Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: -0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Exosome Analysis in Prostate Cancer: How They Can Improve Biomarkers' Performance.

Exosomes are extracellular nanovesicles (EV), that is, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in cases of tumorigenesis open up different scenarios on their possible application to research into new biomarkers. The first purpose of the present review was to specifically analyze and compare different methodologies available for the use of exosomes in prostate cancer (PC). The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA), and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, thereby determining an increase in labor time and costs. The second purpose was to describe clinical results obtained with the analysis of PSA-expressing exosomes in PC; this provides an incredibly accurate method of discriminating between healthy patients and those with prostate disease. Specifically, the IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH). An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy controls. The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease. However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for large-scale use.

The Impact of Ethnicity and Age on Distribution of Metastases in Patients with Upper Tract Urothelial Carcinoma: Analysis of SEER Data.

Upper tract urothelial carcinoma (UTUC) constitutes a rare and aggressive entity accounting for 5% to 10% of all urothelial tumors. The importance of stratification and disparities according to ethnicity and age has never been tested in a sufficiently large sample of patients with metastatic UTUC (mUTUC). We conducted this study to address this void, and we hypothesized that the distribution of metastases may vary according to age and ethnicity. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified 1115 patients with mUTUC. The chi-square and t-test tests were used to examine statistical significance in terms of proportions and mean differences. A total of 925 (83.0%) patients were Caucasians, while 190 (17.0%) were African Americans. Among both ethnicities, lungs were the most common metastatic site (39.1% vs. 48.9%). Brain metastases were infrequent among both ethnicities (1.2 vs. 2.6%; p = 0.13). The trends in the lung metastases decreased with age from 42.3% to 36.6% (p = 0.010) among Caucasians, whereas they increased among African Americans from 34.0% to 51.7% (p = 0.04). Overall, 32.8% of Caucasians and 40.5% of African Americans exhibited more than one metastatic site. Among Caucasians, increasing age was associated with lower rates of having multiple metastatic sites (from 34.3% to 30.2%) (p = 0.004). According to our multivariable analyses, younger age was associated with an increased risk of lung (OR: 1.29, 95% CI 1.04-1.71; p = 0.045) and bone metastases (OR: 1.34, 95% CI 1.07-1.79; p = 0.046). Racial differences exist in the distribution of mUTUC metastasis and vary according to age. Our findings may also be considered in the design of randomized trials.

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis.

BACKGROUND: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. METHODS: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. RESULTS: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. CONCLUSION: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Translation and validation of the Italian version of the Wisconsin Stone Quality of Life Questionnaire (I-WISQOL) for assessing quality of life in patients with urolithiasis.

BACKGROUND: Urolithiasis is a chronic condition, and it has been associated with a significant negative impact on patients' health-related quality of life (HRQOL). Several tools to assess patients' HRQOL have been validated in Italian, however disease-specific HRQOL instruments are still lacking. We aimed to develop and validate the Italian version of the WISQOL (I-WISQOL) in patients with urolithiasis. METHODS: The Italian version of the WISQOL was developed in a multistep process involving primary translation, back-translation, and pilot testing among a group of patients (N.=10). Patients presenting with urolithiasis were prospectively recruited from the outpatient stone clinics and completed both questionnaire WISQOL and SF-36. Demographic information, as well as medical and surgical data, were obtained through an interview. Internal consistency of the I-WISQOL was obtained with Cronbach's α. Correlation of total scores of the I-WISQOL and SF36 was assessed to determine convergent validity using Spearman Rho. Correlations between clinical variables and results from the I-WISQOL were analyzed to descriptively assess the association of interest. RESULTS: A total of 93 participants were evaluated and completed the Italian version of the I-WISQOL. The I-WISQOL demonstrated excellent internal consistency (Cronbach's α 0.95) and good convergent validity with the validated SF-36 (Spearman Rho r=0.70, P<0.001). Using ANOVA analysis, a significant decline in WISQOL Score was noted with the increasing number of renal colics (P=0.0543), ER visits (P=0.037), number of inpatient hospitalization (P=0.025). At multivariate analysis, worse WISQOL total score was predicted by a greater number of renal colic events (ß=-4.92 [-8.81-1.04], P=0.014) and by a greater number inpatient hospitalization (ß=-7.31 [-14.35 -0.26], P=0.042). CONCLUSIONS: The I-WISQOL is an internally consistent and valid instrument to assess HRQOL in Italian-speaking patients with kidney stones. Its use in clinical practice should be implemented in order to tailor the management of each patient.

