Benign Prostatic Hyperplasia Nodules Research Articles

Benign prostatic hyperplasia nodules in patients treated with celecoxib and/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain.

Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is acyclooxygenase-2inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS. To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3(NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed. NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.

Assessment of T2-weighted Image Quality at Prostate MRI in Patients with and Those without Intramuscular Injection of Glucagon.

Purpose To assess whether administration of intramuscular (IM) glucagon improves T2-weighted image quality at multiparametric MRI (mpMRI) of the prostate. Materials and Methods In this Health Insurance Portability and Accountability Act-compliant single-center study, the authors retrospectively analyzed radiology reports from 3960 mpMRI examinations (2495 after exclusions) performed between September 2013 and September 2019 and performed outcome comparisons and semiquantitative image assessment of axial T2-weighted images from 120 consecutive mpMRI examinations performed between May 2015 and February 2016. Three experienced radiologists blinded to administration of IM glucagon assessed images using a five-point Likert scale (5 = no motion or blur) for overall image quality, anatomic delineation (prostate capsule, rectum, and lymph nodes), and identification of benign prostatic hyperplasia nodules. Wilcoxon rank sum and χ2 tests were used to assess quantitative parameters. Results The number of mpMRI radiology reports (599 examinations performed with glucagon; 1896, without glucagon) mentioning blur or motion were similar between groups (P = .82). Regression analysis of semiquantitative image quality assessments of T2-weighted images from mpMRI examinations (60 performed with glucagon; 60, without glucagon) demonstrated that images with glucagon were more likely to receive higher scores (4 or 5 rating) than those without glucagon only when the rectum (P = .001) and lymph nodes (P = .01) were evaluated, not when the prostatic capsule, benign prostatic hyperplasia nodules, or overall image quality was evaluated. No evidence of differences was found in identified Prostate Imaging Reporting and Data System (PI-RADS) lesions or targeted-biopsy Gleason scores. Conclusion Administration of IM glucagon did not improve T2-weighted image quality in prostate MRI examinations and showed similar PI-RADS scores and biopsy yields compared with examinations without glucagon. Keywords: MRI, Genital/Reproductive, Urinary, Prostate, Oncology, Observer Performance © RSNA, 2023 Online supplemental material is available for this article. See also commentary by Eberhardt in this issue.

The Symptoms of Benign Prostatic Hyperplasia Patients with Stromal-Dominated Hyperplasia Nodules May Be Associated with Prostate Fibrosis.

The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

MRI Features Associated with Histology of Benign Prostatic Hyperplasia Nodules: Generation of a Predictive Model.

Background: Histologic phenotypic variation of benign prostatic hyperplasia (BPH) has been hypothesized to underlie response to medical therapy. We evaluate preoperative MRI of robot-assisted simple prostatectomy (RASP) specimens and determine imaging features associated with histologic phenotype. Materials and Methods: All patients undergoing RASP from November 2015 to November 2019 with a multiparametric MRI ≤1 year before RASP were included. Patients without identifiable BPH nodules on histologic specimens were excluded. Histology slides were obtained from whole mount adenoma specimens and corresponding MRI were reviewed and graded independently by a blinded expert in BPH histopathology (D.W.S.) and an experienced radiologist specializing in prostate imaging (D.N.C.), respectively. Each nodule was assigned a phenotypic score on a 5-point Likert scale (1 = predominantly glandular; 5 = predominantly stromal) by each reviewer. Scores were compared using the sign test and univariate analysis. Signal intensity relative to background transition zone and nodule texture were noted on T2, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging sequences. Univariate and multivariate stepwise linear regression analysis were conducted to identify MRI features associated with histology score. All analyses were performed using Statistical Analysis System (version 9.4). Results: A total of 99 prostate nodules in 29 patients were included. Median phenotypic scores by histology and MRI were comparable (2, interquartile range [IQR] 2-3 vs 2, IQR 2-4, respectively; p = 0.63). Histology scores were positively correlated with MRI scores (Pearson's correlation 0.84, p < 0.0001). Multivariate stepwise linear regression analysis showed that low apparent diffusion coefficient (ADC) signal intensity (p < 0.001) and DCE wash-in (p = 0.03) were positively associated with more stromal histology, whereas ADC standard deviation (p = 0.03), DCE wash-out (p = 0.001), and heterogeneous T2 texture (p = 0.003) were associated with more glandular histology. Conclusion: There is a strong correlation between MRI features and the histologic phenotype of BPH nodules. MRI may provide a noninvasive method to determine underlying BPH nodule histology.

