Dysplasia Surveillance in Patients With IBD
In this podcast, Samir Shah, MD, speaks about the controversies in dysplasia surveillance in inflammatory bowel disease (IBD), virtual chromoendoscopy vs dye spray chromoendoscopy, the risk of developing cancer in people with IBD, and the future of dysplasia surveillance in IBD. Dr Shah also spoke about these topics at the American College of Gastroenterology Annual Scientific Meeting 2022 during a session titled “Updates in Dysplasia Surveillance in IBD.”
- Shah S. Updates in dysplasia surveillance in IBD. Talk presented at: ACG 2022; October 21-26, 2022; Charlotte, NC. Accessed October 12, 2022. https://acgmeetings.gi.org/
Samir Shah, MD, is a clinical professor of medicine at Brown University, chief of gastroenterology at Miriam Hospital, and the President of the American College of Gastroenterology (Providence, RI).
Jessica Bard: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator Jessica Bard with Consultant360 Multidisciplinary Medical Information Network.
Dr Samir Shah is here to speak with us today about his session at ACG 2022 titled "Updates in Dysplasia Surveillance in IBD."
Dr Shah, it's a pleasure to have you on the podcast today. If you don't mind just introducing yourself for the audience, please.
Dr Samir Shah: Sure, happy to and thanks for having me. I'm Dr. Samir Shah, I'm a clinical professor of medicine at Brown University and chief of Gastroenterology at The Miriam Hospital. I have a longstanding interest in inflammatory bowel disease, particularly dysplasia detection using chromoendoscopy. This past year I have had the pleasure of serving as the president of the American College of Gastroenterology (term ended October 24, 2022).
Jessica Bard: Let's start with an overview of your session at ACG.
Dr Samir Shah: It is well recognized that patients with inflammatory bowel disease, both ulcerative colitis and Crohn disease (if they have at least 30% of their colon involved) are at higher risk for colon cancer over time. We start doing screening and surveillance for colonoscopies, usually eight years after they've had symptoms of the disease looking for dysplastic lesions and removing them to prevent cancer. There are certain scenarios where patients are at much higher risk because they have other conditions like primary sclerosing cholangitis (PSC)--those patients with both sclerosing cholangitis and IBD get annual colonoscopies right from diagnosis of the PSC and IBD. Other risk factors like family history of colon cancer are also factored into how often to perform surveillance. We've also learned that the risk was not as high as we once thought based on newer population-based studies that don’t have referral population bias seen in older studies with patients from only tertiary referral centers. Also, the lower risk is now seen is partially because we're better at finding precancerous lesions and removing them, and partially because our therapies are much better in terms of controlling inflammation and thereby decreasing the risk of cancer by healing the mucosa and eliminating or reducing inflammation.
Jessica Bard: What would you say are the controversies in dysplasia surveillance in IBD? We know there are quite a few.
Dr Samir Shah: Everyone agrees that patients should have the colonoscopies for surveillance and there's actually general agreement in the recent guidelines that have come out. A few years ago, the ACG guidelines came out and last year the AGA guidelines, and they both agree that we should be doing colonoscopy using a high-definition scope if available. The high-definition scope has much better clarity allowing us see sessile flat and subtle lesions better. The controversy is then what to do after the high-definition scope. Should we be doing any sort of chromoendoscopy? Broadly speaking, there are two forms of chromoendoscopy: one is virtual chromoendoscopy, where we use some sort of electronic enhancement. On an Olympus scope there's something called narrow-band imaging (NBI) and on Pentax scopes iscan. There are other platforms that are being developed with their own version of electronic enhancement of the image. Basically, they all use technology to help see subtle and flat lesions better.
Dr Samir Shah: It (the virtual chromoendoscopy) helps highlight things. It's almost like if you were driving at night and you had suddenly had night vision, you can see those subtle things much better. The other way is dye spray chromoendoscopy and this dye spray endoscopy was first described in a randomized trial by Dr Ralf Kiesslich in 2003. There are two dyes that we commonly use. One is methylene blue, which is a vital dye--it gets taken up by normal tissue and not by abnormal tissue. In that way, it highlights abnormal areas. The other dye is indigo carmine (or a substitute for indigo carmine called FD&C #2). Now indigo carmine does not get absorbed. It just kind of hangs out in the grooves in the mucosa. It can be easily washed away, but by hanging out in the grooves in the mucosa, it lets you see subtle things a lot better. The older studies with standard definition scopes showed that the yield of dysplastic lesion improved 3-5 fold if you used chromoendoscopy with dye spray regardless of which dye you used.
