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Background: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). Purpose: To develop and validate radiomics and kallikrein models for the detection of csPCa. Study Type: Retrospective. Population: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. Field strength/Sequence: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. Assessment: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores. Statistical Tests: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant. Results: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488). Data Conclusion: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains. Level of Evidence: 1. Technical Efficacy: Stage 2. publishedVersion more...

PurposeWe aimed to develop and externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx should be performed in addition to TBx in man with suspicious prostate MRI.Materials and methodsRetrospective analyses of single (IMPROD, NCT01864135) and multi-institution (MULTI-IMPROD, NCT02241122) clinical trials. All men underwent a unique rapid biparametric magnetic resonance imaging (IMPROD bpMRI) consisting of T2-weighted imaging and three separate DWI acquisitions. Men with IMPROD bpMRI Likert scores of 3–5 were included. Logistic regression models were developed using IMPROD trial (n = 122) and validated using MULTI-IMPROD trial (n = 262) data. The model’s performance was evaluated in the terms of PCa detection with Gleason Grade Group 1 (clinically insignificant prostate cancer, iPCa) and > 1 (clinically significant prostate cancer, csPCa). Net benefits and decision curve analyses (DCA) were compared. Combined biopsies were used for reference.ResultsThe developed nomogram included age, PSA, prostate volume, MRI suspicion score (IMPROD bpMRI Likert or PIRADsv2.1 score), MRI-suspicion lesion volume percentage, and lesion location. All these variables were significant predictors of csPCa in SBx in multivariable analysis. In the validation cohort (n = 262) using different nomogram cutoffs, 19–43% of men would have avoided SBx while missing 1–4% of csPCa and avoiding detection of 9–20% of iPCa. Similar performance was found for nomograms using IMPROD bpMRI Likert score or v2.1.ConclusionsThe developed nomogram demonstrated potential to select men with a clinical suspicion of PCa who would benefit from performing SBx in addition to TBx. Public access to the nomogram is provided at:https://petiv.utu.fi/multiimprod/. more...

IntroductionEuropean Association of Urology and UK National Institute for Health and Care Excellence guidelines recommend that all men with suspicions of prostate cancer should undergo prebiopsy contrast enhanced, that is, multiparametric prostate MRI. Subsequent prostate biopsies should also be performed if MRI is positive, that is, Prostate Imaging–Reporting and Data System (PI-RADS) scores 3–5. However, several retrospective post hoc analyses have shown that this approach still leads to many unnecessary biopsy procedures. For example, 88%–96% of men with PI-RADS, three findings are still diagnosed with clinically non-significant prostate cancer or no cancer at all.Methods and analysisThis is a prospective, randomised, controlled, multicentre trial, being conducted in Finland, to demonstrate non-inferiority in clinically significant cancer detection rates among men undergoing prostate biopsies post-MRI and men undergoing prostate biopsies post-MRI only after a shared decision based on individualised risk estimation. Men without previous diagnosis of prostate cancer and with abnormal digital rectal examination findings and/or prostate-specific antigen between 2.5 ug/L and 20.0 ug/L are included. We aim to recruit 830 men who are randomised at a 1:1 ratio into control (all undergo biopsies after MRI) and intervention arms (the decision to perform biopsies is based on risk estimation and shared decision-making). The primary outcome of the study is the proportion of men with clinically significant prostate cancer (Gleason 4+3 prostate cancer or higher). We will also compare the overall biopsy rate, benign biopsy rate and the detection of non-significant prostate cancer between the two study groups.Ethics and disseminationThe study (protocol V.2.0, 4 January 2021) was approved by the Ethics Committee of the Hospital District of Southwest Finland (IORG number: 0001744, IBR number: 00002216; trial number: 99/1801/2019). Participants are required to provide written informed consent. Full reports of this study will be submitted to peer-reviewed journals, mainly urology and radiology.Trial registration numberNCT04287088; the study is registered at ClinicalTrials.gov. more...

Background: The objective of this study was to compare the prevalence of clinically significant prostate cancer (CSPCa) in men with biparametric prebiopsy prostate magnetic resonance imaging (MRI) ... more...

