E72b Mobile tissues: liver, HCC and colorectal metastases

Topic

The liver is unique in the physics of cancer treatment because it receives blood from two distinct circulatory systems simultaneously: the hepatic artery and the portal vein. This dual blood supply enables a type of treatment not possible in any other organ: selective arterial embolization.

A liver tumor relies almost exclusively on the hepatic artery for its blood supply, whereas normal liver cells—hepatocytes—receive the majority of their blood via the portal vein. This distinction allows for the selective blockage of the hepatic artery feeding the tumor; when this artery is blocked, the tumor becomes ischemic—deprived of the blood supply it needs to survive—while normal hepatocytes continue to receive sufficient blood through the portal vein and remain unharmed.

This physical principle—the ability to selectively block the hepatic artery without damaging healthy liver tissue—underpins two treatments currently used in clinical practice: one combining hepatic artery blockage with the local administration of chemotherapy directly into that same artery, and another combining that same selective blockage with the local delivery of internal radiotherapy via the hepatic artery.

Hepatocellular carcinoma, the most common primary liver tumor, frequently develops in a liver already affected by fibrosis or cirrhosis—that is, a liver where normal tissue has become scarred and hardened due to prior damage. This scarred liver tissue creates a fibrous stroma around the tumor that impedes the diffusion of drugs into the tumor's interior, making it difficult for administered chemotherapy to reach tumor cells in sufficient quantities. Colorectal liver metastases are the quintessential example of a tumor reaching the liver via the portal vein, as blood draining from the large intestine—where these tumors originate—flows directly into the liver through the portal vein before circulating to the rest of the body. The likelihood of a colorectal tumor cell successfully colonizing the liver depends on both the volume of blood flow reaching the liver via the portal vein and the presence of specific adhesion molecules—integrins—on the tumor cell's surface; these molecules are specific to liver tissue and enable the tumor cell to anchor itself there.

It is this combination—a dual blood supply allowing for treatments selectively targeted at the tumor without damaging healthy liver tissue, the tendency of hepatocellular carcinoma to develop on previously scarred tissue, and the direct route the portal vein provides for metastatic spread from the intestine—that makes the liver an organ where the physics of oncological treatment differs completely from that of any other tissue in the body.

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