This is really meant to be an interactive case discussion where you see the thought process of when we are seeing patients with dysthasia, and Dr. Gonzalez is going to be walking through three cases with us. And it is, like I said, meant to be interactive. If you have a question, I will come and pass the microphone to you so that we can record this as best we can. Please don't feel shy about asking questions about decision-making and steps, so we'll go ahead and get started. All right. Sounds good. This is, we will be presenting three different cases today, highlighting very common presentations of dysthasia that we see on the adult side. And I know Dr. Lightdale will be doing the same for adolescent patients. So let's start off with an adult patient with dysthasia. So the first case, he's a 34-year-old Caucasian male who presented to the emergency room for a sudden onset of the inability to swallow water or even his saliva while eating chicken. While in the emergency room, his symptoms suddenly resolved, and he was able to swallow water. And he now presents in the office for evaluation. So at this point, what is the first thing that is going through your mind in what I just told you of this patient? First diagnosis that comes to mind. Portion control. If I've done my job well, EOE should be top of mind for you at this point. So he luckily resolved his food impaction, which isn't often the case, but he resolved and he was able to go home. And he now presents in the office for evaluation. That's a really key critical point, too, is when patients are coming in for food impactions, we really want them to have good follow-up to make sure that they are getting treated because we know that 50% or more have EOE. In the office, he reports several years of occasional sense of an uncomfortable, slow transit of foods. Solids more so than liquids, and that's an important piece of the history for EOE. And he describes it in the middle portion of his chest. He denies any weight loss. His past medical history is notable for asthma when he was a kid and seasonal rhinitis, so he does have other allergies. His medications include just over-the-counter antihistamines for his allergies. He's never used tobacco or alcohol. His physical exam is normal. So again, possible causes of dysphagia. I think you guys nailed it. EOE should be coming up as top of mind for this patient. Young, male, intermittent difficulty swallowing, solid food, atopic condition, lack of what we call alarm signs like weight loss. Other things this could be is a Schottky ring. A Schottky ring is a benign mucosal ring in the bottom part of the esophagus, which we see in about 14% of adults. It typically doesn't cause problems unless it gets too significantly narrow, ideally under 13 millimeters, but it's not necessarily associated with EOE. Peptic stricture, what that means is it's a narrowing that occurs in patients with longstanding reflux disease. So if this patient were older and he didn't have any of these atopic conditions, it could be a peptic structure, so damage from acid reflux. Motility disorders, we always want to think about motility disorders, meaning the esophagus is not contracting in a coordinated way. They're not having normal peristalsis, but the history does not suggest them. And other things like malignancy, infections, pilosophagitis, which you heard about yesterday, or neuromuscular disorders, there was nothing in that clinical history to suggest any of those other features. So at this point, what, if you were there, would you recommend for the care of this patient? Would you want a CT scan of his chest? Would you want a barium swallow or an esophagram? A high-resolution motility study? An endoscopy? Or a trial of proton pump inhibitors for eight weeks? So endoscopy, right. And so that's really the right answer here. Back in the day, some people would just say, oh, it's probably EOE, we'll put patients on an acid reducer and then we'll do the endoscopy afterwards. That was really when PPIs were part of that diagnostic process of EOE. We really moved away from that because, as I showed you with the data, 40% or more of patients can respond to the PPI. So if we start them off the bat on a PPI, we don't do an endoscopy first. We repeat that endoscopy. It's normal, biopsies are normal. We don't really know what this patient had at baseline. So it's really important to get that baseline endoscopy. So the EGD is what we would proceed with. And his EGD and biopsies are performed and the findings are listed below. So what are the findings that you see on this picture? Hopefully you can see this well. Right, so he definitely has a lot of edema. So loss of that vascular pattern, right. So definitely part of that EREFs. He has rings. You can see these rings here. So these are probably grade two rings. They're not just subtle ridges, but they're not narrow enough to obscure that scope. And he has exudates, more than 10% of the circumference of the lumen, so E2. And then furrows are pretty deep. You can see here pretty deep furrows. Do you see my marker? Okay, yeah, you do see my pointer. And ideally, probably a stricture here at the bottom for the EREFs. Biopsies were taken, and here are classic biopsies. This is a normal pathology slide that you saw from Dr. Salaria earlier. Nice mucosa here, no pretty pink cells at all. These are examples of eosinophilic esophagitis. Those bilobe nuclei at the top surface of the esophagus, clusters of more than four