[Ultrasonography of the prostate gland : From B­image through multiparametric ultrasound to targeted biopsy]. / Ultraschall der Prostata : Vom B­Bild über den multiparametrischen Ultraschall zur gezielten Biopsie.

BACKGROUND: Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. STANDARD PROCEDURE: The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. PERFORMANCE: Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. CONCLUSION: In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.

ProPSA and the Prostate Health Index as predictive markers for aggressiveness in low-risk prostate cancer-results from an international multicenter study.

BACKGROUND: One of the major challenges in prostate cancer (PCa) treatment is distinguishing insignificant PCa from those forms that need active treatment. We evaluated the impact of PSA isoforms on risk stratification in patients with low-risk PCa as well as in active surveillance (AS) candidates who underwent radical prostatectomy. METHODS: A total of 112 patients with biopsy confirmed Gleason score (GS) 6 PCa of four different international institutions were prospectively enrolled in the study. Blood withdrawal was performed the day before radical prostatectomy. In addition, patients were classified according to the EAU and NCCN criteria for AS candidates. PSA, free PSA (fPSA) and proPSA were measured using dual monoclonal antibody sandwich immunoassays. In addition, the Prostate Health Index (PHI=proPSA/fPSA × âˆšPSA) was calculated. Final histology of the radical prostatectomy specimens was correlated to PSA, its isoforms and PHI. RESULTS: Serum proPSA levels were significantly elevated in those patients with an upgrade in final histology (GS⩾7). In addition, higher proPSA levels were predictive for extraprostatic extension (⩾pT3a) as well as for positive surgical margins. Interestingly, PHI had an even higher predictive power when compared with proPSA alone concerning GS upgrading, extraprostatic extension and surgical margins in both the total and the AS patient group. CONCLUSION: We showed in a multicenter study that proPSA is a valuable biomarker to detect patients with aggressive PCa in a cohort of GS 6 patients, who would benefit from active tumor therapy. Combining proPSA with the standard markers PSA and fPSA using PHI further increases the predictive accuracy significantly. Moreover, our data support the use of PHI for monitoring PCa patients under AS.

Real-time elastography of the prostate.

Palpation of organs is one of the oldest clinical examination techniques, for instance, if you think of the palpation of the breast or the digital rectal examination of the prostate, where hard palpable regions are suspicious for cancer. This is the basic principle of real-time elastography, an ultrasound technique, which is able to visualise tissue elasticity. Since prostate cancer features an increased stiffness due to the higher cell and vessel density than the normal surrounding tissue, real-time elastography has been used for several years for prostate cancer detection. This review introduces the different techniques of ultrasound elastography and furthermore summarises its limitations and potentials.

[-2]proPSA is an early marker for prostate cancer aggressiveness.

BACKGROUND: The aim of the study was to evaluate the correlation between preoperative [-2]proPSA, the Gleason Score (GS) and the risk of non-organ-confined (NOC) disease in patients undergoing radical prostatectomy (RP). METHODS: Beckman Coulter Access immunoassay was used to study serum specimens of 381 patients enrolled in a prostate cancer (PCa) early detection program. Inclusion criteria were three or more available serum specimens over 4 years before diagnosis. The values obtained were correlated with the GSs and pathological stages of specimens obtained at RP. RESULTS: [-2]proPSA levels were significantly higher in the cancer group (n=208) than in the benign group (n=173). Already 4 years before diagnosis [-2]proPSA differed significantly between PCa and benign prostate in all measured time points, however, highest prediction value was 2 and 1 years before diagnosis (P<0.001). When stratified [-2]proPSA levels according to GS of RP specimens, [-2]proPSA was highest in patients with ≥GS8 and lowest in those with ≤GS6.The difference in [-2]proPSA values between GS≥8 and GS≤7 was highly significant (P<0.01) already 3 years before diagnosis. Investigating the correlation between extraprostatic extension and the preoperative [-2]proPSA levels we found preoperative [-2]proPSA values significantly higher in men with NOC PCa compared with organ-confined (OC) cancers.The highest predictive value of [-2]proPSA to differ between OC and extraprostatic extension was found 3 and 2 years before RP. CONCLUSIONS: Patients with high [-2]proPSA levels in the years before cancer diagnosis are at a higher risk of having aggressive PCas. Thus, the [-2]proPSA should be included in the treatment decision-making for managing screen-detected PCa.

Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer.

