Hello, everyone, and welcome to this edition of ASGE's Thursday Night Lights, GERD, Current Landscape of Testing and Management in 2025. We're glad to have you join us this evening for this important update and discussion. This session is designed where you can learn and grow together. My name is Michelle Akers, and I am the announcer this evening. We encourage you to engage actively by submitting your questions and comments throughout the evening via the Q&A box and not the chat box. That will keep us organized. Your participation is invaluable to us as you advance in your knowledge of GERD and grow with your colleagues. A Q&A session will be held at the conclusion of the presentations, so let's make the most of this opportunity to learn and share. A recording of tonight's session will populate your GILeap account when it's available in about two weeks, so you can review the content anew or watch it with others. Now it is my pleasure to introduce our moderators, Drs. Knotts and Mahadev. Dr. Rita Knotts is an assistant professor of medicine at NYU Langone Health Center for esophageal health. Current clinical and research focus includes esophageal swallowing and motility disorders, GERD, and EOE. She currently serves as the chair of ASGE's ETED GERD special interest group. Dr. Hari Mahadev is the director of endoscopic resection and assistant professor of medicine specializing in advanced endoscopy at Weill Cornell Medicine. He currently serves as the vice chair of ASGE's ETED GERD special interest group. I will now hand the proverbial floor over to Drs. Knotts and Mahadev. Good evening, everyone. Dr. Mahadev and I are so pleased to have you all join us this evening to discuss the current landscape of testing and management for gastroesophageal reflux disease. We're joined this evening by a team of gastroenterologists and surgeons who are experts in esophageal diseases. GERD remains one of the most prevalent and complex conditions affecting millions worldwide. But despite decades of research, the area just continues to evolve and new treatment paradigms are emerging with ongoing developments in diagnostic techniques, therapeutic options, and surgical innovations. Our agenda tonight is filled with fascinating sessions led by experts in the field who will guide us through the latest evidence as well as present current techniques that are revolutionizing the way we approach this condition. So our first speaker this evening is Dr. Shreya Chablani. She's trained at various prestigious institutions around New York City prior to joining the NYU Langone Center for Esophageal Health as an esophageal specialist. And it's wonderful to have her with us tonight to tell us about how and who we should test for GERD in 2025. Thank you, Dr. Knotts, for that kind introduction. Let me get my presentation off. OK. So as Dr. Knotts mentioned, I'm going to be talking about the workup of GERD in 2025 and how and who are we testing. The objectives of my talk, I'm going to discuss the pathophysiology of GERD and its phenotypes. We'll discuss the diagnostic approach to GERD. And lastly, I'm going to talk about the indications for reflux testing and who we test. What is GERD? GERD is a condition where retrograde reflux of stomach content causes troublesome symptoms and or complications. It is a complex multifactorial disease process involving an imbalance between both the aggressive forces of refluxate and the defensive forces of the esophagus. There are two phenotypes of GERD, erosive and non-erosive disease, namely, which patient gets erosive esophagitis and which one has a completely normal and dusty one. In a normal patient, there are several factors that protect us from the effects of physiologic acid reflux. Destruction of any of the components can lead to pathologic reflux and its associated complications. The major component driving esophageal mucosal damage is the refluxate, which can overcome built-in defenses of the esophageal epithelium due to its potency, composition, and time of exposure to the lining. Refluxate is made up of varying levels of acid, bile, pepsin, food contents, amongst other things, each of which has a unique mechanism by which it can destroy mucosal integrity. Intact saliva production, intact reflux-induced swallow, and intact peristalsis all facilitate clearance of retrograde reflux. As such, xerostomia and hypomotility disorders of the esophagus can all worsen it. Disruption to the antireflux barrier, such as with a hiatal hernia, and decreased LNES tone can also shift the balance. Delayed gastric MDA, an increase in the size of the acid pocket or the area of unbuffered gastric acid that accumulates in the proximal stomach after meals can also lead to GERD. And lastly, increased abdominal pressure and the setting of obesity is an important contributor. It's clear that when thinking about treatment for these patients, it's not just about acid exposure and suppression. Because if that were the case, PPIs would work on almost everyone. If we can think about testing for GERD in terms of its physiology and how this becomes disrupted, we can truly understand how to approach this diagnosis and ultimately understand how to treat each individual patient in a personalized fashion. The label of GERD has become associated with a laundry list of signs and symptoms. There are typical symptoms, including heartburn, regurgitation, and chest discomfort. But there are also several atypical symptoms or extra esophageal symptoms that have been oftentimes mistakenly attributed to GERD, such as cough, hoarse voice, halitosis, sore throat. But are these really GERD? This has led to frequent misdiagnosis and misuse of medical therapy. And thus, it is our responsibility as gastroenterologists to tease these apart and to either diagnose or exclude a diagnosis of GERD with confidence. There are a variety of diagnostic tools in our alimentarium to diagnose GERD, starting with, first and foremost, the clinical history, probably the most important. There are several symptom scores that we can use, such as the GERD HRQL, to help us make the diagnosis. We can use the response of typical symptoms in a patient to empiric PPI therapy. Radiologic tests, such as esophagram, can suggest GERD, though this can be subjective and does not always correlate. And of course, endoscopy, which is always our go-to diagnostic tool of gastroenterologists. However, up to 70% of patients with symptoms have normal endoscopies without any conclusive evidence of GERD. Conclusive evidence of GERD counts as Los Angeles grade B, C, or D esophagitis, biopsy-proven barreth, and a peptic stricture. Furthermore, one in three patients with ongoing symptoms despite PPI treatment do not actually have GERD, which is why our recent ATG guidelines recommend taking patients off PPI for two to four weeks prior to endoscopy to maximize discovery of possible erosive phenotype of GERD. However, most patients have normal endoscopies, and thus, advanced diagnostics come into play. I'm going to now be talking about wireless pH testing and pH impedance testing. First, wireless pH monitoring. This involves placement of a 3-centimeter capsule during sedated endoscopy. There is an option to place this transnasally, but that can be quite uncomfortable. The capsule is attached to the esophageal mucosa using an oral delivery device that you see here. This employs suction and subsequent deployment of a clip onto the esophageal mucosa, and the chip is placed approximately 6 centimeters above the squamous columnar junction. The capsule is later expelled an average of 7 to 10 days via the stool. While the capsule is in place, it wirelessly transmits pH data to a recording device that you see here, and the patient can wear this device as a cross-body bag for up to 96 hours. Previously, we used to perform wireless pH monitoring for 48 hours. However, data has shown that extended monitoring increases the sensitivity of reflux detection and symptom events, and it allows us to measure day-to-day variability in acid exposure. The patient can press buttons on this recording device to denote meal times so we don't confuse alcohol for acid reflux, supine periods, and then these shapes represent different symptoms that that patient may be experiencing. This study is conducted off of acid suppressive medication so that you can accurately diagnose skirt. Here's an example of a patient diary that we give to patients along with pushing the buttons on the device. This is important because patients, you want to confirm what they're actually eating to see if there's any dietary correlation to their acid reflux, and most importantly, you want to confirm those meal start and end times and the supine period so you can accurately look at their study. Here's an example of a wireless pH tracing. This is what you're going to get back once you upload the data from that device. The line in the center is pH of four. Below that, lower pH and reflux events can be seen. On top, you see some green bars, blue bars, and diamonds. These diamonds represent the times where the patient pushed a button for a symptom. The