What motivated you to do this study on liver cancer?
Dr. Thuluvath: Liver cancer is increasing in this country because of what we call the silent epidemic of hepatitis C. It is also due to what we call cryptogenic cirrhosis, which we presume is due to non-alcoholic fatty liver disease. This is secondary to obesity, hyperlipidemia and diabetes. So, there is an increase in liver cancer due to these diseases in the community. Two million people die from liver cancer every year.
What did you look at in your study?
Dr. Thuluvath: The question of our study is what is the best form of treatment for liver cancer in someone with cirrhosis of liver. In this country, most of the liver cancer patients have cirrhosis at one point. In our own transplant circle, we know liver transplantation is perhaps the best treatment modality, because it not only removes the cancer but also the diseased liver. So, we decided to look at the nationwide database of about 1,000 patients transplanted for this condition. We divided the last 20 years into three time periods to look at the trends. Over the last 10 years, we have learned a lot about who got transplants, how to pick the right patients, the selection, and how to get the best results.
The study looked at data nationwide and found there has been a major improvement in the outcome of liver cancer in this country. In the early part, 1987-1991, the survival was around 25 people, and the next period it was up to 96 people, and then in the most recent period up to 2001, it has gone up to almost 260 people. That’s pretty good for cancer. When you say five years, it is almost like a cure for this patient because if liver cancer were to recur it would happen within one or two years. So, that’s what prompted us to do the study, and we were quite pleased to see we can cure liver cancer in somebody with cirrhotic liver, an advanced cirrhosis, and 60 percent or more can live for five years or more.
Have there been many studies looking at trends in liver cancer?
Dr. Thuluvath: There was a major paper published in The New England Journal of Medicine in 1996, which gave recommendations about how to get the best results for liver transplant, and it is since known as Milan criteria. Since then there have been many small papers on the subject.
What’s the message you want to send to patients?
Dr. Thuluvath: Liver cancer, if it is detected early, is curable. The key here is to make that diagnosis early. For that, the patients and doctors have to work together. We have different ways to do surveillance. We can do blood tests, ultrasounds, computed tomography (CT) scans or magnetic resonance imaging (MRI). But, the majority of patients with cirrhosis don’t get any of these tests.
The commonly available techniques, whether we use MRI, blood test or a combination, still miss a third of liver cancer. We, myself and some of my colleagues, are focusing on finding ways to diagnose cancer at an earlier stage. Then, we can offer them many more options, including a liver transplant, and we can probably improve the survival of patients with liver cancer in this country. This may not apply to every country in the world, where they don’t have the access to liver transplantation, but at least in the United States, we can improve the survival by early detection and the offering of the best modality of treatment.
Do you feel like liver cancer does not receive as much attention as it should to be able to properly prevent it?
Dr. Thuluvath: I think you get a lot of publicity for prostate cancer and to some extent breast cancer. But liver cancer, because it’s not as common as these cancers, has not come to that attention of the public. Liver cancer is the sixth most common cancer in the world, but it seems to affect the part of the world where there is a lot of hepatitis B and poverty. In Africa and parts of Asia, this is like an epidemic. Now, it looks like liver cancer has come to the United States and Western Europe. I think there is now more attention being given to liver cancer.
One cancer we think we can prevent early is colon cancer. Early detection is key there. I think in a way that is the best example for early detection and cure of all cancers. Simple tests can prevent or cut down a significant proportion of this cancer.
Are there specific reasons why liver cancer is more aggressive now?
Dr. Thuluvath: That’s a very interesting question. We addressed this in a small study we did in Maryland. Worldwide, Africans and Asians seem to have a higher incidence. That is perhaps due to hepatitis B. If you go to the Western part of this country, you see a lot of cancers in Asians because they had what we call transmission of hepatitis B from their parents. But, the difference between the races has decreased significantly in the last 10 years in this country. When we looked at the reason they differ Maryland, we actually found Caucasians and blacks have the same incidence of liver cancer. There was a big gap that seems to have closed significantly. It could affect anybody.
What are the risk factors for liver cancer?
Dr. Thuluvath: The risk factors are important. Hepatitis C, B, hemochromatosis, and cirrhosis for many reasons could predispose someone to liver cancer. This patient should be carefully monitored. Once they develop cirrhosis, the risk increases significantly. They need close monitoring at least every six to 12 months with some sort of scanning. They can have either an ultrasound, CT scan or MRI; it depends on the expertise of the local hospital. And, they should have regular blood work to look for this cancer. This is a treatable cancer, and the early detection is the most important aspect of the management.
Are transplants given early after diagnosis, or does the disease have to develop extensively before a transplant is approved?
Dr. Thuluvath: I think the important part of our studies tells us the faster the transplantation the better the outcome will be. You don’t want the liver cancer to advance because there is a high probability that cancer may spread elsewhere, like to the blood vessels or lymph nodes. The earlier the better.
Now that you have this exciting new information, are you still dealing with the shortage of organs?
Dr. Thuluvath: That is something we have not been able to solve. The organ donation in this country, unfortunately, has not gone up in the past 10 years. It’s almost plateaued. I think a shortage of this nature may help people to learn more about liver transplantation. Many of these patients would have died within a year if they were not transplanted, and many of them may have contributed significantly to the community and the families.
In the future, we may be able to find ways to use organs from other species, and the research has to develop in that field. Hopefully, maybe 10 or 20 years later, we will be thinking of stem cell research to help us to develop these organs. But, I think in the immediate future, the focus should be to increase the organ donation and also to perfect the technique of live donor liver transplant. That can save many people.
What do you see as the impact of this study?
Dr. Thuluvath: I’m excited about the possibilities. I think the public needs to know all these things because unless they’re educated, they’re not going to go to their physician and say, “Time for me to have a screening test.” Once the patient is educated, he or she can remind the physicians too. Also, they need to learn that cancer, if you diagnose it early, is a curable disease
Who should be talking to their doctors about screening?
Dr. Thuluvath: Anyone with cirrhosis of liver should talk to their doctors about screening for liver cancer, and this is more important for those with hepatitis C, hepatitis B, and a condition called hemochromatosis, where there is too much iron in the body. These are the three major risk factors. But, we have recently seen increased incidence of cancer in people with cryptogenic cirrhosis, which means we really don’t know what caused cirrhosis, but we assume most of them may have progressed from fatty liver disease. This population is going to increase substantially because of obesity in this country. Two out of three people we see in this country are obese now, and the significant number will have fatty liver disease. A small proportion will progress to cirrhosis, which is a substantial number of patients, and many of them may end up with cancer of the liver. So, they should also get the early screening. I think that is the most important thing.
What do you hope to see in the immediate future of this field of study?
Dr. Thuluvath: From my point of view, I think we need to develop better techniques to detect this cancer. We don’t have very good tests yet. I would sense the detection rate is still around 60 percent to 65 percent. That means one out of three cancers could be missed even if you do all this screening. The screening has to be something that is easily applicable to a majority of patients, like a blood test, which has a very high sensitivity and specificity.
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