Case Based Question & Answer Session on GERD, Motility Disorders of Esophagus, Eosinophilic Esophagitis, Barrett's Esophagus, Functional Upper GI Disorders, Peptic Ulcer Disease, Celiac Disease, Non-variceal Upper GI Bleeding, Upper GI Pathology, Introduction to Statistics for the GI Boards
see, I would like to welcome everybody to our first, uh, question. Live question and answer session. That's part of the eighth annual Mount Sinai. Um, intensive border view and gastroenterology and hepatology. I'd like to introduce the other panel members that air here. Um, today is you may have seen on the original introduction slide. We're gonna cover upper GI eye diseases. Primarily esophagus stomach do of them on dso on our Panelists here first is Dr Tony Weiss on. He prepared the lecture on peptic ulcer disease and in H. Pylori, Dr Marina Jihadi. Hello. She's faculty here at Mount Sinai Hospital and has prepared her talk on us. And I feel like esophagitis Dr Pascal White, who was still on mute, but she's the one who prepared talk on celiac disease. Dr. Ari Greenspan. Hello. And he is our local expert on fecal microbial transplants that also for the talking upper G I, uh, functional disorders and dyspepsia. Dr. Alexia Palla droids. Well, from the Department of Pathology, Dr. Mary Jeff in our one of our motility experts here at Mount Sinai like and then Dr Mike Smith, chief of G I at Mount Sinai, ST Louis and Mount Sinai West, who is also an expert in all things esophagus. Welcome, everybody. I'd like to direct our attention down to the bottom. The screen. It's It's totally different from a normal zoom meeting. There's a Q and a tab that's down there. You can feel free thio type in your questions there, and we'll certainly relate them. Thio the appropriate moderators or open up them, open them up for discussion. We have a couple of goals tonight, Uh, certainly one of which is to go over sort of a keyboard relevant material, but additionally also to make sure everyone is sort of up to date on the current practicing guidelines of various upper G I disorders. So when you ask a question, you can certainly directed towards one of the speakers. But we'll certainly open up to discussion. Um, we do have some prepared board review questions. Um, Thio kind of go through. But before we go through to those, we want to see if there any questions from the audience to start. I'm going to assume that you are all busy furiously typing away into the Q and a box. Andi, as you were doing that I'm gonna ask Pascal to go ahead and put up the first question. All right, Hold on a sec. Yeah. Alright. So 29 year old woman is heartburn and acid regurgitation several times a week. E g d is completely normal. No hiatus. Hernia is seen. A pH study demonstrates asset exposure time of 7%. Barium swallow demonstrates significant reflex among patients with non arose of reflux disease. Which of the following factors predict symptom improvement with proton pump inhibitor therapy? Um, a abnormal barium swallow. Be some type of regurgitation. See esophagitis and biopsy D abnormal Ph. D. E. No evidence. Hide a hernia. I'm gonna drive server Thio. Mike. Um although there many people on the panel who could probably address this. But Mike, let's see what you can offer. Well, yeah. So they're the the answer there is. I see that there's there's ah, highlight Thio E. So I think Let's just go back and look at the questions. Stem a little bit. There are a couple accused in here and some very important things, right? The first of which is they talk about the lack of ah Heidel hernia or other abnormality on endoscopy. and you have to remember that about three quarters of patients with clinically significant reflux disease have no findings on endoscopy, and that includes the even the lack of a high it'll hernia or significant Heidel hernia, which would be one greater than two centimeters in axial length. And so the fact that they have a normal endoscopy and no Heidel hernia does not exclude them from having quantitatively abnormal or clinically significant reflux disease. And in fact, that that's what you see on the Ph study results on DNA. Very um, Asafa Graham, demonstrating significant reflux is great, but it's not. Not as good a test is quantitative reflux, testing and making the diagnosis, and it's certainly one reflects event that scene on Asafa Graham and demarcated as such by the radiologist in there Read does not define someone is having good either. So in these patients, Mike E. Will say, there's a little bit of a trick here that we've highlighted the wrong answer. E was going to say e going and I was trying to figure out, but and I was sort of giving a chance for the Question e before. Before you try to spin the wrong answer is the right one. Let's just say I agree with your e. Think where we should be highlighting, uh, we should be highlighting d here, I think is the correct answer. Right? And I'm