Barrett's esophagus endotherapy is the talk before lunch, before Q&A and lunch. My objectives for this are to talk about which patients with Barrett's esophagus should be treated. That's always a big question, not only in community practice, but also at academic centers, and it's a hotly debated issue. So we'll talk a little bit about that. And then differentiate which patients with early esophageal neoplasia or cancer can be effectively treated with endoscopic therapy versus referring them on to surgery. So remember, about two decades ago, surgery was the go-to place destination for most of these patients, but the paradigms have shifted over the years. And then finally, review some of the limitations of the current therapeutic regimens, because no matter how good the care paradigms are, there's always some gaps and always something we need to research or do better with. So it's important to realize this is a concept that is relatively less known, even in the GI community, is that between the United States and our colleagues across the pond in Europe, there is actually quite a stark difference in the definition of what constitutes Barrett's. So in the United States, you need at least a one centimeter of columnar lined epithelium at endoscopy, which shows specialized intestinal metaplasia on pathology, with specifically goblet cell metaplasia, whereas in Europe, an endoscopic view of a one centimeter columnar lined epithelium is good enough. So it's kind of an interesting dichotomy that exists, but we follow the pathology here, and we combine that with the requirement that there should really be at least a one centimeter segment of Barrett's columnar lined epithelium that's visible on endoscopy, along with goblet cell metaplasia. Which is why this becomes important, is because this is the typical irregular Z-line or GE junction, which does not meet these criteria. We generally discourage that that should not be biopsied. So we discourage that from folks from biopsying that. So it's an important concept that becomes a very hotly debated topic at national meetings and seminars. So this is the definition of Barrett's, and then further classification is based on the length of the segment of columnar lined epithelium, such that if it's less than three centimeters, so in length, in axial length, then it's short segment Barrett's, and if it's three centimeters or longer, then it's classified as long segment Barrett's. And occasionally, there are patients who have almost their entire esophageal segment as Barrett's, and those are really very difficult to manage because of the segment length. And that's more of a technical issue and the number of sessions of treatment and so forth. The other important take home message is that Barrett's is a precancerous condition, with a finite annual progression rate to esophageal carcinoma, between 0.1 and 0.4% per year. So the takeaway here is that if one does have a patient with Barrett's esophagus, that is a bona fide Barrett's esophagus, pathology confirmed, and that patient for one reason or another is not enrolled in a surveillance protocol and or falls through the cracks, that's somebody that could present down the road with dysplasia and cancer, and that could be a medical legal issue as well, as well as a quality issue related to patient care. This slide talks about the natural history of Barrett's esophagus. And most of us are born with and stay with a normal esophagus, which is not Barrett's, but obviously a certain percentage of the population will convert to what we call Barrett's and the vast majority of them will remain what we call non-dysplastic, which means they don't have any degree of dysplasia or any degree of further disorganization of the cells, which would then preclude them, position them for cancer down the road. A small percentage of patients will be labeled as indefinite for dysplasia. This means that the pathologist, regardless of their level of expertise, cannot determine whether this patient does not have dysplasia or actually does have dysplasia. And this is kind of a gray zone. It's quite frustrating in clinical practice sometimes, but it has been well-recognized over the years and has stood the test of time, and we have come to recognize it as a particular intermediate category where, you know, there's more information to come one way or the other. The most common reason for indefinite for dysplasia is inflammation. So if you have concomitant inflammation, and I remember Dr. Martin and Saril had discussed this particular issue, is that if you biopsy a patient in the setting of esophagitis and the patient has Barrett's, no pathologist in the world will be able to confidently say whether there is dysplasia or not. And that's exactly the scenario in which indefinite for dysplasia becomes a very high probability of diagnosis. Then we have a confirmed low-grade dysplasia, which is the next level of disorganization of the cells. So we have Barrett's, low-grade dysplasia, and then high-grade dysplasia. Now once you have high-grade dysplasia, you're literally only one step away from developing esophageal cancer. So most patients who are referred with high-grade dysplasia will definitely undergo some form of therapy. And of course, in the natural sequence of events, intramucosal carcinoma is the next disorganized state in which the cancer is limited to the upper lining or the inner lining of the esophagus, known as the mucosa, and has not gone into the submucosa. Once the cancer goes into the submucosa, which is the third layer of the esophagus, it is