Riccardo Bartoletti

Orchiectomy and Nilutamide or Placebo as Treatment of Metastatic Prostatic Cancer in a Multinational Double-Blind Randomized Trial

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

The Role of Asymptomatic Bacteriuria in Young Women With Recurrent Urinary Tract Infections: To Treat or Not to Treat?

BACKGROUND Little is known about the role of asymptomatic bacteriuria (AB) treatment in young women affected by recurrent urinary tract infection (UTI). We aimed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI. METHODS A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospectively enrolled. Patients were split into 2 groups: not treated (group A, n = 312) and treated (group B, n = 361). Microbiological and clinical evaluations were performed at 3, 6, and 12 months. Quality of life was also measured. Recurrence-free rate at the end of the entire study period was the main outcome measure. RESULTS At baseline, the 2 most commonly isolated pathogens were Escherichia coli (group A, 38.4%; group B, 39.3%) and Enterococcus faecalis (group A, 32.7%; group B, 33.2%). At the first follow-up visit, there was no difference between the 2 groups (relative risk [RR], 1.05; 95% confidence interval [CI], 1.01-1.10), whereas after 6 months, 23 (7.6%) in group A and 98 (29.7%) in group B showed recurrence with a statistically significant difference (RR, 1.31; 95% CI, 1.21-1.42; P < .0001). At the last follow-up, 41 (13.1%) in group A and 169 (46.8%) in group B showed recurrence (RR, 3.17; 95% CI, 2.55-3.90; P < .0001). One patient in group A and 2 patients in group B were found to have pyelonephritis. CONCLUSIONS This study shows that AB should not be treated in young women affected by UTI, suggesting it may play a protective role in preventing symptomatic recurrence.

Urinary symptoms, quality of life and sexual function in patients with benign prostatic hypertrophy before and after prostatectomy: a prospective study

To evaluate urinary symptoms, sexual dysfunction and quality of life in patients with benign prostatic hypertrophy (BPH) before and after open prostatectomy, using the International Prostate Symptom Score (IPSS), the International Continence Society (ICS)‐‘BPH’ (ICS‐male, ICS‐sex and ICS‐QoL) and International Index of Erectile Function (IIEF) questionnaires.

Epidemiology and risk factors in urolithiasis.

Stone formation in the urinary tract affects about 5–10% of the population in industrialized countries, although it is very rare in other countries such as Greenland or Japan. The high incidence and recurrence rate contribute to making the urolithiasis a serious social problem. Nowadays, urolithiasis must be considered a ‘disease in evolution’ for several reasons, such as epidemiological changes, evolution of the methods used for diagnosis, and the treatment and prophylaxis of the population considered ‘at risk’ of stone disease. Some features of stone disease have changed over the last few years due to many social, economical and cultural factors that are described here. The increased prevalence of small urinary calculi has brought about a change in clinical symptoms, with frequent episodes of renal-ureteral colic, persistent pain and hydronephrosis. Similarly, the presence of residual fragments after extracorporeal shock wave lithotripsy has induced a radical change in the management of small calculi through the use of mini-invasive surgical techniques.

Chlamydia trachomatis infection is related to poor semen quality in young prostatitis patients.

BACKGROUND The impact of chronic prostatitis resulting from Chlamydia trachomatis infection on male fertility is controversial. OBJECTIVE To investigate the correlation between C. trachomatis infection and semen quality in young male patients affected by chronic prostatitis resulting from C. trachomatis infection and to evaluate the correlation between anti-C. trachomatis immunoglobulin (Ig) A against heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and semen parameters. DESIGN, SETTING, AND PARTICIPANTS All patients with clinical and instrumental diagnosis of chronic prostatitis underwent microbiological cultures for common bacteria, DNA extraction, mucosal and serum antibody evaluation for C. trachomatis, and semen parameter analysis. Western blot analysis of mucosal anti-C. trachomatis IgA was performed. INTERVENTIONS Subjects were split into two groups: Group A consisted of patients with chronic prostatitis resulting from common bacteria (uropathogens), and group B consisted of patients with chronic prostatitis resulting from C. trachomatis infection. MEASUREMENTS The relationship between C. trachomatis infection and semen parameters as well as the correlation among IgA levels, IgA characterisation, and semen analysis were determined. RESULTS AND LIMITATIONS We enrolled 1161 patients (mean age: 36.5 yr). Of these, 707 patients were placed in group A, and 454 were placed in group B. Significant statistical differences were reported between groups in terms of sperm concentration (p<0.001), percentage of motile sperm (p<0.001), and normal morphologic forms (p<0.001). Strong correlations between mucosal anti-C. trachomatis IgA and sperm concentration (p<0.001) and normal morphologic forms (p<0.001) were reported. Correlations among positivity to HSP60, HSP70, and sperm concentration (p<0.003) and normal morphologic forms (p<0.001) were also reported. CONCLUSIONS This study demonstrated the role of chronic prostatitis resulting from C. trachomatis in male fertility decrease, highlighting probable immunomediated damage to germinal cells because of C. trachomatis infections.

Long-term results of anterior and posterior urethroplasty with actuarial evaluation of the success rates.

