Presented by C. Prakash Gyawali MD, Washington University School of Medicine, St. Louis, MO.
Good afternoon, everyone. My name is Stew Wildhorn and I would like to welcome you to the diverse A tech healthcare Webinar Syria, our webinar today systematic interpretation of this official testing and Burge we presented by Dr Prakash Diwali. Dr Guy Wally is currently a professor of medicine director of neuro gastroenterology, motility and program Director of Gastroenterology Fellowship Training at the Division of Gastroenterology Washington University School of Medicine in ST Louis, Missouri. He has an extensive academic practice and the SAF ecology and functional bowel disorders is actively involved in clinical research involving euro gastroenterology and motility with over 130 original peer reviewed manuscript within these fields. Before we get started, I just have a few housekeeping notes. First, we will be recording this webinar and we'll be posting it on diversity Tech University online in the very near future. Well, commuting everyone for the quality recording. Lastly, please type in your questions and we will respond to them this time permits. And now, without any further ado, it is my honor and privilege to introduce Dr Prakash Diwali. Thank you, Stew and welcome everyone to this webinar. I'm going to try and take you through evaluation off Asafa Jill testing and gird, And this is going to be, um, how I'm going thio my slides air not advancing, but I'm going to try and troubleshoot these. There we go when talk about initial diagnosis and then talk about reflux monitoring the role of Manama Tree and then finally, evidence and Fino types. And we'll wind down with the final summary. I just like to say at the at the beginning that this is the result off a census process that started about three years ago and allow the world's leading reflux experts met at various sites in Europe and North America and talked about all these different elements off the esophageal testing in the context of reflux disease. We agreed on most parameters, and there, there somewhere, there isn't a clear cut up and down or clear cut threshold, and we'll touch on those coming up. For those of you who would like to read about this, there are four manuscripts, uh, that came out nor gastroenterology earlier this year, and in nature reviews on Ben. There's a new manuscript that's going to be coming out in the journal gut sometime in the first half of 2018. So everything that ises part of this, uh, presentation can be found in one or another of these, uh, manuscripts. All right, let's start with the initial diagnosis. So, uh, when when assessing the validity or the sensitivity and specificity of initial diagnosis of reflux symptoms, uh, studies have used various gold standards. The issue with reflux disease is that it does not have a fixed gold standard. And so every test or every approach has a modified pseudo gold standard that that that particular approaches assessed against. So in this setting, clinical diagnosis, a diagnosis made in the office is assessed against the gold standard of esophagitis and endoscopy, or abnormal pH monitoring in the Sophocles sometimes symptom association. Probability of reflux symptom association is also utilized. So let's see how our standard approaches perform. You can see that the usual questionnaires used in reflux disease have modest sensitivity and specificity. A PCP history is marginally mawr sensitive than some of these approaches, and the G I history is also marginally better, but you can see that these numbers are not particularly exciting, so you cannot get past the 60 to 70% sensitivity and specificity just by history. Take it. If you were to give the patient a P p, I try ALS. And if this was for just any four gut symptoms again, the performance is worse than that obtained from a history or a questionnaire. Now, if you want to take a more detailed history and figure out that the person indeed is having troublesome GERD symptoms. So in other words, Asafa Jewel symptoms heartburn regurgitation, then your sensitivity goes up. But specificity is still not very good now. A couple years ago, there was some interest in salivary Pepsi having somebody spit on a commercial device and use the presence of Pepsi in in saliva as a marker for reflux disease. Onda, The thinking behind that is steps in comes from the stomach. So if you have pets in your mouth or saliva, then they might have been regurgitation. But the performance characteristics of salivary Pepsi and against the gold standard of acid exposure time of reflux Symptom association was abysmal, suggesting that we still are not very good at office based clinical diagnosis off gastroesophageal reflux disease. What about endoscopy? So if you take patients with D T. I failure in other words, people who are on pp i and compare those two people who have not ever been treated with the PP I. This is the yield of finding a rose of esophagitis. So if you were to endoscope somebody on pp the chances of finding a rose of esophagitis less than 10% and it's at best 30 to 40% in p p I naive patients suggesting that endoscopy is not a very good way of making a diagnosis of reflux disease. But endoscopy has some other benefits. You can identify Barretts esophagus. You can find the hiatus hernia, which can contribute to the path of theology of reflux. You confined peptic strictures, so there is some added yield. But if you're just going to look at arose of esophagitis, the likelihood of making a conclusive diagnosis