Hi, we're going to get started with the afternoon session, so we'll start out with a clinical case discussion with Dr. Gonsalves. Hi, thanks, Dr. Snyder. Hopefully, you guys can all hear me okay and see the slides. Welcome back, everybody. So, this next part of the session are going to be three separate sessions, and it's going to be very interactive. I will do my best to hear your questions, but, yeah, please turn on your microphone and hopefully I can hear you. And this is the opportunity to kind of ask questions about management, and we'll do an adult case of dysphagia, we'll do a pediatric adolescent case, and then the highlight will be we'll have the unique opportunity and privilege to talk to one of my patients with EOE about their EOE journey. So let's get started. Okay, so I flipped around these cases a little bit just so we can focus a little bit more on the EOE case. This is a 34-year-old white male who presented to the emergency room for a sudden onset of inability to swallow water or even his saliva while eating chicken. In the emergency room, his symptoms suddenly resolved and he was able to swallow water. He was discharged and then went to the gastroenterologist, and he presents in the office for evaluation. He reports several years of an occasional sense of an uncomfortable, slow transit of food, solids more than liquids in his chest while eating. He denies any weight loss. His past medical history is notable for asthma as a kid and seasonal rhinitis. He takes over-the-counter antihistamines for his allergies. He's never used tobacco or ethanol. His physical exam is completely normal. So as we think about and as you remember the initial slides of dysphagia and the breakdown of how we break apart dysphagia, what do you think could be the possible causes of his dysphagia in terms of a differential diagnosis? What are the top things that kind of come to your mind here? Don't be shy. I heard people talking. Correct answer. Say it louder. EOE. EOE. And I can't hear anybody, so I'm just going to assume that you're saying EOE. EOE and achalasia came up. Okay. Thank you. So, I mean, those are great thoughts. So EOE and achalasia. I mean, as we're talking about these diagnoses, just remember how we can break that apart. Like EOE, structural condition, dysphagia to solid foods, achalasia, motility problem, usually dysphagia to solids and liquids. And we'll talk about that in a little bit. Let's see if this will advance here. Hold on one second. So what are the possible causes? Okay. EOE should be at your top of mind. So EOE is now one of the top causes of difficulty swallowing in younger patients that we see as a gastroenterologist. That should be number one, two, and three on the differential. Schottky ring, which you saw those pictures of yesterday, can also be a possibility here. Peptic stricture. Peptic stricture just means scar tissue from acid reflux damage. So if this clinical scenario was saying the patient was having a ton of heartburn, a ton of regurgitation, slightly older individual, that could be an acid-induced stricture, which is a peptic stricture. A motility disorder and achalasia and others. So yes, that is a possibility, but less likely based on that history. Again, you have a young male atopic who is having solid food dysphagia. So again, EOE, top of mind. And other things like malignancy. I mean, that's also going to cause a blockage in the esophagus. The lower down, but not likely based on his history. Infectious esophagitis can cause these symptoms, right? We talked about that yesterday. But he didn't have any obvious risk factors, no recent infections. Medication-induced esophagitis, no recent high-risk medications. And neuromuscular disorders, no exam or history to suggest any of that. So what would you recommend next in the care of this patient? What do you guys think? What do you want to do with him? Dr. Gonsalves, so we hear EGD in the room, and I think I heard a barium swallow. Can you walk us through what we should do? Yeah, great question. So, I mean, there are different ways to approach this. EGD is number one, right? You want to go in and take a look and see what is going on in that esophagus. Because at the end of the day, the endoscopy is not only going to be diagnostic, meaning figure out the problem, but it can actually be therapeutic, meaning you can improve that structure, dilate that structure. So EGD is really the right choice. Now let's walk through a couple of other choices here. Chest CT scan, not really relevant here. If you were thinking that someone had had a lot of weight loss, you were concerned, they were a smoker, that maybe this was an esophageal malignancy, you could consider that. But really, that's the wrong choice. Barium swallow, or an esophagram, this is a really interesting choice. And I will tell you, we don't often use a barium swallow before we do an endoscopy, with the exception of one time. And that's when a patient may come to me and they say, listen, I really have had difficulty swallowing for 30-something years. I'm always having to drink so much water. I can't take any pills. Their