Variability of mpMRI diagnostic performance according to the upfront individual patient risk of having clinically significant prostate cancer.

BACKGROUND: To assess the variation of multiparametric magnetic resonance imaging (mpMRI) positive predictive value (PPV) according to each patient's risk of clinically significant prostate cancer (csPCa) based exclusively on clinical factors. METHODS: We evaluated 999 patients with positive mpMRI (PI-RADS ≥ 3) receiving targeted (TBx) plus systematic prostate biopsy. We built a multivariable logistic regression analysis (MVA) using clinical risk factors to calculate the individual patients' risk of harboring csPCa at TBx. A second MVA tested the association between individual patients' clinical risk and mpMRI PPV accounting for the PI-RADS score. Finally, we plotted the PPV of each PI-RADS score by the individual patient pretest probability of csPCa using a LOWESS approach. RESULTS: Overall, TBx found csPCa in 21%, 51%, and 80% of patients with PI-RADS 3, 4, and 5 lesions, respectively. At MVA, age, PSA, digital rectal examination (DRE), and prostate volume were significantly associated with the risk of csPCa at biopsy. DRE yielded the highest odds ratio (OR: 2.88; p < 0.001). The individual patient's clinical risk was significantly associated with mpMRI PPV (OR: 2.49; p < 0.001) using MVA. Plotting the mpMRI PPV according to the predicted clinical risks, we observed that for patients with clinical risk close to 0 versus patients with risk higher than 90%, the mpMRI PPV of PI-RADS 3, 4, and 5 ranged from 0% to 75%, from 0% to 96%, and from 45% to 100%, respectively. CONCLUSION: mpMRI PPV varies according to the individual pretest patient's risk based on clinical factors. These findings should be considered in the decision-making process for patients with suspect MRI findings referred for a prostate biopsy. Moreover, our data support the need for further studies to create an individualized risk prediction tool.

Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.

INTRODUCTION: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. MATERIALS & METHODS: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. RESULTS: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. CONCLUSIONS: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

Surgical outcomes of novel retroperitoneal low anterior vs posterior and transperitoneal access in single-port partial nephrectomy.

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.

Single-Port Transvesical Vesico-Vaginal Fistula Repair: An Initial Experience.

INTRODUCTION: Vesicovaginal fistula (VVF) is the most common urogenital fistula due to iatrogenic cause, primarily associated with gynecologic surgery (1). Although both conservative and surgical management may be considered, the optimal treatment is still uncertain and several studies were published using different techniques (open, laparoscopic or robotic) and approaches (extravesical, transvesical or transvaginal) (2-5). In this context, we aim to report our initial experience repairing VVF with Single-Port (SP) Transvesical (TV) access. MATERIALS AND METHODS: Four patients with a diagnosis of VVF underwent SP-TV VVF repair between May 2022 and December 2023. Diagnosis was confirmed by cystoscopy, cystogram and in two cases by CT Urogram. Under general anesthesia, before robotic time, patients were placed in lithotomy position and a preliminary cystoscopy was performed. Fistula was noted and a 5fr stent was placed through the fistulous tract. Two ureteral stents were placed. Then, with patient supine, a transverse suprapubic 3cm incision and 2cm cystotomy were made for SP access. First step was to mark and remove fistula tract to the vagina. The edges of the vagina and bladder were dissected in order to have a closure free of tension and to create three different layers to close: vagina, muscularis layer of the bladder and mucosal layer of the bladder. A bladder catheter was placed, and the two ureteral stents were removed at the end of procedure. RESULTS: Mean age was 53 years old and three out of 4 patients developed VVF after gynecologic surgery. Two patients underwent VVF repair 6 and 8 months after total hysterectomy. One patient developed VVF after total hysterectomy and oophorectomy followed by radiation therapy. Last patient developed VVF after previous urological procedure. Fistula diameter was between 11 and 15mm. Operative time was 211 min, including preliminary cystoscopy, stents placement and SP-access. All patients were discharged on the same day with a bladder catheter, successfully removed between post-operative day 14-18 after negative cystogram. Only in one case a ureteral stent was left because the fistula was closed to the ureteral orifice and we reported one case of UTI twelve days after surgery, treated with outpatient antibiotics. Mean follow-up was 8 months, patients were scheduled for regular follow-up visits and no recurrence was reported. All patients have at least 3 months of post-operative follow-up. CONCLUSIONS: Our experience suggests that SP Transvesical VVF repair may be considered as a safe and feasible minimally invasive treatment for small/medium fistulae (10-15mm).

