In this lecture, Stavros Stavropoulos, MD, compares the POEM vs Heller approach in the treatment of achalasia citing recent clinical data and case examples.
Okay. Welcome back. We're going. Thio, proceed with a poem Lecture on Ben. You know, the next case will be the full thickness resection. And then there is the lecture on Then the colony is day. So we're gonna talk about Caroline. This coming mountain again with a focus on the big debate with color reflects what to do about it. Onda, like eso. Let's start. Obviously this is basic stuff. But rural that's going madam is really a note's version off the Heller, My auto me using a tunnel to secure absence of leak Onda First one was done by new it in 2008. We presented at the DW April of 2019, 2009 and six months later we did the first one outside of Japan and now we have the largest, still the largest single center public. Siri's, I believe we published in the I in 2017 with 318 poems with a particular subset comparing the 48 post Heller patients with 270 without prior Heller. But this is still I think the largest single center Western Siri's were about toe. Submit now our update on that with 610 poems followed for 10 years. And this is where I'm gonna be drawing the data from for this presentation. Largely. So there are technique has remained relatively stable in the past few years, meaning that we go posterior early. Um, at around five o'clock, if the spine is at six on the hybrid knife again Thio Thio, enter the tunnel. This is also type three patients. This case is from 2013 actually has two years of video because, as I said, the technique has remained very similar. So we are, Yeah, we are complete a very long tunnel using the hybrid knife as you saw today. And then we are We do the posterior my autumn e full thickness even since 2013 on. Then, after completion of this long tunnel down to the Saros A and the media Stan upload, I would try not to injure this membranes. Then, um, see, at the top, we did live a few longitudinal fibers. It doesn't matter then Then we we suitor if you want to see more poems that, uh, seven years of Long Island lives archived. There are three poems every year one by me, one by Louis on one by Joe with all our particularities demonstrated and also demonstrates how each of us change the technique over the past seven years. And it includes generally challenging patients apart from type threes, post Heller, pediatric patients, jackhammer and state sigmoid patients, etcetera. So good, uh, good cases that a lot of people starting have used Thio get themselves into Poland now. As I said, I'll talk about our Siri's things is an interesting slide that shows our case accumulation. Initially from 19 4011. 2 years we did about 15, but then it rapidly took off 2012, 13 14. Then we hit a stall from 2014 to about 2017. We hit a bit of a stall because of insurance denials that started in 2014, fueled also by resistance by Heller Surgeons. In fact, a lot off a lot off a lot off prettier with Okay, uh, this is gay. Annoying. Can you tell them Sorry about the dot com. Um so basically a lot of the peer reviewers in the U. S. That insurance is used when you appeal, are surgeons. Many, not even surgeons, have any relation to Heller, Like bariatric surgeons and my insurgents or even Thor ASIC surgeons and Alexa. They have Ah, a lot of them have a poem of version. So we got the stall. In fact, fact, we backtracked a little, but then in 2017, we broke through. I think that people started. Most insurance companies started getting the message, but now we have a police, maybe 15% denials. And with careful appeals, we win most of them. So it has. In the same period, technique has evolved. I mean, our technique really hasn't stayed extremely constant in its details for this period. So, for example, the length of my autumn E all experts centers, um, had to realize that we're we're doing too long. My autumn is now Interestingly, when we started very, very early, I was following in new is lead in doing 3 to 5 centimeter my autumn ease because of fear, mainly of extending into the media Steinem. Once it proved safe, I think we all got a bit trigger happy and moved up to 10, 11, 12, 13. If you look, most of these had I mean my autumn is in the 11 to 13 range, but then right around poem 250 a few years back realized that maybe too much. We started cutting down, down, down. And I were model in the 5 to 6 centimeter range for at least the last 100. 200 poems on Ben. What about the rial learning curve of problem? Now, with all these cases, it has gotten very, very easy to do. A detailed analysis of the operators learning er so you can see if you use poem duration as a surrogate marker for operator um, experience and learning. You can see the multiple so called plateaus, which shows what the fallacy off just using, say, the first plateau. You see, after you've done 50 poems to declare victory. So you can see here like we had a plateau at about 100 cases, uh, almost 1.5 to 2 hours for a poem. Then it sort of plateau that 300 or so cases to something like just over a now, er or an hour. And now we are routinely in the 20 minutes to a half hour range, and it doesn't because we are rushing. It's because you get very efficient at how to deal with things and you get faster and faster naturally, so you can see there are many plateaus here. So just using one initial plateau say up here as the end all it doesn't make any sense, and this is what happened. So there were published learning thresholds from, say, Hopkins, Northwestern and Portland, Oregon, when they had only done 36 to 40 cases. Obviously, if your whole cohort disturbing for the cases, what kind of learning threshold are you gonna find something less than that by necessity? Hopkins, I think, was 13 cases as a threshold. But you know, if it takes 250 cases to get competent at ERCP, I really don't know how 13 cases will make a comment in the poem, especially if you don't do a lot of the S. D. S on the Northwestern. Portland was also in the 20 Case range, but again, it's a bit of a fallacy now. We published in 2015, Ah, 60 cases, um, for proficiency somewhere there, where you can see probably the first plateau happened, this one at about 1.5 hours. In fact, Arm Indian procedure time then was, I think, 70 minutes. So it was really the first plateau. Then, interestingly, the most. The operator with highest poem volume in the world. Um uh, Ping Kong Draw and Sungai published 100 cases as the threshold, which again appears reasonable, at least for competence or proficiency. So, interestingly, the centers with the biggest volumes would publish the higher thresholds and the patient. The centers that had accumulated lower volumes were published in lower numbers, which doesn't make any sense because high volume centers would, you know, go through the learning curve faster, presumably for various reasons anyway. So you can see you know, there's constant learning. I mean, now this is a really plateau I don't think you can. There's any way you can get the poem, uh, to a less than 20 to 30 minutes on average. Now, the another way to look at the learning curve is to look at the mucosal injury rate. But this has its up and down, as you see here, and I'll tell you what happened so very quickly. Within 100 cases to 150 them because all injuries dropped to near zero. But then what happened? We started going up again, and that's because we started our anterior posterior randomized trial with 250 cases. So right about 1 50 to 200 to about for 50 or so was the anterior posterior