Regenerative Medicine-Based Treatment of Stress Urinary Incontinence with Mesenchymal Stem Cells: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. METHODS: We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. RESULTS: 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 - 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96]. CONCLUSION: Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.

Comparative Prospective and Longitudinal Analysis on the Platelet-to-Lymphocyte, Neutrophil-to-Lymphocyte, and Albumin-to-Globulin Ratio in Patients with Non-Metastatic and Metastatic Prostate Cancer.

PURPOSE: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases. METHODS: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR. RESULTS: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis. CONCLUSION: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed ("prostatic cancer", "albumin", "globulin", "albumin to globulin ratio") following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.

External validation of Resorlu-Unsal stone score in predicting outcomes after retrograde intrarenal surgery. Experience from a single institution.

OBJECTIVE: Pre-operative assessment of renal stones is essential in selecting treatment options and achieving high success rates for retrograde intrarenal surgery (RIRS). Several nephrolithometric scoring systems have been developed using pre-operative clinical data and stone characteristics. Resorlu-Unsal stone score (RUSS) is composed of four different parameters, and each of them adds 1 point to the final score. One point is added in patients with stone size > 20 mm, lower calyceal stones and infundibulo-pelvic angle < 45°, stone number > 1, and abnormal anatomy, respec-tively. RUSS categorizes patients into four distinct groups and aims to predict stone-free rates (SFR) after RIRS. We externally validated RUSS and evaluated its predictive accuracy. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent RIRS for renal stones between January 2020 and December 2021. Patient age, pre-operative hydronephrosis, stone size, stone density as Hounsfield Unit (HU), operative time and RUSS were investigated as potential preoperative predictive factors for stone-free status. RUSS was applied to all patients, and the nomogram was externally vali-dated. Area under the curve (AUC) was used for clinical validity assessment. RESULTS: The present study included a total of 79 patients. Mean patient age was 55.1 ± 15.4 years with a mean stone size was 14.2 ± 4.4 mm. Overall, 62/79 (78.4%) patients were stone free after the initial treatment. After applying RUSS, 36 (45.6%), 29 (36.7%), 10 (12.6%), and 4 (5.1%) patients had a score of 0, 1, 2, and 3, respectively. On multivariate logistic regression RUSS (OR = 0.220; 95%CI: 0.086-0.567; p = 0.002) was identified as the only predictor of postoperative stone-free status. CONCLUSIONS: RUSS is a user-friendly scoring system that may predict postoperative stone-free rate after RIRS with great effi-cacy and accuracy.

An original mininvasive corporoplasty technique for penile curvature without circumcision.

OBJECTIVE: We describe an original minimally invasive penile plication technique with scrotal or infrapubic access, not requiring circumcision, for penile curvature of different severity and types. This technique can be used to correct both congenital and acquired curvatures, mono or bidirectional deformities. MATERIALS AND METHODS: Between 2012 and 2018 we treated 134 patients suffering from congenital curvature (33) and acquired curvature from Peyronie's disease (101). The average curvature was 62.2° (± 30.4°). Preoperative evaluation included prostaglandin E1 injection with photographic documentation and measurement of penile angulation, administration of IIEF- 15, vasoactive penile Doppler ultrasound, analysis of thermal and vibratory sensitivity with Genito-Sensory-Analyzer (GSA) and assessment of nocturnal penile stiffness with Rigiscan, performed twice, for a detailed evaluation of patient's erectile function. Scrotal access was performed in patients with dorsal and/or lateral penile curvature; the infrapubic access was performed in patients with ventral curvature. After preparation and incision of Colles' fascia, penis was partially degloved and an original plication technique called "binary corporoplasty" was performed at the site or sites established at preoperative assessment, with non-resorbable synthetic multifilament (Premicron®) suture. RESULTS: Complete correction of penile curvature was achieved in 96.8 % of patients. No major complications were reported, and no patients suffered worsening in erectile function or in penile sensitivity. The average shortening of convex side was 1.65 cm (± 0.7 cm) and all patients report easy intercourse after correction. The average time of surgery was 46 minutes (± 11 min) and all procedures were performed as a day-hospital or ambulatory settings, with local anesthesia and light sedation. Overall satisfaction rate is 96%. CONCLUSIONS: This is a simple and rapid technique that perfectly corrects even the most severe and complex penile curvatures. In comparison to traditional techniques, such as Nesbit procedure, this technique is associated with low morbidity, a very low recurrence rate and a great aesthetic results. Aesthetic and functional patients' satisfaction was excellent.

