So we are coming back to Hopkins next, and it's my great pleasure to introduce my beloved mentor, Dr. Marcia Canto, who will be demonstrating a cryotherapy procedure. Dr. Canto, you are live on, can you hear us? Thank you, everybody. It's nice to see you all. I missed a lot of Uzma's case, but I just want to show you an alternative, a blade of method that involves cryotherapy. It's called cryo-balloon ablation. We've been working with this both clinically and in trials for at least six years. And I want to show you today the next generation C2 cryo-balloon system. What it does is it works through an electrically connected handle, which Dr. Sridhimony here is going to show you. And we also use this to activate the cryo-balloon ablation using two catheters, which are shown here. The one on the left is the focal balloon, which will inflate now. Just to show you the shape of it, it's a three centimeter long balloon with compliant balloon. And then the other shape that we use is the pear-shaped balloon on the right, which we will inflate. So it's a little bit kind of like fatter at the end, about 27 millimeters long, fatter. Both balloons are about 30 millimeters long. And again, very important to know that they're also compliant balloons, kind of one size fit all. And so that's the basic system. I'll show you much of the handle, which is really nicely controlling the dosage, et cetera, which Dr. Sridhimony is actually holding. But also part of the system, which I will show here, is the pedal, which Sophia will show because she will not see this during the demonstration. What this is different from the first generation, which was activated by moving the handle, is it's now all controlled by the operator. So now you have complete control over directionality, over deflation, deflation. And so this balloon, this pedal, the blue, inflates it with a puff of nitrous and also delivers the cryogen. This pedal, the gray one, deflates the balloon. Basically this knob can toggle between the directionality of the diffuser, and you'll see that in a minute, going longitudinally, like in the z-axis, as well as circumferentially if you switch it over. So you can go clockwise or counterclockwise. And so the nice thing about this focal cryo-balloon system is that you can really control the delivery. You don't have to injure normal tissue. And so that's what's really nice about this focal system. This is a system we've used for the last six years, and we've published the results. As you know, or don't know, it's actually quite good. The efficacy rate is over 92% for all dysplasia, approaching 95%. And the CRIM rate, the complete eradication of menoplasia, is also quite high, somewhere in the high 80s to low 90s. We all just recently published our durability paper in TIGE, just came out, where in fact we're seeing very little or comparable recurrence of menoplasia, about 14% at three years, and durability of the response. So it's pretty exciting to use something that actually evolves and improves over time and also has efficacy and durability. Now one thing that is the direction of this technology is to use wider area ablation. And I just want to show you a short video, because we cannot demonstrate it in this patient, but it is an FDA-approved improvement in the delivery system. So can you play the short video, please? So what you're seeing here is the diffuser in the esophagus, and you might see that there is a patch of ice that is making its way, coming from distal to proximal. This is a 180 wide area device, and you can see you can actually start. It's three centimeters long, it's going to cycle through. But what I want to show you is the idea that we can treat wider areas, like 180 circumference, for example, using this delivery system. Bas Wooten and his group just published also their pilot study, 25 patients, showing a really high efficacy rate, 94%. So it's really promising. So do you mean this? Are you rotating the catheter at all, or it's just doing it by itself? For the 180? Yeah. Yeah, so that's still being decided. I think there's an opportunity to decide if you would rotate it the other way and do 180 here, 180 there for circumferential treatment, or do it differently in terms of stack. So that's something that we need to study. But great question. Okay, got you. Yeah. So I just wanted to show you that. So now we're going to go live on the endo. We have first examined this patient, it's very interesting. We could turn lights on, please. We have a patient who's 71, but he has father and brother died of esophageal cancer at about the early 70s. And he's been quite nervous, I met him about six years ago, about him dying from cancer as well. He's had Barrett's esophagus for at least 16 years. And initially, he had indefinite for dysplasia, low grade dysplasia. And we actually recommended a discipline application to fix a six centimeter parasoftal hernia. Unfortunately, the parasoftal hernia, the hernia recurred, and he has about a four centimeter hernia today. So what you're seeing is the hernia. And since I haven't seen him in two years, you have to do a really good examination of the circumferential Barrett's as you're seeing here. And the extent that we've measured it is about C5M6. So here's the Z line at six o'clock. Here's the circumferential extent right here. And up to the top of his gastric folds right here, it's about six centimeters. Now you can see also from the anatomy that he has a kind of curved shape esophagus based on the hernia recurrence. And so this potentially also adds a little bit of technical decision making regarding what device you would use. And so when people ask me about do I do cryo versus RFA, who do you use it on? There are many things that go into it, not only the anatomy of the patient, the size of the hernia, whether they've had prior failed treatment or not. And again, there's some data to indicate that it actually is pretty good at that, but also patient involvement. So we go through the pros and cons. And one thing that's borne out when you do some indirect comparative trials comparisons is that there's clearly less pain with cryo than with RFA. So many patients opt for cryo and that certainly both types of ablation are part of my practice. So now what I want to show you is we've selected this focal cryocatheter. It comes out of the package like this. There is a plastic that is