Risk Of Developing Liver Cancer After HCV Treatment

Friday, October 8, 2010

Understanding Liver Cancer

Understanding Liver Cancer - Basic Information
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What Is Liver Cancer?
The liver continuously filters blood that circulates through the body, converting nutrients and drugs absorbed from the digestive tract into ready-to-use chemicals. The liver performs many other important functions, such as removing toxins and other chemical waste products from the blood and readying them for excretion. Because all the blood in the body must pass through it, the liver is unusually accessible to cancer cells traveling in the bloodstream.

The liver can be affected by primary liver cancer, which arises in the liver, or by cancer which forms in other sites and then spreads to the liver. Most liver cancer is secondary or metastatic, meaning the malignancy originated elsewhere in the body. Primary liver cancer, which starts in the liver, accounts for about 2% of cancers in the U.S., but up to half of all cancers in some undeveloped countries. This is mainly because of the prevalence of hepatitis, caused by contagious viruses, that predisposes a person to liver cancer. Worldwide, primary liver cancer strikes twice as many men as women, making it the most common type of cancer in males, with it mostly affecting people over 50.

Because the liver is made up of several different types of cells, several types of tumors can form in the liver. Some of these are benign (noncancerous), and some are cancerous and can spread to other parts of the body (metastasize). These tumors have different causes and are treated differently. The outlook for your health or recovery depends on what type of tumor you have.

The more common benign tumors of the liver include:

Hemangioma
Hepatic adenoma
Focal nodular hyperplasia
Cysts
Lipoma
Fibroma
Leiomyoma

None of these tumors are treated like liver cancer. They may need to be removed surgically if they cause pain or bleeding.

Liver cancers include:
Hepatocellular carcinoma (HCC, also called malignant hepatoma) is a primary malignancy (cancer) of the liver. Most cases of HCC are secondary to either a viral hepatitis infection (hepatitis B or C) or cirrhosis (alcoholism being the most common cause of hepatic cirrhosis).In countries where hepatitis is not endemic, most malignant cancers in the liver are not primary HCC but metastasis (spread) of cancer from elsewhere in the body, e.g., the colon.
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Treatment options of HCC and prognosis are dependent on many factors but especially on tumor size and staging. Tumor grade is also important. High-grade tumors will have a poor prognosis, while low-grade tumors may go unnoticed for many years, as is the case in many other organs, such as the breast, where a ductal carcinoma in situ (or a lobular carcinoma in situ) may be present without any clinical signs and without correlate on routine imaging tests, although in some occasions it may be detected on more specialized imaging studies like MR mammography.
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The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months. This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. This is a rare tumor in the United States. A new receptor tyrosine kinase inhibitor, sorafenib has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function .


What Causes It?
Primary liver cancer (hepatocellular carcinoma) tends to occur in livers damaged by birth defects, alcohol abuse, or chronic infection with diseases such as hepatitis B and C, hemochromatosis (too much iron in the liver), and cirrhosis.

More than half of all people diagnosed with primary liver cancer have cirrhosis (a scarring condition of the liver often caused by alcohol abuse, hepatitis B and C, and hemochromatosis that can cause permanent damage and liver failure), and those who suffer from a genetic condition called hemochromatosis, or iron overload, are at even greater risk.

FAQ: The Link Between Hepatitis C and Liver Cancer

By Paul Hansen, M.D, director, Providence Liver Cancer Clinic, Providence Cancer Center; and Ken Flora, M.D., gastroenterologist/hepatologist with The Oregon Clinic and consulting physician to Providence Liver Cancer Clinic
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I heard recently that liver cancer is on the rise.
Why is that?

