Role of targeted biopsy, perilesional biopsy, and random biopsy in prostate cancer diagnosis by mpMRI/transrectal ultrasonography fusion biopsy.

PURPOSE: It is still not clear the role of perilesional biopsy (PL) and the extension of the random biopsy (RB) scheme to be adopted during mpMRI-guided ultrasound fusion biopsy (FB). To evaluate the increase in diagnostic accuracy achieved by PL and different RB schemes over target biopsy (TB). METHODS: We collected prospectively 168 biopsy-naïve patients with positive mpMRI receiving FB and concurrent 24-core RB. The diagnostic yields of the different possible biopsy schemes (TB only; TB + 4 PL cores; TB + 12-core RB; TB + 24-core RB) were compared by the McNemar test. Clinically significant (CS) prostate cancer (PCA) was defined according to the definition of the PROMIS trial. Regression analyses were used to identify independent predictors of the presence of any cancer, csPCA. RESULTS: The detection rate of CS cancers increased to 35%, 45%, and 49% by adding 4 PL cores, 12, and 24 RB cores, respectively (all p < 0.02). Notably, the largest scheme including 3 TB and 24 RB cores identified a small but statistically significant 4% increase in detection rate of CS cancer, as compared with the second largest scheme. TB alone identified only 62% of the CS cancers. Such figure increased to 72% by adding 4 PL cores, and to 91% by adding 14 RB cores. CONCLUSIONS: We found that PL biopsy increased the detection rate of CS cancers as compared with TB alone. However, the combination of those cores missed about 30% of the CS cancers identified with larger RB cores, notably including a considerable 15% of cases located contralaterally to the index tumor.

Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction.

In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches.

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients' quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients' quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

The impact of COVID-19 pandemic on urological emergencies: a single-center experience.

PURPOSE: COVID-19 pandemic represents a novel challenge for healthcare systems, and it affects even the daily urological practice. Italy was the first country after China to experience a lock-down period. Our objective is to determine whether, during the COVID-19 period, there has been any modification in urological emergencies. METHODS: we retrospectively reviewed urgent urological consultations requested by the Emergency Department (ED) of Padua University Hospital in the 36-day period between February 22nd and March 30th, 2020 and compared them to the prior year cases within a similar time frame (February 24th to March 31st, 2019). Pediatric population (age < 15 years); surgical complications and traumas were excluded to avoid confounding from the reduction of activities during the lockdown. The number of daily consultations, the number of invasive procedures performed and admissions were evaluated, together with the predictors of admission were identified through multivariate logistic regression models. RESULTS: The final sample resulted in 107 consultations performed in 2020 and 266 in 2019. A higher number of daily consultations was performed during 2019 (7.33 vs 2.97, p < 0.001). Similarly, the number of daily-invasive procedures was higher in 2019 (p = 0.006), while there was no difference in the number of daily admissions (15 vs 12, p = 0.80). On multivariate analysis, the year (2020 vs 2019, OR 2.714, 95% CI 1.096-6.757, p = 0.0297) was a significant predictor of admission. CONCLUSIONS: Urgent urology practice was affected during COVID-19 pandemic with a remarkable reduction in urgent urological consultations; furthermore, a higher risk of admissions was observed in 2020. The consequences of a potentially delayed diagnosis remain to be determined.

Morbidity, mortality, and quality assessment following open radical cystectomy in elderly patients with bladder cancer.

