Chapters Transcript Video Mucosal Impedance: The Better Way to Diagnose GERD and EoE Presented by Michael F. Vaezi MD, PhD, MSc, FACG, Vanderbilt University Medical Center, Nashville, TN. the opportunity to talk to everybody about you coastal impedance and reflux disease. So the aim of this is to really update everyone about how we're currently diagnosing reflux Thio go over. What are the issues with the way we diagnose? What are the limitations of those tests that we currently use and how to potentially improve and where mucosa limp? Eaton's might have a place in our armamentarium off how we diagnose three Fox but also is center Phillip Esophagitis. So with that, let's go to the next slide. And, um, so reflux disease right now, as it stands, is divided into Asafa Jill syndrome, an extra Safi geo syndrome. And, um, that distinction is really based on how patients present. So patients, typically on the esophageal syndrome present with heartburn regurgitation the classic symptom mythology with the exception of chest pain. Chest pain used to be on the what we used to call the Atypical Reflux group, but now is put under the esophageal syndrome. We also have patients that have esophagitis, stricture, or barretts esophagus. That is in contrast to those that have extra esophageal syndromes and those air patients that we often see with reflux induced cough or laryngitis or asthma, dental erosion, sinusitis, pulmonary fibrosis or fair INGE itis and otitis media. This distinction is important because the Association of Reflux is stronger for the esophageal syndromes and less strong for extra Safi Jill syndrome. Not that they're not associate it. It's just that we depend mawr on our diagnostic strategies to really delineate who has the disease and who does not. Now, in patients that we currently see out in the community as well as an academic centers, Uh, it's kind of divided into this acid reflux group where we treat patients empirically, and that treatment may or may not be effective and the patient where it is effective. Apparently, there's this presumptive diagnosis of reflux patients in whom we do endoscopy. We might come up with esophagitis, so that group is the acid exposure group shown on this slide on the left. Now the non erosive group are those that truly have the disease. But endoscopic lee, we don't see any evidence of erosion, and then Rome four has distinctions between the functional heartburn and reflux hypersensitivity reflux. Hypersensitivity by this criteria is defined as those patients that have, um, reflux. That's within normal by ph monitoring. But yet it is felt that the patient's symptoms still related to reflux and then functional heartburn eyes the The definition is essentially those where everything is normal, where patients may not respond to P p I therapies, they may there don't have esophagitis, they don't have erosive disease. And that's the group that we reach out for. Neuromodulation Torrey agents a za way of treating patients So we talked about how we essentially currently are using symptoms to guide our treatment. And M. Peric therapy is the way we, the current recommendation suggests. Uh, if a patient presents with heartburn regurgitation or any of the extra Safi Jill syndromes, the initial treatment should be and or diagnosis should be an impaired thought. Trial of PP ice, once or twice daily for 1 to 2 months and then depending on response, is when we depend on our diagnostic testing strategies. So what's important to know about indications for testing is that they're different reasons why we do tests in patients that have incomplete or lack of response to the therapy that I just talked about in that group. The question is, what is the likelihood that we're actually gonna see reflux is the cause for that Patients continued symptoms versus the patient that we're going to evaluate to send for potentially anti reflux intervention, either endoscopic or surgical. So the pre just probability for these are different in that invasion that has incomplete or lack of response to therapy. Our tester designed to tell us who does not have the disease while in those were evaluating four re thoughts, intervention I e. Surgery or endoscopic therapy. We want the phenotype of the patient that truly has the disease. So we're looking for abnormality in our tests. Now, what are these tests? This is a pictorial of some of the tests that are currently available. You'd be familiar with barium swallow on the left hand side of the bottom. We do endoscopy, and we biopsied biopsy the mucosa to look for certain diseases that relate to reflux disease, obviously symptoms that are classic for reflux. That's where imperiled therapy comes in A to very bottom of this picture. We also showed the either intra nasal trans nasal pH or pH impedance monitoring or the wireless device, the Bravo pH. Testing. Um, and we have salivary peps in and endoscopic Lee. We could depend on narrow band imaging, especially in patients that might have Barretts esophagus, uh, Nikos Olympians that shown on the right hand side is what we're gonna talk about on the second half of this presentation to really just discuss where it fits within this, uh, group of endoscopic and diagnostic tests. So in a perfect world, when I am a gastroenterologist and the SAF Ecologist So when I see a patient that I'm trying to evaluate when I do endoscopy, if I see esophagitis has shown on the left hand side or Barretts esophagus shown on the right hand side that tells me the patient has the disease. I don't need to do any further testing. You don't need to do ph monitoring. You don't need to do salivary Pepsi. NASA. You don't need to do any other test to show that the patient truly has reflux disease because there is endoscopic um, findings of that. However, we also could do in ph monitoring pH. Monitoring is where we, um, did endoscopy and endoscopy was normal. So we're still trying to find reflux. The next test would be doing ph testing. This is unexamined. tracing of a patient that has heartburn shown by H and chest pain by sea. And you see in red the pH tracing over a 24 hour period where, by convention, any pH less than Ph of four is considered abnormal. And the way we calculate whether or not this patient truly has the diseases. We