Welcome and good evening. The American Society for Gastrointestinal Endoscopy appreciates your participation in tonight's webinar. My name is Ed Dellert. I'm the Chief Publications and Learning Officer here for ASGE, and I will be one of the facilitators throughout tonight's presentation. Our program tonight is entitled Managing Refractory GERD Symptoms, What to Do Next. Please note that this presentation is being recorded and will be posted on G.I. Leap, ASGE's online learning management platform. You will have ongoing access to the recording in G.I. Leap as part of your registration. I would also like to acknowledge the gracious educational programming support from Olympus for the remainder of the 2021 ASGE Thursday Night Live program. Thank you. So before we get started, please note a number of features in tonight's platform so you are aware of the many resources available to you during and after tonight's program. 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Finally, I would also like to guide participants tonight to the virtual exhibit hall that's located in the lower menu footer of your screen. There's where you can find a number of exhibitors that have been available to us to provide information and resources on all of our Thursday Night Light webinars, including an ASGE booth. If you do have questions, swipe your virtual badge, and a representative will get in touch with you. Thank you for noting all of these features available to you during the webinar and any time following the program. And as a reminder for tonight, I want to make sure that you all are engaged with our presenters. Please use that Q&A box that's circled there. We would ideally like you to put your questions there, not the chat function, and we will be monitoring questions throughout the presentations. And at the end of Dr. Smith's presentation, we'll get to as many questions as possible. Tonight's objectives are twofold. One, define the appropriate steps to assess symptoms concerning refractory gastroesophageal reflux. And two, delineate options for dietary, lifestyle, pharmacological, and anatomic interventions to treat GERD that has not responded fully to current management. It is now my great pleasure to introduce to you Drs. Michael Smith and Kimberly Cavalieri. Dr. Cavalieri? Good evening, everybody. I'm Dr. Kimberly Cavalieri. In August, I will be starting as the Associate Director of the esophageal program at Mount Sinai West and Mount Sinai Morningside. I have the great pleasure of introducing my future boss, Dr. Michael Smith. He holds many titles, including Chief of Gastroenterology and Hepatology at Mount Sinai West and Mount Sinai Morningside. He's the Director of the esophageal program, as well as the Director of the GI Motility Center. This evening, I'll be following the questions and answers and help moderating the discussion at the end of Dr. Smith's talk. And with that, I turn it over to him. All right. Kim, thank you so much. And Ed, and everyone at ASGE, it is such a pleasure to be here under the Thursday night lights, where we'll get a chance to talk a little bit about how we manage refractory GERD symptoms. When you have a patient that you think may have reflux that is not under control, what do we do next? How do we manage those patients? And again, it's such a pleasure to be here. Thanks so much to the ASGE for the invitation to spend the evening with all of you. I have no relevant disclosures for this presentation. So before we get into discussing managing refractory GERD, we really need to go back and define what GERD is. And I know that there are a number of folks on the talk this evening, and I'm sure we'll be accessing it later, at all different levels of experience and training. And so it's really important to recognize when we talk about GERD, what does that mean? Well, first of all, it's normal for all of us to have gastroesophageal reflux. There is always times that the gastroesophageal flap valve is open, that the lower esophageal sphincter relaxes, and we have the opportunity for gastric contents to flow retrograde into the esophagus. It's normal for that to occur at some time in everybody. When it becomes gastroesophageal reflux disease, or GERD, is when we develop symptoms and or tissue damage when their retrograde flow of gastric contents occurs. And it's very important to recognize that the gastric contents can be normal gastric contents. And we're not talking about necessarily a hyperacidic syndrome like a Zollinger-Ellison syndrome. We're talking about when normal gastric contents, which yes, can include acid, flow retrograde into the esophagus. And as a result of that, the patient develops symptoms and or tissue damage. So as you can see in the bottom there, I wrote not all reflux is acid reflux. And the fact is that not all GERD is caused by acid refluxing into the esophagus. There are other caustic substances that can cause those symptoms and or tissue damage. And of course, there are lots of factors that can contribute to the pathogenesis of GERD. I've listed a number of them for you here, and you can see that they involve a whole bunch of different organs and not just the esophagus, right? We're talking about intraesophageal issues like reduced protective measures from salivary secretion to decreased peristalsis and dysmotility of the esophagus that maintains contents that have been refluxed in the organ longer than there should be, decreased mucosal resistance, and then lower esophageal sphincter dysfunction. I alluded to that on the very first slide, but anytime that you have inappropriate or prolonged relaxation of the lower esophageal sphincter due to a congenital defect or to pharmacologic means or anatomic changes, such as with the hiatal hernia, which we'll discuss in a few minutes, any of those can contribute to GERD occurring as well. It's important to recognize that just like when you hire a plumber for a slow emptying sink, the fact is that you can get GERD because there's a downstream backup as well. So delayed gastric emptying or slow gastric emptying, gastroparesis, is also an important cause of GERD. It's secondary GERD, it's not primary GERD, but it is important and it's something that we need to think about. And of course, again, all of the contents in the stomach that flow retrograde, the more caustic they are to the patient, the more likely they are to cause those symptoms or tissue damage. So if you have duodenogastric or bile reflux, that can add to the causticity of the refluxate and may cause those findings that lead to the diagnosis of GERD. So what are the pathogenic factors in developing reflux esophagitis? Well, the more fluid that comes into the esophagus, the longer it stays there, the type of the fluid that you have, the mix of the different ingredients, your ability or inability to clear that reflux once it occurs, and anatomic disruptions like a hiatal hernia that may facilitate that reflux occurring in the first place, are all things we have to consider as to why somebody might be developing reflux esophagitis. And here's a nice description, depiction of the normal anatomy, where we have a one-way gastroesophageal flap valve that's designed to prevent GERD from occurring. It's really supposed to be a one-way valve where esophageal contents come down through the lower esophageal sphincter, pass through that flap valve into the gastric lumen, and can't really work their way back because of the angle of hiss, that angulated entry. It's not a tangential entry from the esophagus into the stomach. But when we have a hiatal hernia and the lower esophageal sphincter and the diaphragm are now separated, as you can see in this depiction, you've got now a hernia sac above the diaphragm where the contents of that part of the stomach only need to overcome the lower esophageal sphincter to reach the esophagus and cause those symptoms and or tissue damage. And remember as well that there is a reflux reservoir, otherwise known by some as the acid pocket that sits at the top of the gastric contents, and that's an area that can be particularly irritating to the esophagus and lead to those symptoms that we end up defining GERD as. So remember that all of us in gastroenterology see only a fraction of the patients who have gastroesophageal reflux disease. We refer to this as the GERD iceberg as it's depicted here, and you can see that the vast majority of folks, they're getting their medical care from their primary care doctor, perhaps more likely Larry the Cable Guy on TV or things that they read with Dr. Google on the internet. And they're treating themselves now that we have over-the-counter treatments that are widely available in many, many places. Those who have more frequent symptoms are getting to their primary care doctor, and only the group that have more chronic symptoms and or complications of it are the folks that we're seeing. You could add some of the folks who have some hypochondriasis and are very much fixated on their symptoms as well, sure. And you'll see that little red dot I put on the very top, those are the few who are referred to for anatomic intervention, even though there are probably a lot larger component of the GERD population that would be eligible and appropriate to consider that intervention. So remember that we have both typical or classic symptoms and atypical symptoms of gastroesophageal reflux disease. The most common typical or classic symptom is heartburn. And we've got to remember that patients don't know what our definition of heartburn is. We in the GI community and the medical community refer to that as a retrosternal or substernal burning, often accompanied by regurgitation, the other classic symptom of GERD that's aggravated by position change and promptly relieved with antacids. You'd be amazed though if you stop for a second and ask your patients when they tell you that you have heartburn, how many of them point to their epigastrium or to their throat or up into their sinuses and their ears. It's really very interesting what people think heartburn means. And so I remind you and suggest to you that as you're seeing a patient who says that they have a lot of heartburn, ask them what they mean by that. And that's a perfectly appropriate question to ask and could be very helpful to you as you figure out how you want to move forward with their care. Here's just a partial list of atypical GERD symptoms. As you can see here, a lot of times these folks are referred to us from our ENT colleagues or our pulmonology colleagues, dentists, and our cardiology colleagues who often see patients with non-cardiac chest pain that turns out to be GERD-related. And you could see a number of these folks here, and I'll just point out just as an interesting one on the bottom of the pulmonary side, there's increasing data and literature that suggests a connection between pulmonary fibrosis and GERD. And so our patients who are coming in with what we thought was idiopathic pulmonary fibrosis probably have had long-standing reflux and with aspiration of those gastric confines into the lungs leading to that fibrotic change and now often the need to have very intensive therapy or even a lung transplant. So when we think about our treatment goals for GERD, they're very important, right? We want to eliminate the patient's symptoms first and foremost. That's probably why they came to see you. We certainly want to heal their esophagitis so it doesn't do more permanent damage or more severe damage than it's already caused. We want to manage or prevent the complications of GERD, which we'll