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The gallbladder is a small, pear-shaped organ located beneath the liver, positioned behind the right lower ribs. In adults, it typically measures about 3 to 4 inches in length and no more than an inch in width. The primary function of the gallbladder is to store and concentrate bile, a digestive fluid produced by the liver. Bile aids in the breakdown of fats as food passes through the small intestine.
During digestion, particularly of fatty foods, the gallbladder contracts and releases bile through a small tube called the cystic duct. The cystic duct connects with the common hepatic duct from the liver to form the common bile duct. This duct then merges with the pancreatic duct and empties bile and pancreatic enzymes into the duodenum (the first part of the small intestine) at the ampulla of Vater.
While the gallbladder plays a role in digestion, it is not essential for survival. Many individuals live normal, healthy lives after gallbladder removal.
Gallbladder cancer is challenging to detect early because the gallbladder is located deep within the body, making tumors difficult to identify during routine physical exams. There are no reliable blood tests or screening methods for early detection in asymptomatic individuals. As a result, many cases are only diagnosed once the cancer has grown and begun causing symptoms.
In some instances, gallbladder cancer is discovered incidentally when the gallbladder is removed for other reasons, such as gallstones. Pathological examination of the removed gallbladder may reveal small cancers or pre-cancerous cells that had not previously caused any symptoms.
The American Cancer Society’s estimates for cancer of the gallbladder and nearby large bile ducts in the United States for 2024 are:
Gallbladder cancer is often diagnosed at an advanced stage when symptoms have already appeared. Only about 20% of cases are detected early, before the cancer has spread beyond the gallbladder. The prognosis for gallbladder cancer patients largely depends on the stage at which the cancer is identified. Early detection significantly improves survival outcomes.
At CU Cancer Center, we offer exceptional care for patients with gallbladder cancer, a rare and complex disease. Our experienced, high-volume liver surgeons specialize in advanced techniques, including minimally invasive and robotic-assisted procedures. Robotic-assisted surgery for gallbladder cancer is available at only a handful of centers in the United States, making CU Cancer Center a leader in this innovative approach. These techniques allow for greater surgical precision, faster recovery, and less postoperative discomfort, providing our patients with the highest standard of care. The Liver Multidisciplinary Clinic is a great option for patients with gallbladder cancer looking for a comprehensive, specialized care or a second opinion.
Our team also includes medical oncologists and radiation oncologists who are dedicated to treating gastrointestinal cancers, including gallbladder cancer. This rare malignancy requires specialized expertise, and at CU Cancer Center, our multidisciplinary team collaborates to create personalized care plans tailored to each patient's unique needs.
Gallbladder cancer is rare, with nearly all cases classified as adenocarcinomas. Adenocarcinomas arise from gland-like cells that line various surfaces of the body, including the digestive system. A noteworthy subtype is papillary adenocarcinoma, characterized by cells arranged in finger-like projections. Papillary cancers typically exhibit a lower tendency to metastasize to the liver or nearby lymph nodes and generally present a more favorable prognosis compared to other gallbladder adenocarcinomas.
Other rare types of gallbladder cancers include adenosquamous carcinomas, squamous cell carcinomas, and carcinosarcomas.
Several risk factors have been identified that increase the likelihood of developing gallbladder cancer, often linked to chronic gallbladder inflammation:
Research indicates that inflammation may induce DNA changes in cells, leading to uncontrolled growth and cancer formation. Key genes involved in this process include oncogenes, which promote cell growth, and tumor suppressor genes, which normally inhibit excessive cell division.
While some individuals may inherit gene mutations that increase cancer risk, most gallbladder cancers result from acquired mutations over a person's lifetime. Common gene mutations associated with gallbladder cancer include TP53, KRAS, BRAF, and PIK3CA. Some mutations may arise from chronic inflammation, while others occur randomly without identifiable causes.
Gallstones: The most prevalent risk factor, affecting approximately 80% of diagnosed gallbladder cancer patients. However, gallstones are common, and most individuals with them do not develop gallbladder cancer.
