Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.

PURPOSE: Benign Prostatic Hyperplasia (BPH) is a result of prostate inflammation, frequently occurring in metabolic syndrome (MetS). Low testosterone is common in MetS. A randomized clinical trial was designed to evaluate if 24 weeks of testosterone therapy (TTh) in BPH men with MetS and low testosterone improve urinary symptoms and prostate inflammation. METHODS: One-hundred-twenty men with MetS waitlisted for BPH surgery were enrolled. They were categorized into normal testosterone (TT ≥ 12 nmol/L and cFT ≥ 225 pmol/L; n = 48) and testosterone deficient (TD) (TT < 12 nmol/L and/or cFT < 225 pmol/L; n = 72) then randomized to testosterone gel 2% (5 g/daily) or placebo for 24 weeks. At baseline and follow-up, questionnaires for urinary symptoms and trans-rectal ultrasound were performed. Prostate tissue was collected for molecular and histopathological analyses. RESULTS: No differences in the improvement of urinary symptoms were found between TTh and placebo (OR [95% CI] 0.96 [0.39; 2.37]). In TD + TTh, increase in prostate but not adenoma volume was observed (2.64 mL [0.07; 5.20] and 1.82 mL [- 0.46; 0.41], respectively). Ultrasound markers of inflammation were improved. In a subset of 61 men, a hyper-expression of several pro-inflammatory genes was found in TD + placebo when compared with normal testosterone. TTh was able to counteract this effect. For 80 men, the inflammatory infiltrate was higher in TD + placebo than in normal testosterone (0.8 points [0.2; 1.4]) and TD + TTh men (0.9 points [0.2; 1.5]). CONCLUSIONS: Twenty-four weeks of TTh in TD men with BPH and MetS improves ultrasound, molecular and histological proxies of prostate inflammation. This does not result in symptom improvement.

Gynecomastia in subjects with sexual dysfunction.

PURPOSE: To analyze possible relationships between gynecomastia and clinical and biochemical parameters in a large cohort of subjects with sexual dysfunction (SD). METHODS: A consecutive series of 4,023 men attending our Outpatient Clinic for SD was retrospectively studied. RESULTS: After excluding Klinefelter's syndrome patients, the prevalence of gynecomastia was 3.1 %. Subjects with gynecomastia had significantly lower testosterone (T) levels; the association retained statistical significance after adjusting for age and life-style. However, only 33.3 % of subjects with gynecomastia were hypogonadal. Gynecomastia was associated with delayed puberty, history of testicular or hepatic diseases, as well as cannabis abuse. Patients with gynecomastia more frequently reported sexual complaints, such as severe erectile dysfunction [odds ratio (OR) = 2.19 (1.26-3.86), p = 0.006], lower sexual desire and intercourse frequency [OR = 1.23 (1.06-1.58) and OR = 1.84 (1.22-2.78), respectively; both p < 0.05], orgasm difficulties [OR = 0.49 (0.28-0.83), p = 0.008], delayed ejaculation and lower ejaculate volume [OR = 1.89 (1.10-3.26) and OR = 1.51 (1.23-1.86), respectively; both p < 0.05]. Gynecomastia was also positively associated with severe obesity, lower testis volume and LH, and negatively with prostate-specific antigen levels. The further adjustment for T did not affect these results, except for obesity. After introducing body mass index as a further covariate, all the associations retained statistical significance, except for delayed ejaculation and ANDROTEST score. When considering gynecomastia severity, we found a step-wise, T-independent, decrease and increase of testis volume and LH, respectively. Gynecomastia was also associated with the use of several drugs in almost 40 % of our patients. CONCLUSION: Gynecomastia is a rare condition in subjects with SD, and could indicate a testosterone deficiency that deserves further investigation.

Interferon-γ release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a literature review.

