It is with pleasure and honor to present the next speaker. We have Dr. Peter Dragunov. He's a professor of medicine at University of Florida. Peter is a master advanced endoscopist and an academician and a dear friend. Peter, the floor is yours. Thank you very much. I will try to give you an answer to a very complex problem. I mean, you see how much issues we have on the diagnosis side, but let's assume for the purpose of this talk that we have secured the diagnosis of achalasia. Then the question is, what do you do about that? And just to pick up where John led us, that if you're doing your diagnosis on a single test, probably you're not doing the right thing. I will say the same thing about therapy. If you're doing POEM on everybody, you're probably not doing the right thing. Some patients will benefit from alternative therapies. I want to point out to you that we have not been left short on guidelines. Those have proliferated, and with two of those being relatively recent, came in 2020. In most part, they concur, but there is some differences. So I will try to extract from that and take it a step further to be relevant more to the everyday practice. So we have pneumatic dilation, laparoscopic hellermyotomy, POEM, and Botox. Let me start from the bottom down, Botox. The biggest advantage of Botox is that it's easy to apply. Multiple cons, initial response is seen roughly in half of the patients. It is not durable. It lasts a few months. With multiple applications, the response can decrease. And what has been frequently my problem, because physicians from the referring practices use it without any specific diagnosis, then it messes up interpretation of manometry because we catch the patients without diagnosis that already have been Botoxed. That's why Botox is typically not a first-line therapy for achalasia due to the multiple shortcomings. Pneumatic dilation, it is less invasive, relatively short procedure time. It is effective and it has the least GERD compared with POEM or laparoscopic hellermyotomy. But typically, serial treatments are frequently needed for the initial success and even if you achieve that initial success, patients may require retreatment in the future. Not to be ignored, perforation is seen roughly in about 1.5% to 2% of the patients and those may be difficult to manage endoscopically because they are right at the lower esophageal sphincter and the clips and stents may not necessarily work, suturing may be helpful, but it is a challenge. And then going to hellermyotomy, it is durable. It has less GERD than POEM, but it's more invasive than pneumatic dilation of POEM, higher complication rate, limited myotomy length, which is very pertinent in spastic esophageal disorders, specifically type 3 achalasia. It is durable, but far from perfect. The failure rate at 10 years is around 25% and goes up there further. We know that it does require additional fundaplication, but keep in mind, even with fundaplication, reflux is still seen in a good 15% to 40% of the patients. And the new kid on the block POEM, and I'm saying new, but it has been around now for about 12, 13 years, it is minimally invasive, shorter procedure time than Heller, short hospital stay and rapid recovery are clear benefit, unlimited length of the myotomy, which is pertinent in type 3 achalasia or jackhammer esophagus, less complication than pneumatic dilation or Heller. It is durable. It can be easily revisited because you can pick up different spot for your tunnel. And about the main limitation of POEM is that it has more reflux. And by the way, I'm using the acronym GERD, although this is not truly a gastroesophageal reflux disease. It's a disease that we create, but it's just easier to say GERD than probably the more correct terminology. Because POEM is the newest procedure, I just wanted to very briefly review the two randomized control studies, the first comparing it to pneumatic dilation. And basically, it is easy to appreciate that POEM is significantly better than pneumatic dilation. That comes with a price with more reflux in the POEM group compared to pneumatic dilation. Probably no surprise. The more effectively you bridge the lower esophageal sphincter, the more reflux you will get. But at the same time, you'll get a better relief of the dysphagia. The important thing to remember is twofold. First of all, that if you look at the bad guys of C and D LA-grade esophagitis, actually that is quite uncommon in the POEM group. And the vast majority of reflux esophagitis, it was A and B. The second thing about this trial, that this was conceived in the very early days of POEM. Actually, the trial was initiated around 2012 in Europe. And it took a while to complete because they needed at minimum two years of follow-up. So things have changed since then. We have better refined our POEM technique. And that leads me to the comparison of POEM with Heller myotomy with door fundoplication. Just as a reminder, the door fundoplication is anterior plication. And the primary outcome was decrease of the Eckhart score below three at two years. And here is the bottom line. At any particular time point, including at two years, POEM was better than Heller myotomy. Of course, it is statistically significant difference at two years. But you can argue that 83.0 versus 81.7 probably does not make any clinical difference to the patients. When you look at reflux esophagitis, the reflux esophagitis was seen in 44% of the POEM patients, 29% of the Heller myotomy patients. But again, the C and DLA-grade esophagitis was not different in between the POEM group and the Heller group. So yes, you do get more reflux esophagitis as judged by endoscopy. But that esophagitis tends to be of the milder variety. If you look at acid exposure as measured by pH testing, there was no difference in between the two groups. Not every patient in this study got a pH study. They rely on EGD as their primary modality of detecting reflux esophagitis, which obviously has its own limitations. So now coming to the main question that was asked to me to give you a guidance how to individualize management of akalasia. And here I'm going to give you my take on this, which is in a way an expert opinion. And expert opinion has been tarnished, like we want randomized control studies for everything. But expert opinion does play a role. And here is one definition of expert, which is somebody who has succeeded in making decisions and judgments simpler through knowing what to pay attention and what to ignore. And John's talk was wonderful. I truly enjoyed it, because indeed, rather than staying within the fine confines of Chicago 4.0, he gave us his expert opinion of the intricacies and the limitations of these fine confines. Unfortunately, this is another definition of expert. An expert knows more and more about less and less until they know absolutely everything about nothing. So with that in mind, here is my expert opinion on how to individualize the approach