joining us from Italy, live here from Humanitas University. And she's going to speak to us about the fundamentals of evolution of poem as a treatment of choice. Thank you very much, Roberta. And we look forward to hearing your presentation. Thank you for your introduction. And I'm very glad to be part of this course. I'm Roberta Mazzelli, I work in Italy. I'm assistant professor in Humanitas Research Hospital and Humanitas University in Milan, Italy. And today, my talk is about fundamentals and evolution of poem as a treatment of choice. So again, I hope that you're able to see my slides. Yes, I think so. And you know that everything started in 2010 when Professor Inoue from Japan, from Tokyo, he published this paper on parole endoscopic myodamy for esophageal akalasia. And from that point, a real revolution has become because now we are talking about the so-called third space. So if we assume that our endoluminal side is the first space and the second space is everything that is outside, I mean, the peritoneum or in the thorax, in the surgical point of view, I say that everything that is in between in the submucosa and in the muscle, we can call it a new space that we are creating that is the so-called third space. And this is why we are assisting as an evolution because what Professor Inoue thought even reading also some other papers, as for example, the one from Professor Padrica, is that we can use this new space, the third space as a working space to do something on the muscle layer. And this is why we are entering in the third space to cut the muscle for the myodamy, for the esophageal side, for the poem, but also for other type of treatment. So from that point of view, we started talking in naturally about this new technique and this new procedure that is the poem. Nowadays, we know a lot of things. And in my presentation, I will try to go through all the results that we have from different point of view. But nowadays we know that the procedure is really standardized and we have four main steps. I know that during this course, you will be able to try all of them and to go deeply in details about all of them. But basically, we inject the salmucosa to create a bump and to enter while making the mucosal incision to enter into the space. And then we dissect the salmucosa through the gastric side in the so-called tunneling, in the tunnel. And then we use this tunnel as a working space to make the myodamy and to cut the muscle. And finally, we close our entrance by clipping or with other method that we'll see later on. We have different techniques and different method. So from 2010, we really had this poem revolution, just typing on PubMed, the two words of poem and accalasia. You can see here how many papers has been published throughout the years. It is up to 2020 and then 21 and 22 also, we have a very lot of paper. And with this third space revolution now, we know that we can use that working space for different diseases. So depending on the disease we are trying to treat, we have different procedural acronyms. So the esophageal poem, the standard poem is for accalasia, but then we can use it also to remove subepithelial tumors for the steroid poem, different acronyms, but also on the gastric side for refractory gastroparesis. It has been described also for zinc diverticulum, with the Z poem or POES, but also for other diseases, like for example, esophageal stricture. But let's focus on esophageal poems on the standard poem, because this is the focus of this course. So we know now that we have a standardized procedure that has been done, and this usually done under general anesthesia, in prone position with CO2, and mainly we have two needles that are mainly used, the TT knife or the hybrid knife. But the main important thing is that we have two approaches, two different approaches that can be done. One is the anterior approach, and the other one is the posterior approach. So the anterior one is when you make the first mucosal incision in, let's say from 12 to 3 p.m. or three o'clock, or the posterior one from six to nine o'clock, more or less. And then the other thing is that we can do with a partially, so limited to circular layer myotomy, or a full thickness myotomy. Let's go ahead. I had a chat box because I'm not able to hear you, so they need to chat and to understand if you can hear me, and they say that everything is perfect, so I will proceed. So let's see briefly one video about a standard poem. This is an achillesic esophagus. So after cleaning all the esophagus, this is an anterior poem. Nowadays, I always also do posterior. So after the first injection via standard needle, the injection is made with saline usually, with methylene blue or indigo carmine to always remember which one is the layer we are cutting on. And then here I'm using an ivory knife T-type to make the longitudinal mucosal incision, and to step-by-step get the access, cutting and dissecting the submucosa to get the access to the third space. And see, I have to, and you have to face the muscle because later on will be your target. So differently from esophageal ESD, you have not to cut really in the middle of the submucosa to prevent damage on the muscle and on the mucosa, but here, one of the trick is to be very close and to cut very close to the muscle side, because again, later on, it will be our target. So sometimes it's good to come back in the luminal view in the first space to check if the target is there. If the tunnel is going properly right and straight, if we had make any mucosotomy accidentally, and then when your tunnel, that is just the working space is done and you are sure that you arrived to the gastric side, you have some landmarks, and I know that in this course you will go through all of them. You will be able to use the same knife or a different knife. I use again the T-type ivory knife to selectively cut the circular muscle and the space you have. It's very nice, but it's depending on the tunnel you made before. And step by step, you will arrive in this way to the gastric side. Always take care of your hemostasis and the vessels. And once you arrive in the gastric side, in the cardiac side, you will find much more vessel than what you have in the esophageal one. So every single bleeding spot you have and every single vessel you see, you should go there and selectively try to coagulate to prevent any further complication. So at the end, you will have a very nice myotomy, as in this case, that is almost full thickness, because most of the time, even if you want to go for selective myotomy, the muscle, the longitudinal