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.

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.

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.

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.

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.

Comparison of laparoscopic partial nephrectomy performed with AirSeal® system vs. standard insufflator: results from a referral center.

Objective: To compare perioperative and oncologic surgical outcomes during laparoscopic partial nephrectomy (LPN) performed by standard carbon dioxide insufflation, with those from surgeries in which the AirSeal® intelligent insufflation system was used for renal tumors. Materials and methods: A total of 27 patients with renal tumor were identified, 14 underwent LPN with AirSeal® (group A) and 13 LPN with standard insufflator (group B), respectively. Demographic baseline characteristics were similar in the two groups. Results: The size of the tumor was largest in group B (29.64 vs. 32.1 mm). The mean operative time was shorter in the AirSeal® group [group A: mean 109.0 min, median 107.5 min, interquartile range (IQR) 85; group B: mean 121.0 min, median 120.0 min, IQR 50.0]. Positive margin rates were absent in the two groups. Estimated blood loss presented a difference in the perioperative period (group A: mean 1.5 g/dL, median 1.45 g/dL; group B: mean 2.15 g/dL, median 2.2 g/dL). Time to ischemia was found to be shorter in group A with a median of 18 min compared to a median of 20 min in group B. No subcutaneous emphysema, pneumothorax, and pneumomediastinum cases occurred in either group. A postoperative complication developed in one patient requiring superselective embolization. Conclusion: In selected patients, our preliminary surgical experience has shown that the LPN procedure performed with the aid of the AirSeal® intelligent insufflation system can be used to treat even medium-/high-complexity kidney lesions, with a reduction in operating times, lower rates of complications, and perioperative blood loss. Clinical trial registration: AirSealV1.

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.

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.

Comparison of Four Validated Nomograms (Memorial Sloan Kettering Cancer Center, Briganti 2012, 2017, and 2019) Predicting Lymph Node Invasion in Patients with High-Risk Prostate Cancer Candidates for Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: Clinical Experience and Review of the Literature.

BACKGROUND: The indication for extended pelvic lymph node dissection (ePLND) at the time of radical prostatectomy (RP) is based on nomograms predicting the risk of lymph node invasion (LNI). However, limited data are available on the comparison of these predictive models in high-risk prostate cancer (PC) patients. Therefore, we compared the accuracy of the most used nomograms (MSKCC, Briganti 2012, 2017, and 2019) in the setting of high-risk PC patients submitted to ePLND. METHODS: 150 patients with high-risk PC disease treated from 2019 to 2022 were included. Before RP + ePLND, we assessed the MSKCC, Briganti 2012, 2017, and 2019 nomograms for each patient, and we compared the prediction of LNI with the final histopathological analysis of the ePLND using pathologic results as a reference. RESULTS: LNI was found in 39 patients (26%), and 71.3% were cT2. The percentage of patients with estimated LNI risk above the cut-off was significantly higher in pN+ cases than in pN0 for all Briganti nomograms. The percentage of patients at risk of LNI, according to Briganti Nomogram (2012, 2017, and 2019), was significantly higher in pN+ cases than in pN0 (p < 0.04), while MSKCC prediction didn't vary significantly between pN0 and pN+ groups (p = 0.2). All nomograms showed high sensitivity (Se > 0.90), low specificity (Sp < 0.20), and similar AUC (range: 0.526-0.573) in predicting pN+. Particularly, 74% of cases patients with MSKCC estimated risk > 7% showed pN0 compared to 71% with Briganti 2012 > 5%, 69% with Briganti 2017 > 7%, and 70% with Briganti 2019 > 7%. CONCLUSIONS: Despite the high-risk disease, in our patients treated with ePLND emerges a still high number of pN0 cases and a similar low specificity of nomograms in predicting LNI.

Unexpected discovery of surgical gauze during a robotic radical prostatectomy identified as a capturing lymph node on magnetic resonance.

Multiparametric magnetic resonance, plays a crucial role in several steps of the management of prostate cancer. Various factors could alter the interpretation and reduce the accuracy of MR. Among these the group of the retained surgical items, can produce serious implications for the health of patient, as well as medical-legal consequences. Here we report the case of a patient, with a prostate tumor, who performed a mp-MRI of the prostate, where it was reported as collateral finding, compatible thesis with lymphadenopathy. During robotic assisted radical prostatectomy, was found a gauze, which persisted asymptomatic, retained after a previous right inguinal hernioplasty.

Contemporary trends in the surgical management of urinary incontinence after radical prostatectomy in the United States.