Porcelain Gallbladder: Characterized by calcium deposits on the gallbladder wall, often due to long-term inflammation, this condition increases cancer risk.
Sex: Gallbladder cancer is diagnosed 3 to 4 times more frequently in women than in men, likely due to higher rates of gallstones and inflammation in women.
Obesity: Overweight individuals are more likely to develop gallbladder cancer, potentially due to obesity's association with gallstone formation.
Age: The average age of diagnosis is 72, with most cases occurring in individuals aged 65 and older.
Ethnicity and Geography: Higher risks are observed among Mexican and Latin Americans and Native Americans, while the lowest risk is found in African Americans. Globally, gallbladder cancer rates are notably higher in regions such as India, Pakistan, and parts of Central and South America.
Choledochal Cysts: These bile-filled sacs can grow large and contain pre-cancerous changes, increasing gallbladder cancer risk.
Bile Duct Abnormalities: Defects in bile duct junctions may contribute to gallbladder cancer risk by causing pancreatic juice reflux.
Gallbladder Polyps: Polyps larger than 1 centimeter may indicate cancer risk, leading to recommendations for gallbladder removal.
Primary Sclerosing Cholangitis (PSC): This condition causes bile duct inflammation and scarring, increasing the likelihood of gallbladder cancer. It is often associated with ulcerative colitis.
Typhoid Infection: Chronic infection with salmonella can cause gallbladder inflammation, increasing cancer risk, though typhoid is rare in the U.S.
Family History: While most gallbladder cancers occur in individuals without a family history of the disease, a familial history can slightly elevate risk.
Other Possible Risk Factors: Additional factors that may be associated with increased risk include smoking and exposure to certain chemicals.
Gallbladder cancer often remains asymptomatic until advanced stages. However, some symptoms can present earlier, potentially aiding in timely diagnosis. Common symptoms include:
Less common symptoms include:
It is important to note that gallbladder cancer is rare. Symptoms may be indicative of more common conditions, such as gallstones or hepatitis, which can also cause abdominal pain and jaundice. Prompt medical consultation is advised for any concerning symptoms to identify and address the underlying cause effectively.
After a diagnosis of gallbladder cancer, healthcare professionals assess whether the cancer has spread and, if so, to what extent. This evaluation process is known as staging, which describes the amount and seriousness of cancer in the body and guides treatment options. The stage of cancer is also referenced when discussing survival statistics.
Gallbladder cancers are classified into stages ranging from 0 to IV. The earliest stage, known as carcinoma in situ, is classified as stage 0. The staging system progresses from stage I (1) to stage IV (4), where a lower number indicates less spread of cancer, while a higher number, such as stage IV, indicates more extensive spread. Within a stage, an earlier letter signifies a lower stage.
While each individual's cancer journey is unique, cancers that share similar stages generally exhibit comparable outcomes and are often managed similarly in treatment.
Most gallbladder cancers originate in the epithelium, the inner lining of the gallbladder. Over time, these cancers may infiltrate the layers of the gallbladder wall and can expand to occupy some or all of the gallbladder's interior.
The most widely used staging system for gallbladder cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on three critical components:
The latest AJCC system, effective January 2018, is utilized for staging gallbladder cancers and cancers originating in the cystic duct, which carries bile from the gallbladder.
Gallbladder cancer staging often relies on the pathologic stage (also known as the surgical stage), which is based on tissue samples examined post-surgery. In cases where surgery is not immediately possible, a clinical stage is assigned based on physical examinations, biopsies, and imaging tests. Clinical staging aids in treatment planning; however, it may not always accurately reflect the extent of the cancer, as it can underestimate the spread.
Further details about each component are indicated by numbers or letters following T, N, and M, with higher numbers indicating more advanced cancer. Once these categories are established, they are combined in a process known as stage grouping to assign an overall stage.
In addition to stage, several factors can influence prognosis:
Cancers deemed resectable are believed to be removable through surgery, while unresectable cancers have spread too extensively or are situated in challenging locations, making complete removal impossible. A small percentage of gallbladder cancers are classified as resectable upon initial discovery.