green bars are meals, and the blue bars are supine periods, so you can really get a global assessment of this study over the 96 hours, and you can zoom in and look at each individual day as well. So what are the basic metrics that we're looking for from this data, and how do we interpret everything? The most important metric that we look at is the acid exposure time, or the AET. This is the percent of time the pH is less than four in the esophagus. An AET of greater than 6% is conclusive evidence for pathologic birth, and this is the most reproducible metric and most predictive of a response to therapy. You can further look at the upright AET, the supine AET, and you can look at postprandial periods and times after meals to look further at that patient's reflux burden. You can also assess the temporal relationship between symptoms and reflux events with the SI and the SAF. The SI, or the symptom index, represents the percent of symptoms preceded by a reflux episode. The SAF, or the symptom association probability, is a much more complex statistical calculation where P is the probability value obtained from a Fisher's exact test, which determines the likelihood that the observed association between symptoms and reflux events occurred by chance. Essentially, SAF represents the percentage probability that a symptom is associated with a reflux event, with a higher SAF indicating a stronger correlation. Now these measures are both only reliable when there are more than three or more of each symptom recorded during that test. And you want, ideally, both the SI and the SAF to be positive for it to be considered a significant association. Shifting gears to pH impedance monitoring, pH impedance involves the placement of a transnasal catheter 5 centimeters above the proximal LAS border as found on manometry. Because there's a catheter in this patient's nose, you can really only do this for 24 hours of ambulatory monitoring. The recording device looks somewhat similar. There's a meal button, a supine button, and a symptom button, but there's also an additional pill button, which patients can use if they're performing it on PPI stone. You get additional information from pH impedance tests. In addition to there being an esophageal pH sensor 5 centimeters above the LAS, there's also a gastric pH sensor at the end of the catheter, and there are six impedance sensors throughout its length. As a reminder of what impedance is, impedance is the opposition to the flow of current. Current needs ions to conduct. Impedance is inversely proportional to conductivity, therefore air has fewer ions, low conductivity, and higher impedance, whereas a typical bullet, refluxate liquid, for example, has a high conductivity because there's many ions, and thus lower impedance. This allows us to detect anterograde and retrograde bolus flow. What other additional information can we glean from pH impedance tests beyond the vital AET, which is our most important metric? We can see anterograde and retrograde bolus flow, as I mentioned. You can characterize each reflux event as acidic, weakly acidic, non-acidic, and you can also assess the proximal extent of reflux, which can be helpful sometimes in assessing extra esophageal symptoms. You can correlate these symptoms to reflux events as you do in wireless capsule testing, but you can also see air swallows and belching and gas, and this can be helpful in a patient who your suspicion is high for aerofasia or supergastric belching. You also have a gastric pH sensor, which is helpful in an on-PPI study, and also to serve as a control to ensure your catheter has not migrated. However, the most important metric remains the AET. Here's an example of a pH impedance tracing. On the bottom, you have two pH sensor tracings, the red. On the bottom is the gastric marker, and the one above it is the pH sensor. You can see these red reflux events throughout that sensor. And this blue and white contour plot here is basically the impedance. PPI equals low impedance equals a reflux event. You still have those same supine and mealtime periods up top with the diamonds denoting symptoms. Here's a close-up of an acid reflux event. On the left, you have a nice line tracing of a retrograde bullet flow. You can see that line tracing with the impedance falling as you go up each sensor, and there's the corresponding acid reflux period as seen by the pH sensor. And then on the right, you have the corresponding contour plot to that line tracing with the triangular-shaped white impedance event. So this is an acid reflux event. The report, what are you going to see when you get these patients referred back to you after testing is done. For wireless pH testing, you'll get an acid exposure time, and you'll get a symptom association. And some further details that the reading provider may notice when they're looking through the studies, such as dietary correlation. On pH impedance testing, look at that theme information, but you'll also get a gastric pH, and you'll also get the number of reflux events. You can also see a Demester score reported occasionally, which is a compound score used to assess esophageal acid exposure calculated by summing up scores of six different parameters. So how do we incorporate pH testing into our practice? So that patient comes into your clinic presenting for GERD evaluation. They have typical symptoms, heartburn, regurgitation, and atypical chest pain. And they have no alarm features. That patient gets an empiric trial of 8 to 12 weeks of PPI. On the other hand, if they have alarm symptoms, like dysphagia, weight loss, or anything else, you send that patient to endoscopy straight. If that patient has persistent symptoms, despite an adequate PPI trial of 8 to 12 weeks, you also go to endoscopy. On the other hand, if you have atypical symptoms, such as throat clearing, hoarse voice, cough, et cetera, you really should go straight to endoscopy. And if available, you should be considering doing reflux testing, or wireless capsule testing in this case, at that index endoscopy for those atypical symptoms before you even try PPI. So once you perform that endoscopy, and you find conclusive evidence of GERD, esophagitis, grades B, C, and D, haptic stricture, biopsy-proven barracks, what do you do for that patient? You optimize their acid suppression first. On the other hand, if there is no conclusive evidence of GERD on that endoscopy, which happens in almost 70% of cases, you want to refer that patient straight for wireless pH testing or pH impedance testing. If the patient with conclusive GERD has persistent symptoms, that's the patient you want to refer for pH impedance testing on PPI. And again, just to note, if you have a patient with atypical symptoms, consider referring for that reflux testing on an index endoscopy. Now to the biggest question, do I test on or off PPI? It's all about your pretest probability of GERD. If you have no conclusive evidence of GERD on that index endoscopy, you refer them for testing off PPI, because the question you're asking is, is reflux really the cause of this patient's symptoms? On the other hand, if that patient with conclusive evidence of GERD has symptoms despite optimization of acid suppression, you want to do an on-PPI pH impedance test, because your question is, why is treatment failing in my patient with evidence of reflux? So just a summary of some of the indications we discussed, and some we didn't. Indications for reflux testing include normal endoscopy without any GERD equivalents, preoperative workup prior to antireflux surgery consideration, atypical symptoms, recurrent or persistent symptoms despite PPI, and despite antireflux surgery. And there's also an emerging role in preoperative workup of lung transplantation. More to come on that in another talk. So how do we use this data to make a diagnosis for these patients? How do we make it a conclusive diagnosis of GERD versus refractory GERD or no GERD at all? So for pathologic reflux, for conclusive evidence of that, you're going to have those key features I mentioned on endoscopy, an acid exposure time of greater than 6%. And for borderline GERD or inconclusive evidence for GERD, you'll see grade A esophagitis or an acid exposure time between 4% and 6%, or maybe total number of reflux episodes that's borderline between 40% and 80% or down. So what do we do in the case where our studies are borderline? We use adjunctive or supporting evidence. If that patient has a hiatal cardia, if their biopsies using some scoring systems actually show evidence of GERD, if they have a manometry and you find a hypotensive LES or ineffective esophageal motility or any sort of hypomotility of the esophagus, these are all features amongst others that you can use as supportive evidence. Or they don't have GERD. And you can confidently say if your endoscopy is normal, your acid exposure time is less than 4%, you have less than 40 reflux events a day, you can say that patient does not have GERD. Other possible diagnoses can be made using ambulatory reflux testing. Obviously, you can confirm GERD in a patient with