Let's get started. I'm pleased to introduce Dr. Prasad Iyer. He'll be speaking to us today on looking at the way in and out, how to maximize esophageal endoscopy. He is the director of Esophageal Interest Group, co-director of Advanced Esophageal Fellowship, director of postdoctoral programs at Mayo Clinic Center for Clinical and Translational Sciences. Please welcome Dr. Iyer. Thank you so much, Prashanthi, for that kind introduction. And indeed, it's a privilege to be invited to co-direct this course with you. I am honored and looking forward to this wonderful course. So I will begin by sharing my slides. So the first talk is, I think, very appropriately titled, I suspect many of us on this meeting today are endoscopists and have an interest in esophageal and foregut endoscopy. So we thought we would start with a few tips on what is the best way of looking on the way in and out and how to maximize the esophagogastroendoscopy with special emphasis on the esophageal evaluation. So these are my disclosures. So this is a slide that I actually took from a presentation made by one of our previous co-directors, Dr. Katz, who was kind enough to share this with me. And I think one of the things we have to think of as we are focusing on the esophagus is, this is a bit tongue-in-cheek, that the esophagus is not a conduit just to get into the stomach. And as he likes to say it, in fact, there is little reason to enter the stomach except to retroflex if the symptom is related to the esophagus. So we'll go through a few tips in terms of how to do a good esophageal examination. So the first thing we have to always remind ourselves is that why do we do endoscopy in patients with reflux? A common reason is to assess continued symptoms, particularly if the patient has been on a proton pump inhibitor. And the goals for this are to assess for the presence of esophagitis, any other complications such as Barrett's esophagus, a stricture, or maybe even an early cancer. And of course, we are also thinking at the back of our minds, is there an alternate etiology for this patient's symptoms, say achalasia or eosinophilic esophagitis? Second, if there are GERD symptoms accompanied by dysphagia, we are especially concerned in terms of any alarm symptoms, particularly if there is weight loss, change in appetite, change in energy level. And again, we are looking for complications like a stricture or maybe even a mass. And of course, there are guidelines which suggest that in patients who have chronic reflux symptoms, who may have other risk factors such as male gender or Caucasian ethnicity or obesity or prior history of smoking, we are also thinking, does this patient have Barrett's esophagus? And of course, if we see any signs of that, we have to do a careful examination and sampling. So what are some tips to performing high quality endoscopy? And just like the real estate principle of location, location, location, I think what we need to think about is time, time, time. So we have to allot a reasonable amount of time. This is particularly important because the esophagus is not a still structure, there is peristalsis. If the patient is not adequately sedated, they might retch. And of course, all of this is going to make the examination, particularly of the G-junction difficult. So adequate sedation is important. The second important tip I would give you is to ensure that you clean the esophagus, wash the mucosa with even just plain water. Many of our recent endoscopes now have washing channels in them, wash off the saliva, wash off the mucus and inspect carefully. Something to also remember is that the first biopsy is likely the most important because as soon as we biopsy, we know that there is some bleeding and subtle findings might be obscured. And of course, do not underestimate the power of a good retroflex examination. And I'll go through some of these in some amount of detail. So again, this is a theme we are going to keep coming back to, is to remember that the concept of a high quality exam is not just reserved for the colon, but indeed should apply to upper endoscopy as well. So again, this is just an example of mucus and saliva that we usually encounter as soon as we get into the esophagus. Now, if this is particularly persistent, you may think of abnormal motility. It can obviously obscure findings, and therefore it is important to wash and spend some time inspecting the esophagus. Now, let's get, the way I've sequenced the slides is to go through the esophagus, then come to the GE junction, do a retroflex exam, and then come back out. So of course, anytime we are thinking of persistent reflux, particularly if there is associated dysphagia, we should have eosinophilic esophagitis at the back of our minds. And we should be looking for some specific features such as rings, white spots, which might be eosinophilic microabscesses, or these longitudinal furrows, which may suggest that the patient has eosinophilic esophagitis. And indeed, we should be aware of this score called EREFS, which is an endoscopic reference score that has been developed and validated to correlate with the severity of esophageal histologic inflammation, which consists of five components. So we have edema, and you can score that as grade 0, grade 1, grade 2. Rings or trachealization, again, from grade 0 to grade 3. Exudate, which are typically white plots. Two grades, furrows, which are vertical lines. And then lastly, the presence of a stricture. So this is software that is oftentimes integrated into some of our endoscopy reporting software like Provation. But again, it emphasizes the importance of looking for these individual features as well. Now, obviously, if we see these, we are alerted to the presence of eosinophilic esophagitis. But