Franco Di Silverio

Comparison of phytotherapy (Permixon®) with finasteride in the treatment of benign prostate hyperplasia: A randomized international study of 1,098 patients

Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).

Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: A retrospective analysis

OBJECTIVES We analyze our experience on BPH through 20 years of histopathological examinations performed by the same pathologist. METHODS We retrospectively reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery in our urological clinic who were diagnosed with BPH. We limited our evaluation to the following variables in each BPH case analyzed: inflammatory aspects associated with BPH, presence of focal acinar atrophy, atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN), incidental prostate carcinoma (IC). These histological variables were analyzed according to some clinical parameters such as age, prostate volume and serum PSA. RESULTS The study population was comprised of 3942 cases with histological diagnosis of BPH. The mean patient age was 68.85+/-7.67 years. In particular, inflammatory aspects were associated with BPH in a high percentage of cases (43.1% =1700 cases), predominantly as chronic inflammation. Observation of focal acinar atrophy significantly increased according to patient decade of age (p=0.027). There was a significant trend to increase with age decades (p=0.036) for high grade PIN. A significant difference was found in IC (T1a, T1b) distribution in the different decades of age and especially in regards to both T1a and T1b tumors, there was a trend to increase with patient age (p=0.020 and p=0.025, respectively). On the contrary, the distribution of inflammatory aspects (p<0.001) and AAH (p=0.003) significantly varied according to prostate volume, and particularly in regards to chronic inflammation, there was a trend to increase depending on the prostate volume (p=0.002). Only the presence of T1b tumor but not of the other histological parameters associated to BPH, was able to significantly influence serum PSA. CONCLUSION In our analysis different histological variables associated to BPH are differently influenced by the age of patients and prostate volume, and they differently influence serum PSA levels.

Role of Dynamic Contrast-Enhanced Magnetic Resonance (MR) Imaging and Proton MR Spectroscopic Imaging in the Detection of Local Recurrence after Radical Prostatectomy for Prostate Cancer

OBJECTIVES To assess the accuracy of magnetic resonance (MR) spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced MR (DCEMR) in the depiction of local prostate cancer recurrence in patients with biochemical progression after radical prostatectomy (RP). MATERIALS AND METHODS 1H-MRSI and DCEMR were performed in 70 patients at high risk of local recurrence after RP. The population was divided on the basis of the clinical validation of MR results with the use of a transrectal ultrasound biopsy examination in a group of 50 patients (group A) and the prostate-specific antigen (PSA) serum level restitution after external beam radiotherapy, in a group of 20 patients (group B). RESULTS In group A, 1H-MRSI analysis alone showed a sensitivity of 84% and a specificity of 88%; the DCEMR analysis alone, a sensitivity of 71% and a specificity of 94%; combined 1HMRSI-DCEMR, a sensitivity of 87% and specificity of 94%. Areas under the receiver operating characteristic (ROC) curve for 1HMRSI, DCEMR, and combined 1HMRSI /DCEMR were 0.942, 0.93,1 and 0.964, respectively. In group B, 1HMRSI alone showed a sensitivity of 71% and a specificity of 83%; DCEMR, a sensitivity of 79% and a specificity of 100%; combined 1HMRSI and DCEMR, a sensitivity of 86% and a specificity of 100%. Areas under the ROC curve for each of these groups were 0.81, 0.923, and 0.94, respectively. CONCLUSION Our results show that combined 1H-MRSI and DCMRE is an accurate method to identify local prostate cancer recurrence in patients with biochemical progression after RP.

Prostate growth and inflammation.

