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Objectives Castration is any action, surgical or chemical, by which an individual loses use of the gonads, most commonly referring to loss of the testicles. Reference to elective castration has been, according to Diodorus, as old as the human record itself, first being practiced in pharaonic Egypt. Castration has been practiced as a means to produce eunuchs, a punitive measure in military and secular courts, and a source of trophy-taking in warfare. The role of castration in the control of advanced and metastatic prostate cancer became a well recognized standard of care in the mid-20th century earning Nobel Prizes for its pioneers. Our aim was to better understand the history of human castration and its transformation from an instrument of terror to a standard and sometimes life-saving urological treatment. Methods A literature review on human castration was performed through Medline, PubMed, the Gutenburg Project, and Google Scholar searching words “castration”, “eunuch”, “orchiectomy” and “androgen deprivation”. We accessed the public archives of the British Museum (London) and digital classical libraries as cited. Reports were collected to create a timeline. Results First reports of human castration date back to the 21st century (BCE) in the ancient city of Lagash, Sumeria when used for the creation of court eunuchs. Castration figured prominently in most ancient cultures from myth to jurisprudence. The god Uranus was castrated by his son, Cronus (Saturn), with an adamantine sickle, throwing the severed gonads into the sea. There is at least conjectural evidence of castration on medical, criminal, and even volitional grounds from pharaonic and classical history through medieval and modern times. Primitive medical observations recognized the different phenotypes of pre-pubertal and post-pubertal eunuchs especially on the voice which may account for the popularity of some castrati in the history of choral music. Castration was a well-established procedure in the domestication of animals for millennia but it was only in 1941 that Charles Huggins and others first demonstrated the effects of bilateral orchiectomy in the control of prostate cancer. Medical castration, now with special androgen receptor inhibitors, continues to be a mainstay in the management of metastatic and hormone refractory prostate cancer. Conclusions Medical or surgical castration plays an important role in the modern management of advanced prostate cancer. Castration has existed in human cultures for thousands of years, although its true prevalence is unknown, accounted for in the folklore and sparse records typical of ancient times.

To confirm the correlation between post-void residual urine ratio (PVR-R) and BOO diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS) and to develop a clinical nomogram.A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment for BOO including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies, suprapubic ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BTW). PVR-R was defined as follows: PVR-R = (PVR/total Bladder Volume [BV]) × 100). Logistic regression analysis was used to investigate predictors of pathological bladder emptying (BOO) defined as Schafer II. A nomogram to predict BOO based on the multivariable logistic regression model was then developed.Overall 335 patients were enrolled. Overall, 131/335 (40%) presented BOO on PFS. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 2.21 per mm; 95% confidence interval [CI], 1.57-3.09; p = 0.001), PVR-R (OR: 1.02 per %; 95% CI, 1.01-1.03; p = 0.034) and prostate volume (OR: 0.97 per mL; 95% CI, 0.95-0.98; p = 0.001) were significant predictors for BOO. The model presented an accuracy of 0.82 and a clinical net benefit in the range of 10-90%.The present study confirms the important role of PVR-ratio in the prediction of BOO. For the first time, we present a clinical nomogram including PVR-ratio for the prediction of BOO.

Available data on medical treatment of metastatic castration resistant prostate cancer (mCRPC) support the use of more than one therapy line to delay chemotherapy. We evaluate in a longitudinal real life multicenter cohort, the oncological outcome of mCRPC patients treated with Abiraterone Acetate (AA) and Enzalutamide (EZ) in a chemo-naïve setting, who received locoregional treatments for subsequent development of oligorecurrent disease.We prospectively collected data on chemo-naïve mCRPC patients, who received either AA or EZ as first or second line treatment between Oct-2012 and Nov-2020 at 5 centers. High-volume disease at mCRPC onset was defined as bulky positive nodes (≥5 cm) or more than 6 bone metastases. Survival probabilities were computed at 12, 24, 48 and 60 months after treatment start. The impact of loco-regional treatments on progression free survival (PFS) were assessed with the Kaplan-Meier method and the log-rank test was applied.Overall, 117 chemo-naive mCRPC patients received a first line therapy. Fifty-seven (48.7%) patients received AA and 60 (51.3%) received EZ. Eight (6.7%) patients underwent salvage chemotherapy after first line failure. Overall, 28 patients shifted to a second line therapy. Two-yr progression-free, cancer-specific and overall survival probabilities were 65.5%, 82.2% and 78.4% respectively. Since diagnosis of mCRPC, oligo progression occurred in 25 patients who received stereotactic radiation therapy (23/25, 92%) focused on metastasis (4 nodal sites and 19 bones) or salvage lymph node dissection (2/25, 8%). At Kaplan-Meier analysis, patients with low volume disease displayed higher PFS probabilities (log rank p = 0.009) and in this subgroup of patients loco-regional treatments had a significant impact on PFS (p = 0.048), while it was negligible in the whole cohort and in patients with high volume disease (p = 0.6 and p = 0.75).Low-volume mCRPC patients are exposed to improved PFS and seem to benefit from locoregional treatments.

