Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Figure 1 Structure of the peritoneum. The peritoneum is composed of a mesothelium supported by a basement membrane that rests on a layer of submesothelium. The mesothelium consists of a monolayer of either flattened, stretch, squamous-like or cuboidal mesothelial cells. The luminal surface of mesothelial cells has numerous microvilli varying in shape, size and density. Cilia have also been identified on the surface of resting mesothelial cells. The basement membrane consists of a thin laminar network containing type I and IV collagen, proteoglycans and glycoproteins. The submesothelium consists of a complex network of extracellular matrix made up of different types of collagen, glycoproteins, glycosaminoglycans and proteoglycans. Blood vessels, lymphatics, and various cells types (fibroblasts, resident tissue macrophages, and mast cells) are also found is this layer. ECM: Extracellular matrix.

Figure 2 Pathophysiology of colorectal peritoneal carcinomatosis: the peritoneal metastatic cascade. The emergence of PC is the result of a molecular crosstalk between tumor cells and host elements, comprising several well-defined steps. A: Individual or clumps of tumor cells detach from the primary tumor and gain access to the peritoneal cavity. Spontaneous exfoliation of tumor cells from the primary tumor can be promoted by the down-regulation of E-cadherin, increased interstitial fluid pressure, and iatrogenically during surgery; B: The free tumor cells become susceptible to the regular peritoneal transport. Peritoneal transport is due to changes in the intra-abdominal pressure during respiration, gravity and peristalsis of the bowel; which results in a clockwise flow from the pelvis, along the right paracolic gutter and to the subdiaphragmatic space and finally towards the pelvis again; C: Attachment of tumor cells to distant peritoneum occurs via two processes, denominated transmesothelial and translymphatic metastasis. During transmesothelial metastasis, loose tumor cells directly adhere to distant mesothelium through adhesion molecules. During translymphatic metastasis, free tumor cells gain access to the submesothelial lymphatics through lymphatic stomata. Preferential tumor growth in the milky spots of the greater omentum has been observed; D: Tumor cells invade the submesothelium. In areas of absent or rounded (cuboidal) mesothelial cells, tumor cells interact with the laminar network of the basement membrane through integrin-mediated adhesion. Subsequent invasion of the submesothelial tissue occurs via degradation by proteases (MMPs); E: Systemic metastasis. PC: Peritoneal carcinomatosis.