is very low. And even when a savage itis is seen, the grades of esophagitis that are encountered are low grade L. A Grade A or L. A great beasts of these air just limited erosions in the distal esophagus. The problem with these low grades of esophagitis is that these can overlap with asymptomatic control. So up to 8% of asymptomatic controls can have l. A grade A or L a great d esophagitis, which tells us that using these lower grades of esophagitis to make a permanent change to somebody's this Africans, in other words, to send somebody for anti reflux surgery is probably not reasonable. Thes grades, especially L a grade B, may be enough to start somebody on an asset suppressant. It is very unusual to find L. A great c o L a great d esophagitis on in asymptomatic control. So these high grade findings in the esophagus off esophagitis are conclusive for reflux disease. So endoscopy has high specificity when abnormal but very low sensitivity for the presence of Gert. What about Barrett's esophagus? Well, we do much better with Barrett's esophagus, so the likelihood of having an abnormal pH study is in the high 95 97% range. In patients with biopsy proven Barretts esophagus. Here is another study that has acid exposure time on the Y axis, and you can see healthy volunteers. The rows of esophagitis short segment Barrett's long segment barrettes and clearly, patients with Barrett's esophagus have a higher acid exposure time, suggesting that endoscopy proven or biopsy proven Barrett's esophagus is a conclusive finding is a is, you know, adds ah, lot of confidence to the presence of GERD. What about taking biopsies in the esophagus? And then the reason to take biopsies would be if you scope somebody. There was no esophagitis, and you're looking for microscopic esophagitis. Ah, better reason to biopsy somebody's esophagus is to rule out using the Phillips Esophagitis. But let's say you've already excluded that there are some findings that can be suggestive of reflux disease. One is allegation of the population in the mucosa. Second is hyperplasia, inflammatory cell infiltration in the base layer, and the third is dilated inter cellular spaces. Now, if you just took one of these are just took these at face value, the confidence in a good diagnosis is not very strong. But if you were to find a dedicated pathologist and used a history pathology score, taking all of these features into consideration, um, you can see from this life that you can segregate arose of esophagitis clearly from functional heartburn and from controls. But this there is still difficulty in separating non arose of reflux disease from somebody who has normal ISAF geo acid exposure time but has sensitivity and feels the reflux episodes more often. Now you can use electron microscopy to identify increased inter cellular space, diameter or dilated inter cellular spaces. And this performs a little better in segregating patients with functional heartburn of controls from those with reflux or true reflux mediated symptoms. However, this is cumbersome and you need a dedicated pathologist. So Routine has to Pathology, even in expert hands, is not conclusive. As a standalone test for good, we'll talk about where it might fit in into the big picture later on. Now let's talk about ambulatory reflux monitoring. This is the point where you were transition to doing invasive testing of this kind because the patient is probably still symptomatic after PP I trial and endoscopy has not been conclusive. The conventional technique is a catheter based study. This is actually a PH. Catheter with two sensors, one in the distal esophagus and 1 15 centimeters approximately two, that, uh, pH impedance catheter looks the same. It just has additional impedance catheters, so this is a reliable, time tested technique. There is no dislodge mint because the catheter is taped to the nose and it is placed by a new experience technician. The problem is, patients hated. It limits the activity. And there is also the issue off the tip of the catheter dangling in the middle of the esophagus, which means that the esophagus can shorten around the catheter and the tip could potentially dip into ah, hiatus hernia, for instance, and elevate acid exposure time. Nevertheless, pH study of this kind of catheter based study has been used for decades now and does provide information on this official acid exposure time and symptom reflux association. So this is what a NAB, normal pH pattern might look like on the raw tracing. Uh, the white line in the middle represents a pH of four, so any drops below Ph. Of four is considered a reflux episode that is usually a sharp drop, followed by stepwise. Return to baseline Um, which is related to secondary parastatals, is as well as primary parastatals is bringing saliva into this Africa's to neutralize new coastal acidification. So the metric that is addressed or extracted from these air all values is the acid exposure time, which is the cumulative time. The pH is less than four as a percentage of the duration of the recording, so each drop the duration of each drop is calculated by software and expressed as a percentage of the duration of recording. The other entity that can be extracted is what's called reflux symptom Association or symptom reflux associations. The patient work to have heartburn at that time point, and if this was within two minutes off the onset of the reflux episode, then that symptom is considered. Associate it with that reflux episode. And there are tests both a simple tests