Chapters Transcript Video Mucosal Integrity Testing: Clinical Application in Day-to-Day Practice Presented by: Dan A. Patel MD, Vanderbilt University Medical Center, Nashville, TN. Good afternoon, everyone. Thank you for joining us today for our webinar, mucosal Integrity, Clinical Application and Day to day Practice. My name is Carrie Delugash. I'm the senior product manager at Diversity Healthcare. Just wanted to cover a few technical details before I introduce our speaker. Today's webinar is being recorded and it may be shared for educational or marketing purposes in the future. At the conclusion of the presentation, we will have a brief Q&A session. Questions can be submitted throughout the presentation by clicking on the Q&A icon in the menu bar at the top of your team's screen. We are very pleased to have Doctor Danan Patel as our presenter today. Doctor Patel is an associate professor of medicine in the division of Gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center. His clinical focus is on esophageal disorders, with research focused on acchiasia, esophageal motility disorders, GERD, and extra esophageal reflux. Doctor Patel has also been involved in the development of novel diagnostic tools that reduce diagnostic latency and can monitor therapy response in patients with esophageal disorders. Doctor Patel has over 50 peer-reviewed publications and is also the editor for two books, Obesity and esophageal Disorders and Evaluation and Management of Dysphagia, an Evidence-based Approach. He's been invited to give lectures at multiple national and international venues due to his expertise in esophageal disorders, and serves on editorial boards for two of the highest impact journals in our field, gastroenterology and clinical gastroenterology and hepatology. Thank you for your time today, Doctor Patel. Please feel free to share your screen and begin when you're ready. Perfect, uh, thank you so much, Carrie and Stu and Diversitech for actually hosting this, um. Let me make sure. You guys can see, well, can you see my presentation, Carrie? Yep, looks great. All right, perfect. So I think I'm very excited about this talk because um I mean coastal integrity testing is a novel tool that we feel like can make a huge difference in our day to day practice for gastroenterologists, because it's a point of care test that can allow us to make instant decisions, right? And I think that's huge from a patient and provider perspective. So as a disclosure, uh Vanderbilt and Diversitech Healthcare co-owned the patent for this device. So I'm gonna focus on primarily two deceased states, uh, where this is very, very helpful currently, which is reflux and EOE, right? And so I always start out with a broad question. Um, that all GI doctors struggle with on a day to day basis, right? What is GERD's, right? So this definition has evolved over a long, long time. Is it really presence of symptoms? So is it when a patient tells you that they have heartburn or they have regurgitation? Is it when not only do they have symptoms, but you can actually detect abnormal acid exposure in the esophagus. This is what we currently do with pH testing, or should it be defined when that reflux actually causes damage to the lining of the esophagus, right? Or changes to the epithelial lining, this is what mucosal integrity measures, right? The problem in our current diagnostics, as a lot of you guys have noticed, is we have a huge diagnostic conundrum and reflux, right? We have so many different tests. That all have different cutoffs, and that has created this wheel of confusion where you have some things that are conclusive for reflux, so someone who has Los Angeles CND esophagitis, and the peptic stricture of Barrett's, some things that are supportive of reflux, and then some things that are inconclusive or under investigation, and then what happens if you have multiple of these, or you have one or two of these, right? And this often leads to these unfortunate spin of wheel um where patients undergo repeated testing over and over again because it's hard to Contextually, uh, postulate, well, is that acid exposure time really causing the patient's symptoms and is it causing damage to the lining, right? So the idea behind mucosal integrity testing was, well, rather than just detecting what is coming up in the esophagus, can we actually detect, is there damage to the lining of the esophagus instantly during endoscopy? So on the left you see kind of nice healthy epithelial tissue, um, and on the right you see damaged tissue. So in diseased states like reflux or eosinophilic esophagitis, the inflammation creates more dilated intercellular spaces and the epithelial barrier will get leaky, and that's what mucosal integrity testing measures, is what is the impedance to the flow of current, right? Cause if you have a healthy epithelial uh uh on the left, you will notice that the impedance to flow of current is high, so the values will be high. And then when you have damage to the lining, it'll cause lower impedance or uh lower values on MIT testing. So if we can detect that instantly during endoscopy, now we can define reflux or eosinophilic damage instantly during endoscopy. And the reason this is so um uh uh you know, beneficial from a provider and a patient perspective is it not only gives you an instant diagnosis, so it delays this problem of the patient has to return the receiver, they might or might not receive the return the receiver if the patient is driving from 4 or 5 hours a week, and they set up a follow-up, right? It reduces this diagnostic latency. It detects chronic damage to the lining of the esophagus rather than just capturing how much reflex is coming up. It's really an endoscopic metric of histologic activity. You can actually monitor treatment response. If you have a damaged lining and you treat the patient, you can see restoration of the epithelial barrier and because it's done instantly during endoscopy, it's comfortable from a patient perspective, uh, which is very