The role of interferon-gamma release assays (IGRAs) for immunologic diagnosis of tuberculosis in children is under debate. We carried out a narrative review on the studies on IGRAs in paediatric populations. A literature search was conducted using multiple keywords and standardized terminology in Medline, EMBASE and Cochrane databases, up to January 27th, 2011. Study quality was assessed using the MOOSE checklist and results of relevant studies were summarized. Sixty-seven paediatric studies (study population ranging from 14 to 5,244 children) were identified. Non-commercial ELISPOT assay (by means of ESAT-6 and CFP-10 antigens) had been carried out in 11 studies. QuantiFERON-TB Gold (QFT-G), QuantiFERON-TB Gold In-tube (QFT-G-IT), and T-SPOT.TB assays had been performed in 10, 44 and 18 studies, respectively. Most studies reported higher specificity of IGRA than tuberculin skin test (TST), but interpretation of the results is complicated by the fact that a gold standard for the diagnosis of latent TB is lacking. The reported sensitivity for active TB ranged from 51-93 percent for QFT-G/QFT-G-IT and 40-100 percent for ELISPOT assays, suggesting that a negative IGRA result may not exclude tuberculosis. Combining TST and IGRA results increased the diagnostic sensitivity. Rates of indeterminate results largely varied (0 to 35 percent). Most of the studies on young (less than 5 years) or immune-compromised children reported a proportion of indeterminate results exceeding 4 percent. Agreement among TST and IGRA, assessed by the k statistics, ranged from -0.03 to 0.87. Higher rates of discordance were reported in BCG-vaccinated than in non-BCG-vaccinated children. Studies on children less than 5 years and immunocompromised children reported conflicting results, as did studies on serial IGRA determinations. Despite the large amount of literature data, the role of IGRA in the pediatric population is still unclear, especially in young children. Combined use of TST/IGRA may increase diagnostic sensitivity but interpretation of discordant results remains a challenging issue.

Interferon-γ release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a systematic review and meta-analysis.

Data regarding the use of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis are accumulating. We systematically searched PubMed, EMBASE and Cochrane and performed pooled estimates of sensitivity and specificity of QuantiFERON-TB Gold In Tube (QFT-G-IT) and T-SPOT.TB compared to tuberculin skin test (TST). For studies assessing sensitivity, children had to have active tuberculosis. Specificity data were derived from children classified as non-infected. Eleven studies were included in the sensitivity analysis for TST, 10 for QFT-G-IT, and 9 for T-SPOT.TB. Eight studies were included in specificity analysis for TST, 8 for QFT-G-IT, and 7 for T-SPOT.TB. Pooled QFT-G-IT sensitivity was 0.79 (95% CI:0.70-0.89) pooled T-SPOT.TB sensitivity was 0.74 (95% CI:0.59-0.90) and pooled TST sensitivity was 0.82 (95% CI:0.72-0.93). Pooled QFT-G-IT and T-SPOT.TB specificities were 0.95 (95% CI:0.93- 0.97) and 0.96 (95% CI:0.93-1.00), respectively. Pooled TST specificity was significantly lower 0.83 (95% CI:0.74-0.92). IGRA performance in children showed no better sensitivity than TST, but higher specificity.

A simple ultrasound score for the identification of candidates to fine needle aspiration of thyroid nodules.

BACKGROUND: Cytological examination of fine needle aspirates (FNA) is the standard procedure for discriminating potentially malignant thyroid nodules to be referred to surgery. In a fraction of cases, ultrasound (US) examination could provide information theoretically sufficient to avoid FNA, when typical US features suggesting malignancies are lacking. AIM: The aim of this study was to construct a simple US score predicting malignant nodules so as to reduce the number of unnecessary FNA. SUBJECTS AND METHODS: In a series of 1632 consecutive patients undergoing US-guided FNA (1812 nodules), echostructure, echogenicity, margins, halo, microcalcification, and vascularization were assessed. RESULTS: At multivariate analysis, the following parameters showed a strong predictive value for positive cytology (Thy 4 and Thy 5, suspicious and diagnostic for malignancy, respectively, according to the Thyroid British Association): solid echostructure, irregular margins and hypoechogenicity [adjusted odd ratio (OR) 5.13 (1.58-16.66), 3.03 (1.70-5.39), 2.05 (1.17-3.57), respectively]. A 10-point Thyroid Risk Ultrasound Score (TRUS) was constructed on the basis of the adjusted OR. A TRUS≥6 identified malignant nodules with sensitivity and specificity of 73% and 65%, respectively. Among the patients with follicular lesions (Thy 3) and final diagnosis of carcinoma, about 65% had a TRUS≥6.0. CONCLUSIONS: The sensitivity of TRUS, although higher than that of other scores, could still be insufficient for the identification of patients who could avoid FNA in routine clinical practice, whereas its predictive value for Thy 3 lesions deserves further investigations.