retrial. And clearly, Interior Poem has a higher rate of mucosal injuries and posterior poem. Other studies than our own, including the random myself from India, has shown this. And it's it makes sense because of the mechanics of getting into the car, the interior early versus posterior early so you can see there was a bit of a bump on the road. But then, once we got good at it, dropped again because we got good at the interior poem, it dropped again. But now we're back to our posterior ways, and it's now has been zero for the last 100 poems. So it's Ah, there's a learning curve there, too, and it's not 23 cases or 18 cases. It's more like 100 200 whatever. Not sure what this was showing, but okay, all right, so now let's move to the data on the outcomes So again I will draw from our 610 analysis that includes all the poems I did consecutive poems from my very first in October 2009 until October 2019. So £610 we submitted this, by the way. I did a double in 2020 and it was selected as a poster so meaningful up 35 months. Mean AIDS much older than the Agent Siri's that the men ages in the thirties like in the Sungai Siri's. I think it's 38 55 Western Siri's much older patients, 11% older than 82% older than 90. You can see the B. M. I will get obese patients, even the Cal Asia Group in America beyond my more than 30 a quarter of the serious slightly more than a quarter. And this goes with the old people, Uh, s a class three or four in ah, one third of the patients. So a lot of comparability also duration of disease more than 10 years. This can be very difficult poems slightly over a quarter. So these are highly manipulated patients with dilated the Sophocles and whatnot that also shows on the stage where approximately one out of five where end stage with stigmatization type three, as I said, can be difficult to I put in red basically things that make more and more challenging. So type three accolades. A 16%. The little on the high side. Um Na nach Alicia disorders can be a thorn. As I mentioned in my life case, especially the the Atlas Traction, we have managed to keep it to a minimum, being very selected 4% of our poems where it is the outlawed jackhammer and D s prior treatment. Half of the patients, including 14% Prior Heller, a quarter prior buttocks, fifth pneumatic dilation and 3% failed Heller's mostly from other operators. But a few of our own do a very small number. Now. How does efficacy look long term again? There's no point anymore. Toby looking at three months or six months or even one year studies, it's It's pointless. There's, you know, decent studies with now offering data 234 and five years at least. So if you look at this data, um, you can see basically the 2 to 3 years success rate being in the 78% is in a barren study from three centers are a lot of failures for some reason. But, you know, about, you know, 90 to 100% and 80 to 90% of three years they're not four years, five years. You get to around 80 to 90 now, the two big Siri's that Yokohama in new series with 500 patients in the Sungai Cities with 5 64 had followed problems missing. Follow up in 42% of patients at three years missing. Fall up 37 58% of patients at three and four years. So this couple of my estimates have a lot of error bars around them. Um, and but generally these are the numbers. Also, you are numbers, um, in detail. So this is the in our upcoming publication, the couple admire graph that will have in the submission with you can see here, um, very well maintained success all the way to nine years off close to 90%. So you can see that 1 to 6 years data, um, the rest doesn't make as much sense because at seven years, we have 26 people at risk and the success money was 90%. And then it doesn't really makes any sense to make estimates for six patients and one patient. So if you look at the six year success is 91% on the 64 patients that are over six years old between six and 10, and you can see there's love very slow attrition with data that much better than every Parliament. These are data you can take to the bank. You can see how small the Arabs Barry's because you have. We have only missed 22.3% of follow ups. That doesn't mean we don't have polo fall up into 4.3% of patients. That means that if one patient we missed follow up at three years, but we got follow up at four years. We count these three years as a missed follow up 2.3% includes that so very way, courtesy of Running Rodeo, my collaborator and Maria Kalaris, my nurse. We have even looked at obituaries and every possible source to get full up on every single patient. Now, if you compare type one versus two versus three and we had close to 100 patients that were type three. You can see the type ISS slightly worse, Um, using the record score less than three success criterion. But that can hide some things. For example, the mean of the mean Eckhart score for the type threes is closer to 1.5 to 2, whereas the mean occurred. Scoring the type one than twos is more in the 0 to 1 territory. So the quality of success, even though the success it just looks the same because it's defined within a binary way as a neck guard scored less than three. If you look grand largely at their cards score, there is a bit more of a difference on type threes we know from other treatments are a bit difficult patients. They also have paying some of them that have have issues. Now, what about the Nonaka Leisure patients? The non Ecologist parties disorders that there there's a even bigger difference. And again, this is using the binary criteria. If you look at that catch courses maybe even slightly worse than that so clear, clear difference. Uh, even though we're highly selective on only 4% of our Siri's has these patients. If you look at, uh, I I said what we do with the outflow obstruction and why it's a thorny diagnosis during my life case. So if you look at the Cox regression model for risk factors for failure, the only thing that became significant was the Nonaka Leisure Disorders versus typical local Asia, with a risk of failure of 3.5 times higher history of prior treatment. Learning Curve Type three, Ankle Asia and State versus and non in states, although in positive territory did not except for the estate, did not reach statistical significance. The prior treatment almost reached statistical significance. What about adverse events? This is from our our Siri's. You can see no mortality, obviously no need for surgery or even any I odd range. No leaks, no aborted poems on prolonged hospitalization for more than five days for any reason in the 4%. But this was all mild stuff, requiring a few extra days. Um, that was not significant. Delayed bleeding. As I said, we had some shooter bleeds where the shooter broke and some vessel wasn't adequately synced, and then they had a delayed bleed from the puncture side that just needed clipping. Then what? Two patients? Ah, that had had to be on anti calculation immediately after the poem and then tunnel bleeds without anti coagulation involved. It was one patient on one patient we admitted for food impact Shin and then also over the tunnel where the ulcer bled and no treatment was needed. So this is the 11.1% of the bleeds. As I said, no leaks. There was partial the hit sense off clips when we used to use clips in the beginning of the Siri's off the tunnel that was seen on Second Look and a Scorpion. We but no leak. And we clip that, UM, 0.3% to patients and then 30 day readmission due to poem adverse events or non poem related adverse events. 