A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.

Multiparametric magnetic resonance imaging progression predicts the risk of pathological progression. Patients with stable multiparametric magnetic resonance imaging findings have a low rate of progression. Incorporating fusion guided biopsy in active surveillance nearly doubled our detection of pathological progression compared to systematic 12-core biopsy.

Purpose Multiparametric MRI (mpMRI) and fusion biopsy (FBx) detect more high-risk prostate cancer (PCa) and less low-risk PCa than systematic biopsy (SBx). However, there remains a small subset of patients where SBx captures higher grade disease than FBx. We aim to identify potential mechanisms for failure of FBx biopsy in detection of clinically significant (CS) PCa. Methods We reviewed a prospectively maintained database of patients undergoing mpMRI followed by FBx and SBx from 2007-2014. In patients disease upgraded to CS disease (Gleason ≥ 7) by SBx over FBx, independent re-review of MR imaging, archived biopsy imaging, and whole mount pathology, as well as needle coordinate mapping were conducted. Multivariate logistic regression analysis was performed to determine predictors for upgrading by SBx. Results Disease upgrading based on SBx over FBx occurred in 135/1003 (13.5%) patients, of which only 62 (6.2%) were to intermediate (Gleason=7) [N=51, 5.1%] or high risk PCa (Gleason≥8) [N=11, 1.1%]. On multivariate analysis, lower PSA (p <0.001), higher MRI prostate volume (p <0.001), and lower number of target cores (p=0.001) were predictors of upgrading by SBx. Main mechanisms for under-grading by FBx included mpMRI reader oversight, presence of MR invisible cancer, FBx technique error, and intra-lesion Gleason heterogeneity. Conclusions MRI and FBx rarely misses CS PCa, as only 62/1003 (6.2%) cases were upgraded to CS disease by SBx. Imaging and biopsy techniques are continually refined and further studies will help to clarify mechanisms of FBx failure and patient populations which benefit from SBx in addition to FBx.

ANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase () and proteinase 3 () in leukocytes of patients with ANCA-associated vasculitis observed longitudinally (=82) and of healthy controls (=32). Patients with active disease demonstrated hypomethylation of and and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, and expression correlated with DNA methylation. Kaplan-Meier estimate of relapse revealed patients with increased DNA methylation at the promoter had a significantly greater probability of a relapse-free period (<0.001), independent of ANCA serotype. Patients with decreased DNA methylation at the promoter had a greater risk of relapse (hazard ratio, 4.55; 95% confidence interval, 2.09 to 9.91). Thus, changes in the DNA methylation status of the promoter may predict the likelihood of stable remission and explain autoantigen gene regulation.

We demonstrate that TCL is an independent predictor of+pEPE, +pLN, and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.

Using a large multi-institutional cohort, we were able to demonstrate that FBx outperformed SBx in patients with prior negative systematic biopsy. This was due, in part, to the decreasing CS CDR by SBx with increased number of prior biopsies. The yield of FBx stayed constant and did not decrease with increased number of prior negative biopsies. Therefore, repeat SBx alone in patients with multiple prior negative biopsies will be hindered by lower yield and FBx should be utilized concurrently in these patients.

Introduction and Objective Multiparametric MRI (mpMRI) and MR targeted biopsy have a growing role in the screening and evaluation of prostate cancer. We aim to evaluate the current knowledge, attitude, and practice patterns of urologists regarding this new technique. Methods An anonymous online questionnaire was designed to collect information on urologists’ beliefs and use of prostate mpMRI and MR targeted biopsy. The survey was sent to members of the Society of Urologic Oncology (SUO), the Endourological Society (ES), and European Association of Urology (EAU). Multivariate logistic regression analysis was performed to determine predictors for use of prostate MRI and MR targeted biopsy. Results A total of 302 responses were received [ES: 175, EAU: 23, SUO: 104]. The majority of respondents (83.6%) believe MR targeted biopsy to be moderately to extremely beneficial in the evaluation of prostate cancer. 85.7% of responders utilize prostate MR imaging in their practice, and 63.0% utilize MR targeted biopsy. The two most common settings for utilization of MR targeted biopsy include patients with history of prior negative biopsy (96.3%) and monitoring patients on active surveillance (72.5%). In those who do not utilize MR targeted biopsy, the principal reasons were lack of necessary infrastructure (64.1%) and prohibitive costs (48.1%). On multivariate logistic regression analysis, practice in an academic setting (1.86 [1.02–3.40], p = 0.043), and performing > 25 radical prostatectomies per year (2.32 [1.18–4.56], p = 0.015) remained independent predictors for utilizing MR targeted biopsy. Conclusions A majority of respondents to our survey look favorably upon use of prostate MRI and MR targeted biopsy in clinical practice. Over time, reduction in fixed costs and easier access to equipment may lead to further dissemination of this novel and potentially transformative technology.

Proteinase 3 (PR3) and myeloperoxidase (MPO) are two major autoantigens in patients with vasculitis with ANCA. The genes encoding these autoantigens are abnormally expressed in peripheral granulocytes of patients with active ANCA-associated vasculitis. This study provides evidence that this transcriptional dysregulation results in a variety of mRNA processing events from the PRTN3 gene locus. In addition to elevated levels of PR3 message, leukocyte RNA from patients contained PR3 transcripts with an alternative 39 untranslated region. Furthermore, we detected usage of an alternative transcription start site within intron 1 of the PRTN3 gene locus that coincided with active disease (odds ratio, 3.3; 95% confidence interval, 1.3 to 8.4; P=0.01). This promoter may be developmentally regulated, because it was active in normal human bone marrow, multiple leukemia cell lines, MCF-7 cells, and subjects after GM-CSF treatment but not subjects with a neutrophil left shift. This transcript, which lacks exon 1 of PRTN3, encodes a 24-kD protein (p24 PR3/MBN ) with a sequence similar to that previously described for myeloblastin. Notably, PR3, p24 PR3/MBN , and MPO were synthesized in cultured neutrophils from patients with active ANCA-associated vasculitis, indicating that increased transcription results in newly synthesized autoantigens in peripheral neutrophils of patients. The synthesis of p24 PR3/MBN seems to expand the autoantigen repertoire, because immunoblots showed that sera from patients recognized p24 PR3/MBN .These findings emphasize the importance of transcriptional dysregulation of the autoantigen in autoimmune disease.