1/32. A phase Ib/II trial of granulocyte-macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases: a case of fatal central nervous system thrombosis.BACKGROUND: interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF. methods: patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19. RESULTS: Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS: The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.- - - - - - - - - - ranking = 1keywords = disease progression, progression (Clic here for more details about this article) |
2/32. Gamma surgery for intracranial metastases from renal cell carcinoma.OBJECT: The goal of this study was to evaluate the effectiveness and limitations of gamma surgery (GS) in the treatment of renal cell carcinoma that has metastasized to the brain. methods: The authors performed a retrospective analysis of a consecutive series of 21 patients with 37 metastatic brain deposits from renal cell carcinoma who were treated with GS at the University of virginia from 1990 to 1999. Clinical data were available in all patients. No patient died of progression of intracranial disease or deteriorated neurologically following GS. Eight patients clinically improved. Follow-up imaging studies were available for 23 tumors in 12 patients. Nine patients did not undergo follow-up imaging. One patient lived 17 months and succumbed to systemic disease: no brain imaging was performed in this case. Another patient refused further imaging and lived 7 months. Seven patients lived up to 4 months after the procedure; however, their physicians did not require these patients to undergo follow-up imaging examinations because of their general conditions-all had systemic progression of disease. Of the 23 tumors that were observed posttreatment, one remained unchanged in volume, 16 decreased in volume, and six disappeared. No tumor progressed at any time, and there were no radiation-induced changes on follow-up imaging an average of 21 months after GS (range 3-63 months). CONCLUSIONS: Gamma surgery provides an alternative to surgical resection of metastatic brain deposits from renal cell carcinoma. Neurological side effects were seen in only one case; freedom from progression of disease was achieved in all cases.- - - - - - - - - - ranking = 0.026953271591023keywords = progression (Clic here for more details about this article) |
3/32. Chromophobe renal cell carcinoma with sarcomatoid change. A case report.Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.- - - - - - - - - - ranking = 0.017968847727349keywords = progression (Clic here for more details about this article) |
4/32. Sarcomatoid renal cell carcinoma of papillary origin. A case report and cytogenic evaluation.Sarcomatoid renal cell carcinoma (SRCC) is an aggressive tumor variant thought to arise predominantly from dedifferentiation of clear cell carcinoma. A few reports of SRCC associated with non-clear cell tumors led to the presumption that SRCC may arise from any renal cell carcinoma, although direct evidence of this is lacking. Cytogenetic studies on 3 previously documented SRCCs associated with papillary renal cancers showed either 3p deletions or absence of trisomy 7, 17 in the sarcomatoid tumors, suggesting origin from a coexistent clear cell tumor. The present case represents the first conclusive evidence of direct progression of non-clear cell carcinoma to SRCC with both tumor components containing multiple copies of chromosomes 7 and 17. Many genetic anomalies, including p53 mutations, frequently recognized in SRCC were not recognized in this case, highlighting the importance of cytogenetic evaluation of all SRCC. The patient is well and without evidence of tumor progression 1 year after surgery, and the sinister outlook of SRCC in association with clear cell carcinoma may not apply in SRCC of non-clear cell origin.- - - - - - - - - - ranking = 0.017968847727349keywords = progression (Clic here for more details about this article) |
5/32. Intramedullary spinal cord metastasis as a first manifestation of a renal cell carcinoma: report of a case and review of the literature.The authors report the case of a 70-year-old woman who developed a Brown-Sequard-syndrome within 6 weeks caused by an intramedullary spinal cord metastasis of an occult renal cell carcinoma. Intramedullary metastases are rare and represent only 4-8.5% of central nervous system metastases. An important feature of intramedullary metastases is the rapid progression of neurological deficits which necessitates rapid treatment. There are only eight earlier reports of intramedullary metastasis due to renal cell carcinoma (Schiff D, O'Neill BP. Intramedullary spinal cord metastases: clinical features and treatment outcome. neurology 1996;47:906-12; Belz P. Ein Fall von intramedullaerer Grawitz-Metastase im Lumbalmark. Frankfurt Z Pathol 1912;10:431-44; Gaylor JB, Howie JW. Brown-Sequard-syndrome. A case of unusual aetiology. J Neurol Neurosurg psychiatry 1938;1:301-5; Kawakami Y, Mair WGP. Haematomyelia due to secondary renal carcinoma. Acta Neuro Pathol 1973;26:85-92; Strang RR. Metastatic tumor of the cervical spinal cord. Med J Aust 1962;1:205-6; Von Pfungen. Uber einige Falle von Haematomyelie nichttraumatischen Ursprungs. Wien Klin Rdsch 1906;20:44-50; Weitzner S. Coexistent intramedullary metastasis and syringomyelia of cervical spinal cord. Report of a case. neurology 1960;674-8). To the best of our knowledge this is the first report on a patient in whom symptoms from the metastasis of a renal cell carcinoma preceded the detection of the primary tumor. This report presents the clinical, neuroradiological and histopathological findings of an intramedullary metastasis of a renal cell carcinoma and provides an overview of the literature on intramedullary spinal cord metastases.- - - - - - - - - - ranking = 0.0089844238636743keywords = progression (Clic here for more details about this article) |
