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Background: Many potential chemopreventive agents have been used in PCa prevention, including selenium (Se) and lycopene (Ly). However, their role has been matter of debate over the years, due to potential of promotion of PCa., Purpose: In this study we aimed at evaluating the incidence risk of prostate cancer (PCa) in a cohort of patients treated with Se and Ly., Methods: The Procomb trial design has been previously published (ISRCTN78639965). From April 2012 to April 2014 209 patients were followed and underwent prostate biopsy when PSA ≥4 ng/ml and/or suspicion of PCa. The all cohort was composed by patients treated with Se and Ly (Group A = 134 patients) and control (Group B = 75 patients)., Results: During the follow-up time of 2 years, a total of 24 patients (11.5%) underwent prostate biopsy, of which 9 (4.3%) where diagnosed with PCa and 15 (7.2%) where diagnosed with benign prostatic hyperplasia. We did not observe statistical differences in terms of mean changes of PSA between the two groups (p-value for trend = 0.33). The relative risk (RR) for PCa was 1.07 and 0.89 in group A and B, respectively (p = 0.95). At the multivariate Cox regression analysis supplementation with Se and Ly was not associated with greater risk of PCa (hazard ratio: 1.38; p = 0.67)., Conclusion: In this analysis we did not show evidences supporting a detrimental role of Selenium and Lycopene supplementation in increasing PCa after 2 years of therapy, nor supporting a protective role., (Copyright © 2017. Published by Elsevier GmbH.)

Objective: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines., Materials and Methods: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded., Results: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index  > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04)., Conclusion: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription., Methods: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B)., Results: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT., Conclusion: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Currently, men are younger at the time of diagnosis of prostate cancer and more interested in less invasive surgical approaches (traditional laparoscopy, 3D-laparoscopy, robotics). Outcomes of continence, erectile function, cancer cure, positive surgical margins and complication are well collected in the pentafecta rate. However, no comparative studies between 4th generation 3D-HD vision system laparoscopy and standard bi-dimensional laparoscopy have been reported. This study aimed to compare the operative, perioperative data and pentafecta rates between 2D and 3D laparoscopic radical prostatectomy (LRP) and to identify the actual role of 3D LRP in urology., Methods: From October 2012 to July 2013, 86 patients with clinically localized prostate cancer [PCa: age ≤ 70 years, prostate-specific antigen (PSA) ≤ 10 ng/ml, biopsy Gleason score ≤ 7] underwent laparoscopic extraperitoneal radical prostatectomy (LERP) and were followed for approximately 14 months (range 12-25). Patients were selected for inclusion via hospital record data, and divided into two groups. Their patient records were then analyzed. Patients were randomized into two groups: the former 2D-LERP (43 pts) operated with the use of 2D-HD camera; the latter 3D-LERP (43 pts) operated with the use of a 3D-HD 4th generation view system. The operative and perioperative data and the pentafecta rates between 2D-LERP and 3D-LERP were compared., Results: The overall pentafecta rates at 3 months were 47.4% and 49.6% in the 2D- and 3D-LERP group respectively. The pentafecta rate at 12 months was 62.7% and 67% for each group respectively. 4th generation 3D-HD vision system provides advantages over standard bi-dimensional view with regard to intraoperative steps. Our data suggest a trend of improvement in intraoperative blood loss and postoperative recovery of continence with the respect of the oncological safety., Conclusions: Use of the 3D technology by a single surgeon significantly enhances the possibility of achieving better intraoperative results and pentafecta in all patients undergoing LERP. Potency was the most difficult outcome to reach after surgery, and it was the main factor leading to pentafecta failure. Nevertheless, further studies are necessary to better comprehend the role of 3D-LERP in modern urology.

