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Purpose: We aimed to evaluate the genitourinary function and quality of life (QoL) following the ablation of different prostate segments with irreversible electroporation (IRE) for localized prostate cancer (PCa)., Methods: Sixty patients who received primary focal IRE for organ-confined PCa were recruited for this study. Patients were evaluated for genitourinary function and QoL per prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base, unilateral vs. bilateral). IRE system settings and patient characteristics were compared between patients with preserved vs. those with impaired erectile function and urinary continence. Data were prospectively collected at baseline, 3, 6, and 12 months using the expanded prostate cancer index composite, American Urological Association symptom score, SF-12 physical and mental component summary surveys. Difference over time within segments per questionnaire was evaluated using the Wilcoxon's signed rank test. Outcome differences between segments were assessed using covariance models. Baseline measurements included questionnaire scores, age, and prostate volume., Results: There were no statistically significant changes over time for overall urinary (P = 0.07-0.89), bowel (P = 0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within each segment. Deterioration of sexual function scores was observed at 6 months within each segment (P = 0.001-0.16). There were no statistically significant differences in QoL scores between prostate segments (P = 0.08-0.97). Older patients or those with poor baseline sexual function at time of treatment were associated with a greater risk of developing erectile dysfunction., Conclusion: IRE is a feasible modality for all prostate segments without any significantly different effect on the QoL outcomes. Older patients and those with poor sexual function need to be counseled regarding the risk of erectile dysfunction.

Background: The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies., Methods/design: In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols., Discussion: This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification., Trial Registration: The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.

Objective: To investigate the value of dynamic contrast-enhanced (DCE)-ultrasonography (US) and software-generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores., Materials and Methods: For 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE-US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE-US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false-negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value (NPV) and positive predictive value (PPV) on a per-prostate level., Results: Based on DCE-US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false-negatives (5.6%). In the per-prostate clinical analysis, DCE-US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE-US alone and 91, 56, 57 and 90%, respectively, with parametric maps., Conclusion: The interpretation of DCE-US with parametric maps allows good prediction of biopsy outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Several transrectal ultrasound (TRUS)-based techniques aiming at accurate localization of prostate cancer are emerging to improve diagnostics or to assist with focal therapy. However, precise validation prior to introduction into clinical practice is required. Histopathology after radical prostatectomy provides an excellent ground truth, but needs accurate registration with imaging. In this work, a 3D, surface-based, elastic registration method was developed to fuse TRUS images with histopathologic results. To maximize the applicability in clinical practice, no auxiliary sensors or dedicated hardware were used for the registration. The mean registration errors, measured in vitro and in vivo, were 1.5±0.2 and 2.1±0.5mm, respectively., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

As the prostate abundantly expresses muscarinic receptors and antagonists for such receptors are increasingly used in the treatment of men with voiding function and large prostates, we have explored an association of the mRNA expression of human M1, M2, M3, M4, and M5 receptors in human prostate with patient age, prostate size, prostate-specific antigen level, pathological diagnosis, and concomitant medication. mRNA was isolated from prostate chips of 110 consecutive patients undergoing transurethral resection of the prostate for the treatment of benign prostatic hyperplasia or prostate cancer. Expression of each of the five muscarinic receptor subtype transcripts was assessed by real-time PCR and association with patient age, prostate size, prostate-specific antigen level, pathological diagnosis, and concomitant medication were explored. M1 and M4 receptors were the most and least prevalently expressed subtypes in the human prostate, respectively. M1 receptor mRNA expression was weakly but significantly associated with prostate size (r = 0.2494, p = 0.0451), but mRNA expression of none of the five subtypes was significantly associated with age, prostate-specific antigen level, pathological diagnosis (benign prostatic hyperplasia vs. prostate cancer), or concomitant medication (5α-reductase inhibitors, α1- or β-adrenoceptor antagonists). We conclude that human prostate muscarinic receptor subtype transcripts apparently undergo only a very limited regulation by a variety of physiological, pathophysiological, or treatment factors. In light of the growing use of muscarinic receptor antagonists in men with voiding dysfunction including those with large prostates, the functional role of the weak association between M1 receptor mRNA expression and prostate size merits further investigation.

