Our next speaker is Felice Schnell-Sussman. She's a professor of medicine at Cornell. She's the director of endoscopy and the director of the Jay Monahan Center. She'll be giving a talk on GERD diagnosis, when to use what. Thank you, Felice. Great. Thank you so much for the course organizers for allowing me to speak today. It's my pleasure to be here. I'm so excited to be in person with all of you. So that's Bob the Builder. I hope everybody knows that. That's his little toolbox, his ASGE toolbox. And what I'm going to talk today about is GERD diagnosis, when to use what. These are my disclosures. So GERD is not a one-size-fits-all kind of diagnosis. The symptom generation is multifactorial. Patient to patient, they can have a variety of different complaints when they present, even with similar endoscopic findings. An algorithmic approach to GERD really can only be a guide in how you actually look at a patient. So ideally, we would all do a personalized approach. Every patient you would approach in its own unique manner. But what's interesting is when we do that, we actually use a lot of techniques and technology that when you look at the quality of the data that's out there, some of it, when you look at the grading, it's actually not as high as one would think. So I'm going to go through a lot of that in our talk, and we're going to get really a look at the whole landscape of what we actually have in our little toolbox. So I want you to take a look at this for a second, because the first time I looked at it, I actually didn't even understand what the picture showed. But this is showing that the diagnosis of GERD is not necessarily easy to make. Everybody gets it, right? It's cute, right? It's so cute. So obviously, this crossword puzzle wasn't easy to do, and we found the fastest way to get to the presumptive end, and that's not what we want to do. And certainly, it's not what we want to do on an upper endoscopy, as what was just elegantly explained to us. But what's in our GERD diagnostic toolbox? So it's actually quite profound, what we have available to us to actually be able to use to diagnose GERD. And includes things like the PPI test, and upper endoscopy, reflux monitoring, esophagram, biopsies. And I'm going to go through this laundry list of things, and we're going to work together where it would actually play a role in making a definitive diagnosis. So to start with, there's actually one very often underutilized technology, and that is listening to the patient. And Sir William Osler actually had this quote. It's interesting. He only said he. Obviously, there are many patients that are not he, but listen to your patient. He's telling you the diagnosis. And the truth is, with GERD in particular, patients come in with many, many, many complaints. Some of them may actually be attributed to the esophagus. Some may be outside the esophagus. But heartburn and regurgitation, those are the most sensitive and specific of the GERD symptoms. So if a patient is presenting with those two symptoms in particular, you already feel a little bit more sort of in love with what they're saying to you, and the fact that GERD may actually be part of this patient problem. Now with that in mind, patient-reported symptom questionnaires, which many of us hand out, they really should not be used to decide conclusively whether or not someone has GERD. And even in expert hands and expert history taken by gastroenterologists, the sensitivity is only about 70%, and the specificity, 67%, for a diagnosis of GERD when you do reflux monitoring. It's not perfect, but we should all still do an excellent history as well. Now, PPI trial has been around forever, and this is very commonly spoke about in every single conversation related to diagnosing GERD. It's in guidelines. It's in consensus statements. It's in expert opinion. And basically, most people advocate for an empiric diagnostic test in patients with the typical symptoms that I spoke about. And in that arena, it would be a patient has no alarm features as well. That's when you would proceed with doing this PPI test. So what is a PPI test? It essentially means giving a patient one tablet of a PPI once a day, half an hour before the meal, for up to eight weeks. Some of the literature shows four to eight weeks, but in general, for the purpose of our talk, we'll say eight weeks. And then you might give an attempt to discontinue if the patient responds. Now why do we do this? It's low cost. It's low risk. And basically, when you look at the methodology around this, it actually is a strong recommendation with a moderate level of evidence. That is actually superior when you look at all the different things that we do on our patients. Now, although it's practical and efficient, there's really limited diagnostic utility to conclusively, based upon a PPI identified patients with GERD. Look at the sensitivity. The sensitivity is only 78% and specificity of 54% for diagnosis of GERD. So when we look at the algorithm, and this is the most recent ACG algorithm for the diagnosis of GERD, this is where it would be a patient would present with heartburn or regurgitation. You would offer them an eight-week, once-before-meal daily PPI trial. If they had incomplete relief on that, that's when you would advance. And one would advance at that point in time to a high-quality upper endoscopy. And you