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Biomedical subjects

Vincenzo Gentile

Publications and source records attributed to Vincenzo Gentile.

18 recordsLinked to original sources

Treatment of varicocele in subfertile men: The Cochrane Review--a contrary opinion.

OBJECTIVE: A recent Cochrane meta-analysis of randomised clinical trials (RCTs) concluded that surgical or radiological treatment of varicocele in men from couples with otherwise unexplained subfertility cannot be recommended. The aim of the present study is to address criticisms of this review carrying out a critical analysis of all available RCTs. MATERIALS AND METHODS: The eight randomised clinical trials selected in the last Cochrane Library systematic review have been evaluated. All RCTs including patients either with normal semen analysis or subclinical varicocele have been excluded. Inclusion criteria, number and clinical characteristics of randomised patients, and outcomes reported in terms of pregnancy rate one year after randomisation have been described in the remaining studies. RESULTS: Only 3/8 RCTs included patients with abnormal semen analysis and palpable varicocele. Overall 120 patients in the treatment group and 117 in the control group were randomised. The studies turned out to be heterogeneous in terms of inclusion criteria and clinical characteristics of the analysed patients. Their methodological quality and statistical power have to be considered poor. Moreover, the "as treated" cumulative analysis showed a significant increase in pregnancy rate in patients who underwent varicocele treatment (36.4%) compared with the control group (20%) (p = 0.009). CONCLUSIONS: The RCTs included in the last Cochrane review concerning the efficacy of varicocele treatment in subfertile couples were heterogeneous and methodologically poor. The pooling of these studies cannot result in a good quality meta-analysis. The Cochrane meta-analysis conclusions should not support guidelines recommendation against varicocele treatment in subfertile patients. Data from ongoing studies should provide more information in this topic.

Adult↗

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↗

Smoking as a risk factor for erectile dysfunction: data from the Andrology Prevention Weeks 2001-2002 a study of the Italian Society of Andrology (s.I.a.).

OBJECTIVE: To analyse the relationship between smoking and erectile dysfunction (ED). METHODS: To provide further data on this issue, we analysed information gathered from men attending a free andrologic consultation in 234 Italian medical centres, in the setting of a project focused on andrologic prevention. Men were asked about "their ability to achieve and maintain an erection sufficient for satisfactory sexual performance". If they were dissatisfied, they were defined as having ED. RESULTS: Out of 16724 subjects, ED was diagnosed in 4081 men (24.4%). After adjustment for age, marital status, education, alcohol consumption, physical activity and concomitant pathologies, in comparison with never smokers, men who currently smoked more than 10 cigarettes/day and former smokers showed significantly higher odds ratio (ORs 1.4 and 1.3, respectively) for ED. These results were confirmed performing analysis in strata of diabetes, hypertension, cardiovascular disease and hypercolesterolemia. COMMENTS: This transversal observational study shows that the risk of ED is influenced by smoking. A dose- and duration-response effect is present; changes in smoking habits do not seem to significantly affect the risk to develop ED.

Adult↗

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↗

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↗

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↗

Efficacy and safety of tadalafil in a Western European population of men with erectile dysfunction.

OBJECTIVE: To evaluate, in a randomized, double-blind, placebo-controlled, multicentre trial, the safety and efficacy of on-demand tadalafil (an oral phosphodiesterase type-5 inhibitor approved in many countries for treating erectile dysfunction, ED) in a Western European population of men with mild-to-severe ED. PATIENTS AND METHODS: Patients were randomized according to baseline severity of ED in a ratio of 3 : 1 to receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and percentages of 'Yes' responses to Sexual Encounter Profile (SEP) diary Question 2 ('Were you able to insert your penis into your partner's vagina?') and Question 3 ('Did your erection last long enough for you to have successful intercourse?'). Secondary endpoints included mean changes from baseline to endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains, selected questions of the IIEF, and the percentage of 'Yes' responses to Global Assessment Questions (GAQ) at the last visit. Other analyses included the percentage of patients in each treatment group at endpoint with IIEF EF domain scores in the normal range (>26), the frequency of intercourse attempts and mean per-patient intercourse success rate at various times after dosing. RESULTS: The mean age of the patients was 53 years and 80% had a history of ED of > or = 1 year. The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo (P < 0.001). In addition, 73.9% of sexual intercourse attempts were successful (SEP-Q3) in tadalafil-treated patients, compared with 29.9% in placebo-treated patients during the period after baseline (P < 0.001). Tadalafil significantly improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo) and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P < 0.001. GAQs used to assess the overall effect of the treatment indicated that tadalafil was superior to placebo (P < 0.001) in improving erections (82.1%, tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most common treatment-emergent adverse events more frequent (>2%) with tadalafil than placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia. These adverse events were mostly mild to moderate. CONCLUSIONS: Tadalafil improved erectile function and was well tolerated when taken by men from Western Europe with mild-to-severe ED.

