Chapters Transcript Video DDW 2021 Product Theater: Mucosal Integrity Testing Q&A Presented by Michael F. Vaezi MD, PhD, MSc, FACG, Vanderbilt University Medical Center, Nashville, TN um if you click on your conference will now be recorded. Ask any questions you have. So please feel free to ask if you are asking your muted so you may have to click on that red button, audio on your screen. There's also a chat function I think on this go to meeting. So if you feel more comfortable clicking on that and typing your question, happy to answer. I hope that uh we'll be able to talk about reflux. It doesn't have to be mucosal integrity per se. Although I hope you will ask about that. It can be about reflux, about diagnostic testing, um about how this device fits within the current diagnostic tests. So are there any normal parameters established? So one of the questions that was just typed in was about normative parameter for mucosal integrity. So remember as we were talking about the normative data, the answer is yes. And that normative data is based on um how it fits within norm and abnormal. And what do I mean by that? We're used to a cut off say ph anything above say 5% is abnormal. Or if you use the Leon classification if anything above six is abnormal. Right? As I was outlining there's a problem with that because it's so dichotomous. So the abnormal values that are defined by M. I. Is more of a spectrum. So what it does is it takes the probability of the disease based on all of the sensors. So remember their 10 sensors along the esophagus From this due to proximal and then there are two strips of those E 180° apart. It takes all of that data. It integrates it into an algorithm where then it says does this fit more than normal or does it fit more the abnormal I eager or does it fit more ceo. So it uses all of the data within the measurements. You're getting five second measurements under six of them. And it integrates all of that data. So you can imagine it's a lot of data but the machine and the software takes care of that. I hope that answered the question. Yeah, you're welcome. It's good. I think that was critique asking the question. Thank you so much. Any other questions? Okay. I have a question. Yeah. Mm. Oh hi nelson. How are you? How fine. Thank you. Can you speak louder? I have a hard time hearing. I have two questions. How about you? How do you measure symptom correlation if you obviates reflux monitoring to still living folks monitoring for symptoms correlation? Uh that's a great question. So what nelson And again, nelson is well informed in this area and uh he he knows this area better than a lot of us. So the thing about symptoms indices that nelson's asking about is using symptom index or symptom association, probability. We're used to doing that in that the software will if you use ph testing takes the symptoms that the patients push and then it uses a chi square and it sort of comes up with an association possibility. I don't use nelson, I don't use something appendices in assessing disease and whether it correlates. Because we've published studies that essentially shows that if there are many reflux events by ph testing only, you're always going to get a positive response no matter what the symptom is. I e if you push a few times or a lot more because it's highly dependent on reflux events, then if you go to people that don't have much reflux, um I know you probably have these patients where they come to us, they have no heartburn. Let's say they have call for sore throat but they have 100 events. Right? And your symptom association will be positive because they push the button enough to show an association. So there's some artificial nature to symptom and disease. I don't use it commonly and um we don't use it in Newcastle. And I hope that answered your question. You have a second question is which is how do you explain the viability of basil impedance at night? During impedance page monitoring? Yeah. So that's a good question. So I showed that slide of variability, some people say why can't I just put that catheter down and measure the same thing that you saw that slide. In fact, if you look at any of us, if we have ph impedance tracings, the variability is great because you don't know at what point the catheters really touching the mucosa? Is it touching the saliva? The patient just swallowed? Is it dangling in the air? If you will as the patients move from right to left back. So there's a lot of variability nelson. So that's a great question. But with this is like, should you use the lowest impedance? Because then it's the time when the character touches mucosa. Um you could. But the problem is now you don't know whether that's because of the saliva. So the artificial nature, you know, you don't know and that's the point when you don't know and you can't guide it right on the mucosa and you don't know whether it's artificially affected. You're sort of going all over the place. You could use the lowest, you could be biased, you could use the highest, you could be biased and you saw that spectrum, right? It is all over the place. What about the suffering measurement of the entire period night period? You could do that again, you're sort of combining the entire night data to average. You're hoping that average estimate is close to reality. But then when you look at your confidence interval will be all over the place. Okay. You know, I see you're on Good morning Michael. Uh Excellent, very nice. I thought it was so good. I