labeled as T1B. And at this point, this is where the cancer becomes invasive. Invasive means it has invaded from the mucosal layer, through the basement membrane, into the submucosa, and now the cancer is fully eligible to spread throughout the body through lymphatic channels, vascular channels, and such. And then once the cancer is invasive, unfortunately, the vast majority of patients still present with what we call locally advanced cancer, which means cancer that is well into the wall of the esophagus, into the muscle layer. Remember, the esophagus doesn't have the true fifth layer. There is a mucosa, there is submucosa, there is the muscle, but there is no cirrhosis as such that protects our stomach, for example, or the colon. So as soon as you're through the muscle layer, you're basically into the mediastinal tissues where the heart and lung reside. So invasion is relatively easier conceptually in the esophageal context compared to, let's say, in the rectal context. So once you have locally advanced cancer, then obviously these patients also, not infrequently, will have metastatic carcinoma, which is stage four disease, which means patients may have liver lesions such as the one I showed yesterday in one of my other talks, or bone lesions and lung lesions and so forth. So the question becomes is, who should be treated for Barrett's esophagus? This is really the main question when it comes to the topic of Barrett's because endoscopic therapy has evolved so nicely in the last two decades. So if you focus on this slide here on the left, it is clear at this point that surveillance seems to be the go-to approach for patients who have indefinite for dysplasia. And one can argue whether you go back in six months or a year, and what the practice kind of policies in that, what's your personal comfort level, and what concern you have with regards to prevalent dysplasia versus inflammation and so forth. But some time frame for follow up, which is significantly shorter than three years, is the way to go here in terms of surveillance. It is also generally agreed upon that non-dysplastic Barrett's is something that really should be under surveillance, and most of the guidelines will support that right now. I have a question mark next to low-grade dysplasia because the guidelines still suggest that low-grade dysplasia is something that you can continue surveillance on, provided certain caveats are met, and I'll talk a little bit about that. As opposed to proceeding with endoscopic eradication therapy, which includes ablation and resection, so EET is the acronym, so some patients with low-grade dysplasia can also be considered for treatment, which I'll talk about. Potentially almost all patients with high-grade dysplasia should be considered for treatment, and most certainly early esophageal cancer limited to the mucosa should be considered for endoscopic therapy. And then some cases, potentially with early esophageal cancer that is invasive, but is only limited to the superficial layers of the submucosa may be considered. And that's also another hot topic for debate internationally right now. It is clear that the indications for surgery are invasive cancer that goes deep into the submucosa or beyond, and this is T2 into the muscle, T3 outside the muscle, and then in certain cases some locally advanced cancers after what we call neoadjuvant therapy may also become eligible for surgery. So these are generally agreed upon categories. There is some controversy around the T1Bs and the low-grade dysplasias, and I'll try to address them as simplistically as I can in the next few slides. So the management of low-grade dysplasia is basically ablation or surveillance, all right? And the guidelines still basically talk about both options as being reasonably acceptable. The controversies that argue against ablation is that, in general, low-grade dysplasia has been to progress relatively slowly, and that there is significant inter-observer variation amongst pathologists as to what really constitutes low-grade dysplasia, and that is a fact that's borne out in the studies of the data. However, the counter-argument and the argument that we should treat low-grade dysplasia includes these particular caveats, which means if low-grade dysplasia is confirmed by an expert pathologist and or there is a family history of esophageal cancer or family history of Barrett's and the patient does not have significant comorbidities and is relatively young, has a persistent low-grade dysplasia on multiple sessions of biopsies, has multifocal, it means multiple levels of low-grade dysplasia in a long segment Barrett's, you know, these are the conditions in which one would lean relatively easily towards treatment. And of course, if the patient has nodules in the Barrett's segment that have not been resected and only biopsies have been taken that show low-grade dysplasia or indefinite for dysplasia for that matter, then I think certainly the endoscopic resection and further evaluation is warranted with a kind of a shift towards the treatment side rather than just surveillance. A lot of this with low-grade dysplasia becomes shared decision-making, and a lot of our clinics that see Barrett's patients, we do them together with our advanced APPs who specialize in therapeutic endoscopy practices or Barrett's-related practices or GI cancer practices. And a lot of these discussions are taken together with multiple people in the room, perhaps over some few visits, not just one single visit. And this is why it becomes very important to have initial consultative