Purpose: To improve the specificity in prostate cancer diagnosis and to prevent unnecessary prostate biopsies, especially in the serum prostate-specific antigen (PSA) ''gray zone'' between 3 and 15 ng/mL, the implementation of prostate cancer^specific markers is urgently needed. The recently discovered prostate cancer antigen 3 (PCA3) is such a promising prostate cancer marker. In a previous single institution study, the PCA3 urine test clearly proved to be of diagnostic value.Therefore, the diagnostic performance of the PCA3 urine test was validated in a multicenter study. Experimental Design:The first voided urine after digital rectal examination was collected from a total of 583 men with serum PSA levels between 3 and 15 ng/mL who were to undergo prostate biopsies. We determined the PCA3 score in these samples and correlated the results with the results of the prostate biopsies. Results: A total of 534 men (92%) had an informative sample. The area under the receiveroperating characteristic curve, a measure of the diagnostic accuracy of a test, was 0.66 for the PCA3 urine test and 0.57 for serum PSA. The sensitivity for the PCA3 urine test was 65%, the specificity was 66% (versus 47% for serum PSA), and the negative predictive value was 80%. Conclusions: In this multicenter study, we validated the diagnostic performance of the PCA3 urine test in the largest group studied thus far using a PCA3 gene-based test. This study shows that the PCA3 urine test, when used as a reflex test, can improve the specificity in prostate cancer diagnosis and could prevent many unnecessary prostate biopsies.

No abstract

Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance.

In vitro 1H and 31P magnetic resonance spectra were acquired from perchloric acid extracts of human prostate tissue obtained by transurethral resection. This included tissue of patients with benign prostatic hyperplasia and prostatic adenocarcinoma; one tissue sample was obtained from a patient without any sign of BPH or malignancy. Major resonances in the magnetic resonance spectra were assigned to prostate compounds and were quantified. The citrate/lactate, citrate/total choline, phosphocholine/total creatinine, choline/total creatine, alanine/total creatine, phosphoethanolamine/total phosphate, phosphocholine/total phosphate and glycerophosphoethanolamine/total phosphate ratios were statistically different for the prostate cancer samples as compared with the BPH specimens. These observations may contribute to the understanding of in vivo magnetic resonance spectra of the prostate and indicate that magnetic resonance spectroscopy can aid in the diagnosis of prostate malignancy.

Abstract-The hypothesis that exposure of a solid tumor to high-energy shock waves (HESW) could lead to an increase of metastases was investigated in an animal model. The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted in the hind limb of a Fisher-Copenhagen rat and was exposed to 6000 shock waves delivered by an experimental lithotripter, or sham-treated, as soon as the tumor had reached a volume of 175-225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases was examined 12 weeks thereafter at autopsy. Metastases were seen in 82% of the animals exposed to HESW and in 25% of the sham-treated animals. There was no significant difference in weight of the lungs that contained metastases, between sham and treated animals. These results were confirmed in a second experiment. We conclude that the metastatic spread of tumors with a high metastatic potential may be enhanced by shock-wave exposure.

No abstract

Newborn screening programs for severe metabolic disorders using tandem mass spectrometry are widely used. Medium-Chain Acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid oxidation defect (1:15,000 newborns) and it has been proven that early detection of this metabolic disease decreases mortality and improves the outcome. In previous studies, data mining methods on derivatized tandem MS datasets have shown high classification accuracies. However, no machine learning methods currently have been applied to datasets based on non-derivatized screening methods. A dataset with 44,159 blood samples was collected using a non-derivatized screening method as part of a systematic newborn screening by the PCMA screening center (Belgium). Twelve MCADD cases were present in this partially MCADD-enriched dataset. We extended three data mining methods, namely C4.5 decision trees, logistic regression and ridge logistic regression, with a parameter and threshold optimization method and evaluated their applicability as a diagnostic support tool. Within a stratified cross-validation setting, a grid search was performed for each model for a wide range of model parameters, included variables and classification thresholds. The best performing model used ridge logistic regression and achieved a sensitivity of 100%, a specificity of 99.987% and a positive predictive value of 32% (recalibrated for a real population), obtained in a stratified cross-validation setting. These results were further validated on an independent test set. Using a method that combines ridge logistic regression with variable selection and threshold optimization, a significantly improved performance was achieved compared to the current state-of-the-art for derivatized data, while retaining more interpretability and requiring less variables. The results indicate the potential value of data mining methods as a diagnostic support tool.

Median ADC is able to predict the presence and grade of PCa in CSRs identified by MP-MRI.