A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelo... more A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In...
Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) ha... more Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) have usually been analyzed in overall populations with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories due to the different incidence of clinically significant PCa (csPCa). The objective of the study was to analyze PSA density (PSAD), MRI-ERSPC risk calculator (RC), and Proclarix to properly select candidates for prostate biopsy regarding PI-RADS categories. We performed a head-to-head analysis of 567 men with suspected PCa, PSA > 3 ng/mL and/or abnormal rectal examination, in whom two to four core transrectal ultrasound (TRUS) guided biopsies to PI-RADS ≥ three lesions and/or 12-core TRUS systematic biopsies were performed after 3-tesla mpMRI between January 2018 and March 2020 in one academic institution. The overall detection of csPCa was 40.9% (6% in PI-RADS < 3, 14.8...
INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-maki... more INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-making process for prostate cancer (PC) management. Sectioning and haematoxylin-eosin (HE) staining tech...
Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the di... more Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the diagnosis and modified the epidemiology of prostate cancer (PCa). Although it lacks of many characteristics of an ideal tumor marker, it is the marker most used for diagnosis and follow up of any kind of cancer. It represents the best clinical tool we have available today for screening and staging of PCa. On the contrary, its greatest limitation is the lack of tumor specificity. The use of PSA by-products and molecular isoforms tries to solve, at least partially, its limitations. Indeed, the use of FreePSA ratio (%fPSA) ad PSA density (PSAD) increase significantly the specificity of the diagnostic test and, the use of derivatives that evaluate time kinetics of PSA (PSA velocity (PSAV) and PSA doubling time (PSADT) represents a very useful tool for prognosis estimation during treatment and follow up of the disease. The greatest advance over the last years comes from the analysis of the pred...
PURPOSE Functional and anatomical changes associated with prostate removal coincide with alterati... more PURPOSE Functional and anatomical changes associated with prostate removal coincide with alterations in pelvic structures. Posterior rhabdosphincter reconstruction was designed to improve urinary continence after radical prostatectomy. The aim of this study was to determine magnetic resonance anatomic predictors of urinary recovery after radical prostatectomy, and to assess their relation to the type of reconstruction. MATERIAL AND METHODS Forty patients were randomly selected from a trial (NCT03302169). Two independent radiologists determined the situation of the anastomosis in the pelvis according to MRI performed a month after the radical prostatectomy: vertical situation assessed as the distance to the line coccyx-inferior pubic margin (ACPv) and anteroposterior situation as the distance from the pubis (Distance A), and from the coccyx (Distance B). RESULTS The Pearson correlation of ACPv, Distance A, and B between readers were 0.975, 0.940, and 0.711, p < 0.001. Patients with the reconstruction presented more cephalic situation of the anastomosis (higher ACPv) than patients with standard reconstruction technique. A multivariate analysis was performed including age, BMI, prostate volume, PRRS, and the MRI parameters. ACPv and Distance B were the only two independent predictors of no need for any urinary protection at 6 months after the surgery. CONCLUSIONS This is the first study that suggests positional differences according to the type of reconstruction after radical prostatectomy related to early urinary recovery. Magnetic resonance measurements to determine anastomosis positioning are reliable and have a strong correlation between readers. Anatomic MRI features are independent predictors of urinary recovery after robotic radical prostatectomy.
Background: Circulating testosterone remains the main source of androgens, however only 1%-2% cir... more Background: Circulating testosterone remains the main source of androgens, however only 1%-2% circulates as free testosterone (fT), hormone active form. To compare the performance of serum fT and total testosterone (tT) as predictors of prostate cancer (PCa) detection and aggressiveness. Methods: Serum fT (RIA, pg/mL) and tT (LC/MS, ng/dL) were prospectively determined in 3364 consecutive men with PCa suspicion scheduled to TRUS guided biopsy. Tumor aggressiveness was assessed by Gleason grade (8 to 10) and D ́Amico risk (cT3a+ or PSA>20 ng/mL or Gleason 8 to 10). Recodification of fT and tT in four groups according to percentile (ptile) distribution were done. tT/1 (min to 10 ptile): 62-291 ng/dl, tT/2
Purpose To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomogr... more Purpose To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). Methods A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. Results Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing < 18% as the cutoff of probability for not performing PBx; the percentage of saved PBx was 47% (474 avoided PBx in 1000 proposed). Conclusion We developed clinical and mpMRI-based nomograms with a high discrimination ability for three different scenarios of PCa aggressiveness ( https://urostatisticalsolutions.shinyapps.io/MRIfusionPCPrediction/ ). Specific clinical cutoff points allow us to save a high number of PBx with a minimum of missed diagnoses.
