Gallbladder Cancer

Gallbladder cancer, also known as a malignant neoplasm of the gallbladder, is a rare cancer with just over 12,000 new cases expected to be confirmed in the U.S. in 2018. 1

The gallbladder is a small, pear-shaped organ which sits under the liver on the right side of the body. It stores bile, a digestive fluid produced by the liver, and releases it during eating. Bile helps break down fatty foods.

Treatment of gallbladder cancer depends on the size of the cancer and whether it has already spread at the time of diagnosis. If it is diagnosed early enough, it can be cured by removing the gallbladder, part of the liver and associated lymph nodes. A person does not need a gallbladder to live a normal life.

There are normally no early symptoms of gallbladder cancer, or they may go unnoticed, since many symptoms, such as burping or stomach pain, are non-specific. As a result, the condition is often diagnosed at an advanced stage. Later symptoms include a lump in the upper right part of the abdomen and yellowing of the skin.

This condition most commonly affects people older than 65. Women are affected over two times more often than men. Gallstones and persistent inflammation of the gallbladder, known as cholecystitis, are known to increase the risk of gallbladder cancer, though most people with these conditions never develop gallbladder cancer. 2

There are different types of gallbladder cancer, with different treatments and outcomes, depending on which cells the cancer develops in. For example:

About 85 percent of gallbladder cancers are adenocarcinomas developing from the gland cells in the lining of the gallbladder, which normally produce mucus.

There are two main types of gallbladder adenocarcinoma: 3 4

• Non-papillary adenocarcinoma: This is by far the most common type of gallbladder cancer.
• Papillary adenocarcinoma: About 6 percent of gallbladder cancers are papillary adenocarcinomas. This type of gallbladder cancer tends to have a better outlook than most other types of gallbladder cancer, as it is less likely to spread to the liver or lymph nodes.

Other types of gallbladder cancer are extremely rare. These include: 3 4

This develops from the skin-like cells that line the gallbladder. Squamous cell cancers are treated similarly to adenocarcinomas, with removal of the gallbladder as the best treatment, if still possible at the time of diagnosis.

These have both squamous cancer cells and glandular cancer cells. Adenosquamous cancers are treated similarly to adenocarcinomas, with removal of the gallbladder as the best treatment if still possible at the time of diagnosis.

Gallbladder cancer does not normally have early symptoms. Signs of gallbladder cancer tend to appear when the tumor is fairly large and may have spread. If symptoms do appear sooner, earlier diagnosis can lead to prompt treatment and a better prognosis.

The most common gallbladder cancer symptoms include: 5 6

Stomach pain: Commonly in the upper right part of the abdomen, often described as a dragging feeling, though it can also be a sharper pain if the tumor blocks the bile duct. Most people with gallbladder cancer will develop stomach pain.

Nausea and/or vomiting: This symptom is common in the later stages of gallbladder cancer.

Yellowing of the skin and whites of the eyes, known as jaundice: This occurs if the tumor grows big enough to block the bile ducts, which normally drain bile from the liver into the intestines. This can lead to a yellowish chemical found in bile, called bilirubin, building up in the blood and settling in different areas of the body.

Lumps on the right side of the stomach: The gallbladder may swell if the tumor blocks the bile ducts. Gallbladder cancer may also spread to nearby parts of the liver, which may also present as lumps.

Less common signs of gallbladder cancer may include: 5 6

• Loss of appetite and/or weight
• Indigestion, such as bloating and burping
• Swollen stomach
• Fever
• Itchiness
• Dark urine
• Greasy or light-colored feces

Good to know: These symptoms are much more likely to be caused by other conditions, as gallbladder cancer is rare. For instance, hepatitis is a common cause of jaundice. However, if any of these symptoms are present, it is important to seek medical attention as soon as possible to treat the underlying cause. The Ada app can help you check your symptoms. Download it for free..

It is not known what causes most gallbladder cancers. However, there are factors that can increase the risk of developing it.

