All right. Welcome back. Let's resume the afternoon session. We have four remaining wonderful talks by world experts. You do not want to miss these. And I would like to first invite Dr. Anne-Marie Lennon. Dr. Lennon is very well known in the world of pancreatic cysts. You must have read all the papers and been on guidelines and on the cutting edge of innovation. We look forward to learning from Dr. Lennon about pancreatic cysts. And that's one thing you'll see a lot of from day one of your practices. Wonderful. Thank you so much. So has anybody here? I had this earlier on, and I admit it. I have a confession. Has anybody here had a computer issue? If you raise your hand if you've ever had a computer issue. OK. Oh, I'm so pleased. I'm not alone. So I got a new computer. And when I looked at my new computer around 10 days ago, I suddenly realized that the 15 years of videos that I'd collected are now all gone. And so my plan B, which was to email one of my prior fellows saying, hey, can you send me some videos? That worked wonderfully, except that when I opened them, none of them worked. So we're going to go on to plan C, which is I wrote a book chapter about it. And I'm going to share with you some beautifully edited videos courtesy of our advanced fellow. But they also have some wonderful logos on them, which are added on for free. So let's get started. How many people here have seen a pancreatic cyst? Any hands up? OK, fantastic. I'm relying on you for support. Now, does anybody know why we care about pancreatic cysts? Cancer risk. That's it exactly. So we don't care about them because they're common, OK? So I'm just going to put that straight out there. The only reason we care about pancreatic cysts is because pancreatic cancer currently has a survival of just over 12% in the United States. So 88% of the patients that you see will die from pancreatic cancer within five years. There are three precursors to pancreatic cancer, pan and lesions, which we currently cannot detect, IPMNs and MCNs. So IPMNs and MCNs are pancreatic cysts. So two of the three precursors to pancreatic cancer are cysts. And that is the only reason that we care about them. So we're just really trying to identify those precursors. So if you take on one thing from today's talk, it's that. OK, I have no relevant disclosures. You've made it through the weekend. It's Monday morning. And you are going into endoscopy, and this is your patient, a 72-year-old lady. You are very good. You go and take a good history because when you go and you check and you say, double check if she's got any symptoms related to any pancreatic type of down pain, any anorexia, any weight loss. And the great news is she doesn't. You also check if she has a history of pancreatitis. And then you also check if she's got a family history of pancreatic cancer or related cancers. These, taking a good history, it takes you three minutes, but it's really, really, really important. And it's going to make your life as an endoscopist so much easier. You also note when you're doing your prep that she had a recent A1C and a CA99 that were normal. This is her imaging. She has a 2.8 centimeter cyst in the body. Her pancreatic duct is reported as being normal. It may possibly connect with the pancreatic duct, and there's no neural nodule or sciatic component. You guys okay with that? Okay, should we do an EUS? I'm getting a no here. I'm getting no, no, no. Okay, so before we get to that, what are the questions we need to know? Two questions. One, what type of cyst are we dealing with? And number two, if it's an IPMN or an MCN, remember most of them do not progress to cancer. So is there high-grade dysplasia or cancer there? Because we would then send those patients to surgery, the rest of them are going to follow. So here is sort of an outline of the, so question one, what type of cyst are we going to deal with? So I have three buckets. Bucket one, cysts that have got minimal or no risk of cancer. Pseudocysts, everybody, I think, has seen pseudocysts, isn't that right? Cirrhosis, you guys seen cirrhosis? Yeah, I'm getting nodding. Lymphoepithelial cysts, retention cysts, congenital cysts, lymphangioma. Much rarer, but again, you guys are advanced endoscopists, so something you need to know about. If you have patients with these, great news, you can tell them these are benign. You don't need to see them again. So these patients should not undergo routine surveillance. Bucket two, malignant transformation. So cystic degeneration of malignant cysts. Pancreatic adenocarcinoma, you've all seen. Cystic degeneration of neuroendocrine tumor, anybody here seen it? Yeah, okay. Solid pseudopapillary tumor, rare. As the name suggests, it's both solid and cystic. Occurs in young women, typically, almost exclusively in women, and typically in their teens, 20s, or early 30s. Okay, so again, if you see a young woman with a solid and cystic lesion, think of a solid pseudopapillary tumor. But it's very rare. Pancreatic oblastoma, astner cell cyst adenocarcinoma, again, rare. And then finally, of course, the middle one, IPMNs and MCNs. Okay, we come back to our questions, when should we do in the US? And if we look at the new guidelines published in 2024, they're very broad, and they say, if it changes your management, okay? So let's look at this in a little bit more detail. So let's presume that a 2.8 centimeter cyst, and let's, I would probably do in the US, because I wanna know. So if we take it, if you got a little old lady like this, and she's 92, is that gonna change her management? I would say no, probably not. In fact, I would probably argue we shouldn't be doing surveillance, all right? Or could we do significant harm? If you perforate her, she's probably