combine all the pH less than four, and we see within a 24 or 48 hour time period. What is the percentage of the time that the pH is less than four e aesthetic reflux? And by convention there metrics, we used to say, If it's normal or abnormal now, in a re a world, that's not what we see. What we see in this comically is that when we see patients that have reflux and they have not responded to impaired therapy there, endoscopy is actually normal, and that doesn't help us. And when we do pH monitoring, it looks something like this or again. It's normal. So neither tests really helped us in deciding whether the patient has reflux related conditions. A little bit of history on the current technology that's available for our patients that have potentially reflux or how we use these tests in diagnosing reflux really dates back to all the way to 1935. And when you look on this craft, ambulatory pH testing, which were all used to now really didn't start till the late seventies early eighties has shown in the middle of this chart and then subsequently, early 2000 is when we started the development of wireless pH monitoring, impedance monitoring or the rest tack or offering JAL pH monitoring. And it's really been over the past couple of years where mucosal impedance. We're seeing Mawr data on the role of mucosal impedance and how to utilize this in our patients in making it easier so that we can quickly, efficiently make a diagnosis. If someone has the disease or they don't have the disease, I'll talk about in detail about that now. One thing to remember is what reflux was back then. When those pH testing started development in 19 eighties. Back in the 19 eighties, early eighties and late eighties, the issue with reflux diagnosis was we weren't treating patients with aggressive asset suppression first, as we are today and that we didn't have PP ice, so what we would do is before anything we would either do endoscopy or pH monitoring. We would see a lot of patients that truly have the disease. What's changed today? We live in the era of em. Peric therapy I e patient has the symptom. We treat them empirically. Now we do the tests not in those that truly have the disease, because they're better the ones that have the disease air gonna improve. So we're now utilizing our tests endoscopy, pH monitoring or anything else in those where you know, mostly they don't have the disease. And it's really the sub portion that we're looking to see if they continue tohave it despite empirical therapy. So this really highlights it slightly differently is that the search for what we're doing is different. Back then, many had the disease. We would do endoscopy, NC at ph. Testing would help us, but now it's that smaller portion of the pie graph, if you will, or our patient population where they've already tried once a day p p i or off label, twice daily PP. I they're not better. And now we're using it in that sub population that hasn't responded to therapy so that's important to keep in the back of our mind in that it's It's the global overview off when we are doing testing and why it is so many of our patients. When we do test, the test may be normal, and the reason is because they've already tried PPS. And here is a slide really summarizing what would happen and what does happen in our patients when we do endoscopy pH monitoring either on therapy or impedance ph. Testing on or off therapy on What you see is that the prevalence of normality I eat normal findings in all of these is a lot more than abnormality. So by default, many of our patients will have normal test. That's important because whatever diagnostic test we employ has to be good enough to tell us whether something is normal or abnormal. And that's what gets to mucosal impedance, where it will really be able to tell us whether they're changes within the esophagus of these patients that are either normal tests or abnormal. So I hope to clarify that later. Now that gets to all of these diagnostic tests, and what we see here is, uh, the catheter based system. This is the Billy Tech that monitors Billy Rubin impedance pH Testing. We have the wireless Bravo test these air the tracings. We can take biopsies and look at the biopsies under microscope for dilated inter cellular spaces. The rest ph or the aural for NGO pH Monitoring. This is a tracing off impedance monitoring where there's a couple of new parameters off PSP W post swallow parasol tick wave that is being highlighted here. And then there's a Pepsi and test shown here, which is almost like a pregnancy, Um, kit, where you put saliva in here and you see whether it's positive or negative, the key about all of these cells. And I'm not going to cover them in detail if you have questions happy to answer them. But all of these tests is that we are using these tests in patients that have been sub optimally treated or, if they're optimally treated there, then partially or not, not responsive at all. So that tells us that these tests are not gonna have the sensitivity, um, that one needs and and or the specificity for that matter. And we really need better diagnostic tools. So the limitation of these diagnostic tests currently is that they're suboptimal. They have limited sensitivity or specificity. They're constrained by measuring reflux on a single time. Points on. By that, I mean, you put the capsule either in the distal esophagus or the catheter through the nose in the distal esophagus. And you're monitoring that patient at that single point and location for Onley, a day in a patient that has chronic disease. Reflux is chronic and varies day today, and that one test may or may not pick up the disease. And the presence of reflux is really not what these, uh, test measuring their only measuring presence of acidity within that time point within that time. And I'm sorry, that location in the esophagus and that may actually not be sensitive enough nor specific enough to tell us if someone has reflux or not. And that leads to the concept of mucosal impedance that I'm going to talk about. But I'll pause here in case there are questions, um, to address. Okay, are there any everyone's unnoted now? So if you have any questions on the first part of Dr Vases discussion, this is a good time to ask their all