Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

OBJECTIVE: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded. RESULTS: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04). CONCLUSION: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Celecoxib for the prevention of nonmuscle invasive bladder cancer: results from a matched control study.

OBJECTIVES: New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC. METHODS: Treatment with celecoxib was administered orally for 12 months and compared with a contemporary series of patients treated with intravesical mitomycin C (MMC), given weekly for 4 weeks and then monthly for 11 months. Primary endpoints were time to first recurrence and adverse events. RESULTS: From 2003 through 2006, 58 patients were treated with celecoxib and compared with 66 patients receiving MMC. After a median follow up of 75 months, 49 patients were disease free, including 23 (34.85%) in the MMC group and 26 (44.8%) in the celecoxib group. Median disease-free interval was 67 months [95% confidence interval (CI) 35.8 to NA] versus 41 months (95% CI 27.1-67.1; log-rank p = 0.25) for patients treated with MMC and celecoxib, respectively. In the multivariate analysis, treatment was not found to be an independent predictor for recurrence [hazard ratio (HR) 0.76, 95% CI 0.47-1.22, p = 0.25). Overall, 45 AEs were recorded in 35/124 patients. There were no differences between the two groups. CONCLUSIONS: Our data support a clinical benefit of celecoxib and encourage future trials in which COX-2 inhibitors may be tested in selected patients with NMIBC.

[Urethral injuries secondary to implantation of penile prosthesis. Analysis of the causes, prevention and treatment]. / Lesioni uretrali da impianto di protesi peniena. Analisi delle cause, prevenzione e trattamento.

Urethral injuries due to penile prosthesis implant represent a rare complication of the intervention to position penile prosthesis, but unfortunately scientific literature about this is poor. This rare complication may occur during surgery and in the postoperative period, both early and late. It recognizes a variety of causes that may include anatomical or functional conditions, for example cavernosal fibrosis or outcomes of inflammations or previous urethral lesions and pathological sensibility due to diabetic neuropathy or other forms of neuropathy including those from spinal cord injury or myelopathy. This review evaluates the possible predisposing conditions, the clinical presentations, and the devices in the surgical procedures to use to minimize the risk of onset of this lesions and the measures to take if they occur.

Long term patient satisfaction and quality of life with AMS700CX inflatable penile prosthesis.

OBJECTIVE: Penile prosthesis implantation is the solution of choice in patients who have failed or present contraindication to the use of all conservative treatment for erectile dysfunction (ED). Overall, satisfaction rates are high, with more than 80% of patients and partners fully satisfied with cosmetic and functional result of surgery. Chronic postoperative pain, penile shortening, soft or hyposensitive glans, pencil like penis syndrome and difficulty to cycle the device represent the most common causes of patient's dissatisfaction. Satisfaction rates are better assessed with the use of validated questionnaires such as the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) The aim of our study was to analyze the long-term mechanical reliability of the AMS 700CX/CXM inflatable penile prosthesis and the patient's satisfaction rate using IIEF and EDITS questionnaire as standard reference. MATERIALS AND METHODS: A retrospective case notes review of all patients who have undergone implantation of a three pieces inflatable penile prosthesis AMS 700 CX and CXR between October 1997 and December 2010. Overall, 80 patients have undergone implantation of 3 pieces inflatable penile prosthesis AMS 700 CX InhibiZone. Patients have been administered the IIEF-5 and EDITS questionnaires in combination with a non validated 9 domain questionnaire that assesses penile rigidity, sensation, orgasmic function, frequency of intercourse, impact of surgery on the quality of life, satisfaction rate. RESULTS: Overall 10 years survival estimate according to the Kaplan Meier method of AMS 700 CX touch pump and AMS 700 CX momentary squeeze pump are respectively 77.6% and 82.5%. The median postoperative IIEF5 and EDITS score were respectively 21.46 and 73.11, which show a high level of satisfaction. 59 patients (90.8%) were able to cycle the device and were engaging in penetrative sexual intercourse. CONCLUSIONS: Penile prosthesis implantation yields excellent results in terms of cosmetic and functional outcome and therefore has a significant impact on patients' satisfaction, sex life and overall quality of life. Overall, long term reliability has been significantly improved and complication rates are low in the hands of experienced surgeons.

