Welcome to ASG Endo Hangouts for GI Fellows. These webinars feature expert physicians in their field, and I'm very excited for today's presentation. The American Society for Gastrointestinal Endoscopy appreciates your participation in tonight's event, entitled Esophageal Motility. My name is Marilyn Almodore, and I will be the facilitator for this presentation. Before we get started, just a few housekeeping items. We want to make this session interactive, so please feel free to ask questions at any time by clicking the Q&A feature on the bottom of your screen. Once you click on that feature, you can type in your question and hit return to submit the message. Please note that this presentation is being recorded and will be posted within two to three business days on GILeap, ASG's online learning platform. You will have ongoing access to the recording in GILeap as part of your registration. Now it is my pleasure to hand over the presentation to our two GI fellow moderators who will help with the incoming questions, Dr. Masan Muftah and Dr. Ryan Flanagan. I will now hand the presentation over to them. Hello, everyone. My name is Masan Muftah. I'm a second year fellow at the Brigham and Women's Hospital. Thank you all for joining us this evening for this session on esophageal motility. I'm going to start off with the faculty introductions. So first we have our moderator, Dr. Walter Chan. Dr. Walter Chan is director of the Center for Gastrointestinal Motility at Brigham and Women's Hospital. He's the director of clinical research education within the division of gastroenterology and assistant professor of medicine at Harvard Medical School. He completed medical school and residency training in internal medicine at Washington University School of Medicine, followed by gastroenterology fellowship at Brigham and Women's Hospital. He also received an MPH from the Harvard School of Public Health. His clinical and research expertise are in the evaluation and management of gastrointestinal motility and esophageal disorders. He focuses around understanding the pathophysiology and optimizing the management of esophageal motility disorders, particularly GERD and its extraesophageal manifestations, such as pulmonary complications, lung transplant outcomes, and LPR. He currently directs the gastrointestinal motility and physiology laboratory at Brigham and Women's Hospital. And then our first panelist is Dr. Amit Patel. Dr. Amit Patel is associate professor of medicine at Duke University and the Durham VA Medical Center. He earned his undergraduate degrees in history and biology from Duke University. He then completed medical school, internal medicine residency, and gastroenterology fellowship at Washington University School of Medicine before returning to Duke University in 2016 to join the division of gastroenterology. Dr. Patel's academic and clinical pursuits focus on the esophagus, particularly esophageal diagnostic modalities. He's published widely on the esophagus, including first author or senior author publications and chapters across multiple textbooks. He co-authored the ACG clinical guidelines on esophageal physiologic testing. He is a dedicated educator and mentor and was awarded the Duke University Division of Gastroenterology Paul Kilenburg Faculty Teaching Award in 2021. I'm going to hand it off now to my co-moderator, Ryan Flanagan, to finish the introductions. Hi, everybody. I'm Ryan Flanagan. I'm also one of the GI fellows at Brigham and Women's Hospital. It's my pleasure to introduce the other two panelists. Dr. Daniela Jodakowski is the Director of Gastrointestinal Motility and Physiology as well as Program Director of the Gastroenterology Fellowship in the Division of Digestive and Liver Diseases at Columbia University Medical Center. After graduating Harvard University with a Bachelor in Cognitive Neuroscience, she received her MD in 2006 from Mount Sinai School of Medicine, where she also completed her residency in internal medicine. Her Gastroenterology Fellowship was completed at Johns Hopkins Hospital, where she received specialized training in esophageal and other motility disorders, and her clinical interests include diagnosing and treating conditions such as GERD, swallowing disorders, achalasia, gastroparesis, irritable bowel syndrome, chronic constipation, as well as fecal incontinence. And then our third panelist is Dr. Priya Kathpalia. She's the Director of Gastrointestinal Motility at UCSF and also serves as an Associate Program Director for the GI Fellowship Program there. After earning her medical degree at Loyola University Chicago Stritch School of Medicine, she completed a residency in internal medicine at Loyola University Medical Center, where she also served as a chief resident. She then completed a fellowship in gastroenterology at UCSF, where she trained with international experts in esophagology. She has a special interest in esophageal and other GI motility disorders. And I'd like to hand it over to Dr. Chan to get us started. Thank you, May and Ryan, for the introduction, and welcome everyone to our session today. We're going to go through a few clinical cases to highlight some of the main basic key points of diagnosing and managing esophageal motility disorders. And with that, we're going to go through the performance and analysis of esophageal manometry. We're also going to cover a few other diagnosing modalities, such as flip analysis and barium swallow and time barium swallow. So without further ado, we're going to get started. We have no relevant disclosure on the panel. So we're going to start with going through the basic primer for esophageal manometry in the Chicago classification that's used to analyze this manometry tracing. And Dr. Jorokoski is going to be talking to us a little bit about that. Thanks, Walter. So as you all know, there's a few indications to perform esophageal manometry. Probably the biggest indication we see is evaluation of patients with non-obstructive dysphagia. But we can also use manometry to aid in the placement of a pH probe for reflux monitoring. So we find the LES on the manometry, and then we know where to place the pH probe five centimeters above. It's also strongly recommended to do an esophageal manometry prior to esophageal surgery and fundoplication because you want to look for a major motility disorder that may either contraindicate the procedure or may alter the type of procedure they do. And then finally, in the evaluation of patients with non-cardiac chest pain, assuming it's not a GERD-related chest pain because these hypercontractile conditions are a little more rare. So let's go over the technique. This is an awake procedure. Patients don't love it, but it can give us a lot of information. First, we only use topical lidocaine in the NARES, no anesthesia. The probe is placed transnasally, crosses the LES into the stomach where at least a few sensors are below the diaphragm. The patient then lies supine on a stretcher, and they're given a series of 10 sips of liquid for single swallows. So we only evaluate one swallow at a time at this moment. Then we do a few maneuvers, including multiple rapid swallows, upright swallows, so the patient's now sitting upright in the stretcher, a rapid drink challenge, and then in some situations a viscous or solid challenge, and then the probe is removed. So there's a picture of a probe on the right. There's a few different companies that make them, but they all have circumferential pressure sensors that are giving us a wealth of information of what the esophagus is doing when the patient's swallowing. And so the way the data of that is transmitted to us on the screen is really this plot called the pressure topography. So to orient you, this is a baseline measurement where the patient's not doing anything, not swallowing. The y-axis is the position of the catheter in the esophagus, so you can see on the top there's a band of pressure that's the upper esophageal sphincter, and at the bottom is the choral diaphragm and LES. The x-axis is time, and the z-axis is the colors, so the colors indicate pressures. So the warmer the colors, the higher the pressures. So kind of purple, reddish are higher pressures, and blue and green are lower pressures. So this is baseline measurements. Next we're going to go through what a typical swallow in peristalsis will look like and the sequence of events that happens. So when the patient swallows, first the first step of the UES relaxes. Then there's a striated muscle contraction on the top third of the esophagus. Finally there's a transition zone, so there's a mixture of striated and smooth muscles, so it's normal on the manometry to have a break in peristalsis there. Then there's sequential smooth muscle contraction down the length of the esophagus. About two seconds after the UES relaxes, the LES should be relaxing. So you can see there at the bottom the pressure of the LES is kind of dropping off. As the contraction is going down the esophagus, there is a point where the velocity kind of slows down. That's called the contraction deceleration point, and that's the arrow pointing to it. And then finally after the peristaltic wave, the LES has an after contraction. So that's a normal swallow. When we analyze manometry, we take all the information of the individual swallows and our challenges, and we come up with a classification scheme to really make a diagnosis. So the most common classification we use is the Chicago classification. So this was started by an international working group. They came out with version one in 2008. It's now on its fourth iteration, which was published about a year ago. And the objective was to apply standardized reproducible metrics to high-resolution manometry to classify esophageal motility disorders. So these metrics that we're talking about, we analyze each swallow, and we're looking at these metrics for each swallow. So the IRP is the area where the LES is supposed to be relaxing. It's the lowest mean EGJ pressure of four continuous or non-continuous seconds. And essentially it's the measurement of whether the LES is relaxing appropriately. The DCI is the distal contractile integral. This is not only the amplitude or the height of the contraction, but also the duration and the length. So it's a measurement of how vigorous the contraction is. And there's a very wide range of what's normal between 450 and 8,000 would be considered normal. If it's less than 450, it's either failed or ineffective, and then greater, it's hypercontractile. And then the distal latency is probably the one that is a little less commonly known. It's the interval between the UES relaxation and the contractile deceleration point. And this tells us whether a swallow or a peristaltic comes prematurely. If it's short, which is less than 4.5 seconds, that's abnormal. So here are just some examples of peristaltic patterns you could see in the esophageal body. The first panel is basically, you can see there's really no pressure going on, no peristalsis. The DCI is very low, it's less than 100, and it's considered a failed swallow. The next one, you can see a little bit more pressure going on. There's a nice peristaltic wave, but it's very weak, and the DCI is 187 here. The next one is a hypercontractile swallow. You can see not only is it very, very pink, which is high amplitude, but it's really long. So the DCI is 11,000, so it's above 8,000, so it's hypercontractile. And then