like the Symptom Index and a more complex tests, like the Symptom association probability that provides some quantitative of Symptom Reflux Association. Let's talk about PH for a minute. So if you look at studies that have tested normal, healthy individuals and recorded the acid exposure time, you can you see a range, um, between the various studies and based on this range threshold of 4.0 or thereabouts, four point our 4.2 has generally been accepted as the upper limit of normal. Now, if you look at patients with a soft edge itis visible esophagitis, they're acid. Exposure tends to be much higher. Patients without esophagitis is a mix, and therefore there is a gray area he can throw in wireless data there, too. There is a gray area where there is overlap between patients with or without esophagitis and healthy controls. The GERD Consensus Group agreed that a threshold of six could segregate patients with esophagitis, a pathologic girl from those without such that if the pH is more than excuse me if the acid exposure time is more than six, that is conclusive for reflux disease. In addition to consensus, this is partly based from the fact that patients with high acid exposure times tend to respond to enter reflux surgery. Where is it's a mix in that borderline area between 4 to 6. So pH thresholds, excuse me, are partly based on evidence, but I'm mostly arbitrary and based on consensus. What about prolonged pH monitoring? We have the ability to place pH probes in the esophagus that are wireless and much better tolerated by patients. So this is a very interesting study from a few years ago where 50 patients with normal normal acid exposure time on day one we're followed out through the four days of the study and, um, at day four, only 35 were still normal. The remainder had abnormally acid exposure times on one of the other days other than day one. So if you had somebody with elevated acid exposure time that fulfills criteria modern criteria for the diagnosis of non Arosa reflux disease or nerd. So if you looked only at Day one data, you would have missed these 15 patients, which actually had nerd and not functional heartburn, as the day one data would suggest where there was normal acid exposure. So there is day to day variation in asset exposure times and prolonged pH monitoring is particularly useful if the standard pH tests does not show this day Today variation. In other words, you caught the patient on a good day. Prolonged monitoring is also useful for symptom reflux. Association of symptoms are infrequent, and generally this is better tolerated by patients. The importance of making a nerd diagnosis here is that if you make a diagnosis of acid based disease in the esophagus, response to anti reflux therapy is much, much better than if there is no acid triggering symptoms, but interpretation and clinical value prolonged pH monitoring needs better clarity and we don't have good metrics. Should you use the worst day should use the average values. Should you take too bad days, we don't really have consensus just yet. We do know that prolonged monitoring can help clear situations where values are near the threshold off normal, especially if something invasive needs to be done. And then there is impedance. So let's start by talking about what impedance is. Impedance is actually the resistance to passage off a current through electrodes embedded in the catheter. So tiny current is passed and the resistance to passage of current between the electrodes place in this Africa's is what is measured and that resistance is a function off the baseline tissues around this Africa's, but also the presence off content in the esophagus. If air is present, the resistance is high, impedance is higher. You can see that spike. If there is a bullish liquid Bullis, then impedance goes down and then comes back up to baseline when the bolas passes. If you have multiple impedance electrodes on a catheter, then you can look at the directionality of the impedance drop anta great for swallows, retrograde for reflux episodes. So when impedance was first introduced. There was a lot of excitement about this technology. It detected Mawr reflux episodes compared to ph monitoring, and you did not need a pH drop so you could detect reflux episodes even in patients who remained on their assets. Suppressive medication. So with pH monitoring, you need them off because otherwise you wouldn't be able to detect the pH episodes PH drops, whereas with impedance, you don't necessarily. You didn't necessarily need to have them off their P p. I and most people believed about 20 years ago that this would really revolutionized how we did this article testing. But the problem is impedance based metrics, for the longest time, have not necessarily been found to correlate with symptomatic, Um, and so there is a nuance to how impedance is used, and we'll talk about that minute. The other benefit of impedance is that you can look at Bullis consistency. You can differentiate liquid versus gashes. Boulis is so people with air swallowing Belgian can be identified mixed. Bolasie's can be seen as well. You can also define how far up in this topic is. The bullets comes to belching syndromes and rumination can be diagnosed. Okay, Now that we have talked about these three methods off Asafa Jill reflux monitoring, how do we choose which one to use again? There's a lot of consensus guidelines that go into this. Andi. There is hard evidence, but then the evidence is modified into guidelines. So if you have somebody