Background: This study aimed to compare the pentafecta rates between laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RALP) and to identify prognostic factors predicting the pentafecta for each technique., Methods: This prospective comparative study enrolled 248 consecutive male patients 70 years of age or younger with clinically localized prostate cancer [PCa: age ≤ 70 years, prostate-specific antigen (PSA) ≤ 10 ng/ml, biopsy Gleason score ≤ 7] who were fully continent, potent, and candidates for bilateral nerve-sparing (BNS) LRP or RALP. The pentafecta rates between LRP and RALP were compared. A logistic regression model was created to evaluate independent factors for achieving pentafecta., Results: In the final analysis, 91 LRP and 136 RALP patients were evaluated. The median follow-up period was 21 months for the 91 LRP patients and 18 months for the 136 RALP patients (p = 0.07). Of the 227 patients, 87 reached pentafecta [25 LRP patients (27.5 %) vs 62 RALP patients (45.6 %), p = 0.006]. Of the 140 patients who failed pentafecta, 90 (64.3 %) missed a single parameter. In these cases, erectile deficit was the leading cause of pentafecta failure, with a significant [corrected] difference between groups (80 % LRP cases that missed potency recovery [corrected] vs 53.3 % RALP, p = 0.007). Lower age, lower pathologic stage, and RALP are significantly associated with pentafecta as independent factors. For the pT3 disease, the two techniques did not differ significantly., Conclusions: Patients submitted to BNS RP have low possibilities of achieving pentafecta. Use of the robotic platform by a single surgeon significantly enhances the possibility of achieving pentafecta independently of age and pathologic stage. Potency was the most difficult outcome to reach after surgery, and it was the main factor leading to pentafecta failure. LRP and RALP provide equivalent pentafecta rates for the pT3 disease and similar "tetrafecta" outcomes when potency recovery is not included among the postoperative expectations of the patient.

Objective: To test high-intensity focused ultrasound (HIFU) as salvage first-line treatment for palpable, TRUS-evidenced, biopsy-proven locally recurrent prostate cancer (CaP) after radical prostatectomy (RP)., Materials and Methods: Nineteen patients with palpable, TRUS-evidenced, biopsy-proven local recurrence of CaP after RP, unwilling to undergo salvage radiotherapy (SRT), underwent HIFU as a single-session procedure. Pre-, intra-, and postoperative data including early and late complications, and oncologic outcomes (PSA nadir, biochemical recurrence (BCR)-free survival, and need of secondary adjuvant treatment) were prospectively evaluated. Success was defined as PSA nadir ≤0.1 ng/ml obtained within 3 months from HIFU. In case of PSA nadir >0.1 ng/ml or PSA increase ≥1 ng/ml above the PSA nadir, a biopsy of the treated lesion was performed, and if negative, maximum androgen blockade (MAB) was adopted. In case of positive biopsy, RT was performed. Failure was defined as use of secondary adjuvant treatment (MAB or RT)., Results: Median follow-up was 48 months. All cases were performed as overnight procedure. No case of urethrorectal fistula or anastomotic stricture was observed. Two cases of acute urinary retention were resolved with prolonged urethral catheterization. Four cases of stress urinary incontinence were observed; 2 (mild incontinence) were resolved after pelvic floor exercises within 6 months, while 2 cases of severe incontinence required surgical minimally invasive treatment;17/19 patients (89,5%) were classified as success. Two patients failed to show a PSA nadir <0.1 ng/ml. During follow-up, 8/17 patients (47%) were classified as failure, with consequent total rate of failures 10/19 (52.6%). A statistically significant difference was observed in pre-HIFU median PSA (2 vs. 5.45 ng/ml, respectively, P = 0.013) and Gleason score of the RP specimen (P = 0.01) between the success and failure group., Conclusions: Salvage first-line HIFU for palpable, TRUS-evidenced, biopsy-proven local recurrence of CaP is a feasible, minimally invasive day-case procedure, with an acceptable morbidity profile. It seems to have a good cancer control in the short- and mid-term. Patients with lower pre-HIFU PSA level and favorable pathologic Gleason score presented better oncologic outcomes. A prospective randomized trial with an adequate recruitment and follow-up is necessary to confirm our preliminary oncologic results., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: We offer an overview of the intra-, peri- and postoperative outcomes of laparoscopic radical prostatectomy (LRP) with the endpoint to evaluate potential advantages of this approach., Materials and Methods: We conducted an extensive Medline literature search (search terms "laparoscopic radical prostatectomy" and "radical prostatectomy") from 1990 until 2007. Only full-length English language articles identified during this search were considered for this analysis. A preference was given to the articles with large series with more than 100 patients. All pertinent articles concerning localized prostate cancer were reviewed., Conclusion: Pure LRP has shown to be feasible and reproducible but it is difficult to learn. Potential advantages over open surgery have to be confirmed by longer-term follow-up and adequately designed clinical studies.