Background: Pooled data from randomised controlled trials (RCTs) with short-term follow-up have shown a safety advantage for bipolar transurethral resection of the prostate (B-TURP) compared with monopolar TURP (M-TURP). However, RCTs with follow-up >12 mo are scarce., Objective: To compare the midterm safety/efficacy of B-TURP versus M-TURP., Design, Setting, and Participants: From July 2006 to June 2009, TURP candidates with benign prostatic obstruction were consecutively recruited in four centres, randomised 1:1 into the M-TURP or the B-TURP arm and regularly followed up to 36 mo postoperatively. A total of 295 patients were enrolled., Intervention: M-TURP or B-TURP using the AUTOCON II 400 electrosurgical unit., Outcome Measurements and Statistical Analysis: Safety was estimated by complication rates with a special emphasis on urethral strictures (US) and bladder neck contractures (BNCs) recorded during the short-term (up to 12 mo) and midterm (up to 36 mo) follow-up. Efficacy quantified by changes in maximum urine flow rate, postvoid residual urine volume, and International Prostate Symptom Score was compared with baseline, and reintervention rates in each arm were also evaluated., Results and Limitations: A total of 279 patients received treatment after allocation. Mean follow-up was 28.8 mo. A total of 186 of 279 patients (66.7%) completed the 36-mo follow-up. Posttreatment withdrawal rates did not differ significantly between arms. Safety was assessed in 230 patients (82.4%) at a mean follow-up of 33.4 mo. Ten US cases were seen in each arm (M-TURP vs B-TURP: 9.3% vs 8.2%; p=0.959); two versus eight BNC cases (M-TURP vs B-TURP: 1.9% vs 6.6%; p=0.108) were collectively detected at the midterm follow-up. Resection type was not a significant predictor of the risk of US/BNC formation. Efficacy was similar between arms and durable. A total of 10 of 230 patients (4.3%) experienced failure to cure and needed reintervention without significant differences between arms. High overall reintervention rates, withdrawal rates, and sample size determination not based on US/BNC rates represent potential limitations., Conclusions: The midterm safety and efficacy of B-TURP and M-TURP are comparable., Trial Registration: Netherlands Trial Register, NTR703 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=703)., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the perioperative efficacy and safety of bipolar (B-) and monopolar transurethral resection of the prostate (M-TURP) in an international multicentre double-blind randomized controlled trial using the bipolar system AUTOCON(®) II 400 ESU for the first time., Patients and Methods: From July 2006 to June 2009, consecutive transurethral resection of the prostate (TURP) candidates with benign prostatic obstruction were prospectively recruited in four academic urological centres, randomized 1:1 into an M-TURP or B-TURP arm and followed up for 6 weeks after surgery. A total of 295 eligible patients were enrolled. Of these, 279 patients received treatment (M-TURP, n= 138; B-TURP, n= 141) and were analysed for immediate postoperative outcomes and perioperative safety. In all, 268 patients (M-TURP, n= 129; B-TURP, n= 139) were analysed for efficacy, which was quantified using changes in maximum urinary flow rate, postvoid residual urine volume and International Prostate Symptom Score at 6 weeks compared with baseline. Safety was estimated using sodium and haemoglobin level changes immediately after surgery and perioperative complication occurrence graded according to the modified Clavien classification system. Secondary outcomes included operation-resection time, resection rate, capsular perforation and catheterization time., Results: No significant differences were detected between each study arm except that postoperative decreases in sodium levels favoured B-TURP (-0.8 vs -2.5 mmol/L, for B-TURP and M-TURP, respectively; P= 0.003). The lowest values were 131 mmol/L (B-TURP) and 106 mmol/L (M-TURP). Nine patients ranged between 125 and 130 mmol/L and the values for three patients were <125 mmol/L after M-TURP. The greatest decrease was 9 mmol/L after B-TURP (two patients). In nine patients (M-TURP) the decrease was between 9 and 34 mmol/L. These results were not translated into a significant difference in TUR-syndrome rates (1/138: 0.7% vs 0/141: 0.0%, for M-TURP and B-TURP, respectively; P= 0.495)., Conclusions: In contrast to the previous available evidence, no clinical advantage for B-TURP was shown. Perioperative efficacy, safety and secondary outcomes were comparable between study arms. The potentially improved safety of B-TURP that is attributed to the elimination of dilutional hyponatraemia risk, a risk still present with M-TURP, did not translate into a significant clinical benefit in experienced hands., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: In light of recent interest in the use of muscarinic receptor antagonists for the treatment of male lower urinary tract symptoms, understanding how such drugs work not only on the bladder but also on the prostate is important., Methods: A literature review was conducted to identify studies on the cholinergic innervation and presence and function of muscarinic acetylcholine receptors in the human prostate., Results: The available studies demonstrate a dense cholinergic innervation within both stromal and epithelial compartments of the prostate. Concomitantly, the human prostate expresses muscarinic receptors at densities exceeding those of alpha(1)-adrenoceptors. They mainly belong to the M(1) subtype and are found on epithelial cells, but a smaller population of M(2) receptors is found on stromal cells. Both populations have been shown to be functional in signal transduction assays. However, in line with the sparse receptor density on stromal smooth muscle cells, contractile responses of the prostate are only small. Data from prostate cancer cell lines and from botulinum toxin injections into the benign prostate raise the possibility that muscarinic receptors may promote prostatic growth. Animal data suggest that muscarinic receptors may be of primary importance in the genesis of prostatic secretions, but this needs to be confirmed in humans., Conclusions: Taken together it appears that direct effects on the prostate need to be considered when using muscarinic receptor antagonists in men. They may primarily involve alterations of glandular secretion and prostatic growth.

Photoselective vaporization of the prostate (PVP) with a potassium titanyl phosphate (KTP) laser may be the most promising new technology applied to the treatment of benign prostatic hyperplasia (BPH). The specific laser light characteristics and the ideal interactions between KTP lasers and prostatic tissue result in an even and efficient vaporization of the prostate and the formation of a clearly deobstructed prostate cavity. PVP can be a day-care procedure, with few hours of catheterization and minimal postoperative discomfort, offering outcomes at least equivalent to the reference standard transurethral resection of the prostate. Although larger studies are necessary to further define where PVP stands in the management of BPH, this review focuses on contemporary treatment techniques and their limitations, and comments on the outcomes of its current use.

