Alessandro Tizzani

Morbidity and Quality of Life in Elderly Patients Receiving Ileal Conduit or Orthotopic Neobladder After Radical Cystectomy for Invasive Bladder Cancer

OBJECTIVES The objectives of the study were to evaluate morbidity, survival, and quality of life (QoL) in elderly patients with invasive bladder cancer who received an orthotopic neobladder or an ileal conduit. METHODS The charts of 85 patients, aged 75 or older (median age 78), who had received an ileal conduit (n = 53) or an orthotopic neobladder (n = 32) after radical cystectomy at 3 Italian institutions in the period January 2000 to September 2004 were retrospectively reviewed. Perioperative and postoperative complications were recorded, as well as survival data at last follow-up. QoL was evaluated in 34 of 37 patients who were alive at the time of analysis by using the European Organisation for Research and Treatment of Cancer (EORTC) instruments quality of life questionnaire C30 (QLQ-C30) and QLQ-muscle-invasive bladder cancer module (QLQ-BLM). RESULTS Multiple regression analysis showed that stage significantly affected survival whereas the type of urinary diversion did not. Global Health Status (GHS) scores in the neobladder group were higher than in the ileal conduit group but the difference was not statistically significant. The scores of all the QLQ multi-item scales and single-item measures were comparable in the 2 groups. Overall, 56% and 25% daytime and nighttime complete continence rates were observed in patients with an orthotopic neobladder. CONCLUSIONS The results of our retrospective analysis suggest that an orthotopic neobladder can be suitable for elderly patients with no additional morbidity compared with an ileal conduit. Both types of diversion seem to result in acceptable scores for most aspects of QoL, including urinary symptoms and continence rate. These figures may be helpful in the preoperative counselling of elderly patients with bladder cancer.

Outcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients

BACKGROUND Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary. OBJECTIVE Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] > or = 8 or clinical stage 3-4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20. DESIGN, SETTING, AND PARTICIPANTS In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy. MEASUREMENTS Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer-specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied. RESULTS AND LIMITATIONS Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p<0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS < or =7 resulted in 10-yr PCSM of 5%; when associated with bGS > or =8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities. CONCLUSIONS PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling.

Identifying the Best Candidate for Radical Prostatectomy Among Patients with High-Risk Prostate Cancer

BACKGROUND The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. OBJECTIVE To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. DESIGN, SETTING, AND PARTICIPANTS We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins. INTERVENTION All patients underwent radical retropubic prostatectomy and PLND. MEASUREMENTS Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates. RESULTS AND LIMITATIONS Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram. CONCLUSIONS Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.

Critical issues in current comparative and cost analyses between retropubic and robotic radical prostatectomy

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A pilot phase‐II prospective study to test the ‘efficacy’ and tolerability of a penile‐extender device in the treatment of ‘short penis’

To assess a commonly marketed brand of penile extender, the Andro‐Penis® (Andromedical, Madrid, Spain), widely used devices which aim to increase penile size, in a phase II single‐arm study powered to detect significant changes in penile size, as despite their widespread use, there is little scientific evidence to support their potential clinical utility in the treatment of patients with inadequate penile dimensions.

Prognostic factors in a prospective series of papillary renal cell carcinoma

To prospectively assess the clinical outcome of a series of papillary renal cell carcinomas (PRCCs) to identify possible prognostic clinical variables and tumour markers, as previous retrospective series of PRCC do not provide unanimous results on the prognostic utility of clinicopathological variables.

Circadian antidiuretic hormone variation in elderly men complaining of persistent nocturia after urinary flow obstruction removal

