Liver Cancer

Liver Cancer, or Hepatocellular carcinoma (Hepatoma) is one of the major causes of cancer deaths worldwide especially in Africa and East Asia; it is the 4th commonest cancer among males in Singapore. Chronic hepatitis B (HBV) and hepatitis C (HCV) infection, ethanol, aflatoxins, hemochromatosis, Wilson’s disease and alpha1-antitrypsin deficiency are risk factors for hepatoma. They cause cirrhosis that predisposes to development of hepatoma.

Among asymptomatic patient with risk factors such as chronic HBV carrier, screening has the best chance of detecting small hepatoma and thus curative resection.

Outside of screening program, the presentation of hepatoma is non-specific. The dominant symptoms may be related to the underlying cirrhosis eg. liver function decompensation or complications from portal hypertension such as ascites or variceal bleeding. Some patients may present with vague abdominal discomfort, unexplained weight loss or abdominal mass. Occasionally, patients can present with acute abdominal pain from rupture of hepatoma. In rare instances, metastatic hepatoma to the brain, bone or lung may be the initial presentation.

Due to its non-specific symptomatology, diagnosis of hepatoma requires a high index of suspicion. The actual detection of hepatoma relies on combination of identifying common risk factors, serum tumor marker (alpha-fetoprotein) and the characteristic features of the tumor on radiologic imagings.

In endemic countries, the incidence of chronic HBV infection among patients with hepatoma can be as high as 90%. 70-80% of hepatoma has elevated serum alpha-fetoprotein. Alpha-fetoprotein level of more than 200ng/ml in the present of a solid space-occupying lesion in the liver is highly suggestive of a hepatoma.

Ultrasound scan is a very good screening tool for mass lesion in the liver in high risk patient. It is inexpensive, non invasive and readily available. However, it is operator dependent and lacks ability to provide a topographic picture that is needed in planning surgical intervention.

Contrast enhanced triphasic computerized tomography scan (CT scan) can provide high quality images of the liver and the tumor within it. Hepatoma is typically a hypervascular solid tumor with/without a clear capsule in the background of liver cirrhosis. The tendency of the tumor to invade portal veins and hepatic veins can also be clearing see on the CT scan. The added advantage of CT images is ability in studying the adjacent organs at the same time.

Magnetic resonance imaging (MRI) is a newer imaging technology that does not involve ionizing radiation. Its accuracy in detecting hepatoma is similar to CT scan but the cost is higher.

Characterizing small tumors (those <2cm) can be difficult on CT scan or MRI especially when the tumor marker is not elevated to diagnostic level. In such cases, short of doing a biopsy of the tumor, lipoidol CT scan may add confidence to the diagnosis of hepatoma. This works on the principal that hepatoma retains lipoidol (an oil based contrast) after injection through hepatic arteriography. A non-contrast enhanced plain CT scan is done 10 days to 2 weeks later, the retained lipoidol in the heptoma will light up brightly on the background of non-enhanced uninvolved liver parenchyma.

Hepatic artery angiography may also demonstrate the characteristic tumour blush of hepatoma.

In majority of patients, the diagnosis of hepatoma can be reached confidently with the combination of positive HBV or HCV viral serology, raised alph-fetoprotein and a CT scan showing a characteristic space-occupying lesion in the liver. Biopsy of the tumor is usually not necessary prior to surgical resection. Biopsy of the tumor is needed when the radiologic features of lesions are atypical; especially when the serology and tumor markers are not also supportive of the diagnosis; in patient whose tumor is technically unresectable or those who are deemed not suitable for operation due to other reasons.

Biopsy of the tumor can be done percutaneously under ultrasound or CT guidance; or laparoscopically (with keyhole operation). Core biopsy has better yield than fine needle aspiration but is associated with small risk of tumor bleeding and seeding along needle tract.

Hepatoma is one of the more aggressive malignant tumor. The chance of cure is related to the stage of the tumor and the severity of the underlying liver cirrhosis at the time of diagnosis. A patient with well preserved liver function and a small size tumor (less than 3cm) confined to one lobe of the liver has a good chance of cure after adequate resection of the tumor.