would, at that point in time, take them off of the PPI. Ideally, you would take them off the PPI to two to four weeks prior to that. And at the time of the endoscopy, we would be looking to see the LA grade. If the LA grade was B, C, or D, specifically C or D, or Barrett's long segment, which means greater than three centimeters, that would be a GERD confirmation at the time of upper endoscopy. And we're going to go a little bit deeper into this. So when would you perform an upper endoscopy? We just had an elegant talk about upper endoscopies. But specifically with reference to GERD, that's when GERD symptoms are accompanied, or if you have GERD symptoms and they are accompanied by alarm symptoms, this is not when you're doing a PPI test. This is a patient that is going to go on for an upper endoscopy. And alarm symptoms are things like dysphagia, weight loss, bleeding, anemia. That is an individual that deserves an upper endoscopy done up front. The other case would be you do a PPI test, inadequate response. Person doesn't feel better. You're going to go on and do an upper endoscopy. If you do a PPI test and the symptoms recur after you've now discontinued the PPIs, ideally you would wait two to four weeks before you do the upper endoscopy. But here also you would do an upper endoscopy. If a patient has chest pain without the heartburn and has a normal cardiac workup, that's going to be an upper endoscopy. And then also we spoke briefly before about patients with Barrett's esophagus. Those that have multiple Barrett's esophagus risks, you would probably want to do an upper endoscopy as well to make sure that Barrett's wasn't part of the situation as well here. So we looked at what is a high quality exam. I'm going to just limit my comments to what constitutes a complete endoscopic evaluation for GERD. And so there are many things that you should be talking about in your report when you're looking at someone with GERD. And we have a tendency to not necessarily say all these things. Very often we go and we're looking for erosions, but there's many things that we actually want to pay attention to, to give us a sense of the possibility that GERD is actually at play. So the other thing I want to mention is we should all be talking the same language. So there are many classification systems that are vetted. And the reason why we use them, like the LA grade classification and the Prague classification, is because then when you look at your report, let's say in two years from then, you actually really know what the patient had. Or if another colleague of yours is, let's say, if it's a surgeon or an advanced endoscopist is going to be the person who's going to do anti-reflux procedure, they really know what you are seeing at your endoscopy. So we should refrain from doing things like mild or moderate or small or large. We actually have these well vetted ways to actually be able to talk to one another. So what are those? One would be to grade the erosive esophagitis, and that's through LA grade classification. Select the diaphragmatic hiatus, and you would give the hill grade of that flap valve. Measure the axial hiatus length, and you would do three measurements. What's the diaphragmatic pinch at? What is the top of the gastric folds? And also the Z line. You want to assess for Barrett's, obviously. And when you talk about Barrett's, we're going to talk with that Prague classification, with the C and M classification. And then, of course, you want to exclude anything else that you might see on the upper endoscopy. So what on upper endoscopy is confirmatory for GERD? There are three things. If you look in and you see grade C or D erosive esophagitis, that is confirmatory for GERD. So you don't actually have to then go on necessarily for further testing. If there's a long segment Barrett's esophagus greater than three centimeters, this patient now gains a diagnosis of GERD. And if there's a peptic stricture, of course, excluding other reasons for a stricture, they could actually gain a diagnosis of GERD. What's important to recognize, however, is erosive esophagitis, seeing that upper endoscopy, is actually only seen in the minority of times. So only 30% of patients that are treatment naive and only 10% of patients that have been on a PPI. Now, there are some caveats about erosive esophagitis in terms of the diagnosis. So LA grade A erosive esophagitis is not a definitive diagnosis for GERD. LA grade B erosive esophagitis, if you have the typical symptoms that we spoke about, it might be. But the thing you can really hang your hat on is that C and D. And below here, you can see what those grade. I'm sure all of you are probably familiar with it, but I included a table of what that grading would actually look like endoscopically. Now this is not a peptic stricture. And so sometimes we see a lot of potentially Schottky's rings at upper endoscopy. But it's one of the things, if you were to see a Schottky's ring, you should become familiar with what that looks like as well, so that you don't push the diagnosis and that you would go on for third and definitive testing in a patient. What about biopsying in a patient? So is it helpful in the diagnosis of GERD? Many of us have the compulsion to take out our biopsy forceps to biopsy the distal esophagus. So what this is looking at is there are three pathological findings that