BACKGROUND: Open radical cystectomy (ORC) with pelvic lymph-node dissection (PLND) for bladder cancer (BCa) and urinary diversion is a morbid procedure, and advanced age has been associated with a higher incidence of Clavien-Dindo ≥ 3 complications. AIM: To investigate the association between chronological age, survival outcomes, incidence of perioperative complications, and quality parameters in patients undergoing ORC. METHODS: We reviewed 413 patients who underwent ORC and PLND at a single academic centre between December 2009 and June 2018 for cT2-T4N0M0 BCa. Complete clinical, demographic, and pathological data were collected in the preoperative, preoperative, and postoperative setting. Patients were categorized as ≥ 75 years or < 75 years and statistical analysis was performed accordingly. Besides descriptive statistics, Kaplan-Meier log-rank test was used. Cox regression univariate and multivariate analyses were used to assess any potential predictor of OS and CSS. RESULTS: There were 285 (69%) patients < 75 years and 128 (31%) patients ≥ 75 years old. There was no significant difference between the two age groups neither in terms of distribution of pathological stage nor in terms of overall incidence of postoperative complications. Chronological age was not significantly associated with survival outcomes on multivariate analysis. Finally, the comorbidity index was the only significant risk factor for the incidence of any complications (OR = 0.83, p = 0.002) at multivariate binary logistic regression. CONCLUSION: Open radical cystectomy (ORC) is a feasible and safe procedure in patients with high-risk non-metastatic bladder cancer. Uro-oncologists should consider evaluating elderly patients for surgery according to a thorough geriatric assessment despite chronological age.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer: Morbidity and Functional Outcomes from a Large Multicenter Series of Open versus Robotic Approaches.

PURPOSE: Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches. MATERIALS AND METHODS: We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis. RESULTS: We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p <0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p <0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique. CONCLUSIONS: In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

Is it worth to perform salvage radical prostatectomy for radio-recurrent prostate cancer? A literature review.

PURPOSE: Salvage radical prostatectomy (sRP) represents a curative option for prostate cancer (PCa) biochemical recurrence (BCR) after radiation therapy (RT). In this review, we aimed to outline the contemporary results and use of sRP. METHODS: A web search was performed on the Ovid platform using Embase and Medline databases from January 2010 using pre-defined search terms. Web search was implemented by manual search. Oncological and functional outcomes and complications were summarized using standard classification systems, when feasible. RESULTS: sRP is currently underused, being chosen for radio-recurrent PCa treatment in around 1% of the cases. Surgery is complex due to radiation-induced tissue changes making posterior planes and apex dissection particularly challenging. Patient selection is paramount to maximize the oncological benefit. Most series report a BCR-free survival > 60%, mainly at the end of a short- to intermediate-term follow-up. Five-year progression-free survival is nearly 50% and 5-year cancer-specific survival rates are around 90%. Major peri-operative complications, anastomotic leaks and strictures, still more frequent than in a primary RP setting, have been steering towards more acceptable rates in recent years, when compared to historical series. Continence rates are widely variable, often in between 39 and 60%. Potency remains difficult to recover. CONCLUSIONS: sRP represents a curative option with promising short- to medium-term oncological results and acceptable side effects, in high-volume institutions. In appropriately selected patients, the procedure should not be underused due to the fear of poor functional outcomes and/or complications. Prospective studies are needed to assess the long-term outcomes and to further refine patient selection criteria.

Impact of metabolic syndrome on functional outcomes and complications of surgical treatment of prostate cancer.

BACKGROUND: Metabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures. AIM: To assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: Complete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10-year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF-AHA/NHLBI criteria. Outcomes included 1-year continence and potency rates, early (≤90 days) and late (>90 days) complications. RESULTS: Postoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non-MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed. CONCLUSIONS: In the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post-RP incontinence and impotence.

Does 1.5 T mpMRI play a definite role in detection of clinically significant prostate cancer? Findings from a prospective study comparing blind 24-core saturation and targeted biopsies with a novel data remodeling model.