Abstract Purpose: It remains unclear whether patients with prostate cancer suspicion and negative... more Abstract Purpose: It remains unclear whether patients with prostate cancer suspicion and negative magnetic resonance imaging (M.R.I.) can safely obviate biopsy. The purpose of this study was to assess the clinical negative predictive value (N.P.V.) of M.R.I. in excluding prostate cancer. The secondary end-point was to compare N.P.V. to detect significant prostate cancer of M.R.I.The secondary end-point was to compare N.P.V. to detect significant prostate cancer in M.R.I. classified as P.I.-R.A.D.S.1 and as P.I.-R.A.D.S.2 Methods: From December 2012 to January 2017, 1128 M.R.I.s were performed consecutively due to prostate cancer clinical suspicion. The absence of suspicious and presence of low-risk areas were considered as negative M.R.I., P.I.-R.A.D.S.1 and 2. Biopsy results were compared according to P.I.-R.A.D.S. classification. The clinically significant disease was defined as International Society of Urological Pathology group higher than 1. Results: Two hundred and twenty-two (20%) M.R.I.s didn’t highlight targetable imaging suspicious areas, which were recorded as negative tests: 130 (59%) P.I.-R.A.D.S.1 and 92 (41%) P.I.-R.A.D.S.2. Detection of clinically significant prostate cancer in at least one biopsy core was higher in the P.I.-R.A.D.S.2 group, 9% (8/92) vs 3% (4/130), p = 0.047. The N.P.V. in biopsy-naïve men and P.I.-R.A.D.S.1 was 95% for significant disease, while in patients subjected to repeated biopsies and P.I.-R.A.D.S.1, the N.P.V. found was 99%. Those rates differ from the P.I.-R.A.D.S.2 group: N.P.V. in biopsy-naïve patients was 84%, and 95% in repeated biopsy. Conclusions: P.I.-R.A.D.S.2 shouldn’t be considered as a negative M.R.I. A biopsy cannot be routinely omitted in biopsy-naïve men with clinical suspicion of cancer and a low-suspicious area in M.R.I., giving the possibility of missing clinically significant tumors.
INTRODUCTION AND OBJECTIVES: Epitelial-to-mesenchymal transition (EMT) is a well characterised pr... more INTRODUCTION AND OBJECTIVES: Epitelial-to-mesenchymal transition (EMT) is a well characterised process linked to tumour progression and metastasis in a number of carcinomas. EMT enables carcinoma cells to lose cell to cell contacts and endows them with stem cell-like properties to invade and initiate metastasis. Recent reports have identified EMT as potentially playing a significant role in RCC disease recurrence, invasion and metastasis. Several signalling pathways like HIF/2 and IL-6/STAT, are well known inducers of the EMT phenotype. Protein kinase CK2 is a constitutively active serine/threonine kinase consisting of two catalytic subunits (CK2alpha/alpha’) and two regulatory subunits (CK2Beta) and is present in the nucleus and cytoplasm of all eukaryotic cells. The imbalance of CK2 catalytic and regularory subunits, due to underexpression of CK2Beta subunit, has been correlated with the expression of EMT markers. In clear cell renal cell carcinoma (ccRCC), the alterations in the ratios between CK2 subunits during the neoplasic process seems to participate at different stages of tumour progression METHODS: We analyzed the expression and distribution of CK2 subunits in samples of clear cell renal carcinomas (ccRCC) and renal healthy tissue from the same patients by immunohistochemistry on TMAs and Western-blot in a total of 98 patients. Tumour registry data and patient outcome were retrospectivelly collected and correlates with clinicopathological data (F€ urhman grade, pT stage and Risk group) and with IL-6/STAT inmunoexpression RESULTS: We observed an increase of CK2 in tumors. Regarding the subcellular distribution in normal tissue CK2alpha is predominantly cytoplasmic whereas tumors markedly increased in the core, with only a slight decrease in the cytoplasm, indicating nuclear overexpression CK2alpha tumors. CK2Beta changes are more discreet and its nuclear accumulation in tumors could be due to translocation from the cytoplasm, which is a marked decrease. Using 786-O cells, derived ccRCC pVHL deficient, and 786-O cells stably transfected with an