Actually, the debate on the next part, it is our guest, Dr. Tanya Kotenberg, a professor of medicine at UC San Francisco, and she is the author, the primary author for the famous CYNIC trial, and then Tanya has a discussion on the thiospray, the chromoendoscopy detection of the dysplasia on IBD. Tanya, the platform is yours. Thank you so much, and good morning, good afternoon, everyone. I've been asked to speak about chromoendoscopy for surveillance of colitis, associated neoplasia in all IBD patients, and it's great to discuss this in the session today. I hope we can review the indications for dysplasia, dysbalance, and IBD, and mainly discuss the yield and impact of the guideline-based IBD-associated colorectal dysplasia techniques. I want to address briefly random biopsies, targeted biopsy, and I know my main focus is on the chromoendoscopy. And with this, in order to talk about finding lesions, I want us to be able to describe the endoscopic features of dysplasia to recognize dysplastic lesions that we could endoscopically resect. There may be some parallel to what Maria said. I think both of our goals is that we want to optimize colorectal cancer surveillance in this higher-risk group of IBD patients. I thought I'd start briefly with a case so that we can have a context. This is a 52-year-old man with pan-ulcerative colitis at the age of 40 when he presented with new-onset rectal bleeding, mild anemia, and elevated inflammatory markers. He'd been well for the past year after he started aminosalicylate therapy until he discontinued aminosalicylate therapy, and then he recently noticed increased stool. So he underwent colonoscopy for reevaluation. And for us just to think about, in addition to describing the extent of disease for such a patient and the involvement of continuous or skip areas, how do we describe a patient when we perform colonoscopy when they have inflammatory bowel disease? How do we describe and score the severity of his disease activity? And so just look through these and think about it. And the reason I'm bringing it up is because when we do IBD dysplasia surveillance, we are doing this in the majority of patients who have mild disease activity. Their disease is well under control. And so knowing ahead of time through images or through the reports of standard nomenclature, we're able to know if we can optimize their dysplasia surveillance. So you can see here, of course, there was lots of erythema. The extent of disease was throughout the colon. There was friability. There was erosion. So we want to have some uniformity in how we would describe that so we know when we're doing the dysplasia surveillance what we may be encountering. So these are some of the different words we use. And, of course, I think everyone is familiar with the endoscopic scoring systems, Mayo endoscopic scoring system used for ulcerative colitis from normal, mild, moderate to severe. And so in that particular case, we would employ that. And we would really survey patients for dysplasia in that zero to mild category. So the patient's symptoms improved. He restarted therapy. He was seen in follow-up clinic six months later. And he told you his younger brother who also has ulcerative colitis was recently diagnosed with colon cancer. So you discussed scheduling him for actually surveillance colonoscopy because at the last one, he had that Mayo 2 where it was very severe. So you didn't do dysplasia surveillance then. But now he comes in and tells you he has increased risk factors. And you're going to now consider is that an increased risk factor enough that we go on and do colonoscopy? So thinking about inflammatory bowel disease patients, at what level do they start to have an increased risk for colon cancer? And what other factors contribute to their increased risk of colon cancer? So here's a list of some of the potential ones. And just I want everyone to sort of just think through, get our minds primed as to when we're approaching a patient for colorectal cancer screening with IBD. So certainly, IBD patients have a high risk for colorectal cancer. Both ulcerative colitis and Crohn's colitis patients, typically after eight years of disease, we consider their risk to increase. And there are risk stratification systems in place based on other risks, such as the presence of prior dysplasia, presence of their disease activity severity, presence of pseudopolyps, family history, if they have primary sclerosin cholangitis. All of these increase a patient's risk for potentially increase their risk for colorectal cancer. So currently, we have every one to three years where we bring these patients in, and depending on their risk stratification, we may lengthen that to three years, or we may need to do it every one year. But I would advocate that when we bring them in, regardless of the time, we do that optimal exam that provides the highest yield for dysplasia detection, because that's the purpose of why we're doing the exam. And we had a bit of a pause a few years ago when they looked at the data to say, well, what is the interval colorectal cancer rate in patients with ulcerative colitis and Crohn's colitis? This is a higher risk group than average risk patients. Do we miss, do they have interval cancer rates? And the rate of missed colorectal cancer after a colonoscopy in these patients who undergo frequent surveillance was three times higher compared to patients without inflammatory bowel disease. So it again highlights this is a higher risk group at baseline. These lesions are harder to find, and they may be more prone to be missed. What lesions are missed? This study showed that 45% of IBD patients are, cancers are interval cancers, meaning they could have been preventable potentially, and that most of these are due to being missed or incompletely resected. So that just informs us further that the way that we do surveillance, really these lesions are subtle. We need to optimize how we look for them. So in considering this patient's surveillance colonoscopy planning, what would the optimal surveillance method for detection of dysplasia be? Would we do CT colonography, high resolution white light with random biopsy, high definition white light with targeted chromoendoscopy with targeted virtual chromoendoscopy with targeted virtual chromoendoscopy with random, lots of choices to think about. And the goal again is for us to do the one where we can optimally detect. I would advocate that chromoendoscopy is that method. What does chromoendoscopy do? Let's take a step back. I've mentioned a few times these lesions are subtle. These colons are difficult. They've been inflamed and they've been scarred. And so what chromoendoscopy does is it's dye, and that dye, indigo carmine that is, gets in those grooves and