Background Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate-specific antigen (PSA). However, long acquisition time, high cost, and inter-center/reader variability of a routine prostate multiparametric MRI limit its wider adoption. Purpose To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa). Study type Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI-IMPROD, NCT02241122). Population 161 and 338 prospectively enrolled men who completed the IMPROD and MULTI-IMPROD trials, respectively. Field strength/sequence IMPROD bpMRI: 3T/1.5T, T2 -weighted imaging, three separate diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b values 0, 1500 s/mm2 ; 3) values 0, 2000 s/mm2 . Assessment The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa. Statistical tests Logistic regression models were developed using IMPROD trial data and validated using MULTI-IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2. Results A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89-0.97), and 0.88 (0.84-0.92), respectively. Further addition of the quantitative DWI-based score did not improve AUC values (P Data conclusion A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/ Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1556-1567. more...

BACKGROUND Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI. PURPOSE To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa. STUDY TYPE Prospective single-institutional clinical trial (NCT01864135). SUBJECTS Eighty men with cSPCa. FIELD STRENGTH/SEQUENCE 3T, surface array coils. Two T2 -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b-values 0,1500 s/mm2 ; 3) b-values 0, 2000 s/mm2 . ASSESSMENT IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction. STATISTICAL TESTS Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC). RESULTS IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert. DATA CONCLUSION The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers. LEVEL OF EVIDENCE 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553. more...

Although it has been evaluated that even 76% of men with chronic obstructive pulmonary disease suffer from erectile dysfunction, the association has been poorly characterised. The aim of the study was to describe the association between forced expiratory volume in first second and erectile dysfunction in apparently healthy men. All together 331 men aged 45–70 years old were randomly drawn from a cross-sectional population-based study conducted in 2005 in Finland. Decreased forced expiratory volume was defined by performing mini-spirometry and erectile dysfunction by International Index of Erectile Function short form questionnaire. After adjustment for age and depressive symptoms predicted forced expiratory volume (FEV1 more...

PurposeAlthough prostate cancer is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies or differences in lifestyle. Gut microbiota has been recently associated with cancer progression, but its role in prostate cancer is unclear.MethodsIn a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of prostate cancer were assessed utilizing 16S rRNA gene sequencing. Sequences were assigned to operational taxonomic units, and differential abundance analysis, α- and β-diversities, and predictive functional (PICRUSt) analyses were performed. Additionally, plasma steroid hormone levels were correlated with the predicted microbiota functions.ResultsSeveral differences in the gut microbiota between the subjects with and without prostate cancer were noted. Prevotella 9, members of the Erysipelotrichaceae family and Escherichia-Shigella were higher, and Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were lower in the cancer group. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinal metabolism in the prostate cancer associated microbiome. Plasma testosterone associated negatively with the microbial 5-α-reductase activity (p=0.030). In a subgroup of men taking 5-α-reductase inhibitors (n=17), plasma estrone (p=0.027) and estradiol (p=0.059) levels were lower in men with predicted elevation of the microbial 5-α-reductase function.ConclusionsGut microbiota of the prostate cancer patients differed significantly compared to benign subjects. Microbial 5-α-reductase, copper absorption and retinol metabolism are potential mechanisms of action. These findings could explain the observed association of lifestyle, geography, and prostate cancer incidence. more...

Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective: To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice. more...

Prostate Magnetic Resonance Imaging (MRI) is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). Performing prostate MRI without the use of an intravenous contrast (IV) agent in men with a clinical suspicion of PCa can lead to reduced MRI scan time. Enabling a large array of different medical providers (from mid-level to specialized radiologists) to evaluate and potentially report prostate MRI in men with a clinical suspicion of PCa with a high accuracy could be one way to enable wide adoption of prostate MRI in men with a clinical suspicion of PCa. The aim of this pictorial review is to provide an insight into acquisition, quality control and reporting of prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa, aimed specifically at radiologists starting reporting prostate MRI, urologists, urology/radiology residents and mid-level medical providers without experience in reporting prostate MRI. Free public access ( http://petiv.utu.fi/improd/ and http://petiv.utu.fi/multiimprod/ ) to complete datasets of 161 and 338 men is provided. The imaging datasets are accompanied by clinical, laboratory and histopathological findings. Several topics are simplified in order to provide a solid base for the development of skills needed for an unsupervised review and potential reporting of prostate MRI in men with a clinical suspicion of PCa. The current review represents the first step towards enabling a large array of different medical providers to review and report accurately prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa. more...