INTRODUCTION There is emerging evidence that prostatic inflammation may contribute to prostate growth either in terms of hyperplastic (BPH) or neoplastic (PC) changes. Inflammation is thought to incite carcinogenesis by causing cell and genome damage, promoting cellular turnover. METHODS We reviewed our personal experience and the international recent literature on the clinical data supporting a role of inflammation on BPH and PC growth and progression. RESULTS BPH: Among those patients with self-reported prostatitis, 57% had a history of BPH. MTOPS study showed that men with inflammation had a significantly higher risk of BPH progression and acute urinary retention. We showed that the use of a COX-2 inhibitor in combination with a 5 alpha reductase inhibitor could increase the apoptotic index in BPH tissue. Prostate cancer: A PCR-based analysis of bacterial colonization in PC specimens and normal prostate tissue showed highly suggestive correlation of bacterial colonization and chronic inflammation with a diagnosis of PC. Evidence from genetic studies support the hypothesis that prostate inflammation may be a cause of prostate cancer. De Marzo proposed that proliferative inflammatory atrophy (PIA) is a precursor to PIN and cancer. CONCLUSION The concept that inflammation can promote prostate growth either in terms of BPH and PC risk remains highly suggestive.

Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors

The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch™ technology raise additional issues regarding the biological value of this information. We postulated that a drug‐resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug‐resistance profile was correlated with disease‐free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24‐months follow‐up. Objective response correlation was a secondary end point. Fifty‐one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug‐resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug‐resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.

Neoadjuvant therapy with sorafenib in advanced renal cell carcinoma with vena cava extension submitted to radical nephrectomy.

A 71-year-old man with advanced left renal cell carcinoma (lymph node involvement and vena cava thrombus) was submitted to 6 months of neoadjuvant treatment with sorafenib before open radical nephrectomy. After sorafenib treatment and before surgery a new CT scan confirmed the presence of a 9.0 cm in diameter solid mass in the left kidney but a reduction in thrombus extension, limited to the left renal vein. At histological examination after radical nephrectomy, over 90% of the renal mass was substituted by necrotic tissue.

Prognostic significance of survivin‐expressing circulating tumour cells in T1G3 bladder cancer

To evaluate the prognostic significance of survivin in tumour tissues and that of survivin‐expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors.

Insulin-like growth factor-I and -II in human benign prostatic hyperplasia : Relationship with binding proteins 2 and 3 and androgens

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma-epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3 alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean +/- SE), were 0.51 +/- 0.05 for testosterone, 5.3 +/- 0.16 for DHT, and 1.1 +/- 0.07 for 3 alpha diol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 +/- 3.7, 121 +/- 14 ng/g tissue and 0.44 +/- 0.05 and 1.2 +/- 0.17 micrograms/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT (r = 0.78; p = 0.003) and 3 alpha diol (r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma-epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.

Relationship among symptom score, prostate volume, and urinary flow rates in 543 patients with and without benign prostatic hyperplasia.

Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest.

p53 Gene Mutational Rate, Gleason Score, and BK Virus Infection in Prostate Adenocarcinoma: Is There a Correlation?

Prostate cancer represents the second leading cause of cancer deaths in Western countries. Viral infections could play a role in prostate carcinogenesis. Human polyomavirus BK (BKV) is a possible candidate because of its transforming properties. In this study, BKV sequences in urine, blood, fresh, and paraffin‐embedded prostate cancer samples from 26 patients were searched using Q‐PCR analysis. T antigen (TAg) and p53 localization in neoplastic cells were evaluated by immunohistochemical analysis. Also, the presence of mutations in 5–9 exons of p53 gene was analyzed. Results showed that BKV‐DNA was found in urine (54%), plasma (31%), and in fresh prostate cancer specimens (85%). The analysis of p53 gene evidenced several mutations in high Gleason patients, according to tumor advanced stage. Immunohistochemical analysis results evidenced the localization of p53 and TAg into cytoplasm, whereas in TAg‐negative tumors, p53 was nuclear. This study suggests that BKV acts as cofactor in the pathogenesis of prostate cancer. These observations emphasize previous studies regarding the cellular pathways that may be deregulated by BKV. J. Med. Virol. 80:2100–2107, 2008.