The Recanati/Miller Transplantation Institute
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Programs Liver Transplantation: Adult Liver Transplantation for Liver Tumors Can I have a liver transplant for my liver cancer?
Introduction | Referrals |
Evaluation | Pre-operative Experience |
Liver transplantation for cancer: History Liver transplantation began in the late 1960's, and from the beginning liver cancer was one of the main reasons people received liver transplants. Until the 1980's, there was no reliable way to prevent rejection of transplants, so few were performed and results were poor. With the discovery of the drug cyclosporine, the first really effective anti-rejection medicine, the success rate rose dramatically- to about 75% after one year- and the number of transplants began to rise rapidly, as well. Before long, it became clear that most people transplanted for liver cancer did poorly because the cancer returned, and most transplant programs stopped transplanting patients with cancer entirely. Over the past ten years, however, a greater understanding of the behavior of liver cancer and the development of better tests to determine its extent have enabled us to identify some people with liver cancer for whom a liver transplant is indeed the best treatment. Liver transplantation: General aspects Even now, a liver transplant is about as major an operation as you could undergo. In order to make it through, you have to be in good general condition; the evaluation process gives particular attention to making sure your heart, lungs, and kidneys are in good shape. There is no formal age limit, but most people past 70 are not ideal transplant candidates. Most of the technical problems in performing liver transplants have been figured out, but complications after transplant are still a major problem. Infection is the most serious complication; the medicines required to prevent rejection weaken your immune system, and germs that are normally harmless can cause big trouble. Transplant-related complications claim the lives of 10-15% of patients undergoing liver transplantation within the first year. After the first year, transplant-related complications are much less of a problem, and the main thing that determines your long-term survival is whether the problem for which you received the transplant comes back (for example, hepatitis C or liver cancer). Most people with liver cancer have cancers that began somewhere else (for example, the colon or the breast) and have spread to the liver. Such cancers are called metastatic. How do metastatic cancers get to the liver? By the blood stream. Cancer cells enter the bloodstream at the site of the original (primary) tumor, circulate through the body, and lodge themselves in the liver, where they start to grow. If you have metastatic tumors in the liver, it is very unlikely that there are no tumor cells anywhere else in the body- even if all tests seem to show that everywhere else is clear. Cancer grows faster in the liver than in other places, because the liver has a rich blood supply and contains plenty of the nutrients cancer cells need. The experience around the world over the years has been that when liver transplants have been tried for metastatic cancer, the cancer has nearly always come back. There are a few unusual, very slow-growing types of metastatic liver cancer, for example neuroendocrine tumors, for which transplantation may have a role even it isn't a cure- we'll discuss this subject later. Primary liver cancer: Hepatocellular carcinoma If your cancer originated in the liver- this is called a primary liver cancer- then there may be a role for transplantation, but the subject is not at all simple. The most common form of primary liver cancer is called hepatocellular carcinoma, HCC for short. In 90% of cases, HCC is the result of another liver disease- usually some form of cirrhosis. Cirrhosis, or scarring of the liver, is the end result of any condition that causes continuing liver damage over a period of years. In the United States, the most common cause of cirrhosis leading to HCC is hepatitis C; around the world, however, hepatitis B is the most common cause of HCC. Natural history of Hepatocellular Carcinoma In the early stages of HCC, the cancer usually grows slowly and produces a round mass with a membrane (called a capsule) separating it from the surrounding liver. The cancer cells look quite similar to normal liver cells (this is called well-differentiated). As the HCC grows to a size of about 2 inches (5 centimeters), its cells start to look more abnormal, and it begins to break through its capsule and invade into blood vessels. At this point, the cancer begins to gain the ability to metastasize to other places, most commonly the remaining liver, the lungs, and the bones. Advanced cirrhosis with small HCC Let's look at a few different scenarios. The easiest is if you are so sick because of advanced cirrhosis that you need a liver transplant, and you just happen to have a small (less than 5 cm) HCC. In a person with advanced cirrhosis, it is very risky to try to remove the part of the liver that contains a cancer. Small HCC's almost never come back after transplant. A transplant will cure both the cirrhosis and the cancer, and should be done as soon