Thanks, Linda, and I appreciate the invitation to talk at a great conference. What a great lineup of talks, and I'm really excited to tell you about technology and an approach that's evolving at expert centers that's pretty exciting to talk about, a minimally invasive treatment option for pancreatic cysts and pancreatic tumors. Now, Tom, if the guys at your institution were a little nervous about pancreatitis with FNA, they're really not going to like what I'm talking about. This is where we're going to bring up the pancreatitis level here a little bit. But let's talk about it overall here a little bit. Hey, pancreatic cancer, a big problem? Well, everybody here knows it is. It's one of the major cancers. It has the worst five-year prognosis. And you know what? It's only getting worse. Unless we make breakthroughs in the early detection and the treatment of this disorder, it's expected to surpass everything but lung cancer by 2030 to be the second leading cause of cancer death. If only we had a precursor lesion that we could remove, much like colonoscopy polypectomy, remove that lesion and prevent its progression into not colon cancer, but pancreatic cancer, much like we've seen in screening colonoscopy. Well, I'm here to tell you, at least for a proportion of patients, we can. We're talking about the progression of mucinous pancreatic cysts. Common? Yes. 2% of Americans. And it gets up through the decades to be 37% in your 80-year-olds. And a portion of these patients, remember, most of these cysts are low risk. They're found incidentally. They're never going to do anything. But a portion of them, much like colon polyps, are going to progress over time to become progressively dysplastic and finally cancerous. And so if you see here on the bottom, this histology of a resected specimen, you can see that the mucinous columnar, mucinogenic lining of this cyst has become progressively more dysplastic. These cells have lost their contact inhibition. They're piling on top of each other. And that can be appreciated by, whoops, let's go back here, that can be appreciated on EUS by this thickened wall, thick septations, neural nodules, finally. Some of them are going to go on and create pancreatic adenocarcinoma over years. So I think what most people don't really appreciate is that there are two pathways to pancreatic cancer. There is, on the bottom, you'll see these two split into two categories. And you can see the classic pan-in lesion. That's your classic pancreatic adenocarcinoma. This is an aggressive adenocarcinoma. It happens at the very periphery of the pancreatic ducts. It occurs as a microscopic event. And when it goes to surgery, even when it's resected, it has those terrible outcomes that we've become used to over the years, a 5-year, 15% to 20% survival. Mucinous cysts follow a different pathway. This is a macrocystic event. They tend to happen in the central parts of the ducts. They occur progressively picking up a loss of tumor suppressor or a pickup of oncogenic deletions, and they become progressively just plastic over time. Even if they develop adenocarcinoma and end up in surgery, you can see here in this paper published in Gastro that the survival is much different, even when cancer does go to surgery. It's two different phenomena or two different animals on some level. We don't know as much about it as we know from the colon polytadenocarcinoma sequence, but more is being come clear all the time. So what do we do? As Tom alluded to, most of these cysts are low risk. They can just be followed by consensus criteria over time using standard guidelines. The ones we follow and the ones I would recommend, it's the ACG guidelines or the Fukuoka guidelines. We could talk about cysts all day long. If you give me appropriate bathroom breaks, I'll talk about this all day. But the fact is, just pick a guideline that you like and follow it. And that really is most of the cysts that you're ever going to see. However, some of those cysts that grow over time and start becoming more just plastic, there's no therapeutic option here, obviously. And it causes patients a lot of anxiety. There's good studies out there that patients finally are looking at that three-year MRI, that one-year MRI, and it causes them a lot of distress. And it's expensive. So surgery is your gold standard. Obviously if you have stigmata, malignancy, it looks like you might be dealing with malignancy and multiple high-risk features, surgery is your gold standard. For most centers, this is what you're looking at. But it's not to be trifled with. These really should be done at high-volume centers. They're complicated surgeries. And even when done at high-volume centers, you can see that the risk of morbidity, mortality is not insignificant at 20 to 40 and 1 to 5%. And that's pancreatic cysts, mind you, not pancreatic