Mechanisms of peritoneal dissemination in gastric cancer.

Peritoneal dissemination is the most frequent metastatic pattern of gastric cancer, but the mechanisms underlying peritoneal dissemination are yet to be elucidated. Paget's 'seed and soil' hypothesis is recognized as the fundamental theory of metastasis. The 'seeding' theory proposes that the formation of peritoneal dissemination is a multistep process, including detachment from the primary tumour, transmigration and attachment to the distant peritoneum, invasion into subperitoneal tissue and proliferation with blood vascular neogenesis. In the present review, the progress of each step is discussed. Milky spots, as a lymphatic apparatus, are indicative of lymphatic orifices on the surface of the peritoneum. These stomata are open gates for peritoneal-free cancer cells to migrate into the submesothelial space. Therefore, milky spots provide suitable 'soil' for cancer cells to implant. Other theories have also been proposed to clarify the peritoneal dissemination process, including the transvessel metastasis theory, which suggests that the peritoneal metastasis of gastric cancer develops via a vascular network mediated by hypoxia inducible factor-1α.