This will lead to our next presentation in the sculpture management of the Colitis Associate Neoplasia. I hope Marietta and Tony can stay for the question and answer session. And our next speaker is our course co-director, Dr. Udai Namanathan, medical director of the IBD Orlando Health and professor of medicine at Central Florida University. Udai. Thank you, Bo, and thank you again. I think Marietta and Tony have covered most of the stuff which I wanted to cover initially, so I think I'm going to skip some initial slides because I think the description of lesions they have covered really beautifully. So these are my disclosures related to this. It's not a simple case presentation, and I think this is probably one of the common scenarios where we get referred. So patient's long-standing UC for 15 years or so, extensive colitis in the past, but he's been doing in deep remission for six years or so. The referring doctor did a colonoscopy. They saw multiple pseudopolyps, which is a common thing sometimes in patients with IBD. They said they saw a doll and they removed with a hot snare, which showed low-grade dysplasia. They did four random biopsies, and one focus in the right side showed flat, low-grade dysplasia. So we don't know where it got from. So the patient's referred for a colonoscopy or referred to us for the evaluation. I think the first step is the question which everybody asks is, what do you do with this patient? Do all patients with dysplasia need to refer to colorectal surgery? And our job is to see and describe that it's not the case, and we'll talk about different options for approaching these patients. So cancer and ulcerative colitis or Crohn's colitis actually is much different than a regular cancer, which occurs in a patient's adenoma in a setting of non-IBD. So normally, adenoma goes to a polypoly lesion. You see a typical polypoly lesion in ALC adenoma. You can basically dissect them, and you prevent cancer. And obviously, the mutations that happen in these are much different than in a non-colorectal patient. So the APC is lost first. The P53 is the last mutation happened before the transition to cancer happens. In a colitis-assisted cancer, it's much more different because, as we say, it's usually non-polypoly. The typical polypoly is not seen in these patients. They're very subtle, very flat. And the P53 happens much earlier, and the mutations are much different compared to a non-IBD patient. And if you look at it, APC happens last. And if you see the sequence from, I didn't mean dysplasia to cancer, it's very subtle to the entire sequence. They don't see the typical appearance you see in a non-IBD patient. So that's why recognition is difficult. Management is difficult. And that's why we need to have a consensus statement on how to manage these patients long-term. We look at subtle lesions here, and over the next six months, that's what happened in this patient. So if you're not very active in recognizing these lesions, I think you will be in trouble. I think Tanya and Marietta covered the CENI guidelines and the beyond CENI guidelines published earlier this year in GIE. And I think the most important thing is for the listeners to abandon these terms which we've been using for a long time. In a patient with IBD, if you look at a lesion, you should drop terms like adenoma-like, non-adenoma-like, DALM, OMS, all those stuff anymore, because all those terms are not recommended anymore. So when you see a patient, what does DALM mean? Because a patient is referred to as a DALM, seen with short-located dysplasia. Could be the original paper from St. Mark's in London described this in a patient's IBD, but these are in a setting of standard coronoscopy, standard definition coronoscopies, no clear margins at that point. So we don't have any definitions of what they mean at this point. So in the CENI guidelines, I clearly mentioned that when you see a lesion, the most important thing is to define the lesion clearly and remove these terms, avoid using these terms like ARMS and DALMS and talk about endoscopic resectable, non-resectable lesions and describe the lesion carefully before attempting resection. So my hope is endoscopic resection, the most important principles I want to emphasize is assess the lesion because assessment helps you, helps out assess the depth of invasion of the lesion in case the patient needs a surgical assessment right away at that point. You only want to talk about the tools and techniques of resection or talk about EMR or ESD or surgery when you come to the end of the talk. So I think Marietta was part of this ACOE guideline, which described this lesion. So whenever a patient has a lesion in IBD, you want to describe that lesion carefully. So this is what I expect from every report on IBD patient was the lesion. You want to describe the lesion and there's no polyploid or non-polyploid is the first important step. You want to see if the ulcerations present around the lesion are the borders are clear or not. You also want to describe the size of the lesion and location of the lesion is in the area of active colitis. For example, in the patient has left-sided colitis in the sigmoid colon or the patient is in a non-colitis area. For example, patient has left-sided colitis, but this lesion is actually in the cecum and you should describe that clearly. You also want to describe the acute pit pattern is very, very important. I think we'll go a little bit more and then you look with the activity of the