Nocturia is one of the most prevalent and bothersome lower urinary tract symptoms (LUTS) in men, leading to increased morbidity and mortality and a considerable economic burden on healthcare systems. Understanding its natural history, effect of pharmacotherapy, and predictors of failure of pharmacotherapy would allow optimised patient management.To evaluate the prevalence and effect of clinically relevant nocturia (crN) on quality of life in a contemporary cohort of European men aged ≥50 yr in a "real-life" setting, to understand its natural history, to detect any effect of pharmacotherapy, and to identify predictors of pharmacotherapy failure.This is a secondary analysis of the data from the Evolution Registry-a European, multicentre, prospective, observational registry, conducted in five European countries within a sample of general practitioners' and urologists' clinics. A consecutive sample of 2175 men aged ≥50 yr with LUTS in association with benign prostatic enlargement was enrolled between February 2010 and April 2011, and followed up for 2yr. Overall, data from 1838 men were suitable for analysis.The primary outcome was evaluation of the baseline incidence of nocturia in the study population. Secondary outcomes included the impact of nocturia on quality of life, efficacy of pharmacotherapy, and predictive factors associated with persistence of nocturia. Descriptive statistics were used to examine the data. Logistic regressions were used to analyse associations between comorbid conditions and risk factors in men with nocturia.Overall, 1198 men (65%) reported crN (two or more voids per night). This increased age dependently from 59% in the 50-59-yr age group (n=74) to 89% in the 80-99-yr age group (n=25). Overall, the incidence of crN improved in those who commenced pharmacological treatment at study entry, from 69% at baseline to 49% at 24 mo (p0.00001). This was statistically significant only in those80 yr old. A weak correlation was found between the severity of nocturia at baseline and quality-of-life scores on the International Prostate Symptom Score questionnaire (r=0.33, p0.001). Of the patients treated with an alpha-blocker or a 5-alpha reductase inhibitor, 62% still had crN at 24 mo.Almost two-thirds of men in the Evolution Registry reported clinically significant nocturia with increased incidence with age. Despite prostate-targeted treatment, most patients, especially older men, still had persistent or worsening nocturia at 2-yr follow-up, and in this study, it was not possible to identify specific clinical factors that predicted those who could respond well to treatment in this regard.This large study of men from five different European countries has shown that waking up at night to pass urine (nocturia) is very common and becomes more common with older age, and treatments that target the prostate do not significantly improve symptoms over 2yr in most men.

The Reporting and Data System (RADS) have been used in the attempts to standardize the results of oncological scans in different scenarios, such as lymph nodes, adding configuration criteria to size determination. We analyze the predictive value of preoperative Node-RADS determination at imaging for pelvic lymph node (PLN) involvement in cases of prostate cancer (PC) considered for radical prostatectomy (RP) with extended lymph node dissection (eLND) and we compare it with validate predictive nomograms (MSKCC, Briganti and Gandaglia).150 patients with a histological diagnosis of PC (high risk or intermediate with an estimated risk for pN+ higher than 5% using the Briganti or 7% using the Gandaglia nomogram) submitted for RP with an ePLND from 2018 and 2021 were retrospectively examined. Node-RADS determination was performed in all cases using the preoperative magnetic resonance (MR), performed by a radiologist blinded for pathologic results and compared with the MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms.PLN involvement at final pathology (pN+) was found in 36/150 (24.0%) of cases and the mean percentage of positive LNs in pN+ cases was 15.90 ± 13.40. The mean number of PLNs removed at RP was similar (p = 0.188) between pN0 (23.9 ± 8.0) and pN+ (25.3 ± 8.0) cases. Considering a Node RADS 4-5 positive and a Node RADS 1-2 negative, the PPV was 100% and the NPV was 79.6%. A Node RADS score 4-5 showed a lower sensitivity (0.167 versus 0.972, 1.000, 0.971, 0.960 respectively), a higher specificity (1.000 versus 0.079, 0.096, 0.138, 0.186 respectively) and a similar AUC (0.583 versus 0.591, 0.581, 0.574, 0.597 respectively) when compared to MSKCC, Briganti 2012, Gandaglia 2017 and Gandaglia 2019 nomograms.Our evaluation suggests that Node RADS score, combining configuration criteria to size determination could improve specificity in terms of pathologic PLN prediction but a very low sensitivity has been also described.

Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP).From 2012 onwards, 335 consecutive men undergoing RRP for PCa at three centers in Italy were enrolled into a prospective database. Body mass index (BMI) was calculated before RRP. Blood samples were collected and tested for total prostate-specific antigen (PSA) levels and chromogranin A (CgA). We evaluated the association between serum levels of CgA and upstaging and upgrading using logistic regression analyses.Median age and preoperative PSA levels were 65 years (interquartile range [IQR]: 60-69) and 7.2 ng/ml (IQR: 5.3-10.4), respectively. Median BMI was 26.1 kg/mIn our multicenter cohort of patients, CgA is not a predictor of poorly differentiated PCa on radical prostatectomy. According to our experience, CgA should not be considered a reliable marker to predict poorly differentiated or advanced prostate cancer.

About 75% of urothelial bladder cancers are non-muscle invasive (NMIBC), and limited to mucosa (Ta or CIS) or sub-mucosa (T1). An increase of androgen expression and androgen receptors has a positive effect on oncogenic expression. We aimed to evaluate whether 5-alpha reductase inhibitors (5-ARI) have a role in NMIBC.We retrospectively evaluated the clinical and pathological data of 423 patients with NMIBC who underwent transurethral bladder resection. We considered the number of resections, number of total recurrences, time of recurrences, and histopathology details. The population was classified into two groups: treated and untreated with 5-ARIs. The enrolled patients were in treatment with 5ARIs for symptomatic prostatic hyperplasia for at least 12 months. Mean follow-up time was 30.43 months.Patients treated with 5-ARIs had a lower rate of recurrence (14%) than the untreated group (37%). There was a significant difference in the mean number of recurrences between the untreated and the treated group (P=0.006). Furthermore, the treated group showed a significantly greater number of low than high grade tumors, compared to the untreated group (P≤0.05). There was a significant decrease in the number of muscle invasive tumors in treated patients (P=0.032). The recurrence-free survival rate of patients treated with 5-ARIs was significantly higher (P=0.0001).Long-term treatment with 5-ARIs might reduce the risk of bladder tumor recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs.

To develop an easy tool to predict cancer specific (CSS) and disease-free survival (DFS) in patients with bladder cancer treated with radical cystectomy.Data from a consecutive series of 2395 patients with primitive or progression to muscle invasive bladder cancer (MIBC) undergone to radical cystectomy and lymph nodes dissection in 5 centers were evaluated. Using Cox proportional hazards analyses, the Cancer of the bladder risk assessment (CRAB) nomogram was generated. Accuracy of the nomogram was evaluated by Harrell's C test. Internal validation of the model was performed using 200 bootstraps.Median age was 66 (IQR 58/73) years; 612/2395 (26%) patients presented an advanced pathological stage (≥pT3a); 478/2395 (20%) presented positive lymph nodes. Overall, 729/2395 (30%) presented local or distant recurrence with a median DFS of 42 (IQR 14/89) months. Overall, 642/2395 (27%) died of bladder cancer with a median follow up of 48 (IQR 22/92) months. On univariate Cox proportional hazards analyses, age, stage, and lymph nodes density were a significant predictor of 3 and5 years CSS and DFS. Accuracy of the CRAB nomogram was 0.73 and 0.71 respectively.CRAB nomogram can be a practical and easily applicable tool that may help urologists to classify the long-term CSS and DFS of patients treated with radical cystectomy and to predict the oncological outcome.

