We'll next go to Northwestern University to watch some challenging Echolasia cases by Dr. John Pandolfino. What I was asked to do is really focus on challenging cases in Echolasia with POEM and really give more of a lecture format around how we approach these patients with difficult presentations, both before and after POEM. These are my relevant disclosures. And, you know, it's interesting because Echolasia in and of itself is really kind of a new disease. Over the years, everyone thought there was just one type of Echolasia, maybe two you had regular Echolasia and vigorous Echolasia. But now, you know, given the new technologies we have, we've really appreciated the heterogeneity of these particular presentations. And the fact that it lends itself to more of a precision approach in that we can really tailor therapy and really focus on the things that are driving abnormal function and target those in these particular patients. And really this was born out of the fact not just that we had this evolution in technique, but we also had this evolution in technique around treatment strategy in that now with POEM, this really lends itself to this kind of precision approach. Now, before we go into this, I do wanna talk a little bit about some mistakes that we make sometimes before we even start. And I think some of this has to do with not understanding the subtypes. And, you know, not all EGJ outflow obstruction is the same. And certainly we all know that probably the most common form of EGJ outflow obstruction is an artifact, right? It's a false positive. But then you get into the concept of whether or not this is truly Echolasia versus a mechanical problem. That mechanical problem could be missed stricture, it could be abnormal curl anatomy, a small hiatus hernia. In addition, it's also important to realize that EGJ outflow obstruction, when we treat this with POEM, there needs to be some consideration in regards to the length of the myotomy, because once again, there will be some preserved peristalsis left behind. In addition, what we're learning too is that not all type two is the same. You heard me mention this morning when we talked about manometry that certainly the cutoff between type two and type one is difficult, but also on the other side, we can see these patients evolve into a spastic pattern after treatment and effective treatment. And then of course, there's the quandary of jackhammered spasm. As you've also seen over and over today, not appreciating anatomy is also an important mistake that people make. Not understanding the relevance of dilatation, not understanding how diverticulum comes into play, and certainly negating the effect of a hiatus hernia and curl anatomy. And then last but not least, I'll touch upon is not appreciating the interplay of psychological distress in their outcome. So in terms of the evolution of the Chicago classification, 4.0 was really not that dramatic in terms of achalasia, but did have a major impact in terms of EGJ outflow obstruction, with the idea that in order to have a conclusive diagnosis of EGJ outflow obstruction, meaning that this was a motility issue, you really needed to have further studies and complementary studies with either an abnormal TBE or esophagram or a functional lumen imaging probe. And really you could not make a diagnosis of EGJ outflow obstruction on its own. Now, certainly there are some adjunct maneuvers and provocative swallows that can give you a higher pretest probability, but I will tell you that there are many patients that you see with those particular patterns, that the artifact does kind of translate across positions and even during RDC. This is just our first kind of iteration, expanded a little bit in terms of the neuromyogenic function in achalasia to give you a kind of a description of the subtypes. And I do think that this subtype classification helps, but I don't want people to forget that there's a lot of metadata within the HRM that allow you to think about these patients. Many times you'll see these spastic events that occur and I'm pointing to this EGJ outflow obstruction patient that occur in between swallows or maybe during a dry swallow that show you that this patient does have a significant spastic pattern at the lower esophageal sphincter. So once again, raising your suspicion that this is more likely a motility problem at the esophageal gastric junction. And then of course, type 3 achalasia, which also may be a completely different entity. There may be a type 3 achalasia that is really an evolving pattern to type 2 and then eventually type 1. And then there may be this type 3 achalasia pattern that just sits in this form. And I think this is most relevant when we start to think about the opiate variance in this particular patient group. Now, this is just an example of the heterogeneity of the EGJ outflow obstruction when you start to think about these patients and these difficult cases. So these are three examples, A, B, and C of patients who would be defined as having an EGJ outflow obstruction. They have evidence of peristalsis and they have evidence of obstruction at the esophageal gastric junction. Now, when you look at FLIP and esophagram though, you can clearly see that there are very different patterns here. So on the top pattern, that particular pattern looks like an achalasia evolution. The FLIP corroborates that with absent contractile response and an EGJ that's not opening. And you see that beautiful achalasia esophagram with dilatation and the beginnings of a nice bird's beak starting. If you waited a little bit longer, you'd probably see a little leak there with the bird's beak. So really classic achalasia evolution. Then in contrast, when you