thought you were doing it live but obviously not. Um, you've educated us very nicely in this evolution from the standard cut off points to probability. But the fact of the matter is we're still left with at what level of probability are we confident enough to pull a trigger? And that trigger particularly is for surgery whether or not it be traditional or endoscopic. I can see the utility of the device when you're normal because I don't need that much confidence to say something is normal. That means I do nothing. Had them on the back and they go on their way. But how about the converse do you think we'll get to the level Of confidence? And probability is 50% probability enough. Do you need 70? I don't think I ever saw in the examples that she had 100% probability confidence. Yeah, that's a great question, Joel. I mean you more than anyone knows it. So I'll start up asked the question by saying what we're currently doing. So what are we doing with ph testing to send someone to surgery? So you use a cut off to call someone abnormal. But you don't use that to necessarily say yes, you're a good candidate for surgery. You use other factors. Right? So we use is there a hernia? Is there regurgitation? Are there heartburn better? But regurgitation not. Is the ph abnormal and hopefully moderate to severe rather than just barely abnormal? So I think we use a constellation. I don't think any tests including me is going to be one where we will solely rely on a value of let's say 60% likely to be good or 80% to say that patient is a candidate. All it's going to tell us is there's enough evidence here of reflux then we sort of put it in perspective of all the other factors. That's what I do. I would never use any test impedance ph on therapy off therapy bravo. Just endoscopy without all of those factors. And I think that's what you do joe. So what do you you know what do you think of that? No I think that's true when we're doing our traditional test um I think the question becomes with the new technology that you're doing again when you're moving away from the normal where I think, but I have maybe a major impact of cutting down on some unnecessary state, particularly bravos. Uh But when you does the impedance, have you seen particularly in your nerd patients? And these are the ones that are most problematic when we're talking about doing something that this, is there any signed from the impedance that would correlate with the severity of their acid reflux? Using the traditional quote gold standard that would be, say bravo ph testing off medication. Uh In other words, the more you've talked about and we've always liked the idea of using a 10% total acid exposure cut off as the patients that are more likely to have severe disease that we might consider for surgery. Is there any uh thing that the mucosal impedance would allow us to have some correlation with that? 10% or higher number? Yeah, that's good. You know, with grades of esophagitis. So if you look at someone that has great cnd esophagitis, absolutely. Then all of a sudden, then there's a mix within a B as we all know. And also non erosive, there's a mix of possibilities And the main reason, you know, as we were doing this for the past 10 years, we sort of tried to say, how does it correlate the problem is there are two different devices measuring completely separate things. Right? So one is measuring mucosal integrity. The other is measuring exposure to acid at a specific point. So the correlation and non erosive disease is not going to be there and it isn't and I don't expect it to be. But when you look at great cnd to get to your point because we know CND are going to have a lot more acid exposure then. Yes. So it's going to identify those that clearly have the disease. But in non erosive because it's a mix of things, you know what is a 6%, what's a 7%? It may tell us that patient is normal. So in fact, if anything, I'm wondering if this is not a more specific test to help us where we are today. What do I mean by that? We don't want someone that's 7% because they didn't respond to PPS, which is why we took them off and we're now testing them. We want someone that hasn't yet. So for that reason uh if you could mute your mic if you're not talking. Um but So in that group than it is more specific in that it's identifying more severe disease. Yes. And not the less severe getting to your point of 5-10 do I really am. I really interested in the 5 to 10 when V. I. D. Therapy didn't help their something. And you have data mike you were referring to to graze of esophagitis and we know that we don't really need ph testing when you have C. And D. Esophagitis with large high hernias and you're not worried about bill. Do you have data or as your group gathering data about the cut off level of say ph criteria that the impedance would be abnormally because you're alluding to the impedance is more likely to be abnormal when you have a larger acid load. That certainly makes sense. Are you gathering that data now? We are And in fact you know there was a pause in um uh the M. I. Issue because of Covid and what have you. And now we've garnered a lot more balloons and we purchased a lot more balloons. And we're doing all of these studies to just extend what you're saying Joel. Which is important is can we see what it is identifying? So let's say the more severe disease and then within the less severe disease, can we identify that? We don't want to call a cut off. I hate that. Cut off verb. Ege. But can we identify which