Papers by Vincenzo Gentile

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2014
The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with seve... more The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with severe endometriosis, in order to demonstrate the effect of the disease on ovarian reserve. Prospective case-control study. One hundred and ninety-five patients were enrolled: 130 fertile patients (group A) and 65 patients with stage III and IV endometriosis, diagnosed by laparoscopy and histological examination (group B). AMH serum levels were measured in both groups and were compared using Student's t-test. The two groups were homogenous for main demographic data. Group B had statistically significantly lower mean AMH serum levels (0.97±0.59ng/ml) than group A (1.72±0.63ng/ml) (p=0.001). This study is a demonstration of the damage of endometriosis on ovarian reserve, leading to a form of incipient ovarian failure, which is considered as an early sign of advanced ovarian depletion in young women. These findings suggest that AMH could be used in the follow-up of patients with endometriosis, in order to assess promptly the decrease of ovarian reserve.

Current Genomics, Jul 1, 2012
Bladder cancer is one of the most frequent malignancies in developed countries and it is also cha... more Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small noncoding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using "bladder cancer" as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up-or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genomewide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up-or downregulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.
European Urology Open Science, 2021

The Journal of Urology, 2016
INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is inability to achieve and maintain an er... more INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is inability to achieve and maintain an erection to permit satisfactory sexual activity. Homocysteine (Hcys) is a sulphur-containing amino acid synthesized from the essential amino acid methionine. Experimental models have elucidated the role of Hyperhomocysteinemia (HHcys) as a strong and independent predictor for atherosclerosis progression and impaired cavernosal perfusion. The aim of this study is to investigate the serum levels of Hcys in our cohort of patients with ED, to compare these values with these of control population and to examine Hcys as a predictive marker for those patients who are beginning to complain mild-moderate ED. METHODS: A total of 431 patients were enrolled in the study. The whole cohort was asked to complete the IIEF questionnaire. The study population was divided in 3 main groups: Group A: 145 patients with no ED serving as a control group; Group B: 145 patients with mild or mild-moderate ED; Group C: 141 patients with moderate or severe ED. Each participant underwent blood analysis. All patients underwent baseline and dynamic penile Doppler ultrasonography. RESULTS: We found in our cohort mean Hcys plasma concentrations significantly higher than the cut-off point in both groups B and C (18.6 AE 4.7 and 28.38 AE 7.8 respectively). Mean IIEF score was 27.9 AE 1.39, 19.5 AE 2.6 and 11.1 AE 2.5 for group A, B and C, respectively (p<0.0001). In the Penile Doppler Ultrasonography studies, a high significant inverse correlation was detected between the mean values of the 10th minute's PSV and Hcys levels for the group B and C. CONCLUSIONS: This establishes a dose dependent association between Hcys and ED. Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler studies, as the Hcys increase was present in patients with mild ED even before abnormal Doppler values.

International journal of impotence research, Jan 11, 2016
We present the use of a modified corporoplasty, based on geometrical principles, to determine the... more We present the use of a modified corporoplasty, based on geometrical principles, to determine the exact site for the incision in the tunica or plaque and the exact amount of albuginea for overlaying to correct with extreme precision the different types of congenital or acquired penile curvature due to Peyronie's disease. To describe our experience with a new surgical procedure for the enhancement of penile curvature avoiding any overcorrection or undercorrection. Between March 2004 and April 2013, a total of 74 patients underwent the geometrical modified corporoplasty. All patients had congenital curvature until 90° or acquired stable penile curvature 'less' than 60°, that made sexual intercourse very difficult or impossible, normal erectile function, absence of hourglass or hinge effect. Preoperative testing included a physical examination, 3 photographs (frontal, dorsal and lateral) of penis during erection, a 10 mcg PGE1-induced erection and Doppler ultrasound, admini...