Impact of prostate MRI central review over the diagnostic performance of MRI-targeted biopsy: should we routinely ask for an expert second opinion?

PURPOSE: There is substantial variability in multiparametric MRI (mpMRI) protocols and inter-readers' agreement. We tested the effect of a central mpMRI review on the detection of clinically significant PCa (csPCa) in a tertiary referral center. METHODS: We retrospectively analyzed a cohort of 364 consecutive men with a positive externally performed mpMRI (PI-RADS ≥ 3) who underwent a targeted biopsy (TBx) plus a systematic biopsy at a single tertiary referral center (2018-2020). Of those mpMRIs, 32% (n = 116) were centrally reviewed. We compared the detection of csPCa between the non-central-reviewed vs reviewed group. Multivariable logistic regression models (MVA) tested the relationship between mpMRI central review and the detection of csPCa at TBx. RESULTS: The detection of csPCa at TBx in non-central-reviewed vs central-reviewed group was 41 vs 63%, respectively (p = 0.001). The distribution of PI-RADS 2, 3, 4, and 5 at initial assessment vs after mpMRI central review was 0, 37, 47, and 16% vs 39, 9, 35, and 16%, respectively (p < 0.004). Of 43 patients with initial PI-RADS 3 score, respectively 67, 21, and 12, and 0% had a revised PI-RADS score of ≤ 2, 3, 4, and 5. At MVA, mpMRI central review (OR: 1.65, CI 0.85-0.98) was significantly associated with higher csPCa detection at TBx. CONCLUSIONS: We demonstrated that a central review of external mpMRIs may decrease the overcall of equivocal lesions, namely PI-RADS 3, and should be considered to maximize the clinical benefit of TBx in terms of increasing the detection of csPCa and eventually decreasing the rate of unnecessary biopsies.

Single Port Radical Prostatectomy as a Viable Option for Highly Complex Patients: A Single Center Experience.

OBJECTIVE: To explore the safety and feasibility of the Da Vinci single-port (SP) platform in robotic-assisted radical prostatectomy (SP-RARP), aiming to provide a viable option for patients with surgical and medical complexities that might otherwise limit their access to common minimally invasive technique. METHODS: Data from 60 medically and surgically highly complex patients undergoing SP-RARP between December 2018 and December 2023 were analyzed. Variables included patient characteristics, surgical history, intraoperative and postoperative outcomes. Statistical analysis was conducted using Stata 17.0. RESULTS: Fifty-three percent of cases had a hostile abdomen (HA) (≥1 major abdominal surgery), and 47% were medically highly complex (American Society of Anesthesiologists score ≥3, Charlson Comorbidity Index ≥5, and a body mass index ≥30). The extraperitoneal approach was used in 56% of HA cases and 68% of MHC cases. Intraoperative complications occurred in 12%, exclusively with the transperitoneal approach in HA cases. Postoperative complications (Clavien-Dindo ≥3) were 6% and 14%, respectively, with no significant difference between approaches. Same-day discharge was possible in 44% of HA cases and 54% of MHC cases, with significant statistical differences favoring the extraperitoneal approach in both groups. CONCLUSION: SP-RARP, particularly the extraperitoneal approach, is a viable option for highly complex and challenging cases, providing acceptable oncological and functional outcomes. Prospective studies are crucial for further validating the safety and feasibility of SP-RARP in this patient population.

Learning Curve for Single-port Robot-assisted Urological Surgery: Single-center Experience and Implications for Adoption.