Aims: To test the hypothesis that improvements of lower urinary tract symptoms (IPSS) upon treatment with an alpha-blocker are due to reduction of bladder outlet obstruction (assessed as the bladder outlet obstruction index, BOOI); relationships of either with free flow Q(max) were also explored., Methods: The database of a large placebo-controlled, randomized, double-blind study with the alpha-blocker tamsulosin was analyzed retrospectively. Patients were stratified into lower and upper halves according to baseline IPSS, Q(max) or BOOI and treatment-associated alterations thereof. In these strata differences between values for the other two parameters were analyzed, for example, improvement of IPSS and Q(max) were compared in patients with below and above median improvement of BOOI., Results: Patients with below and above median baseline for one parameter, for example, IPSS had rather similar values for the other two parameters, for example, Q(max) and BOOI. Likewise, patients based upon baseline strata for one parameter had rather similar improvements of the other two parameters. Most importantly, patients with below and above median treatment-associated improvements of one parameter, for example, BOOI exhibited only small if any difference for alterations of the other two parameters, for example, IPPS and Q(max)., Conclusions: We conclude that IPSS, free flow Q(max) and BOOI are only loosely related at baseline. More importantly, treatment-induced improvements of these parameters are also only loosely related. These data do question the hypothesis that alpha-blockers largely improve lower urinary tract symptoms by reducing bladder outlet obstruction and suggest that they may also act independent of prostatic smooth muscle tone., ((c) 2007 Wiley-Liss, Inc.)

Objectives: The aim of this prospective study was to compare the diagnostic accuracy of detrusor wall thickness (DWT), free uroflowmetry, postvoid residual urine, and prostate volume (index tests) with pressure-flow studies (reference standard) to detect bladder outlet obstruction (BOO) in men., Methods: During a 2-yr period, men older than 40 yr with lower urinary tract symptoms and/or prostatic enlargement had the following tests: ultrasound measurements of DWT, free uroflowmetry (Q(max), Q(ave)), postvoid residual urine, and prostate volume. Pressure-flow studies were used to divide obstructed from nonobstructed bladders., Results: One hundred sixty men between 40-89 yr of age (median: 62 yr) were included in the study; 75 patients (46.9%) had BOO according to pressure-flow studies. The results of all investigated index tests differed significantly between obstructed and nonobstructed men. DWT was the most accurate test to determine BOO: the positive predictive value was 94%, specificity 95%, and the area under the curve of ROC analysis 0.93. There was an agreement of 89% between the results of DWT measurement and pressure-flow studies., Conclusions: Measurements of DWT can detect BOO better than free uroflowmetry, postvoid residual urine, or prostate volume. In clinical routine, DWT measurements can be used to judge BOO noninvasively., (European Association of Urology.)

Objectives: To investigate the prognostic role of prostate-specific antigen (PSA) level and prostate volume (PV) for the need for benign prostatic hyperplasia (BPH)-related invasive therapy among patients initially treated with an alpha1-blocker or watchful waiting (WW) in real-life clinical practice., Methods: Data were collected from 2264 consecutive patients with clinical BPH. Patients initially treated with an alpha1-blocker or WW were included in this study. They were stratified by baseline PSA level (less than 1.5, 1.5 to less than 3.0, 3.0 to 10.0 ng/mL) and PV (less than 30 and 30 to 200 cm3), and analyzed for the time to BPH-related invasive therapy., Results: Of the 2264 patients, 389 treated with alpha1-blockers and 553 who chose WW were included. Across the PSA and PV strata, the alpha1-blocker group had worse symptoms, peak flow, postvoid residual urine volumes, and obstruction than did the WW group. Increasing PSA levels produced an increase in the 5-year cumulative risk of invasive treatment: 20%, 34%, and 44% in the alpha1-blocker and 8%, 9%, and 15% in the WW group for a PSA level of less than 1.5, 1.5 to less than 3.0, and 3.0 to 10.0 ng/mL, respectively. The hazard ratio for the highest compared with the lowest PSA strata was 2.8 for alpha1-blocker and 2.7 for WW patients. An increasing PV increased the 5-year cumulative risk from 21% to 35% in the alpha1-blocker group and 8% to 11% in the WW group. The hazard ratio for the large versus small prostates in the alpha1-blocker group was 1.8 and in the WW group was 1.0., Conclusions: A higher PSA level and larger PV resulted in a greater risk of BPH-related invasive therapy that was more pronounced in the alpha1-blocker than in the WW patients. However, symptom severity, flow parameters, and obstruction grade may have contributed to the difference in risk between the two treatment groups.

Objectives: To assess the ability of serum prostate specific antigen (PSA) to estimate prostate volume (PV) to aid in the management of patients with benign prostatic hyperplasia (BPH)., Methods: From 1989 to 2002, data were collected from 2264 patients complaining of lower urinary tract symptoms (LUTS) who visited the Department of Urology of the University Medical Centre Nijmegen, The Netherlands. Baseline PV and serum PSA was determined using standard techniques. All patients who had a baseline PV < or =200 ml, as well as a baseline serum PSA 0-10 ng/ml, were included. Patients with a history of prostate surgery, prostate cancer and conditions other than BPH at baseline were excluded. A log-transformed linear regression model was used to estimate PV. Receiver-operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to estimate threshold PVs in men with BPH, and to select the optimal serum PSA cut-off values., Results: The analyses included 1859 patients with a mean age of 63.5 years, mean baseline PV 43.9 ml, and mean baseline PSA value 3.1 ng/ml. PV as well as serum PSA increases with age. Linear regression analyses showed that PV and serum PSA have an age-dependent log-linear relationship, where 42% of the variance of PV can be explained by PSA and age. ROC's area under the curves (AUC) reveal that PSA has a good predictive value for assessing 'prostate enlargement', with AUC around 82% in the overall age groups irrespective of the PV cut-off values. Optimal serum PSA cut-off values for the overall study population irrespective of age are 2.0 ng/ml to detect PV >30 ml and 2.5 ng/ml to detect PV >40 ml., Conclusions: This study suggests that serum PSA can estimate prostate enlargement sufficiently accurately to be useful for therapeutic, especially medical, management. It is well accepted that the outcome of pharmacotherapy for BPH depends on baseline PV. Therefore, in the absence of reliable direct measurement of PV, serum PSA determination may be used to optimise patient management.