Non-operative treatments of HCC have a place in non-resectable disease and in patients who are poor surgical candidates.

Surgical resection, when possible, remains the best chance of cure in patients with hepatoma. The objective of surgical resection is to excise the tumor with clear margin and at the same time preserve as much normal functioning liver as possible to sustain life. This is a very difficult balance to achieve because of the often associated underlying liver cirrhosis in majority of patient with hepatoma. In general, the prerequisites for surgical resection are:

” Good cardio-pulmonary fitness for major operation
” No other serious medical conditions
” Relatively well preserved liver function – not jaundice, no bleeding tendency, adequate protein in the blood, no excessive fluid in the abdomen and normal cognitive state.
” Tumor confined to one lobe of liver and without invasion of major vessels in the liver

In order to better select patients for surgical resection, a specially dye clearance test of the liver maybe necessary prior to the operation. This involves injection of the diluted dye (Indocyanine green) into a vein in your arm and collecting blood sample from you at 5mins interval for the next 20mins. Poor clearance of the dye after 15minutes predicts poor outcome following operation.

Surgical resection of liver and liver tumor has evolved to become a safe operation with less than 5% surgical mortality. This is largely due to better understanding of the anatomy and physiotherapy of the liver, improvement in surgical techniques as well as the advances in the anesthesiology and surgical care of patient after liver surgery.

Liver transplantation remains an option for patients with hepatoma confined to the liver but not suitable for resection either due to poor liver function reserve, multi-focal disease or strategic location of the tumor precluding safe resection.

Non-operative treatment

In patients deem not suitable for surgical resection, several alternative therapeutic option are available.

This is in truth a dual treatment. It entails performing a hepatic angiography via the femoral artery in the groin and selectively canulating the feeding vessel/s to the tumor and infusing combination chemotherapy drugs mixed with lipoidol (to increase tumor uptake and retention of the drugs) to the tumor; after which the feeding vessel to the tumor is embolised with gelfoam to cause ischemic damage to the tumor. This technique is suitable for multiple lesions and bilobar disease. Involvement of major vascular structures is a relative contraindication. This treatment may need to be repeated 4-6 weeks later and several sessions may be required. Side effects and complications from TACE are relatively few and minor.

This new modality of treatment can be done percutaneously with CT scan or ultrasound guidance; it can also be done laparoscopically under ultrasound guidance. The treatment involves delivery of radiofrequency wave to the core of the tumor via a small probe, this produces thermal injury and ablation of the tumor. It is suitable for lesions less than 5cm in diameter. Tumors in close proximity to a large vessel are more difficult to treat and there is higher risk of rupture in tumor on the liver surface during or following RF treatment. These situations require special consideration when planning RF ablation.

This is a relatively simple and expensive treatment. This can be done percutaneously under imaging guidance and is effective for small lesions less than 3cm diameter. It is a good alternative for patients with small tumor (<3cm) but not suitable for operation because of poor general health or poor liver function reserve. Intra-tumoral ethanol injection can be administered intra-operatively and is especially useful in the situation of acute tumor rupture. Contraindications to treatment include renal insufficiency and thrombosis of the main portal vein.

Systemic therapies with various chemo-agents either alone or in combination regime have been tried, they include chemotherapy, immunotherapy and hormonal therapy. The response rate is generally poor and they have not been successful in improving overall survival nor disease free survival.

Liver cirrhosis is the major predisposing factor to development of hepatoma and there are identifiable risk factors for cirrhosis. Patient at risk should have regular screening and surveillance for hepatoma. Diagnosis of hepatoma requires combination of viral serology, tumor marker and characteristic features of tumor on contrast enhanced CT scan or MRI. Surgery remains the treatment of choice for resectable lesion and long term survival is good, especially for small tumor. Orthotopic liver transplantation is a possible option for patients with end stage liver cirrhosis and who have low tumor load HCC confined to the liver.

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