talk about, and we want to maintain remission of those symptoms for some time after the treatment is initiated so that the patient isn't coming back again saying that they're feeling no better than they are when they first walked into your office. So there are lots of medical options for GERD treatment, and we're going to talk about these in greater detail in just a few minutes. And they include dietary and lifestyle modification, as we know the easiest thing in a lot of cases to institute, but often the one that gets the least compliance or buy-in from patients. We have antacids and topical therapy. We have prokinetics potentially and baclofen, H2 receptor antagonists or H2 blockers, H2RAs, and of course PPIs. So let's talk a little bit about these, and I'm going to talk about them in the context of the ACG's 2013 guidelines. We were talking about it earlier before the webinar began that there's been such a forward push in the management of GERD from the endoscopic perspective that really the guidelines that are being revised right now are going to be a lot more relevant to what the ASGE thinks about on a daily basis. Although we all manage GERD and we all have to manage endoscopically the complications of GERD, I'm going to use the ACG guidelines just to get us started. So it's important to recognize that there are things that we can do to help with GERD, one of which is weight loss. And certainly for patients who are overweight or have had recent weight gain, it is recommended for reflux patients that the less pressure they have on their abdomen pushing on their stomach, the less chance that they're going to have reflux of those gastric contents. Head-to-bed elevation and avoidance of meals before bedtime is a recommended intervention for patients who have nocturnal GERD symptoms. But unfortunately, as much as we always like to tell our patients that getting rid of spicy foods or chocolate, caffeine, alcohol, acidic foods is something that they should do to help, actually, the literature has not particularly suggested that that is a good intervention to be made. And as much as we like to tell our patients not to smoke or to drink alcohol and that that can be helpful to them, likewise, the data here are not as in favor as we would like them to be. So that being said, from an overall health perspective, they can be helpful. And certainly in some patients, it does provide some benefit. Now, how about antacids and topicals? These are frequently reached for by our patients as they're trying to get a quick fix to their discomfort. And we know that antacids can include things like calcium carbonate, aluminum hydroxide, magnesium trisilicate. As we know, they're really a band-aid. They don't prevent GERD. They treat the symptoms by neutralizing the gastric pH, which decreases the acidity of the refluxate that then gets into the esophagus. And while they have a rapid onset of action, they have a short duration of efficacy as well and can lead to side effects such as bloating because of the gas that is produced by the chemical reaction to neutralize the acid. Now, sucralfate is another important one that you've probably prescribed or had a patient that took before. It's available in both a tablet and a suspension form. I'll remind you that for esophageal disease, the suspension form is much preferred because it coats the wall of the esophagus to adhere then to the wall and protect it from peptic injury via some unknown mechanism, but probably something related to improvement of the barrier. Again, it has a short duration of action and limited efficacy compared to other drugs that we're going to be talking about. And it's important to recognize that in those ACG guidelines I referenced, there is no role for sucralfate in the management of GERD in a patient who is not pregnant. It does help to heal erosive esophagitis. It can be used, for example, after Barrett's ablation therapy or endoscopic resection in the esophagus. But in terms of managing GERD, it's not really a great long-term option. One option, though, that can be considered in the topical therapy is sodium alginate, though. And this is Gaviscon is the brand name, so just so that everybody's familiar with it. It's a seaweed-derived product, and it forms a viscous gum that floats on the surface of gastric contents, right where that acid pocket that I mentioned before can form postprandially, which is the first thing to be refluxed up into the esophagus after a meal. So especially in the setting of mild postprandial symptoms, sodium alginate has been shown to be potentially very beneficial for patients. So if you have a patient with mild GERD that generally occurs in the postprandial setting, you may not need to put them on standing therapy, but you may tell them they should have some Gaviscon handy to take after meals and see if that leads to symptomatic resolution, which it may in more mild cases of GERD. So let's talk about some other non-acid-reducing medical therapy. Prokinetics. So prokinetics, I put two of the more famous ones on here, metoclopramide and domperidone. We also see the macrolide antibiotics erythromycin and azithromycin used. There's some other compounds that are thought to have some prokinetic effects and they can be used, but the thinking is that, you know, as we know with metoclopramide and domperidone, both of them have known potential side effects. Metoclopramide has a black box warning from the FDA due to the small risk of tardive dyskinesia that may be irreversible even with cessation of the medication. And domperidone currently is only available through a compassionate use protocol via the FDA with one pharmacy in the United States dispensing it, though our patients often can go to Canada or look through the internet to obtain it in different ways. Those are certainly good options, but the data recommend, the studies recommend and the data shows that you really want to use these only in the setting of where you know that you have delayed gastric emptying, you have slow gastric kinesis, and you want to improve that by using a medication to expedite emptying of the stomach when it would be otherwise delayed. Similarly, baclofen has been shown as a GABA-B agonist to decrease transient lower esophageal relaxations and therefore reflux events. It is not FDA approved for the treatment of GERD, there's a lack of long-term data regarding its efficacy, and it does carry some potential side effects. There are some folks out there in the GERD community who absolutely love this drug and think that they should use it all the time for patients with more significant GERD or refractory GERD, but there are many of us out there who have not been using it on a routine basis and it is not in the current guidelines. So let's move to H2 blockers, something that I'm sure all of us have been using at one time or another. As you know, we're really down to, we're down a significant one with ranitidine being off the market at this time, but we do still have a number of other options available. These medications act on the type two histamine receptors, which are on the basal side of the parietal cell. And I'll show you a schematic of that shortly. It does have a faster onset of action than PPI therapies, but does also have a shorter half-life. You can hear that theme of all of the options that we've discussed so far. The dosing for mild reflux disease generally is as needed or up to BID, and studies have certainly shown superiority for relief of heartburn in non-erosive reflux disease patients for PPIs over H2 blockers. So remember that for H2 receptor antagonists, you wanna use these for a maintenance option in patients who do not have erosive esophagitis, who achieve symptomatic relief from mild GERD. And you can add them to PPI therapy as a bedtime dosing, often at a double dose QHS to achieve some improvement in symptoms when you have a patient with some refractory nocturnal GERD. But compared to PPIs, they just don't measure up, and we'll show you why here as we go. Again, this is the schematic I was mentioning before, where we're looking at a parietal cell. And on the left side, you see the basal side, the three different receptors that can ultimately lead to the cascade, activating the ATPase, the proton pump as the final common pathway, and then leading to secretion of hydrogen ions into the gastric lumen. And you could see that there are three such levers that are available. This is taking everybody all the way back to the beginning of medical school, but acetylcholine, histamine, and gastrin. And that histamine is histamine type two. So if you take an H2 blocker and you block that histamine pathway, that's great. That's one of the three levers that leads to gastric acid secretion. However, it does nothing to the acetylcholine pathway or the gastrin pathway, which means that you still have those two pathways that are leading to acid secretion. It does not shut down acid secretion, and it doesn't turn it off, and it therefore is less effective than something that acts more downstream on the ATPase, the proton pump. So we know in the discussion now of PPIs that we've got an expanding family that last grew with the presence of dexlansoprazole in 2009. And so there are a number of different drugs that are out there, and all but dexlansoprazole are now available in a generic form, which seems amazing when you look back at those of us who've been treating reflux disease for a long time. And here's why PPIs have become so popular, right? This is a study now that's over 20 years old, but it really demonstrates very nicely the healing of esophagitis in patients taking a PPI versus an H2 blocker versus placebo. And you can see the efficacy of the PPI in the 90% or so range for healing of esophagitis compared to about 55 to 60% range for H2 blockers, quite a difference. And here's a really nice study that Dent did now quite some time ago, but really drives home the point about the power of a PPI in affecting the final common pathway for acid secretion compared to H2 blockers, just turning off that histamine type two receptor on the basal side of the parietal cell. You can see along the top folks who took omeprazole every morning, 20 milligrams, and their ability to maintain long-term remission of esophagitis up to a year out. And that number was again, about in the 90% range. Now go to the blue line and you can see the folks who took 150 milligrams twice daily of ranitidine. So that's 14 tablets a week. And their long-term remission of the year was at about 25 to 30%. Now look at the line in the middle. And these are the weekend warriors who only took 20 milligrams of omeprazole on the weekends. Their ability to maintain remission from erosive esophagitis was better than that of those who took 14 H2 blocker pills every week. So you can see here a really nice demonstration of the potency of the PPI compared to the H2 blocker to keep the patient's erosive esophagitis in remission, even when it wasn't used on a daily basis. And I'm not recommending PRN use. I'm not recommending weekend only use. I wanted to show you this as a powerful example of the relative ability of the PPI to shut down gastric acid secretion and heal erosive esophagitis compared to the H2 blocker. So why would we want to change from a PPI then? These are great drugs. They're very successful. And clearly based on our prior discussion, more efficacious than all of the other options that we talked about. Well, there are lots of reasons. People may be intolerant of them, developing side effects. People may develop incomplete