1.6 and 3.3 again mild staff C dif dehydration. Just pain in type three patients that persisted. Nothing really requiring anything surgery or I R or anything. So now poem obviously looks super safe and looks super effective. But the question is, and obviously it gets easy to do as you learn. So now let's compare it to balloon briefly because balloon is really has been obliterated by poem. And then, obviously, the Heller is the main course off this lecture. So balloon, we have Level one Evidence. The European randomized trial. Uh, interesting. It was initially presented at the double in 2017 and then published in JAMA two years later. But some of the D. D W things disappeared in the publication. I included them here because it's curious. So let's look at success at one year. 95% in the poem, versus 66 in a Balloon. Two years, 92 versus 50 54. So there's there's no comparison. Um, if you look at Type three patients now, this was in the abstract but did not make it in the publication. 83% in the poem, versus 33% the balloon. So the balance as we know worse in type three patients, um, now you may say, Okay, fine. Yeah, we know it works less, but but, you know, it's probably safer than a poem. Not true. Zero severe adverse events in the Palm Group to severe adverse events, including a perforation in the balloon group, which makes sense If you're gonna put a huge balloon and rip the sphincter, sometimes you will love er rip and sometimes you will under rip. And you didn't really have no good way of controlling that in the poem. You can If you know what you're doing, you can cut the muscle and nothing else. So it makes sense. Really. Now, if you look at reflex interesting the other you know, the balance is not a major, um, issue of contention with regards to reflect. But interestingly, at the DW presentation, pH studies at one year 49% positive in the poem group, 39% positivism balloon. So if you do a good balloon ripped, that's finger you should get similar reflects to cutting it with a poem which obviously makes sense. Um, also the girl Q score was reported similar. Now what did make it in the publication interestingly and heart upon in the abstract was the reflexes of anxieties. Interestingly, which shows the biggest difference 41%. Any reflexes for sofa dads versus seven. If you look at severe meaning more than class a 10 vs zero, much less of a difference. You go from 30% points to 10% points. Now this is this I call discussed this caveat. What does it mean? Reflects Asaf anxieties. If you see an answer in a poem on an endoscopy that is done toe two months or three months after a poem, it may not mean reflections of anxieties, but I'll discuss this in more detail. Now this is our data. We have been able to get a good question there in all but two off this. All but one of the 610 patients pretty impressive on thank you to Dr Model um grade to grade three, meaning 2 to 4 times a week reflects, or more than four days a week, reflects was a quarter of the patients. Now, if you look at the pH that the end again courtesy of Dr Model, you have been able to drag back two thirds of our patients for a Bravo and we get a positive study in 57% of those. But we're not adjusting for Stasis and fermentation, and I'll and a T least a third of this positives could be due to fall sports, but I'm going to discuss this in detail now. if you look at reflexes off anxieties again, a caveat there that I will discuss. We have been able to scope endoscope 69% off all patients and reflexes about that. As you can see here was seen in 49% mostly class A 33% and very little class C. And now great D class direct detected. So But again, we have to discuss this, that we do the endoscopy at about three months again. Maybe doing it later would make more sense. Asyl show you. So how do other studies lineup now? These are studies specifically selected, Toby only on Western patients because Asian patients have less reflects all across the board whether a collision Nonaka Lesia any other condition So western Siri's that have tried to collect symptoms. Asaf, a giant This data nph study all three. I think the quality studies you need to look at so if you look at symptoms starting to 28% had positive symptoms. So fat that is 20 to 49% and positive. Ph study 38 to 57%. Um, we have the highest number. But again, uh, this is you know, we are the ones that have done the most testing. I mean, look at these numbers here. Like, for example, the Cleveland Group only tested 36 people. The biggest study would be the cost, Amanda, with 103. So we are very much, and that's interesting shows also high rate of 50%. So maybe the less you test unless you find So what are the caveats here That I was alluding to first symptoms. We know what the problem with doing a symptom questionnaire is. And a lot off centers depend on just a questionnaire. And interestingly and more importantly, ah, lot of the older Heller studies that show very little reflects allegedly dependent on, you know, the surgeon, the surgeons, nurse retrospectively collecting guard symptom questionnaires. Now we know that a massively underrepresented reflects because 50% of patients with objective reflects have no symptoms. This has been shown repeatedly by many studies. And also conversely, you get people would have heartburn chest pain regurgitation on this maybe actually symptoms off. Poor empting and maybe a badly done poem. You know, they can some of the symptoms off local Asia overlap symptoms of reflects and their misinterpreted by patients on but by physicians often. Now, if you look at the rest of esophagitis, there's a number of the problem here. Like look at this. Also here. Okay, right over the five o'clock position off the poem channel. So if you cannot dissect one third of the circumference of the esophagus obliterating all the blood vessels feeding the mucosa, um, this and then you feel the space under them because I would scar tissue. This Mukasa is gonna be susceptible to injury. It's a vulnerable ischemic because a so it wouldn't be surprising if you get a solitary elsewhere there, even with a reflex exposure of 3% or 4% or something minimal. So the whole concept of a resource about that this has to be put in perspective. Now there's no If you start not counting disasters or manipulating them, you could get spurious data. So it's not clear how to distinguish this from that. And that's why p. A s, that these are more important than I think than a Roosevelt's of anxieties, although they do have the potential for error there too. So anyway, so 11 possibility. Also, instead of doing the repeated endoscopic three months or six months, maybe do it in a year and keep the patient on PPS until then. And it's something that we may consider moving to. Um, there is obviously selection bias. If you only test selectively with pH testing or endoscopy patients that are troublemakers and they're complaining clearly you're gonna overestimate girl because you're gonna be testing a group that is enriched for patients that have good. So there's a selection bias. And then finally, when you do a pH study and Steve the Mr When I went to Proctor him in USC in 2012 alerted me to that, obviously is the son of the Tom, the Mr who made the score. I started complaining to him about this big reflect scores and the Mr Scores on the Ph studies I was doing then in 2012. And he said, Well, you know, the Mr Score can be influenced by, um, spaces and fermentation on, and I found out that Mr identified this himself in a publication that I will review. So you have to you have to you have to really