with what we call unproven GERD, in other words, endoscopy doesn't show much. Endoscopy does not show those high grades of esophagitis that we said were conclusive girl. No. Barrett's mucosa proven with biopsy and no peptic strictures, unproven GERD. Or if patients have a typical symptoms, not harder, not regurgitation. One of the others or patients were status post anti reflux surgery or patients who have a persistent symptom, Um, which is not resolved with a P p I. And in these instances, testing should be done off BP I. And when you do off PPL testing, you can choose between Ph, uh or ph impedance, catheter based monitoring or wireless monitoring. There's some nuance access to which you choose, but in general this is a situation where any one of these tests would tell you yes, acid, no acid. Um, yes, high acid. Um, yes, physiologic asset you know, you'd be able to sort out whether somebody has pathologic reflux, and we'll talk about how to put this together into a nice clinical algorithm later on. On the other hand, if somebody has proven GERD so in other words, somebody has high grade esophagitis. Has biopsy proven Barrett's mucosa or peptic stricture or ah, prior positive pH study. Then, in these instances, the test should be on double those peopIe and has to include impedance. So, in other words, you're trying to sort out if somebody's persisting symptoms are related to their known GERD or if there is an ultimate making them for their symptoms. In that setting, testing has to include a pH and people study on full. Does PPR Now, um, we touched briefly on non rows of reflux. So why is pH testing in this setting off PP I in unproven GERD so important? It is important because with the modern definition for non arose of reflux disease, in other words, a negative endoscopy and a positive pH study, the response to anti reflux therapy P. P. I, or anti reflux surgery is the same as what you would see but arose of esophagitis if your level of evidence does not quite reach this so heartburn, negative endoscopy or heartburn, no endoscopy. Your response rates are 50%. So if you can document abnormal list after reflux burden the likelihood of symptom improvement. What treatments directed at reflux disease is going to be much higher. And we we showed this in a study that was done in our center a few years ago when we took patients, studied them both on and off BP I, and looked at change in their symptoms before and after anti reflux therapy, both medical and surgical and the the entities from a Ph impeding study that predicted symptom outcome was abnormally 80. Uh, symptom reflux association from all reflux episodes was also a borderline predictor of outcome, and you could see that study off BP I was what was partly what made the difference. So as it remains the dominant mechanism dominant factor in reflux disease and targeting management towards acid, using acid as a surrogate for the diagnosis of conclusive reflux remains the main factor from ambulatory reflux monitoring. In fact, the most recent Rome criteria uses the same paradigm unproven GERD and proven GERD and recommends testing, off PP I, uh, in unproven GERD and on PP I had proven GERD so using acid exposure time and reflux symptom association, you can come up with three different syndromes if you look at the off PP I side. You have non rows of reflux disease. If the acid exposure is abnormal, with or without symptom association, if acid exposure is normal and symptom association is positive, that's turned reflux hypersensitivity and if neither are positive, that's functional heartburn. So that's like having, uh, the I. B s of the esophagus. So it's completely functional. There is no association with reflux even though the patient's symptoms may be identical to reflux. So if you think about how you're going to treat them, the need for assets suppression obviously its highest with Nana Rose of reflux disease and some with reflux hypersensitivity may benefit on the other side. On PP I both functional heartburn and reflux Hypersensitivity can overlap with proven GERD, but those are very infrequent now. We always talk about numbers of reflux episodes when we look at impeding studies. But there is a problem with this You can see in this study from Savary knows group in Italy that patients with arose of esophagitis, Nana Rosa, soft Ghitis and even healthy volunteers have a significant degree of overlap in the numbers of reflux episodes, even though the mean values are different. So they have been various thresholds that have been proposed, UH, 53 to 57 which is the 95th percentile of normal and honor off B P I 21. The the to medium director Theo Good Consensus Group recommends using 80 as the threshold above which values they're probably not seen very often in healthy controls, whereas values below 40 would suggest physiologic levels. But the overall value in measuring numbers of reflux episodes remains to be better defined, and you cannot make a diagnosis of conclusive reflux based just on numbers of reflux episodes. Now they have been a few new metrics introduced that are markers of longitudinal esophageal injury. Remember, the acid exposure time reflux infamous association are cross sectional metrics, their true for the day of the recording. These longitudinal metrics give us an idea as to how the esophagus has, uh responded to acid over time. It's kind of like checking hemoglobin a one c. It's like looking at, uh, the exposure, the the effects off reflux exposure in the esophagus. And it turns out that