Management of Biliary Obstruction in Patients With Cholangiocarcinoma

With rare diseases such as cholangiocarcinoma, one potential barrier to receiving optimal care is the fact that given their rarity, medical staff outside of a patient’s cancer care team, such as emergency department staff, may not be up-to-date on best practices and optimal approaches for treatment. When a patient with cholangiocarcinoma who has a biliary stent or drain presents in an emergency department with symptoms of biliary obstruction, for example, it can be a complicated situation for staff who does not often deal with such complications in this specific patient.

At the 15th Cholangiocarcinoma Foundation Annual Conference, Juan Valle, MD, professor of medical oncology at the University of Manchester and medical oncologist at the Christie NHS Foundation Trust, gave an overview of biliary obstruction before discussing guidelines for the management of urgent symptoms in patients with cholangiocarcinoma who have biliary stents or drains. Biliary obstruction, or blockage of the bile ducts, can be caused by cholangiocarcinoma tumors and is potentially life-threatening or even deadly if not managed.

Signs of biliary obstruction include malaise, jaundice, itching, pale stools, dark urine, and fevers when there is an infection. Blood tests can also identify it, and radiological scans can confirm the obstruction and identify the location of the blockage. Coming up with an efficient and effective plan to stabilize the patient and relieve the obstruction is important, Valle explained, because it can become an emergency.

Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous trans-hepatic cholangiography (PTC) are both treatment methods to get bile flowing again, which is the top priority after a blockage is identified. A stent or drain can be used to ensure the flow does not get blocked again, but that is not the end of the story.

“Once in place, stents and drains are highly prone to getting clogged by tumor ingrowth, which means that a tumor grows in along some of the holes in the mesh and that then causes a blockage of the small bile ducts,” Valle explained. “Bile can be gritty, which is why people get gallstones, so you can develop sludge or indeed gallstones. And you can also get superadded infection on top of that.”

He then got into detail about the Delphi Process, which was an initiative to develop “consensus guidelines for the management of cholangiocarcinoma patients with a biliary stent or catheter in place who present for emergency management in the outpatient acute setting.” Physicians, nurses, interventional radiologists, and oncologists from academic and community hospitals made up the consensus panel.

The guidelines assume that a patient has recovered post-surgery, has access to the necessary care, may receive a higher level of care if needed, that they are not terminal and do not have a “do not resuscitate order” in place. They also would not be awaiting liver transplant, had access to palliative care and counseling, would be under active management by an oncologist, had all necessary tests, and that any recommendations for antibiotics are outside of the procedure at hand.

A literature review identified important variables, including bilirubin levels, liver function levels, fever, white blood cell count, ECOG performance status, biliary tract imaging findings, antibiotic recommendations, whether or not stent manipulation was recommended, and whether patients were actively on other treatment such as chemotherapy.

The broader recommendations broke down into 2 main categories: patients with normal bilirubin levels, and patients with elevated bilirubin.

In patients with elevated bilirubin, they determined that:

• Stent manipulation is appropriate
• For patients with a fever, inpatient antibiotics are appropriate; however, in patients with no new or worsening biliary dilatation, outpatients may be an appropriate alternative, unless they present with neutropenia
• Inpatient antibiotics may still be appropriate in a patient without a fever but with elevated white blood cells or neutropenia following chemotherapy; however, the panel was unsure if outpatient antibiotics are an appropriate alternative
• A patient without a fever and with a normal white blood cell count does not need antibiotics

For patients with normal bilirubin:

• Stent manipulation is appropriate in patients with new or worsening biliary dilatation, fever, and a good ECOG performance status; but it is not appropriate in patients with no new or worsening biliary dilatation
• For patients with a fever, inpatient antibiotics are appropriate; unless a patient has neutropenia, then outpatient antibiotics may be an appropriate alternative
• If a patient with no fever has new or worsening biliary dilatation and is neutropenic or has an elevated white blood cell count, inpatient or outpatient antibiotics may be appropriate
• A patient with no fever and a normal white blood cell count does not need antibiotics

The guideline was published in the journal Cancers in 2020, and emergency information cards are also available for patients to have on hand in case of an emergency room visit to inform physicians.

Renuka Iyer, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, NY, took over to discuss real-world emergency department data for cholangiocarcinoma patients. Data from Komodo Health’s claims database was used to pull data from a 5-year period (2016-2020) for all cholangiocarcinoma diagnostic codes. They included patients with 2 or more encounters, amounting to 124,056 total patients. There were nearly 3 million unique encounters overall.

Findings included that intrahepatic cholangiocarcinoma patients made up the majority of the patients (62%) and that 18,203 were classified as both “not otherwise specified” biliary cancer and intrahepatic cholangiocarcinoma, highlighting the need for accurate documentation to collect data on these patients. The analysis also found that the majority of patients were diagnosed in the community setting (55,938 vs, 45,506 in academic settings) but that 22,612 were classified as unknown. More work is needed to classify those patients, Iyer said.

When cholangiocarcinoma patients presented in the emergency department or urgent care, Iyer pointed out that frequent diagnoses were elevated white blood cell count, fever, dehydration, and other symptoms of cholangitis. Yet, cholangitis itself fell much lower on the list. The same went for patients with cholangiocarcinoma with stents and tubes, although cholangitis was higher on the list.

Another highlight in the data regarding claims for cholangitis was that intravenous antibiotics were prescribed for cholangiocarcinoma patients with stents at a rate of about 41%, but the majority of providers caring for patients when they had cholangitis were not oncology subspecialists. According to the data, only about 5% were oncology subspecialists.

“These are folks that we need to reach and perhaps spread this information or alert about this complication,” Iyer said. One important message for urgent care centers, she said, is that they need to be aware of cholangiocarcinoma as a cause of biliary obstruction, as well as standards for proper stent management. Carrying a card with information like the card discussed by Valle is one way patients can potentially assist medical staff, Iyer added.

“The last takeaway message here for the cholangiocarcinoma community is that we need to continue the efforts that we have started already to raise awareness of the diagnosis, including the importance of coding properly, so we can identify these patients and do this kind of work,” Iyer concluded. “And also use of the consensus guidelines that you just heard about for optimal management of our patients with cholangiocarcinoma.”