Penile lenghthening original technique using a pubo-cavernous spacer. Long term results from a series of over 200 patients.

INTRODUCTION: We report our long experience in the surgical treatment of patients requesting penile lengthening by suspensory ligament release and placement of a custom-made soft silicone pubo-cavernous spacer. The aim was to show that with this surgical technique the results obtained are maintained over time. It is crucial to achieve postoperative satisfaction of these patients who show fragility and self-esteem problems. METHODS: From 1999 to 2020, we treated 245 patients with congenital or acquired penile brevity. We carefully analysed the preoperative and postoperative (at 6, 12, 24 and 48 months) penile size of the patients to evaluate whether this technique could allow the long-term maintenance of aesthetic results. We also assessed preoperative erectile function and we focused on the psychological aspects to avoid surgery in patients with dysmorphophobia. This original technique involves the section of the suspensory ligament and the implantation of a silicone spacer between the pubic symphysis and the corpora cavernosa. This spacer is conformed to the patient anatomy and maintains the relationship between the anatomical structures unchanged over time. Sexual self-esteem and patient satisfaction were assessed with the APPSSI questionnaire. RESULTS: The mean increase in penile length was about 2.5 cm in flaccid state and 1.9 cm in stretched state. There were no injuries of the neurovascular bundle or urethra, and no erectile dysfunction was noted. These results persisted at 6, 12, 24 and 48 months without significant differences. Over 80% of patients stated that they were completely satisfied with the results obtained. This satisfaction remained stable along follow up. CONCLUSION: The section of the suspensory ligament and the implant of the soft silicone spacer provide real penis elongation with satisfactory results that persist over time. This technique avoids the frequent complication of short-term shortening due to the scar adhesions of the edges of the dissected ligament. The high aesthetic satisfaction of patients is stable at controls at 6, 12, 24 and 48 months.

Comparison of Different Invasive Devices for the Treatment of Urinary Incontinence after Radical Prostatectomy.

Purpose: To compare different forms of invasive treatments for postradical prostatectomy (RP) urinary incontinence (UI) in terms of quantitative and qualitative parameters and continence recovery rate. Methods: We distinguished five categories of treatment: A = bulking agents, B = fixed slings, C = adjustable slings, D = circumferential compressor devices (artificial sphincter), and E = noncircumferential compressor devices (ProACT). A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across groups at postoperative follow-up. We compared the available treatment arms using standardized mean difference (SMD) and event rate (ER) for questionnaire results, number of pads/day, and percentage of pad-free patients. Evidence synthesis. 36 clinical trials were selected. At baseline, in the different populations, mean number of pad-day varied from 1.1 to 8.8, 24-hour pad weight varied extremely from 17.3 g to 747.0 g, and mean ICIQ-UI-SF questionnaire score varied from 4.8 to 18.6. Considering a random effect model among eligible studies, ER of continence recovery was 0.33 (95% CI -0.12-0.78), 0.63 (95% CI 0.55-0.71), 0.65 (95% CI 0.58-0.72), 0.50 (95% CI 0.34-0.66), and 0.53 (95%CI 0.36-0.70), respectively, in groups A, B, C, D, and E (I 2 85.87%; Q 249.82-P > 0.01) (test of group differences P=0.22). Conclusion: In our analysis, the use of adjustable and fixed slings is associated with the highest whereas the use of bulking agents is associated with the lowest recovery rate of continence after treatment. Results are conditioned by an elevated rate of heterogeneity in part explained with a high variability of consistence in urinary leakage at baseline among populations.

Endoscopic laser en bloc removal of bladder tumor. Surgical radicality and improvement of the pathological diagnostic accuracy.