relief of symptoms or have refractory reflux on quantitative testing. And you can see the first of many thought bubbles that I'm going to pass to you. Are they taking their PPI correctly? This is a good drug that should be very efficacious. Are they even using it as they're supposed to take it 30 to 60 minutes before a meal and on a daily basis, not a PRN basis. Now we've all heard about patient concerns regarding adverse effects of PPI use, everything from osteoporosis to kidney disease and even dementia, cardiac issues, infectious risk, et cetera, et cetera. And the point of this talk is not to go through those tonight, but just as a reminder that patients may come to you, even if they're well controlled from a GERD perspective on their PPI, very ready to do something different because they're concerned about the 30, 40, 50 years or more that they may have to take this medication and what that may do to their body. And so if they have a patient preference not to take medication long-term, we have to think about alternative therapy. So going back to that, a lot of folks, as we go back to the ACG guidelines, switching PPIs is something that a lot of people will do. As we manage these folks, they may get incomplete relief from one. So you say, okay, let's just hop on the carousel and try the next one on the list. In the setting of insurance these days, that may be a little bit more difficult, but with more OTC options, certainly something that patients are even trying more on themselves. You certainly can consider it from the setting of side effects, but from the efficacy perspective, it doesn't really seem to make a big difference. So if you've got someone on a healthy dose of PPI and one of one type, and they're not having a complete response and they're taking it correctly and they're tolerating it well, chances are not particularly good that you're going to be able to take them to complete symptom relief or adequate symptom relief just by changing the brand or the compound in the PPI. Now, there are a couple of other important guidelines on here that are relevant to us in our discussion about whether or not patients need to be removed from PPI therapy given comorbidities. Patients who have known osteoporosis can remain on PPI. Just because they have a low bone density score does not mean that they have to stop taking this medication. It's important to have them followed and they can have their DEXA scan followed, but it is not a contraindication to PPI use. PPI therapy may be a risk factor for, and you can see my, I haven't updated my slide here, Clostridioides difficile infection and should be used in care with care and patients who are at risk of it. And short-term PPI usage, for example, in hospitalized patients may increase the risk of community-acquired pneumonia. And so that's something that's very important. Another one that has come up quite a bit, but seems to be a little bit less of a controversy than in the past is that PPI therapy does not need to be altered when a patient is taking clopidogrel at the same time. So let's go back to our hypothetical patient here who has not improved or gotten to adequate symptom relief on PPI therapy. Here's a list of questions that I ask myself, or maybe I ask the patient as I'm formulating my plan of attack, okay? Are we actually taking the medication, right? Is this something that they're just using when they have symptoms, or are they taking it as prescribed? As I said, 30 to 60 minutes before meal would be the optimal timing. Are they taking the proper dose of it? Did the pharmacy dispense the correct dose? Did insurance pay for the dose that you were looking for? Did they buy the over-the-counter version at a lower number of milligrams and are substituting that for the prescription that you thought that they were utilizing? Are they not responding to this particular PPI as I mentioned a little bit before? Unlikely, but certainly something to consider. And then do they have refractory acid reflux? Certainly something that we've got to think about. Can you incompletely control their acid with the medication that they're on? And even more importantly, perhaps, do they have refractory GERD, but not necessarily refractory acid reflux? As I said before, not all reflux is acid reflux, particularly for patients who are on PPI therapy and have good acid suppression. It may be the other components of the refluxate that are leading to the patient's symptoms and or tissue damage. And then the last one, again, thinking about this in the context of Occam's razor versus Hickam's dictum, are their symptoms not due to GERD or not just due to GERD? Do they have GERD plus something else going on that we have to be managing two conditions at a time or are we perhaps barking up the wrong tree altogether? So how do we approach this? I'm gonna give you my approach. This is not the definitive approach. And certainly this has come from years of practice and working with several mentors over the years to develop my own algorithm. But I wanna focus here on how I go about doing things and recognizing that there's an art to this and an individuality of each case. This is not the definitive approach for every single patient that you'll see that you think might have refractory GERD. First of all, do we have a compliant patient? As I mentioned before, that is certainly a theme I want you to walk away with. Second, what exactly are the symptoms the patient has at this time? Is it really heartburn? Is it something else? Are they typical or atypical symptoms? Are they not even in the esophagus? And have they improved or changed at all with the patient's prior PPI or other acid reduction therapy use? And then, and again, this is to some degree your own gestalt as you put this together, how likely is it that the patient has GERD? And could there be another etiology for the symptoms that you think could explain the presentation that they have as they talk to you about their condition? Either another primary cause for their symptoms or like gastroparesis, an exacerbating factor for reflux disease. So step two in my algorithm is to complete a BID-PPI trial if not already done. And you see my asterisks there because I have a lot of patients who come in who are not necessarily willing to go higher than once daily dosing, whether because of what they've read about the potential side effects of PPIs or quite frankly, their ability to remember to take them consistently on a BID basis before breakfast and before dinner. But if I can convince them to do it, and the majority were generally able to get them to do it for about two to three months for BID therapy before they're deemed a true PPI failure when I suspect that there's GERD, that's where I go. I give them an eight to 12 week trial, BID before breakfast and dinner. And I see if they take it consistently over that time, where we go. And the reason why I use that two to three month window is that we know that atypical symptoms of GERD, symptoms other than heartburn and regurgitation often take longer to resolve than the typical symptoms. So when you're counseling a patient with potentially refractory GERD and these atypical symptoms, make sure the patient knows to complete that whole two to three month trial rather than giving up after two weeks if they don't feel 100% better. I wouldn't expect that their globus sensation or their voice change or their sore throat is going to change in two weeks time the way that heartburn might respond if you had a more typical symptom presentation. Step three for me is risk stratification. I hinted at this before. I'm really need to make my best clinical guesses. I've spoken to the patient and I look at the objective and subjective data in front of me. How likely is it that the patient really has reflux disease? And is there at least partial response to PPI? And if that's the case, it increases the likelihood in my mind. If they've been on BID dosing and there's been absolutely no change at all, or they've been on several month long trials of daily PPI, and I just sit there and they say they're 0% better no matter what they've tried, here's where I think I might be going in the wrong direction and I might want to exclude GERD as a cause of the symptoms and move on to other diagnoses on my differential. That risk stratification really affects the choice of what we're going to do next as we move to the testing phase or the detective phase of working up the patient. So there are lots of different tests out there that we could consider for assessing GERD and looking for other potential etiologies. You see a few of them listed here, esophageal manometry, quantitative reflux testing, endoscopy, radiography, and nuclear medicine syntagraphy. So let's talk about those in a little bit more detail. What does manometry evaluate? Well, the upper esophageal sphincter is certainly the gateway to the esophagus and we can look to see what the resting pressure and the relaxation pressure are in that muscle. And why is that important? Well, if you've got someone who has atypical symptoms and they have a failure to relax their upper esophageal sphincter completely, that might indicate that we've got more of an oropharyngeal problem, such as cricopharyngeal achalasia or a cricopharyngeal bar. And they may be describing heartburn to you, but what they really have is burning in their throat and their hypopharynx because they're not able to clear very easily what they're doing. And their dysphagia that they may be presenting with is more oropharyngeal than it is esophageal. What else does manometry look at? It looks at esophageal contraction. We look whether it's present or absent. We look at its pattern. Is it ordered or disordered? We look at how quickly that propagation of the contraction wave works its way from the top to the bottom of the esophagus. Is it too fast? And therefore we get an inefficient emptying of the esophagus as a result. We look at the amplitude or strength of the swallow. Is it too weak to push the contents down where they need to be, below the lower esophageal sphincter and into the stomach? And then of course, we can look at the LES as well. We're looking at the resting tone. Does it provide a good break wall to reflux and the residual pressure during the swallow? Does it open up well enough to be able to let the contents through? Or is this an esophageal outflow obstruction process causing the symptoms with which the patient presents? So a normal swallow on high resolution esophageal manometry looks like this. Along the X axis, you have time and you have the altitude or the anatomic positioning along the Y axis. Here you can see that upper esophageal sphincter and then the skeletal muscle component of the swallow before we get to a transition zone where we go between skeletal muscle and smooth muscle. And the smooth muscle contraction is a lot of the work is where a lot of the work that we do in evaluating the strength and the coordination of the swallow takes place when we're evaluating esophageal manometry studies. And then of course, we have the lower esophageal sphincter looking at both its resting and its relaxation pressures, as I mentioned before. Now, we're all familiar with the ability of manometry to diagnose a kalasia and its different subtypes as you see here on the screen, but it also can show us major and now minor peristaltic disorders. This were the classifications in the previous Chicago classification. I'm not showing you the new Chicago version 4.0 today. That's a whole different topic, but I just wanted to show you as