helps us see subtle things. It helps us by providing that contrast for us, not with light, but with dye in order for it to outline the mucosa and show us when there's changes in the lines, changes in those grooves. So as was presented, the Scenic International Consensus recommended a high definition colonoscope and suggested chromoendoscopy with targeted biopsy based on the few studies at that time with chromoendoscopy and high definition. Okay. So, and we did not recommend narrowband imaging based on the literature. So why do an augmented or enhanced procedure? Why do targeted biopsy? Well, at the time, we also looked at the current practice, which was random biopsy. At the time, random biopsy was sort of widespread practice. So we wanted to look, what's the yield of current practice? All the effort that we're doing, is it yielding dysplasia? So in looking at the published literature at the time of close to 50,000 random biopsies from over 1500 patients, the yield of those random biopsies was 0.09%. So a lot of effort, a lot of resources, a lot of time, a lot of money, but little protection from those efforts for colon cancer screening in this patient group. And so essentially what that sort of redirected is, should we be doing random biopsy? Should we be doing more visualization and targeted biopsy? And that's where the CENIC recommendations came up with the chromoendoscopy suggestion. Now, since CENIC, which was published in 2015, there have been many studies, some presented in the forum today, that have shown, that have looked at narrowband imaging, virtual chromoendoscopy, comparing random to targeted. And when you do all of these different studies, you're able to perform a network meta-analysis actually. And in doing network meta-analyses of these many different studies, it actually continues to show the superiority of high definition chromoendoscopy compared to other modalities. So chromoendoscopy, how do we do it? Since this should be our method when we approach that high yield surveillance? Well, we want to start by washing as we insert the instrument. This isn't a colon we want to be dirty. We want it to be dry so that we don't dilute our solution and we want it to be clean. Once we get to the cecum, we start to spray the dye. It's a diluted indigo carmine. We use a foot pump to spray it. We spray on the anti-gravity side so that it can drop over to the gravity side for efficiency. And then we suction the lumen after we do this spraying. You can see it pulling to the other side so it can be very efficient. And then we suction the lumen and that allows us to then apply it to everywhere. Now we wouldn't want to do chromoendoscopy, for example, as I mentioned earlier, if there is a severe disease activity, if there is a limited quality bowel preparation, or if there is severe and extensive pseudopolyposis. Or even if there is a stricture. Because you can see that a stricture, the examination with any modality is going to be quite limited. So there are limitations for any surveillance methods. It was mentioned earlier, artificial intelligence is a potential additional tool to use to aid in our detection. There has been applications of this clearly for non-colitic lesions. In the field of IBD, its main application to date has been in the scoring systems and I believe it's being studied for use for detection, but there's nothing available currently. Although that may be the next steps of some of the progress of our technologies. So this patient was referred to an endoscopist with expertise in chromoendoscopy and she examined the colon using diluted indigo-carmine chromoendoscopy, found a 16-millimeter sessile serrated lesion in the transverse, removed it by hybrid endoscopic semicostal dissection, and then what we'd like to know is in looking at this lesion, how would we describe it using high-definition chromoendoscopy? So would we describe it as an invisible dysplasia, visible dysplasia, visible dysplasia with distinct border, visible dysplasia depressed with distinct border. The nomenclature that Maria presented from CENIC on colitic lesions, how would we describe the lesion? And so for this particular lesion that was found, you can see it here, this 14-millimeter or so serrated looking lesion, how would we describe it more than that? We would describe it as visible dysplasia, non-polyploid, superficial elevated with a distinct border, because we can see there clearly the border with the dye, we don't see an ulceration. This is a lesion that would be amenable to endoscopic resection. And with endoscopic resection, why is that important? It's important to see our borders because in endoscopic resection, we want to completely remove these. We're trying to find lesions to prevent colon cancer, we're trying to remove lesions to prevent surgeries and ultimately prevent colon cancer and death. These are typical lesions of what we find, again all very subtle, subtle for me looking at them even with the dye. And so I'm always humbled in these patient groups when I'm looking for lesions as I know they're the hardest ones to find. This would be the nomenclature that was shared earlier, the terminology being visible dysplasia and then applying Paris classification with modifications on those descriptors of ulcerations or the distinction of the borders. This is just some schematics that help us to visualize and show the polyploid, non-polyploid and then with the CENIC descriptors. And then lastly, I'll just mention about the management and even the chromoendoscopy dye is helpful for when we're managing these lesions. CENIC had strong recommendations and conditional recommendations for polyploid and non-polyploid lesions respectively with based on very low quality evidence that we should not be automatically referring patients with dysplasia for colectomy or surgical management, but we should consider endoscopic resection with with surveillance thereafter. This is that lesion you can see the borders were defined, they were then marked and circumferential incision was performed, some dissection until snare resection could be performed. So what's remarkable in all of the IBD cases and I know they've been shown is the severe degree of fibrosis in them making them really stuck, difficult to separate and difficult to often remove with a simple snare technique, often requiring other techniques for removal, but in all of these techniques the use of dye is helpful for us to continue to see the entirety of the lesion in order to completely remove it. I'll end there and I appreciate the opportunity to share my experiences and the literature and again our ultimate goal is to prevent colorectal cancer in this higher risk group. Thank you.

chromoendoscopy

surveillance

IBD patients

dysplasia

endoscopic resection