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Biomedical subjects

Franco Di Silverio

Publications and source records attributed to Franco Di Silverio.

At least 19 recordsLinked to original sources
PubMed2007

Characterization of circulating blood dendritic cell subsets DC123+ (lymphoid) and DC11C+ (myeloid) in prostate adenocarcinoma patients.

PURPOSE: We verified whether prostate adenocarcinoma produces specific modifications in DC subsets count. METHODS: Twenty-one untreated prostate adenocarcinomas were divided on the basis of clinical stage in localized and metastatic disease. As control we used a population of 18 healthy male subjects. For DCs enumeration, peripheral blood (PB) samples were obtained in all cases. A single-platform flow cytometric assay based on Tru-COUNT was used for the enumeration of the two DCs subsets, myeloid (mDCs) and plasmacytoid (pDCs). RESULTS: We showed a statistically significant reduction in pDCs count in prostate cancer population when compared to healthy controls (P = 0.002). Comparing each clinical stage with healthy controls, significant differences were found between controls and the metastatic group in both pDCs and mDCs (P = 0.005 and P = 0.023 respectively) but not between controls and the localized group (P = 0.055 and P = 0.829 respectively). CONCLUSIONS: We showed that DCs count in PB is significantly affected by prostate adenocarcinoma progression in a metastatic disease.

Adenocarcinoma↗
PubMed2005

Can p503s, p504s and p510s gene expression in peripheral-blood be useful as a marker of prostatic cancer?

BACKGROUND: The aim of the study was to investigate whether p503S, p504S and p510S gene expression in peripheral-blood be useful as a diagnostic or prognostic marker of prostatic cancer. METHODS: Circulating cells were identified by reverse transcription-polymerase chain reaction (RT-PCR) to detect p503S, p504S and p510S mRNA in peripheral blood (PB) from 11 patients with treated prostatic carcinoma (CaP), 11 with newly-diagnosed untreated CaP and 20 with benign prostatic hyperplasia (BPH) (controls). RESULTS: RT-PCR amplified P503S in 7 of 11 untreated and 2 of 11 treated patients with CaP and 5 of 20 with BPH; p504S in 7 of 11 untreated and in 9 of 11 treated patients with CaP and 11 of 20 with BPH; whereas it amplified p510S in all subjects with CaP and in 15 of 20 with BPH. CONCLUSION: These findings suggest that the investigated genes are poorly specific and probably of little use as diagnostic or prognostic prostatic markers in peripheral blood for monitoring disease progression and recurrence.

Aged↗
PubMed2005

Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).

PURPOSE: Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays either a pro-inflammatory effect or a proliferative effect on prostate cells. The aim of this study is to analyze whether combination therapy with rofecoxib, a COX-2 inhibitor, and finasteride offers an advantage compared to finasteride monotherapy in patients with BPH. MATERIALS AND METHODS: This is a single centre unblinded trial. Forty-six consecutive men with LUTS and BPH were entered into the study and were randomized to receive rofecoxib 25mg/day plus finasteride 5mg/day (group B) versus finasteride 5mg/day alone (group A) for 24 weeks. Inclusion criteria included also a prostate size greater than 40 cc. The efficacy and safety of treatments were assessed at baseline and at week 4, 12 and 24. RESULTS: In our population, both treatments (groups A and B) produced statistically significant improvements in total IPSS and Q(max) from baseline during follow-up, although they were very low in particular for the finasteride alone group at 4 weeks. We found that finasteride monotherapy produces very little improvement at the 1 month interval. In comparing group A with group B, a significantly higher improvement in IPSS (p=0.0001) and Q(max) (p=0.03) was obtained in group B at 4 weeks interval (% cases with IPSS reduction >4 points: group B=34.7, group A=0; % cases with Q(max) improvement >3 ml/s: group B=8.7, group A=0), whereas at week 24, the differences between the two treatments were not significant (p>0.05). CONCLUSIONS: In our population, the advantage of the combination therapy compared to finasteride alone is significant in a short-term interval (4 weeks). It can be hypothesized that the association of rofecoxib with finasteride induces a more rapid improvement in clinical results until the effect of finasteride becomes predominant.