INTRODUCTION: Bladder cancer is one of the most common tumors among the general population. The first surgical approach to the tumor is often the transurethral resection with monopolar or bipolar loop. Recently, laser energy has become an alternative for resection of small bladder tumor, because it allows to obtain high quality samples with the "en bloc" technique. Our study aims to show the results of endoscopic diode laser treatment of bladder tumor up to three centimeters in maximum diameter. MATERIALS AND METHODS: 189 patients underwent "en bloc" resection with diode dual length laser (980 nm-1470 nm). Follow up was over 12 months. Patients age range was from 45 to 75 years. Maximum diameter of the lesions was 3.0 cm. For each patient, a cold forceps biopsy sample was performed. RESULTS: All samples collected presented detrusorial layer. Pathological exam showed: 28 (14.8%) Ta, G1-G2; 7 (3.7%) T3, G2-G3; 14 (7.4%) T1, G2-G3 and 140 ( 74.1%) Ta, G2-G3. No complications occurred during or after surgery. At a median follow-up period of 6 months, we had no recurrence in the previous site of tumor. In the follow up at 3/6/12 months in 4 cases we had recurrence in different sites of bladder wall. CONCLUSIONS: Laser "en bloc" resection is an effective, feasible, and safe treatment for bladder tumor. It could be a valid alternative to monopolar and bipolar resection in small bladder cancer treatment.

Contemporary Trends of Systemic Neoadjuvant and Adjuvant Intravesical Chemotherapy in Patients With Upper Tract Urothelial Carcinomas Undergoing Minimally Invasive or Open Radical Nephroureterectomy: Analysis of US Claims on Perioperative Outcomes and Health Care Costs.

INTRODUCTION: New evidence indicates that minimally invasive surgery (MIS) (laparoscopic or robotic-assisted [LNU, RANU]) reaches oncologic equivalence compared with Open Radical Nephroureterectomy (ORNU) for high-risk upper-tract urothelial carcinoma (UTUC). Recently, European Association of Urology (EAU) Guidelines suggested implementing neoadjuvant chemotherapy (NAC) to standard treatment to improve oncologic outcomes of high-risk UTUC. We aimed (1) To explore contemporary trends of MIS for RNU in the United States and to compare perioperative outcomes and costs with that of ORNU. (2) To determine the trends of NAC and postoperative intravesical chemotherapy (PIC) administration for high-risk UTUC and to assess their contribution to perioperative outcomes and costs. PATIENTS AND METHODS: The Optum Clinformatics Data Mart de-identified database was queried from 2003 to 2018 to retrospectively examine patients who had undergone LNU/RANU or ORNU with or without NAC and PIC. We evaluated temporal adoption trends, complications, and health care cost analyses. We obtained descriptive statistics and utilized multivariable regression modeling to assess outcomes. RESULTS: A total of n = 492 ORNU and n = 1618 LNU/RANU procedures were reviewed. The MIS approach was associated with a statistically significant lower risk of intraoperative complications (adjusted Odds Ratio [aOR], 0.48, 95% CI:0.24-0.96), risk of hospitalization costs (aOR: 0.62, 95% CI:0.49-0.78), and shorter hospital stay (aOR: 0.20, 95% CI:0.15-0.26) when compared to ORNU. Overall, adoption of NAC and PIC accounted for only n = 81 and n < 37 cases respectively. The implementation of NAC and higher number of cycles were associated with an increased probability of any complication rate (aOR: 2.06, 95% CI:1.26-3.36) and hospital costs (aOR: 2.12, 95% CI:1.33-3.38). CONCLUSION: MIS has become the approach of choice for RNU in the US. Although recommended by guidelines, neither NAC nor postoperative bladder instillation of chemotherapy has been routinely incorporated into the clinical practice of patients with UTUC.

How the Analysis of the Pathogenetic Variants of DDR Genes Will Change the Management of Prostate Cancer Patients.