BACKGROUND AND OBJECTIVE: Understanding the learning curve for the da Vinci single-port (SP) surgical robot is crucial for adoption, training, and enhancement of surgical safety and efficiency. Our aim was to assess the impact of both overall experience (O-EXP) and procedure-specific experience (PS-EXP) on perioperative outcomes across various SP surgeries. METHODS: We analyzed data for 387 consecutive SP surgeries conducted by a high-volume surgeon from December 2018 to July 2023. These included SP robot-assisted radical prostatectomy (SP-RARP), robot-assisted simple prostatectomy (SP-RASP), and robot-assisted nephrectomy (SP-RANP). We used multivariable logistic regression to evaluate the relationship between surgeon experience and outcomes, and locally weighted scatterplot smoothing analysis to graphically explore the risk of postoperative complications according to O-EXP. KEY FINDINGS AND LIMITATIONS: The 387 SP procedures assessed included 172 (44%) SP-RARP, 53 (14%) SP-RASP, and 162 (42%) SP-RANP cases. Overall, 17% of patients had a complication of any grade, 6% experienced severe complications (Clavien-Dindo grade ≥3), and 8% required readmission. Both O-EXP and PS-EXP were associated with a lower risk of complications. The odds ratios for the incidence of complications per increment of 10 procedures were 0.83 (95% confidence interval [CI] 0.76-0.89) for PS-EXP and 0.93 (95% CI 0.90-0.96) for O-EXP. PS-EXP was also associated with a shorter operative time (ß = -3.9, 95% CI -4.9 to -2.9). The risk of complications reached a minimum at 30 SP-RASP, 70 SP-RANP, and 150 SP-RARP cases. Our study is limited by its retrospective design, single-surgeon experience, and lack of functional outcome assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Robot-assisted surgery with the da Vinci SP robot has a distinctive learning curve that is influenced by the platform and procedure-specific characteristics. For surgeons new to SP surgery, RASP and renal procedures had the earliest learning curve success and should be approached first, with RARP attempted only when the surgeon has become accustomed to the SP platform. PATIENT SUMMARY: We investigated the learning curve for a surgical robot that uses just one keyhole incision. We found that the time to reach proficiency for urological surgeries with this specific robot, measured as the rate of complications, is faster for some procedures than for more complex operations. This information can help in improving surgeon training and patient safety.

Mitomycin C vs. Bacillus Calmette-Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients-A comparative analysis from a single center.

BACKGROUND: Induction followed by 1 year maintenance instillation of intravesical Bacillus Calmette-Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. METHODS: We retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan-Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. RESULTS: Optimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. CONCLUSIONS: Optimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Extraperitoneal Single Port vs Transperitoneal Multiport Robot assisted radical prostatectomy in frail patients: A propensity score matched comparative analysis.

PURPOSE: The rise of frail patients in the worldwide population poses a challenge in the prostate cancer surgical care. In this light, we aimed to compare perioperative and early surgical outcomes of Extraperitoneal Single Port (SP)- vs Transperitoneal Multiport (MP) - Robot Assisted Radical Prostatectomy (RALP) in different frailty settings. MATERIALS AND METHODS: Clinical and surgical data of all consecutive patients treated with RALP between March 2014 and October 2023 were gathered. Propensity score matching was performed to adjust for potential baseline pre-operative confounders. The 5-miFI score was calculated for each patient and then five risk categories were identified (5-mFI score = 0, 1,2,3 and ≥ 4). RESULTS: A total of 549 patients were assessed in the unmatched analysis. After the propensity score, 126 patients for each treatment group were matched. When stratified in different frailty-groups, 30-days postoperative complications occurred significantly more frequently in case of 5-mFI score=3 and >4 (p = 0.001). Moreover, higher rate of both overall (52 vs 23 %, p = 0.01) and major (19.6 vs 8.2 %, p = 0.02) postoperative complications was found in these patients in case of transperitoneal MP RARP as compared to the extraperitoneal SP procedures. Exploring predictors of postoperative early complications in patients with 5-mFI score = 3 and 4, extraperitoneal SP robotic approach showed a significant protective role on both overall (OR 0.21, p = 0.001) and major (OR 0.33, p = 0.001) complications occurrence. CONCLUSIONS: In a matched cohort of patients treated with Robot Assisted Radical Prostatectomy, extraperitoneal Single Port approach significantly reduced the overall and major early complications rate in frail patients.

Versatility of Single Port Retroperitoneal Low Anterior Access: Early Outcomes in Multiple Procedures.