MP22-12 MAGNETIC RESONANCE IMAGING FEATURES ASSOCIATED WITH HISTOLOGY OF BENIGN PROSTATIC HYPERPLASIA NODULES: A PREDICTIVE MODEL

You have accessJournal of UrologyImaging/Radiology: Uroradiology II (MP22)1 Sep 2021MP22-12 MAGNETIC RESONANCE IMAGING FEATURES ASSOCIATED WITH HISTOLOGY OF BENIGN PROSTATIC HYPERPLASIA NODULES: A PREDICTIVE MODEL Jessica Dai, Tara Morgan, Ramy Goueli, Daniel Parrott, Douglas Strand, Daniel Costa, Claus Roehrborn, and Jeffrey Gahan Jessica DaiJessica Dai More articles by this author , Tara MorganTara Morgan More articles by this author , Ramy GoueliRamy Goueli More articles by this author , Daniel ParrottDaniel Parrott More articles by this author , Douglas StrandDouglas Strand More articles by this author , Daniel CostaDaniel Costa More articles by this author , Claus RoehrbornClaus Roehrborn More articles by this author , and Jeffrey GahanJeffrey Gahan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002013.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Histologic phenotypic variation of benign prostatic hyperplasia (BPH) has been previously described and is hypothesized to underlie response to medical therapy. In this study, we evaluate pre-operative magnetic resonance imaging (MRI) of robotic simple prostatectomy (RASP) specimens and determine imaging features associated with histologic phenotype. METHODS: All patients undergoing RASP from 11/2015 to 11/2019 with multiparametric MRI ≤1 year before surgery were included. Those with no obvious BPH nodules on histologic specimens were excluded. Histology slides and corresponding MRI were reviewed independently by a blinded cell biology Ph.D. and radiologist, respectively. Each nodule was assigned a phenotypic score on a 5-point Likert scale (1=predominantly glandular, 5=predominantly stromal). Scores were compared using the sign test and univariate analysis. Signal intensity relative to transition zone and nodule texture were noted on T2, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE) sequences (Figure 1). Univariate and multiple stepwise linear regression analysis were conducted to identify MRI features associated with histology score. All analyses were performed using Statistical Analysis System (SAS v 9.4). RESULTS: 99 prostate nodules in 29 patients were included. Median phenotypic scores by histology and MRI were comparable (2, IQR 2-3 vs. 2, IQR 2-4, respectively; p=0.63). Histology scores were positively associated with MRI scores on univariate analysis (p <0.0001). Multiple stepwise linear regression analysis showed apparent diffusion coefficient (ADC) low signal intensity and DCE wash-in to be positively associated with more stromal histology score, and ADC SD, DCE wash-out, and heterogeneous T2 texture to be negatively associated with more stromal histology score (Table 1). CONCLUSIONS: There is strong correlation between MRI features and the histologic phenotype of BPH nodules. MRI may provide a non-invasive method to determine underlying BPH nodule histology. Source of Funding: DK115477 (DWS) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e395-e396 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Dai More articles by this author Tara Morgan More articles by this author Ramy Goueli More articles by this author Daniel Parrott More articles by this author Douglas Strand More articles by this author Daniel Costa More articles by this author Claus Roehrborn More articles by this author Jeffrey Gahan More articles by this author Expand All Advertisement Loading ...

Prospective PI-RADS v2.1 Atypical Benign Prostatic Hyperplasia Nodules With Marked Restricted Diffusion: Detection of Clinically Significant Prostate Cancer on Multiparametric MRI.