the last panel is not the most obvious example, but it's a premature contraction because the latency period is four seconds. So once you analyze the 10 swallows, Chicago classification 3.0 used a hierarchical scheme that was based on 10 supine liquid swallows. And I'm not going to go through this whole algorithm, but just to point out that you first think about this as whether there is GE junction relaxation or not. And that's the median IRP. If there is abnormal relaxation, that's a disorder of EGJ outflow obstruction, whether it's a Echolasia or EGJ outflow. If the IRP is normal, then you start looking at the peristaltic patterns, and then whether there's enough criteria for the variety of disorders like DES, hypercontractile lapse and contractility, et cetera. So the benefits of the Chicago classification were that they provided a standardization in our clinical and research realm, provided a common language for all of us to talk about these studies. It also increased the sensitivity to detect Echolasia. And then with the development of high-resolution manometry, it became clear there were three manometric subtypes of Echolasia, and that provided us with some prognostic and therapeutic implications, which we'll talk about in a bit. And then they changed the definition of DES from velocity to using this distal latency, and that defined a more homogeneous population. So there is a very clear role of the Chicago classification in the major motility disorders. And this is 4.0. So, again, I'm not going to go through the entire slide. It's similar to the 3.0. We still base our initial kind of categorization whether the GE junction relaxes or not. So first you look at the median IRP. If it's abnormal, you're going along one pathway to look for whether it's an Echolasia, EGJ outflow, depending on the peristalsis. We'll talk more about EGJ outflow and the various maneuvers that we can do to support that criteria. And then if it's a normal IRP, then you start thinking about whether the patient meets criteria for the various peristaltic disorders like absent contractility, DES, et cetera. So thank you, Daniela, for that great overview. And don't worry, we're going to really go into the detail of analyzing these tracing and going through Chicago classification version 4 as we go through each case. So I'm going to start with the first case. And as we go along the case, I'm going to ask the panel to chime in. And then feel free to send in your questions. And after each case, we'll leave some time to do some question and answer according to each case. So this first case is a 65-year-old woman with a history of GERD, hypertension, and hyperlipidemia who came in with a six-month history of increasing heartburn and regurgitation. She also reports some other symptoms, including difficulty swallowing, initially with solids, but now with both solids and liquids. She also reports some atypical chest pain. And because of all these symptoms, she's also lost about 15 pounds in the last three months. She had no alcohol or tobacco use and denies other symptoms. So first of all, I just want to ask the panel, at this point, what are you thinking? What would you do next? Priya, maybe, do you want to chime in with your? Yeah, sure. So this patient has GERD, but she also has alarm symptoms, dysphagia, as well as atypical chest pain. And so she's definitely bought herself an endoscopy, plus or minus an esophagram. That would be what you would get, these two studies that you got, a barium esophagram and an endoscopy. And on the barium esophagram, you can see this pattern that doesn't seem very typical of what we normally should see in a normal barium esophagram. There's these, what we call a coarse-grained pattern, also some narrowing down in the GE junction area. On endoscopy, the lumen itself didn't look terribly abnormal, although you can see that down in a GE junction area, the LDS seems a little hypertonic, so it requires a little more pushing to get the scope through. And at this point, what are we thinking, especially given these findings, what are we suspicious of? Yeah, so at this point, we're worried about a motility disorder, so given the largely unrevealing endoscopy, it would be reasonable to proceed with an esophageal motility study at this point. I think somebody mentioned in the chat, could this be a malignancy, and I think they bring up a really good point that in somebody who's elderly, who has weight loss, you should also rule out other causes, in addition to a motility disorder. And so it's really reasonable to perhaps get a CAT scan in this patient as well, concurrently. Yeah, I was going to comment, if there's a really big concern for malignancy, even if the endoscopy looks normal, you want to make sure you do a really good retroflexion as well to look at the cardia, and if you really are concerned about malignancy, then you might also, as Priya mentioned, a CT scan or an EUS. But in this case, we had a very thorough look, the esophogram did not look like a malignancy. And the next step that we suggested by Priya is to do an esophageal manometry, and Priya, do you want to tell us what you see here? So here you can appreciate that the LES, first and foremost, is not relaxing well, as indicated by the elevated IRP of 28. In addition, it does appear that the distal latency is short, and it is in fact 3.2 seconds, which is below the cutoff of 4.5 seconds. So if we were going through the Chicago classification based on those information, first of all, as Priya mentioned, the IRP, it's abnormally high, so there's an abnormal IRP, so as we go down the algorithm, we see an abnormal IRP. Then the next question is, are there absence in normal peristalsis? As we can see, we could see from the manometry image there, there's no normal, that sequential contraction pattern that we would see with a normal swallow, with any of the swallows. So there's 100% absent normal peristaltic swallows. So all the swallows are either failed or premature. Then with that, then you go to the left-hand side, which is, basically brings you to one of the three classes of achalasia. So if it is, you have 100% failed swallow, then that would be type 1 achalasia. If you have these pen and soft gel pressurization in more than 20% of the swallows, and that will be type 2 achalasia. And if you have more than 20% of swallows with these premature contractions, like what we saw in the last, in the tracing, with a short distal latency, then that would be type 3 achalasia. And I think as a lot of people mentioned on the chat, the findings are consistent with type 3 achalasia in this case, as you can see from the image. I just want to ask the panel a little bit more too, in terms of classifying this Chicago classification. Sometimes when we do a tracing, when we do a study, we might see a combination of failed or pen and soft gel pressurization, or these premature contractions. If you see more than one of these type in some of the swallows, how would you classify them? What kind of ways do you, how do you subtype them in that case? So achalasia obviously is a spectrum, when we talk about achalasia spectrum disorder. So when we have swallows that might have features of different types, I think it is important to identify perhaps the dominant feature. And the reason that's so important, I think we'll probably discuss in this case, is when there are any features of type 3 achalasia, I think that really helps guide our treatment for those patients, and perhaps matters a little less than for types 1 and 2. So I think that the general rule is that if you think of type 3 as the highest level of severity, you usually want to classify them based on sort of the highest level of severity. So if you see some premature contractions, then you will err on treating it like a type 3 achalasia. Even if there are some swallows that might be failed or have pen and soft gel pressurization. So just a few very quick things from Priya, maybe, about achalasia. So it's interesting to note that the word achalasia is derived from the Greek word kalasis, which means not loosening or relaxing. And it generally has an incidence of about 1 in 100,000 worldwide. It's associated with a loss of myenteric plexus ganglion cells in the distal esophagus in the LES. And the cause of this kind of initial reduction of inhibitory neurons in achalasia is largely unknown, but there are various theories. Perhaps one theory is that there's a viral process that may have triggered kind of an autoimmune response in these patients. And this is further supported by the fact that oftentimes studies have suggested that these patients tend to have concomitant autoimmune diseases higher than the general population. But the truth is, there's not enough studies on this to really say for sure. Another manifestation, which you probably all know from your step exams, your boards, is that that one manifestation could be Chagas disease, though very rare. It is caused by the parasite trypanosoma cruzii, so something to keep in mind for patients from endemic areas. So this is a slide just showing what the various symptoms that patients can present with and what might prompt a motility evaluation in patients once you rule out GERD and once you rule out a mechanical obstruction such as strictures or rings. Progressive dysphagia to both solids and liquids, as was what we saw in our patient's case here, is really the hallmark symptom of achalasia. It should be noted, too, that respiratory symptoms are not uncommon because as the esophagus has decreased peristalsis and achalasia, there can be decreased clearance of both food and liquid, predisposing the patient to aspiration. It should also be recognized that dysphagia tends to precede these respiratory symptoms on average by two years, so hopefully it's caught well before then. But unfortunately, the average symptom duration at time of diagnosis is generally two to five years in these patients because they're either thought to have GERD or other disorders that prevent them from getting a motility evaluation. So I really want to stress that if you have any suspicion for it, that you should send these patients to GI subspecialists. So overall, we saw in our patient that she had an esophagram, not necessarily the first test that needs to be done, but in this case, it was actually done by the primary care provider before being sent to GI, but it can help complement other findings from other studies. Upper endoscopy is, of course, necessary to rule out, as we talked about, strictures, rings, malignancy. And then esophageal manometry remains the gold standard for diagnosing achalasia and other major motility disorders. We're not going to talk about endoflip so much in this case, but it's going to come up in the next case and is a newer tool that can help us understand the distensibility of the esophagus and is a complementary tool for diagnosing these patients. So this is a slide just showing the various ways that achalasia can present on esophagram. In the first one, you see your classic bird's beak esophagus with a very dilated esophagus. In the second example, again, very similar, more of a dilated esophagus with tapering more distally. And then in the third case, in the third image, you can appreciate more of a corkscrew esophagus, much like the patient who we just presented had. So our patient had a normal upper endoscopy, but it's important to recognize that achalasia can present in a