PURPOSE: To identify trends, costs, and predictors in the use of different surgical procedures for post-radical prostatectomy incontinence (PPI). MATERIALS AND METHODS: We identified 21,589 men who were diagnosed with localized prostate cancer (PCa) and treated with radical prostatectomy (RP) from 2003 to 2017. The primary outcome was the incontinence procedure performances. Optum's de-identified Clinformatics® Data Mart Database was queried to define the cohort of interest. The average costs of the different incontinence procedures were obtained and compared. Also, demographic, and clinical predictors of incontinence surgery were evaluated by multivariable regression analysis. RESULTS: Of the 21,589 men with localized PCa treated with RP, 740 (3.43%) underwent at least one incontinence procedure during a median of 5 years of follow-up. In total, there were 844 unique incontinence procedures. Male slings were the most common procedure (47.5%), had an intermediate cost compared to the other treatment options, and was the first-choice treatment for the majority of patients (50%). The use of an artificial urinary sphincter (AUS) was the second most common (35.3%), but also was the most expensive treatment and was first-choice-treatment for 32.3% of patients. On multivariable analysis, metabolic syndrome related disorders, adjuvant/salvage radiation therapy as well as a history of neurological comorbidities were independently associated with an increased likelihood of incontinence surgery. CONCLUSIONS: The receipt of male slings increased and then subsequently decreased, while AUS utilization was stable, and the use of urethral bulking agents was uncommon. From a cost standpoint, AUS was the most expensive option. Finally, patient's comorbidity history and RP related factors were found to influence the choice for primary or subsequent PPI interventions.

Predictive role of node-rads score in patients with prostate cancer candidates for radical prostatectomy with extended lymph node dissection: comparative analysis with validated nomograms.

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

Regenerative Medicine-Based Treatment of Stress Urinary Incontinence with Mesenchymal Stem Cells: A Systematic Review and Meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. METHODS: We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. RESULTS: 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 - 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96]. CONCLUSION: Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.

Management of the incidental adrenal mass, continued surveillance versus surgical excision: analysis of US claims data on contemporary socio-demographic predictors and perioperative outcomes.

BACKGROUND: Incidentally diagnosed adrenal masses represent an entity that can result in either long term follow-up, surgical excision, or both. Understanding when and which adrenal masses are ultimately excised surgically is not well understood. We sought to understand the ultimate fate of these incidentalomas using a large population-based dataset. METHODS: The primary outcome of the study was determining the trend in adoption of surveillance vs. surgical excision according to socio-demographic, economic, and pathologic indices, and also provider specialty. Secondary outcomes were the assessment of perioperative complications, operative time, surgical approach, hospital stay, and provider specialty (general surgery vs. urology) among the cohort that underwent excision. RESULTS: Out of a total of N.=91,560 adrenal masses, ultimately N.=3375 (3.83%) of these underwent surgical excision. In the surgical excision cohort, the incidence of aldosteronoma, functional adenoma/Cushing's disease, and adrenocortical carcinoma was higher than in the surveillance cohort. Those patients who were older, female, and with higher Charlson Comorbidity indexes (CCI) were less likely to undergo surgical resection. Factors that predicted for an increased probability of resection included obtaining more CT/MRI scans as well as general surgeons as primary physician providers. Over the study period, the vast majority of surgeries were performed by surgeons other than urologists (12.9%) and open and laparoscopic approaches dominated, with the robotic-assisted approach accounting for a minority of the surgical cases (23.9%). The minimally invasive surgery (MIS) approach independently predicted for both lower rates of complications and shorter hospital stay. CONCLUSIONS: In the US, adrenal incidentalomas are more likely to undergo surveillance rather than surgical resection. In our study, surgery is mainly offered for functional or malignant disease and the receipt of surgery can vary by physician specialty. A MIS approach independently predicted for both lower rates of complications and shorter hospital stay.

Comparative Prospective and Longitudinal Analysis on the Platelet-to-Lymphocyte, Neutrophil-to-Lymphocyte, and Albumin-to-Globulin Ratio in Patients with Non-Metastatic and Metastatic Prostate Cancer.

PURPOSE: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases. METHODS: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR. RESULTS: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis. CONCLUSION: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

Prognostic Value of Albumin to Globulin Ratio in Non-Metastatic and Metastatic Prostate Cancer Patients: A Meta-Analysis and Systematic Review.

The aim of our meta-analysis is to analyze data available in the literature regarding a possible prognostic value of the albumin to globulin ratio (AGR) in prostate cancer (PC) patients. We distinguished our analysis in terms of PC staging, histologic aggressiveness, and risk of progression after treatments. A literature search process was performed ("prostatic cancer", "albumin", "globulin", "albumin to globulin ratio") following the PRISMA guidelines. In our meta-analysis, the pooled Event Rate (ER) estimate for each group of interest was calculated using a random effect model. Cases were distinguished in Low and High AGR groups based on an optimal cut-off value defined at ROC analysis. Four clinical trials were enclosed (sample size range from 214 to 6041 cases). The pooled Risk Difference for a non-organ confined PC between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) with a very low rate of heterogeneity (I2 < 0.15%; p = 0.43) among studies (test of group differences p = 0.21). In non-metastatic PC cases, the pooled Risk Difference for biochemical progression (BCP) between High AGR and Low AGR cases was −0.05 (95%CI: −0.12−0.01) (I2 = 0.01%; p = 0.69) (test of group differences p = 0.12). In metastatic PC cases, AGR showed an independent significant (p < 0.01) predictive value either in terms of progression free survival (PFS) (Odds Ratio (OR): 0.642 (0.430−0.957)) or cancer specific survival (CSS) (OR: 0.412 (0.259−0.654)). Our meta-analysis showed homogeneous results supporting no significant predictive values for AGR in terms of staging, grading and biochemical progression in non-metastatic PC.