Milind Javle, MD: Ruth, you’ve certainly treated a lot of biliary tract cancers, both with immunotherapy as well as with standard therapy. We’ll get to that, but I’m going to talk to you a little about the presentation. The Cholangiocarcinoma Foundation did a survey about the latent period between symptoms and actual diagnosis. I was shocked that the duration was something like 22 months. That was the median duration for the time when the diagnosis was established. In your practice, what percentage of patients are found with incidental findings or findings on a routine scan? [How many] people have elevated LFTs [liver function tests] while getting a statin? What are the common symptoms of presentation in your clinic for the different types of biliary tract cancer that Flavio discussed?

Aiwu Ruth He, MD: That’s a very interesting question. It depends on the source of the referring physician. We have patients who present with advanced-stage biliary cancer because they’ve developed symptoms of weight loss and jaundice. We also have patients under surveillance because they have chronic liver disease and cirrhosis. For patients under surveillance, we tend to make the diagnosis a little earlier, but the majority of patients are still diagnosed with locally advanced or advanced-stage disease. That emphasizes the importance of surveillance on patients with chronic disease, as Anjana presented earlier. In my practice, It’s probably half and half. Half the patients are diagnosed at a relatively early stage. They’re resectable or borderline resectable with some downstaging bridging them to resection. Half the patients are diagnosed with advanced-stage disease, with palliative therapy as the main treatment option for those patients.

Milind Javle, MD: I just saw a patient who had a perihilar mass, a biliary duct dilation, and went from hospital to hospital in Texas to get a diagnosis and pathology. It saddens me to see these patients under multiple work-ups with abscesses and problems. They sometimes reach a stage when they can’t be treated at all. Ruth, how much of the poor prognosis that we see in our patients is related to this problem and difficulty in diagnosis? There’s a long period by the time they get care for the cancer.

Aiwu Ruth He, MD: We’ve seen that in some patients. Sometimes it takes multiple tries to get the tissue diagnosis. Getting tissue to make a diagnosis, especially for hilar cholangiocarcinoma, is very challenging. Sometimes we use SpyGlass for ERCP [endoscopic retrograde cholangiopancreatography]. Sometimes we try to biopsy the perihilar lymph nodes with EGD [esophagogastroduodenoscopy] or EUS [endoscopic ultrasonography]. It’s challenging. Sometimes it takes many tries. There’s an urgent need for additional diagnostic measures to make a diagnosis. This is a very active field. How we can make the diagnosis earlier when the tissue biopsy, the diagnosis, is very challenging?

Milind Javle, MD: Flavio, the extrahepatic perihilar cholangiocarcinoma was described by a surgeon, [Gerald] Klatskin. In his original definition, the only way to diagnose this is by surgery. Surely there are other mechanisms and methods that you use to make a clinical diagnosis in the absence of pathology. How do you deal with this situation in practice?

Flavio G. Rocha, MD, FACS, FSSO: Milind, this is a very important and timely topic because this highlights some of the changes in biliary tract cancer. Unlike intrahepatic cholangiocarcinoma, where you have a mass that you can stick a needle in, hilar cholangiocarcinoma can be extremely difficult to diagnose on pathology preoperatively. A lot of the delay happens because there’s this persistent attempt at trying to obtain endoscopic brushings and all these other modalities. To be honest, the sensitivity is a flip of a coin. This is a big issue.

The problem is once the biliary tract is cannulated and obstructed, you’ve contaminated that liver. The patient ends up having this spiral of cholangitis with trapped ducts. I’m always very keen on seeing these patients right away just when you get the imaging before they’ve had any procedure. For a fair amount of the time, we’re making this diagnosis based on the imaging alone. I take plenty of patients to the operating room without a clear pathologic diagnosis of a cholangiocarcinoma, because a biliary stricture and a patient who doesn’t have PSC [primary sclerosing cholangitis] is a cancer until proven otherwise. There are some other very rare autoimmune entities that can present with biliary strictures. But at the hilum, unless you’ve had a bile duct injury or you have known PSC or IBD [inflammatory bowel disease], that’s a cancer.

Milind Javle, MD: Thank you, Flavio. I just want to reiterate that the diagnosis of perihilar or hilar cholangiocarcinoma is often a clinical 1. As Flavio mentioned, it’s often hard to get a pathologic diagnosis, and these patients are often treated based on radiological findings of CA 19-9 levels and sometimes FISH [fluorescence in situ hybridization] findings, and these patients are honestly best managed at a tertiary center where these patients can get a quick diagnosis and start treatment.

I’m going to move on a little to staging, but I don’t want to miss the opportunity of discussing the diagnosis of intrahepatic cholangiocarcinoma. Mark, these are often diagnosed as adenocarcinoma in the liver. Based on the current immunochemical information radiology, do you believe that a mass presenting in the liver needs extensive work-up to prove it’s not intrahepatic cholangiocarcinoma? Or can you rely mostly on pathology and radiology today?

Mark Yarchoan, MD: That’s a good question. As everybody knows, many cancers spread to the liver. When you have adenocarcinoma of the liver, it can be quite unclear whether it’s a primary liver cancer or a metastasis. One thing that our pathologists have started doing often is adding on albumin FISH, which can give you some confidence that this is a primary liver tumor and not a metastasis. In general, we attempt to get EGD and colonoscopy to feel a little more confident that there’s no other GI [gastrointestinal] malignancy that’s mimicking a cholangiocarcinoma. Often, we’ll get PET [positron emission tomography] scans or some other modality to rule out some other primary if the pathology is a little unclear. But increasingly, all these patients do get molecular subtyping. We’ll be talking about this, and there are some mutations that if you find them, they increase your confidence that this is a primary cholangiocarcinoma.

Transcript edited for clarity.