look at everything with a critical life. Let me give you an example. This was case number 33 in 2012 is probably one of the cases I was complaining to him about back then, so you can see your total time pH less than 44.7%. Barely a positive study. But look at the look at the reflux episodes. There's really one big one, not those spikes that you see. Usually there is an initial spike, but this asset balls that hangs out for hours while the patient is sleeping. That green area is the supine position, sleeping on the on the journal. So he it's the dinner and then, like right here on the yellow then, as he was told a few hours later, goes to bed and then gets a nasty episode that hangs out for who knows 23 hours, giving immediately a positive that Mr Score and mind you. Most of the time it's It's between three and four. Not really one or two, which is what causes most of them because all injury. So it's ah, you know, basically perhaps an activation that studies that's really the critical factor. Maybe not before, maybe more like three less than three is where you get the rial injury. So if you look at this, um, you're like, Well, okay, how do you correct for that? You know, we try to correct it because I'll show you why. Um, but we encountered the recriminations from off the colleagues. Anyway, So this is this is the problem. If you if you discount anything but the acute episode here, you get because this may be due to fermentation or spaces or both. You get ph less than 41.6% which, obviously no significant reflects. So this is this is this is the asia I'm talking about. So, Tom Mr back in 97 identified this. He did fermentation experiments. Um, and for those of you out there, that will still my slide here, please give me some credit on occasion, because that happens a lot. I have to say so anyway, So he did this fermentation experiments. Looking at pH. Less than four in hey, put food and fermented it at 37 degrees Celsius on the petrol is And that that fermentation on the lactic acid created gotta ph less than four in the third of the samples. Ex vivo Then he used 12 of his Heller patients, 50% of whom had abnormal pH after the Heller. And then he showed, uh, that half of those have had a very slow, steady drift. Opiates less than four, consistent with station fermentation. Like what I showed you on our poem patient. So he said, these are probably false positives that don't mean riel reflects. So maybe the rial reflects is 25%. Then, he said, use off Ph. Three as a threshold. Clearly distinguished this patients from patients with true reflects, since the patients with reflux all had an abnormal percentage of time below Ph. Three. So he said, you should just ph less than three rather than less than four. Um, we did. We did a study to look at that. Okay, So partially in response to me. This is 2016 W intended Double 2015. When I said that, we asked under Mr recommended, we look at our bravos to try to separate stages of fermentation from two reflects. I was accused them, you know, in the middle of a large BTW room while on the podium by Joel Richter of maybe trying to fudge the data. So at that point, you know, I think it's still valuable to do that. But a twist from the point off generalize, generalize ability between studies, maybe we shouldn't correct. So some of the Ph studies I showed you are probably false policies, but we stopped correcting it. But just out of curiosity, we said, What if we use the misters recommended analysis using pH less than three as the threshold instead of ph less than four. How would that work? So we got we had then 117 brothers 91 had been done in our institution, so we had all the road data. So we took the road data on a thumb drive and send them toe Parkman, a temple, obviously a motility and Bravo maven to interpret the road data himself, both with the standard analysis pH less than four. And with the ph less than three analysis and they are normal data published on what's normal for Ph. Less than three. It's about 1.9% of the time. The pH should be less than three. So we did. Based on this normative data and this analysis, we found out that 33% of patients had reflects based on the Ph less than three analysis that Tom that Mr Himself recommended Fraggle Asia. If you use the standard analysis 55% and I show you the data are most recent data so pretty consistent? And what about the So what is right? Well, if you look at because I'll injury with the Roosevelts off anxieties, which one predicted best arose over. So what? That is clearly the pH. Less than three analysis, with three quarters of them having a row service of anxieties. Whereas if you look at the Ph less than for analysis barely, it's a flip of a coin whether this patient will have a Roosevelt's of anxieties. However, as it turns out, convincing companies to introduce an algorithm off Ph. Less than three in the Bravo machine is like asking for the moon on this analysis, although fanciful, is difficult to apply clinically unless you do it manually, like we did it with Henry. So these are These are the caveats there. So let's now that we have a good understanding about the reflex, caveats and issues. Let's look at Heller vs Poem um in terms of GERD. Um, and, you know, efficacy will review this data. So, you know, the surgeons are getting pretty entrenched and combative about this debate, and they come out with teachers like this, you know, it's off a poem. Nice little poem that doesn't mind. By the way, once there was a man with this Vega, his surgeon diagnostic Alicia. He performed the heller. The patient swallowed better. How does this master? I understand because poems cause embarrassment. A pleasure. So, um yeah. So, you know, I also have this desert make Heller great again, Obviously saying of our president, I kid the face of the surgeon here, so he's not embarrassed years from now, when poem has one eso. Now, let's seriously look at data. So what? The lowest evidence, I think is this dirty meta analysis that are popping up like mushrooms everywhere. I think the best done is, um, the repeat C one where they looked at, for example, for ph studies. They tried to do good quality studies that did analysis for publication bias heterogeneity analysis. Very well done. So if you look at poem positive pH studies 39%. If you remove the Iguacu Japanese study because it's heterogeneous in having very low reflects. It goes up to 47%. If you look at Heller Lap Heller again, 16%. But there's a lot of poor studies is corrected for publication bias. By removing the bias studies, it gets to 22%. So either way, there's a riel difference, at least in the first year, off somewhere between 15 to 20%. I would say another meta analysis that I like that there's another meta analysis by Slot Hman, which is a not so well done because it includes hundreds. I think off, if I remember correctly. Akhil Asia Heller studies from single centers with small volumes in Europe and everywhere else. That grossly underestimate reflects I'm talking about reflects rates less than 10% which obviously are science fiction. Or actually, if you do a very tight Dora to pay, I'm not science fiction, but then you get terrible efficacy results, and if you only look at reflects, it will look great. But you have to always look at efficacy with reflects because you can make a reflects data perfect by doing it very tight to pay our door. But you are gonna pay for it on the Eckhard score, so you should really report both. So this meth analysis I like because they looked at centers that published comparisons