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Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.

Background Female urethral stricture (FUS) represents a sporadic condition. There is a lack of data and standardized guidelines on diagnostics and therapeutics. Several surgical techniques have been described for FUS urethroplasty, among which the flap-based or graft-based ones are most reported. Buccal mucosa graft (BMG) represents the gold standard for male urethroplasty, and this can theoretically be applied also to FUS treatment. Objective To describe and present preliminary results of a novel minimally invasive technique for buccal mucosa dorsal graft (mini-dorsal BMG) urethroplasty for the treatment of FUS. Design, setting, and participants This is a retrospective study on buccal mucosa dorsal graft urethroplasty for the treatment of FUS. Surgical procedure Every patient was placed in lithotomic position. Two stiches were placed at 10 and 2 o’clock positions to facilitate the dorsal median urethrotomy. The margins of the incised dorsal urethra at the 12 o’clock position are then dissected from the periurethral tissue. This dissection results in an elliptical raw area between the edges of the urethra over the periurethral tissue. The harvested BMG was fixed with several quilting sutures, using 5-0 and 4-0 absorbable sutures, to cover the raw area. The margins of the graft were sutured to the edges of the incised urethra. Measurements A chart review was performed. Results and limitations Thirteen patients underwent the mini-dorsal-BMG technique. The median preoperative uroflow was 5.6 (3–13) ml/s, and the median postoperative value was 23.4 (14–58) ml/s. Conclusions The mini-dorsal-BMG technique for the treatment of FUS gives good results with low complication rates. Other series and long-term follow-up are necessary to confirm the reproducibility of this technique. Patient summary We present the technical aspects and the promising preliminary results of a novel surgical technique for the treatment of female urethral stricture by using the buccal mucosa to correct this invalidating disease.

To report stoma stenosis rates and efferent channel (EC) complications at long term follow-up for Turin pouch (TP). This is a retrospective analysis of the prospectively maintained database of patients who underwent TP between March 2006 and May 2018. The TP is a U-shaped right colon pouch. The EC was conceived by the tubularization of 5 cm of the colon wall with the use of a stapler and sutured to the skin (EC-cutaneostomy). The ureters are sutured separately to the last 10 cm of ileum before the ileocecal valve. In literature, catheterization problems have been described on average in 20.3% of patients and stoma stenosis in 19.5% of the patients with flap valve systems. Thirty-eight consecutive patients underwent a TP procedure. The median age was 55 years (IQR: 52–60). Median operative time was 201 min (IQR: 170–210), median reconstructive time was 61 min (IQR: 55–65) and the blood loss was 244 ml (IQR: 150–300) and 4 patients (10.5%) needed blood transfusions. The median follow-up was 52 months (IQR: 37–92). Complete 24h continence was achieved in 34 (89%) patients. Seven (18.4%) patients reported difficulties in EC catheterization and 4 (10.5%) patients had stoma stenosis. This study is limited by the relatively small number of patients. In relation to similar systems, the TP seems to offer comparatively good functional results but EC and stoma complications were lower than other pouch variants in literature.

INTRODUCTION AND OBJECTIVE:Multiparametric MRI is nowadays paramount for prostate cancer (PCa) diagnosis and local staging. When choosing between focal or radical treatment, however, MRI accuracy i...

INTRODUCTION AND OBJECTIVE:According to the literature, PIRADS 3 lesions are associated with prostate cancer (PCa) in 30 to 50% of cases. Our aim was to assess the cancer detection rate (CDR) of el...

INTRODUCTION AND OBJECTIVE:We evaluated the accuracy of elastic fusion biopsy in different European Centers using a standardized approach with the Koelis system. Our aim was to assess the added val...

Recently, Computer Aided Diagnosis (CAD) systems have been proposed to help radiologists in detecting and characterizing Prostate Cancer (PCa). However, few studies evaluated the performances of these systems in a clinical setting, especially when used by non-experienced readers. The main aim of this study is to assess the diagnostic performance of non-experienced readers when reporting assisted by the likelihood map generated by a CAD system, and to compare the results with the unassisted interpretation. Three resident radiologists were asked to review multiparametric-MRI of patients with and without PCa, both unassisted and assisted by a CAD system. In both reading sessions, residents recorded all positive cases, and sensitivity, specificity, negative and positive predictive values were computed and compared. The dataset comprised 90 patients (45 with at least one clinically significant biopsy-confirmed PCa). Sensitivity significantly increased in the CAD assisted mode for patients with at least one clinically significant lesion (GS > 6) (68.7% vs. 78.1%, p = 0.018). Overall specificity was not statistically different between unassisted and assisted sessions (94.8% vs. 89.6, p = 0.072). The use of the CAD system significantly increases the per-patient sensitivity of inexperienced readers in the detection of clinically significant PCa, without negatively affecting specificity, while significantly reducing overall reporting time.

