Hello, thank you for joining us for the ASGE Peroral Endoscopic Myotomy, Pearls to Practice. My name is Vani Konda. It is my pleasure to provide a pre-course presentation on the Patient Selection and Chicago Classification 4.0 for the POEM Oscopist. Here are my relevant disclosures. My objectives are to understand how the overall assessment provides context needed to make a diagnosis for esophageal motility disorders, review updates to Chicago Classification 4.0, and implications on what you should do to ensure proper interpretation of motility studies coming to your practice, highlight specific disorders relevant to the management options of intervention at the LES such as POEM. Monitor the spectrum of diagnostic certainty for proper patient selection for intervention and appreciate tailored decision-making approaches based on function, severity, and extent of dysfunction. As we know, achalasia is the major motor disorder of the esophagus. We characterize this disorder with aparistalsis and failure of relaxation of the lower esophageal sphincter. We recognize there is often a delay in the diagnosis of patients with achalasia. This is commonly because regurgitation is often mistaken as gastroesophageal reflux disease. When considering a diagnosis of achalasia, it is important to consider GERD, eosinophilic esophagitis, and malignancy, which can mimic achalasia either by direct compression at the gastroesophageal junction or through a paraneoplastic syndrome. Confounding states manometrically include post-surgical states, complex hernias, and distal esophageal strictures, underscoring the need for an endoscopic examination to establish non-obstructive dysphagia and the importance of taking the manometric evidence in the overall clinical context. In order to obtain the clinical context required for a proper diagnosis of an esophageal motility disorder, multiple modalities may be involved. A good history is fundamental in the evaluation of esophageal motility. A physical with some key elements we will touch on, an endoscopy, which is critical to rule out common causes of dysphagia, high-resolution manometry, which in non-obstructive dysphagia provides the gold standard for diagnosis of esophageal motility disorders with the Chicago classification version 4.0, barium studies such as barium esophagram with or without tablet and specific protocols such as time barium esophagram, and the newest modality functional luminal imaging probe or FLIP. A detailed history for dysphagia includes what kinds of boluses get stuck, solids, liquids, and or pills, characterization of the onset of the symptoms, if the course is progressive or intermittent. When the bolus gets stuck, where does it get stuck? Also knowing that when patients point to the suprasternal notch, it may or may be reflective of actually a bolus getting stuck more distal with the referred sensation. Also determining what happens after a bolus gets stuck. Do patients stop eating? Do they get up, walk around? They have a certain maneuver like taking their shoulders and pushing it back in order to help release the bolus. And determining what associated symptoms may exist, reflux, regurgitation, coughing, choking, or nocturnal drooling. Now I always feel like asking about dysphagia, which is not included in the layperson's language, and even asking about swallowing can be challenging because different people have concepts of swallowing that may vary from focused on pharyngeal swallowing to including both pharyngeal and esophageal phases of swallowing. And so we don't really have a good common language, even with our patients, to discuss swallowing disorders and dysphagia. I always tell my fellows, you can't ask about dysphagia unless you've asked about it five different ways. So first I ask, do you have trouble swallowing? But again, some people don't think about swallowing beyond the actual gulp or pharyngeal component. So I also want to ask if foods or liquids get stuck. And sometimes some patients don't think that it gets stuck, but they do still have trouble because it's slow to go down. So I always ask about if food is slow to go down. And I also ask if food feels like it stacks in the chest. And some patients don't recognize that it's having trouble getting down to the stomach and think their symptoms are simply vomiting. So I also ask if patients are vomiting, specifically undigested food or spew for that fifth S. In terms of physical examination, key elements for dysphagia histories include weight and trajectory of the weight, BMI, hydration status, signs of malignancy, including cervical lymphadenopathy and looking specifically for signs of connective tissue disorders. Looking at skin, joint, and hand changes. I always take a careful look at my patient's hands, looking for any signs of sclerodactyly that may be present in disorders like Crest syndrome or systemic sclerosis. And looking for signs of a neurologic disorder. Endoscopy should be done to evaluate for any hiatal hernias or complex hernias. Rule out masses, mucosal strictures, rings, signs of reflux esophagitis or complications of reflux disease, and biopsies to rule out eosinophilic esophagitis. We can also characterize the behavior of the lower esophageal sphincter. Having said that, it is