Good morning, or actually good afternoon, everyone. After we all got this beautiful lecture about hyponatremia and about the differential diagnosis of pulmonary emboli, we go back to gastroenterology, and we – as a matter of fact, this is important, and I thank Peter for doing this because it reminds me of one of my Dutch colleagues when he was presenting data in one of the meetings regarding the RFA and how there is increased apoptosis. And I asked him, so what are the cellular mechanisms that are involved in this? He said, I don't know, I'm just a scope guy. So obviously, we're not just scope guys. We basically need to remember these things because they can come in very, very handy. Okay, so I'm going to take a little bit different approach. I'm not going to basically shower you with information that you know regarding a very common entity, pancreatic cystic lesions. I would want to introduce you to certain techniques we do and how this should go into your mind when you're thinking of endoscopic solutions regarding managing the pancreatic cystic lesions. We know that they are common. We know that we are seeing them more and more because of increased imaging, because basically of the age where we're getting these images. And we know that as far as the prevalence, it's high, both in studies done in the United States and in Europe. So they are quite commonly seen. You're going to be seeing a lot of pancreatic cystic lesions. So I'm going to just discuss a few cases, very short cases, to tell you what are the techniques that we do, both in diagnosis and potentially in management of these lesions. The first is a case of a 65-year-old woman who comes in with a one-month history of pain, no other symptoms, complicated past medical history, AFib, CAD, COPD, CHF, and she comes with already labs and CT scans. The labs are pretty normal. Notice that this is not commonly done in the United States, high-density serology, but in Lebanon, high-density disease is common. And we often see patients with pancreatic cysts that are high-density cysts. I don't think I've ever seen anything like this in the United States. So there is a cystic lesion that is 30 millimeters in size at the neck-body junction of the pancreas. MRI was done. Again, the patient already had it. That showed that there are a few septations, but the duct MPD is fine, and there are no lymph nodes. So basically, what can we do? AUS would show you morphologically how this cyst looks. The issue is, are these cysts, do they have no malignant potential, or they do have malignant potential? I think that's the best way of looking at them. So to do that, AUS and imaging, other radiological imaging, would be helpful. But it's not perfect. We cannot know for sure if these are things that would become malignant, or they don't have malignant potential. In this case, we did an AUS, and we did not find, except that there was this cystic lesion, 26 millimeters in size, no solid component. The FNA was done. Of course, we need to do that because the patient has multiple medical problems. We need to know pretty much, ahead of sending her to a potential surgery, what this lesion is. So FNA was done for fluid analysis. In addition, we have an additional technique, which is a microbiopsy, which is through the needle biopsy, a microbiopsy that we can put through the 19-gauge needle and get some tissue from the wall of the cyst. And it is superior to the AUS FNA in terms of the fluid analysis, and definitely better than the cytology. So when we get the fluid out, a very simple and easy thing to do is the string sign, which is basically putting this fluid between your fingers. And if it is one centimeter that persists more than one second, that's a positive sign. Very easy, very simple. Tells you if this is mucinous material, and this is very important in your differential diagnosis. So the aspiration, we get this fluid out. We can send it for a CA. Of course, it's important. If it's low, then it's probably a serious cyst or pseudocyst, the benign, the ones with no malignant potential. Otherwise, more than 192 is the set limit. Then it probably would. Cytology is important. Not very, very yielding, but it's important with high specificity. And molecular markers, we're doing them more often, but again, they have their problems. This is a quick table that shows you what we do for different cysts, being the first one which is serious and the last one pancreatic pseudocyst. These are the ones with the very low malignant potential, or no malignant potential. So moving to basically the... Asad, I would like to add that the table should have cyst glucose. Yes, of course. I will mention that in the numbers. We did get glucose, and this is something that we are doing very often. Actually, it can be more helpful than the CA. Again, as you can see, this is how the needle is introduced, and we get it through the biopsy forceps through the needle, and we can get the tissue from the wall. On the right side, you saw the... When do you use this biopsy technique, or what type of lesions? Who's using this technique? It's been available recently. Peter is using it. Do you use it only for cystic lesions, or when you have, like, a nodule you want to target? I have tried it for nodule, and I don't find it to work very well. I'm kind of trying to tunnel with the forceps, but then it usually does not open within the heart tissue. Particularly for cancer of the cyst, it looks pretty good. And the new data is suggesting that the diagnostic yield is pretty good. It's in the 80s. So that's not bad. It's a little bit of higher risk of bleeding, and basically pancreatitis, but it's still acceptable, and it's better than cytology. That's for sure. We know that. Diagnostic yield in what? Or just say it's a cystic needle out of the heart? Well, differentiating the cysts with low malignant potential with the cysts with high malignant potential, or no with high. That's at least the data that has been recently published on, if I'm not mistaken, 400 patients, 11 studies. And that looked at, this is the diagnostic yield for this particular endpoint. So this is one technique that can be helpful in basically us. And in this particular patient, the CEA was high. The glucose level was