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Objective: To assess the most effective local analgesia during transrectal ultrasound-guided prostate biopsy., Methods: A total of 123 consecutive patients undergoing transrectal ultrasound-guided prostate biopsy for elevated prostate-specific antigen levels and/or a suspicious digital rectal examination were randomized to three groups. Patients received a 60-mg lidocaine suppository (group 1, n = 41), a periprostatic nerve block (10-mL injection of lidocaine hydrochloride; group 2, n = 41) or a combination of both (group 3, n = 41) before a 10-core transrectal ultrasound-guided biopsy. A total of 80.5% (n = 99) of the patients underwent their first biopsy, 27.1% (n = 22) their second and 2.4% (n = 2) the third. Pain was evaluated on a 10-point visual analog scale for each step of the procedure., Results: Prostate-specific antigen values ranged from 0.39 to 90.1 (mean [SD] 8.76 ng/mL [11.08 ng/mL]). Comparison of the median visual analog scale scores between groups 1 and 2 showed a significant difference (P = 0.004). The differences in the outcomes between groups 1 and 3 (P = 0.001), and groups 2 and 3 (P = 0.001) were also significant. Patients of group 3 had the best output corresponding to the pain sensations and therefore the lowest visual analog scale scores., Conclusion: The combination of lidocaine suppository and periprostatic lidocaine infiltration is more effective for pain control than either lidocaine suppository or periprostatic lidocaine infiltration alone in patients undergoing transrectal ultrasound-guided prostate biopsy., (© 2014 The Japanese Urological Association.)

Objectives: To assess the applicability of the Prostate Cancer Prevention Trial High Grade (Gleason grade ≥ 7) Risk Calculator (PCPTHG) in ten international cohorts, representing a range of populations., Methods: A total of 25,512 biopsies from 10 cohorts (6 European, 1 UK and 3 US) were included; 4 implemented 6-core biopsies, and the remaining had 10 or higher schemes; 8 were screening cohorts, and 2 were clinical. PCPTHG risks were calculated using prostate-specific antigen, digital rectal examination, age, African origin and history of prior biopsy and evaluated in terms of calibration plots, areas underneath the receiver operating characteristic curve (AUC) and net benefit curves., Results: The median AUC of the PCPTHG for high-grade disease detection in the 10- and higher-core cohorts was 73.5% (range, 63.9-76.7%) compared with a median of 78.1% (range, 72.0-87.6%) among the four 6-core cohorts. Only the 10-core Cleveland Clinic cohort showed clear evidence of under-prediction by the PCPTHG, and this was restricted to risk ranges less than 15%. The PCPTHG demonstrated higher clinical net benefit in higher-core compared with 6-core biopsy cohorts, and among the former, there were no notable differences observed between clinical and screening cohorts, nor between European and US cohorts., Conclusions: The PCPTHG requires minimal patient information and can be applied across a range of populations. PCPTHG risk thresholds ranging from 5 to 20%, depending on patient risk averseness, are recommended for clinical prostate biopsy decision-making.

Objectives: To evaluate the discrimination, calibration, and net benefit performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) across five European randomized study of screening for prostate cancer (ERSPC), 1 United Kingdom, 1 Austrian, and 3 US biopsy cohorts., Methods: PCPTRC risks were calculated for 25,733 biopsies using prostate-specific antigen (PSA), digital rectal examination, family history, history of prior biopsy, and imputation for missing covariates. Predictions were evaluated using the areas underneath the receiver operating characteristic curves (AUC), discrimination slopes, chi-square tests of goodness of fit, and net benefit decision curves., Results: AUCs of the PCPTRC ranged from a low of 56% in the ERSPC Goeteborg Rounds 2-6 cohort to a high of 72% in the ERSPC Goeteborg Round 1 cohort and were statistically significantly higher than that of PSA in 6 out of the 10 cohorts. The PCPTRC was well calibrated in the SABOR, Tyrol, and Durham cohorts. There was limited to no net benefit to using the PCPTRC for biopsy referral compared to biopsying all or no men in all five ERSPC cohorts and benefit within a limited range of risk thresholds in all other cohorts., Conclusions: External validation of the PCPTRC across ten cohorts revealed varying degree of success highly dependent on the cohort, most likely due to different criteria for and work-up before biopsy. Future validation studies of new calculators for prostate cancer should acknowledge the potential impact of the specific cohort studied when reporting successful versus failed validation.

Objectives: To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume., Methods: We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves)., Results: The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts., Conclusions: Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume.

