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«Bile Duct Cancer (Cholangiocarcinoma) What is cancer? The body is made up of trillions of living cells. Normal body cells grow, divide into new ...»

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Bile Duct Cancer


What is cancer?

The body is made up of trillions of living cells. Normal body cells grow, divide into new

cells, and die in an orderly way. During the early years of a person’s life, normal cells divide

faster to allow the person to grow. Once the person becomes an adult, most cells divide only

to replace worn-out or dying cells or to repair injuries.

Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells.

Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. In most cases the cancer cells form a tumor.

Cancer cells can also invade (grow into) other tissues, something that normal cells can’t do.

Growing out of control and invading other tissues are what makes a cell a cancer cell.

Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA is damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesn’t die like it should.

Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first abnormal cell does.

People can inherit damaged DNA, but most often the DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment.

Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found.

Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

No matter where a cancer may spread, it is named (and treated) based on the place where it started. For example, colon cancer that has spread to the liver is still colon cancer, not liver cancer.

Different types of cancer can behave very differently. They grow at different rates and respond to different treatments. This is why people with cancer need treatment that is aimed at their particular kind of cancer.

Not all tumors are cancerous. Tumors that aren’t cancer are called benign. Benign tumors can cause problems – they can grow very large and press on healthy organs and tissues. But they can’t grow into (invade) other tissues. Because they can’t invade, they also can’t spread to other parts of the body (metastasize). These tumors are rarely life threatening.

What is bile duct cancer?

Bile duct cancer starts in a bile duct. To understand this cancer, it helps to know about the normal bile ducts and what they do.

About the bile ducts The bile ducts are a series of thin tubes that reach from the liver to the small intestine. The major function of the bile ducts is to move a fluid called bile from the liver and gallbladder to the small intestine, where it helps digest the fats in food.

Different parts of the bile duct system have different names. In the liver it begins as many tiny tubes (called ductules) where bile collects from the liver cells. The ductules come together to form small ducts, which then merge into larger ducts and eventually the left and right hepatic ducts. All of these ducts within the liver are called intrahepatic bile ducts.

The left and right hepatic ducts exit from the liver and join to form the common hepatic duct in an area called the hilum. Lower down, the gallbladder (a small organ that stores bile) joins the common hepatic duct through a small duct called the cystic duct. The combined duct is called the common bile duct. The common bile duct passes through part of the pancreas before it joins with the pancreatic duct and empties into the first part of the small intestine (the duodenum) at the ampulla of Vater.

Types of bile duct cancers by location Cancers can develop in any part of the bile duct system and, based on their location (see

picture below), are classified into 3 types:

• Intrahepatic bile duct cancers

• Perihilar (also called hilar) bile duct cancers

• Distal bile duct cancers

Cancers in these different areas can cause different symptoms.

Intrahepatic bile duct cancers These cancers develop in the smaller bile duct branches inside the liver. They can sometimes be confused with cancers that start in the liver cells, which are called hepatocellular carcinomas, and are often treated the same way. Only about 1 in 10 bile duct cancers are intrahepatic.

Perihilar (also called hilar) bile duct cancers These cancers develop at the hilum, where the left and right hepatic ducts have joined and are just leaving the liver. These are also called Klatskin tumors. They are the most common type of bile duct cancer, accounting for more than half of all bile duct cancers. These cancers are grouped with distal bile duct cancers as extrahepatic bile duct cancers.

Distal bile duct cancers These cancers are found further down the bile duct, closer to the small intestine. Like perihilar cancers, these are extrahepatic bile duct cancers because they start outside of the liver. Distal bile duct cancers make up 2 to 3 of every 10 bile duct cancers.

Types of bile duct cancer by cell type Bile duct cancers can also be divided into types based on how the cancer cells look under the microscope.

Nearly all bile duct cancers are called cholangiocarcinomas. Most of these are adenocarcinomas, which are cancers that start in glandular cells. Bile duct adenocarcinomas develop from the mucous gland cells that line the inside of the duct.

Other types of bile duct cancers are much less common. These include sarcomas, lymphomas, and small cell cancers. This document does not discuss these other types of bile duct cancer.

The rest of this document refers only to cholangiocarcinomas.

Benign bile duct tumors Not all bile duct tumors are cancerous. Bile duct hamartomas and bile duct adenomas are examples of benign (non-cancerous) tumors, which aren’t discussed further in this document.

Other cancers in the liver The most common type of cancer that starts in the liver – much more common than intrahepatic bile duct cancer – is hepatocellular carcinoma, which develops from liver cells.

Hepatocellular carcinoma is discussed in more detail in our document Liver Cancer.

Cancers that start in some other organs can spread to the liver. These are called secondary liver cancers or liver metastases. Their outlook and treatment are not the same as cancer that starts in the liver (such as hepatocellular carcinoma) or bile ducts (like cholangiocarcinoma), but instead depend on where the cancer started. For this reason, it’s important to know whether an adenocarcinoma in the liver started in bile ducts (and is a cholangiocarcinoma), or whether it started in another organ (such as the colon) and then spread to the liver.

What are the key statistics about bile duct cancer?

Bile duct cancer is not common. About 2,000 to 3,000 people in the United States develop bile duct cancer each year. Bile duct cancer is much more common in Southeast Asia, mostly because a parasitic infection that can cause bile duct cancer is much more common there.

