Monday, May 11, 2009

Surgical Treatment of Hepatocellular Carcinoma ( HCC )

The treatment options are dictated by the stage of liver cancer and the overall condition of the patient. The only proven cure for liver cancer is liver transplantation for a solitary, small (<3cm)>

Liver resection


The goal of liver resection is to completely remove the tumor and the appropriate surrounding liver tissue without leaving any tumor behind. This option is limited to patients with one or two small (3 cm or less) tumors and excellent liver function, ideally without associated cirrhosis. As a result of these strict guidelines, in practice, very few patients with liver cancer can undergo liver resection. The biggest concern about resection is that following the operation, the patient can develop liver failure. The liver failure can occur if the remaining portion of the liver is inadequate to provide the necessary support for life. Even in carefully selected patients, about 10% of them are expected to die shortly after surgery, usually as a result of liver failure.

When a portion of a normal liver is removed, the remaining liver can grow back (regenerate) to the original size within one to two weeks. A cirrhotic liver, however, cannot grow back. Therefore, before resection is performed for liver cancer, the non-tumor portion of the liver should be biopsied to determine whether there is associated cirrhosis.

For patients whose tumors are successfully resected, the five-year survival is about 30 to 40%. This means that 30 to 40 % of patients who actually undergo liver resection for liver cancer are expected to live five years. Many of these patients, however, will have a recurrence of liver cancer elsewhere in the liver. Moreover, it should be noted that the survival rate of untreated patients with similar sized tumors and similar liver function is probably comparable. Some studies from Europe and Japan have shown that survival rates with alcohol injection or radiofrequency ablation procedures are comparable to the survival rates of those patients who underwent resection. But again, the reader should be cautioned that there are no head-to-head comparisons of these procedures versus resection.

Liver transplantation

Liver transplantation has become an accepted treatment for patients with end-stage (advanced) liver disease of various types (for example, chronic hepatitis B and C, alcoholic cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis). Survival rates for these patients without liver cancer are 90% at one year, 80% at three years, and 75% at five years. Moreover, liver transplantation is the best option for patients with tumors that are less than 5 cm in size who also have signs of liver failure. In fact, as one would expect, patients with small cancers (less than 3 cm) and no involvement of the blood vessels do very well. These patients have a less than 10% risk of recurrent liver cancer after transplant. On the other hand, there is a very high risk of recurrence in patients with tumors greater than 5 cm or with involvement of blood vessels. For these reasons, when patients are being evaluated for treatment of liver cancer, every effort should be made to characterize the tumor and look for signs of spread beyond the liver.

There is a severe shortage of organ donors in the U.S. Currently, there are about 18,000 patients on the waiting list for liver transplantation. About 4,000 donated cadaver livers (taken at the time of death) are available per year for patients with the highest priority. This priority goes to patients on the transplant waiting list who have the most severe liver failure. As a result, in many liver cancer patients, while they are on the waiting list, the tumor may become too large for the patient to benefit from liver transplantation. Doing palliative treatments, such as TACE, while the patient is on the waiting list for liver transplantation is currently being evaluated.

The use of a partial liver from a healthy, live donor may provide a few patients with liver cancer an opportunity to undergo liver transplantation before the tumor becomes too large. This innovation is a very exciting development in the field of liver transplantation.

As a precaution, doing a biopsy or aspiration of liver cancer should probably be avoided in patients considering liver transplantation. The reason to avoid needling the liver is that there is about a 1-4% risk of seeding (planting) cancer cells from the tumor by the needle into the liver along the needle track. You see, after liver transplantation, patients take powerful anti-rejection medications to prevent the patient's immune system from rejecting the new liver. However, the suppressed immune system can allow new foci (small areas) of cancer cells to multiply rapidly. These new foci of cancer cells would normally be kept at bay by the immune cells of an intact immune system.

In summary, liver resection should be reserved for patients with small tumors and normal liver function (no evidence of cirrhosis). Patients with multiple or large tumors should receive palliative therapy with intra-arterial chemotherapy or TACE, provided they do not have signs of severe liver failure. Patients with an early stage of cancer and signs of chronic liver disease should receive palliative treatment and undergo evaluation for liver transplantation.

Is there a role for routine screening for liver cancer?

It makes sense to screen for liver cancer just as we do for colon, cervical, breast, and prostate cancer. However, the difference is that there is, as yet, no cost-effective way of screening for liver cancer. Blood levels of alpha-fetoprotein are normal in up to 50% of patients with small liver cancer. Ultrasound scanning, which is non-invasive and very safe, is, as mentioned before, operator-dependent. Therefore, the effectiveness of a screening ultrasound that is done at a small facility can be very suspect.

Even more disappointing is the fact that no study outside of Asia has shown, on a large scale, that early detection of liver cancer saved lives. Why is that? It is because, as already noted, the treatment for liver cancer, except for liver transplantation, is not very effective. Also, keep in mind that patients found with small tumors on screening live longer than patients with larger tumors only because of what is called a "lead time bias." In other words, they seem to liver longer (the bias) only because the cancer was discovered earlier (the lead time), not because of any treatment given.

Nevertheless, strong arguments can be made for routine screening. For example, the discovery of an liver cancer in the early stages allows for the most options for treatment, including liver resection and liver transplantation. Therefore, all patients with cirrhosis, particularly cirrhosis caused by chronic hepatitis B or C, hemochromatosis, and alcohol, should be screened at six- to 12-month intervals with a blood alpha-fetoprotein and an imaging study. I favor alternating between an ultrasound and CT scan (or MRI). Patients with chronically (long duration) elevated alpha-fetoprotein levels warrant more frequent imaging since these patients are at even higher risk of developing liver cancer.

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