Persistence of nocturia after prostatic resection in healthy patients without symptoms referred to residual bladder instability and to pathological polyuria seems to be caused by an increased urine production at night. The more accreditate mechanism involved is the relevant decreased ADH secretion pattern which occurs at night. In our study, patients with nocturnal poliuria showed significantly low plasmatic vasopressin levels compared with a control group. The aim of this study was to evaluate whether the persistence of nocturia after prostatic resection in healthy patients, without symptoms referred due to residual bladder instability and important polyuria, could be due to a decrease or a lack of increase in antidiuretic hormone (ADH) nocturnal levels following increased urine production at night. Serum ADH, atrial natriuretic peptide (ANP) and osmolality were assessed at 4-h intervals in 12 patients complaining of residual nocturia (group A) and in a control group of 13 patients who had undergone a complete resolution of nocturia after prostate ablation (group B). In the 25 patients involved in the study (mean age 65.8 years), no significant differences were observed in the two groups concerning mean age (67.5 years for group A, 64 years for group B). Mean nocturnal urine volume (1080 +/- 490 ml) in group A patients was significantly higher than in group B (500 +/- 100 ml) (p < 0.001), while no significant differences were found in diurnal diuresis. Mean plasma vasopressin levels of the 12 patients showing an increased nocturnal micturition were found to be significantly lower at all 4-h intervals when compared with the control group (p < 0.05). Individual fluctuations in serum osmolality were slight and insignificant within the normal range in all patients. The diurnal variation of plasma atrial natriuretic peptide was within the reference limits for all subjects during the 24-h period. Our results lead us to believe that residual nocturia after prostatic resection seems to be caused by an increased urine production at night due to a decreased ADH secretion pattern.

ERCC1 haplotypes modify bladder cancer risk: a case-control study.

Bladder cancer risk is highly influenced by environmental and/or predisposing genetic factors. In the last decades growing evidence of the major role played by DNA repair systems in the developing of bladder cancer has been provided. To better investigate the involvement of DNA repair genes previously reported to be significantly associated with bladder cancer risk, we examined in a case-control study (456 cases and 376 hospital controls) 36 single nucleotide polymorphisms (SNPs) in 10 DNA repair genes, through a better gene coverage and a deep investigation of the haplotype role. A single SNP analysis showed a significantly increased risk given by XRCC1-rs915927 G allele (OR=1.55, CI 95% 1.02-2.37 for dominant model) and a protective effect of the rare alleles of 3 ERCC1 SNPs: rs967591 (OR=0.66, CI 95% 0.46-0.95), rs735482 (OR=0.62, CI 95% 0.42-0.90) and rs2336219 (OR=0.63, CI 95% 0.43-0.93). Haplotype analysis revealed that cases had a statistically significant excess of XRCC3-TAGT and ERCC1-GAT haplotypes, whereas ERCC1-AAC, MGMT-TA, XRCC1-TGCC and ERCC2-TGAA haplotypes were significantly underrepresented. Together with other published data on large case-control studies, our findings provide epidemiological evidence supporting a link between DNA repair gene variants and bladder cancer development, and suggest that the effects of high-order interactions should be taken into account as modulating factors affecting bladder cancer risk. A detailed characterization of DNA repair genetic variation is warranted and might ultimately help to identify multiple susceptibility variants that could be responsible for joint effects on the risk.

Bladder Pheochromocytoma: A 3-Year Follow-Up afterTransurethral Resec tion (TURB)

We report a case of a 75-year-old female with pheochromocytoma of the bladder. Clinical evaluation included ultrasonography, intravenous pyelography, CT scan, I-MIBG scintiscan. A transurethral resection was performed for a exophytic tumor of 2 cm diameter. The histological result indicated the diagnosis of bladder pheochromocytoma. Three years later the patient remains disease free. Preoperative diagnosis is established by determination of blood and urine levels of catecholamines and their metabolites is a nonspecific diagnostic tool. The sensitivity of CT scan is 82%. Iodine-methyliodobenzylguanidine (I-MIBG), used by scintiscanning, specifically accumulates in pheochromocytomas. Life-long follow-up is necessary to diagnose late recurrences.

Efficacy and Safety of Tadalafil 20 mg on Demand vs. Tadalafil 5 mg Once-a-Day in the Treatment of Post-Radiotherapy Erectile Dysfunction in Prostate Cancer Men: A Randomized Phase II Trial

INTRODUCTION The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated. AIM To compare the efficacy and safety of on-demand 20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC). METHODS Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks. Main Outcome Measures.  Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates. RESULTS Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm. CONCLUSIONS In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients.