A technique called transcatheter chemoembolization (TACE) is used for some patients with liver cancer that cannot be treated surgically or by radiofrequency ablation (RFA). The procedure is a way of delivering cancer treatment directly to a tumor through minimally-invasive means.
Although the procedure is rarely a cure for liver cancer, studies have shown that in 70 percent or more of patients the cancer shrinks and patients may live longer. In a number of studies, 20-60% more patients were alive 2 years after TACE compared to untreated patients. Chemoembolization also may relieve pain and other symptoms, make patients more comfortable and improve the quality of their lives. Another advantage is that the procedure may be repeated multiple times.
Explaining The Procedure
An angiogram, a real-time X-ray that highlights where blood flows, is performed to help the interventional radiologist look in the liver at the tumor without the need for an open incision. The interventional radiologist uses the x-ray images on the TV monitors to insert the catheter (which is like a piece of spaghetti) through a small nick in the skin at the groin and guide it through the artery that feeds the tumor. A combination of chemotherapy drugs and tiny particles, as small as grains of sand, are then injected directly into the tumor. The particles block off (embolize) the blood supply to the tumor, starving it of oxygen.
At the end of the procedure, the catheter is removed and pressure is applied to the entry point to prevent bleeding and a band-aid is applied. Patients remain in bed for six to eight hours and leave the hospital within two days.
Chemoembolization can be performed repeatedly on a patient. Typically, patients wait ten to twelve months between treatments. This procedure can also be used in conjunction with other cancer therapies.
Chemoembolization may not be appropriate for patients who have blockages of the veins that supply blood to the liver, very advanced cirrhosis of the liver or blockage of the bile ducts.
How Chemoembolization Works
The liver is unique because it has two blood supplies. The portal vein provides 75% of the livers blood supply and the hepatic artery supplies the remaining 25%. Tumors that grow in the liver typically receive their blood supply from the hepatic artery making chemoembolization possible. The drugs can be injected into the artery feeding the tumor while sparing most of the healthy liver tissue that feeds from the portal vein.
The treatment works in three ways to attack the cancer. First, because the chemotherapy is delivered directly to the tumor and doesn’t spread throughout the body, stronger doses of cancer-killing drugs can be administered compared to the doses used for standard systemic chemotherapy which is injected through a vein in the arm. Secondly, the tiny particles embolize, or block, the artery and decrease the flow of blood to the tumor causing it to shrink. Finally, by blocking the artery, the particles help contain the chemotherapy keeping it in direct contact of the tumor for a longer period of time—in some cases as long as a month.
This technique also may reduce some of the side effects of standard chemotherapy because the drugs are trapped in the liver instead of circulating throughout the body.
What You Can Expect After Treatment
After the procedure, you will receive prescriptions for oral antibiotics, pain, and nausea. Once home, you may experience fevers for up to a week. For the first two weeks, fatigue and loss of appetite are common. These are all signs of a normal recovery. However, if your fever suddenly becomes higher or your pain changes in intensity or character, contact your physician.
Although a majority of patients can resume their normal activities within a week, most are back to their usual state of health in about one month. Throughout this time it’s important to let your physician know how your recovery is progressing.
Eventually, you will get a follow-up CT or MRI scan, as well as blood tests, to determine the size of the treated tumor and how well the chemoembolization worked. CT and MRI scans will continue every three months thereafter to determine how much the tumor ultimately shrunk.
Benefits vs. Risks
- Chemoembolization can stop liver tumors from growing or cause them to shrink in 2/3 of cases treated. This benefit, on average, lasts 10-14 months.
- Chemoembolization can be used in conjunction with other cancer treatments including tumor ablation, radiation and chemotherapy.
- Most patients don’t die from the spread of cancer if it is confined to the liver, but rather from liver failure caused by the tumors growth. Chemoembolization can help prevent the growth of a tumor, preserving liver function and a relatively normal quality of life.
- Two randomized controlled trials published in 2002 showed improved survival in patients with hepatoma (primary liver cancer) after chemoembolization compared to supportive care alone. Additional studies showing benefit of TACE have been published since.
- Embolus (tiny particles) can lodge in the wrong place and deprive normal tissue of its blood supply.
- Even if antibiotics are given, there is always a risk of infection after embolization.
- There is a risk of an allergic reaction to the dye used in the angiography x-ray.
- There is a risk of kidney damage in patients with diabetes or other pre-existing kidney disease due to the angiography.