sorry. Symptoms. I'm sorry, not in this patient, but in general, is the reflux esophagitis? Maybe there, but But certainly the lack of behind learning, as I said, should exclude E and not go with it. The barium swallow again should not be something that's going to steer you one way or the other. A regurgitation is less likely to respond to the reflux symptoms, too. Acid reduction therapy, which is what we're talking about here. It's really a B and e come out very quickly. And then the question is reflux Esophagitis versus an abnormal ph study. Andi, in this particular situation, you really could narrow it down to the two of those on DSO. Maybe we could go to the answer and go through the quantitative or the reasoning that comes out on the board. The answer here and that will get into a little bit more detailed. So the next one and we you wanted to see the answer? Well, I think? Do we want to show people the answer here? Yep. Let's do that. Do that. Uh huh. So, just by reasoning and what you know about GERD in general, you can really get this down toe one out of two, right? And so So what's really important here is the importance of the pH monitoring the asset exposure time or the Dem Easter score, which is a multifactorial score. Remember that dim Easter score that is elevated in your own practice does not is not meant to predict and answer the question. Does the patient have reflux? It really was designed to say, Does the paint will the patient benefit from anti reflux surgery? Tom de, Mr Being the person who developed the score is a surgeon. He was trying to figure out what is a predictive model for response. Tow anti reflux surgery. So elevated, abnormal or abnormal acid exposure time certainly can predict your response. Toe asset toe antacid therapy. Whether that be an atomic or pharmacologic again, the microscopic esophagitis on routine biopsies does not predict d p. I response, that's for sure. The situation because you can have cases of Israel hypersensitivity, which I did talk about in my recorded lecture that you can access is part of the course. Hi. A hernia again can be. Doesn't have to be there. Toe Have, uh, reflects that. That is responsible. D p i regurgitation less likely is a symptom to respond. Theus av program we talked about before. And actually, are we missing one of, uh but either C or D? I'm not sure if we go back to the question stem. I think that the the answer possibilities may have changed a little bit or I'm uh uh, Right, So that s o I of those to really see and deer there, and this would be a tough question, but the bestest answer is probably D because of the elevated acid exposure time. But reflects Esophagitis, um, you know, probably is a close second. And the reason why in this case it's not as good and answer is because the sausage itis can come from lots of different things and it may not be acid reflux. There may be some kind of a Stasis esophagitis. There could be pill induced esophagitis, and in this case, it's not as specific and answers relating to this particular question. So s so. I think that Zatz important here that the abnormal pH study is really the best answer here and see would be a close second, but not specific enough to be the number one answer. Mike, do you draw a distinction between microscopic evidence of esophagitis versus over like l A grade of rows of esophagitis? Yeah. So I think that's an important point here. And I think if I remember correctly my slides I talked a little bit about the Los Angeles classifications. It's important that we use that because we know that the hired classes of L. A. A savage itis, the more significant the reflux disease, the thinking, the conventional wisdom right now is a great A is probably not, um, significant enough that we would act on it, but be a sort of borderline and certainly cnd uh, if they're truly reflux esophagitis, Remember, don't use the l A classification to grade non reflux esophagitis. So if you see Stasis esophagitis and a patient with a coll Asia, for example, that's untreated. That's not Los Angeles classifications. You don't need to use that classification. It's really for GERD based Arose of esophagitis. Um Thanks. Make no, Barry. Um, sometimes on the boards, they will ask you questions like this and that that will be anchored around a value on a Ph study like here. It's 7% on for those of us who don't read pH studies, do you have a couple of numbers that I think people should try to keep in mind? If you're on one of these online versions of the test, you could look him up on up to date. But it's nice to have a number in your mind. You have a couple numbers you think are useful. Yeah, there's a difference between upright reflux and supine reflux. Upright reflux. They uses about 6.4% and recumbent is about 1.2% for a total of 4.5%. So if it's under 5% and is considered more illness, normal above certainly is abnormal. Uh, the other thing I'd like to echo that, Mike