Good morning, and welcome back. I'd like to invite our speakers for the next session, Dr. Raina Yadlapathy, Dr. Andy Thao, and Dr. Crystal Lee-Lange, if you can come up to the stage, please. So our first speaker for this session is Dr. Raina Yadlapathy. Dr. Yadlapathy completed her GI fellowship and an esophageal physiology fellowship at Northwestern University in Chicago. She's a professor of clinical medicine and the director for the Center for Esophageal Diseases, medical director for the GI Motility Lab at the University of California, San Diego. So she'll be speaking to us today on GERD, more specifically, Moving Beyond Medical Therapy for Refractory GERD. Welcome, Dr. Yadlapathy. Thank you. Good morning. Thank you so much to the ASGE for the invitation to present today on a topic that's very near and dear to my heart. So first of all, in terms of disclosures, these are my disclosures, but I will say I'm an esophagologist, and I very strongly believe that when we talk about patients with GERD, we need to personalize our therapy for them to their phenotype and their preference. And I really do believe that a majority of our patients with GERD do improve quite a bit with medical and lifestyle optimization. And we're going to talk about how we're very fortunate now in 2024 that we have a multitude of surgical and endoscopic options to treat them as well. So refractory GERD, this is a patient that already has proven GERD. So somebody that either on endoscopy had evidence of erosive reflux disease or you did ambulatory reflux monitoring that was positive. This is someone that's been optimized on lifestyle and medical management, and they continue to have troublesome symptoms. Now thus far, this just is a patient that has persistent GERD. The true definition of refractory GERD is then someone who has had additional testing to confirm that there's ongoing GERD despite all of the above. I'm going to touch on optimizing lifestyle and medical management because many times patients think they've been on a PPI, they're not responding, what is the next step? But there's more than just PPIs for optimizing their management. So the figure on the left is created by Dr. Kouroulas to demonstrate the different mechanisms of GERD. This is very complex and sophisticated, but what I often tell my patients is that GERD is much more than just the acid. So we need to really use the right extinguisher to put out their fire. Certainly, acid suppression is one of the treatments, but there's much more than that. But even in terms of acid, we have more than PPIs. Now if your patient's on a PPI, keep in mind that not all PPIs are created equal. They have varying levels of intergastric pH suppression. They're metabolized differently through the CYP2C19 pathway. So first of all, just ensuring that your patients are taking it appropriately before meals. Sometimes they're taking it prior to breakfast, but then before bedtime. So switching them to before dinner can make a big difference. And then if payers reimburse it, you want to switch them to a PPI that's more potent if they're not responding adequately. And that tends to be the Ribeprazole, Esomeprazole, or Dexlansoprazole. That switch alone has led to complete relief for many, many patients. Also keep in mind that histamine 2 receptor antagonists are still around and particularly useful for patients that you feel are having breakthrough acid exposure at nighttime and breakthrough symptoms. Up to 50% may experience tachyphylaxis, but it does work quite quickly. And then important to know that there is now a novel class of acid suppressive agents, potassium competitive acid blockers, or PCABs. We're going to be hearing a lot more about them. These are currently approved across the world for peptic ulcer disease, erosive esophagitis, specifically in the US for H. pylori and erosive esophagitis. An important landmark study to know about, the Phase 3 trial published in Gaster last year by Lauren Lane, where in erosive esophagitis, both classes A and B, as well as C and D, PCABs were not inferior to PPI and actually outperformed PPI in terms of healing and maintenance of healing. Tomorrow, also, Lauren Lane is going to be presenting on PCABs for non-erosive reflux disease at one of the plenary sessions. So I won't spend too much time on the latter two boxes here, but I really want to emphasize that many patients with reflux have had chronic symptoms and the free nerve endings in the esophagus can become sensitized, and addressing the sensitivity is really important. So with neuromodulation or behavioral therapy, and also patients can become vigilant and anxious about their symptoms, and then if they undergo surgery, but they continue to have that vigilance, their symptoms will persist, so it's important to think about this and address it. But I did want to touch on the other mechanisms, which is why is your patient actually having reflux? So the increased gastroesophageal reflux events and the clearance from the esophagus. This is a nice handout. It's through the AGA. It's two-sided. Front side is a little bit of information about what causes reflux, and the backside routine modifications that all of us can adopt to reduce reflux, and I always tell patients