Dr. Al-Haddad, you're live on. Yes. Hey, good afternoon everybody, this is Dr. Stuart Sherman and Dr. Mohamed Al-Haddad will be doing the procedure. We're going to present a more straightforward case to you today. This is 74 year old female with a history of chronic gastroesophageal reflux disease and a prior endoscopy. A CT scan in July 2021 for post-colonoscopy abdominal pain revealed a septated cystic lesion in the neck of the pancreas with no main duct dilation. The patient has no prior history of pancreatitis and no current symptoms suggesting weight loss, abdominal pain or steatorrhea. No history of smoking or alcohol use. The family history is significant for pancreatic cancer in a first degree relative that was older than 60 when they got the pancreatic cancer. A follow-up MRI done at an outside institution in January 2022 showed a 2.2 by 1.7 by 2 centimeter septated pancreas neck lesion with mild septal and peripheral enhancement. There was no upstream pancreatic duct dilation or gland atrophy. Here you can see the MRI. You can see the cyst at the neck. It looks a little septated here. The patient also has gallbladder disease you can see. Here we can see a better view on a coronal image of the MRI. We have a multi-septated cystic lesion in the neck of the pancreas. The patient was referred to us for EUSFNA of the lesion due to its size of more than 2 centimeter, the uncertainty about its underlying pathology, whether it's cystic or non-cystic, and whether it communicates with the duct or not. And also the concern was there's a family history of pancreatic cancer. So our objectives today are to demonstrate an EUS exam of the pancreatic cyst, discuss the FNA technique, demonstrate advanced imaging using needle-based confocal laser endomicroscopy, demonstrate tissue acquisition from the cyst wall, and discuss the diagnostic role of biochemical and molecular cyst fluid markers. Dr. Aldat. Thank you so much, Stuart. Can everyone hear me okay? Yes. Yes. Wonderful. Thank you. Welcome back to IU. You heard the presentation from Dr. Sherman. This is a patient who has an incidental finding of a multi-loculated cyst in the neck of the pancreas. She's not symptomatic, but she's certainly concerned about it due to her family history. And due to the size of the lesion, we thought it's appropriate to bring her in for an endoscopic ultrasound and for further assessment of this lesion. Right now, I got my scope just past the GE junction. I'm talking to demonstrate the body and tail of the pancreas. You probably see there are some changes, brachial changes, including lobularity, strands, and foci. The pancreatic duct in the tail does not appear to be dilated, and I don't know if you can still see my EOS images right now. And the duct is just about under one millimeter in size or so. So that's a remarkable duct. So as we get close to the neck of the pancreas, we start to see the first locule of that lesion. And as you can see, the pancreatic duct runs right by the lesion. And in my opinion, and I know if the audience agrees as well, there is a communication right there. I'm going to kind of scene it back and show you how the duct actually, the side branch comes off into the lesion right there. So we believe this is a side branch IPMN, although you could argue the morphology is consistent with a serocyst because it has multiple locules, and especially the age of the patient and the gender, the location is also consistent with that. But this is why we go with endoscopic ultrasound. Again, here's the main duct, main duct running right into the lesion and the main duct in the neck, as I will point you all out right here, is also non-dilated. So we believe this is an IPMN, but we're going to demonstrate that when we puncture the cyst, we can hopefully get some of the characteristics, features of an IPMN and demonstrate to you a needle-based confocal laser endomicroscopy of the wall of the cyst. So I'm going to ask for a 19 flex. This needle is already primed with the NCLE probe. We prime this right before the case. And I'm getting my needle down here. Yep, let's get that closer. And I'm just checking my trajectory for FNA. We are in a good spot. Again, we see there the communication with the side branch of the main duct. And here is... Okay, so we are now in the cyst. And we need to start projecting some of the still visual images. So now we will put this out. The probe comes out typically about two to three millimeters beyond the tip of the needle. And the goal, I think you can see on the screen the tip of the probe right here. The goal is to have adequate contact with the wall of the cyst. And without adequate contact, the imaging quality may not be as good. And right now, I don't know if you can see, we're starting to prime our cell video system. And I'm going to keep my needle right there as close to the wall as possible. Good, so now we're seeing some vascular patterns in the background. Ignore the