BACKGROUND. On the basis of expert consensus, PI-RADS version 2.1 (v2.1) introduced the transition zone (TZ) atypical benign prostatic hyperplasia (BPH) nodule, defined as a TZ lesion with an incomplete or absent capsule (T2 score, 2). PI-RADS v2.1 also included a revised scoring pathway whereby such nodules, if exhibiting marked restricted diffusion (DWI score, 4-5), are upgraded from overall PI-RADS category 2 to category 3 (2 + 1 TZ lesions). OBJECTIVE. The purpose of this study was to compare the rates of detection of clinically significant prostate cancer (csPCa) in prospectively reported 2 + 1 TZ lesions, as defined by PI-RADS v2.1, and conventional 3 + 0 TZ lesions with targeted biopsy as the reference standard. METHODS. This retrospective study included men with no known PCa or with treatment-naïve grade group (GG) 1 PCa who underwent 3-T multiparametric MRI of the prostate with prospective reporting by means of PI-RADS v2.1. Patients with at least one PI-RADS category 3 TZ lesion who underwent targeted biopsy formed the final sample. Biopsy results were summarized descriptively for 2 + 1 and 3 + 0 lesions. Generalized estimating equations were used to compare csPCa detection rates between groups. Associations between csPCa in 2 + 1 lesions and patient age, PSA level, prostate volume, PSA density, biopsy history, lesion size, and lesion ADC were tested with Kruskal-Wallis and Fisher exact tests. RESULTS. Among 1238 eligible patients who underwent MRI reported with PI-RADS v2.1, 2 + 1 lesions were reported in 6% (n = 69) and 3 + 0 TZ lesions in 7% (n = 87) of patients. No PCa, GG1 PCa, or csPCa was found in 84% (n = 41), 10% (n = 5), and 6% (n = 3) of 49 patients with 2 + 1 lesions who underwent targeted biopsy. Nor were they found in 74% (n = 45), 15% (n = 9), and 11% (n = 7) of 61 patients with 3 + 0 lesions who underwent targeted biopsy. The csPCa detection rate was not significantly different between 2 + 1 and 3 + 0 lesions (p = .31). All cases of csPCa were GG2, except for one 3 + 0 lesion with a GG3 tumor. No clinical or imaging variable was associated with csPCa in 2 + 1 lesions. CONCLUSION. The rate of csPCa in atypical BPH nodules with marked restricted diffusion was low (6%) and not significantly different from that of conventional 3 + 0 TZ lesions (11%). CLINICAL IMPACT. The results provide prospective clinical data about the revised TZ scoring criterion and pathway in PI-RADS v2.1 for atypical BPH nodules with marked restricted diffusion.

Editorial Comment on "Prospective PI-RADS v2.1 Atypical Benign Prostatic Hyperplasia Nodules With Marked Restricted Diffusion: Detection of Clinically Significant Prostate Cancer on Multiparametric MRI".

This Editorial Comment discusses the following AJR article: Prospectively-Reported PI-RADS Version 2.1 Atypical Benign Prostatic Hyperplasia Nodules with Marked Restricted Diffusion (‘2+1’ Transiti...

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

Purpose:Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic.Materials and Methods:A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests.Results:ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file.Conclusions:This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

Prostate MR: pitfalls and benign lesions.

Multiparametric MRI (mpMRI) of the prostate has evolved to be an integral component for the diagnosis, risk stratification, staging, and targeting of prostate cancer. However, anatomic and histologic mimics of prostate cancer on mpMRI exist. Anatomic feature that mimic prostate cancer on mpMRI include anterior fibromuscular stroma, normal central zone, periprostatic venous plexus, and thickened surgical capsule (transition zone pseudocapsule). Benign conditions such as post-biopsy hemorrhage, prostatitis or inflammation, focal prostate atrophy, benign prostatic hyperplasia nodules, and prostatic calcifications can also mimic prostate cancer on mpMRI. Technical challenges and other pitfalls such as image distortion, motion artifacts, and endorectal coil placements can also limit the efficacy of mpMRI. Knowledge of prostate anatomy, location of the lesion and its imaging features on different sequences, and being familiar with the common pitfalls are critical for the radiologists who interpret mpMRI. Therefore, this article reviews the pitfalls (anatomic structures and technical challenges) and benign lesions or abnormalities that may mimic prostate cancer on mpMRI and how to interpret them.

Differentiation of prostate cancer and benign prostatic hyperplasia: comparisons of the histogram analysis of intravoxel incoherent motion and monoexponential model with in-bore MR-guided biopsy as pathological reference.

