Summary Estimates were made of the rates at which cancer cells were released directly into the renal vein in patients undergoing radical nephrectomy for primary renal cancer. Cancer cells were counted in blood samples taken from the renal vein using a density gradient centrifugation procedure, and identified using immunocytochemical techniques, on the basis of their cytoskeletal intermediate filament proteins. Cancer cells were released as single cells and multicell emboli in 8/10 patients, in numbers varying widely between 14-7509 emboli ml -of blood. Despite a calculated median input into the metastatic process of 3.7 x I07 cancer cells per day for at least 180 days, only 3/10 patients had extraperitoneal metastases prior to surgery and only of the remaining disease-free patients subsequently developed distant metastases over a maximum 35 month period. These results are discussed in terms of primary tumour kinetics and metastatic inefficiency.
The majority of patients dying from malignant disease are killed by metastases rather than by the primary tumour mass. The possible influence of immunological factors upon the progress of established tumours in both patients and experimental animals is receiving increasing attention and has been much discussed (Morton, 1973). However, less attention has been paid to the role, if any, that these factors play in the initial arrest of metastatic cells or their pattern of localization in different organs. In the present studies, isotopically labelled tumour cells were introduced into the systemic circulation of mice as a model of the haematogenous dissemination of metastatic cells, in situations where the host is sensitized to tumour antigens. In addition, since neuraminidase treatment has been shown to influence the organ distribution of transformed normal cells (Woodruff and Gesner, 1969), experiments were also included to examine the effects of neuraminidase on the pattern of localization of injected tumour cells in animals with different tumour-bearing status.
MATERIAL AND METHODS
TumoursA fibrosarcoma (MC-1) originally induced by methylcholanthrene was routinely passaged as an ascites tumour in syngeneic C3H/He Ha female
The efficiency of a gravity-dependent autotransfusion system (ATS) for filtering tumor cells from blood was examined under laboratory and clinical conditions. In laboratory studies, reconstituted whole blood was seeded with known numbers of cultured A431 human vulva carcinoma cells then filtered through the ATS. Cancer cells were recovered from blood samples taken before and after filtration using a density gradient centrifugation procedure, and identified by immunocytochemical techniques, based upon their cytoskeletal intermediate filament proteins. It was estimated that 55%-76% of the A431 cells were retained by the ATS filters, and of those cancer cells that passed through the ATS, 62% suffered lethal trauma and the remainder showed morphologic damage. In clinical studies, blood was harvested from the surgical site during resection of primary cancers from three patients. In agreement with the laboratory studies, 50%-68% of tumor cells were filtered by the ATS from blood harvested during surgery. These results are discussed in terms of metastatic inefficiency and the potential for use of autotransfused blood salvaged during cancer surgery.
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