symptoms are progressing. And they're localizing things very high up in the neck. The two times I try, I will do a barium swallow before an endoscopy, is if I think someone has a really, really narrow caliber esophagus, secondary to long-standing disease, I might do that barium swallow up front, just to get a roadmap of the esophagus. Or if I were to think that they were having that cervical stricture, remember I showed you those pictures yesterday of those cervical stricture, or the Zenker's diverticulum, that pouch up in the upper part of the esophagus, those would be things that I would do the barium swallow for. We no longer do the trial of the PPI first, because like I said, those agreed guidelines have changed that approach of needing to use the PPI before the endoscopy. So EGD. Dr. Snyder, I'm going to have you walk through these slides for just a second. So now we have an upper endoscopy with biopsy that's performed, and so here's the findings that you can see. So on the left-hand side particular, what we're seeing are the longitudinal furrows there, so those nice train tracks. In addition, we're also seeing what looks like the exudates, so those are the eosinophilic abscesses that we see visually. On the right side, we can also see the train tracks as well, some rings. There's some edema. Really, you're not seeing a lot of those red patterns of blood vessels, so that's what we mean by the edema. Can we advance this? Thank you. I can advance. Okay. Hold on one second. Okay, and here are his biopsies. The top panel on the left side you see looks very normal, just like Dr. Salaria was showing you. Lots of eosinophils here in this right panel. And then, Dr. Snyder, I'm losing my voice for a second. Can you walk through those other two? Yep. And then in the bottom panels, we're seeing clusters of eosinophils. So, particularly, you can see that in panel D, so where the arrow is pointing, you see how it looks a lot more pink there in the H and E staining, so those are the eosinophils that are clustering there. Perfect. Thank you. Okay. Which of the following would you recommend next? And choose all that apply. Perform an esophageal dilation. Start a meprazole, 20 milligrams daily. Perform endoscopic mucosal ablation. Start oral butadenide suspension, one milligram twice a day. Start a gluten-free diet. Start oral prednisone, 40 milligrams daily. Or repeat an endoscopy in two months after medical treatment. What do you guys think? So, they're saying perform dilation and start omeprazole now, then repeat endoscopy in two months after medical treatment. Yeah, so if you have someone with a significant structure who is having dysphagia and was having, you know, recurrent food impactions, then absolutely, we're going to dilate them at that session, starting omeprazole, repeating the endoscopy in two months is very reasonable. So let's move on in the case. All of those are reasonable options. And you saw the slide from Dr. Snyder's talk. And Diana, I'm gonna have you walk through your decisions on these things with the patient. Yeah, so like we talked about before, so we care about several things. Of course, efficacy, this is really important. So I'll tell patients, I'll give them actual percentages. So here's a general response rate for PPI is gonna be 40 to 50%. Steroid is gonna be somewhere between 60 and 85%. Dupilumab, I'll tell them, depending on what cutoffs we're looking at, 60 to 80%. So patients are pretty intelligent and they're happy to have actual numbers and hear those different things. Patient preference, like we talked about, again, when you give them the risks and benefits and how the medication's given and spend time with them, that's usually enough for them to get a sense of what their preferences are. Disease severity, everyone's practice is a little different. You can still, as I showed you in that data earlier, you can still give a proton pump inhibitor if there is fibrosis or stenosis there. I tend to move more towards swallow topical steroids, but there isn't really a correct answer. A lot of it's based on the patient and what your comfort level is. Again, insurance coverage, very challenging, especially for these non-FDA approved formulations. Thankfully, we've had a lot of help from your group in terms of getting Dupilumab approved, so we appreciate that. Dietary resources depend on the institution, whether you have a dietician that's available for education and all of its shared decision-making. Yeah, so I think it really comes down to that conversation that we talked about that you're having with your patient to really go over the pros and cons of these options. I think some of us do have some added benefit that we have some time cushioned into our patient appointments where we can go through some of this and some of the APPs are really helpful in this regard. And here is the AGA algorithm for using this clinical decision support tool. And so here we see that when you're diagnosing someone with EOE, these are all the available options that you have, medical therapy, talking to them about protein pump inhibition, swallow topical