Well, you guys are stuck with me again, and I feel really humbled to be a part of this group in particular, you know, along with all the brilliant people that are here today. Today I'm going to talk to you about the approach to neuroendocrine tumors. And as you're starting to see these lesions less incidentally and more intentionally as an advanced endoscopist, think about them like icebergs. Often you're seeing a little something that's above the surface, but there may be a lot more going on underneath the surface. Gastric neuroendocrine tumors are a fairly common occurrence. The most common way that we will see these lesions is that we've had an outside endoscopist who's found a quote-unquote polyp in the stomach, removed it partially, impartially, or biopsied it, and it turns out, oh man, it's a neuroendocrine tumor. Of course, there are different types, and this is, you know, for those of you that are preparing for the boards, this is pretty high yield in terms of the subtype. I work with Jonathan Strossberger, who's one of the lead authors and lead thought leaders in the neuroendocrine space, and he always subclassifies these, of course, very eloquently for us. Of course, type 1 patients usually have presenting symptoms like anemia. Type 2 have things like diarrhea associated with Zollinger-Ellison syndrome. And type 3 and 4 think of these more like a gastric adenocarcinoma. So I submit to you, again, a thought quandary here is that you're doing an endoscopy, and here at the pyloric opening, you find this, and this actually is a G2 neuroendocrine tumor. You can see it fits well within the complexity of your cap, so it's around 8 to 9 millimeters, and the CHI-67 is 2%. So how would you approach this lesion? Which of the alphabet soup techniques would you use? Don't be shy. I don't bite. I promise. Low-grade neuroendocrine tumor. So would you EMR, ESD, EFT-R, S-LUB, BWR? So CHI-67 expression was low, so it's, I mean, you said 2%, right? It's a low-grade neuroendocrine tumor. From a management standpoint, I'm not sure. Okay. Anybody want to throw anything out? It's less than 2 centimeters, you said? Yes, it's less than 9. It's less than 2 centimeters. It looks like one single lesion. It is low CHI-67, but I'd say it's like type 3, so I'd probably go for endoscopic resection, and of the ones that you mentioned, like EFT-RD would possibly be the best option for this. And remember the location, right? We're at the pyloric channel. So this can be a little bit of a precarious location for us third space people. Why EFT-R? Because it's an iceberg, and there might be more underneath. I think I've biased him. Anybody want to take any other alphabet soup concepts? I agree with that. I think in the past I've approached these low-grade endocrine tumors or neuroendocrine tumors with like band EMR, just suck them up, put a band on them, and then resect them. But the location would concern me about the ability to get a good enough resection at the pylorus. And I agree with it being potentially deeper lesion, despite its low grade. We may be missing part of that with just a simple EMR. So, Schaefer, can I ask you a question? I know that you guys have already decided this is a neuroendocrine tumor. When you look at the NBI, do you think it's a neuroendocrine tumor? Yeah, so we're going to go through a little bit of the endoscopic approach and appearance of certain lesions. It depends upon the sub-phenotype of gastric neuroendocrines what appearance you're going to see. But this tends to be more of a bland phenotype that type 1s and 2s endoscopically. Pat, what would you do? We would probably EMR this, actually, just with band ligation with close follow-up as well, too. I am personally a fan of the band and leave it. So, you know, we get referrals for these all the time. And there are these type 1s. They may never cause you any trouble. Why spend an hour or two resecting it or resecting it and causing bleeding? I put a band on it, bring them back in three months, and it's usually gone, right? And the data on the whole, is the margin positive or negative? We don't even know if that even matters, right? So I think that, you know, we're finding these more because we have these high-def screens and, you know, great scopes. And we could have a whole career taking these out. So you band it but don't take it out? I just band it and go back. And you can go back. You can see the scar very easily. Yeah, that's BWR, band without resection. Yeah, so that's my question. I'm sorry, do we know this is type 1 for sure? Did you give that information yet? Yeah, no. Right, exactly. I mean, why are you even treating it if there's only G1? Well, because maybe patients feel better about it. No, but, I mean, that's sort of the argument a little bit for piecemeal EMR of colon polyps, right? If you take out most of the polyp and there's a little bit residual and you take that out, is the patient going to die of colon cancer? Probably not. But I think your EMR, your risk is pretty darn low. You're bleeding, right, but I think you're not going to hurt the patient. I would want more information at this point before making a decision on resection. So is this type 1, type 2, type 3, right? I think the management should really be steered by the type of gastric carcinoid. I completely agree with Amit there. I mean, if it's type 1, I mean, what's the point of doing anything? I mean, banding, leaving, or even banding EMR. Just leave them if they're type 1 for sure. Yeah, and I intentionally deceived you all because this is often how the patients are coming to us, right? We have this beautiful chart that we're tested on on the boards, right? What's the gastrin level and pH? But who does a gastrin and pH on their patients? I mean, we do, but, you know, often you're not coming in with that information. So the first thing that you should try to determine is what else is going on below the surface, right? Also the location. We're at the pyloric channel, but there may be more going into your duodenal bulb. And so this may be a bigger lesion than what you see initially. Type 3s and 4s, you should not mess with these patients. Look at the rates