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Primary liver cancer — cancer that starts in the liver, rather than spreading to the liver from somewhere else — is increasing rapidly right now. This increase is linked mainly to the spread of hepatitis C infection in the ’60s, ’70s and ’80s.
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Hepatitis C, a virus that inflames the liver, is one of the main causes of primary liver cancer, or “hepatocellular” cancer. It wasn’t until the late 1980s that we began to understand hepatitis C and how it was spread — through blood. Until then, blood donations weren’t screened for hepatitis C, so a lot of people were exposed to the virus through transfusions, as well as other ways, such as using shared needles used to inject drugs.
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Since the hepatitis C virus progresses very slowly, we’re just now starting to see complications arise among this large population that was exposed 20, 30 or 40 years ago. Liver cancer is one of the potential complications.
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Does everyone with hepatitis C eventually develop liver cancer?
No — in fact, most don’t. Only people who develop cirrhosis as a complication of hepatitis C have a higher risk of developing liver cancer. About 20 percent of people with hepatitis C develop cirrhosis — advanced liver scarring caused by decades of inflammation. Of those who do develop cirrhosis, about 20 percent eventually develop liver cancer. So overall, among all people with hepatitis C, the chance of developing liver cancer at some point in your life is about 4 percent.
What makes some people with hepatitis C more or less likely to get liver cancer?
If you don’t develop cirrhosis, then you are at no higher risk of liver cancer than the general public. Having cirrhosis is what raises the risk, so anything that increases your risk of developing cirrhosis will also increase your risk of developing liver cancer.
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Alcohol consumption is the key risk factor here. People with hepatitis C should not drink alcohol, since it can accelerate liver damage. Certain prescription and non-prescription drugs also can damage the liver, so people with hepatitis C should review their medications with their physician to make sure they aren’t taking anything that could put further stress on their liver. Finally, smoking increases the risk of all cancers, including liver cancer, so people with hepatitis C should not smoke.
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How does hepatitis C lead to liver cancer?
Hepatitis C inflames the liver, and over the course of many years, this inflammation can lead to scarring. Most people with hepatitis C never experience significant scarring or complications, but about 20 percent develop cirrhosis, which is advanced scarring throughout the liver.
Because hepatitis C is a slowly progressive virus, it can take 30 or 40 years for cirrhosis to develop. Meanwhile, the liver is resilient — when damage occurs, the liver goes to work to regenerate itself. We believe that cancer occurs during this ongoing cycle of injury and regeneration. The more cells the liver regenerates, the higher the chances that a mutation will occur in one of those cells, and it’s these mutations that can lead to hepatocellular cancer.
Is there a way to screen people with hepatitis C to check for liver cancer?
Yes. Ultrasound is the main screening tool used to check for tumors in the liver. Ultrasound is non-invasive and can detect tumors when they are quite small.
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Should everyone with hepatitis C get ultrasound screenings?
Since liver cancer is a complication of cirrhosis, people who don’t have cirrhosis don’t need to be monitored closely for liver cancer. But people who do have cirrhosis should definitely get regular ultrasound screenings to check for liver tumors.
How often should a person with cirrhosis get screened for liver cancer?
At the Providence Liver and Pancreas Clinic, we recommend that people with cirrhosis get an ultrasound screening twice a year. The more vigilant you are about getting these screenings regularly, the better your chances of catching cancer early, when treatment is most likely to be successful.
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Are there any symptoms of liver cancer that a person should watch for?
Liver cancer usually doesn’t present any outward symptoms in its early stages, which is why regular screening is so important. Signs of advanced liver cancer may include pain, tenderness or a lump on the upper right side of the abdomen; enlargement of the abdomen; jaundice (yellowing of the skin and whites of the eyes); easy bruising or bleeding; nausea; fatigue; loss of appetite; unexplained weight loss; or pain around the right shoulder blade.
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Can liver cancer be treated?
In many cases, yes. The treatment options generally depend on the size and the number of tumors in the liver. That’s why we say that the best treatment for liver cancer is appropriate surveillance, which means keeping your ultrasound appointments so we can catch cancer when it is most treatable.
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What are the options for a person whose cancer is caught early?
If tumors are found when they are small and there aren’t many of them, we can remove them either through surgery (“resection”) or through radiofrequency ablation.
Advances in minimally invasive surgery are making it possible to perform many tumor resections through tiny half-inch incisions, rather than opening up a large incision. These “laparoscopic” techniques minimize trauma to surrounding tissues and leave patients with just two or three tiny scars.
While resection involves cutting tumors out, radiofrequency ablation involves zapping or burning tumors with localized electrical energy, which destroys the tumor and a small margin of tissue around the outside of it. This procedure can be performed laparoscopically, as well.
Both tumor resection and radiofrequency ablation have the potential to cure a patient of liver cancer.
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What if a person has a large tumor, or a large number of tumors?
In this case, we can’t cut out or burn out the tumors, because a person with cirrhosis wouldn’t have enough healthy liver tissue left in reserve to tolerate it. Instead, we use interventional therapies, such as radiation and chemotherapy, to try to slow the growth or reduce the size of the tumors
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One of the most promising new interventional therapies is yttrium-90 bead implantation. This non-invasive procedure uses millions of tiny beads coated with a radioactive element — yttrium-90 — to deliver radiation directly to tumors. The beads are inject into a catheter leading to the main blood vessel that feeds the tumors. Once they reach the tumors, they stay there, blocking the blood supply that feeds tumor growth and destroying the tumor cells with radiation. The treatment is extremely effective at slowing down cancer growth, and can shrink tumors in many cases, as well. In some cases, tumors shrink so much that they become small enough for resection or ablation.
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What if a patient isn’t a candidate for these therapies. Are there any other options?
The final treatment option is a liver transplant. A person whose primary tumor is less than 5 centimeters in diameter, or who has no more than three small tumors (each less than 3 cm), can get on the transplant list. However, only about 7,000 livers become available for transplant each year, and there are about 55,000 people on the waiting list in the United States. Preference is given to people who will have the best prognosis after transplantation.
What is the prognosis after a liver transplant?
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Even if it cures the liver cancer, doesn’t the patient still have hepatitis C?
A transplant won’t cure hepatitis C, but it will remove the cancer and the cirrhosis. Remember that hepatitis C is a slowly progressing virus, and it can take decades to lead to cirrhosis — the main risk factor for liver cancer. After a transplant, the new liver will become infected with hepatitis C, but it will take at least 10 or 15 years for cirrhosis to develop. That gives patients an extra 10 or 15 years of health and hope, during which time scientists will continue to develop more effective therapies.