disease around that area. So this is a standard PAS classification, which most of you are aware of in a non-IBD patient who has polyps. You just have a modified PAS classification described as polyploid, non-polyploid and describe these lesions. There's a described different appearance of lesions. I mean, there's a polyploid, you see a polyp appearing lesion. There's 01SSI lesion, 2A with 1S. You talk about different lesions as you do. So the most important, it is actually a depressed lesion. We see a 2A plus C component here. So you want to describe the lesion carefully. When you look at a lesion, you also want to describe the acute pit pattern, which can be described clearly with the chromatoscopy, which I use in my practice to define this routinely. And you're worried about a four or five lesion because the pit pattern is very concerning. So I think Marietta had this slide. So I think this is a very nice slide of describing lesion. For example, this is a clear lesion seen in an IBD patient. You want to describe this lesion. It is non-polyploid or polyploid clearly. You want to describe the 02A elevated lesion here and you have a flat lesion in this part of the area. You also want to see the acute pit pattern, which is a combination of 3L and 4L in different locations. I see something here, it's ulcerations. So yes, there's some ulcerations around there, which is concerning. And you also want the histology, biopsies came at low grade dysplasia. So you clearly find a lesion, the good borders, then you can attempt resection at this point because you have a border to resect around it. So this is another patient who actually had low grade dysplasia and the random biopsies. But again, high definition picks up some things settled there. But I think if you spray the blue dye, it actually helps me to clearly see the lesion better with the margins. And also I could clearly see the pit pattern on the surface. And it's clearly a 02A lesion, which can be easily resected endoscopically. So I can see a clear border. This is more important. I don't see any ulcerations and I see a clear border. And if you see a past classification, the acute pit pattern looks clear that this could be easily resected on block with an EMR very simply. So I think not every lesion is the same. As I said, these are different appearances in the patients. Granular 02A lesion, which can be seen pretty extensively. I always feel that a portion of the lesion is easier to resect compared to a non-granular lesion because they usually tend to have deeper invasion. So the most important thing, I think this holds good for both IBD and non-IBD, I think, because non-granular lesions are usually tend to be more invasive. They're more deeper and they usually tend to have a C component, a depressed component to the appearance and the acute pit pattern is also concerning. So if you have any of these appearances, obviously, most likely the patient is going to have cancer rather than lesions can endoscopically resectable. But again, the most common lesion in IBD is a 02A granular lesion, which can be resected endoscopically as long as they have a clear border around it. So the principles of resection, I think I'm talking about EMR first and talk about ESD afterwards. I think it all depends on what the choice you want, either a delta peaks coronoscope, you need a carotid artery for injection. I use voluvin or heterostarch for injection. You can use endocardinol or epinephrine along with it to light it up. And then obviously, you can do different techniques, including snares, clips, all you want to acquire a grasper for decreasing the bleeding eventually. So the most important technique is submucosal injection or injecting into the mucosa. You want to inject under the submucosa. Again, raise the lesion nicely around and then cut the lesion. So injecting like this is probably a wrong injection technique. You want to inject under the mucosa, lift the lesion for resection. And you can use a different snares depending on what you want to do. Obviously, the lesion is small. You can do on-block resection with a snare anywhere from 15, 20 millimeters on-block and resect the lesion entirely. For on-block resection, you always want the endocue setting. This is the setting I usually use for all my EMR resections. And I always have a soft coag panel along with it for decreasing the bleeding risk. Obviously, if you're bleeding during the procedure, you can use a soft coag mode, which can easily go back with the effect of 400 watts of AD to ablate this at the time of bleeding to control the bleeding. I also use a setting to ablate the areas around the resection site after I take biopsies in the area. Because I think in non-IBD patients, there's some benefit. So I think whatever we can do to decrease the risk of recurrence, I tend to do it. So again, there's no data to support it, but I tend to do my practice. Again, if you want to use a stiffer snare, because I think it's very important when IBD patient has a lot of scar tissue. So I think you want to use a stiff snare, which actually grabs the tissue better. And there are different snares in different companies. Again, I have no affiliation with any companies, but you can use a combination of different snares for achieving the goal. Obviously, you want to do one step at a time. So this is a lesion in the rectum. So you can clearly see the lesion. You can clearly see a border all around the lesion. It's a granular lesion, which is actually good. I