3',5'-Cyclic-GMP Phosphodiesterases↗

Evolution in varicocele sclerosing treatment: the ante/retrograde (A/R) approach.

OBJECTIVE: To evaluate diagnostic and therapeutic efficacy of simultaneous ante/retrograde (A/R), trans-scrotal and trans-brachial approach in sclerotherapy of varicocele. MATERIALS AND METHODS: Between June 2000 and June 2002, 99 patients with varicocele were submitted to simultaneous A/R sclerotherapy of internal spermatic venous plexus. All presented grade III left varicocele, 39 also had right varicocele. Recurrent left varicocele was present in 25 following surgical ligations, in 1 following retrograde sclerosis, in 3 following both surgical and sclerosing techniques. Simultaneous A/R approach was performed using transbrachial percutaneous access for retrograde catheterization which does not obstruct trans-scrotal surgical field. The procedure is performed without need for general anaesthesia. RESULTS: Sclerotherapy of spermatic veins was always completed. At minimum 12 months follow-up (mean 18 months), only 1 failure was observed. CONCLUSION: Trans-scrotal access allowed to guide, by means of antegrade venography, retrograde selective cannulation of spermatic vein. A/R procedure allows a complete diagnostic evaluation of collateral circulation, with possibility to occlude all vessels draining varicocele. Results at long-term follow-up show very low incidence of recurrence.

Adolescent↗

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↗

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↗

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↗

Bilateral varicocele: single transscrotal approach for Tauber antegrade sclerotherapy.

OBJECTIVE: To describe the results of a new simple technique of single transscrotal approach for Tauber antegrade sclerotherapy in bilateral varicocele. MATERIALS AND METHODS: During the period March 1998-June 2001, overall 341 patients were treated for varicocele using Tauber antegrade sclerotherapy. In 39 of these patients, sclerotherapy was performed bilaterally in the same session whilst in 34, rather than making two incisions at the root of the two hemiscrotums, a single incision was made on the median raphe. During this period, the same approach was used in 4 patients with left varicocele and right hydrocele, 2 patients with left varicocele and right epididymis cyst, 1 patient with bilateral varicocele and bilateral hydrocele, 1 patient with bilateral hydrocele and left varicocele. RESULTS: Maximum ray exposure time was 58 seconds (mean 30). Oro-tracheal intubation was not necessary in any of the patients. In 12 patients, besides local anesthesia, additional sedation was given. Slight bleeding of the wound, occurring in 3 patients, was medicated in the outpatient department. CONCLUSIONS: Patients prefer a single incision. When the incision is made on the median raphe, no scars remain. In bilateral varicocele, the single approach reduces invasiveness and increases patient satisfaction.

Adolescent↗

Insulin-like growth factor (IGF)-I, IGF-II and IGF type I receptor (IGFR-I) expression in prostatic cancer.

Despite evidence implicating the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, its precise role remains unclear. In this study we investigated the differential expression of IGF-I, IGF-II and their type I receptor (IGFR-I) in the epithelium and stroma of prostate neoplastic tissues. Using immunohistochemistry and in situ hybridization techniques, we analyzed 43 paraffin-embedded prostatic samples and compared prostatic cancer (Pca) with prostatic intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. We then determined a possible correlation of the immunohistochemical and in situ findings with two known prognostic clinical-pathological indices: Gleason score histological tumor grade and TNM clinical stage. In 22 of the 43 frozen prostatectomy specimens, IGF-I, IGF-II and IGFR-I mRNA expression were also evaluated by semiquantitative RT-PCR. Non neoplastic and neoplastic tissues examined contained detectable amounts of epithelial and stromal IGF-I, IGF-II and IGFR-I protein and mRNA; all levels increased significantly from normal tissue to PIN to Pca. In all three areas examined, IGFR-I expression was invariably higher in epithelium than in stroma, whereas expression of IGF ligands differed. In normal prostatic tissue, IGF-I and IGF-II expression was higher in stroma than in epithelium. Conversely, in Pca tissue, both factors were more strongly expressed in epithelial malignant cells. PIN areas showed IGF-I lowest, and IGF-II and IGFR-I levels highest in the epithelium. IGF-II protein and mRNA reached their highest levels in prostate tumors with high Gleason scores. These findings indicate that the IGF system changes as prostate tissue progresses from a normal to a malignant state. Differential expression of certain IGF system components in Pca may be associated with the malignant phenotype and more aggressive tumor behavior. Hence IGFs could serve to predict the outcome of prostatic cancer.

