Independent external validation of nomogram to predict extracapsular extension in patients with prostate cancer.

INTRODUCTION: The objective of this study was to perform an independent external validation of the Giganti-Coppola nomogram (GCN), which uses clinical and radiological parameters to predict prostate extracapsular extension (ECE) on the final pathology of patients undergoing radical prostatectomy (RP). MATERIAL AND METHODS: Seventy-two patients diagnosed with prostate cancer (PCa), who were RP candidates from two institutions, were prospectively included. All patients underwent preoperative multi-parametric magnetic resonance imaging (mpMRI) at 1.5 T, without the use of an endorectal coil, with multiplanar images in T1WI, T2WI, DWI, and DCE. The AUC and a calibration graph were used to validate the nomogram, using the regression coefficients of the Giganti-Coppola study. RESULTS: The original nomogram had an AUC of 0.90 (p = 0.001), with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 5.1%, 47.1%, 100%, and 48%, respectively. The calibration graph showed an overestimation of the nomogram for ECE. CONCLUSION: The GCN has an adequate ability in predicting ECE; however, in our sample, it showed limited accuracy and overestimated likelihood of ECE in the final pathology of patients with PCa submitted to RP. KEY POINTS: • Knowledge of preoperative local staging of prostate cancer is essential for surgical treatment. Extracapsular extension increases the chance of positive surgical margins. • Imaging modalities such as mpMRI alone does not have suitable accuracy in local staging. • Giganti-Coppola's nomogram achieved an adequate ability in predicting ECE.

PTEN-deficient prostate cancer is associated with an immunosuppressive tumor microenvironment mediated by increased expression of IDO1 and infiltrating FoxP3+ T regulatory cells.

BACKGROUND: Accumulating evidence shows that tumor cell-specific genomic changes can influence the cross talk between cancer cells and the surrounding tumor microenvironment (TME). Loss of the PTEN tumor suppressor gene is observed in 20% to 30% of prostate cancers (PCa) when first detected and the rate increases with PCa progression and advanced disease. Recent findings implicate a role for PTEN in cellular type I interferon response and immunosuppression in PCa. However, the way that PTEN inactivation alters antitumor immune response in PCa is poorly understood. MATERIALS AND METHODS: To investigate the changes associated with PTEN loss and an immunosuppressive TME in PCa, we used CIBERSORT to estimate the relative abundance of 22 immune-cell types from 741 primary and 96 metastatic tumors. Our in silico findings were then validated by immunohistochemical analysis of immune cells and IDO1 and PDL1 checkpoint proteins in a cohort of 94 radical prostatectomy specimens. RESULTS: FoxP3+ T regulatory cells (Tregs) were significantly increased in PTEN-deficient PCa in all three public domain cohorts. Loss of PTEN in bone metastases was associated with lower CD8+ T-cell abundance, but in liver metastasis, FoxP3+ Tregs were present at higher levels. PTEN-deficient lymph node metastasis had a distinct profile, with high levels of CD8+ T cells. Moreover, we found that metastatic PCa presents higher abundance of FoxP3+ Treg when compared to primary lesions. Since PTEN-deficient tumors are likely to be immunosuppressed as a consequence of increased FoxP3+ Tregs, we then evaluated the localization and expression of IDO1, PDL1 immune checkpoints, and the corresponding density of FoxP3+ Treg and CD8+ T cells using our validation cohort (n = 94). We found that IDO1 protein expression and FoxP3+ Treg density were higher in neoplastic glands compared with benign adjacent tissue. Moreover, higher densities of FoxP3+ Treg cells in both stromal (P = 0.04) and tumor (P = 0.006) compartments were observed in PTEN-deficient tumors compared to tumors that retained PTEN activity. Similarly, IDO1 protein expression was significantly increased in the tumor glands of PTEN-deficient PCa (P < 0.0001). Spearman correlation analysis showed that IDO1 expression was significantly associated with FoxP3+ Treg and CD8+ T-cell density (P < 0.01). CONCLUSIONS: Our findings imply that PTEN deficiency is linked to an immunosuppressive state in PCa with distinct changes in the frequency of immune cell types in tumors from different metastatic sites. Our data suggest that determining PTEN status may also help guide the selection of patients for future immunotherapy trials in localized and metastatic PCa.