all too common that people actually have their scope at the gastroesophageal junction when they're commenting on the lower esophageal sphincter. As we can see in the top row, we can see a diagram with the picture of the scope essentially at the top of the stomach. Here we can actually imagine the scope is pushing open the lower esophageal sphincter itself and showing what we would consider a patent or open lumen. However, if we bring the scope back proximal to the gastroesophageal junction, in our institution we try and park that scope about three centimeters above as we assess the lower esophageal sphincter to make sure we're sufficiently proximal to the proximal aspect. We can see on the left endoscopic view a picture of a patient without a motor disorder of the esophagus, and on the right we can see a closed LES in a patient with achalasia, whereas that was not apparent in the corresponding pictures above. In terms of watching the LES, it's important to be patient. Sometimes, especially in spastic disorders of the esophagus, things may be dynamic and evolve over time. In this example, we can see endoscopic photographs taken over the course of a minute in a patient with spastic achalasia, initially showing an unremarkable lower esophageal sphincter and then a tightening of the lower esophageal sphincter in the middle picture, and then essentially such tightening that it causes blanching of the lining as well as appreciation of a proximal lift of the lower esophageal sphincter up into the tubular esophagus as shown in the picture on the right. At our institution, we have tried to standardize our endoscopic assessment of motility findings, specifically those that might indicate delayed esophageal clearance and achalasia. And we look at these four following components, retained contents, including retained secretions which could just be little bubbles indicating frothy retained saliva, and secretions that remain in the esophagus and haven't been cleared, retained liquids, and then obviously retained solids, esophageal dilation with no dilation, mild dilation, moderate or severe, lower esophageal sphincter appearance with a patchless LES, one that opens and closes, one that minimally opens, and one that has a tight appearance, and resistance upon passage of the scope through the LES and esophagogastric junction complex with no resistance, some that is mild, moderate, or severe. High resolution manometry is indicated in non-obstructive dysphagia to evaluate for esophageal dysmotility and is the gold standard to diagnose achalasia. It allows for assessment of the lower esophageal sphincter with the Integrated Relaxation Pressure or IRP. It can diagnose achalasia and characterize EDG outflow obstruction as well as characterize primary peristalsis and disorders of peristalsis. It's gone through several iterations with the most recent being 4.0 and key updates to this include protocol changes that include both supine and upright positions as well as provocative testing, redefined EDG outflow obstruction, made ineffective esophageal motility more stringent, and explored conclusive versus inconclusive diagnoses. You want to ensure that you are using an updated and quality protocol for your studies. If you're unable to read motility studies yourself, make sure you have communication with someone who does. The PDF and computer-generated information, typically consistent and obvious in classic cases, does reflect older classification and caution should be applied when completely relying on these as a sole method to evaluate cases, especially in borderline or inconclusive cases. The protocol updates for Chicago Classification 4.0 include position changes, provocative maneuvers, and supportive testing. After a period of adaptation of a minute, it's important to take three deep breaths followed by a baseline period of 30 seconds. And then in the supine position, 10 wet swallows are performed followed by one multiple rapid swallow sequence in the supine position. And this is to establish if there is additional reserve for vigor. Then the patients are moved to an upright position. And again, the adaptation period with the three deep breaths as well as the 30-second baseline period is re-established followed by five wet swallows in the upright position and then followed by a rapid drink challenge in the upright position for additional supportive information in cases of outflow obstruction in looking at the IRP as well as the presence of panesophageal pressurization during that sequence. If no major motor disorder is found but is suspected, consideration may be made for additional maneuvers such as solid test swallows and pharmacologic provocation. And if there's equivocal or inconclusive results, supportive tests may include time-barium esophagram with tablet or FLIP. This diagram demonstrates the algorithmic approach for Chicago Classification 4.0, and we're going to focus on specifically those disorders that are geared towards that POEM intervention. We're going to start with disorders of EGJ outflow obstruction, and these have an elevated IRP. It's important to recognize that the threshold is different per software system, and it's important to know what your software system's threshold is. For example, the Medtronic