low. If it's less than 50, 50 is the cutoff limit. It would be suggestive of mucinous lesion, be it IPMN or MCN. Amylase was low, and the biopsy showed mucinous epithelium. So we have our diagnosis. And then there would be an argument, because now we have a diagnosis, then management will be facilitated. Any more questions before we go to the other case? Yes. So I'm going to, what did this tell you, though, actually? It was an IPMN from the beginning, right? Right. But remember, we did this before. Like we took the fluid, we got the biopsy. We do it pretty much routinely. I do understand that a priori, it's easier. But that was done immediately. I mean, the cyst was there. Because many times, we don't get these classic numbers for the cyst analysis. So it's probably an additional way. In our institution, it's easier to do it. So I think this is an additional way of getting better tissue diagnosis. I'm just sort of doing the devil's, you know, as far as what does this tell you that you didn't know. It's almost every cyst over two centimeters is going to be an IPMN. So it's going to, you know, CA, does it change your management at all? So you know it's an IPMN now, but you probably knew it was an IPMN before. What you really need to know is, is it an aggressive cyst or not, actually? And that's a harder thing to tease out. And do these numbers help you at all with that? Well, not much in this case. But this is just to introduce to the fellows what is a technique that can be helpful in some cases. So this is just to illustrate the techniques. But I agree with what you said. Yeah. I think what Patrick is trying to say is my practice, we don't start with a biopsy from the get-go. We start with the FNA first, radiographic findings, patient's presentation. This is a 65-year-old woman, tail cyst, unilocular, likely MCN, body neck, likely MCN, no ductal communication. So you start with the standard fluid analysis first. And if that is non-confirmatory, then you can go with additional techniques. That's absolutely correct. But remember, doing another procedure is extremely expensive. So at the same time, doing it at the same time might be more cost effective. And that's the argument. Because when you get the fluid, you need time. You have to wait until the results come out. And then you have to check the cytology. And then if it's not yielding, or you still don't know, you have to get the patient again for another procedure. Right. The risk of pancreatitis up to 5% to 7% of bleeding. Correct. So I think that's very important to keep in mind. Right. Of course. That's why I said it's usually in the 5% to 7%. It's higher than. But it's another technique. And fellows need to be aware of this possible technique that can be helpful. So the second case quickly is a young woman who comes to the emergency with right flank pain, ended up with a kidney stone. But incidentally, there was a 3 by 4 centimeter lesion, predominantly hyperechoic. Or actually, on the CT, it's just a round structure at the level of the head with mixed fluid and soft tissue density, according to the report. EOS showed that the lesion appeared predominantly hyperechoic with patchy hypoechoic areas. There was no evidence of any pancreatic duct changes or any abnormality in the body and tail. And again, looking at the lesion, it's kind of hard to see it very well. But we do a listography, which is quite easy. And we do it routinely. It's a part of our examination. We did that. And again, the lesion looks solid. But it's not. It's solid and cystic. And you can see that clearly on the listography. You can see areas of bluish discoloration, which involves basically harder tissue, and areas of greenish, which is softer tissue. So it's not really actually mandatory to do this here, because the biopsy gave us a diagnosis. And the diagnosis is a solid pseudopapillary tumor, a young woman. This is in the head of the pancreas. And of course, she would need surgery, because it does have a malignant potential. So to introduce people who don't know about the listography, it is basically a test that we do that can be helpful in defining the elastic properties of tissue. Is it hard? Is it soft? And this can be helpful in two cases. It can be helpful for us to characterize lesions as malignant or benign, be it in the pancreas, be it lymph nodes, et cetera. And at the same time, it can be used as a way to target a particular part of the lesion or to target a lymph node if we have a collection of lymph nodes. So it's good to have this technique. And now people are doing the second generation with strain patterns and calculating the area under the curve. So we're getting more data on that. But it's, I think, a good supplemental way of adding more information that is basically free during the procedure itself. I don't think everybody does elastography. Anybody does elastography on a routine basis here? So it's a part of the US exam. And we do it on every time we do an endoscopic evaluation. I think it just became available recently. I don't think it's been available in the US until recently. Yeah. It's mostly started with the Pentax and with the Hitachi. It wasn't available, to my knowledge, with Olympus. But now it is becoming available. But now there are more advancement in the elastography. So there are more ways of looking more precisely at the elastic properties of tissue. So this is quickly, again, the third case. A 40-year-old woman comes with symptoms of fullness, nausea, vomiting. Occasional vomiting, I would say. Labs are OK. CA99, still upper limit of normal. AGD showed an extrinsic, I would say, impression, not compression, at the level of the duodenum. And she had an EUS that showed a lesion that is cystic, basically. There are large cysts, smaller cysts, et cetera. And that was actually done before she came. So this case was already done. And the CAA was low. Amylase was low. And the fluid that came out is clear fluid, negative for malignant cells. So there is no cytology, no cells, acellular, and no mucin. So this is most probably a serious cyst. But at the same time, I want to introduce to you another technique that can be used, that can be helpful. Of course, in this case, it's not really basically—it wasn't done. But in