Aged↗
PubMed2005

Chromogranin A expression in familial versus sporadic prostate cancer.

OBJECTIVES: To evaluate whether a significant difference in chromogranin A (CgA) levels exist between patients with familial and sporadic cancer. METHODS: The study included 146 patients with clinically localized prostate adenocarcinoma (Stage T2N0M0), who underwent radical prostatectomy between June 1999 and June 2004. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first-degree relative (brother or father). On the day of surgery, a blood sample for the determination of serum prostate-specific antigen and CgA levels (radioimmunoassay) was obtained from all patients. In a subgroup of 20 patients, CgA mRNA expression was also evaluated by reverse transcriptase-polymerase chain reaction at the prostatic tissue level. RESULTS: A positive familial history was found in 28 (19.2%) of the 146 patients. The mean patient age in the familial group was significantly (P < 0.0001) lower than that in the sporadic group. No significant difference between the familial and sporadic groups was found in terms of prostate-specific antigen level (P = 0.9625) or Gleason score distribution (P = 0.4891). The familial group had significantly (P = 0.0013) lower serum CgA levels (43.3 +/- 12.7 ng/mL, median 39.9) compared with the sporadic group (55.9 +/- 19.4 ng/mL, median 54.1). The familial group also had significantly (P = 0.0432) lower expression of tissue CgA mRNA compared with the sporadic group. CONCLUSIONS: The result of significantly lower CgA expression in familial compared with sporadic prostate cancer cases suggests that neuroendocrine activity is not increased in familial cases and also confirms that familial cancer is not a more aggressive disease.

Adenocarcinoma↗
PubMed2005

Use of cyclooxygenase-2 inhibitor for prevention of urethral strictures secondary to transurethral resection of the prostate.

OBJECTIVES: To analyze whether the addition of a cyclooxygenase (COX)-2 inhibitor after transurethral resection of the prostate (TURP) offers an advantage compared with TURP alone in reducing postoperative urethral strictures. At urethroscopy, stenosis of the urethra with a circumference of less than 19 mm was defined as stricture. METHODS: This was a prospective, unblinded, randomized, single-center study. Between December 2001 and December 2003, 96 consecutive men with benign prostatic hyperplasia underwent TURP. After TURP, patients were randomly assigned to receive or not receive a COX-2 inhibitor (rofecoxib 25 mg/day). In the group given the COX-2 inhibitor, the therapy was started at catheter removal and continued for 20 days. Follow-up was performed on an outpatient basis after 1 month. A diagnosis of postoperative urethral stricture was assessed during a follow-up of 12 months. RESULTS: At the 1-month visit, the mean and median improvement in the peak urinary flow rate from preoperative values was +6.25 +/- 3.76 mL/s (median 7.30) in the no COX-2 inhibitor group and +9.42 +/- 3.06 mL/s (median 8.75) in the COX-2 inhibitor group. The improvement was significantly (P < 0.0001) greater for the group treated with the COX-2 inhibitor. At 1 year of follow-up, a urethral stricture had been diagnosed in 8.3% of all cases; in particular, in 17% and 0% of cases in the no COX inhibitor group and COX-2 inhibitor group, respectively. Post-TURP COX-2 inhibitor therapy was significantly (P = 0.0039) and inversely (r = -0.2876) associated with urethral stricture development. CONCLUSIONS: We suggest that limited postoperative treatment with a COX-2 inhibitor can effectively prevent post-TURP urethral stricture development by specifically interfering with the inflammatory processes that can precede scar formation.

Aged↗
PubMed2005

Superselective embolization of bladder arteries in the treatment of intractable bladder haemorrhage.

