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Screening and Education Are Crucial to the Prevention and Early Diagnosis of Cholangiocarcinoma

Targeted drugs and immunotherapies are still on the horizon for people with cholangiocarcinoma, or bile duct cancer.
BY Beth Fand Incollingo
PUBLISHED February 06, 2019
The targeted drugs and immunotherapies that have been making headlines for numerous cancer types are still on the horizon for people with cholangiocarcinoma, or bile duct cancer.

That’s a problem, since five-year survival is low for people with the rare disease, which is treated with surgery, chemotherapy and radiation.

The patients who have the best outcomes are the 35 percent with early-stage, localized disease who are eligible for treatment with potentially curative surgery — and that’s why it’s crucial to put preventive and screening measures into place, decreasing the incidence of the disease and its diagnosis at later stages, said Mairead McNamara, a medical and surgical oncologist at the University of Manchester and The Christie NHS Foundation Trust in the United Kingdom. McNamara addressed the topic in Utah Jan. 30 during the Cholangiocarcinoma Foundation’s annual conference.

Specifically, she called for identification of high-risk populations around the world, and efforts to both screen and educate these groups.

For most patients, the only risk factor for cholangiocarcinoma is older age, McNamara said. Still, there are some groups that are predisposed to the cancer for other reasons, some because they live in the countries where it’s most prevalent: East and South Asia and parts of South America.

Risk factors for cholangiocarcinoma include:
  • Inflammation caused by issues such as gastrointestinal stones; hepatitis; primary sclerosing cholangitis (PSC), a syndrome that inflames the biliary tract; or the ingestion of liver flukes, which are common in bodies of water in Asian countries
  • Developmental abnormalities, such as biliary duct cysts
  • Environmental or metabolic problems caused by smoking, diabetes or the side effects of drinking alcohol or taking the medication praziquantel to treat parasitic worms
  • Hereditary factors, such as Lynch syndrome, which raises the risk for many types of cancer, although these are rare

Factors that protect against cholangiocarcinoma include eating fresh vegetables and becoming educated about modifiable risk factors, such as the dangers of eating raw freshwater fish in Thailand, McNamara reported. She cited a 2018 study done in that country that demonstrated success in using education to change health behaviors linked to the development of cholangiocarcinoma.

Currently, she said, there are no clinical surveillance guidelines for early detection of sporadic cholangiocarcinoma. To date, she added, the most effective screening program was one recommended by a research team in 2011 for patients with PSC, who face a 5 percent to 36 percent lifetime risk of developing the cancer. The patients in this surveillance program would receive annual magnetic resonance imaging, as well as magnetic resonance cholangiopancreatography or ultrasound, and their blood would be tested for carbohydrate antigen 19-9, a biomarker that can be helpful in diagnosing cholangiocarcinoma.

If dominant strictures — meaning narrowing of bile ducts — were found, these patients would undergo endoscopic retrograde cholangiopancreatography, an imaging technique, along with brush cytology, which examines cells brushed off the narrowed ducts and aims to uncover malignancies.

“These surveillance recommendations are invasive and costly but are currently the most effective strategy for detecting early (cholangiocarcinoma),” McNamara said.

Some promising studies have been conducted on potential medical strategies for lowering risk in those who are predisposed to cholangiocarcinoma.

McNamara cited a large, retrospective study done at Mayo Clinic that demonstrated that taking aspirin lowered cholangiocarcinoma 2.7- to 3.6-fold. However, “This was a retrospective study, and we need to do a prospective one next to be sure,” she said.

Likewise, a large, case-controlled study of statins — drugs used to lower cholesterol — to prevent cholangiocarcinoma saw some success. The study included more than 3,000 patients with biliary tract cancers and over 15,000 cancer-free people and showed that these drugs lowered the risk of cancers affecting the biliary tract by 12 percent. This may have occurred because statins suppress biliary cholesterol secretion and have anti-inflammatory effects, McNamara said.

On the other hand, she said, studies of vitamin D did not show a benefit in preventing cancer, and studies of cannabis to control cancer pain have lacked statistical power, so randomized, placebo-controlled studies need to be done to find out more.

While it has been proposed that early liver transplant could help patients with PSC to avoid developing cholangiocarcinoma, it has been reported that the chance of death after transplant exceeds the risk of developing the cancer, McNamara said.
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