static black dots. This is probably some debris on the tip of the probe. But if you look beyond that into the wall of the cyst, you'll see some of the background vascular patterns. In IPMN, we hope to usually demonstrate the finger-like projection. And I usually run this on recording so we can see back, right there, Jay, if you can, see back some of these finger-like projections that I think we had just maybe a fraction of a second of a little bit ago. Can you comment on your technique of using the Infield Probe? Because, you know, I know you don't want to drag it along the wall of the cyst there as you're trying to interrogate different parts of the wall there. And you also don't want to do it for too long. So I was hoping you could just comment on that. Yeah, that's correct. So that's actually one of the images that you can start to appreciate some of these finger-like projections and the background vascular pattern, which is what they describe as a rope and a ladder morphology. So you don't want to be, you're right, you don't want to be driving this needle kind of tangentially up and down the wall, but you'd rather be on fuss with the wall as much as possible, have just enough pressure to demonstrate what's in the morphology of the epithelium, because that's what's going to help with the case. But at the same time, you don't want to spend also too much time. My limit is usually six to seven minutes. The studies have demonstrated that anything beyond that slightly increases the risk of pancreatitis. Now, as I'm doing this, you may not be able to see my EUS images now, but I am slowly advancing the needle to touch the cyst wall. And some like to use torque, right and left, to enhance the contact with the wall. Right there, if you will, Jay. So we're getting some of these projections that, can you freeze this scene back if possible? Yeah, there's some nice papillary projections there. Yeah, so this is probably one of the better images that we have from this case. There's minimal debris. There are just a few clumps there, but if you look at the background, you'll see some of these projections. Some of the more recent studies looked at things like the optical density of the projections, as well as the thickness of these projections as criteria for high-grade dysplasia or even cancer. And I think we need more data on that, but I think we have supplemented our initial impression that this is a side branch IPMN by the view of these finger-like projections. Can I ask a different question? Because you demonstrated the communication with the duct there so beautifully on the EUS. So I'm just wondering, why do NCLE? Because it really looked like a branch-duct IPMN from the EUS imaging. And you can answer a broader question of when should somebody think about using NCLE with these pancreatic cysts? Do you not do it on every cyst that's over one and a half, two centimeters in size? Or do you use it selectively? Correct. I agree with you, Linda, that this was kind of an easier target today. But coming into this case, I had two differentials in mind. One of them is a serocystinoma, which if I diagnosed today on NCLE, I would have told the patient, go home and don't bother because she's not symptomatic. But my other differential was definitely side branch IPMN. I wasn't as much concerned about mucinocystic neoplasm. The morphology was not very suggestive of that. But what I can say in this case is that this would be kind of on-the-spot diagnosis that you would want to consider in a situation like this. And also, this is probably a good case to run something like that if you did not see the communication with the side branch that we saw, or the main duct communication. And if your first line testing, including CA and cytology, has not been helpful, if this patient has been sampled before and this is labeled as indeterminate cyst, this might be another layer of investigation that you can throw in and come to a conclusion. Obviously, a lesion of this size proven to be mucinous, you probably would want to either monitor this at some level of intensity. We can use MRI or repeat EOS in a year and then maybe do that annually from that point on. But definitely sorting out whether this is a mucinous or a cirrhosis is sort of the main purpose of this. So I agree with you, this wasn't necessarily something that we had to struggle with because of the morphology. And there may be additional views of some of these finger-like projections that we have demonstrated earlier in the wall of the cyst. Obviously, you have other things like molecular pathology, you can check glucose on the cyst fluid. I don't use CA as much now to guide my decisions in cysts because I think we've moved on to things beyond that. But yes, this is one of the things you can use to sort out what pathology is the cyst belonging to. Yeah, no, I completely agree with you. I think it can be helpful in those indeterminate cases where you're just not