The impact of tumor size on outcomes in patients with upper urinary tract urothelial carcinoma.

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.

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.

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

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. CONCLUSION: Tumour location is unable to predict outcomes in a single-centre series of consecutive patients who were treated with radical nephroureterectomy for UUT-TCC.

[Incidence of surgical site infections in a urology department].

OBJECTIVES: To determine the incidence of surgical site infections (SSI) in the urology wards as well as the SSI incidence in relation to the ASA score and surgical site contamination class. MATERIALS AND METHODS: One-year prospective cohort study was conducted in the Urologic department, General hospital, Sabac. The patients were daily examined and their diagnoses were made according to the definition of hospital infections using concurrently the ASA score and surgical site contamination class. RESULTS: Out of 241 operated patients, 32 patients were diagnosed with 33 SSI. The overall incidence rate of patients with SSI was 5.9% while incidence rate of SSI was 6.1%. There were not the differences in the incidence rates according to the ASA score of patients (p > 0.05). The incidence of SSI was 5.0% in the clan wounds, 11.2% in the clean-contaminated, and 20.7% in the contaminated wounds (Chi2 = 8.2 DF = 2 p < 0.016). The patients with SSIs were hospitalized approximately 2 times longer than the patients without SSI (t = -6.28; df = 239; p < 0.001). CONCLUSION: This study suggests that it is necessary to maintain continuous surveillance of surgicical site infections and to implement the preventive measures, especially for clean and clean-contaminated surgery.

Bladder cancer after managing upper urinary tract transitional cell carcinoma: risk factors and survival.

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.

[Pax-2 antigen expression in kidney tumours].

UNLABELLED: Pax-2 transcriptional factor is expressed during kidney development and could re-express in renal tumors. The aim of this study was to examine Pax-2 expression in different types of renal cell carcinoma (RCC) in order to see whether it is good immunohistochemical marker. METHOD: We analyzed 48 different renal tumours stained with Pax-2 antibody. Pax-2 positive reaction was noticed in nucleus or cytoplasm. Expression of this antigen in tumours tissue was correlated with tumour stage and nuc-lear grade. Pax-2 expression between different histological RCC types was analyzed by chi2 test and Fishers test for two in-depended samples. RESULTS: Pax-2 is expressed by a high percentage of re-nal tumors regardless of histologic type. Significant diffe-rence of Pax-2 expression between oncocytomas and chromofobe RCC was found. CONCLUSION: Nuclear expression of Pax-2 is useful diagnostic kidney tumour marker. Pax-2 showed stronger expression in lower malignancy kidney tumours and in oncocytomas, than in high grade RCC like in those with sarcomatoid differentiation

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.

Clinical challenge: heparin-induced thrombocytopenia type II (HIT II) or pseudo-HIT in a patient with antiphospholipid syndrome.

Treatment of patients with heparin-induced thrombocytopenia type II (HIT II) and thrombosis in some cases that represents a clinical challenge, which, if unrecognized, may lead to treatment delay or disease progression with potentially lethal outcome. We present a case of a 19-year-old patient with antiphospholipid syndrome, factor V (FV) Leiden mutation in heterozygous state, and venous thromboembolism. The patient was subjected to intravenous infusions of unfractionated heparin (UFH), and 16 days after the beginning of the treatment, his condition worsened, with thrombocytopenia and extension of thrombosis. Whereas the patient had a high clinical score for HIT II, functional and antigenic assays for the presence of HIT antibodies were negative. After repeated negative functional and antigenic assays, pseudo-HIT was suspected and nadroparin was introduced, which resulted in further worsening of the clinical presentation. Disease remission, along with complete normalization of platelet count, was finally accomplished with the introduction of lepirudin. The presence of multiple comorbid states, such as antiphospholipid syndrome, can potentially make laboratory confirmation of disease more difficult in patients with HIT II. In our opinion, it is of great importance that HIT II diagnosis be primarily clinical and that laboratory test results are carefully interpreted, especially when HIT is indicated by high clinical score values.

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

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.

Glutathione S-transferase-P1 expression correlates with increased antioxidant capacity in transitional cell carcinoma of the urinary bladder.

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 (gamma-glutamylcysteine synthetase, gamma-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 gamma-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 gamma-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.

Upper urothelial tumors in emigrants from Balkan endemic nephropathy areas in Serbia.

