Now we go outside of the GI lumen, and Dr. Dennis Yang is going to teach us the poem alphabet. Dennis is at AdventHealth Orlando. Welcome Dennis. Thank you everyone. Thank you Peter, James, and Alisma for having me today. It's my pleasure to give this talk. So when I think about the poem alphabet, I think about all the letters that have emerged since the evolution of poems. So it kind of reminded me of the subway system in New York City with all its numbers and letters and how I had to learn these when I was living there, and therefore the reason for this caption. These are my disclosures. So let's start with the letter E because that's where it all starts, right? So esophageal poem is considered the prototype procedure that was launched by Dr. Noh into clinical practice approximately 12 years ago now, and it's probably the most successful clinical third space procedure that we have up to date. And the reason for that is because it's perhaps the first procedure that truly validated the concept that the submucosa can be safely accessed and used as a working space in this particular scenario to access the esophageal muscle to perform esophageal myotomy and thereby treat patient esophageal dysmotility. So since the introduction of poem, there's been multiple centers across the globe that continue to document the response rate to poem, often defined with clinical success with an Ecker score of three or less. As you can see from this table, the sustained clinical response is fairly good, even up to 10 years out, ranging anywhere between 80 to 95%. So in aggregate, this data continues to support the efficacy of poem, and it also helps us put things into perspective into a framework when discussing outcomes with our patients. But in addition to these observational studies, we also have high-quality studies that compare poem with other established treatment modalities. Randomized trial demonstrated superior treatment success of poem when compared to pneumatic balloon dilation, and a subsequent randomized trial demonstrated that poem was associated with similar clinical success when compared to surgical myotomy. And it's because of all this data that in 2022, poem is no longer an experimental procedure, but rather a standard of care for many patients, and in some cases, even the first-line treatments such as those with spastic achalasia. But certainly over recent years, there's been increasing focus on the incidence of post-poem reflux, and rightfully so. But what we need to remember is that reflux is not an adverse event, but it's a byproduct of any procedure that adequately ablates at the lower esophageal sphincter. So we know that reflux esophagitis can be commonly found in these patients, but most of these cases are mild and adequately managed with PPI. The rates of severe esophagitis are generally in the low single digits and not different from those with surgical myotomy. Abnormal acid exposure, again, it's common, but it's not that different from surgical myotomy. And unlike surgery, recent data have suggested that this actually may decrease over time, perhaps due to remodeling at the LES. Importantly, we need to remember that not all episodes of reflux in these patients are actually due to acid reflux. It requires a comprehensive assessment because many of these patients may have simply stasis in the esophagus with fermentation of food or visceral hypersensitivity that may be attributed to acid reflux. Now even though POEM is the standard of care nowadays, many questions still remain, center around how can we continue to optimize efficacy while mitigating the risk of reflux. Questions still remain whether an anterior-posterior approach is better, the optimal length of the myotomy with recent data suggesting that surgery, a shorter myotomy may be equivalent. And then there's the question of selective versus full thickness myotomy. And therefore, there's been increasing interest of tools that we can use in real time to perhaps assess the adequacy of the myotomy. One of these is the endoflip procedure or impedance planimetry, which allows us to assess the physiological changes at the LES while performing the actual myotomy. And the idea is that this may potentially help guide us on the extent of the myotomy and whether this is adequate or not. So now let's jump from the E to the G. G stands for GPOEM, and GPOEM was introduced by Dr. Kashab and colleagues in 2013 as a pyloric directed treatment for patients with medically refractory gastroparesis. It follows the same principles as esophageal POEM, where a mucosal incision is made in the antrum. We then tunnel until the pyloric rim is identified. Then we perform the pyloric myotomy followed by closure. And here's just a video demonstrating the actual therapeutic portion of the procedure, which is the pyloric myotomy. There's the pyloric ring in this particular case. We're using the insulated tip type of ESD knife in order to protect the duodenal side beyond the pylorus. So again, just like any emergent technology, since the introduction of GPOEM, there's been multiple observational studies reporting on clinical outcomes with this technique. This systematic review meta-analysis, they included 10 studies in nearly 500 patients with a one-year follow-up, demonstrated that clinical success, which was defined by an improvement in gastroparesis cardinal symptom index, was 61%. So I don't have to highlight that the response is okay, but certainly not as impressive or robust as compared to esophageal POEM, which leads us to the next question of why is this the case? And the answer may be relatively evident in the setting that gastroparesis is a heterogeneous condition with a complex pathophysiology that's poorly understood. So there's an interplay of multiple factors here, including an overlap with functional disorders. As you can see from this slide, pyloric dysfunction may only represent a small subset of these patients. So if we were to think about comparing esophageal POEM to GPOEM, it's like comparing apples to oranges because we're dealing with completely different diseases. Gastroparesis is not a well-defined disorder, as I previously mentioned, and we don't even have a very validated, accurate test to measure the abnormality at target. And importantly, prior therapies aimed at this target, including Botox injections, have had very mixed results. So when thinking about how can we improve treatment outcomes, perhaps it's not that much about the technique, but rather how can we continue to improve better patient identification to determine who may really actually benefit from this procedure. But not everything is grim. We did have a pylor-randomized sham control trial just published in Gut, in which this study was stopped at interim analysis because it showed an overwhelmingly superior clinical response with GPOEM when compared to sham control, with also improvement gastric emptying those patients that underwent GPOEM. Now certainly this is very reassuring data, but it's a very small study, and more importantly, it has a very short follow-up period, and thereby we need further studies to corroborate this. Now in conclusion, we know that we still need more data for GPOEM. We do have the ACG clinical guidelines published this year on gastroparesis, in which they suggest that there may be a role for endoflip to evaluate pyloric function. They recommend against