And now, just this lends into Peter Karelis' talk, which is about tailoring treatment in patients with achalasia. And this has become even more important with the advent of endoscopic therapy in this arena. So Peter, welcome, and looking forward to your presentation. Good morning. I'm Peter Karelis from Northwestern University in Chicago, and I'll be discussing tailoring treatment in achalasia. My only financial disclosures are that I serve as a consultant for Ironwood and Reckitt Benckiser. In contemplating achalasia, you have to understand high-resolution manometry and how we define it. This is a typical HRM plot, and in analyzing it, three key metrics are derived, the integrated relaxation pressure, describing outflow resistance, the latency of the peristaltic contraction, which is the key metric for defining spastic contraction, and the distal contractile integral, which summarizes the strength of peristalsis. These are put together in an algorithmic way to develop the Chicago Classification of Motility, currently in its fourth version and just published in NGM. So as in prior iterations of the Chicago Classification CC, version 4.0 recognizes subtypes of achalasia. So there's type 1, or classic achalasia, where there's outflow obstruction with a high IRP, but no contractility in the body of the esophagus here. There's type 2, where you still have a high IRP, but now you have these bands of pressurization spanning from the upper sphincter to the lower sphincter. These are contractions, but they're not lumen-obliterating contractions. In type 3 achalasia, on the other hand, you have spastic, kind of corkscrew-y type contractions in the distal esophagus. These are obstructive in nature. This is the most difficult type to treat. That's a spastic contraction there. Low latency is the key to making that observation. And then there's type, sometimes called type 4, but EGJ outflow obstruction, where you have a high IRP, but some preserved peristalsis. This was a major problem in CC 3.0, because this was getting way overdiagnosed. So in 4.0, there have been Herculean efforts made to restrict this diagnosis to clinically significant cases, where there are symptoms of dysphagia, and confirmation with a secondary test, such as a time-varying esophagram, or a FLIP study showing a confirmation of outflow obstruction. With that preamble, let's move on to treatments. I have to mention botulinum toxin injection. This is a safe and easy treatment. It's reversible, which is both a strength and a weakness, because it wears off over time. It was popularized in the late 1980s. It has some key disadvantages, though, and these pretty much outweigh the advantages. It's temporary. It's less effective than the alternatives. It's expensive, considering that limited efficacy. It loses effectiveness after two or three repeats, and it doesn't halt the dilatation of the esophagus, which is the key mediator of morbidity of this disease. Now this is me, pre-COVID, doing a Botox injection. You'll notice all the PPE that isn't there, but it's a simple technique. One simply uses a sclerotherapy catheter and dilutes 100 units of Botox into 5 mLs of sterile water and basically inject it in five aliquots into the lower esophageal sphincter. Quick and easy was very popular for a while. So another treatment option is pneumatic dilation of the esophagus. This is the microvasive dilator. These are available in three diameters, three, three and a half, or four centimeters. This is accomplished also endoscopically with the aid of fluoroscopy. This is pneumatic dilation in progress. You'll notice the silhouette of the dilator and the impingement on that silhouette by the lower esophageal sphincter. As you inflate it, you need to capture that sphincter on the dilator surface and watch it gradually efface. As you hold that for a period of time, you achieve this conformation where there is now complete effacement of the waste and that signifies that you have, in fact, done your thing. Thinking about the pros and cons of pneumatic dilation, it's less invasive than surgery. It stops the process of esophageal dilatation. There's less of a problem with reflux afterwards. It's very inexpensive and very effective for subtype 2 achalasia. Disadvantages, there's very poor standardization of technique and variable outcome among practitioners. There are very few practitioners. It may require a series of two or three successive dilations increasing the diameter of the dilator. There is a perforation risk, which is quite operator dependent, and you may need to repeat this periodically every so many years, not months, but years. That brings us to the laparoscopic helaromyotomy, which is a surgical technique approached through the abdomen and that does a surgical incision across the circular muscle fibers of the distal esophagus, lower esophageal sphincter, and proximal stomach. It's coupled with a fundoplication, in this case, a partial anterior or dora fundoplication. Alternatively, that can be a posterior partial toupee fundoplication. In contemplating its pros and cons, you have a certainty of a surgical myotomy, so you know you've cut the sphincter and it certainly halts progression of esophageal dilatation. Doesn't reverse it, but it certainly prevents advancement. Disadvantages, well, it has surgical morbidity and mortality associated with it. There is a 1% perforation risk requirement intervention, so similar to pneumatic dilation. It's expensive and postoperative reflux is relatively common. It also can be inadequate for type 3 spastic achalasia because one simply can't get high enough onto the esophagus from the abdominal approach. Pneumatic dilation and laparoscopic helaromyotomy were compared in a randomized controlled