the baseline impedance value has has importance in that. So a lower baseline impedance is seen much more often in pathological reflux disease and that is thought to be related to damage to mucosal integrity. So loss of tight junctions, dilated inter cellular spaces and so on and so forth. In fact, the baseline impedance value correlates with acid exposure time. Ah, high acid exposure time equals low baseline impedance. So there is another new impedance metric known as the post reflux, swallow induced parastatal tick way. And what that represents is a swallow that follows a reflux episode so soft you'll acidification from the reflux triggers a primary swallow so that saliva can be brought into the esophagus so the patients neural networks are intact. Each reflux episode will be followed by a post street flux. Swallow induced Paris faulted wave. The normal numbers off reflux episodes, followed by a PSP W is about 60 to 65% so values below that would be considered abnormal. In other words, the esophagus would sit if I and there wouldn't be an adequate number of swallows bringing saliva into the esophagus. This is a very cumbersome metric to measure, and it has to be manually done right now. But hopefully in the future there will be automated analysis possible. So if you took the PSP W index, the value is able to segregate patients with reflux esophagitis, both active and healed from functional heartburn. Now, if you were to put the baseline impedance on a similar graf again, you're able to segregate these reflux induced esophageal syndromes from functional heartburn. Now baseline impedance and PSP W are available. They're already there in every page, impeding study that we perform. They just need to be extracted. It's a little easier to extract baseline impedance. We like to do it at night when there are no swallows and artifacts. So that's why I mean nocturnal baseline impedance. It's taken from 3 10 minute periods around 12 and 3 a.m. At night, and there are the software programs now that are going to be incorporated into th impeding studies so that this can be automatically extracted. How do they perform? You can see that their performance characteristics in differentiating a rose of reflux disease and non arose of reflux disease. Functional heartburn are quite impressive. We're not ready to say that this is the metric to use. But this adds confidence to a reflux conclusion, especially if there is some ambiguity in other evidence or reflux. And there is yet another novel, impedance methodology. And this involves mucosal impedance using a probe that has impedance electrodes and the tip. So this was first studied as a through the scope probe that was touched on the mucosa. And using this technology, uh, reflux based pathology could be differentiated from non good pathology with very, very nice separation of the graphs. Here, you can see that using a filic esophagitis, which is a new inflammatory condition, was associated with the lowest mucosal impedance values and those with Asafa Ghitis That c plus, uh, also had lower values than those with, um e minus ph minus Richard. No esophagitis and ph negative. No esophagitis ph positive, which is the traditional nerd with somewhere in between. This is the second generation probe. Actually did one of these studies this morning. This is a balloon that has an array off impedance electrodes to a raise, actually, and you can place it in the Sophocles distended balloon with air so that the electrodes can touch the mucosa. And you can you can get a graph that looks like this. So this is a topographic where red, as you can see on the scale, represents low impedance and blue represents high impedance. And this is what you would see in a normal where there's a mixture of blue and green. This is what you would see with reflux. You see a lot of reds, meaning of areas with low mucosal impedance. This is what you would see with using the Philip Esophagitis. Very low impedance all through. So, in other words, impedance is, uh, low. If there is information and the conclusion here is whether the information is driven by Houston Filic information or by reflux and use information, you would still see Halo bi coastal impedance. Now, where exactly new coastal impedance fits into our current algorithms is not clear yet, but this is actively being investigated in many centers, including ours. Now let's talk about Manama tree and Manama Tree is performed very often in the setting reflux. In fact, that's how we decide where to place thes ph in ph. Impedance catheters. So why classified motor function incurred? You might say we already have the Chicago classifications, but the issue is the Chicago classification was designed for evaluation. This faded chest pain we used in the reflux setting. But it's not really meant to be for this city now. We have these studies already. It's just like with the pH impeding study in the baseline. Impedance. We have these studies. They performed this part of this article Testing gird for various reasons. Um, and there is good data, new data as well as all data suggesting that the software gastric function in the software body motor function, um, can predict reflux burden. In other words, it's part of the path of theology, of reflux, that new paradigms that are available to interrogate this awful gastric junction and the soft your body. And there is a need for standard standardization of terminology. So let's first start with E G J barrier function. You can see this is the high resolution Manama