Regional therapies for cancers in the liverRegional Hepatic Chemotherapies in the Treatment of Colorectal Cancer Metastases to the Liver
Section snippets
Physiology of the Liver and the Rationale for Regional Hepatic Chemotherapy
The liver is unique in that it has two blood supplies. The portal vein supplies 75% of the blood flow to the normal liver and the remaining 25% is supplied by the hepatic artery. In CRC, initial systemic spread of tumor cells occurs via the portal venous system to enter the liver. Larger metastases (>5–10 mm) obtain their blood supply predominantly from the arterial circulation, while the remaining normal hepatic parenchyma is perfused by the portal system. It is therefore rational to access
Portal Venous Infusion of Chemotherapy
PVI of chemotherapy targets micrometastases in the liver by directing chemotherapy to these deposits before they are sufficiently large to require an arterial blood supply.
The potential benefit of PVI of 5-FU as adjuvant therapy has been studied in patients with colon and rectal cancer in a series of clinical trials to determine whether the incidence of metachronous liver metastases could be reduced and survival thereby improved using this technique11, 12, 13, 14, 15, 16 (Table 1).
The first
Intrahepatic Arterial Chemotherapy
Intrahepatic arterial chemotherapy allows a high concentration of chemotherapy to be delivered directly to the site of the tumor and maximizes local concentration. HAI of chemotherapy can be considered for patients with CRC liver metastases that are not amenable to surgical resection. This field has been advanced by improvements in catheter and pump technology that allow safe, continuous, or intermittent access to the hepatic arterial vascular arcade. The catheters are inserted at laparotomy,
Chemoembolization
Chemoembolization is the process of injecting chemotherapy drugs into the artery that supplies blood to the tumor in the liver. As liver tumors are supplied with blood almost exclusively from the hepatic artery, blocking the artery with a mixture of oil and microparticles made of albumin or starch causes ischemia, reduced blood flow, and therefore more time for the cytotoxic agent to diffuse down the concentration gradient between the vascular and tumor compartments, thus increasing local
Selective Internal Radiation Therapy or Radioembolization
Radioembolization or SIRT is a means of administering radiotherapy internally to unresectable hepatic tumors in a single procedure. This technique involves the injection of resin (SIR-Spheres, Sirtex Medical Limited, Sydney, Australia) or glass microspheres (Thera-Spheres, MDS Nordion, Ottawa, Canada) that contain radioactive yttrium 90 into the hepatic artery. The advantage of radioembolization over other local techniques is that the scope of therapy is not limited by the number and
Conclusions
The current literature suggests regional therapy may have a role in combination with systemic chemotherapy, in patients with liver-only metastatic disease, either in an advanced disease setting or following resection of metastases. However, further larger randomized trials with modern systemic chemotherapy regimens will be needed to anchor HAI therapy more firmly in the therapeutic mainstream for CRC.
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