An untargeted analytical workflow based on Kendrick mass defect filtering reveals dysregulations in acylcarnitines in prostate cancer tissue.

BACKGROUND: Metabolomics is nowadays considered one the most powerful analytical for the discovery of metabolic dysregulations associated with the insurgence of cancer, given the reprogramming of the cell metabolism to meet the bioenergetic and biosynthetic demands of the malignant cell. Notwithstanding, several challenges still exist regarding quality control, method standardization, data processing, and compound identification. Therefore, there is a need for effective and straightforward approaches for the untargeted analysis of structurally related classes of compounds, such as acylcarnitines, that have been widely investigated in prostate cancer research for their role in energy metabolism and transport and ß-oxidation of fatty acids. RESULTS: In the present study, an innovative analytical platform was developed for the straightforward albeit comprehensive characterization of acylcarnitines based on high-resolution mass spectrometry, Kendrick mass defect filtering, and confirmation by prediction of their retention time in reversed-phase chromatography. In particular, a customized data processing workflow was set up on Compound Discoverer software to enable the Kendrick mass defect filtering, which allowed filtering out more than 90 % of the initial features resulting from the processing of 25 tumoral and adjacent non-malignant prostate tissues collected from patients undergoing radical prostatectomy. Later, a partial least square-discriminant analysis model validated by repeated double cross-validation was built on the dataset of 74 annotated acylcarnitines, with classification rates higher than 93 % for both groups, and univariate statistical analysis helped elucidate the individual role of the annotated metabolites. SIGNIFICANCE: Hydroxylation of short- and medium-chain minor acylcarnitines appeared to be a significant variable in describing tissue differences, suggesting the hypothesis that the neoplastic growth is linked to oxidation phenomena on selected metabolites and reinforcing the need for effective methods for the annotation of minor metabolites.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. METHODS: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). RESULTS: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. CONCLUSIONS: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

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

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

Diagnostic Accuracy of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Muscle-Invasive Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a diagnostic tool that is gaining popularity for its ability to improve overall diagnostic accuracy in bladder cancer (BC) staging. Our aim is to determine the cumulative diagnostic performance of CEUS in predicting preoperative muscle invasiveness using a comprehensive systematic review and pooled meta-analysis. METHODS: A systematic review until October 2023 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patients with BC suspicion were offered CEUS before the transurethral resection of the bladder tumor (TURBT). The diagnostic performance of CEUS was evaluated based on non-muscle-invasive bladder cancer (NMIBC) vs. muscle-invasive bladder cancer (MIBC) confirmed at the final histopathological examination after TURBT. The outcomes were determined through pooled sensitivity, specificity, pooled positive likelihood ratio (PLR+), negative likelihood ratio (PLR-), and area under the summary receiver operating characteristic (SROC) along with their respective 95% confidence intervals (CI). RESULTS: Overall, five studies were included. In these studies, a total of 362 patients underwent CEUS prior to TURBT. The pooled sensitivity and specificity were 0.88 (95% CI: 0.81-0.93) and 0.88 (95% CI: 0.82-0.92), respectively. SROC curve depicted a diagnostic accuracy of 0.94 (95% CI: 0.81-0.98). The pooled PLR+ and PLR- were 7.3 (95% CI: 4.8-11.2) and 0.14 (95% CI: 0.08-0.23), respectively. CONCLUSIONS: Our meta-analysis indicates that CEUS is highly accurate in the diagnosis and staging for BC. Beyond its accuracy, CEUS offers the advantage of being a cost-effective, safe, and versatile imaging tool.

How the Management of Biochemical Recurrence in Prostate Cancer Will Be Modified by the Concept of Anticipation and Incrementation of Therapy.

