It’s no coincidence that “full of bile” is a phrase used to describe ill-tempered people. When the transit of this life-sustaining fluid is disrupted, as happens in the rare bile duct cancers called cholangiocarcinomas, things can get nasty. Bile duct cancer affects the pathways within and leading from the liver, a football-sized organ tucked between the diaphragm and the stomach that performs a variety of important functions.
Historically, these cancers have been tough to treat. The American Society of Clinical Oncology (ASCO) estimates the five-year survival rate for people with what’s known as extrahepatic bile duct cancer (which occurs outside the liver) at around 10 percent (17 if diagnosed early). That drops to 9 percent (up to 25 percent if diagnosed early) for intrahepatic bile duct cancer, which occurs within the liver.
Devoting a medical career to this complicated disease has been an admittedly tough challenge, says Tim Greten, MD, a medical oncologist trained in gastroenterology and the senior investigator and co-director of the liver cancer program at the National Cancer Institute in Bethesda, Maryland.
Still, he has seen remarkable “super responders” persist long after their diagnosis — enough for him to cultivate a “glass half-full” approach to these cancers. He discussed work with patients, who’s at risk, the difficulties of diagnosis, and other aspects of bile duct cancer with Everyday Health.
Everyday Health: What is bile duct cancer?
Tim Greten: Bile duct cancer, also known as cholangiocarcinoma, is a disease of the tiny tubes that carry bile from the liver, where bile is made, and the gallbladder, where it’s stored, to the small intestine, where it helps digest fats in food and detoxify potentially harmful substances.
The disease varies according to its origination point in the biliary tract. A tumor or lesion in the ducts within the liver is an intrahepatic bile duct cancer. One that forms at the junction, or hilum, where two smaller ducts fuse into the larger common bile duct, is a perihilar or hilar cancer. A cancer found outside the liver, where the duct pumps bile into the small intestine, is a distal or extrahepatic cholangiocarcinoma.
Since we define cancer by its origin site, cholangiocarcinoma is a kind of liver cancer, but one that develops in the biliary (bile-transporting) system rather than in the body of the organ.
EH: What effect do bile duct cancers have on the body?
TG: As the body’s toxin remover, the liver scrubs potential poisons before digested material enters the small intestine, where nutrients are absorbed. In addition to detoxifying, the liver also manufactures clotting factor, which seals and protects wounds.
Bile does its work while traveling through the biliary (bile circulating) system. When the flow is disrupted, the greenish-yellow liquid can accumulate, tinting the skin and the whites of the eyes yellow in a condition called jaundice. Jaundice signals a problem and can result from a tumor lesion that’s already reached a size adequate to impede bile’s transit of the liver. In advanced cases, individuals might also develop ascites, fluid build-up around the abdomen that resembles extreme bloating.
EH: What are other early symptoms of bile duct cancer?
TG: There usually aren’t other symptoms in the disease’s early stages. Sometimes, a liver function blood test (a metabolic panel that also assesses kidney and other functions) uncovers a serious condition. But the results are nonspecific. And since liver enzymes can be altered by drug reactions, systemic illness, excessive drinking, or other diseases, cholangiocarcinoma is rarely the first thing that comes to mind.
EH: Who’s at the greatest risk for bile duct cancer?
TG: We don’t have a clear profile. Anything that creates chronic inflammation is believed to increase risk. That includes bile stones, cirrhosis, hepatitis B or C, and heavy drinking. Obesity, diabetes, hypertension, and high blood pressure also may contribute to the disease.
We do know that it occurs more often in parts of Asia where locals consume raw and uncooked fish that harbor a parasite called the liver fluke.
Genetics may play a role, but very few patients have any family history of the disease.
EH: Given the lack of symptoms and known risks, how difficult is this to diagnose?
TG: It can be quite difficult. I wish an early screening test existed. There is none. And even the liver function blood test is imprecise. A tumor marker blood test that reveals high levels of CEA (cancer embryonic antigen) and CA19-9 (a particular cancer antigen) can suggest the possible presence of a malignancy, but not the type of cancer. There can be subtle symptoms — itchiness caused by excess bilirubin, or discolored or unusual stool or urine — but they accompany other conditions, too. The same is true of the general weight loss and pain below the ribs on the right side that some patients mention.