Risk factors for gallbladder cancer may include: 7 8

• History of gallbladder disease: Conditions such as gallstones – also known as cholelithiasis, cholecystitis, gallbladder polyps, porcelain gallbladder, and bile duct abnormalities increase risk for gallbladder cancer.
• Being female: Women are twice as likely as men to get gallbladder cancer in the U.S.
• Being over the age of about 65
• Family history of gallbladder cancer may increase the chance of getting gallbladder cancer, though it is not normally associated
• Being obese: This may be related to the increased risk for developing gallstones
• Chronic typhoid: An infection that can cause irritation of the gallbladder wall, but that is very rare in the U.S.
• Ethnicity and geography: Incidence of gallbladder cancer varies widely between racial groups and people living in different parts of the world, likely due to genetic and socioeconomic factors. Rates of gallbladder cancer are highest in areas including Latin America, Asia, and Eastern and Central Europe
• Being of particular ethnic groups: In the U.S., Native American Indians and Hispanics of Mexican descent have the highest risk, while African-Americans have a lower risk

Good to know: Gallbladder cancer is rare, and the risk normally remains low, even if a person has known risk factors. Having one or more risk factors doesn’t mean that any one person will get gallbladder cancer. Equally, a person can have no known risk factors and still develop it.

COVID-19 can cause severe symptoms in patients being treated for anal cancer. This is because cancer therapy weakens the immune system, which puts you at a higher risk of contracting the coronavirus. Taking the necessary precautions and getting tested as soon as possible if you start experiencing symptoms is essential. Talk to your doctor to determine whether you're eligible for antiviral medication.

Gallbladder cancer can be difficult to detect and diagnose for several reasons:

• There are normally no noticeable signs or symptoms in its early stages
• The typical symptoms are similar to the symptoms of many other conditions

For this reason, gallbladder cancer is sometimes found when the gallbladder is removed to treat another condition.

Otherwise, as the first step, a doctor will typically take the person’s medical history and perform a physical examination. In addition, a doctor may perform the following diagnostic tests: 9 10

Blood tests may be done to test for: 9 10

Liver and gallbladder function: Bilirubin, albumin, liver enzymes and certain other substance blood levels can help diagnose liver, bile duct or gallbladder disease.

Tumor markers: People with gallbladder cancer may have high blood levels of markers called CEA and CA 19-9, usually only in the advanced stages. It should be noted that other health conditions can also raise these markers. These markers can be followed during treatment to see how well it is working.

There are many possible imaging tests that may be used to test for gallbladder cancer: 9 10

Ultrasound: A probe on the skin over the right upper abdomen or an endoscope – a thin tube with a light and camera on the end – passed through the mouth and down into the first part of the small intestine produces an image of the internal area using soundwaves.

Endoscopic retrograde cholangiopancreatography (ERCP): An ERCP uses an endoscope to examine and X-ray the gallbladder and other connected organs. After the endoscope is passed through the mouth and into the first part of the small intestine, a smaller tube known as a catheter is inserted through the endoscope into the bile and pancreatic ducts. A dye is then injected through the catheter into the ducts, and an X-ray is taken. Sometimes, a similar procedure may be performed by injecting contrast materials through keyhole surgery.

Computed tomography (CT) scan: A CT scan uses X-rays to make detailed cross-section images of the gallbladder. Often, contrast material is injected through a drip to the vein. Sometimes a person may also be asked to swallow contrast material, such as barium, which coats the digestive tract, before being X-rayed. Additionally, a CT angiogram may be performed.

Magnetic resonance cholangiopancreatography (MRCP): This is a specialized type of MRI scan that produces detailed images of the bile duct and other connected organs. An MRI uses a magnetic field rather than X-rays to take detailed pictures of internal body structures. It involves lying on a bed inside an MRI scanner for between 20 minutes and an hour. Often, in the case of an MRCP, a contrast material has to be injected into a vein to make details of structures inside the gallbladder easier to see.

These imaging methods may be used to create a picture of the structures inside the body. These may help:

• To look for areas that may contain cancer
• To help a doctor guide a biopsy needle to take a tissue sample from a suspicious area
• To see how far cancer has spread
• To help check if the treatment is working
• To see if there are signs that the cancer has returned after treatment

A biopsy is often the only way to be certain of a gallbladder cancer diagnosis. This involves removal of a small amount of tissue or sometimes fluid from an area. Cells are then examined under a microscope and further tested to check for the presence of cancer.

The treatment of gallbladder cancer depends on the size of the cancer, the exact type of cancer and whether the cancer has spread. The combination of these factors decides the stage of the cancer.

The three main treatments used are: 11

• Surgery
• Radiation therapy
• Chemotherapy

Alternative treatments are also being developed in clinical trials.

If the gallbladder cancer is found early enough and has not yet spread, then the gallbladder and surrounding tissues will be removed in a surgery known as cholecystectomy. This is known as a resectable gallbladder cancer, and may be cured. 12

However, most gallbladder cancers are found when they have spread too far to be removed by surgery, when they are known as unresectable. Doctors may then focus on treatments to relieve symptoms and help an affected person to live longer.