Purpose: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score, patient age, and tumor markers., Materials and Methods: Of 58 patients with prostatic carcinoma, 36 were included for analysis. Patients underwent MR imaging at 1.5 T with an endorectal-pelvic phased-array coil and subsequently underwent prostatectomy. A T2-weighted turbo spin-echo sequence, an intermediate-weighted sequence, and a fast T1-weighted gradient-echo sequence (seven sections in 2.03 seconds) during bolus injection of 0.1 mmol gadopentetate dimeglumine per kilogram of body weight were performed. Contrast agent concentration-time curves were obtained for prostatic carcinoma and normal PZ and CG tissue by using whole-mount sections to guide placement of regions of interest. Onset time, time to peak, peak enhancement, relative peak enhancement, washout, and T2 relaxation rates were calculated. Multivariate receiver operating characteristic analysis was performed with and without relative peak enhancement., Results: Results of multivariate receiver operating characteristic analysis showed that relative peak enhancement demonstrated the highest area under the receiver operating characteristic curve (AUC) in the PZ and the CG (AUC = 0.93, 0.82). Results of multivariate analysis without relative peak enhancement showed that relative peak enhancement in the PZ and washout in the CG demonstrated the highest AUC (AUC = 0.9, 0.81). Pearson correlation coefficients between the dynamic parameters or T2 relaxation rates in carcinoma and the tumor stage, Gleason score, patient age, and tumor markers ranged between 0.02 and 0.44., Conclusion: The optimal parameter for discrimination of prostatic carcinoma in the PZ and CG was relative peak enhancement. If relative peak enhancement was not used, then peak enhancement was optimal in the PZ, and washout was optimal in the CG. Poor-to-moderate correlation was present between the dynamic parameters or T2 relaxation rate in carcinoma and the tumor stage, Gleason score, patient age, tumor volume, and prostate-specific antigen., (Copyright RSNA, 2003)

Transrectal three-dimensional (3-D) contrast-enhanced power Doppler ultrasound (US) is a novel technique for studying possible prostate malignancy. Before studies can be performed to investigate the clinical validity of the technique, reproducibility of the contrast US studies must be proven. Reproducibility of contrast US was studied in 10 patients with biopsy-proven prostate cancer. The studies performed included static investigations and dynamic investigations of the prostate vasculature. All studies were double performed. The assessment of reproducibility was done objectively using a computer program and, subjectively, by visual assessment. The results indicate high reproducibility of static contrast investigations, for both the objective and subjective assessment. The subjective assessment of the dynamic studies was also highly reproducible. The objective assessment of the dynamic contrast studies, however, was less reproducible, mainly due to motion artefact. We concluded that, especially static 3-D contrast-enhanced, power Doppler investigations of the prostate are highly reproducible.

Background: Blood perfusion regulates intraprostatic temperatures during transurethral microwave thermotherapy (TUMT). We evaluated baseline intraprostatic vasculature, as a predictor of efficacy of TUMT., Methods: Twenty-two patients, with lower urinary tract symptoms (LUTS) suggestive of bladder outflow obstruction, were treated with TUMT (Prostatron). At baseline, three-dimensional contrast-enhanced power-flow-Doppler prostate ultrasonography (3D-CE-PFD) was performed. Assuming that the percentage of perfused area (PPA) is a realistic measure of blood flow, it was used to quantify intraprostatic vasculature., Results: The median (range) age, prostate size, and energy delivered were 66 years (48-80), 47 cm(3) (30-121), 110 kJ (29-136), respectively. The response was 77% (5 failures). The median (range) PPA was 2.76% (0.7-11.3). No difference in PPA among good and poor responders was detected nor was any correlation between PPA and baseline parameters., Conclusions: The baseline intraprostatic vascularization, documented by CE-PFD studies, has no predictive value for the efficacy of TUMT. It seems that "static" baseline blood flow does not reflect the "dynamic" thermoregulatory role of blood flow during treatment., (Copyright 2001 Wiley-Liss, Inc.)