Background Multiparametric prostate magnetic resonance imaging (mpMRI) can be considered the gold standard in prostate magnetic resonance imaging (MRI). Biparametric prostate MRI (bpMRI) is faster and could be a feasible alternative to mpMRI. Objective To determine the negative predictive value (NPV) of Improved Prostate Cancer Diagnosis (IMPROD) bpMRI as a whole and in clinical subgroups in primary diagnostics of clinically significant prostate cancer (CSPCa). Design, setting, and participants This is a pooled data analysis of four prospective, registered clinical trials investigating prebiopsy IMPROD bpMRI. Men with a clinical suspicion of prostate cancer (PCa) were included. Intervention Prebiopsy IMPROD bpMRI was performed, and an IMPROD bpMRI Likert scoring system was used. If suspicious lesions (IMPROD bpMRI Likert score 3–5) were visible, targeted biopsies in addition to systematic biopsies were taken. Outcome measurements and statistical analysis Performance measures of IMPROD bpMRI in CSPCa diagnostics were evaluated. NPV was also evaluated in clinical subgroups. Gleason grade ≥3 + 4 in any biopsy core taken was defined as CSPCa. Results and limitations A total of 639 men were included in the analysis. The mean age was 64 yr, mean prostate-specific antigen level was 8.9 ng/ml, and CSPCa prevalence was 48%. NPVs of IMPROD bpMRI Likert scores 3–5 and 4–5 for CSPCa were 0.932 and 0.909, respectively, and the corresponding positive predictive values were 0.589 and 0.720. Only nine of 132 (7%) men with IMPROD bpMRI Likert score 1–2 had CSPCa and none with Gleason score >7. Thus, 132 of 639 (21%) study patients could have avoided biopsies without missing a single Gleason >7 cancer in the study biopsies. In the subgroup analysis, no clear outlier was present. The limitation is uncertainty of the true CSPCa prevalence. Conclusions IMPROD bpMRI demonstrated a high NPV to rule out CSPCa. IMPROD bpMRI Likert score 1–2 excludes Gleason >7 PCa in the study biopsies. Patient summary We investigated the feasibility of prostate magnetic resonance imaging (MRI) with the Improved Prostate Cancer Diagnosis (IMPROD) biparametric MRI (bpMRI) protocol in excluding significant prostate cancer. In this study, highly aggressive prostate cancer was excluded using the publicly available IMPROD bpMRI protocol ( http://petiv.utu.fi/multiimprod/ ). more...

Purpose: To create a pre-operatively usable tool to identify patients at high risk of early death (within 90 days post-operatively) after radical cystectomy and to assess potential risk factors for... more...

BackgroundMagnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption.Methods and findingsThe aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings.ConclusionsIMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial.Trial registrationClinicalTrials.gov NCT02241122. more...

Background Biparametric magnetic resonance imaging (bpMRI) combined with prostate-specific antigen density (PSAd) may be an effective strategy for selecting men for prostate biopsy. It has been shown that performing biopsy only for men with bpMRI Likert scores of 4–5 or PSAd ≥0.15 ng/ml/cm3 is the most efficient strategy. Objective To externally validate previously published biopsy strategies using two prospective bpMRI trial cohorts. Design, setting, and participants After IMPROD bpMRI, 499 men had systematic transrectal prostate biopsies and men with IMPROD bpMRI Likert scores of 3–5 had an additional two to four targeted biopsies. Outcome measurements and statistical analysis Various IMPROD bpMRI Likert score and PSAd thresholds were assessed using detection rates for significant prostate cancer (sPCa; Gleason score ≥3 + 4), predictive values, and proportion of biopsies avoided. Net benefits and decision curve analyses (DCA) were compared with the aim of finding an optimal strategy for sPCa detection. Combined biopsies were used for reference. Results and limitations The negative predictive value (NPV) for sPCa in IMPROD bpMRI Likert 3–5 and 4–5 score groups was 93% and 92%, respectively, while the corresponding positive predictive value (PPV) was 57% and 72%, respectively. In DCA, the optimal combination was IMPROD bpMRI Likert score 4–5 or Likert 3 with PSAd ≥0.20 ng/ml/cm3, which had NPV of 93% and PPV of 67%. Using this combination, 35% of the study patients would have avoided biopsies and 13 sPCas (6%, 13/229, of all sPCas diagnosed) would have been missed. Conclusions IMPROD bpMRI demonstrated a good NPV for sPCa. PSAd improved the NPV mainly among men with equivocal suspicion on IMPROD bpMRI. However, the additional value of PSAd was marginal: the NPV and PPV for IMPROD bpMRI Likert 4–5 score group were 92% and 72%, respectively, while the corresponding values for the best combination strategy were 93% and 67%. Patient summary We investigated a rapid prostate magnetic resonance imaging protocol (IMPROD bpMRI) combined with prostate-specific antigen (PSA) density for detection of significant prostate cancer. Our results show that IMPROD bpMRI is a good diagnostic tool, but the additional value provided by PSA density is marginal. more...