Certain types of surgery are sometimes used to relieve symptoms caused by the tumor blocking the bile duct and bile building up in the gallbladder: 11 13

This involves a doctor cutting the gallbladder or bile duct in an area before the blockage and sewing it to the small intestine to create a pathway around the blocked area.

A thin tube called a stent is fed in from the mouth and through the digestive system to drain bile that has built up in the area, either into the small intestine or into a bag outside of the body.

If endoscopic stent surgery is not possible, then the stent is placed by cutting the skin. This procedure may be done to relieve jaundice before other surgical procedures are carried out

Also known as radiation therapy, radiotherapy uses X-rays to destroy cancer cells.

Chemotherapy is the use of medication to destroy cancer cells. Most of the chemotherapy medications for gallbladder cancer are administered into the bloodstream, though some may be given in tablet form.

Radiotherapy and chemotherapy may be used to treat gallbladder cancer, but, used alone, they are unlikely to cure this type of cancer. Radiotherapy and chemotherapy are not usually used to treat early gallbladder cancer but may be used in cases of advanced gallbladder cancer, 14 often in combination with each other.

Radiotherapy and/or chemotherapy may be used to treat gallbladder cancer in the following cases: 15 16

Palliative care: Chemo and radiotherapy may be used to help relieve symptoms of the cancer, for instance pain caused by the tumor pressing on nerves, as it can help shrink tumors or slow their growth. However, these treatments, in particular chemotherapy, cause side effects, and may themselves require palliative care.

After surgery to remove tumors: Chemotherapy is given after surgery, sometimes with radiation therapy, to try to reduce the chances of the cancer returning.

As part of treatment for advanced gallbladder cancer: Chemotherapy may be used for more advanced cancers that cannot be surgically removed or which have spread, not to cure them, but to help people live longer.

Good to know: These treatments, in particular chemotherapy, can sometimes have unpleasant side effects. For example, chemotherapy may cause hair loss, nausea and vomiting, fatigue and pain. Radiotherapy may cause, for example, skin irritation and nausea. A doctor will be able to advise on how best to manage side effects, should they occur (see chemotherapy side effects).

Once gallbladder cancer is diagnosed, doctors will try to find out whether it has spread and if so, how far, in a process known as staging.

Gallbladder cancers usually undergo pathologic staging, which is determined during surgery to remove the cancerous tissue.. 17

The cancer maybe given a number stage from 1 to 4. The lower the number, the less the cancer has spread. 0 is the earliest stage gallbladder cancer, also known as carcinoma in situ.

Gallbladder cancer is considered to be stage 3 or stage 4 gallbladder cancer once the tumor has grown through all of the outer layers of the gallbladder.

The staging system most often used to determine the stage for gallbladder cancer is the American Joint Committee on Cancer (AJCC) TNM system.

Adenocarcinomas and papillary carcinomas may have a better prognosis than rarer cancers, such as squamous and adenosquamous carcinomas.

Gallbladder cancers, which are seen under the microscope in small blood vessels or lymph vessels, tend to have a poor prognosis, as there’s a greater chance they have spread outside of the gallbladder.

Resectable cancers – those that are thought to be completely removable by surgery – have a better outlook. Most gallbladder cancers are unresectable by the time they’re found, as they have already spread too far or are in too difficult a place to be entirely removed by surgery.

• Malignant neoplasm of gallbladder

Q: Is gallbladder cancer rare?
A: Yes, gallbladder cancer is quite rare. There are various risk factors which may put a person at increased risk of developing gallbladder cancer. For instance, incidence rates of gallbladder cancer are higher in women than in men. 18 However, the risk remains low across populations: In the U.S., there are about 1.4 cases of gallbladder cancer per 100,000 women and 0.8 cases per 100,000 men. 19

Q: Is gallbladder cancer curable?
A: Gallbladder cancer is more likely to be curable if it is caught in the earliest stages, when it may be completely removed by removing the gallbladder and sometimes surrounding tissues, such as part of the liver and the surrounding lymph nodes, to lower the risk of the cancer coming back. Sadly, because gallbladder cancer does not normally have symptoms in these early stages, it is often diagnosed in the later stages when treatment is unlikely to result in cure.

Q: Is there immunotherapy for gallbladder cancer?
A: Current clinical trials are testing immunotherapy, also known as biologic therapy, as a way to treat gallbladder cancer. This is a type of cancer treatment that boosts the body’s natural defences to fight cancer, using substances made by the body or in a laboratory to improve or restore immune system function.