EH: Once cancer is suspected, how do you perform a biopsy?
TG: We biopsy the lesion, not the bile duct, and the approach we choose varies according to each individual. The easiest, most straightforward way to do this is from the outside, by passing a needle through the body and into the organ after a radiologist has injected a special dye to “light up” the affected area. This angiography X-ray test pinpoints the spot where cells should be sampled. It’s been in general use for decades as a quick outpatient procedure.
Another option uses an imaging test called a cholangiogram that pairs an MRI with an endoscope (a long tube that’s passed down the throat and into the digestive tract) to extract a small tissue sample. Still another utilizes a tiny “brush” that’s inserted into the duct to gently “rake” the tissue, removing fragments for testing.
Some clinicians hesitate to do biopsies because they fear inadvertently spreading cancer cells beyond their original site. But we can prevent that with needles that are nested inside other needles and completely sealed. I can’t recall a single instance where testing spread the cancer.
EH: What happens after bile duct cancer is confirmed?
TG: Depending on the disease’s stage and location, the options include surgery, chemotherapy, or radiation. We can remove the duct; take out part of the liver (a partial hepatectomy); or use the Whipple procedure (pancreaticoduodenectomy) to excise part of the pancreas, the small intestine, the gallbladder, and the bile duct. In some cases, we’ll need to follow that with chemotherapy or radiation, delivered externally or internally.
EH: What about a liver transplant?
TG: You’d think that would be a permanent solution, but 70 to 80 percent of bile duct cancers recur after the operation, and immunosuppressive drugs meant to prevent organ rejection create their own problems. There’s also a serious shortage of transplantable organs, with many diseases competing for a few livers. It’s tough deciding who’d benefit the most from a transplant.
EH: What’s the general prognosis?
TG: It depends on the stage of the disease, but this isn’t a good cancer. With surgery, the median five-year survival rate can reach 25 percent to 40 percent, but few people are candidates for an operation. Without it, patients survive about a year after diagnosis, depending on the number and size of the lesions.
When patients ask about the odds, I answer honestly. But I remind them that statistics don’t accurately represent every case. Some people fall outside the numbers. I also assure people, even with advanced cases, that there are numerous ways to relieve discomfort and reduce pain. Palliative care can include radiation, surgery, chemo, immunotherapy, pain medication, or a combination of those.
People with the discomfort caused by excess bile can have it drained with a small tube or stent, and we can eliminate water retention, or ascites, to improve breathing and diminish distress. There are also chemotherapies that can lessen pain and fatigue and reduce itching. All these enable people to live better and longer.
EH: How do you help patients navigate this journey?
TG: Back to the glass half-full approach; I stress that each case is unique. I’ve treated truly exceptional responders. One such woman invited her family on a European farewell vacation, returned, and went on to live for many years. I find those cases so gratifying.
EH: What is the single most important advice for the newly diagnosed?
TG: Find a doctor who has significant experience with cholangiocarcinoma, preferably a specialist affiliated with one of 71 National Cancer Institute–designated centers based in 36 states and the District of Columbia.
The NCI’s Cancer Information Service (CIS), available free of charge, can also help answer cancer-related questions from patients, family members, or friends.
Also, connect with other patients through support groups and nonprofits. Facebook has a bile duct cancer awareness and support group and the Cholangiocarcinoma Foundation lists qualified doctors and financial aid resources. Connections are critical.
EH: What should we be watching in terms of new developments?
TG: Immunotherapy, focusing on ways to improve the body’s own immunological response to cancer, show some promise in cholangiocarcinoma. [According to Rare Disease Advisor,] in September, the U.S. Food and Drug Administration (FDA) approved a drug called durvalumab (Imfinzi) that, in combination with chemotherapy for advanced biliary cancer patients, modestly reduced bile cancer risk among clinical trial participants.
Overall, I’m encouraged by the many medical breakthroughs we’ve seen lately. We’ve reduced the incidence of cardiovascular disease by finding and treating it earlier. I’m convinced we’ll eventually do the same for cholangiocarcinoma.