L-Methionine inhibits growth of human pancreatic cancer cells.

We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 days or for 3 days, followed by 4 days of culture without L-methionine (recovery). Cell proliferation, apoptosis, and cell cycle effects were assessed by flow cytometry after staining for Ki-67 or annexin V/propidium iodide. Cell proliferation was reduced by 31-35% after 7 days of methionine exposure; the effect persisted in BXPC-3 and HPAC cells after 4 days of recovery. Methionine increased apoptosis by 40-75% in HPAC cells, but not in BXPC-3 cells. Continuous exposure to methionine caused accumulation of BXPC-3 cells in the S phase and HPAC cells in both the G0/G1 and S phases; however, after 4 days of recovery, these effects disappeared. In conclusion, L-methionine inhibits proliferation and interferes with the cell cycle of BXPC-3 and HPAC pancreatic cancer cells; the effects on apoptosis remarkably persisted after methionine withdrawal. Apoptosis was induced only in BXPC-3 cells. Some of the differences in the effects of methionine between cell lines may be related to disparate p53 status. These findings warrant further studies on the potential therapeutic benefit of L-methionine against pancreatic cancer.

The incremental value of Histogram Analysis in the differentiation between hyperdense cysts and solid renal masses on unenhanced CT images.

PURPOSE: To investigate the utility of voxel histogram analysis (HA) for differentiating hyperdense renal cysts from small solid masses on unenhanced computed tomography (CT) scans. METHODS: A retrospective analysis of 99 hyperdense cystic lesions and 28 solid malignant lesions was conducted using a radiological database (from 2015 to 2021) and a pathological database (from 2010 to 2020). The study investigated the distribution of voxel attenuation values using percentiles to establish reliable criteria for differentiation after drawing a region of interest (ROI) in the centre of the lesions. The standard of reference was a histopathological diagnosis for malignant masses and contrast-enhanced CT or magnetic resonance imaging (MRI) for cysts. RESULTS: HA provided higher diagnostic accuracy than the conventional mean attenuation value of 70 Hounsfield Units (HU). For the 75th and 90th percentiles ± 1 standard deviation, accuracies of 77.2% (95% confidence interval 68.9-84.2%) for the 75th and 68.5% (59.7-76.4%) for the 90th were found, versus 37.0% (28.6-46.0%) for the 70 HU threshold criterion. A Gaussian distribution of voxel attenuation values was observed in 88.9% of the lesions, suggesting that it is feasible to calculate these parameters from a single measurement. CONCLUSION: The study underscores the potential of HA as a valuable tool for characterizing hyperdense cysts on unenhanced CT by using the same ROI for measuring lesion attenuation. HA could offer additional value beyond the 70 HU criterion and possibly influence clinical decisions. Multi-institutional studies are necessary for external validation to confirm its generalizability and more extensive applicability.

Association between family history of prostate cancer and positive biopsies in a Brazilian screening program.

PURPOSE: To test the association between family history of prostate cancer (FH) and prostate cancer (PCa) risk in a large screening program in Brazil, as no conclusive study has yet investigated this. METHODS: Between 2004 and 2007, 17,569 men were screened in 231 small municipalities using mobile screening units. Positive FH was defined as any relative having PCa among screened men. Men were biopsied if they had digital rectal examination suggestive of PCa or PSA >4.0 ng/mL or PSA of 2.5-4 ng/mL with percent free PSA ≤ 15 %. We analyzed the association between FH and PCa using multivariable logistic regression in the first screening round of the program. RESULTS: Positive FH was present in 735 men (4.2 % of total), and they were younger, better educated and more likely to have had previous PCa screening (41.5 vs. 28.5 %; P < 0.001) compared to men with negative FH. FH status did not affect compliance rates in men recommended to undergo biopsy (P = 0.94). In first round, PCa was detected in 3.1 % of screened men (n = 552). In multivariable analysis, positive FH was associated with increased PCa risk (OR = 1.79; 95 % CI, 1.21-2.65; P = 0.003). However, Gleason scores (P = 0.78) or percent of positive cores (P = 0.32) among men with positive biopsies were similar, regardless of FH status. CONCLUSIONS: In Brazil, men with positive FH were at increased PCa risk, which could not be explained by differential biopsy rates. This finding suggests that FH is also a true PCa risk factor in Brazil, a country with highly diverse population in terms of race, ethnicity, culture and socioeconomic status.