an abnormal reflux burden. But if the burden is normal and their symptom association is calm, meaning that patients actually feel like every episode of active reflux they're having, even though it's still within normal range, you want to think about reflux hypersensitivity in these patients. And if there's a normal burden and negative symptom correlation, that should raise the question, there's no GERD. Is there a functional disorder or a disorder of gut-brain interaction? Or is the diagnosis something else altogether? And in a non-PPI study, you can also have an overlap with GERD. You can still have... I think Rubenstein would be fine. What did you say? Oh. Oh. You can also have an overlap. He's conflicted. So in summary, GERD, we discussed a little bit about the pathophysiology of GERD, wireless pH testing, and pH-O-P testing. And we discussed some of the indications for testing, how good we test. Thank you. Thank you so much, Dr. Choblany, for that wonderful review of testing and management. It's my great pleasure to introduce our next speaker, Dr. Philip Katz. Most people in GI know Dr. Katz as a result of his distinguished academic career. He's a national authority on esophageal diseases. He's been a key author and contributor for our GERD guidelines and for the clinical trials examining the efficacy of venosopran. And we're honored to have him with us this evening to discuss the role of PCABS in the management of GERD. And just as a reminder, please keep your questions to the end, but also please continue to log them in our Q&A section. Thank you, Dr. Knauts, Dr. Mahadev, and the ASGE. Nod if you can hear me, please, since I've just come in. Thank you. So I'm going to give you a very brief but hopefully focused commentary discussion on potassium competitive acid blockers in their potential role as pharmacologic therapy for GERD. And I guess that means I have to be able to change my slides. There we go. So everyone's aware on this call that PPIs are currently the medical therapy of choice for acid control. They have been the mainstay of treatment for gastroesophageal reflux disease now for 36 years. Since 1989, wenomiprasol was first approved in the United States as LOSEC, changed to Prilosec because it was confused with Lasix. Anybody who's on the call who remembers that is therefore older than me and always makes me smile. The issues with proton pump inhibitors are that they have holes. And the holes are potentially filled by this new class of agents called potassium competitive acid blockers. They have a different mechanism of action than PPIs. And said another way, they are not super PPIs as they were originally alluded to and probably will be by many, which will be a mistake in both intellectual logic and in therapeutic care. Now the limitations of PPIs have long been known, but because they are the best drug and there are only a few occasions when they are not effective in real GERD, these are now important to refocus. There is tremendous inter-individual variability in gastric acid control. I don't have time nor am I going to show you slides that most of you have seen. It's not clear whether this is related to CYP2C19 polymorphism or if it's simply due to the way people actually take their drugs in this setting of food, not food, and real life. In the pharmacodynamic laboratory, dose timing relative to food is very important. If you take your PPIs without subsequent meals, they're not as effective. And they're not as effective when they are dosed at bedtime because they require active pumps in order to be maximally effective. And the way one activates pumps is to eat or to think about eating. But in general, it's to put food in the stomach. They're acid labile. They require some element of protonation. So they actually have to be transported in their active form into the duodenum where they're actually absorbed in the blood. And it's never been clear how they're affected by gastric emptying, by different body mass index, and whether in the setting of regular use, they are subtly changed. Steady state takes five to seven days to work. And double dose is needed for maximum acid control, which is where the PCABS usually come in. And it's long since been known, since basically 2001, actually 1997, that there is a loss of overnight pH control because pumps are not active when you're asleep. And although gastric volume is not very high, the pH is low. So if you reflux when you're asleep, you have the potential to cause damage. Now what potassium competitive acid blockers do is bind both to active and inactive forms of the pump, which basically means they block them all, regardless of whether they're active or not. They have reversible binding, which means that you can stop the drug and the pump will reactivate relatively quickly. They happen to be independent of genetic polymorphism, which means they have no racial, ethnic, or otherwise reason why they shouldn't be affected. And to date, they are believed to be meal independent, which means you can take them at bedtime. You can take them before a meal, after a meal, with a meal. I don't think that's probably actually true in real life, but in general, there's some dosing flexibility. And incredibly, there is some evidence of a steady state, at least by the second dose, meaning they are onset is very active. It's not really crucial when you're talking about healing erosions and long-term management of GERD, but it does open up the possibility of an on-demand drug. And this table, which either I can send you, you can find in almost every article, really highlights three things at the bottom. The bottom three things of the table are really the most pertinent. Full effect from the first dose, need repeated doses with PPIs, meal independence, meal dependent for PPIs, and no effect by genetic polymorphism, which is the case with PPI. So the dosing flexibility of these drugs on paper should be much better and easier for a clinician to use than a PPI. I won't take a lot of time with this, but again, it's always worth reminding people that the pharmacodynamic lab is where the drugs start, and they become the basis for how good we think they can be, and we extrapolate that to clinical trials. So when you compare Vinoprazan, which is the first PCAB available in the United States, there are three or four of them available in Japan, but this one is the one that we have the most experience with in the U.S. And compare it to Esomiprazole 20, a little bit cheating because the maximum dose would be 40 once a day. If you look on the left-hand part of this at day one, there's really rather rapid onset of Vinoprazan, which is not the case with Esomiprazole. And although Esomiprazole catches up, by day seven, Vinoprazan is still statistically better and spends a greater deal of time with the pH above 4. And for anyone on the call thinking about helicobacter pylori, actually gets the pH above 5 better than PPIs, and therefore is probably the drug of choice for managing people with helicobacter pylori. Comparing to Ribeprazole, again, a Japanese study, so they cheated and used the lower dose of Ribeprazole to show that they were better, but it's probably the case with 20 as well. Again, the main thing is, is how fast the drug works compared to the traditional PPIs, and that has potentially some bearing in real life for people who don't want to take their pills every day. Now, 10 years in Japan, really did nothing for our FDA. So the company, when it was reformed, put together a phase three clinical trial, a standard phase three clinical trial that most of you on this call are familiar with, particularly the people I know as colleagues and faculty. People were randomized in this case to Vinoprazan versus Lanzoprazole at the erosive esophagitis dose. Everybody should be reminded that the reason that this comparison has to occur is that the FDA will not give you a superiority claim if you don't compare it to something that is already approved, in which case you might as well go against placebo, which would be useless for clinicians. So they did a 30 milligram Lanzoprazole versus Vinoprazan study. Part of that is because the same company is the parent, and you get the drug for free, and you don't have to apply for an NDA. So it makes doing the study easy. They looked at all erosive esophagitis patients versus LA grade C and D, and they threw a two week endoscopy in, in a substantial number of patients, as you look across the board on the bottom, with almost a 35 or 30% C and D population, which also should remind clinicians on the call that there are a lot of people out there with C and D. We just don't see them because we endoscope people on a PPI all too often. But if you have people who are not taking medication, then C and D is not uncommon. And I focus a little bit on the two week data in the overall aggregate, where there's some advantage in everybody at two weeks. There's clear advantage for C's and D's at two weeks. This may have some interest to people who are thinking about money, because this is not an easy drug to approve. It actually is reasonably affordable