BACKGROUND: Multiparametric-magnetic resonance imaging (mpMRI) can accurately detect high-grade and larger prostate cancers (PC). AIMS: To evaluate the ability of 1.5 T magnetic field mpMRI-targeted Prostate Biopsies (PBx) in predicting PC in comparison with blind 24-core saturation PBx (sPBx). METHODS: We prospectively collected data from patients undergoing transrectal sPBx and, if needed, targeted PBx of suspected lesions based on the 16-'region-of-interest' (ROI) PI-RADS graph. Data remodeling: for each 'target' (each suspected lesion at mpMRI), we identified all the 16 'ROIs' into which the lesion extended: these single 'ROIs' were identified as 'macro-targets'. For each 'ROI' and 'macro-target', we compared the mpMRI result with that of a saturation and targeted biopsy (if performed). RESULTS: 1.5T mpMRI showed a PI-RADS value ≥ 3 in 101 patients (82.1%). We found a PC in 50 (40.6%). Negative-positive predictive values for mpMRI were 82-45%, respectively. Of the 22 patients with normal mpMRI, four had a PC, but none had a clinically significant cancer. After the data remodeling, we demonstrated the presence of PC in 228 'ROIs': (a) only in targeted biopsies in 15 'ROIs'/'macro-targets' (6.6%); (b) only in sPBx in 177 'ROIs' (77.6%); (c) in both targeted and sPBx in 36 'ROIs' (15.8%). DISCUSSION: 81.8% of patients with normal 1.5T mpMRI were negative at PBx. Performing only targeted PBx may lead to lack of PC diagnosis in about 50% of patients. CONCLUSIONS: In patients with suspected PC and a previous negative PBx, a normal mpMRI may exclude a clinically significant PC, avoiding sPBx.

Comparison of Pathological and Oncologic Outcomes of Favorable Risk Gleason Score 3 + 4 and Low Risk Gleason Score 6 Prostate Cancer: Considerations for Active Surveillance.

PURPOSE: Recent NCCN® (National Comprehensive Cancer Network®) Guidelines® show that patients with biopsy Gleason score 3 + 4/Grade Group 2 but otherwise favorable features are active surveillance candidates. However, little is known about the long-term outcomes compared to that in men in the low risk Gleason score 6/Grade Group 1 group. We sought to clarify the risk of adverse features and oncologic outcomes in surgically treated, favorable Grade Group 2 vs 1 cases. MATERIALS AND METHODS: We queried our prospectively maintained radical prostatectomy database for all 8,095 patients with biopsy Grade Group 1 or 2 prostate cancer who otherwise fulfilled the NCCN low risk definition of prostate specific antigen less than 10 ng/ml and cT2a or less, and who underwent radical prostatectomy from 1987 to 2014. Multivariable logistic regression and Kaplan-Meier methods were used to compare pathological and oncologic outcomes. RESULTS: Organ confined disease was present in 93.9% and 82.6% of Grade Group 1 and favorable intermediate risk Grade Group 2 cases while seminal vesicle invasion was noted in 1.7% and 4.7%, and nodal disease was noted in 0.3% and 1.8%, respectively (all p <0.0001). On multivariable logistic regression biopsy proven Grade Group 2 disease was associated with a threefold greater risk of nonorgan confined disease (OR 3.1, 95% CI 1.7-5.7, p <0.001). The incidence of late treatment (more than 90 days from surgery) in Grade Group 1 vs 2 was 3.1% vs 8.5% for hormonal therapy and 6.0% vs 12.2% for radiation (p <0.001). In the Grade Group 1 vs 2 cohorts the 10-year biochemical recurrence-free survival rate was 88.9% vs 81.2% and the 10-year systemic progression-free survival rate was 99% vs 96.5% (each p <0.001). CONCLUSIONS: Men at favorable risk with Grade Group 2 disease who are considering active surveillance should be informed of the risks of harboring adverse pathological features which impact secondary therapies and an increased risk of cancer progression.

Vaginal cuff recurrence after radical cystectomy: an under - studied site of bladder cancer relapse.

