All About Gallbladder Cancer

Neha Vapiwala, MD
Modified By: Christina Bach, MBE, MSW, LCSW, OSW-C
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: April 4, 2016

What is the gallbladder?

The gall bladder is a small pear-shaped organ that stores and concentrates a substance called bile. Bile is a greenish liquid substance produced by the cells of the liver (hepatocytes) that aids in the digestion of fats. It emulsifies fats, causing the fats to accumulate into droplets, which can be easily absorbed in the small intestine. It also aids in the absorption of so-called "fat soluble vitamins, such as vitamins A, D, E and K. Bile is also the way the body disposes of hemoglobin from old red blood cells that are no longer functional. This component is what makes bile green and stool brown. Once hepatocytes (liver cells) have produced bile, it is transported to the duodenum (the segment of small intestine right after the stomach) via the common bile duct, where it is secreted through a small opening known as the Ampulla of Vater. It can then form droplets together with fat particles exiting the stomach. The bile also goes to the gallbladder where it can be stored. The gallbladder and liver are connected by the hepatic duct.

When you eat fatty food, the food passes from the stomach into the small intestine, and triggers the lining of the small bowel to release a hormone called CCK (cholecystokinin). CCK is then carried in the bloodstream to the gallbladder, where it causes the gallbladder to contract and send bile through the common bile duct and into the small bowel (duodenum). Gallstones form when the substances contained in bile crystallize into small, hard rocks.

What is gallbladder cancer?

Gallbladder cancers occur when malignant cells form in the gall bladder. These cells can spread to other organs and tissues (metastasis). The majority of gallbladder cancers (9 out of 10) are adenocarcinomas (named for the type of cell the cancer affects), with subtypes such as papillary, nodular, and tubular, depending on the appearance of the tumor cells under the microscope. Less common subtypes include: squamous cell, signet ring cell, and adenosquamous carcinoma.

Am I at risk for gallbladder cancer?

Gallbladder cancer is a rare disease, though it accounts for 80-95% of all biliary duct cancers. The American Cancer Society estimates in 2016 that about 4000 people will be diagnosed with gallbladder cancer. Gallbladder cancer is most often seen in older individuals. The average age at diagnosis is 72; while 2 out of 3 cases are diagnosed in individuals who are 65 or older. In the US, Native Americans have a higher risk of developing gall bladder cancer. It is also more common in other developing countries in southeast Asia, central Europe, and South America as well as Israel and Japan. There is some evidence that Typhoid can increase risk of gallbladder cancer, which may account for higher rates in under-developed countries.

A prior history of gall bladder inflammation, gallstones, gallbladder polyps, bile duct abnormalities, choledochal cysts and porcelain gallbladder (calcium buildup in the gall bladder), can increase your risk for gallbladder cancer. Obesity and family history of gallbladder cancer may also increase risk.

What screening tests are available for gallbladder cancer?

There are no standard screening tests used for gall bladder. Be sure to tell your health care providers about any history of gall stones, gall bladder inflammation or polyps as these can be a precursor to call bladder cancer.

What are the signs of gallbladder cancer?

There are no specific symptoms that suggest a diagnosis of gallbladder cancer. Typically, patients present with problems resulting from blockage of the bile ducts, such as jaundice, loss of appetite and weight loss. There may be a mass and/or pain in the abdomen, especially on the right under the ribcage. However, people often have no symptoms, or their symptoms closely mimic those of gallstones. The most common way gallbladder tumors are diagnosed is incidentally, during surgery performed to remove the gallbladder (cholecystectomy). Approximately 1-2% of cholecystectomies reveal gallbladder cancer.

How is gallbladder cancer diagnosed?

Your healthcare team will perform a number of tests if gallbladder cancer is suspected. These may include blood tests and radiologic exams. Blood tests should include metabolic chemistry and liver function panels to look for abnormal levels of various substances in the blood that are suggestive of general hepatobiliary disease. A urinalysis is usually done to evaluate urinary levels of some of these substances as well.

Ultrasonography (US) is the standard study done first in patients presenting with right upper quadrant pain. It allows HCPs to make a diagnosis of gallbladder cancer in about half of patients, and can also detect disease spread into the liver or bile ducts about half of the time. This is an important test, as it can help differentiate people who are having pain from gallstones from those who have gallbladder cancer. Endoscopic ultrasound (EUS), where a camera is inserted down through the mouth (while under sedation) allows the ultrasound probe to be placed closer to the gallbladder and appears to be more accurate than the traditional ultrasound which is placed against the abdominal wall. EUS may also better detect nodes and whether the tumor has spread beyond the gallbladder. EUS is considered the preferred method of diagnosing and staging (through fine needle biopsy) gallbladder cancer.