threshold is a median IRP of 15. Looking at type 1 achalasia, we can see an elevated IRP. This is where we see a failure of the lower esophageal sphincter to relax after the wet swallow has initiated, and there's 100% failed peristalsis as characterized as a mean DCI of less than 100 as an indicator of vigor. In type 2 achalasia, we see 100% failed peristalsis in the setting of an elevated IRP again, and we also see 20% or greater of swallows with panesophageal pressurization. This should be determined at the 30-millimeter isobaric contour. Type 3 achalasia can have an elevated IRP with no peristalsis, meaning only failed or premature contractions, and 20% or greater should have premature contractions as characterized by a distal latency of less than 4.5 seconds. There can be a mix of panesophageal pressurization, failed swallows, as well as premature contractions. A reminder of distal latency. It's important that it's measured from the start of the UES contraction to the CDP or contractile deceleration point, and that CDP point is within 3 centimeters, the proximal aspect of the EGJ high-pressure zone. This value is really subject to artifact and incorrectly placed markers, and both the UES markers and the CDP markers really need to be placed correctly in order to have the correct DL, and sometimes it's difficult to see if they are placed correctly on the PDF. So just want to call attention specifically when looking at premature contractions to make sure your distal latency values are correct. These subtypes of achalasia can be associated with prognosis and response to specific treatment. For example, type 1 is typically the end stage of disease and manifested with a dilated esophagus, and accordingly only has a fair response to treatment. Type 2, on the other hand, is touted as the subtype with the best treatment response and can benefit from any of the major treatment strategies. While type 3 is associated with the worst prognosis, an identification of spastic achalasia does warrant consideration for a POEM approach which can allow for a longer myotomy. It is important to understand that though these classifications fall into three very specific boxes with specific criteria, it is possible to have symptomatic cases of achalasia-like dysfunction that fall outside of these boxes. An inconclusive diagnosis of type 1 or 2 achalasia includes absent contractility with no peristalsis in the setting of IRP values that may not reach above the upper limit of normal in both positions, with or without panesophageal pressurization. Sometimes with changing position in the setting of a type 1 or type 2 pattern that's found in the primary position may demonstrate some appreciable peristalsis in the secondary position, thus can shift the diagnosis towards an inconclusive diagnosis and may require additional supportive testing. In these situations, we may consider a time-variant esophagram, ideally with a tablet, flip study, and also in these situations I do consider testing for connective tissue disease, specifically scleroderma. In cases where we have an elevated IRP but criteria for types 1 through 3 achalasia are not met, we may have EGJ outflow obstruction which is a heterogeneous condition. EGJ outflow obstruction has an elevated IRP, some peristalsis is present, and as mentioned, criterias for type 1 through 3 achalasia are not met. This is inconclusive by HRM alone. EGJ outflow obstruction may be an early or incompletely expressed achalasia or variant form of achalasia, may have variable forms of presentation, variable progression, and variable impact on nutrition and quality of life. In looking at EGJ outflow obstruction by high-resolution manometry, we want to ensure the study is done off of opioid medicines. In addition to looking at the supine IRP, we want two additional criteria, including an elevated IRP in the upright position, and again these are specific to the software system with the Medtronic system being the upper limit of normal being 12, and also look at the intrabolus pressurization, and here we can see that vertical line showing the distal esophageal pressurization pattern as shown by the red arrows, and we can also see that at the 20 millimeter per mercury isobaric contour. EGJ outflow obstruction, even with all these criteria met, is still inconclusive by HRM alone and requires supportive testing. We can also characterize the pattern of peristalsis and comment on whether it's EGJ outflow obstruction with spastic features or premature features, such as those seen in type 3 achalasia but not meeting type 3 achalasia, those with hypercontractile features, those with ineffective esophageal motility, and those with no evidence of disordered peristalsis. It's important to remember that not all EGJ outflow obstructions are achalasia variants. Certainly we can have intraluminal disease with distal esophageal obstruction, such as stricture or mass. We can have disease within the wall that might include failure of lower esophageal sphincter relaxation, but also can include infiltrative or inflammatory diseases. We can have pathology at the hiatal complex, including a large or complex hernia or simply a prominent choral diaphragm. We can have pathology outside the esophagus, including extrinsic compression