sure. And obviously, it's important to know if it's a cirrhosis versus a mucinous cyst. And there's a question from the audience in terms of the learning curve of learning to interpret these images. How many cases would you say? That's actually not as bad as practicing in the sonographer might think it is. There's actually data on good inter-observer agreement after viewing videos, not necessarily doing live cases, just viewing videos. Because here, it's all about pattern recognition. And you want to just have this pattern of what's an IPML-like, what's a mucinous-like, and what is a cirrhosis adenoma-like. Those are the most common three types you'll encounter in this case. And I would say if you have good skills in the sonographically, obviously, and you watch at least 10 to 20 videos of that, and maybe be proctored through the first few cases, I think you would probably not struggle with that as much. Some technical stuff, including using a 19-gauge needle, obviously, might sway you to use this more often in the body and neck and tail cysts rather than the onset and the head because of the ease of penetration of the puncture by a 19-gauge. But that's not something any endosinographer should have any struggle with. And in addition to antibiotics for the patient, do you ever give these patients rectal indecine? I know there's no data about it, but with the concern from me, these slight increases. Very good point. We have not done this on sort of a protocol of any sort. But yes, any time you spend a few minutes or several minutes inside the cyst with a needle, you are increasing the risk of pancreatitis. Initial studies quoted this as high as 7% to 9% after a needle probe CLE examinations. But the more recent data actually puts this back down to under 5% or maybe even 4%, which is quite acceptable. We obviously give antibiotics and IV fluids. Obviously, these patients need fluorescein before the beginning of the case, so you can actually enhance the visualization. But we have not routinely done that. I have done this in high-risk patients in other situations. I think it's a reasonable thought. I hope one day we'll see a study that tells us a little bit more about this. Okay, here are additional pictures. I don't know if you can still see our feet. Obviously, the quality of the image changes every time you go to a different site. And here we get another site, actually. This is more of a – it's actually the septum that separates this locule from the next one. And we can see that right there, you see these finger-like projections come in and out of view. Remember, this system will visualize you all the way down to 10 microns. So you can see the cellular features in some of these cases. And you definitely could – when you talk to the patient before they go home, you have kind of a fairly good idea about what you are dealing with, rather than wait for the molecular pathology or your biochemical studies to come back from the cis fluid. I still do the cis fluid analysis on everyone, because I think the cytology still can tell you things that you may not have discovered, can show some dysplastic changes. I like personally to check for KRAS and GNAS mutations, just to identify any high-risk molecular features that might make me bring this patient sooner than every other year in this case, especially with our family history of pancreatic cancer. There is a prospective study from Ohio State comparing Salvizio to standard CEA and cytology, and it found that the sensitivity, specificity, and accuracy was much, much better for Salvizio. So they don't get the CEA and cytology, but they found that it was much more sensitive and specific than what we usually use of CEA cytology. Right, but I don't think there's any studies yet looking at like cis glucose or DNA and whether it's superior to that. But absolutely with just CEA and cytology. So you'll do the cis fluid aspiration and send it for what CEA? Do you do CEA anymore? Glucose, DNA, cytology? I like glucose. I think glucose performs better than CEA at this day and age, and we have just seen a recent meta-analysis that showed that the levels below 50 are highly sensitive, 90% sensitive, which makes it a great exclusion criterion for mucinous cysts. But I do also get, especially in higher risk cases, I do obtain molecular pathology, especially KRAS, GNAS, and tumor suppressor genes. There are a couple of platforms now on the market that do this commercially, and I like to supplement my decision making, especially in lesions that I'm leaning towards potentially referring to surgery, but I need a little bit more ammunition to be able to have a stronger recommendation for a pancreatectomy. I could lean on those a little bit more. Yeah, I have to admit, I really like cis-glucose as well. Um, I still do CEA, but I do glucose as well. I don't do DNA in everybody, I tend to do it a little bit more selectively. But yeah. Does it matter to you, Mo, if you do