Semen sampling as a simple, noninvasive surrogate for prostate health screening.

The detection rates for prostate cancer (pCa) by invasive biopsy are high, fully justifying its use in confirmatory testing. False-positive results of prior, relatively insensitive screening tests, however, can lead to expensive and often unnecessary surgery. Several reports have suggested the potential use of the ejaculate to screen for prostate conditions. Hitherto, the potential impact of sterilization on the diagnostic potential of seminal plasma screening has not been examined. Herein, we report cellular and molecular comparisons of semen samples obtained from normal (N = 5), vasectomized (N = 5) and prostate pathology patients (N = 4; confirmed by a biopsy) that were centrifuged over 60% PureSperm cushions. Non-penetrating cells were washed prior to immunocytochemistry with prostatic epithelial cell markers including PSMA, NKX3.1 and CD24. KRT18 was used to highlight epithelial cells in these samples. RNA sequencing was then used to identify differentially expressed small RNAs associated with vasectomy and prostate pathology. Specific gene transcripts were confirmed by RT-qPCR. PMSA+/KRT18+, CD24+/KRT18+ and NKX3.1/+KRT18+ cells were observed, albeit infrequently in most processed semen samples by indirect immunocytochemistry. Targeted RT-qPCR supported their enrichment, along with their putative designation as prostatic luminal cells. Small RNAs in seminal plasma were highly heterogeneous, with tRNAs and miRNAs being the dominant forms. Hsa-miR-143 and hsa-miR-199 were among the most prominent of the differentially expressed miRNAs upregulated in samples with prostate pathology but not vasectomy. The targets of these small RNAs illustrate biological processes involved among others in transcription regulation and collagen metabolism. Our outcomes strongly support an appraisal of selected biologically meaningful small RNAs of ejaculate semen for prostate health screening. A long-term goal would be a simple, routine, noninvasive test for monitoring prostate health, potentially among younger men.

Detecting and grading prostate cancer in radical prostatectomy specimens through deep learning techniques

OBJECTIVES: This study aims to evaluate the ability of deep learning algorithms to detect and grade prostate cancer (PCa) in radical prostatectomy specimens. METHODS: We selected 12 whole-slide images of radical prostatectomy specimens. These images were divided into patches, and then, analyzed and annotated. The annotated areas were categorized as follows: stroma, normal glands, and Gleason patterns 3, 4, and 5. Two analyses were performed: i) a categorical image classification method that labels each image as benign or as Gleason 3, Gleason 4, or Gleason 5, and ii) a scanning method in which distinct areas representative of benign and different Gleason patterns are delineated and labeled separately by a pathologist. The Inception v3 Convolutional Neural Network architecture was used in categorical model training, and a Mask Region-based Convolutional Neural Network was used to train the scanning method. After training, we selected three new whole-slide images that were not used during the training to evaluate the model as our test dataset. The analysis results of the images using deep learning algorithms were compared with those obtained by the pathologists. RESULTS: In the categorical classification method, the trained model obtained a validation accuracy of 94.1% during training; however, the concordance with our expert uropathologists in the test dataset was only 44%. With the image-scanning method, our model demonstrated a validation accuracy of 91.2%. When the test images were used, the concordance between the deep learning method and uropathologists was 89%. CONCLUSION: Deep learning algorithms have a high potential for use in the diagnosis and grading of PCa. Scanning methods are likely to be superior to simple classification methods.

The Learning Curve for Magnetic Resonance Imaging/Ultrasound Fusion-guided Prostate Biopsy.