INTRODUCTION: Vaginal cuff recurrence of tumor following radical cystectomy is a rare site of disease recurrence, however it has never been specifically studied. The aim of the study is to evaluate incidence, risk factors, and long-term oncologic outcomes of vaginal cuff recurrence in a cohort of female patients treated with radical cystectomy for invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS: From 1985 to 2012, a prospectively maintained institutional bladder cancer registry was queried for vaginal cuff recurrence post radical cystectomy. Overall mortality and cancer-specific mortality were reported using the Kaplan-Meier method for patients with vaginal cuff recurrence, recurrence at another local or distant site, and those without evidence of recurrence. Comparisons were performed using the log-rank test. Cox proportional hazards regression model was performed to assess predictors of vaginal cuff recurrence. RESULTS: From 469 women treated with radical cystectomy for bladder cancer, 34 patients (7.3%) developed vaginal cuff recurrence, 130 patients (27.7%) had recurrence involving either a local or distant site, and 305 patients (65%) had no evidence of recurrence. The 5-year overall mortality-free survival rate was 32.4% for vaginal cuff recurrence, but 25.0% for other sites of recurrence. Cancer-specific mortality-free survival rate was 32.4% for vaginal cuff recurrence, and 30.3% for the other sites of recurrence. Multivariate Cox proportional hazards regression analysis demonstrated that the presence of tumor in posterior location at radical cystectomy (Hazard Ratio [HR], 0.353 [95% CI, 0.159-0.783]) and anterior vaginectomy, compared to no vaginectomy (HR, 2.595 [95% CI, 1.077-6.249]) were independently associated with vaginal cuff recurrence. CONCLUSION: Anterior vaginectomy, despite our best attempts, is perhaps not sufficient to prevent vaginal cuff recurrence. Therefore, follow-up evaluation is essential, and further studies are necessary to address the optimal approach for initial management. Patient Summary: Although vaginal cuff recurrence is an unusual site of recurrence, careful evaluation is needed before cystectomy and during follow-up to identify patients at risk.

Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: a multi-institutional study of 62 patients.

OBJECTIVES: To identify which patients with macroscopic bladder-infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC). MATERIALS AND METHODS: We evaluated 62 patients with cT4cN0-1 cM0 PCa treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan-Meier method and log-rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression-free, PCa-specific and overall survival. RESULTS: Of the 62 patients, 19 (30.6%) did not have clinical progression during follow-up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PCa and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis-free at last follow-up was 86 (1-314) months, 8/19 patients had a follow-up of >5 years, and five patients survived metastasis-free for >15 years. Patients without seminal vesicle invasion (SVI) had the best outcomes, with an estimated 10-year PCa-specific survival of 75% compared with 24% for patients with SVI. CONCLUSION: For cT4 PCa RC can be an appropriate treatment for local control and part of a multimodality-treatment approach. Although recurrences are probable, these do not necessarily translate into cancer-specific death. Men without SVI had a 75% 10-year PCa-specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.

Systematic review of surgical treatment of post radical prostatectomy stress urinary incontinence.

Context Stress urinary incontinence (SUI) after radical prostatectomy (RP) continues to be a significant problem with several implications including patient quality of life and other critical postoperative outcomes. Objectives To report the results in terms of efficacy (pad count, 24 hr pad test, QOL questionnaires) and safety (complication rate and type of complications) of all surgical devices approved for the treatment of SUI after RP. Evidence Acquisition A systematic review was conducted in accordance with the PRISMA Statement. A literature search was carried out through the PubMed/Medline, SCOPUS, and Web of Science databases using the keywords "incontinence," "radical prostatectomy," and "'treatment". Inclusion criteria were: number of patients higher than 30, mean follow up longer than 12 months and definition of a successful outcome as the use of 0 to 1 safety pads a day. Evidence Synthesis 113 papers underwent primary review. 51 papers met the inclusion criteria with a total sample size of 4022 patients. Efficacy (0-1 safety pads) was on average 65.7% for AUS, 48.2% for Invance Sling, 48.8% for Advance Sling, 64.2% for ProACT. Twenty four hour pad test and QOL questionnaires were respectively available only in 4 and 18 studies. The overall complication rate was 19.43% for AUS, 7.4% for Invance Sling, 12.3% for Advance Sling, 12.3% for ProACT. Authors' Conclusions Due to the poor overall quality of available studies, it was impossible to identify or refute clinically important differences between the alternative surgical procedures. Although our data seems to suggest that AUS has the highest efficacy in the treatment of SUI following RP it is also associated with the highest complication rate, but this may be due to the longest follow up. Larger rigorous trials are needed in order to support this evidence. Neurourol. Urodynam. 35:875-881, 2016. © 2015 Wiley Periodicals, Inc.