Bladder hemorrhage following radiation therapy is a serious complication in patients undergoing this treatment. Several methods have been proposed to control this particular situation; however, results have been far from satisfactory, with the exception of drastic measures such as hypogastric artery ligation and radical cystectomy. We recently used a method of superselective embolization of the bladder arteries which enabled us to control severe intractable bleeding in a patient submitted to bladder irradiation for a transitional cell infiltrating carcinoma. Compared to selective embolization and other methods, the advantages of superselective embolization are a lower recurrence rate concerning bleeding, fewer side-effects and the possibility of using adaptable embospheres (150-1000 micron) which, on account of their marked plasticity, offer better occlusion of the vessels. For these reasons, superselective embolization of the bladder arteries should be considered as the treatment of choice in intractable bladder hemorrhage.

Aged↗
PubMed2004

Clinical understaging in patients with prostate adenocarcinoma submitted to radical prostatectomy: predictive value of serum chromogranin A.

PURPOSE: To evaluate whether the pretreatment determination of serum chromogranin A (CgA) can provide information beyond that obtained with serum prostate specific antigen (PSA) and Gleason score at biopsy as a predictive factor of clinical understaging (T2-pT3) of prostate adenocarcinoma. MATERIALS: In this prospective study, we analyzed 83 consecutive patients with clinical T2N0M0 prostate adenocarcinoma submitted to radical prostatectomy (RRP). On the same day of RRP, before surgery, a blood sample for the determination of serum total PSA and CgA levels (RIA) was obtained. RESULTS: After RRP, 27 of the 83 cases (32.5%) showed extracapsular disease extension (pT3) at the final pathological examination and were considered clinically understaged. A significant association between serum CgA and pathological stage (r = 0.3830; P = 0.0004) was found. At the multivariate analysis, serum CgA and PSA, but not biopsy Gleason score, were found to be significant pretreatment independent predictors of pT3 at RRP (P = 0.00004 and P = 0.0018, respectively). The relative risk of clinical understaging significantly varied according to serum CgA levels. Using a CgA cut-off value of 60 ng/ml, PPV and NPV for clinical understaging were 0.5161 and 0.7885, respectively (P = 0.0072). CONCLUSIONS: Serum CgA could be incorporated into risk assessment models of newly diagnosed prostate cancer.

Adenocarcinoma↗
PubMed2004

Effect of nonsteroidal antiandrogen monotherapy versus castration therapy on neuroendocrine differentiation in prostate carcinoma.

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 = 0.60, 95% confidence interval 0.28 to 0.92; P = 0.004) than in the castration group (slope = 0.29, 95% confidence interval 0.08 to 0.50; P = 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.

Adenocarcinoma↗
PubMed2004

Long-term response to combination therapy with estramustine and somatostatin analogue in a patient with androgen ablation-refractory prostate cancer.

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Adenocarcinoma↗
PubMed2004

Somatostatin analogues and estrogens in the treatment of androgen ablation refractory prostate adenocarcinoma.

PURPOSE: Prostate cancer progression to androgen ablation refractory stage D3 corresponds to cancer cell escape from androgen withdrawal induced apoptosis. Of note, salvage chemotherapy can extend the median survival of approximately 10 months in patients with stage D3. Therefore, novel therapeutic strategies that target the molecular basis of androgen resistance are required. MATERIALS AND METHODS: The MEDLINE and Current Content databases were used to find studies of the use of estrogens and somatostatin analogues for D3 prostate adenocarcinoma. We also analyzed the rationale and clinical results of our combination therapy using lanreotide and ethinylestradiol. RESULTS: Negative experiences have been reported with somatostatin analogues as monotherapy. On the other hand, the median progression-free survival reported in our experience using lanreotide acetate plus ethinylestradiol clearly surpassed the 10-month survival historically described in stage D3 cases. CONCLUSIONS: The use of somatostatin analogues in combination therapy for D3 prostate cancer sustains the novel concept in cancer treatment in which therapies may target not only cancer cells, but also the microenvironment in combination, which can confer protection from apoptosis.