as possible. Let's say that you have a small HCC and you have cirrhosis, but your liver is still working pretty well and (apart from the tumor) you really don't need a transplant. The only reliable way to cure HCC is to take it out. We can do this either by removing the part of the liver that contains the cancer (this is called liver resection), or by removing the entire liver and putting a new one (or part of one) in its place. Each of these options has both pluses and minuses. Liver resection is a much simpler process than a transplant. We can schedule a liver resection within a week, and you'll be home within 5-6 days. If you meet the criteria for safe resection, the risk is low- about 1-2%. Plus, you don't have to take all the medications that transplant patients require to prevent rejection. Resection doesn't cure cirrhosis, though. The same cirrhosis that led to your cancer may get worse and cause liver failure, or may cause new HCC's to develop. The chances you'll be alive five years after a liver resection for HCC are about 50-50; however, about 2/3 of those who make it to five years will have had other tumors diagnosed and treated along the way. Safety of liver resection for HCC How do we decide if liver resection is safe for you? We can safely remove up to 75% of a normal liver, and within 4-6 weeks the liver will grow back to normal size. When the liver has cirrhosis, however, it does not grow back very well when part is removed. The worse the cirrhosis, the higher the risk. Cirrhosis causes two problems with the liver- it reduces liver function, and it causes scar tissue that restricts the flow of blood through the liver, resulting in high pressure in the veins draining all the organs in the abdomen (this is called portal hypertension). To judge how well your liver is working, we use a scoring system called Child's classification. Using both laboratory tests and findings on examination, we grade your cirrhosis as Child's A, B, or C. The easiest way to judge how much portal hypertension you have is to check your platelet count (platelets are small cell fragments in the blood that are important to make the blood clot normally). Portal hypertension causes your spleen to enlarge and platelets get trapped inside, resulting in a low platelet count in the blood. If you have Child's A cirrhosis and a normal platelet count, and your cancer is located at a spot in the liver that can be removed without removing much functioning liver tissue, then liver resection should be safe. Otherwise, transplant should be seriously considered. Transplantation for HCC in early cirrhosis On the surface, a liver transplant seems like a great choice if you have cirrhosis and a small HCC. It will almost certainly cure the cancer, and will get rid of the cirrhosis at the same time. Transplants are risky, though- much riskier than resections. There's about a 15% chance that if you have a transplant you won't make it through the first year, due to complications of the transplant. That's much higher than for resection. After a transplant, you will have to take a number of very potent drugs for the rest of your life to block your immune system and prevent rejection, and these medicines have significant side effects. Even though the transplant gets rid of the cirrhosis, it doesn't necessarily get rid of the underlying cause. For example, hepatitis C, the most common cause of cirrhosis leading to liver cancer in this country, is transmitted through infected blood. If you have hepatitis C, the new liver is exposed to the virus as soon as your blood begins to flow through it. Because your immune system is blocked by the anti-rejection drugs, the virus often grows faster than before, and in some cases causes severe damage within a year or two. The biggest problem with transplants these days, however, is finding a donor. Liver transplantation: Finding a donor If a transplant center decides that you need liver transplant, you will be placed on the national waiting list. The way the system is set up in the United States, patients are graded as to how sick they are according to rules made up by the United Network for Organ Sharing (UNOS), and the sickest patients get the most priority. Status 1 is reserved for people who have sudden liver failure or who have just had a transplant that failed. Status 2A patients have cirrhosis that is so advanced that they have to be in intensive care and have only a week or two to live. Status 2B means that you've already had significant complications of cirrhosis, while Status 3 patients have cirrhosis but so far haven't had any major complications. Priority for patients with early HCC If you have a single HCC less than 5centimeters in diameter (about 2 inches), or two or three HCC's none of which is more than 3 centimeters in diameter, you can qualify as Status 2B. In many regions of the country, however, livers are so scarce that most of the transplants are performed in Status 1 or 2A patients, and even as Status 2B the waiting time can be very long- often over a year. Another important thing that influences how long you will have to wait for a liver donor is your blood type. The livers from donors who are blood type O will work in any recipient, and in emergencies type O donor livers often get used in recipients