Objectives: To evaluate prostate cancer (PCa) detection rates of real-time elastography (RTE) in dependence of tumor size, tumor volume, localization and histological type., Materials and Methods: Thirdy-nine patients with biopsy proven PCa underwent RTE before radical prostatectomy (RPE) to assess prostate tissue elasticity, and hard lesions were considered suspicious for PCa. After RPE, the prostates were prepared as whole-mount step sections and were compared with imaging findings for analyzing PCa detection rates., Results: RTE detected 6/62 cancer lesions with a maximum diameter of 0-5 mm (9.7%), 10/37 with a maximum diameter of 6-10 mm (27%), 24/34 with a maximum diameter of 11-20 20 mm (70.6%), 14/14 with a maximum diameter of >20 mm (100%) and 40/48 with a volume ≥0.2 cm(3) (83.3%). Regarding cancer lesions with a volume ≥ 0.2 cm³ there was a significant difference in PCa detection rates between Gleason scores with predominant Gleason pattern 3 compared to those with predominant Gleason pattern 4 or 5 (75% versus 100%; P = 0.028)., Conclusions: RTE is able to detect PCa of significant tumor volume and of predominant Gleason pattern 4 or 5 with high confidence, but is of limited value in the detection of small cancer lesions.

Objective: To correlate a subjective blood-flow rating scale from contrast-enhanced colour Doppler (CECD) transrectal ultrasonography-targeted prostate biopsy with the histopathological outcome of the biopsy., Patients and Methods: In all, 760 men with a serum total prostate-specific antigen (PSA) level of ≥ 1.25 ng/mL and a free-to-total PSA ratio of < 18% were included. CECD-targeted biopsies with five cores were taken only in hypervascular areas of the peripheral zone using a second-generation ultrasonography contrast agent, followed by a 10-core systematic biopsy. Prostate blood flow was scored using a subjective 5-point scale in which 1 indicated 'benign', 2 'probably benign', 3 'indeterminate', 4 'probably malignant' and 5 'malignant'., Results: Overall 37% (283 of 760) patients had prostate cancer in the biopsy. All 100 patients with a score of 5 had cancer; 153 had a score of 4, of whom 130 (85%) had cancer and 23 had benign histology (15%); 131 had a score of 3, of whom 34 (26%) had cancer and 97 (74%) had benign histology; 284 had a score of 2, of whom 17 (6%) had cancer and 267 (94%) had benign histology; 92 had a score of 1, of whom two (2%) had cancer and 90 (98%) had benign tissue. Statistical evaluation showed that the subjective blood-flow rating scale correlated strongly and significantly (r = 0.75, P < 0.01) with the histopathological outcome of the biopsy., Conclusion: The present study shows that a subjective CECD blood-flow rating scale is a reliable tool to predict the pathological outcome of biopsy cores., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Purpose: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study., Experimental Design: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing., Results: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005)., Conclusions: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.

Objective: To compare the results of contrast-enhanced colour Doppler (CECD)-targeted prostate biopsy with a systematic 10-core grey-scale biopsy scheme in patients initially diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN), as although HGPIN is thought to be a precursor to invasive adenocarcinoma, its diagnosis is no longer considered an indication for repeat prostate biopsy and patients should be followed by prostate-specific antigen levels and a digital rectal examination., Patients and Methods: In all, 104 patients (aged 45-78 years) diagnosed with HGPIN on initial prostate needle biopsy were referred for a repeat biopsy within 6 months. Two independent examiners evaluated each patient; one used CECD-targeted biopsy (up to five cores) into hypervascular regions in the peripheral zone only, and subsequently the second took a systematic 10-core grey-scale biopsy. Cancer detection rates of both techniques were compared., Results: Overall, 26 of the 104 men (25%) had prostate cancer in the repeated biopsy. Using the CECD technique cancer was detected in 21% (22 of 104). The positive re-biopsy rate using the systematic technique was 9.6% (10 of 104; P < 0.001). The total incidence of HGPIN with no evidence of tumour on re-biopsy was 8.7% (nine of 104). The Gleason score in all 22 cancers detected with the CECD technique varied between 6 and 8. The systematic technique detected cancers with Gleason scores of 6 or 7. There were no adverse events or complications., Conclusion: CECD increased the detection rate of prostate cancer, and using fewer biopsy cores than the systematic biopsy technique in patients previously diagnosed with HGPIN.

Purpose: To describe the current and new developments in transrectal ultrasound (US) imaging of the prostate., Patients and Methods: Grayscale imaging of the prostate is the standard method for diagnostic evaluation and biopsy guidance. Color Doppler (CD) imaging, including CD and power Doppler US, allows for detection of macrovascularity and may therefore be helpful for assessment of prostatic blood flow. The use of US microbubbles for CD imaging and new contrast-specific techniques enable assessment of prostate microvascularity associated with prostate cancer (PCa). Recently, real-time elastography has been introduced to improve detection of cancer based upon changes in tissue stiffness., Results: Contrast-enhanced CD imaging has shown to enable PCa detection by performing targeted biopsies into suspicious areas. Comparisons between systematic and contrast-enhanced targeted biopsies have shown that the targeted approach detects more cancers and cancers with higher Gleason scores with a reduced number of biopsy cores. New microbubble-specific US techniques can improve sensitivity and specificity of US imaging for PCa detection. Real-time elastography has been demonstrated to be useful for the detection of PCa, and may further improve PCa staging., Conclusions: The new US techniques seem to have the potential to improve PCa detection, and also PCa grading and staging. As these diagnostic methods improve, the ultimate hope is to eliminate biopsy in patients without cancer.