cancer. So in patients that have a higher-risk cyst, but perhaps have higher risk for undergoing surgical resection, a less invasive treatment option would really be exciting. So can we replace the resective strategy in appropriately selected patients with its morbidity, its mortality, its destruction to patients' lives, and its expense with a minimally invasive option where we can use EUS-guided chemoablation to take these patients, get rid of their cysts, much lower complication profile, less disruption to them, and certainly less expensive? Well, I'm here, obviously, to convince you that for some patients, we can. So this is not a new idea. John DeWitt and Brugge years ago published the EPIC trial, where they actually, under EUS, put the needle in the pancreatic cyst, lavaged it with ethanol over 3 to 5 minutes, and they saw that, well, for the low 30% efficacy rate, this actually works. So proof and concept, it truly works. If you look at the histology on one of those patients that went to surgery, you'll also see that it's sort of uncontrolled. The alcohol caused a lot of inflammation here, actually disrupted right through the wall into the surrounding area, and missed half the cyst. You can see that the cyst lining here was preserved and not touched. So that was followed up by the South Koreans, who improved on this with a very innovative idea of doing alcohol ablation for the same idea. This is 98% dehydrated alcohol. And then, after removing the alcohol, replaced it with Paclitaxel. And they saw that ablation rates went up to 79%. Now that's talking. That's real efficacy. So if we look at all the trials that have been done up to date that have used a prospective design, now you can look all through this data and find lots of retrospective case series and case reports. But if we really just concentrate on prospective data, a couple of things I'd like to point out to you here. One is the relative ineffectiveness of alcohol-only lavage, or alcohol-only ablation. You can see that those complete ablation rates run about 9% to 35%. That's pretty low. The other thing that falls out here is that when you follow it with chemotherapy infusion, so alcohol lavage followed by chemotherapy, ablation rates rise to 50% to 79%. Now I would say that that's pretty effective. The problem is that any time that alcohol is involved in your ablation protocol, you're going to have a serious adverse event rate somewhere between 4% and 10%. And that's a significant rate. That's what blocks its adoption to more widespread use in appropriate patients. If I told you I could take your screening colonoscopy and get rid of your risk of colon cancer, you'd probably be glad to do it. But if I told you you had that rate of ending up in the hospital, you'd probably think twice. That was the idea. Where I came in was the CHARM trial. So our first hypothesis is this. Look, if there's been such a boost in efficacy with chemotherapy, perhaps alcohol is not even required for an effective pancreatic cyst ablation if it is replaced by a chemotherapy admixture that's specifically designed for pancreatic neoplasia, essentially, gemcide being mixed with paclitaxel. The second hypothesis is similar. If we take alcohol out of the picture, then adverse event rates should fall. Remember that we probably don't know this, but all investigators in the previous studies I showed blame their adverse events on the inflammatory and toxic events of alcohol. This is not the friendly IPA-level alcohol. You might have in the cocktail party tonight. This is 98% dehydrated alcohol. It destroys everything it touches. If you look at the interventional radiology literature, it's replete on warnings not to get it somewhere where it shouldn't be. So if we take it out of the picture, we should have a much safer procedure. And our third hypothesis is that if we tailor this admixture to pancreatic neoplasia, it should be even more effective than historical controls. This is our inclusion-exclusion criteria. In the interest of time, I'm going to blow through it pretty quickly. But we only want to do mucin assist. We don't want to be ablating serocyst adenomas and other benign lesions. Technically, we need assist. It's not full of different cells. So we want no more than four cells in it, because technically, it's difficult to ablate something that has lots of different chambers. We don't want to have signs of adenocarcinoma. That's not something we want to be ablating. And finally, a patient's got to have a three- to five-year life expectancy. Otherwise, it doesn't really make sense to get rid of their pre-cancerous lesion, right? You're subjecting them to a procedure and possibly some risk and not really giving them a clinical benefit. So this was a randomized prospective trial where we put patients in a control group. That group was their