eosinophils, and that counts as a microabscess. And these areas up here called superficial layering are also even abscesses, eosinophilic abscesses. When you have 200 eosinophils, that's pretty significant in there. So which of the following would you recommend next? And there could be multiple things that you would recommend. Performing an esophageal dilation, starting Omeprazole, 20 milligrams daily, performing an endoscopic mucosal ablation. Go ahead. My question is even before that, why don't you start also a trial of PPIs? At the very first part of the question, you only had C because it missed the diagnosis. If they start them early and she pulls it, then it would be a false negative. So he never had an endoscopy in the ER. His food bowl is resolved. So he just presented to you in the clinic. So he can't have it prior to? The treatment has really shifted pretty significantly from that empiric PPI trial up front. Because if you do an empiric PPI trial up front and then you do your endoscopy and he falls into that 42% of people where this is completely resolved, I have no diagnosis for this gentleman. I can't say, well, yeah, you probably have EOE. It's probably responded to the PPI. You're going to stay on a PPI. So it's really helpful. The tide has turned. Ten years ago, even seven years ago, we would always just place people on a PPI, repeat the endoscopy after a PPI because the PPI was part of that diagnostic criteria. Now it is not. Now it's an actual treatment. So you really want that baseline endoscopy. So when that patient initially presents, initial presentation, you want that biopsy first before you place them on a PPI. And a lot of times what will happen, patients will have empiric treatment. So if someone comes to me and they've already been put on a PPI by their primary care, I'm not going to take them off the PPI. I'll say, okay, let's do your endoscopy and see what happens. But if it's all normal and I truly suspect EOE, at some point they want to know their diagnosis, and they'll go off the PPI and do an endoscopy, and then we'll see these eosinophils. So that's the rationale why we don't just need to do the PPI up front. All right, so at this point, you haven't started them on anything. We talked about dilation, a PPI, endoscopic mucosal ablation, oral budesonide suspension, one milligram twice daily, starting a gluten-free diet, oral prednisone, and then repeat an endoscopy in two months after medical treatment. So which things here do you think would be reasonable to do? And you can throw on dupilumab on that list too. This is a slide from last year. Yeah, so there's no right or wrong answer, right? Well, there is a wrong answer. The oral prednisone is wrong. There's no indication for oral corticosteroids in EOE. There's been a nice study by Dr. Gupta at Indiana University 12 years ago or so now showing that there's no benefit with oral steroids versus topical corticosteroids, but it has some downstream effects. So starting a PPI with a follow-up dilation, very reasonable. But now you can go directly to topical corticosteroids. You can go directly to dietary therapy. You could potentially go directly to the dupilumab. I would start on a PPI, something very simple, and see how they respond after 8 weeks. So I noticed that you have 20 milligrams there. Is there a reason you start on the lower dose and not the higher dose? This is an old slide. I would start with 40 milligrams. Okay. So the data in terms of the PPI dosing for the EOE studies is the equivalent of 20 milligrams twice a day, or a meprazole 20 milligrams twice a day, or a meprazole 40 milligrams once a day. And that data is based on the data needed and the dosing needed to heal erosive esophagitis. So that's where all that came in terms of those consensus guidelines. And 8 weeks, because that's the duration required to heal erosive esophagitis. So based on the endoscopic findings, I'm not trying to label, but would you say that's a more severe presentation of EOE? For sure. So let's go back to that endoscopic feature. So definitely, they have a lot of inflammation. They have a lot of exudates, and they have some scarring in here too. So yes, moderate to severe. I wouldn't say they're in the severe category, but moderate to severe. And food impaction already puts you in the severe category. You think there's some fibrosis there too, right? Sure. So is it just a personal preference or protocol preference not to start heavy and try to vastly change this so that you can stop that fibrosis progression versus going a little bit of a meprazole, a little bit of a steroid, like dilate and throw everything at it to stop that process? Yes. I mean, you want to stop the process. I think this is where it comes down to that shared decision making, right? And so you're sitting with a patient in front of you, and you're saying, okay, here are our options to be able to suppress this inflammation. We have this, we have this, we have that, we have a combination, and it's that person's choice on what they would do. A lot of people will pick something simple up front and say, hey, if something like a pill will work for me, let me try that first. So, again, a lot of it is patient-driven. And this thing about the algorithm, medical management versus that more mechanical and more, I guess, extreme approach, we get a lot of those conversations. It's like this case study just kind of fits that bill. Which vein of the Y do you take? Right. So, I mean, that