Purpose: This study aimed to assess early outcomes of the single port (SP) robotic low anterior access (LAA) for all upper urinary tract surgeries. In addition, it aimed to explore the impact of clinical factors, notably Body Mass Index (BMI), on post-operative outcomes and length of hospital stay. Materials and Methods: Overall, 76 consecutive patients underwent SP robotic surgery with LAA involving all upper urinary tract pathologies, with data collected prospectively. Baseline characteristics, intra- and post-operative outcomes, pain levels, and opioid use were analyzed. Statistical methods, including logistic regression and locally weighted scatterplot smoothing analysis, were used to assess same-day discharge (SDD) predictors and the association between BMI and SDD probability. According to the Institutional Review Board (IRB) protocol, only data recorded in our electronic medical record system was included. Results: Ten different procedures were performed with LAA, with no need for conversion to open surgery and complication rates in line with the literature (30 days: 5%, 90 days: 6.6%). Notably, 77.6% of patients were discharged on the same day. A significant association was found between BMI and prolonged hospital stay, particularly in obese patients (BMI ≥30 kg/m2). Post-operative pain was generally low (median VAS: 4), with over 70% discharged without opioid prescriptions. Conclusions: The novel LAA is a versatile approach for various upper urinary tract surgeries, including in obese patients. While achieving satisfactory post-operative outcomes, increased BMI correlated with a reduced likelihood of SDD. Further studies, including larger cohorts and multicenter collaborations, are warranted to explore anesthesiologic management and validate these findings.

Pelvic Lymph Node Dissection: A Comparison Among Extraperitoneal Single-port and Transperitoneal Multiport Radical Prostatectomy-A Single-center Experience.

Background and objective: The role of pelvic lymph node dissection (PLND) for prostate cancer is still controversial. This study aims to compare the outcomes of PLND between extraperitoneal single-port (SP eRARP) and transperitoneal multiport (MP tRARP) robotic-assisted radical prostatectomy. Methods: This was a retrospective analysis from our single-center database for patients who underwent SP eRARP or MP tRARP with PLND between 2015 and 2023. The primary endpoint was to analyze and compare specific data related to PLND between the two populations by the detection of pN+ patients, the total number of lymph nodes removed, and the number of positive lymph nodes removed. The secondary endpoints included comparing major complications, lymphoceles, and biochemical recurrence between the two cohorts of the study. Key findings and limitations: A total of 293 patients were included, with 85 (29%) undergoing SP eRARP and 208 (71%) undergoing MP tRARP. SP eRARP showed significant differences in PLND extension from MP tRARP, while MP tRARP yielded more lymph nodes (p < 0.001). There were no differences in pN+ patient detection (p = 0.7) or the number of positive lymph nodes retrieved (p = 0.6). The rates of major complications (p = 0.6), lymphoceles (p = 0.2), and biochemical recurrence (p = 0.9) were similar between the two groups. Additionally, SP eRARP had shorter operative time (p = 0.045), hospital stay (p < 0.001), and less postoperative pain at discharge (p = 0.03). Limitations include a retrospective, single-center analysis. Conclusions and clinical implications: Despite the SP approach in RARP resulting in fewer retrieved lymph nodes, outcomes were comparable with the MP approach regarding the detection of patients with positive lymph nodes and the number of positive nodes. Additionally, the SP approach led to lower pain levels and shorter hospital stays. Patient summary: With this study, we demonstrate that pelvic lymph node dissection performed via the extraperitoneal approach during robotic-assisted radical prostatectomy with a single-port system provides comparable outcomes with the standard transperitoneal multiport approach in detecting patients with positive lymph nodes and retrieving positive nodes. In addition, it offers significantly reduced pain levels and shorter hospital stays.

Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during robot-assisted radical prostatectomy: a systematic review and meta-analysis of comparative studies.

BACKGROUND: To compare surgical, pathological, and functional outcomes of patients undergoing NeuroSAFE-guided RARP vs. RARP alone. METHODS: In February 2024, a literature search and assessment was conducted through PubMed®, Scopus®, and Web of Science™, to retrieve data of men with PCa (P) undergoing RARP with NeuroSAFE (I) versus RARP without NeuroSAFE (C) to evaluate surgical, pathological, oncological, and functional outcomes (O), across retrospective and/or prospective comparative studies (Studies). Surgical (operative time [OT], number of nerve-sparing [NS] RARP, number of secondary resections after NeuroSAFE), pathological (PSM), oncological (biochemical recurrence [BCR]), and functional (postoperative continence and sexual function recovery) outcomes were analyzed, using weighted mean difference (WMD) for continuous variables and odd ratio (OR) for dichotomous variables. RESULTS: Overall, seven studies met the inclusion criteria (one randomized clinical trial, one prospective non-randomized trial and five retrospective studies) and were eligible for SR and MA. A total of 4,207 patients were included in the MA, with 2247 patients (53%) undergoing RARP with the addition of NeuroSAFE, and 1 960 (47%) receiving RARP alone. The addition of NeuroSAFE enhanced the likelihood of receiving a nerve-sparing (NS) RARP (OR 5.49, 95% CI 2.48-12.12, I2 = 72%). In the NeuroSAFE cohort, a statistically significant reduction in the likelihood of PSM at final pathology (OR 0.55, 95% CI 0.39-0.79, I2 = 73%) was observed. Similarly, a reduced likelihood of BCR favoring the NeuroSAFE was obtained (OR 0.47, 95% CI 0.35-0.62, I2 = 0%). At 12-month postoperatively, NeuroSAFE led to a significantly higher likelihood of being pad-free (OR 2.01, 95% CI 1.25-3.25, I2 = 0%), and of erectile function recovery (OR 3.50, 95% CI 2.34-5.23, I2 = 0%). CONCLUSION: Available evidence suggests that NeuroSAFE might represent a histologically based approach to NVB preservation, broadening the indications of NS RARP, reducing the likelihood of PSM and subsequent BCR. In addition, it might translate into better functional postoperative outcomes. However, the current body of evidence is mostly derived from non-randomized studies with a high risk of bias.