muscle, just passing with your scope will open a bit. And finally, you will close your incision, your first incision, your gap, with some clips or with other techniques. The important thing is that you have a very secure closure of the gap, because otherwise, there will be a perforation. And the procedure is done. This is a standard procedure. And then let's go through all the data that finally we have in literature and we can learn from them. So we're not talking about indication that POEM was originally proposed just for type 1 and type 2 uncomplicated akalasia. The fact is that, step-by-step, our knowledge were growing, but also our experience. So I mean, nowadays, we have some extended indication. So we can also move to type 3 akalasia, semi-desophagus, but also failure of elder door myotomy, in pediatric patient, and also some other esophageal motor disorders. So if we also look at the NOSCAR white paper, now we know that we can go for all type of akalasia. And if we go for results, we have more than 82% of clinical success in all the center that was rated for this paper. And all together, the success can range from 92 to 97%. So starting from this point, we know that this procedure is successful, but it's not enough. So we have to compare with what was the gold standard until now, that is the Heller myotomy, and also with the pneumatic dilation. So we also have some papers talking and showing the results about this. So let's go through the clinical and functional results. The first one is the comparison, as I was saying, with POEM and laparoscopic Heller's myotomy. This is a review of all the randomized control trial that was comparing, and they were able to collect more than 200 patients. And at two years, so we're starting also having some medium and long-term results, we see that the clinical success was 83% for POEM and 81.7% for Heller myotomy. And focusing on adverse events, there were 2.7% in the POEM group and 7.3% in laparoscopic Heller myotomy. And what's about esophagitis, because you know what they used to say, that POEM is less effective in a functional point of view for reflux, because we are not able to add any antireflux procedure, but we are just cutting the muscle, while the surgeon is able to do the myotomy and then to do the door from duplication, so to have something to prevent the reflux. The fact is that if we look at the esophagitis at 24 months, it means two years, it's true that it's 44% in POEM group and 29% in laparoscopic Heller group. And this is a little bit shocking to me now, because I was expecting then the rate in the laparoscopic Heller group was around, now let me say zero, because zero in medicine does not exist, but less than 5%, and this is 29. So it means that if still the gold standard is the laparoscopic Heller myotomy, this procedure is not effective 100%. So maybe POEM can be much more effective, but let's see the results. And if we look at the high grade esophagitis that mean Los Angeles grade C and D, it was observed only in 5% in the POEM group and 6% in Heller group. So even this one has been taken into account. And let's compare also not only to laparoscopic Heller, but also to pneumatic dilation. This is a systematic review and meta-analysis with 900 patients. So a lot of patients are very big series, and the results is that POEM and Heller are equally effective. No differences in this series in POEM's POEM reflux, and PD is less effective, but we must be honest, leads to fewer adverse events than POEM, because it's a very simple procedure compared to POEM. POEM is a endoscopic surgical procedure, while PD is a very simple pneumatic dilation done ambulatory. And let's focus also about safety. This is one of the biggest series we can find in literature is more than 3,000 patients, and they have found 8.2% of all adverse events, so all together, taking all together. Then we can differentiate in between mild, moderate, or severe. But what I want to underline here with these slides is that finally we have some predictors of adverse events. They are mainly two. So air insufflation, so this is from a technical point of view, we should not perform POEM under air insufflation, but only using CO2. And then the mucosal injury, and this is again a technical point of view because it depends on our skillness, or sometimes it also depends on the easiness or not that we found during the procedure. And also I want to underline the third one, that is the long operation time, more than 60 minutes. And this is what I usually take into account also during training. So with my fellows, I look at the clock and I don't want that the procedure will be longer than 60 minutes. So we have really to focus on these three. Finally, we're having also some long-term outcomes about efficacy and also functional efficacy. In this paper, with the media follow-up of 30 months, they were collecting more than 600 patient with a very few patient lost to follow-up, less than 2%. And more or less 50% of them, they had prior treatment. And if we look at the Kepler-Meyer at three, five, and seven years, it were 96, 92, and 91% of success. The, let me say, is one of the highest that we have with a surgical endoscopic procedure. So the poem is working. It's working from a clinical point of view, and also the post-operative reflux is really well-controlled, and it's not less, it's a little bit more, but not less than the Heller myotomy one. And focus on GERD and barrettes, because you know that one of the long-term complication of GERD is the barrette esophagus. We see that pH study tend to normalize over time, maybe because we are dissecting from inside. Going inside the tunnel, it means that we are not making any dissection just around the cardiac, and we have some other, some other structure that are responsible of the reflux, and we are not cutting them. That is what the surgeon is doing to arrive at that area. And also that PPI use is high more than two-thirds, but leads to symptom post-stroke. So it's simple to control that GERD that we can have after poem. Focusing on barrettes, to date in literature, I found just seven case of post-poem barrette esophagus. One was an intramucosal adenocarcinoma after four years. One was a non-displastic barrette esophagus after five years. And then five cases of non-displastic short barrette ranging from two to 60 years after the procedure. And also it has been described some strictures after poem, but there are very few patients, less than 1%, and not immediately, but ranging from three to 60 years. And all of them, they responded well to dilation and also PPI