PURPOSE To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). MATERIALS AND METHODS Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. RESULTS TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. CONCLUSION Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. more...

Although it has been evaluated that even 76% of men with chronic obstructive pulmonary disease suffer from erectile dysfunction, the association has been poorly characterised. The aim of the study was to describe the association between forced expiratory volume in first second and erectile dysfunction in apparently healthy men. All together 331 men aged 45-70 years old were randomly drawn from a cross-sectional population-based study conducted in 2005 in Finland. Decreased forced expiratory volume was defined by performing mini-spirometry and erectile dysfunction by International Index of Erectile Function short form questionnaire. After adjustment for age and depressive symptoms predicted forced expiratory volume (FEV more...

Background Prostate MRI is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). However, development and validation of methods for focal therapy planning are still lagging. Purpose To evaluate the diagnostic accuracy on lesion, region-of-interest (ROI), and voxel level of IMPROD biparametric prostate MRI (bpMRI) for PCa detection in men with a clinical suspicion of PCa who subsequently underwent radical prostatectomy. Study type Prospective single-institution clinical trial (NCT01864135). Population Sixty-four men who underwent radical prostatectomy after IMPROD bpMRI performed in prebiopsy settings. Field strength/sequence IMPROD bpMRI consisted of T2 -weighted imaging (T2 w) and three separate diffusion-weighted imaging acquisitions with an average acquisition time of 15 minutes. Assessment The diagnostic accuracy of prospectively reported manual cancer delineations and regions increased with 3D dilation were evaluated on the voxel level (volume of 1.17 mm3 , 1 mm3 , 125 mm3 ) as well as the 36 ROI level. Only PCa lesions with a diameter ≥ 5 mm or any Gleason Grade 4 were analyzed. All data and protocols are freely available at: http://petiv.utu.fi/improd STATISTICAL TESTS: Sensitivity, specificity, accuracy. Results In total, 99 PCa lesions were identified. Forty (40%, 40/99) had a Gleason score (GS) of >3 + 4. Twenty-eight PCa lesions (28%, 28/99) were missed by IMPROD bpMRI, three (7.5%, 3/40) with GS >3 + 4. 3D dilation of manual cancer delineations in all directions by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve sensitivity approaching 100% on a voxel level. Data conclusion IMPROD bpMRI had a high sensitivity on lesion level for PCa with GS >3 + 4. Increasing 3D lesion delineations by ~10-12 mm (corresponding to the Hausdorff distance) was needed to achieve high sensitivity on the voxel level. Such information may help in planning ablation therapies. Level of evidence 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1641-1650. more...