Dr Samir Shah: The newer studies are mixed. Some studies show that you don't need it, the dye spray doesn't add anything and other studies show that it still adds something. I'm in the camp where I believe the dye spray still adds something. What's really exciting is the newer studies also show that the virtual chromoendoscopy, which is much easier and less messy (you don't get dye everywhere) works probably as well as the dye spray chromoendoscopy. You see on Zoom I'm in a shirt and my white jacket, but about an hour ago I was in scrubs because I was doing a chromoendoscopy case with dye spray and I did not want to risk getting the dye on my clothes because it's hard to wash off.
Jessica Bard: So you mentioned your view and kind of where you stand on those controversies. Is there anything else that you'd like to add, Dr Shah?
Dr Samir Shah: Definitely! There is one study I particularly like from Spain published around 2016. It's a little bit older, but they did a really nice job and they self-described their study as a "real world study". They had both community GI doctors as well as specialists in IBD that had experience in chromoendoscopy. In the study, they had about 350 patients and who underwent white light regular colonoscopy and immediately afterward went colonoscopy a second time this time with dye spray with indigo carmine. Just less than half the patients were done with standard-definition scopes, the remaining (slightly more than half) with high-definition scopes. They showed that they found a lot of dysplastic lesions with the dye spray that they missed before the dye spray and didn't matter whether it was a standard definition scope or a high definition scope.
Dr Samir Shah: Furthermore, it didn't matter whether the person performing the colonoscopy was an IBD expert with experience in chromoendoscopy or non-expert, community-based GI doc and no learning curve was observed. The take-home message is dye spray increases the yield regardless of what kind of scope you're using and regardless of whether you're an expert or not. I think that's really good evidence from a “real world” test of chromoendoscopy. Also, there were two recent studies in 2020 with high-definition scopes, one from China, which was a multi-center study, another single center study from Sweden, both used chromoendoscopy, one used methylene blue (China), the other one used indigo carmine (Sweden). Both showed that even with high-definition scopes, the chromoendoscopy dye spray increased the yield of finding dysplastic lesions. Therefore, I think it makes sense to do chromoendoscopy even with a HD scope. And the training's not that hard to get comfortable with chromoendoscopy. In the studies that showed no difference, they had only one or a few people doing the chromoendoscopy and the other techniques. And these were highly trained people who are good at finding polyps regardless of what you give them--I'm not sure that's applicable to everybody else.
Jessica Bard: I think you make a compelling argument there. How has the research in people with IBD and the risk of developing cancer evolved over the years? I know you had mentioned before that the risk is not quite as high as we originally thought.
Dr Samir Shah: Yeah, so the older studies were from referral centers and they had the sicker patients. Also, back then our scopes weren't as good and our preps weren't as good. The newer studies that are population-based show that the risk is lower (about 2 fold higher than the general population). It's a hard thing to study because it takes many years for lesions to develop and turn into cancer. Therefore, we use surrogate endpoints like finding dysplastic lesions, but ultimately we want to know whether we're really preventing colon cancer and cancer death or at least decreasing the frequency patients have to go through scopes with longer intervals in between scopes.
Dr Samir Shah: A lot of our studies are retrospective or single-center; to do the prospective study studies takes a lot of time and effort. What's exciting is now that there are some in initiatives underway to look at patients long term and to answer these questions in terms of what's the best way to do it with a high-definition scope with dye spray chromo endoscopy, virtual chromoendoscopy and do we need random biopsies? The most exciting development, I think is incorporating artificial intelligence using computer technology to help us find polyps and not miss them. And those studies are just starting to come out now.
Jessica Bard: I know you had mentioned some differences while talking about the controversies because you go a little bit deeper and provide an overview of a comparison between the different imaging modalities.