variety of different ways on endoscopy. First and foremost, if you are doing an endoscopy on somebody who is suspecting a kalasia, it's important to tell them to probably stay NPO for at least 24 hours prior to the procedure or just on liquids so that you can get a more accurate assessment of the underlying mucosa. So this first image, you can really appreciate retained food and liquid in the esophagus itself. Here you can appreciate more of a sigmoidized or tortuous esophagus, which can result from the distal LES pressure being increased. And then at times you can also see more of a puckering of the LES, which tends to signify the tightening of the LES. These findings certainly don't need to be present, as we saw in our case, but will make you think more of a kalasia if you do see them. And I want to add to one of the clues sometimes, especially if the endoscopy is otherwise fairly normal in the esophagus, is that when you get close to the lowest off your sphincter, a lot of times when we sit above the LES and we start blowing air in there, you will see this LES start relaxing, allowing it to pass through. And a lot of times in these akalasia patients, even if you just sit on top and just keep blowing air at the LES, it's not going to relax for you. And sometimes that could be one of the clues for you too, especially if the endoscopy is otherwise normal. Another more subtle feature that might be in an earlier akalasia is a retained frothy saliva that you might see. And obviously you suction right away, but before you suction, you can see that there's not specific for akalasia, but for esophageal dysmotility. And I think Daniela mentioned earlier, doing a good retroflexion is important because one thing I want to rule out is an EG junction tumor that can also cause a kind of obstructive pattern and almost an akalasia finding as well. The next thing to talk about is, once we make a diagnosis, how do we treat akalasia? And there are really several different ways that we can treat akalasia with the main aim to decrease the lower esophageal sphincter pressure to basically relieve that obstructive physiology. The more invasive ones are either pneumatic dilation, which is bigger than a usual balloon dilation that we do. Usually you start at a three centimeter, they can go up to four centimeter or a type of myotomy to basically cut the lower esophageal sphincter to relieve the pressure. This can be done either surgically or through endoscopy with a procedure called POEM, which is newer. Pneumatic dilation, surgical myotomy, POEM had pretty similar efficacy, especially in the first year in a lot of the clinical trials. And these effects tend to, these benefits tend to last up to five years with over 80% of patients still reporting good response. There are some risks with these procedures. There's a two to five percent perforation risk associated with pneumatic dilation, which is a little bit higher than would see with the regular CRE balloon dilations. With myotomy, with the two types of myotomy, there's an increased risk of reflux, not surprisingly, as you cut the lower esophageal sphincter. And in more recent studies, it's been shown that the amount of reflux might be more severe with up to 37% of patients with increased reflux on pH monitoring after undergoing POEM. And about 18% of patients actually develop reflux esophagitis afterwards as well. This tends to be a little bit less for patients who undergo surgical myotomy because the surgeon often can do a partial fundoplication after doing the myotomy to help relieve some of the reflux. And a two less invasive way of treating this is through Botox injection to the lower esophageal sphincter to relax it or using medication to relax them. The good thing is that these are relatively safe, although with Botox, even though it's effective immediately, the response rate decreases to about 60% at one year. So a lot of these loses effect over time and people often need repeated injection. Medication just overall doesn't have nearly as good of a treatment effect, up to only about 50% or so in some clinical study and probably even less. So Priya, how, you know, we talk about this patient being type 3 echolasia, how does it affect our treatment choices? Yeah, so let's go through some studies that all kind of help delineate this. So this was a study by Pandolfino and colleagues first, just showing that patients with type 2 echolasia, regardless of the treatment, tend to have kind of the best response, you know, recognizing this was a study of 83 patients, you know, in 2008. There's a more recent study from 2013 by Roholf and colleagues of 176 patients showing that patients with type 3 echolasia in general tend to respond better to myotomy than pneumatic dilation. I think currently the mainstay of therapy for type 3 echolasia tends to be POEM, just because you can really not only focus on relieving the pressure at the LES, but tailoring the length of the myotomy to the spastic component, which seems to provide the greatest benefit in these patients. But it seems like from this study for type 1 and type 2, they both respond fairly well to both pneumatic dilation and myotomy, that both have pretty good outcomes. Yeah, that's true. I think a lot of what treatment you end up deciding on depends also on the institutional expertise in addition to the patient's overall comorbidities, and really requires a careful discussion of risks and benefits of each of the procedures or therapies with the patient. So with these data in mind, so how would we usually approach these echolasia patients in terms of management? I think one of the first things you have to determine is how well is this patient a candidate for more invasive procedure? Do they have a high or low surgical risk? In patients who are otherwise relatively healthy, who had a low surgical risk, then you really want to go for the more effective therapy. And once you've decided that, then you want to split them into whether they're type 1 or 2 or type 3 based on the data we just talked about. For type 1 or 2, you really can choose either pneumatic dilation or myotomy as they are both fairly effective in these two subtypes. For type 3, as we saw, myotomy seems to be the better choice. Now, how do we determine if a patient should get surgical versus myotomy versus POEM? One of the ways to determine is to think about their reflux risk, because we talk about the high risk of developing reflux esophagitis in patients who undergo POEM. So in patients who have a low risk for GERD, then either POEM or surgical myotomy would be a good option. But in patients who have a high risk of reflux, for example, patients who are obese or have other risk factors or have no reflux or Barrett's, then the surgical myotomy might be a better choice to help decrease the amount of reflux post-procedure. Now, if they fail treatment, you can always cross over to the other one. And if they continue to have symptoms and continue to fail treatment, then you can even do repeat myotomy or dilation. Obviously, as a very last resort in some end-stage patients who have very dilated esophagus, they may actually require more invasive treatments such as esophagectomy to relieve their symptoms. For patients of high surgical risk who are not good candidates for any type of surgery or invasive procedures, then you can consider doing Botox injection. Even though it's done through endoscopy, it's still relatively safe. The complication risks are low. The problem is that then you have to keep bringing these patients back for repeat Botox. If they fail Botox, the other thing you can also try is by medication. So some smooth muscle relaxants such as nitrates and calcium channel blockers. The key thing here is that if you have a low surgical risk, there's really no reason to try these Botox or medical therapy because their efficacy is so low. And you should really just go for the more definitive therapy. They're more durable. One potential concern with Botox injection, especially if these patients are good candidates for other more better procedures, every time you inject, you might cause some fibrosis in the area, which may then affect the procedural risk later if you do proceed towards myotomy or pneumatic dilation. I just want to ask the panel here, is there any other things that you would consider in choosing therapy for achalasia patients? And also for those type one and two patients relatively healthy, how do you determine if you do want to do myotomy or pneumatic dilation? Is there a specific algorithm do you think about? I think with the development of POEM and the popularization of POEM has really lowered our threshold for what we consider surgical risk in these patients. And so I found that using Botox injection, doing less and less frequently, Walter, you mentioned the big risk with it is that maybe not once, but repeated administrations of Botox, we have decreased efficacy and durability of that effect. But not only that, it takes these other options off the table potentially in the future. So particularly in younger patients who have clear cut achalasia compatible symptoms, we really try to guide them towards more durable interventions. And when we're having the discussion about which one, so let's say there's a type two achalasia patient with a new diagnosis without a lot of comorbidities, then kind of lay the options on the table and primarily focus on more durable ones, the pros and cons of each. Sometimes we'll have patients that meet with our surgeons, for example, to learn more about what might be entailed. And this is a big decision for these patients. The good news is that all of these options are generally pretty good, but it is an individualized approach to this. And a lot of things come into play, including their risk for reflux afterwards. If they've had prior surgeries, that can affect the ability to do our myotomy, for example, or the surgical approach for that. So I think having a discussion with patients, tailoring their decision to their individual values is a necessity. And again, really want to emphasize the point that if there are any features of type three achalasia in these patients that they're really better off with an intervention that's tailored to the spastic segment with POEM as opposed to just intervention limited to the LES, which might lead to a suboptimal outcome for them. Great. Since this is ASGE, I also figured I'd throw it out there. I know that in the interventional world, they're talking about trying to combine POEM with TIF to try to reduce the post POEM reflux. So stay tuned, but we'll see how that goes. And just wanted to emphasize what Anit said, that a multidisciplinary approach is really necessary in taking care of these patients. So having your patients see not just a surgeon, but your advanced endoscopist in addition to yourself will be really valuable and give them the tools necessary to help kind of make the best decision going forward. And great. We had a question in the chat just to that, kind of address that having input from a surgeon, having to meet with a surgeon is definitely appropriate to help guide their risk for these procedures relatively. And again, the difference between a POEM and Botox when we're talking about things like sedation or anesthesia is not as big as you potentially other procedures. So that's definitely been an option that can be less invasive in some ways to certain patients, especially those who might