Chapters Transcript The Role of Endoscopic Ablation Course: Big Gut Seminars: Focus on Complex Pancreatic Disease Uh, so today, I just wanna talk a little bit about the role of endoscopic, uh, ablation for pancreatic neoplasm. Um, There are various interventions that we can do through EUS for cancer directed therapies. They are ablative techniques, and those can be either chemical or non-chemical. Today I'm going to focus on radiofrequency ablation. We can also directly deliver therapy, whether that's immunotherapy, chemotherapeutic agents through a viral vectors. So a lot of opportunities here. A radiofrequency ablation through EUS is a low risk, minimally invasive procedure. We're using heat waves to cause a tumoral tissue burn, and that effect is mediated by coagulation necrosis, and it will lead to cellular damage, apoptosis, but it doesn't significantly affect normal surrounding tissue, and we do think that there's also an anti-cancer effect that's induced by immunomodulatory activity. So, uh, radiofrequency ablation has been described in neuroendocrine tumors and inoperable pancreatic cancers, and now starting to be looked at as a treatment prior to operations. It's also been shown in lymph nodes and pancreatic necrosis metastasis and in cystic neoplasms. But today, in the interest of time, and I know everybody's very hungry, I'm going to follow, uh, focus on some solid tumors. So, Uh, radiofrequency ablation, uh, really got most of our experience in pancreatic neuroendocrine tumors first. It's an increasing problem, um, in terms of how we're managing the, these patients, and you can see that the incidence is, is rising, and that's probably mostly because of an increase in, um, incidentally found lesions on cross-sectional imaging. Uh, and the majority of these are really localized disease. So, uh, this is a good option for this patient population. And we can talk about neuroendocrine tumors, uh, whether we'll break them down into functional and non-functional tumors. Um, when you're doing your workup, you want to first confirm um whether there's any kind of metastatic disease, so you do need imaging, uh, and we do EUS FNB to establish the grade of the tumor. If possible, uh, and you want to do a biochemical workup to see if it's a functioning or non-functioning tumor. So speaking about nonfunctioning tumors, insulinomas have a small risk of metastasis and malignancy. Um, so we do have some experience in these patients. And for those who have tumors that are less than 2 centimeters, you can consider ablation or surgery, but those that have either a higher grade tumor or a larger tumor greater than 2 centimeters, we want to consider surgery. For other functioning tumors, the risk of malignancy and metastasis is much harder, it's much higher, um, and we don't really have a great understanding of the impact of that size and grade, so the patients are going to surgery. For nonfunctional tumors, uh, the same things. We want imaging to understand if there's metastatic disease. We're biopsying to understand the grade. Uh, for grade one lesions, um, the risk of lymph nodes or mets are pretty low, and so we can consider doing ablation or Simply surveilling these patients for the higher grades, risk of lymph node metastasis is much higher. And so we're going to consider surgery, and there is a bit of a gray zone in patients who are not surgical candidates, whether we can consider ablation, that the higher grades should be considered for surgery. So this is our equipment. Um, there is a, a 19 gauge FNA needle that's used, and you can see that there is a radioactive uh part on the distal tip of the, of the needle, and it does require its own generator, which may be cost prohibitive for some institutions, but the company that we're using does allow us to lease as needed. So that is helping other institutions. There are things to consider when, when you're talking about doing these cases. The anatomic considerations really come into play here. One of the most important things is to understand the close proximity to the pancreatic duct. If it's too close to the duct, you can get thermal injury that can cause damage to the duct, an injury. We want to know its proximity to larger vasculature. There can be concern for a thrombus formation or also even just dissipation of the electrical activity across the vasculature that may decrease the ablative. Uh, effect and also of course technically difficult areas for us to access predominantly in the tenant process or head of the pancreas. We also want to know if there's a cystic component to the lesion, especially if it's a macrocystic component, because we'll aspirate that prior to the ablation. There are 3 different sizes of the needle that basically is tailored based upon the size of the of the lesion. Um, we want to, as we're assessing this lesion with EUS, sometimes they're very difficult to see these little neuroendocrine tumors and contrast enhanced EUS can help with that. Um, and of course we're doing real-time imaging guidance as we're, we're doing the ablation, and I'll, I'll show you an example of that in just a minute. So this is um ablation of a neuroendocrine tumor. Um, and here we're showing this hypochoic lesion. You can see the pancreatic duct is right below it. Uh, just a second here, I'll show again. There's the duct right below it. Uh, we're gonna advance the needle into the lesion, and you'll start to see this white hyperechoic, uh, bubbling as the ablation is taking place, um, which shows that we've gotten a good effect. So there's, you know, everything that we're going to talk about today is similar to what Dr. Hewitt said. All of this is a very small volume, um, you know, case series, case reports, as we're getting our experience with these techniques. So for neuroendocrine tumors, these are some of the major studies, and there's a great variability in the number of patients included in these studies, um. And you're seeing a higher volume down towards the bottom as we're getting more experience. This is about 200 patients that we're looking at, and we're looking at the percentage of no response to ablation, partial or complete response, and the majority of the patients are getting at least partial or complete. Response. And when we talk about the adverse events, which we'll we'll go into a little more detail on that, they're generally minor issues, and that is quite variable between 10 and 20%, but mainly is mild abdominal pain. So when we think about what could be a predictor of response, there are, um, there was an abstract submitted to DDW last year. Is it related to the size of the needle? Is it the wattage that we're using? And you know, this is certainly