expression vector pVHL, we have observed that the presence of VHL not decrease but it increases CK2alpha levels by altering the ratio between CK2alpha/CK2Beta. It was observed higher survival in the subset patients with underexpression of CK2sBeta although log-rank was not significant (0,301). The combination of overexpression of STAT3 and underexpression ok CK2Beta seems to provide a higher survival hazard ratio of 4,252 (95% IC, 1,182-18.413) CONCLUSIONS: The results indicate CK2alpha overexpression in clear cell renal cell carcinoma by a mechanism that does not appear due to inactivation of VHL. In patients with underexpression of IL-6/STAT3, CK2Beta was no able to discriminate any behaviour, but the patients defined as poor prognostic when STAT3 was overexpressed has similar survival than those that had underexpression of STAT3. The combination of overexpression of STAT3 and underexpression of CK2Beta provided a higher survival rate
International journal of molecular sciences, Jan 6, 2014
The aim of this study was to analyze the relationship between statin use along with serum cholest... more The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p<0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p<0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p=0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p=0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p=0.012). NSC men had a 53.8% rate of HGPCa...
Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation ther... more Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive. We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P < .001). The serum testosterone levels, measured using LC MSMS, were < 20 ng/dL i...
The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation t... more The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.
A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelo... more A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In...
Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) ha... more Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) have usually been analyzed in overall populations with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories due to the different incidence of clinically significant PCa (csPCa). The objective of the study was to analyze PSA density (PSAD), MRI-ERSPC risk calculator (RC), and Proclarix to properly select candidates for prostate biopsy regarding PI-RADS categories. We performed a head-to-head analysis of 567 men with suspected PCa, PSA > 3 ng/mL and/or abnormal rectal examination, in whom two to four core transrectal ultrasound (TRUS) guided biopsies to PI-RADS ≥ three lesions and/or 12-core TRUS systematic biopsies were performed after 3-tesla mpMRI between January 2018 and March 2020 in one academic institution. The overall detection of csPCa was 40.9% (6% in PI-RADS < 3, 14.8...
INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-maki... more INTRODUCTION AND OBJECTIVE:Lymph node (LN) status is a key prognostic factor in the decision-making process for prostate cancer (PC) management. Sectioning and haematoxylin-eosin (HE) staining tech...
Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the di... more Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the diagnosis and modified the epidemiology of prostate cancer (PCa). Although it lacks of many characteristics of an ideal tumor marker, it is the marker most used for diagnosis and follow up of any kind of cancer. It represents the best clinical tool we have available today for screening and staging of PCa. On the contrary, its greatest limitation is the lack of tumor specificity. The use of PSA by-products and molecular isoforms tries to solve, at least partially, its limitations. Indeed, the use of FreePSA ratio (%fPSA) ad PSA density (PSAD) increase significantly the specificity of the diagnostic test and, the use of derivatives that evaluate time kinetics of PSA (PSA velocity (PSAV) and PSA doubling time (PSADT) represents a very useful tool for prognosis estimation during treatment and follow up of the disease. The greatest advance over the last years comes from the analysis of the pred...