do not forget that in a patient who presents for endoscopy for dysphagia, and the mucosa appears normal, there is a definite yield to biopsying the normal appearing esophagus. Indeed, we had published this now several years ago, wherein we looked at the prevalence of eosinophilic esophagitis in biopsies from normal appearing mucosa. Our reported rate was about 15%. And indeed, this has since been replicated by other authors as well with prevalences of 12%. And something to note in some of these studies is that almost half of patients with eosinophilic esophagitis diagnosed on histology can have normal endoscopy. Again, another case series which showed that almost 7% of patients undergoing endoscopy had eosinophilic esophagitis. And again, not to belabor the point, the sensitivity of these classic findings is not 100%. So you can miss eosinophilic esophagitis if you're only looking for the classic features. This was another paper published several years ago now, which looked at patients presenting with even food impaction in the emergency room. And they specifically looked at a subset of patients who did not have obvious features to explain why they had a food impaction and almost half of them had POE on biopsy. So we talked about entering the esophagus, cleaning the esophagus, looking at the mucosa of the esophagus. And I think one of the most critical pieces to evaluating the esophagus and G-junction is the esophagogastric junction itself. And again, I have a nice diagram here from the Cleveland Clinic, wherein we are talking about the three anatomic slash endoscopic landmarks that should be assessed, evaluated, and likely reported in every complete upper examination. So we have the first landmark is the Z-line or the sphemoculmonary junction. This is usually easily visible. This is where the squamous mucosa turns into the columnar mucosa of the stomach. The next is the G-junction. And this is typically measured by the proximal end of the gastric folds. Now to adequately visualize the proximal end of the gastric folds, we want to make sure that we are not overly inflating the esophagus. We may have to partially deflate and do this a couple times. In East Asia, there is the proposal to actually mark the G-junction by the end of the palisade vessels. And one of the challenges with this is that this landmark may not be consistently identifiable. So typically the end of the tubular esophagus is thought of as the top of the gastric folds in a partially deflated examination. And the third landmark would be the diaphragmatic hiatus, which again is typically very easily identifiable as the patient reads in and out. So I will again walk through my process of evaluating the G-junction. So again, another cartoon. In a patient with normal findings, these three landmarks should really be coinciding. So again, we have the Z-line, which is a spemocolumnar junction. We have the top of the gastric folds, and then we have the diaphragmatic hiatus. Now what happens when there is a hiatal hernia? The hiatal hernia basically is the anatomic herniation of the proximal part of the stomach into the thoracic cavity. And in this case, you would have the gastroesophageal junction and the spemocolumnar junction proximal to the diaphragmatic hiatus. The third important condition that we should be all aware of is that when the spemocolumnar junction is proximally displaced from the gastroesophageal junction, we then begin to suspect if the patient has intestinal metaplasia of the esophagus or barrett's esophagus. So in this instance, you can see that the spemocolumnar junction is proximally displaced. This is the top of the gastric folds. And then typically, a lot of these patients will have a hiatal hernia. So all three landmarks are now separated from each other. And in this case, we should be thinking if the patient has barrett's esophagus. So again, to reiterate, we should be assessing the GE junction and the spemocolumnar junction carefully, defining the end of the tubular esophagus, avoiding overinflation, sometimes partially inflating and deflating with the help of the endoscope. And of course, any time you're suspecting a columnar-lined esophagus, wherein the spemocolumnar junction is proximally displaced from the GE junction, we should be looking for any focal abnormality and biopsying that separately. And of course, one of the important findings that we look for at the GE junction is esophagitis. And so this gives us a good segue into how should we be looking, assessing, and reporting esophagitis. And in this instance, the recommendation from societies is to use the Los Angeles classification system. So why do we use the Los Angeles classification system? We use this because this is the best standardized description of reflux esophagitis. And in fact, this was a long process of developing the grades of esophagitis, assessing inter-observer agreement. And it has been shown that when multiple observers report esophagitis with the Los Angeles classification, the inter-observer agreement, though not perfect, is still reasonable. It defines erosions as indicative markers of esophagitis and really has four grades of erosive esophagitis. And this is just an example of severe esophagitis with not only esophageal inflammation and erythema, but also ulceration. And I will talk to you a bit about what the grades would be from grade A through B to C to D. So again, so let's start with grade A esophagitis. So grade A esophagitis is reported when you have a linear erosion, which is less than equal to 5 millimeters in diameter and does not straddle any of the gastric folds. So this is isolated. It is 5 millimeters or less. So this would be grade A esophagitis. Grade B esophagitis, as you can see, is wherein the erosion is longer. So