said, was if see it had said Barrett's esophagitis on biopsy, the answer would still be D, because your patients with Barrett's who certainly do not have symptoms necessarily of significant reflects on the PP, I may not be helpful also. So I agree with Mike that the abnormal pH study is really the answer here. Excellent. Alright. Eso pascal if you can jump to the next question So which of the following is most likely to respond to a trialist PP I therapy thes air These frustrating symptoms that we all see regurgitation, non cardiac chest pain, chronic cough, global sensation hoarseness. Barry, you have any thoughts on this, Aziz? Always. There's easy to rule out. I mean, chronic cough is definitely no. And Mike and his talk gave a couple of cases regarding chronic cough and reflux. And that's not helpful. Global sensation. Likewise, uh, FBI is not helpful, and LPR with hoarseness isn't so. You're really down toe a and B non cardiac chest pain can be from reflex, but it also could be functional, so I would end up choosing a regurgitation. Mike, what are your thoughts? I think that if there are a couple of pieces here that are important for everybody to remember, if you think about GERD questions certainly the question of typical versus a typical symptoms of reflux and that heartburn and regurgitation are your typical symptoms. And a lot of the other ones that you see her atypical Andi and in your mind that conventional wisdom is the typical symptoms are less light, are more likely to respond to P P I. However, regurgitation is the exception to that in the literature that's been coming out more recently. In that, because a lot of folks are volume regurgitate er's there that symptom even on P p, I is more likely to persist then heartburn. And there's advanced knowledge. There's advancing data that actually non cardiac chest pain, um, is more likely whether that is good related or an inflammatory condition that one actually is there. And so this is a bit of a trick question on the Berries, exactly right that heartburn and regurgitation being the typical symptoms. But there's been a little bit of a flip in the last decade or so that that non cardiac chest pain over regurgitation because of the volume regurgitate er's and the prevalence of Heidel hernias is more likely to respond to a P p I. So it's a trick question here, but I see it highlighting, and hopefully this one is highlighting the correct answer. Yeah, we just wanted to kick it off with a bang. So right, I agree. Certainly A and B is it, although there are patients with vegetation that will respond to the FBI's and others with atypical chest pain that may or not respond. But I guess for the board question, Michael is correct. So and again, this is a tricky one. And that's just one, that they like the heart bun because they want you to divide typical and atypical, and then they want you to flip back and find the exception to the rule. Also, remember, from my talk that the atypical symptoms of reflux often require B. I D therapy and for a prolonged course of 2 to 3 months to see if the inflammation will go down to the point that the symptoms improve. So Barry's point about hoarseness and chronic cough and asthma and all of these other things, not global sensation not responding readily to P. P. I is absolutely correct. But if they are truly due to GERD, then you need a high dose p p I for an extended period of time as a trial to say that they truly failed acid reduction therapy. Excellent. Uh, let's move on to the next question. All right. 40 year old male presents your office with regurgitation. Initially presented six months prior with heartburn and regurgitation. E g. Did initial presentation demonstrates l a grade C esophagitis we started on PP I'd be I d with improvement in heartburn. But ongoing regurgitation re ped demonstrates a three centimeter Heidel hernia, complete resolution of esophagitis and no barrettes. What is the next step in evaluation, Mike. So yeah, this is this is really they like this regurgitation thing, and then we're running with that with that issue here. But there are a couple of things here. The question You have to figure out what the question is that you need to answer in the next step for this patient. And some people would say, Well, you know, do we need toe quantitatively decide that somebody has reflux? Well, if you've got you've got the symptoms, you've got improvement of the symptoms on a p p. I. You have the high it'll hernia. Um, in this and you've got great See esophagitis, the great sea esophagitis. Really? As I said in the last discussion of that, that steel seals the deal. The patient has clinically significant reflux disease. So if you're trying to figure out well, what comes next? Um, you know, the question here is, Well, what else is going on? Well, it's symptoms have have improved except for regurgitation. Right? You know, you have a high, it'll hernia. You