BACKGROUND: The TMPRSS2-ERG gene fusion resulting in ERG overexpression has been found in around 50% of prostate cancers (PCa) and is a very early event in tumorigenesis. Most studies have reported on selected surgical cohorts with inconsistent results. We hypothesized that ERG gene rearrangements impact tumor development and investigated the frequency of ERG overexpression in the context of clinicopathological tumor characteristics. METHODS: ERG overexpression (ERG+ or ERG-) was determined by immunohistochemistry (IHC) in 1039 radical prostatectomy (RP) tumors and association with PSA, D'Amico risk score, histopathology, biochemical recurrence, body mass index and age of PCa cases was analyzed. RESULTS: ERG+ was associated with younger age at diagnosis (P<0.0001), lower serum PSA (P=0.002) and lower prostate volume (PV) (P=0.001). It was most frequent in the youngest age quartile (≤55 years, 63.9% ERG+) and decreased constantly with increasing age to 40.8% in the oldest age quartile (≥67 years, P<0.0001). In the PSA range <4 ng ml(-1) the frequency of ERG positivity was 60.2% compared with 47.5 and 49.1% in the PSA ranges 4-10 and ≥10 ng ml(-1), respectively. In the first age quartile, ERG+ patients had lower median serum PSA and fPSA% and smaller PV. In the highest age quartile tumor volume (TV) was increased. Similar differences were observed in the low PSA range. Multivariate analysis identified the first age quartile as a predictor for ERG status (odds ratios (OR) 2.05, P=0.007). No association was found with the D'Amico progression risk score and with biochemical tumor recurrence. CONCLUSIONS: ERG+ tumors manifest clinically at lower PSA levels and their prevalence is age dependent. This suggests acceleration of tumor development by ERG overexpression that results in earlier tumor detection in young patients. Long-term results are warranted to determine the impact of ERG overexpression on disease outcome.

The efficacy of dihydrotestosterone transdermal gel before primary hypospadias surgery: a prospective, controlled, randomized study.

PURPOSE: We sought to evaluate the efficacy of transdermal dihydrotestosterone treatment based on the results of hypospadias repair in children with primary hypospadias. MATERIALS AND METHODS: A total of 75 randomized consecutive children who were a mean of 33.4 +/- 3.7 months old and had primary hypospadias were included in the study between September 2004 and April 2006. While 37 children were treated with 2.5% transdermal gel daily, applied directly onto the penile shaft and glans for 3 months (group 1), 38 children did not receive any treatment preoperatively (group 2). All children underwent hypospadias repair using tubularized incised plate urethroplasty. Postoperative complications were analyzed using the Mann-Whitney U test with respect to fistulas, urethral strictures, diverticula, meatal stenosis, glanular dehiscence and scar formation according to the results at 1-year followup. RESULTS: Mean ages of the children in groups 1 and 2 were similar (30.8 +/- 5.4 months and 35.1 +/- 5.1 months, respectively). The urethral meatus was coronal in 70%, penile in 24% and penoscrotal in 5% of the patients in group 1, while it was coronal in 84% and penile in 16% of the patients in group 2. Postoperative complications included urethrocutaneous fistula in 4 patients (11%) in group 2, compared to 1 patient (3%) in group 1 (p >0.05). While 3 patients (8%) in group 2 had glanular dehiscence, no patient in the dihydrotestosterone group had this complication (p <0.05). There were 2 patients with meatal stenosis in group 2 (5%), and no patient with meatal stenosis in group 1 (p >0.05). In addition, there were 16 patients (42%) with moderate to severe postoperative scar formation in group 2, compared to only 2 patients (5%) in the dihydrotestosterone group (p <0.05). Finally, there was a significant difference between the overall reoperation rates of group 2 (9 patients, 24%) and group 1 (1 patient, 3%, p <0.05). None of our patients had signs or symptoms of urethral stricture or urethral diverticulum. CONCLUSIONS: Pretreatment with dihydrotestosterone transdermal gel was effective in decreasing the complications and improving the cosmetic results after hypospadias repair.

Genome-wide analysis of deoxyribonucleic acid in endometrial cancer using comparative genomic hybridization microarrays.

The aim of this study was to identify amplified oncogenes in endometrial cancer using array-based comparative genomic hybridization (array CGH). Despite its prevalence, the molecular mechanisms of endometrial carcinogenesis are still poorly understood. The selected array CGH allows the simultaneous examination of 58 oncogenes commonly amplified in human cancers and is capable of achieving increased mapping resolution compared with conventional CGH. A subset of 8 specimens from a bank of 60 malignant and normal specimens was selected for array analysis to identify potential genes of interest. TaqMan polymerase chain reaction was carried out on the 60 specimens to examine if aberrations at the genomic level correlated with gene expression and to compare expression in normal and malignant samples. Oncogenes amplified in the endometrial cancers included AR, PIK3CA, MET, HRAS, NRAS, D17S1670, FGFR1, CTSB, RPS6KB1, LAMC2, MYC, PDGFRA, FGF4/FGF3, PAKI, and FGR. Three genes were examined at the messenger RNA level. AR and PIK3CA were higher in normal specimens, and MET was higher in malignant samples, suggesting a role for MET in endometrial cancer. Newer arrays examining more genes and larger sample numbers are necessary to elucidate the carcinogenic pathway in endometrial cancer.