something that is a topic of discussion right now. We did find that the number of. Medications, uh, had a significant difference. So, um, I'll give you an example of how we do this in a video in a minute, but essentially, as you're inserting your needle into the lesion and, and, um, performing your ablation, you really want to scan the entirety of the lesion and make sure that we're going at different angles to get a more complete ablation. And this, at least preliminarily suggests that that maybe, uh, give us a better effect. Um. They also looked at lesion type, whether a solid versus those with a cystic component uh made a difference and, and the grade of the lesion, but it was really just the um RFA applications. So there is a small study that looked at RFA versus surgery in patients with functional neuroendocrine tumors, and you know, as you would expect, we see less adverse events with US RFA and of course reduced hospital stays, but we do see that there is a higher relapse rate in patients who did not have surgery. So I want to switch gears a little bit and, and we're starting to consider doing this in patients with pancreatic adenocarcinoma, and what we know is that the pancreatic cancer microenvironment really is a barrier to systemic therapy and, and local control can be associated with a survival benefit, at least we think that in locally advanced pancreatic cancer, possibly a metastatic. Disease. So an ablative strategy may offer an alternative or an adjunct to surgery when we're talking about achieving local control. It's, as we said, it's minimally invasive, and we can also combine that with systemic therapies. Um, directly delivering therapy, um, to the tumor itself, the primary tumor itself, might help us to overcome this barrier that we're talking about with fewer side effects. So the US is really the safest and most effective way that we can do that. Um, so what would be our goal in pancreatic cancer with using RFA? It would be really helpful to downsize lesions to improve surgical candidacy. We could use it to ablate unresectable cancers as part of a multidisciplinary approach, and in some patients it may be a palliative option. So here is just a video of us. You can see this gray hypoechoic lesion, the spleen, this is in the body of the pancreas. The splenic vein is right underneath of it, and this will be a good example where you can see us doing um. The kind of fanning technique. So here the needle inserted from distal to proximal. We'll start doing ablation here and you'll start to see those white hyperchoic bubbles here showing our ablative effect. But we'll also, uh, just pull, as we pull back on the needle, um, kind of redirect to another tangent and another angle to make sure that we're getting, which you can see right here, we'll redirect the needle. To just get that other side of the tumor so that we have kind of a more complete ablative effect. And you could see here we're just going in that other side. So, um, there are very few case studies looking at the use of RFA in these patients, um, but Dr. Thesani did a small case series of 10 patients using US RFA along with first or second line chemotherapy and those with locally advanced pancreatic cancer or metastatic cancer. Um, there was no limit on the size of the tumor, um, and patients got 1 to 5, um, sessions of a USRFA along with chemotherapy. Um, so 2 of those patients had no response at all, but 6 had either stable disease or a reduction in size of the tumor by 30%, and 2 patients had a 50% regression in the size. So promising. Um, this is just a case series of 3 patients, uh, who had borderline, um, resectable pancreatic cancer, and, um, they looked at doing neoadjuvant chemotherapy along with US RFA, uh, and you can see, uh, just to highlight the size of the tumor, uh, prior and after chemotherapy and RFA, uh, this was at 4 months. Um, you can see the size was reduced in, in all the tumors, all 3 of these, uh, pathologically, um. One patient had very minimal response, but two patients did have near complete response. So I certainly need more data here. Uh, finally, uh, Doctor Ganda has a clinical trial that's going on now looking at USRFA here at NYU, um, and, uh, in patients who are on 2nd or 3rd line chemotherapy and locally advanced pancreatic cancer, and there's some promising data here, uh, a few patients, um, but. We're seeing at least a partial response or stable disease in short-term follow-up. We're seeing some reduction in the diameter of the lesion and stable disease in upwards of 75%. So these are all quite preliminary but promising. Um, very briefly to talk about adverse events that are associated with the US RFA, these are just some summaries of patients who had RFA for neuroendocrine tumors, cysts, and cancer, and generally speaking, these are all mild to moderate. Adverse events, namely abdominal pain or pancreatitis. Two patients did have necrotizing pancreatitis. There was a report of a patient who had pancreatic duct stenosis as a result and required ERCP with stenting, uh, one episode of peritonitis, but generally speaking, um, a safe option. So to summarize, uh, USRFA is technically feasible for solid pancreatic neoplasms. Uh, most of our data in the US, at least, is with neuroendocrine tumors that are small, and you know, there's, uh, this population of of pancreatic neuroendocrine tumors that are between 1 and 2 centimeters that are a bit of a gray zone, whether we should be considering surgery and patients have hesitancy about doing just surveillance. So this may be a problem. Promising option for them. It's well tolerated, safe. We're seeing that it's quite effective. Uh, we at least see that there are partial or complete response rates which are very promising, but certainly long term data is needed, and we really need to validate the efficacy of this. And I think that there are a lot of questions, uh, and a lot that we can do to study this, you know, uh, there's quite a bit of variability in the power that we're using for the ablation, how long we should be doing it, um. So I think we need to standardize our technique alone. Um, but, you know, other points that we would like to study is just the, the treatment strategy. Are we doing this alone? Are we doing this, uh, along with targeted chemotherapies? Um, what are we doing for surveillance thereafter? Are there any kind of early markers of treatment efficacy, and then really understanding the effect of the treatment and how that looks on the, um, the surveillance imaging. Uh, but I think it's a really, um, promising technique for our patients. Thank you. Published January 10, 2025 Created by
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