Various cancer-causing substances are associated with primary liver cancer, including certain herbicides and such chemicals as vinyl chloride and arsenic. Smoking, especially if you abuse alcohol as well, also increases risk. Aflatoxins, cancer-causing substances made by a type of plant mold, have also been implicated. Aflatoxins can contaminate wheat, peanuts, rice, corn and soybeans. These are rare problems in most developed countries like the US.
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How Is Liver Cancer Staged?

Staging is the process of finding out how widespread a cancer is. The stage of a liver cancer is one of the most important factors in considering treatment options.

A staging system is a standardized way for the cancer care team to summarize information about how far a cancer has spread. Doctors use staging systems to get an idea about a patient's prognosis (outlook) and to try to determine the most appropriate treatment.

There are several staging systems for liver cancer, and not all doctors use the same system.

The American Joint Committee on Cancer (AJCC) TNM system

The American Joint Committee on Cancer (AJCC) TNM system is a major system used to describe the stages of liver cancer. It is based on the results of the physical exam, imaging tests (ultrasound, CT or MRI scan, etc.) and other tests, which are described in the section "How is liver cancer diagnosed?"

The TNM system for staging contains 3 key pieces of information:

T describes the number and size of the primary tumor(s), measured in centimeters (cm), and whether the cancer has grown into organs next to the tumor.
N describes the extent of spread to nearby (regional) lymph nodes.
M indicates whether the cancer has metastasized (spread) to other organs of the body. (The most common sites of liver cancer spread are the lungs and bones.)
Numbers or letters that appear after T, N, and M provide more details about each of these factors:

The numbers 0 through 4 indicate increasing severity.
The letter X means "cannot be assessed" because the information is not available.
T groups

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: A single tumor (any size) that hasn't grown into blood vessels
T2: Either a single tumor (any size) that has grown into blood vessels, OR more than one tumor where no tumor is larger than 5 cm (about 2 inches) across
T3a: Multiple tumors with at least one tumor that is greater than 5 cm (about 2 inches) across
T3b: At least one tumors that has grown into a major branch of the large veins of the liver (the portal and hepatic veins)
T4: The tumor has grown into a nearby organ (other than the gallbladder), OR the tumor is growing into the thin layer of tissue covering and surrounding the liver (called the visceral peritoneum)
N groups

NX: Regional lymph nodes cannot be assessed.
N0: The cancer has not spread to the regional (nearby) lymph nodes.
N1: The cancer has spread to the regional lymph nodes.
M groups

MX: Distant spread cannot be assessed.
M0: The cancer has not spread to distant lymph nodes or other organs.
M1: The cancer has spread to distant lymph nodes or other organs.
Stage grouping

The T, N, and M groups are then combined to give an overall stage:

Stage I: T1, N0, M0: There is a single tumor (any size) that has not grown into any blood vessels. The cancer has not spread to nearby lymph nodes or distant sites.

Stage II: T2, N0, M0: Either there is a single tumor (any size) that has grown into blood vessels; OR there are several tumors, and all are less than 5 cm (2 inches) in diameter. The cancer has not spread to nearby lymph nodes or distance sites.

Stage IIIA: T3a, N0, M0: There are several tumors, and at least one is larger than 5 cm (2 inches) across. The cancer has not spread to nearby lymph nodes or distant sites.

Stage IIIB: T3b, N0, M0: At least one tumor is growing into a branch of the major liver blood vessels (portal vein or hepatic vein). The cancer has not spread to nearby lymph nodes or distant sites.

Stage IIIC: T4, N0, M0: A tumor is growing into a nearby organ (other than the gallbladder); OR a tumor has grown into the outer covering of the liver. The cancer has not spread to nearby lymph nodes or distant sites.

Stage IVA: Any T, N1, M0: Tumors in the liver can be any size or number and they may have grown into blood vessels or nearby organs. The cancer has invaded nearby lymph nodes. The cancer has not spread to distant sites.