Association between literacy, compliance with prostate cancer screening, and cancer aggressiveness: results from a Brazilian screening study.

PURPOSE: Little is known about the effects of literacy levels on prostate cancer screening. This study evaluates the association between literacy, compliance with screening, and biopsy findings in a large Brazilian screening study. MATERIALS AND METHODS: We analyzed 17,571 men screened for PCa with digital rectal examination (DRE) and total and free prostate-specific antigen (PSA) from January 2004 to December 2007. Of those, 17,558 men had information regarding literate status. Full urological evaluation in a specialized cancer center was recommended in the case of: a) suspicious DRE, b) PSA > 4.0 ng/mL, or c) PSA 2.5-3.9 ng/mL and free/total PSA (f/tPSA) ratio 15%. Transrectal ultrasound guided prostate biopsy (14 cores) was performed upon confirmation of these findings after the patient's consent. Patients' compliance with screening recommendations and biopsy results were evaluated according to literacy levels. RESULTS: an abnormal PSA, a suspicious DRE, or both were present in 73.2%, 19.7%, and 7.1% of those men who underwent biopsy, respectively. PCa was diagnosed in 652 men (3.7%). Previous PSAs or DREs were less common among illiterate men (p < 0.0001). Additionally, illiterate men were less prone to attend to further evaluations due to an abnormal PSA or DRE (p < 0.0001). PSA levels > 10 mg/mL (p = 0.03), clinical stage > T2a (p = 0.005), and biopsy Gleason > 7 (p = 0.02) were more common among illiterate men. CONCLUSIONS: In a screened population, literacy levels were associated with prior PCa evaluations and with compliance with screening protocols. Illiterate men were at higher risk of being diagnosed with more advanced and aggressive PCa.

Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence.

The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers (n=53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN, SFRP2, and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR, we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1, PGR, VCAN, and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-ß. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer.

What is the impact of dynamic contrast-enhancement sequence in the Vesical Imaging, Reporting and Data System (VI-RADS)? A subgroup analysis.

