Aleksandar Vuksanovic

Survival of patients with transitional cell carcinoma of the ureter and renal pelvis in Balkan endemic nephropathy and non-endemic areas of Serbia

An interesting reminder about TCC of the ureter and renal pelvis in Serbia is presented, comparing endemic and non‐endemic areas. The authors found similarities between the areas, but also that survival was influenced by female sex, and tumour size, grade and stage.

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma

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.

Enhanced GSTP1 expression in transitional cell carcinoma of urinary bladder is associated with altered apoptotic pathways

OBJECTIVES Glutathione S-transferase P1 (GSTP1) provides an important link between activity of regulatory stress kinases and apoptotic pathways. It can be hypothesized that up-regulated GSTP1, in TCC, might enhance apoptosis inhibition. We aimed to establish whether relationship between GSTP1 expression and executive (pro-caspase 3, cleaved caspase 3) and regulatory (Bcl-2) apoptotic pathways in TCC exists. MATERIALS AND METHODS Samples were obtained from 84 TCC patients (41 consecutive patient with muscle noninvasive and 43 consecutive patients with muscle invasive TCC tumors), who underwent surgery at the Institute of Urology and Nephrology, Clinical Centre of Serbia, during 2006 and 2007. Expression of GSTP1, pro-caspase 3 (CPP32), and Bcl-2, as well as cleaved caspase-3 labeling index (LI) were determined by immunocytochemistry. Levels of expression were correlated with tumor stage, grade, and invasiveness. RESULTS GSTP1 protein expression was demonstrated in all tumor samples examined. According to GSTP1 status, all tumors were divided into groups with low, moderate, or high GSTP1 status. Expression of CPP32 and cleaved caspase 3 was positive in 80% of TCC patients. Their levels differed significantly between groups with various GSTP1 expression (P < 0.05), with the lowest CPP32 expression and cleaved caspase 3 LI in tumors with high GSTP1 status. Moreover, significant negative correlation was found between GSTP1 level and cleaved caspase 3 LI (r = -0.459, P = 0.041). The positive rate of Bcl-2 protein expression was 48%. Most of the Bcl-2 positive patients exhibited at the same time high GSTP1 positivity (P = 0.078). Significant association with tumor grade and stage was found for all examined parameters except for CPP32 regarding tumor grade. CONCLUSIONS Based on results obtained, we conclude that enhanced GSTP1 expression in TCC of urinary bladder is associated with altered apoptotic pathways. Molecular interplay between GSTP1 and members of apoptotic cascade might, at least partially, play a role in development of invasive characteristics of TCC.

Comparison of Open Nephroureterectomy and Open Conservative Management of Upper Urinary Tract Transitional Cell Carcinoma

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.

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis.

Study Type – Therapy (case series)

Diagnostic Value of the Nuclear Matrix Protein 22 Test and Urine Cytology in Upper Tract Urothelial Tumors

Objective: To investigate the diagnostic value of the nuclear matrix protein 22 (NMP22) test in comparison to urine cytology for the detection of upper tract urothelial carcinoma. Patients and Methods: Patients with transitional cell carcinoma of the upper urinary tract (n = 34) and patients with renal calculosis (n = 25) were included in this study. Voided urine samples and separated catheter urine specimens were assayed for NMP22 and cytological examination. Results: The sensitivity of the NMP22 test in separated and voided urine was 73.2 and 70.5%, respectively, compared to 64.7 and 58.8% of urine cytology. The specificity of the NMP22 test in separated and voided urine was 88 and 92%, respectively, compared to 96 and 96% of urine cytology. The combination of separated and voided urine is the best method because the sensitivity is 79.41% and specificity 88%. There is a high agreement of the NMP22 test in voided and separated urine (kappa = 0.795, p < 0.01), indicating that the voided urine is adequate for diagnosis. Conclusions: The NMP22 test has higher sensitivity but lower specificity than cytology. The combination of these two tests could be a very useful diagnostic method for detection of upper urothelial tumors.

Testis sparing surgery in the treatment of bilateral testicular germ cell tumors and solitary testicle tumors: A single institution experience.

To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience.