The ileal neobladder produces good functional results and can be constructed with acceptable complications. Our data suggest that although it is not a complication-free procedure, we advocate its use when possible.
Summary Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease.
The treatment of choice for non-disseminated renal cell cancer (RCC) is surgery. However, the 5-year survival rates for all stages do not exceed 60%, even in contemporary series. Further improvement will most likely have to await the development of a more effective systemic therapy and the application of combined treatment modalities to counter the relatively high number of patients presenting with advanced stages. Whereas textbook belief up to the 1990s suggested refraining from surgical antitumor-therapy in the case of metastatic RCC, current strategies clearly advocate debulking tumor nephrectomy in the context of modern immunotherapies. This dramatic change of attitude stemmed from two randomized phase III trials conducted by EORTC and SWOG, including a combined analysis of both studies, in which cytoreductive tumor nephrectomy conveyed a significant survival benefit over immunotherapy alone. Concepts and progress in this field appear to be of major interest for modern oncologic urologists following the advent of immunotherapeutic strategies that require surgical intervention at some stage of the treatment cascade.
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