Bile duct cancer ( also known as cholangiocarcinoma) is a form of cancer that is composed of mutated epithelial cells (or cells showing characteristics of epithelial differentiation) that originate in the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.
Bile duct cancer is a relatively rare neoplasm that is classified as an adenocarcinoma (a cancer that forms glands or secretes significant amounts of mucins). It has an annual incidence rate of 1–2 cases per 100,000 in the Western world, but rates of cholangiocarcinoma have been rising worldwide over the past few decades.
The most common physical indications of bile duct cancer are abnormal liver function tests, jaundice (yellowing of the eyes and skin occurring when bile ducts are blocked by tumor), abdominal pain (30%–50%), generalized itching (66%), weight loss (30%–50%), fever (up to 20%), and changes in the color of stool or urine. To some extent, the symptoms depend upon the location of the tumor: patients with cholangiocarcinoma in the extrahepatic bile ducts (outside the liver) are more likely to have jaundice, while those with tumors of the bile ducts within the liver more often have pain without jaundice
- Primary sclerosing cholangitis.
- Chronic ulcerative colitis.
- Choledochal cysts.
- Infection with a Chinese liver fluke parasite.
The three most effective steps to reduce your chances of developing bile duct cancer are:
- giving up smoking (if you smoke)
- drinking alcohol in moderation
- minimising your exposure to the hepatitis B and hepatitis C viruses
Not smoking is the most effective way of preventing bile duct cancer, as well as other serious health conditions, such as stroke, heart attack and lung cancer.
It is particularly important to stop smoking if you have the liver condition known as primary sclerosing cholangitis (PSC). If you have PSC, smoking will significantly increase your chances of developing bile duct cancer.
If you are a heavy drinker, reducing your alcohol intake will help prevent liver damage (cirrhosis). This may in turn reduce your risk of developing bile duct cancer. Reducing your alcohol consumption is particularly important if you have a pre-existing liver condition, such as PSC or hepatitis B or C.
The recommended maximum levels of daily alcohol consumption are:
- three to four units of alcohol for men
- two to three units of alcohol for women
A unit of alcohol is equal to about half a pint of normal-strength lager, a small glass of wine or a pub measure (25ml) of spirits.
In England, those most at risk of getting a hepatitis C infection are people who regularly inject illegal drugs, such as heroin.
If you regularly inject drugs, the best way to avoid getting hepatitis C is to never share any of your drug-injecting equipment with others. You shoud also avoid sharing any object that could be contaminated with blood, such as razors and toothbrushes.
There is less risk of getting hepatitis C by having sex with someone who is infected. However, as a precaution, it is best to use a barrier method of contraception, such as a condom, with a new partner.
A vaccine is available that provides immunisation against hepatitis B. However, hepatitis B is a relatively rare condition in England, so the vaccination is not given as part of the routine childhood vaccination schedule.
Vaccination would usually only be recommended for people in high-risk groups, such as:
- people who inject drugs or have a sexual partner who injects drugs
- people who change their sexual partner frequently
- people travelling to or from a part of the world where hepatitis B is widespread
- healthcare workers who may have come into contact with the virus
Pregnant women are also screened for hepatitis B. If they are infected, their baby can be vaccinated shortly after birth to prevent them also becoming infected.
Bile duct cancer is definitively diagnosed from tissue, i.e. it is proven by biopsy or examination of the tissue excised at surgery. It may be suspected in a patient with obstructive jaundice. Considering it as the working diagnosis may be challenging in patients with primary sclerosing cholangitis (PSC); such patients are at high risk of developing cholangiocarcinoma, but the symptoms may be difficult to distinguish from those of PSC. Furthermore, in patients with PSC, such diagnostic clues as a visible mass on imaging or biliary ductal dilatation may not be evident.
There are no specific blood tests that can diagnose bile duc cancer by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of bile duct cancer.
Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice. Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose bile duc cancer.Computed tomography (CT) scanning may also play an important role in the diagnosis of bile duct cancer.