be at higher surgical risk because of prior procedures or potentially other anesthesia risks or wound healing risks or anything like that. And then Danielle mentioned the idea of we've gotten new interventions, anti-reflux interventions that can be done endoscopically. And we're actually going to have a DDW session through the ASG on that because there is a lot of interest in whether same session, transoral incisional splenification, for example, at the time of POEM, whether that makes sense for all patients, some patients at risk, et cetera. So that's really an exciting time in endoscopy and esophagology in particular. I think there was one comment in the chat about what do we think the outcome in practice, I assume the questions in real world that we see about POEM and patient akalasia. I can start off with saying that generally at our center, we have a really great interventional endoscopist doing these and our outcome has been actually excellent. We have not really had any major complications in most of the patients, in almost all the patients we had it done with. The outcome really actually goes along with a lot of the published data where type 1 and 2 patients, unless they already have a very dilated end stage looking esophagus, tend to do fairly well. But type 3 patients, especially if you do an extended myotomy, those patients actually do fairly well as well. And I think that 80%, 90% percent data that we see in some of the study that have been published so far, it's actually pretty close, I think in real world, as long as you're not talking about those end stage esophagus patients. What about the others? Yeah, not just the performance of the procedure, but selecting the right patient for the procedure is incredibly important. And I just wanted to mention that I think it was a case series from Cleveland published recently that even in patients with advanced achalasia, when we start thinking about things like sigmoidization of the esophagus or quote unquote end stage, POM can be a reasonable option for some of these patients. And some of them do do pretty well. And then the other thing that we do see is patients who have had prior attempts at treatment for their achalasia, but still have evidence of LES dysfunction. And for a lot of these patients, salvage POM has been pretty effective as well. So I think it's really expanded our options in our toolbox for these patients, particularly those with longstanding disease or prior failed attempts at treatment as well. Yeah, I agree. And then the data is the best for type 3 achalasia for POM, but patients with type 1 and type 2 achalasia are doing this as well with POM, as we've seen at our institution as well. Type 3 patients tend to have over 90 percent success rate. And though some of them may tend to get GERD afterwards, that's something that's easily treatable and overall, they're feeling so much better that that's the least of their concerns, as long as you can keep them on PPIs, at least short-term post-procedure. I know there are a number of questions. Let's finish the case and we can come back to some of these questions, just so that we can know what happened to our patient. So the patient ultimately underwent POM with an extended myotomy to about 10 centimeters. And within a week of the procedure, patient's dysphagia resolved, and he later gained back some weight after the procedure. And interestingly, we actually have a post-POM barium study. You can see that the improvement in the findings on the barium study after POM, the corkscrewing is resolved probably because of the extended myotomy, and you see less tapering down the GE junction as well. So this is a patient that with type 3 achalasia that responded well to an extended myotomy performed through POM. And then the next slide is just a few summary points, but maybe we can see what questions there are from our moderators. Yeah, we have a lot of great questions here. One of them is, is there any way to topographically mark the area on myotomy, or for the myotomy on manometry, so to understand how far the myotomy should be extended? That's actually a great question, and I actually do that quite a bit with our interventional endoscopist when planning procedure for these patients, because we can actually on manometry look at the distance. We can measure the distance above the LES region of how far the hypercontract, or the dysplastic contractile fragment extends. So from that distance, I can tell the endoscopist how far they should go up from where the GE junction or the lowest of those fingers. So it is very useful, particularly in type 3, and that's why having a multidisciplinary team is useful. I'm going to piggyback on the poem questions. There is a question about what the maximum length of the myotomy should be when doing a poem, and the preferred site of the myotomy, and then another poem question is, does having a previous pneumatic dilation make a poem later on more difficult to do? So how long of a myotomy you do really depends on the spastic component. There's no upper limit cutoff for that, but in general, the maximum I've seen is about 15 centimeters. But again, it requires a careful discussion with your advanced endoscopist and review of the manometry to decide that. Does pneumatic dilation make poem harder to do? I'll just kind of jump on that for interest of time. Theoretically, with pneumatic dilation, you can get some degree of fibrosis afterwards that could make poem harder to do, but certainly not an absolute contraindication to somebody who hasn't responded to pneumatic dilation. Yeah, so I can just jump on that a little bit as well. There's really no data to show that currently, so it's theoretical going from pneumatic dilation to myotomy. There had been data on Botox injection to myotomy that showed that if you do Botox first, the outcome from the myotomy is worse, mainly on the surgical side. But from pneumatic dilation to myotomy or poem, there's no data really to support that just yet, but theoretically, there could be some level of fibrosis that can happen. But I can tell you that in our center, we actually have quite a number of patients who undergo that, and we have not had issues with those patients either. I think it makes it just tougher for the interventional endoscopist, but obviously, you want to send to someone who has done a lot of poems and has a lot of experience with it to deal with those little things that come up like fibrosis, bleeding, etc. If we have time for more questions... Yeah, let's do another question before we move on. So there's a certain number of questions on pneumatic dilation. So one is what your typical protocol is for performing pneumatic dilation, and then do you ever consider that pneumatic dilations are potentially less effective in young males because their lower esophageal sphincter might be stronger in men than women? So there were some suggestions in the past, and there are even some guidelines in the past that says that maybe you just start the dilation balloon size higher in young patients, particularly young male patients, starting at 35 millimeter rather than 30 millimeter. But in the most recent randomized trial, the protocol is always starting everybody, male or female, at 30 millimeter. That has been shown to have an overall lower risk of perforation by doing this sequentially like that rather than starting at higher based on gender, and the clinical efficacy is about the same. So I would say that our current protocol is always starting them at 30 millimeter regardless of gender and age if we're going to pursue pneumatic dilation. Just to follow up on that question, so you say start at 30, do you then go up on subsequent pneumatic dilations or would you potentially even do higher in the same procedure? The rest of the panel can chime in, but generally I would not go up. I would do one size per procedure, and then if their symptoms don't improve, we bring them back for a step up in terms of sizes. So unlike the CRE type balloon that we do, we can do several sizes during one treatment for pneumatic, we usually just stick with one, and then we bring them back for sequential dilation if needed. I'm going to, just in the interest of time, we're going to move on. We can come back to some of these questions later if we have time. We'll save them here. And case two is a patient who is a 48-year-old woman with a history of heart failure coming with a year history of intermittent dysphagia. A patient had dysphagia to solids only in the upper chest region. Severity has been worsening over the last six months, now having daily symptoms. She denies any heartburn or regurgitation or any weight loss. She does use inhaled steroid but denies any NSAIDs, potassium, doxycycline, no history of asthma, eczema, or atopic dermatitis. So with this clinical history, mostly with a lot of the regurgitation and dysphagia, the patient underwent some studies to evaluate for these symptoms, including upper endoscopy, which showed basically a normal esophagus. Biopsies in the esophagus were normal. The barium esophogram showed mostly a normal caliper esophagus, but with some tapering down in the GE junction. So these are the information that I have so far. So I'm going to go back to the panel. What would be your next step of evaluating these patients given these information? It sounds like esophageal phase dysphagia on history. I've got an EGD that's pretty unrevealing. The barium raises our suspicion for potentially an achilles spectrum disorder if there's some tapering at the GEJ. I guess in this setting, I'd probably go to manometry next if the patient is amenable. So the patient underwent an esophageal manometry. Amit, do you want to take us through this really quickly and here's what you're seeing here, the main features? Sure. So the main thing after Danielle's primer, we know where the upper and lower esophageal sphincters are. The main thing that sticks out here is that the IRP is elevated across these representative swallows above that threshold of 15 on this equipment. But the morphology of the swallows looks okay in terms of the distal latency or timing of the swallow, as well as the vigor of the swallow measured by the distal contractile interval. So if all the single swallows are like this, this would meet criteria for EGD outflow obstruction. So let's go back to our Chicago classification and look at how we go through this. So this is a patient, as Amit talked about, had an abnormal IRP. And so the next thing, just like the last case we think about is, were there normal peristaltic contraction esophagus. As Amita mentioned, they were fairly normal peristaltic morphology. Unlike the achalasia patients, these patients have some normal peristaltic swallow. According to the third version, the prior version of Chicago classification, that would get you to the diagnosis of esophageal gastric junction outflow obstruction or EGTOO as a diagnosis. This is an example of a swallow associated with EGTOO. Amit, can you tell us a little bit about EGTOO outflow obstruction? Sure. Under Chicago 3.0, which is the 10 supine swallows, if that IRP was elevated, but the swallows themselves did not meet criteria for the three subtypes of achalasia, then that met this diagnosis of EGTOO. The problem was it's very heterogeneous and it was common. We're seeing it in 10-15 percent of studies interpreted with Chicago 3.0 criteria, but it's very heterogeneous. Now, there are a subset