sessions with Barrett's patients when they're referred for treatment from an outside facility. So one of the things I wanted to show up front is a new guideline that just got published actually two weeks ago. It's an update on the ACG guidelines from 2016, but now it's 2022. And so I just wanted to highlight what's new in these guidelines compared to what exists in any other guideline on Barrett's as of now. So one of the things that just came up in this guideline is that swallowable non-endoscopic capsule devices and biomarkers are now becoming more of an acceptable alternative to screening endoscopy. Some of these are commercially available in the United States, but for the most part, these are currently under a very robust investigation based on multicenter trials nationally, and we happen to be part of some such trials as well. The other big thing that has come out for clinical practice is that there is now an expert opinion recommendation that for short segment Barrett's that is less than three centimeters, five years is an okay time frame for surveillance interval if the patient remains non-displastic. However, for long segment Barrett's, the opinion now is saying that you need to bring them back in three years. This is different from before. In the past, it used to be three to five years for all comers that were non-displastic. So this is an important take-home point from today is that this new guideline is suggesting that for long segments, we need to bring them back in three years. There was no specific recommendation made for predictive markers such as a tissue cipher, which is also commercially available now and is also undergoing a rigorous investigation through multicenter process or adjunctive tools such as the Watts 3D brush biopsy catheter, which has been in play for several years. Although the Watts 3D brush biopsy catheter, which enhances the tissue sampling rates in esophagus has received a conditional recommendation in the ASGE guidelines. In this particular guideline, it did not receive any comment. And of course, one caveat that we have always used in clinical practice is that we really need to seriously consider stopping endoscopic surveillance in patients who are no longer candidates for either endoscopic eradication therapy due to their comorbidities or age or candidates for surgery for the same reason. This is an area which I think would benefit from some more concerted effort on all our parts to really pick out those patients through a shared decision-making process where we can explain to them the risks and benefits and the burden and the cost and the morbidity of undergoing endoscopic therapy or surgery when juxtaposed with their clinical comorbidities, their age, and also their personal preferences and their risk for intolerance for complications. So how do you determine endoscopic therapy that's appropriate in Barrett's, right? So first, confirm what you're treating. I find this study published in Gut in 2015, a really fascinating study, so I'll spend a minute on this. This is a study of 239 low-grade dysplasia patients, patients who were billed as low-grade dysplasia coming in. 73%, three-fourths of these patients were downstaged the moment an expert pathology person looked at these slides. Downstage means from low-grade, they went to regular Barrett's. Now, further looking into this, 40 patients or 14% of these patients were downstaged to indefinite for dysplasia, and only 3% of them developed cancer in follow-up. 60% of them were downstaged to non-dysplastic Barrett's, and only 2% of them eventually had esophageal cancer. So extremely low rates of progression once you downstage an outside pathology. But look what happens over here. You have a third of the patients who were confirmed to have low-grade dysplasia, and about 30% of them went on to have high-grade dysplasia or esophageal adenocarcinoma. It's a British study, so esophagus starts with O. So this is kind of a stark contrast. If you have a confirmed low-grade dysplasia by an expert pathologist, the long-term natural history and outcome is quite different compared to if you're in some of these colder territories where the esophagus was downstaged by pathology. A really remarkable study looking at this particular importance of why it is so important to confirm the pathology and understand what you're buying, what you're treating, and what you're getting involved with, both for the patient as well as for the provider. So based on this study, it is extremely critical that if a pathology of Barrett's has not been reviewed by an expert pathologist wherever, it doesn't matter where that second opinion is obtained, please do take a moment to get that opinion so that the patient might not fall into one or the other of these categories and might then entertain a different algorithm than they necessarily needed to undergo. So it's an important point. The second step is, which is an important point, and this is a board question in GI boards, and we teach this to fellows almost every day, is that when you're examining the esophagus for Barrett's, and that's obviously more relevant to the endoscopists, we really have to spend time looking at the esophagus in high-definition white light and narrowband imaging, but also looking for areas of nodularity, we call them focal-raised nodules or lesions, and they should be subjected to what we call endoscopic resection, either with EMR or with endoscopic submucosal dissection. And then, depending on what the pathology is, because not only is it a therapeutic intervention, it's