Early salvage radiation therapy post-prostatectomy: key considerations.

Post-prostatectomy radiotherapy (RT) is commonly employed to maximize oncologic outcomes in patients with pathologic adverse features (adjuvant RT]) or to treat men with prostate-specific antigen or local recurrence after initial observation (salvage RT [SRT]). Randomized controlled trials have been unable to compare adjuvant RT versus SRT; however, there is growing retrospective evidence that observation and early SRT (eSRT) may be a suitable. The issue of patient selection is crucial; several clinical tools and some newer biomarker-based tools might help in this process. Moreover, the optimal prostate-specific antigen threshold for eSRT, the RT dose, the irradiation field and the use of hormonal therapy are still open questions. In this article, we review the current literature on eSRT and provide some insights on what's happening for the future.

Open versus robotic-assisted partial nephrectomy: a multicenter comparison study of perioperative results and complications.

PURPOSE: To compare surgical results, morbidity and positive surgical margins rate of patients undergoing robotic partial nephrectomy (RPN) versus open partial nephrectomy (OPN). METHODS: This is an observational multicenter study promoted by the "Associazione GIovani Laparoscopisti Endoscopisti" (AGILE) no-Profit Foundation, which involved six Italian urologic centers. All clinical, surgical, and pathological variables of patients treated with OPN or RPN for renal tumors were gathered in a prospectively maintained database. Tumor nephrometry was measured with PADUA score, and complications were stratified with modified Clavien system. Differences between RPN and OPN group were assessed with univariate analysis. Perioperative variables independently associated with complications were assessed with multivariate analysis. RESULTS: A total of 198 and 105 patients were enrolled in OPN and RPN group, respectively. Both had similar demographics, indications to surgery, tumor nephrometry, renal function, WIT (18.7 vs. 18.2 min; p = NS), positive margin rate (5.6 vs. 5.7%; p = NS), intraoperative complications, and postoperative medical complications. Compared to OPN, RPN group was significantly more morbid (p = 0.04), included tumors with smaller size (p = 0.002), had longer operative time (p < 0.001), lower blood loss, surgical postoperative complications (5.7 vs. 21.2%, p < 0.001), Clavien 3-4 surgical complications (1 vs. 9.1%, p = 0.001), and shorter hospitalization. The surgical approach resulted independently correlated with surgical complications on multivariate analysis. CONCLUSION: In the present series, RPN was associated with a significant reduction of blood loss, surgical complications, including the reintervention rate for urinary fistula and postoperative bleeding, and with a shorter hospitalization.

Mechanical characterization of porcine ureter for the evaluation of tissue-engineering applications.

Introduction: Clinics increasingly require readily deployable tubular substitutes to restore the functionality of structures like ureters and blood vessels. Despite extensive exploration of various materials, both synthetic and biological, the optimal solution remains elusive. Drawing on abundant literature experiences, there is a pressing demand for a substitute that not only emulates native tissue by providing requisite signals and growth factors but also exhibits appropriate mechanical resilience and behaviour. Methods: This study aims to assess the potential of porcine ureters by characterizing their biomechanical properties in their native configuration through ring and membrane flexion tests. In order to assess the tissue morphology before and after mechanical tests and the eventual alteration of tissue microstructure that would be inserted in material constitutive description, histological staining was performed on samples. Corresponding computational analyses were performed to mimic the experimental campaign to identify the constitutive material parameters. Results: The absence of any damages to muscle and collagen fibres, which only compacted after mechanical tests, was demonstrated. The experimental tests (ring and membrane flexion tests) showed non-linearity for material and geometry and the viscoelastic behaviour of the native porcine ureter. Computational models were descriptive of the mechanical behaviour ureteral tissue, and the material model feasible. Discussion: This analysis will be useful for future comparison with decellularized tissue for the evaluation of the aggression of cell removal and its effect on microstructure. The computational model could lay the basis for a reliable tool for the prediction of solicitation in the case of tubular substitutions in subsequent simulations.