corticosteroids, of course, Dupilumab, also thinking about dietary therapy and the different approaches to diet therapy. And then after starting them on one of these two things, doing that follow-up endoscopy to make sure that it's working, if there's still a clinically relevant esophageal structure, thinking about esophageal dilation, and ultimately after that, keeping patients on maintenance therapy. So here you saw those pictures before in Dr. Snyder's talk on the dilation. And in this case, I mean, there are different ways to do dilations, both with a savory, the bougie dilator, that long dilator, or a balloon dilator. And what you're seeing on these slides, this is a pretty significant structure here, probably about 10 millimeters or so. And here is that rent that you're seeing in the esophagus. You can see some deep muscle fibers here. And I mean, this can be very scary after you've done a dilation, but ultimately this is the type of mucosal defect that you wanna see, because that's when you know that you're breaking apart and opening up that structure. So that is what we mean by dilation effect. That's when we know that we've achieved a good dilation. And the ASG recent guidelines do talk about a target goal of diameter and a target mucosal disruption. So when we're thinking about esophageal dilation, we wanna best reserve it until after the effects of medical or dietary therapy. So medical or dietary therapy can open up that structure about two millimeters in size. So if someone doesn't have a critical structure, you can use medical or dietary therapy ahead of time before you do that dilation. If someone's coming to you with a lot of symptoms and a lot of self-limited food impactions have been in the ER, you wanna dilate them upfront like you've already heard. Dilation effect can last a long time. Typical effect is over a year. And the goal is a luminal diameter of 16. We usually say 15 to 17 millimeters is that sweet spot where people will have less of a risk of getting food impaction under 15 millimeters, higher risk of food impaction over 17 millimeters, no real added benefit to doing additional dilation. So about 15 to 17 millimeters is what we would say. Now, it's important to also know that just doing dilation doesn't affect the underlying disease. So the ASG guidelines, the ACG guidelines, they all talk about using dilation as an adjunctive tool, not as primary therapy. So just doing periodic dilations aren't what we would recommend. So that was the EOE case. I wanna stop here and have a little bit of a discussion because there are two additional cases with other etiologies, but I know there's so many questions that people have about EOE management and how do we approach our patients. And I wanna give you the opportunity to kind of ask those questions while you have us available. And if there aren't any questions, we can go on to the other two cases, but Dr. Yoon, Dr. Snyder, let me know if there are questions. Well, I can repeat it. There's a question coming, Dr. Gonsalves. I'll let you know. Their mic's having trouble. Oh, okay. Can you repeat it for me? Try now. Try now. Teamwork got the job done. Okay. So, my question is dilation. It's an interesting concept to me, and trust me when I say I know it's necessary medical practice in this disease state and in others. My mental understanding of what's going on is, specifically in EOE, is you have chronic inflammation in the esophagus, and your body naturally is going to want to fix because inflammation chronically anywhere in your body is not natural, so your body's trying to fix that. But because this inflammation doesn't necessarily go away because your allergen is theoretically keep coming in, you're going to have inflammation on top of your body trying to fix it, which produces scar tissue, but here's more inflammation with your body trying to fix it with more scar tissue, so you start to perpetuate the fibrosis process. So, when you're going into dilation and you're essentially breaking, you're introducing another wound, that's, like, where my mind is going. So now, our body's going to want to naturally try to fix that tear, correct? And so, aren't we just creating more fibrotic tissue and worsening the situation? I'm sure the answer's not necessarily yes, but that's why it's hard for me to wrap my head around, especially clinicians who like to do repeated dilations. Sure. No, I mean, that's actually a really good question. When we're thinking about healing, right, healing is part inflammation, part fibrosis, part remodeling. It doesn't work like that in the esophagus and esophageal dilations. So ideally, you're doing these dilations in the setting of concomitant medical and dietary therapy, whatever medical therapy that might be. So you're working on that anti-inflammation piece of things. You're not just dilating and inflamed esophagus over and over again. You're really cutting down that inflammation. And then when we talk about serial dilations, we're talking about dilations at set intervals to slowly and gradually open up that esophageal diameter to that target endpoint. The esophagus