Cancer of the gallbladder and bile ducts

Doctors refer to cancer in the gallbladder and bile ducts as biliary tumors.

Bile duct cancer and gallbladder cancer are rare. Men are more commonly affected by tumors in the bile ducts, while women develop gallbladder cancer much more frequently.

Gallbladder cancer starts in the gallbladder mucosa. 

Tumors in the bile ducts are categorized into groups according to their location:

• So-called intrahepatic cholangiocarcinomas develop in the liver.
• Experts refer to tumors in the bile ducts outside the liver as extrahepatic cholangiocarcinomas. Depending on where the cancer in the bile ducts is located outside the liver, there are special types. Examples are the Klatskin tumor at the junction of the right and left liver bile duct or ampullary carcinoma at the opening of the bile duct in the small intestine.

This article only concerns extrahepatic cholangiocarcinomas. Intrahepatic cholangiocarcinomas (intrahepatic bile duct carcinomas) are discussed in the article about liver cancer.

Bile duct cancer can cause different symptoms, depending on its location. These often only occur when the cancer is advanced.

A tumor in the bile duct outside the liver typically causes yellowing of the eyes and skin (jaundice) as it blocks bile drainage. This is not painful. An enlarged palpable gallbladder without pain (Courvoisier’s law) also points to a bile duct tumor outside the liver.

Other possible symptoms are:

• severe itching
• discolored feces
• dark urine
• abdominal pain, frequently on the upper right-hand side
• nausea, vomiting
• loss of appetite and weight loss
• fatigue
• fever
• inflammation of the bile ducts (cholangitis)

Similarly, tumors in the gall bladder do not usually cause any typical symptoms for a long time. Symptoms may occur that generally indicate a disease of the biliary tract:

• nausea and/or vomiting
• loss of appetite
• pain in the upper abdomen (on the right)

Symptoms such as yellowing of the skin and eyes (jaundice) rather point to an advanced gallbladder tumor. This may then be felt through the abdominal wall. Patients often receive their diagnosis in late stages, because it is only then that the tumor causes symptoms.

The most significant risk factor for bile duct tumors is older age.

Possible risk factors for gallbladder carcinoma are:

• gallstones
• obesity (severe overweight)
• major benign tumors in the gallbladder (gallbladder polyps)
• abnormal development of the bile ducts
• gallbladder inflammation
• chronic inflammation of the bile ducts, especially primary sclerosing cholangitis 
• diabetes mellitus
• hardening of the inner wall of the gallbladder with calcium deposits following inflammation (a condition known as “porcelain gallbladder”)

Other risk factors for biliary tract/bile duct cancer outside the liver are:

• congenital malformations of the bile ducts (Caroli­ disease)
• bile duct stones in the common bile duct outside the liver
• a cystic enlargement of the bile ducts outside the liver
• chronic inflammatory bowel disease

What everyone can do: Leading a healthy lifestyle can reduce the risk of developing bile duct cancer.

When cancer of the bile ducts outside the liver or gallbladder is suspected, various and complementary diagnostic procedures are available to doctors:

• Case history: the doctor asks about the patient’s pre-existing conditions and symptoms.
• Physical examination: it is preferable to palpate the patient’s right upper abdomen.
• Blood test: there is no specific tumor marker. However, altered blood values may indicate an illness, for example a backlog of bile.
• Imaging techniques: to clarify the suspicion of a biliary tumor, various imaging techniques are available.
• Biopsy: a biopsy ensures the diagnosis, especially if the tumor is inoperable.
• Other possible tests: it may be useful to test tumor cells for molecular changes. Targeted therapy drugs can then be used based on the results.

An ultrasound examination of the abdomen offers initial guidance when a biliary tract disease is suspected. The most important imaging techniques for confirming a suspected bile duct or gallbladder carcinoma are magnetic resonance imaging (MRI) or computed tomography (CT). With these, contrast agents and special investigative techniques are used to assess a tumor and the degree to which it has spread. Possible supplementary techniques include a three-dimensional display of the bile ducts in MRI (MRCP) and a dynamic MRI with contrast agents.

Depending on the findings of the imaging diagnosis, other diagnostic methods are used:

• an ultrasound examination “from the inside” (endosonography)
• endoscopic techniques for seeing inside the bile ducts and pancreatic ducts with contrast agents and x-rays (this is called endoscopic-retrograde cholangiopancreatography or ERCP for short) or for direct imaging of the bile ducts (cholangiography) and selective removal of tissue
• alternatively, doctors can also image the bile ducts “from the outside” with contrast agents and x-rays by using a thin needle, in a procedure known as percutaneous transhepatic cholangiography (PTC)
• in certain individual cases, an inspection of the abdominal cavity (laparoscopy)

As part of various examinations, tissue samples can be taken to confirm the diagnosis histologically (i.e. on a cellular level). Medical specialists recommend investigating the cell forms and molecular properties of tumors in the bile ducts and gallbladder if necessary.

For some people, a gallbladder carcinoma can sometimes be found serendipitously: after surgical removal of the gallbladder due to gallstones for instance, doctors discover a tumor. It must then be clarified with the aforementioned methods how extensive the tumor is and whether it has already spread into the organs.