with other blood types. If you are type O, on the other hand, you can only accept a type O donor liver. This means that you will have to wait longer that people with other blood types. In New York, a patient with blood type O and a small HCC will have to wait nearly two years- and in that time, it's very likely that the tumor will have grown to more that 5 centimeters and begun to spread. Control of HCC while awaiting transplant In order to try to prevent your HCC from growing while you are waiting for a transplant, we usually decide to treat the tumor. The three most commonly used treatments are injection of the tumor with 95% alcohol, injection of chemotherapy and microscopic plastic beads into the artery bringing blood to the tumor to cut off its blood supply (chemoembolization), and heating of the tumor using an electrical device (radiofrequency ablation). No one method applies to all cases, and the choice of which one to use depends a lot on how expert your doctor is at the various techniques. In some cases, these treatments will completely destroy an HCC, but they are not reliable enough to count on. Almost everyone agrees, however, that they are useful to buy some time. Transplant for HCC > 5 cm.: Living donor transplants What about if your HCC has already grown past that 5 centimeter limit, or if you have more that three tumors, or if there are other signs that your tumor is already more advanced? If there is evidence that the tumor has spread out of the liver to lymph nodes or other organs, or if it has grown into the veins that bring blood into the liver (portal vein) or drain its blood out (hepatic veins), then a transplant has no chance of curing you and would be a mistake. If after a careful search there is no sign of spread, transplant might be your best option. We know that the more advanced your HCC is before transplant, the greater the chances of your HCC coming back after transplant, even if we cannot detect spread preoperatively. The process of tumor metastasis begins microscopically, and may not become evident until a year or two after your transplant. Because of the increased risk that the tumor will come back, the doctors who created the system that decides who gets priority for donor livers felt that giving priority to patients with advanced tumors would not be a wise way to use the scarce donor resource. As a result, while you can get onto the waiting list, you can't get any more than Status 3 priority, which means that (in most regions, at least) you will never get transplanted. In light of this situation, many transplant centers have just decided that patients with HCC over 5 centimeters are not transplant candidates at all. However, while the chance that the tumor will come back is higher than if the tumor was small, there is still a significant chance that it will not. From your standpoint, since there is no other treatment with any chance of curing you, transplant is by far the best option. The development of programs for adult-adult living donor liver transplantation at a number of centers in the US and around the world offers promise in this situation. At our hospital, over 1/3 of our adult living donor transplants have been for patients with tumors. The techniques, as well as the ethics, of living donor living transplantation are still in the process of being defined, but results to this point have encouraged us to actively pursue this approach. What if you are one of the 10% of people with HCC who do not have cirrhosis? We liver surgeons have gotten very good at removing tumors from otherwise normal livers, even when they are very large. If you have an HCC in an otherwise normal liver and an expert liver surgeon cannot remove it, chances are that your tumor is too advanced to be cured by a transplant. You should be evaluated carefully at a center that offers both resection and transplantation, as decisions have to be made on a case by case basis. Transplant for cholangiocarcinoma There are a couple of other types of primary liver tumors for which a liver transplant might be considered. Cancer can develop from your bile ducts- the passages that collect the bile from within the liver, through which the bile flows into the intestine. This type of cancer is variously called cholangiocarcinoma, bile duct carcinoma, or Klatskin tumor. If you have the liver disease called primary sclerosing cholangitis, you have a greatly increased chance of developing this kind of tumor. Bile duct cancer spreads in a totally different way from HCC- it finds its way into lymphatic channels and along the course of nerves running alongside the bile ducts at an early stage, and often has already traveled a distance away from the main tumor by the time it is discovered. In an attempt to remove all cancer cells, transplant surgeons have gone so far as to remove the liver along with part of the stomach, the first part of the small intestine, the pancreas, and the entire bile duct. This massive operation, called a cluster transplant, has been abandoned because of the high rate of complications and the low rate of cure. If you have cholangiocarcinoma, most transplant centers these days do not consider you a transplant candidate. A few hospitals have begun experimental programs using combined radiation and chemotherapy