Ultrasound is a widely used imaging modality for evaluation of the prostate. The main topic of diagnostic imaging is an improvement of prostate cancer diagnosis. The current available systematic prostate biopsy is performed only under ultrasound guidance, but new imaging techniques allow prostate cancer visualization and therefore improved detection. Evolving methods such as contrast-enhanced colour Doppler imaging, contrast-specific ultrasound techniques and elastography may dramatically change the role of ultrasound for prostate cancer diagnosis. The purpose of this review is to provide an overview of ultrasound and its different techniques for imaging of the prostate and to discuss current trends and future directions.

Objective: To evaluate contrast-enhanced ultrasonography (US) using cadence-contrast pulse sequencing (CPS) technology, compared with systematic biopsy for detecting prostate cancer, as grey-scale US has low sensitivity and specificity for detecting prostate cancer., Patients and Methods: In all, 44 men with suspicious prostate-specific antigen (PSA) levels and CPS findings were assessed; all had CPS-targeted and systematic biopsy. Transrectal CPS images were taken with a low mechanical index (0.14). A microbubble contrast agent (SonoVue, Bracco International BV, Amsterdam, the Netherlands) was administered as a bolus, with a maximum dose of 4.8 mL. CPS was used to assess prostatic vascularity. Areas with a rapid and increased contrast enhancement within the peripheral zone were defined as suspicious for prostate cancer. Up to five CPS targeted biopsies were taken and subsequently a 10-core systematic biopsy was taken. Cancer detection rates for the two techniques were compared., Results: Overall, cancer was detected in 35 of 44 patients (80%), with a mean PSA level of 3.8 ng/mL. Lesions suspicious on CPS showed cancer in 35 of 44 patients (80%) and systematic biopsy detected cancer in 15 of 44 patients (34%). CPS-targeted cores were positive in 105 of 220 cores (47.7%) and in 41 of 440 systematic biopsy cores (9.3%) (P < 0.001). Lesions suspicious on CPS were false-positive in nine of 44 patients (20%). The mean Gleason score for systematic biopsy was 6.7 and for CPS-targeted biopsy 6.8 (P > 0.05). The sensitivity of CPS for detecting cancer was 100% (confidence interval, 95%). However, limitations in the series included that only CPS-positive cases were investigated, and CPS-targeted biopsy should be evaluated in a more extended biopsy scheme., Conclusions: Contrast-enhanced US using CPS enables excellent visualization of the microvasculature associated with prostate cancer, and can improve the detection of prostate cancer compared with systematic biopsy.

Objective: To present early functional and oncological data for the athermal trizonal nerve-sparing technique of robotic radical prostatectomy (RP), that addresses the concerns about deviations from the principles of open RP and revisits the anatomical foundations of this surgery from the robotic perspective., Patients and Methods: The study involved close collaboration between the Cornell Institute of Robotic Surgery in New York, USA, and the Institute of Urology at the University of Innsbruck in Austria. The cadaveric studies and standardization of the athermal technique were conducted at Innsbruck, and the technique was used in 215 patients in New York., Results: The athermal technique addresses concerns about the use of thermal energy and bulldog clamps during nerve sparing, and emphasizes the importance of the trizonal neural architecture. We analysed the surgical outcomes of 215 consecutive patients from January 2005. The operative duration was 120-240 min and the mean blood loss was 150 mL. In patients potent before RP the potency rate at 1 year after bilateral nerve-sparing was 87%. The overall surgical margin rate was 6.5% and positive margin rates for organ-confined cancer were 4.7%., Conclusion: We describe the athermal technique of robotic RP and introduce the concept of trizonal nerve preservation. The immediate oncological and sexual outcomes were encouraging.

Objective: To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate-specific antigen level (4-10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy., Patients and Methods: In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0-10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated., Results: Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years., Conclusions: These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.