Background The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care.

INTRODUCTION AND OBJECTIVES:In a large multicenter series, we assessed the impact of performing a standard systematic sampling of the prostate in addition to mpMRI-targeted biopsies, in terms of pr...

INTRODUCTION AND OBJECTIVES:Recent studies have evaluated the possible role of MRI in first set biopsy, however only few nomograms include fusion biopsies to predict prostate cancer. The aim of our...

International audience; OBJECTIVE:To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens.MATERIALS AND METHODS:Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation® and Trinity®) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies.RESULTS:Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p

Aims To present the long term-results and complications of a large series of stapled ileal orthotopic neobladders. Materials and methods From 1992 to 2012 we performed 606 radical cystectomies with stapled orthotopic neobladder substitution in male patients. The median patient age was 65 years (interquartile range [IQR]: 58–71). Results Median operative time was 205 min (IQR: 180–225). The overall survival rates at 5, 10, 15, and 20 yr were 68% (336 of 494), 55% (207 of 376), 38% (98 of 259), and 23% (14 of 62), respectively, and the disease specific survival rates were 75% (371 of 494), 59% (222 of 376), 50% (130 of 259), and 35% (22 of 62), respectively. After a median follow-up of 81 months (IQR: 30–144), a total of 147 early (less than 90 days) complications (38 diversion related, 109 diversion unrelated) occurred in 144 patients (24%); 163 late complications (141 diversion related, 22 diversion unrelated) affected 141 patients (23%). At 60 months, daytime and nighttime continence was complete in 96% and 72% of cases, respectively. Urodynamic studies showed that maximum capacity, residual volume, maximum flow rate, pressure at maximum capacity, and maximum outlet closure pressure were not statistically different at 12 and 60 months postoperatively. Conclusions The use of a stapler when performing orthotopic neobladders significantly reduces the operating time, and offers good functional results with acceptable complication rates. Our results could encourage the use of a stapler when performing an ileal neobladder during laparoscopic and robotic radical cystectomies.

International audience; OBJECTIVES:To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice.METHODS:We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables.RESULTS:The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer.CONCLUSIONS:Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate.

Objective To demonstrate the oncologic and functional results of seminal-sparing cystectomy (SSC) in patients with bladder cancer (BC) and to describe the evolution of our surgical technique over a 20-year period. Methods From 1990 to 2009 we performed SSC in 88 patients with non–muscle-invasive BC and in 10 patients with muscle-invasive BC away from the bladder neck. Sixty-one of the 98 patients (1990-2002) underwent cystoadenomectomy with ileocapsuloplasty (ICP), consisting of the anastomosis between the Camey II ileal reservoir and the upper edge of the prostatic capsule. This technique was affected by a relevant percentage of anastomotic stricture (11%). From 2003 to 2009, we performed the endocapsular ileourethral anastomosis (EIUA) in 30 patients, on the basis of the direct anastomosis between the ileal reservoir and the urethral stump inside the prostatic apex. Seven patients were lost to follow-up. Results After a mean follow-up of 102 months, 81 patients (89%) were alive, and 10 patients (11%) had died (8 of disease progression). Early and late complication rates were 25% and 24%, respectively. Complete daytime continence was obtained in 87 patients (95.6%), and nighttime continence was achieved in 34 patients (37%). In the ICP group, stricture of the prostatic fossa affected 7 patients (11%), whereas no neobladder-urethral anastomosis stricture was noticed in the EIUA group. Normal erectile function was preserved in 87 patients (95.6%). Conclusion SSC offers good oncologic and functional results in carefully selected patients. EIUA represents an evolution from ICP because EIUA reduces the risk of stenosis.

