Browsing by Author "Djokic, Milan (15019194000)"

Objective To identify independent risk factors for the development of bladder cancer after surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC). Patients and methods Between January 1999 and December 2008, 154 patients were treated surgically for UUT-TCC at the Clinic of Urology, Clinical Center of Serbia. Patients with a previous history of bladder cancer and patients with concomitant bladder cancer were excluded from the study. In all, 92 patients were then available for evaluation. The median follow-up after surgery was 39.5 months. Univariate and multivariate analyses using the logistic regression model were performed. The intravesical disease-free rate and survival were calculated using the Kaplan-Meier method, and the log-rank test was used to determine statistical differences. Results and limitations In this study, 21.7% patients treated for UUT-TCC developed subsequent bladder tumors. Tumor multifocality was the only independent predictor associated with the development of subsequent bladder cancer (P = 0.028, RR = 3.52). Intravesical recurrence-free survival rates for these 92 patients at 1, 3, 5, and 7 years were 85.8, 80, 79.3, and 78.3%, respectively. Patients with tumors extending to multiple sites were significantly more likely to present subsequent intravesical recurrence (P = 0.006). The development of bladder cancer had no significant effect on the survival of patients who underwent surgical treatment of UUT-TCC, compared to patients without bladder cancer development (P = 0.660). Neither did the type of surgery mode affect patient survival (P = 0.245). This study is limited by biases associated with its retrospective design. Conclusion The multiplicity of the UUT-TCC is an independent risk factor for the occurrence of bladder cancer. © Springer Science+Business Media, B.V. 2011.

Introduction: The treatment preserving the kidney for upper urinary tract (UUT) transitional cell carcinoma (TCC) is still controversial. We aimed to elucidate the results of open conservative surgery and compare them with the results of radical nephroureterectomy (RNU). Patients and Methods: The study included 107 patients with UUT TCC treated by open conservative surgery (21 patients) or nephroureterectomy (86 patients). Epidemiological, clinical and pathological characteristics of patients as well as 5-year survival rates were compared between groups. Results: Patients treated by conservative surgery had a significantly higher rate of bilateral tumors (38% vs. 3%, p = 0.0001) and smaller tumor size than those treated by radical operations (2.60 ± 1.24 vs. 3.99 ± 3.94 cm, p = 0.060). Five-year survival rates for patients treated by conservative and radical surgery were 59 and 55%, respectively. Within the group of patients treated by conservative surgery, 5-year overall survival rates of patients operated due to imperative and elective indications were 41 and 75%, respectively. In univariate analysis, RNU was a statistically significant predictor of poorer outcome of the disease in comparison with conservative surgery (HR = 2.2, 95% CI 1.1-4.6, p = 0.030). Conclusions: The mode of operation affects the outcome of UUT TCC patients, in addition to factors such as tumor grade, stage and size. © 2009 S. Karger AG, Basel.

Objectives: Our aim was to perform a comprehensive analysis of the antioxidant capacity of transitional cell carcinoma (TCC) of urinary bladder and discern the role of enzymes associated with glutathione (GSH) in maintaining high GSH levels in these tumours. Because the redox-sensitive protein glutathione S-transferase P1 (GSTP1) might provide an important link between high antioxidant capacity and inhibition of apoptotic pathways, we also explored how the redox state in tumour cells interacts with the expression of GSTP1. Methods: We examined spectrophotometrically the specific activities of GSH-replenishing enzymes involved in GSH synthesis (γ-glutamylcysteine synthetase, γ-GCS), GSH regeneration (glutathione reductase, GR), and antioxidant protection (glutathione peroxidase, GPX; superoxide dismutase, SOD) in the cytosolic fraction of tumours and the surrounding normal tissue of 30 TCC patients. GSTP1-1 expression was also analyzed. Results: We found a significant increase in the activity of both GSH-replenishing and antioxidant enzymes as well as enhanced GSTP1-1 expression in tumours in comparison with adjacent normal uroepithelium. Mean γ-GCS and GR activities in tumours were about 4- and 2-fold higher, respectively, than in corresponding normal tissue. Expression of GSTP1 correlated significantly with GSH level and γ-GCS and GR activities. GPX and SOD activities in TCC were also markedly increased. Conclusions: Enhanced GSH-replenishing pathways account for increased GSH levels in TCC. Upregulated GPX and SOD also contribute to high antioxidant potential in TCC. Under such conditions, expression of redox-sensitive GSTP1 protein is upregulated. © 2007 European Association of Urology.