important, um, overall. And so going through briefly through evolution of how am I testing, this has been ongoing for a long, long time, and initially it was a proof of concept catheter that we put through the scope and we can measure spots in the esophagus and look at the impedance. Then we had a balloon catheter that allowed us to measure a larger segment of the sensors, but it's only 10 centimeter. And now, um, we have a cap that you can actually put on the scope and you can actually map the entire esophagus in less than 60 seconds. So how do we actually perform this study, and I'll show you this video how to set it up and do the procedure. OK, we're going to insert the scope actually into the sensor, and what we do is just move it up slightly and insert the scope right into. At that position, and what I tend to do is make it so that the sensor is in the direction, as you can see of the insertion. And then what we do is, again, the direction of the scope and the sensors in that direction when you swi. So now this is a patient uh with eosinophilic esophagitis who's already been treated and you're trying to assess uh normalization of the mucosa, right? The patient still has dysphagia. Uh, but, uh, as you look through the esophagus, you'll kind of start to see there is some fibrosis in the esophagus. So again, uh, when you do this MI testing and if it shows normal pattern, it tells you you gotta dilate the patient, improve the fibrosis, right? So here you see the stricture right at the GE junction, and then we're measuring the MI. And you can actually start to see this bluish color on the mucosal integrity pattern, and we're mapping this as we go uh proximal in the esophagus starting at 2 centimeters above the GE junction. 29 And then you can see kind of nice blue uh mucosal integrity pattern which shows that the EOE at inflammatory activity is actually in remission and you can actually dilate this patient at fibrosis, which is probably the cause of the dysphagia. Yeah that's it. So when we look at this MIT contours, really the values are color maps, right? So lower impedance values are red or damaged mucosa, healthier mucosa is blue, and you can see someone with untreated EOE when you Map the entire esophagus, they'll have this classic pattern of red throughout, which, which is very typical of Eoyific esophagitis because it's a pan esophageal disease, and you can see how the number of eosinophils are noted on there. When you treat the same patient, uh, you tend to get this normalization and blue healthy mucosa. And then similarly for GERD, because GERD primarily involves the distal esophagus, you'll tend to get this red closer to the GE junction, and then you'll start to see this blue normalization as you get proximal esophagus, or if someone has heartburn, they haven't. Previously responded to multiple PPI. You do an endoscopy. It looks like a healthy esophagus. You do MIT and it's completely normal like blue. It tells you the symptoms might be more driven by esophageal hypersensitivity or nerve mediated pathway, and that's what you should target, right? So when we look at um uh studies that we've done including even in healthy volunteers, um this is from a recent uh presentation at our DDW um uh the X axis here is distance from schemascar junction, and the Y axis is proportion of endoca values in the esophagus that are above healthy normative cutoff of 3300, right? So here you can see healthy tend to have most values close to that 3300 level suggesting a normal mucosa. And then when you look at EOE you can see majority of the values are low impedance in an active EOE patients. When you treat these people with EOE, you can see their uh esophagus will tend to normalize and get closer to healthy in remission. When you take patients who don't have esophagitis or pH negative, again, their values are closer to healthy. When you take patients with esophagitis, they'll tend to have more values lower than 3300 closer to GE junction, and then they'll start to normalize as you get farther away, and the same pattern you see with no esophagitis but positive pH, right? So when we look at these performance characteristics compared to healthy. Volunteers, what we noticed is a very good uh C index, right? So an ROC curve looking at esophagitis, looking at EOE discrimination, as well as abnormal period non neurosive reflux disease, and that tells you this allows you to better do uh instant test during endoscopy and help differentiate this pathology. So the whole idea of doing this testing, right, is can we simplify reflex testing, right? I showed you that wheel when we started out the presentation, we always have to remember who are we actually testing and who are we seeing in clinic, right? So there is what we call pre-test probability of a disease. Most people that make it to GI clinic with heartburn or suspected GERD have already tried and failed multiple PPIs, and when they're, they've already failed multiple PPIs, the likelihood that they have true pathologic reflex is already down as a cause of their symptom, and esophageal hypersensitivity might be the. Major contributor to the symptom generation. So what is the goal of testing in these people is we want to check the anti-reflux barrier, right? Do they have a had a hernia that makes them more predisposed mechanically to develop regurgitation or heartburn? And we wanna look at any mucosal damage, right? This is what patients want to know. Address the fear of untreated GERD, right? So, is there damage to the lining of the mucosa? Are they gonna be at risk long term of Barrett's or esophagitis? And that's what MIT allows you to do. So I'm gonna go through some cases that highlight this and how we apply this in a day to day practice. So, this is a great example, 25 year old female who presented with heartburn and dysphagia. Uh, when you look at the endoscopic images, they look pretty good in terms of esophagus, right? But because it's a young female, your differential really is it GERD or is it EOE, right? So how can you distinguish