general, confocal laser endomicroscopy is a technique where you can put this microscope fiber inside a 19-gauge needle and put it against the wall. And again, I have to admit that it is not risk-free, so it can end up with bleeding, pancreatitis occasionally. But it can also be helpful in looking at the vascular network of the cystic wall, like you can see on the image here, that can be very suggestive of a serious cyst. And you can look at papillary projections, like you're doing here on this video, that are papillary projections that are characteristics of IPMN. So this is another way of, again, adding to our armamentarium of diagnostic weapons that we can use in case the cyst needs further characterization. Two more quick cases. This is a case that came to us, 52-year-old, came already with an EOS that was done, small cyst in the head of the pancreas with the big nodules. And the question is, is this nodule a neural nodule that is this plastic, a malignant nodule, or is it a mucus plug? Morphologically, you cannot know for sure, even if you know, have the halo and the smooth margin. What we do, again, routinely in this case is we do the contrast enhancement. And we do give contrast in the vein. And we look at its microbubbles, go to the areas of the microvessels. And if this is a mucus plug, for example, like you can see here, it looks actually quite malignant if you look at this one. But it's not because it did not take the contrast. So it is nothing. It's a mucus plug. While these ones look smaller on the lower part of the screen, but they lit up when you gave the contrast. So these are highly suggestive of malignancy. And this is a technique that I find very, very useful, not only for this, but occasionally for lymph nodes. The first case that was presented by Amit, remember the one with the lymph nodes, adding elastography and contrast enhancement may probably add to our yield for a lymph node in case we cannot go through the tissue and get the lymph node biopsy because of the tumor between the needle itself and the lymph node. So this is another way of doing it. The second technique is microbubble. We use Sonovu. This is the one that was available for us for years. Microbubbles, it is basically sulfur hexafluoride. You give it in the vein. There are certain contraindications. We have to use a certain caliber of an IV. And we have to look at the early phase, which is 10 to 30 seconds. The timer will start immediately when you inject it. You have to keep your eyes open. We record it, of course. But then the delayed phase is 30 seconds to two minutes. And the last one quickly, what can we do when the patient is a poor surgical candidate, if there is a cyst that is probably a malignant cyst, or the patient refuses surgery? There are many modalities, but I have to tell you that they are still not being done routinely on kind of one-to-one basis and in big academic centers. Alcohol ablation is losing the – it's just injecting alcohol into the lesion, into the cyst after we aspirate it. There is data. It can result in basically ablation of the cyst. But the chemo ablation is more effective as far as ablation with better long-term studies regarding the persistence of the effect. And lately, there is more data that is emerging on radiofrequency ablation, which I've used before for locally advanced pancreatic solid tumors if the patient is not a candidate for surgery. But for cysts, there is more data because it can induce cytotoxic effects, vascular effects, and can lead to necrosis and the resolution of the cyst. But, again, this is just for the future, for research purposes. All of you will be doing this in the future. So this is basically food for thought. And, of course, this is a discussion, so any questions from anybody? It was very clear. Any of your sites doing any research on ablation? There are many centers doing this now, right? Any of these centers in Indiana? We're part of the CHARM. Yeah, CHARM, yes. I think there are over 300 patients published for alcohol, paclitaxel, or the combination of these. The combination, right, right, right. Of course, alcohol itself alone is no longer an option, I think. A combination is the pattern. And, again, so the idea was here to just introduce you to what we do, and then, of course, you have to use your decision, and you have to individualize, and then the decision will be made accordingly. I think the thing with peggers cysts, at most centers, these are generally indolent lesions, actually. And I think we may be going to hell in the future of how much stuff we have done to cysts and how much surveillance and FNAs in these cases because most patients don't have cancer and will never have cancer. And the data is about 0.25% per year, and that's probably exaggeration, actually. So these are generally, I think the key point is these are indolent lesions. These are rarely aggressive lesions. I completely agree with you. And this is basically when, I didn't even go through it. This would be like another lecture or lectures. When we do FNA, I mean, that's a different story. So we don't do FNA or even EUS on every cyst we see. I mean, there are so many of them. But when we decide to do something to characterize the cyst, this is what we have at our disposal. So that's the idea to introduce you to. But again, absolutely, we don't have cyst means EUS. No, absolutely not. And there are a variety of guidelines out there, guys, consensus guidelines, ACG guidelines, HEA guidelines, and then there's a radiology guidelines and surgical literature guidelines, and there's subtle nuances in each one of them. So it's good to get yourself aware of what your center is doing. If you look at all these guidelines, they are nothing beyond experts' opinions. They are all experts. There are so many of them. There are like the Fukuoka 1 and 2, and then there is the ACG, the ASGE, the AGA, and there are the European ones, and there are the radiological ones, and there is no consensus. And even the definition of when to do a test and how to follow the patient and what are the worrisome criteria is completely heterogeneous. For more information, visit www.ISGlobal.org

pancreatic cystic lesions

diagnosis

management

endoscopic ultrasound

fluid analysis