BACKGROUND: A scoring system focusing on the risk of muscle layer invasion by Bladder cancer (BCa) has been released, Vesical Imaging - Radiological and Data System (VI-RADS), with a growing interest in evaluating its diagnostic accuracy. Our goal was to assess the accuracy and reproducibility of the VI-RADS score for assessment of the vesical muscular layer with (multiparametric-mp) and without (biparametric-bp) a dynamic-contrast enhancement (DCE) sequence. METHODS: Retrospective study conducted from July 2018 to July 2020. All patients had suspicions of BCa and underwent Magnetic Resonance Imaging (MRI) before any intervention. MRI was interpreted by two radiologists with different levels of experience, and a VI-RADS score assigned in two different sessions (3 months apart) without and with DCE. After exclusions, 44 patients with 50 lesions were enrolled. The standard of reference was transurethral resection in 18 patients (40.9%) and cystectomy in 26 patients (59.1%). RESULTS: Twenty-five lesions (50%) were muscle-invasive. There was no significant difference between the two groups for gender and presence of a stalk, but mean age of NMIBCa group was significantly higher (p = 0.01). The sizes of lesions were significantly different between groups for both readers at 2.42+/- 1.58 vs. 5.70+/- 2.67 cm for reader 1 (p < 0.0001) and 2.37+/- 1.50 vs. 5.44 +/- 2.90 cm for reader 2 (p = 0.001). The area under the curve (AUC) for muscle invasion with mpVI-RADS, considering all lesions, was 0.885 +/- 0.04 (95% CI-0.79-0.98) for reader 1 and 0.924 +/- 0.04 (0.84-0.99) for reader 2, and for bpVI-RADS was 0.879+/- 0.05 and 0.916 +/- 0.04 (0.85-0.99), respectively, both differences not statistically significant (p = 0.24 and 0.07, respectively). When considering only small lesions (< 3.0 cm), the accuracy for mpVI-RADS was 0.795 +/- 0.11 (0.57-1.0) for reader1, and 0.80 +/- 0.11(0.57-1.0) for reader 2, a non-significant difference (p = 0.56) and for bpVI-RADS was 0.747 +/- 0.12 (0.50-0.99) for reader 1 and 0.80 +/- 0.11(0.57-1.0) for reader 2, a significant difference (p = 0.04). The intraclass correlation coefficient for the final score was 0.81 (0.60-1.0) for mpVI-RADS and 0.85 (0.63-1.0) for bpVI-RADS. CONCLUSION: The VI-RADS system was accurate in demonstrating muscle-invasive BCa, for both experienced and less experienced reader, regardless of the use of a DCE sequence. However, when only small lesions were assessed the difference between the two readers was significant only for the biparametric analysis. The reproducibility was similar between multiparametric and biparametric approach.

Implications of Regionalizing Care in the Developing World: Impact of Distance to Referral Center on Compliance to Biopsy Recommendations in a Brazilian Prostate Cancer Screening Cohort.

Given growing specialization in medical care, optimal care may require regionalization, which may create access barriers. We tested this within a large prostate cancer (PC) screening program in Brazil. In 2004-2007, Barretos Cancer Hospital prospectively screened men for PC throughout rural Brazil. Men with abnormal screen were referred for follow-up and possible biopsy. We tested the link between distance from screening site to Barretos Cancer Hospital and risk of noncompliance with showing up for biopsy, PC on biopsy and, among those with PC, PC grade using crude and multivariable logistic regression analysis. Among 10,467 men undergoing initial screen, median distance was 257 km (IQR: 135-718 km). On crude and multivariable analyses, farther distance was significantly linked with biopsy noncompliance (OR/100 km: 0.83, P < 0.001). Among men who lived within 150 km of Barretos Cancer Hospital, distance was unrelated to compliance (OR/100 km: 1.09, P=0.87). There was no association between distance and PC risk or PC grade (all P > 0.25). In Brazil, where distances to referral centers can be large, greater distance was related to reduced biopsy compliance in a PC screening cohort. Among men who lived within 150 km, distance was unrelated to compliance. Care regionalization may reduce access when distances are large.

Predicting Adherent Perinephric Fat Using Preoperative Clinical and Radiological Factors in Patients Undergoing Partial Nephrectomy.

BACKGROUND: The decision to perform a partial nephrectomy (PN) relies largely upon the complexity of the renal mass and its surrounding anatomy. The presence of adherent perinephric fat (APF) can increase surgical complexity and extend operative times. The accurate prediction of APF may improve surgical planning and aid in decision making for the surgical approach. OBJECTIVE: We sought to develop and externally validate a score that predicts APF based on preoperative clinical and radiological prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed 495 consecutive patients who underwent open or minimally invasive PN. APF was defined as the presence of "dense," "adherent," or "sticky" perinephric fat at the time of dissection by the surgeon, and this did not require subcapsular dissection. Additionally, we analyzed an independent cohort of 285 patients for external validation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A score model was developed using multivariate logistic regression analysis. Calibration of the fitted model was assessed graphically with a plot of the predicted versus the actual probability of APF, and discrimination was assessed by calculating the area under the receiver operating characteristic curve. RESULTS AND LIMITATIONS: Of the 495 patients, 95 (19%) had APF. Patients with APF had longer operative (p=0.02) and arterial clamp (p=0.01) times than non-APF patients. On multivariate analyses, diabetes mellitus (p=0.009), posterior perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) were predictors of encountering APF in PN. A risk score ranging from 0 to 4 was developed based on these three variables to predict APF. The scoring system demonstrated good discrimination of 0.82 and 0.84 for the development and external validation cohorts, respectively. CONCLUSIONS: The APF score can accurately predict the presence of APF in patients with a small renal mass who are planning to undergo PN. This score could aid in pre- and intraoperative planning and impact the surgical approach. PATIENT SUMMARY: The presence of "sticky" fat surrounding the kidney in patients undergoing partial nephrectomy has previously been linked to longer operative times, intraoperative complications, and surgical conversion. In our study, we found that this feature is more often presented in patients with diabetes mellitus, and thicker and more inflammatory fat on renal imaging. Based on these findings, we developed a risk score that can accurately predict this feature before surgery, in order to improve surgical planning and better counsel the patients.