The Impact of Second Opinion Expert Pathology Review in Patient Management at the Time of Transurethral Resection of the Bladder.

BACKGROUND AND OBJECTIVE: Pathological features in non-muscle-invasive bladder cancer specimens are pivotal in determining correct patients' therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. METHODS: The study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. KEY FINDINGS AND LIMITATIONS: Among 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. CONCLUSIONS AND CLINICAL IMPLICATIONS: The second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. PATIENT SUMMARY: We investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.

En Bloc Versus Conventional Transurethral Resection of Bladder Tumors: A Systematic Review and Meta-analysis of Oncological, Histopathological, and Surgical Outcomes.

BACKGROUND AND OBJECTIVE: En bloc resection of bladder tumor (ERBT) has been introduced to enhance the quality of resection of bladder cancer. This review aims to compare the perioperative and oncological outcomes of ERBT and conventional transurethral resection of bladder tumor (cTURBT). METHODS: A literature search was conducted using the PubMed/Medline, Embase, and Web of Science databases to identify randomized controlled trials published until May 2024. The primary outcomes were the risk of recurrence and progression. The secondary outcomes were detrusor muscle (DM) presence, muscularis mucosae (MM) detectability, bladder perforation and obturator nerve reflex rates, operative time, length of catheterization and hospitalization, and residual tumor at repeat transurethral resection of bladder tumor (reTURBT). KEY FINDINGS AND LIMITATIONS: Seventeen studies met our inclusion criteria. No statistically significant difference was observed in 12-mo recurrence (risk ratio [RR] 0.81, 95% confidence interval [CI]: 0.65-1.02; p = 0.08), 24-mo recurrence (RR 1.02, 95% CI: 0.85-1.22; p = 0.8), and 12-mo progression (RR 0.68, 95% CI: 0.05-10.14; p = 0.8) rates. ERBT was significantly associated with a higher DM presence (RR 1.10, 95% CI: 1.01-1.20; p = 0.02), while no statistically significant difference emerged in the residual tumor at reTURBT and MM detectability (all p > 0.05). ERBT was significantly associated with a lower risk of bladder perforation (p = 0.002) and obturator nerve reflex (p < 0.001). Finally, ERBT was significantly associated with longer operative time, lower catheterization time, and lower length of hospital stay. The main limitation was heterogeneity among the included studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: ERBT is safer due to fewer intraoperative events, but there was no significant difference in oncological outcomes compared with cTURBT. Higher DM detection with ERBT enhances initial disease stratification, potentially improving clinical decision-making and care delivery. PATIENT SUMMARY: En bloc resection of bladder tumors is associated with lower intraoperative complications than and superior histopathological information to the conventional resection technique. However, the absence of a difference in oncological outcomes underscores the influence of factors such as tumor characteristics, surgeon expertise, and postoperative care on subsequent events.

Development of L-Lysine-Loaded PLGA Microparticles as a Controlled Release System for Angiogenesis Enhancement.

