Prognostic factors of 'high-grade' Ta bladder cancers according to the WHO 2004 classification: are these equivalent to 'high-risk' non-muscle-invasive bladder cancer?

OBJECTIVE: To determine the impact of prognostic factors of a series of high-grade Ta non-muscle-invasive bladder cancers (NMIBCs) according to the new International Society of Urological Pathology (ISUP) 1998/WHO 2004 grading system (previously classified as either TaG2 or TaG3). METHODS: One hundred and thirty-one high-grade Ta (105 G2 and 26 G3) cases were identified after independent review by two pathologists. Univariable and multivariable Cox regression models addressed recurrence and progression-free survival. Progression was defined as appearance of any T ≥1 recurrence after complete TUR (type 1) or occurrence of T ≥2 (type 2). RESULTS: Ten-year recurrence, type-1 and type-2 progression-free survival were 60, 75 and 95%, respectively. The previous grading system (G3 vs. G2) significantly predicted type 1 progression in the univariate model only. In the multivariate model, Ki67 was the only independent predictor of progression according to both definitions (HR = 5.25, p = 0.002 and HR = 6.16, p = 0.03, respectively). CONCLUSIONS: High-grade Ta NMIBC as defined by the WHO 2004 grading system cannot be equated with high-risk NMIBC. The risk of progression to muscle-invasive disease (type 2) is low, more in keeping with an intermediate-risk category of NMIBC. The previous WHO 1973 subcategorization into G2 and G3 is of little help in the prediction of outcome. Ki67 is a strong independent predictor of progression worthy of consideration for a clinical setting.

Prostate-specific antigen kinetics after I125-brachytherapy for prostate adenocarcinoma.

PURPOSE: To investigate a potential correlation between the achievement of a cut-off of nadir PSA (nPSA) after brachytherapy (BRT) with biochemical Disease-Free Survival (bDFS) and to define the rate of post-BRT PSA bounces. METHODS: Retrospective analysis was carried out in 105 consecutive patients affected with early-stage prostate adenocarcinoma who underwent (125)I BRT. Only patients with a minimum follow-up ≥24 months were included. Biochemical DFS was chosen as primary endpoint. RESULTS: At a median follow-up of 51.2 months, 3- and 5-year bDFS were 96.8 and 91.2%, respectively. Median time to biochemical failure (BF) was 54 months. By Kaplan-Meier analysis, patients achieving nPSA ≤ 0.35 ng/mL had significantly higher bDFS (3- and 5-year bDFS: 100 and 98.5 % vs. 83.3 and 66.7 %, respectively; p = 0.001). Bounce PSA occurred in 28.6% of patients, at a median time of 21.5 months. No BFs were observed in the bounce group. Achieving a nPSA ≤ 0.35 ng/mL was the only factor independently associated with long-term bDFS on both univariate (p = 0.000) and multivariate analysis (HR 3.82; p = 0.003). CONCLUSIONS: Patients attaining a nPSA ≤ 0.35 ng/mL are significantly more likely to experience long-term freedom-from-biochemical failure. Bounce PSA occurs in approximately 30% of patients. Time to onset of PSA increase seems the most reliable feature to distinguish bounce from failure. Tailored follow-up strategies are needed for patients at higher risk of recurrence, and caution is advised in interpreting an early increase in PSA levels in the first 24-30 months after BRT.

External validation of the preoperative Karakiewicz nomogram in a large multicentre series of patients with renal cell carcinoma.

PURPOSE: To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC). METHODS: Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration. RESULTS: A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 %, P < 0.001) and non-metastatic (92.2 vs. 88.1 %, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 % (95 % CI, 84.4-91.4) at 1 year, 87.0 % (95 % CI, 84.4-89.5) at 2 years, 84.7 % (95 % CI, 82.3-87.1) at 5 years, and 85.9 % (95 % CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot. CONCLUSION: The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting.

Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy: profile comparison.