cysts were lavaged with alcohol for three to five minutes. And then the admixture, the Charm cocktail, gemcitabine paclitaxel, was infused and left. In the experimental group, normal saline lavage only, no alcohol, followed by infusion of the same admixture. Then we followed those patients and had an MRI follow-up to be compared with the pretreatment MRI at one year. And serious adverse and minor adverse events were measured within 30 days of the procedure. Very standardized definition for adverse events. This is what it looks like. The US needle goes into the cyst. All the cyst fluid comes out. You then introduce the lavage agent, the same amount that you brought out, lavage at three to five minutes, and then bring it out, replace it with the admixture that you see here in the lower right, and the patient is then discharged. What were the results? Well, here they are. You can see if you look at this column, alcohol lavage, and the bottom column here, alcohol-free lavage, you can see alcohol patients ablated at a rate of 61%. Their alcohol-free arm ablated at a rate of 67%. So alcohol is not required for effective pancreatic cyst ablation. But the exciting part is over here, serious and minor adverse events. You can see that serious and minor adverse events occurred in 6% and 22% of the alcohol arm, 0% in the alcohol-free arm. When you take alcohol out of the picture, adverse events fall significantly. And the third hypothesis is, do they ablate better than historical controls? Was not satisfied. 64% is right in what previous trials had reported, so no improvement there. So this is what it looks like. This is a patient who came through the CHARM1 trial. You can see their preoperative MRI on the left. That's just under a 3-centimeter IPMN. Here's their follow-up at 12 months. You can see they've had nice response. That's complete ablation. There's no residual cyst identified. Now you know how these conferences go, that whoever's presenting presents their best cases, right? I mean, I do a lot of EMR ESD. In that group, we are famous for only showing our absolute best stuff. So here is the objective data I want to show you, just to make sure you know I'm not making this up. Here is the measurements of all the patients who went through the trial. You'll see that at six months, most patients have a really exuberant response. Also, it's obvious that a full year is required for some patients to undergo complete ablation. It takes a full year to really see who is entirely going to ablate. And also, it's important to acknowledge that not every patient ablates. There are so-called treatment failures. Not everybody is a responder. Figuring out why some people are resistant to our current approach is something that we're going to be looking at in future trials. All right, so is pancreatic cyst ablation effective? I do want to get across the concept, because historically, this is what was most common, that alcohol lavage alone is really not effective, and this really should be avoided. Alcohol lavage followed by Paclitaxel increases complete ablation rates to 50% to 79%. And alcohol-free ablation, we're talking 67% at one year. Is it safe? This is a big issue to a lot of people. So any ablation involving alcohol is going to have a serious adverse event rate of about 3% to 10%. And these are going to be pancreatitis, thrombosis, and peritonitis. But in the randomized prospective CHARM trial, we showed that alcohol-free ablation has an adverse event, well, at zero. But what larger trials are going to show is still unclear. So we're now under, I guess, about halfway through the NIH-funded CHARM2 trial, which is a joint effort between Penn State and University of Indiana, Indiana University, I keep saying that backwards. And we're going to see those on a much larger, better-designed trial, and we'll see what those results are in about two to three years. OK, is it durable? This is a big, big question, because a lot of people had said, well, hold it, how do you know it's gone? How do you know radiographic response equals clinical response? What's your long-term results? It's all the same way of saying, what's your long-term data? So Choi's group from South Korea, they reported on their prospective data, 164 patients who underwent ablation, 72% of those patients achieved complete ablation. And of those patients who achieved complete ablation, what was it, 98% achieved complete ablation, kept that ablation long-term, and they followed these patients out to six years. The authors concluded that the treatment approach is an effective and durable alternative to surgery in appropriately selected patients. I actually added that, appropriately selected patients, and we're going to get to that shortly. Now, the Koreans had a protocol where they'll ablate all types of pancreatic cysts. So if we just want