podium here by my colleagues, Dr. Olaya Brewer-Gutierrez and Dr. Barham Abudaye. We have the next session, which is focused on esophageal motility, and we will begin this session with a talk on the basics of high-resolution manometry and the Chicago classification by Dr. Prakash Giawale, who is professor of medicine at the Washington University School of Medicine. Welcome, Prakash. Thank you, Prasad. Thank you to the organizers, and I think I should say thank you to American Airlines because they finally got me here in time. It looked like it wasn't going to happen for a few minutes this morning. But thank you again for inviting me to speak on a topic that's near and dear to my heart. My connection with esophageal manometry is through my mentor, Ray Klaus, who was the pioneer of high-resolution manometry. And I happened to be at the right place at the right time in the early, mid-1990s. These are my disclosures. So what Ray thought about was what was hiding between those widely separated sensors or pressure recording sites on a conventional manometry catheter. So he introduced this concept where recording sites were one centimeter apart on a recording catheter. Obviously, the first, earliest catheters were water-perfused. And you got a jumble of tracings, pressure tracings, that look kind of like this. Now, modern high-resolution manometry software fills in the space between these recording sites and assigns colors to the amplitudes so that you can look at this as if you were looking at a weather map. This is the pressure trace or a contour trace of a water swallow in the supine position. And it is now known as a Klaus plot in Ray's honor. So this is anchored. This Klaus plot is anchored by two bands of pressure. As you can see, the brighter colors, the green and the oranges and the reds, are higher amplitudes. And the blue colors are lower, lower color amplitudes. So you can see both sphincters in the same window. And so you can have a real-time visualization, at least the operator can, as the procedure is being performed. And you can absolutely make sure that the catheter has traversed both sphincters, especially the lower sphincter. You see a pattern that looks like this, a butterfly pattern. This usually indicates to the operator that the catheter has not made it through and you need to reposition this. This is actually a three-dimensional intuitive depiction of motor function with esophageal length along the y-axis, time along the x-axis. And you have the z-axis from color, because the color actually gives you the vigor or the amplitude of contraction. It also allows you to recognize motor patterns. When Ray would teach manometry, he would have people look at these swallows as if you were looking at a chest X-ray, and then go back to the numbers and confirm what you were seeing in these colors. But we do have software tools to assess motor function. The one that is used initially in an hierarchical system is the integrated relaxation pressure. And this is the nadir pressure, the lowest pressure that is achieved during swallow-induced relaxation of the esophagal-gastric junction of the lower esophageal sphincter. It can be either continuous seconds or discontinuous seconds, a total of four seconds during a window of 10. So that is the IRP. You can look at timing of peristalsis using distal latency, or DL. That is the time from the initiation of the swallow, so relaxation of the upper sphincter, to the time when the esophageal peristalsis transitions from a fast esophageal body phase to a slower emptying phase. And that point is known as the contractile deceleration point. In simple terms, this tells you if the peristaltic sequence is moving from top to down. If it isn't, if the entire esophagus is squeezing or contracting at once, that would be a premature swallow and not be peristaltic. The third metric is the distal contractile integral, which measures vigor of peristalsis. Now, the location of the sphincter can be quickly identified for placement. And if you have impedance incorporated into the high-resolution catheter, you can see the bolus. In this instance, you see it as a purple image just in front of the contraction sequence. So high-resolution manometry improved the diagnostic yield for identification of achalasia. And achalasia is one of these motor outflow obstruction syndromes, which is an important condition to identify from performing manometry. One of the main reasons for doing manometry is to identify or exclude the presence of these obstructive motor disorders. Now, there is better interrater agreement, and learners favor high-resolution manometry. So high-resolution manometry is recommended for the evaluation of obstructive esophageal symptoms without a mechanical cause over conventional manometry. And these are some of the indications for when a high-resolution manometry can be useful. So transit symptoms not otherwise explained or a suspected motor disorder are among the most important ones. Now, how do we analyze? We analyze using an hierarchical system known as the Chicago classification, which actually started out in a bar in Paris. And one of the protagonists of that initial Chicago classification is John Panolfino. He can tell you stories about people sitting at a bar and coming up with Chicago 1.0. Of course, we are at 4.0. We have a democratic process that assigns these different diagnoses and criteria now. We start out with the IRP. And if the IRP is abnormal, median IRP, and the swallows all fail or are premature, you have the three achalasia subtypes. And these are the classic images of the three subtypes. There is no visible contraction in subtype one and two. The difference between the two is that there is compartmentalization of pressure in subtype two. Subtype three has some contraction, but premature. And that's because of an inhibitory defect, the same inhibitory defect that results in abnormal relaxation of the lower esophageal sphincter. Now, even if the supine IRP were abnormal, we look at other markers to identify if there is an