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LIVER CANCER- Causes,
Risks, Symptoms & Treatment Options
WHAT IS LIVER CANCER
Liver cancer (hepatocellular carcinoma)
is a cancer arising from the liver. It is also known
as primary liver cancer or hepatoma. The liver is made
up of different cell types (e.g., bile ducts, blood
vessels, and fat-storing cells). However, liver cells
(hepatocytes) make up 80% of the liver tissue. Thus,
the majority of primary liver cancers (over 90 to 95%)
arises from liver cells and is called hepatocellular
cancer or carcinoma.
However, they are often referring to
cancer that has spread to the liver, having originated
in other organs (such as the colon, stomach, pancreas,
breast, and lung). More specifically, this type of liver
cancer is called metastatic liver disease (cancer) or
secondary liver cancer. Thus, the term liver cancer
actually can refer to either metastatic liver cancer
or hepatocellular cancer. The subject of this article
is hepatocellular carcinoma, which I will refer to as
liver cancer.
WHICH NATIONS ARE AT RISK OF HAVING LIVER CANCER
There are more than 16,000 new cases
of primary liver cancer diagnosed each year in the United
States. The worldwide numbers are higher, and appear
to be increasing. Some areas of Africa and Asia have
incidence rates ten times as high as those in the United
States. In the U.S. the highest frequency of liver cancer
occurs in immigrants from Asian countries, where liver
cancer is common. The frequency of liver cancer among
Caucasians is the lowest, whereas among African-Americans
and Hispanics, it is intermediate. The frequency of
liver cancer is high among Asians because liver cancer
is closely linked to chronic hepatitis B infection.
THE INITIAL SYMPTOMS OF LIVER CANCER
The initial presentation (symptoms)
of liver cancer in patients in areas of high liver cancer
frequency is quite different from that seen in low frequency
areas. Patients from high frequency areas usually start
developing liver cancer in their 40's, and the cancer
is usually more hostile. That is, the liver cancer presents
with severe symptoms and is too advanced for surgery
at the time of diagnosis. Also, in these areas, the
frequency of liver cancer is three to four times higher
in men than in women, and most of these patients are
infected with chronic hepatitis B. In contrast, liver
cancer in lower risk areas occurs in patients in their
50's and 60's and the predominance of men is less striking.
The initial symptoms (the clinical
presentations) of liver cancer are variable. In countries
where liver cancer is very common, the cancer generally
is discovered at a very advanced stage of disease for
several reasons. Abdominal pain is the most common symptom
of liver cancer and usually signifies a very large tumor
or widespread involvement of the liver. A very general
appearance of liver cancer in a patient with compensated
cirrhosis (no complications of liver disease) is the
sudden onset of a complication. For example, the sudden
appearance of ascites (abdominal fluid and swelling),
JAUNDICE also known as Yellow fever (yellow color of
the skin), or muscle wasting without causative (precipitating)
factors (e.g., alcohol consumption) suggests the possibility
of liver cancer.
Further more, the cancer can invade
and block the portal vein (a large vein that brings
blood to the liver from the intestine and spleen). When
this happens, the blood will travel paths of less resistance,
such as through esophageal veins. This causes increased
pressure in these veins, which results in dilated (widened)
veins called esophageal varices.
HOW IS LIVER CANCER DIAGNOSED
Blood tests
Liver cancer is not diagnosed by routine
blood tests, including a standard panel of liver tests.
This is why the diagnosis of liver cancer depends so
much on the vigilance of the physician screening with
a tumor marker (alpha-fetoprotein) in the blood and
radiological imaging studies. Since most patients with
liver cancer have associated liver disease (cirrhosis),
their liver blood tests may not be normal to begin with.
If these blood tests become abnormal or worsen due to
liver cancer, this usually signifies extensive cancerous
involvement of the liver. At that time, any medical
or surgical treatment would be too late.
Another abnormal blood test, high serum
cholesterol (hypercholesterolemia), is seen in up to
10% of patients from Africa with liver cancer. The high
cholesterol occurs because the liver cancer cells are
not able to turn off (inhibit) their production of cholesterol..