to patient with akalasia. POEM, I can safely say at this point, is a guideline-supported first-line therapy for akalasia, and it is the primary modality for most patients. It is specifically beneficial for patients with type 3 akalasia or jackhammer esophagus, because you can make a longer myotomy, and most importantly, you can tailor the length of the myotomy to the length of the spastic segment. It is also the therapy of choice of patients with prior upper abdominal surgeries, prior fundoplications, prior obesity surgery, such as royal white gastric bypass, or any surgery that may have caused scarring in the area of the upper abdomen, and certainly makes sense for morbidly obese, because laparoscopic approach may be more difficult to the lower esophageal sphincter in these patients. And then we have Heller myotomy. I am starting with patients unwilling to take PPI, and this was covered already in the panel discussion, but despite our best evidence pointing against any detrimental effects from long-term PPI use, the patients come routinely to us with the impression that humanity will be extinct because of PPI overuse. And they will absolutely not take PPI, even in the face of well-documented peptic strictures or bad great deesophagitis, because of various badness associated with PPI, the latest being that of course, you're more likely to get COVID if you're taking PPI. There are studies that have pointed to that association. But I talk with the patient because if they're not willing to get PPI and they develop postmyotomy reflux, then you may have a patient that is very difficult to manage after PON. Patients with gastroparesis, my anecdotal experience is that they don't do well with the PON because of the obvious connection in between delayed gastric emphysema and worse gastroesophageal reflux. And I'm putting the morbidly obese category here as well, because yeah, the surgery may be more difficult, but on the other hand, morbidly obese people are more prone to develop reflux. So it's kind of like one of those, do we do PON on those or do we do laparoscopic heller myotomy? And then pneumatic dilation, by the way, as you can see, I cannot make my mind where to put the morbidly obese category. I have listed them everywhere. And this will be a good point to discuss during our panel. But certainly in older patients, I tend to favor that or in patients that have recurrent symptoms after heller myotomy or PON, although you can certainly redo both the heller myotomy and the PON. Pneumatic dilation then comes into play as one of the primary modalities. And then finally, you have Botox. Patients with severe comorbidities, I mean, we have patients referred for PON with pulmonary artery pressures of 70 millimeters of mercury and putting them through roughly what is a one hour procedure under general anesthesia, probably not a good idea. Patients that are unable to stop anticoagulation fresh after a stroke or placement of cardiac stent, there is nothing wrong to give them Botox to buy some time. Advanced age and in pregnant women that happen to be diagnosed with achalasia during pregnancy, again, you can tread some water until some more definitive therapy can be applied after delivery. Because certainly the PON expertise tends to be on the gastroenterology side and heller myotomy is clearly on the surgical side, we tend to run into this problem, which is that if you have a hammer, everything looks like nails to you. Because I have the PON expertise, I have tried very hard to guard against this and I will share with you the category of patients which I am very careful and thoughtful whether to do PON or not. I already mentioned patients that are unwilling to take a long-term PPI. Data vary, depends on the modality used to how evaluate postmyotomy reflux, but roughly 40 to 50% of patients after PON will have some degree of reflux and the vast majority of that responds beautifully to lifestyle modifications and PPI, but that means they have to take the PPI. I already mentioned gastroparesis and now I've been doing PON for about 11, 12 years and my totally anecdotal experience is a chronic opioid users. It is a potential category of patients that are hard to manage and I'm talking about the chronic back pain that has been for 10 years on oxycodone and they will never ever stop taking it and it is something that usually contributes to the gastroparesis and I find that maybe in some of those patients, the diagnosis up front may have not been the right one and that esophageal motility disorder was actually opioid effect rather than true achalasia. So if you don't have a true achalasia, obviously the therapy aimed at achalasia may not work. And finally, we had a brief hallway discussion about CYP2C19 ultrarapid metabolizers. This is the enzyme that is responsible to PPI metabolism and ultrarapid metabolizer clear it very quickly from the system and they are less responsive to PPI. But we have had a series of patients that did not respond to PPI, then we checked it and in those we had to tailor the management of the PPI. Usually switching to robeprazole, it was nicely shown that that is the most potent PPI and sometimes switch to three times a day PPI management and in two cases do a anti-reflux type of surgery in the form of Roux-en-Y gastric bypass configuration. To summarize, POEM is becoming the preferred first-line therapy for achalasia but GERD after POEM does occur, most patients can be managed with lifestyle modifications and PPI, ongoing POEM techniques are still happening and we are trying to refine our approach. We were discussing with John in the hallway that we do need the US data and study of tailored myotomy versus standard myotomy and there is some new management strategies such as FPOEM, which F stands for fundoplication POEM, which is done at the time of the POEM, which I'm not conceptually very in favor of, or TIF after POEM, which to me makes more sense. I mean the main limitation of TIF is the presence of hiatal hernia. If you have achalasia, I mean I'm still to see that patient with achalasia and hiatal hernia, it's an uncommon combination, I guess it does exist, but as a rule patients with achalasia do not have hiatal hernia, which will make them a good candidate for TIF. Some people have done the TIF at the same session as POEM, conceptually I don't buy into that because 50% of the POEM patients may get reflux but 50% do not, which means that if you're doing TIF on everybody, you will be overtreating at least half of your patients. TIF as a second procedure certainly makes sense, we don't have a lot of data on that so that needs to be studied in more detail, but conceptually makes sense. And of course laparoscopic heteromyotomy, pneumatic dilation, and Botox still play an important role in achalasia management. I try to outline specific patients in which I will use those procedures. Thank you.

achalasia

esophagus

treatment options

Botox injections

laparoscopic hellermyotomy