of those patients who are a variant of achalasia and should be treated as such, but then there's a lot of patients for whom it's either an artifactual finding, vascular artifact, from hiatus hernia, from obesity, and then there are also several from opioid use that we might discuss later if we have time, although it's a whole topic unto itself. But the key was to identify what subset of these patients with this finding should be managed as achalasia and which the rest that perhaps should just be observed. Now, there was that mention of EUS or CT for these patients with the idea of being to rule out malignancy. In a lot of different studies or series, including our own at Duke, there was not a lot of utility to this in terms of detecting malignancy. With that being said, when there are patients that are older, have a smoking history, a lot of weight loss, I think it's reasonable to consider these to rule out something like that. Having an elevated IRP based on the prior criteria has been associated with a number of different clinical symptoms for patients who report them. Dysphasia being most common, just like dyspatians. Sometimes patients report mostly regurgitation or heartburn type symptoms, or some atypical reflux symptoms. There had been a study that would perform to show that maybe the peristaltic pattern of the esophageal body may correlate with symptoms. For example, if you have EGGL flow obstruct or a high IRP, but a hypercontractile pattern in your esophageal body, maybe you are more likely to have chest pain and regurgitation versus having an ineffective peristaltic pattern. The natural history of having EGGL flow obstruction or an elevated IRP really is dependent on the underlying cause. As Amit said, there's a number of different causes to it. Many of them are either secondary to anatomical changes or medications. In prior studies based on just having an elevated IRP alone, evolution to full-blown akalasia was rare. In one series, only two of 72 patients. A lot of these patients, the symptoms just spontaneously resolve, so making it even harder to manage these patients. It seems like if you don't have a structural cause, but more functional cause of these EGGL flow obstruction, you're more likely to have resolution of symptoms. Unless you have a reason to see that there's a structural cause to their EGGL flow obstruction or high IRP on manometry, then a lot of up to 50 percent of these patients might have spontaneous resolution of symptoms at six months. What are some of the ways for us to determine if this is actually true EGGL flow obstruction, Amit? That was one of the feature developments of the new Chicago classification, 4.0, was a better arbitration of these EGGL findings that we're seeing a lot under 3.0. 3.0 was just 10 supine wet swallows, but obviously, that doesn't reflect what we do clinically. We're not lying flat and swallowing water. We're oftentimes sitting upright, we're eating food, taking multiple bites at once. Provocative maneuvers were important in helping to better understand esophageal physiology and to challenge the esophagus. Particularly for EGGLO, we found there's a lot of patients when they sat upright, the IRP would resolve. In these kinds of patients, there was usually not any functional obstruction at the EGGL going on. One of the big developments of Chicago 4.0 was requiring an elevated IRP in a primary and secondary position to make a manometric diagnosis of EGGLO. We talked about that cutoff of 15 with Medtronic equipment for supine swallows. For upright, that cutoff is 12. But patients need to have elevated IRPs in both the primary and secondary positions to make a manometric diagnosis of EGGLO under Chicago 4.0. This is an example that Ahmed was talking about regarding upright swallows. That had been studied to show that for upright swallows, IRP greater than 12 had 98 percent sensitivity to identify radiographic evidence of EGGLO obstruction, meaning tablet hang up at the G-junction area. Another important advancement in Chicago 4.0 was we talked about how that elevated IRP in a primary and secondary position to make a manometric diagnosis of EGGLO, also requires increased intrabolus pressure. But for that diagnosis to be clinically relevant, patients have to have dysphagia or chest pain, as well as we'll talk about alternate modalities to confirm that there truly is obstruction at the EGGL in these patients. With that information, now going back to this patient, we know that this patient with Chicago 4, this patient had normal IRP, had some normal peristaltic contractions, and we know that this patient also had upright position swallows that actually will also show abnormal IRP. Again, as we talked about in the past, that will be enough to make the diagnosis having abnormal IRP for EGGLO obstruction per Chicago 3.0. But as Ahmed mentioned, to really further identify patients where this finding is clinically relevant, you actually need other supportive elements to it. So in addition to having elevated IRP in both positions, you also should have an evidence of what we call elevated intrabolus pressure or penesophageal pressurization. And what this is, is basically when you look at a manometry, you will see that there's an increase in pressure between where the contraction starts and the GE junction area. And I will point it out to you here. So you're supposed, basically, this area right here, I don't know if you can see my cursor at all, the area under, when you look at the picture on the EGGLO obstruction, the area under where the peristalsis starts, you can see there's a greenish color on the topography versus the baseline bluish color. That signifies an increase in pressure associated with the contraction. And what this is telling you is that your esophagus is contracting against a closed LES, and that's why there's a buildup of pressure there. So this is what's an increase in intrabolus pressure. So in addition to seeing elevated IRP in both position, you also want to see an elevated intrabolus pressure like that to tell you, as a supportive evidence, that there's actually a truly obstructive physiology. If you don't have that, then the question is, well, even though the IRP is high, it seems like things are not really getting built up to cause a high pressure. So it makes you question whether or not this is actually a significant obstruction or not. And in addition to that, you also need a secondary supportive feature, which is either an abnormal time barium swallow or a flip analysis. So you have to have all these elements together before we can arrive to the diagnosis of EGGLO obstruction. There could also be just add in there other findings on the manometry that could be supportive of EGGLO. So things like abnormal bolus transit on impedance, I know we didn't discuss that today, but also potentially inadequate deglutitive inhibition with some of the provocative maneuvers like multiple rapid swallows or rapid drink challenge that we'll look at a little later. Yeah, so tell us a little bit about some of these supportive things, such as flip. Sure, so we'll try to keep this brief because I know we have a lot to get through, but the two alternate modalities that we can go to are endoflip or the functional lumen imaging probe or a timed upright barium swallow. So the endoflip is an example of how the tower looks, but basically the idea is at EGD after diagnostic EGD, while a patient's sedated, we place the catheter and start it trans orally across the LES. Go to the next slide, Walter. This is an example on the left of how the balloon looks across the LES. Comes in eight centimeter and 16 centimeter lengths. And it generates these images when we distend this infinitely compliant balloon to different volumes. And so the original iteration in the center there, you kind of see how that looks. It looks like probably a patient with EOE with non-compliant esophagus and a waste at the LES. And then on the image on the right is the 2.0 where we see contractile patterns in the esophageal body in response to that volumetric distension. So in terms of kind of cutoffs for what we see, we get distensibility indices at the esophagogastric junction based on the volume and the pressure and the diameter. And so less than two is typically considered abnormal or supportive of EGD outflow obstruction. These are examples of some of those contractile patterns the esophageal body can have in response to volumetric distension. On the left are RACs or repetitive anterograde contractions. These are what are typically seen in health. And then all the way over on the right are RRCs, repetitive retrograde contractions. These are thought to be pathologic, might be seen in spastic disorders. And these are just examples of how those might look for different patients. So at the top panel A, I think that's an example of a patient who ended up having type 1 achelation. There's actually absent contractility in the esophageal body, but a decreased distensibility index at the LES. You can see that tight waist there. Panel B in the center are repetitive retrograde contractions in the esophageal body with a decreased distensibility of the EGJ. I think that was a patient that actually had type 3 achelation as a correlate. And finally at the bottom on panel C is a patient with repetitive anterograde contractions and a nicely distensible EGJ, like you would hope to see in a healthy control. And just a reminder that endoflip looks at secondary peristalsis, whereas manometry looks at primary peristalsis. And the second modality that we talk about that's supportive is time barium swallow. And just very quickly, this protocol that's different from the regular barium esophagram studies, the idea of doing this is really to quantify esophageal emptying. And the way this is done is that patients are given a standard amount of barium to ingest and a spot radiograph are taken at one, two and five minutes after the ingestion. And with each film, the barium column height and width remaining each time point are measured. And using that, then you can quantify how much barium is retaining at these different time point. We expect complete emptying in one minute in most of the healthy individuals, but definitely by five minutes in all healthy individuals, we expect complete emptying of the barium. So no column. There've been studies that show that a column height greater than two centimeter at five minute has been proposed as a cutoff for achalasia. It's been shown to help differentiate achalasia from regular EGGF obstruction and non-achalasia dysphagia with about 85% sensitivity or specificity. So this is a good study to use to help us tell us whether or not the emptying is normal. So going back to this patient, what we found on the left, you can see this endoflip on patient. You can see that the dissensibility index, I know the numbers are kind of small. It's about 1.92 with a diameter of 11 millimeter. So it's kind of bordering on that two of dissensibility that Ahmed was talking about as being what we consider abnormal. And on the right-hand side, you can also see some anti-grade contractions. Not a lot of the repetitive anti-grade contractions that we see in some normal individuals, but there are definitely some normal anti-grade contractions that we see here. So maybe some low dissensibility index in this patient with a metametric pattern made of possible EGGF obstruction. And then there's this time barium swallow as