To evaluate the diagnostic performance of histogram analysis of intravoxel incoherent motion (IVIM) parameters for differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH), and compare with the monoexponential model, with in-bore MR-guided biopsy as pathological reference. Thirty patients were included in this study. DWI images were processed with Matlab R2015b software by IVIM and monoexponential model for quantitation of diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC). The multiparametric data were compared between PCa and BPH group. Correlations between parameters and Gleason scores of PCa were assessed with Spearman rank test. ROC analysis was used to evaluate and compare the diagnostic ability of each parameter for discriminating PCa from BPH. Logistic regression model was used to evaluate the diagnostic performance of combination of different histogram parameters. Sixteen PCa lesions and 20 BPH nodules were analyzed in this study. For IVIM-derived D, the histogram mean, 75th, 90th, and max of PCa were significantly lower than BPH. PCa had significantly lower min and 10th D* than BPH. For f, histogram mean, min, 10th, 25th, 50th, 75th, 90th, max and skew showed significant differences between PCa and BPH. For ADC, PCa were significantly lower than BPH in terms of histogram mean, min, 10th, 25th, 50th, 75th, 90th, max and kurtosis. Histogram mean D and min, 25th D* show significantly negative correlation with Gleason score (r = - 0.582, - 0.534, - 0.554, respectively). Histogram max D and mean f and min ADC showed higher diagnostic performance than other parameters (AUC = 0.925, 0.881, 0.969, respectively). The IVIM model (combined with max D, min D* and mean f) (AUC = 0.950 [0.821, 0.995]) didn't show significant difference from the monoexponential model (AUC = 0.969 [0.849, 0.999], p = 0.23). Besides, combination of the IVIM and monoexponential model didn't improve diagnostic performance compared with the single model (p = 0.362 and 0.763, respectively). Histogram analyses of IVIM and monoexponential model were both useful methods for discriminating PCa from BPH. The diagnostic performance of IVIM model seemed to be not superior to that of monoexponential model. Combination of IVIM and monoexponential model did not add significant information to the single model alone.

Transition zone prostate cancer: Logistic regression and machine‐learning models of quantitative ADC, shape and texture features are highly accurate for diagnosis

The limitation of diagnosis of transition zone (TZ) prostate cancer (PCa) using subjective assessment of multiparametric (mp) MRI with PI-RADS v2 is related to overlapping features between cancers and stromal benign prostatic hyperplasia (BPH) nodules, particularly in small lesions. To evaluate modeling of quantitative apparent diffusion coefficient (ADC), texture, and shape features using logistic regression (LR) and support vector machine (SVM) models for the diagnosis of transition zone PCa. Retrospective. Ninety patients; 44 consecutive TZ PCa were compared with 61 consecutive BPH nodules (26 glandular/35 stromal). 3 T/T2 -weighted (T2 W) fast spin-echo, diffusion weighted imaging. A radiologist manually segmented lesions on axial images for quantitative ADC (mean, 10th , 25th -centile-ADC), T2 W-shape (circularity, convexity) and T2 W-texture (kurtosis, skewness, entropy, run-length nonuniformity [RLNU], gray-level nonuniformity [GLNU]) analysis. A second radiologist segmented one-fifth of randomly selected lesions to determine the reproducibility of measurements. The reference standard was histopathology for all lesions. Quantitative features were selected a priori and were compared using univariate and multivariate analysis. LR and SVM models of statistically significant features were constructed and evaluated using receiver operator characteristic (ROC) analysis. Subgroup analysis of TZ PCa vs. only stromal BPH and in lesions measuring <15 mm was performed. Agreement in measurements was assessed using the Dice similarity coefficient (DSC). Mean, 25th and 10th -centile ADC, circularity, and texture (entropy, RLNU, GLNU) features differed between groups (P < 0.0001-0.0058); however, at multivariate analysis only circularity and ADC metrics (P < 0.001) remained significant. LR and SVM models were highly accurate for the diagnosis of TZ PCa (sensitivity/specificity/AUC): 93.2%/98.4%/0.989 and 93.2%/96.7%/0.949, respectively, with no significance difference between the LR and SVM models (P = 0.2271). Reproducibility of segmentation was excellent (DSC 0.84 tumors and 0.87 BPH). Subgroup analyses of TZ PCa vs. stromal BPH (AUC = 0.976) and in <15 mm lesions (AUC = 0.990) remained highly accurate. LR and SVM models incorporating previously described quantitative ADC, shape and texture analysis features are highly accurate for the diagnosis of TZ PCa and remained accurate when comparing TZ PCa with stromal BPH and in smaller lesions. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:940-950.