Prolactin levels independently predict major cardiovascular events in patients with erectile dysfunction.

The physiological role of prolactin (PRL) in men is not completely clarified. We previously reported that in subjects consulting for sexual dysfunction, lower PRL plasma levels were associated with worse lipid and glycaemic profile, as well as with a higher prevalence of metabolic syndrome and arteriogenic erectile dysfunction (ED). The aim of this study was to assess possible associations between PRL levels and incident major cardiovascular events (MACE) in subjects with ED. When only subjects without pathological hyperprolactinaemia (PRL < 735 mU/L or 35 ng/mL) and pituitary diseases were considered, both unadjusted and adjusted analyses showed a significantly lower incidence of MACE in subjects with PRL levels in the highest PRL quintile (246-735 mU/L or 12-35 ng/mL) when compared with the rest of the sample. In particular, the risk of MACE was reduced by 5% (1-9%; p = 0.03) for each 10 ng/mL increment of PRL. Conversely, comparing patients with hyperprolactinaemia with matched controls, no significant difference was detected between cases and controls in MACE. In subjects at high risk for cardiovascular diseases, such as those with ED, a relatively high PRL plasma level is associated with an overall decreased chance of MACE, independently from other known risk factors.

Premature and delayed ejaculation: two ends of a single continuum influenced by hormonal milieu.

Although it is well established that all the aspects of male reproduction are hormonally regulated, the endocrine control of the ejaculatory reflex is still not completely clarified. Sex steroids, thyroid and pituitary hormones (oxytocin and prolactin) have been proposed to control the ejaculatory process at various levels; however, only a few reports are currently available. The aim of this study was to evaluate the contribution of testosterone, thyrotropin (TSH) and prolactin (PRL) in the pathogenesis of ejaculatory dysfunction in a large series of subjects consulting for sexual dysfunction. Among the 2652 patients studied, 674 (25.2%) and 194 (7.3%) reported premature and delayed ejaculation (PE and DE), respectively. Categorizing ejaculatory difficulties on an eight-point scale starting from severe PE and ending with anejaculation (0 = severe PE, 1 = moderate PE, 2 = mild PE, 3 = no difficulties, 4 = mild DE, 5 = moderate DE, 6 = severe DE and 7 = anejaculation), PRL as well as TSH levels progressively increased from patients with severe PE towards those with anejaculation. Conversely, the opposite was observed for testosterone levels. All of these associations were confirmed after adjustment for age (adjusted r = 0.050, 0.053 and -0.038 for PRL, TSH and testosterone, respectively; all p < 0.05). When all hormonal parameters were introduced in the same regression model, adjusting for age, ΣMHQ (an index of general psychopathology) and use of selective serotonin reuptake inhibitor antidepressants, they were independently associated with ejaculatory problems (adjusted r = 0.056, 0.047 and -0.059 for PRL, TSH and testosterone, respectively; all p < 0.05). This study indicates endocrine system is involved in the control of ejaculatory function and that PRL, TSH and testosterone play an independent role.

Prevalence and distribution of melanocytic naevi on the scalp: a prospective study.