Adenocarcinoma↗
PubMed2004

Histopathological aspects of transitional cell carcinoma of the bladder: analysis of 20 years experience.

BACKGROUND: In this study we used histopathological examinations performed over a 20-year period to describe the characteristics of newly diagnosed transitional cell carcinoma (TCC) of the bladder in relation to patient age, and to verify changes in the TCC over different periods of observation or in relation to patient age. METHODS: We reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery who were newly diagnosed with TCC of the bladder. All examinations were performed by the same pathologist and reviewed by two pathologists. In each case analyzed, we evaluated T classification of the tumor, histological grade, size, localization, growth type, multiplicity and carcinoma in situ (CIS). RESULTS: The study population included 3113 men and 620 women. The mean patient age was 66.31 +/- 10.84 years. A high percentage of Ta (52.2%) and T1 (27.7%) tumors were found. The number of cases observed and, in particular, the percentage of Ta tumors increased significantly and progressively from the first (1979-1983 = 376 cases; Ta = 37.8%) to the last (1994-1998 = 1732 cases; Ta = 56.3%) period of observation (P < 0.001). A significant difference in the distribution of histological grade and T classification in the different age decades was apparent (P < 0.001); in particular, for G1 and Ta tumors there was a trend to decrease, whereas for G3, T1 and T2 tumors there was a tendency to increase with age decades. CONCLUSION: In our analysis, age of patient and the period of examination significantly influenced different pathological characteristics of newly diagnosed TCC of the bladder.

Aged↗
PubMed2004

Antiandrogen monotherapy: recommendations for the treatment of prostate cancer.

OBJECTIVE: The concept of antiandrogens as monotherapy for the treatment of prostate cancer is discussed. METHODS: Both Medline and Current Contents were used to identify studies on antiandrogen monotherapy in prostate cancer. We tried to analyze this database critically to establish whether or not there is evidence for using this monotherapy. RESULTS: In particular, bicalutamide in monotherapy has been compared with castration in large international trials. Results show that antiandrogen monotherapy is inferior to castration in patients with metastatic tumour but the difference in median survival is limited. In locally advanced M0 prostate cancer bicalutamide 150 mg monotherapy seems equivalent to castration in terms of overall survival and time to progression. Analysis of quality of life showed that there is evidence of some benefits from bicalutamide when compared to castration in both sexual interest and physical capacity. CONCLUSION: Antiandrogens in monotherapy can be effective and well tolerated. However, more research is needed because none of the available compounds have definitively been proven to be equivalent to castration.

Androgen Antagonists↗
PubMed2003

Variation in chromogranin A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma.

OBJECTIVES: It has been hypothesized that continuous androgen-suppression therapy produces hyperactivation of neuroendocrine (NE) cells and an increase in chromogranin A (CgA) in prostate carcinoma (PC). The aim of this study was to verify whether the intermittent administration of androgen deprivation (IAD) reduces the risk of CgA increase in PC cases treated with complete androgen deprivation (CAD). MATERIALS AND METHODS: We analyzed changes in serum CgA levels in patients with PC who successfully responded to the first 24 months of IAD versus continuous CAD therapy. Two different populations were analyzed: Type 1 = pT3pN0M0 prostate cancers with biochemical (PSA) progression after RRP; Type 2 = metastatic PC directly submitted to CAD. Cases in Type 1 and Type 2 population were randomly assigned to IAD versus continuous CAD therapy. Forty cases each in Type 1 and Type 2 population were included in the analysis. At 1, 3, 6, 12, 18, 24 months of IAD versus continuous therapy, serum levels of CgA compared to PSA levels were analyzed. RESULTS: In population Type 1 and Type 2, in the group of cases continuously treated with CAD (Group 2), there was a significant trend to increase for CgA levels from baseline to 24 months of therapy. On the contrary, no significant variations were found in cases treated with IAD (Group 1). Either in population Type 1 or Type 2, at 12- and 24-month follow-up, mean and median serum levels of CgA were significantly (P < 0.005) lower in Group 1 than in Group 2. CONCLUSIONS: The present study represents the first evidence in the literature that the intermittent administration of CAD therapy significantly reduces the increase in serum CgA levels during CAD therapy.