obstructive pattern. And one of those is a provocative test, like the rapid drink challenge, where you challenge the esophagus with a volume of water, with 200 ml of water in the upright position. And we will see later that a normal esophagus can handle that. An obstructed esophagus, maybe not. We also look at the IRP in different positions, in the upright position. So the idea, again, is to identify motor obstruction. Why? We know how to treat motor obstruction. We don't treat many of the other motor disorders. They are distractions. But obstruction, motor obstruction, we know how to treat. Sometimes, you have suggestion of motor obstruction by IRP, but intact esophageal body peristalsis. That is a clinical conundrum known as EGJ outflow obstruction. It is a cause for a lot of distress in a lot of people who interpret and review manometry. The problem with EGJ outflow obstruction is that both mechanical and non-mechanical etiologies can contribute. Obviously, you could identify a mechanical etiology using other tests, such as endoscopy and varium. But among the idiopathic causes, there is no differentiation from symptoms between true achalasia-like patterns and other unclear etiologies. And you can see that it's just a small proportion that has a true achalasia-like pathophysiology. And indeed, those patients with true motor EGJ outflow obstruction respond to treatments similar to that offered for achalasia. What about the rest? Many of those patients have unclear etiologies. Some have pathophysiologic patterns that would be the opposite of what a motor obstruction would be, like reflux. Reflux would not be possible in true motor obstruction to any significant degree. So it is important to step back when EGJ outflow obstruction is identified on a motility testing and look at the clinical context, and perhaps look at other studies that might be necessary to confirm or refute the presence of outflow obstruction. But it's also important to remember that achalasia spectrum disorders could manifest with intact esophageal body peristalsis. So how do we adjudicate EGJ outflow obstruction? One method is to look at upright swallows. So if the outflow obstruction metric, so abnormal IRP, persists in the upright position, and you see pressure compartmentalization in the distal esophagus between the contraction and the EGJ, that tells you that maybe there is something going on there. And the other test, the rapid drink challenge. So a normal esophagus should behave like this. When you give somebody 200 ml of water, the esophagus should have no problems handling that. You see no pressurization in contrast to a pressurized esophagus that looks like this. Now, if you compare a timed upright barium to this rapid drink challenge in patients with treated achalasia, that kind of pressurization with an IRP during rapid drink challenge of around 10 to 12 gives you decent performance characteristics in predicting obstruction. And there's this recent data that maybe in EGJ outflow obstruction, it performs well as well, with a slightly higher threshold of 16 here, IRP during rapid drink challenge. So these supplementary or complementary approaches are useful. But in many of these outflow obstruction syndromes that are not definitive with just the manometry, you have to go to alternate studies. This is a timed upright barium swallow. The first panel before treatment of achalasia looks classic. The second one after treatment. And you can see there is no barium retention at five minutes in the upright position in this instance. In contrast, you can see that the two images before and after treatment are exactly the same in this. So a timed upright barium is particularly useful in looking at this esophageal emptying phenomenon, which would tell you, if the emptying is abnormal, that there is something going on. There is poor emptying here. This is the methodology that is used for a timed upright barium. And a standardized timed upright barium with and without a barium pill swallow is generally useful as a secondary confirmatory step when you find outflow obstruction. Great for evaluating treatment response as well. And then we have FLIP. I'm sure John's going to talk a little bit more about FLIP. But this uses impedance planimetry technology. It has a balloon. It has a catheter with impedance electrodes. And part of what it does is calculate cross-sectional area at different levels, at each level that there is a pair of electrodes in the catheter. And looking at the cross-sectional areas and looking at the pressure within the balloon as volumetric distension progresses, you can come up with this calculated metric known as the distensibility index. And it is well known that the distensibility index is low when there is an obstructive element, particularly motor obstruction, like in this case. In contrast to this image, where the distensibility index is 5.8, so higher than 2, higher than even 3. 2 to 3 is considered indefinite. And the diameter here is lower than what is expected. This is a patient with a mechanical process and not necessarily a motor obstruction. How does this compare against IRP? This was a very nice study from Dusty Carlson, where a timed upright barium was used as the gold standard. And you can see performance characteristics of supine IRP of 15, upright IRP of 12, to distensibility index of 2, and diameter of 13. Flip was a little better than IRP, but you can see that the IRP functions very well. So these tests are complementary. So how do we move forwards in this obstructed esophagus realm? So with compatible symptoms, initial tests, you rule out mechanical obstruction. You do a manometry. You have the three achalages subtypes. There are a few caveats. Short history, weight loss, think pseudo-achalasia. Opiates think opioid-induced motor dysmotility. Absent contractility with significant dysphagia. Think type 1 achalasia, even if the IRP is normal. Do additional tests to rule that out. And motor EGJ outflow obstruction, confirmed conclusive motor EGJ outflow obstruction, so no