for two weeks, and at 70% healing, you can get a nice jumpstart if you can't get it approved. So leaving it off the board because of cost is not necessarily absolute while we get a little bit more understanding of the drug. An 8% overall improvement in all people, that's a number needed to treat of about 12, substantially more for C's and D's. So on paper, this is a better drug. It's not arguable. When you look at maintenance, again, you got to go against the 15, and FDA always wants a half dose. So it's 10 milligrams of venoprazole, venoprazen, excuse me, against 15 milligrams of Lanzo. Again, maintenance of healing is really substantially better for C's and D's. I don't believe there's a tremendous incremental advantage, even though it's statistically that way for all comers. But if you chew on it, the data suggests that, again, it's better than the OTC Lanzoprazole dose at the present time, or the 15 milligram prescription. So reminder, key clinical difference, full effected first dose, meal independent, and not affected by genetic polymorphism. At present, all FDA warnings should be considered for PCABS because we just don't know. The early returns are that the side effects in the short term are the same. That's really not relevant for people who know that these drugs are incredibly safe in the short term. The dramatic increase in acid suppression may be a problem, and it has to be adjudicated. It's as simple as that. My suspicion is that it will not be harmful in a greater extent, but people will try to prove that it is, and we'll try to say that it isn't, depending a little bit on subtle bias, but hopefully good science. And then I remind people, not because you're going to read this in the 30 seconds or less that the slide will be up, but we did spend a tremendous amount of time trying to get this into the GERD guidelines so that people could actually read a statement that would have the backup of a reviewed organization relative to PPIs. So I encourage you to look at this. If you agree with it, use it as, what do you call one of those smart phrases in your electronic medical record, and you can use this to talk to patients when they come in with their long list of things that tell you that they should stop their drug. And I will not spend any more time there. So today I'm using this class exclusively in Cs and Ds. I'm using it in a lot of Bs, but it will need to be adjudicated because of cost. People with objective GERD not responding to once a day PPI, I think should go to a PCAB if they can afford it, and compliance will be better. Incomplete relief with grade A or B, not a major deal. And there are a few people who really have major difficulty with meal compliance or substantial nighttime symptoms, work and shifts. They do things where it's just not easy for them, and I think PCABs are really nice here. I'm not using them as first line empiric for any GERD symptom that's not proven. I think failure is not what we need with this class, and most people who fail PPI trials don't have GERD. And most people who are treated for unusual symptoms empirically, because you can, also don't have GERD. So they're not going to get better with this drug. GERD patients will, but I don't want to use it empirically. In refractory GERD symptoms, in people who have been treated with a PPI, I want objectivity to know that they're continuing to have GERD, that's just the way I practice. People who have symptoms and a non-erosive EGD who have not had a pH study, I don't think should be put on a PCAB, despite the FDA approval for same, because I think the improvement rate of 40% is going to minimize how good people think this drug is. And similarly, symptoms refractory to twice daily PPI, or any regimen greater than once a day PPI, I believe should have a workup. So that's me today. I think Barrett's is a place where this drug will have ample help during and post Barrett's ablation, I think should be very well studied. And then post-gastric sleeve GERD, which is the bane of every gastroenterologist's existence who sees patients in this category, they're impossible to treat, as most of you know, if you see them. And I think we need to look at PCABs here, and need to understand exactly how they actually work in this population, not just empirically, but in a clinical trial of some type, to see if they have the same pharmacodynamics in people who've had sleeves. So, short, sweet, I hope to the time I was allowed, I usually do remember what I've said, but I always do invoke Yogi if you're old enough to remember, since Yogi never knew anything or didn't remember, even though he was a genius. And one of Don Castel's favorite quotes, it's more important for a philosophy to be interesting than true. I sincerely, Rita and Hari, appreciate the opportunity to join this group, and I look forward to questions. Thank you. Thank you so much, Dr. Katz, and we will be saving our questions for the end of the session. So it's my pleasure to introduce our next speaker, who will be speaking about Digesting the Alphabet Soup of Endoscopic Antireflux Procedures. Dr. Petrus Benias is the Chief of Endoscopy at Rutgers Robert Wood Johnson Hospital, and the Director of Endoscopic Surgery. And he's an innovator in advanced endoscopy, and has done a lot of work, in fact, on novel endoscopic therapies for GERD. So we hope you enjoy his talk. Thank you, Hari. Thank you, Rita, and the ASG for the invitation. I'm going to take a second to share my screen. OK, so again, thank you for the task of presenting the most esoteric techniques possible, ARMS, ARMA, RMV, and RAP. And I have had the pleasure of being involved in this space early on, and attempting to innovate in this space, and kind of move the space along. So I will try my best to kind of present to you what I think is the foundation of why we would even consider doing something this outrageous. So we have to understand the anatomy we're trying to fix, first of all, give you an overview of the different techniques that are available, the alphabet soup, so to speak. And then simply think about, can mucosal remodeling really be helpful in GERD? Because this is what we're doing. We are not, in these particular techniques, addressing major anatomical deficiencies in GERD, but simply focusing on this concept of mucosal remodeling. OK, so what are the components of the LES? And I think this is where the talk really starts. It's a complex anatomy, obviously, and we identify three high-pressure zones in this complex anatomy that come together to form this anatomy that we identify endoscopically as a mucosal flap, and we talk about the hill grade of the G-junction. So where is the deficiency? Is it the crural ligaments, or the extrinsic sphincter, the intrinsic sphincter, or the so-called sling clasp mechanism, all of these giving the cumulative effect of the mucosal flap valve. So I was lucky enough to sort of spend part of my early career after being in attending with Dr. Larry Miller and partaking in some of these experiments where we sort of suppressed with atropine muscarinic receptors in the skeletal muscle, and sort of took away and sort of dissected out the skeletal muscle component of the high-pressure zone. And when you do that, you identify that there's a total pressure surrounding the lower esophageal sphincter. There are individual pressures of the proximal and distal esophageal intrinsic sphincters and the extrinsic sphincter of the diaphragm. And when you start to suppress that, you can kind of clearly delineate each of these pressures. In fact, when you suppress with muscarinic receptors, you can see that you can drop out the extrinsic sphincter. And you can create a three-dimensional kind of topographic map of the different pressures, and you can clearly see that when you subtract out the diaphragm that we have two major esophageal mechanisms that are at play here for preventing GERD. And of course, they fail in large hiatal hernias, but we are really talking in this presentation about dynamic failure of the intrinsic sphincters of the esophagus, okay? So there's the lower esophageal and then the sling clasp fibers. I'm going to sort of look at this a little bit more in depth and some of the procedures we've kind of innovated on to try to sort of boost this mechanism. In fact, you can actually see through micro-CT that this concept of sling clasp, although debated for many years, is in fact real. And if you're looking at the stomach and you're doing endoscopy, the clasp fibers are the ones that you see towards the cardia, and the sling is the majority of the circumference that you see towards the fondus and anterior to posterior. But they do kind of integrate as one distal complex. And it turns out that in GERD patients is this distal sling clasp peak that is actually missing. So if you look at some of these comparisons between normal volunteers and GERD patients, on the left side being distally towards the stomach, on the right side of this kind of pressure measurement being proximal towards the esophagus, you see that GERD patients have a drop-off and a missing distal peak. So