of metastasis to lymph nodes. It's really high. I mean, for type 4, it's 100% in some studies. So there are certain things endoscopically that you can use to differentiate this, but the sensitivity of these features is not 100%. Obviously, if you have a large ulcerated lesion, you should most likely shy away. But for those that are type 1 or type 2, you're right. Sometimes you don't have to do anything with these lesions. But can I make an argument about that? So in the world of open access endoscopy, I mean, you have referral doctors, and this is something you guys are going to have to deal with, right? You get a referral for a cyst. You know, does it need an EOS? It's 1.5 centimeters. I mean, you know, these are the challenges that you will face. Someone comes with you with a bump, and they were told that you are the expert and you're going to get it out. I'm not saying you should do the wrong thing, but sort of to my banding and leaving it thing, I think the risk is very, very low, especially in the stomach. And so you could actually offer something that will potentially get rid of this thing. And I'm just saying it's challenging. It's not always as easy. Obviously, if you're going to do some wide ESD, I mean, that's a little bit different. But, you know, you are going to deal with getting these referrals, rectal neuroendocrines. You know, they send them for an EOS or, you know, whatever. It's just the world we live in now. Yeah, and I think like Dr. Bott's case, you know, there's no harm in bringing that patient in for a second set of eyes. And your eyes may look at things slightly different than the initial endoscopist did. And you can also do some additional due diligence, right, making sure that your chromogranin A level is done off of walnuts and avocado and off of PPI and that you get a gastrin level and a pH level so you can properly differentiate. Also remember that, you know, these lesions travel with atrophic gastropathy and pernicious anemia. So do your due diligence in differentiating the subtype. Most of these patients will get an EOS. And we looked at the data. Again, we're not great at T-staging these lesions and should get usually some sort of cross-sectional imaging. We tend to use the copper PET dotatate scans as kind of our go-to. Here's the appearance of most of your type 1s and 2s. They'll be these vague little bumps that, again, often are just read as some sort of inflammatory polyp. But this is actually a type 3. And look at how ulcerated and nasty that is. So actually with this lesion, there was more to it on the duodenal surface. And so we elected to do an ESD on this particular patient for that reason. And they are a type 2, given their serologic studies that were done. And so I'll fast forward through our resection. So we have a lot more to talk about. Much bigger. So gastric neuroendocrine tumors, you know, this is kind of a great schema on how to think about things. You know, type 3s, again, usually you want to shy away from those. Some people will say that if it's smaller, you can consider endoscopic resection. But I think that the field is kind of moving away from it. Type 1 and type 2, again, look at your size and then your degree of aggressiveness. Now, duodenal neuroendocrine tumors are a little bit of a different beast. Remember that these lesions that involve the ampulla usually are surgical. And that's because of a high degree of lymph node metastasis. But those that are in the bulb, you may actually be able to resect these. And a lot of these tend to actually be nonfunctional. But some of them can fall into these functional tumors. And then I'm certain that all of you at some point or another have seen the periogangliocytic paraganglioma, which is greatly debated amongst the experts, I think the world experts at the NIH actually, and state that a lot of these can be left alone. Again, the clinical presentations are variable. Most of these are found incidentally. And then if you find an ampullary lesion, you leave it to your surgical colleagues. Anything that's G3 or poorly differentiated, likely you should stay away from those neuroendocrine tumors as, you know, there's a high degree of lymph node involvement. But again, you know, I just wanted to submit to you, here's a lesion that's in the duodenal bulb. And it's tiny. How would you approach this particular lesion? Anybody? I didn't bite the first time, so I won't this time. EMR? BWR? EMR. Why? Probably enough margin to evaluate the death. We could also consider an EUS, actually, prior to the EMR. Actually, EUS and then the EMR. Any other thoughts? Okay. Why is that? Duodenum makes me nervous. Like, can I get EMR there because of the high risk of perforation that has to go? So I think the full thickness might be more of an issue. Yeah, I mean, the duodenum still scares me. Maybe not Dr. Bott and Dr. Dragunov, but it's a very thin-walled area, easy to perforate, and there's a lot of very important things that are there. So with this particular lesion... Don't forget, abandon, let go. Is a margin on a net important? Is a deep margin important? Right, so... Deep margin is going to be positive with EMR. These are submucosa. They're always positive. Right. They're icebergs. It doesn't matter. There's more going on under the surface. They usually originate from the submucosa. And I don't think that there's a lot of great data on margins being positive or negative in the neuroendocrine-specific world. I mean, stop me if I'm wrong. I actually think you were part of our study on positive margins for duodenal carcinoids. I'm interested to see what you're going to say. I still do band EMR for these patients. I think they've done well historically. We haven't really seen much metastases coming from these lesions. I think the band actually pulls these neuroendocrine tumors up from the wall. We published in GIE, actually, the impact of positive deep histologic margins after band EMR. And there was some recurrences, but most of those were taken care of endoscopically. But I'm wondering if you do full thickness for these. I look forward to it. I think a number of us that have been doing this five years... Can somebody