PURPOSE Functional and anatomical changes associated with prostate removal coincide with alterati... more PURPOSE Functional and anatomical changes associated with prostate removal coincide with alterations in pelvic structures. Posterior rhabdosphincter reconstruction was designed to improve urinary continence after radical prostatectomy. The aim of this study was to determine magnetic resonance anatomic predictors of urinary recovery after radical prostatectomy, and to assess their relation to the type of reconstruction. MATERIAL AND METHODS Forty patients were randomly selected from a trial (NCT03302169). Two independent radiologists determined the situation of the anastomosis in the pelvis according to MRI performed a month after the radical prostatectomy: vertical situation assessed as the distance to the line coccyx-inferior pubic margin (ACPv) and anteroposterior situation as the distance from the pubis (Distance A), and from the coccyx (Distance B). RESULTS The Pearson correlation of ACPv, Distance A, and B between readers were 0.975, 0.940, and 0.711, p < 0.001. Patients with the reconstruction presented more cephalic situation of the anastomosis (higher ACPv) than patients with standard reconstruction technique. A multivariate analysis was performed including age, BMI, prostate volume, PRRS, and the MRI parameters. ACPv and Distance B were the only two independent predictors of no need for any urinary protection at 6 months after the surgery. CONCLUSIONS This is the first study that suggests positional differences according to the type of reconstruction after radical prostatectomy related to early urinary recovery. Magnetic resonance measurements to determine anastomosis positioning are reliable and have a strong correlation between readers. Anatomic MRI features are independent predictors of urinary recovery after robotic radical prostatectomy.
Background: Circulating testosterone remains the main source of androgens, however only 1%-2% cir... more Background: Circulating testosterone remains the main source of androgens, however only 1%-2% circulates as free testosterone (fT), hormone active form. To compare the performance of serum fT and total testosterone (tT) as predictors of prostate cancer (PCa) detection and aggressiveness. Methods: Serum fT (RIA, pg/mL) and tT (LC/MS, ng/dL) were prospectively determined in 3364 consecutive men with PCa suspicion scheduled to TRUS guided biopsy. Tumor aggressiveness was assessed by Gleason grade (8 to 10) and D ́Amico risk (cT3a+ or PSA>20 ng/mL or Gleason 8 to 10). Recodification of fT and tT in four groups according to percentile (ptile) distribution were done. tT/1 (min to 10 ptile): 62-291 ng/dl, tT/2
Purpose To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomogr... more Purpose To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). Methods A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. Results Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing < 18% as the cutoff of probability for not performing PBx; the percentage of saved PBx was 47% (474 avoided PBx in 1000 proposed). Conclusion We developed clinical and mpMRI-based nomograms with a high discrimination ability for three different scenarios of PCa aggressiveness ( https://urostatisticalsolutions.shinyapps.io/MRIfusionPCPrediction/ ). Specific clinical cutoff points allow us to save a high number of PBx with a minimum of missed diagnoses.
Abstract Purpose: It remains unclear whether patients with prostate cancer suspicion and negative... more Abstract Purpose: It remains unclear whether patients with prostate cancer suspicion and negative magnetic resonance imaging (M.R.I.) can safely obviate biopsy. The purpose of this study was to assess the clinical negative predictive value (N.P.V.) of M.R.I. in excluding prostate cancer. The secondary end-point was to compare N.P.V. to detect significant prostate cancer of M.R.I.The secondary end-point was to compare N.P.V. to detect significant prostate cancer in M.R.I. classified as P.I.-R.A.D.S.1 and as P.I.-R.A.D.S.2 Methods: From December 2012 to January 2017, 1128 M.R.I.s were performed consecutively due to prostate cancer clinical suspicion. The absence of suspicious and presence of low-risk areas were considered as negative M.R.I., P.I.-R.A.D.S.1 and 2. Biopsy results were compared according to P.I.-R.A.D.S. classification. The clinically significant disease was defined as International Society of Urological Pathology group higher than 1. Results: Two hundred and twenty-two (20%) M.R.I.s didn’t highlight targetable imaging suspicious areas, which were recorded as negative tests: 130 (59%) P.I.-R.A.D.S.1 and 92 (41%) P.I.-R.A.D.S.2. Detection of clinically significant prostate cancer in at least one biopsy core was higher in the P.I.-R.A.D.S.2 group, 9% (8/92) vs 3% (4/130), p = 0.047. The N.P.V. in biopsy-naïve men and P.I.-R.A.D.S.1 was 95% for significant disease, while in patients subjected to repeated biopsies and P.I.-R.A.D.S.1, the N.P.V. found was 99%. Those rates differ from the P.I.-R.A.D.S.2 group: N.P.V. in biopsy-naïve patients was 84%, and 95% in repeated biopsy. Conclusions: P.I.-R.A.D.S.2 shouldn’t be considered as a negative M.R.I. A biopsy cannot be routinely omitted in biopsy-naïve men with clinical suspicion of cancer and a low-suspicious area in M.R.I., giving the possibility of missing clinically significant tumors.