well. And you can see at five minute, there is a five centimeter column still remaining. And the barium tablet also retained above the GE junction. So you have really two supportive evidence in this case of EGGF obstruction. So at this point, given this, what treatment strategy would you choose from the panel? I was thinking about this question because I think my strategy has probably changed since 4.0. I think when it was Chicago 3.0 and we were finding just a lot of possible artifactual EGJ outflow, I went very conservative and then escalated. Now, I think with all this other supporting evidence and the kind of fine tuning the definition, there are no outcome studies yet, but possibly we're now capturing a kind of a real population of EGJ outflow patients. So probably, you know, I think I would still probably start with medications. My favorite very benign thing to try is peppermint that relaxes the esophageal body and LES. I would probably still try medications, but I would escalate quicker to something more endoscopic like Botox or dilation, or even Palm in some cases. Great, and let's talk about some of the treatment options that Daniela talked about. First of all, you want to aim to correct any anatomical abnormalities if there are. Smooth muscle relaxation, as Daniela mentioned, such as peppermint or even smooth muscle relaxant like calcium channel blockers or nitrates might be possible. Similar to echolasia, you know, things like Botox injection, dilation, myotomy are some of the options, obviously a little more invasive with dilation and myotomy, but, you know, with Chicago Fluor, as Daniela mentioned, we're more certain that these patients are actually having clinically significant outflow obstruction. These may come into play more often. Acid suppression, anti-reflux therapy may also be useful, especially a lot of times people may have reflux and they don't clear it really well because of the outflow obstruction. And in the past, especially with Chicago 3, conservative treatment or no therapy is always an option as well, as we see a lot of patients with spontaneous resolution. These outcome data are all really based on Chicago 3 criteria, but again, a lot of patients with spontaneous resolution, hopefully we'll see less of them with Chicago Fluor. And we still have very limited treatment response data overall with this condition. I think we're about to start case three, but is there any questions from the chat before we move on to the next case? You had one question about how to choose between pneumatic dilation and POM for highly symptomatic EGGL outflow obstruction, which I know we were just discussing that there's not a lot of data, but what sort of things might drive you towards one or the other? Basically approach these patients like type 2 achalasia where all the options are on the table. Again, I want to highlight the importance of assessing for opioid use in these patients because opioid associated soft-shell dysfunction includes EGGL, and so I think that's also important to keep in mind when we're evaluating these patients, but I basically treat these as type 2 achalasia patients if they're supporting data and symptoms are consistent. Yeah, and similar to when we talk about achalasia patients, if you think about POM, always think about the reflux risk. And so for patients with known high-grade esophagitis with Barrett, patients who are obese, those are some of the risk factors for reflux and post-procedural reflux. And with those patients, you probably want to avoid doing POM and airdrop towards other type of therapy, at least with our current technology. Now, things might be different in the future, as Danielle mentioned, if we start doing more TIF-type procedure associated with POM, but at least with just POM itself, you really have to think about the reflux risk after, and that should be one of the determining factors, in my opinion. Here's a question about heidel hernia that I think relates to that. Hernias that are two centimeters, maybe even three, usually don't represent absolute contraindications to POM. Obviously, when we do talk about things like TIF, then hernias become more of an issue. In those rare cases where there are heidel hernias that are larger than three centimeters, I think we really think twice about going for POM with those. Type of hernia, patients that have parasophageal hernias, sometimes those can cause a lot of symptoms, as well as manometric abnormalities, and those should be surgically repaired if that's the case. Yeah, and I think that's actually an important point. There's known anatomical or structural abnormality that's causing the alpha obstruction. That should be corrected before any sort of the other LES-related therapy, because a lot of times by doing that, you basically can fix the problem. Let's move on to the next case, and then we can come back to some of these questions. I think we probably have time to do one more case. So this case is a 40-year-old woman with a history of interstitial lung disease and Raynaud's who presents with heartburn, reflux, and intermittent dysphagia. She reports a longstanding history of heartburn and reflux symptoms all her life, treated with mostly once-daily PPI. However, in the past year, she noticed worsening symptoms that are now refractory to her PPI use. She also developed intermittent dysphagia, mostly to solids in the last six months, but denies any odonophagia, abdominal pain, and nausea. I think as we talked about in the last couple patients, one of the things given the dysphagia, dysphagia to solids, one of the things that we have to, first thing we would do is think about doing an endoscopy given the dysphagia symptoms, which is what we did. On endoscopy, these patients had high-grade esophagitis, L-grade D, had a Hill-grade 2 GE junction of retroflex view, and there was also a distal esophageal stricture that was dilated. And after the procedure, her swallowing symptoms got better after dilation. She was also placed on high-dose twice-daily PPI because of the esophagitis, and her reflux symptoms also decreased, but did not completely resolve. So at this point, what would you do? What is the next step of management in a patient like this? Refractory reflux symptoms, dysphagia, high-grade esophagitis, now treated with high-dose PPI, but still having some symptoms. What would you be thinking next? It'd be reasonable to do a manometry next. You don't need to do a pH test because this patient has severe reflux esophagitis on endoscopy, but a manometry might help guide further therapies in this patient, so I'd go to that next. Yeah, and what are you thinking at this point? Like maybe refractory reflux symptoms that you might think about more stepping up on therapy for the reflux, such as antireflux surgery, right? And I think Daniela mentioned earlier, it is really strongly recommended if you're considering antireflux surgery on any patients that you should do a preoperative manometry to identify any significant esophageal dysmotility that might affect your management strategy. So this patient had an esophageal manometry, and what do we think with this analysis? Daniela, do you want to walk us through this really quickly? Sure. So, I mean, obviously you can see there's a whole lot of nothing going on in the middle of the screen. So there's no contractility, absent contractility, assuming all the swallows are like this. And then the bottom bar, it's not kind of the continuous bar that we have been seeing with the achalasia tracings. It looks like there's a lot of periods where it is relaxed or maybe even hypotensive. The little kind of yellow pressure dots probably are somewhat just diaphragm contraction pressure and not necessarily LES pressure. So we see that there's absent contractions, but the normal IRP, right? So going back to the Chicago classification, now, the first step, abnormal median IRP, the answer will be no in this situation. So we go down to no pathway. And in different positions in this patient, the IRP remain in a normal range. And then the next thing we look at with a normal IRP will be to think about the esophageal peristaltic pattern. In this case, we see that the first thing is 100% failed peristalsis, which is what we saw, basically nothing. And this is exactly what the patient has among these peristaltic pattern. Now, as you can see in this hierarchy, you should basically go down the list for patients as if they have a normal IRP to kind of look at whether or not they satisfy the criteria for any of these diagnoses. And for this patient, because there's 100% failed peristalsis, this will be consistent with absent contractility given a normal IRP. So one question is, as we saw, both absent contractility and hyponechalasia basically have nothing going on in esophageal body, right? The only thing that distinguished them is what the IRP is measuring, with the hyponechalasia showing and with an increase in IRP versus absent contractility patients had a normal IRP. So sometimes it might be a little hard to distinguish, especially if the IRP number is a very borderline, especially since we were taking just a median number. So how do you distinguish them? Is it important to distinguish them? Do we need to take this particular population into special consideration? Amit, what do you think? Oh, absolutely. One of the weaknesses of the Chicago classification is IRP, particularly when there's no pressurization in the esophageal body like we'd see in type 1 achalasia. And so when we see absent contractility in esophageal body, it's important to be vigilant for type 1 achalasia that might have an IRP that's below the threshold. So for the Medtronic equivalent, potentially even as low as 10, we can still diagnose type 1 achalasia. And this is where things like provocative maneuvers and manometry, or even endoflip or barium can be helpful in making that distinction if there's any question, because the two are treated very differently. Yeah, and the way to think about it is that if you have no contraction, no pressurization, no movement at all in your esophageal body, you don't have anything to overcome even a lower esophageal sphincter pressure to try to move things through. So even if the number is technically under the normative cutoff, sometimes it might still be enough to create an obstructive physiology that is consistent with the type 1 achalasia. So- Walter, I did want to stress, so this patient had a stricture, but you dilated it prior to doing manometry, because that could look like a pseudoachalasia pattern on manometry. So it's really important to take care of any strictures or rings that may confound the picture before proceeding to manometry, like you did. Great, that's a great point, thank you. And the next, I just want to, Amit, how would you, what are some of the ways to help you distinguish between these two types? One of the advantages of Chicago 4.0 is that in the protocol, we can include things like multiple rapid swallows, particularly rapid drink challenge that can help differentiate absent contractility from type 1 echolasia. In lieu of that, we still have things like barium and endoflip at our disposal. And we talked about barium and endoflip already. What about some of these provocative maneuvers like rapid drink challenge and multiple rapid swallows? Can you tell us a little more about that? Sure, so briefly, rapid drink challenge is where when patients are sitting upright in a manometry