algorithm is actually kind of fascinating, and we had a large kind of conversation at a DDW presentation. We just don't know where those kind of systemic therapies fit in that algorithm, whether it should be right at the top or further down. In this gentleman, I don't think it's wrong to do a PPI or diet, a PPI or topical corticosteroids, PPI, you know, dupixent, I mean, dupilumab. This is where combination therapy and someone that you really want to shut down would be fine to do, and then you de-escalate therapy. But, again, it's a conversation. You have to have that with the patients, and a lot of patients are kind of tippy-towers into this disease process. They've never had this diagnosis. They've never been on medications. They want to start a little slow, so it's just a matter of what they will choose. But these are all really good questions. Yeah, to kind of piggyback on that, I was going to ask about dilation. Like, I have a few providers that they see as they're dialing every time and then putting them on CPR. So for this, dilating up front is completely safe, completely safe to do. When I choose to dilate up front is when there's a critical stricture, so a really narrow stricture, or a patient who has had food impactions, right? So I ask them about their dysphagia and how frequent that dysphagia is leading up to that endoscopy, and if they're having a lot of self-limited food impactions or they've already been in the ER, even if this esophagus looks really irritated like this, it is fine and safe to dilate. About 10 years ago, everyone was very scared to dilate in this circumstance, and they would say, let's get this person cooled down, let's get this inflammation quiet, and then let's dilate. And that's perfectly fine to do also, but data in the last 10 years has shown dilation up front is very, very safe if you do it conservatively. So I determine it based on how severe that stricture is, how severe those symptoms are in terms of those food impactions, and that's where the whole severity comes into play. Any other questions before we move on? Okay. All right, so any number of things that you can start for this patient would be perfectly reasonable to do, but also, again, following up that endoscopy in eight weeks, if you're going to do a PPI. If I were to do a topical corticosteroid, I would do for a little bit longer, 8 to 12 weeks, really give some more time to remodel. Dietary therapy, we typically do for the shortest amount of time possible because it's hard for people to be on dietary therapy, so about six weeks. And then the dupilumab, usually I would suggest about four months after. You had a question? For the dilation, what would your follow-up be? I wouldn't do only dilation. So if I did that as my first endoscopy and I did a dilation then, I wouldn't just leave them alone. I would do another type of medical dietary therapy to help that inflammation and then set them up for the follow-up endoscopy to know that it's working and then potentially dilate again if I haven't met my target. And my target dilation, again, is at 15 to 17 millimeters, yeah. Okay, so perform esophageal dilation. Yes, that is appropriate in addition to adding these additional things on. Let's see. And start omeprazole, but 40 milligrams or 20 milligrams twice a day. There was a DDW abstract that showed that doing the omeprazole 20 milligrams twice a day is a little bit more effective at controlling histologic eosinophilia than once a day dosing, but you have to worry about adherence and putting people on twice a day of anything is not optimal. They forget that second dose. So we just say, okay, let's just do the omeprazole 40 milligrams once a day with a hope that that they'll actually take it if that's what they choose to do. Yeah, I mean omeprazole is a fairly potent medication. It's also very cheap and what a lot of insurance will cover. Again, at the end of the day, I always think about it from my patient standpoint, right? If I can get them to do something that will achieve histologic and like maximal efficiency, they would much prefer the cheaper alternative. So we've just started that as our go-to because it, at least in Illinois where we are, that's the one that tends to get covered more often. If we try to prescribe a different one, then we have to go through all these hoops and then we have to go to back to omeprazole. So that's what we've traditionally started with. If there's someone with a really small esophagus, I will do rubeprazole 20 because it's a teeny tiny pill. So it's easier to go down that esophagus than, you know, some of these other pills or even oral disintegrating lanseraprazole because that will be an oral disintegrating pill. So you have to kind of couch it in that particular patient, but if they don't have a critical narrowing where pills will go down, then omeprazole is a very reasonable thing to start with. But it, and it may be a slight difference geographically in terms of what insurances tend to cover most. Okay, all right, so we've done all of these different options and again the initial choice of therapy variables to consider are the following. The efficacy, how effective are these treatments going to be, that patient preference, and I would say that's by far the number one thing in terms of treating patients in our center is what the patients are actually preferring and asking for. Disease severity, absolutely, and there is, didn't have time to actually go into this in great detail, but