Biochemical recurrence (BCR) after primary treatments for prostate cancer (PC) is an extremely heterogeneous phase and at least a stratification into low- and high-risk cases for early progression in metastatic disease is necessary. At present, PSA-DT represents the best parameter to define low- and high-risk BCR PC, but real precision medicine is strongly suggested to define tailored management for patients with BCR. Before defining management, it is necessary to exclude the presence of low-volume metastasis associated with PSA progression using new-generation imaging, preferably with PSMA PET/CT. Low-risk BCR cases should be actively observed without early systemic therapies. Early treatment of low-risk BCR with continuous androgen deprivation therapy (ADT) can produce disadvantages such as the development of castration resistance before the appearance of metastases (non-metastatic castration-resistant PC). Patients with high-risk BCR benefit from early systemic therapy. Even with overall survival (OS) as the primary treatment endpoint, metastasis-free survival (MFS) should be used as a surrogate endpoint in clinical trials, especially in long survival stages of the disease. The EMBARK study has greatly influenced the management of high-risk BCR, by introducing the concept of anticipation and intensification through the use of androgen receptor signaling inhibitors (ARSIs) and ADT combination therapy. In high-risk (PSA-DT ≤ 9 months) BCR cases, the combination of enzalutamide with leuprolide significantly improves MFS when compared to leuprolide alone, maintaining an unchanged quality of life in the asymptomatic phase of the disease. The possibility of using ARSIs alone in this early disease setting is suggested by the EMBARK study (arm with enzalutamide alone) with less evidence than with the intensification of the combination therapy. Continued use versus discontinuation of enzalutamide plus leuprolide intensified therapy upon reaching undetectable PSA levels needs to be better defined with further analysis. Real-world analysis must verify the significant results obtained in the context of a phase 3 study.

Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients.

A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary-gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n = 18 series with n = 1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (- 3.25 nmol/L, 95%CI - 0.57 and - 5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (- 5.04 nmol/L, 95%CI - 1.26 and - 8.82) but similar for Covid-19 survivors and non-survivors (- 3.04 nmol/L, 95%CI - 2.04 and - 4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

Prospective Validation Study of a Novel Integrated Pathway Based on Clinical Features, Magnetic Resonance Imaging Biomarkers, and MicroRNAs for Early Detection of Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is the most diagnosed cancer in men, with an increasing need to integrate noninvasive imaging and circulating microRNAs beyond prostate-specific antigen for screening and early detection. OBJECTIVE: To validate magnetic resonance imaging (MRI) biomarkers and circulating microRNAs as triage tests for patients directed to prostate biopsy, and to test different diagnostic pathways to compare their performance on patients' outcome, in terms of unnecessary biopsy avoidance. DESIGN, SETTING, AND PARTICIPANTS: A prospective single-center cohort study, enrolling patients with PCa suspicion who underwent MRI, MRI-directed fusion biopsy (MRDB), and circulating microRNAs, was conducted. A network-based analysis was used to identify MRI biomarkers and microRNA drivers of clinically significant PCa. INTERVENTION: MRI, MRDB, and blood sampling. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The decision curve analysis was exploited to assess the performance of the proposed diagnostic pathways and to quantify their benefit in terms of biopsy avoidance. RESULTS AND LIMITATIONS: Overall, 261 men were enrolled and underwent MRDB for PCa detection. A total of 178 patients represented the entire cohort: 55 (30.9%) were negative for PCa, 39 (21.9%) had grade group (GG) 1 PCa, and 84 (47.2%) had GG >1 PCa. The proposed integrated pathway, including clinical data, MRI biomarkers, and microRNAs, provided the best net benefit with a biopsy avoidance rate of about 20% at a low disease probability. The main limitation is the monocentric design in a referral center. CONCLUSIONS: The integrated pathway represents a validated model that sees MRI biomarkers and microRNAs as a prebiopsy triage of patients at a risk for clinically significant PCa. The proposed pathway showed the highest net benefit in terms of unnecessary biopsy avoidance. PATIENT SUMMARY: The proposed integrated pathway for early detection of prostate cancer (PCa) allows accurate patient allocation to biopsy and patients' stratification into risk group categories, reducing overdiagnosis and overtreatment of clinically insignificant PCa.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression.

