The 2012 Briganti nomogram not only predicts lymph node involvement but also disease progression in surgically treated intermediate-risk prostate cancer patients with PSA <10 ng/mL, ISUP grade group 3, and clinical stage up to cT2b.

PURPOSE: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models. RESULTS: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading. CONCLUSIONS: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues.

Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation.

[Figure: see text].

Advanced age is an independent prognostic factor of disease progression in high-risk prostate cancer: results in 180 patients treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection in a tertiary referral center.

OBJECTIVES: This study aimed to assess more clinical and pathological factors associated with prostate cancer (PCa) progression in high-risk PCa patients treated primarily with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) in a tertiary referral center. MATERIALS AND METHODS: In a period ranging from January 2013 to October 2020, RARP and ePLND were performed on 180 high-risk patients at Azienda Ospedaliera Universitaria Integrata of Verona (Italy). PCa progression was defined as biochemical recurrence/persistence and/or local recurrence and/or distant metastases. Statistical methods evaluated study endpoints, including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial logistic regression models. RESULTS: The median age of included patients was 66.5 [62-71] years. Disease progression occurred in 55 patients (30.6%), who were more likely to have advanced age, palpable tumors, and unfavorable pathologic features, including high tumor grade, stage, and pelvic lymph node invasion (PLNI). On multivariate analysis, PCa progression was predicted by advanced age (≥ 70 years) (HR = 2.183; 95% CI = 1.089-4377, p = 0.028), palpable tumors (HR = 3.113; 95% CI = 1.499-6.465), p = 0.002), and PLNI (HR = 2.945; 95% CI = 1.441-6.018, p = 0.003), which were associated with clinical standard factors defining high-risk PCa. Age had a negative prognostic impact on elderly patients, who were less likely to have palpable tumors but more likely to have high-grade tumors. CONCLUSIONS: High-risk PCa progression was independently predicted by advanced age, palpable tumors, and PLNI, which is associated with standard clinical prognostic factors. Consequently, with increasing age, the prognosis is worse in elderly patients, who represent an unfavorable age group that needs extensive counseling for appropriate and personalized management decisions.

Advanced age portends poorer prognosis after radical prostatectomy: a single center experience.

INTRODUCTION AND OBJECTIVE: Although advanced age doesn't seem to impair oncological outcomes after robot-assisted radical prostatectomy (RARP), elderly patients have increased rates of prostate cancer (PCa) related deaths due to a higher incidence of high-risk disease. The potential unfavorable impact of advanced age on oncological outcomes following RARP remains an unsettled issue. We aimed to evaluate the oncological outcome of PCa patients > 69 years old in a single tertiary center. MATERIALS AND METHODS: 1143 patients with clinically localized PCa underwent RARP from January 2013 to October 2020. Analysis was performed on 901 patients with available follow-up. Patients ≥ 70 years old were considered elderly. Unfavorable pathology included ISUP grade group > 2, seminal vesicle, and pelvic lymph node invasion. Disease progression was defined as biochemical and/or local recurrence and/or distant metastases. RESULTS: 243 cases (27%) were classified as elderly patients (median age 72 years). Median (IQR) follow-up was 40.4 (38.7-42.2) months. Disease progression occurred in 159 cases (17.6%). Elderly patients were more likely to belong to EAU high-risk class, have unfavorable pathology, and experience disease progression after surgery (HR = 5.300; 95% CI 1.844-15.237; p = 0.002) compared to the younger patients. CONCLUSIONS: Elderly patients eligible for RARP are more likely to belong to the EAU high-risk category and to have unfavorable pathology that are independent predictors of disease progression. Advanced age adversely impacts on oncological outcomes when evaluated inside these unfavorable categories. Accordingly, elderly patients belonging to the EAU high-risk should be counseled about the increased risk of disease progression after surgery.

Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review.

INTRODUCTION: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. METHODS: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. RESULTS: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0-7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). CONCLUSIONS: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1-2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.