PURPOSE We analyzed the long-term results of different urethroplasty techniques. MATERIALS AND METHODS We performed a retrospective review of 98 patients who underwent different procedures for anterior (78) and posterior (20) urethral strictures. Mean followup was 53 months. A total of 20 patients underwent end-to-end anastomosis (group 1), 30 underwent 1-stage procedures (group 2), 28 underwent 2-stage procedures (group 3), and 20 underwent bulboprostatic anastomosis (group 4). The results were analyzed using Kaplan-Meier curves and log rank test. RESULTS The success rate was 95% for group 1, 93.4% for group 2, 78.6% for group 3, and 70% for group 4. Statistical evaluation of the actuarial success rates failed to show significant differences among the 4 groups. CONCLUSIONS The stricture recurrences were uniformly distributed over time. Urethroplasty patients must be followed for the rest of their lives.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Can Early Single Dose Instillation of Epirubicin Improve Bacillus Calmette-Guerin Efficacy in Patients With Nonmuscle Invasive High Risk Bladder Cancer? Results From a Prospective, Randomized, Double-Blind Controlled Study

PURPOSE We evaluated the impact of epirubicin perioperative instillation in improving subsequent bacillus Calmette-Guerin instillation efficacy in high risk patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS Between January 2005 and June 2007, 161 patients affected by high risk nonmuscle invasive bladder cancer were enrolled in this prospective, randomized, controlled, double-blind study. A total of 80 patients were assigned to group A (perioperative epirubicin 80 mg/50 ml normal saline) plus delayed bacillus Calmette-Guerin instillations (5 x 108 colony-forming units in 50 ml saline) and 81 to group B (delayed bacillus Calmette-Guerin alone). The main outcome measures were time to first recurrence and recurrence rate. All data obtained from a median followup of 15.3 months in group A and 14.8 months in group B, were analyzed. RESULTS At the end of followup 46 of 80 patients in group A (57.5%) had no evidence of disease, just like 41 of 81 in group B (50.6%). No statistical difference was observed between the 2 groups in terms of recurrence rate (p = 0.82) or time to first recurrence (p = 0.095). Kaplan-Meier analysis of recurrence showed no significant differences between group A and group B (p = 0.0952). On multivariate analysis the early single dose instillation of epirubicin was not indicated as an independent prognostic factor (HR 0.50, 95% CI 0.32-1.18). CONCLUSIONS The present study showed no statistically significant differences in terms of disease-free time and recurrence rate between high risk patients with nonmuscle invasive bladder cancer who had undergone perioperative epirubicin instillation plus delayed bacillus Calmette-Guerin and those who had undergone delayed bacillus Calmette-Guerin alone.

Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections.

BACKGROUND Women suffering from recurrent urinary tract infections (rUTIs) are routinely treated for asymptomatic bacteriuria (AB), but the consequences of this procedure on antibiotic resistance are not fully known. The aim of this study was to evaluate the impact of AB treatment on antibiotic resistance among women with rUTIs. METHODS The study population consisted of 2 groups of women who had previously been enrolled in a randomized clinical trial: group A was not treated, and group B was treated. All women were scheduled for follow-up visits every 6 months, or more frequently if symptoms arose. Microbiological evaluation was performed only in symptomatic women. All women were followed up for a mean of 38.8 months to analyze data from urine cultures and antibiograms. RESULTS The previous study population consisted of 673 women, but 123 did not attend the entire follow-up period. For the final analysis, 257 of the remaining 550 patients were assigned to group A, and 293 to group B. At the end of follow-up, the difference in recurrence rates was statistically significant (P < .001): 97 (37.7%) in group A versus 204 (69.6%) in group B. Isolated Escherichia coli from group B showed higher resistance to amoxicillin-clavulanic acid (P = .03), trimethoprim-sulfamethoxazole (P = .01), and ciprofloxacin (P = .03) than that from group A. CONCLUSIONS This study shows that AB treatment is associated with a higher occurrence of antibiotic-resistant bacteria, indicating that AB treatment in women with rUTIs is potentially dangerous.

Adherence to European Association of Urology Guidelines on Prophylactic Antibiotics: An Important Step in Antimicrobial Stewardship

BACKGROUND The evolution of resistant pathogens is a worldwide health crisis and adherence to European Association of Urology (EAU) guidelines on antibiotic prophylaxis may be an important way to improve antibiotic stewardship and reduce patient harm and costs. OBJECTIVE To evaluate the prevalence of antibiotic-resistant bacterial strains and health care costs during a period of adherence to EAU guidelines in a tertiary referral urologic institution. DESIGN, SETTING, AND PARTICIPANTS A protocol for adherence to EAU guidelines for antibiotic prophylaxis for all urologic procedures was introduced in January 2011. Data for 3529 urologic procedures performed between January 2011 and December 2013 after protocol introduction were compared with data for 2619 procedures performed between January 2008 and December 2010 before protocol implementation. The prevalence of bacterial resistance and health care costs were compared between the two periods. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The outcome measures were the proportion of resistant uropathogens and costs related to antibiotic consumption and symptomatic postoperative infection. We used χ2 and Fishers exact tests to test the significance of differences. RESULTS AND LIMITATIONS The proportion of patients with symptomatic postoperative infection did not differ (180/3529 [5.1%] vs. 117/2619 [4.5%]; p=0.27). A total of 342 isolates from all patients with symptomatic postoperative infections were analysed. The rate of resistance of Escherichia coli to piperacillin/tazobactam (9.1% vs. 5.4%; p=0.03), gentamicin (18.3% vs. 11.2%; p=0.02), and ciprofloxacin (32.3% vs. 19.1%; p=0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after implementation (p<0.001). Antibiotic drug costs (€76,980 vs. €36,700) and costs related to postoperative infections (€45,870 vs. €29,560) decreased following introduction of the protocol (p<0.001). CONCLUSIONS Adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing post-operative infection rate and lowered the prevalence of resistant uropathogens. PATIENT SUMMARY We analysed the impact of adherence to European Association of Urology guidelines on antibiotic prophylaxis for all surgical urologic procedures on the prevalence of infections and resistant bacterial strains and on costs. We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the guidelines as an important part of antibiotic stewardship programmes.