this instantly during endoscopy? We do MI. So here's we did MI on this patient and you classically see a reflux pattern, right? You see low or red uh impedance value closer to the GE junction. It starts to normalize as you get to proximal. Now, because of the current guidelines, we also biopsied this patient to look for this Eosinophils, and this patient actually. Came back as 26 ESNFils per high power field, right? So this is a great example of technically based on guidelines, the patient would be classified as EOE, but this is clearly not an EOE patient, right? This is a reflux pattern on MIT, even though it pathologically shows the Eosinophils, right? So this patient has heartburn. Post testing, the patient wakes up and you can kind of clearly go over that, hey, you have a reflux pattern. Let's start you on PPI therapy and then when we followed up with this patient in 3 months, they had resolution of symptoms and then despite meeting this pathologic definition of EOE from biopsy, this is actually not EOE, right? Another patient here, 33 year old female, right, with heartburn, you clearly see a nice endoscopic view of the GE junction. You don't see esophagitis. You have a retroflex view of the anti-reflex barrier showing that it's an intact anti-reflex barrier. You do mucosal integrity. Testing and you see this nice blue throughout the esophagus that tells you they have a healthy mucosal integrity, no reflex damage, no signs of EOE, right? So now you gotta think about, OK, so what do I tell the patient when they wake up, right? This is the best part about MIT. You can instantly tell someone what the plan is when they wake up. There's no longer this need to be like, hey, I'm waiting on biopsies. I'm waiting on things to come back and let's set up a follow-up in 3 months while the patient is still suffering from the same symptoms and looking for a diagnosis, right? So, they remember the pre-test factors, right? This is someone who has had lack of response to omeprazole 40 twice a day. Has heartburn. You did an EGD they have an intact anti-reflex barrier, and then you have an MI showing a normal mucosal pattern. This is likely functional heartburn, and the mechanism of heartburn that's uh driving the symptom is actually opal hypersensitivity. So the. Best treatment in this patient who's already failed PPI and has lack of response and resolution heartburn is to target the nerve hypersensitivity pathway, start him on a neuromodulator like a TCA, and when you follow it up in this patient in 3 months, they had resolution of symptoms, right, of their heartburn. The key is, can we predict outcomes as you do MIT, right? So we recently did a study that we, that is currently under review, uh, for publication. That looked at can MI predict outcomes of PPI need looking at over 2.5 years and turns out that MI can actually predict outcomes in PPI need at 2.5 years. And what we found, if you look at this heat map is the higher the MI values um and the lower the slope, which is this healthy uh area. They're less likely to need PPI long term, but if you have this red GERD pattern where you have low MI closer to GE junction with higher flow, it tells you they are much more likely to have a reflux related inflammation and the likelihood of PPI goes up. In fact, in our study, if MI was normal, nearly 1 in 3 patients were successfully not able to not only Able to stop the PPI but remain off of PPI without recurrence of symptoms at 2.5 years, right, which is a strong message is can I actually take people off of medicines that actually are not helping and they can still do well. The same thing happens to assess um fundo plaation response, right? So this was published recently that looked at the role of MI in evaluating. The reflex barrier afterness and fundoplication at one year and they found that lower MI values are suggestive of anatomical failure after fundoplication while patients that had higher MI values post fundoplication showed that they did well long term and that that wrap was intact. So anatomical failure MI patterns might indicate persistent reflux, right? So it is important to recognize that because our current paradigm includes pH testing and MI, that these are two different metrics of reflux, right? So PH looks at capturing how much reflexate is coming into the esophagus at a set point, right? So 5 or 6 centimeters above GE junction. It is susceptible to day to day variability of reflux patterns, right? If someone is not feeling well, they're not eating much, they might not detect a lot of reflux. It's susceptible to patient behavior. And the biggest thing I think we've seen in our field over the last 20 years is it's hard to determine cutoffs of what is true actionable reflux if a patient has already failed multiple PPI therapies, right? On the other hand, mucosal integrity testing captures this end result of reflux. So is that reflux causing damage to the esophageal lining? You can detect changes in the entire uh esophagus, and then maybe this is a better marker of actionable reflux is that if you have acid exposure that's actually causing damage, we need to intervene and they're more likely to respond, right? Rather than an arbitrary cut off on acid exposure time. So I, I'll show you this another case of a 39 year old male comes in with again, heartburn or dysphagia, classic internal question that all GI doctors ask, right? Is it GERD or EOE? And in this patient, you can kind of see the esophagus looks pretty good in the proximal mid esophagus, but you can see some furrows in the distal esophagus, and now you're like, well, could this be EOE, right? And when you do MI, you see this kind of reflex pattern. You see red closer to GE junction, blue healthy as you go. So you know this is not EOE and this is a reflex pattern because this patient has dysphagia, now you're like, OK, much more likely to have Schotsky's ring. We dilate the patient instantly during endoscopy. You see the mucosal tear and the scar tissue in the dyspi esophagus that improves this dysphagia. The