OBJECTIVE To describe the trends and occupational variation in the incidence of testicular cancer in the Nordic countries utilising national cancer registries, NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic Occupational Cancer) databases. PATIENTS AND METHODS We obtained the incidence data of testicular cancer for 5-year periods from 1960-1964 to 2000-2014 and for 5-year age-groups from the NORDCAN database. Morphological data on incident cases of seminoma and non-seminoma were obtained from national cancer registries. Age-standardised incidence rates (ASR) were calculated per 100 000 person-years (World Standard). Regression analysis was used to evaluate the annual change in the incidence of testicular cancer in each of the Nordic countries. The risk of testicular cancer in different professions was described based on NOCCA information and expressed as standardised incidence ratios (SIRs). RESULTS During 2010-2014 the ASR for testicular cancer varied from 11.3 in Norway to 5.8 in Finland. Until 1998, the incidence was highest in Denmark. There has not been an increase in Denmark and Iceland since the 1990s, whilst the incidence is still strongly increasing in Norway, Sweden, and Finland. There were no remarkable changes in the ratio of seminoma and non-seminoma incidences during the past 50 years. There was no increase in the incidences in children and those of pension age. The highest significant excess risks of testicular seminoma were found in physicians (SIR 1.48, 95% confidence interval [CI] 1.07-1.99), artistic workers (SIR 1.47, 95% CI 1.06-1.99) and religious workers etc. (SIR 1.33, 95% CI 1.14-1.56). The lowest SIRs of testicular seminoma were seen amongst cooks and stewards (SIR 0.56, 95% CI 0.29-0.98), and forestry workers (SIR 0.64, 95% CI 0.47-0.86). The occupational category of administrators was the only one with a significantly elevated SIR for testicular non-seminoma (SIR 1.21, 95% CI 1.04-1.42). The only SIRs significantly more...

Adenocarcinoma of the paraurethral gland is a rare tumour with no published prevalence in male patients. This report presents a case of bulbourethral gland adenocarcinoma in a 25-year-old man without comorbidities. After resection of the proximal urethra, sphincter and prostate, Mitrofanoff-type appendicovesicostomy was performed. In this case, chemotherapy or radiation was not included in the treatment as the surgery was estimated to be radical. The patient achieved good surgical and quality of life results. This case shows that macroscopic haematuria should be examined even in young age groups without comorbidities. more...

Background Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is typically considered a safe procedure. However, infectious complications have been increasing. Objective To determine the contemporary rate of biopsy-related infectious and noninfectious complications after TRUS-Bx, and identify potential risk factors associated with the complications. Design, setting, and participants This was a prospective multicenter study and a substudy of a trial investigating the role of magnetic resonance imaging (MRI) in prostate cancer diagnosis (multi-IMPROD, NCT02241122). Intervention TRUS-Bx was performed for all patients included in the study. Ciprofloxacin, levofloxacin, or fosfomycin was administered for antibiotic prophylaxis. Outcome measurements and statistical analysis On inclusion, patients completed a detailed questionnaire and underwent MRI scanning. Antibiotic prophylaxis was prospectively recorded. After collection of a rectal swab, TRUS-Bx (total of 14–18 biopsy cores) was performed and. The rectal swabs were cultured and the antimicrobial susceptibility profile of Escherichia coli strains was analyzed. Biopsy complications leading to a visit to a health care unit were recorded and potential risk factors for complications were analyzed. Results and limitations Twelve of the 294 patients (4.1%) had a biopsy-related complication, of which two (0.7%) were infectious and managed in the outpatient setting. Some 11% of the patients had an E. coli strain resistant to the prophylactic antibiotic administered. Conclusions The risk of an infectious or noninfectious complication after TRUS-Bx is very low, although the FQ resistance rate in the study population was significant. Accordingly, the present TRUS-Bx procedure and antibiotic prophylaxis are efficient in guarding against biopsy complications, but regional resistance rates may affect the generalizability of the results. Patient summary We examined the rate of complications after prostate biopsies in 294 patients. The risk of having a biopsy-related complication was low (4.1%). The rate of infectious complications was reasonably low (0.7%) although antibiotic resistance to the prophylactic antibiotic regimen was significant (11%). more...

BACKGROUND Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown. METHODS In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle-brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System. RESULTS The prevalence of PAD (defined as ABI < or =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P < 0.001). CONCLUSION Subclinical PAD is common in hypertensive patients even without comorbidities. The measurement of ABI is an efficient method to identify patients with increased cardiovascular risk and worth performing to hypertensive patients, particularly those with pulse pressure above 65 mmHg. Uniform criterions of defining PAD and borderline PAD would aid physicians in clinical decision-making. more...

We hypothesized that erectile dysfunction is associated with impaired fasting glucose and impaired glucose tolerance and could be used in primary screening of pre-diabetes. Although erectile dysfunction is known to be closely associated with diabetes, we demonstrate that it is not associated with pre-diabetes in 926 apparently healthy men. more...