OBJECTIVES: A dendritic cell-based cancer vaccine has recently received Food and Drug Administration approval in the USA based on its ability to prolong the survival of prostate cancer patients with advanced disease. However, tumor-mediated immunosuppressive mechanisms might represent an obstacle to optimal performance of this therapy. We have recently shown that monocytes from the blood of prostate cancer patients can fully mature to dendritic cells only after the tumor is removed. Here, we have tested the hypothesis that these tumor-driven monocytes correspond to the recently described subset of CD14(+) HLA-DR(low) immunosuppressor cells. METHODS: Prostate cancer patients were studied before and 1 month after prostatectomy. Pre- and postsurgical patients with colorectal cancer were also included for comparison. Flow cytometric analysis was applied to define CD14(-) HLA-DR(low) CD33(+) CD11b(+) (myeloid) and CD14(+) HLA-DR(low) (monocytic) suppressor cells. Interferon-γ release was used to assess the immunocompetence of lymphocytes. RESULTS: In both prostate cancer and colorectal cancer patients, the percentage of CD14(+) HLA-DR(low) cells was several-fold higher compared with normal subjects. This was not the case for CD14(-) HLA-DR(low) CD33(+) CD11b(+) cells. Furthermore, postsurgical normalization of CD14(+) HLA-DR(low) cells only occurred in prostate cancer patients. In all patients, the interferon-γ response of T lymphocytes to phorbolmyristate acetate-ionomycin was higher compared with normal donors, but it was further increased after tumor ablation only in prostate cancer patients. CONCLUSIONS: The direct link between CD14(+) HLA-DR(low) increase and presence of primary tumor suggests a distinguishing immunosuppressive profile of prostate cancer. This observation supports the principle that the appropriate setting for prostate cancer vaccine therapy is a minimal disease status.

Prostatectomy restores the maturation competence of blood dendritic cell precursors and reverses the abnormal expansion of regulatory T lymphocytes.

OBJECTIVE: To verify the presence of deviated dendritic cell (DC) precursors and of suppressor lymphocytes (Treg) in tumor bearing prostate cancer (PCa) patients and to monitor the corrective effect of tumor ablation. METHODS: Monocytes isolated from the blood of patients before and 1 month after prostatectomy were allowed to reach complete maturation (mDC) ex vivo in a clinical grade two-step process. T-regulatory cells were identified in the lymphocyte cell fraction by the CD4(+)CD25(high)FoxP3(+)/CD4(+)CD25(high)CD127(low/-) phenotype. RESULTS: Despite loss of the monocytes marker CD14, cytokine-matured DCs of tumor bearing patients expressed lower levels of the costimulatory molecule CD80 and of the maturation markers CD83 and CCR7 compared to mDC of normal subjects (NS, P = 0.001, 0.001, and 0.008, respectively). Prostatectomy restored CD80, CD83, and CCR7 expression to values not different from those of NS (P = 0.15, 0.60, and 0.71) and significantly higher than those of the pre-surgery state (CD83, P = 0.0003 and CCR7, P = 0.002). The frequency of Tregs, identified as either CD4 + CD25(high)FoxP3(+) or CD4(+)CD25(high)CD127(low/-), was significantly higher in pre-surgery patients than in NS (P = 0.0001 and 0.0003) and significant recovery of the CD4(+)CD25(high)CD127(low/-) (P = 0.0005) was observed after surgery. CONCLUSIONS: The presence of defective DC precursors and suppressor lymphocytes in the tumor-bearing, but not tumor-free stage, positions the latter as the ideal setting for clinical success of PCa vaccine therapy.

Is there a prostate-specific antigen upper limit for radical prostatectomy?