BACKGROUND: Few studies have examined the incidence and characteristics of naevi on the scalp. Most studies of scalp naevi have been performed in children, whose incidence of scalp naevi is relatively high, at about 0.5-11.7% of the total body count of common naevi. OBJECTIVES: To investigate the prevalence and distribution of scalp melanocytic naevi in patients of all ages. To our knowledge, ours is the first study to analyse in detail the relationships between melanocytic naevi on the scalp and total body naevi and total body atypical naevi. METHODS: We conducted a prospective study of patients visiting the dermatology outpatient clinic at the University of Florence, for examinations unrelated to the presence of naevi or melanoma. The study enrolled 795 subjects (417 females; 52.4%), with a median age of 35 years (range 4-80). RESULTS: The number of melanocytic naevi on the scalp increased significantly (r = 0.2057, P = 0.0008) as the number of total body melanocytic naevi increased and a correlation was found between the number of clinically atypical total body naevi and the number of scalp naevi. Relatively few naevi (15.5%) were located at the frontal region compared with other regions of the scalp, although the frontal region is more exposed to ultraviolet (UV) rays. Compared with subjects without alopecia, whose hair shields the scalp from UV rays, subjects with androgenetic alopecia showed no significant increase in number of scalp naevi. CONCLUSIONS: Despite practical difficulties, early diagnostic screening for melanoma or screening during follow-up examination for previous melanoma should involve examination of the entire skin surface, scalp included.

Sexual dysfunction in subjects with Klinefelter's syndrome.

While the association of Klinefelter's Syndrome (KS) with infertility is well-known, very few investigations have evaluated the prevalence of sexual dysfunction in KS. The aim of the present study was to systematically analyse the prevalence of KS in a consecutive series of adult male patients consulting for sexual problems and to investigate its specific correlates. Among a consecutive series of 1386 men (mean age 48.9 +/- 12.7 years old), 23 (1.7%) subjects with KS were found. Patients with KS were younger and more often hypogonadal when compared with the rest of the sample. Among patients with KS, five (22.7%) subjects reported severe erectile dysfunction, 14 (60.9%) hypoactive sexual desire (HSD), two (9.5%) premature and two (9.5%) delayed ejaculation. Only the association between KS and HSD was confirmed after adjustment for age [HR = 3.2 (1.37-7.5)], however, when patients with KS were compared with age, smoking habit, and testosterone matched controls, even the association between KS with HSD disappeared. In comparison to matched hypogonadal controls, subjects with KS had lower levels of education, a higher frequency of cryptorchidism and poorer pubertal progression. In conclusion, our results indicate that sexual dysfunction present in KS is not specifically associated with the syndrome but is caused by the underlying hypogonadal state. Further studies are needed to evaluate the efficacy of testosterone substitution in ameliorating the hypoactive sexual desire often reported in subjects with KS.

Clinical and microbiological efficacy of prulifloxacin for the treatment of chronic bacterial prostatitis due to Chlamydia trachomatis infection: results from a prospective, randomized and open-label study.

The purpose of this study was to compare the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy for the treatment of chronic prostatitis due to Chlamydia trachomatis (Ct) infection. All patients with clinical and instrumental diagnosis of bacterial chronic prostatitis (CP) due to Ct infection were enrolled. After randomization, all patients were administered oral prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days. At enrollment and 30 days after beginning treatment, all patients underwent microbiological cultures for uropathogens bacteria and yeasts, DNA extraction and mucosal IgA evaluation for Ct diagnosis, seminal plasma IL-8 evaluation and serum IgA and IgG anti-Ct analysis. The National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) was given to each patient. A total of 109 patients received prulifloxacin and 102 received standard therapy. Prulifloxacin had clinical efficacy rates equivalent to standard therapy (82.5% vs. 79.9%) (P = 0.08) and showed superior microbiological efficacy rates compared to standard therapy, in terms of decreasing mucosal IgA (P < 0.001) and IL-8 levels (P < 0.001). Prulifloxacin was also equivalent to standard therapy for clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Ct infection.

The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction.