Objective: Knowledge regarding cell biologic characteristics of small solid glandular buds in the prostate and their relationship with branching activity in the human prostate is still fragmentary. Our object was to demonstrate, on the basis of immunophenotype, loci that harbor the potential for branching activity within the adult human prostate., Materials and Methods: Semiserial sectioning was performed on 13 adult prostates in an effort to identify structures in the prostate that could be considered foci of growth. Selected slides were stained with biomarkers for basal/luminal cells (keratins), proliferation (MIB-1), apoptosis inhibitor (bcl-2), intercellular adhesion (E-cadherin), and stromal-epithelial interactions (tenascin-C). Results were compared with fetal and prepubertal human prostates and microdissected rat prostates., Results: Five histologic epithelial structures were identified in 19 paraffin blocks, which on serial sectioning showed morphologic transitions with a common pattern, consisting of reduction in number and caliber of acini until small solid buds of epithelial cells were reached. Immunophenotypically, the small solid glandular buds had a basal-cell keratin phenotype, expression of bcl-2 in virtually all cells, high proliferative activity, prominent intracellular localization of E-cadherin, and enhanced periglandular tenascin-C immunoreactivity. The budding tips in fetal and prepubertal prostates revealed an immunostaining pattern identical to the small solid glandular buds in the adult, but different to the rat prostate., Conclusions: Our data suggest that dispersed small solid glandular buds have a capacity for growth, and as such may be considered foci of resumed reawakening branching activity with in the adult human prostate.

Transurethral microwave thermotherapy is being applied as a minimally invasive treatment for alleviating the symptoms of urinary outlet obstruction associated with benign prostatic hyperplasia. Treatment progress has traditionally been guided in its effective power by rectally and urethrally measured temperatures, whereas intraprostatic temperatures would be preferred for feedback purposes. A critical evaluation is presented of intraprostatic thermometry techniques that have been suggested, the techniques currently being used and investigated, and the problems that remain to be solved. Techniques for noninvasive temperature measurement and detecting tissue response during thermal therapy are discussed in more detail. Results presented in the literature have shown magnetic resonance imaging and ultrasonic imaging to be adequate thermometry modalities. For treatment monitoring of transurethral microwave thermotherapy, ultrasonic imaging is especially promising. Future research will indicate whether the promise evolves into a sound clinical technique.

Tenascin (tenascin-C), a mesenchymal glycoprotein, is expressed in many tissue remodeling processes. We evaluated tenascin expression during androgen-deprivation-related involution of the rat prostate. At set intervals following castration and subsequent testosterone repletion, prostates were removed in 30 adult rats. Each prostate was immunostained with a polyclonal antiserum against rat tenascin and keratin antibodies specifically directed against exocrine basal cells and luminal cells in the prostate glandular structure. Morphologic impressions were semiquantatively evaluated using a computer-assisted image analysis system. Rat prostates showed a transient increase in the periglandular tenascin expression directly following castration that reached a maximum at day 3. At day 6, tenascin expression was similar to control prostates. This was accompanied by a decrease of cells in the luminal cell layer. The weakest tenascin immunoreactivity was noted on day 14 after androgen withdrawal. This process was reversed by androgen repletion. This study shows that in the rat prostate tenascin expression may be androgen dependent and that during androgen deprivation-related involution tenascin expression is probably associated with tissue remodeling by stromal-epithelial interactions.

Objectives: A feasibility study to evaluate whether analysis techniques adapted from X-ray angiography can be used to analyze the transient enhancement of prostate blood flow patterns in color Doppler maps as obtained after administering ultrasound contrast agents., Methods: Injections of ultrasound contrast agents were given to dogs and humans, and color Doppler blood flow patterns in fixed transverse sections through the prostate were recorded on video tape. Computer assistance of Doppler signals over time is used to evaluate the transient enhancement of flow patterns obtained with contrast-enhanced Doppler ultrasound. Results are compared to indicator dilution curve theory as used in, e.g., X-ray angiography., Results: Administering a contrast agent to improve color Doppler evaluation of prostate blood flow resulted in clear enhancement of Doppler signal intensities without unwanted side effects. Using the computer, the perfused area of the prostate could be obtained quantitatively over time showing profiles of individual heartbeats. Averaging the perfused area over one heartbeat resulted in an indicator dilution curve, and correlation with dilution theory indicated the feasibility of applying wash-in and wash-out analysis of contrast agents in color Doppler images., Conclusion: Frame-by-frame interpretation by the computer indicated the feasibility of analyzing the transient enhancement of blood flow visibility in the Doppler image over time using techniques such as wash-in and wash-out time. This technology provides researchers in the field of ultrasound evaluation of the prostate the opportunity to apply a new diagnostic tool, contrast angiosonography, in their research. This method for analysis of prostatic blood flow can be helpful in any application that affects the blood supply of the prostate such as heat treatments and hormonal treatments.

Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.

Objectives: To review the current clinical practice concerning prostate biopsies and indications for prostate biopsies and to study the value of biopsies in grading and staging of prostate cancer., Methods: The literature from 1990 onwards was reviewed systematically. A selection out of the huge number of publications concerning the subject was made based on the relevance of the study (e.g., number of patients, study design)., Results: Transrectal ultrasound-guided biopsies have become a routine procedure in urological practice and can be performed safely. Antibiotic prophylaxis is recommended generally. Sextant biopsies should be performed when no lesion is visible or added to lesion-directed biopsies in case of a visible lesion. The indications for biopsies and for repeat biopsies are discussed. The indication for biopsies remains a problem in spite of prostate-specific antigen and prostate specific antigen derived indexes and in spite of new imaging techniques. The value of prostate biopsy in grading and staging is limited, and care should be taken not to base treatment decisions on prostate biopsy results only and not to compare treatment results based on biopsy data., Conclusions: Prostate biopsies have become a routine procedure in urology. Although very helpful in many cases, their limitations should be kept in mind. More efforts will have to be made to reduce the (too) large number of negative biopsies by improvement of imaging techniques and development of more sensitive and specific tumor markers.