muted. I got uneven. Morning time e don't know. Okay, one of the people who have questions, I don't know where he went. Well, Dr Baby, one of the questions is what is the benchmark test for Silent GERD? And do you think impedance Ph has underpowered sensitivity? Yeah, that's a good question. So silent GERD Eso that we all know what silent GERD means essentially, is that the patient has reflux, but yet they're not presenting with a symptom classic for reflux. We hear that term often in our patients that might have chronic cough may have asthma may have Lauren Geul symptoms and or other extra Safi Jill symptoms. So in many of those patients they may not have the classic symptoms. They have other symptoms, and those symptoms don't necessarily clue us in that re thoughts may be playing a role. So that's why the words silence in that they have reflux. But it's not saying that it's not presenting its heartburn. Let's say it's presenting his chronic cough. Now it's silent because in a subgroup of those patients, when we do pH testing or impedance pH testing or a zoo, we'll talk about mucosal impedance testing, we'll see that there is clearly reflux disease. There's evidence of either acidity by ph testing or impedance pH testing that measures not only asset but also non acid or weekly asset, and then, with mucosal, impedance will see consequence of chronic acid exposure. So as far as the question off the sensitivity of mucosal I'm sorry. Not mucosal but impedance ph testing impedance pH Testing is more sensitive than regular pH testing, and the reason for that is it's measuring more than just ph measuring more than just asset. It measures liquid. It measures gas, so its sensitivity is more. But whether or not that's still the optimal strategy is what we're going to talk about in the next few slides. Okay, it doesn't appear. Is we have any more questions on the first part. So Dr Vaizey last time to learn all about mucosal apiece? All right, so let's dive into it. So again, on this slide, we talked about the limitation of our current strategy. So we really wanna look outside the box. What is outside the box? Me. So when you look at this is ah, a picture of impedance ph monitoring device and not the catheter, but the monitor itself to make the point that mucosal impedance came about from really the concept of impedance pH testing in that when we do impedance pH testing in patients that have esophagitis or Barrett's esophagus. Traditionally, we say that that value, or that test is not going to be as accurate because the baseline measurement with impedance pH testing is really low. So you can't tell if someone is truly reflux ing so impedance pH monitoring. We were telling people, Don't use it. If you know someone has essentially esophagitis or Barrett, who are your disease? Essentially reflux disease reflux patients. So we're saying to use it in the non erosive group and or in patients to distinguish the hypersensitivity from functional disease. Well, the concept of mucosal impedance came about from that, and that if patients truly those that truly have the disease have alteration on the mucosa. And also they've been publications from our group and others that have shown that when you biopsy the esophageal mucosa, they're dilated inter cellular spaces. So those taken together suggest that perhaps during endoscopy we could just touch the lining of the esophagus and the alteration in the lining of the esophagus or the epithelium could be enough to tell us whether someone has reflux or not. So it's a simple concept, but what's interesting is sometimes good things happen when you think simply and in this case, can we diagnose it quickly by just touching the lining of the esophagus to see if their alteration. So that's where the concept came about. And in the original studies that we've published in 2012 during endoscopy, we actually inserted a catheter through the channel of the endoscope, and we had a catheter that had impedance rings on it, and we actually opposed those impedance sensors onto the lining of the esophagus. We could tell whether, obviously, endoscopic we someone had esophagitis, but we were touching that mucosa above or below it to see if their alterations. And if those alterations can make the diagnosis in someone that doesn't have new coastal changes. Ie esophagitis So and this is a pictorial of what we did there. This is the catheter. This is a bit of esophagitis right here. You see, it's about great esophagitis. We were touching the sensors along the epithelium, but really, these sensors can be anywhere on this epithelium to see if someone has reflux. This is this is the result of many of a couple of years. At least 23 years of research on this. I'm gonna focus on this group in the middle. Esophagitis. So each of these dots represent patients. Um So what you see is patients with the salvage itis eat positive. Those patients had lower mucosal impedance. This is that five centimeters above squamous columnar junction, then patients that had normal. That's the negative. PH negative, Normal pH and normal endoscopy ie your normal subjects. So mucosal impedance is lower i e. The mucosa altered in those with esophagitis. Well, what's important here is we're not saying it's lower at the esophagitis site. It's lower in the normal appearing mucosa above the esophagitis site. That's important because what this concept tells us is that mucosal impedance can tell us alteration from reflux. Then we said, What about someone that is endoscopic Lee completely normal? But pH is abnormal. That's this group here. And what will you see is that it's very similar as faras the mucosal improvements fine compared to normal Akhil Asia. We did a few patients with that Kal Asia as our second control group. So ignore that for now. But we also observed was that this finding was not unique to a salvage itis or abnormal pH that our patients with Usain, a fellow cassava Ghitis, also had very low mucosal impedance. This is theologically make sense because that's the group that also has alteration under Asafa Geo Epithelium. But then the question becomes, Can we distinguish e o e from reflux? But before we get to that, I want to show you about pre imposed therapy with acid reflux. What happens and someone where the