followed by transplantation in carefully selected cases with good early results, but the word is still out on this approach. Transplant for epithelioid hemangioendothelioma Epithelioid hemangioendothelioma is a rare type of cancer that often appears to originate in the liver, though it is actually a blood vessel tumor that may also begin in other places like the bone marrow or the spleen as well. If you've been given this diagnosis, take a deep breath, slow down, and relax- don't rush into anything. There's a lot we don't understand about this tumor, but one thing we do know is that is slow-growing- often very slow-growing. There were reports from the early days of liver transplantation that results of transplants for patients with epithelioid hemangioendothelioma were good- even if the tumor was present in places outside the liver. We have patients with this disease who we have been following for a number of years with little change in the size of the tumors, and we are increasingly wondering whether the same good results reported with transplantation might have been achieved without surgery. Epithelioid hemangioendothelioma probably always develops in multiple sites within the liver. We have seen a few cases where, after an attempt to remove what seemed like a localized tumor by liver resection, tumors in the remaining liver appeared and started growing at a very rapid rate. We are concerned that the same factors that cause the liver to regenerate after resection may stimulate growth of this type of tumor, so we do not recommend resection for this disease. The best thing to do, if you have epithelioid hemangioendothelioma, is to wait. If the tumors progress in your liver to the point where they are causing trouble, a transplant may solve that trouble and prolong your life, even though it will probably not cure you. As with advanced HCC, you are not eligible for priority on the waiting list if you have epithelioid hemangioendothelioma; practically speaking, the only way to get a liver may be from a living donor. Metastatic neuroendocrine tumors At the beginning of this article, we mentioned that most liver tumors are metastatic, and that transplant is not the answer for patients with metastatic tumors. There are a few exceptions, however. The most important of these is if you have one of the group of closely related tumor types that fall into the general category of neuroendocrine tumors. These tumors usually arise in the pancreas, the intestine, or the lung. The liver is the most common site to which they spread, and because the liver is such a good place for tumors to grow, your liver metastases may well be much larger than the primary tumor. In fact in some cases, despite a careful search, the primary site cannot even be identified (there may be some cases in which neuroendocrine tumors arise within the liver, but this is quite rare). Neuroendocrine tumors are, as a group, quite slow-growing. The tumor cells often produce hormones or other substances that can cause you a variety of problems including diarrhea, stomach ulcers, low blood sugar, and flushing that can be more troublesome than the mere presence of the tumor masses. Many different treatments have been proposed for liver metastases from neuroendocrine tumors, including resection, chemoembolization, and liver transplantation. While none of these is likely to cure your disease, all can give good results in terms of relieving symptoms, and the chances are that you will live more than five years. Because a liver transplant is so risky, we believe that other treatments, mainly chemoembolization, should be used first. Most likely, you will be able to live a fairly normal life for a long time with periodic chemoembolization. If the time comes when the tumors in the liver grow or are producing hormones so that you are having bad symptoms that don't respond to chemoembolization, a transplant will give you a number of years with good quality of life. Once again, due to the fact that having this sort of tumor does not qualify you for priority on the transplant waiting list, a living donor transplant may be your most realistic option. Are there other metastatic tumors for which liver transplant makes sense? Following the same line of reasoning as in cases of neuroendocrine tumors, if you have a particularly slow-growing type of tumor, if the primary site has been identified and removed, if a careful search reveals no tumor outside the liver, and if other treatment options have been exhausted, a liver transplant may be the right thing to do. Such tumors are far and few between, for the most part in patients with unusual low-grade malignancies rather than the more common tumor types such as colon or breast cancer. Naturally, the same problem in obtaining donor livers discussed in regard to advanced HCC and neuroendocrine metastases applies in this setting as well. In summary, a liver transplant is not the solution for most people with liver cancer. If you have cirrhosis and HCC, or one of the other types of tumor discussed above for which a transplant is among the options that should be considered, you should seek evaluation at a center with extensive experience in liver surgery and transplantation and with a special interest in the care of patients with liver cancer. |