also a diagnostic intervention when you remove a large chunk of tissue, if the pathology is T1A, which means the tumor is restricted to the mucosa, then endoscopic therapy can continue. If the pathology is T1B, that means the tumor has now gone into the submucosa, then we need to bring this to a multidisciplinary discussion and have a discussion about what's the best option, esophagectomy or continued therapy in some selected cases. So the basic principles of endoscopic eradication therapy in patients with dysplastic or neoplastic Barrett's are listed on this slide. Resection of all visible lesions, ablation of the residual Barrett's epithelium, which is typically high grade or low grade in the background, that needs to go because that's a fertile ground for future development of neoplasia. And then with the aim of what we call complete eradication of dysplasia, or CED, or complete eradication of intestinal metaplasia, or CEIM, these two acronyms you will see almost repeatedly in the Barrett's literature, CED and CEIM, and they both have different implications. Many studies and many clinical practices will stop at CED, which is a relatively lower threshold to meet, lower bar to meet. But most good studies, most expert centers, and more data is supporting the fact that we really need to aim to hit the CEIM mark, which is a harder endpoint, but actually portends a better long-term outcome for the patient. Endoscopic eradication therapy consists of these interventions, some of which have been discussed yesterday, and I will just show a couple of videos on these. Flat Barrett's can be treated with radiofrequency ablation, with cryoablation, and our European colleagues have shown us very effectively that it can also be treated quite effectively with argon plasma coagulation, and with a relatively fancy technology known as hybrid APC, where mucosal injection is involved. Many patients require multimodal therapy. We had a paper on this a few years ago, stating that high rates, very high rates of CED and CEIM can be achieved in the high 90s when you combine multiple eradication therapies, and that's why a lot of this work typically is performed and likely should be performed at centers that have a comprehensive armamentarium of technologies, techniques, expertise, and meticulous follow-up. The patient on their part must commit to a fair number of sessions, depending on the length of the segment for treatment, and then subsequently a protocol for surveillance, which also should be quite robust. In all of this, it's very important to maintain a very, very strong acid control with not infrequently double dose PPIs and additional adjunct anti-acid medications, lifestyle modification, diet control, removal of alcohol and smoking and such insults. And that's a discussion with the patient. It does take a little bit of convincing in some cases. And very occasionally, you'll run into a patient who has a true PPI allergy and that becomes a very difficult clinical scenario to manage. And in some cases, those are the patients, whereas even though endoscopic therapy would have been very successful in the typical scenario, in that particular patient, the allergy to PPI or anaphylaxis in a couple of cases I've seen, that would shift the balance towards surgery. So now this patient will have to undergo surgery because their dysplasia cannot be managed due to lack of acid control. Very rare, but it does happen. So here is an example of endoscopic resection. This is a band EMR device which is loaded onto the gastroscope. You can see here the lesion has been marked and now it is suctioned into the barrel. And in this particular case, a band is deployed after suctioning, a couple of mock trials, and then right below the band or above the band, we can deploy a dedicated proprietary snare that comes in the kit. And there's the snare right there. The snare will now be open. It's attached to an electrocautery unit and the pseudopolyps, so to speak, is resected very safely and retrieved. And we examine the base. There's no perforation, there's no bleeding, and the muscle layer is intact. So that is a very efficient way of delivering a chunk of tissue from a suspected nodular area in Barrett's. It is the right thing to do. As I said, it's a board question. It's an important practice paradigm because if you don't resect this lesion and you simply ablate over it, you're going to have buried cancer in a few months to a couple of years. And that's not a good outcome, very difficult to manage that scenario. Another one we have here is we call CAP EMR. Yesterday, somebody had asked a question about how does the CAP EMR work? What is the role of the CAP? Well, here it is. This is one of my favorite devices in endoscopy. It's a fairly robust CAP. And you can see here, this is a fairly large tumor at the GE junction. And the CAP EMR technique requires submucosal injection of saline or another agent. And here's the snare that's seated, ready to go. And then the next thing you do is suction up this tumor using a nice cuff of normal mucosa and proceed towards the gastric cardia. We are at the GE junction. You can see the large chunk of tumor has been swallowed, so to speak. And the snare is ready at the bottom to squeeze it and then snare resect it using electrocautery. It's a fairly large defect that develops almost the size of endoscopic submucosal dissection level defect, as you will see. And it takes a fair amount of work to get this lesion out. But you can see it's been done safely. And the base looks very nice. There is no perforation here. And