patient wakes up, right? In the PACU, you discussed this is likely reflux mediated. We started them on omeprazole, right? And then when you do a follow up, uh, scope, long term, 3 months later, you can see this nice normalization, right? Of the esophagus along with mucosal integrity testing showing now nice healthy esophageal barrier. Another case that we commonly see is oh, the LA grade A esophagitis, right? When we frequently see this in clinical practice, our question is always, well, is it truly GERD? And when you have LA grade A esophagitis, the patient's gonna wake up an endoscopy and always ask you, well, doctor, do you think I have reflux? And the question is a little bit hard to tell, right? If you look at the Leon consensus, which is our current guidelines on reflux, they classify LA grade A esophagitis as borderline or inconclusive evidence, right, of reflux. So technically, If you have LA grade esophagitis, patients wake up, your answer could be, well, according to our guidelines, you have borderline or inconclusive evidence of reflux. We need more PS testing. Now, even as doctors or patients, that's not a satisfying answer, right? That doesn't answer, well, I just paid all this money to do a. Test, but yet you don't know what the answer is. Now, in the same patient, if you have LA grade A esophagitis, you do mucosal integrity testing like we did on this patient, and you see this classic reflex pattern, right? You see damage in the lower part of the esophagus, normalization uh up top. The patient wakes up and now you can actually tell them yes, a definitive answer your testing shows reflux related inflammation. Let's get you on the medicine to get you feeling better, and now there's much more closure to that patient knowing exactly what they have, rather than waiting on a lot of different testing them that later on delays the diagnostic latency, right? So the same diagnostic conundrum happens in eosinophilic esophagitis, right? We know that this disease can be patchy. The histology can vary and misclassify activity because we sample small areas of the esophagus. There is a wide inconsistent practice patterns, right? The guidelines recommend that you should biopsy during foot infection. A lot of people don't. The guidelines say if it looks normal, they're younger patients, you should biopsy. A lot of people don't. It leads to a massive cost burden because a lot of these patients are lost to follow up after they come. And then there's significant overlap that I showed you in those prior cases with reflux. So how do you distinguish the two conditions and get them on the right pathway, right? So when we look at MIT and Eosinophilic esophagitis patients, we clearly see that um there is histological. Correlation of impedance with not only the number of ESinophils but also other metrics of Eoinophilic esophagitis like dilated intercellular spaces or spongiosis um and so what you'll notice is the higher the number of ESinophils. Or the more leaky barrier, which we think is more severe disease, you'll see a lower impedance and you see this uh pattern with both. And we actually did a study looking at a blinded prediction of EOE where we blinded the person who was doing MI. We did a EGD and MI and just solely on MI pattern, they had to tell you if someone had EOE or not. And you can clearly see MI has a very high sensitivity and specificity for EOE and it tells you this is a great tool for instantly diagnosing someone and delaying diagnostic delay, right? And I think that is a very, very key message in this people. We want to do things in one setting. Determine a plan in one setting where you get this, you, you don't have to worry about this loss to follow up until they come in for the next. So here's a great patient with 21 year old male with dysphagia. You look at the esophagus, they got this uh white uh patches. Consistent with Eynehilic macropsis, you see the rings, classic appearance on the endoscopy, and you do the MI testing and you clearly see this EOE pattern. You see red throughout the esophagus and you know this is EOE. Now when you look at studies. That the normal pattern of practice is we're gonna biopsy, we're gonna wait on this pathology to come back, and then the patient might or might not show up, and we have to track them down, right? In fact, if you look at studies on follow-up in EOE, 1 in 4 are lost to follow up after an EGD and diagnosis of EOE. It is massively hard to get these people back into clinic, right? So if we now have a way to instantly diagnose this disease. This patient wakes up in the PACU and you can clearly tell them, hey, you have eosinophilic esophagitis. Let's talk about treatment options with the family and the patient, right? So medical management options or food elimination. This patient started to go with the PPI route as he was going to college and didn't wanna do uh food elimination, so we went ahead and sent him a prescription. Now you not only made a fast diagnosis, you got them on the treatment and you're like, hey, let's set up a follow up EGD in 3 months on the acid blocking pill to see if it gets you in remission, right? So now you do this follow up EGD in 3 months on twice a day PPI and again, the esophagus looks better. But if you look at the MI pattern, you clearly see there's still active inflammation, right? You see red, there's patchy healing, so you see a little bit of these areas of blue, but you still see that this is an active disease. Again, the patient wakes up, you're like, hey, your esophagus is still active in terms of EOE Again, lack of response to. So now you talk about other options, right? So whether that's swallow topical corticosteroids or dilimumab or food elimination, the preferred topical corticosteroids, we started them on it. You follow up again easily in 2 months, and now you see nice esophagus but nice normalization of the mucosal integrity testing. Now this patient still had the phara, even though MI now looks normal, and now this is the perfect time where if you notice that there's