The Influence of Endogenous Testosterone Density on Unfavorable Disease and Tumor Load at Final Pathology in Intermediate-Risk Prostate Cancer: Results in 338 Patients Treated with Radical Prostatectomy and Extended Pelvic Lymph Node Dissection.

OBJECTIVE: The aim of this study is to evaluate the influence of endogenous testosterone density (ETD) on features of aggressive prostate cancer (PCa) in intermediate-risk disease treated with radical prostatectomy and extended pelvic lymph node dissection. MATERIALS AND METHODS: Density measurements included the ratio of endogenous testosterone (ET), prostate-specific antigen (PSA), and percentage of biopsy positive cores (BPC) on prostate volume (ETD, PSAD, and BPCD, respectively). The ratio of percentage of cancer invading the gland (tumor load, TL) on prostate weight (TLD) was also calculated. Unfavorable disease (UD) was defined as tumor upgrading (ISUP >3) and/or upstaging (pT >2) and/or lymph node invasion (LNI). Associations of ETD with features of aggressive PCa, including UD and TLD, were evaluated by logistic and linear regression models. RESULTS: Evaluated cases were 338. Subjects with upgrading, upstaging, and LNI were 61/338 (18%), 73/338 (21%), and 25/338 (7.4%), respectively. TLD correlated with UD (Pearson's correlation coefficient, r = 0.204; p < 0.0001), PSAD (r = 0.342; p < 0.0001), BPCD (r = 0.364; p < 0.0001), and ETD (r = 0.214; p < 0.0001), which also correlated with BMI (r = -0.223; p < 0.0001), PSAD (r = 0.391; p < 0.0001), and BPCD (r = 0.407; p < 0.0001). TLD was the strongest independent predictor of UD (OR = 2.244; 95% CI = 1.146-4.395; p = 0.018). In the multivariate linear regression model predicting BPCD, ETD was an independent predictor (linear regression coefficient, b = 0.026; 95% CI: 0.016-0.036; p < 0.0001) together with PSAD (b = 1.599; 95% CI: 0.863-2.334; p < 0.0001) and TLD (b = 0.489; 95% CI: 0.274-0.706; p < 0.0001). According to models, TLD increased as ETD increased accordingly, but mean ET levels were significantly lower for patients with UD. CONCLUSIONS: As ETD measurements incremented, the risk of large tumors extending beyond the prostate increased accordingly, and patients with lower ET levels were more likely to occult UD. The influence of ETD on PCa biology should be addressed by prospective studies.

The Influence of Endogenous Testosterone on Incidental Prostate Cancer after Transurethral Prostate Resection.

OBJECTIVE: The aim of the study was to test the hypothesis that endogenous total testosterone (TT) may relate to incidental prostate cancer (iPCA) in patients with lower urinary tract symptoms (LUTS) associated with prostate enlargement undergoing transurethral resection of the prostate (TURP). METHODS: The hypothesis was tested in contemporary cohort of patients who underwent TURP because of LUTS due to prostate enlargement after excluding the suspect of PCA. In period running from January 2017 to November 2019, 389 subjects were evaluated. Endogenous testosterone was measured preoperatively between 8:00 and 10:00 o'clock in the morning. Relationships between TT and iPCA were evaluated by statistical methods. RESULTS: Overall, iPCA was detected in 18 cases (4.6%) with clinical stage cT1a or International Society of Urologic Pathology (ISUP) < 2 in 11 patients (61.1%). Endogenous testosterone was inversely associated with age and BMI in the study population but not in the subgroup with iPCA in wholly endogenous TT strongly correlated to both number of chips involved by cancer (Pearson's correlation coefficient, r = 0.553; p = 0.017) and ISUP > 2 (r = 0.504; p = 0.033). The positive association of endogenous TT with both tumor load and tumor grade was confirmed by the linear regression model with high-regression coefficients for the former (regression coefficient, b = 0.307; 95% confidence interval, 95% CI: 0.062-0.551; and p = 0.017) as for the latter (b = 5.898; 95% CI: 0.546-11.249; and p = 0.033). CONCLUSIONS: Preoperative endogenous TT is associated with features of iPCA. The influence of iPCA on endogenous testosterone needs to be addressed by a large multicenter prospective trial.