patient gets better with surgical intervention versus not right at the end of the day. That's what we're interested in. Can it predict response to a surgical outcome in someone that may be partially responsive or to your first point, can you tell us this patient doesn't have the disease? That's easy. It can do that. But the second important question is the surgical outcome. And we do. We are studying that we're looking at the severity were also on the E. O. E. Part. By the way there are other diseases that affect the mucosa. In the entire esophagus. I see tons of like and planets. Well how does this distinguish? Even though it's easy because clinically looks different endoscopic lee. But what is the alteration in the two? How is it specific? How can we identify it? So those are the kind of studies that we're currently doing as well? Well this has been I mean I need to sign off and I don't want to dominate. But this has been an excellent presentation And very exciting for me to see you be able to present all this data that you've been working on for 10 years. So congratulations to everyone in a nice way to kick off virtual d. d. W. Thank you. Thanks so much joe. Other questions. Uh There was a question about um can one use it And unsaid ated patients without endoscopy? Uh The answer is it's gonna be hard. Right so you're putting a balloon through the mouth. I would not do it because the patients uncomfortable. It's a lot like doing a dilation and an incident dated. Um You can try it but the patient is not going to be comfortable and you're going to get variability because of that. I usually do it in patients to dated either conscious sedation. We've done it both ways or dipper sedation with propofol. The key is the placement. So during endoscopy you measure where the squamous columnar junction is. You then pass the balloon. Make sure that distal sensors two centimeters above square more Coloman are. Now then you're collecting data 10 centimeters along the esophagus and at 180 degrees separation. So that's how I would do it. I think the idea of doing it um un sedated all uh right now. No, but could future generation of M. I as we come up with those the you know, allow us to do it just like we do manama tree. We're looking into those as well. Um Let's see. Jack was asking as a follow up to the nerd question, what data do you have? A nerd severity versus reflux? And my measurement. So we do have patients. So we're studying non erosive disease and erosive disease as you know erosive diseases. Less common nowadays than non euros. It but we do have a lot of data in non erosive disease. Our goal is to really find out what um that overlap is we we know that in more severe disease there's more consistency and non erosive disease. We want to know um At what point can we say really? Um This is not anything to worry about. Remember the way we define. Non erosive now is based on ph Someone has seven and the 24 hours we're gonna call them reflux occurs. But I'm hoping with me coastal integrity. What will tell us is that group is actually normal. I even though ph picked it up as quote abnormal. Am I is gonna tell us this patient is normal? And the only way to do that is to have outcome studies, surgical outcome, medical outcome studies. And that's where we're going with that. The other question is, do we do this on or off therapy? And will it affect the results? We've done it both ways. So we took those patients that had reflux, studied them off therapy and the mucosal integrity was the pattern that it showed. So it showed. The probability is reflux when we treated them with PPS. What do we expect the Nikko cell integrity to recover? I eat your healing the mucosa and in fact it does go to look more like normal. So if you do this study on therapy and the patient doesn't have acid or bile reflux to a point where the mucosa is affected. You should see a normative data. However, if the patient has severe enough reflux, where let's say on once a day therapy, there's still alteration in the mucosa, then it will tell you that as well. And in fact, we're extending disturb patients with barrettes because a patient with barrettes that may have had a blade of therapy, we can assess whether or not that is that asset suppressive therapy is enough to allow that area to heal without continued exposure to asset. So, those are the studies were doing. I hope that answered your question. Now will the presence of a hernia effective procedure? Yes. In that if you follow the protocol iii find out where the squamous columnar junction is, then you're going to be above the hernia and you put this above that, then you won't be within the hernia. If you put it across the hernia accidentally or it's pulled in, then you're gonna get a false air and or liquid reading. So the key is placement of the device during endoscopy. You hold onto the balloon so it doesn't migrate forward. But otherwise, no. So that's really about how we place it. How long does it take for PPR to improve the dilated inter cellular space? In other words, if you're gonna do this on and off therapy, how long do you allow them? That's a great question. No one really knows the complete answer but we do know from esophagitis, healing studies on P. P. I. Is that if you do the endoscopy a couple of months later the majority of those should have healed. We know we have six month data as well but I normally bring them back in a couple of months after they've been on there. So it says can you go over where you place the