to look at mucinous cysts, which is really, really what we want to do, we followed our CHARM trial out for long-term data as well. And this was our results. Just looking at mucinous cysts, we found that 87% of our patients who achieved complete ablation kept it at 36 months. No patients who had been treated went on to develop high-grade pathology. And interestingly and pleasantly, 4% of patients who were non-responders originally went on to get complete response long-term, showing a delayed treatment effect. And you'll see that in lots and lots of other data that I'm going to point out later on RFA. The inflammatory and immune reaction has an effect here. It's not just your primary treatment. So it's a minimally invasive treatment option in carefully selected patients. Here are some of the other patients who went through the trials. Here's a 55-year-old male who had a growing 3.3 centimeter cyst. You'll see the MRI on the top, MRCP on the bottom of this pancreatic neck IPMN. Here is the results at 12 months. You can see that if you look real hard, you see a little nub in here of what's left of the cyst at one year. And here in MRCP, we always want to look in that, too, because sometimes it might be apparent on one and not another. That's complete ablation. Here is a 82-year-old female, 3.5 centimeter growing cyst in her pancreatic head. You can see there's even some mass effect on the common bile duct. There's the MRCP on the bottom. And here is her results at three years. There's absolutely no cyst identifiable. That's complete response. So, which pancreatic cysts are appropriate for EOS-guide keempan ablation? It's an important slide, and I want to make sure that I'm not confusing anybody. So as Tom pointed out in the first lecture, most pancreatic cysts are small. They're less than two centimeters, and lots and lots of data showing that they can just be followed per whatever treatment algorithm or guideline that you follow, and that's all that will ever be required. I also want to make it clear that if a pancreatic cyst has stigmata of malignancy, that patient needs to be seen at a high-volume center by a multidisciplinary committee and surgery required if appropriate. But for middle-ground patients, those that have a higher-risk cyst are technically amendable to ablation. That is a group that you would like to offer treatment as part of your multidisciplinary team if appropriate. And I would point you to a consensus position paper that we published a few years ago, a multinational position paper on this, and it's in the citation with your slides if you want to look at that. So here are the indications and the contraindications. As I said before, the indications are really mucinous cysts, two to six centimeters in size, and you want to make sure that you've done due diligence to make sure you're looking at a mucinous cyst. The contraindications, as I said, stigmata of malignancy, lesions that appear to be benign, and there's a few others that make sense. Obviously, you want somebody who can undergo the procedure and is going to live three to five years because you're talking about a precancerous lesion. These are the relative contraindications. You should think twice, but it may make sense in a patient who doesn't have surgical alternatives. Patients with the following high-risk features, main duct dilation greater than five millimeters. That's because if you look at IPMNs, the highest-risk pathology is going to be in the main duct, and you're not going to be ablating in there. So you're not treating the highest-grade pathology. Well, I won't say it's never been done, but generally speaking, you shouldn't. A large mural nodule, pathologically thick walls or septations, signs of common bile duct or pancreatic duct obstruction, pathologic lymphadenopathy, and as I said before, more than four discrete sections. Okay, informed consent. Patients need to be seen in a clinic if you're considering this. This is you're seeing at your referral center. That patient can see the specialist in clinic. They really need to understand the natural history of what we're talking about. They need to understand all their treatment options and plenty of time to ask questions. And patients should also be aware that this is an area of evolving data. And like the data Tom presented first, this is evolving data. There's not a whole lot out there, and it's an area that is in rapid evolution. Patients need to understand that, that it does not appear on any major guidelines as far as strong advocation, and they also need to understand that there are no FDA devices specifically designed for this. So who should be doing a US-guided chemoablation? This is a procedure that appears easy. The needle goes in, the fluid comes out, the chemo goes in. It's not. It's part of a complex workup. It's careful patient