Thank you, Sumit. Another terrific set of talks. We're now ready to hear from you, our colleagues, and we do have some questions. So for any of the faculty, specifically, John and Sumit, please turn your cameras on, but anyone else is also welcome to join in. We do have some questions, and there are three questions around the concept of GLP-1 agonists. Sumit did a great job in outlining it, so I'm going to ask John if he has any comments on the use of GLPs prior endoscopy. How should we handle that and the differing opinions between the ASA and then the rapid clinical update from the AGA in the fall? And since it's such an important topic, I'll ask Sumit one more time to repeat his comments after John's done. So, yeah, I mean, particularly, I think, you know, the question comes up frequently with upper GI endoscopy for obvious reasons. And, you know, I think the way to look at this is these are new, and so all of this is fluid. And to remember that guidelines are guidelines for a reason. You know, they generally exist where good, hard data is lacking. This hasn't been a thing or a problem long enough to have accumulated lots of good, hard data to provide us with an excellent evidence-based way to work. And so I think if there are guidelines out there, then you should pick a guideline that you believe to be the one that you're most in agreement with in terms of your practice and follow it and feel free to reference it. I don't think that it makes sense to argue the different recommendations, but you should look at the recommendations there and make a decision as to which one you're going to follow. There have been several questions about, you know, how long you need to hold them and this and that. And the ASA generally says, you know, hold them the day of. And if they only take them once a week, then hold them for one week. Because you do have to think about the pros and cons, right? There's the safety of the endoscopy. There's how good a job you can do at endoscopy. But there's also the negative implications for the patient's health by holding the GLP-1 inhibitor. And there's also the consideration of what is the indication for the patient taking the GLP-1. They're used for different conditions. And, you know, I would argue that the diabetes one is probably more of an importantly urgent indication than just, you know, obesity for cosmesis alone. So I think that's my long answer. I hope that answers the question. Excellent, John. Thank you, Sumit. Anything else to add, or do you think your comments in the talk covered it? I think the comments covered it, but basically just to summarize it, you know, our anesthesia societies have made these recommendations, and our GI societies, particularly AGA, issued their guidance back in the fall, basically saying that, exactly as Dr. Martin alluded to, there's not enough data really to make clear recommendations, and these are more expert opinions. So I think it's really important to have an open conversation with your anesthesia providers who are going to be providing, particularly the MAC anesthesia for these patients. It's not only, we have to consider their risk as well, the risk to the patients for aspiration, the risk or the risk of exposure for our anesthesia colleagues as well. But I think it's worth an open conversation. We have not yet had any hard and fast guidelines by our anesthesia providers, but I think they're always open to conversation. Just to add that I think, you know, part of the good news is that there is still room for thinking beyond algorithms. It's not just a cookbook. The fun part of medicine is that you get to think about it, and you get to figure it out. That's always been the fun part of medicine, and while we have more checklists and algorithms than we've ever seen, and there's AI now layering on top of that, thank goodness there's still room for your brain and your expertise and your experience, which is priceless. That's the art part of medicine, and it's probably always going to be there. Thank goodness. Thanks, guys, for an important summary, and I think, John, your comments are so important. As I said earlier, we can't become artificial physicians. There's so much more to medicine and algorithms and AI and the algorithms it brings, so really important points. Okay, next question. I'll throw this back to you, John. The question is, I have looked up screening guidelines for family history of gastric cancer. What I have seen is to perform endoscopy 10 years before the diagnosis age of the family member. What do you do in your practice? Yeah, that's tough. We're much more individualized than that. There aren't any hard and fast guidelines for screening, unless we're talking about patients who have known familial syndromes. That's screening a high-risk individual because they're known to have a genetic syndrome that leads to a high risk of gastric cancer, and that's a completely different story. But when we're talking about screening individuals because, say, their grandfather had gastric cancer, which was probably due to undiagnosed H. pylori, there's no screening recommendation for that. That doesn't exist. So that is an individual decision made based on various risk factors that you will elicit from that patient during the history that you take, anything that you glean from physical examination and necessary studies to determine if they have some underlying risk factors, and then having a discussion with the patient with respect to things as subjective as the level of anxiety that they may have, understanding that, objectively, the risk is extremely low, but they may be so anxious that their anxiety would be helped tremendously by your performing an endoscopy to screen them. That can be a legitimate indication. So I guess my point is there is no recipe or cookbook that's general for screening all comers who have a family history of gastric cancer. It's not like colon cancer that way. We do not have the data in this disease that we have for colon cancer that tells us that that makes sense. So it's an individualized decision. Again, an opportunity to use your beautiful mind to help the patient make a good, well-thought-out, educated decision. Sameet, next question is for you. Are positive occult stool tests or positive FIT tests and or a positive Cologuide always an indication for colonoscopy? So I think it's important to take those in context, of course. These are meant to be screening tests for colon cancer. And certainly, if you have a patient who is averse to the idea of doing a screening colonoscopy, these are reasonable alternatives. And certainly, if they're positive in that situation, then yes, I would agree that these need to be followed with a colonoscopy, both for diagnostic reasons to try to elicit the source of that positive test and then potentially provide polypectomy or biopsy samples if an abnormality is encountered. I think it's also important to consider, was that test done in the setting of certain kinds of symptoms? Was it done as an inpatient versus