So, to seek and destroy, thanks, Greg, for that wonderful title, so I'll try to live up to that. So, let's start off by, what do you mean by seek? And of course, that's to look at and recognizing early neoplastic lesions in Barrett's esophagus. So, how can you detect them? And it's only if you detect them can you actually treat them, which is the second part of destroying those lesions. So, here's a high-definition, white-light endoscopy of a patient with early Barrett's adenocarcinoma. If you pay attention to the 12 o'clock position, you will see a subtle Paris II A lesion, which just went from view. And this patient was referred to us with a random biopsy diagnosis of low-grade dysplasia. So, this is key, is wash the esophagus. There's no saliva. There's no bile. Do a gradual pullback, and the inspection time, I think, is key in recognizing and seeking these lesions. The second thing that you need to do in all of these patients is a very good retroflexed examination. This is an early cardiac cancer occurring at the gastroesophageal junction within the hiatus hernia. And on an anti-grade view, you can easily miss this lesion, so subtle movements. The endoscope doesn't get stuck. If you do a retroflexed examination, we have highly flexible endoscopes now, so go ahead and do these maneuvers in order to seek early neoplastic lesions in your patients. How to destroy is the next thing, and how do you do it? And I think the first step of destruction is resection. And resection, I think, is key in all our patients with early neoplastic lesions. And here is, again, a subtle lesion at the distal esophagus of a patient with a C0M2 Barrett's esophagus. And we are using the CAP technique, injecting saline, and then using a snare and resecting this lesion out. And you can imagine that from a 2-millimeter biopsy, you now have a 2-centimeter specimen that your pathologist can look at. And here's the divot, which is left behind. And the majority of these complications can be treated endoscopically if they do occur after the resection has been done. Here's the EMR specimen, and it helps not just for treatment, but also is the first diagnostic step. Here are the high-power and the low-power, you know, pictures of this EMR specimen. And your pathologist can see cancer in there. And so this is definitely a cancer. But the issue is, is it a T1A cancer, which is restricted to the mucosa? Or is it a T1B cancer, which is in the submucosa? And here, the submucosa is free, which shows that this is a T1A cancer, which can then be resected endoscopically or treated endoscopically. And you don't have to worry about lymph node metastases in this situation. So resection is key. Patients demand that we have five-year data on treating cancer. And I think we do have it for Barrett's adenocarcinoma now. Here are data from the Wiesbaden group looking at more than 1,000 patients that have been resected primarily with endoscopic resection techniques and not by mucosal ablation. If you look at the complete response rate, it's virtually 100%. And recurrences do happen. But again, the majority can be treated endoscopically. Less than 4% of the patients in this expert center required surgery to treat Barrett's cancer. And complications and mortality were very similar to an age- and gender-matched German population. So we have evidence that endoscopic treatment can destroy Barrett's adenocarcinoma, which is a T1A cancer, as well as high-grade dysplasia, effectively. The next step is that if there's any Barrett's left behind after your resection, that's when mucosal ablation comes into play. And mucosal ablation mainly is done in the form of radiofrequency ablation, or RFA. You can use the balloon device on the left if there's circumferential residual flat Barrett's. Or you can use the focal device on the right if there are small islands left. But the key is, it has to be flat Barrett's mucosa for ablation to occur. And if there's anything visible, it just needs to be resected. What's the evidence that this works? And is complete resection better than focal resection followed by radiofrequency ablation? And this is a meta-analysis of the published literature published by Mada, one of our fellows, looking at more than 750 patients in each arm, either with a hybrid therapy of focal EMR plus RFA on the left, or complete resection. And what you can see is that complete eradication is achieved in more than 90% of the patient using either technique. However, strictures tend to occur more if you do circumferential resection, or more than 50% of the resection of the circumference of the esophagus. So you have to keep that in mind, that you may be dealing with a higher rate of strictures if you do decide to do more than 50% of circumference resection in the distal esophagus. What's new on the block? It's old, but it's relatively new. It's called hybrid APC. APC is old, but the technique of injecting fluid into the submucosa using the same catheter with which you can then ablate the mucosa is called hybrid APC. And here's an example of that, is that there's methylene blue, and therefore you can see that with the saline, there's a bluish tinge. It lifts the submucosa, and the mucosa layer can then be ablated by using argon plasma coagulation. And now this was done by Dick Sampliner and Brian Fennerty decades ago, and it was sort of stopped out of favor because of the increased risk of complications, strictures, perforations, because of that. Now, here's an initial study looking at the concept of hybrid APC in patients with barotasophagus, EMR, followed by hybrid APC. And of note, the eradication rates appear to be similar, but the stricture rates are lower with the concept that you're protecting the muscle layer by injecting the fluid. A randomized controlled trial of comparing RFA with hybrid APC has just begun this year, and hopefully we'll have results by next year showing if one technique's better than the other in trying to resect this thing. Of course, I've shown you all the good part, but again, endoscopy does come with complications, and you need to be aware of that. And this is a meta-analysis of the published literature looking at close to 10,000 patients who undergone Barrett's endoscopic therapy, showing that the overall complication rates is about 8%. So here's important information to share with your patients, that complications do happen. The most common are strictures, about 6%. Bleeding, perforation can also occur, but they're relatively less common with that. Now, this truly isn't a complication, is that if you do a resection, you may see some areas of bleeding right after the EMR has been done, and you have different tools at your disposal. You can apply tamponade with the cap itself while you're waiting to pick up a tool of your choice. You can use the tip of your snare with soft coag current. Or if that doesn't work, then you can also use a coag grasper forceps, as is shown here, to try to control the bleeding. So the key message here is that if you do enough of these, complications will happen. If you do decide to do Barrett's endotherapy, you should be able to take care of these complications which happen at the same time as well. So where do we go from now? And I think that's where the title comes in, is to seek and destroy. And I think John's already shown you that machines will seek. And so this is the most scientific video of my talk here. And some of you may recognize this. This is from The Predator, about 15 years ago. So Hollywood did lead the way in AI. And you can see that they're recognizing the human being and trying to attack that right there. So I think that's how, you know, detection of neoplasia and seeking neoplasia in Barrett's will happen. We have just started some studies on artificial intelligence in the colon, and very soon we'll apply this in Barrett's esophagus. And you can see the screen on the top is regular HD endoscopy. On the bottom is an AI machine, which is telling you where the polyp is. So I think seeking will very soon be done by machines, or helping by machines as well. And another similar example here of machines telling us where the neoplastic lesion is in Barrett's very soon, and so that we can go ahead and then destroy it as we can. So to conclude, I've shown you that neoplasia in Barrett's usually presents with very subtle lesions. If we are going to have an impact on the rising incidence of esophageal adenocarcinoma, we should be able to recognize it at a very early stage rather than late cancer. Early recognition and treatment does lead to better patient outcomes, and it has been shown in the endo studies that I've shared with you thus far. Resection is critical. If you see anything abnormal, lumpy, bumpy, it needs to be resected and not ablated, otherwise you will not get good results, and recurrences and invasive cancer will occur. And finally, complications happen, but the majority of them can be managed endoscopically. Thank you all very much for your attention.

early detection

neoplastic lesions

Barrett's esophagus

high-definition endoscopy

resection procedure