Dionisios Mitropoulos

Nitric oxide synthase and xanthine oxidase activities in the spermatic vein of patients with varicocele : A potential role for nitric oxide and peroxynitrite in sperm dysfunction

PURPOSE The oxidative and reductive stresses within the varicocele veins were estimated. Nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, S-nitrosothiols and superoxide release within the spermatic vein in patients with varicocele, and the role of the noxious oxidant peroxynitrite formed from nitric oxide and superoxide in sperm dysfunction were determined. MATERIALS AND METHODS Whole blood samples were drawn from a peripheral vein and a dilated varicocele vein before ligation. Nitric oxide synthase, xanthine oxidase, nitric oxide and peroxynitrite were measured by novel spectro-fluorophotometric methods. S-nitrosothiols were estimated by a luminol-chemiluminescence method. Serum and red blood cell antioxidant capacity was determined by a chemiluminescence reaction. RESULTS Serum nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, peroxynitrite and S-nitrosothiol levels were greater in the spermatic vein compared to the peripheral vein. Serum antioxidant capacity was greater in varicocele veins compared to peripheral veins. In contrast, the antioxidant capacity of red blood cells was less in the varicocele veins, which was consistent with an increased rate of peroxynitrite production. CONCLUSIONS Our data suggest a high oxidative stress due to the release of nitric oxide synthase and xanthine oxidase within the dilated spermatic vein. The reaction resulted in dramatic formation of nitric oxide, peroxynitrite and S-nitrosothiols, which are biologically active. Formation of peroxynitrite from the reaction of nitric oxide with superoxide could be a causative factor for impaired sperm function in patients with varicocele.

Comparative evaluation of the BTAstat test, NMP22, and voided urine cytology in the detection of primary and recurrent bladder tumors

OBJECTIVES This prospective study was undertaken to evaluate the diagnostic efficacy of the BTAstat test and nuclear matrix protein (NMP22) compared with voided urine cytology (VUC) in the detection of primary and recurrent bladder cancer. METHODS A total of 147 patients provided a single voided urine sample for the BTAstat test, NMP22, and cytology prior to cystoscopy. Eighty-five of them had no bladder cancer history, whereas the remaining 62 were monitored for superficial bladder cancer. A group of 21 healthy age-matched volunteers were also enrolled in the study. RESULTS Bladder cancer was confirmed histologically in 99 patients, of which 62 had primary tumors and 37 had recurrent ones. The overall sensitivity and specificity were 71.7% and 56.5% for the BTAstat test, 62.6% and 73. 9% for NMP22, and 38.4% and 94.2% for VUC. The optimal threshold value for NMP22 calculated with receiver operating characteristics curve, was 8 U/mL. BTAstat test was significantly more sensitive than VUC in detecting bladder cancer in all stage and grade subgroups, except GIII. On the contrary, NMP22 was significantly more sensitive than VUC only in stage Ta, grade I and II patients. BTAstat test had higher but not significantly different sensitivity than NMP22. CONCLUSIONS Our data indicate a superiority of both BTAstat test and NMP22 over VUC in the detection of bladder cancer. Comparing BTAstat test with NMP22, the former proved to be more sensitive, whereas the latter was more specific. Ruling out diseases with potential interference can increase the overall specificity of both tests. False-positive results of either test in patients followed up for bladder cancer seem to correspond to future recurrences.

Androgens and bladder outlet obstruction: a correlation with pressure-flow variables in a preliminary study.

To determine the relationship between androgens, lower urinary tract symptoms (LUTS) and urodynamic variables of bladder outlet obstruction (BOO) in patients with LUTS/benign prostatic hyperplasia (BPH), as androgens are important in the pathogenesis of LUTS.

Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Purpose: The aim of this study was to assess the clinical efficacy of distigmine bromide, an anti-cholinesterase agent, deemed to improve detrusor function thereby restoring normal voiding patterns in patients suffering from detrusor underactivity. Materials and methods: A total of 27 patients (11 men and 16 women) with poor detrusor function were included in the study. The diagnosis was established using pressure-flow studies. All patients received distigmine bromide at a dose of 5 mg three times daily for 4 weeks and re-attended for a follow-up urodynamic investigation. The results of baseline pressure-flow studies were compared to those after completion of treatment. Results: Treatment with distigmine bromide resulted in a statistically significant reduction of residual volume and percent residual volume, obviating the need for intermittent self-catheterisation in 11 patients. In addition, maximum flow rate and detrusor pressure at maximum flow increased, although not significantly. The drug was generally well tolerated by the majority of patients. Conclusion: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.

