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Liver Cancer and Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the more common causes of cancer deaths worldwide. Not unexpectedly, the highest incidence of this disease is in hepatitis B endemic areas, although I think we all are expecting more of an impact from hepatitis C over the next few decades liver cancer, hepatocellular carcinoma.

Surgical resection exists in those patients with well maintained liver function. Percutaneous ethanol injection, if you have a radiologist with a steady hand. Of course, orthotopical re-transplantation for a selected group of patients, chemo-embolization, transarterial chemo-embolization, or simply transarterial embolization without chemotherapy, and experimental medical therapy.

Liver transplantation for hepatoma initially gave poor results, unacceptable results, because these early studies basically included patients with advanced disease. I think that after this initial attempt, most people in the transplant community became disappointed and disillusioned about transplanting for this disease. However, after 1990 we began to understand that we simply had to be more selective in who was transplanted for hepatocellular carcinoma.

When one of our liver fellows several years ago first pulled out our data from the early days of our transplant program, looking at patients who were transplanted for hepatoma in various stages, he discovered that this group who presented with a rising alpha-fetoprotein - and this was not a level necessarily associated with the lower values one might see with an active hepatitis C - these were patients who had significant values. Frequently over 400 nanograms per milliliter. When we looked at the survival on these patients, as you might expect, it was really quite good. In other words, we got these patients before the tumor became large or had a chance to progress. But when you looked at the data on any patient who had an identifiable mass lesion.

Letís look then at transarterial embolization, or chemo-embolization, not necessarily in a setting of patients who are transplant candidates. This very important paper from Spain came out last year in Hepatology, where they looked at the probability of progression of the initial presenting tumor in patients who were treated with transarterial embolization without chemotherapy added. As you can see, the probability that the tumor would progress over a very short time was really quite high in both groups and there was no significant difference in either group, either embolized or the group that were treated "symptomatically". As you might expect, the survival curves also fail to show an advantage from transarterial embolization. This nice paper from the French group several years ago in Hepatology had looked at the effect of chemo-embolization.

Letís talk now about surgical resection. Surgical resection continues to come up I think, not only with regard to those patients who donít have cirrhosis and therefore can undergo segmental or subsegmental resection, but also in regions of this country where waiting lists for liver transplantation may exceed two years. Fortunately United Network of Organ Sharing has made it possible for patients with hepatocellular carcinoma to be listed as a status II-b.

Whether or not adjuvant treatment protocols are going to improve the outcome from these trials, I think remains to be seen. Again, I think that if you donít have a surgeon who understands the scheme of the segmental anatomy of the liver, then these operations are going to be fraught with a great deal of risk. But as every surgeon knows, that even if you restrict these resections to patients with childís A cirrhosis, many of these patients very quickly act like childís B or childís C cirrhotics after theyíve had part of their liver wiped out. So the Spanish group proposed a couple of years ago that there were two variables that really were important in trying to determine which of these patients would deteriorate after surgical resection and which wouldnít, and they settled on the fact that the bilirubin needed to be normal and that these patients should have hepatic venography done and they should have the absence of portal hypertension. These are perhaps the true indicators of how a patient may do.

Percutaneous ethanol injection, on the other hand, can be considered for patients with worse liver function but still the tumor size has to be limited and it usually is ineffective in patients with tumors larger than 5 centimeters in size but can be considered for patients with multiple lesions, 3 centimeters in size or less. The treatment has to be thorough, and this should be in quotation

But point of fact, in patients with isolated lesions smaller than 5 centimeters in size, the Castellís paper from four or five years ago showed that patients who are thoroughly treated with alcohol injection do about as well as patients with surgical resection. This shows the recurrence rates, one group compared to another, and you will note that it is discouragingly high in both groups within 24 months of treatment, but there is no significant difference between the two and certainly after 36 months there is no significant difference.