the DNA, if they have multiple mutations or high clonality, low clonality? Yeah. In terms of surgical referrals? Yeah, a high-risk molecular pathology report, in my opinion, it still has to be coupled with a morphological change or some sort of a clinical piece to make this stand as a full picture. I don't send patients with a completely bland-looking cyst, even if they had high-risk molecular pathology results, to the surgeon yet. However, I would watch them a little bit more carefully, especially if you have, for example, a high clonality care asthma, high clonality gene asthma, and you have one or two other loss of heterozygosity mutation, this is a patient you really want to monitor closely, maybe with a six-month interval exam, tumor markers, either MRI or EUS tumor markers, and go from there. I still think those are best dealt in integration with the clinical picture and the morphology and what you see on the US. So having said that, do you routinely get DNA markers when you suspect it's an IPMN or not? I usually I save the fluid and don't ask for it until I get things like glucose and CEA and cytology back, because sometimes those are very helpful. If your CEA is over 1000, your glucose is 25, I think you got your answer right there. It's a bucephalic cyst. So I bank some of the fluid until I get my first-line testing back. If it's back and it's not conclusive, as it is in many cases where your CEA is 150, and your glucose is 75, then I would definitely go to the next level. And in that case, I would go to molecular pathology, because I would like to know if the patient I need to commit to surveillance or not, and what do I do? Obviously, if it comes back with a VHL mutation, I get my answer. It's a serious cyst, and I may not need to continue to monitor that patient long term. Yeah, I completely agree with you, Mo, that that's exactly the way I use glucose and CEA in my practice. If they're not conclusive, then I'll move on to the DNA in the hopes that it will bring some clarity as to what the cyst is. And also, I know you're using a 19 gauge needle, you know, because you have to do selvisio, the confocal endomicroscopy right now. But if you weren't doing that, and you were just, you know, doing EOS, FNA, do you tend to use FNA needle or FNB needle? Do you have a preference? I only use FNB needle if I see substantial thickening or asymmetry of the lesion or nodular. For standard cyst aspiration, which I think 95% of them don't have these features, I would use just a standard, non-FNB, standard FNA device. And I aspirate fluids with with a 22 gauge, usually in that case. Now, bearing in mind, viscosity will sometimes weigh in on that. The higher viscosity, the more likely that you're going to get sufficient fluid with a 19 gauge rather than 22. And that's the beauty of the molecular markers, because if you don't have enough for CEA or glucose, you know, just about 50 to 100 microliters will be sufficient to run the DNA analysis, which is another added benefit to going with some of these molecular platforms. I agree. If you don't have like close to half a cc of fluid to send off for CEA and or glucose, then send it for DNA. Exactly. That's exactly my strategy. Any questions from the audience about the technique? I think at this point, what I might do is go ahead and remove this. If there's interest to demonstrate the Moray forceps, if we still have time on this case, I don't know if you have other centers ready to go, but I'd like to demo that as well, either on this case or maybe on a separate case. I think you can go ahead. We have time. Okay, let me go ahead and get this probe pulled out, please. And can I have the forceps now? Yes, we're good. I think we have it open here. So Mo, there's a question from the audience. There's a question asking, I believe, has NCLE being used to assess response after ablative therapies? Not to my knowledge. So after either paclitaxel or alcohol, can we bring the US picture back to the live feed, please? Yeah, let's just unplug the television. So to my knowledge, this has not been done, Linda. I know that we've actually published on the molecular analysis post ablation, and you can show that they're actually regression of markers like KRAS post ablation. But to my knowledge, I don't know, I don't know what would be the kind of the footprint or the molecular sort of signature or the visual signature, I would say, of NCLE post ablation. So can you talk about the forceps now and your technique? I'm sorry, this is about the forceps, correct? Oh, yeah. Now moving back to the micro... Yeah, this is the Morin forceps. This is a through the needle forceps. You can see it has a very bright leading edge here. It's a 0.8 millimeter in diameter. So actually it goes nicely through a 19 flex. And the jaw is about 4.3 millimeter in width. Once it's open in full capacity, go ahead and open that Amanda, please. And, and usually, go ahead and close. I'm not sure. Okay, go