Vascularization is a highly conserved and considerably complex and precise process that is finely driven by endogenous regulatory processes at the tissue and systemic levels. However, it can reveal itself to be slow and inadequate for tissue repair and regeneration consequent to severe lesions/damages. Several biomaterial-based strategies were developed to support and enhance vasculogenesis by supplying pro-angiogenic agents. Several approaches were adopted to develop effective drug delivery systems for the controlled release of a huge variety of compounds. In this work, a microparticulate system was chosen to be loaded with the essential amino acid L-lysine, a molecule that has recently gained interest due to its involvement in pro-angiogenic, pro-regenerative, and anti-inflammatory mechanisms. Poly (lactic-co-glycolic acid), the most widely used FDA-approved biodegradable synthetic polymer for the development of drug delivery systems, was chosen due to its versatility and ability to promote neovascularization and wound healing. This study dealt with the development and the effectiveness evaluation of a PLGA-based microparticulate system for the controlled release of L-lysine. Therefore, in order to maximize L-lysine encapsulation efficiency and tune its release kinetics, the microparticle synthesis protocol was optimized by varying some processing parameters. All developed formulations were characterized from a morphological and physicochemical point of view. The optimized formulation was further characterized via the evaluation of its preliminary biological efficacy in vitro. The cellular and molecular studies revealed that the L-lysine-loaded PLGA microparticles were non-toxic, biocompatible, and supported cell proliferation and angiogenesis well by stimulating the expression of pro-angiogenic genes such as metalloproteinase-9, focal adhesion kinases, and different growth factors. Thus, this work showed the potential of delivering L-lysine encapsulated in PLGA microparticles as a cost-effective promoter system for angiogenesis enhancement and rapid healing.

Added Value of Prostate-specific Antigen Density in Selecting Prostate Biopsy Candidates Among Men with Elevated Prostate-specific Antigen and PI-RADS ≥3 Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate: A Systematic Assessment by PI-RADS Score.

BACKGROUND: A significant proportion of patients with positive multiparametric magnetic resonance imaging (mpMRI; Prostate Imaging-Reporting and Data System [PI-RADS] scores of 3-5) have negative biopsy results. OBJECTIVE: To systematically assess all prostate-specific antigen density (PSAD) values and identify an appropriate cutoff for identification of patients with positive mpMRI who could potentially avoid biopsy on the basis of their PI-RADS score. DESIGN, SETTING, AND PARTICIPANTS: The study included a cohort of 1341 patients with positive mpMRI who underwent combined targeted and systematic biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression analysis (MVA) was used to assess the association between PSAD and the risk of clinically significant prostate cancer (csPCa, grade group ≥2) after adjusting for confounders. We used locally weighted scatterplot smoothing to explore csPCa risk according to PSAD and PI-RADS scores. PSAD utility was observed only for patients with PI-RADS 3 lesions, so we plotted the effect of each PSAD value as a cutoff for this subgroup in terms of biopsies saved, csPCa cases missed, and clinically insignificant PCa (ciPCa, grade group 1) cases not detected. RESULTS AND LIMITATIONS: Overall, 667 (50%) csPCa cases were identified. On MVA, PSAD independently predicted csPCa (odds ratio 1.57; p < 0.001). For PI-RADS ≥4 lesions, the csPCa risk was ≥40% regardless of PSAD. Conversely, among patients with PI-RADS 3 lesions, csPCa risk ranged from 0% to 60% according to PSAD values, and a PSAD cutoff of 0.10 ng/ml/cm3 corresponded to a threshold probability of 10% for csPCa. Using this PSAD cutoff for patients with PI-RADS 3 lesions would have saved 32% of biopsies, missed 7% of csPCa cases, and avoided detection of 34% of ciPCa cases. Limitations include selection bias and the high experience of the radiologists and urologists involved. CONCLUSIONS: Patients with PI-RADS ≥4 lesions should undergo prostate biopsy regardless of their PSAD, while PSAD should be used to stratify patients with PI-RADS 3 lesions. Using a threshold probability of 10% for csPCa, our data suggest that the appropriate strategy is to avoid biopsy in patients with PI-RADS 3 lesions and PSAD <0.10 ng/ml/cm3. Our results also provide information to help in tailoring an appropriate strategy for every patient with positive mpMRI findings. PATIENT SUMMARY: We investigated whether a cutoff value for PSAD (prostate-specific antigen density) could identify patients with suspicious prostate lesions on MRI (magnetic resonance imaging) who could avoid biopsy according to the PI-RADS score for their scan. We found that patients with PI-RADS ≥4 should undergo prostate biopsy regardless of their PSAD. A PSAD cutoff of 0.10 should be used to stratify patients with PI-RADS 3.