Herein, we analyze answers achieved, open questions, and future perspectives regarding the analysis of the pathogenetic variants (PV) of DNA damage response (and repair) (DDR) genes in prostate cancer (PC) patients. The incidence of PVs in homologous recombination repair (HRR) genes among men with metastatic PC varied between 11% and 33%, which was significantly higher than that in non-metastatic PC, and BRCA2 mutations were more frequent when compared to other DDR genes. The determination of the somatic or germline PVs of BRCA2 was able to define a tailored therapy using PARP inhibitors in metastatic castration-resistant prostate cancer (mCRPC) progression after first-line therapy, with significant improvements in the radiologic progression-free survival (rPFS) and overall survival (OS) rates. We propose testing all metastatic PC patients for somatic and germline HRR mutations. Somatic determination on the primary site or on historic paraffin preparations with a temporal distance of no longer than 5 years should be preferred over metastatic site biopsies. The prognostic use of DDR PVs will also be used in selected high-risk cases with non-metastatic stages to better arrange controls and therapeutic primary options. We anticipate that the use of poly-ADP-ribose polymerase (PARP) inhibitors in hormone-sensitive prostate cancer (HSPC) and in combination with androgen receptor signaling inhibitors (ARSI) will be new strategies.

Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection.

The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 is causing a severe health emergency, and an individual's hormonal milieu may play an important role in both susceptibility to infection and severity of clinical course. We analyzed the role of testosterone in the immune response, and we hypothesized possible mechanisms to explain the high incidence of COVID-19 infection and a worse clinical course in elderly male patients. Testosterone may impair the immune response, and this effect could explain the greater susceptibility of men to infection. Transmembrane serine protease 2 (TMPRSS2) plays a crucial role in the entry of the virus into the respiratory epithelial cells, leading to COVID-19 disease. It is crucial to emphasize that testosterone levels and chemical castration (e.g. by androgen deprivation therapy for prostate cancer) may have contrasting roles in the phases of COVID-19 infection. Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm. If testosterone levels play these different roles, it is necessary to carefully identify patients for any indicated testosterone manipulation.

A biofeedback-guided programme or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: A meta-analysis and systematic review.

PURPOSE: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis were conducted to compare different forms of non-invasive treatments for post-RP UI and to analyse whether the addition of biofeedback (BF) and/or pelvic floor muscle electric stimulation (PFES) to PF muscle exercise (PFME) alone can improve results in terms of continence recovery rate. MATERIALS AND METHODS: A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across subgroups during a 12-months follow-up. RESULTS: Twenty-six articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-months intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-months: PFME 111.09 g (95%CI 77.59-144.59), BF 213.81 g (95%CI -80.51-508-13), PFES 306.88 g (95%CI 158.11-455.66), BF + PFES 266.31 g (95%CI 22.69-302.93); P < .01), while at 6- and 12-months differences were similar (P > .04). At 1- and 3-months intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-months: PFME 0.40 (95%CI 0.30-0.49), BF 0.49 (95%CI 0.31-0.67), PFES 0.57 (95%CI 0.46-0.69), BF + PFES 0.75 (95%CI 0.60-0.91); P < .01), while at 6- and 12-months ERs were similar. CONCLUSIONS: Regarding non-invasive treatment of UI secondary to RP, the addition of guided programs using BF or/and PFES demonstrated to improve continence recovery rate, particularly in the first 3-month interval, when compared with the use of PFME alone.

Influence of operative time and blood loss on surgical margins and functional outcomes for laparoscopic versus robotic-assisted radical prostatectomy: a prospective analysis.

INTRODUCTION: The aim of this article was to analyze whether operative time and blood loss during radical prostatectomy (RP) can significantly influence surgical margins (SM) status and post-operative functional outcomes. MATERIAL AND METHODS: We prospectively analyzed prostate cancer (PC) patients undergoing RP, using robot-assisted (RARP) or laparoscopic (LRP) procedures. Blood loss was defined using the variation in hemoglobin (Hb, g/dl) values from the day before surgery and no later than 4 hours after surgery. RESULTS: From a whole population of 413 cases considered for RP, 67% underwent LRP and 33.0% RARP. Positive SM (SM+) were found in 33.9% of cases. Mean surgical operative time was 172.3 ±76 min (range 49-485), whereas blood loss was 2.3 ±1.2 g/dl (range 0.3-7.6). Operative time and blood loss at RP were not significantly correlated (r = -0.028275; p = 0.684). SM+ rates significantly (p = 0.002) varied by operative time; a higher SM+ rate was found in cases with an operative time <120 min (41.2%) and >240 min (53.4%). The risk of SM+ significantly increased 1.70 and 1.94 times in cases with an operative time <120 min and >240 min, respectively, independently to the surgical approach. The rate of erectile disfunction (ED) varied from 22.4% to 60.3% between <120 min and >240 min procedures (p = 0.001). According to blood loss, SM+ rates slightly but significantly (p = 0.032) varied; a higher rate of SM+ was found in cases with a Hb variation between 2-4 g/dl (35.9%). CONCLUSIONS: Independently to the surgical approach, operative time, more than blood loss at RP, represents a significant variable able to influence SM status and post-operative ED.