mucosa showed low mucosal impedance when you and it is from reflux, when you treat it, those values go up to normal sizes, which makes sense. You're now healing the esophagus and this semi technology is able to tell us whether that's true post therapy. Now, this is the pattern I wanted to show you in distinguishing reflux. Which are these? The two graphs in the middle esophagitis positive and blue ph positive Onley in green. On What you see is the pattern off that epithelium is different than patients that have these center filic esophagitis in e o E patients have abnormal mucosa and the distal esophagus. At two centimeters, it's abnormal at five, and it's abnormal. Attend IE along the ISAF figures that petroleum is an abnormal. That makes sense because E O is a pan esophageal condition where the whole epithelium is affected and that's what am I shows us in reflux. What do we see? What we see is that the distal esophagus is more so effective than the proximal. That makes sense because this still esophagus is in proximity to the stomach, where gastric juices and bile acids. And that's where you should see changes and or esophagitis and the mucosal impedance shows us that, and that's different than in patients that are normal. So again, there's a nice distinction between the three important diseases. What's important to know about this is that we can give this diagnosis within 5 10 15 seconds during endoscopy so patients don't really have toe have a catheter through their nose for 24 hours, have a wireless pH testing for 48 or 96 hours. We can actually distinguish reflux from non reflux from E O. E. Within 10 seconds or so during and dusk, so that's very important. Now here's an example of a patient with girl. This is an actual tracing. You see, this is mucosal impedance shown on the access here, and you notice that the values are low. And then this blip is when we shift from two centimeters toe five centimeters, it goes higher and then attended normalizes. So remember, low in the distal esophagus and normal in the proximal. That's the reflux pattern. And this is low that stays low along the esophagus. That's the E O E. Pattern. And then when you look at the test characteristics we see that has very high positive predictive value specificity of 95% sensitivity close to 80%. And you see these positive likelihood ratios, negative likelihood ratios. The point being very good test to decide whether someone has reflux or not. What about Ellie? What happens if you treat patients with Joey? Well, this is a nice example. Doctor Catskill from the Mayo Clinic employed this device and his patients, and you see mucosal impedance values here and you see 25 10, 15 are along the esophagus at two centimeters, 5, 10 and 15 above the G junction. What you see in someone that has active disease. Yo is lo, and it stays low across the esophagus. But when you inactive, meaning you treat the patient notice it normalizes, it actually comes up, and controls are appear, so the values come up close to controls. The point being. You can tell whether someone happy Oh, and you can tell if they're eo is treated and how well it's treated based on the measurements with them. I and when you look whether or not this actually correlates with use NFL counts, there's a nice inverse correlation between impedance values and Eos. So what does that mean? That means the higher eo count, the more likely your M. I will be low or show that the patient has E O. And that's very important to them. The other thing is, then you could ask the question. Well, then why do you need to biopsy? And I would agree with you. You, you know, look at the sensitivity, specificity, positive predictive and negative predictive value. This was This was one that it's actually now in not impressed. It's published already on. What we showed was what if, during endoscopy, before we even biopsy the patient, we would determine if the patient has the Oh, you're not solely based on em. I Then we use histology to confirm if m I was correct. And as you can see, obviously everything is beautiful. I eat You don't even need the biopsy results. You can have the report based on M I and diagnosed the patient right at endoscopy while the patients sleep. When the patient wakes up, you can tell them if it's b m I pattern versus not, it's up to you to biopsy. There's big controversy right now about should one really biopsy, um in the esophagus? Because do eo counts really mean a whole lot, especially early on. Alright, some have questioned Well, can you use the currently available impedance pH testing and tell whether someone's mucosal impedance is abnormal? Thea answer is you could but the problem is, the values you get will be all over the place. As shown at the bottom two graphs. The catheter that is placed in the esophagus is uncomfortable. The patient is awake, they have to be monitored for 24 hours and you don't know if those impeding springs are touching the mucosa or not. So that's where the variability comes in. While the ones up here are the mucosal impedance values, you see how tight those values are. So to me, um, it's a no brainer as far as using the am I while the patient sleep, Then you don't have to quote torture the patient, but putting a catheter through their noses. All right, this is the M I sensor. Um, that was next developed. Remember, the first generation had the catheter that we put through the endoscope. The question became, Well, you know, it's a bit tedious to touch it. A to touch it at five. Touch it. A 10 have to move it up. Why not have the sensors on a balloon where you could just blow up the balloon touch the entire esophagus in the radio and an actual fashion I e. 3 60 all the way up and down the esophagus? And that's that led to this device where you can see a balloon that has all of these sensors. This is where the balloon's deflated to the right is when that balloon is inflated and you see each of these small, um, squares are actually the sensors, so nine sensors per strip and then you can see that in this generation of mucosal impedance, we have four strips. So each of them were 90 degrees separated to see whether or not that gives us additional yield un diagnosing reflux from e o E from control. And this is a picture off that