Can Negative Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Avoid the Need for Pelvic Lymph Node Dissection in Newly Diagnosed Prostate Cancer Patients? A Systematic Review and Meta-analysis with Backup Histology as Reference Standard.

CONTEXT: The role of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA) in the primary staging for patients with prostate cancer (PCa) is still debated. OBJECTIVE: To analyze published studies reporting the accuracy of PSMA PET/CT for detecting lymph node invasion (LNI) at pelvic lymph node dissection (PLND). EVIDENCE ACQUISITION: A search of PubMed/MEDLINE, Cochrane library's Central, EMBASE and Scopus databases, from inception to May 2021, was conducted. The primary outcome was to evaluate the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of PSMA PET/CT in detecting LNI on a per-patient level. As a secondary outcome, NPV of PET PSMA was tested on a per-node-level analysis. Detection rates were pooled using random-effect models. Preplanned subgroup analyses tested the diagnostic accuracy after stratification for the preoperative risk group. PPV and NPV variation over LNI prevalence was evaluated. Only studies including extended PLND (ePLND) as the reference standard test were included. EVIDENCE SYNTHESIS: Twenty-seven studies, with a total of 2832 participants, were included in quantitative synthesis. The sensitivity, specificity, PPV, and NPV of PSMA PET/CT for LNI were, respectively, 58% (95% confidence interval [CI] 50-66%), 95% (95% CI 93-97%), 79% (95% CI 72-85%), and 87% (95% CI 84-89%), with overall moderate heterogeneity between studies. At bivariate analysis, the diagnostic accuracy of PSMA PET/CT estimated through summary receiver operating characteristic-derived area under the curve was 84% (95% CI 81-87%). On a per-node level, NPV of PET PSMA was 97% (95% CI 96-99%). At subgroup analyses, according to preoperative risk groups, sensitivity, specificity, PPV, and NPV were 51%, 93%, 73%, and 81%, respectively, in high-risk patients. Over the LNI prevalence range of 5-40%, PPV increased from 59% to 91%, while NPV decreased from 99% to 84%. CONCLUSIONS: PSMA PET/CT scan provides promising accuracy in the field of primary nodal staging for PCa. The high NPV in men with a lower risk of LNI might be clinically useful to reduce the number of unnecessary PLND procedures performed. Conversely, in high-risk patients, negative PSMA PET/CT cannot replace staging ePLND. PATIENT SUMMARY: In this systematic review and meta-analysis, we demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scan may optimize the primary nodal staging and surgical management of prostate cancer patients candidate to radical prostatectomy. The high negative predictive value in men with a lower risk of lymph node invasion might be clinically useful for reducing the number of useless pelvic lymph node dissection (PLND) procedures performed. Conversely, in high-risk patients, negative PSMA PET/CT cannot allow avoiding of PLND.

How to optimize follow-up in patients with a suspicious multiparametric MRI and a subsequent negative targeted prostate biopsy. Results from a large, single-institution series.

OBJECTIVE: We aimed at optimizing the follow-up for patients with a positive multiparametric magnetic resonance of the prostate (mpMRI) and a subsequent negative targeted biopsy (TBx) plus systematic biopsy (SBx). MATERIALS AND METHODS: A total of 308 men with a clinical suspicion of PCa and a positive mpMRI (PI-RADS ≥ 3) with concomitant negative systematic and targeted Bx performed at a single tertiary referral center. All patients were then followed with serial PSA measurements, digital rectal examination and eventual follow-up mpMRI and/or repeat Bx. The primary outcome was to evaluate the overall clinically significant PCa (csPCa)-free survival. The secondary outcome was to assess the role of a repeat mpMRI (Fu-mpMRI) and PSA density as predictors of csPCa diagnosis (defined as Gleason score ≥ 3 + 4) during follow-up. Kaplan Meier analysis and univariable Cox regression were used for survival and predictive analyses. RESULTS: Median follow-up was 31 months (IQR: 23-43). During the study period 116 (37.7%) and 68 (22.1%) of men received a Fu-mpMRI and a Fu-Bx, respectively. Overall, 51 (16.6%) and 15 (4.9%) patients had a positive mpMRI and clinically significant (csPCa) diagnosis during follow-up, respectively. Among 68 men who received a Fu-Bx, the 2- and 3-years csPCa diagnosis-free survival in men with negative vs. positive Fu-mpMRI was 97% vs. 65% and 92% vs. 65%, respectively. At univariate Cox-regression analysis the presence of a positive Fu-mpMRI resulted to be significantly associated with the presence of csPCa at Fu-Bx (HR: 5.8, 95% CI: 1.3-26.6, P = 0.008). The 2- and 3-years csPCa diagnosis-free survival in men with PSAd <0.15 vs. ≥0.15 was 89% vs. 77%, and 86% vs. 66%, respectively (HR: 2.6, 95% CI: 0.75-8.87, P = 0.13). The combination of negative Fu-mpMRI and PSAd<0.15 furtherly reduced the probability of csPCa diagnosis at Fu-Bx at only 6% at 3years (HR: 9.9, 95% CI: 1.9-38.6, P < 0.001) in this subgroup of patients. CONCLUSIONS: After a negative TBx for a positive mpMRI, more than half of Fu-mpMRI were negative. A persistent positive mpMRI was associated with a significant risk of csPCa. The risk of csPCa diagnosis in men with negative mpMRI performed after negative TBx and low PSAd was negligible.

