Bilateral axillary lymph node metastases occurred after intradermal (id) injection of line 10 hepatocellular carcinoma cells over the thoracic spine of inbred guinea pigs. Excision of the dermal tumor 7 days after injection of tumor cells did not prevent the development of metastases. Injection of BCG into dermal tumors without surgery led to their regression and prevented the growth of microscopic metastases in both right and left superficial distal axillary lymph nodes. Bilateral id injection of BCG between the dermal transplant and each of the regional lymph nodes followed by excision of the dermal tumor also prevented progression of metastases. Unilateral id injection of BCG before excision of dermal tumors failed to retard metastases in contralateral superficial distal axillary lymph nodes. These results suggested that elimination of microscopic lymph node metastases required delivery of adjuvant to or near each metastatic site. Systemic tumor immunity alone may be inadequate to eradicate lymph node metastases.
A majority of guinea pigs, each with a growing syngeneic tumor implant in the skin and no other outward sign of malignancy (clinical stage I disease) but with tumor cells in the regional lymph nodes, was cured by tumor-specific immunization after limited surgery consisting of excision of the dermal tumor (1, 2). Animals treated by limited surgery alone were not cured; they developed palpable tumors in the draining lymph nodes, and at autopsy, 70-80% of the animals were found to have pulmonary metastases (3) . We now report the results of studies to test the efficacy of limited surgery and tumor-specific immunization in the treatment of animals, each with a dermal tumor and a palpable draining lymph node (clinical stage II disease) . We also tested limited surgery and immunization for the treatment of animals with clinical stage II disease and pulmonary tumors that had been implanted intravenously . Information from these studies may be useful in the design of clinical investigations to evaluate proposed treatments for humans with cancer.
Materials and MethodsAnimals . Male Sewall Wright strain 2 guinea pigs 3-4 mo old and weighing 500-550 grams were obtained from the Laboratory Aids Branch, Division of Research Services, National Institutes of Health (NIH) Bethesda, Md . and from the Experimental Animal Breeding Facility of the National Cancer Institute, Frederick Cancer Research Center, Frederick, Md . Caged in groups of six, the animals were maintained on a diet of NIH guinea pig ration and filtered tap water, which were available to the animals at all times.Tumor Line . We used a transplantable, syngeneic hepatocellular carcinoma-designated line 10 (L10)'-in transplant generations 9-19 . This diethylnitrosamine-induced tumor has been converted to ascites form and is passed intraperitoneally in weanling strain 2 guinea pigs . Inoculation of 10 6 L10 tumor cells intradermally in the flank 2 cm posterior to the axillae of animals that are left untreated leads to progressive intradermal tumor growth, metastasis of tumor cells to draining lymph nodes, and death. At autopsy, 30-40% of the animals are found to have gross, visible pulmonary metastases (3). Limited surgery designed to remove the dermal tumor and to leave microscopic lymph node metastases in place is not curative, but prolongs survival of the guinea pigs ; at autopsy, the majority of them are found to have pulmonary as well as lymph node metastases (3).
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