between Poem and Heller from the same operators. These are usually surgical centers where the surgeons used to be heavy Heller surgeons and when the switch to poem that compared their 1st 30 or 40 poems Thio their most recent 50 60. Heller is not not a fair comparison because these people were experts in Heller, and they were just learning poem. But nevertheless, um, Poem had a significant lower Eckert score than Heller, so it's better. A lot of meta analysis, including the slot Hman one, have shown clearly that are two years even. There's a differential in efficacy, not huge, but there's a clear differential with a poem being modifications. There was a trend for the poem being faster. Um, this is because this was learning. This was the 1st 30 £40 of a surgeon clearly promise faster than a Heller. But you know, this is this is affected by the studies, included Trent for the poem. Having a shorter hostile state makes sense. Ah, similar now looks at the Reflects reflects scores similar across the board. These are poems and Heller's by the same groups in the same hospital comparison. So you know pretty good way to the meta analysis. That's a fact that isn't poem more didn't quite reach statistical significance again. You have to think about how much of this Israel Rococo judges and then pH studies. Two studies looked at Ph. Um, very little difference did not reach statistical significance. For example, in the Swanstrom study, it was 39% positive studies versus 30 in favor of off Heller, but by only a 10%. That's point difference at night. Now the next level of medicines with the case control your in the same center. Try to match as the best you can your poems with similar Heller's and look at the difference. So there's a case control from this surgical group on. Do you look at the scores? The grades course not Huge difference. No significant. Not significant. If you look at the Roosevelts off anxieties. 32% versus 54% with about half and three quarters of the patients tested with endoscopy and then pH study, they checked about a third in its group, and they found 50% positive. PH studies in the poem, versus 30% together again. You see this about 20% of point difference acutely in the first month after these procedures, and I'll get back to that now. There's some case control studies that are a bit irritating to me because there are all kinds of biases, and, according to me, repeatedly as evidence of how bad poem is with nobody really reading before beyond the abstract to see everything that is hiding in the methods. So this is, Ah, a case control study that mats 31 poems with 88 Heller's in a surgical group that again went from Keller's two poems. And they found, amazingly, an abnormal. The MR Scoring 55% of the poems and 17% off the Hello plus door like almost a 40%. That's point difference immediately. You know something is afoot here, so when you look at the details, everything becomes obvious. The pH study was performed at two months, when the poem is not even healed yet and is at its most open, and the Heller probably still has a demon and its at its tightest problem number one. Then you look at selection bias off the 66 poems that they perform in this two year period. In that center, only 31 had the pH study, meaning less than half clearly for the poem group that probably tested the troublemakers. And reaching the mix with reflects on the Heller Group based on what they say in their methods from the patients that were included in the case control study out of the 93 Heller's that they matched, uh, to the poems 88 had the eight studies 95% which means they were testing everyone, and thus a lot of patients that did not have reflects the big source of potential selection bias. Then you're like, Okay, is that all? No, it's not all if you look at the prior treatment money. This is a case control study. Shouldn't you? Shouldn't you control for prior treatments? Um, 71% of the poem patients had prior treatment, versus 44% of the killer patients and look at prior Heller's. One third of the poem group had a previous together, meaning another cat on this winter and 0% in the Heller Group, had obviously a previous Heller Prior pneumatic dilation over a third in the poem group, 18% in the Telegraph, again disrupting this finger. So clearly, the Poem group had a much more disrupted sphincter than the Heller Group. Duration of disease. Very important. Three years in the poem, two years in the hill. And it makes you wonder this case control. What kind of matching methodology was was used here? Finally, you like. Okay, so the Reflects was low on the Heller group. Okay, that must. That may imply that you guys are making a very tight from the application. So maybe you paid for it by having a lower efficacy in on the poem group. If you try to find efficacy data in the study, you will be disappointed. There's no record score. I don't believe there is even clinical success in in the two groups. You can get a hint about that by looking. They do mention regurgitation, obviously, because they consider it here as a reflect symptom, not as a persistent this pages symptom. And interestingly, even though they argued that poem had a lot more reflects than Heller, there was more regurgitation in the Heller Group. 10% regurgitation. The Heller Group. 0%. The poem making you think that? You know, maybe the Heller Group has a very tight from the application, and things get stuck there. All right now, that's what I have to say about being alert on case control studies about the methodology. Now let's get to the highest level of evidence, which is the European randomized trial and poem vs Heather um They compared 112 points to 109 Heller's. There are some caveats here to the enrollment was 2012 and 2015, when every European center was at its infancy. In terms of poem technique, UM, eight centers had, um, enrolled patients, but most of them worried. The top three, um, there were in the top three. There were no by the top three centers. The remaining five centers performed less than 20 points per year, so in 2012 and 2015. The experience in those centers is arguable for to try and safeguard against that, the study investigators required 4 to 5 observed poems and 10 toe 8 to 10 run in poems very long numbers, and I showed you the learning curve data. This is This is a bare minimum requirement, and I'm not sure if that's enough to do a random my style against Heller with experience. Keller operators. They also pick a very low challenge. Population. 64% treatment. Naive Onley, 9% type vehicle Asia and no patients with prior Hello were allowed to be enrolled, and no patients with torches and Sava goods or dilation beyond seven centimeter were allowed to be enrolled. So a very pizza group Thio do poem on. Nevertheless, Um, pretty amazingly, the success at one year was 85%. That's about 10% of points lower than what it should be in this kind of group of patients. Lab Keller, interestingly, was also 83%. It's up interesting. Fortunately, they even themselves out. Um uh, two years. It's nearly the same, which means that this is all technical failures. All the failures happened in the first year, and then they stopped. Uh, it stopped getting worse on the second year because now you are left with the successful patients. So these are early failures, meaning in experience of the operator now success in type three patients at two years was 83% on the poem, 78% of the Heller. Not as big a difference as you would expect, is it? As I said, this may have been overblown, frankly. So, thankfully, for us, it made it all the guidelines, and it helps with insurance companies. But whether it's reality, it's a different story you might not need as long my autonomy as people think. So. Serious adverse events. 