Comparative analysis of transperineal template saturation prostate biopsy versus magnetic resonance imaging targeted biopsy with magnetic resonance imaging-ultrasound fusion guidance.

PURPOSE: Multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsy may improve the detection of clinically significant prostate cancer. However, standardized prospective evaluation is limited. MATERIALS AND METHODS: A total of 294 consecutive men with suspicion of prostate cancer (186 primary, 108 repeat biopsies) enrolled in 2013 underwent 3T multiparametric magnetic resonance imaging (T2-weighted, diffusion weighted, dynamic contrast enhanced) without endorectal coil and systematic transperineal cores (median 24) independently of magnetic resonance imaging suspicion and magnetic resonance imaging targeted cores with software registration (median 4). The highest Gleason score from each biopsy method was compared. McNemar's tests were used to evaluate detection rates. Predictors of Gleason score 7 or greater disease were assessed using logistic regression. RESULTS: Overall 150 cancers and 86 Gleason score 7 or greater cancers were diagnosed. Systematic, transperineal biopsy missed 18 Gleason score 7 or greater tumors (20.9%) while targeted biopsy did not detect 11 (12.8%). Targeted biopsy of PI-RADS 2-5 alone overlooked 43.8% of Gleason score 6 tumors. McNemar's tests for detection of Gleason score 7 or greater cancers in both modalities were not statistically significant but showed a trend of superiority for targeted primary biopsies (p=0.08). Sampling efficiency was in favor of magnetic resonance imaging targeted prostate biopsy with 46.0% of targeted biopsy vs 7.5% of systematic, transperineal biopsy cores detecting Gleason score 7 or greater cancers. To diagnose 1 Gleason score 7 or greater cancer, 3.4 targeted and 7.4 systematic biopsies were needed. Limiting biopsy to men with PI-RADS 3-5 would have missed 17 Gleason score 7 or greater tumors (19.8%), demonstrating limited magnetic resonance imaging sensitivity. PI-RADS scores, digital rectal examination findings and prostate specific antigen greater than 20 ng/ml were predictors of Gleason score 7 or greater disease. CONCLUSIONS: Compared to systematic, transperineal biopsy as a reference test, magnetic resonance imaging targeted biopsy alone detected as many Gleason score 7 or greater tumors while simultaneously mitigating the detection of lower grade disease. The gold standard for cancer detection in primary biopsy is a combination of systematic and targeted cores.

Inhibition of VCAM-1 expression in endothelial cells by CORM-3: the role of the ubiquitin-proteasome system, p38, and mitochondrial respiration.

Carbon monoxide (CO) abrogates TNF-α-mediated inflammatory responses in endothelial cells, yet the underlying mechanism thereof is still elusive. We have previously shown that the anti-inflammatory effect of CO-releasing molecule-3 (CORM-3) is not completely mediated via deactivation of the NF-κB pathway. In this study, we sought to explore other potential mechanisms by which CORM-3 downregulates VCAM-1 expression on TNF-α-stimulated HUVECs. By genome-wide gene expression profiling and pathway analysis we studied the relevance of particular pathways for the anti-inflammatory effect of CORM-3. In CORM-3-stimulated HUVECs significant changes in expression were found for genes implicated in the proteasome and porphyrin pathways. Although proteasome activities were increased by CORM-3, proteasome inhibitors did not abolish the effect of CORM-3. Likewise, heme oxygenase-1 inhibitors did not abrogate the ability of CORM-3 to downregulate VCAM-1 expression. Interestingly, CORM-3 inhibited MAPK p38, and the p38 inhibitor SB203580 downregulated VCAM-1 expression. However, downregulation of VCAM-1 by CORM-3 occurred only at concentrations that partly inhibit ATP production and sodium azide and oligomycin paralleled the effect of CORM-3 in this regard. Our results indicate that CORM-3-induced downregulation of VCAM-1 is mediated via p38 inhibition and mitochondrial respiration, whereas the ubiquitin-proteasome system seems not to be involved.