an illustrative way of demonstrating the different patterns very easily seen on high resolution manometry can tell you in what way is the swallowing potentially abnormal. Is it too quick? Is it too strong? Is it too weak as you see across the top? Is it inconsistent and weak? Or is it not consistent enough from top to bottom that we have spaces where the peristaltic pressure and wave may be lost? So let's turn now to talking about quantitative reflux testing options. And again, this goes back to your gestalt. Do you have a low or a high likelihood that you may have reflux at play for this patient? If you think it's unlikely that the patient has GERD, then I would strongly recommend getting a 48-hour wireless pH metri or a 96-hour wireless pH metri probe or the Bravo probe off of acid reduction therapy or a 24-hour pH impedance catheter placement and test, again, off acid reduction therapy. The reason why you wanna do all of these studies off therapy is you're answering the key question that comes with that low likelihood on your assessment. Does this patient even have GERD in the first place? And if they do, great, you were wrong. And you move forward and you manage them and you think about additional ways to test them on therapy potentially. But if the quantitative reflux testing is negative off therapy, it's very, very unlikely that this patient has excess reflux of any kind, acid or non-acid, that is contributing to the symptoms with which they're presenting. However, if you have a patient who, in your estimation, has a higher likelihood of having reflux disease, at least as a component of what might be causing their problems, you wanna do 24-hour pH impedance testing on therapy and preferentially BID therapy. Now, there are a number of different schools of thought about managing this, and some folks are not believers in managing the patient this way. I'm a strong believer in this approach, and I'll tell you why. I think what we're looking for here is to prove that the patient is not a volume regurgitator who has excess reflux above and beyond what the medication is able to control. And so being able to quantify the reflux from a number of reflux episodes perspective, from an acid exposure time perspective, looking at symptom correlation to reflux events, all of those can be very helpful to tell you whether or not you're able to control the reflux in the setting of medical therapy. And here is a nice graphic illustration of this woman who has got both a wireless pHmetry probe. Again, it says 48 hours, but I would say it's 48 or 96, depending on your protocol. For the off-PPI as a preferred option if you think that the patient is unlikely to have GERD, and if they're more likely to have GERD, you do the 24-hour pH impedance testing, preferably on BID-PPI therapy, maximum medical therapy, to see whether or not they truly have refractory disease. Here's a nice list of the data that pH testing provides, and you can see that for the wireless pHmetry on the left and the 24-hour pH impedance testing on the right, there are a number of data points that both of them will pick up for you. The number of reflux events, acidic reflux events, the percent time the pH is less than 4, known as the acid exposure time, the calculation of the demister score, which is not a score to say do you have reflux or not, but to predict your response to antireflux surgeries, anatomic interventions, the ability to correlate those symptoms with acid reflux events and see if that correlation is statistically significant. And in the case of the 48-hour probe, as I said, now the ability to expand up to 96 hours of data. But if you look on the right side of the screen, you can see that the pH impedance testing doesn't just look at acidic reflux, it looks at non-acidic and weakly acidic reflux events, and that gives you a lot of extra data that allows you to say, well, is the reflux that the patient is having despite PPI therapy a significant amount and a likely cause of the symptoms? If you test someone on BID-PPI, it's very likely that their acid score, their demister score, their acid exposure time and the number of acid reflux events is going to be normal or close to normal. So you might not be thinking, well, that's likely not the cause. Right. You're right about that. But if there are a tremendous number of weakly acidic and non-acidic reflux events, then that's going to increase your suspicion that this is truly refractory reflux, particularly if they correlate with the symptoms. So remember also that you can evaluate GERD using endoscopy, which is, of course, very resource intensive and expensive and really is only good for looking for endoscopic complications of GERD. As you can see, the erosive esophagitis with a peptic stricture here on the left hand side of the screen, or for anatomic predisposition to GERD like a large hiatal hernia. You can use radiology as well. Barium esophagram is a great way to look at the esophagus. It's kind of a poor man's motility test as well. It gives you a chance to look and see at a basic level, particularly if you get a video esophagram or cine loop images that allow you to see the peristalsis, the peristaltic wave, and whether it's able to strip the barium down the esophagus and into the stomach. You can look for things like a Schottky ring, as you can see on the right hand side, and a hiatal hernia. And you can look for evidence of abnormalities in peristalsis as well. Though, again, this is a limited exam and the data shows that looking at the esophagram is not nearly as good as looking at a manometry for diagnosing esophageal dysmotility. And as you can see here in a nice graph, the relative values of each of those diagnostic tests in GERD is important. And I wanted to show you, just as I put the red circle around those two there, that ambulatory pH monitoring, quantitative reflux testing is very, very helpful when you want to figure out how much reflux someone is actually having. And in particular, if they have atypical symptoms, and you're trying to figure out if this person really does have reflux disease. But again, this is a very much an individualized approach to management based on how the unique patient is presenting to you with their history of success or lack thereof of medication trials, lifestyle, dietary modification, what you have on your other objective testing, how you decide to move forward to complete your diagnostic workup and make a decision for what the next steps are. I want to mention gastric emptying scintigraphy as an important test to consider for patients who have refractory GERD or a suspicion of refractory GERD, and remind you a few things that are important to make sure that your center is obtaining as part of a gastric emptying scintigraphy exam. In the past, they used to do these until half of the gastric contents were emptied. On scintigraphy, they would give you what was called the T1 half and call it a day. That is no longer the standard of care for how you look at gastric emptying exams. You want to have a four-hour test to assess the rate of gastric emptying. It's done with a standardized meal. It's generally an egg and toast meal that has a set portion. And the compound that's visible in the scintigraphy, the labeled compound, is within the eggs. There is a liquid version that's available as well. And the key measurements that you need to make sure that your nuclear medicine specialist, your radiologist, is giving you is the percent of the meal either retained or emptied at both two hours and four hours. And you can see on the screen here the normal amounts are less than 60% or less than or equal to 60% at two hours, and up to 10% retained at four hours, which means that 90% of the stomach should be empty by that time. And since those are really abnormal values, when you get to 11% or 12%, it is an abnormal test. Those are multiple standard deviations above the mean from the tests that were done to come up with the normal ranges. So it may be mildly delayed gastric emptying, but it's still delayed, and you can't just wash it off and say, oh, it was 11, if it had been nine, it would have been okay. Yeah, take it into context, but it is delayed emptying. And this is not an uncommon cause of refractory reflux, and especially if the patient is presenting with nausea, vomiting, early satiety, things that would make you suspect a gastric disorder. Think about getting a gastric emptying scintigraphy as part of your workup. Okay, let's go on to step five now that we've talked about those diagnostic options. Once you put all of your data together, find your diagnosis or find your diagnoses. As I said, they may have more than one at play. Is there an underlying esophageal motility disorder? Is there a eosinophilic esophagitis, particularly in a younger patient who's presenting with maybe some dysphagia as well as chest pain or burning? Is there a peptic stricture at play that's affecting the ability of the esophagus to empty? Is there a parasophageal hernia causing outflow obstruction? Not just a hiatal hernia that's facilitating reflux, but now do we have a parasophageal component that's causing extrinsic compression of the distal esophagus and impairing the ability of swallowed food or other contents to work their way into the stomach? Do they have delayed gastric emptying, as I mentioned before? And then we can get into the functional issues as well, right? Do they have esophageal visceral hypersensitivity, where the sensitivity of the nerve endings that are evaluating the esophagus and sending a message up to the brain are dialed way, way up? And so what really should not cause discomfort is resulting in a message of a five-alarm fire when the brain receives the input from the esophagus and from the enteric nervous system. Certainly something that needs to be considered, and we see this quite a lot in our practice here at Mount Sinai. I will mention functional dyspepsia to you again as well. Remember, functional dyspepsia is the visceral hypersensitivity syndrome of the stomach. And again, if the patient is referring to heartburn, but really means dyspepsia, epigastric discomfort, you've got to think about the fact that this patient may not have a GERD issue. This may be more down in the stomach. And so, again, history is really important here in clarifying what the patient means if there's any ambiguity. And then, of course, does the patient have refractory GERD? So step six, fix refractory reflux, right? If it turns out that, yes, indeed, the patient has excess reflux on quantitative testing, you are sure that this is what's going on, then you've got to think about, well, how do you go after that refractory disease? Well, you've got medical and anatomic interventions and really combinatorial chemistry, right? Combination therapy of both a medical and an anatomic intervention may be the way to get the patient to adequate relief. For example, as I mentioned before, you may want to use an H2 receptor at double dose at bedtime in addition to high dose PPI therapy. You may want to add that sodium alginate, the Gaviscon, with meals to see if the postprandial component improves. And you may want to put in the sucrophate to heal the erosive esophagitis if that's refractory to therapy that you've had so far, and you've confirmed that on endoscopy. Anatomic interventions, lots of options from traditional surgery to newer surgical approaches and some endoscopic approaches that we'll talk about shortly. And, again, don't be afraid to use combination therapy. And we talk about PPI failure all the time. PPIs