comment on the sloping of the wall of the lesion? Yeah, the bulb can be a precarious place to operate, I think, is what Dr. Raju is discussing. Great place for a cap, clear cap. If you're not going to do, use a device that has a cap. Yep. And there's also, remember, now that you all are learning EUS, there's a lot of very important stuff right outside of the wall here, right? Your GDA, your bile duct. But with this particular lesion, we actually, we did spray chroma. We elected for FTRD. There's our settings. So what was the EUS finding on that? So the EUS just appeared T1. But again, you know, EUS is not very predictive of depth of T invasion. And we actually discussed that in Dr. Dragunov's book. With these, you know, because of the device being so big, you do have to predilate up to around 20 millimeters, both the upper esophageal sphincter and the pylorus. And then you mark around the lesion. The reason being, you know, you may think that you can find this thing with this giant device sitting in front of you, but it's often hard to tell where the target is unless you mark it well. And then you grab it with a grasper and pull it into the transparent cap. And you'll get a – yeah, which is easier as I've been done. I don't know. I usually use the anchor and the duodenal bulb because the little forcep can tear the lesion pretty often, actually. Right, Dr. Shake? And then there's a very high cutting current, almost like surgical level. And there you can see the muscularis propria, which is the only time that you want to see a muscularis propria, right? This actually ended up being a T1B lesion, believe it or not. So, again, you know, in the duodenum, you want to assess the size of the lesion and also the degree of CHI 67 and the grade to determine your approach. Leave the ampulla alone. Now what about the rectum? You know, here's a lesion that we found using EUS and it has to be referred from the outside. And there you can see it. How would you guys stage this little lesion in the rectum, echosonographically? Schaefer, can I just ask a question? So T1B, I don't know what does that mean for a neuroendocrine well-differentiated tumor. So, again, back to my procedure of band and let go. Not to keep it simple, but, you know, this is, again, the question. How is this going to change management of this patient? If you screwed up that FTRD, which you did a great job and it was lovely, but it is a little bit of a scary device, you know, especially if you go to the training. I went to the training for this device and I decided that I don't know that I ever want to use it because they just show you, like, the worst things that can happen. But, again, in deciding sort of what you're going to do, like how did that change the patient's management? They go on and get chemotherapy for their, you know, T1B. It's not esophageal T1B, right? This is a different ballgame. No, you're right. I want to ask a question. So when you're talking to the patient and say, hey, I'm going to do the band and remove it, how do you counsel that patient? Some patients may say, hey, how do I know that you got it out? So I just want you to tell me how do you actually counsel your patient when you're trying to do band and let go? That's a very important thing. Absolutely. Sure. So I usually say I'll follow them up. You know, we don't know that it really matters if there's a positive margin because at least the data that I had seen. And the only reason I know kind of a lot about this is that I had to give a lecture in front of 1,000 or so people at DDW, so I really read a lot about it. 1,000 people came up to your lecture? It was at the presidential thing day, you know, whatever. And my son was there. It was not virtual. It was for real. Okay. Let's focus on what you're going to tell us. I think Dr. Raju brought up a really good point is that patient preference is really important. We know neuroendocrine patients are really anxious and hyped up patients, and so they may not want a DWR approach. Thank you. I've never had a patient say that they don't like my medicine. So you tell them that. You're going to take it out and say it for a minute. Move on. Then I'll repeat it. I've never had a patient die of metastatic. There's a lot of expectations versus reality. I'm just going to skip ahead. You know, I think just to a more common clinical scenario, rectal nets overall have a pretty good prognosis, but what do you do with a patient where somebody else has removed a net and they didn't get positive margins but the patient's still really symptomatic, just diarrhea and flushing? How do you consolidate that scar site? So we actually have been doing FTRD of the scar site to actually determine whether or not you got a, quote, unquote, negative margin if that's not available otherwise. And, again, you can use one of these devices to do that same thing. I think also helpful for polyps with a little focus of cancer and an unclear margin too, right? Otherwise you're talking colectomy or LAR. And that gives the patient peace of mind and you and the oncology team a little more peace of mind as to whether or not you got this lesion the first time. I'm just going to make a quick comment about rectal full thickness resection. This was actually something that was a piece of advice given to me from a minimally invasive colorectal surgeon. With rectum, as endoscopists, we're not typically trained on knowing when you put the scope in how do you know what's anterior, posterior, left, and right. If you're doing, like, big full thickness resections in the rectum, especially in a female patient, do not go after an anterior lesion. The rectovaginal septum is about 2 millimeters thick. I've had cases before where I was referred endoscopic resection for, like, a 1 centimeter anterior wall gist, and you can feel it on a bimanual exam. So just be very careful with that location. Yeah, and I think the EUS helps you with determining the proximity between the target lesion and other intervening structures, too.

neuroendocrine tumors

gastric neuroendocrine tumors

duodenal neuroendocrine tumors

clinical presentations

management options

endoscopic techniques