Predictors of Lymph Node Invasion in Patients with Clinically Localized Prostate Cancer Who Undergo Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: The Role of Obesity.

OBJECTIVE: In patients with intermediate- and high-risk localized prostate cancer (PCa), improving the detection of occult lymph node metastases could play a pivotal role for therapeutic counseling and planning. The recent literature shows that several clinical factors may be related to PCa aggressiveness. The aim of this study is to investigate the potential associations between clinical factors and the risk of multiple lymph node invasion (LNI) in patients with intermediate- and high-risk localized PCa (cT1/2, cN0, and ISUP grading group >2 and/or prostate-specific antigen (PSA) >10 ng/mL) who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: In a period ranging from January 2014 to December 2018, 880 consecutive patients underwent RP with ePLND for PCa. Among these, 481 met the inclusion criteria and were selected. Data were prospectively collected within an institutional dataset and retrospectively analyzed. Age (years), body mass index (BMI; kg/m2), PSA (ng/mL), prostate volume (mL), and biopsy positive cores (BPC; %) were recorded for each case. BMI and BPC were considered continuous and categorical variables, respectively. The logistic regression models evaluated the association of clinical factors with the risk of nodal metastases. RESULTS: LNI was detected in 73/418 patients (15.2%) of whom 40/418 (8.3%) harbored multiple LNI (median 2, IQR: 3-4). On multivariate analysis, BMI was independently associated with the risk of multiple LNI in the pathological specimen when compared with patients without LNI (OR = 1.147; p = 0.018), as well as the percentage of biopsy positive cores (OR = 1.028; p < 0.0001) and European Association of Urology high-risk class (OR = 5.486; p < 0.0001). BMI was the only predictor of multiple LNI when compared with patients with 1 positive node (OR = 1.189, p = 0.027). CONCLUSIONS: In intermediate- and high-risk localized PCa, BMI was an independent predictor of the risk of multiple lymph node metastases. The inclusion of BMI within LNI risk calculators could be helpful, and a detailed counseling in obese patients should be required.

Prostate volume index and prostatic chronic inflammation predicted low tumor load in 945 patients at baseline prostate biopsy.

PURPOSE: To assess associations of prostate volume index (PVI), defined as the ratio of the volume of the central transition zone to the volume of the peripheral zone of the prostate and prostatic chronic inflammation (PCI) as predictors of tumor load by number of positive cores (PC) in patients undergoing baseline random biopsies. METHODS: Parameters evaluated included age, PSA, total prostate volume, PSA density, digital rectal exam, PVI, and PCI. All patients underwent standard transperineal random biopsies. Tumor load was evaluated as absent (no PC), limited (1-3 PC), and extensive (more than 3 PC). The association of factors with the risk of tumor load was evaluated by the multinomial logistic regression model. RESULTS: The study evaluated 945 patients. Cancer PC were detected in 477 (507%) cases of whom 207 (43.4%) had limited tumor load and 270 (56.6%) had extensive tumor load. Among other factors, comparing patients with limited tumor load with negative cases, PVI [odds ratio, OR = 0.521, 95% confidence interval (CI) 0.330-0.824; p < 0.005] and PCI (OR = 0.289, 95% CI 0.180-0.466; p < 0.0001) were inversely associated with the PCA risk. Comparing patients with extensive tumor load with negative patients, PVI (OR = 0.579, 95% CI 0.356-0.944; p = 0.028), and PCI (OR = 0.150, 95% CI 0.085-0.265; p < 0.0001), predicted PCA risk. Comparing extensive tumor load with limited tumor load patients, PVI and PCI did not show any association with the tumor load. CONCLUSIONS: Increased PVI and the presence of PCI decreased the risk of increased tumor load and associated with less aggressive prostate cancer biology in patients at baseline random biopsies.