it is 10 millimeters or more. It again does not straddle the top of the gastric folds. And the only difference between A and B is that this is 5 millimeters and this is 10 millimeters or more, but they are not straddling the gastric folds. Now, what happens when they do straddle the gastric folds? Then we enter into Los Angeles classification C or D. And the only difference between when they straddle the gastric folds is whether the circumference involved is less than 75% or it is more than 75%. So if it is less than 75%, that is Los Angeles classification C. And if it is more than 75%, as you can see in this picture, this would be LA classification D. So again, this is something that we should all be looking at and indeed has been incorporated into some of the endoscopy reporting software as well. So why is this important? Why does this make a difference? It makes a difference because the presence and grading of the esophagitis, if a patient with reflux symptoms has erosive esophagitis, we know that from from prospective randomized studies, that these patients are going to need PPI therapy indefinitely. If we take them off a proton pump inhibitor, they are going to have a high rate of recurrent esophagitis. So that's number one. The second important thing to remember is that it also changes our follow-up recommendation. So given the instance, the severity of the esophagitis and the presence of Barrett's, if you treat patients, particularly with the severe ends of esophagitis, Los Angeles classification B, C and D, we want to confirm that the esophagitis has healed in about eight to 12 weeks. And second, we also want to make sure that they don't have underlying Barrett's, which may not have been evident on the initial endoscopy. And that rate can be as high as 10 to 12%. And then the third is a softer standpoint that at least some institutions use, including ourselves, that if we do an endoscopy for someone with, for a Bravo pH probe placement, and they have severe esophagitis, particularly if they have LA grade C or D esophagitis, it may obviate the need for even placing a Bravo, because then we are thinking that this patient has severe reflux enough that we don't need additional testing to confirm whether they have reflux or not. So again, these are some of the reasons why looking and grading the esophagitis would be clinically important. So let's move on to some examples as to whether, how do, how can normal appearing G junctions look like? So again, this is an endoscopic picture where we are looking at the landmark. So again, we have the squamous columnar junction, which is right here. We have the top of the gastric folds, nicely deflated and the folds and the top of the gastric folds are coming together. And then this would be really, we don't have a video here, but I think we can all appreciate that this would be the diaphragmatic hiatus as well. So again, this would, there's some irregularity perhaps on the left side, but this is maybe a few millimeters and this is not someone we would really think about whether they have Barrett's esophagus or not. Now, what about this patient? Now here we can again, see a little bit of irregularity here. And we might think, well, is this someone with quote unquote, an irregular Z line? In my opinion, again, this does not exceed one centimeter. And we will in subsequent talks, we will talk about what is needed for the diagnosis of Barrett's. And again, this is a patient I would probably not biopsy as with a concern for Barrett's esophagus. So why is this important? We know that if we are not careful about the assessment of these landmarks and we don't spend some time in assessing the G junction, we can over-diagnose Barrett's. This was a result of a study that was actually performed in Minnesota, published about eight years ago now, where three referral practice endoscopists actually got education in landmark identification, very similar to what we are just talking about in terms of assessing the anatomy on endoscopy. And then they reassessed about 130 patients who had been diagnosed with Barrett's in the community. And again, these are some pictures, which I think make this very, very clear. So again, if you over-inflate the esophagus, you might think that this side of the esophagus in section A may be in the tubular esophagus. But as you can see, when you deflate with panel B again, compare panel C and panel D, you see that the top of the gastric folds are really coming well up to the squamous columnar junction. So again, here we are making the assessment that the G junction and squamous columnar junction are coinciding. And as long as they are coinciding, we would not think that they actually have Barrett's esophagus. And again, if you over-inflate, you might overestimate the presence of Barrett's esophagus. So in this study, almost a third of the patients actually had the diagnosis of Barrett's reversed. And they were reversed because there was no evidence of columnar-lined esophagus proximal to the top of the gastric folds, and goblet cells were not found on histology either. So again, it's important to reassess and carefully evaluate the G junction with some time and effort. So again, this is important for a variety of reasons. If we biopsy an irregular Z line, and we think that they have intestinal metaplasia of the G junction, does it really matter? And at least our current evidence seems to suggest that if you biopsy an irregular Z line with a zigzag line of only less than a centimeter versus true Barrett's wherein the length of the tubular esophagus intestinal metaplasia is at least a centimeter or more, the natural history is very different. So these were two studies published by us from Mayo Clinic and as well as from Dr. Thota's group, which