- Nausea, hair loss, decreases in white blood cells and platelets, and anemia may occur due to the chemotherapy drug.
- After 1 in 20 procedures, serious complications occur and typically include liver infection or damage to the liver. Liver failure is usually the cause of the 1 in 100 deaths related to this procedure.
What is Chemoembolization?
Chemoembolization is a way of delivering cancer treatment directly to a tumor. The liver is the most common part of the body for chemoembolization to be used, although it can be done in other areas. Under x-ray guidance, a small catheter is inserted into an artery in the groin. The catheter’s tip is threaded into the artery in the liver that supplies blood flow to the tumor. Chemotherapy is injected through the catheter into the tumor and mixed with particles that embolize or block the flow of blood to the diseased tissue.
Chemoembolization works to attack the cancer in two ways. First, it delivers a very high concentration of chemotherapy directly into the tumor, without exposing the entire body to the effects of those drugs. Second, the procedure cuts off blood supply to the tumor, depriving it of oxygen and nutrients, and trapping the drugs at the tumor site to enable them to be more effective.
What are some common uses of the procedure?
Chemoembolization is most beneficial to patients whose disease is limited to the liver, whether the tumor began in the liver or spread to it (metastasized) from another organ. Some success has been demonstrated with patients whose cancer has spread to other areas. Cancers that may be treated by chemoembolization include:
- Hepatoma (primary liver cancer)
- Metastasis (spread) to the liver from:
- colon cancer
- islet cell tumors of the pancreas
- ocular melanoma
- a primary tumor in another part of the body
Depending on the number and type of tumors, chemoembolization may be used as the sole treatment or may be combined with other treatment options such as surgery or radiation.
How should I prepare for the procedure?
Several days before the procedure you will have an office consultation with the physician who will be performing the procedure—an interventional radiologist. You will have blood drawn at the hospital or at a local clinic to learn how well your liver and kidneys are functioning and whether your blood clots normally. Staff also will advise you if there is to be a change in your medication schedule; be sure the physician is aware of all the medications you take regularly, particularly those that affect clotting, such as blood thinners like Coumadin. You will be admitted to the hospital the day before or the morning of the procedure.
What does the equipment look like?
The x-ray equipment and catheters are the same as those used for catheter angiography. Several materials can be used to embolize the arteries feeding the tumor, but the most common are oil and a plastic particle made from polyvinyl alcohol (PVA).
How does the procedure work?
The liver is unique because it has two blood supplies—an artery (the hepatic artery) and a large vein (the portal vein). The normal liver receives about 75 percent of its blood supply through the portal vein and only 25 percent through the hepatic artery. But when a tumor grows in the liver, it receives almost all of its blood supply from the hepatic artery. Chemotherapy drugs injected into the hepatic artery reach the tumor very directly, sparing most of the healthy liver tissue. Then, when the artery is blocked, the blood is no longer supplied to the tumor, while the liver continues to be supplied by blood from the portal vein.
Tumors, like all tissues, depend on a steady supply of oxygen and nutrients carried by the blood. Once the blood supply is cut off by embolization and the chemotherapy begins its work, the tissue begins to break down and, in successful cases, the tumor dies. It will appear as a scar or dead area on subsequent computed tomography (CT) scans or magnetic resonance imaging (MRI). Over time it may grow smaller.
How is the procedure performed?
The first step is to obtain x-ray pictures showing the arteries to the liver and the tumor by performing angiography. A sedative will be injected through an intravenous (IV) line to relax you. The radiologist will numb an area of the groin with a local anesthetic. A thin catheter is introduced through a very small incision into the femoral artery, a large groin vessel, and guided by TV monitoring into the arteries feeding the liver. Then contrast material is injected and a series of x-rays are taken allowing even tiny thread-like vessels to be seen. The catheter is then guided into the branches feeding the tumor and the chemoembolic material is injected. Repeated x-ray pictures will be taken to confirm that the tumor has been completely treated.
At the end of the procedure, the interventional radiologist removes the catheter and pressure will be applied to the groin area for a short time to prevent bleeding from the site of catheter insertion. You can expect to stay in bed for six to eight hours afterward.
What will I experience during the procedure?
In some instances, you will be admitted to the hospital on the day before your procedure, although commonly you will come to the hospital the day of the procedure. An intravenous (IV) line will be started and you will receive intravenous fluids. This helps to protect your kidneys during chemoembolization. In some cases, you may be given a medication called Allopurinol, which may help protect the kidneys from the chemotherapy and the products produced by the dying tumor cells. Your nurse will instruct you in how to use a breathing apparatus called an incentive spirometer. The purpose of this is to help you inflate your lungs so that you will not develop pneumonia. Prior to the procedure, you will be given additional medications to prevent nausea and pain, and antibiotics to prevent infection.