The extent of gallbladder cancer plays a crucial role in determining treatment options. Surgery is the primary treatment whenever feasible, offering the best chance for a cure. Physicians generally classify gallbladder cancers into two categories:
Stage I, II, and some stage III gallbladder cancers may still be treatable through surgery, provided the cancer has not spread into major blood vessels. Other factors, such as overall health, also influence whether surgery is a viable option. For instance, if the cancer has spread only to one area of the liver and not too deeply, it may still be possible to remove all cancerous tissue. However, if it has spread to both sides of the liver, the abdominal lining, distant organs, or has wrapped around a major blood vessel, surgery may not be able to remove it entirely.
How gallbladder cancer is first discovered can also impact treatment decisions. In some cases, it is detected during imaging tests before surgery, while in others, it is found after the gallbladder has been removed for other reasons, such as gallstones.
Because gallbladder cancer is rare, it is recommended that individuals with a suspected or confirmed diagnosis consult a surgeon experienced in treating this specific type of cancer. Surgeons familiar with more complex operations are often needed for gallbladder cancer treatment.
Regardless of the stage, understanding the goals of treatment—whether aimed at curing the cancer or managing symptoms—is essential. Discussing the potential benefits and risks can help in making informed treatment decisions.
Gallbladder cancer may be suspected on imaging tests done for unrelated reasons or done for symptoms associated with the gallbladder cancer like jaundice.. If these tests indicate resectable gallbladder cancer and the patient is healthy enough for surgery, a more extensive surgery may be performed to remove part of the liver, nearby lymph nodes, and possibly parts of the bile duct. If jaundice is present, a stent or catheter may be placed in the bile duct before surgery to relieve symptoms and improve overall health for surgery.
Sometimes, gallbladder cancer is discovered during or after gallbladder removal to treat gallstones or chronic inflammation. If. the surgeon suspects cancer at the time of the operation, they may take tissue samples for analysis during the procedure. If cancer cells are present, the next steps depend on the surgeon's expertise and the resectability of the cancer. An experienced surgeon may proceed with a more extensive surgery to remove the tumor. If unsure, the surgery may be paused to allow for further imaging tests before proceeding with a more extensive operation.
In some cases, the surgeon may not suspect cancer but cancer is found by the pathologist as they examine the gallbladder under the microscope. If cancer is found in the inner layers of the gallbladder (T1a) and has not spread, no further treatment may be necessary, as the entire cancer may have been removed. If the cancer is found in deeper layers (T1b or greater), additional tests, such as CT or MRI scans or staging laparoscopy, will be performed to determine if any remaining cancer can be removed.
Following surgery, adjuvant chemotherapy, with or without radiation, may be recommended to prevent recurrence (see additional information below – vs add a link)
If additional tests or surgical findings show that the cancer is unresectable, treatment options similar to those for unresectable cancers will be explored.
When surgery is not an option, treatment focuses on controlling the cancer, managing symptoms, and improving quality of life. Many patients with unresectable gallbladder cancer respond to a combination of immunotherapy and chemotherapy. Immunotherapy may also be used alone if the tumor exhibits specific genetic traits such as a defect in a mismatch repair gene (dMMR) or a high tumor mutational burden (TMB-H). Targeted therapy is another potential option for tumors with specific mutations.
In cases of jaundice caused by bile duct blockage, a stent or catheter may be placed to relieve the blockage, or surgery to bypass the bile duct may be performed if the patient is healthy enough. Relieving bile duct obstruction is typically the first step before starting other treatments, such as chemotherapy.
Due to the difficulty in treating these cancers, participation in clinical trials for new treatments may be considered.
Palliative Care
Palliative care is a form of supportive care designed to alleviate symptoms and complications associated with gallbladder cancer. It is integrated with all treatment approaches at every stage of the disease. Palliative care encompasses a variety of interventions, including medications to manage nausea, pain relief strategies, and procedures to ensure proper bile flow when a tumor obstructs it. The primary focus of palliative care is to enhance patient comfort and well-being, rather than to cure the cancer itself.