3% in the poem, 8% in the Heller, including three perforations. In two cases where the patient had to go back to the ER, it didn't reach statistical significance. But it makes sense. I mean, poem is really safer now. If you look at the reflex stuff, this gets really interesting. I mean, I think exposure at three months 7.1 by 6.7 Whoa. This is identical acid exposure. A two years, same thing. 5.75 point four. Um, now, if you look at percent, that had, uh, the percent of president had abnormal studies, 44% versus 33% in the first year, Onley 10% points and then that evens out to both 30% of two years percent off, patient with abnormal The Mr scored three months and two years 49 versus 37 in the first year. But see as the hell as the door loosens and the poem heals and gets tighter, it obliterates the difference. 39% off patients and 34% of patients matching. For example, The data from from Swan Strums uh, study of comparing his point to his colors that are, if you don't the meta analysis that showed the centers that compared their points to their Heller's. Now, if you look at the veers off anxieties at three months and two years, uh, you can see it goes down at two years because of healing off those ulcers, whereas the Heller one goes up from 20 to 29%. The net difference for overall is 44 verses 29. But if you look at severe C. D. S of anxieties, it was numerically higher in the hell a group than the poem room. 6% versus 5% and then overall heartburn symptoms. 41% in both groups identical. So on Lee, the Reflects Asaf anxieties reached statistical significance, and only at three months. And we know what that is, because at three months you have all kinds of ulcers caused by the tunnel. Now, I keep alluding to the fact that checking at one year or less favors Heller vs Poem on the data. And this is why these are long term evolution off the reflex data in in Heller, plus door to pay. And I picked random my studies to make sure this is high quality data. This all random my studies, for example, this one compared door to nothing. This one compared, um, this one Look at door versus Heller, plus door versus balloon and this one looked at door verses to pay, and this one looked at door verses to pay. So if you look at one year, um, you see that the reflects rate is 20 to 40%? That's a prospective blinded randomized trial. So now you can see the rial reflects. These are the best centers in the U. S. And the best centers abroad doing a randomized trial to prove whether door to pay is better. Interesting, that God conflicting results. But the overall rates are similar in lying between 20 and 40%. So this data that my favorite churches quote that will do it. They're Heller plus door on you and you have zero reflects that's common, or less than 10% are imaginary data or bad retrospective data. Now, if you look at this rich, our study that checked door versus nothing at 11 years, the people that got no funds application that people that got door found application 69 57% had symptoms 77 71% were on PP ice and the girl dates Q R l was very similar whether you got the door or nothing. Now, if you look at the New England Journal study comparing Balloon and Heller Plus Door at one year, the Reflects on the door was 23% at four years, which was published later in God was 34% a 50% increase within three years. So it's all consistent now. You want more data? This is a 30 year study off Heller, plus door or to pay with 67 patients followed over 30 years positively. And they did pH studies on them, which is, you know, remarkable positive. P eight study was 28% at greater than 10 years and 53% at greater than 20 years, 22% were long term failures due to reflects and 13% developed by it. If you look at this study that looked at 51 patients with laparoscopic Heller plans to pay. If you look at six years mean range 1 to 12 27% had heartburn and 65% who runs on acid suppression therapy. Okay, so I hope I convinced you that the difference is small at one year and becomes essentially negligible in my book at 45 10 years and beyond. No reason to have an invasive surgery in my mind anyway. So so PPS work. They are the cornerstone of our management again notwithstanding poorly done data mining studies that drag ah 100,000 patients into some computer algorithm, the cardiology randomized study Clearly so that we shouldn't worry about the PPS too much thanks to the cardiologist for doing a good study for us. Um, s o p p. I is work. This is from Boston minus group where you know the people go into clinical remission with P p I. And this is the group that has 50%. UM, reflection pH that the and the group with the most pH studies after our own on that little table, I show it's a very reliable data for us investors had that is that Dubai DPP for six weeks and then they go back to Q D and they all hell. And they stayed reasonably that none of the none of the patients would get consider their symptoms or the need for continuous medication as a significant problem when compared to their pre operative this page, another symptoms off accolade. So basically, they're very happy to trade a Cal Asia for a pill a day. Now things are getting better with time on the poem side. As I said that my autumn heels and things get better and P p I works better and better now that that's why I like this study from Mexico. Uh, they did. They were ableto almost do that followed 65 patients and they had pH studies at one months, six months, one year, two year, three year and four year on at least 50 of them. 59 65 55. So most of them got Create studies and all this time points, and you can see the quality of life in blue green here, and you can see the clinical score light orange and does copy erosive esophagitis. Class A B C D. I know you can see that. Ah, here on the darker orange and this very dark currents that the mistress core pH studies you can see at one month's things looks bad at Sigma's. I look a little better and then, mind you, most of the studies were with people using P P I as needed, so that don't necessarily so. That reflects disappear with time. But it's all that is extremely manageable. Would say at four years, 5% having an abnormal than Mr Score on and 5% having class a sofa. That is that maybe announcer and no B C. D. And 2% have symptoms while on PP I treatment, the quality of life remains great. Even though it declines a little bit. It remains very good, so people management looks like it's very effective. Look at it in a different way is how many patients are disgusted with PPR management and wonderful duplication to get off the PP ice. Um, very few. As I said, I can hardly convince them to have a thief. And I'm talking about the most severe ones quite apart from convincing them to have a daughter to pay, which I do offer on the severe ones along with the teeth Onley. Four people out of 6. 10 took us upon this offer 0.7% in the Japanese retrospective Multi center study 0.1%. 