that it's normal for everyone to have up to 40 episodes of reflux a day. That's a physiologic occurrence, and then these are some ways that we can actually modify that. So simple things, keeping in mind that weight loss has been shown over and over, and this is from the New England Journal of Medicine, that modest reductions can lead to significant symptom resolution. Some patients are even able to come off their acid suppression therapy. Many randomized controlled trials have shown sleep position is very important, particularly sleeping on the left side. So oftentimes my patients will say, I don't want to sleep on a wedge pillow. It's not comfortable. But just switching to the left side has been shown to reduce acid exposure and symptoms at nighttime. And then again, from randomized controlled trials, diaphragmatic breathing, first of all, is a great stress reducer, but it also increases the pressure at the lower esophageal sphincter and reduces reflux episodes. Now in terms of pharmacotherapy, keep in mind that alginates, so alginate plus an antacid creates that raft between the top of the acid pocket and the esophagus, again, compared to placebo, has been shown to reduce symptoms. One limitation was that Gaviscon Advanced is not available in the US. Our patients were getting it off of Amazon, but there are now more formulations of alginates in the US. So important to know about and provide those resources to your patients. And then the last pharmacotherapy are those that are targeted at the transient lower esophageal sphincter relaxations. These are the primary mechanism of reflux episodes. So GABA agonists effectively reduce TLESRs. This is agents such as Baclofen. It's not something that we commonly use because, first of all, the side effects can be prohibitive, including CNS side effects and drowsiness. And it tends to work for patients that have TLESR-mediated symptoms. So that would be more the regurgitation and gastric belching. So if you want to personalize it to that, it is in the armamentarium. So now coming back to this, we have our patient with persistent GERD. And the question is, do they have refractory GERD since they have ongoing symptoms? Now, do we need to do further testing for all of these patients? And the answer is not all the time. There are some scenarios where you have a high pretest likelihood that this patient has GERD and they're continuing to have volume-mediated GERD that we wouldn't have expected pharmacotherapy to effectively address. And these are patients that have a large hiatal hernia or symptoms that are very volume-predominant like regurgitation. So if your index of suspicion is high enough, you don't necessarily have to move forward with testing. But if there's a question as to, you know, this patient seems that they're completely optimized and we're not quite sure why they have ongoing heartburn, for instance, it may be worthwhile to test. Because again, you don't want to do an invasive intervention for a patient and their symptom persists because it was not actually due to refractory GERD. So the ways to test for refractory GERD are, first of all, endoscopy. And on endoscopy, the presence of erosive esophagitis and peptic stricture, if they're on optimized therapy and these are present, that confirms refractory GERD. Keep in mind that the presence of Barrett's esophagus is not an indicator of refractory GERD, nor are findings on biopsy. And then if the endoscopy does not reveal refractory GERD, the other test is pH impedance. So we do not recommend wireless pH because when you're on PPI, likelihood is that that will be a normal study, and that's why pH impedance is recommended. The findings that are supportive of refractory GERD are having an acid exposure time that's over 4% and a positive symptom reflux association. So these findings will increase your confidence that that patient will respond to an antireflux intervention. In terms of the role of other tests like manometry, this is integral to assess the esophageal physiology because you want to rule out a mimicker of GERD. Is there something else that's causing these refractory symptoms? Most importantly, achalasia. Certainly don't want to do a fund duplication on a patient that has achalasia. 30% of patients with a diagnosis of achalasia were told that they had GERD, and many times they have years and years of therapy until they arrive at their diagnosis. Also, rumination syndrome. These patients present with regurgitation, and when you have a high enough index of suspicion and you test for it, the diagnostic yield can be up to 20%. So an important thing to consider, particularly if in that clinical visit you suspect that there may be some rumination or behavioral process. You also don't want to do a fund duplication on these patients, but rather direct them to behavioral therapy. I'll just highlight that on Tuesday, there is a symposium on the role of high-resolution manometry in refractory GERD, where there will be a deep dive into this, and that's due to the formation of the PodBot consensus that was a collaboration between surgery and GI. So for anyone that's more interested in this topic, please attend that symposium. Okay, so now moving on to what are our options for a