INTRODUCTION: To analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). PATIENTS: 170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. METHODS: we retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. RESULTS: no significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). CONCLUSIONS: in our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Mid-term outcomes of minimally invasive infrapubic approach for inflatable penile prosthesis implantation: A single-center study and literature review.

BACKGROUND: The minimally invasive infrapubic approach (MIIA) for inflatable penile prosthesis (IPP) placement has shown favorable peri-operative safety and efficacy profile, but scarce data exist on long-term follow-up. OBJECTIVES: We investigated the safety and efficacy of IPP implantation via the MIIA after a minimum 5-year follow-up. MATERIALS AND METHODS: We identified data of implanted patients prospectively included in our institutional database. Complications and functional outcomes were assessed by using validated tools. Specifically, quality of life and patient satisfaction were evaluated by the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire. Kaplan-Meier method was used to analyze IPP survival (defined as a working IPP). RESULTS: Overall, 67 patients implanted by MIIA with a median (IQR) age of 64 years (61-70) were included. The median (IQR) follow-up duration was 71 months (63-80). Fifteen (22%) patients experienced complications: minor (Clavien ≤2) events included changes in penile sensitivity (n = 1; 1.5%), orgasmic dysfunction (n = 1; 1.5%), pain (n = 5; 7%), urinary tract infection (n = 2; 3%), and chronic discomfort (n = 1; 1.5%); major (Clavien 3) complications were represented by mechanical failure (n = 3; 4.5%), IPP infection (n = 1; 1.5%), and cylinder protrusion (n = 1; 1.5%). The estimated IPP survival was 94% (95% CI, 91.4-96.6), 92.5% (95% CI, 89.7-95.3), and 92.5% (95% CI, 89.7-95.3) at 3, 5, and 7 years after implantation, respectively. In patients using the device at follow-up (n = 61; 91%), median (IQR) scores for QoLSPP domains demonstrated favorable functional outcomes and patient satisfaction: functional 21 (19-23), personal 16 (15-18), relational 14 (12-15), and social 12 (11-14). DISCUSSION AND CONCLUSION: This study represents the longest follow-up using validated tools to assess the outcomes of IPP implantation via MIIA so far. IPP placement via MIIA confirms to be safe and to offer high satisfaction to both patients and partners at mid-term evaluation.

Design of a magnetic resonance imaging-based screening program for early diagnosis of prostate cancer: preliminary results of a randomized controlled trial-Prostate Cancer Secondary Screening in Sapienza (PROSA).

OBJECTIVES: The main objective is to propose an MRI-based screening protocol, investigating the role of MRI without the injection of contrast media (bi-parametric MRI, bpMRI) as a secondary prevention test for prostate cancer (PCa) early diagnosis, comparing MRI with the prostate specific antigen (PSA) test. For this reason, preliminary results of Prostate Cancer Secondary Screening in Sapienza (PROSA) are presented, to investigate the efficiency of an MRI-based screening protocol. PROSA is a prospective, randomized, single-center study. To date, 351 men have been enrolled and blindly randomized into two different arms: (A) Men underwent a bpMRI regardless of their PSA values (175); (B) Men followed as per clinical practice: those with increased PSA (61) were referred to bpMRI, while those with normal PSA (112) were not. Men who screened positive on MRI were directed to MR-directed targeted biopsy. On arm A, 4 clinically significant PCa have been detected, while none was found on arm B (p = 0.046). To evaluate the efficiency of the screening protocol, we calculated the experimental event rate (EER, 3.6%), control event rate (CER, 1.2%.), absolute risk reduction (ARR, 2.5%), and number needed to treat (NNT, 40.3). PROSA represents an interesting experience in the field of imaging-based PCa screening. The preliminary data from this trial highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. Further data will finally validate the most appropriate screening program. CLINICAL RELEVANCE STATEMENT: PROSA depicts an interesting experience in the field of research focused on imaging-based prostate cancer screening. Its preliminary data highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. KEY POINTS: • Promotion of an MRI-based screening protocol, investigating the role of non-contrast MRI as a secondary prevention test for prostate cancer early diagnosis, comparing MRI with PSA test. • Prostate Cancer Secondary Screening in Sapienza (PROSA) represents an interesting experience in the field of research focused on imaging-based prostate cancer screening; its preliminary results indicate that it is possible to use non-contrast MRI as a screening tool for early detection of PCa. • This new approach to PCa screening could facilitate the early diagnosis of clinically significant prostate cancer while reducing the number of unnecessary prostate biopsies and the detection of clinically insignificant prostate cancer.