gonna be in big trouble. So for her, I would absolutely, I probably wouldn't do my US. A young lady here, like this lady, what happens if you find it's a serious cyst? Well, that's important to know, because then she doesn't need any further follow-up. What happens if you find it's an IPMN or an MCN? Then you're gonna wanna watch her very carefully. So in her 2.8 centimeter cyst, I would do it. So again, it takes a little bit of thought. So we go ahead with our US, and this is what we find. Hopefully it'll play. Okay, so what are you guys seeing? It's a cyst? Okay. Okay, so you're seeing small, so multiple small cysts, is that correct? So a cyst with multiple tiny compartments. Honeycomb, probably if you measure them, they're probably less than a centimeter, which we would define as microcystic. So this looks great. So we're gonna go ahead and do a test. So we're gonna do a test. We're gonna do a test. I have congratulations. So fantastic, we've got the diagnosis. So the next question is, as you look at imaging, and this is what you see, how good are we as endosynographers in saying what type of cyst somebody has? Are we much better than the radiologist? So let's look at the data. So this is the data from a prospective study by the Dutch. And what it shows is our ability as endosynographers to look at something and say, this is what it is, to differentiate IPMNs and MCNs, or mucinous cysts from other types of cysts, you can see here is not bad. Sensitivity of 78%, specificity of 67%. So not bad, but far from perfect. So as you can see on the left-hand side, classic microcystic cirrhosis, that's easy to do, but the one on the right, what do you think that could be? Call out some ideas. MCN, yeah. Anything else? You can't go wrong. What, IPMN, yeah, absolutely. Anything else? Could be a pseudocyst, yeah, but you were unbelievably good and you took your history at the beginning to make sure she didn't have a history of pancreatitis. So in the absence of a history of pancreatitis, very unlikely to, but again, another really good reason to take a good history. Okay, anything else? I got IPMN, MCN. It could be, and you'd want to know, is it inside the pancreas or outside? Macrocystic cirrhocyst, okay. So more than 50%, less than 50% of cirrhocysts have got that microcystic appearance. Over 50% will either have a mixed appearance, a macrocystic, and this cyst was actually a cirrhocyst, or they can also, 5% of cirrhocysts come as a solid component. So again, remember, imaging is not perfect. So what else are we going to look for? We're going to look at the pancreatic duct, isn't that right? So remember, three in the head, two in the body, one in the tail. If you go over 70, we add one millimeter, 432. So you're going to measure the maximum diameter. So here we got it, we've got a dilated duct. If you've got a focal dilation, trace your duct to the transition point. Okay, you want to see where is that pinch and look for your mass. And then if you don't see a mass, consider biopsy there. If you've got focal dilation of the entire duct, make sure you have a look at the ampulla, look for obviously mucin coming out of it, and make sure you're not missing anything. Okay, what else we got? So it is Friday, it's 4.30 in the evening, you've just had a really busy day, you're going to the cinema with your friends, you're dead late, you've got a person who's got a family history of pancreatic cancer, you've got an eight millimeter cyst in the head of the pancreas, you have a look at it, you go, fine, and you pull the scope out. So I put this in just to remind all of you that IPMNs are a field defect, they affect the entire pancreas. And particularly in familial with small cysts, you can get a cancer which is totally unrelated to your cyst. So when you're busy and you're tired and it's the end of the day, and you go in and you just go and needle a cyst, please remember, it's an entire examination, so you should look at the head, the neck, the body, the tail, and you're looking for a small cancer. That's your job, not just to go in and have a look at the cyst and stick a needle into it. So let's have a look at a few other things. Here's a couple of more videos. And again, this is courtesy of Linda, did a wonderful job labeling all this. So here you are, body, tail, in a second she's gonna tell you here's the cyst, you guys can see it coming in here. And then she's gonna highlight for you the wall. So if you have a look at this, what do you think? You think it's thickened, do you agree with her? Okay, and you can see that there's something inside of the cyst, so there's actually mucin in a thickened wall. So again, you're just gonna start thinking about this. Okay, so let's move on to the next one. Okay, so here's a still image, so let me show you, can you guys see? So here's a cyst, you see the cyst here, maybe a slightly thickened septation, but as you look towards the edge, you see it's irregular, and then here you can see again the thickened wall. So let's move to the next one. Okay, can you see the cyst? And then if you look at the edge of it, okay, so there's something in it, and again, do you see this thing here? Okay, as we come through, so that's concerning, okay. And here, so do you see this? It's a well-defined cyst, but you were told it was a cyst, so if you look at this you're saying, hmm, not much too much cyst there, fairly solid. So if I told you this was in an 18 year old young lady, what do you guys think it could be? Wonderful, so and this is a solid pseudopipillary tumor, this is classic for it, so solid and cystic. Okay, and here's another example, so you can see here, here's your cyst here, and you look at the edge of it, but when you see the edge, it seems a little