catheter? I think we did that. Um But as a way of reviewing it again, what I do protocol was is I go in I measure where the squamous columnar is but I make sure if there's saliva or any liquid gastric liquid, I suction that up. This is important. You watch the mucosa, you go to the gastric cardio or body and suction any liquid. The reason we do that is we don't want the liquid to regurgitate during the test and give us a false reading. So watch the mucosa suction out anything in the esophagus or the stomach cardi especially and fungus. Then you can take the scope out and you put the balloon down. Make sure that The measurements are markers on the balloon, the Catheter, you put it essentially two cm above wherever the squamous columnar is. Then you inflate the balloon. The software will essentially capture six separate times and each of them five seconds. So it's really gonna be about a 32nd measurement. So you blow up the balloon, it takes a measurement. You let the balloon down, you do it again, you let it down, you do it again. So when you do that six times. The software then takes those six readings and says which two best correlated I. E. The most accurate data. And it uses that to give you the probability of the disease whether it be reflux disease or E. O. E. Or normal and then based on your knowledge of the patient's information, the patient had this phase asia and it looked like yo and if The probability says Yes 60% of the O. E. or 80%. Then you say consistent with the oh you make the diagnosis or however if it's a patient with heartburn and you want to know whether it's good or not and that's what we do in the future iteration by the way of the software will be able to switch the O. E. Diagnosis off so that if you're not interested in, you know, you know this is a patient either GERD or non gert then the probability will spill out is one of those two. So that's what we're working on. I hope that helps. And then you just pulled a balloon out and you're done nothing to come back for. Let's see what other questions it says. Where do you think that currently fits in the bird algorithm which is based on PHP. S. Classification? Well, that's where we I'm hoping this is my hope and the future. As we do more studies, I'm hoping this will eventually really replace the way we do diagnosis of refunds. So here's what I envisioned. I have a patient that I'm suspecting has reflux and it's bad enough that I'm considering surgical intervention. I've taken them off their P. P. I. I do the endoscopy as we normally do. Then I do mucosal integrity testing and it's going to give me information about whether there's disease or not right If there is no disease, I pause, I go, well, could that be a functional patient? I look for other causes. However, if it's abnormal, then it fits within my clinical ideology of could this be reflux, then I could potentially send the patient to have surgery. Now, if a patient has chronic cough, that's extra substitute and hasn't responded to twice daily therapy, they have no heartburn, they have no regurgitation. I really don't think this is reflux, but we still do this to prove to the patient and the referring doctors and to ourselves. It's not. I take them off therapy, I do the test, I do endoscopy, put the balloon down, it looks normal. I'm done. I tell the patient you don't have reflux. This is not going to be reflux related even in a patient with heartburn which could be functional. If it's normal, I'm going to look for other causes, essentially. We're going to use it the way we currently use ph testing or impedance testing, except what it measures is whether the patients had a lot of changes in the mucosa, as a way of diagnosing reforms. I hope that answered the question now, how do you interpret it? An abnormal on PP. I study insufficient acid blockade. Can this be non asset? So the point of this is for us to think outside of what we currently do, and sometimes that's hard because we've been doing this for 30 years, right? All we've done is ph tests. All we've done is cut off of normal abnormal is that acid is a non acid? What this test is gonna tell us is what's the consequence of any reflux. So if you reflux acid and vile and it causes damage to the mucosa, it's going to pick it up. If you reflux acid only and noble and it damages the mucosa, it's gonna pick it up if you re flux by alone, let's say someone's on therapy and that bile affects the mucosa. They'll pick it up. What will it not pick up? Well what if you reflux pile? But that bile doesn't cause damage to the mucosa and it's just regurgitation as a symptom. Well, it won't pick that up because it doesn't cause mucosal damage. But that's where your clinical judgment comes in. Just like we do now we're using impedance ph for 24 hours on therapy to say, is it non acid reflux? We don't need that because the patient tells you I'm on therapy. My heart burns better. I got tons of regurgitation. You do endoscopy, there's a 45 centimeter hernia. And the clinical picture picture fits. That's a regurgitation patient because of mechanical defect. So that's what it's going to pick up and not pick up. But I would argue clinically it's gonna pick up what you need. I eat any damage from any type of reflux onto the mucosa. I hope that answered that question. Let's see what else will will it be on or off therapy? You can do either. Right. We talked about that. You could do. I normally would take them off to see what the baseline is and then if I want to know if that that