are potentially associated with erosive esophagitis. And that would be papillary elongation, basal cell hyperplasia, and dilated intercellular spaces. And so when we look at this study to see is there microscopic esophagitis, meaning those findings seen at biopsy, on routine histopathology, even in expert hands, it's not sensitive or specific for a diagnosis of GERD. So if there's erosive esophagitis, of course they typically will see these findings. But in those other patients where you really are not sure, like the NERD patients or reflux hypersensitivity, a biopsy alone is actually not going to be confirmatory for you. What about an esophagram? Is it helpful in the evaluation of patient with GERD symptoms? Well, there are multiple things that it is actually excellent to help us with. It's very sensitive for rings and subtle strictures and to assess the luminal diameter. It's an excellent test to be able to look for hiatal hernias and parasophageal hiatal hernias. And a well-performed esophagram will almost always eliminate a diagnosis of achalasia. But what about in the diagnosis of GERD? Should you perform a barium swallow? Well, only 50% of patients with abnormal reflux on an esophagram are actually found to have an abnormal pH monitoring. So a barium esophagram is really not recommended as a sole diagnostic test for GERD. And I know there are many times that you might get findings where they say reflux to the nose. But we should not use that as our sole definitive testing. Now, we've spoken about a lot of different things. I'm going to dive a little bit deeper into some of the different guidelines. And over the past two years, there have been so many wonderful pieces of the literature that are guidelines and expert opinions. And I'm going to try to show you a balance of them. This one was the ACG clinical guidelines that recently came out. And what I just want to pay attention to here is there are different types of patients. There are patients that have had previously, this is on A, previously empirically treated patients with a PPI that have not had a definitive endoscopic workup or any definitive endoscopic workup. So the first thing I want to mention is there might be many patients who come in that say they're on a PPI. We need to be sure that it is optimized. So you need to actually have them verbalize for you how they're taking it, when they're taking it, what they're actually taking before we say that they're a failure of PPI therapy. So in a patient that's been optimized on their PPIs, if they have unsatisfied symptoms, we said you would undergo an upper endoscopy. If that upper endoscopy was now normal, that's when reflux monitoring is going to start to play a role. And in this patient, that will be off of a PPI. And that's typically going to be the capsule, the Bravo test that we would do at that point in time, looking to see if there's evidence of abnormal acid exposure. In a patient in B, in table B, that had previously objectively defined growth, so they've had an upper endoscopy that showed C or D, or they've had reflux testing in the past, and they're coming now in with symptoms, you would again optimize them. If they had symptom relief, obviously you'd be done, but if they had unsatisfied relief in this patient population that had been previously defined, this is the group that you might do impedance pH monitoring on a PPI. So that's sort of the breakdown between these two groups, and we'll go through this a little bit more. But what metrics actually make the diagnosis at reflux testing? So this is a list of the different things when we do reflux testing, either with the capsule, you know, the Bravo testing, or with probe-based testing. These are the different types of metrics we're looking at. Acid exposure time, the Demester score, the number of reflux events, symptom correlation, whether or not there's weakly acidic or non-acidic reflux episodes, and the mean nocturnal baseline impedance. And I'm going to go through some of this as well for us. But the amount of acid exposure time, is it diagnostic? So on this slide, you're seeing all these historical studies that have actually been done to help us understand, how much time does the esophagus need to be exposed to acid to be diagnostic of actually GERD? And there really has been a lot of studies looked to see, what should the lower level and upper level be? And basically, for purposes of this talk, when we're talking about abnormal acid exposure time, greater than 6% of time is considered abnormal. What about the number of reflux events? How many reflux events is it required to be considered abnormal? So the one thing I want to mention, unlike acid exposure time, which is much more vigorous in the diagnosis of GERD, the number of reflux events is not solely able to be used for a diagnosis of GERD. It's usually an adjunctive type of measure. So if someone has an inconclusive acid exposure time, like let's say they're not greater than 6%, let's say they're 4% to 6%, the number of reflux events could be very helpful for you. So in patients that have greater than 80 reflux events over 24 hours, that is considered abnormal. Another thing I'd like to mention is that very often when we use a Bravo in our studies, we are doing this now over a prolonged period of time. So in the past, many people had used 48 hours. There's a lot of evidence