device. Closer up with all the sensors. This would be introduced. Wilder patient is that it's sleeping at endoscopy. The balloon would be inflated for about 15 20 seconds and you get the values. Now, this is the picture you get with the balloon. So I'm gonna guide you through this. Remember? I said nine sensor, so 1 to 9 and then you have the four different strips. A LPR is anterior lateral posterior. And right, So what you got our the four different strips at different location, each of them providing the mucosal impedance values. But we're not going to depend on those values. The computer is going to tell us the pattern off normal versus GERD versus yo Yo, This is a normal pattern and you see the contour plot. What the blue and the green are showing us our that these values are well within the norm. They're very high. You noticed? Here the numbers, Aaron the 9 9000, 6000. This is a normal pattern. Here's the comparison of this normal pattern to someone with Joey Red indicating very low and my values all along the esophagus. Remember, patients with the O. E. The mucosa is affected the whole way. So you expect Am I to below the whole way and remembering GERD am I would be low in the distal esophagus shown here in red, but yet it would be green or blue. I e normal as you come up. So this is a GERD pattern. So let me now show you a video and tell you so this is live while we're the patients sleep the balloons inflated and this is in seconds were actually obtaining all of this. And we're getting a nice contour. And you can tell you can tell from this while you're scoping the patient that this patient, the values air normal thes air all normal contour us. It's next. Well, this is good. Remember, I showed you low in the distal esophagus. Normalized higher. This is a good pattern So let me show you a video of that. Here you go. This is live while the patient sleeping and my values air low and higher. Approximately. So this is a beautiful contour off someone with girl. We didn't have to do pH testing. We didn't have to do catheter testing in this patient. Next, remember, this is the contour of the O E. And my values are low. There are low all over this still and proximal esophagus and in all direction. So here's a patient with the O. E. While we're obtaining the values so quickly we obtained the data. We tell the patient we don't do any further testing and then we guide our treatment based on the data. So the aim of this is really to help us as well as help the patient and reduce the comfort and the cost for the patient. Alright, So next was what we had four sensors. Can we really just due to censor strips as opposed to four sensor strips? And we did a study that showed really, um, one or two sensor strip would be as good as the force of the four. Didn't add much. So where we are now with the current design is the balloon that has to sensors. I'm sorry. Um, two strips of nine sensors each. As you see here, there are 180 degrees apart, and this would be placed at endoscopy when the patient sleep. And the distal part, which is shown up here, would be at the square mall. Colombia are junction, and the rest would be in the proximal esophagus. And you get the contours that I showed you to see if someone has any of the conditions we discussed. This is these are now the data from the balloon, which are this day. This paper is actually submitted for publication and is being reviewed. And again, it highlights what we found with the other system. But the data are more tight because we have it on a balloon system that, um, takes away the confounding of liquid and air around the catheter. And what you see is eo is low and well, let me go forward. I'm sorry. Yo is low, and it stays low along the esophagus. GERD is low, increases as you come up along the esophagus and the normal stays high. So that's the pattern for the mucosal impedance that's very consistent with the balloon. The current generation vs deal. And this tells us about the This is an or OSI analysis showing us the sensitivity, specificity and the test characteristic for diagnosing each of those three diseases by, um, this current balloon Emma. So finally, cut offs versus probability. What's important to know that the way we currently use ph testing or impedance pH testing really anything is by saying All right, if you're above a certain point and it's abnormal, then you're abnormal. I e. Your test is abnormal. However, what we do clinically is really based on probability that someone what is the probability someone has a disease? If I present with this Feige a two solids, I have food impact shin and then someone goes down and looks endoscopic. Lee sees furrows. All of those are adding probabilities. Then when I biopsy comes back high and your center fills, that adds further to that probability of the diagnosis. So, with mucosal impedance, we're hoping that will be more than just the cut off that will really give you a probability. So what does that mean? Um, I'm gonna actually skip through this and show you This is the software that were, uh, that will be coming out. Hopefully regarding impedance monitoring. Focus on the right hand side. Actually, let's talk about in the middle in the middle will show you the strips and the values. There will be a nice contour off the impedance to help you, but that doesn't really help you. Just looking at the contour. The probability will tell us in a in this patient, what is the likelihood that they have disease based on that contour in this patient says 67% likely it's reflux. 