irregular, and then if you trace it back here, you can see there is this solid component here. So let's say you see a mural nodule, does that mean your patient has cancer? And again, here's the data, so if you look at this, it's a systematic review of mesh analysis, what you can see is the presence of a mural nodule, has 63% sensitivity and just 75% specificity for the presence of high-grade dysplasia. There's a lot of debate about mural nodules, height, etc., and this, and so this is what's, I think, one of the best papers that I could find. You can see the bottom line, take-home message, the bigger the height of the mural nodule, the higher the risk of high-grade dysplasia, and you can see if it's five to ten millimeters in height, you've got an odds ratio of three, if you go up to greater than ten, you can see the odd ratio goes up to eight for the presence of cancer. So you want to, you're going to document the height, aren't you, when you do it. Okay, so one of the problems is that not every lump in a cyst is a mural nodule. So how do you differentiate a mural nodule from mucin? You guys think you're going to see this? Anybody seen a lump and thought, hmm, I think it's a mural nodule? And then you need to make a decision, if it's a mural nodule, you're probably going to send the patient to surgery. That could be a whipple that carries a significant risk of death. So you guys know you don't want to send them for mucin, isn't that right? That would be a really bad mistake. So this is a study from the Mayo Group, but I like it, I find it very useful. So you've got your mural nodule on your left, I think, and the mucin on the other side. So the first thing you're going to do is you're going to look at the edge. So do you see the edge of the mural nodule? It's irregular. In contrast, the edge of the mucin is smooth. The second thing you're going to look at is the center of it, and do you see how the center of the mural nodule is the same color as the surrounding tissue? So it's iso or hypochloric. In contrast, if you look at the center of the mucin, it's dark or hypochloric. And then finally, if you look at the edge, you can see the mucin has got a rim, while there's no rim present in the mural nodule. And if you have all three of those features, you've got your accuracy around 90%, and I actually find that very useful. The other thing we should all be doing is contrast-enhanced EUS. This was the largest systematic review and mesh analysis in patients who all went to surgery, and you can see how incredibly useful it is. So here, we've got this little thing here. You think, hmm, I wonder if it is something. Maybe it's just a slightly irregular, maybe that, you know, the cyst comes in and out here, and then you look over here and you can see it's enhancing. So again, very useful. Okay, yes. Yes, you can absolutely put Doppler on. There's been studies which have used Doppler versus contrast harmonic, and the contrast harmonic is better, but absolutely. So my next question for you guys, should we do, so next question, should we FNA something? And I've just put this up as a picture. So big, big cyst, should you, should you biopsy or not? What do the guidelines say? And if so, what would you send it for? So I'm going to put you out of your misery, and I also want to keep to time if I can. So when do we do an FNA? And the answer, again, is when it alters your patient management, okay? So on a large cyst, like the one that we're looking at, I would biopsy it because I want to know is this a macrocystic cirrhosis, in which case I'm going to discharge the patient. Is it an IPMN or an MCN? If it's really big, I might think about surgery. If you know, is there anything else concerning? So what are we going to send it for? Ideas. What am I going to send the biopsy for? FNA? What are we going to send? CEA? Amylase? Cytology? Glucose? Okay. I'm just going to put amylase straight out there. Amylase, I didn't bother, again, because I did want to stick to time, so I didn't pop it. There have been several studies done which show that there is no difference in the amylase level. So you think an MCN, no communication with the duct. IPMN, communication. And you think, oh, amylase is going to be high in the IPMN and low in the MCN. It's not. Amylase is high in both. Amylase is also high in cirrhosis. The only use of amylase is a low amylase in helping exclude a pseudocyst. So again, I will not personally send it unless I'm looking for that. So let's have a look and see what we have. Antibiotics. Who gives antibiotics here? Okay. So absolutely, if you look at the guidelines, they say we should give antibiotics. However, the guidelines were written many, many years ago. So again, guidelines are only updated, usually, every couple of years. So this is a multicenter randomized controlled trial in just over 220 patients. You can see that the infection rate in the individuals who got antibiotics and who didn't was identical. There was no difference. There are two prospective randomized trials which also show no difference. And these data suggest that routine use of prophylactic antibiotics is not justified. And there will be an ACG and ASGE best practice article coming out at some point in the next six months which will quote this new data. You guys are therapeutic endoscopists, so I'm going to make sure – please make sure you read this very carefully. Prophylactic antibiotics should be considered in immunosuppressed patients or in those with multiple comorbidities in whom infectious complications might prove particularly dangerous. So there is a little proviso in it, okay? Okay, here we go. CEA. You guys, I think, know all this. I'm going to go through it quickly. So IPMNs and MCNs. High