A systematic review of robot-assisted partial nephrectomy outcomes for advanced indications: Large tumors (cT2-T3), solitary kidney, completely endophytic, hilar, recurrent, and multiple renal tumors.

Objective: Robot-assisted partial nephrectomy (RAPN) has become widely used for treatment of renal cell carcinoma and it is expanding in the field of complex renal masses. The aim of this systematic review was to analyze outcomes of RAPN for completely endophytic renal masses, large tumors (cT2-T3), renal cell carcinoma in solitary kidney, recurrent tumors, completely endophytic and hilar masses, and simultaneous and multiple tumors. Methods: A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed in December 2022 for English language papers. The primary endpoint was to evaluate the role of RAPN in the setting of each category of complex renal masses considered. The secondary endpoint was to evaluate the surgical and functional outcomes. Results: After screening 1250 records, 43 full-text manuscripts were selected, comprising over 8500 patients. Twelve and thirteen studies reported data for endophytic and hilar renal masses, respectively. Five and three studies reported outcomes for cT2-T3 and solitary kidney patients, respectively. Four studies focused on redo-RAPN for recurrent tumors. Two studies investigated simultaneous bilateral renal masses and five reports focused on multiple tumor excision in ipsilateral kidney. Conclusion: Over the past decade, evidence supporting the use of RAPN for the most challenging nephron-sparing surgery indications has continuously grown. Although limitations remain including study design and lack of detailed long-term functional and oncological outcomes, the adoption of RAPN for the included advanced indications is associated with favorable surgical outcomes with good preservation of renal function without compromising the oncological result. Certainly, a higher likelihood of complication might be expected when facing extremely challenging cases. However, none of these indications should be considered per se an exclusion criterion for performing RAPN. Ultimately, a risk-adapted approach should be employed.

Is It Time to Anticipate the Use of PARP Inhibition in Prostate Cancer Patients?

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes.

Robot-Assisted Sacrocolpopexy versus Trans-Vaginal Multicompartment Prolapse Repair: Impact on Lower Bowel Tract Function.

BACKGROUND: This study evaluated the effectiveness, safety, and possible changes in bowel symptoms after multicompartment prolapse surgery by comparing two different surgical approaches, transvaginal mesh surgery with levatorplasty (TVMLP) and robot-assisted sacrocolpopexy (RSC). METHODS: All patients underwent pelvic (POP-Q staging system) and rectal examination to evaluate anal sphincter tone in the lithotomy position with the appropriate Valsalva test. The preoperative evaluation included urodynamics and pelvic magnetic resonance defecography. Patient Global Impression of Improvement (PGI-I) at follow-up measured subjective improvement. All patients completed Agachan-Wexner's questionnaire at 0 and 12 months of follow-up to evaluate bowel symptoms. RESULTS: A total of 73 cases were randomized into the RSC group (36 cases) and TVMLP group (37 cases). After surgery, the main POP-Q stage in both groups was stage I (RCS 80.5% vs. TVMLP 82%). There was a significant difference (p < 0.05) in postoperative anal sphincter tone: 35%. The TVMLP group experienced a hypertonic anal sphincter, while none of the RSC group did. Regarding subjective improvement, the median PGI-I was 1 in both groups. At 12 months of follow-up, both groups exhibited a significant improvement in bowel symptoms. CONCLUSIONS: RSC and TVMLP successfully corrected multicompartment POP. RSC showed a greater improvement in the total Agachan-Wexner score and lower bowel symptoms.