doesn't scar back down substantially after a dilation. If you're treating the esophagus appropriately, that esophagus is going to stay open and continue to stay open. So that's really our goals of therapy. When you saw that slide in Dr. Snyder's talk, there was a treat-to-target mantra there. We're trying to aim at symptoms. We're trying to aim at histology. We're trying to aim at endoscopic improvement, and that includes strictures. So those slow dilations will help remodel the esophagus, will help keep it open. It's not that I'm opening that esophagus, you're seeing that big kind of rent there, and it's scarring back down because it's creating this healing process. Thankfully, it doesn't work like that. Thankfully, it stays open. I will say there's one caveat to that. There are some patients that you'll get open, you'll march along these serial dilations, and they'll do beautifully. And then they may take one step back with their last dilation. That's not uncommon. But overall, they're going on an improved trajectory. As best as we want to do, like we love to avoid all dilations, right? It can cause some chest discomfort, it can cause pain. But if we've maximized our medical therapy and our dietary therapy, and there's still that scar tissue, nothing's going to fix that other than kind of getting rid of that scar tissue. But those are excellent questions. There are some patients that have refractory strictures, where no matter how many dilations we do, they're still there, they're still present. They have some really profound fibrotic process, and we don't know why that is. Those are patients that we would actually use an intralesional injection of steroids. And so through the scope, we would put a needle into that focal stricture, inject it with steroids, and then do a dilation. But that's only in the cases of those true refractory strictures. That's a great question. Thank you. I have another quick question too. And it relates to treating the target and what you said earlier about learning from IBD folks, because on the IBD side, whenever they treat a target, they go with the top-down approach. But with EOE, it's the bottom-up approach. What are your thoughts on that? Yeah, I mean, I think the IBD world has decades more experience in that space than we did. I mean, from a top-down approach, that wasn't always the case in the world of IBD. It was a step-up approach. So I think as we enter the world of more systemic therapy and biologic therapies than EOE, I think we're going to need more research and more longitudinal studies to really understand the benefit of a top-down versus step-up approach in this scenario. There are definitely patients that I think would benefit from a top-down approach in EOE. And we've heard several clinical case presentations on patients with multiple atopic disorders and stricturing and very active disease that would fall into that category. But yeah, I think we're going to learn a lot more. The EOE space and research is very active. I think partnering with the industry like yourself to really understand and break apart some of the data from your clinical trials will help answer those questions. But I don't think we're there yet to suggest a top-down approach for everybody, but really looking at that specific severe patient and maybe focusing on them to start. Any other questions right now? All right. It looks like we can go to the next case then, Dr. Goncalves. Okay, perfect. So we're going to move on. So the second case is a 56-year-old Caucasian male referred for difficulty swallowing. He's had two months of a sensation of solid food hanging up in his mid-chest. His symptoms are worsening, and now he has to fully chew his food before swallowing, but swallowing liquids without difficulty. He reports a 15-pound weight loss. His past medical history is notable for high blood pressure. Medications include licinopril for high blood pressure, over-the-counter omeprazole several times a week for heartburn. He reports smoking one pack of cigarettes a day for 30 years, but quit six months ago. He is overweight, has a BMI of 29. So what are the possible causes of his dysphagia? So what do you guys think might be on the differential for this gentleman? Exactly. We heard someone say tumor. Yeah. So I would say for him, number one should be a concern for a malignancy, an adenocarcinoma more often than a squamous cell carcinoma. We can talk a little bit about that. Peptic stricture, again, could be a possibility for him because he has had long-standing problems with that. He's taking acid-reducing medications. POE is always on every differential, but likely not in this scenario, less likely all these other things. So what would you recommend next in the care of this patient? We're hearing a lot of EGDs. Okay. And that is the correct answer. EGD is what we should be doing for this gentleman because of the concern about a malignancy. So EGD is performed with the findings below and forceps revealed adenocarcinoma use. So you can see here this large tumor in the esophagus. So a couple of things of importance when we're thinking about