Objective: To evaluate the effectiveness of a well-controlled programme of early detection and treatment of prostate cancer in the population of Tyrol, Austria, where such a programme of early detection and treatment was initiated in 1988 and where prostate-specific antigen (PSA) testing was offered for free to all men aged 45-75 years from 1993., Subjects and Methods: Comparison of prostate cancer mortality rates in Tyrol and the rest of Austria was accomplished through a generalized additive model. A piecewise linear change-point Poisson regression model was used to compare mortality rates in Tyrol and the rest of Austria. Standardized mortality ratios were calculated with reference to the mortality rates in 1986-1990., Results: In all, 86.6% of eligible men have been tested at least once since 1993. Cancer deaths in Tyrol in 2005 were 54% (95% confidence interval [CI] 34-69%) lower than expected compared with 29% (95% CI 22-35%) in the rest of Austria. The decreasing trend in prostate cancer mortality was significantly greater in Tyrol compared with the rest of Austria (P = 0.001). A significant migration to lower stage disease occurred and radical prostatectomy was associated with low morbidity., Conclusions: In the Tyrol region where treatment is freely available to all patients, where widespread PSA testing and treatment with curative intent occurs, there was a reduction in prostate cancer mortality rates which was significantly greater than the reduction in the rest of Austria. This reduction in prostate cancer mortality is most probably due to early detection, consequent down-staging and effective treatment of prostate cancer.

Objectives: This study assessed the effect of premedication with dutasteride, a dual 5alpha-reductase inhibitor, on prostatic blood flow prior to prostate biopsy and its impact on prostate cancer detection., Methods: Thirty-six patients, aged 52-74 yr, with elevated prostate-specific antigen (PSA) levels (>or=1.25 ng/ml and free-to-total ratio of <18%) were treated with dutasteride 14 d prior to prostate biopsy. Contrast-enhanced colour Doppler (CECD) ultrasound was performed before and 7 and 14 d after dutasteride treatment. Contrast-enhanced targeted biopsies (

Objective: To evaluate the influence of prostate volume (PV) on the detection of prostate cancer using a combined approach of contrast-enhanced ultrasonography (CEUS) and grey-scale US-guided systematic biopsy (SB)., Patients and Methods: We evaluated 345 patients with prostate cancer and a total prostate-specific antigen (PSA) level of >/= 1.32 ng/mL (1.32-35.3, mean 6.6). Biopsies were taken by two independent examiners; one took five CEUS (Doppler) targeted biopsies of hypervascular regions in the peripheral zone, and subsequently the other took 10 systematic prostate biopsies. We assessed the cancer detection rates for the five different subgroups of prostate volumes, i.e. <20, 20-30, 30-40, 40-50 and > 50 mL., Results: Each technique, SB and CEUS, detected 73.4% and 77.1% of all detected cancers, respectively, but there were statistically significant differences in detection rate only in small glands. Only 69.0% and 70.4% of all cancers were detected by SB in glands of <20 and 20-30 mL, respectively, whereas 88.1% and 80.8% were detected by CEUS., Conclusion: The prostate cancer detection rate for CEUS was significantly higher in prostates of <30 mL (48.1% of the study population) than for SB. Therefore the combined approach of CEUS and SB allows improved cancer detection in patients with small glands and low total PSA values.

Purpose: Prostate cancer grading with Gleason score is an important prognostic factor. This prospective randomized study compares ultrasound systematic biopsy vs contrast enhanced color Doppler targeted biopsy for the impact on Gleason score findings., Materials and Methods: We examined 690 men (mean age 56 years, range 41 to 77) with a serum total prostate specific antigen of 1.25 ng/ml or greater, a free-to-total prostate specific antigen ratio less than 18% and/or a suspicious digital rectal examination. Contrast enhanced color Doppler targeted biopsies with a limited number of cores (5 or less) were performed in hypervascular areas of the peripheral zone during administration of the ultrasound contrast agent Sonovuetrade mark (Bracco, Milano, Italy). Ten systematic biopsies were obtained in a standard spatial distribution. Cancer detection rates and Gleason score were compared., Results: Prostate cancer was identified in 221 of 690 subjects (32%) with a mean prostate specific antigen of 4.6 ng/ml (range 1.4 to 35.0). Prostate cancer was detected in 180 of 690 subjects (26%) with contrast enhanced color Doppler targeted biopsy and in 166 of 690 patients (24%) with systematic ultrasound biopsy. The Gleason score of all 180 cancers detected on contrast enhanced color Doppler targeted biopsy was 6 or higher (mean 6.8). The Gleason score of all 166 cancers detected on systematic biopsy ranged from 4 to 6 and mean Gleason score was 5.4. Contrast enhanced color Doppler targeted biopsy detected significantly higher Gleason scores compared to systematic biopsy (Wilcoxon rank sum test p <0.003)., Conclusions: Contrast enhanced color Doppler targeted biopsy detected cancers with higher Gleason scores and more cancer than systematic biopsy. Therefore, contrast enhanced color Doppler seems to be helpful in the grading of prostate cancer, which is important for defining prognosis and deciding treatment.

