Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis.

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Metabolic syndrome is associated to an increased risk of low bone mineral density in free-living women with suspected osteoporosis.

PURPOSE: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. METHODS: 13,182 free-living Caucasian women referring to "COMEGEN" general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. RESULTS: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08-1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. CONCLUSIONS: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

Safety and efficacy of low intensity shockwave (LISW) treatment in patients with erectile dysfunction.

UNLABELLED: The primary goal in the management strategy of a patient with ED would be to determine its etiology and cure it when possible, and not just to treat the symptoms alone. One of the new therapeutic strategies is the use of low intensity extracorporeal shockwave (LISW) therapy. The mechanism of shockwave therapy is not completely clear. It is suggested that LISW induces neovascularization and improvement of cavernosal arterial flow which can lead to an improvement of erectile function by releasing NO, VEGF and PCNA. MATERIALS AND METHODS: 31 patients between February and June 2013 with mild to severe ED and non-Phosphodiesterase 5 inhibitors responders were enrolled. Patients underwent four weekly treatment sessions. During each session 3600 shocks at 0.09mJ/ mm2 were given, 900 shocks at each anatomical area (right and left corpus cavernosum, right and left crus). Improvement of the erectile function was evaluated using the International Index of Erectile Function (IIEF-EF), the Sexual Encounter Profile (SEP) diaries (SEP-Questions 2 and 3) and Global Assessment Questions (GAQ-Q1 and GAQ-Q2). RESULTS: At 3-month follow-up IIEF-EF scores improved from 16.54±6.35 at baseline to 21.03±6.38. Patients answering 'yes' to the SEP-Q2 elevated from 61% to 89% and from 32% to 62% in the SEP-Q3. A statistically significant improvement was reported to the Global Assessment Questions (GAQ-Q1 and GAQ-Q2). CONCLUSION: In conclusion, we can affirm that LISW is a confirmed therapeutic approach to erectile dysfunction that definitely needs more long-term trials to be clarified and further verified.

Safety and efficacy of low intensity shockwave (LISW) treatment in patients with erectile dysfunction

ABSTRACT The primary goal in the management strategy of a patient with ED would be to determine its etiology and cure it when possible, and not just to treat the symptoms alone. One of the new therapeutic strategies is the use of low intensity extracorporeal shockwave (LISW) therapy. The mechanism of shockwave therapy is not completely clear. It is suggested that LISW induces neovascularization and improvement of cavernosal arterial flow which can lead to an improvement of erectile function by releasing NO, VEGF and PCNA. Materials and Methods: 31 patients between February and June 2013 with mild to severe ED and non-Phosphodiesterase 5 inhibitors responders were enrolled. Patients underwent four weekly treatment sessions. During each session 3600 shocks at 0.09mJ/ mm2 were given, 900 shocks at each anatomical area (right and left corpus cavernosum, right and left crus). Improvement of the erectile function was evaluated using the International Index of Erectile Function (IIEF-EF), the Sexual Encounter Profile (SEP) diaries (SEP-Questions 2 and 3) and Global Assessment Questions (GAQ-Q1 and GAQ-Q2). Results: At 3-month follow-up IIEF-EF scores improved from 16.54±6.35 at baseline to 21.03±6.38. Patients answering ‘yes’ to the SEP-Q2 elevated from 61% to 89% and from 32% to 62% in the SEP-Q3. A statistically significant improvement was reported to the Global Assessment Questions (GAQ-Q1 and GAQ-Q2). Conclusion: In conclusion, we can affirm that LISW is a confirmed therapeutic approach to erectile dysfunction that definitely needs more long-term trials to be clarified and further verified.

Treatment of bilateral varicocele and other scrotal comorbidities using a single scrotal access: our experience on 34 patients.

INTRODUCTION: Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. MATERIALS AND METHODS: 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. RESULTS AND DISCUSSION: At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. CONCLUSION: Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities.

Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptor α and ß.

Raloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen-dependent and -independent prostate cell (PC) lines via activation of ERß and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen-dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERß and lacked ERα. In EPN cells, there was an increase in the pre-G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment; bcl-2 mRNA and Bcl-2 protein levels were significantly reduced, while activated caspase-3 and Par-4 levels increased significantly after either E2 or RAL treatment; in addition, c-myc transcript was inhibited after 10(-6) M RAL treatment. A dose-dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase-3 activation and Par-4 increase after either E2 or RAL treatment; while c-myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell-specific, depending on ERß or ERß/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non-genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression.

[Antibacterial prophylaxis in endourological procedures]. / La profilassi antibatterica nelle manovre endourologiche.

AIM: Antibiotic prophylaxis for the prevention of postsurgical infections is a common practice in urologic surgery, as well as in endourologic procedures, both in at risk patients (local or systemic risk factors: age, immunological status, metabolic disorders, poor general conditions) or with a positive urine culture, but also in patients with urine previously sterile. As Gram-negative strains are the most common pathogens, it is reasonable to use a quinolone or a beta-lactam. METHODS: One-hundred and thirty-one patients (range 21-89 years) underwent transurethral cystoscopy (52 cases), vesical catheterism (44 cases), extracorporeal shockwave lithotripsy (17 cases) and transrectal prostatic biopsy (18 cases). An antimicrobial prophylaxis with ciprofloxacin 500 mg (22 patients, 16.8%), levofloxacin 500 mg (54 patients, 41.2%) and prulifloxacin 600 mg (55 patients, 42%) was administered. RESULTS: Globally, the incidence of urinary tract infections during 15 days after surgery was 8.4% (11 cases out of 131): ciprofloxacin 9.1%, levofloxacin 11.1% and prulifloxacin 5.5%, respectively. The patients compliance with the prophylactic treatment was good or excellent in 122 cases (93.1%) and poor in 9 cases (6.9%). No major differences between antibiotics used in prophylaxis were detected, keeping into account the limited size of the global population and subgroups defined by the endourological procedures. CONCLUSIONS: Prulifoxacin, with a broad antimicrobial spectrum, favourable pharmacokinetic properties and easy to use, can be considered a valid and well tolerated therapeutic option for the antibacterial prophylaxis in endourological procedures, both in hospital and in outpatient setting.

Home and office uroflowmetry for evaluation of LUTS from benign prostatic enlargement.

A group of 107 patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE) participated to the HOUSE Study (Home and Office Uroflowmetry Specific Evaluation). Patients received routine investigation, consisting of medical history taking, physical examination including digital rectal examination, prostate-specific antigen (PSA), assessment of symptoms listed both on the International Prostate Symptom Score and on ICS-male questionnaire. We examined the results of uroflowmetry evaluation in this population; data were analysed to observe if any circadian changes of parameters obtained with home uroflowmetry could be detected. We searched a correlation between Q(max), Q(ave) and ICS-benign prostatic hyperplasia symptom score: a significantly inverse correlation was found only for Q(max), confirming Q(max) as a reliable parameter to quantify subjective symptoms. When examining the multiple flow curves recorded in the same patient with home uroflowmetry, voided volume and flow time had usually higher values during night-time: the existence of circadian changes of uroflowmetry parameters in patients with LUTS from BPE was confirmed, and lower values of average and maximum flow rates during sleep hours were recorded in the same patient. In conclusion, when evaluating the natural history or treatment outcome of individual patients or group of patients in clinical trials for evaluation of BPE and LUTS, an assessment including multiple measurements may be useful and of value.

Aims and methods. LUTS suggestive of BPH.