Context The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the safety of laparoscopy due to the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diffusion in surgical smoke. Although no case of SARS-CoV-2 contagion related to surgical smoke has been reported, several international surgical societies recommended caution or even discouraged the use of a laparoscopic approach. Objective To evaluate the risk of virus spread due to surgical smoke during surgical procedures. Evidence acquisition We searched PubMed and Scopus for eligible studies, including clinical and preclinical studies assessing the presence of any virus in the surgical smoke from any surgical procedure or experimental model. Evidence synthesis We identified 24 studies. No study was found investigating SARS-CoV-2 or any other coronavirus. About other viruses, hepatitis B virus was identified in the surgical smoke collected during different laparoscopic surgeries (colorectal resections, gastrectomies, and hepatic wedge resections). Other clinical studies suggested a consistent risk of transmission for human papillomavirus (HPV) in the surgical treatments of HPV-related disease (mainly genital warts, laryngeal papillomas, or cutaneous lesions). Preclinical studies showed conflicting results, but HPV was shown to have a high risk of transmission. Conclusions Although all the available data come from different viruses, considering that the SARS-CoV-2 virus has been shown in blood and stools, the theoretical risk of virus diffusion through surgical smoke cannot be excluded. Specific clinical studies are needed to understand the effective presence of the virus in the surgical smoke of different surgical procedures and its concentration. Meanwhile, adoption of all the required protective strategies, including preoperative patient nasopharyngeal swab for COVID-19, seems mandatory. Patient summary In this systematic review, we looked at the risk of virus spread from surgical smoke exposure during surgery. Although no study was found investigating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or any other coronavirus, we found that the theoretical risk of virus diffusion through surgical smoke cannot be excluded.

Item does not contain fulltext Background Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures. Methods Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index. Results The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0-26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients. Conclusions After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy.

Context The nonspecific storage symptom complex overactive bladder (OAB) is an important clinical condition in functional urology. Until recently, pharmacological therapy comprised antimuscarinic drugs, but more recently beta 3 agonists have added to the available agents. Traditional reporting of efficacy and safety of these agents relies upon regulatory placebo-controlled studies. There remains no head-to-head comparison of existing agents in the contemporary literature. Contemporary conclusions on comparative efficacy and safety drawn from the use of these agents are based on systematic reviews of the literature and associated meta-analyses. Objective In this study, we used the analytical model of multicriteria decision analysis (MCDA) to compare contemporary pharmacotherapy for OAB. Evidence acquisition Efficacy and safety data from published, randomised, placebo-controlled trials of antimuscarinic antagonists, the beta 3 agonist, and the combination of an antimuscarinic and beta 3 agonist were used to populate the MCDA model. Evidence synthesis Experts assessed weights of the relative importance of favourable and unfavourable effects, which provided a common measure of benefits and safety that were combined in the MCDA model to give an overall ranking of the OAB drugs. Results When benefits are judged as more important than safety, fesoterodine 4 or 8 mg used in a flexible dosing pattern provides the most favourable therapeutic option, over a wide sensitivity analysis relating to benefits and harms. Conclusions In our analysis using an MCDA model, in both the flexible dosing pattern of fesoterodine and the solifenacin combination with mirabegron, the benefit-safety balance is better in terms of benefits and/or safety than any of the other available OAB drugs. Caution in interpretation of the data has to be expressed as the fesoterodine data are based on a flexible dosing regimen, which adds an additional dimension of personalising therapy. Patient summary Overactive bladder (OAB) is a common condition with a significant impact on the quality of life. Possible symptoms include the following: (1) urgency—a compelling desire to urinate, which is difficult to defer; (2) urgency urinary incontinence—urgency leading to incontinence episodes; (3) frequency—increased frequency of wanting to pass urine; and (4) nocturia—increase in instances of getting up at night to urinate. To date, the mainstay of therapy for OAB has been antimuscarinic drugs and, more recently, the beta 3 agonist mirabegron. Ten international experts in urology, obstetrics, gynaecology, healthy ageing, and data analysis compared the benefit-risk balance of 14 OAB drugs licensed in Europe. The experts considered the importance of a favourable effect on the above four symptoms and also potential for side effects, but only three of these side effects, constipation, dry mouth, and dizziness, showed clinically relevant differences among the six drugs they considered. The observations recorded here suggest interesting differences between drugs across a wide range of possible trade-offs between benefit and safety. The different recruitment criteria used for each study may influence the results seen, so they need to be treated with caution. Comparison of flexibly dosed fesoterodine studies with fixed-dose fesoterodine studies introduces an additional potential bias; definitive conclusions can be drawn only if enough comparable placebo-controlled flexible dosing studies with other drugs were available.

