steps were analyzed by cumulative summation. Univariable and multivariable regression models were built to assess the predictors of the amount of energy delivered on the prostate. Results: Sixty consecutive patients were included in the analysis. Median prostate volume was 56.5 mL. The training program was succesfully completed with no intraoperative or meaningful post-operative complications. The energy delivered reached the plateau after the 40th case. At multivariable analysis, increasing surgeon experience was associated with lower amounts of energy delivered as well as lower operative times. Conclusions: A step-by-step aPVP training program can be safely performed by surgeons with prior endoscopic experience if mentored by a skilled proctor. Considering the energy delivered as an efficacy surrogate metrics (given its potential impact on persistent postoperative LUTS), 40 cases are needed to reach a plateau for aPVP proficiency. Further studies are needed to assess the safety of our step-by-step training modular program in other clinical contexts.

Prostate Cancer Characteristics in Renal Transplant Recipients: A 25-Year Experience From a Single Centre.

Objectives: The incidence of prostate cancer in renal transplant recipients (RTRs) is increasing, but few data are available in the literature. In this study, we reviewed the 25-year experience in the management of prostate cancer after kidney transplantation at the Florence Transplant Centre. Methods: We retrospectively reviewed the data from 617 RTR male patients who underwent renal transplantation at our institute between July 1996 and September 2016. Data regarding demographics, renal transplantation, prostate cancer and immunosuppressive treatment were analyzed. The probability of death was estimated by using the Kaplan-Meier method and differences between patients' groups were assessed by the log-rank test. Results: From July 1991 to September 2016, 617 kidney transplantations of male patients were performed at our institute. Among these, 20 patients were subsequently diagnosed with prostate cancer accounting for a cumulative incidence of 3.24%. After a median follow-up of 59 months, 10 patients underwent radical prostatectomy whereas 10 patients underwent primary radiotherapy. A biochemical recurrence was identified in five (25%) patients while a fatal event occurred in 11 (55%) patients. Univariate Cox regression showed that the basal value of PSA >10 ng/ml was the only significant factor negatively affecting the survival of patients. Conclusions: Standard treatments can be proposed to RTR with satisfactory results on both post-operative and oncological outcomes. Further studies are needed to address the issue of prostate cancer screening based on PSA levels and the optimal management of prostate cancer in RTRs.

Which Drug to Discontinue 3 Months After Combination Therapy of Tadalafil plus Tamsulosin for Men with Lower Urinary Tract Symptom and Erectile Dysfunction? Results of a Prospective Observational Trial.

BACKGROUND: Safety and efficacy of tamsulosin and tadalafil for men with benign prostatic enlargement (BPE) and/or erectile dysfunction (ED) are defined. However, there are only a few pilot studies on combination therapy with these drugs for men with lower urinary tract symptom (LUTS)/BPE and ED. Moreover, preliminary reports are limited to 12 wk, without any information about subsequent therapies. OBJECTIVE: To evaluate the impact of discontinuation of tamsulosin versus tadalafil 12 wk after combination therapy. DESIGN, SETTING, AND PARTICIPANTS: Fifty consecutive patients with moderate-to-severe LUTS (International Prostate Symptom Score [IPSS] > 7) and mild-to-severe ED (International Index of Erectile Function-5 [IIEF-5] < 22) were treated with combination therapy (tamsulosin 0.4mg/d plus tadalafil 5mg/d) for 12 wk. After 12 wk, 25 patients discontinued tamsulosin (Group TAD), while 25 patients discontinued tadalafil (Group TAM). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy variables were IPSS (total, voiding, storage) and IIEF-5. Paired samples t test and analysis of variance were used. RESULTS AND LIMITATIONS: Groups TAD and TAM presented similar features (age, BMI, metabolic profile) including symptoms scores at baseline. Similar and significant improvements in IPSS (total, voiding, and storage) and IIEF-5 were recorded in both groups after 12 wk of combination therapy (all p< 0.001). Total IPSS was similar between the two groups at the end of the trial. However, we found between-group significant differences from baseline to 24 wk and from 12 to 24 wk in storage-IPSS (Group TAD: -3.32 vs Group TAM: -1.24, p= 0.002; Group TAD: +0.24 vs Group TAM: +1.20, p= 0.040, respectively) and in IIEF-5 (Group TAD: +4.64 vs Group TAM: +0.16, p< 0.001; Group TAD: -1.64 vs Group TAM: -4.40, p= 0.003). No significant treatment-related adverse event was recorded in both groups. CONCLUSIONS: After 12 wk of combination therapy, monotherapy with tadalafil for further 12 wk allows to preserve the improvement of storage IPSS and IIEF-5, in addition to total IPSS. PATIENT SUMMARY: In this report we evaluated the discontinuation of tamsulosin or tadalafil after 12 wk of combination therapy. We found that tadalafil monotherapy, for a further 12 wk, aids in retaining the improvement of storage symptoms and erectile function.