clearly showed that if you have an irregular Z line and you biopsied and you follow these patients, you'd really do not develop high-grade dysplasia or cancer over a fairly long time frame. And of course, if you truly have Barrett's esophagus, then there is a definite risk of progression in these patients. So again, it is important for us to carefully evaluate these patients and avoid perhaps biopsying what we may think is just an irregular Z line. And indeed the ACG guidelines talk about the same concept that Barrett should be diagnosed only when there is an extension of at least a centimeter, if not more, proximal to the G junction, and that we should not be biopsying either a normal Z line or just an irregular Z line. And again, these guidelines are very similar to the ASGE guidelines which were updated in 2018 as well. How much should we be biopsying? How many biopsies should we be taking? If we think someone has Barrett's esophagus, if you have adequate length of mucosa, take at least eight random biopsies to maximize the yield of intestinal metaplasia on biopsy. Of course, we know if the segment is very short, eight biopsies may be unobtainable and there you can go with perhaps four biopsies from a circumferential segment and one biopsy per centimeter in tons of Barrett's. Now what happens if you do not see intestinal metaplasia, but you're suspecting that a patient has Barrett's esophagus? In this instance, you can bring the patient back in perhaps a year or two to confirm or exclude the presence of intestinal metaplasia. And up to a third of these patients will turn out to have intestinal metaplasia on repeat evaluation. Other pointers towards biopsying Barrett's appearing mucosa at index endoscopy. Now a common challenge might be if the patient has esophagitis, should you really be biopsying the esophagus? Now it all depends on how comfortable you are, how good of an exam you are getting. If the patient is already on say a PPI and you're doing this for non-responsive disease, you could biopsy the patient. But if the patient has severe esophagitis, then perhaps best to put them on a high dose PPI, bring them back in eight to 12 weeks, allow for the healing to happen and then do a good examination and repeat the endoscopy. And of course, we should always be thinking in patients with known Barrett's, think about the Prague classification, which is another standardized way of reporting Barrett's length. And I'm sure a lot of us have heard about this. And indeed it is a sequential process where we identify the landmarks, we identify the diaphragmatic hiatus, we identify the GE junction, we identify the squamous columnar junction, and then we measure the circumferential extent of the Barrett's mucosa. We then measure the maximal extent of the Barrett's mucosa and then report this as a C number and an M number with the C being a measure of the circumferential extent and the M being a measure of the maximal extent. Just a quick example here. So again, we have the GE junction right here. So we are measuring the C length to the point where we have circumferential Barrett's and then we have the M length to the point where we have the most proximal displacement of the squamous columnar junction. Now islands of note are not really included in the Prague classification and you can make a separate comment, but really this includes contiguous segments of columnar metaplasia from the GE junction. Another example. So this is the GE junction labeled as the black circle. And then you have this, let's say that this is located at 40 centimeters. And then the first measurement is where the circumferential Barrett's ends and that is at 39 centimeters. So that leads to C1 and then you have the maximal extent going up to 36 centimeters and that would be M4. So in this instance, you can, in a very standardized fashion, you can report the, not only the maximal extent, but also the circumferential extent. Again, what should we be reporting? If we see any Barrett's, we should be reporting the Barrett segment length in the form of the Prague criteria. We should be reporting the presence of any visible abnormality at what centimeters from the esophagus, what is the size and what is the o'clock. If you can think of the esophagus cross-section as a clock, always document the presence and size of a hiatal hernia and always document the presence of any esophagitis either above the Barrett segment, or even if you don't have Barrett's, you should still be reporting the esophagitis as a standardized terminology so that anyone who reads the report should be able to understand the findings. Beyond the GE junction, we should be thinking about the type, the presence and the type of a hiatal hernia. And again, this is just a simple cartoon wherein normally the GE junction and the diaphragmatic hiatus is actually present distal to the diaphragm. Now, we have some certain types of hiatal hernias that we should all be recognizing. So the most common is the sliding type of hiatal hernia, also called a type 1 hiatal hernia, where the GE junction is proximally displaced from the diaphragmatic hiatus. And this part of the gastric, of the stomach will just be sliding in and out depending on the intrathoracic pressure. Now type 2 hiatal hernia is wherein the GE junction is still at the level of the diaphragmatic hiatus, but a portion of the stomach, which is usually the fundus, is now proximally herniated above the level of the diaphragm. Now this would be called a parasophageal hernia or a type 2 hernia. What is a type 3 hernia? A type 3 hernia is when you have both of these components, so the GE junction is proximally displaced and the part of the stomach is also above in a parasophageal manner herniated above the diaphragm. And