2 out of 2200 Elected to have a fun duplication for reflects after the pond What happened to these four people that got there? Found application Not good things to have records course off to not idea but all of them are back on pp ice at anywhere between, you know, two and three years or so, Uh, this one on B i d p p I actually after to pay. Ah, and this on you today after a partial mission to pay and this one got the door, this guy had end stage disease. He symptoms were interpreted as reflected by a surgeon that did the door inappropriately. And after the door he went to a self objective. A very sad story. He he went to another surgeon, wouldn't come back to our center because he felt his palm didn't work. And that's how we were responsible. Mind you, he had the 15 centimeter Sigma, the sofa bush. But some surgeon convinced him that it's all reflects, so he got the door. But a year later, he needed a self object on me. So So all of them Not not not success stories, I would say overall, Um so, yeah, so this is This is the This is the landscape over here. Now Can I blame the surgeons? Know the worst thing you can do on a poem patient who is doing fantastically on the eating side. And those three we're doing fantastically. One of them was an anesthesiologist from California that looks like a and Olympic athletes that climbs mountains and stuff. I didn't want to take BP I So all of them had fantastic results on poem those three. So if you take that patient and you do a tight toe pay and now they can't eat again, back where they were before the poem that can't be mad as hell and you will be going back to the O. R to take it down and do a loser one. So the smart surgeon opts for a loser rather than tighter from the black Asian. And obviously the effect is minimal. As you see now, what about you say Okay, fine. So imagine with PPS. But is their barrels and barrels catch numbers all over the place because you guys are not doing a good job with the PP ice. So let's look at long term. So quella, um, on studies that have longer term followed. So this Northwestern study with mean fall up of 2.4 years, they got to peptic strictures in people that were non compliant that responded to dilation In this three center study with minimum follow up of two years ranging between two and four years, one developed peptic stricture, some non compliant older patient that left the country that that the poem was done on and was lost to follow up and to got a short segment barrettes over a mean off about three years. Uh, sorry. This title bomb study um, five minimum five year follow up. This 29 patients had at least five year follow up. One developed short segment barrettes five years after poem. So not terrible. And you have to think about what the background rate of developing viruses in these patients. And what's the rate of pre existing parents that may have been missed by the people that did the palm, especially people that prior Heller that didn't work prior balloon dilation and have developed some barrels from the previous reflects that is blamed on the poem. So you have to be careful about taking the Zeeland before you do upon I'll show you why. So we had five patients that develop short segment buyers with no displays. And mind you, that's like 1%. 2 years, four years, five years, five years and six years. All of them did not want to take their PP ice refused. We're taking them as needed, etcetera. Now, interestingly, more than the people that develop it had it already. 10 patients or another 1% had preexisting bars when we show them, including one that actually had an undetected by the referring doctor Tijuana carcinoma. So we had to do any s d first on the poem day Ah, and then do the poem three weeks later. Now, So no much barrettes, right? What about peptic strictures? We had five patients that develop peptic strictures. At 3445 and six years. All responded dilation. One dilation 23 and one of them for dilation, all PP I noncompliance all resolved with the election BP I on all these patients, mind you that all on back on their p p I is because the learner lesson, uh, now, so get after poem appears manageable with p p I. But is there anything more than we can do here? Um, people think we discussed this a little on the life case. What about anti reflux procedures? This is a news case report from Hopkins. Not fantastic that the Mr Score went from 1 24 to 62. These isis from Kahala five Chiefs. Um, not fantastic, because he did not important it ph data or Gerdes course. Just some qualitative data. But as I said, it's one. It's a reasonable option, for those probably have severe reflects after poem. Whatever. Maybe 5 10 15% at most. That would be, um and we use it that way. There's this fanciful approach poem is a noise innovating again with his point plus f you know, really crazy stuff. This is a notes and tear fund application. He showed this on our Long Island life course in 2018, immediately after he did his first one in August of 2017. This may be the first time he showed it in the United States. You can see it if you go at the archived footage from Long Island 2000 long and 6700 New lecture. You can see this video off his first poem, plus sev. So here I am, and you can see his discussion during the lecture. So? So he doesn't anterior poem. That's the My automate gets through the my Auto me. That's the the peritoneum membrane that's the back of the liver, so it's relatively safe. So he cuts the the peritoneum membrane here until he makes a hole in here and go through, grabs the funds of the stomach, test its mobility with a grasp, er, to see if it's gonna come, and if you can do the fund application. And then once he establishes this, he puts Ananda loop with clips. We can also do freehand structuring our overstates featuring on the funders one attachment and anchor, multiple clips holding the loop. Then he puts the other end of the loop on the edge of the My Autumn E and then closes the end of loop. And while he does that, he looks from inside with an XP scope to see how the fund application looks and it looks, uh, pretty interesting. So you can see here it's beginning to look more and more like a door Israeli. They're not bad, considering how it's made so very good stuff, but I don't think it's ready for primetime. The idea of putting and a clips in the peritoneal cavity forever is one thing. The idea of doing a fund application with just fixing the funders of the stomach in the ends of the My Autumn and the surgeons take it and fix it to the Karura with very nice transmittal suitors and anchors and pledges, and they still have it loosened in a few years. And I showed you the data and how bad they get after 5 10 years. So doing this within the clips and and and a liberal thing is durable. He did publish data and endoscopic, but again, not with repeats, data, any durability data. But we're awaiting that. I'm intrigued and following closely, but I don't think I could sell this on the Western IR be exactly at its current form unless modified in some way. Now, what about technique modifications while you do the poem? Doing it in ways that will be less reflects a genic. So people have looked at full thickness versus secular only long versus short. I don't have time to review all this data, but the if you study is mostly small. Mostly retrospective on the data are weak, equivocal or negative. If you look at orientation and tear versus posterior, there are more data you can see here four and of mice trials ours. As I said, this is the largest with 250 patients. There's the International Multi Center trial with 1 50. They reported some late data on that. Now this is the original data China. But you know nothing different on the most recent data and that this has the problem, that it's seven different centers with small numbers of patients. People that favorite here. People are favorite posterior people with very low experience. It's hard to mix all that up and expect Thio have the power to detect anterior posterior differences. There's the Chinese with 46% on the Indian with 60 patients. Andre found some differences. There's a meta analysis off them now by Rodriguez. The Santiago and I think believe the senior author was Inui looking at the meta analysis off. These not, unfortunately for all of us. And this a disappointing as I said, not much difference on the reflects. The only one that saw the big difference in Reflects was the Indian one, which is the smallest study or the next smallest 30 patients in this group. So it's amazing that they found statistically significant differences in reflects but none of the other studies, including our own so major difference. Eso similar Gert similar garden endoscopy. Similar GERD symptoms. What the difference was less adverse events, mainly less mucus. So Thomas and posterior was faster, faster closure, but really overall faster but statistically significant, faster closure. And there was a slightly less length of stay. The question is coming in, but I'm gonna address them at the end because I'm almost at the end. Um, and we had 11. 