an outpatient, inpatient with acute anemia, maybe melanoma? Maybe that test was already addressed as an inpatient with an upper endoscopy and finding otherwise. So context is very important, but if it's being done for the appropriate indication of colon cancer screening, then yes, it should be followed by a colonoscopy. Sameet, I'll stick with you for a second. Any thoughts on the role of virtual colonoscopy? Virtual colonoscopy, so virtual colonoscopy also is their CT colonography. I think it has a potential role, again, in screening populations. So these should be patients that are average risk, not necessarily elevated risk. So if they have, first of all, not indicated for symptom evaluation, and also shouldn't really be considered in those patients that are already at elevated risk for colon cancer due to a family history or genetic syndrome, for instance. But in those patients who are average risk, I think it is an option for screening in those patients who may be, again, averse to the idea of doing a screening colonoscopy. I also think it's important in that situation to make sure that the patients are properly informed as to what goes into a CT colonography and the risks thereof, both with regards to doing the bowel prep, insufflation, but also risks of incidental findings by CAT scan and what that might entail for the patients subsequently. John, back to you with a PrEP question. Could you just comment again on the timing of the split PrEP dose? And what if you can't give the second dose at the ideal time? How much of a window do you really have before we start losing the effectiveness of that second dose of the PrEP if we give it too long from the procedure onset? So you're worried about giving that second dose too soon? Worried about actually giving that second dose a little too late, meaning too far from – actually, are you giving that second dose a time that's too far away from the onset of the procedure where you might lose its effectiveness? Yeah, for sure. It takes a while for that fluid to traverse the gut, and that's going to vary patient to patient. So you really need to account for all of that. So I think the point's well made. You want to give it a little sooner rather than a little later because you don't want to retain unused PrEP because that's a waste that could have helped get more of the solid matter out of there than you might encounter if you administer that second dose too late. The whole idea here is to flush solid components that you cannot aspirate out with the scope out of the colon lumen before you go in with the scope. And this is why we actually give the first dose a little earlier in the evening because it allows the patient to comply. It gives them time several hours after that PrEP is taken in the early evening to evacuate their colon so that they can then actually get some sleep. But then you're going to need that same sort of situation to give them, I would say, ideally, actually a good four or five hours because you don't want them becoming fecally incontinent on the way to the exam and so on and so forth. So giving it, I think, a little bit earlier is better. So if you're given a five or six o'clock dose and they're coming in for a procedure that morning, they're going to need to get up earlier in the morning and take that dose sometime between 3 and 5 a.m. They're usually not going to complain about that for getting a morning slot because then they're going to be able to leave and eat lunch. So, you know, it all depends on how you couch it. If you tell them, look, you're going to have to get up a little earlier and you're going to have to chug. But, you know, the good news is that you're going to get to go to brunch and you can eat whatever you want. So, you know, positive spin. Get up early. Thank you, John. Eden, do we have time for one more or should we break? I think you have time for one more. All right, John, and then we'll finish up with you. The question reads, Barrett esophagus short segment surveillance is three or five years. And I would ask, do we really still use the term short segment or do we view it differently? Yeah, I think those are both really good points, Joe. I mean, I think we do view it differently because, look, the reason why the whole concept of short segment came up was it's not about the segment. It's really more about the amount of tissue that's involved with Barrett's metaplasia. So, just to recollect the idea here, Barrett's esophagus is a condition that we presume is due to acid reflux. The esophagus is lined by squamous mucosa. It's more like your skin than it is like the rest of your gut. The rest of your gut is columnar mucosa and columnar mucosa to a greater or lesser extent, depending on where it's located, has goblet cells, which produce mucus and mucus protects against acid. Your esophagus is lined by squamous mucosa. Squamous mucosa doesn't have goblet cells and can't protect itself through that mechanism against refluxation of acid. And probably for those reasons, to protect itself, it undergoes a cellular change, which is not normal, called metaplasia, where it starts to look not like squamous mucosa, but it morphs into columnar mucosa, specifically of a kind that mimics the small intestine. And, therefore, has goblet cells that can produce mucus and protect itself. And that all sounds great in the short haul, but anytime you have a cellular change, there's a risk for those cells undergoing a bad sort of change and becoming precancerous. And then those precancerous cells becoming frank cancer and esophagus cancer is a bad thing. And so if you already have Barrett's, then you want to, A, document that you have it and B, survey that Barrett's to make sure that it, so to speak, isn't going bad. With short segments, we're talking about Barrett's that is three centimeters in axial length or shorter. However, how long it is in axial length is not the only dimension that determines the amount of tissue involved, right? It could be three centimeters, but it's just one tongue that doesn't encompass anything like the circumference of the esophagus. So short segment that is three centimeters could be a lot of tissue or it could be not a lot of tissue. So I think as we've gone to things like the C&M classification, where we take into account not only the length, but the amount of circumferential involvement is more important. And whether the tissue has demonstrated any dysplastic change already also is more important than just measuring how long and saying it's short segment versus long segment and then individualizing that decision making and following the guidelines according to the C&M classification. Does that answer the question, Joe? Yes, I think it does, and so I want to thank everybody for participating in the Q&A. We do have a few open questions and we will respond to those in the Q&A chat by a written response, and I will now turn it back to Eden.

GLP-1 agonists

gastric cancer screening

virtual colonoscopy

PrEP dose timing

Barrett's esophagus surveillance