Purpose To investigate the effects of different antibiotic prophylaxis regimens in patients with diabetes mellitus (DM) candidates to trans-rectal ultrasound-guided prostate biopsy (TRUSPB). Methods 143 outpatients with DM who underwent TRUSPB during the period 2018–2020 were selected from a cohort of 1150 patients in 3 different institutions. Exclusion criteria were allergies, concomitant anti-platelet therapies and uncontrolled DM. Different antibiotic prophylaxis regimens were adopted. Bacterial resistance levels to fluoroquinolones into the different communities were also collected. Univariable and multivariable binomial logistic regression analyses were used to assess the odds ratio (OR) with 95% confidence intervals (CIs) testing the risk of infective complications' occurrence after adjusting for clinical covariates. Results Overall, DM patients were significantly associated with infective complications' occurrence (p 37 °C were found in 9.1% and 1.5% (p Conclusion Fluoroquinolones were active in antibiotic prophylaxis of diabetic patients who had undergone to TRUSPB independently from the level of bacterial resistance found in the community. These results conflict with the recent European warning and support the Japanese and American guidelines on the topic.

503 Background: Pts presenting with NMIBC carcinoma in situ (CIS) have a high risk of progression. FGFR inhibition may benefit CIS pts with FGFRalt who are unresponsive to first-line BCG, for whom treatment (tx) options, other than radical cystectomy, are limited. Erdafitinib (erda), an oral selective pan-FGFR tyrosine kinase inhibitor, is approved for locally advanced or metastatic urothelial cancer in adults with FGFR3/2alt who have progressed during or after ≥1 line of platinum-containing chemotherapy. THOR-2 (NCT04172675) is a multicohort phase 2 study of erda in pts with HR-NMIBC. Here we report results from an exploratory cohort of pts with BCG-unresponsive CIS with FGFRalt with or without papillary disease (Cohort 2). Methods: Inclusion criteria: age ≥18 y, with histologically confirmed, BCG-unresponsive HR-NMIBC with FGFR3/2alt (by local/central testing) presenting as CIS, with or without a papillary tumor and who refused or were not eligible for cystectomy. In this cohort, pts received continuous oral erda 6 mg once daily without uptitration in 28-d cycles (dose selected to improve tolerability while maintaining activity to prevent disease recurrence, for this population). Erda was discontinued if no complete response (CR) was observed within 3 mos. Exploratory efficacy end points are CR rates at the Cycle 3 Day 1 (C3D1) disease evaluation and the Cycle 6 Day 1 (C6D1) disease evaluation; safety was a key secondary end point. Results: As of the data cutoff (Sep 2022) (median follow-up of 10 mos), 10 pts have received erda (enrolled population; median age 72 y [range 52-83]; 90% CIS [1 pt with Ta was mis-enrolled]). Pts received erda for a median duration 5.9 mos (range 1.1-17.0). Of 10 enrolled pts, the CR rates at first evaluation (C3D1) and second evaluation (C6D1) were 100% (9/9 evaluable pts) and 75% (6/8 evaluable pts), respectively. The median duration of response was 3.0 mos. The most common tx-emergent adverse events (TEAEs) were dry mouth (60%; n=6), hyperphosphatemia (50%; n=5), dysgeusia (50%; n=5), and diarrhea (50.0%; n=5). 1 pt (10%) had Gr 2 retinal detachment which led to tx discontinuation and 1 pt (10%) had Gr 1 subretinal fluid; both reported as resolved. Gr ≥3 tx-related TEAEs occurred in 3 pts (30%), and included dry mouth, stomatitis, nail disorder, onychomadesis, acute kidney injury, chronic kidney disease, sepsis, and hypotension in 1 pt each. 1 pt (10%) had serious tx-related TEAEs (dry mouth, hypotension, pneumonitis, acute kidney injury, and sepsis), and 1 pt (10%) discontinued tx due to a tx-related TEAE. No tx-related deaths were observed. Conclusions: Data from Cohort 2 of THOR-2 demonstrate efficacy at C3D1 and C6D1 evaluations in pts with HR-NMIBC with FGFRalt. Safety data were consistent with the known safety profile of erda. Clinical trial information: NCT04172675 .