that can reduce the symptom burden and make things palatable for a patient to continue on is good. That's an improvement. It's not getting them to where we want them to be, but it's helpful. Having a surgery that gets rid of most of the patient's symptoms, but then in combination, for example, with a lower dose PPI can make the patient asymptomatic, that's a win. That's not really a failure, and it's important for us to recognize that paradigm shift here in 2021. So what are the indications for anatomic intervention? Well, that the gold patient, the perfect patient for any of these interventions, is a healthy BIRD patient with typical symptoms that are well controlled on PPIs. If you can prove that the patient has quantitative reflux disease and they're doing great on a PPI, that's terrific. They can stay on that PPI if they want, but they also could go for an anatomic intervention. Why might they do that? Again, cost of lifelong PPI, compliance issues, side effects with current use, fear of side effects from long-term use, as we discussed before. So that's really, that's the golden child patient. That's the perfect patient for any of these interventions that we're going to discuss. Well, what about patients with atypical GERD symptoms? GERD proven on quantitative testing, also relieved on PPIs. Again, very good chance that the patient will improve with an anatomic intervention. Important to note that in general, patients with atypical GERD symptoms are less likely to respond to PPIs or to anatomic interventions. But if they have responded to PPIs, then they are more likely to respond to an anatomic intervention as well, if you've got quantitative reflux testing that indeed has proved that there is excess reflux at play. I have a couple of them here that I think maybe folks are not necessarily thinking about on a regular basis, but I think are important for everyone to consider. Refractory esophagitis despite maximum medical therapy. Volume regurgitation and aspiration symptoms, and or aspiration symptoms, not controlled on PPIs, right, where you have particularly significant defects like a large hiatal hernia. Volume regurgitators will not get better on any medication. If they're symptomatic and their primary symptom is regurgitation, medications just really aren't going to do it. You've got to fix the anatomic defect. And then persistent symptoms documented to be caused by refractory GERD. Again, these are the folks who have excess GERD, excess reflux on quantitative reflux testing, as we just discussed. So what are the options that are available to us? Well, the granddaddy of them all on the anatomic side is the Nissen fund application named for Rudolf Nissen. It's a 360 degree wrap of the fundus around the esophagogastric junction to bolster the lower esophageal sphincter. Mostly it's performed laparoscopically, and the data actually, there's lots and lots of studies out there, but the data looks really good and the fact is that if you ask patients 10 years out, would you have the Nissen again? 90% or so of them would say, yeah, I would do it again. And those studies were done at a time where we didn't have ready access to manometry, where we probably exacerbated some of the symptoms like gas bloat and particularly dysphagia by doing 360 degree wraps in patients who had underlying significant esophageal dysmotility where they might not be able to overcome the pressure generated by the Nissen with a weak swallow. And so now that we have manometry more readily available to us, recognizing that the Nissen versus the PPI in this study from Lars Lindell, that's now remarkably 20 years old, we're sort of right on line with each other and no significant difference in the folks who remained in remission from esophagitis. We do have other options that are available and I want to call out the Toupei fund application, in particular a partial wrap 270 to 300 degrees, instead of the 360 degrees of the Nissen, that gives a little bit more wiggle room for a bolus to get through, even in the setting of a weaker bolus. I'm sorry, in the setting of a weaker peristalsis. And it's thought to generate less dysphagia, and in our practice, and several other places, it has become the preferred approach for refractory GERD in the setting of known esophageal dysmotility. And this is a paper from my time at Temple where we looked at a number of our folks, many of whom had very severe dysmotility, including a peristalsis, and significant reflux and underwent Toupei fund application with excellent outcomes in terms of symptom and minimal dysphagia that responded when it did occur to dilation therapy endoscopic dilation therapy. I don't want to forget to mention the Roux-en-Y gastric bypass and you may be saying this isn't a bariatrics talk. Why are you mentioning the Roux-en-Y? The Roux-en-Y is actually probably one of the greatest anti acid reflux interventions that we can possibly do because of the discontinuity of the GI tract. If you think about it, the acid that's made by the parietal cells has to swim down the duodenum, get to the anastomosis between the two small bowel limbs, and then swim upstream retrograde 100 centimeters from the anastomosis point on that Roux limb back up into the gastric pouch, and then get refluxed through the gastroesophageal junction back up into the esophagus to cause the damage. That's pretty unlikely to happen. And so for patients with significant acid reflux, a Roux-en-Y is great. And for your obese patients who have significant reflux, the Roux-en-Y is a great option. And I don't want to get into the sleeve versus Roux-en-Y debate in this talk tonight to keep time for questions, but it's important to recognize that the sleeve gastrectomy is thought to exacerbate reflux, and the Roux-en-Y is thought to be a reflux treatment. Let's talk about some other anatomic interventions on the surgical side. This is magnetic sphincter augmentation or the LINX device, a band of metal magnetic beads about the size of a quarter, multiple sizes available based on the diameter of the esophagus and the procedure placed around the lower esophageal sphincter to buttress it. And the magnetic beads are on an elastic band so that when the swallowing occurs, and I'll show you a cartoon of this now, what we get is a relaxation of the band. And then a stretching of the band to allow the bolus of the food to go through. So here you can see, here's the lower esophageal sphincter and the diaphragm, any hiatal hernia is reduced, the magnetic band is placed, the magnetic beads are placed there. And that provides a buttressed lower esophageal sphincter to prevent reflux, but the ability of the band to stretch when that bolus comes through, as you see there in the cartoon, really allows a more physiologic approach to managing reflux than suturing with a fund application, a Nissen or a toupee. And you can see the five-year data that Bob Gantz and crew presented now five years ago, showing very nice improvement in all of the heartburn and regurgitation, the typical GERD symptoms, as well as PPI dependence with only a small amount of dissatisfaction. And so going back again to these now quite outdated ACG guidelines, surgical therapy certainly is a treatment option for long term management of GERD, people do not have to stay on a PPI long term, even if they're well controlled. And the fact is that surgical and medical therapy can be equally effective in the right patients. It is not recommended in patients who do not respond to PPI therapy. Again, we've got to go looking for why those patients are not responding. It is essential that we get quantitative reflux testing in patients who do not have evidence of significant end organ damage, esophageal damage, as a result of GERD. So if they don't have Barrett's, if they don't have erosive esophagitis, now grade C or D Los Angeles classification, they don't have a peptic stricture, you've got to get pH monitoring. Again, in this situation, if you're deciding if they want to go for surgery, you could just get the testing off PPI to prove that indeed, they have the reflux and that they're a candidate for the surgery. And again, in those obese patients, especially BMI 35 or greater. Think about bariatric surgery that ruin why gastric bypass is a great option for them. So let's talk about some endoscopic interventions as we finish up the talk. The first dimension is radiofrequency energy delivery. This is the strata system for those of you who may be familiar with it where ablation is performed, delivery of that radiofrequency energy delivery at six levels in the area of the esophagogastric junction. It's done as an outpatient endoscopy, and it does not preclude the use of other anti reflux measures in the future. We don't really know why it works. Compliance was thought to be the reason but it can be reversible. There is not necessarily a bulking up of the tissue, but it does seem to work and there's a nice beta analysis that was put out with over 1400 patients showing improvement in symptom scores, as well as improvement in esophageal acid exposure. It does not work in patients who have any significant hiatal hernia, and it is thought to be the weakest of the anti reflux anatomic interventions that we have, but can be durable patients for example those who had a sleeve gastrectomy already, those who are not stable enough to undergo a longer anti reflux intervention and need a temporizing measure like a pre lung transplant patient. this may be something that we can consider for those folks. It is endorsed by our surgical colleagues at Sages. Let's turn to transoral incisionless fund application or TIF, where a series of H-shaped fasteners are applied for a full thickness plication to recreate the gastroesophageal flap valve from the inside out instead of the outside in, as our surgical colleagues would do. We get about a two to three centimeter long valve of approximately 270 degrees, so somewhat akin to a toupee fund application, though there are some folks who are now finding ways to get that number of degrees involved well over 300 with some special maneuvers. You cannot have a hiatal hernia of two centimeters or greater before the TIF. There are some data that are out there now about using a TIF in combination with the hiatal hernia repair to be done either concurrently or in a staged procedure with the hiatal hernia repair first, but we know that a large clinically significant hiatal hernia decreases the likelihood of longevity. Important to note that there have been several evolutions in the technology that we believe have improved the clinical outcomes in this study that Kareem Trad was the presenting author on, now over five years old, showed a second generation approach to the TIF procedure where there was quite impressive response in, again, symptom relief and also the need for PPIs, and you can see that the curves look a lot like what we showed earlier for the magnetic sphincter augmentation. There are a couple of other technologies that have been out there less established with less data out there. One is the ultrasonic surgical stapler or the MUSE procedure that fires a series of five titanium staples to recreate the valve. There was some early data that came out now several years ago that looked promising, although this one has not progressed in terms of its utilization in our community in the last several years. I do want to call out Dr. Inoue, who of course has been revolutionary in multiple aspects of our field for some work that he has published looking at doing both antireflux mucosectomy or the ARMS