Many studies have demonstrated that both normal and malignant prostate cells respond to a variety of growth factors, while several significant differences were found between normal and tumoural cells. The aim of this study was to focus on the localization and distribution of the immuno-reactivity for neurotrophins (NTs) and neurotrophin receptors (NTRs) in normal, hyperplastic and prostate cancer cells, obtained from 40 subjects. We studied samples obtained from 16 prostate cancer (PC, retropubic radical prostatectomy), 20 benign prostatic hyperplasia (BPH, supra-pubic prostatectomy) and normal peripheral prostate tissue from four fresh male cadavers. Samples were examined via immunohistochemical techniques in order to detect the expression of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and their own receptors TrkA, p75, TrkB and TrkC. We observed a high expression of BDNF and TrkB in PC and BPH, though no immuno-reactivity was found for p75. Low expression was reported by other NTs and NTRs in the normal peripheral prostate zone, BPH and PC. These data suggest a possible predictive role for NTs and NTRs, especially for BDNF and TrkB, in the diagnosis and/or management of prostate cancer. The absence of p75 expression confirms its supposed role in apoptotic phenomenon.

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNA-damaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68(GSG) protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

Prostate cancer originates as an androgen-dependent hyperproliferation of the epithelial cells of the gland and it evolves in an androgen-independent, highly aggressive cancer for which no successful therapy is available to date. Neuroendocrine (NE) differentiation plays an important role in the progression of prostate cancer to an androgen-independent state with profound impact on prostate cancer (CaP) therapies. Actually, new approaches on treating advanced prostate cancer are focused on modulators of epigenetic transcriptional regulation. A new class of antitumoral agents is emerging: histone deacetylase (HDAC) inhibitors are interesting for their ability to arrest cell growth, to induce cell differentiation, and in some cases, to induce apoptosis of cancer cells. We studied the effect of valproic acid (VPA), an inhibitor of HDAC, in the human prostate androgen-dependent cancer cell line LNCaP. We observed that VPA promotes neuroendocrine-like differentiation associated with an increase in the expression of neuron-specific enolase, a decrease in prostate-specific antigen, and a down-regulation of androgen receptor protein, suggesting a modulation in the responsiveness to androgen therapy. Furthermore, selective gene expression profiling using a low-density microarray showed that VPA was able to modulate the expression of different androgen metabolism genes. We observed a down-regulation of androgen receptor coregulator (ARA24) and prostate-specific antigen, and an up-regulation of some of the UDP-glucuronosyltransferases (UGT2B11 and UGT2B7) implicated in catabolism of dihydrotestosterone (DHT) was detected. Even though UGT2B7 has only about one-tenth to one-hundredth the activity of UGT2B15 and 2B17 toward active androgens and we did not found any modulation in gene expression of these enzymes, it can be hypothesized that VPA might enhance DHT catabolism in this in vitro model and induces NE differentiation. Our data seem to raise concern about CaP treatment with VPA.

Background: PACAP is a member of the VIP/GHRH family of neuropeptides and has important effects on prostate cell proliferation. Here we analyze the expression and localization of PACAP and its specific receptor variants (PAC(1)-R) in tissues collected from patients undergoing prostate biopsy and surgery for benign prostatic hyperplasia (BPH) and prostate cancer (PCa)., Methods: Reverse transcriptase (RT)-polymerase chain reaction (PCR), DNA sequencing, and immunohistochemistry., Results: PACAP and PAC(1)-R were localized by immunohistochemistry in the prostate tissue. While in healthy and BPH tissues PAC(1)-R positive staining is present in all the epithelial cells lining the lumen of the acini and in some stromal cells (mostly in the apical portion of the cells), in PCa tissues, anti-PAC(1)-R antibody stained the apical portion of the cells. We provide evidence that PAC(1)-R null and SV(1)/SV(2) variants are all present in normal and hyperplastic tissues, while in PCa tissue PAC(1)-R null is the most relevant receptor variant expressed., Conclusions: Our data demonstrates that the PAC(1)-R null variant is the most relevant isoform expressed in human PCa tissue being suggestively related with the events determining the outcome of prostate cancer.