selection. It's a team that knows how to do this. It's the surgeons that understand that and can play part in that while offering a surgical perspective. It's a complex picture and it needs to be done at a high volume center as part of a multidisciplinary team. It needs to be done by interventionists who have formal training in EUS and interventional EUS. I think that goes without saying. And it should be part of an ongoing quality assurance process to make sure that there are not deficiencies, things that need to be addressed on a technical or systems level, and you need to be measuring your outcomes. Here's a video that I hope to show. And in the interest of time, I'm only gonna show the first one, but it kind of demonstrates a little bit about how this is done. So much like anything you do in EUS when you're a little preoccupied with getting in the right spot and staying there, you need to make sure you're in a nice stable position. The needle is gonna go into the direct center of the cystic tumor. You're gonna remove all the mucinogenic fluids you can. You're gonna leave a little rim around the needle because you don't want to damage normal pancreatic parenchyma. And then you're going to measure out and introduce the exact same amount of chemoablation admixture as fluids you removed. In an alcohol-free protocol, you don't need any lavage. The pancreatic cyst is then reconstituted to its original size and dimension, and then the needle is removed. Here's what that looks like in real time. This is a complex cyst that was done off-protocol, too large to include in the trial, not a surgical candidate. You can see it's a complex cyst. There is multiple chambers, but only three, really. The rest communicate. There's an IPMN field defect throughout the pancreas. The needle has now been introduced into the first, all the fluid removed, and then replaced with the chemotherapy. Then the third chamber is now going to be aspirated. It's too small to fill itself. So my colleague, Dr. Dai, has backed the needle out into the larger chamber, then introduced the chemotherapy. Anywhere that the fluid, the chemotherapy is, is replaced by this snow globe appearance. So the anechoic fluid that was originally there has been replaced by the snow globe sign. It's a really nice feature that God has put in place just to show how to do effective pancreatic cyst ablation. And what it is, is all the fluid there you'll see is black. That's the mucingenic fluid. If you've done it right, you've replaced it with this sparkling snow globe. And so now you know exactly where the chemo is and where it's not. I coined that term, snow globe sign, by the way. Follow-up after EUS-guided chemo ablation. Well, the first follow-up is at three months. We bring these patients back, just like your Barrett's patient at three months. If there's more than 1.5 centimeters of cysts left, we hit it again. If not, we just evaluate. And then these patients come back for a follow-up in clinic at one year's time. This is off-protocol patients that aren't part of our CHARM2 trial. If the patient's had a good response, it's our practice to follow that patient then long-term as per guidelines using the new size and dimension of the cyst. There's no data to guide you here. System improvement always needs to be part of a system improvement suit. This is the definitions for response, complete, partial, and non. I'll defer to let you read that on your own because I don't want to run us out of time here. I just need to say that one of the reasons this is so important to be done at a multi-center or a multidisciplinary high-volume center is the team it takes to make this happen. It seems easy. It has a tendency to develop problems, complications, and also mistakes. You have the same team that does it the same way. You standardize it, the same nurses, and that stuff goes away. It's very important to have a nurse team that takes ownership on this. Even if you use an alcohol-free ablation and best technique and careful patient selection, funny things can happen. You are going to have complications. What are some of them? Pancreatitis, you can't extravasate the chemo at the time of the infusion. The FDA has mandated how much we can use for that specific purpose. Fevers, nausea, abdominal pain, you can put up to 30 cc's in a cyst. That's a lot, and those patients can be nauseous for two days. Pancreatitis has always been self-limited in our experience, and in our opinion, antibiotics are not needed. I challenge an antibiotic to live in 39 milligrams per milliliter of gemcitabine, and we recover patients for a full hour and then follow them up using that protocol that I described earlier. Areas of uncertainty, this is important. You could get somebody else up here to give this lecture, and they would probably be a lot more cautious than I am, because