OBJECTIVE: • To assess the feasibility of radical prostatectomy (RP) in a series of patients with prostate cancer with very high prostate-specific antigen (PSA) levels by comparing the clinical outcomes of different PSA thresholds (20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL, respectively). PATIENTS AND METHODS: • Within a multicentre European retrospective database of 712 RP in patients with a baseline PSA level >20 ng/mL, we identified 48 patients with prostate cancer with a preoperative PSA level >100 ng/mL, 137 with a PSA level between 50.1 and 100 ng/mL and 527 with PSA values between 20.1 and 50 ng/mL. • Comparisons between groups were performed using chi-square test, analysis of variance and Kaplan-Meier analysis with log-rank test. RESULTS: • Ten-year projected cancer-specific survival (79.8% in the PSA >100 ng/mL group vs 85.4% in the PSA 50.1-99 ng/mL group vs 90.9% in the PSA 20.1-50 ng/mL interval; P = 0.037) but not overall survival (59.6% in the PSA >100 ng/mL group vs 71.8% in the PSA 50.1-99 ng/mL group vs 75.3% in the PSA 20.1-50 ng/mL interval; P = 0.087) appeared significantly affected by the different PSA thresholds. • At a median follow-up of 78.7 months, 25.8%, 6.6% and 8.3% of patients in the PSA level groups for 20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL respectively, were cured by surgery alone. CONCLUSIONS: • Ten-year cancer-specific survival, while showing significant reduction with increasing PSA values intervals, remain relatively high even for PSA levels >100 ng/mL. • As part of a multimodal treatment strategy, RP may therefore be an option, even in selected patients with prostate cancer whose PSA level is >100 ng/mL.

Pathological features and adverse prognosis of a contemporary series of neuroendocrine bladder tumours.

OBJECTIVE: Neuroendocrine bladder tumours are rare entities known for their aggressive behaviour. The aim of this study was to retrospectively evaluate the outcome of a contemporary series of 14 consecutive bladder neuroendocrine neoplasms observed at 2 institutional hospitals. MATERIALS AND METHODS: The charts of patients with a pathological diagnosis of neuroendocrine bladder tumours observed at 2 institutions in the last 5 years were reviewed. Fourteen cases were retrieved. The main endpoint was to evaluate the pathological features and the cancer-specific survival (CSS) of the cohort. Subanalysis of survival based on the type of treatment received was attempted. RESULTS: Mean age was 70.2 years. The rate of metastatic disease at diagnosis was 57.1%. Mean follow-up was 13.7 months (95% CI 5.1-22.3). The 6-month CSS rate was 57.1%, while the 2-year CSS rate was 21.4%. CSS and overall survival rates overlapped. The median survival for the cohort was 7 months. There was no statistically significant difference in survival between patients who underwent surgery and those who did not. CONCLUSION: Neuroendocrine bladder tumours remain a disease with an extremely unfavourable prognosis. The impact of radical surgery on survival remains questionable. Patients harbouring this rare bladder cancer should be referred for trials assessing neoadjuvant and adjuvant systemic treatment strategies.

Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study.

INTRODUCTION: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of italian centers. PATIENTS AND METHODS: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines. RESULTS: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%. CONCLUSION: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices.

Pharmacokinetic study to optimize the intravesical administration of gemcitabine.

OBJECTIVES: To assess in a phase II pharmacokinetic study whether different pH levels, dilution volumes and exposure times affect intracellular bioavailability and systemic absorption of gemcitabine. SUBJECTS AND METHODS: Six arms of three patients each with a non-muscle-invasive bladder cancer (NMIBC) were planned to receive six combinations of two different dilution volumes (50 mL vs 100 mL), two pH levels (2.5-3.5 vs 5.5) and two exposure times (1 h vs 2 h) of the study drug. Blood samples were taken before, during and 1 h after drug instillation. Cold biopsy specimens from the exophytic tumor, its base of implant and a macroscopically healthy mucosa were taken during transurethral resection. High-pressure liquid chromatography/high-resolution mass spectrometry (HPLC/HRMSn) analysis of plasma and tissue samples was used to determine concentrations of gemcitabine (dFdC) and its inactive metabolite (dFdU). RESULTS: The arm at pH 5.5 in 50 mL was withdrawn as 2000 mg dFdC are insoluble in these conditions. The different instillation conditions resulted in negligible plasma dFdC concentrations but significant differences in intracellular content and metabolism of dFdC. The lowest intratissue concentration of dFdC was detected in a 50 mL solution at a pH of 2.5-3.5 kept in the bladder for 1 h (standard arm). A pH 5.5 solution in 100 mL with a 2-h exposure favored the maximal intratumoral dFdC absorption which was 90 times higher than that recorded in the standard arm. CONCLUSIONS: The most commonly reported administration scheme of gemcitabine produced the lowest tissue bioavailability of dFdC. Other combinations of pH, dilution volume and duration of instillation proved more advantageous and merit testing in clinical trials.

