Now, I have the pleasure to introduce Dr. John Pandolfino, he's Professor of Medicine, Chief of Gastroenterology and Hepatology at Northwestern Medicine. He's going to talk about diagnostic approaches in esophageal motility disorders. Well, first off, I'd like to thank the ASG and the organizers for the opportunity and also giving me the opportunity to talk about something other than Chicago classification. Prakash actually does a much better talk than me anyway, so I probably would have been bored if I would have done that talk. It also gives me the opportunity to shoot through some of the slides I have because Prakash has already done a really good job at taking us through most of this here. Here are my disclosures. I think you really need to keep these in mind, especially when I'm talking about FLIP, because I obviously am biased. I've spent a good part of my life working with balloon technologies as a methodology to assess diagnostics in the esophagus, and certainly that is something important to keep in mind. Now, listening to Gary's talk, I was happy to hear Gary talk about the fact that one test and sitting there and thinking about one test is not going to ever be enough. I think this really holds true when you take care of complicated esophageal patients. No test in esophagology is perfect. They all have strengths and weaknesses, and you can really make a lot of mistakes if you only focus on one particular test. We're not saying that everybody needs every test, like Gary said, but you need to go through these tests in a very logical, sequenced way. Many times, even after I've gotten a really good history, done a good endoscopy, done FLIP, manometry, and esophagram, I still don't know what's going on. Then I'll get reflux testing, and I'll still not know what's going on. I think it's important to remember that these tests need to be used in a complementary way and not a competitive way. Now, that being said, when I do see patients with esophageal complaints, I can sit there in clinic and take a good history, think about what's going on. Most of the time, I actually watch them drink water and eat a piece of bread or a cracker or something like that, because I think that's probably the most important thing that you can do, especially if someone's presenting with dysphagia. But I'll put together a differential that pretty much lists the standard diagnoses, GERD, EOE, obstruction, motor disorder, functional esophageal disorder. I can sit there and guess, maybe this is what it is, and many times I'm wrong. I would be remiss if I went to an ASGE conference and I didn't at least prop up endoscopy. I think endoscopy is still a very important test when we start to think about our workup of esophageal symptoms. In fact, all roads lead to endoscopy. You really can't make a diagnosis of an esophageal motility disorder until you've done a good endoscopy and ruled out obstruction, because the esophagus doesn't like obstruction and will react to an obstruction. You may see spasm, but it might be an obstruction. You may see an achalasia pattern, but it might be an obstruction. So endoscopy still is the king. That's noted in every algorithm that you ever see with an esophageal complaint. I like to use the ROAM algorithms, because regardless of which ROAM diagnosis you look at, everyone starts with either some type of imaging, endoscopy, laryngoscopy, in terms of the algorithm. So you have to rule out an obstruction, extremely important. With that caveat, I like the discussion about the flap valve. Now I agree with Gary that it's not perfect, and there's a lot of disagreement amongst endoscopists when they talk about this. But I think when I see a one, I feel really comfortable. When I see a four, I feel pretty comfortable. The twos and threes are difficult, I will give you that. And once again, it's some adjunct information. It just lets me lean. I'll use that now, Gary. I lean. I don't fall into it, but I'll lean towards a specific diagnosis. And I think it's really important to note this. So when I see these patients, I do my endoscopy. The other thing, too, that I throw in there, and it's really important, I get so many referrals for dysphagia, or chest pain, or regurgitation, or intermittent food impactions. And the person has a three centimeter hernia. And people act surprised that that's the cause. I mean, a hernia, especially a three centimeter hernia, is obstructive. I mean, it certainly could predispose people with reflux, but it is abnormal. And if someone has those symptoms, the hernia is probably implicated, whether it's a structural, functional, anatomical obstruction, or is it leading to more reflux, and that's causing hypersensitivity and perception issues. But when you see a hernia greater than three centimeters, and people coming in with these symptoms, it's likely to blame. And I find that consult an easy consult, because I'm pretty much done there. Now I'm not going to talk too much about Chicago and Klaus's plots. But I think the one distinction that I think Prakash did make was really the beauty of this technology was really taking these tracings and coming up with the great idea of converting them to color, and these pictures. And really, a picture's worth 1,000 tracings, a picture's worth 1,000 measurements. And that was really Ray Klaus's, in my mind, impact