Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

UNLABELLED: What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. OBJECTIVE: • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. PATIENTS AND METHODS: • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. RESULTS: • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. CONCLUSIONS: • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy.

PSA repeatedly fluctuating levels are reassuring enough to avoid biopsy?

INTRODUCTION: Prostate-specific antigen (PSA) levels can show wide fluctuations when repeatedly measured. Here we investigatewd if: (a) biopsy timing influences the prostate cancer (PC) detection rate in patients with fluctuating PSA (flu-PSA) in comparison with patients with steadily increasing PSA (si-PSA); (b) PSA slope estimated in patients with flu-PSA predicts a different risk of cancer detection; (c) flu-PSA and si-PSA patients develop PC in topographically different sites; (d) the behaviour of pre-operative PSA is an expression of a disease with defferent characteristics to the following radical prostatectomy. METHODS: The study involved 211 patients who underwent at least a second biopsy after a first negative prostate biopsy. PSA Slope, PSA velocity (PSAV) and PSA doubling time (PSADT) were estimated. Flu-PSA level was defined as a PSA series with at least one PSA value lower than the one immediately preceding it. RESULTS: 82 patients had flu-PSA levels and 129 si-PSA levels. There were no significant differences between the two groups in terms of cancer detection, clinical or pathological stage, but the si-PSA group with cancer had a higher Gleason score. No difference was found for PSA Slope between flu-PSA patients with cancer and those without. CONCLUSIONS: Our study demonstrates no difference in PC detection rate at repeat biopsy between patients with flu or si-PSA levels. PSA Slope, PSAV and PSADT were not found helpful tools in cancer detection.

Impact of Real-Time Elastography versus Systematic Prostate Biopsy Method on Cancer Detection Rate in Men with a Serum Prostate-Specific Antigen between 2.5 and 10 ng/mL.

The actual gold standard for the diagnosis of prostate cancer includes the serum prostate-specific antigen, the digital rectal examination, and the ultrasound-guided systematic prostate biopsy sampling. In the last years, the real-time elastography has been introduced as an imaging technique to increase the detection rate of prostate cancer and simultaneously reduce the number of biopsies sampled for a single patient. Here, we evaluated a consecutive series of 102 patients with negative digital-rectal examination and transrectal ultrasound, and prostate-specific antigen value ranging between 2.5 ng/mL and 10 ng/mL, in order to assess the impact of real-time elastography versus the systematic biopsy on the detection of prostate cancer. We found that only 1 out of 102 patients resulted true positive for prostate cancer when analysed with real-time elastography. In the other 6 cases, real-time elastography evidenced areas positive for prostate cancer, although additional neoplastic foci were found using systematic biopsy sampling in areas evidenced by real-time elastography as negative. Although additional studies are necessary for evaluating the effectiveness of this imaging technique, the present study indicates that the limited accuracy, sensitivity, and specificity do not justify the routine application of real-time elastography in prostate cancer detection.

Can a Gleason 6 or Less Microfocus of Prostate Cancer in One Biopsy and Prostate-Specific Antigen Level <10 ng/mL Be Defined as the Archetype of Low-Risk Prostate Disease?

Prostate cancer (PC) remains a cause of death worldwide. Here we investigate whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less, ≤5% occupancy) and the PSA <10 ng/mL can define the archetype of low-risk prostate disease. 4500 consecutive patients were enrolled. Among them, 134 patients with a single micro-focus of PC were followed up, and the parameters influencing the biochemical relapse (BR) were analysed. Out of 134 patients, 94 had clinically significant disease, specifically in 74.26% of the patients with PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the patients. Cox regression evidenced a correlation between the BR and Gleason grade at the retropubic radical prostatectomy (RRP), capsular invasion, and the presence of positive surgical margins. Multivariate regression analysis showed a statistically significant correlation between the presence of surgical margins at the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA serum level <10 ng/mL, clinically significant disease was found in 74.26% patients and only positive surgical margins are useful for predicting the BR.

Toker cells of the breast. Morphological and immunohistochemical characterization of 40 cases.

Toker cells are epithelial cells with clear cytoplasm usually free of cytologic atypia localized within the nipple epidermis. Rarely, they can be so numerous and atypical as to require a careful distinction from malignant cells of Paget's disease. The purpose of this paper was to better define the prevalence of these atypical Toker cells and to investigate phenotypic markers that can be helpful in the differential diagnosis with Paget's disease. Forty cases containing Toker cells were identified in the nipples of 390 patients (10.2%) who underwent complete breast mastectomy. In 24 cases (60%), Toker cells were cytologically bland and benign, disappearing after a few consecutive sections ("normal Toker cells"). In 11 cases (27.5%), Toker cells were more numerous and persistent on serial sections, still retaining bland cytologic features ("hyperplastic Toker cells"). In 5 cases (12.5%), hyperplastic Toker cells also became cytologically atypical ("hyperplastic and atypical Toker cells"). On immunohistochemistry, Toker cells were positive for estrogen (25/25) and progesterone (20/23) receptors, and negative for CD138 (18/19) and p53 (14/14); some hyperplastic and atypical Toker cells (4 cases) and hyperplastic Toker cells (1 case) showed faint immunoreactivity for HER2/NEU. For comparison, Paget's disease were negative for estrogen (6/10) and progesterone (7/10) receptors, and positive for CD138 (7/10), p53 (6/10), and HER2/NEU (9/10). Both Toker cells and Paget's disease stained positive for cytokeratin 7 and epithelial membrane antigen, and negative for p63. In conclusion, Toker cells are detectable in 10% of the nipples and are usually cytologically bland, but in 10% of the cases they can be morphologically atypical. The combined use of CD138/p53 is very helpful in distinguishing these atypical Toker cells from those of Paget's disease.