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.

Primary bladder phaeochromocytoma diagnosed by a vet.

Bladder phaeochromocytomas are rare neuroendocrine neoplasms whose diagnosis can be missed in spite of their rather suggestive presentation. It is mandatory to collect a thorough medical history and to recognize their typical symptoms. This study reports the case of a woman, treated for hypertensive crisis, who was diagnosed with bladder phaeochromocytoma thanks to a vet noting her fainting after micturition.

Effect of finasteride on the sensitivity of PSA to detect prostate cancer in rebiopsy series.

OBJECTIVES: To evaluate, in a prospective study, the diagnostic accuracy of PSA in patients with a prior negative prostate biopsy who were given finasteride for 6 months. MATERIALS AND METHODS: 91 men with prior negative biopsy findings, including HGPIN and excluding ASAP, were instructed to take finasteride for 6 months. All patients were evaluated at study onset and after 6 months by clinical examination, digital rectal examination (DRE), International Prostate Symptom Score (IPSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NHI-CPSI). Prostate biopsy was repeated at 6 months. PSA levels were measured at baseline and after 1, 3 and 6 months. We calculated the receiver operating characteristics (ROC) curve of PSA under the effect of finasteride for detecting prostate cancer. RESULTS: The median PSA level decreased similarly both in those with prostate cancer and in those without findings of cancer. There was no statistically significant difference between the two groups. The areas under the ROC curve (AUC) of PSA at study onset and after 6 months of therapy with finasteride were, respectively, 0.48 (95% CI 0.36-0.61) and 0.54 (95% CI 0.42-0.66). There was no statistically significant difference between the two areas. CONCLUSIONS: The results of our study show that PSA itself has a low diagnostic accuracy for detecting prostate cancer in men with prior negative prostate biopsy findings. Finasteride does not seem to improve the accuracy of PSA in this particular population of patients.

Binding of prostate-specific membrane antigen to dendritic cells: a critical step in vaccine preparation.

BACKGROUND AIMS: Dendritic cell (DC)-based vaccines hold promise as a safe therapy for prostate cancer (PCa), and prostate-specific membrane antigen (PSMA) fulfils the requirements for a tumor-associated antigen (TAA) to be clinically effective. We evaluated the actual binding of selected HLA-A2-restricted PSMA peptides to HLA class I molecules on ex vivo-generated mature (m) DC. METHODS: mDC were generated from peripheral monocytes of HLA-A2 normal donors. The PSMA peptides PSMA(711) (ALFDIESKV), PSMA(27) (VLAGGFFLL) and PSMA(663) (MMNDQLMFL) were selected based on computer-assisted prediction programs, documented CTL epitope activity or previous use in clinical trials. The model cell line T2 and the clinical grade (CD83+ CCR7+) mDC were pulsed with fluorescein (FL)-conjugated peptides and an anti-HLA-A2 monoclonal antibody (MAb) and analyzed. RESULTS: Flow cytometry analysis showed best binding efficiency to be by PSMA(27.) Confocal microscopy confirmed coincident fluorescence emission of HLA-A2 MAb and FL-PSMA(27). Virtual co-localization of PSMA(27) and HLA class I molecules was supported further by fluorescence resonance energy transfer (FRET) analysis. The clinical relevance of our findings has to be validated in vivo. CONCLUSIONS: The present report is the first to score selected PSMA peptides based on their detectable binding to mDC. It identifies PSMA(27) as the choice candidate among other PSMA peptides and it should be included in developing DC vaccine protocols for HLA-A2 PCa patients.