again. So we started from classical akalasia, but now we know that poem can be used also for other non-akalasia disorder, like for example, the esophagogastric junction outflow obstruction. This was the first multicenter pilot study collecting, and we were part of this series, collecting 55 patients with a median follow-up of 110 days. And also here, although it was not a classic akalasia, the clinical success was 94%. So again, very, very high. But still we need some long-term data. Also for spastic disorder, and this is again a systematic review and meta-analysis. And again, here, the clinical success is around 90%. So again, very high. Some retrospective study about jackhammer esophagus in 10 cases or in other 15 cases, and taking all together the results, they are showing that is almost as effective as in akalasia. But then we can also add something new, like for example, the endoflip, that maybe will help us in understanding the sensibility of that area that we are trying to treat, and use inside the tunnel during, inside the procedure. I mean, during the procedure, maybe it will help us with the cross-sectional area and also with the distancibility index to predict and to understand if our myotomy is enough or not, or if we are making not enough long myotomy. We are having results also in different target patient, like for example, patient taking antithrombotics or anticoagulants. And also we are finally having some new perspective on what is going after the POEM. I mean, for example, sometimes when you scope the patient years after POEM, you can try this type of ulcer at the esophagogastric junction. That is not really correlated with the symptoms of the patient, and it's not correlated with esophagitis, it's just one single ulcer. And they used to call it a solidary ischemic ulcer. And because it's not correlated most of the time with a pH study that is negative, maybe this can be explained as a significant percentage of negative pH study associated with falsely positive esophagogastric diagnostic. And also it has been reported the so-called blown out myotomy. That is when the relaxation and the very distensibility of the lower third of the esophagus after the myotomy, not only in POEM, but also after Heller, can have this type of radiogram, is a blowout myotomy segment, is an outpatching more than 50% increase in esophageal diameter. And if we compare the two, POEM and laparoscopic, is even more common after laparoscopic Heller than POEM. So it's something that we have to think about and we have to explain a little bit more, but we are going really deeply in this procedure and is what is happening on the patient after the procedure. From the beginning, they try to, after the standard indication to perform POEM also after failed Heller myotomy. And we know that they are very good clinical results up to 90%, but also POEM after POEM. So we must be honest and we know that sometimes the POEM is not working very few times. We don't know still exactly in which patient. So we need further study to understand what is the exact patient that probably will not respond to our treatment. But even in case of POEM phase, we have a lot of different treatment that we can propose to the patient. So again, a rePOEM or a laparoscopic Heller myotomy in case is the case that one, or also the pneumatic dilation. And at 10 months, the most effective treatment was the repeat POEM with a 76% of clinical success. It has been described from a technical point of view also the underwater POEM, mainly and first described by Professor B. Mohler in 2016. We have only a few reports in the literature. And if we guess why we should go for underwater also for POEM, maybe because we are expecting to reduce free air related adverse events. We said that using air is not good for POEM. We should go for CO2, but if the case of a longer procedure, maybe this one can prevent all those effects related to the gas we are inflating. And in case of we have a very spastic esophageal contraction, maybe this type of technique can provide more stability during tunneling, but also during myotomy. And I want to show you just a very small video about this male of 45 years old with a type three akalasia that we've done in our unit. And you see that the vision is wonderful. We must be honest and the stability also because the water can let your scope stay exactly where you want. The fact is that we know that underwater, even with the ESD underwater, the current is not working properly. So we have to adjust the setting of our electrosurgical unit. But step-by-step we can perform the procedure in this way. Also bleeding underwater is much better because for the compression of the water itself, the bleeding is not so severe and you are able to control it in an easier way than usual. And in this way, you can go along with all the procedure. Just very few words, I'm almost at the end of my presentation because we are talking about poem revolution and terse-based revolution. Starting from poem, we can use the same approach also for Zenker diverticulum, starting from the classical septotomy, going through making the mucosal incision, just above the Zenker diverticulum and to create a tunnel to face the muscle and then later on to cut the muscle. But also, as I was mentioned, also from the gastric side for the so-called G-poem that has been introduced the first time in 2013 by Dr. Kashchab. And they said from that time that in very expert hands is safe with good clinical early results. And we are still waiting. We are having some, but we're still waiting for the perfect target for this type of patient. And also for long-term results. So in conclusion, focusing again only on the Z-poem, we have now a lot of data, huge amount of data from different point of view, from clinical, functional, and also long-term results. And for this reason, we can assume that is the gold standard right now. But focusing on long-term outcomes, we still need to understand and to identify failure predictive factors. And also regarding the postpone, let me say much ado about nothing because data show easy symptomatic control with PPI, lower rates of barotrauma esophagus, and also lower rate of stricture rate. Focusing on how to avoid failure, maybe we need a health, like for example, the FLIP. And regarding those patients that they are failure after poem, we do poem is an option, but still we need a standard design approach to be on pneumatic dilation. And with this one, I thank you.

Roberta Mazzelli

poem

peroral endoscopic myotomy

advancements

esophageal disorders

underwater poem technique