Purpose of Review: Prostate cancer is the most commonly diagnosed malignancy in men. Gray-scale ultrasound-guided systematic biopsy is the standard of care for prostate cancer detection in men with an elevated prostate-specific antigen or an abnormal digital rectal examination. Systematic biopsy may miss up to 35% of clinically relevant cancers. Color and power Doppler ultrasound, ultrasound contrast agents, and elastography have and will dramatically change the role of ultrasound in prostate cancer diagnosis., Recent Findings: Several reports have demonstrated that contrast-enhanced ultrasound investigations of the blood flow of the prostate allow for prostate cancer visualization and therefore, for targeted biopsies. Comparisons between systematic and contrast-enhanced ultrasound-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores. Furthermore, contrast-enhanced ultrasound has been shown to detect cancers with higher Gleason scores compared with the systematic approach, which seems to improve prostate cancer grading. In addition, elastography is a new ultrasound technique that allows for the assessment of tissue elasticity., Summary: Contrast-enhanced ultrasound and elastography improve prostate cancer detection and may be useful for prostate cancer grading and staging. Future clinical trials will be needed to determine the promise of these new advances for ultrasound of the prostate evolving into clinical applications.

Objective: To create a nomogram of the fetal growth of the human prostate corresponding to gestational age, and to investigate the relationship between the expansive growth of the fetal prostate and the maternal testosterone surge during pregnancy., Materials and Methods: In all, 27 fetal prostates at 11-40 weeks of gestation, and seven neonatal specimens at 1-20 weeks after birth, were analysed. Serial sections of prostates were immunostained and examined using light microscopy. After modular image acquisition the volumes were calculated using three-dimensional reconstruction. The prostate volumes were correlated with gestational age, and related to reference testosterone levels during pregnancy., Results: There was exponential growth of the fetal prostate with gestational age. The increasing volume of the prostate during the fetal period corresponded with maternal testosterone levels. In the second trimester there was a significant increase in prostate volume in relation to the bladder. In infants, macroscopically there was an inverse proportion between bladder size and prostate volume., Conclusions: Starting from the second trimester there is distinct growth of the fetal prostate, obviously triggered by the maternal testosterone surge. In neonates there is an inversion of the dimensions between bladder and prostate. These results indicating exponential growth of the fetal prostate provide evidence of a gender-related transient infravesical obstruction in human fetuses.

Objective: To evaluate prostatic vascular resistance by measuring the resistive index (RI), and flow velocity using colour Doppler ultrasonography (CDUS), in normal prostates and in patients with benign prostatic hyperplasia (BPH) or prostate cancer, as BPH is considered to be a result of urogenital ageing and studies suggest that hyperplasia in the stromal and glandular compartments might be induced by stromal growth secondary to hypoxia, which in turn results from abnormal blood flow patterns., Patients, Subjects and Methods: Ninety-two men (22 with normal prostates, 45 with BPH and 25 with prostate cancer; mean age 56 years) were prospectively evaluated by CDUS. The RI values for the peripheral, central and transition zones were assessed by one investigator. The diagnosis of BPH and prostate cancer was established from histological findings., Results: The mean (sd) RI in the transition zone was significantly higher only in patients with BPH, at 0.77 (0.05), vs 0.65 (0.05) in the other two groups. In the peripheral and central zones there was no significant difference in the RI among the three groups. Arterial CDUS flow velocity was increased in the transition zone of patients with BPH, but not in the peripheral and central zones., Conclusions: The present results support the hypothesis that an age-related impairment of blood supply to the lower urinary tract might have a role in the development of BPH. Although prostate cancer cannot be excluded by measuring RI, high RI values (>0.75) in the transition zone are indicative of BPH.

Objective: To review the neural architecture around the prostate gland, as it is relevant for nerve-sparing robotic prostatectomy, including in particular the anatomy of the proximal neurovascular tissue, the neurovascular bundle (NVB), and accessory neural pathways (ANPs)., Materials and Methods: The aims of this study were achieved in collaboration between the Cornell Institute of Robotic Surgery, New York, NY, USA and the Institute of Urology at the University of Innsbruck, Austria. The broad steps were: (i) anatomical studies of 10 fresh and two fixed male cadavers; and (ii) collection of videotape and still image data from 200 men undergoing radical prostatectomy by the athermal robotic technique at the Cornell Institute., Results: From a surgical standpoint there was a tri-zonal neural architecture including the proximal neurovascular plate (PNP), the predominant NVB (PNB) and ANPs. The PNP was a mean (range) of 5 (3-10) mm lateral to the seminal vesicles, was 3 (2-7) mm thick, 7 (5-25) mm wide and 9 (4-30) mm long. It was within 6 (4-15) mm of the bladder neck, 5 (2-7) mm of the endopelvic fascia and overlapped 5 (0-7) mm of the proximal prostate. The PNB varied in shape and size from the proximal to distal end, was thickest at the base and most variable near the apex. In eight of 12 cases, there was a medial extension behind the prostate, which converged medially at the apex in four cases. ANPs were noted within the layers of levator fascia and/or lateral pelvic fascia on the anterolateral aspect in five cases and in three on the posterior aspect of the prostate. In nine cadavers, the proximal third of the prostate was covered by the PNP where these ANPs were most prominent. The ANPs formed a plexus on the posterolateral aspect of the apex in four cases., Conclusion: We have created an anatomical map of neurovascular tissue relevant to robotic prostatectomy. A tri-zonal neural architecture is described which has helped in standardizing the steps of robotic prostatectomy.