in this field. And that's why I like to call these Klaus plots in his honor. And it really did provide us with a lot of cool information. We've got this seamless dynamic representation of pressure. Now this is the Chicago classification. And I will tell you, this is a lot more complicated than 3.0. I like 3.0. It's straightforward. You went down the steps, and you kind of were done. This, I think, gets to the point where we're not really sure what we're doing. I always say that when you see these kind of algorithms, and you had to see the arguments that went through and all the discussion to finally come up with this, and it's not that good, to be honest. So I think really common sense, this is a guide to make you think in a very common sense way. I see so many people follow this to the T, and they're like, does it fit in this group or that group? And I'm like, I don't care. I'm not going to do anything for it. And you see people get wound up in these little categories. So my summary is a little bit different on Chicago classification than Prakash's. So I think the achalasia classification is good. There's some subtle issues, the issue about absent peristalsis and making sure that you're not missing an obstruction, because you can have achalasia with an IRP of four. That's important to remember. The catheter is being squeezed by that sphincter, right? And my fist right now is relaxed. Now it's contracted. That's the lower esophageal sphincter. It's opening that matters. And it may be at four, but not open very well. And that can still be achalasia and obstruction. Very important to remember that. We heard about EGF flow obstruction should never be diagnosed with manometry alone. And we've also recognized the limitations of spasm. I think we really don't have a very good handle on that. And jackhammer, too. I think we had a little bit of a pause in terms of incremental improvement in Chicago when it came to spasm and jackhammer. I think there was a lot of opportunity to make jackhammer a better diagnosis and really tease out the clinically relevant group, but we tended to ignore a lot of the studies that were published. And hopefully, something happens in 5.0. Weak peristalsis is still a borderline motor abnormality in my mind. And I think Prakash handedly talked about that. And then the other thing, too, remember that Chicago classification, there's a lot of stuff going on in between the swallows. And don't ignore things. Don't ignore the activity after a swallow or when the patient changes position and you see the esophagus scrunch up like an accordion. That's not normal. So that should at least make you think a little bit. So now going back to this, as Prakash showed, I think one of the highlights was, in my mind for Chicago, 4.0 is really showing that there was this issue of limitation with 4.0 and showing that we needed alternative complementary tests. And I think that's important. Because I will tell you, panel A, if I would have seen that manometry, that's probably Ecclesian evolution. Panel C, that's normal. But that panel B, that's a pretty beautiful looking peristalsis. So when you start to see this propagation and this just little panesophageal compartmentalization there of that pressurization, that's not all that incriminating. But then when you look at the flip and the esophagram on that patient, I mean, those are remarkably abnormal. So it just kind of shows you that you can see different things with different technologies. So just getting to this for a brief minute, I think it's important to remember that the esophagus responds to obstruction. And that obstruction can be old peptic stricture, stenosis, or a small hernia. And you can see profound hypercontractility with those obstructions. So jackhammer or hypercontractile esophagus many times is not a primary motor disorder. If you look at the muscle, it's not very different than what you would find in a normal esophagus. So I think we've got a lot of room to move here in jackhammer esophagus. But that being said, I still do look at the manometry carefully. I look at whether or not there were repetitive peaks. I look at the absolute value of DCI. Are there all these other pieces of information that are going to make me think that this is someone who has a primary hypercontractile motor disorder as opposed to a normal variant or someone who's got a small hernia or old peptic strictures or stenosis? And I do, I go through this kind of algorithm in my head, you know, and I really think about all of these factors. So if someone has a swallow that's abnormal every single time, and they look really abnormal, that makes me think that this is more likely a primary abnormality than someone who has eight beautiful normal swallows and then has a couple of hypercontractile swallows with a DCI of 9,000. That's nothing. That's normal. But yet it fits criteria, and people get all worked over it. You know, they send people for a poem based on that, and that's a mistake. So I'll go through this particular process, and I'll go through, and I'll treat people for GERD. But as Prakash said, I'm going to look for obstruction, and whether that's a mechanical obstruction or a physiologic obstruction, because I do think that spectrum, that jackhammer is on the spectrum of almost like a spastic achalasia motor disorder in many