OBJECTIVE: Few epidemiological studies are available on Italian patients with lower urinary tract symptoms and their QoL. QUIBUS (QUality of life Investigated in BPH patients with Urinary Symptoms) is an observational longitudinal study aimed at evaluating symptoms and QoL in a large sample of Italian patients and investigating their correlation with demographic, social and clinical characteristics of BPH. PATIENTS AND METHODS: Patients with lower urinary tract symptoms and prostate enlargement suggestive of BPH (both old and new diagnosis) were enrolled between November 1998 and May 1999 in 31 Italian centers of urology. This longitudinal investigation consists of an enrollment visit, in which demographic, social and clinical aspects are recorded as baseline data, and a follow-up visit after 1 year of treatment freely assigned by the investigators. Symptoms and QoL are assessed by means of IPSS, ICS-BPH (at both visits) and SF-36 (only at the follow-up visit) questionnaires. RESULTS: 1,033 patients were enrolled. The follow-up visit is still under evaluation. In this series of papers the baseline results are presented and discussed in terms of (i) medical management, (ii) life-style, (iii) symptoms, bothersomeness and QoL, (iv) sexual function of a large and representative sample of Italian patients and (v) uroflowmetry.

Life-style in patients with LUTS suggestive of BPH.

BACKGROUND: Owing to the existing controversy about the role of life-style in the pathogenesis of BPH, the possible associations of LUTS and prostate enlargement with alcohol intake, coffee consumption, smoking, physical activity, body mass index (BMI) and concomitant diseases were studied in the large series of patients of the QUIBUS study. RESULTS: Among concomitant diseases, essential hypertension was the most represented. However no apparent additive or synergistic influence on symptoms was recorded in this subset of the population. Coffee consumption was not associated with prostate volume or LUTS. Alcohol consumption was associated with urgency and intermittence and with an overall higher IPSS. No major influence on symptoms was found in smokers. Physical activity was associated with a lower frequency of incomplete bladder emptying, repeated urination, intermittence and urgency. The postulated existence of an association between BMI and BPH was not confirmed in this study. When a prediction of the IPSS scores was tempted by entering the life-style factors in a multiple regression model, they were able to explain at best 5% of the variance of the dependent variable. CONCLUSION: Life-style patterns bear a greater influence on individual symptoms than on total scores. This difference is sometimes high enough to recommend specific life-style measures to patients with LUTS and prostate enlargement.

Estrogen receptor beta expression in human prostate tissue.

Estrogen receptor subtype beta (ERbeta) is highly expressed in rat prostate epithelium, but its presence in human prostate needs to be confirmed. Here we investigated the expression of ERbeta in five benign (normal and/or hyperplastic) and 10 malignant (Gleasons' score 2-7) prostate tissue specimens using immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections, using a commercially available ERbeta polyclonal antibody developed against the C-terminal amino acid residue. Nuclear ERbeta expression was found in the nuclei of glandular epithelium of benign prostate tissue specimens; faint nuclear ERbeta positivity was also present in a few stromal cells around normal epithelium. Nuclear ERbeta specific immunostaining was undetectable in all prostate cancer sections.

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study.

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.

Changes in tissue transglutaminase activity and expression during retinoic acid-induced growth arrest and apoptosis in primary cultures of human epithelial prostate cells.

We treated primary epithelial cells from human normal prostate (NEPC) and prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it regulates the activity of tissue transglutaminase (tTGase), an enzyme that accumulates in cells undergoing apoptosis. tTGase activity was assessed by [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma), tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA treatment, cell growth inhibition and apoptosis were associated with increased tTGase activity in both NEPC and CEPC, and with increased tTGase protein and messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC, whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme activity in normal prostate cells, and that RA-regulated pathways are impaired in cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR beta suggest that retinoid may act on the genetic defect responsible for prostate cancer progression.

Role of neoadjuvant treatment in clinically confined prostate cancer. Takeda NHT Italian Group.

OBJECTIVE: This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy. METHODS: Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy. RESULTS: Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors. CONCLUSIONS: Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.

galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas.

Galectin-1 and galectin-3 are galactoside-binding proteins involved in different steps of tumor progression and potential targets for therapy. We have investigated the expression of these galectins in 38 human bladder transitional-cell carcinomas of different histological grade and clinical stage and in 5 normal urothelium samples. Galectin-1 mRNA levels were highly increased in most high-grade tumors compared with normal bladder or low-grade tumors. Western blot and immuno-histochemical analysis of normal and neoplastic tissues revealed a higher content of galectin-1 in tumors. Galectin-3 mRNA levels were also increased in most tumors compared with normal urothelium, but levels were comparable among tumors of different histological grade.