tree, uh, topographic block, the upper sphincters at the top, the lowest pictures at the bottom. If you are to take a d. C. I like tool that measures length amplitude and duration and looked at vigor of the Soph Ical Gastric junction over three respiratory cycles and then divided it by the duration of the three cycles. Then you get the E g J contract tile integral, that is independent off time. Why should it be independent of time? Because people breathe at different rates, so you don't want the duration of this recording to be influenced by the frequency of respiration. Now both inspire Torrey pressures and expert Torrey pressures are important in maintaining the e g J barrier function. So the e G J contract I'll Integral has been found to correlate with basal pressures at the gj. The end exploratory pressure, the inspect Ori peak pressure. This is measured at the resting face that this is not swallow induced e g J findings, but just baseline in GJ findings. And this augments if you do, an anti reflux surgical procedure goes down if you do a hell of my out of it. So it does three exact same things that the Elia's basal pressures do on Lee. This is a combination of all the different metrics of the GJ into one single metric if this is low, the likelihood of this article acid burden is higher on the likelihood of medical therapy. Being able to solve the reflux paradigm is lower because if you haven't disrupted the D. J, you need something structural done at this site. The second element the DJs morphology by morphology, we mean the relationship between the intrinsic lower esophageal sphincter and the diaphragmatic crueler. The top one, the two are superimposed. Type one. The second one, you can see the L. E s. And then you can see the diaphragmatic cruel contractions with respiration that separated by less than three centimeters. Type to the third one, separated by more than three centimeters. Type three as you go from type one to type two and type three reflux burden goes up. So it makes sense to make note of this, uh, Manama tree. High resolution Manama tree has been found to be relatively sensitive in identifying hide. Attorney is of this kind. Um, in fact, more sensitive than in the Oscar on the next esophageal body. There are four different patterns in the esophagus intact contractions you can see in the front in the first one where you see an intact, nostalgic sequence. Second one, you see a long break, but an adequate D C I of 7 30. The third one is an ineffective sequence low D. C. I. The fourth one has failed. If you look at reflux burden, the Grady int of reflux burden goes up as you go from normal, too fragmented to ineffective to absent. And therefore it's after a hypo motility is associated with increased reflux burden. Even though some of these terms are utilized in the Chicago classification, your standard Chicago classifications and the Guard classification, we're combining the minor motor disorders fragmented, ineffective Paracelsus with the major motor disorder failed. Paris Talese's in the same spectrum because all of these are within a spectrum of reflux disease. And then there are provocative maneuvers that can be performed during Manama Tree. So the first is the multiple rapid swallows. If you ask somebody to take five swallows quickly, there is no parastatals is during the swallows, but after the last one there is an augmented contraction. And if patients can augment their soft Jill, smooth muscle contraction mawr than what you see with wet swallows that is called having contraction reserves. This evaluates Contraction reserve. There's not other provocative tests called the Rapid Drink Challenge, but the patient is given 100 to 200 Medal of Water and asked to drink the water as fast as they can. Now. This assesses latent obstruction. So if there was a new obstruction of the sophomore gastric junction, you would see Pam, Asafa, Jill compartmentalization of pressure. So how would you use contraction reserve? So if you have normal, what swallows normal multiple rapid swallows, that's a normal response. This person has a low likelihood of having ineffective. It's optional trophy in the future. If somebody has a week contractions during the 10 wet swallows but has augmented contraction after multiple rapid swallows, it means that they have contraction reserve. It means that you can obstruct the distal esophagus with the funding application. They may not get this Faget, the i E. I am may resolve if they have, I am in the preoperative study, and even if if it does not resolve, it may not progress. On the other hand, if you have no contraction reserve, so the patient has no contraction with what swallows no contraction after multiple rabbit swallows those patients have a high likelihood of developing post anti reflux surgery. Motor this page and they may have. I am that persists. So that's ineffective. It's actually utility that persists of develops after anti reflux surgery. So this is the garden motor classifications. First step. Evaluate D D j second step the body and the third step evaluate contraction reserve. And with this, there is a spectrum off soft shell acid exposure that goes up with each step from top to bottom. So intact has the least acid exposure. If patient has both hypertensive el es and hide its hernia likely tive abnormal Sophocles acid exposure is the highest. So how should this classifications be used? So it's meant to complement and augment the Chicago classification? There are the elements in the good classifications that