The sedative will make you feel relaxed and sleepy and you may nod off for brief periods, but generally will remain awake throughout the procedure. You may feel slight pressure when the catheter is inserted but no serious discomfort. Most patients experience some side effects after chemoembolization. This is called post-embolization syndrome and consists of pain, nausea, vomiting and fever. Pain is the most common side effect and occurs because the blood supply to the treated area is cut off. It can readily be controlled by oral or intravenous medication. Most patients leave the hospital within 24 to 48 hours of the procedure, after their pain and nausea have subsided.
You will be sent home with prescriptions for oral antibiotics, pain medicine and medicine for nausea. Fevers may occur normally for up to a week after the procedure. Fatigue and loss of appetite are common for two weeks and may last longer. In general, these are all signs of a normal recuperation. If your pain suddenly changes in degree or character, if your fever becomes suddenly higher than it had been or you notice any other unusual changes, it is important to let your physician know right away. Most patients can resume their normal activities within a week.
During the first month following the procedure, it is important to check in routinely to let the physician know how your recovery is progressing. You will return for a CT scan or MRI and blood tests to determine the size of the treated tumor and how well the chemoembolization worked. If there is tumor on both sides of the liver, commonly only part of the liver will be treated at first and after one month, you will return to the hospital for additional chemoembolization. CT scans are usually done after the completion of the chemoembolization therapy.
CT scans or MRI will be performed every three months thereafter to determine how much the tumors ultimately shrink, and to see if and when any new tumors arise in the liver. The average time before a second round of chemoembolization is necessary (because of new tumor) is between 10 and 14 months. Chemoembolization can be repeated many times over the course of many years, as long as it remains technically possible and you continue to be healthy enough to tolerate repeat procedures.
Who interprets the results and how do I get them?
The interventional radiologist can advise you as to whether embolization was a technical success when the procedure is completed and schedule your return for additional procedures or for follow-up scans.
What are the benefits vs. risks?
- In about two-thirds of cases treated, chemoembolization can stop liver tumors from growing or cause them to shrink. This benefit lasts for an average of 10 to 14 months, depending upon the type of tumor, and usually can be repeated if the cancer starts to grow again.
- Other types of therapy (tumor ablation, chemotherapy, radiation) may be used in combination with chemoembolization to control the tumor.
- When cancer is confined to the liver, most deaths that occur are due to liver failure caused by the growing tumor, not due to the spread of cancer throughout the body. Chemoembolization can help prevent this growth of the tumor, potentially preserving liver function and a relatively normal quality of life.
- There is always a chance that embolization material can lodge in the wrong place and deprive normal tissue of its blood supply.
- There is a risk of infection after embolization, even if an antibiotic has been given.
- Because angiography is part of the procedure, there is a risk of an allergic reaction to contrast material.
- Because angiography is part of the procedure, there is a risk of kidney damage in patients with diabetes or other pre-existing kidney disease.
- Reactions to chemotherapy may include nausea, hair loss, a decrease in white blood cells, a decrease in platelets and anemia. Because chemoembolization traps most of the chemotherapy drugs in the liver, these reactions are usually mild.
- Serious complications from chemoembolization occur after about one in 20 procedures. Most major complications involve either infection in the liver or damage to the liver. Reporting indicates that approximately one in 100 procedures result in death, usually due to liver failure.
What are the limitations of Chemoembolization?
Chemoembolization is not recommended in cases where severe liver or kidney dysfunction, abnormal blood clotting or a blockage of the bile ducts exists. In some cases—despite liver dysfunction—chemoembolization may be done in small amounts and in several procedures to try and minimize the effect on the normal liver. Chemoembolization is a treatment, not a cure. Approximately 70 percent of the patients will see improvement in the liver and, depending on the type of liver cancer, it may improve survival.
Embolization is the process of injecting a foreign substance into the tumor to stop the blood flow. The lack of blood deprives the tumor of needed oxygen and nutrients and eventually causes cells to die. The tumor blood supply is stopped with small pieces of material that have been saturated with chemotherapy drugs. Once the blood flow has stopped, the tumor is soaked in a very high concentration of drugs for a prolonged period of time. Thus, the tumor cells die very quickly. Below is a sketch that demonstrates the mechanism of chemoembolization.