The interaction of celecoxib with MDR transporters enhances the activity of mitomycin C in a bladder cancer cell line.

BACKGROUND: An in vitro model was developed to understand if celecoxib could synergize with Mitomycin C (MMC), commonly used for the prevention of non-muscle invasive bladder cancer recurrence, and eventually elucidate if the mechanism of interaction involves multi drug resistance (MDR) transporters. METHODS: UMUC-3, a non COX-2 expressing bladder cancer cell line, and UMUC-3-CX, a COX-2 overexpressing transfectant, as well as 5637, a COX-2 overexpressing cell line, and 5637si-CX, a non COX-2 expressing silenced 5637 cell line, were used in the present study. The expression of COX-2 and MDR pumps (P-gp, MDR-1 and BCRP) was explored through western blot. The anti-proliferative effect of celecoxib and MMC was studied with MTT test. Three biological permeability assays (Drug Transport Experiment, Substrate Transporter Inhibition, and ATP cell depletion) were combined to study the interaction between MDR transporters and celecoxib. Finally, the ability of celecoxib to restore MMC cell accumulation was investigated. RESULTS: The anti-proliferative effect of celecoxib and MMC were investigated alone and in co-administration, in UMUC-3, UMUC-3-CX, 5637 and 5637si-CX cells. When administered alone, the effect of MMC was 8-fold greater in UMUC-3. However, co-administration of 1 µM, 5 µM, and 10 µM celecoxib and MMC caused a 2,3-fold cytotoxicity increase in UMUC-3-CX cell only. MMC cytotoxicity was not affected by celecoxib co-administration either in 5637, or in 5637si-CX cells. As a result of all finding from the permeability experiments, celecoxib was classified as P-gp unambiguous substrate: celecoxib is transported by MDR pumps and interferes with the efflux of MMC. Importantly, among all transporters, BCRP was only overexpressed in UMUC-3-CX cells, but not in 5637 and 5637si-CX. CONCLUSIONS: The UMUC-3-CX cell line resembles a more aggressive phenotype with a lower response to MMC compared to the wt counterpart. However, the administration of celecoxib in combination to MMC causes a significant and dose dependent gain of the anti-proliferative activity. This finding may be the result of a direct interaction between celecoxib and MDR transporters. Indeed, BCRP is overexpressed in UMUC-3-CX, but not in UMUC-3, 5637, and 5637si-CX, in which celecoxib is ineffective.

[Urethroplasty in hypoplastic-dysplastic corpus spongiosum and short urethra]. / Uretroplastica in paziente con grave incurvamento congenito e uretra corta secondari a corda ventrale e displasia del corpo spongioso.

Congenital penile curvature and chordee are a rare malformative condition most frequently associated with hypospadias, but varying degrees of penile curvature are observed with an orthotopic meatus. Disease becomes evident after puberty, when curvature becomes more apparent with erection. We present a case of a young man (16 years old), with ventral congenital penile curvature without hypospadias and with hypoplastic-dysplastic corpus spongiosum and short urethra, who could not have normal sexual intercourses. The patient underwent first-stage urethroplasty with urethral opening and graft of buccal mucosa and creation of a temporary hypospadic meatus. No post-operative complications were observed. There were no residual penile curvatures. Results are promising and satisfactory after the first surgical stage and provide a solid ground for the final reconstruction.

Bicalutamide failure in prostate cancer treatment: involvement of Multi Drug Resistance proteins.