mechanical etiology. An alternative test abnormal. That tells you something is going on. How do we treat this? Well, we try to destroy the obstructive motor element there, whether that's the LES, where you can do pneumatic dilation or hell or myotomy, or the entire esophagus, where POM, a tailored POM, is probably going to provide the better option. In patients who are poor surgical risks, you may have to think about other options like Botox. Sildenafil doesn't work very well, but can be tried. And in end-stage achalasia, you take the esophagus out, or you feed the patient distal to the esophagus. Similar treatment options may be reasonable in confirmed motor EGJ outflow obstruction. So if you go to the Chicago classification, these alternate tests, these adjunctive tests Barium and FLIP, will bring EGJ outflow obstruction, if abnormal, to the realm of disorders of EGJ function. And if that's negative, then you have no EGJ outflow obstruction, even if the IRP is abnormal in the context of intact esophageal body peristalsis. Now, if you have ruled out obstruction, then you go into the disorders of esophageal body abnormality. So absent contractility, distal esophageal spasm, there are lots of premature sequences, hypercontractile esophagus, and finally, ineffective esophageal motility. These terms have to be used with caution, because they have to be clinically relevant to make sense. The one that is least relatable to patient symptoms is ineffective esophageal motility. And it really pains me when patients come to me and tell me, I have IEM. What symptom do you have? Not really anything other than reflux. Well, treat the reflux, not the IEM. The situations where the esophagus needs to be treated with motor disorders is obstructive motor disorders. The remainder probably don't need the esophagus intervened upon, but the patient's symptoms treated. Now, even in these disorders of esophageal peristalsis, if the symptom is significant dysphagia, you still need to look for obstruction. You may still need to do these adjunctive tests. Now, let's go quickly through some of these diagnoses. 100% failed swallows, normal IRP, that would be absent contractility. Important to rule out achalasia with alternate tests if the symptom is significant dysphagia. Now, prokinetics do not work, do not go there with absent contractility, not useful. You don't need to treat normal variants or asymptomatic patients if they have reflux managed GERD. If they have abnormal bolus transit, help them eat better and treat strictures. What about patients with spastic disorders, spastic esophageal body disorders, hypercontractile distal esophageal spasm? Here you need clinically relevant symptoms, chest pain or dysphagia. If they have heartburn, hypercontractile disorder may not be relevant. It may be a response to acid. It may be a marker for esophageal hypersensitivity. You need to make sure there is no obstructive element. Again, you can use the same thought process, normal variants, asymptomatic, you don't need to do anything associated with reflux, you treat the reflux. So reflux can be an important element here, especially if the symptom is perceptive like chest pain. So you go down the reflux pathway, you treat reflux, the patient has no reflux. If they have perceptive symptoms, neuromodulators. On the other hand, if they have transit symptoms, you have to try and decide if the symptom can be linked to disturbed bolus transit. The answer is no, down the same pathway as for perceptive symptoms. The answer is yes, that's where you may want to do something to the esophageal muscle. I usually start simple. I start something reversible. So this is where smooth muscle relaxants or a Botox trial may be reasoned. What about hypomotility disorders? You see weak and failed swallows. We have a provocative test for this as well, multiple rapid swallows. This is a challenge that is performed in the supine position to see if stressing the esophagus will make the esophagus contract better. And you can measure this using the MRS-DCI to mean DCI from single swallows. When that ratio is more than one, we say there is contraction reserve. What's the relevance? If there is no contraction reserve, the likelihood of post-fundoplication dysphagia is higher in the setting of ineffective esophageal motility. And these patients can have higher esophageal reflux burden. The correlation between IEM and symptoms is poor. And so most of what you do with IEM is make sure there is nothing else going on with these provocative tests. Again, prokinetics don't work. Normal variance, no treatment. Asymptomatic, don't need to treat. Manage GERD. Manage dysphagia. Don't do anything to the IEM. You really can't. Now, a couple other things where high-resolution manometry is useful. You can look at the morphology of the esophagogastric junction by looking at the relationship between the lower esophageal sphincter and the diaphragmatic crural impression. So type 2 is a small hiatus hernia. Type 3 is a bigger hiatus hernia. And sometimes you don't see the diaphragm at all in massive hiatus hernia. Relevance, esophageal reflux burden is higher when you have a hiatus hernia as compared to when you don't. And patients with GERD tend to have hiatus hernias more often than healthy controls. And high-resolution manometry is actually quite reliable. Good performance characteristics to hiatus hernia measured during fundoplication. So to summarize, manometry, high-resolution manometry is the gold standard for characterizing motor function. And the Chicago classification is an hierarchical algorithm to identify motor disorders. The differences with 4.0 is that stringent criteria are now used for EGJ outflow obstruction and IEM. And achalasia or outflow obstruction disorders need to be considered even when the finding is not typical, if the symptom is significant to state. Thank you very much. Thank you.

high-resolution manometry

Chicago classification

esophageal motility

pressure tracings

esophageal motor function

motor outflow obstruction syndromes