Prostate-specific antigen (PSA) is an important tool in the follow-up of prostate cancer after radical prostatectomy (RP). However, the relevance of ultrasensitive PSA (uPSA) after RP is not well defined. The aim of this study was to investigate the value of uPSA in follow-up after RP and to determine whether ultrasensitive PSA doubling time (uDT) correlates with traditional PSA doubling time (tDT).In total, 604 consecutive patients undergoing open RP and pelvic lymphadenectomy between 2004 and 2008 (minimum 5y of follow-up) were studied. To evaluate the postsurgical uPSA level, scatter plot statistics were used. To correlate uDT and tDT in patients with a biochemical recurrence (PSA ≥0.2ng/ml), at least 2 uPSA and 2 PSA measurements without salvage treatment were required and a weighted Cohen kappa statistic and receiver operating characteristic curve were used to test agreement across the categories.There were 229 patients without biochemical recurrence who did not have 3 rising PSA values after nadir within ultrasensitive area. Their highest uPSA value was between 0.003 and 0.1ng/ml. In 97.4% of patients, the highest uPSA value was less than 0.03ng/ml, and in 89% of these patients, the values were less than 0.02ng/ml. The median uDT and tDT were 10.2 and 11.4 months, respectively. The weighted Cohen kappa statistic between these 2 groups was 0.30 (95% CI:-0.09 to 0.50), demonstrating a poor agreement of PSA doubling time across categories. The predictive capability of uDT was tested with tDT9 months. A receiver operating characteristic curve area under the curve value was 0.737 (95% CI:-0.577 to 0.897) demonstrating a fair agreement between the groups.uPSA values0.03ng/ml seems to be valid and can be used in a clinical setting. There was a poor to fair agreement between tDT and uDT. The accuracy of uDT improves when it approaches the traditional PSA threshold of 0.1ng/ml. Also according to our results, there is no prognostic benefit of uDT calculation. more...

Introduction. Erectile dysfunction (ED) is especially common in men with cardiovascular diseases (CVDs). However, the data are scarce concerning populations without manifested CVD. Aim. The aim of this study was to describe factors associated with ED, especially those associated with decreasing risk of ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic renal disease. Methods. In 2004 to 2007, a cross-sectional population-based sample of men 45 to 70 years old in two rural towns in Finland was collected. Men with previously diagnosed CVD, diabetes, or kidney disease were not invited to the study. In total 1,000 eligible men with cardiovascular risk factors, i.e., central obesity, high scores in the Finnish Diabetes Risk Score, high blood pressure, antihypertensive medication, or family history of coronary heart disease, myocardial infarction, or stroke, were included in the analysis. Questionnaires, clinical measurements, and laboratory tests were obtained. The prevalence of ED was studied comparing the means, and risk factors were studied using multivariate logistic regression analysis. Main Outcome Measures. The rate of ED was defined by the International Index of Erectile Function short form (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain an erection. Results. The prevalence of ED was 57% or 68% using IIEF-5 or 2Q, respectively. Age (odds ratio (OR): up to 9.16; 95% confidence interval (CI), 5.00-16.79; P < 0.001), smoking (OR: 1.41; 95% CI, 1.04-1.91; P = 0.028), depressive symptoms (OR: 4.04 for moderate and severe; 95% CI,1.22-13.45; P = 0.001), high-intensity physical activity (OR: 0.50; 95% CI, 0.29-0.86; P = 0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable relation- ship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED. Conclusions. In apparently healthy men with cardiovascular risk factors, decreasing risk of ED is associated with high-intensity physical activity, stable relationship, and high education level. Ettala OO, Syvanen KT, Korhonen PE, Kaipia AJ, Vahlberg TJ, Bostrom PJ, and Aarnio PT. High-intensity physical activity, stable relationship, and high education level associate with decreasing risk of erectile dysfunction in 1,000 apparently healthy cardiovascular risk subjects. J Sex Med 2014;11:2277-2284. more...