2%. It's yo e 31 non io e. I'm sorry, non ger. So then you use this probability based on the probability of all the things you know about that patients such as the patient presented with In this case, let's say heartburn. Heartburn is better on PP I, but they're regurgitation continues. When you did an endoscopy, that was a nice size height, a hernia. You do this and what that tells you is, well, the patient has the disease, they have reflux, and this test alone gives you 67% probability, but your clinical values. Add to that probability, and your diagnosis in this case would be heard. And that's how you essentially utilize this technology toe. Add to your clinical judgment about what the patient might have or might not have. So I have only two other slides to show you, and this is a slide. I don't want you to read it all to just look at how complex our diagnostic strategies on algorithms have become about reflux disease. This is not user friendly, for me is the expert. I don't like to write these guidelines, and these algorithms Simplicity is best that helps our patients more. So what I would suggest, hopefully with the mucosal impedance to really change that algorithm, the future state algorithm would potentially say, If you suspect someone has reflux where there would be a Safi Jeel or extra safi geo, you treat them with once or twice daily therapy for 1 to 2 months. If symptoms improve, you don't need to do diagnostic testing. You have your answer. Start high trading that P P. I to the lowest dose of acid suppression. However, if symptoms don't improve, then that's when you start doing your endoscopy. You could potentially do the coastal impedance. And if it's normal, remember, normality is more common in this group. Then you start looking for other potential diagnoses. What are those potential diagnoses? Well, the patient that comes in and they have epic gastric discomfort and the try PPS they're not better or a patient with heartburn that has tried. Pts they're not better. So maybe they have gastro Parisse is maybe they have functional heartburn. Maybe the diagnosis is really not re folks. It's something different. And could it be that a simple test during endoscopy could really be it? And then we can start looking for other diagnoses, so I'll stop there. Thank you very much, Doctor Vaizey. So we have several questions and we have a little bit of time if people want to type in additional questions as well. So you're ready for some questions? I'm ready. All right. Question number one a. Scleroderma patients. How can you distinguish between nerd herd Barrett's esophagus with mucosal in people's? Yeah, so that's a good question. So it really the condition doesn't make a difference. This words, whether you have scored or um or not in a patient with scored ERM Oh, remember, their motility is affected, right? So the reason you score derma effects esophageal motility, which then leads to either ineffective or no motility at all. Because of that, patients get esophagitis, which we can see during, and that's compete. So that's easy. If you see esophagitis, you don't need to do, um I or ph testing or impedance pH testing or biopsy. You already have the diagnosis, however, Oftentimes you don't see that often times you go in and it looks mucosa looks normal. That's when you could do the Emma. Now what about Barrett barrettes? Visually, you're going to see changes along the epithelium Colome notarization, right? So it's a meta plastic process. The mucosa looks pinkish. If you don't do endoscopy, that's when we biopsy, and we can then look at it and see whether it's barrettes or not. That's usually easy to do during endoscopy. If you see barrettes or suspect parrots, you don't need to do any other tests because you already have the diagnosis. The esophagitis barrettes easy. You don't need any further testing. It's the non erosive group, which is most of our problem. 80% plus of our patients right now where we suspect reflux, whether they have scored them or not, Mucosa looks normal. So that's where all of our diagnostic tests come in. And that's where potentially m I could be offered. Thank you. Here's the next question. Can you Kozulin Petain's differentiate between this plastic and non dis plastic barrettes? Oh, that's a good question. Smart question as well. They're all smart. These are all great questions. Um, we don't know mucosal impedance of the new technology. Likely not. So dysplasia. Remember, Is the history pathologic diagnosis. So can m i. B used to histological Tell us if a few of the cells look this plastic. I would guess again, we haven't done those studies. Interesting to do, um, to see, wouldn't that be interesting? Because then you wouldn't have to depend on all the issues with histology and variability of our pathologist looking at it. So a study to be done, But I'm not sure if a my sensitive enough to pick up cellular changes at that level, but something to look into. Thank you very much. Next question Is mucosal impedance affected at all by anesthesia medications? Um, not that we know of, you know that question comes up about many of our tests. Right? That includes impedance ph testing, Bravo, pH, testing catheter, pH testing. Not that we know. Because what anesthesia might affect ISMM or again, the motility pattern. And that doesn't necessarily impact epithelium. So not that we know. Okay. Do you do you coastal impedance in L. A Grade A and L A grade B patients? Yeah. So there's that controversy about, you know what is l a great A, Some have argued could be normal. Many patients, many subjects normal subjects might have great A. So I would say I wouldn't do it in cnd for sure. Be, I would argue again, depending on if it's just really a subtle change that is more than five millimeter. Because that's how B is defined. I would probably do it in A and B, but not in cnd. Okay, we only have two more questions. So here's the next one you Kozulin people who just got a therapy. So you kozulin Peters for LPR diagnosis. Any possibilities? Oh, that's a great question. Stay tuned. They're actually a few centers. Um, that air looking into this to just give you further information this is really generated. Such excitement because these have been presented at our national meetings digestive disease week, the A G eight meeting as well as a C G meetings and others, and has created a lot of excitement by many investigators. And this device is now being used at various institutions to come up with some of these answers. LPR Wouldn't that be great if by just touching the lining in the esophagus or elsewhere for us to see alteration that distinguishes which of these patients that have either sore throat, hoarseness or cough It's from reflux versus those that it may not be so that that that we're hopeful and a lot of studies on that we've done some of those. But some of our colleagues, other colleagues there doing it as well, Thank you is the sensitivity and specificity for acid and non acid reflux the same using mucosal