A truncated form of the c-Kit tyrosine kinase receptor, originally identified in mouse haploid germ cells, is aberrantly expressed in human cancer cell lines of various origin. This alternative transcript originates in the 15th intron of the human c-kit gene. We have previously demonstrated that sperm-carried mouse truncated c-Kit (tr-Kit) is a strong activator of the Src-family tyrosine kinases both in transfected cells and in mouse oocytes. In the present work, we report that human tr-Kit mRNA and protein are expressed in LNCaP prostatic cancer cells. We have identified two regions in the 15th and 16th introns of the human c-kit gene that show homology with sequences in the spermatid-specific tr-Kit promoter within the 16th intron of mouse c-kit. We also show that nuclear factors present in LNCaP cells bind to discrete sequences of the mouse tr-Kit promoter. Moreover, Western blot analysis of 23 primary prostate cancers indicated that tr-Kit was expressed in approximately 28% of the tumors at less advanced stages (Gleason grade 4 to 6) and in 66% of those at more advanced stages (Gleason grade 7 to 9), whereas it was not expressed in benign prostatic hypertrophies. Sequencing of the cDNA for the truncated c-Kit, amplified from both LNCaP cells and neoplastic tissues, confirmed the existence in prostate cancer cells of a transcript arising from the 15th intron of human c-kit. We also show that tr-Kit-expressing LNCaP cells and prostatic tumors have higher levels of phosphorylated/activated Src than tr-Kit-negative PC3 cells or prostatic tumors, and that transfection of tr-Kit in PC3 cells caused a dramatic increase in Src activity. Interestingly, we found that Sam68, a RNA-binding protein phosphorylated by Src in mitosis, is phosphorylated only in prostate tumors expressing tr-Kit. Indeed, both activation of Src and phosphorylation of Sam68 were observed in all of the three grade 7 to 9 tumors analyzed that expressed tr-Kit. Our data describe for the first time the existence of a truncated c-Kit protein in primary tumors and show a correlation between tr-Kit expression and activation of the Src pathway in the advanced stages of the disease. Thus, these results might pave the way for the elucidation of a novel pathway in neoplastic transformation of prostate cells.

Prostate cancer (PCa) is becoming an increasingly important public health problem worldwide, and anthropometric studies have revealed that body composition is a potential risk factor for this type of cancer. The objective of the present study was to compare Italians with PCa and no history of androgen deprivation therapy or bone metastases with healthy controls in terms of body composition. We recruited 11 PCa patients [mean age (+/-SD), 68.67+/-4.93 years; body mass index (BMI), 28.42+/-2.96 kg/m(2)] and 11 healthy controls matched for age and BMI. Anthropometric and body composition parameters were measured for all participants using dual X-ray absorptiometry and bioelectric impedance analysis techniques. We found that lean body mass, but not fat mass, was significantly lower for PCa patients in comparison with healthy controls (50.24+/-5.03 vs. 53.63+/-5.61 kg, p<0.05). Thus, PCa patients with no history of androgen deprivation therapy and no bone metastasis suffer muscle mass depletion.

The small cell carcinoma is a neuroendocrine tumour characterised by an aggressive clinical course and a high mortality rate. It occurs most commonly in the lung. Small cell carcinomas originating in the genitourinary system have been diagnosed with increasing frequency in recent years, because of the use of immunohistochemistry. Prostatic small cell carcinomas present the same biological behavior and similar histological, immunohistochemical and ultrastructural features to small cell carcinomas of the lungs. We describe the clinico-pathological findings in a 65-year-old male patient with a diagnosis of prostatic small cell carcinoma, obtained by means of a tru-cut needle biopsy. We performed the immunohistochemical tests using neuron-specific enolase and chromogranin A antibodies, according to the literature. On the basis of our experience we stress the malignant features of small cell carcinoma and the difficulty in obtaining an early diagnosis and treatment because of the aggressive course of the lesion and the late symptomatology.