study, we'll have them drink a larger volume of liquid, usually 200 cc's through a straw as quickly as they can. So in health, you would see kind of what's there on the right image where there's a nice deglutitive inhibition and then profound relaxation, the lower soft-shell sphincter. Yeah, and the focus here is really, for this particular patient, will be where the lower soft-shell sphincter is, right? The fact that when they're taking a lot of swallows, there is good relaxation in the LDS when they're taking these quick swallows. And how can you tell that they're taking quick swallows? You see the rapid relaxations of the upper soft-shell sphincter there at the top. Yeah, the rapid contraction relaxation up top at the upper soft-shell sphincter region. That tells you the patient's taking a lot of quick swallows. And this is... Yeah, so this is an example of an abnormal rapid drink challenge response. So on the right there, what you see is pan-soft-shell pressurization with each of those swallows. There's also a lack of relaxation of the lower soft-shell sphincter. So this is what you might expect in a patient with achalasia, or a disorder of the soft-shell inhibition. And so this can help uncover, this maneuver can help uncover latent EGGA outflow obstruction that we might not appreciate on the single swallows for this study. So it's particularly effective for this dilemma that we discussed about type 1 achalasia versus absolute contractility. And this is, I think, another image of what you expect between normal versus abnormal. So you can appreciate them better. Sort of a normal relaxation of LDS with the rapid swallows on the left-hand side. On the right-hand side, you can see that the IRP, the relaxation of the LDS is impaired with the rapid drink challenge in a patient that has achalasia. What about multiple rapid swallows? Sure, so this maneuver is while patients are supine, the idea is to have them take five sips, two to three milliliters of liquid less than two to three seconds apart. And so the primary utility of this is not only to see the deglutitive inhibition, but to assess the soft-shell contractile reserve. So if the DCI, or the vigor of the augmented contraction that happens after this maneuver is greater than that of the single swallows, we say that patients have contractile reserve. And the primary utility of that is when we're planning anti-reflex surgery for these patients. So the example on the left is the normal example where there's nice deglutitive inhibition, there's relaxation of the lower soft-shell sphincter, and then a nice augmented contraction after that. Middle example is an example where you have panoshoftial pressurization, a complete failure of deglutitive inhibition that you might see in a patient with a spastic or hypercontractile disorder. And the last example is one where there is deglutitive inhibition and relaxation of the LES, but there's no augmentation of the swallow afterwards. This might be a patient with absent contractility, for example, or a patient with profound and effective soft-shell motility who can't mount a esophageal response to that. So the reason it's important is when we're planning anti-reflex surgery, patients that do have nice augmentation with this MRS maneuver, they're less likely to have dysphagia after a fundoplication. And so patients, particularly with ineffective esophageal motility, their response to MRS can help surgeons guide whether they should do a complete or nissant fundoplication versus a partial fundoplication, like a toupee or door, particularly for those patients that might be at risk of developing dysphagia post-operatively. And then the LES response in this case, similar to the rapid drain challenge, may also help you determine whether or not they have true functional EGJ outflow obstruction. So in one study, if you have an IRP that's greater than 19 during the multiple rapid swallows, it's associated with a high percentage of patient with EGJ outflow obstruction. So that may be one way to help you determine or distinguish between these patients who may have akalasia versus absent contractility as well. This is a summary of these provocative measures that we talked about. Amit, do you want to give a quick summary of this? To summarize these four basic ones, we didn't talk about the one on the left, which is postprandial high-resolution penis manometry that we'll use when there's a high suspicion for behavioral disorders like supragastric belching or rumination syndrome. But the other three, we talked about upright swallows, incredibly important for making a diagnosis of EGJ outflow obstruction. The multiple rapid swallows, which are particularly useful to help tailor anti-reflux interventions, particularly in patients that have some hypomotility. And finally, the rapid drink challenge, particularly useful when there's suspicion for latent EGJ outflow obstruction in patients that we might not uncover it on a single swallow. So these latter three maneuvers are all now recommended as part of the manometric protocol by Chicago 4.0. So just very quickly about absent contractility. We often see this as part of a connective tissue disorder, including scleroderma. Often patients may have progressive atrophy and sclerosis of the esophageal smooth muscle that leads to frequently loss of LDS tone, but also decreased forces of peristalsis. This occurs in about up to 85% of patients with scleroderma. So it's very common in this population. And the pathogenesis is not completely clear. Autoimmune is thought to be a possible etiology. Also microvessel disease may also cause these fibrosis and atrophy of smooth muscles. Patients often present with reflux type symptoms and dysphagia. And the dysphagia actually mostly comes from complications in their reflux, like severe suffagitis, stricture, and they might even present with chest pain. Patients often have interstitial lung disease, either as part of the underlying cause of their absent contractility or as a result of chronic aspiration because of the dysmotility. And they may also have other systemic symptoms, autoimmune symptoms as well. And the management of absent contractility is a little bit limited and challenging. First of all, you want to do lifestyle and diagnostic modification, treat reflux as much as you can medically, high dose PPI, dilate any strictures that you see as in this case. One controversial part is that because these patients have so much reflux, which you do anti-reflux procedure on them, especially if they are failing their PPI. And this is a little bit controversial because the risk of postoperative dysphagia is really high. If you think about it, it's almost like you're almost creating a type one achalasia type physiology, especially with the full wrap. There have been some suggestions that maybe you can do a partial fundoplication with these patients. Although I think this is still relatively controversial and really surgeon dependent about whether or not they will do them. And I think you should really proceed very cautiously with these patients. So I think that with that, I don't think we have time for our next case, but let's go through the remaining questions that we have. And any other questions people might bring up? So there was a question about whether or not the presence of reflux esophagitis would make you lean more towards somebody having a diagnosis of absent contractility over type one achalasia. So possibly, although it is not uncommon to see high grade esophagitis in patients with type one achalasia as well, especially people who are later stage of the disease because they have so much stasis in their esophagus. And sometimes you even see patients who develop Barrett's esophagus because of that. If you think about it, not just food, but anything that reflux up will tend to stay in their esophagus for a long time, which increases the acid contact time with the esophageal mucosa, which then increases the risk of esophagitis and even complications. So it may, but I don't think that that is enough to point you one way or the other. And we have a question about whether you would re-scope before performing manometry in case three, I think after you've dilated, like would you re-scope before doing manometry or would you feel comfortable going straight to manometry? I think it's reasonable to re-scope given the degree of esophagitis that patient had and to make sure that the stricture has resolved before proceeding. And if it's a non-obstructive stricture, you don't have to worry. But in this case, I suspect it was a clinically significant peptic stricture. And so it's probably beneficial to repeat. Great. And then I think there... There were other questions like about achalasia and EGJ outflow obstruction, if you guys want to go back to that. Yeah, let's quickly go through some of these so that we can answer these questions. We'll do quick answers. So one of the questions in regard to achalasia was after you perform an intervention, do you routinely start a PPI? And if you do, then for how long? Like in anticipation for worsening reflux? Yeah, I think for POM in particular, that's important. Our protocol is typically to start patients on twice daily PPI and then try to wean them off. We do try to re-scope these patients and ideally get reflux monitoring to assess for esophagitis or non-erosive reflux disease, particularly in the setting of symptoms. Yeah, I think for POM, we definitely do more routinely. I think for the other types, like for example, surgical myotomy, who also get a dorsal endoplagiation, usually those I don't routinely start them on it, depending on... And those are more dependent on the symptoms. And similar thing with pneumatic dilation as well. One question here is could severe GERD be manifested as IEM or absent contractility? Definitely, there have been a lot of... The relationship between GERD and hypocontractile esophageal disorder is very complex because we know that reflux and severe reflux can lead to some of these weaker contractions in hypomotility disorders, including IEM. And maybe even if they're very severe, they might even look almost like absent contractility. But on the other hand, having these hypomotility disorder also predispose you to more severe GERD. So it's almost like a cycle, a very bad, vicious cycle, and they kind of feed on each other. So I think that has clinical implication because if you have someone with severe hypomotility or significant IEM, who also have significant reflux, and you're thinking about antireflux surgery, how much do you think that hypomotility would improve with treating the reflux? And I think that goes back to what Amit was talking about with the esophageal reserve with doing the multiple rapid swallows. If you have a good reserve, then the data suggests that the chances of you having a good outcome and improved motility afterwards will be better than if you have a poor reserve. And so that might be one marker that's useful, and that's why these provocative measures are important. Thank you. So there's some general questions in terms of esophageal motility. So one is about endoflip. Is there any role for endoflip for workup of motility disorders other than achalasia and EGJ-alpha obstruction? And then when you do an endoscopy, is hill grading important, and how does that affect your management of specifically EGJ-alpha obstruction and achalasia? So for the first one, for endoflip, obviously