normalization of MI pattern, which suggests that the EOE related inflammation is now in remission, this tells you that this patient is still symptomatic because there's fibrosis somewhere in the esophagus. So rather than waiting on biopsies to come back, when you see this pattern, you can actually diagnose intraoperatively. That hey, this is a normal pattern, but because they're symptomatic, the fibrosis is likely there. You dilate to improve the fibrosis and in the PACU, once the patient wakes up, you can tell them, hey, your EOA is in remission, that you had this patient had a narrowing which we dilated, which resolved the dysphagia and you now decrease the uh medicine to maintenance dosing, right? It allows you to expedite not only diagnosis in. assessment of the next plan and then when they wake up uh uh making a plan so that reduces this loss to follow up, right? And we see this very commonly in mucosal integrity for EOE, right? So here is a classic pattern on the left, uh, where you see red throughout, and this is an active EOE patient. You see the number of Eoiniphil is just for reference for distal proximal. Uh, I'll now show you all these different patterns as we treat, right? So here is a perfect patient with 4 ft elimination diet, and you can see they have some normalization but still activity in the distal part of the esophagus. There is a patient with 6 ft elimination diet that again you see activity distally, even though it just says 16, you can clearly see it involves a large area of the distal esophagus. Here is a great patient that. Actually it was a twice a day PPI and MI shows that there is actually active disease in the mid part of the esophagus, but when the patient's path came back from distal proximal esophageal biopsies, it actually shows less than 15 gsinophils, right? So this is a patient that clearly again would have been misclassified as remission based on pathology but actually has an active disease. and then it kind of can go on and then as you can see is. When you start to get normalization, like this is a patient on dipilimumab and you can see this nice healthy mucosa all throughout that now shows restoration of epithelial integrity, right? So, uh, when we looked at this, you can actually the peak Eoinopilic count can misclassify up to 1 in 5 patients because of the high variability, right? It depends on not only where you biopsy. It also depends on how the pathologists are counting it, and there is a high variability among pathologists on how they count it and the number that comes back, right? And how and and as you can imagine, it's harder because 15 is an arbitrary cut off, right? So what makes 14 normal, but 16 is remission or 16 is active disease, right? So this is why uh um a test that allows you to not rely on small little biopsy in the esophagus to classify remission, but map the entire esophagus gives you much more uh confidence in classifying the patient in the correct category of remission or active disease. So we hope that because of the ability of MIT. To differentiate this patterns instantly during endoscopy, it makes a huge difference from a GI doctor's perspective of not only being able to classify them during endoscopy, making intra-op assessments of do I need to dilate or not, and when the patient wakes up, going, uh, you can actually make a treatment plan where you don't have to worry about follow-up and glos to follow up, right? So, uh, this is how I. See MIT playing into our um practice, right? If you have someone with heartburn, regurgitation, or dysphagia, uh, and most of the people have already tried PPI therapy, if there's no improvement and they're undergoing upper endoscopy and you do MIT, if you see an EOE pattern on the left, um, go ahead and wake up. You can actually start talking to them about treatment options, see what they prefer. If you see a normal pattern and their main issue is heartburn, then the treatment should usually involve neuromodulation because their symptoms are primarily driven by nerve hypersensitivity. If you see a GERD pattern, then that tells you you need to optimize reflex management and particularly GERD pattern with um anti-reflux pair that's not intact, then you need to escalate management, right? So moderate to large hi to hernia, or they have regurgitation as a predominant symptom. So I think, I hope I highlighted that um mucosal integrity testing accurately discriminates esophageal disease instantly. It has this ability to map entire esophagus in less than 60 seconds. You can monitor treatment response to make sure that there's restoration of a healthy esophageal barrier. And it's a reliable endoscopic surrogate of histology in EOE and has an ability to simplify GERD and EOE diagnosis and help our patients not only figure out an answer but not make them go through loops and loops of testing without actually knowing what is actually causing their symptoms. So thank you again for um having me uh um present this webinar and happy to take any questions. Thank you, Doctor Patel. That was, that was excellent. Um, we do have some questions. I just wanna, I'll start, I'll go through those questions, but I do wanna just announce cause uh a handful of people joined us a little bit after we started. If you have questions that you'd like to ask Doctor Patel, please use the Q&A button in the menu bar at the top of your team screen to, um, To or to put them forward. So first question I have, um, is there a gray area of MIT? What about false, negative, and positive? Yeah, so, so certainly, um, there can be false negative. Uh, I think the false positive are extremely unlikely. Um, if you have someone, MI is a much more specific tool compared to PH. PH is a more sensitive tool, right? So you can get someone who has acid exposure time of 6%. Yet they've failed multiple different PPI and the question comes up, well, is that truly reflux, right? That's causing their symptom. Um, it's highly likely that MI is gonna be positive in that patient. So I think MI I would look at as more specific