ahead and open now. There you go. If you appreciate the jaws, that both of them are now wide open. I'm actually up against a septum. So I'm going to ask Amanda to go and take that bite. Go ahead and open one more time. I think you've... Okay, go ahead and take a bite. Okay, now we have it. Oh, you see the wall pulling there, tenting the... Yeah, yeah. Yeah, tenting. So you don't want to have too much tension there. But you close all the way. Okay, because I'm getting a little bit of resistance here. Open one more time for me, please. Close. Okay, open now. Close. Okay, now we got it. So go ahead now. I don't know if we can zoom in on the end of the forceps to see what tissue we have. This might be a little bit difficult. As you know, the amount of tissue you get is fairly small from these. Accuracy has been in the, you know, 70% range, 70-75% range of these. And that is mainly due to the fact that you sometimes end up with stroma and you end up with a cyst wall, which is denuded without epithelium, so you can't make a diagnosis. But overall, the performance is better than what you would get out of cytology and CEA. I usually either do touch prints on a slide, or if I'm not in a rush to get a, you know, kind of a quick review, I put it in formalin, and I send this to the lab for processing. Let's see what we have. We do have a formalin cup ready. You can also use a cellular preservative like Cytorich, if you wish, in this case. And I think... How many bites do you like to take when you're using the Moray forceps? Yeah, so it depends on assessment of how much you get with the first bite. Sometimes if you luck out, and you're getting a good chunk, I may only do another one. But if not, I would do up to but no more than three bites. In this case, I, again, I don't want to increase the risk of pancreatitis or bleeding. And in the Moray literature, the pancreatitis risk is collectively in the most recent meta-analysis up to nine and a half or 9.7%. So it is definitely higher than your standard FNA. So you got to stay mindful of that. And also, in this case, you might want to, you know, not go beyond, in my opinion, those, you know, three, three punctures. Right. And there's been a death report that I think from Europe after the use of the Moray forceps as well. I had a moderate severe case of pancreatitis after using the Moray forceps as well. So completely agree that you need to be mindful of that, if you decide to use this. Which, you know, another question for you, Mo, like, if you're planning on doing NCLE, are you also going to be doing Moray? Or if you've seen the superficial vascular, you know, network pattern that's diagnostic for a serious dysthetnoma, you know, not use a Moray at that point? Yeah, that's a great question. I don't know if I would necessarily combine the two technologies in every case. Obviously, we're, you know, we'd like to demonstrate that to the audience. But I agree that you often get your answers by one or the other. I like to use Moray typically, as I have mentioned earlier, in cases where either my first line testing or even molecular pathology has not been of help to me because there are no mutations and my CA is inconclusive. And or when there is a, either a local thickening, a mural nodule, or that you're not quite sure about, or if you think that you might get some, you know, foci of high grade dysplasia or cancer. Having said that, the main utility, I think, remains in underlying studying or assessing the underlying pathology, whether this is a mucinous or non-mucinous cyst. I think it's a good, it's a good tool to have in hand in some of the cases, not every case. And as you can see here, the cyst has decompressed some since we've done the intervention. The duct communication is still present right there, as you can see from that side branch. And we'll wait for all the studies to come back. Now we'll get some fluid actually for CEA and glucose. And so I have an aspiration, a syringe, please. Linda, can you comment about you mentioned the depth in depth in Europe? Did you know what that was from? The cyst collapsed completely, no. I believe it might have been, I'm not 100% certain, Todd, but I believe it was related to acute pancreatitis developing afterwards. As you can see, if you can see from my feed from EUS, there was a fairly rapid decompression of this lesion after puncture. And we only have kind of a shadow of the cyst anymore here. That's the duct going down in the neck. And this is where the cyst used to sit, completely collapsed here. You can appreciate the wall there. And we had gotten about three mLs of what looks like viscous fluid with no evidence of blood. So that's reassuring. Because with amoria, you have to be mindful of intracystic and extra pancreatic bleed when you do multiple passes as we did. But so far, this looks like we don't see any bright echogenic collection either in the cyst or outside the cyst. I'm going back and