Adenocarcinoma↗
PubMed2003

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.

Age Factors↗
PubMed2003

Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decreases chromogranin a in patients with androgen ablation refractory prostate cancer.

PURPOSE: We evaluated whether a combination therapy of ethinylestradiol and somatostatin analogue can reintroduce objective clinical responses in patients with metastatic androgen ablation refractory prostate cancer (PC). MATERIALS AND METHODS: Ten patients with stage D3 disease and bone metastases who had progression despite initial responses to combined androgen blockade and in whom antiandrogen withdrawal subsequently failed discontinued combined androgen blockade and received 1 mg ethinylestradiol orally daily and 73.9 mg lanreotide acetate intramuscularly every 4 weeks. Serum prostate specific antigen (PSA), chromogranin A (CgA), Eastern Cooperative Oncology Group performance status and bone pain scores were assessed at regular intervals. Median followup was 18 months (range 10 to 24). RESULTS: Nine of the 10 cases (90%, 95% CI 55.5 to 99.8) had an objective clinical response, defined as a greater than 50% PSA decrease (median 87.1%, range 50.2% to 94.4%). PSA normalization (less than 4 ng/ml) was achieved in 3 cases. All patients reported significant and durable improvement in bone pain (median duration 17.5 months) and performance status (median duration 18 months) without major treatment related side effects. Two patients with disease progression died secondary to PC at 16 and 10 months, respectively. All other patients were without progression. We observed a statistically significant decrease in serum CgA during administration and at the response to therapy (median 38.4%, range 28.6% to 64.9%, (p <0.0001). Interestingly CgA was not increased at relapse. CONCLUSIONS: This combination therapy seems to reintroduce an objective clinical response and symptomatic improvement in androgen ablation refractory PC cases.

Administration, Oral↗
PubMed2003

Role of radical retropubic prostatectomy in patients with locally advanced prostate cancer: the influence of Gleason score 8-10.

BACKGROUND: To define whether in locally advanced prostate cancer submitted to radical retropubic prostatectomy (RRP) the presence of a Gleason score 8-10 represents an index of high risk for progression and cancer-specific death. METHODS: Finally, a total of 130 men with pathologically confirmed T3 cancer were included in this analysis. On the basis of the histological grade obtained at RRP, patients were divided into two groups: patients with a Gleason score 8-10 (group 1) and patients with a Gleason score <8 (group 2). Postoperative follow-up ranged from 24 to 120 months (median 60). After RRP no patients received additional treatments until a biochemical or clinical disease progression was found. Kaplan-Meier projections were used in each group. RESULTS: After RRP, 41 patients (31.5%) had a Gleason score 8-10 tumor. The incidence of positive lymph nodes was significantly higher (p = 0.0030) in group 1 (36.6%) when compared with group 2 (12.3%). Significant differences between the two groups were also found with respect to seminal vesicle involvement (p = 0.0045) and positive surgical margins (p = 0.0040). The actuarial cumulative disease-specific survival for group 1 and group 2 was, respectively, 69 and 82% at 10 years. A Kaplan-Meier analysis demonstrated a 100% disease-specific survival, a 92% clinical progression-free survival and a 38% biochemical progression-free survival 10 years postoperatively if patients in group 1 had negative surgical margins and negative lymph nodes (48.8%). CONCLUSIONS: Our data indicate a significant association between Gleason score 8-10 and disease-specific survival, only if patients in group 1 are stratified on the basis of surgical margins and/or lymph node involvement.

Disease Progression↗