AIM: The aim of the study was to investigate upper urothelial tumors (UUT) in emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them with UUT from both endemic and nonendemic areas. MATERIALS AND METHODS: A total of 1,121 patients from the state cancer database, between 1960 and 1998, were investigated. Sixty of them were emigrants from BEN areas. RESULTS: UUT in emigrants from BEN areas occurred after 21.7+/-9.9 years (median 20) spent in a rural environment. The time spent outside of the BEN regions was 33.2+/-12.8 years (median 31, range 10-72). Age at surgery was 55 years (range 31-89). In emigrants from BEN areas, there was a significant association of other diseases with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7% of the patients. Bilateralism was statistically more frequent in emigrants from BEN areas (p=0.04), as were low-grade tumors (p=0.03). There was no statistical difference in tumor stage between patients from BEN areas and from outside of them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT and both of them (33%). CONCLUSIONS: It is concluded that hereditary as well as environmental factors are important for the expression and evolution of the disease. An early period of life spent in the endemic region seems important for the later development of UUT in emigrants from BEN regions. Different time spans spent in the endemic region have no effect on the age of appearance of UUT.

[Bilateral tumors of the upper urothelium].

INTRODUCTION: The incidence of tumors of the upper urothelium is high in our country, apart from their relation to specific regions (BEN and PBEN) and their frequent bilateralism. Bilateral forms are present in significant percentage and are followed, in most cases, by renal failure, which speaks in favor of conservative surgery, if possible. OBJECTIVE: The aim of the study was to present epidemiological, pathoanatomical and clinical characteristics of bilateral tumors of the upper urothelium and evaluate the results of their treatment. METHOD: Our retrospective study analyzed 12 patients with bilateral tumors of the upper urothelium who were treated in the period from 1992 to 1996, according to their epidemiological, clinical, pathoanatomical and pathohistological characteristics, type of surgical treatment and relevant success. RESULTS: In the observed period, bilateral tumors of the upper urothelium were found in 8.2% of our patients. In the group of 12 patients, 5 females and 7 males, 11 cases were from the region of Balkan Endemic Nephropathy (BEN). Renal failure was recorded in high percentage (66%). Radical surgical treatment--total nephroureterectomy was performed in 9 kidney units, and conservative operation in 15 units. Relapse significantly depended on tumor stage and grade, not on type of surgical treatment in the majority of cases. Five-year survival was 58.33%; major cause of death was associated with further evolution of tumor, recurrence and tumor dissemination, respectively, while renal failure complications were the cause of death in one case. CONCLUSION: The success of treatment mainly depends on tumor stage and grade and not on type of surgical method in conservative treatment, but renal failure and its complications are an important risk factor in these patients.

Possibilities and limitations of fibrin glue usage in nephron-sparing surgery: experimental study.

INTRODUCTION: The possibilities and limitations of fibrin glue (FG) usage in nephron-sparing surgery were studied. MATERIALS AND METHODS: A prospective experimental study was carried out in 50 pigs: 30 with polar resection, and 20 with mediorenal wedge resection of the kidney. Hemostatic sutures, FG, and FG with a muscle 'cup' in animals with polar resection of the kidney were compared. FG and sutures in animals with the wedge resection of the kidney were studied as well. Bleeding, hot ischemia time, complication rate, and additional scarring were also analyzed. RESULTS: Suture hemostasis is safe but with significant adverse effects in both polar and wedge resection of kidney. FG was not efficient as a sole hemostatic agent for polar resection. It was as efficient as hemostatic suture for wedge resection of the kidney. FG with a muscle 'cup' on a pole of the kidney achieved good results in animals with polar resection of the kidney. Histological analysis confirmed better results with FG because of both the less intense and smaller area of additional scarring. CONCLUSION: FG is a reliable and efficient hemostatic agent for nephron-sparing surgery whenever both sided gluing is possible.

[Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports]. / Trombocitopenija indukovana heparinom tip II i infarkt miokarda: prikazi dva bolesnika.

Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

[Vascular complications after kidney transplantation]. / Vaskularne komplikacije posle transplanticije bubrega.

INTRODUCTION: Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM: The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS: A total of 463 kidneys (319 from living related donor--LD and 144 from cadaveric donor--CD) were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54) in LD group and 39.8 (19-62) in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS: Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture, obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4%) some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p < 0.0001). Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD). Of these recipients 16 from CD lost the graft, while the rest of two (one from each group) had lethal outcome. DISCUSSION: Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the present study demonstrate that the rate of this complication in LD group was low, only 0.3%, but significantly higher in CD group--11.8%. Many factors should be considered in order to understand for such significant difference among these groups. First of all, cadaveric transplant activity in our country is very low. In our series, median waiting period for renal transplantation was 2.8 years in LD group vs. 4.8 years in CD group (p < 0.01). Also, vascular damages because of long term hemodialysis are contributing factors. Mean age of CD recipients was 7.4 years bigger vs. LD recipients. Primary cadaveric graft damage by accident and further manipulations during cadaveric donor nephrectomy, preservation and perfusion are additional factors compromising the quality of cadaveric renal transplant outcome. Also, preoperative evaluation of cadaveric grafts is not as exact as in cases of LD grafts (excretory urography, arteriography, etc). In the available transplant literature it is almost impossible to find data about vascular complications by different donor types. Mostly, authors offer experiences related to all transplants and most of them agree that in the present time better results are obtained using living donors [17].