Aged↗

[Clinical and diagnostic approach to erectile dysfunction].

Erectile dysfunction (ED), defined as the inability to achieve and/or maintain an erection sufficiently long for a satisfactory sexual performance or intercourse, is an important and common medical problem. ED is not a life-threatening disorder, but it influences the daily routine, social interactions, well-being and quality of life of the patient. Recent epidemiological data have shown a high prevalence and incidence of ED. The Massachusetts Male Aging Study found that 52% of men between the ages of 40 and 70 years reported ED with 9.6% having mild, 22.2% moderate and 17.2% complete or severe ED. In a large Italian cross-sectional study the overall prevalence of self-reported ED was 12.8% and the frequency of ED increases with age. ED may signal serious underlying and potentially life-threatening diseases, such as diabetes, hypertension, cardiovascular disease, peripheral vascular disease and other neurological and endocrine disorders. Also well documented is the role of some drug groups, certain types of surgery, injuries and the role of risk factors related to lifestyle such as smoking, alcohol consumption and inappropriate dietary habits accompanied by an abnormal serum level of cholesterol. The current availability of effective and safe oral drugs for ED in conjunction with the tremendous media interest in the condition, have resulted in an increasing number of men seeking help for ED. As a consequence, many physicians without background knowledge and clinical experience in the diagnosis of ED are involved in making decisions concerning the evaluation of such patients. The result of this is that some males with ED may undergo little or no evaluation before treatment is initiated and, in such circumstances, the disease causing the symptom (ED) may remain untreated. Baseline diagnostic evaluation for ED can identify the underlying pathological condition or the risk factors associated with ED in 80% of patients. This article reports a sequential approach for the diagnosis of ED that may diagnose reversible causes of ED and also unmask medical conditions that manifest with ED as the first symptom.

Algorithms↗

Quantitative immunohistochemical and in situ hybridization analysis of metalloproteinases in prostate cancer.

The role of matrix metalloproteinases (MMPs) as markers of tumor progression in prostate cancer (CaP) is complex and poorly understood. Using computerized image analysis, the differential expression of interstitial collagenase (MMP-1), gelatinase B (MMP-9), matrilysin-1 (MMP-7) and the membrane-type 1-MMP (MT1-MMP) in the epithelium and stroma of human prostate neoplastic tissues were investigated. Using immunohistochemistry and in situ hybridization techniques, 38 paraffin-embedded prostatic samples were analyzed and CaP was compared with prostate intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP) counterpart. The association of MMP protein and mRNA expression with Gleason histological tumor grade and TNM clinical stage was also determined. In most prostatectomy specimens examined, detectable amounts of MMP-1, MT1-MMP, MMP-7 and MMP-9 proteins and MT1-MMP and MMP-9 mRNA were found in the epithelial and stromal components of CaP, PIN and NAP. MMP expression was significantly stronger in the epithelium than in the stroma (p < 0.01). In the epithelium of normal and preneoplastic prostate tissue, MMP-1, MMP-9 and MT1-MMP were preferentially expressed in secretory luminal cells; conversely, MMP-7 was concentrated in basal cells. Epithelial and stromal expressions of MMPs differed in normal, preneoplastic and CaP tissues. Whereas MMP-1 was overexpressed in NAP epithelial glands and progressively decreased from PIN to CaP, MMP-7, MMP-9 and MT1-MMP were more strongly expressed in CaP than in PIN and NAP tissue. The MMPs investigated reached their highest levels in prostate tumors with high Gleason scores. The differential MMP expression in epithelial and stromal prostate tissue supports the previous hypothesis that MMPs may be autocrine and paracrine mediators of the stroma-epithelial interaction, an event that plays a critical role in regulating normal and abnormal prostate growth. MMP gene regulation changes during the early stage of prostate cancer. Differential expression of MMP components in CaP may reflect the malignant phenotype and more aggressive tumor behavior.

Aged↗