Imaging of the biliary tree
While abdominal imaging can be useful in the diagnosis of bile duct cancer, direct imaging of the bile ducts is often necessary. Endoscopic retrograde cholangiopancreatography (ERCP), an endoscopic procedure performed by a gastroenterologist or specially trained surgeon, has been widely used for this purpose. Although ERCP is an invasive procedure with attendant risks, its advantages include the ability to obtain biopsies and to place stents or perform other interventions to relieve biliary obstruction. Endoscopic ultrasound can also be performed at the time of ERCP and may increase the accuracy of the biopsy and yield information on lymph node invasion and operability. As an alternative to ERCP, percutaneous transhepatic cholangiography (PTC) may be utilized. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive alternative to ERCP. Some authors have suggested that MRCP should supplant ERCP in the diagnosis of biliary cancers, as it may more accurately define the tumor and avoids the risks of ERCP.
Surgical exploration may be necessary to obtain a suitable biopsy and to accurately stage a patient with cholangiocarcinoma. Laparoscopy can be used for staging purposes and may avoid the need for a more invasive surgical procedure, such as laparotomy, in some patients. Surgery is also the only curative option for bile duct cancer, although it is limited to patients with early-stage disease.
Histologically, bile duct cancers are classically well to moderately differentiated adenocarcinomas. Immunohistochemistry is useful in the diagnosis and may be used to help differentiate a cholangiocarcinoma from hepatocellular carcinoma and metastasis of other gastrointestinal tumors. Cytological scrapings are often nondiagnostic, as these tumors typically have a desmoplastic stroma and, therefore, do not release diagnostic tumor cells with scrapings.
Surgical resection offers the only potential chance of cure in Bile duct cancer. For non-resectable cases, the 5-year survival rate is 0% where the disease is inoperable because distal lymph nodes show metastases, and less than 5% in general. Overall median duration of survival is less than 6 months in inoperable, untreated, otherwise healthy patients with tumors involving the liver by way of the intrahepatic bile ducts and hepatic portal vein.
For surgical cases, the odds of cure vary depending on the tumor location and whether the tumor can be completely, or only partially, removed. Distal Bile duct cancer (those arising from the common bile duct) are generally treated surgically with a Whipple procedure; long-term survival rates range from 15%–25%, although one series reported a five-year survival of 54% for patients with no involvement of the lymph nodes. Intrahepatic Bile duct cancer (those arising from the bile ducts within the liver) are usually treated with partial hepatectomy. Various series have reported survival estimates after surgery ranging from 22%–66%; the outcome may depend on involvement of lymph nodes and completeness of the surgery. Perihilar Bile duct cancer (those occurring near where the bile ducts exit the liver) are least likely to be operable. When surgery is possible, they are generally treated with an aggressive approach often including removal of the gallbladder and potentially part of the liver. In patients with operable perihilar tumors, reported 5-year survival rates range from 20%–50%.The prognosis may be worse for patients with primary sclerosing cholangitis who develop Bile duct cancer, likely because the cancer is not detected until it is advanced. Some evidence suggests that outcomes may be improving with more aggressive surgical approaches and adjuvant therapy.
Bile duct cancer is considered to be an incurable and rapidly lethal disease unless all the tumors can be fully resected (that is, cut out surgically). Since the operability of the tumor can only be assessed during surgery in most cases, a majority of patients undergo exploratory surgery unless there is already a clear indication that the tumor is inoperable. However, the Mayo Clinic has reported significant success treating early bile duct cancer with liver transplantation using a protocolized approach and strict selection criteria.
Adjuvant therapy followed by liver transplantation may have a role in treatment of certain unresectable cases.
Adjuvant chemotherapy and radiation therapy
If the tumor can be removed surgically, patients may receive adjuvant chemotherapy or radiation therapy after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally excised), adjuvant therapy is of uncertain benefit. Both positive and negative results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors. The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.
Treatment of advanced disease
The majority of cases of bile duct cancer present as inoperable (unresectable) disease in which case patients are generally treated with palliative chemotherapy, with or without radiotherapy. Chemotherapy has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable bile duct cancer. There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced bile duct cancer.