to show that prolonged reflux monitoring does add potential value in the diagnosis. So doing this up to 96 hours at a time for a patient. Now what is the role for reflux symptom correlation in a patient? So when we do reflux symptom correlation, we're talking about two indices. That's the symptom index, as well as the symptom association probability. And those with positive symptom association, they just do better with medical management and with surgery. But as a standalone test, it definitely has limited utility in a GERD diagnosis. Those that do the best, meaning with medical management or surgery, if you have a patient that has a positive acid exposure time, as well as a positive symptom indice, those are the ones they do the best. So obviously, the more metrics that are positive, the higher the likelihood a person is going to do good, no matter what you do for them. Now looking just a little bit more closely, when would you perform pH impedance versus wireless impedance? The wireless or the Bravo, when a patient has infrequent symptoms, because you can do it up to 96 hours, if they can't tolerate the catheter, if they've had a negative 24-hour test and you really believe they have reflux, you would probably do a Bravo. In pH impedance, those are refractory symptoms on a PPI. And also in patients that are ruminators, or belchers, or respiratory symptoms. In our unit, and I think more of the motion, is to go 96 hours with a wireless as a first test as well, just to mention that. So how do we put this all together to make a diagnosis? This was a beautiful piece of literature put out by Rina Gilad-Lapati and her group. And this looked to combine upper endoscopy as well as prolonged ambulatory reflux monitoring. And here you can see, if the upper endoscopy shows BCD esophagitis, and you have greater than two days with an acid exposure time greater than 6%, that is a patient who has GERD. And ambulatory reflux monitoring or PPI, you do not need to do it in that patient population based upon those findings. A patient that does not have GERD based upon this, no erosive reflux disease, all days the acid exposure time is less than 4%, there's no GERD in that patient. The borderline patients are those that have the findings in between. So the last minute, I'm just going to mention three other things. High resolution manometry, where does it play a role? This would be to diagnose major motor disorders in a patient, to look for peristaltic performance before anti-reflux surgery, and also to see if these patients are super gastric belchers or ruminators, which could also present as reflux disease. So this is where high resolution manometry or high resolution manometry with impedance would play a role. What about nocturnal baseline impedance? This is a newer metric. Not all do this. This is something that actually is extracted from the HRM study, and it's an impedance value that's gained at rest. It's when it's done during sleep when the patient's recumbent. And the reason for that is the patient usually has no swallows during that time, and the catheter is in good contact with the esophagus. And on this study, what you're trying to just get is a baseline impedance in that patient. So a lower baseline impedance, as you can see in the graph to the right, that lower baseline impedance is associated with a higher likelihood of pathological reflux. So this is a newer metric that you could actually employ. We do not use this as a sole metric as well. This is typically a metric I will use as an arbiter in cases where the other metrics are inconclusive. I may actually use the M-MBI. There's another type of novel technology called mucosal integrity. Does this play a role? This is actually an impedance device that is embedded in a balloon. This is now commercially available, and it's evolving. And you actually get these impedance types of patterns you can see at the bottom. Reflux shows where you're actually seeing the lower impedance at the bottom. Once you're actually able to get this, a graph that looks somewhat like a regular HRM, but this is actually able to be done during the time of endoscopy. So this is another novel way, perhaps, that can play a role. And then lastly, what about patients with extra esophageal symptoms? The only thing I want to mention in these, if a patient presents with extra esophageal symptoms, those patients are going to go on directly for reflux monitoring off of a PPI and not being done with just a PPI test. So we've reviewed many things in our talk. We've gone through endoscopy, pH, pH impedance, high-resolution manometry. This last graph just shows how you actually can put it all together. You'll all get this as well. But I hope this was helpful as a nice panorama of all the different things that we actually have in our toolbox to be able to look at reflux to help us make a definitive diagnosis. All your labs are back. They show a serious overuse of unnecessary and inappropriate tests and procedures. I hope none of us do that, and I'm sure we're all going to, over the next day, enjoy the opportunity to spend a lot of time talking about the various things that we have to treat our esophageal patients and make sure they get the diagnosis right the first time. Thank you so much for your time.

GERD diagnosis

symptom generation

techniques

PPI test

upper endoscopy

reflux monitoring

Dellert