Background: The aim of the study was to evaluate the diagnostic power of molecular markers in men with a clinical suspicion of prostate cancer (PCa) using apparently benign areas as targeted by magnetic resonance imaging (MRI). Methods: In the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. In addition to 12-core systematic and MRI-targeted biopsies, cores from normal-appearing prostate areas, based on clinical examination, ultrasound, and biparametric prostate MRI, were obtained. The RNA transcript levels of ACSM1, AMACR, CACNA1D, DLX1, KLK3, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 were measured with quantitative reverse-transcription polymerase chain reaction. Results: Of the 99 men, 69 were diagnosed with PCa, 31 with primary Gleason pattern 3 and 38 with primary Gleason 4 or 5. TDRD1 messenger RNA (mRNA) levels were 1.3 times higher (P = 0.029) and the presence of TMPRSS2-ERG mRNAs more frequent in biopsies from men diagnosed with PCa (27/69, 39%) than in men without (5/30, 16%) (P = 0.035). The 2 markers identified aggressive PCa defined as Gleason sum≥7 at biopsy: median TDRD1 mRNA level was 1.4 higher (P = 0.005) and TMPRSS2-ERG expression more frequent (P more...

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = −0.077, p = 0.014), leukocyte count (r = −0.107, p = 0.001), and SCORE (r = −0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p 10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue–driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease. more...

Smoking is a well-known risk factor for peripheral arterial disease (PAD). Data regarding differences in the prevalence of PAD between sexes are somewhat controversial. In addition, most studies indicate that the prevalence of PAD increases with age in both sexes. In the present study, the effects of sex, age and smoking on the ankle-brachial index (ABI) in a Finnish cardiovascular risk population were investigated.To investigate the relationship between the ankle-brachial index, and age, sex and smoking in a Finnish population at risk for cardiovascular disease.All men and women between 45 and 70 years of age living in a rural town (Harjavalta, Finland; total population 7700) were invited to participate in a population survey (Harmonica study). Patients with previously diagnosed diabetes or vascular disease were excluded. In total, 2856 patients were invited to participate in the study. From these subjects, a cardiovascular risk population was screened. Complete data were available from 1028 persons. ABI (the ratio between the posterior tibial or dorsalis pedis artery and brachial artery pressures) was measured, and questionnaires were used to detect smoking status and relevant medical history. Only current smoking status was taken into account.The mean ABI for the entire study population was 1.10 (range 0.56 to 1.64). Current smokers had a lower mean ABI (1.06; P0.001). There was no statistically significant difference in ABI values among age groups, although the majority of patients with ABI values below 0.9 were older than 60 years of age. There was no statistically significant difference in ABI between sexes.As previously reported, the present study shows the significant effect of smoking in the development of PAD. No statistically significant difference was found among age groups, but the tendency was toward lower ABIs in the oldest age groups. Sex had a minimal effect on the ABI. more...

Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = -0.347, p = 0.004) and with ABI-lower (r = -0.424, p more...

Kari Syvänen1, Päivi Korhonen2, Auli Partanen3, Pertti Aarnio11Department of Surgery, Satakunta Hospital District, Pori, Finland; 2Central Satakunta Health Federation of Municipalities, Harjavalta, Finland; 3Department of Biostatistics, University of Turku, Turku, FinlandIntroduction: The diagnosis of peripheral arterial disease (PAD) can be made by measuring the ankle–brachial index (ABI). Traditionally ABI values > 1.00–1.40 have been considered normal and ABI ≤ 0.90 defines PAD. Recent studies, however, have shown that individuals with ABI values between 0.90–1.00 are also at risk of cardiovascular events. We studied this cardiovascular risk population subgroup in order to determine their endothelial function using peripheral arterial tonometry (PAT).Methods: We selected 66 individuals with cardiovascular risk and borderline ABI. They all had hypertension, newly diagnosed glucose disorder, metabolic syndrome, obesity, or a ten year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System (SCORE). Subjects with previously diagnosed diabetes or cardiovascular disease were excluded. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertips using an Endo-PAT device.Results: The mean ABI was 0.95 and mean RHI 2.11. Endothelial dysfunction, defined as RHI < 1.67, was detected in 15/66 (23%) of the subjects. There were no statistically significant differences in RHI values between subjects with different cardiovascular risk factors. The only exception was that subjects with impaired fasting glucose (IFG) had slightly lower RHI values (mean RHI 1.91) than subjects without IFG (mean RHI 2.24) (P = 0.02).Conclusions: In a cardiovascular risk population with borderline ABI nearly every fourth subject had endothelial dysfunction, indicating an elevated risk of cardiovascular events. This might point out a subgroup of individuals in need of more aggressive treatment for their risk factors.Keywords: peripheral arterial disease, ankle–brachial index, cardiovascular risk, endothelial dysfunction&nbsp more...