AB012. E-cadherin is down-regulated in benign prostate hyperplasia and required for tight junction formation and permeability barrier in prostatic epithelial cell monolayer

BackgroundProstate specific antigen (PSA), which is expressed by luminal epithelial cells in prostate was recently shown in the stromal compartment of benign prostatic hyperplasia (BPH). Since the stromal compartment does not express PSA, epithelial barrier integrity in BPH nodules might be compromised through loss of cell junctions, resulting in the leakage of PSA and other secreted proteins into the stromal compartment and subsequently promoting BPH pathogenesis. E-cadherin, an important cell junction regulator, is found to be down-regulated in epithelial cells in clinical BPH specimens. Whether E-cadherin downregulation affects epithelial barrier permeability is unknown. This research is aimed at examining epithelial barrier permeability change in BPH and exploring the potential role of E-cadherin in prostatic luminal epithelial permeability.MethodsExplants derived from BPH patients were used to study epithelial barrier permeability in BPH nodules and its normal adjacent tissues by FITC-dextran assay. These specimens were also used to study tight junctions in BPH nodules and normal prostate tissues using transmission electron microscopy (TEM), and used to study the expression of junctional proteins ZO-1, ZO-2, ZO-3 and E-cadherin using immunofluorescence staining. The expression of E-cadherin in these specimens was also determined by immunohistochemistry staining. Normal prostatic luminal epithelial cell lines BHPrE-1 and BPH-1 were utilized to perform in vitro studies. Two independent siRNAs were used to knockdown E-cadherin expression. Permeability and tight junctions of cell monolayers in trans-well inserts with/without E-cadherin knockdown were evaluated by trans-epithelium electrical resistant (TER) assay and FITC-dextran trans-well assay, and TEM respectively. Expression of E-cadherin following siRNAs treatment was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western-blot (WB).ResultsFITC-dextran assay detected an increased epithelial barrier permeability in BPH tissues but not in the adjacent normal prostate in explants derived from BPH patients. Tight junctions as well as junctional proteins were decreased in BPH tissues as compared to the normal prostate, suggesting the compromise of luminal epithelial barriers in BPH. E-cadherin was down-regulated and displayed a discontinuous pattern in BPH. E-cadherin expression was negatively correlated with prostatic epithelial monolayer permeability, and E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation.ConclusionsEpithelial barrier permeability is increased in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting blocking E-cadherin loss could be a potential approach to prevent or treat BPH.

MRI-Ultrasound Fusion Targeted Biopsy of Prostate Imaging Reporting and Data System Version 2 Category 5 Lesions Found False-Positive at Multiparametric Prostate MRI.

The purpose of this study was to determine imaging and clinical features associated with Prostate Imaging Reporting and Data System (PI-RADS) category 5 lesions identified prospectively at multiparametric MRI (mpMRI) that were found benign at MRI-ultrasound fusion targeted biopsy. Between January 2015 and July 2016, 325 men underwent prostate mpMRI followed by MRI-ultrasound fusion targeted biopsy of 420 lesions prospectively identified and assessed with PI-RADS version 2. The frequency of clinically significant prostate cancer (defined as Gleason score ≥ 7) among PI-RADS 5 lesions was determined. Lesions with benign pathologic results were retrospectively reassessed by three abdominal radiologists and categorized as concordant or discordant between mpMRI and biopsy results. Multivariate logistic regression was used to identify factors associated with benign disease. Bonferroni correction was used. Of the 98 PI-RADS 5 lesions identified in 89 patients, 18% (18/98) were benign, 10% (10/98) were Gleason 6 disease, and 71% (70/98) were clinically significant prostate cancer. Factors associated with benign disease at multivariate analysis were lower prostate-specific antigen density (odds ratio [OR], 0.88; p < 0.001) and apex (OR, 3.54; p = 0.001) or base (OR, 7.11; p = 0.012) location. On secondary review of the 18 lesions with benign pathologic results, 39% (7/18) were scored as benign prostatic hyperplasia nodules, 28% (5/18) as inflammatory changes, 5% (1/18) as normal anatomic structures, and 28% (5/18) as discordant with imaging findings. PI-RADS 5 lesions identified during routine clinical interpretation are associated with a high risk of clinically significant prostate cancer. A benign pathologic result was significantly correlated with lower prostate-specific antigen density and apex or base location and most commonly attributed to a benign prostatic hyperplasia nodule. Integration of these clinical features may improve the interpretation of high-risk lesions identified with mpMRI.