To compare the performance of experienced readers in detecting prostate cancer (PCa) using likelihood maps generated by a CAD system with that of unassisted interpretation of multiparametric magnetic resonance imaging (mp-MRI). Three experienced radiologists reviewed mp-MRI prostate cases twice. First, readers observed CAD marks on a likelihood map and classified as positive those suspicious for cancer. After 6 weeks, radiologists interpreted mp-MRI examinations unassisted, using their favourite protocol. Sensitivity, specificity, reading time and interobserver variability were compared for the two reading paradigms. The dataset comprised 89 subjects of whom 35 with at least one significant PCa. Sensitivity was 80.9% (95% CI 72.1–88.0%) and 87.6% (95% CI 79.8–93.2; p = 0.105) for unassisted and CAD paradigm respectively. Sensitivity was higher with CAD for lesions with GS > 6 (91.3% vs 81.2%; p = 0.046) or diameter ≥10 mm (95.0% vs 80.0%; p = 0.006). Specificity was not affected by CAD. The average reading time with CAD was significantly lower (220 s vs 60 s; p < 0.001). Experienced readers using likelihood maps generated by a CAD scheme can detect more patients with ≥10 mm PCa lesions than unassisted MRI interpretation; overall reporting time is shorter. To gain more insight into CAD–human interaction, different reading paradigms should be investigated. • With CAD, sensitivity increases in patients with prostate tumours ≥10 mm and/or GS > 6. • CAD significantly reduces reporting time of multiparametric MRI. • When using CAD, a marginal increase of inter-reader agreement was observed.

Clinicopathologic parameters of the anterior index tumor and other tumor foci were assessed and compared to non-APC in the same cohort. Previous biopsy information was correlated with RP. RESULTS: Of the 467 patients in this cohort, 72 (15%) had APC: 50 in the anterior peripheral zone (APZ, 69%); 10 in the transitional zone (TZ, 14%); and 12 involving both the APZ and TZ (17%). 25 APC were single tumors (35%), and the rest were multifocal. Clinicopathologic information was available for 72 APC patients and 308 non-APC patients and is compared in Table 1. 15% of APC patients demonstrated a primary Gleason pattern 4 or higher, and 21% had extraprostatic extension (EPE) present. None of the APC, including the high-grade (GS>7) cases, demonstrated seminal vesicle invasion (SVI). 10 APC had a positive surgical margin (13%), most commonly at the apex or base. 56 APCwere preceded by an extended biopsy (78%), while 2 APC had only sextant biopsy (3%) and 14 APC were identified after a combination of extended and perineal saturation biopsies (19%). APC was present on significantly fewer cores and with less tumor involvement of the core. APC patients frequently (54%) had a higher GS or novel Gleason pattern 5 at RP than at biopsy. Distribution of preoperative serum PSA levels was similar between APC and non-APC patients. CONCLUSIONS: APC demonstrate distinct clinicopathologic features (including absence of SVI) and are frequently under-graded and minimally sampled at the time of biopsy. These unique characteristics may have a clinical impact on detection (i.e., need for saturation biopsy) and suitability for inclusion in active surveillance protocols. Future longterm studies are needed to determine the outcome of patients with APC.

Aim: To evaluate the use of cyanoacrylic glue to fix the kidney in laparoscopic nephropexy for symptomatic nephroptosis. Patients and Methods: From 1998 to 2006 w

Purpose: We conducted a randomized study to evaluate the effect of tamsulosin in improving symptoms and quality of life (QoL) in patients with indwelling double-pigtail ureteral stents, using both generic and specific questionnaires. Materials and Methods: We prospectively enrolled 75 patients (29 men, 46 women; mean age, 42.3 years), who underwent ureteral stent positioning and were assigned to one of two study groups. In group A (n = 38), patients were discharged with a prescription for tamsulosin, 0.4 mg once daily. In group B (n = 37), patients received no α1-blocker (control group). Results: One week after stent placement (visit week 1 [W1]), analysis of the ureteral stent symptoms questionnaire showed a significant worsening of urinary symptoms (13.1 v 26.4, P = 0.008) and pain (4.1 v 21.6, P = 0.002) in patients not receiving tamsulosin. There was also a significant difference in the mean visual analog score (VAS) of health scale between the two groups (P < 0.001) compared with the result obtained at the W4 evaluation (visit). The proportion of patients reporting level 2 or 3 for the pain/discomfort domain in the QoL questionnaire from W4 to W1 varied between the two groups in a highly statistically significant manner (P = 0.006). Conclusions: Our findings indicate that administration of tamsulosin has a positive effect on stent-related urinary symptoms and QoL. Further clinical research in this area is warranted to better define the role of α1-blockers in current clinical practice. © 2008 Mary Ann Liebert, Inc.