in peace? Yeah, so good question. So that gets into the physiology off what causes changes in the esophageal epithelium. So when you look and the olden days studies, you know, using rabbits and you know dogs where you infuse asset or acid plus peps in or acid plus peps in and bile assets again, those are what we call non acid reflux, right? So if asset is out of the picture and you still have Pepsi in, it doesn't do much. However, if you have bile acids plus acid, plus Pepsi in the injury goes up and those cells start dilating that dilated inter cellular space. So the question then becomes, Can you look at a patient that solely has bile reflux or non acid reflux, if you will, and see alteration that you don't see with someone that has, say, a combination study to be done because there's only one patient population that you could really study that in. And that's people that have had gastric surgery patients post uh, Gastrectomy, Bill Roth one or Bill Roth to an Eskimo sis, where they have a lot of bile reflux on. One could look at that, um, assed faras the population that we're currently using impedance pH, where it's telling us there's non acid or weekly acid. We don't know what to do with that. Clinically is, you know? So theano, sir, is we don't know. We gotta do studies on it, but we're hopeful that it guides us in patients, no matter what, whether it be acid or non asset, no matter what the ideology off those two that m I can pick up alterations in the mucosa from either one. And that's where the next generation of studies looking. Thank you. Next question. Asian people do not have typical findings of reflux Esophagitis. Did you measure mucosal impedance and Asian people without definitive evidence of reflux esophagitis? Yeah. Actually, that would be a perfect population, because that would be the non erosive group. Right? So, um, uh, many of the countries, actually, you know, esophagitis maybe more common in us and some of the Western societies in Europe. But that's not the case in other countries. So it would be a perfect to to use in that group because you don't have endoscopic evidence for it and what you could do impedance ph and torture the patient, if you will, you could do wireless capsule for two days, or you could just touch the lining with this and tell whether it's normal or not. If it's normal, you're looking for other causes. If it's abnormal, at least you have your diagnosis. So to me, that would be a perfect non erosive patient population to use it. Thank you. Next question. Do you do mucosal on Pete's because I'm being some peopIe I on once a day or twice a day, PP? I check response. Oh, that's a good question because that's the current controversy we have now. So right now we argue. Should we do on therapy testing? Should we do off therapy testing? Should we do Bravo pH testing off therapy? Should we do impedance pH testing on therapy? So that's the controversy. And we've created that by the uncertainty of all of these diagnostic tests, Right? So if you did this off therapy and if it was abnormal, it says you have reflux. If you did it on therapy and it was abnormal, you have reflux. So it really doesn't matter in that if it's abnormal, you have reflux, and that abnormality can be detected right then and there. But if it's normal, then you have your answer as well. So to me, you could really do it either. And that's again subject of studies, to see where it fits and what the possibilities are. But to me, the way I see it, the future state of what we would recommend. I would say you could do it off or on the way I would probably do. It is innovation I want to send to surgery just like we do now. I would take them off, just confirm they have the disease in a patient that, let's say, has cough. No other problems. And I don't think they have the disease clinically again. The probability that they have it is low. I would also take them off to show that they don't have the disease. And someone like asthma patients with asthma. They already have heartburn. They have regurgitation on therapy. Maybe the heart burns better, but the regurgitation continues. I would do the M I on therapy in that group, but the point is, you could do it either. And that's the beauty of this technology. Here's a great question for you. Do we know how long the patient would need to be off therapy in order to develop detectable changes? You have great questions, so we know right now is you all know we recommend patients to be off therapy for 7 to 10 days for PH testing or impedance pH test in, But this gets deeper. This gets into the physiology so very intuitive and smart question. So how long does it take? Let's say I have esophagitis. I took my BP ice for a couple of months myself. Vaginitis is healed. Now I get off of it. How long does it take for my esophagus to show changes that could be detectable with them? I what a great question. And the answer is, we don't know that. In fact, nobody knows that this is all subject of studies that are going on. Like I said, there many centers that are doing various studies, and when this comes out in the market, we hope that we could just take this. And just like we've done with many of our other diagnostic tests, answer all of these questions, which then inevitably will lead to, hopefully a better algorithm for our patients. But right now, I would say, if you have to guess if you will, um, I would have the patients off for a least two weeks, um, to look into it. If you have moderate to severe reflux, that's more than enough. In fact, many of your patients, when they get off therapy, they'll tell you. Oh, my goodness. After the first few days, I was off a miserable. So in that patient, probably seven days is enough. Whether you should see a soft edge. Itis is a different issue. Whether you see alteration, I believe you will see the alteration before you see esophagitis. So for that reason, in someone with more moderate to severe reflux symptomatically you probably could take him off for seven days. And someone where you know, it's not as moderate to severe. You may need longer a couple of weeks, so I would say 1 to 2 weeks would be okay, but we got to do studies to be definitive. Okay, Just two more questions. One Can you touch just a little bit on