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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.)

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.

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.

Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. Therefore, improvement of prostate cancer diagnosis is a main topic of diagnostic imaging. The systematic prostate biopsy ("ten-core biopsy") is now the "gold standard" of prostate cancer diagnosis but may miss prostate cancer. Contrast-enhanced colour Doppler ultrasound (US) and elastography are evolving methods that may dramatically change the role of US for prostate cancer diagnosis. Contrast-enhanced colour Doppler US allows for investigations of the prostate blood flow and consequently for prostate cancer visualization and therefore for targeted biopsies. 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. Furthermore, elastography, a new US technique for the assessment of tissue elasticity has been demonstrated to be useful for the detection of prostate cancer, and may further improve prostate cancer staging. Therefore, contrast-enhanced colour Doppler US and elastography may have the potential to improve prostate cancer detection, grading and staging. However, further clinical trials will be needed to determine the promise of these new US advances.

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.

Objective: To use three-dimensional transrectal ultrasonography (3D-TRUS) to reconstruct the prostate, and thus determine its value in staging clinically localized prostate cancer., Patients and Methods: In all, 180 patients with newly diagnosed clinically localized prostate cancer were assessed using 3D-TRUS for staging. TRUS findings were compared with histopathological staging after radical prostatectomy., Results: Pathological staging of specimens showed extracapsular extension in 69 patients, of whom 53 had pathological capsular perforation and 16 had seminal vesicle invasion. 3D-TRUS identified 58 patients with sites of extracapsular extension with 84% sensitivity, 96% specificity, 94% positive predictive value, 91% negative predictive value and an overall accuracy of 92%. Of the 16 patients with seminal vesicle invasion 14 were identified correctly on 3D-TRUS. Overall the 3D-TRUS staging sensitivity was 84%, specificity 96%, positive predictive value 93%, negative predictive value 91% and accuracy 91%., Conclusions: 3D-TRUS seems to be an accurate technique for staging localized prostate cancer. If 3D-TRUS indicates locally advanced disease, the probability of capsular perforation or seminal vesicle invasion is very high.

Prostatic carcinoma is the most frequent malignant disease in men and associated with very high mortality. The diagnostic work-up of prostatic carcinoma is based on tests to determine the level of prostate-specific antigen (PSA), digital rectal examination, and transrectal sonography. Due to diagnostic limitations, ultrasound-guided prostate biopsy is the method of choice for diagnosis of prostatic carcinoma. New imaging technologies allow detection of prostatic carcinoma, thus facilitating removal of specific biopsy specimens from these regions. Introduction of ultrasound contrast agents ("echo signal enhancers") significantly increased the diagnostic potential of this method, making it possible to visualize tumor vascularization.

Background: Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has a poor specificity for early detection at levels below 10 ng/ml, because it can also result from benign conditions. Our aim was to determine the frequencies of circulating PSA+ macrophages in a blinded study and to examine the suitability of this new method for differentiating between benign and malignant prostate disease., Methods: Between October 2002 and February 2003, 126 patients undergoing transrectal biopsy were enrolled in this study. Peripheral blood macrophages were stained for intracellular content of PSA in all patients. Ten patients' peripheral blood mononulear cells (PBMCs) were also supplementarily stained for cytokeratin (CK) and epithelial membrane antigen (EMA). Macrophages were analysed by flow cytometry. Patients were grouped according to their biopsy histology and bone scan results., Findings: Based on histological data, patients were classified as having no evidence of malignancy (NEM) (n = 59), prostatitis (n = 20), or localised prostate cancer (n = 37). Significantly higher levels of circulating PSA+ macrophages were found in prostate cancer compared to benign conditions. Calculating a 2% cut-off level enabled the detection of localised prostate cancer with 89% sensitivity and 80% specificity. In a subset of patients (65%) with a serum PSA below 4 ng/ml and confirmed prostate cancer, the percentage of PSA+ macrophages was significantly higher compared to NEM and prostatitis. Macrophages of ten patients tested with prostate cancer contained significantly higher amounts of PSA, EMA, and CK compared to ten with NEM., Interpretation: Intracellular PSA in combination with CK and EMA can be found in permeabilized blood macrophages, indicating phagocytosis of complete cancer cells. This study further suggests, that this new method might be suitable for differentiating between prostate cancer and benign conditions especially in patients with low serum PSA., (2004 Wiley-Liss, Inc.)

Although prostate-specific antigen (PSA) is a useful screening marker in prostate cancer, it has limited specificity. Previously it was shown that the amount of surface-bound PSA present on circulating macrophages was different between patients with localized prostate cancer and those with metastatic prostate cancer. It was recently demonstrated that intracellular PSA in macrophages can be measured by flow cytometry. In the context of searching for a noninvasive, highly reliable method for prostate cancer diagnosis, we assessed the extent to which extracellular (ie, surface-bound) and intracellular PSA-positive macrophages might differentiate patients with benign versus malignant prostatic disease. In a pilot study, the levels of complexed, surface-bound, and intracellular PSA were measured in 25 patients with elevated serum PSA values and histologically confirmed disease. In this group, no significant differences for serum PSA and complexed PSA levels, respectively, could be detected among patients with benign prostatic hyperplasia, prostatitis, and prostate cancer. Significant differences, however, were detected in intracellular PSA, although not in surface-bound PSA, among the 3 groups of patients. Intracellular PSA was measured prospectively in a second cohort of 189 patients who had a transrectal biopsy because of a serum PSA constellation suspicious for prostate cancer. In the expanded cohort, highly significant differences in intracellular PSA were observed between benign and malignant disease of the prostate, even in patients with serum PSA level<4 ng/mL. Screening of serum PSA alone or in combination with complexed PSA does not clearly distinguish patients with prostate cancer from those with prostatitis or benign prostatic hyperplasia. Macrophage intracellular PSA might represent a more.

Objective: To evaluate the feasibility of urinary catheter removal 10 days after a radical retropubic prostatectomy (RRP) by assessing the incidence of urinary extravasation and its effect on postoperative stricture and continence rates., Patients and Methods: During a 4.5-year period, 619 patients undergoing RRP were evaluated. If no extravasation was detected on gravity cystography, the urinary catheter was removed 10 days after RRP. In patients with significant extravasation the catheter was left in place for 3 weeks. Overall stricture and continence rates were recorded in patients at 3, 6 and 12 months after surgery., Results: There was extravasation during cystography in 29 patients (4.6%). At 3, 6 and 12 months, continence rates after catheter removal at 10 days were 74.9%, 87.9%, and 93.6%, respectively, while in the late-removal group they were 72.4%, 84.6% and 90.9%, respectively, with no significant difference between the groups. At 3 months the overall continence rate was 74.8% and at 12 months up to 93.5%. There was no difference in stricture rates between the groups, with an overall stricture rate of 0.7%., Conclusions: Catheter removal 10 days after RRP is feasible, giving excellent early and late continence rates, with low anastomotic stricture rates obtained using good surgical technique. Extravasation at 10 days was rare and with proper management did not influence the final results.

In 3-D transrectal ultrasound it is possible, for the first time, to investigate the region of interest in three planes simultaneously. Exact examination of the organs of the small pelvis as well as of pathologic changes in the region of the pelvic floor can be performed with this new imaging technique. The bulbourethral glands can be investigated routinely, which enables the diagnosis of cysts of these glands. The prostatic zones, their relations as well as the growth of the transitional zone during the development of benign prostatic hyperplasia can be visualized. Furthermore, 3-D transrectal ultrasound allows investigation of morphology and function of the rhabdosphincter. The contractility of the muscle can be quantified. 3-D ultrasound guided puncture and drainage of prostatic abscesses represents a minimally invasive therapeutic modality. This technique can be used to place needles as well as implants in the lower urinary tract. Generally, 3-D transrectal ultrasound offers new diagnostic and therapeutic possibilities.

Objectives: To evaluate the incidence and outcome of prostate cancer in men younger than 45 years of age treated with radical retropubic prostatectomy after screening in an early prostate cancer detection program., Methods: Our study group comprised 19,302 men younger than 45 years old who participated in this program. The indications for prostate biopsy were a prostate-specific antigen (PSA) level of 1.25 ng/mL or greater and a percent-free PSA value of 18% or less. Patients with prostate cancer underwent nerve-sparing radical retropubic prostatectomy. Intraoperative and early postoperative complications, clinical and pathologic stage, Gleason score, and surgical margins were reviewed retrospectively. In addition, potency, continence, and biochemical recurrence were assessed at the last follow-up visit., Results: Of the study population eligible for prostate biopsy (1027 patients), only 175 (17%) consented to undergo the procedure (mean PSA 3.8 ng/mL). Twenty-eight men were diagnosed with prostate cancer, corresponding to 0.14% of the screened population and 16% of the biopsied patients. Twenty-six patients agreed to undergo radical retropubic prostatectomy. Pathologic examination revealed organ-confined disease in 22 (84.6%) and extraprostatic extension in 4 (15.4%). Positive surgical margins were seen in 2 patients (7.7%). The Gleason score was 7 or greater in 11 (42.3%) and 6 or less in 15 patients (57.7%). During a mean follow-up period of 15.8 months (range 3 to 36), all patients were continent, and 13 of the 16 patients with a follow-up of 12 months or longer were potent., Conclusions: In a large screening population younger than 45 years old, 16% of biopsied patients were positive for prostate cancer. These tumors were clinically significant but of a low stage and therefore potentially curable by surgery.

Cystoprostatectomy specimens removed for bladder malignancy (1988-2000) at two referral centers (Mayo Clinic, Rochester, MN, The University Hospital of Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of prostate cancer (PCA). Centralized examination of the prostate by a single uropathologist was performed if at the time of surgery the patient's serum PSA was < or =2.0 ng/mL and there were no suspicious lesions by digital prostate examination. Pathologic grade, stage, morphometric volume, number of tumor foci and association with areas of high grade prostatic intraepithelial neoplasia (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative index were assessed through digital image analysis. Clinically significant cancers were defined as tumors with > or =0.5 cc volume, Gleason 4 or 5 architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA content or proliferation index >5%. From nearly 1600 cystoprostatectomy specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this group had PCA identified. Sixty percent of these tumors met the criteria for a clinically significant cancer. Nondiploid nuclear content was present in 17%. HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The biologic activity of PCA appears to be independent of serum PSA. Any future definition of a clinically significant PCA should not be solely based upon histologic criteria, but needs to encompass clinical parameters (age, co-morbidities) and a noninvasive assessment of tumor volume and biologic doubling time.

The value of ultrasound (US) in the diagnosis of prostate cancer has increased in importance in the past decade, which is mainly related due to the increasing incidence of prostate cancer, the most common malignancy in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated. The introduction of US contrast agents has dramatically changed the role of US for prostate cancer detection. Advances in US techniques were introduced to further increase the role of US contrast agents. Although most of these advances in US techniques, which use the interaction of the contrast agent with the transmitted US waves are very sensitive for the detection of microbubbles, are mostly unexplored, in particular for prostate applications. First reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional US technique. We present a critical evaluation of the current status of transrectal US imaging for prostate cancer detection. Furthermore, we give background information on US contrast agents and imaging modalities. Early results of contrast-enhanced US suggest the feasibility of the use of US contrast agents to enhance US imaging of the prostate. The application of US contrast agents for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine the promise of contrast-enhanced US of the prostate evolves into clinical application.