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Liver Cancer

Anatomical facts:

The liver is the largest internal organ in the body and is located behind the ribs on the right side of the abdomen. It is a pyramid-shaped organ divided into right and left lobes. This is the only organ in the body that receives blood from two sources: the hepatic artery delivers oxygen-rich blood from the heart, and the portal vein carries nutrient-rich blood from the intestines. The liver is responsible for a number of essential functions in the body. It processes and stores nutrients, removes toxic materials from the blood and secretes enzymes and bile. It helps in digestion, and produces clotting factors necessary to stop bleeding.

Diagnosis of liver cancer

Approximately 19,000 people are diagnosed with primary liver cancer every year in the United States. Symptoms do not usually appear until the disease is already advanced. As a result, only about 30% of liver tumors are found at stages that allow the removal of the tumor with surgery. The overall five-year relative survival rate from liver cancer is poor. In the United States, the majority of cancerous tumors found in the liver are metastasized from a different site in the body, such as the colon, pancreas, breast and so forth. These secondary tumors are considered a metastatic form of the primary site cancer and are completely different disease entities from cancer that started in liver cells, called primary liver cancer. Before starting to look for information about liver cancer, it is important to find out if the cancer started in the liver or metastasized from a different organ.

Liver infections and cirrhosis

People who have long-term viral liver infection (hepatitis B or C) and people who have cirrhosis of the liver have a higher risk of developing cancer in the liver. Cirrhosis is a condition where scar tissue forms in the liver. In most cases cirrhosis is caused by alcohol abuse, but exposure to other drugs and chemicals and some inherited metabolic disorders also may cause cirrhosis and increase the risk for liver cancer. Obesity and smoking also have been linked to liver cancer. This disease is more common in men than in women and has a higher incidence in developing countries in Asia and Africa than in Europe and the United States.

Sub-types of liver cancer

The most common subtype of liver cancer is hepatocellular carcinoma (HCC), which accounts for about 75% of all primary liver cancers. It is sometimes called hepatoma because it originates in the hepatocytes (the main type of liver cells). About 10% to 20% of primary liver tumors are cholangiocarcinomas that start in the bile ducts located inside the liver (intrahepatic bile ducts). Cholangiocarcinomas can also start in bile ducts located outside the liver (extrahepatic) and the gallbladder. Although intrahepatic cholangiocarcinomas are counted as liver cancer, they are similar to extrahepatic cholangiocarcinomas, and information about treatment and prognosis of these tumors should be found under bile duct and/ or gallbladder cancer. Angiosarcomas and hemangiosarcomas are rare and start in the liver’s blood vessels.

Liver Cancer Treatment

The best possibility for curing liver cancer is with surgery. If the disease has not spread to nearby lymph nodes and other organs, it is possible to remove only the diseased portion of the liver with a procedure called partial hepatectomy. Because the body cannot function without a liver, total removal of the entire organ is not possible, unless a new liver can be transplanted. To alleviate symptoms of patients who have a few small tumors, but for whom surgery is not possible, doctors use ablation techniques to destroy tumors without surgery. Chemotherapy and radiation therapy help improve symptoms; but, unfortunately, these treatments have not proved capable of curing this type of cancer.

Surgery

Surgery can be done to remove the diseased part of the liver (partial hepatectomy) or remove the liver completely and replace it with a new healthy liver of a donor (transplantation).

The kind of surgery depends on the size of the tumor, position of the tumor, stage of the tumor and overall condition of the liver.

Partial hepatectomy is done when

  • Cancer is detected at an early stage
  • Overall condition of the liver is good
  • Size of the tumor is small
  • Tumor does not affect the blood vessels

Transplantation is done when

  • Cancer is detected at an early or slightly higher stage
  • Overall condition of the liver is bad
  • Size of the tumor is large
  • Tumor is in a critical position and cannot be removed (even if small)
  • Many tumors have grown in the liver

Surgery is not an option if the cancer has spread beyond the liver or if the patient is suffering from liver cirrhosis. Liver transplantation is preferred to resection (hepatectomy) in some situations as described above, but it takes time to find a proper donor. In most cases, livers are donated by patients who have died. However, liver transplantation can be done from living donors.  Since the liver is an organ which can regenerate rapidly, it is possible to perform such transplantations or resections.

Ex-vivo hepatic resection and reimplantation for liver cancer is a new form of therapy which is used when patients need immediate surgery and the surgery is difficult. It involves removal of the liver from the body, excision of the diseased tissue, and then putting back the healthy liver tissue.

Chemotherapy

When surgical resection or transplantation cannot be performed, doctors use anti-cancer drugs to kill cancer cells. This form of treatment is called chemotherapy. Chemotherapy helps to reduce the rate of growth of tumor and shrinks those that have already grown. But this mode of therapy comes with a large number of side effects.