Purpose: ATF3 is a member of the basic leucine zipper/cyclic adenosine monophosphate responsive element binding protein family of transcription factors. There is overwhelming evidence that it is a stress inducible factor acting in a signal-type and cell-type dependent manner, and it is involved in cell proliferation and survival. We found that ATF3 was differently expressed in an in vitro prostate cancer tumor progression model and we investigated the possible role of ATF3 in prostate cancer., Materials and Methods: ATF3 up-regulation in vivo/in vitro and androgen regulation were assessed by immunohistochemistry and immunoblot analysis. Results after forced ATF3 transfection were evaluated by proliferation assay and cell cycle analysis., Results: Immunohistochemistry and immunoblot analysis revealed ATF3 up-regulation in prostate cancer in vitro and in vivo, and stimulation of expression by androgens. Antiandrogen treatment decreased ATF3 expression in androgen sensitive cells but acted as a stimulator in long-term androgen ablated cells representing a model for therapy refractory disease. Expression in tumors increased with higher Gleason scores and highest expression was observed in samples of therapy refractory tumor tissue. Forced ATF3 over expression in a prostate cancer cell line induced cell proliferation and accelerated cell cycle progression from G1 to S-phase., Conclusions: These data provide new insight into the role of ATF3 in prostate cancer development and/or progression. They indicate that ATF3 is an androgen regulated gene that is highly expressed in prostate tumors and stimulating cell proliferation. It represents a possible target for prostate cancer therapy.

Objectives: The present retrospective study was designed to investigate the value of transition zone (TZ) biopsies for prostate cancer (PC) detection rate in a combined contrast enhanced color Doppler targeted (CECD) and gray-scale systematic biopsy (SB) approach., Methods: PSA screening participants totalling 1475 with tPSA of >1.25 ng/ml (fPSA< or =18%) were assessed. Ten SB and additionally 5 or fewer CECD were performed. The impact of TZ biopsies on the PC detection rate and the biological significance of the detected TZ-cancers were analyzed., Results: Out of 1475 biopsied patients, 395 (26.8%) were identified as PC patients; 5925 biopsy cores from these patients were analyzed. In 86 patients (21.8% of PC), we found 102 PC- positive cores in the TZ, and only in 9 of them solitary TZ-cancers without any other PC-location (2.3% of PC or 0.6% of all investigated patients). Pathologic findings after retropubic prostatectomy (RPE) revealed multifocal adenocarcinoma including involved peripheral zone (PZ) in eight of these nine patients, and solitary TZ-cancer in one patient. There was no positive correlation between prostate volume and TZ-detection rate and no patient with solitary TZ-PC after rebiopsy., Conclusion: Biopsy revealed 9 solitary TZ cancers (1.8%) and RPE revealed only one of them to be truly TZ-confined cancer (0.6%). Furthermore PC-detection did not improve, even in patients with rebiopsy, and there was no correlation between detection of TZ-cancers and prostate volume. A combined use of CECD and SB to investigate participants of a PSA-screening program suggests that TZ-biopsies do not improve PC detection rate and are therefore unnecessary.

Objective: To assess benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), both considered to be associated with urogenital ageing, in ageing men in a cross-sectional population study, comparing them with healthy controls by using symptom scores and contrast-enhanced colour Doppler ultrasonography (CDUS)., Patients, Subjects and Methods: Transrectal CDUS and quantitative measurement of colour pixel intensity (CPI) are excellent minimally invasive techniques for assessing normal and pathological blood flow. CDUS was performed using the microbubble-based ultrasound enhancer for evaluating prostate, bladder neck and corpus cavernosum vascularity in young healthy men, men with BPH, and men with severe vascular damage (diabetes mellitus type 2). Resistive index measurements and computer-assisted quantification of CPI were used to objectively evaluate perfusion. The International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF) were applied to quantify the symptoms., Results: In patients with BPH, perfusion of the transition zone (TZ) of the prostate was significantly lower and the resistive index of the TZ significantly higher (both P < 0.001) than in healthy controls. The perfusion patterns of men with BPH and those who also had severe vascular damage (diabetes mellitus type 2) showed that vascularity in the latter group was lower in the prostatic TZ and the corpora cavernosa. In patients with BPH the IPSS, quality-of-life and IIEF scores were significantly worse than in the control group. Men with concomitant atherosclerosis had even worse symptom scores., Conclusion: These results strongly support the hypothesis that age-related impairment of blood supply to the lower urinary tract is important in the development of BPH and ED. Vascular damage may cause chronic ischaemia and thus be a contributing factor in the pathogenesis of BPH and ED.