Natural Orifice Transluminal Endoscopic Partial Prostatectomy: A Real-time Image-guided Focal Extirpative Feasibility Study

To assess the feasibility of focal endoscopic excision of prostate cancer (PCa) under guidance of real-time magnetic resonance imaging (MRI) or magnetic ultrasound fusion (MUF). Using a cadaveric model, multifocal PCa was simulated using 2 MRI-compatible fiducial markers. These were inserted transrectally and used to generate regions of interests (ROIs) on a 1.5-T surface-coil MRI. The first marker was placed in the right mid-peripheral zone (ROI 1), and the second marker was placed in the left seminal vesicle as a referent lesion for subsequent imaging. MRI of the specimen was then obtained. The radiologist created ROIs using fusion biopsy system at each marker. Two additional incidental ROIs were identified in the left transitional zone (ROI 2-suspicious for benign prostatic hyperplasia nodule) and in the right anterior peripheral zone (ROI 3-suspicious for PCa). Holmium laser enucleation of the transitional zone of the prostate was performed to gain access to the peripheral zone lesions. MUF was used during endoscopic laser excision to convey targeting accuracy. The cadaver was then reimaged to determine the adequacy of resection and examined for histopathologic correlation. Real-time MUF imaging identified the target lesions consistently at the locations designated as ROIs. Complete endoscopic resection of ROIs was possible. Repeated MUF imaging and the postprocedure MRI confirmed the completeness of resection. Pathologic examination demonstrated complete excision, intact neurovascular bundles, and posterior prostatic capsule. This approach may represent a new minimally invasive frontier for focal surgical resection of PCa, making histopathologic margin status determination possible.

Inflammatory mediators in the development and progression of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men. Epidemiological data suggest a causal link between this condition and prostatic inflammation. The prostate is an immune-competent organ characterized by the presence of a complex immune system. Several stimuli, including infectious agents, urinary reflux, metabolic syndrome, the ageing process, and autoimmune response, have been described as triggers for the dysregulation of the prostatic immune system via different molecular pathways involving the development of inflammatory infiltrates. From a pathophysiological standpoint, subsequent tissue damage and chronic tissue healing could result in the development of BPH nodules.

Differentiating Transition Zone Cancers From Benign Prostatic Hyperplasia by Quantitative Multiparametric Magnetic Resonance Imaging.

The aim of this study was to evaluate the value of quantitative diffusion and perfusion parameters to aid in discriminating between transition zone carcinomas and benign prostatic hyperplasia (BPH). Twenty-four transition zone cancers and BPH nodules were contoured on T2-weighted magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) maps, and raw dynamic contrast-enhanced (DCE) MRI. Benign prostatic hyperplasia nodules were then stratified into 2 groups based on the presence or absence of a capsule. Apparent diffusion coefficient values, per-voxel Ktrans, kep, vp, and ve were all compared across all groups. Average ADCs (×10 mm/s) were 1019.22, 1338.11, and 1272.46 for cancer, encapsulated BPH, and nonencapsulated BPH, respectively. Both subgroups of BPH were found to be significantly different than that of cancer (P < 0.05). No individual DCE-MRI parameter was significantly different between cancer and either BPH group. The area under the curve for ADC alone was 0.83, and no individual DCE imaging parameter improved the area under the curve of ADC. Apparent diffusion coefficient may play a role in distinguishing TZ cancers from non-encapsulated BPH nodules that closely resemble cancer.

