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Introduction: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process., Materials and Methods: A total 172 men with total prostate-specific antigen of 2-10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI., Results: Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors., Conclusions: PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient., (© 2018 S. Karger AG, Basel.)

Introduction: To investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy., Material and Methods: We reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m 2 (normal weight); 25-29.9 kg/m 2 (overweight); and ≥30 kg/m 2 (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve., Results: The obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63., Conclusions: The predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient's BMI., Competing Interests: The authors declare no conflicts of interest.

Purpose: Detection of DNA hypermethylation is emerging as a novel molecular biomarker for different malignancies. We intend to define whether a hypermethylation profile of patients with prostate cancer (PCa) predicts biochemical recurrence (BCR) after radical prostatectomy (RP)., Material and Methods: Genome-wide methylation analysis was performed using the GoldenGate Methylation Cancer Panel-I (Illumina, Inc.) on 10 normal prostate tissues and 58 tumor samples from patients treated by RP followed for prostate-specific antigen (PSA) failure (>0.4 ng/ml) and disease progression. Patients were classified on the basis of D'Amico criteria according to clinical staging, PSA at diagnosis and Gleason score after pathologist review. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Hierarchical clustering analysis was performed and relationships with outcome were investigated using log-rank analysis and Cox regression model., Results: We found 28 genes significantly hypermethylated in >20% of the tumors analyzed. Four clusters of patients were characterized by their DNA methylation profile, one at higher risk to develop BCR (p = 0.005). Multivariate analysis revealed patients in this cluster (HR 2.56), and high-risk patients (HR 4.34) according to D'Amico classification were independent predictors of BCR after prostatectomy. From the selected genes MT1A, ALOX12, GSTM2, APC, MYCL2 and RARB hypermethylation predicted BCR and GSTM2 (HR 3.78) and MYCL2 hypermethylation (HR 2.71) did so independently., Conclusion: Epigenetic silencing of GSTM2 and MYCL2 comprise novel molecular markers to predict BCR after surgery for medium- and high-risk localized PCa undergoing surgical treatment and hypermethylation of these genes could be incorporated to the clinical and pathological factors defining the patient at higher risk of PSA failure after prostatectomy. The limitation of the study is that no independent validation cohort is analysed., (© 2016 S. Karger AG, Basel.)

Objective: To assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms for predicting cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC)., Patients and Methods: This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010. Prognostic scores for each patient were calculated and the primary endpoint was CSS. Discriminating ability was assessed by Harrell's c-index for censored data. The 'validation by calibration' method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored., Results: Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively. The median follow-up (FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan-Meier estimates of CSS (with 95% confidence intervals [CIs]) at 5 and 10 years were 0.86 (0.84-0.87) and 0.77 (0.75-0.80), respectively. Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753-0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816-0.867) for the postoperative one, with a significant difference between the two values (P < 0.001). The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions., Conclusions: The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one. These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC., (© 2013 BJU International.)

Objectives: To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages., Materials and Methods: A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment. Effectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markers. Tolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial., Results: Out of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p < 0.0001). Improved mobility was observed likewise (p = 0.005), as was quality of life. The global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patients. Osteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groups. For safety reasons. 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied., Conclusions: Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.

Background: Tadenan (a Pygeum africanum extract) is a drug used in the treatment of benign prostatic hyperplasia. Its effects on prostate fibroblast proliferation and bladder function after partial outlet obstruction have been demonstrated in various pharmacological studies. However, its effects at the molecular level are poorly documented., Methods: Tadenan was dissolved in peanut oil. Rats were orally given two daily doses of the drug (1 or 10 mg/kg b.w.) for 4 days. Vasoactive intestinal peptide (VIP) binding, adenylyl cyclase stimulation, and expression of G-protein subunits were studied in rat prostatic membranes by established procedures., Results: Tadenan treatment of castrated/testosterone-replaced rats was performed in order to interfere with prostatic cell proliferation. This experimental approach resulted in increases of: 1) VIP effect on adenylyl cyclase stimulation through alpha(s) G-subunit; 2) alpha(i) activation by low Gpp[NH]p doses (in the presence of forskolin); and 3) alpha(s), alpha(i1/2), and alpha(i3/0) levels. However, there were no modifications in membranes from quiescent, nonproliferating prostates (untreated rats)., Conclusions: The observed regulatory role of Tadenan on various prostatic components of the adenylyl cyclase system, together with previous findings on protein kinase C-mediated signal transduction, open a complex array of possibilities of direct actions of this phytotherapeutic agent in the prostate., (Copyright 2000 Wiley-Liss, Inc.)

Purpose: We evaluate comparative volumetric analysis of blood and urinary red blood cells (RBCs) to identify the source of hematuria. Comparative volumetric analysis is defined as the difference between mean corpuscular erythrocyte volume in peripheral blood (MCVB) diluted in urine supernatant after centrifugation and mean corpuscular volume of urinary erythrocytes (MCVU). The potential of MCVB-MCVU to distinguish the origin of hematuria is compared to MCVU alone. The fundamental hypothesis is that RBCs that can go through the glomerulus will be smaller than those from the collecting system or lower urinary tract, thus having a smaller MCVU and larger difference between MCVB and MCVU., Materials and Methods: A prospective detailed urological evaluation was performed on 210 patients with glomerular or nonglomerular hematuria detected by urinary sediment, clinical radiological evaluation, endoscopy, cytology and sometimes bladder or renal biopsy. After evaluation 24 cases with an uncertain source of hematuria were excluded from study. Specialized urinalysis, volumetric analysis and clinical investigation were performed in a blind fashion. MCVU and MCVB-MCVU were registered for every patient. The Technicon H-3 system with angle laser scattering dual system allowed measurement of mean corpuscular volume in a minimal number of RBCs, and resuspension of RBC pellets in the same urinary supinate avoided effects of osmolarity and pH on RBC size and shape. Reproducibility in assessing the index was tested in 50 cases in which comparative volumetric analysis was repeated on 2 consecutive days. Unpaired t test was performed, and a threshold value of MCVB-MCVU with maximum sensitivity and specificity to detect glomerular hematuria was identified. The potential of urinary and comparative volumetric analysis to distinguish the source of hematuria was evaluated and compared by receiver operating characteristics curve analysis., Results: Hematuria was nonglomerular in 53 (28.4%) and glomerular in 133 (71.6%) patients. Mean MCVB-MCVU was significantly different for nonglomerular (0.6 fl.) and glomerular (30.5 fl.) sources (p<0.0001). There was a correlation between repeat independent measures of MCVU and MCVB-MCVU. The highest positive predictive value to detect a glomerular origin is desirable so that unnecessary investigation can be obviated without the risk of missing a nonglomerular source. With a limit of 16 fl. specificity and positive predictive value were 98 and 99%, respectively. Receiver operating characteristics curve analysis to localize the source of hematuria revealed significant differences in favor of comparative volumetric analysis versus urinary volumetric analysis alone., Conclusions: MCVB-MCVU using the Technicon H-3 system is a useful noninvasive and accurate method to locate the source of hematuria. A value of 16 fl. or greater practically rules out a nonglomerular origin and obviates further urological investigation. We have incorporated this investigation in our diagnostic algorithm for hematuria.