there's no significant bleeding. But as you can probably appreciate, there's a fair amount of tumor still left over there. And so we proceed further with the resection of that element of the tumor. Because the worst thing you can do, you know, if you partially resect a tumor, the best resection is done in the same first session. Otherwise, you should not touch it. Otherwise, it becomes very difficult for subsequent endoscopy sessions to remove tumors. So the best resection is the first resection. And it should be a complete resection, you can see an even larger amount of stomach tissue has been taken. And of course, endoscopic submucosal dissection could also be another alternative here, but would take about five to 10 times more time to finish this job. This particular case was finished about 10 to 15 minutes total. Now, this lesion is retrieved with the rock net. And then we'll inspect the base. And this is the level of defect that we have here. It's a large five centimeter defect with no perforation. And essentially, this patient was saved in esophagectomy in a difficult location and care was delivered. Now, obviously, this tumor has to be mucosal in its invasion, it cannot be invasive. If it's invasive, then the patient will still probably need to go to surgery. So a word about endoscopic submucosal dissection. This is a study published in GIE, looking at about 11 studies, 524 lesions. So this is fast becoming a paradigm where you take a bunch of knives, you inject below the tumor and just dissect your way below the tumor and removing it in one piece as opposed to the two pieces that you just saw. So the average procedure time was about two hours, very high rates of resecting the lesion endoscopically, relatively lower rates of R0 resection, which means complete resection of the cancer, but that may have more to do with the fact that the tumor was invasive in a third of these patients. And of course, the bleeding and perforation rates are well known in this realm. One of the things with ESD is the high stricture rate, especially if you take circumferential or near circumferential levels of esophageal tumor. But those strictures mostly can be managed with endoscopic dilation. So a couple of slides on endoscopic ablation. Ablation comes in different flavors, radiofrequency ablation, cryotherapy, and others, as I mentioned. Contraindications to ablation are listed here, including pregnancy, prior surgery was used to be, but is no longer considered a clinical practice. Eosinophilic esophagitis is a scenario where you have to be particularly careful because the esophageal lumen is relatively narrow. The ideal ablation technique balances uniform mucosal injury and leads to low recurrence rates of Barrett's and is safe. It's easy to administer for the physician, well tolerated by the patient, and has long term efficacy. So this is one of the more common and typically the first modern ablation technique, which is radiofrequency ablation. It's a bipolar energy system, and achieved very high rates of dysplasia eradication and Barrett's eradication at a one year follow up. And the most pivotal trial here was the New England Journal published in 2009, where there was a randomized sham trial published on this topic and it's probably the most quoted study in Barrett's RFA ablation. And this is a typical procedure that occurs here, we have a pedal loaded on the gastroscope, we start at the GE junction, and we apply this heat energy, the RFA energy, and you can see the coagulum that forms behind the pedal that is indicative of effective treatment. And the patient generally will tolerate at least pedal based RFA very well. When longer segments are ablated with the balloon device, there is some chest pain, which also can be managed easily. So the pros and cons of ablation, radiofrequency ablation, it's very fast, it's easy to do. That is one of the reasons it gained wide popularity. Over the last two decades, the cons are that it's relatively limited in its depth of injury. And of course, the stricture rates are in the 5 to 10% range. And with long segment Barrett's, as I described, if you do 10, 12 centimeters of Barrett's in the same day, there will be some chest pain, and some cases it will be moderate, and there'll be a few phone calls to the team, which we'll have to manage. Long term outcomes for ablation with low grade dysplasia are listed here. This is a study where basically the median follow up was 73 months, a large number of patients. This is a SURF trial, surveillance versus radiofrequency ablation for low grade dysplasia. And you can see here the 90% of patients treated with RFA achieved CEIM and CED with a relatively low recurrence rate. So RFA is very effective, and the long term data has shown that as well. Now, cryo based platforms have come of age, the carbon dioxide one kind of fell out of favor in recent years. But the two main platforms right now are the liquid nitrogen based cryotherapy and the nitrous oxide based balloon cryotherapy. This is the spray cryotherapy here, and this is the balloon cryotherapy, both are commercially available. And this is the setup for the spray cryotherapy, it's a console. And then there's a dedicated catheter that delivers cryogen at minus 196 degrees centigrade, which is roughly minus 300 Fahrenheit, it's five times colder than the North Pole, but amazingly well tolerated by the patient, even better than the RFA in some cases. And this is a short video clip showing application of spray cryotherapy at the level of the GE junction, you can see there's a gap here