are not part off Chicago classifications. Um, contraction reserve is something that adds. Thio adds a dimension. The evaluation. Now in some patients, both Chicago classification and good classifications, they apply. But you could have patients with normal Egypt function, even if they don't have good. The other big value of misclassification is that there is going to be standardization terminology, just like the Chicago classifications brought standard terms so that future research can use thes parameters and come up with better ways to evaluate motor function in patients. Now we're gonna move on to good evidence and FINA types, So these are some of the conclusions off the consensus process. You can see three modes of esophageal evaluation endoscopy Ph, RPG, Peens and Manama tree. And so what are the findings that are conclusive for pathologic reflex? In other words, if you have these findings, you need to be treating reflux regardless of whether the symptoms got better or not so on. Endoscopy already talked about this and a great CND esophagitis long segment. Barrett's because in a peptic stricture on page or page impedance acid exposure time more than 6% no Manama tree parameters are conclusive for pathologic reflux. In other words, you cannot diagnose reflux based on Manama Tree what our board line or inconclusive evidence lower grades of esophagitis L. A Grade A and B A T that is borderline between four and 6% or reflux episodes that are 40 to 80. So when when findings are borderline of inconclusive, you can add confidence to the diagnosis with adjunctive with supportive evidence in this fashion. So history pathology, Um, you coastal impedance where you talk symptom association. High numbers of reflux episodes, some of these new impedance based metrics and some of the manna metric characteristics. So if you have some of these features and have board line or inconclusive evidence, that may elevate your confidence in reflux to a more conclusive situation and then evidence against pathologic reflux 80 less than 4% where reflux episodes less than 40 and especially if you combine that with the normal endoscopy you practically have ruled out reflux pathologic reflux as a mechanism of symptoms. So let's talk about clinical phenotype. So these are the clinical FINA types based on symptoms, and let's break them down to likelihood of reflux or heartburn acid regurgitation. You're likely with his high chest pain, and two omitted the typical symptoms or low. But you can confound this with hypersensitivity and hyper vigilant with endoscopy again. High grade esophagitis yes, hi. Likely the low grade esophagitis or normal examined PP. I intermediate likely, and this could be confounded by PP I therapy, and by high discerning these are the Rome definitions. The most important take home point from this is that you need abnormal pH Mitri to make a diagnosis with Nana Rosa. Great looks, disease and symptom response to ppd Therapy on Lee has intermediate likelihood. The Leon consensus the criteria that I just presented in the last slide takes elements of all of these and defines conclusive evidence of reflux board line evidence, physiologic parameters and use this not novel metrics as well as motor classifications. If you go beyond just reflux in patients with symptoms suspicious for reflux disease, you can have great flocks. But you can also have functional the soft shell disorders that overlap. There could be non esophageal disorders. They can also be other Softail disorders like Houston Phillip Esophagitis and motor disorders. In all of these contribute to the individual patient. So it's important to think about reflux path of physiology. In this context, so have the E g J dysfunction of the gj transient el es relaxations hypertensive e g. J and hide attorney. We talked about this his official body parameters, impaired clearance, downstream factors and upstream factors. All of these contribute type of motility. Structural mechanisms contribute to abnormal asset burden and reflux disease. So why are these important? These are mechanistic factors that predict reflux disease. So even though we have the clinical parameters, conclusive evidence, supportive evidence for the individual patient, these mechanistic factors may play a role in how we personalized care to the individual patient. Now some patients may have other mechanisms of symptoms that mimic reflux. So this is a patient who had these vertical bars of increased pressure compartmentalization during upper stink to relax ation during a postprandial study. That's they are wave of rumination, and in fact, if you if you put in the impedance, you can see content coming up from the stomach into the esophagus. So even though the story sounded like reflux, this was actually illumination. Here is another patient. Excuse me with air swallowing and burping. So this is super gastric belt. This can also mimic reflux disease. This is a mechanistic issue that may influence how you treat patients. So what are the mechanistic fina types? The pattern of reflux. This is pulled in from the clinical phenotype with increased reflux burden, increased numbers of reflux episodes. But then there modifiers here to for a pH study in detecting patterns of reflux. If somebody has hypochlorite hydra or a chloride ria. You may not detect acid metrics, and that may play a role in how these patients have managed mechanism of reflux. So between Manama Tree and prolonged pH. Monitoring the mechanism off reflux or conditions mimicking reflux can