Prolonged bicalutamide treatment induced pathology regression although relapses with a more aggressive form of prostate cancer have been observed. This failure could be due to androgen receptor mutation. In the present work we hypothesized an alternative mechanism responsible for bicalutamide failure involving activity of ATP-binding cassette (ABC) pumps such as P-glycoprotein, Breast Cancer Receptor Protein (BCRP), and Multi Resistant Proteins (MRPs) that extrude the androgen antagonist from the cell membrane. As experimental models androgen-dependent (LnCap) and androgen-independent (PC-3) prostate cancer cell lines have been employed. Bicalutamide has been tested in the cell lines mentioned above in the absence and in the presence of MC18, our potent P-glycoprotein/BCRP/MRP1 inhibitor. The results displayed that bicalutamide antiproliferative effect at 72 h was ameliorated in LnCap cells (EC(50) from 51.9+/-6.1 microM to 17.8+/-2.6 microM in the absence and in the presence of MC18, respectively) and restored in PC-3 cells (EC(50) from 150+/-2.4 microM to 60+/-3.5 microM in the absence and in the presence of MC18, respectively). Moreover, we established the contribution of each transporter employing stable transfected cells (MDCK) overexpressing P-glycoprotein or BCRP or MRP1 pump. The results displayed that P-glycoprotein and BCRP were involved in bicalutamide efflux while MRP1 was unable to bind the antiandrogen drug.

Contrast-enhanced multislice pneumo-CT-cystography in the evaluation of urinary bladder neoplasms.

PURPOSE: To evaluate the accuracy of contrast-enhanced multislice CT (MSCT) in the study of urothelial tumors after distension of the bladder with air. MATERIALS AND METHODS: We evaluated 43 consecutive patients with endoscopically proven bladder lesions. After air distension of the bladder, unenhanced pelvic and enhanced abdomino-pelvic scans were obtained with the following protocol: thickness 2.5mm x 4mm, increment 1mm, scan delay 40'' and 7-10 min. For each patient we considered the number, size, aspect (papillary or sessile) and contrast enhancement of lesions. Ureteral involvement and the presence of synchronous lesions in the excretory scan were also evaluated. MPR and virtual endoscopy images were reviewed in all cases. RESULTS: Bladder lesions were visualized in 39/43 cases. Compared to conventional cystoscopy, MSCT recognized single lesions in 31/33 patients, two lesions in 4/6, three in 2/2 and more than five foci in 2/2 patients. A papillary aspect was described in 44 cases while 11 lesions were sessile. Conventional Cystoscopy recognized six more lesions as compared with MSCT (four flat and two small papillary lesions). The detection rate for protruding lesions was 100% (52/52) for lesions>5mm and 60% (3/5%) for lesions<5mm. In four patients hydronephrosis was present, while in one case a synchronous lesion was evident in the renal pelvis. CONCLUSION: Contrast-enhanced MSCT with air distension of the urinary bladder is a safe and complete investigation to evaluate the local stage of bladder cancer and to evaluate the ureteral extension of the tumor, as well as the presence of synchronous lesions.

Quality of life evaluation by the EORTC QLQ-C30 questionnaire in patients treated with hormonal treatment in Italy. A QuABIOS group study.

OBJECTIVES: An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities. METHODS: Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment. RESULTS: 587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide. CONCLUSIONS: Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.

Human epididymal and prostatic tracts of vas deferens: different contraction response to noradrenaline stimulation in isolated organ bath assay.