then in this picture, this is again a combination of cartoons. These are barium swallows and then these are the endoscopic correlates. And here you have a sliding hernia and this is something that you can usually see very clearly on endoscopy. This is a type 2 parasophageal hernia where you are seeing the portion of the gastric fundus. The GE junction is actually still located at the level of the diaphragmatic hiatus and here you can see the opening in the endoscopy of the parasophageal hernia itself. Type 3 is where you not only have proximal displacement but also the herniated fundus and again this is something that you can see on retroflex view very carefully. And then what is type 4? Type 4 is a parasophageal hernia where intra-abdominal contents, this can be the colon or maybe the omentum, is now also herniated above the level of the diaphragm and this typically will require some degree of surgical correction. You may have also heard of the HILT classification. This is also available in some of the endoscopy reporting softwares and allows us to quote-unquote grade the GE junction and may have an impact on the type of therapeutic options that we might present to the patient. So a grade 1 GE junction is a HILT classification is wherein on retroflex view the GE junction is snug against the endoscope. So this is an intact GE junction with all three components typically being at the same level and there is no opening of the GE junction in the respiratory cycle. Now grade 2 is wherein this ridge or the angle of angle of hiss is a little bit more lax and this typically will happen only during respiration and the ridge is less well defined and it opens with respiration. Grade 3 is wherein now you're beginning not only to see this laxity of the GE junction but now you're beginning to see some proximal displacement of the GE junction and the ridge is affected and the hiatus now is becoming patchy. So this is an early stage hiatal hernia and then of course grade 4 is wherein now you have a large hernia a substantial hernia with proximal displacement of the GE junction and a sliding hiatal hernia and then this is something that you can easily see and the hiatus is wide open at all times. So this would be grade 4. Also important to get an idea of identify and get a sense of if the patient has had any anti-reflux surgery and there are several kinds of anti-reflux surgery as we know. The commonest is a nascent fundoplication which is a 360 degree wrap wherein a part of the fundus is wrapped all around the esophagus and if you have an intact fundoplication this is typically what you should be seeing. You should clearly be seeing the nipple valve which is the impact of the fundus being wrapped around the stomach and then you should clearly be seeing an anterior groove and a posterior groove and you can see that the wrap is snug around the endoscope. So this would be an intact nascent fundoplication. A toupee fundoplication is a 270 degree wrap so you are you are wrapping about three quarters of the circumference and this might be done for a variety of reasons perhaps in patients who may have some compromise in their esophageal motility and in this instance you are not going to see a full wrap but indeed what is typically or classically described is an omega shaped wrap wherein you have a posterior groove, you have the valve itself and then you have the anterior groove. A door fundoplication is an anterior fundoplication which is only a 180 degree wrap again done for perhaps compromise esophageal motility and in this instance you are not going to see a posterior groove but you are only going to see an anterior groove as you can see in this endoscopic picture. So this would be the best description of an intact door fundoplication. So this is a nascent fundoplication, this is panel A, this is a toupee fundoplication which is 270 degrees and this would be an anterior fundoplication or a door fundoplication. Now oftentimes you are going to see a failed anti-reflux procedure so again this would be an example of what a loose wrap is looking like. The folds are no longer radiating, they are basically just loosely wrapped around the GE junction. You may have a recurrent parasophageal hernia, you can still see portions of the fundoplication here and then of course in this instance the wrap has really not only become loose but is also associated with a recurrent sliding hypohernia. So those are some findings that we have to be able to evaluate and then also report because these may have implications on our management. Coming to the end of the talk, do not forget to see Cameron's erosions which are basically erosions or ulcers at the level of the diaphragmatic hiatus and these might be the only findings you might see in patients with iron deficiency anemia. And then as you're coming back, you may want to pay attention as well to the upper esophageal sphincter, look carefully for any narrowing in patients with proximal dysphagia, look for a cricopharyngeal bar or a stricture and of course we would see inlet patches as well and pay some attention to this as you are withdrawing. So to conclude, the keys to a thorough esophageal exam are to identify and document the landmarks as we talked about, look for signs of eosinophilic esophagitis if dysphagia is a symptom, do consider biopsying even if there is no endoscopically evident cause, use the Los Angeles classification system for grading esophagitis, assess carefully for the presence or absence of barrets, examine and sample any visible lesions, avoid biopsying an irregular z-line and last but not the least, retroflex carefully. Thank you so much.

esophageal endoscopy

thorough examination

esophagus

Barrett's esophagus

classification system

hiatal hernias

optimal care