There are different methods of administration of these drugs. Chemotherapy may be given in the form of tablets or injections in the vein. Injection may also be given directly in the hepatic artery (blood vessel that carries blood from the heart to the liver). Regional chemotherapy can be performed by placing a catherer (a long and thin plastic tube) in the blood vessel supplying the tumor. This helps to reduce the toxic effects of the drugs because it cannot move out to other tissues.

A combined process of local delivery of chemotherapy drugs in the liver tumor together with a technique called embolization is called chemoembolization.  Chemoembolization is the mainstay treatment for patients with liver cancer (hepatocellular carcinoma) since the overall success of systemic chemotherapy (treatment with anticancer drugs that travel through the blood to cells all over the body) is poor for liver cancer. In this process, the drugs are injected into the blood vessel that supplies blood to the tumor. Further, an embolic agent (oil or plastic particle) is placed in the blood vessel to cut off further blood supply which results in trapping the drugs inside the tumor. This treatment is called Transarterial chemoembolization or TACE. This results in increasing the effective concentration of the drug inside the tumor and reduces the side effects of the drugs. This process is performed by an interventional radiologist who is guided by X-ray images.

Chemotherapy is not considered an effective treatment for primary liver cancer. It may be given as a part of clinical trial.  A very few drugs that may be used for treating liver cancer are doxorubicin, cisplatin, fluorouracil (5FU) and gemcitabine. They may be used in single or in combination. Pravastatin is another drug that may work against some cancers.

Radiotherapy

The use of high energy beams to kill the cancer cells is called Radiotherapy.  It is not a convenient treatment for liver cancer, but sometimes may be used to treat cholangiocarcinoma, a form of liver cancer.

Biological therapy

Biological therapies use substances that stimulate the immune system of the body to destroy cancer cells. The use of cancer growth blockers is a form of biological therapy. There are different forms of cancer growth blockers. One form of cancer growth blocker is tyrosine kinase inhibitor. Sorafenib (Nexavar®), a tyrosine kinase inhibitor, may be used to treat advanced forms of liver cancer. It is an oral drug and has proved very successful in recent clinical trials. It can also be given in combination with chemotherapy. This drug can be used when surgical resection or transplantation of liver cannot be done and for hepatocellular carcinoma patients who are intolerant to transarterial chemoembolization (TACE).

Radioembolisation

This is a form of treatment which combines the use of chemoembolisation and radiation rather than chemotherapy. Many tiny beads containing a radioactive substance called yttrrium-90 are inserted in the hepatic artery, which supplies blood to the liver. The radioactive substances help to kill the cancer cells by radioactive emission.

Alcohol (ethanol) can kill cancer cells. In this form of treatment, ethanol can be directly injected through the skin and into the tumor, which should be less than 5cm in size. Ultrasound scan is used to direct the needle to the tumor for injecting ethanol. A local anaesthetic is given before the injection is given.

Cryosurgery or cryotherapy

In this form of treatment, a device called a cryoprobe is inserted into the tumor through which liquid nitrogen is then passed. Liquid nitrogen is very cold and freezes the tumor immediately. Cancer cells are thus killed by freezing them. The treatment may be done during an operation or a laparoscopy.

High intensity focused ultrasound

It is a form of treatment in which high frequency sound waves are delivered specifically to the tumor of the liver which kills the cancer cells.

Conclusion

The results of the various treatments to cure liver cancer other than surgery have not been promising. There have been no systematic study comparisons of the different treatments. For most patients who have liver cancer detected at an early stage, surgery and transplantation are the best options. Standard chemotherapy is still under clinical trials. Stem cell therapy, a new form of therapy helps to improve impaired liver functional reserve prior to liver resection. Ablation of tumor through different techniques like radiofrequency ablation may have palliative effects since the tumor may recur

References

Kim HY, Park JW. Molecularly targeted therapies for hepatocellular carcinoma: sorafenib as a stepping stone. Dig Dis. 2011; 29(3):303-9. Epub 2011 Aug 9.

Kudo M. Future treatment option for hepatocellular carcinoma: a focus on brivanib. Dig Dis. 2011; 29(3):316-20. Epub 2011 Aug 9.

This article was originally published on 7/12/2014 and last revision and update of it was 9/14/2015.

 

Additional Resources:

American Cancer Society. Learn about Bile Duct Cancer and Learn about Gallbladder Cancer. Access at: www.cancer.org and select from the menu under “Choose a Cancer Type or Topic.” Disease-specific detailed guides can be printed by section or as Adobe Acrobat (.pdf) files.

National Cancer Institute. Extrahepatic Bile Duct Cancer and Gallbladder Cancer. Access at: www.cancer.gov and click on “Types of cancer.” The top page of the sections links to patient versions of PDQ@ (Physician Data Query) statements, clinical trial information, and other NCI publications on this topic.

People Living with Cancer. Bile Duct Cancer and Gallbladder Cancer. Access at: www.plwc.org and click on “Cancer Type.” The PLWC oncologist approved guides can be printed in their entirety or by subtopic.