it's this kind of distal pressure, high pressure zone of the slinging clasp that's missing. So is that the deficiency? How do we fix that, right? So there's been a lot of good work early on using innovative devices such as endosynch and trying to grasp the mucosa and trying to bolster it and trying to prevent dynamic failure of the valve. Okay, this obviously didn't work, and we can show why it doesn't work because when you do endoscopic ultrasound and probe-based endoscopic ultrasound, we actually were able to reconstruct these in three dimensions. You can see the placations are really in the mucosa and submucosa, and they're really not full thickness at all. And you can actually see that the placations actually, while each individual placation kind of bolsters the high pressure zone distally by the slinging clasp, they are kind of prone to wear and tear. This is where the story starts. So what is better than an endoscopic placation, right? Well, how about the submucosal scarring that we can create? So Inouye, being the innovator that he is, started doing anti-reflux mucosectomy, or ARMS, in 2014. He publishes a case series published in the Annals of Gastroenterology. And what this really is, is a dissection on fossin and retroflexion of the mucosa around the valve, sparing the cardia fibers, essentially doing 270 degrees, and then allowing for this mucosal scar. Because anyone that's done mucosal resection, or ESD, knows how much trouble it can be when you do have an extensive dissection, and what the natural mechanism of the body is to create that scar. So when he looked at anti-reflux mucosectomy, or ARMS, the first pilot study of 10 patients that were treatment refractory GERD had a significant issue with stricturing. So although they had decreased mean heartburn scores and GERD scores improved significantly, and even 24-hour pH monitoring improved, many of them required serial dilations, and that proved to be problematic. Do you do 180 degrees versus 270 degrees? This was actually, this has actually been studied over the years, and this is one small study that looks like, that looks at the difference between 180 versus 270, again to counteract this idea of stricturing. 180 degrees seems to be not inferior to 270, with similar outcomes in short-term follow-up. I would be remiss if I didn't say that many other people tried to innovate around this topic. In fact, this is Glenn Lehman's CLEAR procedure, where he band-ligated the cardia using simple band ligation. So this concept has been out there and sort of percolating, and everyone's been trying to do it, and what's the simplest way to do it without the complications that you see? Well, we started thinking about this early on in 2015. How do we develop a better procedure that's simpler for this kind of mucosal bolstering? And so we developed a resection and plication technique called RAP. And what we were trying to do is essentially bolster the sling clasp mechanism without creating a hard, scarred-down esophageal stricture. And so how do you do that? And so that really is based on not having an extensive resection, and instead of leaving the body to sort of remodel itself as it will, and most times causing a hard stricture that requires dilation, creating less of a resection, and then actually plicating with overstitch in a back-and-forth manner, sort of giving a three-dimensional structure to the valve. Not only are you closing down the sling clasp fibers and kind of linking them better and bolstering them with this sort of semi-circumferential submucosal scarring, but you're also linking proximal and distal, because the effect of this plication takes place from above the LES to below it. So when we presented our initial pilot study back then of 10 patients, followed up to about two years, we looked at patients that were essentially PPI refractory, picked the worst of the bunch twice a day with esophagitis and small hiatal hernias and hill grades. And I'll show you a video of what this looks like. So you can see that it is actually not so difficult. We used a standard duet banding technique, and we actually widened the resection below the G-junction and narrow it above. This actually creates the conformation that will follow for plication and will create a less narrow stricture above the G-junction where it's more critical and a more significant kind of bolstering of the tissue and bringing together the tissue below the G-junction where there won't be a symptom of dysphagia. You can see that it can be done in retroflexion as well. I'm going to speed this up for time's sake, but it's actually quite simple. Because the resection is limited, it can be quite bloodless. With a single plication, we move in a back and forth manner. We go through the muscle and through the mucosa. So this is a full thickness plication. So it immediately improves upon the original endosynch. And you can see here that we can go from distal to proximal, right to left or left to right, whatever you think is reasonable at that particular position. You can see how we're sort of taking in muscle as well. The effect, in essence, is to bolster the G-junction like this and essentially limit the hill grade. When you look at it over two years, the phenomenal thing about scarring in this part of the body is that it actually stays remarkably stable. And that's one of the real benefits of why mucosal scarring and resection, when combined, actually work really well because of the durability. And in fact, when you looked at the GERD scores going forward over two years, they were remarkably stable and patients stayed off of their PPI. And 80% of our patients eliminated daily dependence on PPIs. We also asked the question, because it was the major criticism, is are you creating a stricture? And the answer is no, because we are not creating a 360 or 270 degree scar. We're not even creating a 180 degree scar. We're essentially taking about 30% of the mucosa in the most vulnerable area towards the class fibers. And you can see that when you use endoflip data, that when we compare what the pre-GERD endoflip data looks like over several volumes, and you can see that it has distensibility, that the diameter does change as the volume goes up. So there is a compliance and there's a peak volume at which it starts to change. Our GERD pre-RAP and post-RAP starts to kind of mimic non-GERD patients. So non-GERD patients here in dark blue and GERD post-RAP patients actually right here in the light blue. You can also see that they mimic each other when we look at pressure over diameter, essentially the distensibility index of the endoflip. So the physiology here is not that of a stricture because that does not actually change. The pressure peaks tremendously. The diameter doesn't change much over balloon volumes, but in fact, it's pliable and compliant valve. It just has a much higher yield pressure. We looked at innovating and kind of redefining how we do this over many, many patients, moving it from posterior to anterior and right to left. And we were lucky enough to be able to go to Australia and teach technique to bariatric surgeons who used it in all their kind of post-bariatric anatomy that was suffering from GERD. This is Patrick Walsh after we had visited Australia and kind of taught the technique and done a number of patients together, publishing on his first 18 cases in sleeves with GERD. So other techniques like arms have been compared to GERD, and they do have a role after Nissen and after TIF that has become floppy. And the key here is that both of these procedures can be added on after a failed Nissen or a failed TIF. In small pilot studies, they do seem to add some level of improvement that is sustainable up to almost three years. So these are interesting techniques to think about when you've had a Nissen and you don't want to redo a Nissen and you're still getting some failure of the valve and the hill grade just seems to be a little bit too much because of course the curve has been corrected and you're just trying to bolster the valve a little bit. Arms has also been compared to StretA, which has a significant amount of data, and this was done in a meta-analysis. And both arms and StretA work well. Of course, though, arms is a much higher risk procedure with a higher risk of stretchering and bleeding and perforation. Again, this goes back to why we tried to, in RAP, alter our technique and minimize the amount of resection. But you can see here that PPI use before and after antireflux mucosectomy significantly drops and the GERD quality of life scoring significantly drops and they do so very similarly in StretA. So both are very, very good techniques if you're having a failed TIF or a failed Nissen. So owing to the fact that there's a significant amount of stretchering in arms, several groups have tried to develop antireflux ablation therapy. This was a very interesting study. I remember when I saw it, I was very excited about it because this came out in 2020, following what we had done, and 118 patients underwent what they called ARAT, antireflux ablation therapy. And the great thing