Irradiation and Anticoagulant Therapy to Prevent Pulmonary Metastases of the V2 Carcinoma in Rabbits

Dissemination of cancer may occur by way of the lymphatics and by the venous blood. Spread by the blood stream is the more serious and is the method about which the least is known. It is presumed that the cancer cells enter the blood stream by invasion of blood vessels and circulate in the blood until they are destroyed or caught in the small vessels. When the cells become fixed, they may pass through the vessel walls and begin to grow (24, 25), or may become fixed by fibrous tissue and be destroyed. It is possible that the majority of the malignant cells released into the circulation are destroyed by lytic properties of the blood (5) or continue to circulate until they are no longer viable. Others may lodge and remain dormant for years (12), and still others will produce obvious early metastatic cancer (6). It has long been known that cancer cells may be found in the circulating blood of patients with cancer (4, 8, 11, 18, 19). During operative manipulation both in man (22) and in laboratory animals (6) there is an increase in the number of cancer cells in the venous blood draining a tumor. That the cancer cells in the blood are viable has been demonstrated by the growth of tumors in animals in which such blood has been injected (6, 15). Viability of human tumor cells in blood (17, 20) has been indicated by their growth in tissue cultures. It has been suggested that chemotherapeutic agents be used to destroy the malignant cells in the blood, but the complications of such treatment may be severe (21). In a previous paper we reviewed our experiments with heparin and fibrinolysin (1, 2, 13, 14) and described the effects of irradiation plus a single injection of heparin or fibrinolysin on the metastases of Walker carcinosarcoma 256 in the rat (3). The present experiments were designed to determine the effects of these agents on a different tumor in a different animal species and to show the effect of prolonged use of heparin and fibrinolysin. Materials and Methods Adult female rabbits (Blue Spruce Farms), average weight 2 lb., were used for these studies. The V2 carcinoma4 was maintained by serial transplantation into the thigh muscles of donor rabbits. A tumor suspension was made as follows: fresh tumor tissue was ground in a glass homogenizer and then suspended in saline. Dilution with saline was continued until a count of 50,000 cancer cells/ml. was reached. The suspension was prepared and injected within two hours of the time of removal of the tumor. Nonirradiated and irradiated tumors were prepared in the same way, and the number of cells per milliliter was the same in the irradiated and nonirradiated tumor-cell suspensions. Irradiation Procedure: The irradiation source was a General Electric Maxitron operated at 250 kvp and 30 ma, emitting a beam having a half-value layer of 1 mm. Cu (0.33 mm. Cu filtration added). The target-source distance was 35 cm.