our center does so much of this. What are some of these areas of uncertainty? These need to be acknowledged and given credit. First of all, as you know, it's not perfect figuring out what cysts are mucous or not, so you need to kind of acknowledge that. If you ablate a growing three centimeter cyst in the head, you haven't eliminated that patient's risk of developing cancer somewhere else. What's the optimal follow-up? Can higher risk cysts be treated? What is the effectiveness, the safety, the long-term results in larger randomized data? And there have been case reports and retrospective series that have brought up the idea of recurrences or progression of cancer. And at this time, there are no dedicated devices. But I'll leave that part before we talk an RFA by saying it is a change in thought process on how we treat pancreatic cysts. But if you're in my generation, which is increasingly old, you probably recognize these guys. You have a preconceived notion, a historical notion about which one of these guys is a good guy and which guy is gonna end up getting crushed and which guy is gonna be victorious. It just always works out that way. But if you follow high quality data, you might find out that the actual reality is a bit different. And I'm just asking you to be open-minded about that, follow the data, and I think it's an exciting area of development. Let's talk about RFA here a little bit. I wanna thank Vanessa Shammy for this video. This is the introduction of a device to apply high-frequency ablative energy to a solid or pancreatic cystic lesion to ablate the lesion using thermal energy. Radiofrequency ablation devices, there's a couple out, and they're kinda going through a lot of evolution of what's available, but they generally can be split into two groups. This is your RFA needle group. This is where the actual ablative energy is in the needle. It kinda looks like an FNA needle. And it actually, once you pull back the sheath and introduce the needle, that's your ablative part. They're generally cooled inside so that there's not a charring process on the needle, which allows more effective RFA ablation. The two that are available would be your Hybritherm from Irvi that has a CO2 cooling mechanism on the inside. And then Taewoo has the saline-cooled version of this, but they're very similar. Irvi is not available in the United States. The second version would be like the Habib needle that was bought by Boston and I think has been shelled for the time being, but that's a through-the-needle ablation where the needle goes in, then a probe is introduced, used to apply the energy. Okay, by now you've probably picked up that I'm a total junkie on prospective data. So if we take a look at this space, loads of retrospective data and case reports, but here's a prospective trial that was published by a French group. It was actually published twice, one at one year and one at three years with their long-term data. And what they did is they followed 29 patients. They had criteria of who they wanted to treat. One was a neuroendocrine tumor less than two centimeters or a pancreatic cystic lesion where they had one high-risk feature. And here were their outcomes. 64% of their pancreatic cysts ablated at one year. And at three years, that ablation rate fell to 40%. Neural nodules all disappeared. And that was followed out, as I said, to three years. Now, the problem is at the bottom, and that is the serious adverse event rate was 6%. And that was a serious one, perforation in the uncinet requiring surgery. They did change their protocol based on that, which they proposed eliminated that risk. The neuroendocrine tumors, they had 14 and 12 patients. They described 12 disappearance, 11 then at three years. So a success rate of 65, or I'm sorry, 85%. Again, adverse events, two patients, 16%. Now, mind you, these are low numbers. So you can have two adverse events and really have a high adverse event rate, but that's what they reported. And I would suggest that, again, if it's thermal energy, if it's alcohol, anytime you use a traumatic or disruptive technology in the pancreas, there's gonna be a certain problem that I'm getting a red light. Now I'm getting nervous. I won't show you this, but this is a similar video that I showed before, the ablative process that's in my other slides. I do also wanna mention that EUS guide alcohol ablation has been used to treat neuroendocrine tumors. Large number of trials, all retrospective, just about. And here is their outcomes. Takes about two sessions to do it. The effectiveness, if it's a hormonally active neuroendocrine tumor, very effective, 93%. If it's not, 60. Again, here are the problems. Pancreatitis, pancreatic necrosis, bleeding, abdominal pain. So that needs to be kept in mind when you're treating these lesions. RFA has also been used for