like granular lesions because it's easier to resect them compared to non-granular lesion. And if you look at it, it can keep... You can start injecting the lesion first as you raise the lesion closely. And when you start raising the lesion, you can inject all around it. So you can see clearly a border all around that lesion. So once you have a clear border, it's always better because you can actually do the resection completely. It doesn't matter the size of the lesion. As long as you have a lesion with a clear border, it can actually resect the lesion sequentially or with a snare as a period of time. You can sequentially resect it. Trying to speed up the video, but it's not working. Let's keep going. Keep resecting the lesion. And the goal is the entire lesion needs to be removed. So I think there's some lesion still left on this side. The goal is to remove the entire lesion sequentially afterwards. So I think as long as you have a good injection, keep... So usually after I resect the lesion, I run to biopsy around that site. Although the evidence is not very strong, I tend to ablate all around the site to complete the resection after the resection is done. Again, this is extrapolated data from non-IBD patients in general. Again, in non-IBD patients, studies from the Michael Brooks group have shown that ablation around that site of resection decreases the risk of recurrence of lesion. That's what they saw here. But I think usually before taking ablation, I usually take a biopsy around that area, making sure you have no dysplasia, which is not missing in the area. Again, there are a lot of random biopsies around the area. It's not very clear. We have one study from the European group in Holland, which I think this study, where they actually showed dysplasia only in 5% of biopsies where they actually, after resection, did biopsies, random biopsies around that area. So 5% is still a significant amount of lesion, which was not seen on the original resection area. So based on this, I tend to biopsy, even though I don't see... I don't see any biopsies showing dysplasia after the resection in my experience. But again, based on this study, I tend to use them routinely. All the evidence is not very strong. Again, how we affect endoscopic resection in a large amount of analysis from our group, we did recently. If all these patients are long-term, the risk of recurrence of any lesion or the risk of hyperdysplasia, pulmonary cancer in these patients long-term is still very, very low. And we put 17 studies, which shows that I think endoscopic resection is the effective way with the overall low risk of complication to risk of bleeding and peripheral lesions overall very, very low. So as long as you follow these lesions carefully and survey them, endoscopic resection is very effective too. So ELC is another technique which you can use for lesions, particularly in the rectum, where I think you have much more better control, better data. But the most important thing is, I mean, is to remove a lesion end block, which is an advantage compared to EMR specimen. Removing the end block with the ESD actually achieves the end point of getting the resection complete in one shot and better diagnosis of the dysplasia. Again, even after ESD, the principle is if you look at the lesion around that colon, the colon looks clean. There is no active inflammation. There is no mucosal inflammation, a Mayo score of zero. So, but not every patient has this appearance. I would say probably among all the dysplasia patients get referred on, only probably 20, 30% actually have a normal endoscopic, no active disease. Almost 60, 70% have some amount of active disease and scar tissue. That's very, very hard to resect any lesion through EMR or ESD in general. ESD in particular, I think most studies of ESD in IBD patients actually came from Japan. This is a specimen which we talked about. And most studies, if you look at it, all from Europe and Japan, not much from the U.S. And as I said, the end block resection rate, if you look at the numbers are very variable. If you look at the numbers here from center to center, the number of lesions is still very, very small. We don't have large data from all over the world in general. And the main problem is, if you look at the data, the recurrence is very, very high with the data. I think the risk of metacronus lesions is 71% in studies. Additional surgeries, sometimes up to 50% in studies. And again, local recurrence up to 15%. So I think we don't have data saying that EMR or ESD is going to cure patients at this point after resection. That's based on this. And for ESD to be successful in all these requirements, you should have endoscopic remission. So, which is not available in most patients. I would say 30% of patient endoscopic remission is scoped for dysplasia. Again, the collider should be controlled medically and endoscopic remission should be the main thing. And it should be a clear border. Again, if you're a distinct border, very, very important, no ulcerations and absolute non-lifting sign. Again, it can be a problem because a lot of these patients have non-lifting sign because of significant scar tissue from IBD. And they should not have any endoscopic features like I mentioned earlier, including the Kudo-Pitt pattern 5 or any features of 2C, 0-2C lesion as invasive cancer. So if you look at the requirements of ESD or EMR, it makes it very difficult to classify all patients to endoscopic resection because quite a few patients