Maintaining quality of life is a fundamental objective of palliative care. Patients are encouraged to communicate openly with their cancer care team regarding pain management, symptoms, and any concerns related to their quality of life.
Recurrent Gallbladder Cancer
Recurrent gallbladder cancer refers to cancer that returns following treatment. Recurrence may occur locally, meaning in or near the original site, or distantly, affecting other organs such as the lungs or bones. The management of recurrent cancer is contingent upon the location of the recurrence, the treatment modalities previously employed, and the overall health of the patient.
In some cases, if the cancer recurs in a localized area close to the original tumor, surgical removal may be considered, potentially followed by chemotherapy or radiation therapy. However, in most instances, recurrent cancer is deemed unresectable and is managed through palliative care.
Treating recurrent gallbladder cancer can be particularly challenging. Patients may wish to explore participation in clinical trials that offer access to innovative treatment options.
Radiation Therapy for Gallbladder Cancer
Radiation therapy employs high-energy rays, such as X-rays or particles, to destroy cancer cells. While the optimal use of radiation therapy for gallbladder cancer remains under investigation, it may be utilized in several contexts:
External Beam Radiation Therapy (EBRT)
For gallbladder cancer treatment, external beam radiation therapy (EBRT) is employed. This technique involves the use of a large machine that generates X-rays or particles directed at the tumor.
Before treatment begins, the radiation oncology team conducts precise measurements to establish the optimal angles for directing the radiation beams and determining the appropriate radiation dosage. The treatment itself is similar to receiving an X-ray, but with significantly higher energy levels. The procedure is painless, typically lasting only a few minutes, although setup time may require additional time. Radiation treatments are generally administered five days a week over several weeks. Various techniques for EBRT include:
Chemoradiation
Chemotherapy may be administered alongside EBRT to enhance the effectiveness of radiation therapy. This combined approach is commonly used for gallbladder cancer. While chemoradiation can lead to increased side effects compared to radiation alone, research indicates that this strategy may improve survival outcomes, particularly for patients with cancer that has spread to lymph nodes.
Possible Side Effects of Radiation Therapy
Radiation therapy for gallbladder cancer can result in several common side effects, including:
Side effects typically begin one to two weeks into treatment and often improve over time once therapy is completed. Patients are encouraged to consult their healthcare team regarding potential side effects and strategies for prevention or relief.
Chemotherapy for Gallbladder Cancer
Chemotherapy (chemo) involves the use of cancer-killing drugs administered either intravenously (IV) or orally. These medications circulate through the bloodstream, targeting cancer cells throughout the body, making chemo particularly useful for cancers that have metastasized beyond their original site.
While chemotherapy may offer benefits for some individuals with gallbladder cancer, its overall effectiveness for this type of cancer remains unclear. It can be utilized in several contexts:
Chemotherapy is administered in cycles, typically lasting about three to four weeks, with treatment periods followed by rest periods to allow the body time to recover. Generally, chemotherapy is not recommended for patients in poor health, although advanced age alone does not preclude treatment.
In certain cases, intravenous chemotherapy may not be as effective for gallbladder cancer. Therefore, a method known as hepatic artery infusion (HAI) has been studied, in which chemotherapy is delivered directly into the hepatic artery—the primary blood supply for most gallbladder tumors. This approach can enhance the concentration of the drug at the tumor site while minimizing systemic exposure and potential side effects. However, this technique may require surgical placement of a catheter in the hepatic artery, and many patients may not be fit for such a procedure.
Possible Side Effects of Chemotherapy
Chemotherapy drugs target rapidly dividing cells, making them effective against cancer cells. However, they can also affect other fast-dividing cells in the body, such as those in the bone marrow, mouth lining, intestines, and hair follicles. This can lead to various side effects, which can vary based on the specific drugs, dosages, and duration of treatment. Common side effects include:
Most side effects are temporary and resolve after treatment concludes. Strategies are often available to mitigate or prevent side effects, such as medications to manage nausea and vomiting. Healthcare providers should be consulted regarding options to reduce side effects.