In males, testosterone (T) levels decline with ageing. Several symptoms characteristic of the ageing process are similar to those related to hypogonadism. The aim of the present study was to evaluate the specific association among hypogonadism-related symptoms and signs and the ageing process. A consecutive series of 1647 (mean age 52.4 +/- 13.1 years) male patients with sexual dysfunction were investigated. Several hormonal and biochemical, instrumental and psychological parameters were studied. The parameters significantly associated with total levels in the entire cohort, after adjustment for confounders, were studied as a function of age and T quartiles. In all age quartiles, low T was associated with higher waist circumference and triglyceride levels and with an increased prevalence of metabolic syndrome. The prevalence of hypoactive sexual desire decreased as a function of T only in the youngest (17- to 42-year old) age quartile as well as the reported reduction in nocturnal erections. In the oldest age quartile, we found an inverse relationship between T levels and the prevalence of severe erectile dysfunction and a positive relationship with intercourse frequency. Accordingly, in the oldest age quartile, subjects with higher T levels showed better penile flow at penile colour doppler ultrasound as well as a better lipid profile. Finally, an inverse association between somatized anxiety and T levels was observed only in the oldest age quartile. In conclusion, our study shows for the first time that in subjects with sexual dysfunction, some hypogonadism-related symptoms can be age-specific. In particular, low T is associated with sexual dysfunction more often in the oldest subjects.

Minimally invasive versus traditional chest surgical approach in patients with reduced renal function.

AIM: All surgical access approaches to the chest wall cause a different degree of muscle damage and freeing of substances as myogloblin into the bloodstream thus compromising kidney function. The aim of this study was to evaluate the potential kidney damage in relation to entity of muscle lesions caused by the different surgical approaches. METHODS: The hematic levels of creatine phosphokinase (CPK), myoglobin, lactate dehydrogenase (LDH), creatinine as well as the amount of the diuresis at different intervals of time were taken of 66 patients who underwent a thoracic surgical operation with diverse surgical access approaches. RESULTS: Surgery determines muscle substances to be freed into the bloodstream. Myoglo-blin levels resulted to be correlated to those of CPK (r=0.83; P<0.00005). Although serum levels of myogloblin are not determined as a routine procedure, high levels of CPK must induce to dose myogloblin. The amount of muscle substances freed depend on the width of the surgical access (r=0.7; P<0.00005) and not upon extension (r=0.36; P=0.18) or duration of surgery. (r=0.4; P=0.093). CONCLUSION: In patients with a reduced renal function or affected by kidney failure a minimally invasive or thoracoscopic approach is indicated whenever possible in order to reduce the amount of myogloblin in the bloodstream.

Most sensitive urinary cotinine cut-off level for environmental tobacco smoke exposure assessment: a pilot study.

The aim of this pilot study was to determine the most sensitive urinary cotinine level able to assess environmental tobacco smoke (ETS) exposure. 54 Florentine subjects (29 males and 25 females), reporting to be nonsmokers and exposed (E) or not exposed (NE) to ETS at home, at work or in places of recreation, were examined. The urinary cotinine concentration was determined using gaschromatographic analysis in samples collected on three consecutive days. 18 subjects (33.3%) reported to be exposed to ETS had a greater median cotinine concentration than 36 ETS-NE subjects (E = 3.3 pg/L vs NE = 2.2 microg/L, median values), with borderline statistical significance (P = 0.05). The 2.5 microg/L cotinine concentration was the only statistically significant cut-off (P = 0.04) discriminating between ETS-E to ETS-NE subjects, identifying 51.9% of the subjects examined as exposed (E). Considering the expanded uncertainty of measurement of the method used (20%), urinary cotinine concentrations higher than 3.1 microg/L, a value whose confidence interval is higher than our proposed cut-off of 2.5 microg/L, mean that to be sure that a subject is exposed to ETS.

[Mobile phone use while driving in Fiorentine area: results of the new survey]. / Utilizzo del telefono cellulare alla guida nel territorio fiorentino: i risultati della nuova indagine.