Detailed information about the procedure and side effects of imaging and surgical techniques in cancer diagnosis is available on the website of the Cancer Information Service of the German Cancer Research Center (in German).

There is no statutory cancer screening program for cancer of the gallbladder and bile ducts for those in good health.

Experts recommend regular ultrasound scans for individuals with gallbladder polyps. Doctors may sometimes also remove the gallbladder as a precaution in this situation. 

In the case of primary sclerosing cholangitis (a certain form of chronic inflammation of the bile ducts), experts recommend that patients be monitored every 6 months using imaging scans (ultrasound, MRI and MRCP in alternation).

When choosing the appropriate form of therapy for bile duct and gallbladder cancer, doctors consider three factors in particular:

• the stage of the disease
• the type of tumor
• the patient’s general condition

When is a cure possible?

A cure is possible if doctors can surgically remove the entire tumor in the bile ducts or gallbladder in the initial stage.

This requires that

• the tumor is limited to the bile ducts or gallbladder.
• the cancer has not invaded other organs.
• there are no secondary cancers (metastases).

An operation is considered if the patient’s condition is sufficiently stable.

According to medical specialists, preparatory (neoadjuvant) chemotherapy should only be provided to patients before surgery in the context of a clinical trial. A procedure known as biliary drainage may be useful before surgery for a gallbladder tumor if the patient is suffering from inflammation of the bile ducts. In this procedure, the bile that has accumulated due to the tumor is drained so that the inflammation can clear up.

The type and extent of the operation is based on the location of the tumor. For example, surgeons may also have to remove parts of the pancreas, duodenum or liver as well as the lymph nodes when removing the bile ducts or gallbladder.

After the operation, experts recommend that patients with bile duct or gallbladder cancer should have follow-up chemotherapy.

Less invasive treatment is considered in cases where surgery is not an option. These include, for example, methods that use localized heat or light combined with a light-activated substance.

Borderline operable?

If the disease is locally advanced but still without metastases, the patient normally receives chemotherapy.

In such situations, many experts recommend “restaging” at a specialist center. After several treatment cycles, the doctors check whether the tumor has decreased in size and can now be operated on.

As part of clinical trials, a liver transplant may be considered for some patients with bile duct cancer, provided that certain medical criteria are met.

What therapy is available if no cure is possible?

If the bile duct cancer or gallbladder cancer is far advanced or if there are metastases, the disease is normally no longer curable. The focus of the treatment is then on the patient’s general condition, on any accompanying conditions, and on the wishes of the patient.

• Palliative tumor therapy with standard methods: Various forms of chemotherapy are generally used as medication. To relieve symptoms, various localized methods for destroying tumors or high-precision radiotherapy may be considered.
• Targeted tumor therapy: Drugs are used to attack specific molecular changes in tumors. They can be used to prolong life if the standard therapies are no longer effective and if the tumor has certain biomarkers.
• Supportive therapies: These help relieve debilitating symptoms and improve the affected person’s quality of life. For patients with biliary tract cancer for instance, there is biliary diversion through a small tube (stent). Drug pain therapy can help with pain. If patients lose a lot of weight, nutritional therapy may be an option.

Doctors sometimes discover gallbladder cancer by accident – for example, when removing the gallbladder. There is no specific approach for subsequent treatment planning in this situation.

What should be considered in relation to surgery? What are the procedures for chemotherapy and targeted therapies and what side effects do they have? There is detailed additional information on the website of the Cancer Information Service of the German Cancer Research Center (in German).

Medical rehabilitation (rehab) after a cancer therapy helps patients deal with the consequences of the illness and treatment in the best possible way. A medical rehab program thus focuses on the personal medical history and existing limitations. 

A medical rehab after therapy of bile duct and gallbladder cancer may include: 

• psychological support 
• nutrition advice
• for younger patients: work-related medical rehabilitation (WMR) to help them get back into a work routine

The website of the Cancer Information Service of the German Cancer Research Center has the addresses of cancer advisory services and psycho-oncologists who provide outpatient psychotherapy. There is also a list of the main contacts for any questions relating to social law.

If the tumor could be completely removed, there are regular check-up appointments for the patients. They include:

• physical examinations
• blood tests
• imaging techniques to examine the rib cage, abdomen and pelvis; computed tomography (CT), ultrasound or magnetic resonance imaging (MRI) are used for this

What if the cancer cannot be cured?

In this case, experts recommend regular follow-up checks. Doctors check a patient’s general condition and blood test results. They moreover use imaging techniques. Medical practitioners use these to check how the illness is developing.

Furthermore, regular examinations help with the detection and treatment of debilitating symptoms. These include, for example, symptoms caused by narrowing of the bile ducts or digestive tract. Suitable therapeutic measures should maintain the patients’ quality of life for as long as possible.

What can aftercare achieve, and what not? And who coordinates it? On the website of the Cancer Information Service of the German Cancer Research Center, you can read about important aspects of oncological aftercare (in German).

Do you have further questions about dealing with the condition in everyday life and additional support options? You can find information about this on the German Cancer Research Center’s Cancer Information Service website (in German).

For all questions about gallbladder or bile duct cancer, you can also make direct contact with Cancer Information Service doctors by dialing the freephone number (0800) 420 30 40 or by sending an e-mail to krebsinformationsdienst@dkfz.de.