there's a disease severity index called IC, which many of the key thought leaders got together to create, and it really assigns different scoring points for bad outcomes, meaning food impactions, esophageal perforations, how frequent dysphagia is, what levels of eosinophils are in there, and that can help a practitioner gauge that severity. Insurance coverage, of course, is going to play a role. Dietary resources, I mentioned earlier, for instance, if someone doesn't have access to a lot of specialty grocery stores, doing diet therapy is going to be hard for them. And then at the end of the day, just having that conversation with the patient in terms of what's important for them. And this is the algorithm I think you were chatting about in terms of this treatment algorithm and the clinical decision support tool, which was put out by the AGA, and so if you have someone with EOE, medical therapy, including PPIs, topical corticosteroids, and this was developed before Dupilumab was approved, so Dupilumab can fall in here, and then, or dietary therapy with empirical elimination diet favored over elemental or allergy testing directed diet. And then if you don't respond, thinking about changing your therapy, adding PPIs if you didn't do so initially. If there's a clinically relevant esophageal stricture, really esophageal dilation is very important in treatment of these patients. And then ultimately, if you have a response, keeping patients on maintenance therapy to prevent that fibrosis or help reverse that fibrosis, and over time trying to de-escalate some of the dosing of medications that you're doing. And hopefully we'll have some more guidance about that with additional research. So dilation in EOE, you saw these slides earlier that I presented to you. Dilation is a really important treatment in EOE, an adjunctive treatment. It's not a primary treatment, so all the societies position it the same, done concomitantly with medical or dietary therapy. In many cases, medical or dietary therapy based on endoflip studies can increase that luminal diameter by two millimeters. So that's some of the rationale why some people might say, if you don't have a critical stricture, and you don't have someone who is having self-limited food impactions all the time, it is fine to start treating them with whatever that treatment choice is, and then doing the dilation after that. Again, dilation best to reserve until after the effects of medical or dietary therapy are assessed, with a caveat if they have significant symptoms. The typical effect can last over a year. Goal luminal diameter is 15 to 17 millimeters, and it's important to know that it doesn't address the underlying disease, and that's what many of the questions came up a little earlier. What if someone just wants to be dilated once a year? We can still do that, but that's not optimal therapy. Does anyone have questions at this point on this case or the therapies? So the idea of a patient coming with a food impaction is sometimes addressed in the ER with things like logogonic nitrates and other medical modalities. Do you think it works, or is it kind of a myth, or is it going to pass on its own? It works in some cases. So it has worked in some cases, and we can have a percent, probably worse than less than 5%, I will say, of time. The nitroglycerin or the glucagon, it's like a smooth muscle relaxant, and so in some cases it's great because it allows that GI fellow to not come in in the middle of the night, but the key is going to be that appropriate follow-up for that patient who's going to go to the GI clinic to follow up and actually get a diagnosis. Sometimes using that nitroglycerin or glucagon just delays the inevitable, which is that endoscopy, and it pushes it back for an hour or two in some cases. So it is something that should be handled pretty quickly and aggressively in the emergency room. Most of the food impactions I'm talking about are complete food impactions, where a patient has a food bolus in their esophagus. It cannot go up or down. They cannot clear their secretions, meaning they're having to spit their saliva in a cup. They cannot swallow that saliva. That is a medical emergency because that saliva that's building up in that esophagus can slip into the lungs, and they can have complications of aspiration. So that is a medical emergency that needs to be handled right away. There are other food impactions where food is kind of like floating around in here. Patients can swallow their saliva. They can drink some water, but there's still some food in there. That needs to be handled urgently as well, but that's not as critical as that first scenario of the patient not being able to handle their secretions. And it can be uncomfortable for the patients. The natural, and you heard a little bit about motility studies yesterday, the natural peristalsis of that esophagus is that your esophagus wants to contract to push food down. When there's food stuck on a speed bump, it's going to contract even more, and very vigorously. And that can result in a lot of pain for that patient. They feel spasms. So some things that your patients may say is, when I have food caught there, I have really bad chest spasms. And it's because that esophagus is trying to do its part at getting that food out, and it's not effective. So, you know, these are things that we just try to think about. This patient is really uncomfortable in the air. We want to get to them as quickly as we can and