Purpose: Transrectal gray scale ultrasound guided biopsy is the standard method for diagnosing prostate cancer (PC). Improved cancer detection with ultrasound contrast agents is related to better detection of tumor vascularity. We evaluated the impact of a combined approach of contrast enhanced, color Doppler targeted biopsy (CECD) and systematic biopsy (SB) for the PC detection rate in men with prostate specific antigen (PSA) 4.0 to 10 ng/ml., Materials and Methods: We examined 380 screening volunteers with a total PSA of 4.0 to 10 ng/ml (percent free PSA less than 18). CECD was always performed before SB. Another investigator blinded to contrast enhanced findings performed 10 SBs. The cancer detection rate for the CECD, SB and combined approaches was assessed., Results: PC was detected in 143 of 380 patients (37.6%, mean total PSA 6.2 ng/ml). The PC detection rate for CECD and for SB was 27.4% and 27.6%, respectively. The overall cancer detection rate with the 2 methods combined was 37.6%. For targeted biopsy cores the detection rate was significantly better than for SB cores (32.6% vs 17.9%, p <0.01). CECD in a patient with cancer was 3.1-fold more likely to detect PC than SB., Conclusions: CECD allows for the detection of lesions that cannot be found on gray scale ultrasound or SB. CECD allows for assessment of neovascularity associated with PC. However, the combined use of CECD and SB allows for maximal detection of PC with a detection rate of 37.6% in our patients with PSA 4 to 10 ng/ml.

This paper is aimed at focusing on the nerve-sparing aspect of the robotic prostatectomy. It reviews the existing principles and presents the arguments based on robotic fresh cadaver dissections and from actual robotic prostatectomy cases.

Objectives: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy., Methods: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared., Results: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy., Conclusions: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.

Background: The present study was designed to investigate whether the clinical or pathologic features of prostate cancer (PCa) are related to the number of repeat biopsies required to establish the diagnosis of PCa., Methods: Between February 1993 and August 2000, 653 patients were evaluated in this retrospective study. All patients underwent transrectal ultrasound-guided biopsy of the prostate prior to radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical prostatectomy and pelvic lymph node dissection as well as PSA levels, findings on DRE, prostate volumes, transition zone volumes, and age were analyzed separately for all PCa patients diagnosed at the first set of biopsies (group A) and compared with the data of those diagnosed at the 2nd-5th set of biopsies (group B). In a second step, we compared the results obtained from patients diagnosed at the 2nd set of biopsies (group B1) with those of patients diagnosed at the 3rd to 5th set of biopsies (group B2)., Results: Gleason scores, pathologic tumor stages, and tumor volumes in group B were found to be significantly decreased compared to group A. But from the 2nd to 5th serial biopsy no further decrease in pathologic stage, Gleason score, or tumor volume was observed. On the contrary, there was a tendency towards higher tumor stages and Gleason scores. Of the tumors detected after the second false-negative set of biopsies almost 70% were lesions with Gleason scores of 6 or higher., Conclusions: False-negative results at the first needle biopsy are predictive of a lower pathologic stage and grade as well as smaller tumor volumes of PCa diagnosed at repeat sets of biopsies. False-negative results on repeat biopsy, however, have no prognostic significance for the tumor stage of PCas detected at subsequent sets of biopsies., (Copyright 2003 Wiley-Liss, Inc.)

Objectives: To evaluate the effect of periprostatic infiltration with local anesthesia on the level of discomfort associated with transrectal ultrasound-guided needle biopsy of the prostate. Transrectal ultrasound-guided needle biopsy of the prostate is the standard procedure to diagnose prostate cancer., Methods: A prospective, randomized, double-blind study was performed on 100 men referred for biopsy of the prostate. Fifty subjects were randomized to periprostatic injection of 10 mL of 2% lidocaine solution without epinephrine, and 50 were randomized to injection of placebo (10 mL of 0.9% NaCl). Each subject completed three 10-point visual analog scales for pain after a series of 15 needle biopsies. Pain was rated during the biopsy, diagnostic investigation, and injection of lidocaine., Results: Patients who received local anesthesia had significantly lower visual analog scale scores compared with the group without lidocaine during the biopsy (mean score 0.76 versus 3.62, P <0.001) and diagnostic examination (mean score 1.08 versus 1.86, P = 0.025). Lidocaine injection caused no adverse effects., Conclusions: Periprostatic injection of lidocaine represents a simple and safe procedure that significantly reduces discomfort during probe manipulation and biopsy. We recommend this procedure in men undergoing transrectal ultrasound-guided prostate biopsy.