will have all these things going on at the same time. That would be impossible to resect them endoscopically. So there is some recent studies on FDRD in non-IBD patients, but I think the data on IBD is not known at this point. So I would not recommend unless you want to experiment a lot of state, but at this point, I don't have any experience with this device at this point for IBD patients. So if you have endoscopic resectable lesion, you can resect it endoscopically either the EMR or ESD and the biopsies are negative around the lesion, you've accomplished a job of resecting the lesion successfully. And obviously, if you look at all the VC or DC techniques we use for detection, the lesions are very subtle to detect that sometimes most of the lesions are actually non-polyploid setting of IBD, that they are not very clear borders, are not clear, sometimes the vascular pattern is not unusually suggestive of adaptive advice, although they may be depressed also, which makes it very hard for resection. Again, if you do a complete resection of the lesion, you can actually just follow them with surveillance colonoscopy rather than a colectomy, as long as they are polyploid. This is the original SINIC guidelines and updated SINIC guidelines suggested that actually even if it's non-polyploid, if you resect them completely, you can actually follow them with surveillance colonoscopy rather than colectomy. Again, the most important thing is it doesn't matter what the lesion looks like, as long as you dissect them completely, no surrounding dysplasia around the lesion, you can follow them carefully with the surveillance rather than colectomy. But again, obviously not everything can be resected endoscopically. If you see this lesion with ulcerations and no clear borders, these patients will need colectomy automatically. So I think in our experience, I think most patients under EMR and our experience with chromatoscopy and endoscopic resection, we have almost 54 patients with low endoscopic EMR, and most patients, thankfully, had a PAS-less lesion, 0-2-ER-1-S lesion, which actually can be resected endoscopically. And only one patient required surgery because of higher dysplasia, this curvature of endoscopy removed. Again, over a short-term follow-up, it appears to be effective. So this is my algorithm for lesions in IBD patients. Again, if you have post-inflammatory polyps, you don't survey them, don't resect them, leave them alone, just follow them with surveillance chronoscopies. They have polyploid lesion. The most important thing is margins. If you don't have a clear margin, I think you're done because there is no known endoscopic resection in these patients. But even a clear margin doesn't matter what the lesion is. If you can lift the lesion adequately, resect the lesion completely, you can actually do a biopsy around the lesion, ablate the lesion around it after the biopsies. And if the biopsies are negative, then you follow them with surveillance after that. But the problem is if the patient doesn't have a clear margin, or the biopsies are surrounding areas still positive for random hygrodysplasia around the lesion, you don't see a clear lesion around the area where you resected, but it should be seen by a co-requisite for constellation of colectomy. So there are a lot of controversies for endoscopic resection in IBD particularly, because I think we don't know what the data is because we're, we said EMRE is just number one. We don't have this data even very good in non-IBD patients. Forget about IBD patients at this point. The problem with the surveillance is how frequently do you survey them? Every six months for how long? For the first two, three years, and then do it every year afterwards, do the data for at this point, we don't have much data. And how long do you follow these patients? For the patient that's 20 years old and you find a polypoly lesion, you resect them. The patient's only 20 years. How long do you follow them? What about the cost of the surveillance? Six months, a year follow up for the rest of their life? It's a huge challenge. It's a huge thing to think about. So, so there's always an option for these patients. And that's why a multidisciplinary team effort is very, very important because every patient with dysplasia, it doesn't matter, they should be displaced in the IBD tumor board. Just like we have tumor boards, we have an IBD tumor board in our institution. And it's related to colorectal surgery and come up with a plan and the patient should be the one who's driving the decision. We can offer a different option and they make the decision. In our practice, at least EMRE is the first modality for majority of lesions in IBD. And again, if you have ESD, it should be for more deeper invasive cancers where you can get an unblocked lesion, unblocked specimen if possible. And then if you obviously, if you have a deeper invasion or early cancer, it should be seen by surgery. Again, rectal sigmoid area with the subtle covert subunit of cancer is possible. You can always consider ESD as well in those patients. But again, EMRE is a predominant technique in more than 95% of our exceptions in IBD patients. So again, the area is wide open in terms of research. We don't have much data on most of this. And I think time will tell how this area will evolve over the next few decades.

management of dysplasia

inflammatory bowel disease

referral to colorectal surgery

endoscopic mucosal resection

endoscopic submucosal dissection