The impact of extended pelvic lymph node dissection on the risk of hospital readmission within 180 days after robot assisted radical prostatectomy.

OBJECTIVE: To evaluate the factors associated with the risk of hospital readmission after robot assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer (PCA) over a long term. MATERIALS AND METHODS: The risk of readmission was evaluated by clinical, pathological, and perioperative factors. Skilled and experienced surgeons performed the procedures. Patients were followed for complications and hospital readmission for a period of six months. The logistic regression model and Cox's proportional hazards assessed the association of factors with the risk of readmission. RESULTS: From January 2013 to December 2018, 890 patients underwent RARP; ePLND was performed in 495 of these patients. Hospital readmission was detected in 25 cases (2.8%); moreover, it was more frequent when RARP was performed with ePLND (4.4% of cases) than without (0.8% of patients). On the final multivariate model, ePLND was the only independent factor that was positively associated with the risk of hospital readmission (hazard ratio, HR = 5935; 95%CI 1777-19,831; p = 0.004). CONCLUSIONS: Over the long term after RARP for PCA, the risk of hospital readmission is associated with ePLND. In patients who underwent RARP and ePLND, 4.4% of them had a readmission, compared to RARP alone, in which only 0.8% of cases had a readmission. When ePLND is planned for staging pelvic lymph nodes, patients should be informed of the increased risk of hospital readmission.

External validation of Cormio nomogram for predicting all prostate cancers and clinically significant prostate cancers.

PURPOSE: Recently, the Cormio et al. nomogram has been developed to predict prostate cancer (PCa) and clinically significant PCa using benign prostatic obstruction parameters. The aim of the present study was to externally validate the nomogram in a multicentric cohort. METHODS: Between 2013 and 2019, patients scheduled for ultrasound-guided prostate biopsy were prospectively enrolled at 11 Italian institutions. Demographic, clinical and histological data were collected and analysed. Discrimination and calibration of Cormio nomogram were assessed with the receiver operator characteristics (ROC) curve and calibration plots. The clinical net benefit of the nomogram was assessed with decision curve analysis. Clinically significant PCa was defined as ISUP grade group > 1. RESULTS: After accounting for inclusion criteria, 1377 patients were analysed. 816/1377 (59%) had cancer at final pathology (574/816, 70%, clinically significant PCa). Multivariable analysis showed age, prostate volume, DRE and post-voided residual volume as independent predictors of any PCa. Discrimination of the nomogram for cancer was 0.70 on ROC analysis. Calibration of the nomogram was excellent (p = 0.94) and the nomogram presented a net benefit in the 40-80% range of probabilities. Multivariable analysis for predictors of clinically significant PCa found age, PSA, prostate volume and DRE as independent variables. Discrimination of the nomogram was 0.73. Calibration was poor (p = 0.001) and the nomogram presented a net benefit in the 25-75% range of probabilities. CONCLUSION: We confirmed that the Cormio nomogram can be used to predict the risk of PCa in patients at increased risk. Implementation of the nomogram in clinical practice will better define its role in the patient's counselling before prostate biopsy.

Association between Basal Total Testosterone Levels and Prostate Cancer D'Amico Risk Classes.