look at the middle pattern, you know, that looks like a pretty normal peristaltic sequence with some early compartmentalized pressurization. When you look at the FLIP, it's absolute chaos in the body and the EGJ doesn't open. So what does the esophagram look like? It looks like the FLIP. There's chaos in the body and the EGJ isn't opening. And what we find is, is that FLIP tends to correlate better with esophagram than high-resolution manometry. And then of course, there's the bottom. This is person with clearly looks like an artifact. If I would have seen this de novo, I would say this is most likely an artifact. You can see this patient has beautiful rack pattern. The EGJ opens, a non-dilated esophagus that opens well. So it's very important to appreciate this heterogeneity when you're thinking about these patients. And it's also important to think about this when you're planning myotomy length. In addition, there's a lot of heterogeneity in type two. And this is a very nice paper that we collaborated with our UCSD group. Eric Lowe was the first author in his paper where we really looked at these type two patterns and could see that they had very different presentations. You can see in the up left here in panel A, this is a patient that looks like a pretty classic achalasia dilated esophagus, maybe some small tertiary contractions, but really having a thin wall on EUS and a classic presentation. But as you look at the patients who start to develop higher panesophageal pressurizations, you can start to see varying patterns where when you start to see these kind of focal contractions in panel C and these sporadic contractions in panel D, these patients that tend to have a more spastic presentation. And when you look at the esophagrans, you clearly can see these occluding contractions or these almost occluding contractions, which suggests that this patient, if you treated them, would be left with a pattern of spasm depending on how long your myotomy was. And we actually looked at this with FLIP. So here are two examples where patients have type two achalasia with panesophageal pressurization, pretty high max PEPS or panesophageal pressurizations. But you can see on FLIP that they clearly have some spastic components to them. And then of course, after these patients are treated, the top panel with a pneumatic dilation and the bottom with a POM, you can see that both of these patients are actually left with now not having achalasia, but in essence having distal esophageal spasm in the context of a good myotomy. And when we've actually looked at this in a very small series, we can clearly see that if you're doing this and the FLIP bag pressure is very high or the panesophageal pressure is very high, there is a possibility that some of these patients will turn into a distal esophageal spasm pattern. And I think it's just important to realize that. I don't think we're at the point now where we're ready to pull and say, we need to do a long extended myotomy to the transition zone in these patients with a high panesophageal pressurization with type two, but we certainly see these patients and you just need to keep a close eye on them because occasionally you will have to go in and extend this myotomy with a poem, a redo poem in some of these patients who continue to have symptoms and in particular dysphagia with chest pain. As I mentioned, anatomy is also kind of the most crucial thing. This is why I still to this day love esophagram. I love reading my own esophagrams, but anatomy really has a very important effect on bolus transit. You can be the best poem endoscopist or poem surgeon, Heller surgeon in the world. If the esophagus can't propel the bolus, if there's no propulsion due to ineffective neuromyogenic function, dilatation or anatomical abnormalities like a diverticulum, fortuosity or a sink trap, there's no myotomy in the world that's going to effectively empty these patients. And once again, you have to remember that this is all plumbing. You need to develop a higher pressure in the esophagus than the esophagogastric junction and the stomach. And if you cannot do that because of poor propulsion related to dilatation, diverticulum, sigmoid or tortuous esophagus, there's no effective treatment at the LDS that's going to effectively deal with that. Now we saw, you know, some of these patients may have an angulation and we saw this cruel myotomy that could potentially take away that angulation. In our practice, we tend to send patients for a Heller myotomy in those instances where they can actually mobilize that area and reduce that angulation. And that's how we've kind of dealt with some of these problems, with some success, but not all the time. John, can I ask you a question? Yep. So about sigmoid esophagus, there is a lot of literature that if you do a short myotomy, including the LDS, patients do better. You know, we talk about S1 and S2. The S2, you know, definitely difficult for the audience. S2, if you do a transverse cut on CT, you're going to see two lumens. So this is the S2. But I will say there is some evidence out there and clinical experience by me and others that a short myotomy in early sigmoid esophagus, S1 esophagus, has a value. Yeah, when you say S1, you know, then you're looking at panel C here. And it all is related, to be honest, to the intraesophageal pressure. If your intraesophageal pressures are four or five millimeters per mercury, you are not going to open that esophagogastric junction because it's just impossible. There, you know, this is purely fluid dynamics and physics principles, and you can't defy the pressure gradient and flow and the flow equation. So yeah, there are some patients that, you know, so if we see