Despite the growing evidence that the use of hand-held mobile phone while driving increases the risk of motor vehicle crashes and the banning by law, in many countries, of this kind of use, this behaviour is more and more spreading. Following a survey we have conducted in 2004, in 2005 we have realized in florentine area a monthly monitoring about this incorrect use of phoning while driving. Overall, 15001 vehicles were observed, and the prevalence of mobile phone use while driving was 2.6%, higher if compared with that referred to the previous year (1.8%). The association between mobile, hand-held, phone use and the considered variables (the same of the 2004 study) is always statistically significant and the conditions with the highest probability of meeting a phoning driver are showed by regression analysis. Intervention for reducing the spread of this behaviour is needed, especially if we consider the recent technological innovations introduced in the new models of mobile phones, which offer new distractions for drivers, the uncertainty of the absence of risk in using hand-free phone and the scarcely proved long-term effectiveness of legislation banning this use.

[Mobile phone use while driving in Florence health district area]. / Utilizzo del telefono cellulare alla guida: l'esperienza fiorentina.

The practice of driving while using hand-held mobile phones is diffused in numerous countries, even though it has been demonstrated that they increase the risk of traffic accidents, and such use has consequently been prohibited. Because of the lack of Italian data on the spread of this behaviour a study was done in June 2004 on drivers' use of hand-held mobile phones in the Florence Health Authority area. The study was performed by direct observation from 4 watching-points (1 for each zone) which allowed for observation of several types of vehicles, on varying road conditions, in 5 hour time bands. Overall, 9387 vehicles were observed and the prevalence of mobile phone use while driving was found to be 1.8%. The greatest prevalence of mobile phone use was found in the following conditions: in the Northwest zone (2.8%), in the city suburbs (2.8%), on Tuesdays (3.0%), among drivers not using safety belts (3.0%), and among subjects driving alone (2.1%). Logistic regression analysis has shown a statistically significant association between mobile phone use and the zone, the number of persons in the vehicle, and seat belt use. Mobile phone use while driving is therefore a diffused practice that is particularly common among drivers who engage in other high-risk driving behaviours.

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination.

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.

bcl-2 protein expression correlates with recurrence and survival in early stage head and neck cancer treated by radiotherapy.

Inherent cellular radioresistance plays a critical role in the failure of radiation therapy (RT). The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death induced by several genotoxic agents, including gamma-radiation. Thus, it is likely that bcl-2 gene expression could be involved in the complex mechanisms of radioresistance in human tumors with some prognostic implications. In this study, we analyzed the predictive relevance of bcl-2 expression on 5-year disease-free and overall survival in patients with early stage squamous cell carcinoma of the head and neck (SCCHN) primary treated with RT. The expression of bcl-2 was analyzed by immunohistochemistry on paraffin-embedded sections from 71 consecutive stage I-II SCCHN patients treated with curative RT. We detected bcl-2 protein in 21% of SCCHN studied. A suggestive association was observed between tobacco exposure and bcl-2 protein expression (P < 0.1); this association was stronger in those patients who failed primary RT (P = 0.03). Moreover, we documented a higher rate of bcl-2 immunoreactive tumors in postirradiated biopsies from relapsed patients than in preirradiated ones (P = 0.03). In both univariate and multivariate analyses, bcl-2 expression was the most important indicator for disease-free survival (P = 0.08 and P = 0.01, respectively) and overall survival (P = 0.004 and P = 0.05) within 5 years of RT. The present study indicates that the proto-oncogene bcl-2 is abnormally expressed in some SCCHN, and its expression may prove to be a useful tool in selecting patients for conventional RT with clear prognostic implications.

An integrated approach with vardenafil orodispersible tablet and cognitive behavioral sex therapy for treatment of erectile dysfunction: a randomized controlled pilot study.