OBJECTIVE: To test the hypothesis that basal total testosterone (TT) serum levels are associated with the D'Amico risk classification at diagnosis of prostate cancer (PCA). MATERIALS AND METHODS: From November 2014 to March 2018, preoperative basal levels of TT and prostate-specific antigen (PSA) were measured in 601 consecutive PCA patients who were not under androgen deprivation therapy or undergoing prior prostate surgery. Patients were classified into low (reference group), intermediate, and high risk classes according to biopsy findings. The association of TT and other clinical factors with risk classes was evaluated using a multivariate multinomial logistic regression model. RESULTS: According to the D'Amico classification, 124 patients (24%) were low risk, 316 (52.6%) were intermediate risk, and 141 (23.4%) were high risk. Median basal TT circulating levels were significantly increased along clinical risk classes. TT along with PSA, percentage of biopsy positive cores, and tumor clinical stage were independently associated with a high risk (OR = 1.002; p = 0.022) but not with an intermediate risk of PCA when compared to the low risk class. In the intermediate-risk group, endogenous TT together with PSA were independently associated with tumor grade groups 2 (OR = 1.003; p = 0.022) and 3 (OR = 1.003; p = 0.043) compared to grade group 1 cancers. CONCLUSIONS: Basal TT levels are positively associated with the D'Amico risk classification, but the association is significant for the high-risk group compared to the low-risk group.

Predictive Factors of the Risk of Long-Term Hospital Readmission after Primary Prostate Surgery at a Single Tertiary Referral Center: Preliminary Report.

OBJECTIVE: To evaluate the predictors of the risk of long-term hospital readmission after radical prostatectomy (RP) in a single tertiary referral center where both open RP (ORP) and robot assisted RP (RARP) are performed. MATERIALS AND METHODS: The risk of readmission was evaluated by clinical, pathological, and perioperative factors. Skilled and experienced surgeons performed the 2 surgical approaches. Patients were followed for complications and hospital readmission for a period of 6 months. The association of factors with the risk of readmission was assessed by Cox's multivariate proportional hazards. RESULTS: From December 2013 to 2017, 885 patients underwent RP. RARP was performed in 733 cases and ORP in 152 subjects. Extended pelvic lymph node dissection (ePLND) was performed in 479 patients. Hospital readmission was detected in 46 cases (5.2%). Using a multivariate model, independent factors associated with the risk of hospital readmission were seminal vesicle invasion (hazard ratio [HR] 2.065; 95% CI 1.116-3.283; p = 0.021), ORP (HR 3.506; 95% CI 1.919-6.405; p < 0.0001), and ePLND (HR 5.172; 95% CI 1.778-15.053; p < 0.0001). CONCLUSIONS: In a large single tertiary referral center, independent predictors of the risk of long-term hospital readmission after RP included ORP, ePLND, and seminal vesicle invasion. When surgery is chosen as a primary treatment of PCA, patients should be informed of the risk of long-term hospital readmission and its related risk factors.

Elevated prostate volume index and prostatic chronic inflammation reduce the number of positive cores at first prostate biopsy set: results in 945 consecutive patients.

OBJECTIVE: To assess the association between prostate volume index (PVI), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA). PVI is the ratio between the central transition zone volume (CTZV) and the peripheral zone volume (PZV). MATERIALS AND METHODS: Parameters evaluated included age, prostate specific antigen (PSA), total prostate volume (TPV), PSA density (PSAD), digital rectal exam (DRE), PVI, PCI and number of positive cores (NPC). All patients underwent baseline 14-core, trans-perineal random biopsies. Associations of parameters with the NPC were investigated by univariate and multivariate linear regression analysis. RESULTS: Between September 2010 to September 2017, 945 patients were evaluated. PCA was detected in 477 cases (50.7%), PCI in 205 cases (21.7%). PCA patients, compared to negative cases, were older (68.3 vs. 64.4 years) with smaller TPV (36 vs. 48.3mL) and CTZV (19.2 vs. 25.4), higher PSAD (0.24 vs. 0.15ng/mL/mL), further PVI values were lower (0.9 vs. 1.18) and biopsy cores less frequently involved by PCI (9.4% vs. 34.2%). High PVI and the presence of PCI were independent negative predictors of NPC in model I considering PSA and TVP (PVI, regression coefficient, RC -0,6; p=0.002) and PCI (RC -1,4; p<0.0001); and in model II considering PSAD (PVI:RC -0,7; p<0,0001; and PCI: RC -1,5; p<0.0001). CONCLUSIONS: High PVI and the presence of PCI lowered the mean rate of NPC and is associated with less aggressive tumor biology expressed by low tumor burden. PVI can give prognostic information before planning baseline random biopsies. Confirmatory studies are required.