Stage IVB: Any T, Any N, M1: The cancer has spread to other parts of the body. (Tumors can be any size or number, and nearby lymph nodes may or may not be involved.)

Other liver cancer staging systems

The staging systems for most types of cancer depend only on the extent of the cancer, but liver cancer is complicated by the fact that most patients have liver damage along with their cancer. This also has an effect on treatment options and prognosis.

Although the TNM system defines the extent of liver cancer in some detail, it does not take liver function into account. Several other staging systems have been developed that include both of these factors:

the Barcelona-Clinic Liver Cancer (BCLC) system
the Cancer of the Liver Italian Program (CLIP) system
the Okuda system
These staging systems have not been compared against each other, and at this time there is no single staging system that all doctors use. If you have questions about the stage of your cancer or which system you doctor uses, be sure to ask.

Child-Pugh score (cirrhosis staging system)

The Child-Pugh score is a measure of liver function, especially in people with cirrhosis. Because people with liver cancer often have 2 diseases, their cancer and cirrhosis, doctors treating liver cancer need to know the extent of liver function. This system looks at 5 factors, the first 3 of which are blood tests:

blood levels of bilirubin (the substance that can cause yellowing of the skin and eyes)
blood levels of albumin (a major protein normally made by the liver)
the prothrombin time (measures how well the liver is making blood clotting factors)
whether there is fluid (ascites) in the abdomen
whether the liver disease is affecting brain function
Based on the score, liver function is divided into 3 classes. If all these factors are normal, then liver function is called class A. Mild abnormalities are class B, and severe abnormalities are class C. People with liver cancer and class C cirrhosis are generally too sick for any treatment.

The Child-Pugh score is actually part of the BCLC and CLIP staging systems mentioned previously.

Localized resectable, localized unresectable, and advanced liver cancer

For treatment purposes, doctors often classify liver cancers by whether or not they can be entirely cut out (resected). Resectable is the medical term meaning "able to be removed by surgery."

Localized resectable cancers: Only a small number of patients with liver cancer have tumors that can be completely removed by surgery. This would include most stage I and some stage II cancers in the TNM system, in patients who do not have cirrhosis.

Localized unresectable cancers: Cancers that have not spread to the lymph nodes or distant organs but cannot be completely removed by surgery are classified as localized unresectable. This would include some early stage cancers, as well as stage IIIA and IIIB cancers in the TNM system. There are several reasons that it might not be possible to safely remove a localized liver cancer. If the non-cancerous part of your liver is not healthy (due to cirrhosis, for example), surgery might not leave enough liver tissue behind for it to function properly. Also, curative surgery may not be possible if your cancer is spread throughout the liver or is close to the area where the liver meets the main arteries, veins, and bile ducts.

Advanced cancers: Cancers that have spread to lymph nodes or other organs are classified as advanced. These would include stage IIIC and stage IV cancers in the TNM system. Most advanced liver cancers cannot be treated with surgery.

Survival rates for liver cancer

The numbers below come from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, and are based on patients who were diagnosed with liver cancer (hepatocellular type) between 1996 and 2001. There are some important points to note about these numbers:

The 5-year survival rate refers to the percentage of patients who live at least 5 years after being diagnosed with cancer. Many of these patients live much longer than 5 years after diagnosis. Five-year relative survival rates assume that some people will die of other causes and compare the observed survival with that expected for people without the cancer. This is a more accurate way to describe the prognosis for patients with a particular type and stage of cancer.
The SEER database does not divide liver cancer survival rates by AJCC stages. Instead, it groups cancer cases into summary stages. Localized means only one or 2 tumors in one lobe of the liver, and includes stage I and some stage II cancers. Regional means many tumors, spread to other lobes or parts of the liver, and/or spread to lymph nodes (includes some stage II cancers and all stage III). Distant means that the cancer has spread to distant organs or tissues and is the same as stage IV.
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These numbers were taken from patients treated several years ago. Although they are among the most current numbers we have available, improvements in treatment since then mean that the survival rates for people now being diagnosed with these cancers may be higher.
Although survival statistics can sometimes be useful as a general guide, they may not accurately represent any one person's prognosis. A number of other factors, including other tumor characteristics and a person's age and general health, can also affect outlook. Your doctor can tell you how these numbers may apply to you, as he or she is familiar with the aspects of your particular situation.

Stage 5-year Relative Survival Rate
Localized 21%
Regional 6%
Distant 2%

For all stages combined, the relative 5-year survival rate from liver cancer is about 10%. Part of the reason for this low survival rate is that most patients with liver cancer also have other liver problems such as cirrhosis, which itself can be fatal.

Studies have shown that patients with small, resectable tumors who do not have cirrhosis or other serious health problems, are likely to do well if their cancers are removed. Their overall 5-year survival is over 50%.





Article Sources
http://www.providence.org/

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