In the present study epididymal and prostatic portions of human vas deferens were separately isolated and stimulated with exogenous noradrenaline to study their contractile properties. The results displayed that the epididymal tract produced a phasic-tonic response, while the prostatic strip produced only a phasic response suggesting a different functional role of each vas deferens segment. Moreover, it has been verified if alpha(1)-adrenoceptor antagonists doxazosin, alphuzosin and terazosin could differently block the noradrenaline response in each segment. Doxazosin, the most potent antagonist, displayed similar potency in epididymal and prostatic tract (pA(2)=8.51 and 8.42, respectively). Analogously, alphuzosin, although less potent than doxazosin, displayed in the same tracts a superimposed potency (pA(2)=7.25 and 7.30, respectively). In contrast with doxazosin and alphuzosin, terazosin displayed higher potency in blocking the contractile response in prostatic tract (pA(2)=7.67) than in epididymal segment (pA(2)=6.43). These results showed that alpha(1)-adrenoceptor antagonists doxazosin and alphuzosin, although with a different potency, did not discriminate between epididymal and prostatic segment while terazosin showed high potency in prostatic tract and only a moderate activity in epididymal section. Moreover, the biological model employed in our experiments could be a valid screening method to test the potential interferences of drugs indicated for bladder outlet obstruction with the peristaltic activity or the global tone of the human vas deferens.

Correlation between sigma2 receptor protein expression and histopathologic grade in human bladder cancer.

Sigma2 (sigma2) receptor proteins are overexpressed in several tissues and tumour cell lines. Although the biomolecular mechanism of this overexpression must be elucidated, sigma2 receptor was considered a potential biomarker for monitoring solid tumour proliferation. In this study, we verified first sigma2 receptor overexpression by saturation analysis with radioligand in six human bladder cancer specimens, then if a possible correlation could be established between sigma2 overexpression and tumour tissue stage and grade. The results displayed that sigma2 receptor protein was normally expressed in human bladder and overexpressed in the case of high-grade transitional cell carcinomas. Moreover, these receptors were undetected in a low-grade squamous cell carcinoma and in a very rare form of anaplastic, large cells plasmacytoid cancer.

Penile Doppler ultrasound assessment of the cavernous arteries.

OBJECTIVE: To evaluate the possible relationship between the basal and dynamic diameter of the cavernous arteries and altered peak diastolic (PDV) and systolic values (PSV) in patients undergoing penile Doppler ultrasound for differential diagnosis of erectile dysfunction (ED). MATERIALS AND METHODS: From December 2003 to December 2004 we examined 132 consecutive patients suffering from erectile dysfunction and 30 controls. All patients underwent penile Doppler ultrasound in basal and dynamic conditions and all the examinations were performed by measurements of the cavernous arteries diameters in basal and dynamic conditions. RESULTS: In the 30 healthy controls the mean cavernous arteries diameter was 0.82 mm (range 0.6-1.3 mm) on the right and 0.8 mm (range 0.5-1.25 mm) in basal conditions vs 1.30 mm (range 0.9-1.6 mm) on the right and 1.25 on the left (range 0.9 -1.60 mm) in dynamic conditions after injection of 10 microg. In the 132 patients with a diagnosis of organic ED, the mean diameter was 0.70 mm (range 0.3-1.3 mm) on the right and 0.76 mm (range 0.3-1.24) on the left in basal conditions vs 1.21 mm (range 0.8-1.93 mm) on the right and 1.24 mm (range 0.9-1.66 mm) on the left in dynamic conditions after injection of 10 microg. CONCLUSION: In our experience, assessment of the cavernous arteries in basal and dynamic conditions provides important additional data. Altered basal and dynamic values are predictive of anomalous PDV and PSV findings.

[Role of power Doppler in the differential diagnosis between organic and functional cavernovenous insufficiency in patients with erectile maintenance deficiency]. / Ruolo del power Doppler nella diagnosi differenziale tra incompetenza cavernovenosa organica e funzionale nei pazienti con deficit del mantenimento dell'erezione.