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

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

Qualitative Assessment of Contrast-Enhanced Ultrasound in Differentiating Clear Cell Renal Cell Carcinoma and Oncocytoma.

BACKGROUND: We aimed to assess whether clear cell renal cell carcinoma (ccRCC) can be differentiated from renal oncocytoma (RO) on a contrast-enhanced ultrasound (CEUS). METHODS: Between January 2021 and October 2022, we retrospectively queried and analyzed our prospectively maintained dataset. Renal mass features were scrutinized with conventional ultrasound imaging (CUS) and CEUS. All lesions were confirmed by histopathologic diagnoses after nephron-sparing surgery (NSS). A multivariable analysis was performed to identify the potential predictors of ccRCC. The area under the curve (AUC) was depicted in order to assess the diagnostic accuracy of the multivariable model. RESULTS: A total of 126 renal masses, including 103 (81.7%) ccRCC and 23 (18.3%) RO, matched our inclusion criteria. Among these two groups, we found significant differences in terms of enhancement (homogeneous vs. heterogeneous) (p < 0.001), wash-in (fast vs. synchronous/slow) (p = 0.004), wash-out (fast vs. synchronous/slow) (p = 0.001), and rim-like enhancement (p < 0.001). On the multivariate logistic regression, heterogeneous enhancement (OR: 19.37; p = <0.001) and rim-like enhancement (OR: 3.73; p = 0.049) were independent predictors of ccRCC. Finally, these two variables had an AUC of 82.5% and 75.3%, respectively. CONCLUSIONS: Diagnostic imaging for presurgical planning is crucial in the choice of either conservative or radical management. CEUS, with its unique features, revealed its usefulness in differentiating ccRCC from RO.

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

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

Low cancer yield in PI-RADS 3 upgraded to 4 by dynamic contrast-enhanced MRI: is it time to reconsider scoring categorization?

OBJECTIVES: To evaluate MRI diagnostic performance in detecting clinically significant prostate cancer (csPCa) in peripheral-zone PI-RADS 4 lesions, comparing those with clearly restricted diffusion (DWI-score 4), and those with equivocal diffusion pattern (DWI-score 3) and positive dynamic contrast-enhanced (DCE) MRI. METHODS: This observational prospective study enrolled 389 men referred to MRI and, if positive (PI-RADS 3 with PSA-density [PSAD] ≥ 0.15 ng/mL/mL, 4 and 5), to MRI-directed biopsy. Lesions with DWI-score 3 and positive DCE were classified as "PI-RADS 3up," instead of PI-RADS 4. Univariable and multivariable analyses were implemented to determine features correlated to csPCa detection. RESULTS: Prevalence of csPCa was 14.5% and 53.3% in PI-RADS categories 3up and 4, respectively (p < 0.001). MRI showed a sensitivity of 100.0%, specificity 40.9%, PPV 46.5%, NPV 100.0%, and accuracy 60.9% for csPCa detection. Modifying the threshold to consider MRI positive and to indicate biopsy (same as previously described, but PI-RADS 3up only when associated with elevated PSAD), the sensitivity changed to 93.9%, specificity 57.2%, PPV 53.0%, NPV 94.8%, and accuracy 69.7%. Age (p < 0.001), PSAD (p < 0.001), positive DWI (p < 0.001), and PI-RADS score (p = 0.04) resulted in independent predictors of csPCa. CONCLUSIONS: Most cases of PI-RADS 3up were false-positives, suggesting that upgrading peripheral lesions with DWI-score 3 to PI-RADS 4 because of positive DCE has a detrimental effect on MRI accuracy, decreasing the true prevalence of csPCa in the PI-RADS 4 category. PI-RADS 3up should not be upgraded and directed to biopsy only if associated with increased PSAD. KEY POINTS: • As per PI-RADS v2.1 recommendations, in case of a peripheral zone lesion with equivocal diffusion-weighted imaging (DWI score 3), but positive dynamic contrast-enhanced (DCE) MRI, the overall PI-RADS score should be upgraded to 4. • The current PI-RADS recommendation of upgrading PI-RADS 3 lesions of the peripheral zone to PI-RADS 4 because of positive DCE decreased clinically significant prostate cancer detection rate in our series. • According to our results, the most accurate threshold for setting indication to prostate biopsy is PI-RADS 3 or PI-RADS 3 with positive DCE both associated with increased PSA density.