Background: Tenascin (tenascin-C) has been suggested to be associated with active epithelial-stromal interactions. We evaluated tenascin expression in tissue remodelling processes presumably associated with PIN and prostate carcinoma (PCa)., Materials and Methods: Tenascin immunoreactivity was evaluated in 38 PIN lesions (low-grade = 5, high-grade = 33) from 27 paraffin-embedded PCa specimens, and compared with expression in pre-existent (normal) prostate, benign prostatic hyperplasia (BPH), and PCa., Results: Periepithelial stromal tenascin expression was low in low-grade PIN, and similar to normal glands and BPH, whereas expression in high-grade PIN was high and partly overlapped that of well-/moderately differentiated PCa. High-grade PCa usually expressed little, if any tenascin., Conclusions: The variable periglandular tenascin expression in high-grade PIN may reflect the biologic behaviour of this lesion, and may be indicative of variable levels of tissue remodelling. In well/moderately differentiated PCa tenascin expression levels may be an indicator of tumour progression.

Purpose: We present a critical evaluation of the use of ultrasound for prostate disease examination in urological practice, and provide perspectives on ultrasound applications that may become important for the future evaluation of prostate problems., Materials and Methods: Based on an evaluation of clinical data in cases suspicious for prostatic malignancy, we addressed the apparent shortcomings of transrectal ultrasound for accurately diagnosing prostate cancer. Future applications presented in the literature were noted., Results: Evaluating the ultrasound data in cases suspicious for malignancy indicated that imaging has little advantage over digital rectal examination for detecting malignant areas. The new applications of ultrasound that hold great promise for use in the urology clinic include the injection of contrast agents to obtain information on blood supply, temperature estimation for the noninvasive assessment of temperature distributions during heat treatment and a therapeutic application for local treatment of prostate cancer., Conclusions: While differential diagnosis with ultrasound appears to result in disappointing sensitivity and specificity values, its use in volume measurement and biopsy guidance is unquestioned. The development of new applications may improve the clinical value of ultrasound in urological practice. The application of ultrasound contrast agents for the detection and clinical staging of prostate cancer is especially promising. Future research will indicate whether the promise evolves in clinical applications.

Background: The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in early stages of prostate development, using keratin antibodies specific for them., Methods: Autoptic tissue from 11 prepubertal and 5 normal adult prostates was immunohistochemically stained with four keratin antibodies capable of specifically detecting basal, luminal, or intermediate cell types., Results: Morphologically, in fetal prostate cells differentiation was often not evident. However, basally located cells usually displayed a basal-cell keratin-phenotype. Morphologically similar cells with more luminal localization expressed keratins typical of luminal cells, or of intermediate cells., Conclusions: 1) In early stages of prostate development, cells with intermediate keratin-phenotype can be identified. 2) Their large numbers comply with a hierarchical pathway of cellular differentiation from basal to luminal cells. 3) The presence of intermediate cells at such an early fetal age may reflect their regulatory function in prostate development.

Objective: We investigated an algorithm to detect grey level transitions with multiple scales of resolution to improve edge detection and localisation in ultrasound images of the prostate., Introduction: We had developed a non-analytical operator for prostate contour determination implemented with minimum and maximum filters and locate edges. We implemented a technique for improved determination of boundary parts in prostatic ultrasound images by adjusting the edge detection parameter to signal information., Methods: First the influence of prefilter settings and edge detection parameters is investigated in a test image and a real ultrasound image. Then, local standard deviation is used to identify or fewer homogeneous regions that are filtered with course resolution, while areas with larger deviation that grey level transitions occur, which should be preserved using smaller filter sizes to improve edge localisation., Results: Analysis of images with different filter sizes indicated that areas are merged for increasing filter sizes: less pronounced edges disappear or displace for larger filters. Two scales of resolution lead to an improved localisation of edges when smaller filter sizes are used in areas with an increased local standard deviation., Conclusions: This paper illustrates an edge detection method suitable as pre-processing step in interpretation of medical images. By adapting input parameters to signal information, object recognition can be applied in images from different imaging modalities. Also, disadvantages are discussed, resulting in a new application combining a localisation algorithm to find the initial contour and a delineation algorithm to improve the outlining of the resulting contour.

Purpose: To assess whether a TurboFLASH (fast low-angle shot) magnetic resonance (MR) sequence can improve the accuracy of fast spin-echo (SE) endorectal coil MR imaging in the staging and localization of prostate cancer., Materials and Methods: In 57 patients with prostate cancer, MR imaging was performed with the following sequences: T1-weighted SE, T2-weighted fast SE, single-section gadolinium-enhanced dynamic subtracted TurboFLASH (one image every 1.25 or 2.5 seconds), and late-phase gadolinium-enhanced T1-weighted SE. Retrospectively, two blinded independent readers graded onset and steepest slope of enhancement and assessed tumor involvement and capsular penetration. MR findings were correlated with histopathologic results., Results: On TurboFLASH images, prostate cancer was characterized by early and rapidly accelerating enhancement compared with that of surrounding tissues. Average sensitivity, specificity, and accuracy for detection of tumor involvement for the two readers with TurboFLASH images were 73.5%, 81.0%, and 77.5%. These values with fast SE images were 57.5%, 80.5%, and 72.0%. Depiction of capsular penetration and delineation and staging of tumor were better when TurboFLASH images were included with fast SE images. Differences between the two sequences, however, were not statistically significant., Conclusion: Because the TurboFLASH sequence did not statistically significantly improve tumor localization and staging results, routine use is not recommended. The technique may be useful for selected patients with equivocal evidence of capsular penetration.