acid suppression is enough, then I would do it on therapy. But remember it's just an add on. When I say add on, it's just a procedure you do during endoscopy that adds maybe a couple of minutes to the procedure. So it's not one where you have to have. The patient must be monitored for 96 hours, 48 hours, 24 hours. How sensitive and specific is that? We published this? So there were two iteration that was the catheter. One another balloon one. So the sensitivity and specificity of a test, you have to compare it to something, right? So if you compare it to ph testing, it's pretty good. If you compare it to the norm, it's pretty good. But what if we compared to um predicting response at the end of the day? Any test we do? Does it help us predict response to an intervention? We're not there yet. Because again, this balloon was just recently improved. So the opportunity to do research here is huge because how will this fit into our clinical operations personally? I think the most important studies here will be when we do this in uh as a way of assessing response to either asset suppressive therapy or more importantly, surgical intervention. I hope that answers your question. Any other questions verbally as I look up text messages. Yeah, I think I've answered all of the ones that were on there. One of them. I think I got a couple about what the cut off or what the normative value is for. Am I? So you don't again as a way of what you the problem this year is the G. W. Is not live. But I assume Jenelle and stew that if you go to the website perhaps I don't know as far as seeing what the software does. I would sort of look look at it, kick the tires so to speak. So you know what the software will allow you to do when you put this balloon down and you um do the measurement. It gives, you go through all those calculations. You don't have to do anything and it really gives you the probability of a disease. And then you put that in clinical perspective for your diagnosis. So, um um I I you know, there's no quote cut off. The cut off. Is there's disease probability versus no disease? Probably. And then we use that to say, is it reflux or isn't it? I know it's a novel approach and we're not used to it because we're used to someone giving us a cut off. But if you like cut off, just used that probability as you're cut off, that if it says 60% likely it's good then it's going to be good. But if it says 40 60% E. O. E. Or not good, then that's what it would be. It says. Do you anticipate a rush of innovative procedural therapies I think by procedural, so there's therapies and then procedural therapy. So by procedural, you mean endoscopic intervention for reflux. There are some as you're well aware and um there are a lot of studies on that we recently published. So they're encouraging as far as their outcome studies for endoscopic therapies of good. But there are only a few of them now. Many of them are no longer available. So will there be a rush of innovative procedural therapies? I don't know if there will be a rush but I think there will be more data on what's currently available so that we can decide where those endoscopic or minimally invasive therapies for reflux fit. For example the links devices not really endoscopic, it's more surgical. Um And journalists to they're asking what the website address is. If you have information on M. I. So if you could post that um I don't know if they need to go to your website. I'll let you guys answer that. You can go to our website diversified healthcare dot com for product information. And then we do have a learning platform diverse attack you dot com. And you'll find more about my view on that platform as well. From a clinical perspective. Alright then there's another question. And does the O E N GERD, do they predispose to cancer? Um So we know GERD does through barrettes? Right. So um there's some studies suggesting even independent of barrettes but we know that chronic GERD that is not treated, there is a link to cancer, but that link is commonly through barrett. Uh E O. E. In fact, if anything, there's some data suggesting its protective of esophageal cancer. So I would say they're not the same. Um I do know that oftentimes we misdiagnosed because there's an overlap between E. O. Yogurt and we somewhat sometimes patients that have GERD we mislabeled as E. O. E. And vice versa because we don't do the biopsies in the right place for the O. E. What I do is I biopsy distal esophagus, proximal esophagus. I look in disk optically to see if there are furrows and rings classic and dystopic all the way up and if the biopsies plus that plus the patient's symptom younger, male or female with this phase asia, then that's the right diagnosis. Otherwise, if it's only in the distal esophagus, it's an E. It's a ger diagnosis. Not um There's a big overlap there, but as far as cancer risk, it's more with reflux through the barretts um And or independent up there, but not with you. Um All right. I think we have answered the questions that I see any other questions that I may have brought up as I've done the talking. All right. If not, you know, I think that was it. Thanks Doctor Baby. I appreciate your time today. Thank you all of you for joining us today. Again, you can go to our website for more information, diversified healthcare dot com or diverse. Thank you dot com from clinical information, um, and enjoy the rest of the G. D. W. Conference. Thank you for joining today. All right, guys, by nelson, by everybody. Created by