BACKGROUND: Magnetic resonance imaging/ultrasound-guided fusion biopsy (FBx) is more accurate at detecting clinically significant prostate cancer than conventional transrectal ultrasound-guided systematic biopsy. However, learning curves for attaining accuracy may limit the generalizability of published outcomes. OBJECTIVE: To delineate and quantify the learning curve for FBx by assessing the targeted biopsy accuracy and pathological quality of systematic biopsy over time. DESIGN, SETTING, AND PARTICIPANTS: We carried out a retrospective analysis of 173 consecutive men who underwent Artemis FBx with computer-template systematic sampling between July 2015 and May 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The accuracy of targeted biopsy was determined by calculating the distance between planned and actual core trajectories stored on Artemis. Systematic sampling proficiency was assessed via pathological analysis of fibromuscular tissue in all cores and then comparing pathology elements from individual cores from men in the first and last tertiles. Polynomial linear regression models, change-point analysis, and piecewise linear regression were used to quantify the learning curve. RESULTS AND LIMITATION: A significant improvement in targeted biopsy accuracy occurred up to 98 cases (p<0.01). There was a significant decrease in fibromuscular tissue in the systematic biopsy cores up to 84 cases (p<0.01) and an improvement in pathological quality when comparing systematic cores from the first and third tertiles. Use of a different fusion platform may limit the generalizability of our results. CONCLUSIONS: There is a significant learning curve for targeted and systemic biopsy using the Artemis platform. Improvements in accuracy of targeted biopsy and better sampling for systematic biopsy can be achieved with greater experience. PATIENT SUMMARY: We define the learning curve for magnetic resonance imaging/ultrasound-guided fusion biopsy (FBx) using targeted biopsy accuracy and systematic core sampling quality as measures. Our findings underscore the importance of overcoming learning curves inherent to FBx to minimize patient discomfort and biopsy risk and improve the quality of care for accurate risk stratification, active surveillance, and treatment selection.

The effect of prostatic inflammation on clinical outcomes in patients with benign prostate hyperplasia.

BACKGROUND: To investigate the effect of asymptomatic inflammatory prostatitis on clinical outcomes of patients undergoing trans urethral resection of prostate due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 514 patients were enrolled in the study. Clinical parameters and pathological results were compared before and one year after surgery. RESULTS: Of the patients 310 were diagnosed with purely benign prostatic hyperplasia and the others were diagnosed with both prostatic inflamation (cathegory IV) and benign prostatic hyperplasia. No statistical significance was observed between two groups among the parameters including age, prostate volume and post voiding residue (P > 0.05). Patients with prostate inflammation presented higher preoperative International Prostate Symptom Score and lower Qmax values when compared to those without inflammation before trans urethral resection of prostate. CONCLUSION: Asymptomatic prostate inflammation can lead to worsen lower urinary tract symptoms and urinary flow rate in patients with benign prostatic hyperplasia. Furthermore, the improvement of the complaints after surgery was worse in patients with asymptomatic prostate inflammation. Further well designed prospective-randomised studies are needed to support our findings.

Effect of hyperprolactinemia on PRL-receptor expression and activation of Stat and Mapk cell signaling in the prostate of long-term sexually-active rats.

The abnormal elevation of serum PRL, referred to as hyperprolactinemia (HyperPRL), produces alterations in several reproductive parameters of male rats such as penile erection or decreased tendency to reach ejaculation. Additionally, this situation produces a significant modification of prostate histology, as observed in the epithelial structure and alveolar area, which could reach a level of hyperplasia in the long-term. In this tissue, HyperPRL produces an increase in expression of PRL receptors and activation of the Stat3 signaling pathway that is correlated with the evolution of prostate pathologies. However, the impact of HyperPRL in long-term sexually active male rats is unknown. In this work, using constantly copulating Wistar male rats with induced HyperPRL, we analyzed the level of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Two procedures to induce HyperPRL were employed, comprising daily IP administration or adenohypophysis transplant, and although neither affected the execution of sexual behavior, the serum PRL profile following successive ejaculations was affected. Messenger RNA expression of the short and long isoforms of the PRL receptor at the ventral prostate was affected in different ways depending on the procedure to induce HyperPRL. The ventral prostate did not show any modification in terms of activation of the pStat5 signaling pathway in subjects with daily administration of PRL, although this was significantly increased in ADH transplanted subjects in the second and fourth consecutive ejaculation. A similar profile was found for the pStat3 pathway which additionally showed a significant increase in the third and fourth ejaculation of daily-injected subjects. The Mapk signaling pathway did not show any modifications in subjects with daily administration of PRL, but showed a significant increase in the second and third ejaculations of subjects with ADH transplants. Thus, although sexual behavior was not modified, HyperPRL modified the expression of PRL receptors and the activation of signal pathways in the prostate tissue. Hence, it is probable that prostatic alterations precede the sexual behavioral deficits observed in subjects with HyperPRL.

Updates in Benign Lesions of the Genitourinary Tract.

The genitourinary tract is a common site for new cancer diagnosis, particularly for men. Therefore, cancer-containing specimens are very common in surgical pathology practice. However, many benign neoplasms and nonneoplastic, reactive, and inflammatory processes in the genitourinary tract may mimic or cause differential diagnostic challenges with malignancies. Emerging clinicopathologic, immunohistochemical, and molecular characteristics have shed light on the pathogenesis and differential diagnosis of these lesions. This review addresses differential diagnostic challenges related to benign genitourinary tract lesions in the kidney, urinary bladder, prostate, and testis, with emphasis on recent advances in knowledge and areas most common in diagnostic practice.