about this study is that they were, unlike many of the studies, including our own, were very regimented in their follow-up, more so than many others, with post-therapy pH studies and they followed GERD symptom scores really well. They looked at the acid exposure time on Bravo's. And what they found is that by doing an extensive ablation, I'll show you what that looks like, you can have an excellent result with controlling acid reflux symptoms. Of course, the factors that are associated with success are that the pre-therapy hill type has to be two or less, esophagitis, if esophagitis is present, it's actually an indicator of success because you know they're having real GERD symptoms, a symptomatic response to PPI, again, owing to the fact that we're sub-selecting patients with real GERD symptoms that are responsive, and a post-procedure hill type one, showing that you've essentially made a difference and had a tightening of the valve. This is what it looks like, and this is actually from the ARAT manuscript. But around the world, you'll see this called many different things. In fact, it's called anti-reflux mucosal ablation, SARM-A, but they're essentially the same thing. And you can use APC, but hybrid APC is most often used to limit the amount of muscular injury. So hybrid APC lifts the tissue away from the muscle and allows you to get extensive burning and removal of the tissue. What this does is essentially mimic a mucosectomy. What is the effect of arm ablation on patients and their motility and their GERD scores? This was actually a fascinating study because in this study, they not only looked at these patients and how they responded with reflux scores before and after, objective measures such as acid exposure time, but they also looked at physiology and did manometry testing. So needless to say that 65% discontinued PPI, and there was a significant reduction in acid exposure time, and even the total number of reflux episodes decreased significantly, and patients felt well overall. And you can see that here in the pre- and post-mucosal ablation data. But what's really interesting is that these patients went on to have actually an improved lower esophageal resting pressure. They went to have an improved 4-second IRP and actually an improved EGJ contractile integral and improved ECI, which means that the esophagus actually started contracting better when it had some kind of structure to the valve. This was actually really interesting and kind of gave us a lot of food for thought. This is, unfortunately, I think it's an extension evolution of arms, and this is the arm V or the arm valvuloplasty. And I'm not sure. I'm a great fan of the technique, although it does seem to work. And the reason I don't like the technique, and to be fair, is that it's complex. It requires technical know-how, like ESD, and sort of creating not only a 270-degree resection, but sparing some of the vascularized tissue and clipping it in a way that creates a ball valve effect. Is this absolutely necessary? I'm not sure. I think this is a little bit cumbersome. The goal of all of these therapies is to produce something simple and more available to the average endoscopist. So what are we really trying to do here? So we have a lot of choices, and there's too many choices, I would say, but there's a lot of promise as well. Okay, so what are some of the common themes for success? Mucosal remodeling works, at least in small studies. It seems to really work. It improves GERD symptom scores. Objective reflux data is improved, and possibly even manometric data. We showed you endoflip data from our own post-RAP data, and also the mucosal ablation motility data. Mucosal remodeling should most likely be done in the simplest way possible, and non-circumferential. Okay, you don't need to do extensive resection. The resection should be beyond the G-junction on the sling clasp sort of area, but it doesn't need to be 270 degrees, and you might get yourself into trouble with requiring serial dilations, etc. And the most important thing I think you can take out of looking at all these techniques, which are basically riffing on the same concept, is that there is many different methods to accomplish the same result. So they are actually technique and platform agnostic, and that's a very important thing, as some of the platforms that we do routinely use can be expensive, not always approved by insurances, okay, and not available worldwide. So this presents a more kind of democratic and, you know, a way of approaching the anatomical deficiencies in GERD. But what are the obstacles for adoption? It's a lack of standardization. I didn't show you a single study with more than 100 patients. There's a lack of large prospective trials with long-term physiologic follow-up. They can be overly complex if you let them be, but they don't have to be, so the simpler the better. But some variations are simple and highly effective. So thank you for the opportunity to sort of introduce you to this very strange and esoteric world of kind of mucosal resection for GERD, but I really do think it has an amazing future. It just really requires more thought and study. Thank you so much, Dr. Benias. That was fascinating and a lot of emerging techniques that I think we need to understand better. So our next speaker will be Dr. Peter Janu. He's a board-certified foregut surgeon, and he trained in Tennessee at Memphis and did his undergrad in medical school at the University of Wisconsin-Madison. He's a member of the AFS and currently serves as director of the Heartburn Center with Fox Valley Surgical Specialists in Wisconsin, and tonight he'll be discussing innovations in antireflux surgery and integrating TIFF into current surgical techniques. Thank you, Dr. Janu. Get to my slide share here. First and foremost, thanks for this opportunity, and it seems very fitting in the landscape of March Madness with the basketball tournament starting today that our talks finish with a surgeon speaking to an audience of gastroenterologists, so I do appreciate this opportunity. And I have some disclosures primarily because I'm a general surgeon, but I'll try to keep this talk as objective as possible. Historically, surgical treatment for reflux was pretty straightforward. You had reflux, you'd get medications, and if the medications fail, you get a Nissen. But there's a spectrum of reflux, and rather than having a broad leap from medical therapy straight to a fundoplication, there's a number of different minimally invasive options and these innovations that have arisen that are trying to fill that gap so that it can be a little bit more personalized for each individual patient. So then the question becomes, where are these surgical options fitting, and where do these innovations fall? And it's certainly kind of much of the decision-making ends up coming from our increased understanding and knowledge of the components that make up this anti-reflux barrier, and the philosophical acceptance of the fact that it's not too much acid in the stomach, but it's actually the barrier that's failed, allowing content of the stomach to go the wrong direction. And it might not just be the LES. That was a really beautiful description of failures of all the different components of a relatively intricate area of the body. But the cura actually plays an active, if not predominant, role in the barrier to reflux, and the configuration of the flap valve and the sling fibers also contribute. And it's this multifactorial combination that drives how the barrier can be restored. And so ultimately, any anti-reflux procedure should try to address all three of the anti-reflux components. There's length, there's width, and then there's the angles. Because of the physics of fluid dynamics, the most important aspect ends up actually being the width, because the diameter is affected by flow to the fourth power. So any small incremental enlargement of the hiatal opening actually has a corresponding greater effect or impact on reflux. And so in determining the surgical treatment options, it's critically important to accurately assess the diaphragmatic hiatus. The Forgot Society updated the somewhat flawed Hill-grade system to better describe the disruption in the cura and help guide appropriate intervention. If you address each of these little barrier aspects, that helps objectively determine the extent of the disruption of the barrier. And that in turn helps determine the extent of surgery that would be required to restore the barrier. Most importantly is reducing the hernia to allow for length, as well as repairing the crura to repair or improve the width. And the mainstay of our surgical treatment is surgical intervention repairs the hiatal hernia or that hiatal defect. And now, you know, technology has improved whether it's done laparoscopically or robotically. Visualization is better. The technology has improved as far as suturing devices that can be used. There's different meshes that are available that can help reinforce this structure to help reduce the chance of the hiatal hernia coming back, which tends to