Within a 7-site prospective evaluation of the Bayer complexed prostate-specific antigen PSA (cPSA) assay, we analyzed the ability of cPSA to predict extracapsular extension (ECE) before radical prostatectomy. Included in this analysis were 152 men diagnosed with cancer, who subsequently underwent radical prostatectomy. Sera were tested with the Bayer total PSA (tPSA) and cPSA assays, and the Beckman free PSA (fPSA) and tPSA assays. Treating surgical pathology result as a binary variable (organ confined vs ECE), mean tPSA, cPSA, fPSA/tPSA (f/tPSA) ratios, tPSA density (tPSAD), and cPSA density (cPSAD) were compared by receiver operating characteristic (ROC) curves and univariate analysis. In all, 28 men (18.4%) had pathologically identified ECE. Between those with and without ECE, significant differences were observed for tPSA (P = 0.0127), cPSA (P = 0.0120), tPSAD (P = 0.0001), and cPSAD (P = 0.0002), but not f/tPSA (P = 0.3774) or c/tPSA (P = 0.2882). All tested parameters except f/tPSA (P = 0.376) and c/tPSA (P = 0.288) predicted ECE (P <0.05) by logistic regression. The ROC area under the curve (AUC) was identical for tPSA and cPSA (0.621) and for tPSAD (0.692) and cPSAD (0.691). Kendall-tau correlation coefficients also demonstrated the strongest correlation with ECE for cPSAD and tPSAD. Either alone or as a tPSAD calculation, cPSA carries equivalent staging ability to tPSA. The use of f/tPSA appears to be less effective in staging than either cPSA or tPSA, whereas the use of either cPSAD or tPSAD provides maximal staging accuracy. Therefore, cPSA could be applied as an accurate predictor of ECE independently or in a nomogram along with other predictive variables.

Objectives: To investigate the relationship between inflammatory cells in prostate biopsies and total serum prostate-specific antigen (PSA) levels in a screening population., Methods: In the study, transrectal ultrasound-guided prostate biopsy specimens from 49 patients were assessed. All patients undergoing biopsy had elevated serum PSA levels (as defined by the biopsy criteria of the Tyrol PSA Screening Project) and/or abnormal findings on digital rectal examination. The prostate biopsy specimens were histologically negative for carcinoma. Immunohistologic characterization of the inflammatory cells was performed using CD3, CD4, and CD8 antibodies for the detection of T lymphocytes, CD20 antibodies for B lymphocytes, and CD68 antibodies for macrophages. The percentage of inflammatory cells and their distribution in stromal and glandular tissue was estimated using morphometric methods., Results: Inflammatory cells in the stroma contained significantly larger numbers of T lymphocytes than B lymphocytes and macrophages. T lymphocytes were also predominant in the glandular region. A significant positive correlation was found between the relative volume (vol%) of macrophages and total PSA levels (P <0.05) and a significant negative correlation between the percent free PSA levels and the relative volumes of T and B lymphocytes., Conclusions: The results indicate a significant positive correlation between total PSA levels and macrophages and a significant negative correlation between percent free PSA levels and T and B lymphocytes. No statistically significant correlation was found between total serum PSA levels and the presence of inflammatory cells in the stromal and glandular compartment. Additional studies are needed to compare the amount and types of inflammatory cells with the stage and grade of prostate cancer in positive biopsies and radical prostatectomy specimens.

Background: The aim of this study was to optimize the core shape of prostatic core needle biopsies using a novel preembedding method, and to investigate the influence of the number of cores per tissue block on the histologic yield per section level., Methods: Twenty-four core needle biopsies were taken from a fresh prostatectomy specimen, using an 18-gauge needle. Twelve core needle biopsies were conventionally fixed floating free in formalin-filled containers, whereas 12 biopsies were stretched between two nylon meshes, and placed in tissue cassettes before fixation. The total number of tissue sections per paraffin block necessary for complete workup of the tissue was determined. Using image analysis, the relation of the area of every fifth section level was calculated in relation to the total projected area of the biopsies. Both methods of tissue processing were compared for both parameters., Results: In contrast to the curved biopsies after conventional processing, the optimized preembedding method generally led to stretched cores after fixation and embedding. This method led to a 100% decrease in total number of tissue sections necessary for complete workup and to higher percentages of the tissue amount per section level compared to the total projected core area. These parameters were also influenced by the number of cores per paraffin block, but to a minor degree., Conclusions: This study shows that optimized preembedding of prostatic needle biopsies improves the histologic yield per section level. The continuous occurrence of representative sections could improve diagnostic accuracy in the histological examination of prostatic core needle biopsies., (Copyright 2000 Wiley-Liss, Inc.)