trial, a European achalasia trial shown here. Note the success rates were similar for helaromyotomy, 90% versus pneumatic dilation, 86%. I put this footnote on this, though, because this was an aggressive pneumatic dilation protocol, and in fact, they initially were using a 35 millimeter dilator for starters and perforated four out of their first 13 patients. They toned that back a bit and had less perforation, but still substantial at 4%. That brings us to the peroral endoscopic myotomy or peroral esophageal myotomy palm procedure. This is an alternative to the laparoscopic helaromyotomy or pneumatic dilation. It's an endoscopic technique introduced in the early 2000s, and the key here is that you're entering the esophagus through a mucosotomy, so you're using an endoscope, you cut partially through the wall of the esophagus, you make that false channel all the way into the stomach, and then come back and perform a myotomy with some sort of cautery device. You then close the incision with endoclips. Very elegant technique. At pros and cons here, well, it's incisionless, so although you're doing a surgical myotomy, you have no surgical morbidity. It halts esophageal dilatation. You can calibrate the length of the myotomy to account for spastic achalasia, and it has maximal treatment efficacy for all achalasia subtypes. Disadvantages, it's relatively new, so you can be in a learning curve situation. There's more post-op reflux than with pneumatic dilation or laparoscopic helaromyotomy. There's no anti-reflux procedure typically associated with it. Now, this too has been the subject of a randomized controlled trial against pneumatic dilation, the POAMAS trial. 133 patients randomized in Amsterdam, Hong Kong, and Chicago, and success rates at three months were 98% versus 80% at two years, 92% versus 54%, so a stark difference. Now you'll notice that there was wide variability in the efficacy of pneumatic dilation between those two trials, the European achalasia trial and the POAMAS trial, and there is an explanation for that. In terms of the algorithm or the protocol for doing the dilation, the European trial was much more aggressive using bigger dilators, more dilations, repeats were okay whereas they were not in the POAMAS trial, and the perforation rate was substantially higher in the European trial. So yes, the success rates were starkly different, but so was the morbidity, and you can look at that as a glass half full or a glass half empty, and you can decide which would be acceptable to you. To me, pneumatic dilation is okay if you do it with a conservative strategy. Now the POAM procedure being new has raised the issue of is it durable, and evolving or emerging information suggests that it is. This is a study showing that it has good durability over a period of six years. Now I mentioned GERD as a potential weakness of the POAM procedure, and this indeed is observed more after POAM than lap-heller, whether it's by symptoms, pH metric, or endoscopy. Up to 30% of POAM patients develop esophagitis of some grade, compared to only about 8% with lap-heller. However, keep in mind that this is mainly mild esophagitis. Over half of it is LAA, so it's generally pretty easily controlled. The other interesting meta-analysis that has been published recently is comparing the outcomes for the different achalasia treatments based on subtypes, and this gets to the crux of my talk today, really, of individualizing treatment. So this meta-analysis looked at BOTAX, pneumatic dilation, laparoscopic hellermyotomy, and POAM, and grouped people according to type 1, 2, 3, or achalasia. 20 studies were included, 1,575 patients. So this is the outcome of that meta-analysis for type 1 achalasia. The four treatments are shown here, and very interesting, the POAM procedure actually was superior to the laparoscopic hellermyotomy with a p-value of 0.03. That of course makes it substantially superior to either pneumatic dilation or BOTAX injection. For type 2 achalasia, something of a different story here, because type 2 achalasia is in fact the easiest to treat, or the one where you're most likely to have a good clinical outcome. It's relatively early, there hasn't been much esophageal dilatation. Anyway, pneumatic dilation, laparoscopic hellermyotomy, and POAM were all very effective here, with no significant difference between the three. BOTAX, much less effective. And that actually was consistent also with the POAMA trial and the European achalasia trial. Type 2 achalasia responds very well. Type 3 achalasia, on the other hand, ends up being the biggest problem, and also the biggest discriminator between these treatments. POAM still extremely effective, and much more effective than laparoscopic hellermyotomy, and even more so a pneumatic dilation of BOTAX. So there's a clear advantage here for POAM with type 3 achalasia. So to summarize that meta-analysis, the success rates for laparoscopic hellermyotomy in type 1, 2, and 3 were 81, 92, and 71% respectively. So yes, subtype matters. Clearly type 2 does the best, and type 3 does the worst. For POAM, this was 95, 97, and 93% respectively. So in all, this is not an experimental treatment at this point. POAM was more successful than laparoscopic hellermyotomy for both type 1 and type 3. And in my view, laparoscopic hellermyotomy is on the way out. Pneumatic dilation had lower but acceptable success rates compared with POAM or laparoscopic hellermyotomy for type 2. And given that it's much less expensive than either of those, this is a solid argument for pneumatic dilation in the type 2 subtype. Thank you very much. It's been a pleasure.

achalasia

tailoring treatment

high-resolution manometry

Chicago Classification of Motility

treatment options