How Serious is Liver Cancer?
Liver cancer or hepatic cancer is a cancer that originates in the liver.
Liver tumors are discovered on medical imaging equipment (often by accident) or present themselves symptomatically as an abdominal mass, abdominal pain, yellow skin, nausea or liver dysfunction.
The leading cause of liver cancer is viral infection with hepatitis B virus or hepatitis C virus.
The cancer usually forms secondary to cirrhosis caused by these viruses. For this reason, the highest rates of liver cancer occur where these viruses are endemic.
Liver cancers should not be confused with liver metastases, also known as secondary liver cancer, which are cancers that originate from organs elsewhere in the body and migrate to the liver.
They are formed from either the liver itself or from structures within the liver, including blood vessels or the bile duct.
Primary liver cancer is the sixth most frequent cancer globally and the second leading cause of cancer death.
The most frequent liver cancer, accounting for approximately 75% of all primary liver cancers, is hepatocellular carcinoma (HCC) (also named hepatoma, which is a misnomer because adenomas are usually benign). HCC is a cancer formed by liver cells, known as hepatocytes, that become malignant.
Another type of cancer formed by liver cells is hepatoblastoma, which is specifically formed by immature liver cells. It is a rare malignant tumor that primarily develops in children, and accounts for approximately 1% of all cancers in children and 79% of all primary liver cancers under the age of 15. Most of these tumors form in the right lobe.
Liver cancer can also form from other structures within the liver such as the bile duct, blood vessels and immune cells.
Cancer of the bile duct (cholangiocarcinoma and cholangiocellular cystadenocarcinoma) account for approximately 6% of primary liver cancers.
Tumors of the blood vessels (angiosarcoma and hemangioendothelioma, embryonal sarcoma and fibrosarcoma are produced from a type of connective tissue known as mesenchyme.
Cancers produced from muscle in the liver are leiomyosarcoma and rhabdomyosarcoma. Other less common liver cancers include carcinosarcomas, teratomas, yolk sac tumours, carcinoid tumours and lymphomas.
Lymphomas usually have diffuse infiltration to liver, but It may also form a liver mass in rare occasions.
Many cancers found within the liver are not true liver cancers, but are cancers from other sites in the body that have spread to the liver (known as metastases).
Frequently, the site of origin is the gastrointestinal tract (such as colon cancer and carcinoid tumors mainly of the appendix), but also from breast cancer, ovarian cancer, lung cancer, renal cancer, prostate cancer.
Because liver cancer is an umbrella term for many types of cancer, the signs and symptoms depend on what type of cancer is present.
Cholangiocarcinoma is associated with sweating, jaundice, abdominal pain, weight loss and hepatomegaly.
Hepatocellular carcinoma is associated with abdominal mass, abdominal pain, emesis, anemia, back pain, jaundice, itching, weight loss and fever.
Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI).
Positron emission tomography (PET) is commonly used for imaging cancers by detecting cells with high metabolic rates; a common feature of cancer cells.
Prevention of cancers can be separated into primary, secondary and tertiary prevention.
Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination for hepatitis C virus is currently unavailable.
Other forms of primary prevention are aimed at limiting transmission of these viruses by promotion of safe injection practice, screening of blood donation products and screening of high risk asymptomatic individuals.
Aflatoxin exposure can be avoided by post-harvest intervention, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.
Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible.
Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.
Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs, and antiviral drugs.
Surgical resection is often the treatment of choice for non-cirrhotic livers. Increased risk of complications such as liver failure can occur with resection of cirrhotic livers.
5-year survival rates after resection has massively improved over the last few decades and can now exceed 50%. Recurrence rates after resection due to the spread of the initial tumor or formation of new tumors exceeds 70%.
Liver transplantation can also be used in cases of HCC where this form of treatment can be tolerated and the tumor fits specific criteria (such as the Milan criteria).
Less than 30-40% of individuals with HCC are eligible for surgery and transplant because the cancer is often detected late stage. Also, HCC can progress during the waiting time for liver transplants, which can prevent transplant due to the strict criteria.
Percutaneous ablation is the only non-surgical treatment that can offer cure. There are many forms of percutaneous ablation, which consist of either injecting chemicals into the liver (ethanol or acetic acid) or producing extremes of temperature using radio frequency ablation, microwaves, lasers or cryotherapy.
Of these, radio frequency ablation has one of the best reputations in HCC, but the limitations include inability to treat tumors close to other organs and blood vessels due to heat generation and the heat sync effect, respectively.
Systemic chemotherapeutics are not routinely used in HCC, although local chemotherapy may be used in a procedure known as transarterial chemoembolization.
Radiotherapy is not often used in HCC because the liver is not tolerant to radiation. Although with modern technology it is possible to provide well targeted radiation to the tumor, minimizing the dose to the rest of the tumor.
Dual treatments of radiotherapy plus chemoembolization, local chemotherapy, systemic chemotherapy or targeted therapy drugs may show benefit over radiotherapy alone.
Resection is an option in cholangiocarcinoma, but less than 30% of cases of cholangiocarcinoma are resectable at diagnosis and even after surgery, recurrence rates are up to 60%.
Liver transplant may be used where partial resection is not an option, and adjuvant chemoradiation may benefit some cases.
60% of cholangiocarcinomas form in the perihilar region and photodynamic therapy can be used to improve quality of life and survival time in these cases.
Photodynamic therapy is a novel treatment that utilities light activated molecules to treat the tumor. The compounds are activated in the tumor region by laser light, which causes the release of toxic reactive oxygen species, killing tumor cells.
Radio frequency ablation, transarterial chemoembolization and internal radiotherapy (brachytherapy) all show promise in the treatment of cholangiocarcinoma.
Removing the tumor by either surgical resection or liver transplant can be used in the treatment of hepatoblastoma. In some cases surgery can offer a cure. Chemotherapy may be used before and after surgery and transplant.