Leuprorelin 1-month depot as neoadjuvant therapy for prostate cancer. Takeda NHT Italian Group.

In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to radical prostatectomy has been largely debated and investigated in randomized multicenter trials as well as in large single-institution studies. We have initiated a prospective randomized comparative trial with parallel groups in patients with clinically limited disease to contribute to the clarification of the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus cyproterone acetate in 'maintaining' the stage of the disease; to reduce the percentage of pathological overstaging, and mainly to accurately assess the pathological modifications induced by NHT. The present paper is an interim report of the results.

Prostate-specific antigen (protein and mRNA) analysis in the differential diagnosis and staging of prostate cancer.

We analyzed complexed and free prostate-specific antigen (PSA), the free/total PSA and complexed/free PSA ratios, acid phosphatase, and prostatic phosphatase in serum from 36 patients with prostatic carcinoma and from 48 non-neoplastic control patients (20 with prostatitis and 28 with benign prostatic hyperplasia). Receiver-operating characteristic plots showed that serum PSA was the most efficient variable, singly used, in discriminating neoplastic from non-neoplastic patients. At a cut-off value of 10.0 ng/ml, serum PSA had a diagnostic sensitivity of 87% and a diagnostic specificity of 83%. In particular, three patients with prostatic carcinoma and twenty non-neoplastic controls had serum PSA levels of between 4 and 10 ng/ml. The subsequent analysis of the serum free/total PSA ratio, in this subgroup, using a cut-off level of 15%, allowed us to classify correctly all prostatic cancer cases and 18/20 non-neoplastic diseases. We next analyzed PSA mRNA in circulating cells using an improved reverse-transcriptase polymerase chain reaction dot blot procedure, from six patients with prostatic carcinoma with distant metastases, and in seventeen with localized cancer. The analysis had a high sensitivity (up to dilutions 1:10(6) of total RNA from prostatic cancer cells vs total RNA from normal blood cells). The analysis revealed circulating micrometastatic cells in 3/6 (50%) cases of metastatic cancer and in 4/17 cases of localized cancer. To conclude, serum total PSA combined with the free/total PSA ratio is a very efficient algorithm in discriminating neoplastic from non-neoplastic prostatic diseases, while other mRNA species must be analyzed, in addition to PSA mRNA, in circulating cells to increase the efficiency in detecting metastatic prostatic cancer.

Different expression patterns of somatostatin receptor subtypes in cultured epithelial cells from human normal prostate and prostate cancer.

The transcripts of five SRIH receptor subtypes (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5) were investigated by RT-PCR in epithelial cells (EC) and stromal cells (SC) from primary cultures of five normal human prostates and six prostate cancers. Primary cultures of prostate EC were established in serum-free keratynocyte medium with 5% FCS, epidermal growth factor, and bovine pituitary extract; SC were cultured in MEM with 10% FCS. Total RNA was extracted from EC and SC using a modified guanidine thiocyanate method. RT-PCR was performed after deoxyribonuclease treatment, using SSTR1-, SSTR2-, SSTR3-, SSTR4-, and SSTR5-specific-primers and adding glyceraldehyde-3-phosphate dehydrogenase-specific primers as internal control. A PCR product of the expected size of 334 bp, corresponding to SSTR1, was expressed only in EC from prostate cancer, whereas the expected 461-bp product of SSTR2 was found only in EC from normal prostate. SSTR3 messenger RNA was undetectable in normal and cancer EC, whereas SSTR4 and SSTR5 were present in both cell types. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 messenger RNAs were not expressed in SC from both normal and cancer prostates. The RT-PCR method clearly demonstrated SSTRs' expression in the human prostate EC in vitro with differences between normal and tumoral samples. Our results may explain the ineffectiveness of some SSTR2 selective SRIH analogues in the treatment of prostate cancer and suggest that the absence of SSTR2 could represent a growth advantage in prostate cancer.