Computed tomography (CT) scans can also be helpful in patients with upper abdominal pain. They are better than US for detecting tumor invasion out of the gallbladder and disease spread to other sites in the abdomen or pelvis. About 70-80% of cases will have some degree of liver invasion, and so the combination of CT and US provides more accurate information.

Magnetic resonance imaging (MRI) has been useful in examining this region for disease spread into the liver or other tissues. This technology is particularly good for planning surgery, by evaluating surrounding blood vessels [magnetic resonance angiogram (MRA)] and bile duct passages [magnetic resonance cholangiogram (MRC)].

Cholangiography, either through the skin or the stomach, is a technique that allows HCPs to not only establish a diagnosis, but to locate a bile duct blockage and place a stent to help alleviate the blockage of bile.

PET scans can also be used in pre-operative staging and post operatively in detecting residual disease.

How is gallbladder cancer staged?

Healthcare providers use the TNM system (also called tumor - node - metastasis system). This system describes the size and local invasiveness of the tumor (T), which, if any, lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. The TNM breakdown is quite technical, but is provided here for your reference. Your healthcare provider will use the results of the diagnostic work up to assign the TNM result.

NCCN Guidelines for Staging of Gallbladder Cancer (American Joint Committee on Cancer, 7th Edition, 2010)

Primary tumor (T)

Tx

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1s

Carcinoma in situ

T1

Tumor invades the lamina proporia or muscle layer

T1a

Tumor invades the lamina proporia

T1b

Tumor invade the muscle layor

T2

Tumor invades perimuscular connective tissue; no extension beyond the serosa or into the liver

T3

Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts

T4

Tumor invades the main portal vein or hepatic artery or invades two of more extrahepatic organs

Regional lymph nodes (N)

Nx

Reginal lymph nodes cannot be assessed

N0

No regional lymph node metastasis

NI

Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein

N2

Metastases to perioaortic, pericaval, superior mesenteric artery, and or celiac artery lymph nodes

Metastases (M)

Mx

Distant metastasis cannot be assessed

M0

No regional lymph node metastasis

MI

Distant metastasis

TNM Groupings by Stage

The above T, N & M are then combined to come up with a stage.

 Stage

T

N

M

0

Tis

N0

M0

I

TI

N0

M0

II

T2

N0

M0

IIIA

T3

N0

M0

IIIB

T1-3

N1

M0

IVA

T4

N0-1

M0

IVB

Any T

N2

M0

 

Any T

Any M

M1

What are the treatments for gallbladder cancer?

As with many tumor types, management is often a multidisciplinary approach involving a variety of treatments.

Surgery

Total surgical removal of all known tumor is the only truly "curative" treatment. For early stage disease (Stage IA), surgery alone (cholecystectomy, removal of the gall bladder) is considered curative. Once the tumor has spread to the muscle layer (Stage IB), a more extensive surgery including removal of the gall bladder and resection of segments of the liver may be necessary. In later stages, more radical surgical procedures may be required to remove as much tumor as possible. This can involve removal of an entire lobe of liver (hepatectomy/lobectomy), regional lymphadenectomy or even pancreaticduodenecctomy (Whipple). Once the disease has progressed to stage IV, the tumor is likely not operable.

Even with improving surgical techniques, the risk of recurrence is high. In such cases, external beam radiation therapy can be used in hopes of eradicating any microscopic cancer remaining in the surgical area and surrounding at-risk regions.

Chemotherapy and Radiation

For patients who are unable to undergo surgery, either because the disease is too advanced or because of other serious medical conditions, radiation therapy can be used with or without chemotherapy in order to improve symptoms, and in some cases, increase survival. Radiation usually targets the tumor (or tumor bed, if post-surgery) and the lymph nodes in that area. Radiation therapy can also be used to palliate symptoms that may develop as a result of tumor and/or metastases.

Adjuvant chemotherapy (chemotherapy given after surgery) may also be used depending on stage and success of surgical resection. The most commonly used chemotherapy medications in the treatment of gallbladder cancer include 5-FU or gemcitabine, combined with ciplatin or oxaliplatin. Some gallbladder cancers can also over-express EGFR (epidermal growth factor receptor). Therapies that target EGFR are being studied in clinical trials and may offer another treatment option for some patients with gall bladder cancer.

Clinical Trials

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow Up Care and Survivorship

After the completion of treatment for gall bladder cancer, your healthcare providers will continue to monitor you closely for a period of time. Routine labs and imaging to monitor for recurrence are recommended every 6 months for the first two years. Your healthcare providers will determine the best follow up plan for you based on the stage of your disease, the success of surgical removal (if performed), and the presence of other symptoms.

Fear of recurrence, relationship challenges, the financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by gall bladder cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

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American Cancer Society, Gallbladder Cancer, http://www.cancer.org/cancer/gallbladdercancer/index

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