procedure, or now antireflux mucosal ablation or the ARMA procedure, which you can see in the bottom two panels, where he either does endoscopic mucosal resection or endoscopic submucosal dissection in the ARM side or mucosal ablation in the ARMA procedure to lead to scarring, which tightens up the gastroesophageal junction and the enlarged cardiac opening as a means of providing an improved degree of control over reflux. These are not the only techniques that have looked at tightening things up at the junction endoscopically. Certainly suturing is one that has been looked at before, and I don't have time to go into all of these in detail, but stay tuned on this because this may be a way in the right patient to provide a durable outcome that could save them a transabdominal approach to surgery. So where are we with endotherapy in 2021? Well, the guidelines back in 2013 said, well, the usage of current endoscopic therapy can't be recommended as an alternative, and that was certainly a very, very long time ago with respect to the data and respect to the number of techniques that are coming out. We've got better data now in terms of immediate efficacy as well as durability that I think are going to change the calculus a little bit when the revised guidelines come out. And so in the right patients, it's worth considering these alternatives when there are comorbidities and or patient preferences that preclude access to surgical techniques. So in conclusion, let me wrap up here and then go to the questions. I saw the Zoom page here lighting up with lots of different folks chiming in, looking forward to talking with you about your questions. Let me just give you a few conclusions and then we can move to the discussion. PPI certainly remain the most potent acid-reducing agent that we have in our medical arsenal. There may be improvements in other categories of drugs to treat reflux in the future, but right now that's the best that we've got and by a long shot. And switching to another medication is unlikely to improve control of reflux, be it acid or non-acid. If a patient continues to be symptomatic despite PPI therapy, it's important to ensure that they are taking their medicine correctly. And then if you indeed are able to confirm that, then do quantitative reflux testing to prove that indeed their reflux is not controllable with optimal medical therapy. Prior to any anatomic intervention for reflux, surgical or endosurgical, it is important to check esophageal function with manometry to exclude dysmotility that may change the way that you manage the patient. Anatomic intervention remains the best option for improving the mechanical barrier to gastroesophageal reflux, as new options show promise as alternatives to the Nissen Fund application, as I outlined, and endoscopic techniques to bolster the antireflux barrier also show promise with sample size and durability data now available for us, not certainly for the decades of data for the Nissen Fund application, but we're getting more data, larger size studies, longer duration studies that are going to make us more comfortable in utilizing those techniques for our reflux patients in the years to come. And with that, I will thank you for your attention and I look forward to talking with you and answering questions in the discussion section. Well, thank you, Dr. Smith for that wonderful talk. It is clearly a very hot topic because as you have seen, a lot of different questions have come in during the talk. I'm just going to start trying to put together, there's a number of questions with people posing the question to you. Do you have a specific dose and choice of PPI that you like to start? And is this at all affected by the type of esophagitis you see? And is there a certain time which you like to stop them? Great series of questions. Let me try and do a little bit of rapid fire because I see the number of folks in the Q&A there. The answer is the PPI that I give is often the one that the insurance company pays for or the patient is willing to pay for out of pocket. We have more and more patients who have a class exclusion for PPIs in our market because of the fact that they are available over the counter and insurance companies are trying to scrimp and save wherever they can. Omeprazole seems to be the one that's most readily available across the different payers that we work with. And I find that to be a very effective drug. And I will freely admit that I don't start a lot of patients on PPIs because I have a referral-based practice. And so when they come to me, they're generally coming because they're not better despite taking the PPI. So when I am precepting in our fellows clinic and we see a patient that we think has GERD, I'm perfectly okay for mild to moderate symptoms starting them on 20 milligrams once a day of Omeprazole 30 minutes before breakfast, or if they have primarily nocturnal symptoms, 20 milligrams before dinner. I really think that the PPIs are generally interchangeable for the vast majority of our patients. I will say that anecdotally, and I think others have seen this as well, but Pantoprazole is probably on the weaker side. But I would say that for the vast majority of patients, it's still viable and it's often one that's on formulary at the 40 milligram dose. I don't use 20 milligrams of Pantoprazole. If a patient I see is well-controlled on 20 milligrams of Pantoprazole, I'm thrilled for them, but that's the exception and not the rule. But I really do think that the patients are, again, what they're able to get access to at a BID dosing, whatever you want to do for your quantitative reflux testing. I'm fine with 20 BID for Omeprazole. I'm fine with 30 BID for Lansoprazole. I'm fine with 20 or 40 BID for Esomeprazole. It really doesn't matter for the quantitative reflux testing. The normal values that are out there in the world, and again, somewhat up for debate, are really on BID data. We don't have any data out there for what a once-daily PPI 24-hour pH impedance test should show us. So I generally try and avoid using that dose for my quantitative testing on therapy unless the patient says, this is the highest dose I will accept, and if I need more than this, I'm going to have surgery. In which case, I will test them, and I will look at their Demester score and their acid exposure time and their number of reflux events and do my best to make a clinical judgment. In terms of stopping the PPI, I think that was one of the ones you mentioned at the very end. Again, I try not to take them cold turkey. I find the patients who don't have GERD often quit cold turkey themselves, and I don't have to do it because they say, this isn't working, and they give it up before they even make it to you. In patients who are concerned, I will ramp them down maybe once every week to two weeks, depending on how they're feeling and how skittish they seem to be. I will mention that in patients where I suspect that they don't have GERD, but they do have visceral hypersensitivity, I will start the neuromodulator therapy and get them to symptom relief before I start weaning off the PPI, unless the patient insists on doing both of those at the same time. I just find it too confusing. There are too many confounding variables to address if you're making medication changes up and down in two classes at the same time. Great. Great. Thank you for those answers. Moving on to a little bit more about our testing of reflux and GERD, there's a couple of questions that came in about pH impedance and Bravo in particular. One of them was, what specific cutoffs are you using for when you're looking at pH impedance as well as Bravo? What are the numbers that you use as your cutoffs, maybe for someone who might be looking at those studies who aren't as used to reading them as you? Sure. There's a little bit of debate about this. It's important to recognize that you've got to look at this in the setting of the total group of results. I am not someone who looks at one result and says, because this result is positive and all the other ones were in the normal range, this is an abnormal study. I will call it out, but I will discuss it in the context of that. I think it's important if you don't do these tests yourself, whoever you are referring to to do the tests, make sure that they don't just send you what the computer spits out. Make sure that they look at it, they think about the patient, and they give you some interpretation beyond just the raw numbers. For patients who are off PPI, I'm generally looking, again, the Demeester score has been set, that's 14.73. Above that number is shown to be likely to respond to anatomic intervention, and below that number is less likely to respond to anatomic intervention. In terms of acid exposure time, 4.5% is certainly one that's out there. Some people are more stringent and want it closer to 5% to 6%. Again, I take it in the context of things. There are folks who sit right on the borderline. I either think have very mild GERD or probably have a functional or visceral hypersensitivity component along with it. They're not people I'm going to be sending off to surgery anyway, because they're already people that I'm a little bit dubious about the diagnosis. I think the number of reflux events is important, and particularly in the 24-hour pH impedance patients who are on therapy. That's a big go-to number for me. When you have a patient who's got 80, 90, 100 reflux events, but good control of their acid, even if the symptoms are not tremendously correlating with it, that's a volume regurgitator where I'm thinking about, okay, I need to get there, particularly in a patient with the atypical symptoms where I think it's the duration and the extent of the reflux that is leading to symptom generation as a result of chronic inflammation, not just the burn at that one moment that the reflux state is reaching that anatomic point. Great. Thank you. Then another question about why would you specifically use impedance testing if GERD is more likely? Do you have a particular reason that you choose that? The important thing to recognize is that a Bravo study, a 48 or 96-hour wireless pH capsule, if you place that in the esophagus and the patient is on therapy, that capsule is only able to measure pH and at that one point. If the test comes back normal, you have no idea whether or not the patient has GERD that's now well-controlled because you're on a PPI or the patient never had GERD to begin with because the data will look the same. The pH impedance test, because it measures weakly acidic and non-acidic reflux, will look at all reflux events. For a patient on PPI therapy, that's really the only option if you're testing on therapy. You really should never be doing a 48-hour or 96-hour wireless test on therapy. They should always be off therapy because they only measure acid reflux as I showed you on that slide with the two columns. Great. Thank you. Then one more question about analysis modalities. A question came in about Bravo. I think this is pertaining to if the Bravo falls off after 24 hours or say it malfunctions. If you only get 24 hours of the study, but it is very positive, how would you interpret that? That happened to me once in my career, luckily. Fortunately, they haven't fallen off a whole lot before the 48-hour testing, which is the duration that I currently use, though I'm considering expanding that. If you get 24 hours of good data and then you see very clearly that the capsule falls off and you see a very deep, heavily acidic exposure time that's prolonged for an hour or two