Background: The diagnostic value of prostate volume results has been evaluated in patients with prostate problems of benign cause., Methods: For 247 patients, automated volume results were compared to manual results of planimetric reference volume and of the classical ellipsoid formula. Also, transition zone volume was estimated and growth curves of the prostate and prostate dimensions over age were investigated., Results: Application of automated volume determination gives accurate results compared to the reference volume (Pearson correlation, R = 0.938). The ellipsoid volume results were slightly less correlated (R = 0.921). Average growth of the entire prostate was 1.7% per year, for the transition zone the growth was 4.3%. Compared to growth rates for a community-based population, comparable growth rates were found for our group that had higher mean prostate volume., Conclusions: The results indicate that the age of onset of volume growth is the determining factor in developing benign prostate enlargement not a change in growth rate.

Background: Standardized estimations of prostate volumes are used for interpretation of prostate specific antigen (PSA) levels., Methods: In 243 patients with clinically benign diagnosis, automated and reference prostate volumes and transition zone volumes are correlated to PSA levels. Besides, growth curves of PSA level when aging are determined., Results: The strongest correlation was found with multiple regression analysis between PSA and transition zone volume and rest volume (R = 0.854). Mean PSA density was 0.092 ng/mL2, its labelling quality for benign disease was 91% (threshold = 0.15 ng/mL2). An average growth factor for PSA levels of 2.9% per year was obtained., Conclusions: The contribution per unit tissue to PSA level was for the transition zone 1.9 times higher than for the rest volume. Average growth of PSA per year is in consonance with the increase in normal levels of age specific PSA ranges, although only weak correlations were found between PSA and age and PSA density and age.

Objective: To assess the reproducibility of estimates of prostate volume determined by planimetry from transrectal ultrasonography (TRUS) images., Materials and Methods: Two sequential sessions of images obtained by TRUS were obtained from 30 patients, with the ultrasound probe removed and inserted between the sessions. The stored images were outlined, both manually and by computer, and measurements of prostate volume obtained planimetrically. In addition, the ability of the urologist to accurately draw the contour was assessed by outlining predefined contours., Results: The mean (SD) variability of manual outlining between sessions was 3.5 (3.4)%, within one session was 1.7 (1.3)% and of computer outlining between sessions was 4.3 (3.8%). Comparing the results of manual and computer outlining showed a mean (SD) variability of 7.5 (5.6)%, with larger values obtained from computer outlining. The mean (SD) variation in manually outlining predefined contours was 1.4 (1.4)%., Conclusions: The variability of computer outlining was slightly higher than expected theoretically. The within-session variability was higher than the variation caused by errors in outlining predefined contours, indicating that the interpretation of TRUS images differed with time. Automated determination of prostate volume can save time during clinical investigation and the variability is within the clinically acceptable range of 5%.

A non-parametric algorithm is described for the construction of a binary decision tree classifier. This tree is used to correlate textural features, computed from ultrasonographic prostate images, with the histopathology of the imaged tissue. The algorithm consists of two parts; growing and pruning. In the growing phase an optimal tree is grown, based on the concept of mutual information. After growing, the tree is pruned by an alternating interaction of two data sets. Moreover, the structure and performance of the constructed tree are compared to the results using a slightly modified corresponding growing and pruning algorithm. The modified algorithm provides better retrospective and prospective classification results than the original algorithm. The use of the tree for automated cancer detection in ultrasonographic prostate images results in retrospective and prospective accuracy of 77.9% and 72.3%, respectively. Using this tissue characterisation, a supporting tool is provided for the interpretation of transrectal ultrasonographic images.

Objectives: Despite disadvantages such as time-consuming and tedious to the user, planimetric volumetry is considered to be the most accurate method for prostate volume determination. This study investigates the possibilities of formula-derived volume determination and reveals the best alternative to planimetric volumetry., Methods: The prostate volume is calculated using prostatic dimensions (length, height and width) in four mathematical descriptions for prostate volume calculations. As reference, the planimetric results obtained with 4 mm step size were used., Results: Compared to the results of planimetric volumetry obtained with 4-mm intersection distance, the best results for volume determination with mathematical calculation were obtained with a formula describing a spheroid volume using half the mean of width, height and length as radius., Conclusion: Although planimetric volumetry remains the most accurate method for prostate volume determination, the spheroid formula is the best alternative method for quick volume assessment with reasonable accuracy.

Planimetric volumetry is used in clinical practice when accurate volume determination of the prostate is needed. The prostate volume is determined by discretization of the 3D prostate shape. The are of the prostate is calculated in consecutive ultrasonographic cross-sections. This area is multiplied by the distance between the cross-sections and the total volume is determined by summation of all contributions. Besides the quality of the automated outlining, the accuracy of this method depends on this intersection distance and on the angle of the scan plane with the probe. Also, the location of the first cross-section is of influence. This paper describes the influences of these parameters on the accuracy of the volume determination using a simple prostate model. This theoretical influence is compared to clinical volume determinations using automated planimetric volumetry with different step sizes. From our data, it is concluded that a step size of 4 mm for planimetric prostate volume determination is a good compromise between investigation time and accuracy in a clinical setting.

