Immunotherapy for Gallbladder Cancer

The purpose of immunotherapy in gallbladder cancer is to remove the cancer cells or control the growth of the cancer cells by restoring the natural function of the immune cells, T cells are stimulated and strengthened in vitro, so that after being introduced back to patient’s body, they will be able to identify the gallbladder cancer cells and destroy them.

Proteins such as CEA, Her-2/neu, MUC-1 and a few others are presented on the surface of the gallbladder cancer cells, they are recognized by the immune system as ‘foreign’ to the human body, and are supposed to be destroyed by the T cells in the immune system. However, immune system’s failure in identifying these proteins, causing uncontrolled growth of the gallbladder cancer cells.

Improvements

  • Possible long-term remission;
  • Preventing from metastasis by destroying cancer cells that are not killed in other treatments;
  • Preventing from recurrence by stopping/controlling the growth of cancer;
  • Relieving symptoms;
  • Improving quality of life;
  • Prolongation of life span.

After the immunotherapy in China, my gallbladder cancer has gone. I’m glad that I chose immunotherapy instead of chemotherapy.

— Tina, Australia

Definition

What is gallbladder cancer?

Gallbladder cancer is a cancer that starts in the gallbladder. To understand this cancer, it helps to know about the gallbladder and what it does.

About the gallbladder

The gallbladder is a small, pear-shaped organ under the liver. Both the liver and the gallbladder are behind the right lower ribs. In adults, the gallbladder is usually about 3 to 4 inches long and normally no wider than an inch.

The gallbladder concentrates and stores bile, a fluid made in the liver. Bile helps digest the fats in foods as they pass through the small intestine. Bile is either released from the liver directly into ducts that carry it to the small intestine, or is stored in the gallbladder and released later. When food (especially fatty food) is being digested, the gallbladder contracts and releases bile through a small tube called the cystic duct. The cystic duct joins up with the common hepatic duct, which comes from the liver, to form the common bile duct. The common bile duct joins with the main duct from the pancreas (the pancreatic duct) to empty into the duodenum (the first part of the small intestine) at the ampulla of Vater.

The gallbladder is helpful, but you do not need it to live. Many people have their gallbladders removed and go on to live normal lives.

Types of gallbladder cancers

About 9 out of 10 gallbladder cancers are adenocarcinomas. An adenocarcinoma is a cancer that starts in cells with gland-like properties that line many internal and external surfaces of the body (including the inside the digestive system).

Papillary adenocarcinoma or just papillary cancer is a type of gallbladder adenocarcinoma that deserves special mention. When seen under a microscope, the cells in these gallbladder cancers are arranged in finger-like projections. In general, papillary cancers are not as likely to grow into the liver or nearby lymph nodes. They tend to have a better prognosis (outlook) than most other kinds of gallbladder adenocarcinomas. About 6% of all gallbladder cancers are papillary adenocarcinomas.

Other types of cancer, such as adenosquamous carcinomas, squamous cell carcinomas, small cell carcinomas, and sarcomas, can develop in the gallbladder, but these are uncommon.

Risk Factors

What are the risk factors for gallbladder cancer?

A risk factor is anything that affects your chance of getting a disease such as 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.

Scientists have found several risk factors that make a person more likely to develop gallbladder cancer. Many of these are related in some way to chronic inflammation (irritation and swelling) in the gallbladder.

Gallstones

Gallstones are the most common risk factor for gallbladder cancer. Gallstones are pebble-like collections of cholesterol and other substances that form in the gallbladder and can cause chronic inflammation. At least 3 out of 4 people with gallbladder cancer have gallstones when they are diagnosed. But gallstones are very common, and gallbladder cancer is quite rare, especially in the United States. Most people with gallstones never develop gallbladder cancer.

Porcelain gallbladder

Porcelain gallbladder is a condition in which the wall of the gallbladder becomes covered with calcium deposits. It sometimes occurs after long-term inflammation of the gallbladder (cholecystitis), which can be caused by gallstones. People with this condition have a higher risk of developing gallbladder cancer (possibly because both conditions can be related to inflammation).