cases. And you have to discern that out, because if you see an obstruction on that esavagram, then you can treat those patients most likely like you would a type 3 achalasia. So just kind of something to think about. I have done some EUSs with deep muscle biopsies, especially in patients where I just didn't believe that this was a primary motor disorder, and most of the time it comes back normal. I've only had one patient come back positive, and that was actually, it was a very odd inflammatory reaction with fibrosis, and really nothing that made me think that this was achalasia as opposed to an inflammatory process. So when I see these patients, I really take a step back, and I get a flip. I get a TBE, and I get all this information to see if there's an obstruction. And I treat them very differently, whether or not I find an obstruction, yes or no. And if there's no obstruction there, I will try a smooth muscle relaxant. And I used to do a lot of this kind of step up with Levsin and Benthol, and then go to calcium channel blocks. And now I just blast them with sildenafil, BID, 50 milligrams, see if it changes anything, and I see if there's a correlation between their manometry improvement and their symptoms improvement. And if there's no difference and there's discordance, I take a step back. I'm not going to do anything. The people that I'm actually really doing POEM on are the people who I show have really profound abnormalities. They get better on sildenafil, and their manometry looks like it's better. Those are the people I've had the best success with. So people have concordance of the manometric changes and their symptoms. Similarly, the ones that I find that actually have an obstruction and who respond to Botox are probably the ones that are going to respond to a POEM. So I try to look at this concordance between these medical empiric trials and what's going on in terms of obstruction. The other thing that I think you have to really consider in all of these presentations is anatomy. Dr. Prakash talked a little bit about barium esophagram. But I love barium esophagram. I read all my own barium esophagrams. I think you cannot care for esophageal patients if you don't know how to read a barium esophagram. I think that this is probably the most important thing that I like to review with my trainees is the importance of this particular test. Because if you see D, there's nothing you can do for that person. When you start to see these type of processes, that's done. That's end-stage achalasia. Similarly, you need to start to appreciate some of the complications that can occur. Now this got a little compressed here, so it looks a little bit more complicated than it is. But lately, what we've been doing at Northwestern is really being a little bit more aggressive in terms of doing our evaluation up front and really doing flip penometry during this index endoscopy. And really what flip is, flip is an evolution of technologies from barostat, from the hydrostat, and now to the functional lumen imaging probe, where we're looking at the mechanical changes that happen in the esophagus in response to volume distention. So it's probably the most important thing that the esophagus does. It responds to volume distention. So if you reflux, what does the esophagus do? It wants to push it back down. If you have a piece of food caught, what is the esophagus supposed to do? Push it into the stomach. How does it respond to that volumetric distention? And really that gets to the distinction between primary and secondary peristalsis. And I will argue that secondary peristalsis, intact secondary peristalsis, is probably more important than primary peristalsis. We know you can eat very comfortably in the upright position and have no evidence of peristalsis in the upright position, but yet clearly empty the bolus. And we know that when you eat solid food after that first initial swallowing, that first primary peristaltic sequence, a lot of that bread or rice is sitting there and you require those secondary peristaltic sequences that are a response to distention to help push that food down. And what we found was that this FLIP device, when you use the Klaus approach and really taking color and changing it to diameter and looking at the representation of diameter changes as peristalsis, you can see some neat things and you can see some nice patterns. You can look at the esophagogastric junction open. You could define essentially normal peristalsis, normal secondary peristalsis. But if you see normal peristalsis here in C, they almost always have normal peristalsis on a manometer. And if they don't, they probably have IM that would probably get better when percostasis multiple rapid swallow. And we did find that if you actually look at opening dynamics of the EGJ and you plot EGJ distensibility index and maximum diameter, it does pretty well. It actually tells you whether or not this person has an abnormality of EGJ opening. And we've done this over and over now, and we've even developed a very simple K-nearest neighbors approach that gives you a probability of obstruction. Prakash showed this slide. It actually does perform slightly better than the IRP in terms of TBE bolus emptying as the gold standard. And there's also this heterogeneity in terms of these patterns that you see. So in type