be the bugaboo of any type of surgical intervention. But ultimately, closing the hiatal hernia component is probably gonna be the most important part of any type of surgical antireflux procedure. So if repair of the hiatus is the mainstay of treatment, surgical, these new innovations of surgical treatment, those nuances fall into how best to augment that flap valve. And traditional valve reconstruction is the Nissen fundamentation. It's a 360-degree full fundamentation, and it's still considered the benchmark for surgical antireflux procedures, but it does come with the potential for side effects, one being dysphagia, another being gas bloat, and then there's this inability to belch or vomit that potentially limits its appeal to patients. Because of those potential side effects, the procedure was modified so that rather than going full 360 degrees around, the procedure is modified so it's just a partial fundamentation that can either be done anteriorly or posteriorly, and that allows the stomach to vent a little bit better as well as decreasing its impact on swallowing. And based on multiple randomized, controlled head-to-head trials, the outcomes are similar, but partial fundamentation tends to have less untoward side effects. And for the most part, today is the preferred traditional laparoscopic valve reconstruction options for most foregut surgeons today. So where then do these new innovations fall? Well, an alternative to a traditional fundamentation is valve reconstruction with TIF or transoral incisionless fundamentation. As treatment paradigms have shifted towards partial fundamentation from full to offset the side effects, there's a natural progression of minimally invasive surgery going from an open surgical approach to a laparoscopic approach or robotic approach, and now switching over towards an endoscopic approach, just like we saw with the last talk. And the procedure allows for a true esophagogastric partial fundamentation that's created endoscopically. And the device is basically segregated into two parts. There's an interface for the physician to use that's outside the patient that allows to manipulate the device inside the stomach. And then there's the end effector, which actually does the grasping of tissue and suturing. It basically serves as a fancy overtube. And if we apply these guiding principles to how a reflux barrier is repaired, it allows for restoration of the proper angles. The device is introduced in the stomach and then flipped around. It allows us to grab where that gastroesophageal junction is and pull it down away so it's achieving length, and then marching in a circle until you create a 300 degree partial fundaplication that's about two and a half to three centimeters in size. That fold in and of itself creates a little bit of width to fill in whatever gaps there might be. So it does address the width of the hiatal opening as well. The group from UC Irvine looked at the physics of the antireflux valve and compared traditional laparoscopic approaches to that of this endoscopic approach. And if you looked at the specific linear pressure forces in relationship to the anatomy that's developed, an omega shaped flap valve that's created with the TIF device recreates the normal anatomical relationships in the angles and probably appears to be the most physiologic of the valve reconstruction options. And from an efficacy standpoint, it's shown to be very durable and effective over time. This is a study, the TEMPO trial, the lead author was Kareem Trad, and it was basically just valve reconstruction using the TIF device alone. And it shows a steady improvement that lasts out to five years. Effective reduction in PPI use as well as improved quality of life. The problem is with any objective measurements of the acid reduction with this device itself, just reconstructing the valve with the TIF device had about a 50% improvement over a variety of different studies. And I think that that kind of was a drawback for people to try to dive into this procedure, mostly because of the concerns that it's not doing a good enough job of an effective barrier, despite the fact that the quality of life scores were improving. But it probably falls into the fact that it's only addressing one component of the valve barrier. Ken Chang and Ninh Nguyen at UCI teamed together to use the most recent innovation of the device and the most recent techniques. And by combining hiatal repair with endoscopic fundoplication, they demonstrated a 94% reduction in Demeester scores, showing that repair of both functional units has a much greater impact on overall control of acid function and better outcomes for those patients rather than just simply doing reconstruction of the flap valve alone. In the study that I spearheaded with Peter Mavralis, a gastroenterologist in Northwestern Indiana, we showed a similar quality of life and durability and efficacy and safety over a one-year period of time that we follow these patients. But I think, if anything, the best thing that we showed out of that is that this is a procedure that can be done with a single surgeon doing both parts or safely performed with a team of a surgeon fixing the hiatus and a gastroenterologist reconstructing the valve. It proves that gastroenterologists and surgeons can work together effectively, and it can be a collegial relationship, not necessarily adversarial. Another alternative is this LYNX device or magnetic sphincter augmentation. It's a simple implant that has no sutures that can pull through or wear down, and it doesn't involve altering the anatomy of the stomach or the hiatus. The device is rare earth magnets encased in titanium on interlocking little links, hence the name. It can only expand to a certain point. It can only collapse to a certain point. And it's encircled around the esophagus just above the gastroesophageal junction. And the idea is that the magnets themselves attracted about 20 to 25 units of pressure, which is typically what a normal functioning valve should be able to hold pressures at. Reflux or intergastric pressures are typically five to maybe up to 15, so it stays snug for that. And a normal esophagus should be able to generate enough pressure to separate the magnets open so that food bullets can fall through and then the magnets draw back shut. If somebody needs to belch or has to vomit, you're adding pressure to the stomach with extrinsic muscles, and it opens up the opposite direction like a pop-off valve. So it does allow proper venting of the stomach if needed. And it's done with a laparoscopic procedure similar to a traditional fundoplication, five ports. It involves repair of any curl defect that exists. It involves sizing the esophagus to the proper size of the device. It comes in different sizes ranging from 13 millimeters to 17 millimeters. And each millimeter on the internal diameter means you're adding another bead or one of those little magnets, but it's individually sized at the time of the surgery. It sits in between the diaphragm and in between the stomach so it can't migrate, and it's typically anchored by the posterior vagus to keep it into place. And what's nice about it is that it's very durable over time, and it's remarkably consistent across all the different studies of patients or centers that have looked at it over time. So it's effective and durable. And it's far superior to medical therapy, particularly with regards to the regurgitation aspect that occurs with reflux disease. And that's not necessarily as well treated with medical therapy as compared to, let's say heartburn symptoms, which is a relatively effectively treated with medicines. Although not yet available in the United States, reflux stop is a new innovation that's showing promise in Europe. It involves a laparoscopic approach similar to traditional fundoplication, and primarily involves reestablishing a proper angle of hiss along with repair of any hiatal hernia defect. But what's added is this imbrication of a puzzle piece type. It almost looks like a little Rubik's cube, and it's placed within the fundus and imbricated in that area. And it's designed to bulk up that area of the fundus and retain the integrity of the angle of hiss. So it makes it less likely for the fundus to try to efface and fade away and flatten, which was one of the potential problems with traditional fundoplication over time that could potentially lead to recurrent symptoms developing. So if we circle back to the guiding principles of reflux treatment, preoperative assessment is critical. And there are very clear cut aspects of the anatomical barrier that need to be assessed and defined. And it's these objective measures that define the most appropriate treatment. And based on that thought process, you'd think, well, gosh, this has gotta be a relatively straightforward way to achieve a path for patients, but it's actually pretty gray. Patient selection actually becomes the primary determinant of outcomes with all of these procedures. And there are so many variables that impact this patient selection. One is whether or not they can undergo surgery at