Background: Human Dachshund homologue 1 (DACH1) is involved in carcinogenesis with opposite roles reported in different tumor types. Four alternatively spliced transcripts encoding different DACH1 isoforms were described but their specific role in human cancers is still unknown. Prostate cancer (PCa) is a heterogeneous disease with a very wide variability, so there is yet a relevant need to find new diagnostic and therapeutic biomarkers to make a safe clinical evaluation. It is well known that the differential expression of protein isoforms can induce distinct transcriptional programs with opposing effects on tumor progression and therapy. Thus, in this study we aimed to correlate the functional role of DACH1 with its splicing variants expression in PCa.Methods: The expression and functional role of DACH1 splicing variants in PCa were investigated using tumor (PC3) and normal (RWPE-1) cell lines, patient biopsies and TCGA dataset. Flow-cytometry, western blots and RT-qPCR were used for in vitro molecular characterization; invasion, adhesion, clonogenic assays and cell cycle analysis for functional characterization. Immunohystochemistry and western blot were performed on human PCa biopsies.Results: RT-qPCR and Western Blot revealed that DACH1-positive PC3 cells predominantly expressed DACH1 variant 4 (DACH1-v4), whereas RWPE-1 cells mostly expressed DACH1 variant 3. Stable DACH1-v4 overexpression enhanced the transformed phenotype of PC3 cells by inducing proliferation, colony formation, invasion ability, epithelial to mesenchymal transition. Given its intrinsic radioresistance, PCa frequently recurs after radiotherapy. Of note, DACH1-v4-overexpressing PC3 cells displayed higher radioresistant behavior. Overexpression of DACH1-v4 also transformed RWPE-1 cells to oncogenic phenotype, suggesting a pro-oncogenic role for this specific isoform. PCa biopsies analysis showed DACH1 nuclear staining enhanced throughout the increase of the tumor grade. Remarkably, tumor glands were found to express a long DACH1 variant, while normal prostate tissue expressed the short DACH1 isoform, in line with data from TCGA-PRAD analysis and our data in RWPE-1 cells. Conclusions: Our findings highlight the oncogenic role of DACH1-v4 in PCa and suggest that the longer DACH1 variants could be associated to pro-tumor function, while the shortest DACH1 variant would perform tumor suppression. The expression of specific DACH1 isoforms could represent a novel diagnostic/prognostic marker in PCa.

Purpose of review To review the most recent data on urinary diversions (UD) surgical outcomes performed at time of radical cystectomy (RC). Recent findings Looking at the recent specific literature, the most recent factors introduced in the field of UDs are the preoperative assessment of patient's frailty and the use of the robotic system. According to the available evidence, frailty status is a good preoperative predictor of surgical outcomes and patient recovery. Several questionaries measuring patient's frailty status have been evaluated as a proxy to prevent RC complications and to improve the choice of the UDs.Robot-assisted RC has gained popularity and both continent and incontinent UD are now performed through an intra-corporeal technique. Studies on Robot-assisted UDs showed that both intra-corporeal and extra-corporeal approaches (ICUD and ECUD, respectively) are safe and feasible. Compared to the open techniques, they improve intraoperative blood loss and postoperative recovery. However, accessibility to the Da-Vinci System and the need of robotic skills limit the application of these techniques to high-volume institutes. Summary Patient's frailty status and the use of robotic surgery are the most recent factors introduced to improve the choice of UD and surgical outcomes.

Introduction Uretero-enteric stricture (UES) is a common post-operative complication after radical cystectomy with urinary diversion. The aim of this systematic review is to discuss the contemporary management of benign UES after cystectomy and to compare the different surgical approaches. Evidence acquisition A systematic review was performed from January 2000 through January 2021. Search engines used included PubMed, Embase and Medline databases. Search query was: ((ureteroileal OR uretero-ileal OR ureteroenteric OR ureteroenteric) AND (stricture OR stenosis)) AND (management OR treatment). Study selection followed the PRISMA statement. Studies tackling management of UES, either through open, endoscopic, laparoscopic or robot-assisted approaches, were included in our systematic review. Evidence synthesis Forty-one studies were finally included in this systematic review. No prospective studies were found; all included studies were retrospective. Open surgical repair had a 78-100% success rate, a significant rate of complications, and a low recurrence rate (6-8%). Endourological management decreased complication rate, length-of-stay, and blood loss, with however lower success (15-50%) and higher recurrence rates (62%-91%) compared to open surgery. Robotic assisted surgery showed comparable success rates to open surgery (80-100%), while limiting the number of major complications and hospital length-of-stay. Conclusions Surgical management of UES remains challenging. Open surgery maintains a role given its high success rate, at the cost however of a significant morbidity. On the other hand, endourological procedures offer a favorable and low complication risk, but a low long-term success rate. Robotic-assisted surgery is emerging with a valid resolution of UES as it offers comparable success rates to an open approach, while reducing surgical morbidity. Head-to-head comparisons are awaited to confirm these findings.