tool with less false positives. Um, there can be false negatives where MI looks completely normal, right? Um, and they can have some degree of reflux, but is it truly pathological? That's what we're trying to answer and try to uh treat, right? OK. Uh, second question we have, do you establish a baseline MIT on all EGD patients with suspected disease? So, uh, I think this tool is very, very helpful in anyone with suspected reflux or eosinophilic esophagitis, right? Um, I think if you, if that's the indication for EGD, then the MIT can help you figure out those two, instantly during endoscopy, and I would, I would, I would think that that's where it's highly helpful for the patient as well as the provider. OK. Thank you. Do you do MIT on PPI or off PPI? So we, um, you can do MIT on PPI, but most of the data is off PPI, and I think that's probably the the best way to go is if you can do EGD MIT 7 to 10 days off of PPI, then you can actually not only answer the question of do they truly have severe reflux to cause damage, and you can answer the question of EOE because there are some studies that show that PPI might mask certain ESinila, right? So I think personally to me off therapy testing as the baseline is very helpful, and then if it's abnormal, you treat them and then you see if you get normalization. Another question we have, if you're doing an EGD on a patient with heartburn refractory to multiple PPIs, do you do MIT while on therapy or off therapy? It's kind of basically the same question. No objective findings of GE. Uh, of good scene, what is your general practice? Yeah, uh, so yeah, I, I do it off therapy because I wanna know. Um, you know, off of medications, what do I see, right? And if off of medications you're not noticing any esophagitis, they have an intact anti-reflex barrier. MIT looks completely normal, then it tells you that that combined with lack of response to multiple PPI that their heartburn is being driven by a nerve hypersensitivity pathway, and you should target that rather than escalating reflux management. Thank you. Can you please expound further on the impact of esophageal fibrosis on MIT interpretation and how this could overlap with esophagitis in interpretation? So, um, uh, the fibrosis, the main impact it has on MIT is if you have uh a strictured esophagus or narrow caliber esophagus, you might not be able to get the, the catheter in there, right? The, the endoca in the esophagus, um, but if you, if the otherwise outside of that, you can still assess it as long as you can get the catheter through. MIT is not a great um metric for fibrosis. Uh, you, if you're looking at more distensibility, right, rather than impact on epithelial barrier integrity. So MIT is a much better metric of inflammation in the lining rather than fibrosis. So what our goal in this patient is, if we see that MIT is normal in patients with EOE tells us that that inflammatory activity is now in remission. And now they're symptomatic, we're gonna try to address fibrosis if we see MIT normal by dilating their esophagus. And if we notice that post dilation, we do a relook and there's mucosal tar it tells you that was what's actually driving their symptom. So I think it helps you kind of narrow it down to why the patient might be still symptomatic. Thank you. Um, next question. What about impact of doing esophageal biopsies on MI readings? Do you do the MI first and then do the biopsies? Yeah, we always do MIT first uh before doing biopsies because when you biopsy the area with the bleeding or that area might affect the reading, right? And so particularly you wanna make sure there's no liquid that's retained in the esophagus because liquid entrapment can make the values look artificially lower. So you wanna make sure you clean the esophagus nicely, suck out any liquid, do your MIT testing, and then get the biopsies. And because it's an endoca, you can actually put the forceps through once you're done with the MIT testing, you can actually do the forceps through the scope, you don't even have to remove the cap and get the biopsies. Uh, do you feel that MI might be falsely low in patients with echiasia and significant esophageal stasis? Yeah, so again, that's an excellent question. So you're exactly correct. If there is stasis changes in the esophagus or liquid entrapment, which is very common in people with echiasia where you go in and you might see a lot of kind of frothy sputum and liquid, then that will affect MIT. So you're exactly correct, that can affect the Eating. So in someone that's again, untreated echilasia, MIT doesn't have a role in that patient. You gotta treat the lower esophageal sphincter and their physiology. If it's post-treatment echilasia and you're trying to evaluate for reflux, then yeah, that can have a role to look to see, well, is it truly reflux that's causing heartburn regurgitation. But, but yeah, and then to know eolasia patient because so many things can affect it, um, there's no indication for MIT in that area. Is MIT useful in patients with suspected LPR? So, um, uh, that needs research in the sense of, um, a lot of the patients with suspected LPR. It is very hard to tell if reflux is the cause of their symptoms, right? So, uh, the biggest thing in extra esophageal symptoms is someone can have throat clearing and chronic cough. They can have, let's say, even if you do pH testing, acid exposure time of 8%. But those two things don't tell you that that 8% is causing the chronic cough, right? So the way we approach it is similar to people with suspected GERD, where if you have someone with suspected LPR where they have throat clearing, chronic cough, um, they have lack of response to PPI they don't have typical symptoms of reflux like heartburn regurgitation. You do an endoscopy, their esophagus looks normal off of any medicines. The anti-reflux barrier is intact. You do mucosal integrity testing, it shows completely normal. Then the chances that they have significant enough reflux causing their throat symptoms is extremely low. And