A systematic review and meta-analysis of bone metabolism in prostate adenocarcinoma.

BACKGROUND: Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (PCa) and with PCa per se. The objective of this review is to determine the incidence of bone loss and osteoporosis in patients with PCa who are or are not treated with hormone therapy (ADT). METHODS: The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published studies on prostate cancer and bone metabolism. The outcomes assessed were: fracture, osteoporosis and osteopenia. RESULTS: Thirty-two articles (116,911 participants) were included in the meta-analysis. PCa patients under ADT had a higher risk of osteoporosis (RR, 1.30; p < 0.00001) and a higher risk of fractures (RR, 1.17; p < 0.00001) as compared to patients not under ADT. The total bone mineral density was lower in patients under ADT when compared with patients not under ADT (p = 0.031) but it was similar to bone mineral density found in healthy controls (p = 0.895). The time of androgen deprivation therapy correlated negatively with lumbar spine and total hip bone mineral density (Spearman's rho = -0.490 and -0.773; p = 0.028 and 0.001, respectively) and with total hip t score (Spearman's rho = -0.900; p = 0.037). CONCLUSION: We found consistent evidence that the use of androgen deprivation therapy in patients with PCa reduces bone mineral density, increasing the risk of fractures in these patients.

Diagnostic accuracy of signal loss in in-phase gradient-echo images for differentiation between small renal cell carcinoma and lipid-poor angiomyolipomas.

OBJECTIVES: To assess the diagnostic accuracy of signal loss on in-phase (IP) gradient-echo (GRE) images for differentiation between renal cell carcinomas (RCCs) and lipid-poor angiomyolipomas (lpAMLs). METHODS: We retrospectively searched our institutional database for histologically proven small RCCs (<5.0 cm) and AMLs without visible macroscopic fat (lpAMLs). Two experienced radiologists assessed MRIs qualitatively, to depict signal loss foci on IP GRE images. A third radiologist drew regions of interest (ROIs) on the same lesions, on IP and out-of-phase (OP) images to calculate the ratio of signal loss. Diagnostic accuracy parameters were calculated for both techniques and the inter-reader agreement for the qualitative analysis was evaluated using the κ test. RESULTS: 15 (38.4%) RCCs lost their signal on IP images, with a sensitivity of 38.5% (95% CI = 23.4-55.4), a specificity of 100% (71.1-100), a positive predictive value (PPV) of 100% (73.4-100), a negative predictive value (NPV) of 31.4% (26.3-37.0), and an overall accuracy of 52% (37.4-66.3%). In terms of the quantitative analysis, the signal intensity index (SII= [(SIIP - SIOP) / SIOP] x 100) for RCCs was -0.132 ± 0.05, while for AMLs it was -0.031 ± 0.02, p = 0.26. The AUC was 0.414 ± -0.09 (0.237-0.592). Using 19% of signal loss as the threshold, sensitivity was 16% and specificity was 100%. The κappa value for subjective analysis was 0.63. CONCLUSION: Signal loss in "IP" images, assessed subjectively, was highly specific for distinction between RCCs and lpAMLs, although with low sensitivity. The findings can be used to improve the preoperative diagnostic accuracy of MRI for renal masses. ADVANCES IN KNOWLEDGE: Signal loss on "IP" GRE images is a reliable sign for differentiation between RCC and lpAMLs.

Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN).

BACKGROUND: Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application. METHODS: PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided. RESULTS: PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment - Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy. CONCLUSIONS: Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery.

Assessing the cytotoxic potential of glycoalkaloidic extract in nanoparticles against bladder cancer cells.

OBJECTIVE: This study proposed to use the nanotechnology to deliver glycoalkaloidic extract (AE) to bladder cancer cells, evaluating their activity in 2D and 3D models and the biological mechanism of cell death. METHODS: NPs were prepared by nanoprecipitation method using polylactic acid (PLA) and characterized considering their size, charge, particle concentration and stability. The cytotoxicity was evaluated in 2D and 3D model, and the apoptosis and cell cycle were investigated using flow cytometry. KEY FINDINGS: NPs loading AE (NP-AE) had diameter around 125 ± 6 nm (PdI <0.1) and negative charge. The encapsulation efficiency of SM and SS was higher than 85% for both compounds. The obtained formulation showed a significant in-vitro cytotoxic effect against RT4 cells in a dose-dependent manner with IC50 two fold lower than the free AE. The cytotoxic effect of NP-AE was mediated by apoptosis and cell cycle arrested in the S phase. RT4 cells cultured under 3D conditions exhibited a higher resistance to the treatments (IC50 ~ three fold higher than in 2D cell culture). CONCLUSION: The NP-AE might be a promising nanocarrier to load and deliver glycoalkaloids against bladder cancer.

Multiparametric MRI of the prostate: diagnostic performance and interreader agreement of two scoring systems.

OBJECTIVE: To compare the diagnostic accuracies and interreader agreements of the Prostate Imaging Reporting and Data System (PI-RADS) v. 2 and University of California San Francisco (UCSF) multiparametric prostate MRI scale for diagnosing clinically significant prostate cancer. METHODS: This institutional review board-approved retrospective study included 49 males who had 1.5 T endorectal MRI and prostatectomy. Two radiologists scored suspicious lesions on MRI using PI-RADS v. 2 and the UCSF scale. Percent agreement, 2 × 2 tables and the area under the receiver operating characteristic curves (Az) were used to assess and compare the individual and overall scores of these scales. Interreader agreements were estimated with kappa statistics. RESULTS: Reader 1 (R1) detected 78 lesions, and Reader 2 (R2) detected 80 lesions. Both identified 52 of 65 significant cancers. The Az for PI-RADS v. 2 and UCSF scale for R1 were 0.68 and 0.69 [T2 weighted imaging (T2WI)], 0.75 and 0.68 [diffusion-weighted imaging (DWI)] and 0.64 and 0.72 (overall score), respectively, and were 0.72 and 0.75 (T2WI), 0.73 and 0.67 (DWI) and 0.66 and 0.75 (overall score) for R2. The dynamic contrast-enhanced percent agreements between scales were 100% (R1) and 95% (R2). PI-RADS v. 2 DWI of R1 performed better than UCSF DWI (Az = 0.75 vs Az = 0.68; p = 0.05); no other differences were found. The interreader agreements were higher for PI-RADS v. 2 (T2WI: 0.56 vs 0.42; DWI: 0.60 vs 0.46; overall: 0.61 vs 0.42). The UCSF approach to derive the overall PI-RADS v. 2 scores increased the Az for the identification of significant cancer (R1 to 0.76, p < 0.05; R2 to 0.71, p = 0.35). CONCLUSION: Although PI-RADS v. 2 DWI score may have a higher discriminatory performance than the UCSF scale counterpart to diagnose clinically significant cancer, the utilization of the UCSF scale weighing system for the integration of PI-RADS v. 2 individual parameter scores improved the accuracy its overall score. ADVANCES IN KNOWLEDGE: PI-RADS v. 2 is moderately accurate for the identification of clinically significant prostate cancer, but the utilization of alternative approaches to derive the overall PI-RADS v. 2 score, including the one used by the UCSF system, may improve its diagnostic accuracy.