A variety of materials may be used in the embolization process. Most embolization materials only cause temporary blockage of blood flow to the tumor cells, though in some cases materials will be used that can cause permanent blockage.
Chemoembolization is most beneficial to patients whose disease is limited to the liver. Some success has been demonstrated with patients whose cancer has spread to other areas. Patients with kidney disease, blood coagulation problems, or known allergies to contrast agents are not good candidates for this procedure.
The chemoembolization procedure takes place in a hospital setting. The actual procedure depends on the embolizing agent being used. Such issues as drug administration, anesthetic requirements, length of time of procedure, and potential side effects differ with each agent.
Chemoembolization is considered to be a relatively safe and effective method of treating unresectable liver tumors. The overall risk of the procedure is related to your general underlying health. People with jaundice, severe cirrhosis or kidney failure have an increased chance of complications.
Under x-ray guidance a small catheter is inserted into the femoral artery (located in the groin) and advanced into the liver artery. The embolic material and drugs are then injected through the catheter into the liver tumor. The procedure usually lasts 2 – 3 hours.
The majority of patients experience some side effects which may include abdominal pain, nausea, vomiting or fever. Various drugs can be administered that will control these symptoms and keep you comfortable. The symptoms will stop after 3 – 5 days. Studies show that patients with hepatocellular cancer undergoing this procedure may experience tumor shrinkage as well as an increased survival rate. The effectiveness of this therapy for patients with metastatic colon cancer is currently undergoing active investigation.
Most patients do very well after this procedure although some have pain in the region of the liver for days to weeks. If so, this can usually be handled with pain pills. Please let your doctor know if you are having pain so appropriate treatment can be provided. This pain occurs as the dead tumor and other liver tissue generates inflammation and is being cleaned up by your body.
Although TACE appears to be safe for the majority of patients with cirrhosis and liver cancer, there are some serious potential complications.
Rare but serious complications include:
1. Infection in the dead tumor tissue – this can be severe and even life-threatening in rare cases. Inform your doctor immediately if you develop a fever or chills within 1-2 weeks of this procedure.
2. Death of sufficient surrounding liver tissue to reduce liver function leading to liver failure. Notify your doctor if you feel seriously ill with nausea, vomiting, pain in the liver area, jaundice, dark “coca cola” urine.
3. Liver rupture or bleeding. Notify your doctor if you feel suddenly weak, dizzy or light-headed.
4. Kidney failure from the contrast dye used to perform the procedure.
Variable complication rates have been reported with a vast discrepancy. In one large series of 351 patients, the reported complications included the following (Chung, 1996):
- Severe postembolization syndrome with pain and reduced liver function (15.1%)
- Hepatic injury (30.8%) – Abnormal liver function tests (most of these patients), acute hepatic failure (rare), and severe hepatic damage (rare)
- Gallbladder damage (14%)
- Death of other tissues (4.6%)
- Gastrointestinal bleeding (2.8%)
- Severe blood stream infection (2.6%)
- Blood clot to the lung (1.7%)
- Severe damage to the spleen (1.1%)
- Tumor rupture (0.8%)
- Leakage of bile into or around the liver (0.8%)
- Liver abscess (0.3%)
- Spinal cord injury (0.3%)
- Death rate within 30 days of the procedure (not all deaths were related to the procedure itself) (2.6%)
Other series report a lower complication rate. One large series describing 2300 chemoembolizations had a lower complication rate of 4.4%, which was related to the use of chemoembolic agents and to the manipulation of the catheter or guidewire (Sakamoto, 1998). The complications included the following:
- Sudden liver failure (0.26%)
- Liver abscess (0.22%)
- Leakage of bile into or around the liver (0.87%)
- Serious damage to liver around the tumor (0.17%)
- Permanent damage to arteries inside the liver that may need repair (0.26%)
- Severe damage to the gallbladder (0.30%)
- Severe damage to the spleen (0.08%)
- Damage to the wall of the small bowel or stomach (0.22%)
- Blood clot to the lung (0.17%)
- Tumor rupture (0.04%)
- Bleeding from esophageal varices in patients with cirrhosis (0.13%)
- Complications related to catheter manipulation (1.52%)
- Making a hole in one of the arteries involved in the procedure leading to serious internal bleeding (0.17%)
- Death due to the procedure cannot be easily estimated but can occur, likely less than 1-2 in 100 or more cases.
Courtesy of Mary Ingalls, Liver Transplant Coordinator, University of Michigan