Resection of renal tumors invading the vena cava.

Surgical resection of renal cell carcinoma remains the mainstay for the management of patients who suffer from this disease. Five percent to 10% of renal cell carcinomas develop a tumor thrombus that propagates into the renal vein or the inferior vena cava. Radical nephrectomy and inferior vena cava thrombectomy can provide longstanding survival rates comparable to those for tumors confined to the renal parenchyma. In general the surgical approach is dictated by the cephalad extension of tumor thrombus. This article reviews the authors' experience with 243 patients who suffered from renal cell carcinoma with extension into the venous system with specific reference to the surgical techniques and the long-term outcomes.

Surgical management of large renal tumors.

In addition to an increased occurrence of small, localized, incidentally discovered renal cell carcinomas (RCCs), there has been an upward trend in the incidence of advanced renal tumors per unit of population and in disease mortality worldwide. As radical nephrectomy remains the standard of care in treating localized RCC, this manuscript focuses on surgical approaches. We defined 'large renal tumors' as those greater than 7 cm or those with venous involvement. We discuss operative strategies in both open and laparoscopic surgery as well as approaches to special circumstances, including patients with tumor thrombus and the indications for nephron-sparing surgery in patients with greater than T2 RCC. The literature pertaining to controversial areas such as preoperative renal artery embolization and the clinical utility of metastectomy and cytoreductive therapy are also reviewed. The theoretical basis and potential applications of neoadjuvant therapy for larger renal tumors is examined as well.

Prognostic significance of altered p120 ctn expression in bladder cancer.

OBJECTIVE: To identify the frequency of change in the expression and localization of p120(ctn) in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120(ctn) in the migratory and invasive behaviour of bladder carcinoma cells. MATERIALS AND METHODS: In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2-T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120(ctn) immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120(ctn) was achieved using small-interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays. RESULTS: The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non-membranous localization of p120(ctn) correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN-positive disease (P = 0.02). A low expression level of p120(ctn) was linked to a poor outcome in cancer-specific survival analysis. Knockdown of p120(ctn) using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells. CONCLUSIONS: Our findings suggest that p120(ctn) acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.

Epidermal growth factor receptor status and the response of bladder carcinoma cells to erlotinib.

PURPOSE: We established the frequency of mutation of the epidermal growth factor receptor in bladder cancer and determined whether the activation status of epidermal growth factor receptor confers sensitivity to erlotinib. MATERIALS AND METHODS: The identification of mutations in the kinase domain (exons 18-21) of epidermal growth factor receptor was performed using single strand conformation polymorphism. The action of erlotinib was established within a bladder carcinoma cell panel using clonogenic assays and Western blot analysis. RESULTS: In 112 invasive bladder tumors a total of 6 mutations in 4 patients (3.6%) were identified in exon 21. Erlotinib demonstrated concentration dependent inhibition of growth where three cell lines showed high and 2 showed low sensitivity to the drug. Erlotinib inhibited activation of epidermal growth factor receptor, mitogen activated protein kinase, Akt and STAT3. However, the activation status of Akt was maintained in cell lines that were insensitive to the inhibitory action of erlotinib and were characterized as having undergone epithelial-to-mesenchymal transition. CONCLUSIONS: Although mutations in the coding region of epidermal growth factor receptor are rare in invasive bladder tumors, differential sensitivity to erlotinib was recorded within a panel of cell lines. Maintenance of the phosphorylation status of Akt in the presence of erlotinib along with epithelial-to-mesenchymal transition correlates with insensitivity to growth inhibition in bladder carcinoma cell lines. Even in the absence of epidermal growth factor receptor mutations erlotinib shows potential as a therapeutic agent for the treatment of bladder cancer.

Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors.

PURPOSE: Epithelial to mesenchymal transition (EMT) is reportedly an important transition in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. In this study, we examined the expression pattern of EMT markers in vivo and determined the occurrence and clinical significance of these events in a series of bladder carcinomas. EXPERIMENTAL DESIGN: Eight hundred and twenty-five tumor samples from 572 bladder cancer patients were assembled in 10 tissue microarrays. Paraffin sections from each tissue microarray were subjected to antigen retrieval and processed by immunohistochemistry for the expression of E-cadherin, plakoglobin, beta-catenin, N-cadherin, and vimentin. RESULTS: Pathologic expression of E-cadherin, beta-catenin, plakoglobin, and vimentin were associated with the clinicopathologic variables of grade and stage with only the cytoplasmic localization of plakoglobin found associated with lymph node status. Associations between the aforementioned markers were found significant as determined by the Spearman correlation coefficient with N-cadherin showing no associations in this analysis. In univariate survival analysis involving patients who underwent cystectomy, the reduction or loss of plakoglobin significantly influenced overall survival (P = 0.02) in which the median time to death was 2 years compared with 4 years when a normal level of plakoglobin was recorded. When the analysis was done for cancer-specific survival, low levels of both plakoglobin (P = 0.02) and beta-catenin (P = 0.02) significantly influenced survival. CONCLUSION: The putative markers of EMT defined within a panel of bladder carcinoma cell lines were recorded in vivo, frequently associated with tumors of high grade and stage. Although multivariate analysis showed no significant influence of the EMT biomarkers on survival, alterations associated with plakoglobin were identified as significant prognostic features in these tumors.

Management of renal cell carcinoma with vena cava and atrial thrombus: minimal access vs median sternotomy with circulatory arrest.

OBJECTIVE: To review our experience with approaches for managing renal cell carcinoma (RCC) with venous thrombi extension at and above the level of the hepatic veins, comparing surgery and peri-operative outcomes in patients with cardiopulmonary bypass (CPB) with deep hypothermic cardiac arrest (DHCA) either by minimal access (MA) or traditional median sternotomy (TMS). PATIENTS AND METHODS: From 1986 to 2005, 50 radical nephrectomies with inferior vena cava (IVC) thrombectomies were performed at our institution using TMS (22 patients) and MA (28) techniques. Patient demographics were compared using Student's t-, Fisher's exact and Pearson chi-square tests. The duration of surgery, CPB, DHCA, mechanical ventilation, length of stay, and peri-operative transfusion requirements, were compared using the Mann-Whitney U-test. Estimates of survival were constructed using Kaplan-Meier curves and analysed with the log-rank test. Subgroups were analysed excluding TMS patients undergoing concurrent coronary revascularization. RESULTS: There were no significant differences in patient demographics or comorbidities between the MA and TMS group. There were significant decreases in the MA vs the TMS group (P < 0.05) in the duration of surgery, mechanical ventilation, length of stay and peri-operative transfusion requirements. When patients with coronary revascularization were excluded, the MA group had significant decreases (P < 0.05) in duration of surgery, hospital stay and transfusion requirements. Peri-operative mortality was not statistically different between the TMS (14%) and MA (4%) patients. Overall and organ system-specific complications also were not statistically different. The overall median survival in the TMS and MA groups was 0.62 and 2.84 years, respectively (P = 0.06, hazard ratio 2.02; 95% confidence interval, CI, 0.97-4.72). Patients with tumour thrombus extending into the right atrium had a median survival of 1.02 years, vs 2.84 years with no intracardiac extension (P = 0.15, hazard ratio 1.82, 95% CI 0.81-4.0). CONCLUSIONS: MA surgical techniques in conjunction with DHCA for the treatment of RCC with extensive tumour thrombus provides quicker surgery and a shorter hospital stay. In addition there was less requirement for mechanical ventilation and transfusion than with TMS. Our findings suggest that MA techniques provide significant advantages over TMS.