patient with refractory GERD in terms of mechanical restoration? So either recreating the flap valve, increasing the integrity of the antireflux barrier. So of course, we have surgical fund duplication, magnetic sphincter augmentation, endoscopic fund duplication, and then Roux-en-Y gastric bypass. I won't go into the detail of radiofrequency, ARMS, MAIS. Those are not recommended by the most recent guidelines, but they are very promising options that are being actively studied right now, and I'm sure more to come. And before we dive into these, I just want to highlight that perhaps the most important factors that have been shown to affect outcomes is making sure that you have the right patient. So that's why we've spent all this time really defining who is that refractory GERD patient, undergoing the correct preoperative evaluation. So again, making sure that they have GERD, they don't have achalasia, and so forth. And then whoever you refer them to, or if you're performing it, that that person has the adequate expertise. So fund duplication has been around for almost 100 years or longer, and this can be done as a NISN or a complete wrap, a partial, so a toupee or a door. There's many, many studies that show its efficacy in refractory GERD. This was in the New England Journal of Medicine by Stu Speckler and the VA group. And some really interesting highlights from this study, they were recruiting patients that had refractory heartburn, and that was refractory based on pH impedance. And they screened and recruited several hundreds of patients and ultimately ended up with 78. Just really speaking to how even though our patients have ongoing heartburn, it's often not due to refractory heartburn. But when you do identify the right patient, they had one arm that was surgery, one active medical treatment, so that was PPI and Baclofen, and then the other was PPI plus a placebo. And the surgery arm performed much more significantly than either of the medical treatments. Now magnetic sphincter augmentation, this is a laparoscopic approach of planting the magnetic sphincter beads around the lower esophageal sphincter. And this can also be done with the hiatal hernia repair and cruel repair, and has been shown up to five years out to lead to sustained improvement in heartburn, regurgitation, lower PPI use, ongoing quality of life improvement. And then endoscopic transoral incisionless fundiplication that's currently in version 2.0, which is of course our endoscopic plication device, and this is what the endoscopic images look like. So a number of studies have been done. In one study comparing TIFF to sham and PPI, there was reduced acid exposure and reflux events with the TIFF. There have been ongoing studies showing improved quality of life and outcomes up to five years out. And more recently, TIFF is being done combined with hiatal hernia repair. It was originally FDA approved for patients with a hiatal hernia of less than two centimeters, but again, nowadays being done with the laparoscopic hiatal hernia repair. People often ask, well, how do these compare? And there are not head-to-head trials, but a network meta-analysis that compared the endoscopic and surgical procedures really showed that there were not significant differences in the physiologic outcomes. Now, there were some limitations in the data that was available, but there was lower rates of postoperative dysphagia with a partial fundiplication. And then overall, when we look five years out, about a third to 40% of patients will be on PPI after intervention. And I always like to highlight to my patients and also my surgeons that this is not a failure of the treatment. If our patient now is improved after undergoing their intervention and being on a low dose PPI, that's a success, right? It's all about the patient. But the reality is that many of them will end up on PPI, so important to inform our patients. And then these are just some bullets from the ACG 2021 guideline on GERD in terms of endoscopic and surgical therapy. I won't read through all of them, but the headlines are that TIF, endoscopic fundiplication, magnetic sphincter augmentation, and laparoscopic fundiplication are options for our patients for refractory GERD. They were not able to comment on streta because of the highly variable and inconsistent evidence. And then Roux-en-Y gastric bypass is an option for patients with obesity, as long as patients are willing to accept some of the risks and requirements of lifestyle alteration. So in summary, in terms of moving beyond medical therapy for refractory GERD, first of all, we need to ensure that we are confident that our patient actually has refractory GERD. If you need to test, the testing is endoscopy or 24-hour pH impedance, but we don't always have to do further testing. Advising medical management goes far beyond just PPI and really needs to be personalized to your patient's presentation. Please remember to exclude achalasia before recommending an anti-reflux intervention. And then we've talked about the many interventions that are available. So thank you very much, and again, thank you to the ASGE.

refractory GERD

personalized treatment

lifestyle optimization

pharmacotherapies

mechanical restoration