Expression of transforming growth factor β in renal cell carcinoma and matched non-involved renal tissue

TGFβ1 is one of several cytokines produced by proximal tubular and renal cancer cells. Previous studies have been mainly focused on determining plasma or serum TGFβ levels, its effect on RCC cultures, and the expression of TGFβ mRNA. Cancerous and autologous normal kidney samples were obtained from 24 patients treated by radical nephrectomy. TGFβ1 expression was determined using a semi quantitative Western blot analysis and immunohistochemistry. Blot densities and immunohistochemical expression intensities in normal and neoplastic tissue were compared, and subsequently correlated to tumor stage, histological type and nuclear grade. All tissue samples examined expressed TGFβ1; mean tumor to non-involved kidney spot density ratio correlated with advancing stage and higher nuclear grade. The overexpression of TGFβ1 in certain RCCs may partially explain their resistance to the growth suppression action of TGFβ. The correlation with tumor stage and grade indicates a possible role in the development of metastatic potential as well as in host’s immune response modulation.

Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study.

INTRODUCTION/BACKGROUND The aim of this study was to evaluate the prognostic role of CN in patients with mRCC and synchronous metastases treated with the VEGF receptor TKI, sunitinib. PATIENTS AND METHODS Patients with a diagnosis of metastases before, at the time of, or within 3 months from the diagnosis of renal cell carcinoma (RCC) and first-line treatment with sunitinib were included. Baseline characteristics were correlated with overall survival (OS) according to hazard ratios estimated from univariate Cox proportional hazards models. Significant factors were then included in a multivariate Cox proportional hazards model. RESULTS One hundred eighty-six patients treated between January 2006 and March 2012 were selected. Thirty-six (19%) had not undergone CN. CN was offered to younger patients with better prognoses. Patients who underwent CN lived significantly longer than patients without CN (median OS, 23.9 [95% confidence interval (CI), 20.8-28.8] vs. 9 [95% CI, 4-16.4] months; P < .001). Multivariate analysis showed that CN had an independent prognostic significance. No specific subgroup benefiting from CN was identified. CONCLUSION CN was an independent favorable prognostic factor in patients with synchronous metastases from RCC, treated with sunitinib. Information regarding the selection of mRCC patients likely to benefit from CN might be derived by ongoing phase III trials.

Patient awareness of smoking as a risk factor for bladder cancer

IntroductionData 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.MethodsThis 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.ResultsOnly 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.ConclusionsUrological 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.

Neoadjuvant Cisplatin and Interferon-α2B in the Treatment and Organ Preservation of Penile Carcinoma

We investigated the antitumor activity and toxicity of cisplatin and interferon-alpha 2B as the primary treatment of penile carcinoma. A total of 13 consecutive patients with nonmetastatic, histologically confirmed invasive squamous cell carcinoma of the penis underwent treatment consisting of 20 mg./m.2 cisplatin intravenously and 5 x 10(6) mu./m.2 interferon-alpha 2B subcutaneously daily for 5 consecutive days. An equivalent dose of interferon was then administered subcutaneously every 2 days for 3 weeks and the regimen was repeated at 28-day intervals. Of 12 evaluable patients 9 responded: 4 achieved a pathologically confirmed complete remission of 38+, 21+, 10 and 7 months in duration (2 with relapse were treated with local therapy and remain with no evidence of disease), and 5 achieved a partial response, underwent surgical removal of residual disease and remained disease-free for 14+ to 24+ months. The most significant toxicities were anemia in 5 patients and reversible renal impairment in 3 but no patient had neutropenic fever or required platelet transfusion. We conclude that primary treatment with cisplatin and interferon-alpha 2B induced responses in 75% of 12 patients with penile carcinoma and allowed for a less radical operation than originally scheduled. A larger number of patients and longer followup will be required to confirm these encouraging preliminary results.

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.

Symptoms of Acute Posttraumatic Stress Disorder in Prostate Cancer Patients Following Radical Prostatectomy

Psychological morbidity is increasingly reported in cancer survivors. The authors’ objective was to determine the presence of acute posttraumatic stress disorder (PTSD) symptoms in prostate cancer (PC) patients following radical prostatectomy. Fifteen patients who underwent radical prostatectomy for localized prostate cancer were assessed for the presence of PTSD-related symptoms by completing the Davidson Trauma Scale (DTS), a month following the procedure. A group of 20 patients who underwent surgery for benign prostate hyperplasia (BPH) served as the control group. PTSD total scores were significantly higher in PC patients when compared with BPH patients, whose PTSD scores did not differ from those reported in the general population (32.6 ± 18.5 vs. 11.3 ± 9.7, p = .001). PTSD did not vary among PC patients when adjusted for educational status. PTSD symptoms are common among patients undergoing radical prostatectomy and independent of their educational level. Research investigating these aspects of posttreatment psychological adjustment is needed for developing well-targeted psychological interventions.