be ascertained. Clearance of reflux. Eight. So you need a salvageable contract. Il ity on an intact GJ for reflux to be cleared back into the stomach. An absence of that may influence clearance of reflux. Eight. Finally, the sensation, element, cognition and perception of sensation. Likely, the pathologic guard is high if symptom perception is adequate. But there's some people would increase perception or hypervigilance visceral hypersensitivity where even though they may have reflux, that's not the dominant issue with them. It's the perception of cognition that is abnormal. And if those patients need to be treated, they has to be anel Ament of treatment of the increase perception. Okay, now this is a new approach. Uh, that, uh, that the slide that I borrowed from John Panel FINA and modified it. This is an approach to patients with esophageal complaints. Andi, let's say this is somebody with any esophageal symptom that has failed the PP I So obviously you're at the point where you're doing a colonoscopy. Would you prefer to do that off BP I And if you found high grade esophagitis, then, uh, the idea would be to treat or escalate anti reflux therapy and consider doing a ph impeding study on medication. Because this is conclusive evidence for reflux disease, a stricture is also conclusive evidence The stricture may itself need to be treated on may contribute to symptoms. Obviously, these days, any endoscopy in this realm of reflux needs biopsies. Ah, hiatus. Hernia may contribute to reflux burden May require surgery. This may need a pre motility study and potentially reflux monitoring. Now, if a Nasaf vigil motor disorder is suspected, remember, you can have reflux soundings into this and have a correlation. So these days we have the option of doing a ah flip study of Manama tree of barium to follow the upper and ask. And obviously if a glacier and a satchel motility disorders found, it needs to be treated beyond that. That is the point where some of these sa vigil ph. Ph, impedance and mucosal impedance type studies may be of values if they're positive and again reflux treatment is escalated. Some kind of monitoring on medicine may be necessary if they do not respond, and these can all be performed at the first visit. Now, if this is negative in a postprandial high resolution in teens, Manama Tree could define some of these conditions that mimic reflux like ruminations, super gastric belching. And if that's all negative, then we end up a functional symptoms that may need alternative treatment. Now, if we suspect functional overlap, if symptoms persist and you think they're all functional, where there is an overlap functional disease, the first step is to treat them at the Luminal and with usual acid type treatments. Algae, in its confused, will not available in the U. S. Viscous lidocaine acid suppression. And then you can use powerful, gut directed regulators. You think symptoms are driven by reflux episodes back Olyphant as an agent that can be utilized? There haven't been any other defined available medications and use a pro kinetics is not generally recommended at this time because they don't necessarily much copra might necessarily doesn't improved great flux. Beyond that central processing modulation, uh, the neuro modulators, tricyclics and the faxing surgery income utilize CO morbid, effective disorders have to be managed, and finally, adjunctive measures such as hypnosis can be utilized in that setting. So this is treatment of persisting esophageal symptoms. So to wind down in summary history and PPE response are not reliable indicators of pathologic girl. But this is how we start managing reflux disease. And, uh, when patients respond, Uh, that is the time point where we have to step back and decide if what we're treating is indeed reflux and tried to taper their acid medication to the lowest. Does that keeps them well, Rows of esophagitis, especially high grades of esophagitis, are good predictors of abnormal acid exposure. So is long segment. Barrett's esophagus. 80 acid exposure time. More than 6% is a reliable predictor of abnormal Sophocles reflux burden. If it is more than four, if eighties more than four with other complementary evidence, that may be adequate. And the new impedance based metrics may add confidence to strength off reflux evidence. Thank you very much. Ladies and gentlemen, for your attention. And I'll be happy to answer questions if we have any. Thank you. That was ah, very thorough presentation. we do have one question. If there are additional questions, please type them into the question section on your link. The current questions says Thank you for clarifying the presentation regarding reflux episodes with proximal extent. Do you think that even in the presence of a few episodes with proximal extent in a study with normal total number reflux episodes makes the study abnormal? Um, the answer to that is, we don't really know. Um, some of this has to be individualized to the patient, but the current understanding is that use of proximal extent alone is not enough to make a conclusive diagnosis of reflux disease. Any other questions? Well, Dr Guy Well, on behalf of diversity healthcare, we certainly appreciate a marvelous, marvelous webinar today. We appreciate that for the listeners out there, we intend to publish this on Diversity Tech University online website. In the coming days on, we'd like to thank everyone for your attendance and again, Doctor God, Wally, thank you very much. Thank you. This now ends our webinar