Impact of E-Cadherin and ß-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava.

PURPOSE: Renal cell carcinoma (RCC) forming tumor thrombus (TT) of vena cava (VC) is characterized by poor prognosis. Nevertheless, the outcome of patients after radical surgery varies. To date only limited data concerning prognostic biomarkers in this RCC subgroup are available. METHODS: Out of 159 patients with pT3b/c RCC, 95 patients without synchronous distant metastases at time of diagnosis were included in the study cohort. After immunohistochemical (IHC) evaluation of E-cadherin and ß-Catenin expression, association with clinical, histopathological and survival was assessed by univariate analysis, multivariate analysis, and Kaplan-Meier-analysis. Cancer-specific survival (CSS) rates and overall survival (OS) rates were estimated using Kaplan-Meier analysis and compared using Log rank test. RESULTS: We found a significant correlation between E-cadherin overexpression and initial lymph node metastasis (ρ = 0.300, p = 0.003), positive surgical margins (ρ = 0.210, p = 0.043), and the development of distant metastases (ρ = 0.258, p = 0.012). Furthermore, we observed a significant correlation of ß-Catenin overexpression with higher tumor stage pT3c (ρ = 0.230, p = 0.028) and initial lymph node metastases (ρ = 0.236, p = 0.025). Survival analysis revealed a statistically significant association of both E-cadherin and ß-Catenin overexpression with worse CSS (p < 0.001 and p = 0.007, respectively) and OS (p < 0.001 and p = 0.041, respectively). Multivariate analysis revealed initial lymph node metastasis as the only predictive factor for worse OS (HR 4.54, 95% CI 2.30-8.93; p < 0.001). E-Cadherin and ß-Catenin expression failed to be significant in multivariable analysis for OS and CSS. CONCLUSIONS: In a large series of RCC with TT of VC high IHC expression of E-cadherin and ß-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS. This might help to identify patients at risk for recurrence who might benefit from adjuvant therapy or stricter follow-up.

Outcomes of extended surgical resections for locally advanced thymic malignancies: a narrative review.

Background and Objective: Thymic malignancies represent the most common anterior mediastinal neoplasms, as well as rare and challenging tumors. Surgery is the cornerstone in the treatment of thymic malignancies, although a multidisciplinary approach is mandatory, for both, locally advanced or metastatic disease. In our narrative review, we explored the recent literature to investigate clinical and radiological assessment, multimodality approach and outcomes of locally advanced thymic tumors. More than one-third of patients affected by an anterior mediastinal mass are asymptomatic at diagnosis. In case of locally advanced thymoma, symptoms are related to compression or invasion of adjacent structures, such as the superior vena cava (SVC), innominate veins and pericardium. Paraneoplastic syndromes, such as myasthenia gravis (MG), are related to release of antibodies, hormones and cytokines. Methods: Diagnostic methods must be chosen accurately to avoid unnecessary surgical resections, to define the best strategy of care, and to plan the surgical strategy. Therefore, each case must be evaluated in a multidisciplinary context, where surgery plays an essential role. Key Content and Findings: In this narrative review, we describe indications and surgical techniques for the treatment of locally advanced thymoma; focusing on oncological outcomes after different approaches. Conclusions: In conclusion, aggressive surgery is always indicated, when possible, and when a complete resection can be planned, yet, the multidisciplinary approach is mandatory, in case of both locally or metastatic advanced disease.

Prognostic Benefit of Surgical Management of Renal Cell Carcinoma Invading the Inferior Vena Cava.

Renal cell carcinoma (RCC) accounts for approximately 3 % of adult malignancies and 90-95 % of neoplasms arising from the kidney. One of the unique features of RCC is the tumor thrombus formation that migrates into the venous system including renal vein (RV) and inferior vena cava (IVC). Only 10 % of patients with RCC present with the classic triad of flank pain, hematuria and defined mass, while 25-30 % of affected patients are asymptomatic. Signs of para-neoplastic syndrome such as hypercalcemia, hypertension, anemia, cachexia and increased erythrocyte sedimentation rate (ESR) are often apparent. Extension of tumor thrombus into the venous system is depicted by radiological examinations, such as contrast enhanced Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and vena cavography. The level of the thrombus is mostly determined according to the Mayo classification. Despite recent research on the therapeutic strategies against advanced RCC, surgical resection appears the only potentially curative approach. Aggressive surgical management including nephrectomy with thrombectomy is currently the standard therapeutic approach for RCC patients with tumor thrombus extending to the RV or the IVC. Pre-surgical down-staging with the use of molecular targeted therapy has also been proposed. Alternative therapies, such as radio- and chemotherapy proved insufficient. The aim of this review is to evaluate the results of surgical treatment for RCC invading IVC with special reference to the extent of its histological spread. Review of recent world literature was accomplished to provide an update on the current concepts of surgical management of the disease.