Edward Loftus, MD, on Primary Sclerosing Cholangitis and Neoplasia in IBD

Dr Loftus reviews the risks of cancer among patients with primary sclerosing cholangitis and inflammatory bowel disease, including bile duct cancer and hepatocellular carcinoma, and how to mitigate those risks for these patients. 

Edward Loftus, MD, is a professor of medicine at the Mayo Clinic in Rochester, Minnesota.

TRANSCRIPT:

Hi, I'm Ed Loftus. I'm a professor of medicine at Mayo Clinic in Rochester, Minnesota. I'm here in Orlando at Advances in IBD. Beautiful weather, great turnout this year. I just gave a talk in the session on neoplasia and IBD, and my talk was specifically about patients with primary sclerosing cholangitis, how to manage their risk of cancer.

As you may know, PSC is a condition that causes inflammation and scarring of the bile ducts, and this can lead over time to hepatic cirrhosis. But these patients also have increased risks of several different kinds of cancer, and that's primarily what we talked about. Again, about 5% of patients with ulcerative colitis get PSC. Conversely, about 80% of PSC patients have IBD; 20% don't. Usually it's diagnosed when a patient with IBD has an elevated alkaline phosphatase. Sometimes the transaminases can be a little bit elevated. When the transaminases are elevated out of proportion to the alkaline phosphatase, you might want to be thinking about an autoimmune hepatitis overlap with PSC.

The diagnosis is typically made, either the patient presents with the elevated LFTs or sometimes they might present with pruritus or an episode of ascending cholangitis, which would be like right upper quadrant pain and fever. Usually the diagnosis is made by an MRCP, which is an MRI of the bile ducts. In the past, it had been an ERCP, which is endoscopic, but MRCP has largely supplanted that. We reserve ERCP for investigating dominant strictures in PSC, making sure they're not malignant, et cetera.

First of all, PSC patients have a unique IBD phenotype. It's often characterized by rectal sparing, extensive colitis, prominent backwash ileitis. If they do require J-pouch surgery, they're more likely to get pouchitis, and they also seem to have a higher risk of colorectal dysplasia and cancer over and above the risk seen with ulcerative colitis itself. That was first recognized about 30 years ago, that risk. For a while we didn't understand why that risk occurred. Was it due to just asymptomatic colitis that patients had for a while subclinical and they were just being diagnosed later? Or was there something about alterations in the bile acid pool that was more carcinogenic, if you will? That still hasn't been fully resolved. I suspect it's a combination of both of those factors.

When you have a patient with PSC, even if they don't have symptoms, you should go ahead and get an initial colonoscopy with biopsies to rule that out. If they already have IBD or you diagnose IBD at the time of that colonoscopy, those patients should have annual surveillance colonoscopy with biopsies. Don't wait the 8 to 10 years that we often say for patients with just ulcerative colitis alone to do the surveillance exam. Start right away. Again, you want to take plenty of biopsies and you should continue that annually. That's how you mitigate the risk of colon cancer.

The other important cancer in PSC patients is cholangiocarcinoma or bile duct cancer. The risk over time is as high as 15%. The annual risk may be roughly 1% or so. The year bile duct cancer is diagnosed most frequently is actually that first year after diagnosis. Again, these patients will present with maybe a worsening of their PSC or a dominant stricture seen on MRCP, and then you go ahead and brush or biopsy it and find cholangiocarcinoma. It's important to detect cholangiocarcinoma early because if it's caught early, it's actually treatable. There are protocols where chemoradiation is given and then you can actually transplant these patients. But I want to stress it's only patients that have earlier stages of bile duct cancer where that's even feasible. But if you're in a situation where you're annually surveying the patient for this, you're going to increase the chance that you will in fact detect the bile duct cancer when it's at an early stage.

The third type of cancer is gallbladder cancer. Patients with PSC should have an annual ultrasound looking for gallbladder polyps. Different societies have different guidelines. One society says, if you find a gallbladder polyp in a PSC patient, even if it's a tiny one, just go ahead and do a cholecystectomy, and other society guidelines say the cutoff for size is 8 mm. In other words, if the polyp is under 8 mm, you can observe, but if it's over 8 mm, go ahead and do a cholecystectomy.

Then the fourth type of cancer that's important are hepatocellular carcinomas. These occur in PSC patients who have developed actual cirrhosis. They've got now fibrosis in the actual parenchyma of the liver, and that increases their risk of hepatocellular carcinoma. The way you would mitigate that would be if they have cirrhosis, to go ahead and do an ultrasound twice a year, so every 6 months, just to rule out masses or anything looking suspicious for hepatocellular carcinoma. Those are the 4 main types of cancer.

The other thing I talked about was the post-liver transplant PSC IBD patient, and it turns out that patients who have a transplant for PSC who don't have IBD, up to 25% of them will develop IBD, de novo IBD. Then amongst the patients who already have IBD, 40% of them will have progression of their IBD, meaning that they need escalation in their medical therapy because of more active disease. I just wanted to make the audience aware about that phenomenon.

Then finally, just like any post-transplant patient, they're at increased risk of certain cancers, most commonly PTLD, which is post-transplant lymphoproliferative disorder. That was really the sum of the talk, was the neoplasia risks that come with the PSC IBD patient. Don't think about just the colon cancer risk, think about those other ones, including bile duct, gallbladder and hepatocellular carcinoma. Thank you.