forth again several times to try to demo that. That's one thing you want to keep looking for after prolonged intervention like what we just did in this case. And I think another point just to mention is that, you know, these cysts are so common, right? I mean, we're seeing them more and more as everybody's getting an MRI or CAT scan done and the image quality is getting better and better. Most of them thankfully, aren't going to cause patients harm, whereas a minority will. So I think, you know, I, again, I just want to, I personally just want to emphasize the point that I don't think we should be necessarily doing more forceps and CLE on like all these cysts. But as Moon said, you know, in select cases, where you feel like using them really is going to change your management somehow, you know, of that patient. Absolutely. And as I said, you can get your answers from a simple FNA or sometimes even with no FNA in some of the lower risk cases, I would say any lesion under two centimeters would probably not lend itself to any enhanced technology or equipment or studies, unless you have some reason to believe that these, either Selvizio or Moray would actually give you additional answers. So I totally agree with you Linda on this. Question from the audience about any difference in tissue yield with the forceps if you do it before or after the aspiration? Yeah, very good question. I'm not aware of data that randomized or even looked at outcomes pre and post. However, my concern usually if I aspirate that I'm going to completely collapse the compartment or the lesion as a whole, if it's a solitary compartment lesion, and then I won't be having as good of a visual on the forceps itself and how it samples the wall of the cyst. I prefer to do it early on before I aspirate fluid. So I have it plump and also I have the, you know, the blackness of the fluid to kind of support my visualization of the forceps. Earlier on when you were tugging a little bit and you said you didn't like that, and open and close, what was your concern at that point that you had too much tissue or? Yeah, so that's a very good question. Yes, I was carefully monitoring the amount of tension I'm putting on the cable and on the wall of the cyst. I do not want to create a, you know, puncture the hole in a full thickness manner where there is leak of the pancreatic juice outside the pancreatic tissue and then cause a collection or pancreatitis. So you have to kind of, you know, just be mindful of how much tension you have and how much able to, you know, how much traction you put on the cable as you pull the moray back. That's a great observation. So you had, again, I know this was a lot for demonstration. If you were an audience member watching and you said, okay, how would I approach this in clinical practice if I'm not going to do that? What would be the downside of just saying, look, I can see direct communication like you did nicely demonstrate ductal communication. There are no worrisome features of the cyst. Let's just say this is clinically consistent with a side branch IPMN and we'll continue to survey it by non-EUS methods per some of the guidelines. Correct. And that's absolutely a very appropriate approach. And I had this discussion actually with a patient before she underwent sedation. And I do emphasize that any intervention you add, whether it's a simple SNA or a moray or, you know, a cell vizio exam will increase the risk of complications. And sometimes you do not need that if you are comfortable with the diagnosis. Clearly in this case, the morphology was highly consistent with the side branch IPMN with no high risk features. So absolutely the appropriate way to shape the discussion with the patient. Yeah, I just, I actually had one patient with a cystic lesion of the tail that I did a diagnostic puncture because she was really worried. And I'm trying to remember when it came back, but she ended up having just with one 19 gauge needle puncture, a pretty bad leak afterwards, which was really unusual. But you know how one case makes you a little skittish. And here I am out there, an interventionalist that's worried, but I worry more about doing things on people that are kind of diagnostic and having a problem that I am doing something therapeutic. You know what I mean? I totally agree with you, Todd. You know that that's why when I got that moderate severe pancreatitis after more, I was like, okay, let me take a step back here and see if I really need to do it for the diagnosis and change my management of the patient or not. So yeah. This is great demonstration, Dr. Al-Haddad. Do you have any closing remarks? No, thank you so much. I hope you guys found this helpful. Very helpful. Very helpful. Thank you so much.

pancreatic cyst

endoscopic ultrasound-fine-needle aspiration

needle-based confocal laser endomicroscopy

Moray forceps

biochemical cyst fluid markers

molecular cyst fluid markers

KRAS and GNAS mutations