or three that doesn't have the little spikes up and down on it, you can be pretty sure it fell off. What you do is you just exclude all of that time from the analysis and you score it as if it's a modified 24-hour pH impedance test, except that you're only getting the acid part of that test. I don't think there's any problem in trying to do that. If you are doing that test and you are reporting it out, though, it's really important to recognize when you are limited by the analysis time that you have. For example, if you're doing a 24-hour pH impedance test and the patient decides to have a four-hour meal three times in the 24 hours and you lose half of your exposure time or they never record any supine time, that's important to call out because it will limit the analysis that you're making, because especially for supine versus erect time, there are different normal values for what's allowed in terms of acid exposure. Very, very important to make sure that you say, hey, this didn't look right and this is how I interpreted in that context. Or if you added supine time from two to six in the morning because you said they had to be sleeping at that time and they just forgot to press the button. The worst part is for your wireless test, if the monitor is further than two to three feet away from the patient and you lose all of the supine time because they go to sleep and they roll to the other side of the bed and you lose that time and that happens two nights in a row, you're really only going to be able to talk about the erect time that you could do the calculations for, and that's going to limit the success of your study. Though if that time is markedly positive, you're going to have a positive test, and that's okay to say. The problem is if it's negative and there's no supine time data that's obtained, you can't rule out supine reflux, which is common and commonly seen in these patients who have more nocturnal symptoms. Great, thank you. People are really loving this discussion on the Bravo and impedance because as we talk, more questions are coming in about it. So I'll just pose you one more sort of subset of questions with the Bravo, PH, and impedance, and then maybe we can move on to some of the other questions. Just for patients with atypical symptoms, so for instance, cough or other symptoms such as that, is there something specific you do with the Bravo and PH impedance in terms of start, when do you jump to that assessment, and is there something different you do with this study? So I would say this. I think the most important thing to remind people is that you can't stop taking your PPI a day or two before the Bravo test and expect to have a reliable result. Most of us who do this on a frequent basis will say at least seven days. Some people say 10. Some people will say 14 days. And actually, believe it or not, that's a really good prognostic indicator and probably one that we should document more. When the patient comes in, if they see you for endoscopy and they're cursing at you when you walk into the pre-admission area because they can't stand how terrible they felt since you made them stop their PPI, that is a really good indicator that they have acid reflux. If they don't really feel all that different, that's a pretty good indicator that your Bravo study is probably going to be negative. But it's really important that they should stop their PPI at least seven days before. And so that's, you know, my management pearl for that is right there. Atypical versus typical symptoms and deciding whether or not to do a Bravo, again, it's going to be in that clinical context and that index of suspicion. So if I, and again, and if you want to hedge your bets and you want to do a 24-hour pH impedance test off PPI, that's perfectly okay too. Again, you're going to get 24 hours of data instead of 48 or 96. So if you happen to catch them on the wrong day, you might miss GERD, right? But you do get that other impedance data, which can be very helpful and might be able to enlighten your management path. So don't feel that just because there's a low index of suspicion, you have to do a Bravo wireless capsule. You know, particularly, let's say the patient was referred to you and a month or two ago had a normal endoscopy. You may not want to repeat it, but you might want to remind your patient that they're going to be walking around with a tube sticking out of their nose. And if, you know, they may or may not be very excited about that, it's really important to warn your patients what a manometry entails and what a pH impedance test entails so that they don't get there, take up a slot, and then refuse it, and now you're stuck and you gotta go back to the drawing board and go back again. So just be careful with that, set expectations well, but again, low index of suspicion, any quantitative testing off PPI is gonna provide a value, but the one-day test just may have a sampling error issue that getting a two or a four-day test may be able to overcome. Great, thank you. So I'm gonna move into some of the management questions now in terms of other therapies. So there's been a couple of questions about sort of like the role of surgery. So the first one that was asked was, for patients who have significant regurgitation symptoms and they've already had like the manometry tests, do you consider anatomical treatments faster in patients with that specific symptom of the actual regurgitation, or is it just another one of the things that can be done? Yes. I think patients whose predominant presenting symptom is regurgitation, and I suspect that they're a volume regurgitator, I will get them thinking about anatomic intervention faster, and I will think about throwing into my mix at an earlier stage if they haven't had an endoscopy already and they're the right age, I might think about an endoscopy, but I also might think about getting them a barium esophagram, because if I suspect that they might have a large volume regurgitation and or a large hiatal hernia, if you see either one of those on an esophagram, it may move you along faster in your algorithm. So that's certainly something to think about. The other thing I will mention just as a sideline to that is that the last two surgeons, primary surgeons I have worked with in my practices in New York and Philadelphia have all started doing preoperative gastric emptying scintigraphy just to get a baseline rule out delayed gastric emptying, and then if there are any symptoms that are concerning for vagal nerve injury and associated gastroparesis or post-op syndromes that involve gastric motility, we know what was going on before and we have a baseline to consider. So as part of our plan, when we get a patient wrapped up with a bow and ready to go for our surgical consultation with my colleague, we get them a gastric emptying scintigraphy, and if we don't, the surgeon will automatically get it as part of the first visit. So I just wanted to pass that along as something that's really changed in our management algorithm for those preoperative patients. Great. It's really important. And that actually was another question that was posed. If you can maybe elaborate a little bit more on for some of the participants, why that is an important test to get, because that was actually a specific question that was asked. Yeah. So in particular, there are two ways to look at that. Let's talk about it first in the context of this talk, which is working up refractory GERD or potential refractory GERD. We know that if your stomach is empty, we can flip you upside down and there's nothing to reflux, right? There's no gastric contents that are there and available to go retrograde. However, if you have a delay in your gastric emptying and you're holding on to more gastric contents, old food, secreted gastric juices, anything that you swallow, any swallowed liquids, they're gonna slosh around in there. And the more that they're there and the longer that they're there, the greater the chance that they're going to backwash into the esophagus. So if you have a patient with refractory GERD where you don't have any other potential cause for it, it's important to think about that as something that may not necessarily present with the typical nausea, vomiting, early satiety, but particularly when it does, that's got to move up your differential diagnosis and get on your radar for testing. In the setting of thinking about managing from the surgical perspective, as I said before, important to recognize that you're going to be manipulating the esophageal hiatus and the diaphragmatic region. And so you're going to be working in the area where the vagus runs. And even though surgeons are very careful to minimize trauma to the vagus and they look for it, they isolate it, they identify it before they complete all of their dissection and do their wrap, it doesn't mean that it works all the time. And some surgeons are better at it than others. And there can be injury to the vagus as a result of the surgery. There also can be plenty of gastric symptoms, gas bloat I mentioned before, for example, after the Nissen fundamentation, dumping syndrome, some other things where there are epigastric symptoms, not reflux symptoms, where you're thinking about postoperatively, how do I need to manage this? Or more importantly, when the surgeon kicks the patient back to you and says, my wrap is fine, you got to figure out what's wrong with them now. Having that gastric emptying scintigraphy may provide you not only a baseline, but also a suspicion for what might be the trigger of these postoperative symptoms. And so for both of those reasons, you need to actively consider this examination as a way of working up your patient. Definitely. I think we have time for maybe one or two more questions. So I'll pose, there's some really great specific questions that I think maybe we can type the answer. So then afterwards, but for some of the more general ones that people have asked, I think this is a hot topic. There was a question posed about the elimination of H. pylori, whether or not it has been found to be beneficial or detrimental for reflux, which I'm sure is going to be a little bit of a complicated answer, but. I'll just give you my personal take, which is that if the patient has H. pylori, I get rid of it. And because I do think that there's a benefit to that, certainly from the oncologic perspective and the risk of gastric cancer long-term, and it certainly could be contributing to symptoms. We've talked before about how dyspepsia can be misnamed heartburn or mischaracterized by patients. And that may be part of what's going on. So I always get rid of the H. pylori, no matter what. I don't think it really, even in significant, with significant atrophy, I'm not sure that it really changes acid secretion all that much. And that if they already are coming to me with refractory GERD, and they have H. pylori, I'm not really at all convinced that I'm going to make the GERD that much worse by restoring the health of the gastric mucosa by eliminating the H. pylori. So for me in the setting of refractory GERD, I still get rid of, I still eradicate, and I prove eradication for all of the patients who are found to have H. pylori. Okay, great, thank you. And then one more general question, and I'll leave some of the specific ones for us to answer in the chat, but are there specific patients who have reflux that you don't end up doing an EGD on? And if so, who are they? So I think if you follow the guidelines that are out there, you're younger, healthier patients with mild