pancreatic insulomas. You'll see here that 29 patients overall. Efficacy, very good. These patients all lose their hormonal activity. The last trial that actually reported their data was Mark's, and this year, seven patients, and they did report one major complication, which resulted in a death. And so the adverse event rate has to be acknowledged. Fine needle infusion of other substances. People have tried to put all kinds of things in pancreatic cancer, and all I can say is some of them have been prospective data. They've shown promise, but nothing has shown a survival benefit as of yet. So in summary for the RFA and infusion of other ablations, I'd say there's reasonable data, especially for insulomas and neuroendocrine tumors using RFA and injection of chemotherapy or alcohol. They have a low, but a very real, rate of serious adverse events, and I think that more convincing data and protocols and standardization of this stuff is required. And once again, I know I've said it three times, but this is part of a multidisciplinary approach. This is not something to do on your own. And with that, I'm gonna stop, and I appreciate your attention. Thank you so much, Matt. Really appreciate that fantastic overview, and I know this is near and dear to your heart, so thank you. So we do have time for some questions here, if people have questions. I can start with one that came through online. Somebody's asking, is imaging sufficient for diagnosis of IPMN before ablation, or do you perform diagnostic fluid aspiration first, routinely? Great question. We had a lot of people involved in answering that question. And as you know, determining if a pancreatic cyst is mucinous based on imaging alone is fraught with problems. And so what we say is if the clinical scenario and imaging is classic, then the patient, knowing that there could be some uncertainty here, has a chance to enroll without putting them through an entire diagnostic, the USFNA, if that hasn't been done. But having said that, I would say the majority of our patients come to us with an USFNA and a relatively firm diagnosis. Keep in mind, based on lots of other things you've seen, even if you get an USFNA, chemical cytologic analysis, there's still a little bit of uncertainty, right? So we think that that is, generally speaking, a good idea to make sure the patient really has something that needs to be treated and you're treating the right thing. David. Yeah. You very clearly expressed how you can do alcohol-free ablation, and almost to the point of saying you shouldn't use alcohol. So why do you need to do the CHARM2 study? Yeah, great question. Mostly because when we published CHARM1 and Gastro, there was a lot of people who were, I think, struck by the novel nature of this, and thought leaders, I think, very rightly so, wanted to see this confirmed in a larger, more rigorously designed study that involved multiple centers. And we also improved the way we were doing this. So a couple mechanistic things were done. The way we do this, the FDA had a couple ideas, and it's really a much better trial. Does it confirm what we already know? It's an honest question, and I don't know the answer to that. I do have some, you know, would I like to do it without alcohol? I think you know I would, but I think we, in due diligence, need to answer this convincingly before we can move on. I mean, just as a quick follow-up, I mean, it seems like you've convincingly answered that alcohol is bad. I mean, we need more data on the follow-up and percentage of ablation, for sure, but if you've almost settled the issue that alcohol's bad, why do you have to continue to test that? Well, we're gonna see at patient 50 whether we have futility or not. I would be shocked if we didn't, but you know, it's my hope that it will be done at that point, even though it would be the end of my support, but that's okay. Yeah. Regarding cyst fluid analysis at your center, do you use glucose also in addition to CEA, and what is your opinion on checking for GNAS and KRAS? I know that that's not always the case, and the second question is, why do you think there's a difference between tumor ablation numbers for PNETs versus adenocarcinoma? Yeah, great question. And so, for anybody who didn't hear that, it is, what do we feel, and I would like to see what some of the other experts have to say, is really required for effective pancreas cyst diagnosis, what do we really need to make sure it's a mucinous cyst? Well, first of all, I would say that a lot gets made on the chemical analysis, but I would step back and say, keep in mind that the diagnosis of mucinous cyst is always built in a larger way on, is it the correct clinical scenario? Is there a competing diagnosis? Radiographically, does it look like it? And then, EUSFNA, what are the results? We do, in addition to CEA, use