from it or an artifact from an adjacent structure. And we can have other issues such as post-surgical anatomy, paraneoplastic syndromes, or medication effects. We should call our attention to the importance of opioid-induced esophageal dysfunction. This appears to dampen the inhibitory signals of esophageal motility, and we can see EGJ outflow obstruction and spastic peristalsis more commonly when there's active opioid use within 24 hours of a high-resolution manometry study. We can induce findings of type 3 achalasia, and patients with opioid-induced esophageal dysfunction often present more with chest pain than specifically esophageal dilation or dysphagia. It can be present in almost a quarter of patients with chronic opioid use, and it's more common in patients taking hydrocodone or oxycodone than with tramadol, and there is a dose-dependent effect. Ideally, we should be performing high-resolution studies off of narcotic medications. Supportive testing includes time-barium swallow as well as FLIP. It's important to explain to patients that inclusive testing does require additional testing, and sometimes in cases where it's unclear if the body dysfunction is reactive to the lower esophageal dysfunction, we may benefit from some sort of trial at the lower esophageal sphincter to better understand the extent of dysfunction and to help guide the length of intervention. These cases may sometimes benefit from a stepwise approach to treatment or additional monitoring just to make sure we're heading in the right direction. Barium esophagram often can pick up the later stages of achalasia, and there is unfortunately variability in how barium studies are conducted and what dynamic information is captured and interpreted. In cases with end-stage achalasia, we could see that obvious signs of dilated and tortuous esophagus with a sump effect and a classic bird's beak as seen in this picture here, but in some patients with early stages of disease may have more subtle findings and can have a reported normal esophagram as shown in this patient who actually had type 2 achalasia on the right. Ideally, we perform these studies with a barium tablet which allows for assessment for a functional or anatomic obstruction at the EGJ. Timed barium protocols allow for a set volume somewhere on the order of 200 milliliters of barium to be adjusted in the upright position, and fluoroscopy is captured at one and possibly a check at two or three minutes and then at five minutes, with column height reported at one in five minutes. Greater than five centimeters at five minutes is a reported cutoff for achalasia. Note that the subtypes do vary with types 1 and 2 more likely to have stasis than types 3 and EGJ outflow obstruction. The functional lumen imaging probe penometry, or FLIP, allows for transoral insertion during a sedated endoscopic procedure, and there are 16 pressure sensors housed in a balloon catheter that allow for both assessment of the gastroesophageal junction as well as pressure topography in the esophageal body. The balloon can be inflated at incremental volumes and assess the esophagus in various states of distension, simulating a solid food bolus. Parameters such as diameter and distensibility may be obtained with distensibility being based on cross-sectional area and pressure. Secondary peristalsis can be characterized by the pressure topography as shown here, with repetitive antegrade contractions being considered as normal as shown in this example. We can see this classification schema for FLIP looking at the probability of EGJ outflow obstruction versus peristalsis and contractile response. On the x-axis, we see a normal EGJ outflow opening moving towards a borderline EGJ opening to a borderline reduced EGJ opening to reduced EGJ opening. On the y-axis, we can see we can move from absent to impaired disordered to borderline to normal contractile response. And then off to the side, we see spastic reactive, which is its own beast in and of itself, and probably requires some additional investigation and understanding, but falls outside within this x and y paradigm. We can see here how the FLIP classification compares to HRM diagnosis. With many of each of these boxes demonstrating patterns that make sense in that specific area of the spectrum of EGJ outflow obstruction and peristalsis, but also recognizing there is some heterogeneity and overlap. Thus, FLIP complements HRM, but is not necessarily identical to HRM. A quick word about hypercontractile esophagus. We can see a hypercontractile swallow which has a high contractile vigor with a DCI greater than 8,000. And in these cases, we can sometimes see that patients don't have a dilated esophagus and may not have much of a remarkable endoscopic examination. They have a variable presentation with a range of symptoms from being near asymptomatic to sometimes being very symptomatic and unable to tolerate PO. There are both medical options, and in some cases, some of these patients also may require interventions such as a POEM. It's important to recognize patient factors, anatomy, and disease factors such as age, comorbidity, the presence of a hiatal hernia, or other factors that may predispose to reflux such as BMI and obesity, and any prior surgery or other