CEA, classically we use 192 cutoff, or a low glucose. So CEA and glucose are opposite, high CEA, low glucose, IPMN, MCN. If you have the reverse, a low CEA classically below 5 or a high glucose, you're dealing with another cyst. It could be cystic degeneration of a neuroendocrine tumor. It could be a PDAC. It could be a serocyst. It could be a pseudocyst, okay? So how good are they? Here's a recent systematic review of mesh analysis, and you can see, not very good. So that's the data for CEA. What about glucose? And you can see here, much better. Little proviso, you note that the number of studies published are much smaller, and the number of patients in it, again, are much smaller. Okay, who here is going to read the cytology report on the patient that you see and call the patient with the results? Probably all of you. Okay. So when you see the report, what are you looking for? Number one, you're looking for mucin. If you see mucin, this likely represents an IPMN or an MCN. If you go through the stomach, occasionally you can get gastric contamination. So that's what I say, supposedly. Other thing you're going to look for is the presence of high-grade dysplasia or cancer. Molecular markers. Anybody send molecular markers? No. Okay, one person, all right. Not that many. If you send them, this is how you interpret them. So firstly, if you have a mutation in VHL, you can see here that this has exquisite specificity for a cirrhosis. So if your patient has that and they say, no, no, doctor, you're wrong, you can not only quote this paper, which has got over 2,000 patients in it, you can also quote the recent systematic review, which said 99.5% specificity. So again, that's very useful. Number two, if you have a KRAS, GNAS, or BRAF mutation, you can see that you're dealing with an IPMN or MCN. So that's what that means. If in an IPMN or MCN, if you also have P53, SMAD4, CTNN, B1, or mTOR gene mutation, you should be very worried. There is a high likelihood that your patient has got high-grade dysplasia or invasive cancer. Depending on which one it is and what other features you have, that patient should be considered for surgery versus very close surveillance. So a SMAD4, I will absolutely send the patient to surgery, irrespective of what I see on imaging. A P53 with no imaging concerning features, I may watch very carefully. Okay, so finish up. Other things you could do. You can also have do NCLE. And this is a beautiful example of a classic finding of an IPMN. You could also do through-the-needle biopsy. And you can see here we can grab a piece of tissue at the edge. So how good are these? So here is a systematic review and meta-analysis comparing them. You can see technical success, similar. Diagnostic yield, minimally higher in NCLE. You can see the ability to identify an IPMN or an MCN, minimally higher in NCLE versus the through-the-needle biopsies with high specificity in both. Concordance with surgical pathology. So here you can see it's 82% for through-the-needle biopsies. So the biopsy versus surgical biopsy. And for the physician saying, hey, I think this is what it is in NCLE versus surgical pathology, you can see it's 65%. A couple of provisos, very small number of patients, wide confidence intervals. One of the important things to note is the risk of adverse events. You guys are going to be consenting the patients and you need to tell them about this. So 3% risk with NCLE, 5% with TTMB. But if you look at the data carefully and you look at most of these are retrospective studies, the largest study and one of only two prospective studies found an adverse event at a rate of 10%. The serious adverse events occurred in 70% of those including one death. So I think that's very important that you're aware of that. Okay. My last slides. We find the patient has an IPMN. These are the new 2024, the latest guidelines. So you are going to look for high-risk stigmata. All of you guys know what high-risk stigmata are? Okay. If you have none of these you're going to move down and you're going to look for worrisome features. And you guys know what those are, isn't that right? If you have none of those, if you have them, you're going to see how many you have because there's now data showing that if you have multiple worrisome features, your risk of high-grade dysplasia or cancer rises. If you have none of them, then you're going to follow your patients. So this has changed. Previously we said 1, 2, 3 centimeters. Again we all have to, you know, if you're writing guidelines you have to change it slightly. So we now say you look at 2 centimeters and under. If you have 2 centimeters and under, your largest cyst, you're going to do repeat imaging in 6 months, then you're going to follow them 18 months later. 2 to 3 centimeters, you're going to repeat in 6 months and again 6 months later. And then follow them every 12 months. If they're greater than 3 centimeters, you're going to follow them on a 6-month basis. And anybody here have a patient they follow with a 5-millimeter cyst who's really anxious and you see him or her all the time and you've seen them for the last 10 years? Anybody got that patient? Okay. So now the data also, again we've got more and more guidelines saying that if they, you've followed them for 5 years, they haven't changed, you can talk to your patient and say we would, your risk of developing pancreatic cancer is the same as an average risk person. That does not mean you're not going to get pancreatic cancer, but it's the same as an average risk person, therefore we recommend that you consider stopping surveillance. So thank you so much for your time.

pancreatic cysts

pancreatic cancer

endoscopic ultrasound

molecular testing

personalized care

patient consent