glucose based on some of the good, high-quality data that was presented at DDW last year. We think that that's real and well-proven, and that we don't check amylase anymore. We think that that's really, there's no point in that, and we would very much, at times, like to run the University of Pittsburgh's next-gen sequencing. It's not that expensive, and I think their data that they showed in GUT was convincing, and we would like, in selected patients, to use that. Why am I not? Because getting that through our complicated approval process at Penn State's been a real headache, but frankly, we should be. We think. How about you, John, what's your thoughts on that? So, I do not check amylase. I check CEA and glucose, and then, at follow-up, if there's something indeterminate, or if it's important enough to know, then I'll run the University of Pittsburgh NGS, but it's not a routine thing for me and everybody. Yeah, we do the same thing. I will do CEA and glucose, and if that's not helpful, which sometimes it isn't, and if there is some kind of concern, then I will move on to the DNA analysis, but I don't do DNA routinely on everybody. And we check glucose, too. For those who do check glucose, are you doing it like a glucometer, or do you send it to the lab like cis fluid? Our lab is not willing to run glucose on cis fluid, so we just check it on a glucometer ourselves, so I'm just curious what other sites are doing. I'll go first. I'll just say that we had to go down to the lab, show them the data, have a talk with them, and then they seemed to be fine with it, but they didn't want to do it at our center, either, but we find it much more convenient that way, and it's a little more standardized, too. That's exactly what you did. You send them all the papers, and then they were able to figure it out. Actually, our lab is just running it, thankfully, so yeah. We try to, I mean, I know there's data to show that the glucometer works as well. Sometimes it was just hard for us, because it's viscous, and it just didn't work, yeah. Yes. Oh, sorry. Yeah, quick question. This comes up a lot for us at our transplant center, pre-specifically liver transplant, a patient who have a sizable or mid-size cyst, and so any experience with ablation in those patients yet? I know that there's some criteria, platelet count and that, that's mandated, but just curious, because this is where we struggle. It gets into this chicken or the egg while they're a transplant candidate if the cyst, and if they're not, and so on, so. Yeah, the transplant groups, I think, in most centers are very nervous about putting a precious organ with immunosuppression in somebody who has high-risk neoplasia, and so this comes up at our center, too. We just trained Cheyenne Tucker how to do this process with his team at University of West Virginia, and he tells me that his number one customer is the transplant group that comes across these things. Now, I would say the same criteria of who's appropriate to ablate applies, but there's no reason not to allow those patients to have that treatment option, and we find at our center that our transplant group is so much happier when that thing's not there. Yeah. So one last question before we move on to the last talk for this session. Is it practically an issue or not when suction of mucinous fluid is not allowing emptying of the cyst before infusion of the Paclitaxel? Yeah, that's a great question, and you put the needle in. I tend to use a lot of the 19-gauge needle because it's faster, it's more effective, and I think the amount of dwell time in that cyst, if you can shorten it, makes sense, because there's always movement, there's always a chance that you could come out, but still, you put the suction on and you can't get that mucinogenic fluid out, and so there's a lot of ideas on how to solve that. You can put in, I've put in mucamyst, and just carefully over time, it'll finally come out. John, I know we've talked about that. What do you think? I'll put half just to one cc of saline to loosen it up. I'll put a half cc or a cc of saline in there to just loosen it up and then try to re-suction it again. Oftentimes, that's enough to break it up a little bit so you can try to get all of this, but you may not get that entire cyst aspirated, so you may not be able to put back in the amount of chemo you want, but that's what I do. Great question, though. It does come up, it's very frustrating, and it can take a long, long time to get it all out. Yeah, you have to have the patience at Jobe for some of these, but it is solvable if you just take your time. All right, thank you so much again. Thank you so much.

minimally invasive treatment

pancreatic cysts

pancreatic tumors

EUS-guided chemoablation

alcohol-free ablation technique

efficacy rates

radiofrequency ablation

patient selection