Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration

Development and Internal Validation of Novel Nomograms Based on Benign Prostatic Obstruction-Related Parameters to Predict the Risk of Prostate Cancer at First Prostate Biopsy

The present study aimed to determine the ability of novel nomograms based onto readily-available clinical parameters, like those related to benign prostatic obstruction (BPO), in predicting the outcome of first prostate biopsy (PBx). To do so, we analyzed our Internal Review Board-approved prospectively-maintained PBx database. Patients with PSA>20 ng/ml were excluded because of their high risk of harboring prostate cancer (PCa). A total of 2577 were found to be eligible for study analyses. The ability of age, PSA, digital rectal examination (DRE), prostate volume (PVol), post-void residual urinary volume (PVR), and peak flow rate (PFR) in predicting PCa and clinically-significant PCa (CSPCa)was tested by univariable and multivariable logistic regression analysis. The predictive accuracy of the multivariate models was assessed using receiver operator characteristic curves analysis, calibration plot, and decision-curve analyses (DCA). Nomograms predicting PCa and CSPCa were built using the coefficients of the logit function. Multivariable logistic regression analysis showed that all variables but PFR significantly predicted PCA and CSPCa. The addition of the BPO-related variables PVol and PVR to a model based on age, PSA and DRE findings increased the model predictive accuracy from 0.664 to 0.768 for PCa and from 0.7365 to 0.8002 for CSPCa. Calibration plot demonstrated excellent models' concordance. DCA demonstrated that the model predicting PCa is of value between ~15 and ~80% threshold probabilities, whereas the one predicting CSPCa is of value between ~10 and ~60% threshold probabilities. In conclusion, our novel nomograms including PVR and PVol significantly increased the accuracy of the model based on age, PSA and DRE in predicting PCa and CSPCa at first PBx. Being based onto parameters commonly assessed in the initial evaluation of men “prostate health,” these novel nomograms could represent a valuable and easy-to-use tool for physicians to help patients to understand their risk of harboring PCa and CSPCa

Clinical Evidence Supporting the Role of Lonidamine for the Treatment of BPH

Glandular prostate epithelial cells of the peripheral zone are unique among normal cells in their dependence on glycolysis for energy production, due to a zinc-mediated enzymatic block in the citric acid cycle. Lonidamine (LND), a derivative of indazole-3-carboxylic acid, is thought to disrupt energy metabolism by interfering with glycolysis and to cause cell apoptosis. We evaluated the efficacy of oral LND treatment in subjects with symptomatic benign prostatic hyperplasia (BPH). The following reports the findings of an open-label study of orally administered LND. Thirty subjects with symptomatic BPH received oral LND (150 mg/day) once daily for 28 days. Subjects were assessed at baseline, at active-therapy assessment visits (days 14, 28), and 1, 2, 3, and 6 months post-therapy, for prostate volume (PV) by transrectal ultrasound (TRUS), maximum flow rate (Q(max)) on uroflowmetry, postvoid residual urine volume (PVR), International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, serum chemistry, and adverse events

Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder

Micropapillary carcinoma of the bladder (MPBC) is a variant type of infiltrating urothelial carcinoma, which portends a poor biological behavior in terms of disease stage at first diagnosis and clinical outcome; its peculiar morphology raises issues concerning the ability of tumor detection by imaging techniques and proper biopsy procedure, and the appropriate treatment for non-muscle infiltrating and muscle-infiltrating MPBC remains a matter of debate. On the basis of its established prognostic and therapeutic role in breast and gastro-esophageal cancer in the first instance, the human epidermal growth factor receptor-2 (HER2) has been investigated in selected case series of MPBC over the last 10 years. The aim of the present review was to summarize the existing evidence on HER2 status in MPBC, and to discuss its present and future utility in risk assessment and treatment choice of this uncommon, yet aggressive, disease

Hem-O-Lok clip: A neglected cause of severe bladder neck contracture and consequent urinary incontinence after robot-assisted laparoscopic radical prostatectomy

Background: Hem-o-lok clips are widely used during robot-assisted and laparoscopic radical prostatectomy to control the lateral pedicles. There are a few reports of hem-o-lok clip migration into the bladder or vesico-urethral anastomosis and only four cases of hem-o-lok clip migration resulting into bladder neck contracture. Herein, we describe the first case, to our knowledge, of hem-o-lok clip migration leading to severe bladder neck contracture and subsequent stress urinary incontinence. Case presentation. A 62-year-old Caucasian man underwent robot-assisted laparoscopic radical prostatectomy for a T1c Gleason 8 prostate cancer. One month after surgery the patient was fully continent; however, three months later, he presented with acute urinary retention requiring suprapubic drainage. Urethroscopy showed a hem-o-lok clip strongly attached to the area between the vesico-urethral anastomosis and the urethral sphincter and a severe bladder neck contracture behind it. Following cold-knife urethral incision and clip removal, the bladder neck contracture was widely resected. At 3-month follow-up, the patient voided spontaneously with a peak flow rate of 9.5 ml/sec and absence of post-void residual urine, but leaked 240 ml urine at the 24-hour pad test. To date, at 1-year follow-up, his voiding situation remains unchanged. Conclusions: The present report provides further evidence for the risk of hem-o-lok clip migration causing bladder neck contracture, and is the first to demonstrate the potential of such complication to result into stress urinary incontinence. © 2014 Cormio et al.; licensee BioMed Central Ltd

Morphological and Immunohistochemical Biomarkers in Distinguishing Prostate Carcinoma and Urothelial Carcinoma: A Comprehensive Review

The differential diagnosis between high-grade prostate carcinoma and infiltrating urothelial carcinoma (UC) in transurethral resection prostate specimens as well as cystoprostatectomy specimens may often be challenging due to morphologic and clinical overlap of the 2 entities. Such distinction has critical therapeutic and staging consequences, yet it is hampered by both issues in morphology and by the low accuracy rates of single immunohistochemical markers, as reported in literature. This review aims to provide a comprehensive analysis of the available morphological and immunohistochemical parameters, which may allow to discriminate between prostate carcinoma and urothelial carcinoma in the proper clinical context and to discuss their diagnostic applications in daily practice