In addition to general side effects, some chemotherapy drugs may cause specific adverse effects. For instance, cisplatin and oxaliplatin can induce neuropathy, leading to symptoms such as numbness, tingling, weakness, and heightened sensitivity to temperature changes, particularly in the hands and feet. While these effects generally improve after treatment, some patients may experience lasting changes.
It is crucial for patients to report any side effects to their medical team promptly to facilitate appropriate management. In some instances, it may be necessary to adjust drug dosages or modify the treatment schedule to prevent complications.
Targeted Therapy Drugs for Gallbladder Cancer
Advancements in research have led to the development of targeted therapy drugs designed to address specific cellular changes associated with gallbladder cancer. These targeted therapies operate differently from standard chemotherapy and may provide benefits when conventional treatments are ineffective.
Immunotherapy for Gallbladder Cancer
Immunotherapy involves the use of medications that enhance the immune system's ability to recognize and destroy cancer cells. Various types of immunotherapy are currently being evaluated in clinical trials, with some already approved for the treatment of gallbladder cancer.
Immune Checkpoint Inhibitors
A crucial function of the immune system is to avoid attacking the body’s normal cells. This is achieved through “checkpoint” proteins on immune cells, which act as switches to initiate an immune response. Cancer cells can exploit these checkpoints to evade detection and destruction by the immune system.
Immune checkpoint inhibitors are drugs designed to target these checkpoints and are utilized in the treatment of certain gallbladder cancers.
Possible Side Effects of Immune Checkpoint Inhibitors
More serious side effects, though less frequent, may occur:
Prompt reporting of any new side effects to a healthcare team is essential. If severe side effects occur, treatment may need to be discontinued, and high doses of corticosteroids may be administered to suppress the immune system.
Palliative Therapy for Gallbladder Cancer
Palliative care focuses on alleviating symptoms caused by cancer without aiming to cure the disease.
When are Palliative Treatments Used?
In cases where gallbladder cancer has metastasized and is inoperable, healthcare providers may concentrate on palliative treatments. This may include medications for pain management, nausea, or itching. Additionally, radiation and chemotherapy can be utilized to alleviate symptoms associated with tumor presence. In certain instances, surgical procedures or other treatments may be employed to improve comfort or prevent complications related to the cancer. Given the aggressive nature of gallbladder cancers, healthcare providers often opt for palliative therapies with fewer immediate side effects.
Examples of Palliative Procedures for Gallbladder Cancer
These procedures can be performed during a cholangiography or surgical intervention and may relieve or prevent symptoms in advanced cancer cases. They can also assist in managing jaundice prior to potentially curative surgery, thereby reducing the risk of surgical complications. Stents or catheters typically require replacement every few months to minimize infection and inflammation risks.
Laparoscopic surgery, utilizing small incisions and specialized tools, may be applicable in some cases. Biliary bypass procedures often provide more enduring relief than stents but require careful consideration of the patient's overall health and a thorough discussion of potential risks and benefits with the healthcare team.
The University of Colorado (CU) Cancer Center partners with UCHealth, Children’s Hospital Colorado, and Rocky Mountain Regional VA to provide clinical care. Please make an appointment with one of our clinical partners to be seen by a CU Cancer Center doctor.
UCHealth Cancer Care - Anschutz Medical Campus
1665 Aurora Court Anschutz Cancer Pavilion
Aurora, CO 80045
720-848-0300
UCHealth Cherry Creek Medical Center
100 Cook Street
Denver, CO 80206
720-848-0000
UCHealth Cancer Center - Highlands Ranch
1500 Park Central Drive
Highlands Ranch, CO 80129
720-516-1100
UCHealth Lone Tree Medical Center
9548 Park Meadows Drive
Lone Tree, CO 80124
720-848-2200
Children's Hospital Colorado:
13123 East 16th Avenue
Aurora, CO 80045
720-777-6740
Rocky Mountain Regional VA Medical Center:
1700 North Wheeling Street
Aurora, CO 80045-7211
303-399-8020