Arterial Chemotherapy Infusion of the Liver Chemoembolization of the Liver (TACE)

Arterial chemotherapy infusion of the liver and chemoembolization of the liver (transarterial chemoembolization or TACE) are similar procedures that are used for the treatment of cancers in the liver. In both procedures, chemotherapy is injected into the hepatic (liver) artery that supplies the liver tumor. The difference between the two procedures is that in chemoembolization, additional material is injected to block (embolize) the small branches of the hepatic artery.

The normal liver gets its blood supply from two sources: the portal vein (about 70%) and the hepatic artery (30%). Primary liver cancer, also known as hepatoma or hepatocellular carcinoma (HCC) gets its blood exclusively from the hepatic artery. These techniques can also be used to treat secondary, or metastatic liver cancer, which is cancer that spread to the liver from other primary sites. These metastases also draw their blood supply from the hepatic arteries. This discussion will focus on primary liver cancer. Making use of this pattern of blood supply, investigators have delivered chemotherapy agents selectively through the hepatic artery directly to the HCC tumor. The theoretical advantage is that higher concentrations of the agents can be delivered to the cancer. The technique takes advantage of the concept of extraction: toxicity can be reduced by relying on the liver to extract or break down some of the chemotherapy after the tumor has been exposed to it before the chemotherapy gets through the liver into the systemic circulation.

In reality, however, depending on the chemotherapeutic agent used, much of the drug does end up in the rest of the body. Therefore, selective intra-arterial chemotherapy can cause the usual systemic (body-wide) side effects. In addition, this treatment can result in some regional side effects, such as inflammation of the gallbladder(cholecystitis), intestinal and stomach ulcers, and inflammation of the pancreas(pancreatitis). HCC patients with advanced cirrhosis may develop liver failure after this treatment. So, what is the benefit of intra-arterial chemotherapy? The bottom line is that there is a greater likelihood of having a therapeutic effect on the cancer. Nevertheless, fewer than 50% of HCC patients will experience a reduction in tumor size.

An interventional radiologist (one who does therapeutic procedures) usually carries out this procedure. The radiologist must work closely with an oncologist (cancer specialist), who determines the amount of chemotherapy that the patient receives at each session. Some patients may undergo repeat sessions at six- to 12-week intervals. This procedure is done with the help of the visualization of the hepatic arterial circulation via fluoroscopy (type of x-ray) imaging. A catheter (long, narrow tube) is inserted into the femoral artery in the groin and is threaded into the aorta (the main artery of the body). From the aorta, the catheter is advanced into the hepatic artery. Once the branches of the hepatic artery that feed the liver cancer are identified, the chemotherapy is infused. The whole procedure takes one to two hours, and then the catheter is removed.

The patient generally stays in the hospital overnight for observation. A sandbag is placed over the groin to compress the area where the catheter was inserted into the femoral artery. The nurses periodically check for signs of bleeding from the femoral artery puncture. They also check for the pulse in the foot on the side of the catheter insertion to be sure that the femoral artery is not blocked as a result of the procedure. (Blockage would be signaled by the absence of a pulse.)

Generally, the liver blood test levels rise during the two to three days after the procedure. This worsening of the liver tests is actually due to death of the tumor (and some non-tumor) cells. The patient may experience some post-procedure abdominal pain and low-grade fever. However, severe abdominal pain and vomiting suggest that a more serious complication has developed. Imaging studies of the liver are repeated in six to 12 weeks to assess the change in size of the tumor in response to the treatment.

Both techniques takes advantage of the fact that liver cancer (hepatocellular carcinoma, HCC) is a very vascular (contains many blood vessels) tumor and gets its blood supply exclusively from the branches of the hepatic artery. Chemoembolization (TACE) is similar to intra-arterial infusion of chemotherapy. But in TACE, there is the additional step of blocking (embolizing) the small blood vessels with different types of compounds, such as gelfoam or even small metal coils.

Thus, TACE has the advantages of exposing the tumor to high concentrations of chemotherapy and confining the agents locally since they are not carried away by the blood stream. At the same time, this technique deprives the tumor of its needed blood supply, which can result in the damage or death of the tumor cells.

The type and frequency of complications of TACE and intra-arterial chemotherapy are similar. The potential disadvantage of TACE is that blocking the feeding vessels to the tumor(s) may make future attempts at intra-arterial infusions impossible. Moreover, so far, there are no head-to-head studies directly comparing the effectiveness of intra-arterial infusion versus chemoembolization.

In Japan, the chemotherapeutic agents are mixed with lipiodol. The idea is that since the tumor cells preferentially take up lipiodol, they would likewise take up the chemotherapy. This Japanese technique has not yet been validated in head-to-head comparisons with conventional TACE.

In one large study involving several institutions in Italy, chemoembolization did not seem to impact overall survival. Patients who did not undergo TACE lived as long as patients who received TACE, even though the tumors were more likely to shrink in size in patients who were treated. Does this mean that TACE or intra-arterial chemotherapy does not work? Maybe, maybe not.

Studies in Japan, however, have shown that TACE can downstage HCC. In other words, the tumors shrank enough to lower (improve) the stage of the cancer. From the practical point of view, shrinking the tumor creates the option for surgery in some of these patients. Otherwise, these patients had tumors that were not operable (eligible for operation) because of the initial large size of their tumors. More importantly, these same studies showed an improvement in survival in patients whose tumors became considerably smaller. In the U.S., trials are underway to see whether doing TACE before liver transplantation increases patient survival as compared to liver transplantation without TACE.

It is safe to say that TACE or intra-arterial chemoinfusion are palliative treatment options for HCC. This means that these procedures can provide relief or make the disease less severe. However, they are not curative (do not result in a cure). Fewer than 50% of patients will have some shrinkage in tumor size. Further, they can be used only in patients with relatively preserved liver function. The reason for this is that these procedures can lead to liver failure in individuals with poor liver function.