Milind M. Javle, MD: We’re going to move on to a case presentation. Dr Koay, this may be typical of a patient you may see in your clinic. This is a 76-year-old who presents with painless jaundice, essentially a 3-month history, and a 15-lb weight loss. The patient was referred to a GI [gastrointestinal] doctor after the PCP [primary care provider] attempted some therapies, which gingerly helped. There’s a BMI [body mass index] of 31, touching on what Drs Shroff and Rocha mentioned. There’s some history of smoking. Unfortunately, the bilirubin is very high at 21 mg/dL. Direct bilirubin is 17.4 mg/dL. Liver enzymes are all very high: an alkaline phosphatase of 385 U/L, AST [aspartate transaminase] and ALT [alanine transaminase] in the hundreds, CA [cancer antigen] 19-9 is also pretty high. AFP [alpha-fetoprotein] is normal. Hepatitis screening is negative. A CT scan is obtained, and it shows that there’s a dilatation of bile ducts. It’s not quite clear, but there may be an ill-defined mass at the hilum of the liver, which is not atypical to what you see. What is your approach, Dr Koay? I also highlight this case because, at least in my experience, there’s a great delay in getting to the diagnosis often in cholangiocarcinoma, especially extrahepatic or perihilar cholangiocarcinoma.

Eugene J. Koay, MD, PhD: This is quite typical of a patient with a bile duct cancer that happens along the bile duct that is outside the liver, the extrahepatic bile duct. They present with this type of elevated bilirubin and jaundice. You often see these types of obstructive pictures on the CT or MRI scan. We would typically work it up with a CT scan, sometimes a biliary protocol CT scan, so that you can look at the bile ducts more specifically. Sometimes an MRI can be helpful. Often times, you have to go in directly with an endoscopic retrograde cholangiogram to be able to see the bile duct and get some brushings or tissue to get the diagnosis and look at it under the microscope. That’s typically what we would have to do.

In addition to all those things, you have to manage the bile duct obstruction. Otherwise, the patient can develop cholangitis or may already have that and needs to get treated for the infection. It can become systemic, it can be life threatening, and they can have sepsis. All those things complicate the initial presentation of these patients. It’s a multidisciplinary evaluation, and you have to have multiple physicians onboard to help take care of that patient in this somewhat emergent situation.

Milind M. Javle, MD: I often try to discuss with my fellows and junior colleagues that we have to educate patients that with bile duct cancers, especially perihilar cholangiocarcinoma, there are 2 different problems that arise here. One is biliary tract obstruction and infection. Often patients die of cholangitis and infection, and not their cancer. It’s very important that they be treated in a multidisciplinary manner, as Dr Koay mentioned, with a good GI team, with an IR [interventional radiology] team, so that we optimize both, the treatment of the cancer and the management of the biliary obstruction. Dr Koay mentioned getting to a diagnosis with an ERCP [endoscopic retrograde cholangiopancreatography] and brushing. In my experience, I find some of the new patients have had a frustrating experience there. They’ve gone to multiple sites to try to get a diagnosis. What is your approach as a surgeon so that we don’t lose all this time in getting to a diagnosis of perihilar cholangiocarcinoma?

Flavio G. Rocha, MD, FACS, FSSO: That’s an excellent question. I think this is what highlights the complexity of treating this disease. It’s very hard to get, unlike other tumors where you have a lump that you can put a needle in, for these hilar cholangiocarcinomas, it’s often just tumor crawling along the bile ducts. When you’re scraping it with the endoscopy, you may not be getting the actual tissue. When I see a patient like this, obviously the first thing to do, typically what the primary care doctor or the GI doctor will do is rule out any intrinsic liver disease, if these enzyme elevations are just due to the liver. But when I look at this pattern of this bilirubin, the alkaline phosphatase, that implies there is an obstruction in the bile duct. In the back of my mind, I’m always thinking, could this be something benign like a stone? But I have to be suspicious for a cancer. To me, when I look at this patient and situation, I almost assume it’s a cancer unless noted otherwise.

The important piece that Dr Koay was mentioning is that we do need to get some specialized imaging to get the proper staging. When patients have multiple procedures and stents before they see a surgeon, it makes it more complicated to do that portion. I for example work very closely with our GI and IR teams because we review the films together and make sure that if they are putting stents, we’re putting them in the right side of the liver, or the correct side of the liver, so that it’s not going to affect any future surgical intervention.

Milind M. Javle, MD: Thank you, Dr Rocha. We are all standing on the shoulders of giants. I want to remind us that when Dr Gerald Klatskin described this tumor at Yale University in New Haven, Connecticut, he said the way to get the diagnosis is through surgical resection. But the majority of these patients are not surgically operable, so this diagnosis is often clinical. We shouldn’t waste time with multiple unneeded modalities. Dr Shroff, we talked about perihilar, extrahepatic cholangiocarcinoma. Now we’re shifting gears to intrahepatic cholangiocarcinoma. Patients often come to me, and they’ve been seen in the community, and they say, “This diagnosis, I’m not sure this oncologist knows what they’re treating. They said it could be arising from the pancreas or the bile duct or the stomach.” How do you explain the diagnosis of intrahepatic cholangiocarcinoma, and the fact that this primary oncologist was correct in their estimation, in the diagnosis of intrahepatic cholangiocarcinoma?

Rachna Shroff, MD: I think it underscores the importance of exactly what Dr Koay was mentioning in terms of multidisciplinary management. It’s the totality of the information you have that helps you come to the diagnosis of an intrahepatic cholangiocarcinoma. These are typically tumors in which you have a little more access to tissue, core needle biopsies, and things like that. You have the ability to hopefully histologically get a diagnosis.

To your point, that diagnosis is often adenocarcinoma, upper GI, pancreatic, or biliary. The immunohistochemistry is not necessarily specific to say, intrahepatic cholangiocarcinoma. That’s why I think you look at that in coordination with radiology and good cross-sectional imaging. There is a very typical look to an intrahepatic cholangiocarcinoma that distinguishes it from hepatocellular carcinoma. There are also more traditional things we think of, not always, but often we see 1 larger mass, multiple satellite nodules, as opposed to just diffuse bilobar disease from metastatic adenocarcinoma of other areas. You have to put all of that information together, and then in a multidisciplinary way, conclude things like this is an intrahepatic cholangiocarcinoma. I think we’re getting better and better at doing that though.

Milind M. Javle, MD: You see these patients in the clinic, Dr Shroff. Sometimes they go through this huge amount of work-up. PET [positron emission tomography] scans, upper/lower scopes and mammograms, a lot of work-up before getting to this so-called diagnosis of exclusion. A lot of time goes by because of this unnecessary work-up. Would it be correct to say that it’s a diagnosis made on pathology grounds and clinical symptoms, and that you don’t necessarily need a million-dollar work-up to get to that correct diagnosis?

Rachna Shroff, MD: Yes, I think so. I think those of us who see a lot of this feel pretty comfortable putting together pathology and radiology and clinical presentation to be able to come to that diagnosis. I agree with you. The honest truth is the time lags that happen waiting for an endoscopy and a colonoscopy and all of that just delay the care for these patients. Trying to be expeditious and looking at the sum of all the parts is really important.

Milind M. Javle, MD: If it’s an adenocarcinoma that is CK7 positive, CK20 positive or negative, CDX2 maybe variable, more than likely if the patient does not have any upper GI symptoms, and there’s no anemia to suggest iron blood loss etc, we don’t need a huge work-up in the era of high-definition CT scans, where you can easily find the primary tumor.

Transcript edited for clarity.