Reproductive Medicine and Biology, 2014
Purpose Regulation of the apoptotic process has an important role in spermatogenesis. p53 has a p... more Purpose Regulation of the apoptotic process has an important role in spermatogenesis. p53 has a prominent function in apoptosis and recent data suggest a relationship between varicocele and p53 codon 72 polymorphism and male infertility. This prompted us to study the relationship between this polymorphism and spermatic parameters. Methods We studied 134 subjects with varicocele admitted consecutively to the outpatients Department of Infertility at the University of Rome La Sapienza. We investigated in these subjects the effect of a strong apoptosis inducer, the p53 codon 72 *Arg/*Arg genotype, on spermatic parameters. The p53 codon 72 genotype was determined by DNA analysis. The proportion of spermatozoa with abnormal (curvilinear) motility is higher in men with the *Arg/*Arg genotype than in men carrying the *Pro allele (p = 0.003). No statistical significant relationship has been observed with spermatozoa concentration and atypical spermatozoa. Conclusions We conclude: the p53 codon 72*Arg/*Arg genotype, with its strong apoptotic effects, negatively influences spermatozoa motility and male fertility.
Annals of Oncology, 2012
Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results fr... more Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 2005; 6: 841-850. 7. Denham JW, Steigler A, Lamb DS et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011; 12: 451-459. 8. D'Amico AV, Manola J, Loffredo M et al. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 2004; 292: 821-827. 9. Lau WK, Blute ML, Bostwick DG et al. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4.

Endocrine-Related Cancer, 2007
The primary aim of the present study was to determine the prognostic role of elevated levels of c... more The primary aim of the present study was to determine the prognostic role of elevated levels of chromogranin A (CgA) in terms of biochemical prostate-specific antigen (PSA) progression after radical prostatectomy (RRP) for prostate adenocarcinoma. Two hundred and sixty-four consecutive men with non-metastatic prostate adenocarcinoma submitted to RRP represented our population. In all cases, a blood sample for the determination of serum total PSA and CgA levels was obtained (RIA). Two different upper reference values for serum CgA levels were used: > 60 and > 90 ng/ml. The main end point of this study was biochemical (PSA) progression-free survival. In our population, 35.0% (91/264 cases) of cases presented a serum CgA level > 60 ng/ml and only 6.4% (17/264) presented CgA > 90 ng/ml. After RRP, during a mean follow-up of 64.59 ± 26.34 months (median 60 months; range 12–120 months), 59 patients (22.3%) showed a biochemical (PSA) progression. Using 60 ng/ml as upper referen...

World Journal of Urology, 2020
Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The c... more Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients’ characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium–high risk diagnosed PCa.
The Journal of Urology, 2007
The 2nd follow up showed a mean maximal uroflow of 24 ml/s and a mean micturition volume of 362 m... more The 2nd follow up showed a mean maximal uroflow of 24 ml/s and a mean micturition volume of 362 ml, mean residual urine of 13 ml, increase of the IPSS from 20 to 7 and an increase of LQI from 4,7 to 2. The morphological assessment of the wide open bladder neck was performed by transrectal sonography. CONCLUSIONS: Ejaculation protective TUR of prostate/bladder neck is possible with excellent functional results with keeping of the antegradic ejaculation and complete erasing of the obstruction. The musculus sphincter internus vesicae is meaningless for the mechanism of ejaculation.
The Journal of Urology, 2015

Rivista Urologia, 2011
Role of neuroendocrine cells in prostate cancer progression Neuroendocrine (NE) cells represent t... more Role of neuroendocrine cells in prostate cancer progression Neuroendocrine (NE) cells represent the third epithelial cell type on normal prostatic tissue (in addition to basal and secretory cells). They are localized in all regions of the human prostate at birth but rapidly decrease in the peripheral prostate after birth, and then reappear at puberty. After puberty, their number seems to increase until an apparently optimum level is reached, which persists between the age of 25 and 54. NE cells were defined by Pearse as APUD to refer to chemical characteristics of amine precursor uptake and decarboxylation, common to the cells of this system. The most predominant product of prostatic NE cells is Chromogranin A, but they also produce serotonin, CgB, secretogranin or CgC, thyroid-stimulating hormone-like peptide, calcitonin, katacalcin, PTHrP and α-human chorionic gonadotropin-like peptide. NE cells in normal and neoplastic prostates are devoid of androgen receptors, but they express epidermal growth factor (EGF) receptor and c-erbB-2. For these reason NE cells are androgen-insensitive. The NE component of prostate adenocarcinoma is resistant to hormone therapy; some studies showed that the number of NE tumor cells and CgA serum levels increase with the recovery of human prostate tumor from hormonal therapy. Currently there are no clinical data available to support an active role of radiotherapy in NE differentiation.
ABSTRACT A Prostate Cancer Unit is a place where men can be cared for by specialists in prostate ... more ABSTRACT A Prostate Cancer Unit is a place where men can be cared for by specialists in prostate cancer (PC), working together within a multi-disciplinary team (MDT). The MDT approach guarantees a higher probability for the PC patient to receive adequate information on the disease and on all possible therapeutic strategies, balancing advantages and related side effects. Objecive: To analyze the role of a MDT in PC management and to compare some results in terms of characteristics and distribution of PC cases, obtained by a MDT, with those reported by a monodisciplinary urological unit. Outcome measurements and results: A high percentage of cases (47.6%) referred to our MDT were in the low risk group. In the Prostate cancer Unit the indications for primary therapies were more equally distributed between surgery (51.5%) and radiotherapy (45.4%).