that maintains the visual field, and and 30 seconds of this treatment are applied times two at each site. And again, the results are very, very good. And these are the indications for spray cryotherapy, primary therapy for flat barrets certainly can be done, secondary therapy where radiofrequency or resection has failed to achieve the job. That's known as salvage ablation. And then of course, palliation for cancer. Right now, this is pretty much the, the only most commonly available endoscopic palliation therapy where you take a bulky tumor like a golf ball or a baseball. And you apply several sessions of spray cryotherapy very aggressively, five, six, seven applications every two to three weeks. And these patients have, you know, many cases shown remarkable improvement in dysphagia scores, avoidance of esophageal stenting and so forth. And now the new paradigm is combining spray cryotherapy with chemo radiation. And those protocols are being written as we speak. So this might represent a new paradigm for palliation in esophageal cancer down the road. This is a multicenter retrospective study of spray cryotherapy, open label 11 academic and community centers. And you can see here again, this 88 patients, 350 treatment sessions, and the primary outcome here, even with invasive cancer, with complete response, even in invasive cancer was pretty good at around 50%. These are not your regular barrets patients. But a lot of the data on cryotherapy has focused on cancer patients that had fewer options, especially those patients who are not candidates for esophagectomy. Every technology, technique, paradigm has a potential for complications. The most important intra-procedural complications of ablation are listed here. Endoscopy, sedation really remains, cardiopulmonary events really remain the main highest complication rates, although with general anesthesia support that is reduced. Bleeding and perforation are relatively uncommon. And when bleeding occurs intra-procedurally, it's most commonly able to be managed endoscopically. As I mentioned before, ablation can produce chest pain and throat discomfort. And this is managed together between the MD and the APP team over the next week or two. Other complications have been described, but are relatively rare due to the nature of the procedure. One of my favorite topics in barrets is challenging scenarios because the easy cases can be done pretty much anywhere by anyone. But these represent some of the more difficult situations. Persistent esophagitis, despite the patient trying to do everything, you're doing everything. And of course, the occasional patient who cannot tolerate PPIs. Persistent esophagitis remains a problem for ablation and even in some cases for a section. But fortunately, these cases are few and far between. Difficult anatomy is a little bit more frequently encountered, including especially difficult upper esophageal insertion in older patients or in patients who had prior surgery or radiation to the head and neck. Remember, esophageal cancer and head and neck cancer kind of travel together because of similar risk factors and genetic predispositions. So the elderly patients and the cognitively impaired patients So the elderly patients and the cognitively impaired patients becomes really difficult how to handle that technically as well as conceptually when a surrogate is making decisions. These are some of the considerations. I think we wrote a paper on this topic, which is not cited here, but key considerations in elderly patients. Cognitive function, do they really understand what they're getting into, their performance status, their ability to comply with post ablation medications, and in some cases, unfortunately, still insurance coverage and so forth. Procedure-related issues in elderly patients with Barrett's are listed here. The goals of treatment really have to be defined. If you have an 89-year-old patient with dysplastic Barrett's, yes, treatment should be considered, but it has to be in the context of the patient's overall condition. Management of antithrombotic therapy becomes really important, and you heard about that yesterday in the anticoagulation talk as well. So how important is surveillance after endoscopic therapy? Very briefly on this slide, what this slide is trying to tell us is that despite the best treatment, when patients are followed up or a mean of 3.6 years, 32% of patients had recurrence of Barrett's or dysplasia despite complete eradication in the first place. So this paper and several other papers makes a good case for ongoing post-ablation surveillance, which is something that we need to keep in mind. We are not yet ready to send these patients out into the sunset, even after doing a bang-up job on their ablation treatments. There is a recurrence rate, and the recurrence rate is mostly related to two things. One, their baseline pathology. If they came in with high-grade dysplasia or esophageal cancer, and you took care of them and you treated them, then they are more likely to recur compared to somebody who came with low-grade dysplasia. And secondly, patients who achieved complete eradication of intestinal metaplasia early on and remained free of intestinal metaplasia at one year follow-up, they are less likely to recur down the road. So we have seen that similar results in our clinical practice. Some patients were really difficult to bring to justice. They remain troublesome throughout their first five to seven years in follow-up, and they have to be even more carefully followed than the average patient. This