There is no reliable or accurate screening
blood test for liver cancer. The most widely used biochemical
blood test is alpha-fetoprotein (AFP), which is a protein
normally made by the immature liver cells in the fetus.
At birth, infants have relatively high levels of AFP,
which fall to normal adult levels by the first year
of life. Also, pregnant women carrying babies with neural
tube defects may have high levels of AFP. (A neural
tube defect is an abnormal fetal brain or spinal cord
that is caused by folic acid deficiency during pregnancy.)
In adults, high blood levels (over 500 nanograms/milliliter)
of AFP are seen in only three situations:
i. Liver cancer
ii. Germ cell tumors (cancer of the testes and ovaries)
iii. Metastatic cancer in the liver (originating in
other organs)
WHAT ARE THE TREATMENT OPTIONS FOR LIVER CANCER
The treatment options are dictated
by the stage of liver cancer and the overall condition
of the patients; the only proven cure for liver cancer
is liver transplantation for a solitary, small tumor.
Now, many physicians may argue that a small tumor can
be surgically removed (partial hepatic resection) without
the need for a liver transplantation. Moreover, they
may claim that the one and three year survival rates
for resection are perhaps comparable to those for liver
transplantation.
However, most patients with liver cancer
also have cirrhosis of the liver and would not tolerate
liver resection surgery. But, they probably could tolerate
the transplantation operation, which involves removal
of the patient's entire diseased liver just prior to
transplanting a donor liver. Furthermore, many patients
who undergo hepatic resections will develop a recurrence
of liver cancer elsewhere in the liver within several
years. In fact, some experts believe that once a liver
develops liver cancer, there is a tendency for that
liver to develop other tumors at the same time or at
a later time.
The results of the various medical
treatments (chemotherapy, chemoembolization, ablation,
and proton beam therapy) remain disappointing. How do
we know if a particular treatment worked for a particular
patient? Well, hopefully, the patient will feel better.
However, a clinical response to treatment is usually
defined more objectively. Thus, a response is defined
as a decrease in the size of the tumor on imaging studies
along with a reduction of the alpha-fetoprotein in the
blood, if the level was elevated prior to treatment
Chemotherapy
Systemic (entire body) chemotherapy
The most commonly used systemic chemotherapeutic
agents are doxorubicin (Adriamycin) and 5-fluorouracil
(5 FU). Octreotide (Sandostatin) given as an injection
was shown in one study to slow down the progression
of large liver cancer tumors, but so far, no other studies
have confirmed this benefit.
Hepatic arterial infusion of chemotherapy
The normal liver gets its blood supply
from two sources; the portal vein (about 70%) and the
hepatic artery (30%). However, liver cancer gets its
blood exclusively from the hepatic artery. Making use
of this fact, investigators have delivered chemotherapy
agents selectively through the hepatic artery directly
to the tumor. The theoretical advantage is that higher
concentrations of the agents can be delivered to the
tumors without subjecting the patients to the systemic
toxicity of the agents.
Surgery
Surgical options are limited to individuals
whose tumors are less than 5 cm and confined to the
liver, with no invasion of the blood vessels.
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 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. 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.
LIVER TRANSPLANTATION
Liver transplantation has become an
accepted treatment for patients with end-stage (advanced)
liver disease of various types (e.g., 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 5cm in size who also have
signs of liver failure.
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 generated the
most severe liver failure.
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. Patients
with an early stage of cancer and signs of chronic liver
disease should receive palliative treatment and undergo
evaluation for liver transplantation.
WHEN A CURE ISN'T POSSIBLE
If liver cancer has been diagnosed
in its later stages, the cancer may have spread to the
point where a cure is no longer possible. Treatment
then focuses on improving quality of life by alleviating
the symptoms. Options may include medications such as
painkillers.
WHERE TO SEEK HELP
? Your doctor
? Specialist
THINGS TO REMEMBER
- The liver will function normally with only a small
portion of it in working order.
- Most liver cancers are secondary liver cancer,
which means a cancer that starts somewhere else in
the body and spreads to the liver.
- Primary liver cancers are one of the less common
cancers.
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