An antimicrobial prophylaxis protocol using rectal swab cultures for transrectal prostate biopsy.

PURPOSE: To evaluate the benefit of an antimicrobial prophylaxis protocol using rectal swab cultures in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy in our Veterans Affairs population. METHODS: Between June 1, 2013, and June 1, 2014, we implemented an antimicrobial prophylaxis protocol using rectal swab cultures on selective media containing ciprofloxacin for all men scheduled for TRUS-guided prostate biopsy. Data from 2759 patients from Jan 1, 2006 to May 31, 2013, before protocol implementation served as historical controls. Patients with fluoroquinolone (FQ)-susceptible organisms received FQ monotherapy, while those with FQ-resistant organisms received targeted prophylaxis. Our objective was to compare the rate of infectious complications 30 days after prostate biopsy before and after implementation of our antimicrobial protocol. RESULTS: One hundred and sixty-seven patients received rectal swab cultures using our protocol. Seventeen (14 %) patients had FQ-resistant positive cultures. Patients with positive FQ-resistant culture results were more likely to have had a history of previous prostate biopsy and a positive urine culture in the last 12 months (p = 0.032, p = 0.018, respectively). The average annual infectious complication rate within 30 days of biopsy was reduced from 2.8 to 0.6 % before and after implementation of our antimicrobial prophylaxis protocol using rectal swab cultures, although this difference was not statistically significant (p = 0.13). CONCLUSION: An antimicrobial prophylaxis protocol using rectal culture swabs is a viable option for prevention of TRUS-guided prostate biopsy infectious complications. After implementation of an antimicrobial prophylaxis protocol, we observed a nonsignificant decrease in the rate of post-biopsy infectious complications when compared to historical controls.

Development of Interpretable Predictive Models for BPH and Prostate Cancer.

BACKGROUND: Traditional methods for deciding whether to recommend a patient for a prostate biopsy are based on cut-off levels of stand-alone markers such as prostate-specific antigen (PSA) or any of its derivatives. However, in the last decade we have seen the increasing use of predictive models that combine, in a non-linear manner, several predictives that are better able to predict prostate cancer (PC), but these fail to help the clinician to distinguish between PC and benign prostate hyperplasia (BPH) patients. We construct two new models that are capable of predicting both PC and BPH. METHODS: An observational study was performed on 150 patients with PSA ≥3 ng/mL and age >50 years. We built a decision tree and a logistic regression model, validated with the leave-one-out methodology, in order to predict PC or BPH, or reject both. RESULTS: Statistical dependence with PC and BPH was found for prostate volume (P-value < 0.001), PSA (P-value < 0.001), international prostate symptom score (IPSS; P-value < 0.001), digital rectal examination (DRE; P-value < 0.001), age (P-value < 0.002), antecedents (P-value < 0.006), and meat consumption (P-value < 0.08). The two predictive models that were constructed selected a subset of these, namely, volume, PSA, DRE, and IPSS, obtaining an area under the ROC curve (AUC) between 72% and 80% for both PC and BPH prediction. CONCLUSION: PSA and volume together help to build predictive models that accurately distinguish among PC, BPH, and patients without any of these pathologies. Our decision tree and logistic regression models outperform the AUC obtained in the compared studies. Using these models as decision support, the number of unnecessary biopsies might be significantly reduced.

Finding a Needle in a Haystack: The Diagnosis of a Rectal Neuroendocrine Tumor by Transrectal Prostate Biopsy.

INTRODUCTION: Prostate biopsy, usually performed by a transrectal approach, is executed when there is a suspicion of prostate cancer. Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation and only 19% of them are localized in the rectum. CASE REPORT: The authors describe a 73-year-old man without a significant past medical history that underwent a prostate biopsy because of urinary complaints and elevated serum levels of prostate specific antigen. The histology revealed a well-differentiated NET characterized as a low-grade tumor (G1). A total colonoscopy revealed a 5 mm sessile rectal polyp and in the splenic flexure a sessile lesion with central ulceration with 5 cm with histological features compatible with an adenocarcinoma. CONCLUSION: This is the first case reported in the literature of a rectal NET diagnosed by transrectal prostate biopsy. This case is particularly unique because the diagnosis of the NET lead to the subsequent timely detection of a colonic adenocarcinoma.