A pilot phase-II prospective study to test the 'efficacy' and tolerability of a penile-extender device in the treatment of 'short penis'.

OBJECTIVE: To assess a commonly marketed brand of penile extender, the Andro-Penis(R) (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. PATIENTS AND METHODS: Fifteen patients were required to test the efficacy of the device, assuming an effect size of >0.8. Eligible patients were counselled how to use the penile extender for at least 4 h/day for 6 months. Penile dimensions were measured at baseline and after 1, 3, 6 and 12 months (end of study). The erectile function (EF) domain of the International Index of EF was administered at baseline and at the end of the study. Treatment satisfaction was assessed using an institutional unvalidated five-item questionnaire. RESULTS: After 6 months the mean gain in length was significant, meeting the goals of the effect size, at 2.3 and 1.7 cm for the flaccid and stretched penis, respectively. No significant changes in penile girth were detected. The EF domain scores improved significantly at the end of study. Treatment satisfaction scores were consistent with acceptable to good improvement in all items, except for penile girth, where the score was either 'no change' or 'mild improvement'. CONCLUSIONS: Penile extenders should be regarded as a minimally invasive and effective treatment option to elongate the penile shaft in patients seeking treatment for a short penis.

Use of penile extender device in the treatment of penile curvature as a result of Peyronie's disease. Results of a phase II prospective study.

INTRODUCTION: Pilot experiences have suggested that tension forces exerted by a penile extender may reduce penile curvature as a result of Peyronie's disease. AIM: To test this hypothesis in a Phase II study using a commonly marketed brand of penile extender. METHODS: Peyronie's disease patients with a curvature not exceeding 50 degrees with mild or no erectile dysfunction (ED) were eligible. Fifteen patients were required to test the efficacy of the device assuming an effect size of >0.8, consistent with an "important" reduction in penile curvature. Changes in penile length over baseline and erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) constituted secondary end points. MAIN OUTCOME MEASURES: Patients were counselled on the use of the penile extender for at least 5 hours per day for 6 months. Photographic pictures of the erect penis and measurements were carried out at baseline, at 1, 3, 6, and 12 months (end of study). The IIEF-EF domain scores were administered at baseline and at the end of study. Treatment satisfaction was assessed at end of study using a nonvalidated institutional 5-item questionnaire. RESULTS: Penile curvature decreased from an average of 31 degrees to 27 degrees at 6 months without reaching the effect size (P = 0.056). Mean stretched and flaccid penile length increased by 1.3 and 0.83 cm, respectively at 6 months. Results were maintained at 12 months. Overall treatment results were subjectively scored as acceptable in spite of curvature improvements, which varied from "no change" to "mild improvement." CONCLUSIONS: In our study, the use of a penile extender device provided only minimal improvements in penile curvature but a reasonable level of patient satisfaction, probably attributable to increased penile length. The selection of patients with a stabilized disease, a penile curvature not exceeding 50 degrees, and no severe ED may have led to outcomes underestimating the potential efficacy of the treatment.

Fatal haematuria in a patient with an orthotopic neobladder and chronic liver failure.

Haematuria in orthotopic neobladder can be due to upper urinary tract recurrence of the primary bladder tumour, the rare occurrence of a primary bowel tumour or benign conditions such as stones and infections. We report the case of a 60-year-old man with chronic hepatopathy who suffered severe bleeding from neobladder varices, which ultimately led to his death.

Prognostic factors in a prospective series of papillary renal cell carcinoma.