[Ultrasound contrast agents and prostate cancer]. / Ultraschallkontrastmittel und Prostatakarzinom.

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.

Vascular damage induced by type 2 diabetes mellitus as a risk factor for benign prostatic hyperplasia.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the relationship between benign prostatic hyperplasia (BPH) and arteriosclerosis shown in a model of type 2 diabetes in a trans-sectional population study using contrast-enhanced colour Doppler ultrasound for exact assessment of prostatic blood flow. METHODS: Contrast-enhanced transrectal colour Doppler ultrasound was performed using a microbubble-based ultrasound enhancer SonoVue for evaluating prostate vascularity (transitional zone [TZ] and peripheral zone [PZ]) in diabetic BPH patients, non-diabetic BPH patients and healthy subjects. Computer-assisted quantification of colour pixel intensity (CPI) was used to objectively evaluate the prostate vascularity. Resistive index measurements were obtained in the TZ and the PZ. Findings were compared between these three groups. RESULTS: TZ-CPI was significantly lower in diabetic patients than in non-diabetic BPH men (p=0.001), whereas the CPI of the PZ showed no difference between these two groups (p=0.978). TZ-CPI of patients with diabetic and non-diabetic BPH were significantly lower than in controls (p<0.001), but no difference was found between diabetic and healthy patients in the PZ (p=0.022) and borderline significance was seen when comparing patients of the BPH group with the control patients (p=0.019). Resistive index values of the TZ in diabetic patients showed significantly higher values (p<0.001) than the BPH and control groups. CONCLUSIONS/INTERPRETATION: The significantly lower CPI and higher resistive index values of the TZ in diabetic patients compared with patients with non-diabetic BPH and healthy subjects indicate considerable vascular damage in the TZ of these patients. Diabetic vascular damage may cause hypoxia and may contribute to the pathogenesis of BPH.

Genes differentially expressed in prostate cancer.

Because of the heterogeneity of prostate cancer knowledge about the genes involved in prostate carcinogenesis is still very limited. Previously, the use of novel high-throughput technologies offered the possibility to investigate broad gene expression profiles and thus helped to improve understanding of the molecular basis of prostate disease. Many candidate genes have been identified so far which have a more or less strong effect on prostate cancer. This vast number of gene expression changes show that it is unlikely that only one gene promotes prostate cancer. Conversely, it seems more likely that a broad network of molecular changes is involved in the complex cascade of events which lead to tumour formation and progression, respectively. A few of these novel molecular targets are currently under clinical evaluation. This paper gives an overview of several interesting candidate genes which may be useful as improved biomarkers for diagnosis or as targets for developing novel treatment methods.

HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro.

Oropharyngeal candidiasis is one of the first and most commonly reported opportunistic infections of untreated AIDS patients. With the introduction of the new antiviral HAART therapy, including HIV protease inhibitors, this mucocutaneous infection is nowadays only rarely observed in treated patients. It was recently shown that HIV protease inhibitors have a direct attenuating effect on Candida albicans secreted aspartic proteinases (Saps), an investigation prompted by the fact that both Sap and HIV protease belong to the superfamily of aspartic proteinases and by the observation that mucocutaneous infections sometimes resolve even in the absence of an immunological improvement of the host. As these Saps are important fungal virulence factors and play a key role in adhesion to human epithelial cells we tried to assess the effect of the HIV protease inhibitors Ritonavir, Indinavir and Saquinavir on fungal adhesion to these cells. The effect on phagocytosis by polymorphonuclear leukocytes was also assessed. Ritonavir was found to be the most potent inhibitor of fungal adhesion. A dose-dependent inhibition of adhesion to epithelial cells was found already at 0.8 microM and was significant at 4 microM or higher, at 500 microM the inhibition was about 55%. Indinavir and Saquinavir inhibited significantly at 4 microM or 20 microM, respectively; at 500 microM the inhibition was 30% or 50%. In contrast, no protease inhibitor was able to modulate phagocytosis of Candida by polymorphonuclear leukocytes. In conclusion, inhibition of Saps by HIV protease inhibitors may directly help to ease the resolution of mucosal candidiasis. In future, derivatives of HIV protease inhibitors, being more specific for the fungal Saps, may form an alternative in the treatment of mucosal candidiasis insensitive to currently available antimycotics.