Prostate Volume Index Is Able to Differentiate between Prostatic Chronic Inflammation and Prostate Cancer in Patients with Normal Digital Rectal Examination and Prostate-Specific Antigen Values <10 ng/mL: Results of 564 Biopsy Naïve Cases.

INTRODUCTION: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies. METHODS: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC. RESULTS: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62-1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81-1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk. CONCLUSIONS: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA.

Lymph Nodes Invasion of Marcille's Fossa Associates with High Metastatic Load in Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection: The Role of "Marcillectomy".

INTRODUCTION: To assess the incidence of malignancy involvement of lymph nodes (LNs) in Marcille's fossa in patients undergoing robot assisted radical prostatectomy (RARP) and extended pelvic lymph nodes dissection (ePLND) for prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: Between January 2014 and December 2017, details of patients who underwent RARP and ePLND were prospectively analysed. All the nodal packets were dissected separately, grouped into left and right nodes and submitted in separate packages to dedicated pathologist. RESULTS AND LIMITATIONS: Two hundred and twenty-one patients underwent ePLND and RARP in the study period. In aggregate, Marcille's LNs involvement was found in 5 (2.3%) of patients, 2 on the left side and 3 on the right side. Per cent of positive cores and Gleason at biopsy are clinical predictors of LNs invasion; moreover, in the surgical specimen, seminal vesicle invasion and high-grade cancer were factors related to loco-regional metastases. CONCLUSIONS: Marcille's nodes involvement is associated to contemporarily multiple LN metastases in other template locations in high-risk PCa patients. The Marcille's lymphadenectomy would be recommended when planning an ePLND in high-risk PCa.

Positive Association between Basal Total Testosterone Circulating Levels and Tumor Grade Groups at the Time of Diagnosis of Prostate Cancer.

INTRODUCTION: To test the hypothesis that basal total testosterone (TT) levels are associated with International Society of Urologic Pathology (ISUP) tumor grade groups at the time of diagnosis of prostate cancer (PCA). METHODS: From November 2014 to March 2018, preoperative TT and PSA were measured in 601 consecutive patients who were not under androgen deprivation and undergoing surgery for PCA. Patients were classified into low (ISUP 1; reference group), intermediate (ISUP 2/3), and high (ISUP 4/5) tumor grade groups. The association of TT and other clinical factors with tumor groups was evaluated by multinomial multivariate regression analysis. RESULTS: 218 patients (36.3%) were biopsy low grade (ISUP 1), 297 (49.4%) intermediate grade (ISUP 2/3), and 86 (14.3) high grade (ISUP 4/5). Median basal circulating TT levels progressively increased as tumor grade groups increased. On multivariate models, TT, among other clinical factors, was positively associated with the risk of intermediate (OR 1.001; p = 0.023) and high tumor grades (OR 1.002, p = 0.022) compared to low-grade cancers. CONCLUSIONS: Increased endogenous circulating basal TT levels were positively associated with ISUP tumor grade groups at the time of diagnosis indicating a close association with tumor biology. Basal TT levels may reflect the heterogeneity of the cancer population.

Positive Association between Preoperative Total Testosterone Levels and Risk of Positive Surgical Margins by Prostate Cancer: Results in 476 Consecutive Patients Treated Only by Radical Prostatectomy.