is a very important point for all of us, including for our APP group here today, who may see these patients in follow-up. There are very clear indications for surgical intervention. Despite the amazing success of endoscopic therapy, it becomes important to note that invasive cancer, particularly in patients who are young, who have poorly differentiated carcinoma, who have lymphovascular invasion, who have invasion into the second or third subucosal layer or beyond, they need to be brought to the tumor board or referred to the surgeon. This is not a joke. This is not something you can play with. The metastatic rates for these patients are upwards of 30% in short- to long-term follow-up. Any patients who are not responding to therapy primarily due to anatomical reasons, or they're not amenable to resection, or we cannot get the scope down to ablate their strictures, whatever the reason is, that patient needs to have an alternative discussion because we are not making progress, and we would be remiss in not affording that discussion. And our surgical colleagues, that's why we work with them so closely, so there is a lot of back and forth on these patients. And finally, the best pathway is chosen. Therefore, the multidisciplinary team approach is very important. Advanced imaging, surgical colleagues, our cancer colleagues, tumor boards, expert Barrett strains pathologists. Back in the day when we first started the program, we had to send our pathologists out to train at institutions where there were known experts. And all of this comes together in the clinic, it comes together at the tumor board, in the pre-endoscopy, post-endoscopy sessions, in phone visits afterwards. And this is a huge area where I personally benefit from my APP supports, and I think many practices collaborate in a similar fashion in this realm. So one slide on the specific roles of the APP in a Barrett's practice. Initial evaluation, certainly we see these patients together almost all the time, but the APPs can also see if some of these patients who are known to the practice as independent visits. Peri-procedure management on the day off becomes really important, especially with the prescriptions and making sure the patient's education folders are complete, and that we communicate around what the patient needs are. Facilitating GI tumor board discussions, and sometimes our APPs will join there as well. Making quick calls to the surgical colleagues and surgical APPs on the other side. A lot of activity on Epic related to the messaging around these patients. And of course, recognizing the contra indications to endoscopic eradication therapy and the indications for surgical referral is really very important for those APPs who are involved in this practice. So one of the things that we have tried to do at our center, and others have as well, is that we like to involve our nurses, endoscopy specialized nurses as well as APPs and fellows in clinical research trials whenever it's feasible as co-investigators or sub-investigators that enforce them another avenue of professional development while they're already taking care of these patients in clinical practice. So final practice pearls, I've already talked about the multi-modality aspect of Barrett's endotherapy, which has come of age, talked about the importance of post-ablation surveillance, which still cannot be let go. The importance of anti-reflux therapy, medical and or surgical is really key. Without that, I think it's very difficult to heal the esophagus during ablation and get the best outcomes. Patients who have a difficult anatomy, difficult progress during endoscopic therapy or have invasive disease should really be referred to a surgeon for discussion. But I think the APPs really can have a very pivotal role from the initial assessment through the treatment process, patient education, and then, of course, getting involved with some of the very active and high-level research protocols that are underway in the country right now. Thank you. I know I went a little bit over time, but hopefully this was valuable to the audience. And I think we have a couple of endoscopy polling questions here. See, all of the below are established indications for endoscopic eradication therapy for patients with Barrett's esophagus except. So established indications, all of them except one. Barrett's with high-grade dysplasia, Barrett's with indefinite dysplasia, Barrett's with intramucosal cancer, and Barrett's with low-grade dysplasia. So which one of them is not an indication for endoscopic therapy? Yeah, I think most of them have chosen the correct answer, which is indefinite for dysplasia. That currently is not an indication, whereas the others are. A patient is referred with the Barrett's esophagus, excuse me, with high-grade dysplasia for further evaluation and management. Which of the following is best practice recommendation? So select one best choice, office visit with detailed assessment and consultation, offer endoscopic ablation treatment from a variety of choices, perform EMR if a raised nodule or lesion is found at endoscopy, and offer a surveillance endoscopy after ablation is completed, or all of the above. So which one, single best choice, is the way to go? All right, all of the above is the majority, and that wins. That is fairly straightforward, but still all the points needed to be made, and I think the audience got it. Well done, guys.

Barrett's esophagus

endotherapy

treatment

esophageal neoplasia

endoscopic therapy

surgery referral

therapeutic regimens

intestinal metaplasia