symptoms, no red flag symptoms, they're perfectly appropriate for an empiric PPI trial. And if they respond well, I don't think that they need necessarily to undergo endoscopy. If they finish that trial and then they develop refractory symptoms or recurrent symptoms when they come off of it, that may be an indication, although the data there is a little bit gray. And again, your older patients, certainly over 55, anybody that has a red flag symptom, you have to think about an endoscoping. If someone had a good quality exam and you have access to the report and the photos, there's no need for you to repeat it just because they're new to you. If you feel confident that you see in their documentation, both photo documentation and written documentation, a sufficient amount of information to say that you don't think that there is an abnormality that you need to exclude that was missed potentially on the prior scope. Great. Okay, and one last question that just came in, which I actually wanna know the answer to, and I applaud them for hanging in there with us at the end. Do you have any specific management advice for patients who only have reflux while jogging? I thought this was quite interesting, so. Well, the jogger question, and since I'm right here a couple of blocks from Central Park, that's a very hot topic in our practice. You know, it's a great question. It goes to the fact that something in the physiology or the pathophysiology of their upper GI tract is predisposing them to getting refluxate with a change in intra-abdominal pressure, positioning. It's still reflux, and it may mean that, you know, particularly if they don't respond to therapy, that it may be a volume issue more than an acidity issue when you've got someone who is actively exercising in a higher impact way, and that may change your management more towards anatomic intervention, but those are also the same folks who don't necessarily wanna be put on the shelf during recovery from surgery. So finding methods that are less invasive or less altering to normal physiology or normal anatomy, for example, the magnetic sphincter augmentation in a young, healthy jogger who's just got a weak sphincter, that might be a great way for them to maintain an otherwise healthy lifestyle without having to disrupt the anatomy that provides symptomatic relief and keeps them off of taking pharmacotherapy for decades, because a lot of these folks, as you know, are in their 20s, 30s, 40s, far earlier than we would expect the sedentary GERD patient to be dragged in by their partner for their visit. All right, I see two open questions in the Q&A. Should we go to those first? Sure. Yeah, and then there's one in the chat that we didn't answer as well that I will call your attention to after. Okay, great. So let's look at the first question here. Obese patient with reflux, what procedure first, bariatric or reflux or both same time? Really important to recognize that depending on what intervention you make for the bariatric piece, as I mentioned with the Roux-en-Y gastric bypass, you're really treating the reflux as well. A lot of these obese patients do have a significant hiatal hernia. So as part of the Roux-en-Y bypass, there will be a hernia repair that's performed to get the anatomy back in the right spot. And that can help an awful lot in terms of managing the reflux. So I would argue that it's not necessarily that you're doing two distinct procedures. You don't have to do, and people don't generally do a fund application in the setting of a gastric bypass. But a hiatal hernia repair in the setting of a Roux-en-Y gastric bypass is a common combination. And so I would say that is a simultaneous way of addressing it. But again, it would relate to the patient. I had a patient today I was speaking with the surgeon where we were talking about the fact that the patient's current BMI is over 35, but he's relatively sure that this young patient who has repeatedly dropped weight in the past when sort of reminded to be more diligent about his eating habits, could very easily get well below 35. And even if he gets down to 32 or 33, then he probably could get down into the high 20s, in which case the surgeon that I work with in that case felt he would be an even better candidate because the less fat that's sitting around, the better operative candidate he is even for a Nissen fund application, which is our planned intervention. So I think he'd gotten from 35 and a half down to 34, 33 and a half. But the thought was still that that was, if there's more medical weight loss that can happen with dietary and lifestyle intervention, that might be even better. So just a few things to consider there in that. I consider them sort of the same intervention here. And then one other question, how many of your patients that do not respond to PPI will require anatomic treatments? I think that's very practice dependent. And to some degree, I sort of wonder if there's a lunar cycling of this as well, because there will be weeks where all we see is visceral hypersensitivity in patients who are PPI non-responsive or have other diagnoses besides GERD. And then there will be weeks where it's just a whole bunch of volume regurgitators and parasophageal and large sliding hiatal hernias and patients with underlying dysmotility and lack of LES tone on manometry who are all great surgical candidates. And I wish I could tell you what the right number is to look for as a target in your practice, but I would argue that it probably depends a lot on who is sending you patients and whether or not you have a motility lab associated with your practice. If you do, you're probably more likely to get a group that is lower likelihood of having GERD when you finish your workup and you get more of those functional visceral hypersensitivity patients. All right, Kim, did you want to go to the chat? Yeah, there was one question that was posed earlier. So basically the question is, patients with liver and kidney transplants are often started on PPI when they're given prednisone. This participant was concerned due to the fact that they're immunocompromised and you had brought up the increased risk of nosocomial opportunistic infections. Would you recommend that these patients be on an H2 blocker instead, or would you still stick with the PPI? That's a really interesting question. And I am not familiar with the most recent transplant literature there. I have a feeling as Mount Sinai is starting up its lung transplant program, and we're getting more involved in that. In fact, I have a meeting with them tomorrow that this will be something that we'll probably think a little bit about. And in the liver kidney area, we don't see a whole lot of folks with liver and kidney transplants. Interestingly, one of my first Barrett's patients was a kidney transplant recipient. And I do wonder whether or not some of the meds predisposed him both to development of GERD, but also to development of dysplasia, some of the anti-rejection medications. I would have to be honest with you, this is something that would be a collaborative discussion. This is something that would be a collaborative discussion with the transplant hepatologist or transplant nephrologist. I'm not averse to starting the PPI therapy. I think that there's a modest, mild to modest increase in the risks of infection as we mentioned before, but not necessarily one that I think would be that significant. And certainly the C. difficile one for a hospitalized patient being started right away would be one that would be even of greater concern that I would wanna think about. The community acquired pneumonia maybe, but the C. diff in a newly transplanted patient would be concerning to me for their initial recovery and getting out of the gate with a new organ on the right foot. So, I think it's a good collaborative discussion and it's one that I would have. I do not remember people avoiding PPIs in these cases when I worked more closely with that population. And I certainly think if you have GERD and need a PPI and are getting a transplant and you've demonstrated that you are not very mild disease that would respond to H2 blockers as we talked about earlier in the talk, I don't see that group being good candidates to downshift to an H2 blocker or some other therapy. Great. And then the last question that just came in like a couple of minutes ago, basically pre-NISN we mentioned motility testing, we mentioned pH impedance and we mentioned gastric emptying. What is your standard protocol? Do you always do all three or is there some variance to that? So, certainly if you're considering, in terms of deciding what kind of surgical fund application NISN versus toupee, the manometry is essential there. I would never do a NISN without getting a manometry. For patients who do not tolerate a high resolution esophageal manometry, there is some growing discussion of using impedance planimetry, the endoflip, as a means of evaluating esophageal function. I don't think that's ready for prime time, but I do think that's something we're gonna wanna watch closely in the years to come. My default is if a patient cannot tolerate a manometry, that we do a toupee. We do a partial fund application in those patients. The toupee works very well for patients with normal motility just as it works well for patients with dysmotility. And I don't think that just because you're leaving a little wiggle room, you're still, that you're putting the patient at significant risk, you're still restoring the gastroesophageal flap valve and the angle of hiss. And those I think are the most important interventions that an anti-reflux surgery makes, not necessarily that extra 60 degrees of wrap. Yeah, thank you, Dr. Smith. Man, what a presentation powerhouse there tonight. You did an awesome job. Thank you. And Dr. Cavalieri, thank you for managing all of those questions that were coming in. So in closing, again, you know, for all of you participants who stayed on for tonight's presentation, I just really wanted to extend our gratitude for you being on with and listening in on such a great presentation by Dr. Smith. Before you log off, we really would really appreciate your feedback on tonight's event by going to the networking lounge in our platform and completing our evaluation. I promise you, it only takes like a minute or two just to answer those questions. That feedback is so important to us so we can continue to get information and improve upon our webinars to you. So thank you for that. This does conclude our presentation for this evening. We do hope that this presentation is useful to you and your practice. As a reminder, again, you can access a recording of this webinar by logging onto GILeap by going to learn.asge.org. You do not have to be an ASGE member to access this content as our goal of these webinars is to provide information and education from our Thursday topics as an open source to all gastroenterologists and endoscopists globally in improving their practices. So feel free to gain access. We usually get that posted in about a day or two after tonight. Our next webinar, as you can see on our slide here, will be next Thursday, July 22nd at 7 p.m. Central on Pharmacotherapy for Obesity. Please plan to attend. Thank you so much again. Enjoy the rest of your evening and have a good night.

refractory GERD

symptom management

PPIs

medical treatment

patient compliance

risk stratification

diagnostic tests

individualized management

sodium alginate

sucralfate

anatomic interventions

endoscopic approaches

combination therapy

acid reflux