OBJECTIVE: To evaluate preoperative total testosterone (TT) as a predictor of positive surgical margins (PSM) in prostate cancer (PCA). PATIENTS AND METHODS: During the period from November 2014 to July 2017, preoperative TT was measured in 476 PCA patients undergoing only radical prostatectomy (RP) and including all risk classes. Surgical margins were stated negative, focal positive (single and less than 1 mL), and multifocal positive (more than 1). The risk of TT and clinical factors associated with the risk of PSM (focal or multifocal versus negative) was evaluated by the multinomial logistic regression model. RESULTS: Overall, PSM were detected in 149 cases (31.3%), which included 99 patients with focal cancer invasion (20.8%) and 50 subjects with multifocal cancer invasion (10.5%). In univariate analysis, PSM associated with higher median levels of TT and prostate-specific antigen than controls. Multifocal PSM associated with higher rates of high-risk PCA (42%) than focal (22.2%) or control cases (18.3%). In multivariate analysis, TT was the only independent factor positively associated with the risk of focal PSM when compared to controls (OR 1.002; p = 0.035). TT (OR 1.003; p = 0.002) and high-risk PCA (OR 1.002; p = 0.047) were independent factors, which positively associated with the risk of multifocal PSM when compared to controls. Risk models were computed. CONCLUSIONS: In a large and contemporary cohort of patients elected to primary RP, TT was an -independent positive factor associated with the risk of focal and multifocal PSM. TT associated with aggressive PCA biology.

Inverse Association of Prostatic Chronic Inflammation among Prostate Cancer Tumor Grade Groups: Retrospective Study of 738 Consecutive Cases Elected to a First Random Biopsy Set.

OBJECTIVES: The study aimed to evaluate associations of prostatic chronic inflammation (PCI) with prostate cancer (PCA) grade groups by the International Society of Urological Pathology (ISUP). METHODS: The study evaluated retrospectively 738 cases. The patient population was sampled into 3 groups collecting cases without and with PCA including subjects with lSUP grade group 1 and grade groups 2-5. RESULTS: PCI was assessed in 185 patients (25.1%) and PCA in 361 patients (48.9%) of whom 188 (25.5%) had ISUP grade and 173 (23.4%) had ISUP groups 2-5 tumors. PCI inversely related to ISUP groups (p < 0.0001). In multivariate analysis, the risk of ISUP grade group 1 PCA compared to negative cases associated positively with age (OR 1.042; p = 0.001) but inversely with total prostate volume (TPV; OR 0.965; p < 0.0001) and PCI (OR 0.314; p < 0.0001). Intermediate-high grade tumors associated positively with age (OR 1.065; p < 0.0001), prostate specific antigen (OR 1.167; p < 0.0001), and abnormal digital rectal examination (OR 2.251; p < 0.0001) but inversely with TPV (OR 0.921; p < 0.0001) and PCI (OR 0.106; p < 0.0001). CONCLUSIONS: PCI decreased the risk of PCA among ISUP tumor grade groups.

Late sodium current and intracellular ionic homeostasis in acute ischemia.

Blockade of the late Na+ current (I NaL) protects from ischemia/reperfusion damage; nevertheless, information on changes in I NaL during acute ischemia and their effect on intracellular milieu is missing. I NaL, cytosolic Na+ and Ca2+ activities (Nacyt, Cacyt) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I NaL blockade. The results indicate that I NaL was enhanced during ISC in spite of changes in action potential (AP) contour; I NaL significantly contributed to Nacyt rise, but only marginally to Cacyt rise. The impact of I NaL on Cacyt was markedly enhanced by blockade of the sarcolemmal(s) Na+/Ca2+ exchanger (NCX) and was due to the presence of (Na+-sensitive) Ca2+ efflux through mitochondrial NCX (mNCX). sNCX blockade increased Cacyt and decreased Nacyt, thus indicating that, throughout ISC, sNCX operated in the forward mode, in spite of the substantial Nacyt increment. Thus, a robust Ca2+ source, other than sNCX and including mitochondria, contributed to Cacyt during ISC. Most, but not all, of RAN effects were shared by TTX. (1) The paradigm that attributes Cacyt accumulation during acute ischemia to decrease/reversal of sNCX transport may not be of general applicability; (2) I NaL is enhanced during ISC, when the effect of Nacyt on mitochondrial Ca2+ transport may substantially contribute to I NaL impact on Cacyt; (3) RAN may act mostly, but not exclusively, through I NaL blockade during ISC.