6/32. Ukrain treatment in a patient with metastatic renal cell carcinoma extending to the vena cava inferior. Case report.A 52-year-old man with renal cell carcinoma was treated with surgery and chemotherapy (vinblastine). Ukrain was administered after tumor progression to the vena cava inferior and appearance of liver metastasis. The drug induced a complete remission, which has lasted 32 months since the first therapy course.- - - - - - - - - - ranking = 0.0089844238636743keywords = progression (Clic here for more details about this article) |
7/32. Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer.interleukin-2 is an effective agent against renal cell carcinoma and melanoma, but it has been associated with autoimmune sequelae such as hypothyroidism and vitiligo. A 64-year-old man with non-insulin-dependent diabetes and metastatic renal cell carcinoma developed insulin-dependent diabetes after his first cycle of therapy with high-dose (HD) interleukin-2. After additional therapy with interleukin-2, the patient developed generalized myasthenia gravis (MG) and polymyositis, both of which responded to treatment with corticosteroids and plasmapheresis. To investigate the role of IL-2 in the development of these autoimmune complications, autoantibody titers were assayed from serum obtained before and after IL-2 treatment and after treatment with corticosteroids plus plasmapheresis. Before IL-2 treatment, the patient had antibodies directed against insulin, islet cell antigens, and striated muscle. acetylcholine receptor antibody levels were normal before starting IL-2. After treatment with IL-2, the patient developed acetylcholine receptor binding antibodies and exhibited an increase in the striated muscle antibody titer from 1:40 to 1:160. Recovery from the MG and polymyositis was associated with substantial decreases in the acetylcholine receptor and striated muscle antibody titers. These findings suggest that HD IL-2 accelerated the progression of latent autoimmune diabetes and myositis in this patient whose tolerance to islet cell antigens and striated muscle had already been broken and precipitated a break in tolerance to the acetylcholine receptor resulting in the development of MG. This case demonstrates the importance of prompt recognition of IL-2-induced MG and shows how this complication can be successfully managed with aggressive therapy.- - - - - - - - - - ranking = 0.0089844238636743keywords = progression (Clic here for more details about this article) |
8/32. Hypertrophic pulmonary osteoarthropathy associated with disease progression in renal cell carcinoma.Hypertrophic osteoarthropathy (HOA) is a paraneoplastic syndrome characterized by periosteal formation and arthritis and usually accompanied by clubbing ofthe digits. Many malignancies have been associated with HOA/clubbing, most being lung cancer and lung metastatic cancer. We herein present a 53-year-old man with lung metastasis from renal cell carcinoma (RCC). HOA occurred one year after the metastasis. Reviewing the literature, only five cases of RCC with HOA have been reported. If their clinical history was traceable, they consistently had disease progression. We reviewed the pathogenesis of HOA/clubbing and linked the prognosis of RCC to relevant cytokines. Therefore, HOA not only heralds a progression of disease but suggests a probable therapeutic choice by targeting some cytokines.- - - - - - - - - - ranking = 4.0179688477273keywords = disease progression, progression (Clic here for more details about this article) |
9/32. Cytogenetic and molecular studies of a familial renal cell carcinoma.In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using dna sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene.- - - - - - - - - - ranking = 0.0089844238636743keywords = progression (Clic here for more details about this article) |
10/32. Clinical course and immune response of a renal cell carcinoma patient to adoptive transfer of autologous cytotoxic T lymphocytes.The cytotoxic T lymphocyte (CTL) is a promising candidate for an effector cell in adoptive immunotherapy for renal cell carcinoma (RCC). Here we report the clinical course and in vivo immune responses of a RCC patient with bulky retroperitoneal lymph node (RPLN) metastases who received adoptive autologous CTL therapy. A 56-year-old woman diagnosed with RCC with multiple RPLN metastases underwent unilateral nephrectomy. Autologous RCC cells were primary-cultured from surgical specimens. Before addition of peripheral blood mononuclear cells (PBMC) for CTL induction, subconfluent RCC cells were irradiated with 50 Gy. The PBMCs were then cultured on RCC cells in the induction medium supplemented with four kinds of interleukins. The induced CTLs showed the potent killing activity against autologous RCC cells in a typical MHC-class I-restricted manner. The patient received three courses of CTL therapy with a total of 10.2 x 10(9) cells, and the RPLN mass decreased markedly in size after the second course. eosinophilia and enhanced CTL inducibility from peripheral blood were observed after CTL administrations. The patient was progression free without further treatment; however, she developed rapidly progressive glomerulonephritis more than 1 year after the last treatment. The patient died of newly developed metastases 27 months after the start of CTL therapy. At autopsy, viable RCC cells were found in multiple metastatic sites. However, only diffuse fibrous tissue was observed in the responding RPLN mass. Apparent histological divergence was observed between primary and metastatic sites.- - - - - - - - - - ranking = 0.0089844238636743keywords = progression (Clic here for more details about this article) |
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