sigmoid esophagus, we do not relegate everyone to an esophagectomy. I think everyone deserves a shot at a good myotomy before you would relegate them to that. But I will tell you that if you see patients who actually have very low esophageal pressures, the likelihood that they're going to respond to any myotomy is still pretty low. So those would more likely be your S2s and the ones with significant dilatation. And John, I'm sorry, this is Joan. Just to clarify, when you're saying esophageal pressure, you're talking about using FLIP like you were demonstrating earlier, pulling the balloon back into the esophagus above the G junction. And is that the pressure you're referring to? Yeah, you can do it either one of two ways. You can look at the HRM and certainly measure the interesophageal pressure in HRM. And you can see that, you've got to remember, when these people swallow, how do they swallow when they have achalasia? They typically drink large volumes of liquid. And what are they trying to do? They're trying to generate an interball's pressure to overwhelm. Many of them can actually hear it and feel that swish that goes down through their esophageal gas or junction. You have to appreciate and never forget that the laws of physics cannot be obviated by techniques that we perform. If the physics is not there to support that this is gonna work, it will not work. There's no way around it. And I think that's where I think pulling that FLIP balloon back, but remember when you pull that FLIP balloon back, you're looking at an artificial scenario where there is some bolus sitting in the esophageal body. And that would tend to like 70 mLs, that would tend to pull with gravity. It's not the same when you're looking at it. So, I do think if you pull that balloon back and that pressure is less than 10 millimeters per mercury, those patients are gonna have a lot of retention. And that's what we do find. It does correlate quite well with retention on the esophagraft. So, what's our rationale for precision approach? Well, I mean, I think that as you've heard and seen today that there's a lot of thought behind this. And I think that for us, I think it's a moot point now that if someone has true type 3 achalasia with premature contractions, these are patients that do much better with POM with a long tailored myotomy. And I think in that instance, that makes quite a lot of sense. In terms of type 2, I think type 2 is more heterogeneous than we give it credit for. I think that they still have a very good response, but you have to be careful in these particular patients because we've seen many of these patients evolve beyond. I see a lot of referrals for POM failures. So, obviously I'm a little bit biased, but many of these patients come back with either evidence of spasm after they are type 2 have been treated effectively with a myotomy, even a nine centimeter myotomy, or potentially BOM, where they have a blown out myotomy, which completely obliterates the ability of the esophagus to empty and also causes impaired reflux clearance related to a reflux event. Hernia is another important thing. I think once you see a significant hernia, I see a lot of people discount a three centimeter hernia as being nothing, but I will tell you that, in those particular patients, I'm very concerned about doing a poem in those patients. Those are typically the patients that, in my practice, I send for hell or myotomy with a door to repair the hernia. Patients with severe dilatation, pneumatic dilation is really not all that helpful. I think it is also very tricky in terms of placing the balloon. Those particular instances, I will try poem, and as we heard, typically a short poem in those particular patients is not a bad idea, but many times when they have significant angulation in a sink trap, what we've tried at our hospital is hell or myotomy with a door, but with mobilization to try to straighten out the esophagus and that has worked in some patients, not all. And then of course, obesity is something that we should always consider when we're dealing with these patients because obviously obesity in the context of a poem is really a setup for significant reflux. So what are the problems after poem? Well, we hear that effectiveness is 80 to 90% and we hear that if we get the ECKRT score to three or below, we're doing pretty good. And to be quite honest, that still suggests that these people have regurgitation or dysphagia every day. I mean, I think actually a very good outcome is an ECKRT score of zero to one with really the patient telling you that their life has been dramatically improved, they're sleeping well at night, they have no nocturnal regurgitation and they're not at risk for pulmonary complications. And I think we pat ourselves a lot on the back for this, but I think there's still a lot of room to move in terms of effectiveness. The other thing too, I think there is this issue of GERD that we talk about, but most GERD is effectively treated with a PPI in these contexts. And I think there's very rare, I think in my career, now I've had to send two people postponed for an anti-reflux procedure because I could not control their reflux medically. And then of course there's incomplete myotomy, which I think is getting to be less and less of a thing the more we use FLIP and then of course BOM. But I will harp on this and in my last few slides we'll focus on not appreciating the interplay of psychological distress and outcome. So this is technically my algorithm and this has been reiterating some of the ACG guidelines and talked about, but really focuses on when I evaluate these patients and I'm really trying to figure out why patients are symptomatic. And I think you heard Mike