INTRODUCTION AND OBJECTIVES: To compare the predictive ability of standard Gleason Score (GS) to a modified one, summing up primary Gleason and the worst score found at the pathologic examination following radical prostatectomy. METHODS: We selected 3490 patients eligible for the study from our database of 3538 radical prostatectomysed cases, collected in the EUREKA-1 multicentric retrospective study on prostate cancer, part of the CHIC European project. We compared the predictive power of standard GS, made up of primary plus second most frequent score at the final pathologic exam after radical prostatectomy, to a simpler one, summing up primary Gleason and the worst score found in the sample (if primary and worst score are the same you have simply to double the score value). The event evaluated was biochemical relapse. Data were analysed with Cox proportional hazard regression model for survival analysis and related Concordance Index (CI). The subgroup of 2707 patients with a follow-up (FU) longer than 30 months was further studied through ROC Area Under the Curve (AUC) analysis. RESULTS: Primary plus worst GS performs slightly better than primary plus secondary GS (CI 1⁄4 0.6587 versus CI 1⁄4 0.6475). In addition, with modified GS it’s possible to split patients into four instead of three risk categories with statistical significance (GS 6, 7, 8 and 9-10 versus 6, 7 and 8-9-10 all together because of a P respectively < 0.001 versus P 1⁄4 0.45 comparing GS 8 and GS 9-10 groups) (Figures 1 and 2). This finding is confirmed by the sub-analysis of patients with a FU longer than 30 months showing a higher ROC AUC of 0.6636 for modified GS versus 0.6523 for the standard one (P 0.0114). CONCLUSIONS: A GS summing up the most frequent score and the worst one performs slightly better than the traditional GS in a huge retrospective cohort of patients. Besides, this modified GS has the advantage of being simpler and quicker during the pathologist’s routine (e.g. no need to report a tertiary higher grade GS), increasing the reliability of pathology reports. SourceofFunding:EuropeanUnionprojectCHIC,Computational Horizons In Cancer, grant agreement number 600841.

Aims To report feasibility, safety and effectiveness of “zero-ischemia” laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. Methods We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Results Mean patients age was 68 years (range 56–74), mean tumor size was 3.5 cm (range 2.2–6.3 cm). STE was successfully completed in 16 patients 12–15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a “zero-ischemia” approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5–22). Mean operative time was 123 min (range 115–130) and mean intraoperative blood loss was 250 mL (range 20–450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. Conclusions STE is a viable option to perform “zero-ischemia” LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases.

Objective To evaluate the functional results of a new cutaneous continent reservoir, the Turin pouch (TP), consisting of an ileocolonic pouch with an innovative efferent channel (EC). Methods Since 2006, we have performed the TP on 14 patients in whom the appendix was absent. The distal ileum (10 cm) and right colon (40 cm) were isolated. The cecum and right colon were folded to obtain a U-shaped pouch through a stapler detubularization. An artificial EC was created by separating with a stapler a 5-cm tubularized flap of colonic wall and anastomosing this to the umbilicus. Results After a mean follow-up of 45 months (range, 12-72 months), 13 patients were alive and 1 died of bladder cancer progression. Early and late complications occurred in 3 and 4 patients, respectively. Daytime continence was 100% and nighttime continence was 93%. No patient has reported stenosis or difficulties in catheterization. Urodynamic studies (12 months postoperatively) showed a mean maximal pouch capacity of 520 mL (range, 360-720 mL), mean end-filling pressure of 23 cm H 2 O (range, 18-30 cm H 2 O), and mean EC closing pressure of 65 cm H 2 O (range, 52-75 cm H 2 O). Conclusion The TP offers good functional results and could be applied in patients undergoing continent, heterotopic, urinary diversion.

Anterior sacral meningocele (ASM) is a rare congenital disorder involving herniation of the dural sac through a defect in the anterior surface of the sacrum. We report the case of a young patient with an enormous ASM that simulated bladder retention in terms of symptoms as well as on physical examination and at ultrasonography. After introducing a catheter that excluded urinary retention, computed tomography (CT) scan and magnetic resonance imaging (MRI) showed the ASM. The patient underwent surgical repair of the ASM through a sacral laminectomy and recovered normal lower urinary tract function.