How to Predict Outcomes from a Biofeedback and Pelvic Floor Muscle Electric Stimulation Program in Patients with Urinary Incontinence after Radical Prostatectomy.

OBJECTIVES: The objective of this study was to analyze the pre-operative and intra-operative variables that can condition urinary incontinence (UI) after radical prostatectomy (RP), as well as continence rate recovery during a pelvic floor rehabilitation program. MATERIALS AND METHODS: A total of 72 cases with UI after RP were prospectively examined. All cases were homogeneously treated by the same surgeon, using the same RP technique. A combination of biofeedback (BF) and pelvic floor electric stimulation (PFES) performed by the same clinician and using the same protocol was used. Clinical, pathologic and surgical variables were analyzed in terms of 24 h pad test results (pad weight and pad-free status). RESULTS: Prostate volume (PV) strongly varied from 24 to 127 cc (mean ± SD 46.39 ± 18.65 cc), and the baseline pad weight varied from 10 to 1500 cc (mean ± SD 354.29 ± 404.15 cc). PV strongly and positively correlated with the baseline pad weight (r = 0.4215; p = 0.0269) and inversely with the three-month pad weight (r = - 0.4763; p = 0.0213) and pad-free status (r =- 0.3010; p = 0.0429). The risk of a residual pad weight >10 g after the rehabilitative program significantly increased according to PV (p = 0.001) and the baseline pad weight (p = 0.002 and < 0.0001). In particular, PV > 40 cc and a baseline pad weight >400 g significantly (p = 0.010 and p < 0.0001, respectively) and independently predicted a 5.7 and a 35.4 times increase in the risk of a residual pad weight at the three-month follow-up, respectively. CONCLUSION: This is the first prospective trial whose primary objective is to verify the possible predictors, such as PV, that are able to condition the response to a pelvic floor rehabilitation program for UI after RP.

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

Purpose: Most of the endourologic procedures along the urinary tract have been widely practiced as outpatient operations, including surgery for benign prostatic hyperplasia (BPH). This systematic review and meta-analysis was conducted to assess safety and feasibility of outpatient surgery for patients suffering from symptomatic BPH candidate for endoscopic disobstruction. Materials and Methods: PubMed, Web of Science, Cochrane, and Embase were searched up until March 30, 2020. Methodological index for nonrandomized studies (MINORS) tool was utilized to assess the quality of included studies, and a pooled measure of failure rate (FR) or event rate (ER) estimate was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate contribution of moderators to heterogeneity. Results: Twenty studies with a total of 1626 patients treated according to outpatient criteria for endoscopic BPH surgery were included. In total, 18 studies reporting data on immediate hospital readmission and/or inability to discharge after endoscopic procedure presented FR estimates ranging from 1.7% to 51.1%. Pooled FR estimate was 7.8% (95% confidence interval [CI]: 5.2-10.3); Heterogeneity: Q = 76.85; degree of freedom = 17, p < 0.001; I2 = 75.12%. Subgroup analysis according to surgical technique revealed difference among the three approaches with pooled FR of 3% (95% CI: 1-4.9), 7.1% (95% CI: 3.9-10.4), and 11.8% (95% CI: 7-16.7) for transurethral resection of the prostate, Green-light, and holmium laser vaporesection, respectively (p < 0.001). At meta-regression analysis, none of the retrieved covariates was able to significantly influence the cumulative outcomes reported. ER for postoperative complications and early outpatient visit showed a pooled estimate of 18.6% (95% CI: 13.2-23.9) and 7.7% (95% CI: 4.3-11), respectively. Conclusions: Our analysis revealed how transurethral procedures for BPH on an outpatient setting are overall reliable and safe. Of note, there were significant outcome differences between groups with regard to type of surgical procedure, perioperative prostate volume, and discharge protocol suggesting the need for further prospective analysis to better elucidate the best strategy in such outpatient conduct.