Vasey also talk about this. Time-barrier mesopogam is really the follow-up test of choice. I mean, it gives you this idea of what's going on with anatomy and retention. And if patients are having symptoms, it really gives you the mindset and the construct to decide whether or not this is truly recurrent dysphagia symptoms or recurrent bolus retention versus reflux disease. And I think that this is an important algorithm that if you follow, you'll do a very good job at effectively managing post-treatment complications or symptoms. Obviously we heard about GERD. I'm not gonna belabor this point. I do wanna give a little bit of time for questions, but I really feel like overall I've been very effective in terms of using medical management and lifestyle modifications in treating this. I do think that some of these patients, as long as they don't have a significant hernia and they tend to have a decent flat valve anatomy that would be conducive to it, TIF could be potentially something that would be useful in that situation. But the two cases that we've had, we've actually sent for a partial door and have done well. I do think the PCAS, which are not FDA approval, also improve our ability to deal with maybe some of these refractory cases. But once again, it's not currently FDA approved for this indication. I do have some kind of little pearls. I think dexlanzoprazole and Zegerid are better medications in the context of achalasia because they're really not reliant on the timing of meals with the parietal cell activation. You know, when you give a PPI, if they're not timed well, you will get pretty inefficient suppression of acid. And it's been shown that dexlanzoprazole and Zegerid work quite well, even in the context of gastroparesis. So those are the PPIs that I jump to if I'm having issues with refractory reflux. I tend to start though, everyone with omeprazole because it's the easiest to get. Here's just a very nice example of a patient, you know, with type 3 achalasia treated with a helomyotomy and door. You know, this was one of the earliest cases that we saw where we kind of realized the potential of POEM where, you know, this effectively treats this. I think now with the education that's occurred, this is a complication post POEM that we rarely ever see. I think most people are really aggressive in terms of type 3 patients where they will treat these patients effectively with a tailored POEM that is based on the HRM documentation. I know there are people now, in particular, some of my friends in Texas who actually have been just using the FLIP during that particular exam to demarcate the length of the spastic segment on FLIP, which can do this very easily also, and using that as their guide for their tailored POEM. And once again, I think this has become less and less relevant. But as I mentioned, one of the things that we are seeing more and more of are these type 2 patients with high panosobial depressurization, maybe a little bit of spastic pattern on the FLIP, who get an effective treatment at their EGJ, but then it unmasks the spastic contractions that were below. And these patients come in with continued chest pain, continued dysphagia with chest pain, have abnormalities on their esophagram that are consistent with spasm. And these are really effectively treated with just a POEM that addresses that esophageal body spastic pattern. Now, we've heard a lot about FLIP today, and it was really great to hear the variety of the approaches and how people are doing this. And it really goes back to the fact that I think we need to standardize the approach of how we utilize this tool. I don't think this is a tool that we should be using, either filling pressures or emptying pressures and emptying volumes. I think we really have to come together as a society and a community who treat these patients and think about standardizing the approach to this. You know, we've done a lot of work on this. There have been a lot of people who've done a lot of work on this intraoperatively. And I think there's a time now where so many people are doing this, where we need to get a standardized protocol for intraoperative FLIP so that we can develop some of these actual accurate thresholds for what is an effective myotomy. And once again, I think, please do not just focus on one measurement, diameter or DI alone. They're very complementary. And if you negate the fact that that has value and you don't look at the pressure, because the pressure of FLIP is an artificial situation at the EGJ. These patients cannot typically generate pressures of 30 to 50 to 70 millimeters per mercury. So you need to keep that in the back of your mind and you need to look at the opening dimensions that are occurring at the lower pressure levels. So I do think there is an opportunity here to standardize this, because I do see many people come in with what appeared to be an effective treatment based on the intraoperative assessments, but lo and behold, they have significant retention. And then as I mentioned too, that you can clearly have a good myotomy and a good effect on this, but if you do not look at the entire pattern you will be left behind. But certainly DI appears to be more effective than just looking at the basal LAS pressure and the IRP. And this is why this has become my methodology of choice to follow patients who have continued symptoms after FLIP. We've heard a couple of different ideas of what kind of change you wanna see after a myotomy, and there have been varying reports with different levels. This is actually just a very nice study from Ian Cook's group out of Australia after pneumatic dilation, where he showed that if the DI improved by about two in terms of a whole number, 