Abstract No. 419 - Evaluation of the prostatic artery anatomy and its variants with cone beam CT scan

Learning Objectives: Cone beam CT scan (CBCT) pictorial review of the Prostatic artery (PA) anatomic variants.Discussion of optimal CBCT protocols in terms of location of the microcatheter, rate and volume of contrast injection as well as reconstruction algorithm during Prostatic artery embolization (PAE) Background: Thorough knowledge of PA anatomy and its variants is important in performing PAE successfully. Significant variability of the antero-lateral PA (AT) and posterolateral PA (PT) is observed in terms of origin, course and anastomosis with other important arteries. Identification and catheterization of these arteries is important during PAE to prevent nontarget embolization leading to ischemic damage to critical pelvic organs. Optimal quality of CBCT is important in identifying these arteries, their origins and atherosclerotic changes guiding the superselective catheterization of these arteries. Clinical Findings/Procedure Details: AT primarily supplies the central gland and benign prostatic hyperplasia nodules and most important artery to embolize. It frequently arises from the superior vesical artery. PT supplies peripheral portion of the gland and has frequent anastomosis with anal and rectal arteries. AT and PT may arise from the single artery (branch of internal iliac artery IIA) in more than 50% of cases. CBCT can identify these arteries and their anastomosis with other critical arteries in great detail. Size and location of the microcatheter, rate and volume of the contrast injection as well as reconstruction algorithm determines the CBCT quality. We have been successfully doing CBCT with microcatheter nonselectively (arterial phase) and superselective at AT or PT (parenchymal phase) without any periprocedure morbidity. Conclusion and/or Teaching Points: PAE can be performed safely and effectively with thorough knowledge of PA anatomy and its anatomic variants as well as optimizing CBCT protocols.

Multi-parametric MRI findings of transitional zone prostate cancers: correlation with 3-dimensional transperineal mapping biopsy.

A preliminary project to correlate MR findings with mapping prostate biopsy to help differentiate malignant transitional zone lesions form benign prostatic hyperplasia (BPH) nodules. Institutional IRB approved retrospective study with 14 patients suspected of having prostate cancer who underwent both prostate 3T MRI using endorectal coil and 3D transperineal mapping prostate biopsy. MR exams were independently reviewed by two abdominal radiologists blinded to pathology with disagreement resolved by consensus. An MRI lesion was defined as having hypointense T2 signal subjectively without corresponding T1 high signal intensity and low signal on ADC maps in the central gland. Mapping biopsy consisted of systematic transperineal US guided biopsy with 55-108 cores per patient. Twenty-nine lesions were detected on MRI. Of these, 13 correlated with Gleason 6 or higher biopsy samples. 16 were biopsy negative. Among the various MRI characteristics assessed, lack of T2 hypointense rim demonstrated the highest specificity (93%) and positive predictive value (89%). Highest sensitivity (85%) and negative predictive value (78%) were seen with ill-defined nodules. When suspicious MR characteristics were combined, the specificity and PPV rose to 100% while sensitivity decreased to 45% and NPV decreased to 73%. Preliminary study indicates MR findings which can help differentiate a BPH nodule from transitional zone prostate cancers which could help direct biopsy in the large and growing number of people suspected of having prostate cancer. Further work will be needed for validation.

Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is an age-related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood. In the current study, proteomics analyses were utilized to identify proteins altered in the BPH stromal compartment from patients with symptomatic BPH. Stromal cells were isolated from histological nodules of BPH by laser capture microdissection (LCM) and subjected to liquid chromatography/mass spectrometry. Proteins identified included several stromal-specific proteins involved in extracellular matrix (ECM) remodeling, focal adhesion, and cellular junctions. Additionally, the proteomics array identified the presence of luminal epithelial secretory protein PSA. Immunostaining, ELISA, and in situ hybridization analyses of BPH tissues verified the presence of PSA protein but absence of PSA mRNA in the stromal compartment. E-cadherin was down-regulated in BPH epithelial cells compared to normal adjacent tissues, suggesting that alteration of cellular junctions could contribute to the presence of luminal epithelial secreted proteins PSA and KLK2 in the stromal compartment. The above findings suggest that the presence of secreted proteins PSA and KLK2 from prostate luminal epithelial cells in BPH stroma is a hallmark of BPH nodules, which could in part be due to alterations in cellular junction proteins and/or increased epithelial barrier permeability. Elucidating the cause and consequence of these secreted proteins in the stromal compartment of BPH may lead to new understanding of BPH pathogenesis as well as approaches to prevent and/or treat this common disease.