provide some relief. All right, that ends our EOE case. So now is your opportunity to ask me any questions about EOE before we go on to the other two. Okay, so these are other cases where we will typically see patients in the esophageal clinic, and it's just how we think through what we call our differential diagnosis, meaning what is the most likely thing that this could be. So this is a 56-year-old Caucasian male referred for difficulty swallowing. He reports two months of solid food hanging up in his mid-chest. So again, so far it sounds pretty similar to the last one. Symptoms are worsening, and now he has to fully chew his food before swallowing, but swallows liquids without difficulty. So it's getting worse and worse over time. He reports a 15-pound weight loss. That is not typical with EOE to have that type of weight loss. His medical history is notable for hypertension. He's on antihypertensive medications. He has had long-standing heartburn. He's been on Omeprazole 20 milligrams several times per week for the heartburn. He has a history of smoking a pack of cigarettes a day for the last 30 years, but he quit six months ago. He is overweight. His BMI is 29. And what are the possible causes of dysphagia? What are the things that you come to mind in this patient? So esophageal cancer really is number one, primarily because of the weight loss. If that weight loss wasn't there and his dysphagia wasn't as progressive, you can think about a peptic structure, that long-standing acid reflux creating erosive esophagitis and creating scar tissue there. But malignancy is really top of mind for this gentleman. So malignancy, adenocarcinoma is more common than squamous cell carcinoma. Thinking about this patient with long-standing reflux, peptic structure again should be on top of mind. EOE, yes, it can affect any age, but this is not the right presentation. Schottky ring and all these other things that you heard about, but they're unlikely, so malignancy is it. So at this point, I'm gonna fast forward because we have just a couple more minutes, I think, for this case. At this point, we would do an endoscopy. We would go with where the money is to get that diagnosis quickly, and here's unfortunately what was found. So what you can see here is this is a large esophageal mass extending from that distal esophagus all the way into that mid esophagus, and that's a prototypical picture of an esophageal cancer, unfortunately, and the biopsies were consistent with adenocarcinoma. So dysphagia is something that we treat very seriously. Anyone who has a complaint of dysphagia, we need to see, we need to get in for endoscopy, we need to do the procedures quickly, especially in older patients, and I think internal medicine doctors are very astute about this in older patients. In younger patients, for many years, it was kind of like, oh, you're young, chew your food, you're eating too fast, but now that EOE has set the stage, internal medicine physicians are sending their patients over much more quickly because of the EOE diagnosis. Just a couple of take-home points about esophageal cancer. Squamous cell cancer typically is in the middle to upper third of the esophagus associated with tobacco and alcohol. There has been a marked decline in the U.S. Adenocarcinoma is usually in the lower part of the esophagus, strong link to reflux and Barrett's esophagus, which you heard about yesterday, and has progressive dysplasia, progresses from low grade to high grade, and here you see the trend that despite kind of a relative flattening of other cancers, esophageal adenocarcinoma still does seem to be a little bit on the rise. Risk factors here for squamous cell versus adenocarcinoma. Adenocarcinoma, reflux, Barrett's, tobacco, obesity, a non-Hispanic white race, male, older age and family history, and squamous cell cancer, smoking, alcohol, other esophageal diseases. So achalasia and caustic injection, just from lots of toxins that sit in the esophagus for a long time, can also predispose to squamous cell cancer and more common in the African-American race. And you saw this I think in one of the talks yesterday about the Barrett's to adenocarcinoma sequence. That is what happens over time in that there is this intestinal metaplasia that takes over that squamous cell mucosa. Cancer symptoms can be very similar to EOE symptoms, that difficulty swallowing, but the hallmarks there are weight loss and it's progressive. It's massively progressive, so that's the thing to really think about with esophageal cancer. It's not just this intermittent, I have difficulty swallowing and I can resolve this bolus. It's over the last month it has gotten progressively worse. You can have bleeding, chest pain, complications such as aspiration and even a recurrent laryngeal nerve injury where you got a lot of hoarseness. So these are common things. There's one more achalasia case which I won't go through because I think there's an important transition that we may need to make to hit the adolescent presentation of EOE. But do you have any questions about the second portion of this talk? Dr. Gonzalez is going to be leading us after this session for a very important family event, so this will be the last time you get to ask her to pick her brain, so please take advantage of that. It is. I get to go to my daughter's eighth grade graduation. Alright, well thank you guys so much.

dysphagia

eosinophilic esophagitis

endoscopy

esophageal cancer

weight loss

malignancy