in that person, if you've done all the other evaluation that can cause like allergy pulmonary, then it might be laryngeal hypersensitivity that's actually driving their symptoms, um, rather than reflux. So, so I think it's a combination of information you have to use to make that call and, and particularly in people with LPR rather than a single test. OK. Got a few more questions. Um, If I see grade A esophagitis, should I place the cap on that side or go to the other side? And then the same question would apply for grade B as well. Uh, same side. OK, um, if MI and biopsy don't correlate in EOE, what do you do? So, um, uh, that, that is an excellent question. So I will tell you that looking at patterns of MIT and EOE MI is a significantly better metric of Eoinophilic activity than biopsies are. Uh, and the reason, uh, we say that is looking at even, uh, we're starting to recognize that EOE is much more than just the Eosinophilic count. So if you look at studies in EOE, you'll notice that when you do a more comprehensive metric of disease activity like EOE HSS score, which is a histopathologic severity score, which not only looks at the Eosinophilic count, it looks at other metrics like basal cell hyperplasia, the DIS, it's a comprehensive metric of damage to the lining. That MI actually correlates much better to a comprehensive damage to the lining with basal hyper with the DIS and Eoinophilic count. So, the reason I say it is because biopsies can be highly susceptible to not only sampling error, you're only getting a few bites in the distal proximal esophagus. These are 12 millimeter bytes. Not only that, it's susceptible to the pathologists reviewing it and how they count Eosinophils. Because of all this variability, now because MI can measure the entire esophageal lining over 40 centimeter, that has a much better chance of detecting activity and active disease than biopsies. So to me, if I had a patient that clearly MI shows there's active disease in the esophagus, let's say mid esophagus proximal distal, and their EOS count come back as 1412, they're not technically in remission. Um, so I think to me, I, my practice is to try and get to normalization of epithelial integrity on MI rather than just normalization of EOS count. Now, whether that long term leads to better outcomes, I think there's gonna be a lot of studies coming out on that, but I think it's a better metric. OK. Thank you. Um, what do I do with non-obvious MI patterns? So, um, uh, nothing much is what I would say. Um, if you see a pattern that's not obvious on MIT, just similar to any tests you do, um, if it doesn't match with the patient's symptoms, your endoscopy, then I wouldn't act on it. Um, what you want is concordants, right? So what you want is, I have this patient, I have a pre-test likelihood of certain things. You do an endoscopy, it's normal, MIT correlates, or MIT is abnormal, and it's definitive, then you act. But if you notice that, hey, it's um it's non-specific, then I wouldn't make too much of it because so many, if you get a little bit of liquid entrapment, something can drive the pattern. So I would more uh not worry about those non-specific patterns. Um, we currently capture 12 centimeters of the esophagus. Are there times we should be capturing more? Yeah, so, um, uh, because endocap makes it so easy um to actually map the entire esophagus in less than 1 to 2 minutes, our practice is to map the whole esophagus, uh, in all patients, whether that's GERD or EOE because if you map the EOE patient with only the distal 12 centimeters, they might actually have activity in the proximal mid that you might miss, right? So I think mapping the whole esophagus, uh, is better than just focusing on the distal. Um, can my view or MIT differentiate? Differentiate bile acid reflux from acid reflux, and if yes, what is the cutoff and is there any research on this? Uh, no, unfortunately, it can't, it can't differentiate between the two, because it's looking at just damage to the lining that that damage could be driven by bile acids, that damage could be driven by acid from stomach, or it could be driven by like, right? So it's more about the pattern, um, the reason we can distinguish. GERD from EOE is because of how much esophagus is involved, right? So GERD is gonna cause damage closer to GE junction, so we can detect that pattern. EOE is gonna be entire esophagus, you see red throughout, but it can't distinguish whether the damage to the GE junction, if you have GERD pattern is from bile or acid. Um, what are the possible causes if we encounter blue in the distal esophagus, but red in the middle of the esophagus? What does this indicate? So, um, uh, it could indicate numerous things. You could have a patient that has EOE that's partially treated, right? So if someone has EOE and they let's say they were placed on PPI, they could have activity in the mid esophagus. It could indicate if you just have activity proximal mid that they might have other ideologies, right? So lichenoid esophagitis, which is another ideology that can cause damage to the lining, that's autoimmune that can cause it. So if you notice that, you should definitely target your biopsies to that area to get higher yield. Um, last question. Uh, if I'm using MI, is there any role for biopsy in GERD patients, or should I still biopsy for Barrett's? So, um, uh, I'll, so the in terms of biopsying for reflux, if you don't see endoscopic signs of Barrett's, you don't need to biopsy the esophagus if you do MIT. If you see endoscopic signs of Barrett's, you should always biopsy, regardless of MIT or not, because you need to you need to evaluate that area for dysplasia and risk and risk stratify whether I need to think about surveillance interval as well as treatment, right? So anytime you have a patient with Barrett's or suspected Barret's that looks like an endoscopy, you should always biopsy. OK. Um, I do have a couple more questions that came in if you're, if you, if you still have time. Yeah. OK. OK, so if you have a patient with