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

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

The impact of radical prostatectomy on global climate: a prospective multicentre study comparing laparoscopic versus robotic surgery.

BACKGROUND: More than 4% of the global greenhouse gas emissions are generated by healthcare system. Focusing on the environmental impact of minimally invasive surgery, we assessed and compared the CO2 emissions between Robot-assisted (RALP) and Laparoscopic Radical Prostatectomy (LRP). METHODS: In patients prospectively enrolled, we evaluated the age, surgical and anesthesiologic time, postoperative intensive care unit and hospital stay, blood transfusion, pre- and postoperative hemoglobin and Gleason score, open conversion need, and complications (Clavien-Dindo classification). We assessed the life cycle to estimate the energy consumption for surgical procedures and hospital stays. We reported the materials, CO2 produced, and fluid quantity infused and dispersed. Disposable and reusable materials and instruments were weighed and divided into metal, plastic, and composite fibers. The CO2 consumption for disposal and decontamination was also evaluated. RESULTS: Of the 223 patients investigated, 119 and 104 patients underwent RALP and LRP, respectively. The two groups were comparable as regards age and preoperative Gleason score. The laparoscopic and robotic instruments weighed 1733 g and 1737 g, respectively. The CO2 emissions due to instrumentation were higher in the laparoscopic group, with the majority coming from plastic and composite fiber components. The CO2 emissions for metal components were higher in the robotic group. The robot functioned at 3.5 kW/h, producing 4 kg/h of CO2. The laparoscopic column operated at 600 W/h, emitting ~1 kg/h of CO2. The operating room operated at 3,0 kW/h. The operating time was longer in the laparoscopic group, resulting in higher CO2 emissions. CO2 emissions from hospital room energy consumption were lower in the robot-assisted group. The total CO2 emissions were ~47 kg and ~60 kg per procedure in the robot-assisted and laparoscopic groups, respectively. CONCLUSIONS: RALP generates substantially less CO2 than LRP owing to the use of more reusable surgical supplies, shorter operative time and hospital stay.

Bladder Cancer and Risk Factors: Data from a Multi-Institutional Long-Term Analysis on Cardiovascular Disease and Cancer Incidence.

Background: Bladder cancer (BCa) is a heterogeneous disease with a variable prognosis and natural history. Cardiovascular disease (CVD), although completely different, has several similarities and possible interactions with cancer. The association between them is still unknown, but common risk factors between the two suggest a shared biology. Materials and Methods: This was a retrospective study that included patients who underwent transurethral resection of bladder tumor at two high-volume institutions. Depending on the presence of a previous history of CVD or not, patients were divided into two groups. Results: A total of 2050 patients were included, and 1638 (81.3%) were diagnosed with bladder cancer. Regarding comorbidities, the most common were hypertension (59.9%), cardiovascular disease (23.4%) and diabetes (22.4%). At univariate analysis, independent risk factors for bladder cancer were age and male sex, while protective factors were cessation of smoking and presence of CVD. All these results, except for ex-smoker status, were confirmed at the multivariate analysis. Another analysis was performed for patients with high-risk bladder cancer and, in this case, the role of CVD was not statistically significant. Conclusions: Our study pointed out a positive association between CVD and BCa incidence; CVD was an independent protective factor for BCa. This effect was not confirmed for high-risk tumors. Several biological and genomics mechanisms clearly contribute to the onset of both diseases, suggesting a possible shared disease pathway and highlighting the complex interplay of cancer and CVD. CVD treatment can involve different drugs with a possible effect on cancer incidence, but, to date, findings are still inconclusive.