Efficacy and safety of antegrade sclerotherapy for varicocele in pediatric patients: A systematic review.

OBJECTIVES: Antegrade sclerotherapy (Tauber's) procedure has been extensively used for the minimally-invasive treatment of varicocele; however, the results in the pediatric population are less defined. This systematic review evaluates the efficacy and safety of antegrade sclerotherapy for varicocele in the pediatric population. EVIDENCE ACQUISITION: The review was conducted following the PRISMA guidelines. Systematic research of available literature in English language from 1980 until May 2022 was conducted through EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials. For each study, information was gathered regarding the study design, the inclusion/exclusion criteria, the indications for treatment, the success rate and the complications. When available, the details about sperm analysis were reported. EVIDENCE SYNTHESIS: The 10 studies were included in the final sample (564 patients). Median age of patients ranged 13.3-15.3 years. The indications for scleroembolization varied in the different studies, while most studies included patients with clinical G2-G3 varicocele and clinical symptoms or testicular asymmetry. The treatment was successful in 88%-98% of the patients, while the complication rate was <5%. CONCLUSION: Tauber's sclerotherapy is a safe and effective treatment for varicocele also in the pediatric population. Further studies with standardized inclusion criteria are needed to provide higher level of evidence and compare the outcomes of antegrade sclerotherapy with the other available techniques.

Role of targeted biopsy, perilesional biopsy, random biopsy, and their combination in the detection of clinically significant prostate cancer by mpMRI/transrectal ultrasonography fusion biopsy in confirmatory biopsy during active surveillance program.

BACKGROUND: Based on the findings of different trials in biopsy naïve patients, target biopsy (TB) plus random biopsy (RB) during mpMRI-guided transrectal ultrasound fusion biopsy (FB) are often also adopted for the biopsy performed during active surveillance (AS) programs. At the moment, a clear consensus on the extent and modalities of the procedure is lacking. OBJECTIVE: To evaluate the increase in diagnostic accuracy achieved by perilesional biopsy (PL) and different RB schemes during FB performed in AS protocol. DESIGN, SETTING, AND PARTICIPANTS: We collected prospectively the data of 112 consecutive patients with low- or very-low-risk prostate cancer; positive mpMRI underwent biopsy at a single academic institution in the context of an AS protocol. INTERVENTION(S): mpMRI/transrectal US FB with Hitachi RVS system with 3 TB and concurrent transrectal 24-core RB. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnostic yield of the different possible biopsy schemes (TB only; TB + 4 perilesional (PL) cores; TB + 12-core RB; TB + 24-core RB) was compared by the McNemar test. Univariable and multivariable regression analyses were adopted to identify predictors of any cancer, Gleason grade group (GGG) ≥2 cancers, and the presence of GGG≥2 cancers in the larger schemes only. RESULTS AND LIMITATIONS: The detection rate of GGG ≥2 cancers increased to 30%, 39%, and 49% by adding 4 PL cores, 14, and 24 RB cores, respectively, to TB cores (all p values <0.01). On the whole, TB alone, 14-core RB, and 24-core-RB identified 38%, 47%, and 56% of all the GGG ≥2 cancers. Such figures increased to 62% by adding to TB 4 PL cores, and to 80% by adding 14 RB cores. Most of the differences were observed in PI-RADS 4 lesions. CONCLUSIONS: We found that PL biopsy increased the detection rate of GGG ≥2 cancers as compared with TB alone. However, the combination of those cores missed a large percentage of the CS cancers identified with larger RB cores, including a 20% of CS cancers diagnosed only by the combination of TB plus 24-core RB.

Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.