Prognostic significance of metallothionein expression in renal cell carcinoma

BACKGROUND: Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. PATIENTS AND METHODS: The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). RESULTS: Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. CONCLUSIONS: The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter

Phosphodiesterase-5 inhibitors in the treatment of lower urinary tract symptoms and benign prostatic hyperplasia

Background: Lower urinary tract symptoms (LUTS) are prevalent in ageing men and commonly coexist with erectile dysfunction. Preclinical data on the involvement of the nitric oxide/cyclic guanosine monophosphate/phosphodiesterase pathway in the regulation of lower urinary tract smooth muscle activity have been available for several years. Phosphodiesterase 5 (PDE5) is expressed in the prostate and bladder and PDE5 inhibitors have been shown to relax precontracted muscle strips from these organs. Objective: To assess the clinical benefit of PDE5 inhibitors in LUTS treatment. Methods: Clinical trials published as full papers in peer-reviewed journals were reviewed. Results/conclusion: Data from early clinical trials show a consistent improvement in International Prostate Symptom Score with PDE5 inhibitor therapy in men presenting with erectile dysfunction or LUTS. The lack of significant changes in objective outcomes in these trials, despite symptomatic improvement, reflects gaps in our understanding of LUTS pathophysiology/PDE5 inhibitors’ mechanism of action. More trials are needed to further establish the clinical benefit of PDE5 inhibitors in LUTS treatment and to set criteria for patient and drug selection

The effectiveness of a scientific symposium to change urologists' attitude towards treatment of LUTS/BPH

Purpose The use of interactive voting systems in continuing education helps to evaluate the alteration in the audience’s views after a presentation. This study was designed to evaluate whether urologists’ attitude towards management of benign prostate hyperplasia can be changed, and to estimate objectively the achievement of educational goals by using an interactive voting system. Methods The audience attitude was repetitively estimated by responding to questions using wireless keypads. Educational goal achievement was calculated by adding the percentage of those changing their opinion from “wrong” to “right” and that of those insisting on their initial “right” opinion. Results Giving a “wrong” answer and the probability of opinion change were independent of age and board certification. Being initially on the “wrong” side resulted in a greater probability of opinion change. The educational goals were achieved in 20.8-86.2% of cases. Conclusions Satellite symposia are helpful learning environments. The use of an interactive voting system may help to evaluate objectively the achievement of educational goals

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the anti-bFGF antibody. In contrast, the same staining in terazosin-treated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy

Purpose: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. Patients and methods: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. Results: Pre-operative total IPSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups, Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). Conclusion: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery

Effect of a Hypercholesterolemic Diet on Serum Lipid Profile, Plasma Sex Steroid Levels, and Prostate Structure in Rats

OBJECTIVES The purpose of this study was to examine the impact of a hypercholesterolemic diet (HD) on serum lipid profile, plasma sex steroid levels, and ventral prostate structure in rats. METHODS Beginning at 120 days of age, male Wistar rats were fed for 5 months with either standard rat chow (15 animals) or standard chow enriched with 4% cholesterol and 1% cholic acid (15 animals). The body and ventral prostate weights (VPWs), plasma sex steroid levels, and lipid profiles were determined, and prostate morphology in fixed tissue sections were studied. RESULTS The body weight of rats fed with HD did not differ from that of controls. However, both absolute and relative VPWs of HD animals were significantly lower than those of controls. HD resulted in significant elevation in total serum cholesterol and LDL levels, whereas HDL and triglyceride levels were comparable. Plasma total testosterone and estriol levels did not differ between groups, but their free fraction, along with sex hormone-binding globulin levels, were significantly affected. HD also affected the microscopic structure of the ventral prostate. Epithelial cells of the distal area formed papillary projections within the acinar lumen and had more cytoplasm than controls. In most cases, vesicular formations within the cytoplasmic area were also noted. CONCLUSIONS Hypercholesterolemia causes marked changes in the ventral prostate, serum lipid profile, and plasma sex steroid profile in rats and possibly alters prostate morphology by affecting the sex steroid axis, thus contributing to prostatic disease pathogenesis. UROLOGY 76: 1517.e1-1517.e5, 2010. (C) 2010 Elsevier Inc

Beta-adrenergic receptor blockade and prostate peptide growth factor expression in the rat

Results: At sacrifice, body weight as well as ventral prostate weight and prostate morphology were not significantly affected by propranolol treatment. Stromal elements and the majority of prostatic epithelial cells in control animals demonstrated positive staining for the anti-bFGF antibody, while positive staining for TGF beta was seen only in epithelial cells. Propranolol treatment resulted in considerable decrease of bFGF staining intensity in both stromal and epithelial cells, while the immunostaining pattern for TGF beta was almost abolished. Results and Conclusions: The results from this study provide evidence to suggest that prolonged propranolol treatment affects peptide growth expression in the rat ventral prostate as in other tissues, and confirms the notion that autonomic nervous system controls, at least partly, prostate gland functional characteristics. Moreover, it may also affect prostate homeostasis by intervening in stromal-epithelial interaction through alterations in the expression of peptide growth factors without affecting prostate volume

Patient awareness of smoking as a risk factor for bladder cancer

Data on general population’s and bladder cancer patients’ perception of smoking as a risk factor for bladder cancer are limited. To determine urological patients’ awareness of smoking as a risk factor for bladder cancer. This prospective observational study included 202 consecutive urological inpatients, using a structured questionnaire. We evaluated urological patients’ awareness of smoking as a risk factor for bladder cancer and other smoking-related pathologies. Smoker-bladder cancer patients were asked whether they believed that smoking was related to their present bladder problem, whether their treating urologist had ever advised them on the same, and whether they intended to quit. Only 118 of 202 patients (58.4%) stated that they were aware of smoking as a risk factor for bladder cancer, as apposed to 94.6% for chronic obstructive pulmonary disease, 91.6% for heart and vascular problems, and 92.1%, for lung cancer. Perception was unrelated to age, gender, smoking habits, or history of heart or chronic lung disease. Of current smokers/TCC patients, 56.4% believed that smoking is related to their problem and 61.5% intended to quit. The majority (84.6%) had been already warned by their attending physicians. Urological patients’ awareness of smoking as a risk factor for bladder cancer is lower than that for other smoking-related entities. The role of the urologist should not be restricted only to diagnosis and treatment, but should also include counseling patients on the need for radical changes of their life style