over the balloon and you want to not take it out the way you normally would when you have a dilating balloon, right? So we're going to now open the channel. This is a therapeutic 190 Olympus endoscope. It has to be a therapeutic channel. And then you pass the catheter into the channel like, so you have to be really careful not to kink the catheter. Otherwise the kinking will actually obstruct the flow of nitrous. So what I do is... Now Mimi, keeping the cap open, does that interfere in your keeping the esophagus inflated or doing that when you're in the middle of the procedure? No, not at all. Because you see it's nice snug with the catheter. So I actually keep it here also for a second reason, the plastic, because it actually, if it's going to kink, it's going to kink right here at this bend with the channel. So I keep it here. It keeps it a little bit stiff and then you advance it. I usually put the scope into the stomach first because it's a bigger area obviously. And then I kind of use my right hand and I just kind of be careful about kinking. So I actually advance it, as you can see with my fingers, close to the plastic so it doesn't kink. And then once I have the catheter out in the stomach, we want to just test it and we want to connect it. So these are different steps that we're using for the next gen system compared to what we were used to in the first gen. So come over please closely. So now we're going to almost put it out. So is the main reason you're using cryo on this patient, is it because of the large hernia or is there anything else that makes you use? Yeah, so large hernia, I think there's a good chance that with this focal device, you'll see in a minute that we can actually have nice, good contact within the hernia. And even if it didn't, and I'll show you, hopefully we'll show you, that you can actually direct the cryogen focally to where it makes contact. So that's one difference with the RFA balloon. The other thing is preference. So a patient really is pain averse and he did not want to have any chance of having significant pain. He's going to fly back to Florida. He's very anxious about having to be able to go home the next day and all kinds of things. So it's individualized. So now we're going to- Besides the large hernias, right? I mean, Reem, one of the other things is just this post-surgical patients, their G-junction area becomes so tortuous that it's really hard to keep it straight and get any good apposition with any of the ablation techniques. So I think that's another thing that Mimi will demonstrate here. Hopefully, yeah. So now what you're going to do is see this, and there's a plastic cap that protects the tip. You're going to now show you the handle now. Insert this into the handle with a nice click so that it's pretty stable. So that's Sophia here trying to, there you go. So there's a nice click. And then after this system has the software, the handle, to recognize the catheter, it knows it's the right catheter. So you say, check. And then now we're going to put the capsule into the cap. So you should not hold that nitrous capsule, it's just going to screw and puncture. There you go. There should be like a puncture sound, a feel. And then we're going to now put it into the handle. So whereas before, as you know, the other cryotherapy systems have liquid nitrogen and big tanks that are kind of warm. This is just straight out of the advanced supply room, and we're now putting it into the handle. So the way it works is this handle will allow the aperture for nitrous oxide gas liquid to come into the catheter when we want it, and then close the valves. So now we're going to choose the cryogen dose, it's 10 seconds by default. That's based on our initial trials with the previous system. But now we're going to go down to eight seconds, which is what we know is currently used for this next-gen system based on the benchtop testing, which this delivers actually 20% more energy than the first system. The other thing I do is we have this, I call it the chip clip, in case you have some strictures or an abnormal junction where the balloon potentially might kind of move distally, we have this to stabilize the catheter potentially. Some people use it, some people don't. So but I'll just, for demonstration reasons, just show that to you now. What you want to do is really first try to inflate in the stomach first. So you see the line, I'm going to step on the blue pedal, and you can see that it kind of has this hello, hello, you know, kind of on and off. And so that shows that it's working, correct? So then once I come back into, I pull the balloon back to my scope so we can see through like this, and then you, now I can clip it if that's where I want it to be, like this. And so now what is different from regular scoping is you want to be able to handle the balloon and the scope so that you actually drop the left arm and you rotate clockwise about 95 degrees. So you're looking exactly through the balloon. And with this scope. So how much have you inflated the balloon, Mimi? How much is it in terms of either PSI or diameter or anything there? So the diameter of the balloon is three centimeters, 30 millimeters. It only makes a puff enough to inflate it. And but because it's compliant, it will not over, it will not over extend, it will not over inflate. So we are now going back into the, this is his hernia now. And as you can see at the very end, it's the diffuser. It's all the way at the end and that's its base, right? So I'm going to now come up, as you can see here, into where I think the gastric folds. So like Pratik, I like to treat also part of the cardia. So you can see here that I'm trying to now pull back the scope and have it at the right level that I want. So that's kind of the first spot to see directionality. So I'm not now going to just apply the first ablation, which is set at eight seconds. And you can see it's a nice control delivery, very focal. It'll beep when it's done, then you can just now systematically move from this area by stepping on the pedal and going clockwise here. So this is where you kind of have a learning curve, where you have to learn where to place the next puff. So that's too far, obviously. And there are some more... Now Mimi, in terms of when you're doing this, how about in terms of overlap? Is there, if there is too much overlap, does it cause