intervention that may need to be taken into account. Ultimately, looking at esophageal motility is putting all these pieces of the puzzle together in terms of the history and making sure you understand their medication use, endoscopy, associated histology, FLIP, manometry, esophagram with the time barium protocol or barium tablet, and even consideration of response to previous treatments. It's important to consider the spectrum of diagnostic certainty when making a decision, especially prior to performing a procedure that's irreversible and essentially renders the esophagus non-functioning. What we want to do is understand that there's a difference when we have suspicion where the findings aren't consistent, and maybe we actually suspect a disorder but we have no major motor disorder found on our manometry study, and then we need additional context and we might want to consider additional testing. We also might find findings that are borderline suggestive, but they don't meet criteria. Again, same thing. If there's suspicion, we might require additional supportive testing and really look and explore that additional context. In inconclusive cases, some aspects of the workup may not match up, and again, exploring all of those pieces of the puzzle is important and putting it together in a thoughtful manner to go the right direction. And then, you know, it's nice when we have conclusive testing when all the diagnostic criteria are met and symptoms and dysfunction and context all fit, and then we can move more confidently towards those next steps, especially of definitive treatments. Supportive testing is usually in the context of high-resolution manometry, those time-varying esophograms with a tablet, flip, solid phase maneuvers, or pharmacologic maneuvers with high-resolution manometry, but we also have a whole host of other options. For example, we can do imaging, CT scan, or EUS, especially in EDJ outflow obstruction cases. In cases where we might consider inflammatory conditions like eosinophilic esophagitis, consider biopsies off of PPIs if previous biopsies were made on PPIs. Things that we also may consider include solid phase barium esophagram with a bagel and marshmallow component. Explore other diagnoses. We mentioned earlier how to consider scleroderma in hypomodal disorders. Always take advantage of multidisciplinary discussions and exploring a consensus diagnosis and considering next steps for either diagnostic or therapeutic trials. Therapeutic trials might include TTS balloon dilation, medication trials, or even consider Botox trials or isoflip trials, which we can sometimes do in cases of EGJ outflow obstruction, especially when there's some preservation of peristalsis. All of these things are tools that you can use to help understand what is going on for that patient and what next steps or what next definitive therapies might be needed. I always tell my patients small steps in the right direction are better than big steps in the wrong direction. Interventions for achalasia, EGJ outflow obstruction, and spastic disorders of the esophagus may sometimes include medications, Botox injection, pneumatic dilation, or isoflip when the intervention is guided at the lower esophageal sphincter and GE junction complex alone, laparoscopic heller myotomy with or without the partial fundoplication, again guided at the lower esophageal sphincter specifically, and paraoral endoscopic myotomy, which enables both the lower esophageal sphincter as well as body intervention. Another way of thinking about the intervention for esophageal motility disorders is to appreciate that we cannot restore function and we can't make anything normal. What we really can do in this situation is render a hypercontractile dysfunctional element to be non-functioning. We can determine what type and the extent of an intervention based on the dimensions of dysfunction and location and that helps us determine whether or not we are looking at just the lower esophageal sphincter or perhaps maybe a long myotomy extending beyond the lower esophageal sphincter into the body. And we're influenced if and when to intervene based on the severity of symptoms, safe oral nutrition, impact on quality of life, and potential for organ damage. And so it's important to remember that various cases of esophageal dysmotility may be in various aspects of this dimensional box that I've created based on function, location, and severity, and ultimately not one size fits all cases of esophageal dysmotility. In conclusion, symptoms, dysfunction, testing for multiple modalities, and certainty of diagnosis provide the context needed to make a diagnosis for esophageal motility disorders and approach for a plan. Ensure protocols for your motility studies have been updated to the Chicago Classification 4.0 and include upright swallows. EDG outflow obstruction is an inconclusive diagnosis by HRM alone and requires supportive testing. And consider the spectrum of diagnostic certainty, extent of dysfunction, and severity for proper patient selection for intervention and appreciate tailored decision-making approaches. Thank you.

esophageal motility disorders

Chicago Classification 4.0

achalasia

diagnosis

treatment options

endoscopic examination

manometric evidence