All About Gallbladder Cancer

Autor: OncoLink Team
Última Vez Revisión: 19 de enero de 2018

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 gallbladder. 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.

What causes gallbladder cancer and am I at risk?

Gallbladder cancer is a rare disease with about 4,000 people being diagnosed each year. Gallbladder cancer is most often seen in older individuals. It is more common in adults over the age of 65. In the US, Native Americans have a higher risk of developing gallbladder 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 gallbladder inflammation, gallstones, gallbladder polyps, bile duct abnormalities, choledochal cysts and porcelain gallbladder (calcium buildup in the gallbladder), can increase your risk for gallbladder cancer. Obesity and family history of gallbladder cancer may also increase risk.

How can I prevent gallbladder cancer?

There is no specific way in which to prevent gallbladder cancer. However, it is important to exercise, don’t smoke, and maintain a nutritious diet to lower your risk of cancer in general.

What screening tests are available for gallbladder cancer?

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

What are the signs of gallbladder cancer?

There are no specific symptoms early on in the disease that suggest a diagnosis of gallbladder cancer. If patients have symptoms they can include jaundice, loss of appetite, nausea and vomiting 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).

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 liver and gallbladder dysfunction. Blood tests may also be done to monitor for tumor marker levels including CEA and CA19-9. These can be elevated when a person has gallbladder cancer, but are not specific to gallbladder cancer. A urinalysis is usually done to evaluate urinary levels of some of these substances as well.

Ultrasound (US) is the standard study done first in patients presenting with right upper abdominal pain. It allows providers to make a diagnosis of gallbladder cancer in about half of patients. It can also detect disease spread into the liver or bile ducts. 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 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 or MRA) and bile duct passages (magnetic resonance cholangiogram or MRC).

Cholangiography, an imaging test that looks at the bile ducts either through the skin or the stomach, is a technique that allows providers to not only establish a diagnosis, but to locate a bile duct blockage and place a stent to help alleviate the blockage of bile.

The tests that you are ordered will be based on your provider’s recommendations and possible course of treatment.

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 at the end of this article for your reference. Your healthcare provider will use the results of the diagnostic work up to assign the TNM result and will then guide your treatment course.

How is gallbladder cancer treated?

As with many tumor types, treatment of gallbladder cancer may involve more than one type of treatment. You may be followed by a number of care providers including a surgeon or surgical oncologist, a radiation oncologist, a medical oncologist and a gastroenterologist. They will work together to create a treatment plan.

Surgery

Total surgical removal of the entire 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.

In some cases, surgery may be used to relieve pain and minimize symptoms. This is called palliative surgery. It can be used to relieve a blockage of a bile duct which can be causing symptoms. This will not cure the cancer, but will help the patient to feel more comfortable.

Even with improving surgical techniques, the risk of recurrence (the disease coming back) 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.

Radiation

Radiation comes in the form of high energy x-rays that are delivered to the patient to kill cancer cells. Radiation can be used after surgery, as part of the primary treatment or to relieve symptoms. 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 relieve symptoms that may develop as a result of tumor and/or metastases.

Chemotherapy

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, cisplatin, capecitabine and oxaliplatin. Some gallbladder cancers can also over-express EGFR (epidermal growth factor receptor). Therapies that inject chemotherapy directly into the hepatic artery are currently being studied. By putting chemotherapy directly into the hepatic artery that goes into the liver and also supplies most gallbladder tumors, potentially chemotherapy can go right into the tumor. Surgery is often needed to place the catheter into the artery and some patients may not be able to tolerate the surgery.

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your 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 typically 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.