all. You know, they have to be able to undergo a general anesthetic. Do they actually have objective reflux, which the first presenter talked about, all the measures that would need to be employed to look at. Do they have a hiatal hernia? Sometimes it's pretty obvious as in the picture up top, but sometimes it can be a little subtle and you have to take a little bit of time and maybe tweak things to see if you could truly assess whether or not a defect in the diaphragm exists. Sometimes it can be a little bit sneaky and you could be fooled into thinking there's no hiatal hernia there, but if you just did an endoscopic approach in that patient, they might not get as good of a valve barrier. Motility plays a role, whether or not patients have dysphagia that can impact the results of, let's say, sphincter augmentation. BMI plays a role and there's comorbid conditions like smoking or steroids or diabetes. Age might play an impact for patients that are looking for durability over many years, might look at something that has a little bit more durability. And then there's certainly the concern for side effects. And then there's a patient awareness of the different options and the concerns for side effects, not only of their medical therapies, but also the side effects and recurrent symptoms that could potentially occur with surgical treatment. And so, where do things fit best? Well, it's very ideologic and it varies based on practice patterns and the individual surgical program and what they have to offer. Traditional fundaplication still plays a role for very severe disease, long segment baritsis, plastic change. You're willing to accept the potential downside of side effects for the improved control of content going the wrong direction. Partial fundaplication remains a mainstay for most foregut surgeons, particularly if dysphagia is concerning or if there's a large hiatal hernia defect that could potentially impact some of the motility during the course of the dissection. TIFF is certainly a fantastic procedure for somebody who truly doesn't have a large defect in the diaphragm and they just simply have a facement of the flat valve itself. It's a 20 to 25 minute procedure. It's very effective. I think it's safe and it's durable and really doesn't necessarily impact motility issues. For patients that have a smaller hiatal hernia without a lot of esophagitis, it provides a nice entry level for valve reconstruction in the sense that you can fix the hiatus along with this valve reconstruction. And it's not necessarily dramatically changing the anatomy. A fundaplication requires typically disconnection of the short gastrics and mobilization of the fundus or around the esophagus. And the TIFF procedure basically just reconstructs the flat valve that's supposed to exist. So it's a little bit more physiologic, a little bit more anatomic. And if the symptoms were to recur, let's say the valve itself deteriorates over time and symptoms recur, it's far easier for a revisional procedure to revise, let's say a CTIF to a fundaplication than it is to redo a fundaplication itself. It's also beneficial, let's say for a patient who might have a little bit of a gap in the muscles of the diaphragm. And then as much as you'd like to try to fix it, if their symptoms are bad enough that warrant an intervention, that they've had multiple prior abdominal surgeries that would make any type of attempt at trying to do a fundaplication very difficult, this at least provides a viable option for them. The LYNX certainly provides durability and there's no stitches that can pull through over time. Additionally, the scar tissue that forms around it does provide a little bit of a protective effect against a hiatal hernias coming back just because of the way the scar tissue forms. It is effective for post-sleeve patients, which can be challenging as discussed earlier. And it's approved for short segment barrets, but it is predicated on a functional esophagus. So if there are some dysphagia issues or motility, then there is a potential increased risk for having swallowed problems after the procedure. And then there's all these other options. There's ARMS, there's RAP, there's STRETA, reflux stop, potentially if approved may provide another option that patients will start to look at and be entertained. Currently we're participating in a multicenter trial randomizing CTF to Nissen fundaplication. Barham Abadaya is the lead investigator of the study. We've accrued all our patients. Patients are randomized to a repair of the hiatus and then either get a Nissen or a TIF for the valve reconstruction. They don't know which valve is done. They still have the same incisions and whatnot. They just don't know. And then over time, they get objective measurements both before, as far as pH studies, and then afterwards, and then we're following them out. The preliminary data should start coming out soon. So be on the lookout for some of the results from this study. So there are certainly opinions and sometimes the opinions can be relatively strong in this space. And this is certainly just one way to look at the surgical treatment options. More than likely, there's gonna be new data that comes out that spins the decision matrix and perhaps new technology will come out to add to the mix as well. None of them are perfect. None of them are best. Defining where patients fall on the disease spectrum and matching the individual treatment options to what those patients are individually hoping to accomplish based on their specific value propositions will likely provide the best formula for a successful outcome. Again, I appreciate the opportunity to present and happy to answer questions. Thank you so much for those wonderful presentations. We're gonna move on to the question and answer. Dr. Janu, when do you think that you would select somebody for, I know the data is still coming out, but when do you think you would select somebody for a C-TIF versus a traditional toupee? So if the defect is small, so typically it's somebody that has a hernia that's somewhere between three and five centimeters without a whole lot of esophagitis and they're looking for a procedure that ideally comes with the least amount of risk for dysphagia or side effects, those are patients that typically fit the profile for having a TIF procedure, particularly if they have some degree of dysphagia or some degree of ineffective esophageal motility during the course of their workup. I think actually that we don't have too many more questions. I'm just gonna ask one question actually of Dr. Katz. Dr. Katz, is your thought on PCABS, do you anticipate them becoming chronic drugs the same way that PPIs have become chronic drugs where patients are just on them for months and years? Or do you anticipate them being used in a more targeted fashion for healing of more intense lesions with plans to deescalate back to PPI or, you know, I'm interested to hear your thoughts on this. It's a phenomenal question. In a perfect world, if the companies could survive without becoming the drugs of choice and chronic drugs, they are ideally pharmacodynamically set up to do exactly what you suggested, deal with the tough people and then have a legitimate step down option. Since I believe that almost everyone with real GERD needs something, whether they end up in Petros' armamentarium or Peter's or some combination thereof, remains to be adjudicated and will continue to be. And for those of us who, well, Tari, you know, you're kind of in the middle of both of those because you can do a whole lot of what Petros does and you can partner with a Peter to do a combined procedure. And I think that needs to be explored. But to answer your question specifically, that's not the goal of the drug companies. So, you know, and it's been very tricky to deal with the modern PCABS because they want all the indications. They're going for EOE now. And they've got an on-demand protocol that they're considering and they're running out of money. So the next one will really be crucial because that's owned by Braintree, Cibella. They've got real money and they're not independent like Fathom. So their phase three data should be ready for next year's DDW because their study is just about done. We'll see. But that's more winded than you asked, but they should be chronic drugs or could be chronic drugs. But whether we really want those, probably not, but they are better. That's clear as rain. Wonderful. Well, I'd just like to take the opportunity to thank all the amazing speakers and to thank the audience to tune in on a Thursday evening and also to my chairperson, Dr. Knotts. Thank you for putting this all together. And finally, thank you to the ASGE for making this all possible. So I hope you got a great rest of your week and hope to see many of you at DDW. Thanks everyone. See you. Thanks all. Stay well and stay safe, please.

GERD

diagnosis

treatment

potassium-competitive acid blockers

PCABs

endoscopic therapies

anti-reflux surgery

personalized management

wireless pH testing

mucosal remodeling

TIF

magnetic sphincter augmentation