more strictures, more pain, deeper ablation, any thoughts there? Yeah, what's too much? So this is kind of like a good overlap. You see, you want to be able to have minimal overlap like this. We don't really have... We have an analysis of the strictures that were developed in our trials, and it's unclear. It's not related to EMR rate. It's not related to the number of pulses. And I think there is a learning curve to how much overlap you develop, but certainly it's not much more pain. So here I'm taking the first puffs to see, you can actually pull back the balloon like I'm doing now, just to make sure I get that Z line and I overlap minimally. So you can see that within this hernia sac, I'm getting a really nice apposition, which is... Sorry, it went around. Yeah. So you can go the other way if you want, if you want to be systematic about it. Because what's nice is you can see where you treat it already, right? You can see the ice puff, ice patch. And you can see, again, I was saying that the round things, markings, which is what we asked for on the catheter, tell you what direction the diffuser is facing. So you know kind of where you want to fire. So that's another nice patch up there. And then you can just go kind of clockwise, keep going clockwise. Yeah, very nicely done, Mimi. I think for a C8, M10, or, you know, I mean, how long would this procedure take in an individual like this? Oh yeah. So we timed that too. The average length is about maybe 10, 15 minutes at most, I mean, for the ablation. The procedure we schedule in 30 minute increments, but I'm just slowing down for demonstration purposes. Sure, sure, sure. So you can see the advantage of the new FDA, hopefully that we'll get FDA approval soon. It will probably cut your time by half. So the wide area is FDA approved. The only reason why we're not using it now is the dosing trials are ongoing. So I had mentioned about the trial by, I think we have to change now. So I delivered about, I think we have to change, yeah, so we have to put more nitrous. It delivers about maybe six ablations in one little capsule. So at one level, do you end up using like two canisters per level of ablation or? Oh no, usually it's just, usually it's just one. Okay. Yeah. So six ablations. This is a wider and more patchless junction than usual. What I was saying was the, in BASA's trial, this was a one millimeter per second dose. That means that with the wide area device, the balloon, it's the same system, but now it creates that 180 ice patch I showed you. So the faster, the faster that the transducer travels from distal to proximal, the lower the dose. And we found in the early dosing trials that a higher dose is bad. It can cause scriptures or et cetera. So now that that's what's pending the clinical use and trials of the wide area device. Good. Right. So I know we have a few more minutes, but I'm going to show you that we can actually now come back with the balloon and just demonstrate to you how we can treat the next level, I call it. So as you can see on the right at two o'clock, where you're treated. So even if the ice patch has melted, so at two o'clock on the screen is the red color change we look for when we have an ablated area. So there's no mystery, you can see the exact demarcation. So it actually helps in not overlapping too much. So you want to see that actually when you have any ablation. So that red colored erythema that you're seeing, that's pretty, that's what's to be expected at the end of the treatment that you do. Correct. And at the end, you'll be surprised that even if we have multifocal, what I call multifocal cryo ablation, that it will look seamless. Like you actually will not see the different patches. They'll all be, it's all going to be confluent. Okay. So we're just changing the nitrous here. The other thing is when you switch from distal to proximal, we can also pull back the balloon now and... Dr. Kanta, this is a nice demonstration, we will switch rooms in around two minutes. Yep. And I'll... So... Okay. Sorry. Can you just also tell us about your post-op care, when you're going to bring them back, what do you discharge them on? Yeah, sure. So the other advantage is that because there's little pain and very, even with long segments like this, I'm going to tell him that, you know, he's going to be on full liquid tonight, my nurse calls him tomorrow, generally they're usually fine, they don't require any narcotics or even any Tylenol, he goes to soft tomorrow and then advanced for dinner to regular diet. So for the patients, it's really well, better tolerated than, for example, RFA. Now, speaking about that case that Uzma had, I caught part of it, but I heard there was some kind of stricture, is that right? Yeah. Mild stricture, yes. Mild, yeah. So that's the other thing that's potentially an advantage, we haven't proven it in a trial, but when you inflate this balloon across a stricture, the compliant balloon will sit in the stricture, it will not actually dilate it, it will not cause any trauma, but you can actually treat within a stricture, which is often, sometimes what we see when you have patients who failed RFA or had post RFA or EMR stricture, you have Barrett's in the stricture. So this is the only modality that I have used at least that can treat in the stricture safely. And so that's another potential reason to use this. Are we good? No, Mimi, do you, in between ablations, do you have to deflate the balloon and then take a break or something like that? Or do you keep it inflated all throughout the entire procedure? Oh, you can inflate, I'm actually going much more slowly than usual and we have some device connection issues here, but no, you can keep it inflated and deflate it all throughout. Yeah, so I'll finish this and then at the end, maybe Q&A, I'll show you the final result. Sure, yeah, that would be great. And Mimi, I want to give a shout out to Sophie next to you, one of our excellent nurses. Yeah, one more thing just to plug is that we are just opened our no fear trial, Nick Shaheen and I are running a random, I think a non-randomized trial of treating patients who failed RFA. So there's, it's on clinicaltrials.gov. So please send your patients who failed RFA. Thank you. Thank you, Mimi. Venkat, back to you.

cryotherapy

cryo-balloon ablation

C2 cryo-balloon system

Barrett's esophagus

dysplasia

menoplasia