Objective: To evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer. Patients and methods: A single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36-88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. Results: Fifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers. Conclusions: Patients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC. © 2013 Elsevier Inc.

OBJECTIVE: To evaluate the characteristics and survival of patients with upper urinary tract (UUT) transitional cell carcinoma (TCC) in Serbia, followed for ≥5 years or until death. PATIENTS AND METHODS: From 1998 to 2005 we analysed 114 cases of pathologically confirmed UUT TCC, divided into two groups according to topographical characteristics, and compared their demographic, clinical and pathological characteristics. The influence of various factors on overall 5-year survival of patients with UUT TCC was also tested. The prognostic value of different variables was assessed by univariate and multivariate Cox proportional-hazard models. RESULTS: The most important change in demographic characteristics of the patients with UUT TCC in Serbia was a similar proportion of patients residing in areas of Balkan endemic nephropathy (BEN) and non-endemic areas. The median (range) follow-up was 67 (46-88) months. The 5-year probability of survival was 51.2 ± 5.8%. There was a significantly lower probability of 5-year survival for patients with a higher histological grade (P = 0.001), higher T stage (P < 0.001) and tumour size >3 cm (P = 0.001) at diagnosis. In this cohort of patients the independent predictors of a poorer outcome of the disease were being female (hazard ratio, HR, 2.2, P = 0.010), tumour size >3 cm (HR 2.8, P = 0.001) and T3 or T4 stages (HR 3.1, P = 0.001). CONCLUSION: Comparative analysis of the characteristics of UUT TCC between patients from BEN and non-endemic areas of Serbia showed similarities in demographic, clinical and pathological features. Factors that significantly influenced survival of patients with UUT TCC were being female, tumour size and tumour grade and stage. © 2007 The Authors.

Purpose: To investigate the association between tumor size and clinicopathologic factors and outcomes of upper urinary tract urothelial carcinoma (UTUC) in patients treated surgically for UTUC. Methods: A single-center series of 235 consecutive patients who were treated surgically for UTUC between January 1999 and December 2011 was evaluated. Patients with a history of muscle-invasive urothelial carcinoma of the urinary bladder, those who received neoadjuvant therapies, and those with previous contralateral UTUC were excluded. Bladder-only recurrence, any recurrence, and cancer-specific mortality after surgery were analyzed. Recurrence-free probabilities and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method and Cox regression analyses. Results: Tumor size was significantly associated with age of the patient (P = 0.001), tumor location (P < 0.0001), tumor multifocality (P = 0.005), higher tumor stage (P < 0.0001), higher tumor grade (P = 0.038), lymphovascular invasion (P = 0.002), and mode of operation (P = 0.001). Tumor size was not associated with bladder-only recurrence (HR 0.91; 95 % CI 0.46-1.80; P = 0.79). The Kaplan-Meier method showed that tumor size >3 cm was significantly associated with worse CSS (P = 0.006, log rank). The 5-year CSS for patients with tumor size ≤3 cm was 70.1 % and for patients with tumor size >3 cm was 56.1 %. Tumor size was not associated with cancer-specific survival in multivariable analysis (HR 1.53; 95 % CI 0.89-2.61; P = 0.12). Conclusions: Tumor size >3 cm was associated with a lower 5-year CSS at Kaplan-Meier analysis, but was not an independent predictor of CSS, bladder-only recurrence, and any recurrence-free survival at multivariable analysis. © 2013 Springer Science+Business Media.

Objective To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT-TCC). Patients and Methods A single-centre series of 189 consecutive patients who were treated surgically for UUT-TCC between January 1999 and December 2009 was evaluated. Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT-TCC were excluded. In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. Results The 5-year recurrence-free and cancer-specific survival estimates for the cohort in the present study were 66% and 62%, respectively. The 5-year bladder-only recurrence-free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non-Balkan endemic nephropathy areas; 95% confidence interval, 1.37-5.98; P= 0.005) were associated with disease recurrence Tumour location was not associated with disease recurrence in any of the analyses. There was no difference in cancer-specific survival between renal pelvis and ureteral tumours (P= 0.476). Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer-specific survival. Conclusions Tumour location is unable to predict outcomes in a single-centre series of consecutive patients who were treated with radical nephroureterectomy for UUT-TCC. © 2011 The Authors. BJU International.