A prospective study of magnetic resonance imaging and ultrasonography (MRI/US)-fusion targeted biopsy and concurrent systematic transperineal biopsy with the average of 18-cores to detect clinically significant prostate cancer.

BACKGROUND: This study compared the detection rates for clinically significant prostate cancer (CSPC) between magnetic resonance imaging and ultrasonography (MRI/US)-fusion-targeted biopsy (TB), systematic biopsy (SB) and combination of TB and SB. METHODS: This prospective study evaluated simultaneous TB and SB for consecutive patients with suspicious lesions that were detected using pre-biopsy multiparametric MRI. A commercially available real-time virtual sonography system was used to perform the MRI/US-fusion TB with the transperineal technique. The prostate imaging reporting and data system version 2 (PI-RADS v2) was assigned to categorize the suspicious lesions. RESULTS: A total of 177 patients were included in this study. The detection rate for CSPC was higher using SB, compared to TB (57.1% vs 48.0%, p = 0.0886). The detection rate for CSPC was higher using the combination of TB and SB, compared to only SB (63.3% vs 57.1%, p = 0.2324). Multivariate analysis revealed that PIRADS v2 category 4 and an age of <65 years were independent predictors for TB upgrading (vs. the SB result). CONCLUSIONS: PI-RADS v2 category 4 and an age of <65 years were predictive factors of upgrading the Gleason score by MRI/US-fusion TB. Thus, MRI/US-fusion TB may be appropriate for patients with those characteristics. TRIAL REGISTRATION: This study was retrospectively registered at the University Hospital Medical Information Network ( UMINID000025911 ) in Jan 30, 2017.

Expression of androgen and estrogen signaling components and stem cell markers to predict cancer progression and cancer-specific survival in patients with metastatic prostate cancer.

PURPOSE: Genes of androgen and estrogen signaling cells and stem cell-like cells play crucial roles in prostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes. EXPERIMENTAL DESIGN: We developed models to predict clinical failure using biopsy samples from a training set of 46 and an independent validation set of 30 patients with treatment-naïve prostate cancer with bone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection. We analyzed the association between clinical failure and mRNA expression of the following genes androgen receptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell-like molecules (Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP. RESULTS: Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under the curve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERα expression in stromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS): Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERα expression in stromal cells; and PSA, Gleason score, and extent of disease. On the basis of these factors, patients were divided into favorable-, intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3 groups were 90%, 32%, and 12% in the training set and 75%, 48%, and 0% in the validation set, respectively. CONCLUSIONS: Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools.

Extracellular matrix dermatopontin modulates prostate cell growth in vivo.

Dermatopontin is a tyrosine-rich acidic extracellular matrix protein of 22 kDa with possible functions in cell-matrix interactions and matrix assembly. We have previously isolated mRNAs expressed in hormone-refractory, but not in hormone-sensitive, mouse mammary cancer by comparing the mRNAs expressed in either tumor. A partial mRNA sequence isolated was later proven to be a part of mouse dermatopontin mRNA sequence. Transfectants of mouse dermatopontin cDNA into PC-3 human prostate cancer cells enhanced tumor growth when those were implanted subcutaneously in nude mice compared with the controls. Those transfectants showed a prominent stroma compared with the controls. Localization of the targets of a fusion protein of mouse dermatopontin and alkaline phosphatase was in the stroma of the PC-3 tumor tissues, but not in the tumor cells themselves. Additionally, we have established mouse dermatopontin transgenic mice under the control of the rat probasin promoter. The prostatic dorsal lobes of dermatopontin transgenic mouse showed prostate intra-epithelial neoplasia at the age of 11 months, but the control littermates did not. Epithelium of other prostatic lobes was not markedly different from that of the controls. In conclusion, dermatopontin may be involved in the pathogenesis and growth of the prostate cancer.

Periurethral injection of sustained release basic fibroblast growth factor improves sphincteric contractility of the rat urethra denervated by botulinum-a toxin.

PURPOSE: We evaluated the effects of sustained release basic fibroblast growth factor injection in rat urethra denervated by botulinum-A toxin (Wako Life Science, Osaka, Japan). MATERIALS AND METHODS: A total of 30 female Sprague-Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce chemical denervation of the urethral sphincter. Leak point pressure in the waking state was determined and a significant decrease in leak point pressure vs that in control rats was confirmed (mean +/- SD 58.7 +/- 6.2 vs 120.7 +/- 13.0 cm H(2)O, p <0.0001). Two weeks later 0, 50 and 200 microg basic fibroblast growth factor incorporating 200 microl gelatin hydrogels in 10 rats each were injected into the urethral sphincter, enabling sustained release of basic fibroblast growth factor for 2 weeks. Four weeks later injection leak point pressure measurement and histological evaluation of the urethra were performed. RESULTS: Leak point pressure in rats with 50 and 200 microg basic fibroblast growth factor injection was significantly higher than in rats with the 0 microg injection (82.7 +/- 9.0 vs 95.1 +/- 6.2 and 119.3 +/- 8.1 cm H(2)O, p = 0.0021 and <0.0001, respectively). Maximum cross-sectional area of the urethral smooth muscle layer in the 50 and 200 microg groups significantly increased compared with that in the urethra in the 0 micro group, which was considered 100% (114.1% +/- 15.8% and 132.5% +/- 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross-sectional area of the striated sphincter in the 50 and 200 microg groups was greater than the 100% in the 0 microg group (112.3% +/- 15.6% and 124.3% +/- 14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri-atrophic zone in the 50 and 200 microg groups was significantly higher than in the 0 microg group (p = 0.027 and <0.0001, respectively). CONCLUSIONS: Sustained release basic fibroblast growth factor injection in the chemically denervated urethral sphincter facilitates regeneration of the urethral muscles and improves sphincteric contractility. Endoscopic periurethral injection of basic fibroblast growth factor incorporating gelatin hydrogels may be an attractive therapy for stress urinary incontinence.