intrapyloric Botox injection, which is still commonly done, but remember, randomized control tries have not shown this to be effective, and they do suggest pylori myotomy over no treatment. Importantly, I think one of the key aspects when performing GPOEM is to discuss these treatments with your patients in order to set expectations as well with the referring physicians. At our institution, we routinely perform endoflip before and after the pylori myotomy in order, again, to try to identify the physiological changes of the pylorus in a more objective manner and hopefully identify potential factors that may help us better elucidate which ones may actually improve with this procedure. So last letter of the alphabet, Z. Z standing for Zanker's diverticulum, which is an outpouching of the mucosa and submucosa in an area of weakness between the curriculopharyngeal muscle and the inferior constrictors. We know that transfocal surgery is effective, but this is rarely done nowadays given the high morbidity. Rigid endoscopic diverticulotomy as performed by our ENT colleagues, it can be much safer, but it can be technically challenging with small diverticulite and associated with a risk for incomplete myotomy. Importantly, the success of this procedure largely also depends on the patient's ability to actually open their mouth wide enough and to extend their neck in order to allow these rigid instruments for fitting in. So as a result of that, there's been an increasing interest of endoscopic therapies for Zanker's diverticulum and it basically is divided in two broad categories. One of them is performing an endoscopic diverticulotomy or basically a septotomy versus the tunneling type of techniques such as Z-POM. So with septotomy, you basically use a ESD type of knife and you cut the septum that separates the diverticulum from the esophageal lumen. With the Z-POM technique, a mucosal bleb is formed proximal to the septum and then you tunnel your way, perform the myotomy, and followed by mucosal incision closure. So now there's definitely pros and cons between both of these procedures. With septotomy, it's a much technically simpler procedure, shorter procedural time. The knock on this procedure is the potential risk for incomplete septotomy as the risk of perforation increases as you start reaching the fundus of that diverticulum. On the other hand, with Z-POM, the theoretical advantage is you can perform a full septotomy with no regard because you still have that mucosal flap above the myotomy site that you can adequately close. There's not a whole lot of data comparing these two techniques. This was a multicenter retrospective study of about 250 patients that they compared Z-POM, flexible septotomy, as well as rigid septotomy. As you can see from the highlighted portions, clinical success was similar between Z-POM, flexible septotomy, although bear in mind these numbers are not very large, and I don't think the study was powered to necessarily detect a difference. But what is interesting and highlighted is that the adverse events were higher with Z-POM compared to flexible septotomy. So as a result of that, nowadays there's been increasing interest in modified techniques for Z-POM. Many people are performing this technique, which is simply instead of doing the tunneling, you inject directly over the septum and you go ahead and perform the mucosal incision over the septum. Following this, you're going to start dissecting the submucosa around that muscular septum to isolate it, and you're going to continue doing so until you reach the fundus of the diverticulum. And given that you're using a tunneling technique, then you can go ahead and perform a septotomy all the way to the base. In this particular case, I believe I used a different type of knife, but nowadays you can probably do the entire procedure just using one single knife. But there's ongoing modifications to this technique. I know Dr. Dragunov recently introduced a technique, a non-injection type of Z-POM where you simply use this scissor type of knife to make the initial mucosal incision and dissect with the scissor into the tunnel without having to inject. And I've tried it a couple times and it appears to be quite effective. So then now you have the potpourri of letters, the C, P, and R, and I'll just briefly touch upon these because they are limited to only a few case reports and case series. So one of them is using POM techniques for the management of cricopharyngeal bars. This was a retrospective study. As you see, only 27 patients with high technical and clinical success. I do want to highlight that cricopharyngeal bars are a common incidental radiological finding. So just because a patient has dysphagia, has a cricopharyngeal bar, it doesn't mean they need a therapy for this. You need to do a more in-depth evaluation to determine if that's the cause of their symptoms before committing them to some type of procedure like this. The poetry technique was introduced by Dr. Mihirwag and Dr. Dragunov a few years ago and it's a nice way of dealing with refractory strictures. The idea is that you can use POM tunneling techniques to tunnel and dissect your way through this long stricture. And with the assistance of a rendezvous second scope through a PECT tube, you can identify the lumen, then go ahead and place a wire and put a stent through it in order to recantilize that esophagus. And then there's some data, again, looking now at peri-rectal endoscopic myotomy for Hirschsprung's disease, again, limited primarily to a few case reports and case series. So in summary, what have I learned or what have we learned about POM since its introduction by Dr. Inoue? So it must be these two are the main points, which is what other potential sphincter can I possibly try to cut by a tunneling technique? And the other one is what letter can I use for my new POM procedure as many of them have already been taken? You know, we can all say, including myself, that we get excited when there's new procedures and rightfully so. That's what we do. But remember that small observational studies will invariably exaggerate treatment effects and minimize adverse events. So when I look at this, I think of back when I was in York City doing the subway. The last thing you want to do is to jump on the wrong letter or the wrong number because that train is going to lead you astray. So similar when it comes to POM procedure, you want to proceed with cautious optimism and have a map before you undertake this. So esophageal POM, we can say nowadays, is a mid- to long-term effective guideline-endorsed therapy for achalasia. G-POM is safe and technically feasible, but we need more high-quality evidence to suggest which patients may benefit. Z-POM and other endoscopic therapies for Zenkers have become primary modality. But again, we need more data, primarily longer-term data, because what we're interested in is to identify which patients will recur. And again, POM-based applications continue to emerge and evolve. And then my last tip to anybody who's training in POM is to just remember your alphabet. Remember always start with procedures with well-defined indications. And remember that esophageal POM comes before the other letters. Thank you.

Peroral Endoscopic Myotomy

esophageal dysmotility

surgical myotomy

Gastric Peroral Endoscopic Myotomy

medically refractory gastroparesis