Urology, 2004
Objectives. To determine whether the administration of the nonsteroidal antiandrogen bicalutamide... more Objectives. To determine whether the administration of the nonsteroidal antiandrogen bicalutamide reduces the risk of an increase in chromogranin A (CgA) levels in patients with prostate cancer who experienced biochemical failure after radical retropubic prostatectomy (RRP) compared with pharmacologic castration therapy. It has been hypothesized that continuous androgen suppression for the treatment of prostate cancer results in hyperactivation of neuroendocrine cells and an increase in CgA levels. Methods. Forty-eight patients with pT3pN0M0 prostate cancer and biochemical (prostate-specific antigen) progression after RRP were randomized to bicalutamide monotherapy or pharmacologic castration. The serum levels of CgA and prostate-specific antigen were measured at 1, 3, 6, 12, 18, and 24 months of therapy. The changes in serum CgA levels were compared for patients who successfully responded to the first 24 months of therapy. Results. In both treatment groups, a statistically significant trend was noted for CgA levels to increase from baseline to 24 months. This trend was lower in the bicalutamide group (slope ϭ 0.60, 95% confidence interval 0.28 to 0.92; P ϭ 0.004) than in the castration group (slope ϭ 0.29, 95% confidence interval 0.08 to 0.50; P ϭ 0.01). Conclusions. The results of this study provide the first evidence to show that in patients with prostate cancer undergoing hormonal therapy, nonsteroidal antiandrogen monotherapy produces a significantly lower increase in serum CgA compared with castration.
The Journal of Urology, 2014
were elevated in the transformed SV-HUC cells as compared to parental SV-HUC cells. CONCLUSIONS: ... more were elevated in the transformed SV-HUC cells as compared to parental SV-HUC cells. CONCLUSIONS: These data, for the first time, demonstrate that exosomes play a role in the early stage of neoplasmic transformation and provide a novel mechanism to explain FEC. More importantly, deprivation of exosome intake resulted in diminished SV-HUC malignant transformation revealing the therapeutic potential of dynasore.

The Journal of Sexual Medicine, 2012
Introduction. To obtain the best results with radical prostatectomy, either from an oncological o... more Introduction. To obtain the best results with radical prostatectomy, either from an oncological or a functional point of view, a correct selection of cases and planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI) promises to make it a successful imaging tool for improving many aspects of prostate cancer management. Aim. The aim of this study is to evaluate whether a modern multiparametric MRI can help either to better select prostate cancer cases for a nerve-sparing radical prostatectomy or to improve the functional evaluation related to neurovascular bundles preservation. Main Outcome Measures. The effect of preoperative MRI on neurovascular bundle management was examined for the frequency and the appropriateness of changes of the surgical plane on the basis of MRI indications. Methods. In a prospective study, 125 consecutive patients with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve-sparing surgery. All patients included into the study were submitted to a preoperative multiparametric MRI. On the basis of MRI evaluation, patients were divided into two groups. Patients in group A were then submitted to a bilateral nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were submitted to unilateral NS or non-NS RP. Results. In group A, the confirmation from the MRI study to perform a bilateral NS procedure was appropriate in 70 of 73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of 32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%) and a non-NS procedure in 11 of 32 cases (34.4%). Conclusions. Multiparametric MRI analysis can significantly improve the standard selection and management of prostate carcinoma cases considered for an NS RP.
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Papers by Vincenzo Gentile