15, 10, 15, 11. 22 are one hour and seven minutes. So we have to start thinking about the next case, too. Eso anyway, so these are the data on anterior posterior. So I didn't really give us the answer we're looking for for Reflects. Um So enter the anti reflex poem, which, as I said, we started doing in April of 2018. The goal of the anti reflex form was to preserve the important anti reflex function off the slink fibers off the sphincter. And I'm glad that this is spreading around. I had some observers from Spain, Um, a year ago, I think who are now doing it and actually publishing it. Um, etcetera. So anyway, so this is our reflects case control study. Um, 122 patients received this technique from April 2018 to September 2019 after we excluded patients with Prior Heller which would not make sense to include because they would immediately have an interior My out of me that may or may not include sling fibers and other forget surgery. So, after excluding those we matched them to conventional poem and to avoid any learning effect. We went immediately before April 2000 and eight in and recruited the 200 patients immediately before that time basically poem to 69 to 4 68 to exclude learning effects, and we call this the control patients. And then with from those 1 78 I did not have a previous Heller, and those 1 22 were able to create 116 pairs that were perfectly matched by propensity Score for the six important call various for reflects AIDS gender B m, my HRM type states and prior treatment. Uh, we submitted Mind you, the study did the double 2020 and it was also selected as a posture just saying so maybe we should have done something better? I guess so. And the reflux versus conventional dramatic results like I didn't expect. That's a difference. The positive pH studies went from 75% to 43. Now this is higher in our whole series is 57%. But this 75% is also by maxing exactly non prior. Hell, it's a It's a subgroup of non prior Heller patients that were exactly matchable to the anti reflect spaces. So it's a small that's why the percent that is higher because when we must exactly those patients to those This group had 75% total acid exposure, 4.1% the May. The average patient in the anti reflex group has has a normal acid exposure. Pretty amazing. Really. Then, uh, you can see the I Q. Are between two and 6.5 now on the control group, the Q R is between five and 17 and the minute standpoint, four clear major reflux Okay, on the average patient. Now, if you look number of reflexes 29 versus 53. Highly significant that the Mr Score was better and the rows of esophagitis was better but didn't quite reach significance. Maybe because of all these caveats, I mentioned about the Mr Score being affected by fermentation and Stasis and all the rows of esophagitis observations and whatnot. Um, get symptoms at least twice a week. 7% in the anti reflux, 22% in the control. So we leave excellent data and did we suffer worse seconds because when you make a point that is tighter you have to worry about. Are you gonna pay for it? In this page? Eckhard score zero on the anti reflux zero on the control, although 25% the that you are the top 25% worst patients had one that cat score of one. Whether it's here, it was still zero. So there is a small difference. Hopefully, this is no control, not translate into a bigger difference as we follow this space and out to one year, five years, 10 years. But we're following them closely and percent of patients with follow up 100% in both. If you look at predictors of positive pH studying the multi via progression, having an anti reflex versus conventional poem was the most important. The six times less reflects in the conventional group. In the anti reflects group versus the conventional group, Male Gender was got to 3.7 and B. M I for every 10% increase for every one person. One point increase in B m. I. You got a 10% increase in guard rate, 10% not absolute 10% 10% relative increase. So in conclusion, Poem has matured with outstanding 2 to 5 year outcomes. Poem represents a first line treatment for Cal Asia that has equivalent or superior efficacy to Heller and can be the absolute difference of great rates between Helen and Poem is less than 20% at one year and erodes further with time. Good after poem is manageable, with PPS, with good patient satisfaction and no evidence off high rate of complications. And the point technique continues to involve including refinements that may result in a significant lower get rates, including our patented anti reflux poem. And this is what I usually do. On August 14, I'm sailing with my brother in Greece, the Greek islands, for a week that has made out there. Uh, the photograph was taken by my crazy brother, who had climbed up the mast to take a overhead picture. But we're in a little isolated cove hanging out and, you know, swimming in that beautiful see there. So that's what I would have been doing. But now I'm gonna go toe Montag instead. Not quite the same. See, I have to say So that's it. Now let's ask, let's answer some questions. Uh, any suggestions? This question says any suggestions Other Than PP I or conversion to gastric bypass for poem in sleeve gastrectomy rim patients or reflect is a problem. Well, that's a good question. Um, definitely conversion toe bypass is a reasonable choice, especially if the patient is not very thin. That's these are very difficult situations. You can also try if you can try, um, overstates with ablation, but can't sang has reported, um, to tighten up over there. You can try the arms procedure that you know he has reported, uh, but definitely converting is a very reasonable option, I think because none of this I clearly don't have a huge faith in this endoscopic techniques in terms of keeping a sleeve patient works reflexes particularly bad. Happy for the rest of their lives. So I would I would maybe be leaning towards a conversion toe a rule. All right. I don't think Do you see any other? No other questions so far. Maybe we could address some cake questions later to maybe even during the FDR. Although the FBI will require a little more concentration on my part than the poem and the Z poem. Oh, So I will start moving towards the FDR. Maybe you can answer many last 12 questions before, before doing before getting thick into the FDR and which guys, maybe we better answer questions on that. All right. Thank you. I'm gonna go move on to the FDR shortly.