the use of mucosal impedance in the pediatric theory population? Yeah. Good question. We actually published on this. There is a studied, um, I want to say a couple of studies from our colleagues uh, the pediatric uh g I group that published this They actually the pictures I showed you were in adults. The data and publications, but it has been published in pediatrics. Have mirrored what we have found in GERD and in E O E that the devices implemented ble and useful there. Where might be different is the size of the balloon. We haven't used the balloon technology in the pediatrics. We've used the catheter, the one the one that you put through the working channel of the endoscope. And that's because of the size of the esophagus, right? It's different and adults than it is in pediatrics. So what I foresee is that we would have potentially balloons that of different sizes for the pediatrics versus adults to be able to be employed. But that has been done in pediatrics, and it's confirmed the adults. So it mirrors what we see there and in the pediatric as well. Um, that they're taking it one step further. And that actually treated some of these patients. And they showed that the mucus Olympians did improve upon therapy again, confirming that the changes were reflux related. So you should look that up, uh, in public. Very good. In the last question that that one of our attendees has asked is more of a technical question. Why did you reduce the strips from 4 to 2? Yeah, so, um, several reasons why have it if you don't need it. So my hypothesis going into it and what really led to having four you can ask that question in reverse. Why not have started with two and then go to four? Right? So we started with four thinking. Could it be that the changes that we see on one side of the epithelium in the esophagus let's say three o'clock would be different than, say, six o'clock or nine o'clock or, um, 12 o'clock? So when we did those studies that showed that you really didn't to distinguish those diseases Theoden sh inal to did not help. In fact, the additional three didn't know we could go with one strip. But the reason to go with two is because what if some of the sensors don't work or there's a dysfunction with them for various reason? Say the balloon was touched and or it was bent, or what have you, then what you don't want to do is miss the opportunity for the diagnosis. So the second strip is really to just allow for that efficiency of the diagnosis and not toe have to use another balloon to do it. That was the main reason you could just go with one strip. What we did the Ford to see whether or not you need any additional. And you don't a good question. One more question. It was just asked, What are the dimensions of the balloon And how do you know how much too inflated? Yeah, that's a good question. So the balloon the maximum diameter of the balloon that we have been using here remember my comment on pediatric That would be a different size balloon. But in adults, the maximum diameters two centimeters. Um, now, in patients with your center Phillip Esophagitis, you can expect some of them have narrow esophagus so the balloon can go up to two balloon sizes. If you will eso You can actually inflated Thio five or 10 p s I. So you could actually go halfway up or fully inflated in e o e. We attempt to go, especially if I see endoscopic lee that they have narrowing. We go up to five in normal subjects. Normal esophagus. We go up to 10. Okay, Good question. E apologize. There was one more question. Uh, I miss before How often is it possible to have normal mucosal impedance results and present with GERD. Uh, well, that really gets Thio. What's the So what was the question? Have normal normal mucosal apiece. Yeah, get. And so that's really the specificity. Remember, the specificity or the negative predictive value is what really helps you. And that's so in e o e. Here's your negative predictive value. 100% essentially doesn't happen. And in here's your negative predictive value, 70% eso It's possible, but not that high. And you're positive. Predictive value 93%. So again the likelihood is low. But it can happen. Remember, no test is gonna be 100%. But the advantage of this device is not only is doesn't have high sensitivity specificity, positive, negative, but it's also more efficient in the way we diagnosis during endoscopy. No added one or two days of monitoring. So that's where the advantage comes in the additional event. And finally, are there any additional risks associated with mucosal impedance? Yeah. So the risk that I would see again remember I made a comment about you, so you have to be careful not to fully inflate specially if narrow esophagus. We've done that and especially in those that we were going to dilate their esophagus anyway, So that became a way of dilating the esophagus. But we didn't see much. Um, I would say probably a few percentage. I would have to pull the paper out, would have some new coastal bleeding, especially in the e o e patients lesson GERD. We don't see much in GERD. Patients could, because you're passing the catheter through the flow just like you do with any dilation. They might get a little scratchy throat for a day or two. We saw that maybe in about 30 40% of patients that the next day they were better but overall very minimal. Haven't seen any serious adverse event, which is, I think, what you're getting at. We didn't have any perforation. We didn't have any hospitalization. We didn't have anyone that had severe paying from this. So it was really just subtle mucosal changes and some scratchy throat from the balloon insertion. Okay? And unfortunately, more questions not coming, but we've run out of time, so we will respond to the questions. I'll send them to Dr Vaizey and we'll get back to you. Each of you who have sent them because we have your email addresses. We certainly appreciate that. And with that said, Dr Bazi on on behalf of the first tech healthcare, we certain like to thank you for a wonderful presentation of mucosal in peace. Thank you very much. And roll Tie Peralta. Uh, okay, thanks. Created by Related Presenters Michael Vaezi MD, PhD, MSc, FACG Professor of Medicine Professor of MedicineGastroenterology, Hepatology, and Nutrition View full profile