Female gender

In the United States, gallbladder cancer occurs more than twice as often in women. Gallstones and gallbladder inflammation are important risk factors for gallbladder cancer and are also much more common in women than men.

Obesity

Patients with gallbladder cancer are more often overweight or obese than people without this disease. Obesity is also a risk factor for gallstones, which might help explain this link.

Older age

Gallbladder cancer is seen mainly in older people, but younger people can develop it as well. The average age of people when they are diagnosed is 72. More than 2 out of 3 people with gallbladder cancer are 65 or older when it is found.

Ethnicity and geography

In the United States, the risk of developing gallbladder cancer is highest among Mexican Americans and Native Americans. They are also more likely to have gallstones than members of other ethnic and racial groups. The risk is lowest among African Americans. Worldwide, gallbladder cancer is much more common in India, Pakistan, and Central European and South American countries than it is in the United States.

Choledochal cysts

Choledochal cysts are bile-filled sacs that are connected to the common bile duct, the tube that carries bile from the liver and gallbladder to the small intestine. (Choledochal means having to do with the common bile duct.) The cysts can grow large over time and may contain as much as 1 to 2 quarts of bile. The cells lining the sac often have areas of pre-cancerous changes, which increase a person’s risk for gallbladder cancer.

Abnormalities of the bile ducts

The pancreas is another organ that releases fluids through a duct into the small intestine to help digestion. This duct normally meets up with the common bile duct just as it enters the small intestine. Some people have an abnormality where these ducts meet that lets juice from the pancreas reflux (flow backward) 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 gallbladder cancer. Scientists are not sure if the increased risk is due to the action of the pancreatic juice or is possibly due to the ducts being exposed longer to damaging substances in the bile itself.

Gallbladder polyps

A gallbladder polyp is a growth that bulges from the surface of the inner gallbladder wall. Some polyps are formed by cholesterol deposits in the gallbladder wall. Others may be small tumors (either cancerous or benign) or may be caused by inflammation. Polyps larger than 1 centimeter (almost a half inch) are more likely to be cancer, so doctors often recommend removing the gallbladder in patients with gallbladder polyps that size or larger.

Primary sclerosing cholangitis

In primary sclerosing cholangitis (PSC), there is inflammation and scarring of the bile ducts. People with this disease have an increased risk of cancer of the gallbladder and bile ducts. Many people with PSC also have ulcerative colitis, a type of inflammatory bowel disease.

Industrial and environmental chemicals

It is not clear if exposure to certain chemicals in the workplace or the environment increases the risk of gallbladder cancer. This is hard to study because this cancer is not common. Some studies in lab animals have suggested that chemical compounds called nitrosamines may increase the risk of gallbladder cancer. Other studies have found that gallbladder cancer might occur more in workers in the rubber and textile industries than in the general public. More research is needed in this area to confirm or refute these possible links.

Typhoid

People chronically infected with salmonella (the bacterium that causes typhoid) and those who are carriers of the disease are more likely to get gallbladder cancer than those not infected. This is probably because the infection can cause gallbladder inflammation. But typhoid is rare in the United States.

Family history

Most gallbladder cancers are not found in people with a family history of the disease. A history of gallbladder 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.

Causes

What causes gallbladder cancer?

Researchers have found several risk factors that make a person more likely to develop gallbladder cancer. (See “What are the risk factors for gallbladder cancer?”) They are also beginning to understand how some of these risk factors might lead to gallbladder cancer.

Chronic gallbladder inflammation is a common link among many of the risk factors for gallbladder cancer. For example, when someone has gallstones, the gallbladder may release bile more slowly. This means that cells in the gallbladder are exposed to the chemicals in bile for longer than usual. This could lead to irritation and inflammation.

In another example, abnormalities in the ducts that carry fluids from the gallbladder and pancreas to the small intestine might allow juices from the pancreas to flow backward (reflux) into the gallbladder and bile ducts. This reflux of pancreatic juices might inflame and stimulate growth of the cells lining the gallbladder and bile ducts, which might increase the risk of gallbladder cancer.

Scientists are starting to understand how risk factors such as 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.

Some genes control when cells grow, divide into new cells, and die. Genes that help cells grow, divide, and stay alive are called oncogenes. Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous.

Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers. But inherited gene mutations are not thought to cause very many gallbladder cancers.

Gene mutations related to gallbladder cancers are usually acquired during life rather than being inherited. For example, acquired changes in the TP53 tumor suppressor gene are found in many cases of gallbladder cancer. Other genes that may play a role in gallbladder cancers include KRAS, BRAF, CDKN2, and HER2. Some of the gene changes that lead to gallbladder cancer might be caused by chronic inflammation. But sometimes what causes these changes is not known. Many gene changes might just be random events that sometimes happen inside a cell, without having an outside cause.

Early Detection

Can gallbladder cancer be found early?

Gallbladder cancer is hard to find early. The gallbladder is deep inside the body, so early tumors can’t be seen or felt during routine physical exams. There are no blood tests or other tests that can reliably detect gallbladder cancers early enough to be useful as screening tests. (Screening is testing for cancer in people without any symptoms.) Because of this, most gallbladder cancers are found only after the cancer has grown enough to cause signs or symptoms.

Still, some gallbladder cancers are found before they have spread to other tissues and organs. Many of these early cancers are found unexpectedly when a person’s gallbladder is removed because of gallstones. When the gallbladder is looked at in the lab after it is removed, small cancers or pre-cancers that did not cause any symptoms are sometimes found.

Treatment

How is gallbladder cancer treated?

General treatment information

After gallbladder cancer is found and staged, your cancer care team will discuss your treatment options with you. The doctors on this team may include:

  • A surgeon or a surgical oncologist (a surgeon who specializes in cancer treatment)
  • A radiation oncologist: a doctor who uses radiation to treat cancer
  • A medical oncologist: a doctor who uses chemotherapy and other medicines to treat cancer
  • A gastroenterologist (GI doctor): a doctor who treats diseases of the digestive system

Many other specialists might be part of your treatment team as well, including physician assistants (PAs), nurse practitioners (NPs), nurses, psychologists, social workers, rehabilitation specialists, and other health professionals. See Health Professionals Associated With Cancer Care for more on this.

It’s important to discuss all of your treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. It’s also very important to ask questions if there is anything you’re not sure about. You can find some good questions to ask in “What should you ask your doctor about gallbladder cancer?”

Take time to think about your choices. In choosing a treatment plan, factors to consider include the stage of the cancer, the possible side effects of treatment, your overall health, and the chances of curing the disease, extending life, or relieving symptoms. The main types of treatments for gallbladder cancer include:

  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Palliative therapy

Your treatment plan will depend on the stage of your cancer and other factors. See “Treatment options based on the extent of gallbladder cancer” for information about comment treatment plans.

If time allows, it is often a good idea to seek a second opinion, particularly for an uncommon cancer such as gallbladder cancer. A second opinion can provide more information and help you feel more confident about your chosen treatment plan.

Thinking about taking part in a clinical trial

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. In some cases they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service at 1-800-303-5691 for a list of studies that meet your medical needs, or see the Clinical Trials section to learn more.

Considering complementary and alternative methods

You may hear about alternative or complementary methods that your doctor hasn’t mentioned to treat your cancer or relieve symptoms. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Complementary methods refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor’s medical treatment. Although some of these methods might be helpful in relieving symptoms or helping you feel better, many have not been proven to work. Some might even be dangerous.

Be sure to talk to your cancer care team about any method you are thinking about using. They can help you learn what is known (or not known) about the method, which can help you make an informed decision. See the Complementary and Alternative Medicine section to learn more.

Help getting through cancer treatment

Your cancer care team will be your first source of information and support, but there are other resources for help when you need it. Hospital- or clinic-based support services are an important part of your care. These might include nursing or social work services, financial aid, nutritional advice, rehab, or spiritual help.

The American Cancer Society also has programs and services – including rides to treatment, lodging, support groups, and more – to help you get through treatment. Call our National Cancer Information Center at 1-800-227-2345 and speak with one of our trained specialists on call 24 hours a day, every day.

The treatment information given here is not official policy of the American Cancer Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor. Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don’t hesitate to ask him or her questions about your treatment options.