INTRODUCTION AND OBJECTIVES: Epitelial-to-mesenchymal transition (EMT) is a well characterised pr... more INTRODUCTION AND OBJECTIVES: Epitelial-to-mesenchymal transition (EMT) is a well characterised process linked to tumour progression and metastasis in a number of carcinomas. EMT enables carcinoma cells to lose cell to cell contacts and endows them with stem cell-like properties to invade and initiate metastasis. Recent reports have identified EMT as potentially playing a significant role in RCC disease recurrence, invasion and metastasis. Several signalling pathways like HIF/2 and IL-6/STAT, are well known inducers of the EMT phenotype. Protein kinase CK2 is a constitutively active serine/threonine kinase consisting of two catalytic subunits (CK2alpha/alpha’) and two regulatory subunits (CK2Beta) and is present in the nucleus and cytoplasm of all eukaryotic cells. The imbalance of CK2 catalytic and regularory subunits, due to underexpression of CK2Beta subunit, has been correlated with the expression of EMT markers. In clear cell renal cell carcinoma (ccRCC), the alterations in the ratios between CK2 subunits during the neoplasic process seems to participate at different stages of tumour progression METHODS: We analyzed the expression and distribution of CK2 subunits in samples of clear cell renal carcinomas (ccRCC) and renal healthy tissue from the same patients by immunohistochemistry on TMAs and Western-blot in a total of 98 patients. Tumour registry data and patient outcome were retrospectivelly collected and correlates with clinicopathological data (F€ urhman grade, pT stage and Risk group) and with IL-6/STAT inmunoexpression RESULTS: We observed an increase of CK2 in tumors. Regarding the subcellular distribution in normal tissue CK2alpha is predominantly cytoplasmic whereas tumors markedly increased in the core, with only a slight decrease in the cytoplasm, indicating nuclear overexpression CK2alpha tumors. CK2Beta changes are more discreet and its nuclear accumulation in tumors could be due to translocation from the cytoplasm, which is a marked decrease. Using 786-O cells, derived ccRCC pVHL deficient, and 786-O cells stably transfected with an expression vector pVHL, we have observed that the presence of VHL not decrease but it increases CK2alpha levels by altering the ratio between CK2alpha/CK2Beta. It was observed higher survival in the subset patients with underexpression of CK2sBeta although log-rank was not significant (0,301). The combination of overexpression of STAT3 and underexpression ok CK2Beta seems to provide a higher survival hazard ratio of 4,252 (95% IC, 1,182-18.413) CONCLUSIONS: The results indicate CK2alpha overexpression in clear cell renal cell carcinoma by a mechanism that does not appear due to inactivation of VHL. In patients with underexpression of IL-6/STAT3, CK2Beta was no able to discriminate any behaviour, but the patients defined as poor prognostic when STAT3 was overexpressed has similar survival than those that had underexpression of STAT3. The combination of overexpression of STAT3 and underexpression of CK2Beta provided a higher survival rate
International journal of molecular sciences, Jan 6, 2014
The aim of this study was to analyze the relationship between statin use along with serum cholest... more The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p<0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p<0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p=0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p=0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p=0.012). NSC men had a 53.8% rate of HGPCa...
Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation ther... more Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive. We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P < .001). The serum testosterone levels, measured using LC MSMS, were < 20 ng/dL i...
The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation t... more The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.
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Papers by Ana Celma