Mechanisms of malignant ascites production

The accumulation of malignant ascites is determined primarily by the obstruction of diaphragmatic lymphatics with tumor inhibiting the outflow of peritoneal fluid. An abnormal increase in peritoneal fluid production has been shown to contribute to ascites formation by a marked neovascularization of the parietal peritoneum. Cell-free malignant ascitic fluid obtained from rats with intra-abdominal Walker 256 carcinoma when infused into the peritoneal cavities of normal animals causes an increase in edema formation and an increase in the permeability of protein from normal omental vessels. Protamine sulfate, a known inhibitor of angiogenesis when infused into the peritoneal cavity along with cell free malignant ascitic fluid, significantly reduces the leak of protein from the intravascular space when compared to ascites alone. Persistent permeability changes continue to exist even after the inhibition of vessel proliferation. These results indicate that angiogenesis is responsible for a major portion of the increase in permeability caused by malignant ascitic fluids. Other tumor-induced factors may be present which alter vascular permeability by other mechanisms which remain to be elucidated.