Erectile Dysfunction is considered a multifactorial disease, where organic and psychological aspects are often interconnected. In a randomized controlled pilot study, we compared the efficacy of combined vardenafil orodispersible tablet (VARD) and cognitive-behavioral sex therapy (CBST) vs. VARD alone in improving sexual symptoms in both male and female partners. Thirty male patients with erectile dysfunction, and their partners were randomly assigned with a 2 : 1 ratio, to two different arms and treated for 10 weeks with VARD (Group A; n = 19) or VARD+CBST (Group B; n = 11). International Index of Erectile Dysfunction (IIEF-15), Female Sexual Function Index (FSFI) and Index of Sexual Satisfaction (ISS) were, respectively, administered to male, female, and both partners at times (T) 0, 1 (+5 weeks of therapy) and 2 (+10 weeks of therapy). Groups A and B were similar in their sociodemographic and clinical characteristics. Pre-treatment (T0) test scores did not significantly differ among the groups. In both group A and B, the IIEF-Erectile Function domain showed a significant improvement from T0 to T1 (p = 0.005 and p < 0.0001 vs. T0, respectively) and from T0 to T2 only in group B (p = 0.013). In group A, FSFI and both male and female ISS did not show any significant change at T1 and T2 vs. T0. In group B, a significant improvement at final time-point in FSFI and male and female ISS scores was reported (p < 0.05, T2 vs. T0 in all scores). The results of our study suggest that both VARD alone and VARD+CBST improved erectile function, however, only VARD+CBST improved couple sexual satisfaction and female sexual function.

Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis.

We evaluated the role of COX-2 pathway in 35 head and neck cancers (HNCs) by analyzing COX-2 expression and prostaglandin E2 (PGE2) production in relation to tumor angiogenesis and lymph node metastasis. COX-2 activity was also correlated to vascular endothelial growth factor (VEGF) mRNA and protein expression. COX-2 mRNA and protein expression was higher in tumor samples than in normal mucosa. PGE2 levels were higher in the tumor front zone in comparison with tumor core and normal mucosa (P<.0001). Specimens from patients with lymph node metastasis exhibited higher COX-2 protein expression (P=.0074), PGE2 levels (P=.0011) and microvessel density (P<.0001) than specimens from patients without metastasis. A significant correlation between COX-2 and tumor vascularization (r(s)=0.450, P=.007) as well as between COX-2 and microvessel density with VEGF expression in tumor tissues was found (r(s)=0.450, P=.007; r(s)=0.620, P=.0001, respectively). The induction of COX-2 mRNA and PGE2 synthesis by EGF and Escherichia coli lipopolysaccharide (LPS) in A-431 and SCC-9 cell lines, resulted in an increase in VEGF mRNA and protein production. Indomethacin and celecoxib reversed the EGF- and LPS-dependent COX-2, VEGF, and PGE2 increases. This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment.

Second solid tumors and leukemia after treatment for Hodgkin's disease: an analysis of 1121 patients from a single institution.

PURPOSE: To define the risk of having a second malignant neoplasm (ST) in different subsets of Hodgkin's disease patients and possibly to identify potentially avoidable therapeutic behaviors, linked with an increased second tumor probability. METHODS AND MATERIALS: Cumulative probability of having a ST has been calculated for the different clinical and therapeutic subgroups of a population of 1121 patients consecutively treated (1960-1988) for Hodgkin's disease. Age groups at diagnosis were as follows: < 20 years, 18%; 20-40, 48%; 41-60, 26%; > 60, 8%. Initial treatment consisted of radiation alone (67%), combined modality treatment (24%), chemotherapy alone (9%). Treatment for relapse was also coded, and the occurrence of ST was related both to initial treatment (considering relapsed patients as censored at relapse) and to the "overall" treatment burden, without censoring at relapse. RESULTS: An increased ST risk has been observed in patients older at HD diagnosis. Second tumors cumulative probability rates were significantly higher in patients initially treated with chemotherapy, especially when associated with subtotal or total nodal irradiation (relative risks of 3.1 and 4.1, p = .03 and .005, respectively, when compared to involved field radiotherapy alone). The same trend was observed for second solid tumors. Acute leukemia was more frequent in patients initially given chemotherapy alone or associated with radiotherapy (p = .01), and in those treated with an increasing number of cycles (p = .004). "Salvage" chemotherapy after radiation alone at presentation does not seem to be linked with an increased risk of leukemia. CONCLUSION: The 15-year cumulative ST probability (11%) should be evaluated in the context of the very good cure rates achieved for Hodgkin's disease. The use of chemotherapy, particularly when associated with subtotal or total nodal irradiation, entails an increased risk of second malignancies and might be inappropriate in early stage Hodgkin's disease patients.