Dr Samir Shah: Sure. The sort of default imaging and modality is standard white light with a high-definition scope. Some people will use virtual chromoendoscopy where they basically press a button on the scope and they get a different view or electronic enhancement. With that you can see subtle lesions better. In fact, some of the more recent studies also show that, that's equivalent to dye spray. In fact, a recent meta-analysis comparing virtual chromoendoscopy to dye spray chromoendoscopy showed that the two techniques are equivalent. There was a nice study presented at DDW this past May from four centers in Europe that compared virtual chromoendoscopy to dye spray. Interestingly, they showed not only was virtual as good as dye spray, but there were less false positives with the virtual chromoendoscopy. With the dye spray, they were picking up the pseudo polyps and little bumps that were nothing on histology.
Dr Samir Shah: Those are some of the subtleties. The other place where people disagree is when should you also do random biopsies. Most people agree that most lesions are visible when using a high-definition scope, but we can still pick up dysplasia with random non-targeted biopsies. Even in the latest studies with high-definition scopes and chromoendoscopy, about 20% of dysplasia is picked up only with a random biopsy. Thus, we recommend is that patients who are at higher risks: for example those with long-standing inflammation with a tubular appearing colon, previous dysplasia, history of primary sclerosing cholangitis (PSC), a family history of colon cancer at a young age, (less than 50) and finally if they have lot of pseudo polyps (making it harder to pick out true polyps). Therefore, for those patients who are particularly high risk, in addition to whatever you're doing, the recommendation is to also do multiple random biopsies-that is taking at least 32 biopsies.
Dr Samir Shah: This takes extra time to do, and you're taking them from each segment of the colon. We take four biopsies from the cecum, four biopsies from the ascending colon, four biopsies from the hepatic flexure and so on. Some people do it by section that way, and other people do it by the number of centimeters in from the rectum. For example, 80 centimeters (corresponding to the cecum), 70 centimeters, 60, et cetera. And that's in addition to taking out anything visibly that you see.
Jessica Bard: What would you say is the future of dysplasia surveillance and IBD? What does that look like? We know artificial intelligence particularly is playing a growing role.
Dr Samir Shah: I think the studies will show that if we use a high-definition scope and a form of chromoendoscopy, whether it's virtual or dye spray, and combine that with artificial intelligence, we'll be much better at finding lesions. And we probably won't need to do the random biopsies, perhaps not even in the higher-risk patients because we won't be missing dysplastic lesions. And then we can increase the interval between scopes and our patients will be grateful not having to prep every year for a colonoscopy if they can even go every three years or even every five years.
Dr Samir Shah: There are other approaches that people are looking into, but the data still emerging. Specifically, is there anything else we can do to chemo-prevent colon cancer? So far there isn't. But there's interest in whether any of the medical therapies we use can do that. Previous studies looking at mesalamine were mixed in whether they worked to decrease colon cancer risk. Also, believe it or not, some retrospective studies suggest the statins, drugs used to treat high cholesterol, may actually decrease colon cancer risk. There are older studies looking at ursodiol or ursodeoxycholic acid, which is a bile acid to decrease colon cancer risk as well. Other studies have looked at looking for stool DNA to try to predict who needs the colonoscopy. Those have not been great, but there is still interest in that approach. And finally, many companies are looking at blood tests to see if they can detect things in the blood (proteins, DNA, RNA, other things) that would signal that there might be dysplastic lesions anywhere in the body. And so that's under development as well and very exciting.
Jessica Bard: That's fascinating. What would you say are the overall take-home messages from our conversation today and from your session?
Dr Samir Shah: Number one is to make sure you risk stratify the patient. A patient with mild who's in remission without major risk factors, you can wait eight years after symptoms and then go every three to five years, especially if you don't find anything. Number two, make sure you have a great prep and take your time doing the colonoscopy. You can do either virtual or dye spray, make sure you're using a high-definition scope, and then remember that in 2022 there's still a role for doing the random biopsies in the highest-risk patients.
Jessica Bard: Well, thank you again for being here today. Is there anything else that you'd like to add, Dr. Shah?
Dr Samir Shah: No, just thank you for having me and I hope I get to see you at Charlotte at our annual meeting for the ACG in at the end of October this year.
Jessica Bard: Wonderful. Thank you.