1.8 to two, he felt that these patients tended to have a better outcome. I don't think we really understand this because once again, it needs to be done in the context of the body pattern. And you can have an effective myotomy, but if the patient has significant dilatation, that myotomy that appeared to be very good might not work in that particular patient. So what are the reasons for poor EGJ opening? Well, yeah, there's a true incomplete myotomy, but there may be patients who don't have an obstruction. They have a stricture that is more mechanical. They may have that angulation that we've heard about, or there could be poor propulsion from dilatation. Certainly the diaphragmatic hiatus, as you saw, is still an extrinsic sphincter. And that extrinsic sphincter still needs to be overcome by the generation of an inter-balls pressure in the body of the esophagus that can drive that particular area open. And that's where occasionally some of these patients will need an esophagectomy. And as we saw today, possibly a crural myotomy. So just to go through a couple of these patients, I think this is an important patient here. You can clearly see a nice example of EGJ outflow obstruction. You can see that there wants to be some peristalsis, but this is purely not spasm, it's compartmentalized bolus pressurization. When you look at the rapid drink challenge, you can see very high pressures. And then in this particular person, you see the five-minute barium, really poor emptying and these non-occluding contractions. If you relieve this pressure, you probably see a spastic pattern. Here's the flip with poor EGJ opening. And then this patient underwent a myotomy. You can clearly see that this patient looks a lot better. You can see that even that compartmentalized pressure has been resolved, despite the fact that there might be some increased IRP here. Now, that being said, this is someone who's still someone that I would worry about because when we've done the rapid drink challenge here, you can see that there's a level of obstruction and some panesophageal pressurization that continues. So when you look at this person's esophagram post-treatment, you can clearly see that this person is still not emptying the esophagus. Now, the EGJ here appears to be quite tight based on this, but remember, there is no information gleaned on the intervals pressure during an esophagram. So when this patient did undergo a flip study, you can see though that this patient still has an obstruction. The DI is 1.2, the maximal diameter is 11.6, and you can see that in order to even come close to getting to 11.6, the pressures need to be 50 millimeters per mercury. The one thing I will say to you, that in that same esophagram, as you watch the esophagram, and that's why it's important to do your own evaluation of the esophagram, you can clearly see that this patient is developing a bomb. And this bomb would have been unmasked, would not have been unmasked if you would have just looked at this particular image. And the bomb can actually affect the opening of the esophagal gastric junction because it can decompress the pressure here that's driving the EGJ open. Now, this patient underwent a second myotomy, and you can clearly see here from the study that the myotomy was quite effective at 60 mLs and 70 mLs. You can see that the DI was 4.4 and 12, and at 70, 16 millimeters in diameter, and then 4.5 in the DI. But you can clearly see this patient is not emptying, despite the fact that the esophagal gastric junction looks open and the fact that the distensibility indexes are normal. So once again, highlighting the fact that this bomb is becoming a problem. Now, in terms of patient two here, there's another example here that I think is important. This is someone who looks like they have a pretty normal IRP, but this is someone who obviously has achalasia. When you're going through the rapid drink challenge, they obviously pressurize here and they're not opening. You can clearly see spasm, and here is the barium tablet stuck. So this is someone with a normal IRP. Their DI looks really abnormal, 0.48, and they have an 8.63 maximal diameter at 70 millimeters. Patient underwent a palm, looks a little bit better here. Still some evidence of obstruction. You can see here another bomb has developed and the EGJ is not opening. But look at the flip. When you put the flip through this area, it opens up pretty wide. It's pretty normal DI and up to 15.95. But remember, this patient is not gonna generate intervals pressures at that level. Dr. Pandelfino, these are great challenging cases, but in the interest of time, do you want to provide some closing remarks? Yeah, so I'll leave this slide up as my closing slide. So in the end, I think there's a lot we're learning about palm. There's a lot we're learning about the subtypes of achalasia and I think there's a lot we're learning about the patient presentation. So in the end, I think that we have to kind of start thinking about this in a more global way. And I think we need to look at all of these factors, anatomy, physiology, but also think about the patient presentation and how well they're actually doing. Because remember, these patients live like this for years. They have a lot of fear. They have a lot of psychological distress that doesn't allow them to live a normal life after this. And there's a lot of psychological interventions that we need to utilize in these particular patients that make this an even more complex disease to care for. So with that, I'll end and I'll bring it back to Moen and Joan.

achalasia

peroral endoscopic myotomy

precision approach

EGJ outflow obstruction

Chicago classification system

functional luminal imaging probe