esophageal cancer that should also be on the differential of dysphagia. Squamous cell cancer is usually in the middle and upper third of the esophagus, strong association with tobacco and alcohol, and a marked decline in incidence in the US. Adenocarcinoma usually in the distal esophagus and a strong association with gastroesophageal reflux disease and Barrett's esophagus. Progressive dysplasia, low grade to high grade, and we talked about that Barrett's adenocarcinoma sequence yesterday. Esophageal versus other cancers. Here's the relative change in the incidence of esophageal adenocarcinoma in other cancers. And you can see here this black line is esophageal adenocarcinoma, which has really been rising over the last several decades. Risk factors for esophageal cancer are many of the things that you heard in this gentleman, tobacco, ethanol, and this is broken down by adenocarcinoma. This is broken down by adenocarcinoma and squamous cell carcinoma. But adenocarcinoma, GERD, and Barrett's esophagus, tobacco, obesity, non-Hispanic white race, male age, and family history. For squamous cell carcinoma, we think about tobacco, alcohol. You heard yesterday from Dr. Snyder that achalasia due to all the stasis, meaning things not moving through the esophagus, can increase the risk of squamous cell carcinoma. Anyone who's had a caustic ingestion has a thousand-fold increase in squamous cell carcinoma. Patients of African-American race also. We talked yesterday about that Barrett's to adenoma sequence. In esophageal cancer symptoms, dysphagia, weight loss, less commonly bleeding, chest pain, pneumonia, cough, aspiration, or hoarseness. Diagnosis is in endoscopy. You then have staging. Patients will get a CAT scan, something called a PET scan, that endoscopic ultrasound that you heard about yesterday. And treatment is really dependent on the stage, meaning how extensive the malignancy is. So role of EGD and adenocarcinoma tissue diagnosis is important to evaluate the extent of the tumor, to evaluate any associated Barrett's esophagus. Sometimes it can play a role in reception for early cancers. That endoscopic mucosal reception can scoop out some of those very small lesions. And palliation and nutrition support with esophageal stent or feeding tube. I don't think we'll go into actual treatment for esophageal cancer. We'll just have a few minutes to go through the last case. A 50-year-old female presents with dysphagia. Progressive over the last four years. A sense of pressure in her chest after solids and liquids. And over the last several months, regurgitates undigested solid food. She denies any weight loss, no prior medical history, and medical illness and no medications for physical exam is normal. What are the possible causes of dysphagia? What do you guys think in that case? They're saying achalasia. So achalasia, definitely. We're thinking about motility causes, solids and liquids. And EGD is performed, which reveals a normal esophagus, stomach and duodenum. What is the next most appropriate step? A, perform esophageal biopsies, dilation, high-res manometry, chest CT or barium swallow. What do you guys think? Anyone have a suggestion on what they'd like to do? I can't hear you if you said something. I'm hearing a lot of dilation, barium swallow. Okay. Biopsies, so a smattering of things. A smattering of things. Okay, and so let's go back to our working diagnosis. We're thinking that this is achalasia. Achalasia is a motility disorder. And so in our practice, if we're thinking about a motility disorder, one of the things we'll do is that high resolution esophageal manometry to check on that peristalsis and confirm what type of motility disorder is going on. So in this case, and of course you're gonna, excuse me, do biopsies for EOE. Biopsies are performed. They're normal. Symptoms of dysplasia persist. What is the next most appropriate care? It will be manometry. Go to that. Okay, and this is what, you know, we're talking about the diagnosis of achalasia. This is one of the types of achalasia. So that manometry catheter, that long tube that goes in the patient's nose and down the esophagus that has those 30 pressure sensors along that tube that's checking for the peristalsis. And what you're seeing here on this manometry, this is a classic manometry for achalasia. This is the lower esophageal sphincter pressure that remains high. It's not relaxing after a swallow. This is a swallow. And it doesn't have normal peristalsis. It's actually having a spasm type look to it, meaning everything is contracting at once. And so this is a classic presentation of type 3 achalasia. High in IRP, which is a lack of relaxation of the LES, no normal peristalsis and premature contractions. So the patient has achalasia. So I'll end this point because I know we have just four minutes or three minutes left for this session, but I'll open it up to our panelists and anyone else if they have any questions about these particular cases.

dysphagia

eosinophilic esophagitis

clinical case discussion

esophagogastroduodenoscopy

proton pump inhibitors

topical steroids

shared decision-making