A method for automated determination of the prostate volume based on planimetric volumetry was developed to overcome subjectivity in prostate volume measurements using ultrasonography. An edge detection method is applied to locate the prostate boundary in sequential ultrasonographic images. During regular examinations, the volume was assessed automatically in 55 patients. The Pearson correlation coefficient of the automated volume compared to the reference prostate volume was 0.93. The estimated ratio of the automated volume to the reference volume was 0.92. This method overcomes the individual subjectivity when interpreting ultrasonographic images, and provides accurate and objective results for followup of benign prostatic hyperplasia treatments and for comparison of multicenter trials. Also, this method is a useful tool for objective determination of prostate specific antigen in proportion to the volume (prostate specific antigen density).

This retrospective study was conducted in 521 men with micturition complaints to determine the relationship between prostate size and bladder-outlet obstruction. Analysis showed a statistically significant correlation between bladder-outlet obstruction and prostate size. Urodynamic bladder-outlet obstruction was confirmed in 90% of the patients with a prostate size of more than 80 cm3. In 32% of the patients with a prostate smaller than 40 cm3, no urodynamic evidence of bladder-outlet obstruction was found. There was no correlation between symptom scores (Madsen and I-PSS) and the grade of bladder-outlet obstruction or prostate size. We conclude that precise determination of the prostate size and urodynamics investigations are important (complementary) parameters in the assessment of elderly men with micturition complaints.

This paper describes a practical method for automated determination of the contour of the prostate in ultrasonographic images. In this method, we use specific edge detection techniques, based on nonlinear Laplace filtering. Possible edges are located at zero-crossings of the second derivative of the image. The strength of the edge is reflected by the value of the gradient of the image at that location. Combining the information about location and strength, an edge intensity image is constructed from the initial ultrasonographic image. In our method, edge enhancement techniques are performed on the edge intensity image. Edges that actually represent a boundary are selected and linked: interpolation techniques are used to fill the gaps between detected boundary edges. The method for contour determination in ultrasonographic images is used for accurate volume measurements in an everyday clinical environment. Its computer implementation is fast, accurate (mean difference within 6% of exact volume) and easy to use.

This paper describes a study on the automated analysis of ultrasonographic prostate images. With image processing, tissue characterization in the prostate was performed to assess the probability of malignancy. During prostate examinations, images were recorded at the positions where biopsies were taken. The used samples were divided into three groups. Two of them were used for the construction of a classification tree, and the third was used for the evaluation of this classification. A sensitivity of 80.6% and specificity of 77.1% were reached retrospectively. In a prospective way, these results were 80.0% and 88.2%, respectively. The prospective predictive value for cancer detection was 85.7%. The presented prospective value for image analysis was almost twice as high as the values normally found for prostate examination.

This article describes a method to investigate the influence of inconsistent histopathology during the development of tissue discrimination algorithms. Review of the pathology is performed on the biopsies used as training set of a computer system for cancer detection in ultrasonographic prostate images. The influence of the discrepancies found between independent pathologists on the discriminating power of the system is investigated. A high diagnostic consistency in histopathology concerning only the categories malignant and nonmalignant is found. Therefore, review of the pathology does not significantly influence the results of tissue discrimination algorithms for cancer detection. However a high interobserver variability is obtained in the differentiation between more histology classes.

The potential value of prostatic imaging in the diagnosis of inflammatory disorders of the prostate is largely unexplored. In several studies, specific ultrasonographic characteristics in patients with prostatitis have been described. Also nonspecific echogenic qualities in prostatitis have been pointed out. To evaluate ultrasound of the prostate in patients with nonbacterial prostatitis in this study, ultrasound images of these patients were compared with those of a healthy control group. In contrast with earlier findings, constant dilatation of the periprostatic venous plexus was seen more pronounced in the control group as well as elongation of the seminal vesicles. Finally, prostatic calcifications were frequently encountered in both groups.

To our knowledge, only 3 patients with an extragonadal germ cell tumor of the prostate have been described in the literature until now. We here present a patient with a germ cell tumor arising in the retroperitoneum, invading the prostate, which was successfully treated by a combination of chemotherapy and nonmutilating surgery.

Ultrasonography of the prostate furnishes images which still cannot be fully interpreted morphologically. In a cadaver study, the ultrasound images of two groups (21 and 19) prostates, obtained in a water bath, were compared with histology slides taken at corresponding levels. In the first part of the study, using a 4 MHz probe, there was a correlation between hyperechoic lesions and stone formations in 9 out of 15 cases. A relation between hypoechoic lesions and the existence of a carcinoma could also be established in 4 out of 12 cases. In the second part of the study, using a 7 MHz probe, there was a correlation between hyperechoic lesions and stone formations in all cases. Hypoechoic lesions correlated with the presence of a carcinoma in 1 out of 8 cases. The technique used appears to be well suited for the comparative study of ultrasound images and histology. Application of the 7 MHz probe is preferable as, because of a better resolution, smaller lesions can be detected. The results of this study are not very encouraging for the use of transrectal ultrasound for the detection of small prostatic carcinomas.