Experimental and computational studies on non-covalent imprinted microspheres as recognition system for nicotinamide molecules.

Molecularly imprinted microspheres obtained by precipitation polymerization using nicotinamide (nia) as template have been prepared and characterised by SEM. How various experimental parameters can affect microsphere morphology, reaction yield and re-binding capacity have been evaluated. Pre-polymerization interactions between template and functional monomer in chloroform and MeCN have been studied by (1)H-NMR. The results suggest that the interaction between nia and methacrylic acid (MAA) is mainly based on hydrogen-bonding between amide protons and MAA. Computational density functional theory (DFT) studies on MAA-nia complexes have been also performed to better understand hydrogen-bonding interactions. The imprinted activity of the microspheres, synthesized in chloroform or acetonitrile (MeCN), has been evaluated by spectrophotometric analysis of nia solutions when chloroform or MeCN are used as incubation solvents. The results suggest that MeCN interferes with hydrogen bonding between template and MAA during either the polymerization step or re-binding process as also observed from theoretical results. Finally, the selectivity towards selected nia analogues has been also confirmed.

Single-Port Transvesical Vesico-Vaginal Fistula Repair: An Initial Experience

ABSTRACT Introduction Vesicovaginal fistula (VVF) is the most common urogenital fistula due to iatrogenic cause, primarily associated with gynecologic surgery (1). Although both conservative and surgical management may be considered, the optimal treatment is still uncertain and several studies were published using different techniques (open, laparoscopic or robotic) and approaches (extravesical, transvesical or transvaginal) (2-5). In this context, we aim to report our initial experience repairing VVF with Single-Port (SP) Transvesical (TV) access. Materials and Methods Four patients with a diagnosis of VVF underwent SP-TV VVF repair between May 2022 and December 2023. Diagnosis was confirmed by cystoscopy, cystogram and in two cases by CT Urogram. Under general anesthesia, before robotic time, patients were placed in lithotomy position and a preliminary cystoscopy was performed. Fistula was noted and a 5fr stent was placed through the fistulous tract. Two ureteral stents were placed. Then, with patient supine, a transverse suprapubic 3cm incision and 2cm cystotomy were made for SP access. First step was to mark and remove fistula tract to the vagina. The edges of the vagina and bladder were dissected in order to have a closure free of tension and to create three different layers to close: vagina, muscularis layer of the bladder and mucosal layer of the bladder. A bladder catheter was placed, and the two ureteral stents were removed at the end of procedure. Results Mean age was 53 years old and three out of 4 patients developed VVF after gynecologic surgery. Two patients underwent VVF repair 6 and 8 months after total hysterectomy. One patient developed VVF after total hysterectomy and oophorectomy followed by radiation therapy. Last patient developed VVF after previous urological procedure. Fistula diameter was between 11 and 15mm. Operative time was 211 min, including preliminary cystoscopy, stents placement and SP-access. All patients were discharged on the same day with a bladder catheter, successfully removed between post-operative day 14-18 after negative cystogram. Only in one case a ureteral stent was left because the fistula was closed to the ureteral orifice and we reported one case of UTI twelve days after surgery, treated with outpatient antibiotics. Mean follow-up was 8 months, patients were scheduled for regular follow-up visits and no recurrence was reported. All patients have at least 3 months of post-operative follow-up. Conclusions Our experience suggests that SP Transvesical VVF repair may be considered as a safe and feasible minimally invasive treatment for small/medium fistulae (10-15mm).