Resources for More Information

CancerCare

Cancer Care provides counseling, support groups, education and financial assistance.

https://www.cancercare.org/diagnosis

Imerman Angels

Imerman Angels provides you with one-on-one support through their cancer support community.

https://imermanangels.org

Rare Cancer Support Forum

A place where patients and caregivers can share support and personal experiences with a rare cancer diagnosis and treatment.

http://www.rare-cancer.org

 

Appendix: Complete Gallbladder Cancer Staging

American Joint Committee on Cancer (8th Edition, 2017)

Primary Tumor (T)

Description

Tx

Primary tumor cannot be assessed

T0

No evidence of primary tumor

T1s

Carcinoma in situ

T1

Tumor invades the lamina propria or muscle layer

T1a

Tumor invades the lamina propria

T1b

Tumor invade the muscle layer

T2

Tumor invades perimuscular connective tissue; no involvement of the serosa or into the liver

T2a

Tumor invades perimuscular connective tissue on the peritoneal side, without involvement of the serosa

T2b

Tumor invades perimuscular connective tissue on the hepatic side, with no extension 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 or more extrahepatic organs or structures

 

Regional Lymph Nodes (N)

Description

Nx

Regional lymph nodes cannot be assessed

N0

No regional lymph node metastasis

N1

Metastases to 1-3 regional lymph nodes

N2

Metastases to 4 or more regional lymph nodes

 

Metastasis (M)

Description

M0

No regional lymph node metastasis

M1

Distant metastasis

 

 

 

Stage

T

N

M

0

Tis

N0

M0

I

T1

N0

M0

IIA

T2a

N0

M0

IIB

T2b

N0

M0

IIIA

T3

N0

M0

IIIB

T1-3

N1

M0

IVA

T4

N0-1

M0

IVB

Any T

Any T

N2

Any N

M0

M1

Referencias

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

Cai, J., Xu, L., Cai, Z., Wang, J., Zhou, B., & Hu, H. (2015). MicroRNA-146b-5p inhibits the growth of gallbladder carcinoma by targeting epidermal growth factor receptor. Molecular Medicine Reports, 12(1), 1549-1555.

Cariati, A., Piromalli, E., & Cetta, F. (2014). Gallbladder cancers: associated conditions, histological types, prognosis, and prevention. European Journal of Gastroenterology & Hepatology, 26(5), 562-569.

Cavallaro, A., Piccolo, G., Panebianco, V., Lo Menzo, E., Berretta, M., Zanghì, A., ... & Cappellani, A. (2012). Incidental gallbladder cancer during laparoscopic cholecystectomy: managing an unexpected finding. World J Gastroenterol, 18(30), 4019-4027.

Hundal, R., & Shaffer, E. A. (2014). Gallbladder cancer: epidemiology and outcome. Clinical Epidemiology6, 99-109.

Liebe, R., Milkiewicz, P., Krawczyk, M., Bonfrate, L., Portincasa, P., & Krawczyk, M. (2015). Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer. A Concise Review. J Gastrointestin Liver Dis, 24(3), 339-348.

Martel, G., & Auer, R. C. (2016). Resection of Gallbladder Cancer, Including Surgical Staging. In Atlas of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery (pp. 599-609). Springer Berlin Heidelberg.

Matos, C., Santiago, I., Maciel, J., & Levy, A. D. (2015). Gallbladder Neoplasms. Gastrointestinal Imaging,474.

National Comprehensive Cancer Network. NCCN Guidelines Version 4.2017 Hepatobiliary Cancers.

Pilgrim, C. H., Groeschl, R. T., Christians, K. K., & Gamblin, T. C. (2013). Modern perspectives on factors predisposing to the development of gallbladder cancer. HPB, 15(11), 839-844.

Sasaki, T., Hiroki, K., & Yamashita, Y. (2013). The role of epidermal growth factor receptor in cancer metastasis and microenvironment. BioMed Research International, article ID 546318, 8 pages, 2013. doi:10.1155/2013/546318

Sicklick, J. K., Fanta, P. T., Shimabukuro, K., & Kurzrock, R. (2016). Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design. Cancer and Metastasis Reviews, 1-13.

Schnelldorfer, T. (2013). Porcelain gallbladder: a benign process or concern for malignancy?. Journal of Gastrointestinal Surgery, 17(6), 1161-1168.

Stinton, L. M., & Shaffer, E. A. (2012). Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver6(2), 172-187.

Surveillance, Epidemiology and End-Results Program (SEER). The four most common cancers for different ethnic populations 2013, Bethesda, MD: National Cancer Institute.

Wernberg, J. A., & Lucarelli, D. D. (2014). Gallbladder cancer. Surgical Clinics of North America, 94(2), 343-360.

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