INTRODUÇÃO: A biópsia prostática transretal é realizada na suspeita de cancro da próstata. Os tumores neuroendócrinos (TNE) são neoplasias epiteliais com diferenciação predominante neuroendócrina e em 19% dos casos localizam-se no reto. CASO: Os autores descrevem o caso de um homem, 73 anos de idade, sem antecedentes médicos prévios, que por elevação dos níveis séricos de antigénio específico prostático realizou biópsia prostática transretal. A histologia revelou TNE bem diferenciado de baixo grau (G1). Foi realizada posteriormente colonoscopia total onde se observou pólipo séssil de 5 mm no reto distal. No ângulo esplénico observou-se ainda um lesão séssil de 5 cm com ulceração central cujas biopsias foram compatíveis com o diagnóstico de adenocarcinoma. CONCLUSÃO: Este é o primeiro caso relatado na literatura de um TNE retal diagnosticado por biópsia prostática transretal. Este caso é peculiar dado que o diagnóstico do TNE do reto permitiu a deteção de um adenocarcinoma do cólon num estadio inicial.

Glucocorticoid receptor in prostate epithelia is not required for corticosteroid-induced epithelial hyperproliferation in the mouse prostate.

BACKGROUND: Glucocorticoids are used as a last resort treatment for prostate cancer but the cell-specific glucocorticoid receptor (GR) mediated actions and the role of endogenous glucocorticoids in prostate are not understood. METHODS: We evaluated the influence of prostate epithelial GR mediated actions of glucocorticoids in prostate structural development by comparing the intact wild-type (WT) and prostate epithelia selective GR knockout (peGRKO) males at 8, 20, and 35 weeks of age. We also determined the cell-specific role of GR on corticosterone treatment induced prostate abnormalities by treating peGRKO and WT male mice with corticosterone depot pellets or placebo for 4 weeks. RESULTS: GR was not expressed in the epithelial cells of peGRKO prostate unlike WT but was expressed in stromal of both peGRKO and WT mice. Nevertheless, prostate weights, histological appearance, and secretory protein probasin expression in peGRKO were no different from WT. Despite lacking epithelial GR, the peGRKO prostate demonstrated corticosterone treatment induced hyperplasia similar to WT suggesting that stromal rather than epithelial GR mediates the hyperproliferative mouse prostate response to corticosterone. As circulating androgen levels were not affected by corticosterone treatment, this effect is likely to be mediated directly via prostate GR. CONCLUSIONS: Sustained administration of corticosterone induces prostate hyperplasia, which is mediated via GR expressed predominantly in the stroma. Thus GR mediated actions in the prostate may have significant cell-specific effects that could be utilized for more rational therapeutic approaches in prostate cancer treatment. This also illustrates the paracrine hormonal mechanisms in prostate pathophysiology.

Predictors of Gleason Score (GS) upgrading on subsequent prostatectomy: a single Institution study in a cohort of patients with GS 6.

BACKGROUND: Biopsy Gleason score (bGS) remains an important prognostic indicator for adverse outcomes in Prostate Cancer (PCA). In the light of recent studies purporting difference in prognostic outcomes for the subgroups of GS7 group (primary Gleason pattern 4 vs. 3), upgrading of a bGS of 6 to a GS≥7 has serious implications. We sought to identify pre-operative factors associated with upgrading in a cohort of GS6 patients who underwent prostatectomy. DESIGN: We identified 281 cases of GS6 PCA on biopsy with subsequent prostatectomies. Using data on pre-operative variables (age, PSA, biopsy pathology parameters), logistic regression models (LRM) were developed to identify factors that could be used to predict upgrading to GS≥7 on subsequent prostatectomy. A decision tree (DT) was constructed. RESULTS: 92 of 281 cases (32.7%) were upgraded on subsequent prostatectomy. LRM identified a model with two variables with statistically significant ability to predict upgrading, including pre-biopsy PSA (Odds Ratio 8.66; 2.03-37.49, 95% CI) and highest percentage of cancer at any single biopsy site (Odds Ratio 1.03, 1.01-1.05, 95% CI). This two-parameter model yielded an area under curve of 0.67. The decision tree was constructed using only 3 leave nodes; with a test set classification accuracy of 70%. CONCLUSIONS: A simplistic model using clinical and biopsy data is able to predict the likelihood of upgrading of GS with an acceptable level of certainty. External validation of these findings along with development of a nomogram will aid in better stratifying the cohort of low risk patients as based on the GS.