the most data that we have for it is in EGJ-O and achalasia, both pre and post-operatively. It's been looked at in EOE, where findings can be predictive of food bolus impactions, for example, as well as GERD, but the data for the latter two are limited. There's some interest in using it intraoperatively, helping to tailor fund application, for example, but what our current data suggests is that the greatest utility for it is in EGJ-O and achalasia. There's also potentially a role for using it as a one-stop shop when you're first doing your scope for dysphagia, which, unfortunately, I never have that luxury because the tertiary care center, they've always been scoped already, but if you're getting there first, you can do your EGD because that's the workup for dysphagia, then do the endoflip. I don't think it's gonna tell you whether there's a minor motility disorder, but if the endoflip is stone-cold normal, it's unlikely they're gonna have achalasia, and the data does support that. That's a really good point. Yeah, so a good negative test, if it's completely normal, or it may be useful for the disorders like achalasia, but for the things in the middle, currently, the data, it's not as consistent yet. For the hill grade question, I think it's important to identify hill grading. I think there's been a recent paper that came out that basically saying that a lot of endoscopists are not really as well-trained in identifying the anatomic structures, these grading of the GE junction. The hill grade basically tells you the risk of a patient having a hiatal hernia, or some sort of hernia, and this is particularly important in patients with EGGL-flow obstruction, because if you have a patient with a high hill grade, hill grade three or four, and they have EGGL-flow obstruction, you really have to think about whether or not there could be some sort of hernia that could be causing some sort of structural obstruction leading to the EGGL-flow obstruction because of the hernia. I think the role of that for achalasia would be a little less. I think it's actually not common to see a hiatal hernia in patients with achalasia, with true full-blown achalasia. And in that sense, I don't think for that population it's as useful, but we routinely, and I encourage everyone to routinely document the hill grade when you do an upper endoscopy. There's another question here about how to do postprandial manometry. I think we mentioned that briefly, but maybe- Yeah, sure. Yeah, just a brief intro to that. There's a great paper by Reni Yadlapati in the Blue Journal in 2018 that kind of gives examples of what supragastric belching and rumination episodes can look like in addition to transient lower soft muscle sphincter relaxations. But briefly, the idea is a patient comes in, ManoLab brings a meal that reproduces their symptoms. They have a fasting standard protocol manometry study, eat their meal and then are monitored for 60 to 90 minutes or until we get enough of these episodes. And that allows us to kind of look for evidence for this. And at least that data showed in patients where there is clinical suspicion for these behavioral disorders like supragastric belching and rumination, that we do pick these up quite a lot. And the reason it's so important is these patients, these are mimickers of GERD, right? And even supragastric belching, these patients will respond best to behavioral interventions not escalation of the antireflux management. So I think it's incredibly important in that subset of patients. So our next question. There are some questions about like, how do you completely exclude a structure in somebody prior to getting motility testing? Like, would you ever recommend doing empiric dilation with a savory and somebody with a normal appearing esophagus prior to proceeding to motility testing? The ones that are clinically significant on manometry are the ones that you're going to see on endoscopy. So you don't have to worry about doing empiric dilation. If you don't see it on endoscopy, you can proceed with manometry without concern. I think along the same lines, there was a question about what about a proximal stricture? Again, if it's non-obstructive, you don't have to worry. And we're more concerned about distal esophageal strictures that we want to exclude prior to manometry. And the next question, I actually can see one question here asking if for a patient with absent contractility, if all measures failed in treating the patient, what other treatment options can we do? This is, I think, a tricky question. I don't think there are very good answers to. Remember, a lot of these symptoms actually come from reflux. So the question really goes back to how do you treat reflux in these patients with absent contractility? We talk about the risks of surgery. There are still surgeons out there that do them, various form of partial fundoplication. I think that's still really risky to do. There are some other medical therapy you can consider for GERD that are beyond PPI, the data with some mixed data. Baclofen is one medication that's been used, that's been shown to decrease TLESR or transient LES relaxation and increases LES pressure, which can help reduce reflux. Another type of things you can consider is actually alginate, especially for people with postprandial reflux that have been shown to actually provide some barrier protection. Basically, this alginate you ingest after eating sits on top of the acid pocket and kind of keep things from coming up. So those are some of the medical therapy that you can consider in these patients and see if they help them. Yeah, to Walter's point, at least in the scleroderma patients, many times their dysphagia is really not from the aparistalsis. There must be some sensory neuropathy from the scleroderma as well. It's like shocking. You have no contractility and they have no dysphagia. So you definitely want to look for the reflux complications to explain that before you just chalk it up to the motility side of things. Another question I see here is that is endoflip alone with typical features of achalasia a confirmatory, would you test for achalasia? Basically, would you treat achalasia if you have endoflip findings are typical and not skip the manometry part? I think we still need a little bit more data before we do that. So it is probably best to proceed with manometry, which remains the gold standard for diagnosing achalasia. But I suspect in the next five years, as we get more data, that is the hope that you wouldn't have to put a patient through kind of a more invasive manometry and could find it at time of index endoscopy. The main problem right now is, especially when we do endoflip, and I think others can chime in regarding the experience, is that the contraction of topography portion don't correlate with manometric finding as well as the sensibility index. So frequently, we have patients where we see no contractions at different volumes during endoflip. When we do a manometry, they have normal peristaltic contractions. That's one of the reasons why, even if you have low DI and no contractions on the endoflip, it's still, you can't really reliably think that that will give you a diagnosis of achalasia, because they very well could have normal contractions when you do a manometry. So I would say, even if you see that, you should definitely still do a manometry. That should still be the gold standard. We have done achalasia treatment when patients absolutely refuse to do the manometry. I mean, sometimes you can also bargain with placing it sedated, but they still have to be awake for the manometry part. But you would definitely want to make sure there's a second modality, like a barium test, to make sure you're really treating the right thing. Great. So one more question. There are multiple about achalasia. So I guess one question is, do you routinely obtain a barium sofagrin for everybody that has suspected achalasia? And then more questions about pneumatic dilation is, do you always start with 30? Can you ever start with 35 or 40 millimeters? And then how many times can you perform a pneumatic dilation before you have to consider an alternative therapy? So I can answer that, and other people can chime in. So basically, the barium swallow is useful as a supportive evidence. I would say that if you have a normal EGD and you have a high suspicion of achalasia, I routinely just proceed to doing a manometry. However, before treatment, I often get a time barium swallow before we undergo treatment to get a baseline idea of their level of emptying, because then you can use that to follow patients up after their treatment to see how much improvement they got. Regarding the pneumatic dilation, as we mentioned earlier, I always start with 30 because from the prospective trial showing that if you start at 30 and sequentially go up, the perforation risk is definitely lower. And so I always start with 30. And how many dilation you do really depends on what sizes you go up to. So if you go up to 35 or 40 and the patient's still symptomatic, most likely that is not adequate in helping the patients. Now, the difference is if a patient got treatment, they feel great. Three years later, they come back and they're like, oh, I have dysplasia again. I would not hesitate to basically restart the dilation sequence. So I don't think there's like a lifetime limit of how many dilations you can get, but more in terms of what sizes you go up to, what your response, how your symptoms respond. You know, anyone with other pointers in these? I do pneumatic dilations much less now that we have a lot of POEM experience. I will say maybe I'm a little risk averse. I never done a 40 dilation because if 30 and 35 hasn't worked, I'm moving on. Well, thank you very much for our panels and our fellow moderators for this great interactive sessions. And thank you so much for everyone's questions. They're very great questions. I think really speaks to a lot of the current limitations and controversy with diagnosing these patients. So, and I want to thank the ASGE for this opportunity for this session. Thank you again to all the panelists and moderators for tonight's presentation. Before we close out, make sure to check out our upcoming ASGE educational events. Registration is now open. The next Endo Hangout session will take place on Thursday, March 3rd at 7 p.m. Central time. Discussion on feeding tubes, registration and more details will be coming up next week. At the conclusion of this webinar, you will receive a short survey and we would appreciate your feedback. Your experience with these learning events is important to ASGE and we want to make sure we are offering interactive session that fit your educational needs. As a final reminder, ASG membership for fellows is only $25 per year. If you haven't joined yet, please contact our membership team or go to our website and make sure to sign up. In closing, thank you again to all our panelists and moderators for this excellent presentation. And thank you to our audience for making this session as interactive. We hope this information has been useful to you. And with that, I will conclude our presentation. Have a good night. Thank you everyone.

Esophageal Motility

ASG Endo Hangouts

GI Fellows

Achalasia

Esophagogastric Junction Outflow Obstruction

GERD

Diagnostic Tests

Treatment Options

Endoscopy

Manometry

Imaging Studies

Medications

Endoscopic Interventions

Surgical Procedures