A or panel A up there, you see those are racks, repetitive antegrade contractions. That's a normal response. If you distend the balloon there, that esophagus is going to keep contracting trying to push that down. That's what happens when someone has a food impaction or when they reflux or they have a piece of bread stuck in their esophagus. B is basically borderline. They're able to manifest antegrade contractions, but they don't have that repetitive nature to it. C is disordered, where these contractions are focal, maybe a little chaotic, not really propagating, not stimulating that descending inhibition that causes LAS relaxation. And then there's absent in D, where you see a scleroderma patient with no peristalsis and an EGJ that opens up widely, so predisposing them to reflux. And then these spastic disorders that you see on the bottom there, we're not exactly sure what those mean yet, but we have an idea that they probably represent a pretty significant abnormality that is associated with symptoms. So how well does this compare with manometry? Well, if you look at peristaltic sequences in terms of intact swallows, failed swallows, it actually correlates quite well in terms of DCI range and also the qualitative analysis of the swallows. So with that now, we can actually put together a classification scheme where you can start looking at patients as whether they have normal motility, abnormal motility, a nonspastic obstruction, a mechanical obstruction, or a spastic reactive pattern. So it's obviously tempting to take the Chicago classification, put it on the top, and then look at the correlate of flipped penometry. And as you can see, a picture's worth 1,000 tracings, a picture's worth 1,000 measurements. It's pretty simple to see when somebody's normal. They have achalasia, type 1, type 2 or 3, spasm in the esophagus, a reactive pattern, and even ineffective esophageal motility in scleroderma esophagus. And where is this going? Well, I think we have now the ability to use these tools in a complementary neuromyogenic model where now we could actually discern out whether or not patients have disorders of primary and secondary peristalsis. So you may see someone who has scleroderma esophagus. So the three panels on the top are all scleroderma esophagus. But look at the difference in the flipped penometry. One person looks completely normal. One person looks like they've got some IAM, and the other one looks like true scleroderma esophagus. And we've actually shown that this actually tracks somewhat with pulmonary function. We need a little bit more sample size, but also with bolus retention. So we can now stage scleroderma esophagus based on flipped penometry. So how do I use this in my practice? Well, in my practice now, I still do a good endoscopy after I take a good history and physical and watch the patient eat. Make sure they don't have oropharyngeal dysphagia, because then I'll send them to my speech pathologist. But if they don't, I'll do a good endoscopy, look for obstruction. And if they don't, I'll do flipped penometry. I'll identify their pattern. I'll assess for obstruction. And then based on what I see, this is how I treat patients. So if I see a normal pattern, I don't do anything for those particular patients outside of assessing them for reflux and then potentially sending them for behavioral therapy, because they most likely have a functional disorder, especially if their reflux testing is negative. Now if their endoscopy looks like achalasia, they have a dilated esophagus, their EGJ is tight, and they have a non-spastic obstruction pattern, I'm done. I'm not going to put that person through a manometry. They have achalasia, because there's concordance between their endoscopy and the flip. Now what do I do with these other things? Well, this is where I may need a little bit of help with either an esophogram or a manometry. So if I have someone with a spastic reactive problem, those people are probably going to get a manometry and an esophogram to figure out what's going on in those patients. Because I will tell you that there's a lot of discordance in those patients. And that will dictate how I treat those particular patients. In terms of the weak, those patients, I tend to just watch and treat them aggressively for their reflux. And if they don't respond to reflux treatment, then maybe I'll get a manometry. So this is where I really think motility testing is going. I think we're going through a process now where we can actually provide an assessment of motility without putting patients through a manometry. And I always ask this question when I finish the talk. How many people in the room have had a manometry? Yeah. All right. How many people have had a COVID test? Now I can use this. How many people would like to have that COVID Q-tip sit there for 45 minutes? It's not very pleasant. It's a horrible procedure. People don't tolerate it. And they don't want to get it again. So if we could do something that is actually less invasive for the patient that they get while they're sleeping during an endoscopy, I think that's the incremental advantage of doing this in this approach. Thank you very much. Thank you.

esophageal motility disorders

diagnostic approaches

endoscopy

ROAM algorithms

Chicago classification

functional lumen imaging probe (FLIP)