OBJECTIVE: 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. PATIENTS AND METHODS: Forty-six patients with PRCC (median follow-up 40 months) diagnosed in one institution from 1989 to 2002 were prospectively followed until May 2006. The pathology was reviewed, the PRCC subtyped (type 1 and 2) and immunohistochemistry assessed for MIB-1, vascular endothelial growth factor (VEGF), CD31 and c-met oncogenic protein, by a referee pathologist. Prognostic values were estimated by fitting a Cox model. RESULTS: The 5-year survival rate was 49.5%; type 2 histology was predominant and was almost significant in the univariate analysis. Stage and MIB-1 were significant prognostic factors only in the univariate model, while the Cox model identified only the Fuhrman grade as an independent predictor of survival (hazard ratio 3.054; P = 0.007). MET expression, CD31 and VEGF had no prognostic utility. CONCLUSION: These patients with PRCC followed prospectively fared worse than in previously reported series. The Fuhrman grade was the sole independent predictor of survival.

New drugs currently available in non-muscle invasive bladder cancer: update on gemcitabine studies.

Intravesical gemcitabine has been tested in several phase I studies. The 2000 mg dose of gemcitabine in 50/100 ml normal saline when administered intravesically for up to 2 hours once a week for 6 weeks has unremarkable systemic and local side effects and therefore should be considered the most convenient schedule. Phase II studies have assessed the activity of intravesical gemcitabine on a marker lesion in intermediate risk non-muscle invasive bladder cancer (NMIBC), showing complete responses in up to 60% of cases. Few attempts have been made to test the activity of intravesical gemcitabine in high risk NMIBC achieving unexpected complete responses in BCG refractory CIS. Initial trials have also documented "clinically relevant" responses in prophylaxis. The current level of evidence indicates that gemcitabine possesses clinical activity but further confirmation is awaited from additional exploratory phase II and preferably phase III trials.

Comparison between two commercially available chromogranin A assays in detecting neuroendocrine differentiation in prostate cancer and benign prostate hyperplasia.

BACKGROUND: Chromogranin A (CgA) is the neuroendocrine (NE) marker most frequently employed in detecting NE differentiation in prostate cancer patients, either at the tissue level or in the general circulation. METHODS: We compared the two commercially CgA assay kits in detecting NE differentiation, in benign hyperplasia (BPH) or prostate cancer (PC) patients (pts). 170 pts with BPH, 107 with BPH+inflammation, and 136 PC pts entered the study. CgA was measured in each patient with the immunoradiometric assay (IRMA) and with the enzyme-linked immunoabsorbent assay (ELISA). RESULTS: A moderate relationship was found between CgA measured with IRMA and ELISA in the whole population (Spearman's R=0.65, p<0.05), in BPH pts (R=0.76, p<0.05), in BPH+inflammation pts (R=0.53, p<0.05) and in PC pts (R=0.60, p<0.05). Twenty-two out of 62 pts (35.4%) with elevated ELISA CgA did not have increased IRMA CgA; by contrast, 21/61 pts (34.4%) with elevated IRMA CgA were not recognized as abnormal by the ELISA kit. CONCLUSIONS: CgA measured by the two assays provided a significant discordance rate, suggesting that the two kits might elicit different information.

Male and female sexual dysfunction (SD) after radical pelvic urological surgery.

Major pelvic urological surgery comprises radical prostatectomy and radical cystectomy in the male patient and radical cystectomy in the female. Postsurgical sexual dysfunction (SD) has been reported with a high prevalence in both sexes and is becoming increasingly important in the patient's view as a result of improved cancer prognosis, refinements in surgical technique, and increased awareness of quality of life aspects that involve sexual satisfaction. The pathophysiology of the problem is essentially related to the disruption of the nerves during the procedure, although a vascular impairment may also be implicated. Nerve-sparing surgery enables the recovery and/or maintenance of sexual functioning in a significant proportion of patients and it is now also adopted for women. Validated questionnaires to assess preoperative baseline sexual function and postoperative outcomes have become available and their use in clinical practice should be promoted. A number of erectile aids are available to treat postsurgical male erectile dysfunction successfully. As far as female SD is concerned, a number of potential treatment options is currently under investigation.