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study.

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.

Radical Prostatectomy for Locally Advanced Prostate Cancer: Current Status.

In the past, prostate cancer (PC) could only be detected clinically, and delayed diagnosis of locally advanced or metastatic disease at presentation was common. Prostate-specific antigen testing and magnetic resonance imaging led to PC detection in a much earlier stage. However, controversy about the best treatment for locally advanced PC remains. Recent refinements in surgery and radiation therapy have improved outcomes, but no comparative study has yet conclusively determined superiority of one option over the other. In this review, we present the most recent evidence about the role of radical prostatectomy for locally advanced PC treatment from a surgeon's perspective.

Using Mitrofanoff's principle and Monti's technique as a surgical option for bladder augmentation with a continent stoma: a case report.

INTRODUCTION: Hydronephrosis, reflux and renal failure are serious complications that occur in patients with neurogenic bladder associated with myelomeningocele. When the bladder compliance is lost, it is imperative to carry out surgery aimed at reducing bladder storage pressure. An ileocystoplasty, and for patients not suitable for intermittent catheterization, using the Mitrofanoff principle to form a continent stoma and the subsequent closure of the bladder neck, can be used. We report here, for the first time to the best of our knowledge, an association between two previously described techniques (the Mitrofanoff principle and the technique of Monti), that can solve the problem of a short appendix in obese patients. CASE PRESENTATION: A 33-year-old male Caucasian patient with myelomeningocele and neurogenic bladder developed low bladder compliance (4.0 mL/cm H2O) while still maintaining normal renal function. A bladder augmentation (ileocystoplasty) with continent derivation principle (Mitrofanoff) was performed. During surgery, we found that the patient's appendix was too short and was insufficient to reach the skin. We decided to make an association between the Mitrofanoff conduit and the ileal technique of Monti, through which we performed an anastomosis of the distal stump of the appendix to the bladder (with an antireflux valve). Later, the proximal stump of the appendix was anastomosed to an ileal segment of 2.0 cm that was open longitudinally and reconfigured transversally (Monti technique), modeled by a 12-Fr urethral catheter, and finally, the distal stump was sutured at the patient's navel.After the procedure, a suprapubic cystostomy (22 Fr) and a Foley catheter (10 Fr) through the continent conduit were left in place. The patient had recovered well and was discharged on the tenth day after surgery. He remained with the Foley catheter (through the conduit) for 21 days and cystostomy for 30 days. Six months after surgery he was continent with good bladder compliance without reflux and fully adapted to catheterization through the navel. CONCLUSION: The unpublished association between the Mitrofanoff and Monti techniques is feasible and a very useful alternative in urologic cases of derivation continent in which the ileocecal appendix is too short to reach the skin (i.e., in obese patients).

Histologic study of urethral extracellular matrix and collagen from aging and long-term alloxan-induced diabetic male rats.

OBJECTIVES: To evaluate the histological alterations of extracellular matrix in long-term alloxan-induced diabetes and aging urethras of male rats with descriptions of total connective tissue, muscle layer and collagen types I and III relative amounts. METHODS: Histologic evaluations were performed in 3 animal groups: group 1, 8 weeks old; group 2, 44 weeks old; and group 3, 44 weeks old with alloxan-induced diabetes. The muscle layer thickness, extracellular matrix fibrosis, and collagen were quantified on digital images of the urethral samples. RESULTS: A higher total thickness and muscle layer thickness and higher connective tissue and collagen content were observed in the urethras of group 3. No changes in the collagen type III/I ratio were found in the urethra of groups 2 and 3. CONCLUSIONS: Our results suggest that the morphologic alterations of the urethra should also be considered in long-term studies of diabetic lower urinary tract dysfunction. These morphologic alterations due to diabetes differ from the changes induced by aging itself and could represent a final stage in decompensate urethras. Further studies are necessary to establish the real influence of the urethral morphologic changes on lower urinary tract diabetes dysfunction.