Bile duct cancer can occur at younger ages, but it is seen mainly in older people. The average age of people diagnosed with cancer of the intrahepatic bile ducts is 70, and for cancer of the extrahepatic bile ducts it is 72.

The chances of survival for patients with bile duct cancer depend to a large extent on its location and how advanced it is when it is found. For survival statistics, see the section “Survival statistics for bile duct cancers.” What are the risk factors for bile duct cancer?

A risk factor is anything that affects your chance of getting a disease like cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even several risk factors, does not mean that a person will get the disease. And many people who get the disease may have few or no known risk factors.

Researchers have found several risk factors that make a person more likely to develop bile duct cancer.

Certain diseases of the liver or bile ducts People who have chronic (long-standing) inflammation of the bile ducts have an increased risk of developing bile duct cancer. Several conditions of the liver or bile ducts can cause this.

• Primary sclerosing cholangitis is a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). People with this condition have an increased risk of bile duct cancer. The cause of the inflammation is not usually known. Many people with this disease also have inflammation of the large intestine called ulcerative colitis.

• Bile duct stones, which are similar to, but much smaller than gallstones, can also cause inflammation that increases the risk of bile duct cancer.

• Choledochal cysts are bile-filled sacs that are connected to the bile ducts. (Choledochal means having to do with the common bile duct.) The cells lining the sac often have areas of pre-cancerous changes, which increase a person’s risk for bile duct cancer.

• Liver fluke infections occur in some Asian countries when people eat raw or poorly cooked fish that are infected with these tiny parasite worms. In humans, these flukes live in the bile ducts and can cause bile duct cancer. There are several types of liver flukes.

The ones most closely related to bile duct cancer risk are Clonorchis sinensis and Opisthorchis viverrini. Liver fluke infection is rare in the US, but it can affect people who travel to Asia.

• Abnormalities where the bile duct and pancreatic duct normally meet can allow digestive juices from the pancreas to reflux (flow back “upstream”) into the bile ducts.

This backward flow also prevents the bile from being emptied through the bile ducts as quickly as normal. People with these abnormalities are at higher risk of bile duct cancer.

• Cirrhosis is damage to the liver from irritants such as alcohol and diseases such as hepatitis that cause scar tissue to form. Studies have found it raises the risk of bile duct cancer.

• Infection with hepatitis B virus or hepatitis C virus increases the risk of intrahepatic bile duct cancers. This may be at least in part due to the fact that long-term infections with these viruses can also lead to cirrhosis.

Other rare diseases of the liver and bile duct that may increase the risk of developing bile duct cancer include polycystic liver disease and Caroli syndrome (a dilation of the intrahepatic bile ducts that is present at birth).

Inflammatory bowel disease Inflammatory bowel disease includes ulcerative colitis and Crohn’s disease. People with these diseases have an increased risk of bile duct cancer. This is not explained completely by the link between ulcerative colitis and primary sclerosing cholangitis.

Older age Older people are more likely than younger people to get bile duct cancer. Most people diagnosed with bile duct cancer are in their 60s or 70s.

Ethnicity and geography In the United States, the risk of bile duct cancer is highest among Hispanic Americans and Native Americans. Worldwide, bile duct cancer is much more common in Southeast Asia and China, largely because of the high rate of infection with liver flukes in these areas.

Obesity Being overweight or obese can increase the risk of cancers of the gallbladder and bile ducts.

This could be because obesity increases the risk of gallstones and bile duct stones. But there may be other ways that being overweight can lead to bile duct cancers, such as changes in certain hormones.

Exposure to Thorotrast A radioactive substance called Thorotrast (thorium dioxide) was used as a contrast agent for x-rays until the 1950s. It was found to increase the risk for bile duct cancer, as well as some types of liver cancer, which is why it is no longer used.

Family history A history of bile duct cancer in the family seems to increase a person’s chances of developing this cancer, but the risk is still low because this is a rare disease. Most bile duct cancers are not found in people with a family history of the disease.

Diabetes When taken together, the data from many different studies show that people with diabetes have a higher risk of bile duct cancer. This increase in risk is not high, and the overall risk of bile duct cancer in someone with diabetes is still low.

Alcohol People who drink alcohol are more likely to get intrahepatic bile duct cancer. The risk is higher in those who have liver problems from drinking alcohol.

Other possible risk factors Studies have found several other factors that might increase the risk of bile duct cancer, but

the links are not as clear. These include:

• Smoking

• Pancreatitis (inflammation of the pancreas)

• Infection with HIV (the virus that causes AIDS)

• Exposure to asbestos

• Exposure to radon or other radioactive chemicals

• Exposure to dioxin, nitrosamines, or polychlorinated biphenyls (PCBs) Do we know what causes bile duct cancer?

We don’t know the exact cause of most bile duct cancers, but researchers have found several risk factors that make a person more likely to develop bile duct cancer (see the section “What are the risk factors for bile duct cancer?”). There seems to be a link between this cancer and things that irritate and inflame the bile ducts, whether it’s bile duct stones, infestation with a parasite, or something else.

Scientists are starting to understand how inflammation might lead to certain changes in the DNA of cells, making them grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look.

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