Dynamic penile eco colorDoppler (ECDP) shows limits of specificity in case of differential diagnosis between functional (adrenergic hypertone) and organic cavernovenous incompetence. The aim of this study is the evaluation of a new flow chart for venogenic erectile dysfunction diagnosis, including power Doppler (PD), avoiding the repetition of ECD with higher concentrations of PGE1. In fact this procedure is invasive, often painful and burdened by a consistent risk of priapism. Patients suspected of caverno-venous incompetence underwent PD during the ECD. 85 of them showed high telediastolic velocity but normal systolic peak flow. All these patient underwent PGE1 redosing, to a maximum of 40 micrograms. Patients with still suspicious ECD were administered RigiScan. 63 patients over 85 had good PD, while 22 had bad PD. Of the 63 patients with good PD, 60 (95%) had normal ECD after redosing, while in 3 (5%) of them the telediastolic velocity remained high. In these 3 patients RigiScan showed normal nocturnal rigidity in 2 cases, abnormal in 1. 18 patients (82%) of the 22 with bad PD never showed improvement of ECD and RigiScan resulted altered in 15. In our opinion concordance between 10 micrograms ECD and PD avoids redosing in demonstrating organic venogenic erectile dysfunction. If PD is good but ECD is altered, 10 micrograms re-dosing could help in differentiating organic or functional erectile dysfunction. The diagnostic flow chart, then, should always include PD.

[Incontinence after retropubic radical prostatectomy: correlation between ultrasonographic morphological data and urodynamic parameters]. / Incontinenza dopo prostatectomia radicale retropubica: correlazione tra dati morfologici ecografici e parametri urodinamici.

OBJECTIVE: The aim of this study is to evaluate the relationships existing between transrectal ultrasound and urodynamics in patients undergone radical retropubic prostatectomy and affected by stress incontinence. MATERIALS AND METHODS: 78 patients were suitabe for the study. They have been divided in three groups: group A, 18 incontinent patients (at least 1 pad a day); group B, 30 patients with occasional dribbling (no incontinence device needed); group C, 30 continent patients. All the patients have undergone urethral pressure profile (UPP), abdominal leak point pressure (ALPP) and transrectal ultrasound (TRUS). ultrasound has been performed injecting saline solution in the spongious and bulbar urethra to dilate it and better visualize a collapsed tract corresponding to the distal sphincter, that was measured. Different doctors performed TRUS and urodynamics, and each ignored the results of the other tests. RESULTS: The mean value of TRUS length of the collapsed urethral segment was 5.47 mm (range 4.9-6.0) for group A, 11.5 mm (9.5-12.9) for group B, 13.8 mm (10.4-14.7) for group C. the mean value of rest FUL was 36.6 (range 23-52) for group A, 31.7 (range 21-37) for group B, 13.8 (range 10.4-14.7) for group C. The mean value of stress FUL was 20.3 (range 5-29) for group A, 20.7 (range 18-27) for group B, 25.0 (range 20-35) for group C. The mean value of VLPP was 61.9 cm H2O for group A, 83.6 cm H2O for group B, > 90 cm H2O for group C. CONCLUSIONS: The ranges of values of VLPP were narrower and showed less overlap among the groups than UPP. TRUS length showed a good correlation with VLPP and permitted to differentiate incontinent patients from continent patients and patients with occasional dribbling. These data correlate well with the possible role of the length of the urethral stump and of damage to genitourinary diaphragm in post-prostatectomy incontinence.

[Tolerability to transperineal prostatic biopsy based on the number of specimens]. / Tollerabilità della biopsia prostatica transperineale in base ai numeri dei prelievi eseguiti.

Prostate biopsy is a fundamental step in the diagnostic flow chart of prostate cancer. We have evaluated the influence of the number of cores taken on the tolerability and morbidity of the transperineal ultrasound-guided prostate biopsy. We have compared a group of 240 pts undergone 16 core prostate biopsy to an historical cohort of 100 pts undergone 10 core prostate biopsy. All the patients in both groups have been investigated about tolerability and morbidity of the procedure. No significant differences emerge between the two groups, and then we conclude that the number of cores taken does not influence the safety and compliance to the transperineal biopsy. This is a significant advantage compared to transrectal biopsy, as the number of cores influences the detection rate of prostate carcinoma.