inconclusive GERD diagnosis on pH testing based on the own criteria, are you solely banking on the MIT to make a conclusion, or are you using, are you using additional factors such as Milan's score, Leon's score, etc. So I think uh that that's again an uh an excellent, excellent question. Um, I think we can make it as complicated as you want, right? So I think there's so many now different tools of how you make a diagnosis. Personally, to me, what I base it on is what is the patient complaining about and what do I see, right? So combining patient characteristics and my likelihood of disease. So if someone has heartburn, um, and they've tried PPIs, they have not responded, if you look at studies on just esophageal hypersensitivity, if you failed BID PPI and you have persistent symptoms, your likelihood of esophageal hypersensitivity driving the symptom is already 50%. So 1 in 2 people, it's gonna be neuromediated reason for their symptoms. So now, if you test that person on EGDPH, pH comes get borderline. MIT is completely normal, and they have no esophagitis, anti-reflux virus intact. I don't need any further testing. This patient likely has symptoms that are driven by nerve hypersensitivity, and I will target that pathway to get them to feel better. The goal of testing is to not continue to do testing to find an abnormality, right? The goal is to try and explain why is the patient feeling bad, right? So I think that's what I would try to. Encourage is combine your pre-test likelihood you've seen the patient, look at their symptoms, what therapies they've been on, combine your endoscopic findings, and then combine, do they have damage to the lining, and most of the time you can make a very good judgment based on that and what is probably driving their symptom. This is very common even on people with, let's say if you reverse that same scenario, right? Where you have someone who has heartburn, they failed multiple different PPIs, you do a therapy pH testing, and let's say it's not even borderline, it comes back as 6.5%. According to Leon, that's reflux, right? But the patients already failed multiple different PPIs. If you do endoscopy, they have anti anti-reflux barrier. You'll find a very few number of people that actually escalate that patient to anti-reflux management, right? Because again, that acid exposure time of 6.5 doesn't necessarily mean that that's actually driving that patient's symptom if they're actually already failed multiple different PPIs. So I would try to be cautious about, you know, uh, being aggressive and escalating anti-reflux management. If other um things don't go together, and I would always try to encourage trying to look for concordance between the test and seeing what physiologically makes sense for the patient. Mm All right. If you suspect LPR and EGD showed no esophagitis, would you do MIT on or off PPI? Yeah, uh, uh, always off for me. I think um the off therapy is better because, um, again, if you do off therapy, you're increasing sensitivity, right? If you take someone off of medicines and you do endoscopy MIT and you see no damage, no esophagitis, normal anti-reflux barrier, MIT is normal, the likelihood to have severe enough reflux to cause LPR is extremely low. Um, sometimes we do encounter redness during MI tests near the proximal esophagus in LPR patients, but it will be all blue from distal to mid esophagus. How can we explain that? Is it LPR? Uh, so, no, uh, that's hard to know. So some people can have a little bit of red in the proximal esophagus because as you get closer to upper esophagal sphincter, sometimes there is saliva that they're swallowing as you do, and sometimes that causes liquid entrapment, so I would make sure to kind of make you're ruling that out. Um, but sometimes if that patient has dysphagia, they might actually even have a little stricture in that area and because proximal area is very, so normally people with dysphagia, if you don't, if you see their esophagus is normal and you empirically so-called dilate, you'll frequently see tears in the proximal. because that's an area we can't, we're not that good at assessing the luminal diameter, so I would just, it, I don't think it necessarily means anything if you have red in that one area, but I would just make sure it's not from artifact because the patient is swallowing saliva and it's coming into that area because it red at the you yes. All right. Well, that was our last question. um Oh, and then I will say one other thing, Carrie, so sometimes people will have this proximal, of course, gastric and lip patches, which are incidental, and remember that gastric and lip patches will have low MI right? cause it's a gastric mucosa, so that doesn't necessarily mean anything in terms of the disease process, but it just tells you that it's, it's a gastric mucosa. Um, all right. I, um, I just took one last question. I apologize after I said it was our last one, we got one more and then we can, we'll conclude the webinar, but, um, how long do you recommend to stop PPI prior to MI test? Uh, 7 to 10 days. OK. And then an easy question. Um, thank you to everybody who joined us. We had a, a really great group of, um, participants. Doctor Patel, thank you so much for your time today. Um, I really appreciate it just hearing your real world experience and um how my view and MI can really simplify the diagnostic process both for the clinician and, and the patient. So, thank you very much. Um. If you have, if anyone has any questions after the webinar, please feel free to reach out to your diverse tech healthcare sales rep. Um, if you don't know who that is, you can find their names on the contact page of our website, um, and then please just look for similar webinars from Diverse Tech Healthcare in the in the near future. Appreciate your participation and your time. Everybody have a great night. Thank you, Doctor Patel. Bye-bye. Created by Related Presenters Dan A. Patel, MD Associate Professor of Medicine Gastroenterology, Hepatology and Nutrition View full profile