know you don't have Barretts esophagus. So really, the question is, Well, what How do you want to manage this patient in the? The fact is, you have to focus on whether or not you are actively inappropriately managing. They're known reflux disease. You've gotten rid of the erosive esophagitis. But are you managing their reflux disease? And so that's the question you have to answer here. Do they have contributing? Gastro Parisse is certainly an interesting question, but not as central to the situation. Do you need to know that they have reflux on Asafa Graham? It's pretty clear they have reflux based on all the stuff that's in the question stem. So that's really irrelevant. And the US here isn't gonna tell you a whole heck of a lot, if anything, and Manama tree would be great, because if you're deciding if you're going to do a fund implication on a hernia repair. What kind of repair might be on the table? Do they have underlying Asafa Jill Dis motility. Do they have something like a scleroderma like esophagus? Really interesting question. Not central to this patient. What you really want to know is are you are you Are you controlling the reflux? And the only one that can do that is E ph impedance testing on PP I Funny point. You need to do a Manama tree to do a 24 hour ph impedance test, so you'd have to order D to get t e. But he is the most central test to order at this time. Andi. I guess the key there is to sort of define whether that you've controlled the reflux. And if you have, then you're moving on to something else. Correct? Correct. And that z really the key here and managing the patient, you have enough objective evidence of good to make the diagnosis. Now you have to make sure you're controlling it. So the fact that they have an ongoing regurgitation is that not enough to suggest that they are still reflecting, and therefore you don't eat objective testing. So that's a That's a really interesting question. Um, potentially. Yes, and I would make an argument that you have enough evidence without a 24 hour ph impedance test here. Toe. Have your surgeon for example, do a high it'll hernia repair with fund implication. Once you get the Manama tree, Aziz for the a c g gridlock guidelines to determine whether or not they're sufficient Paracelsus, for example, to do in this and fund implication versus a partial fund implication. But in this particular case, um, in terms of evaluating the patient because surgical consultation is not an option here, the pH impedance testing is the best answer. Bury any additional comments on that? Well, I agree, although one you have to certainly do Manama tree before the impedance testing. And also you could make an argument that if the patient said they don't want to be on pp I therapy and they're esophagitis is better then to do Manama tree if you're considering surgery because you already have documentation, so really depends on the discussion with the patient, whether they want to continue on medical therapy or not. Got it. I think here you the question is, what's the next best step in evaluation and not treatment, Which is why the pH impedance testing is a little better. But of course, thanks to me. Oh, there's always wiggle room in here. Correct. Barry and Mike, I have a quick question on this. So when you do the Ph impedance on P p, I is one possibility the person has fully treated acid reflux but is now having asked non acid reflux. Yeah, that's right. That's right. And the and the non. The beauty of that is that the Ph impedance testing, unlike the wireless pH Met tree, gives you the opportunity to evaluate weakly acidic and non acidic reflux. And so, by doing this, the right answer for these patients who have partial or complete symptom relief and you're evaluating their good to see if it's controlled is always 24 hour Ph. Impedance testing a not wireless pH Met tree, which should always be done off PP I on again that was in the lecture that that's pre recorded for you. So, Michael, you're trying to see if the reflux it is acidic or not. I guess that's the crux off the question here, right, because the regurgitating so you know you're going to catch some reflux there by the impedance test. So you're just trying to find out if it's acidic or not to see if you should maximize your P P I therapy before you would consider any surgical intervention. E think the most important thing is to go back to the lectures that you have access to and you have access to them through April of 2021. Uh, there's really amazing minutia in there about what? To deal with our patients who have refractory reflux. Those who have atypical symptoms regurgitation LPR type symptoms. How to understand what a Manama tree. What a pH study is telling you thes are incredibly valuable clinical information, not just for your practice, but yes, of course, you need to know them because they're gonna show up on the boards, and they're not gonna be straight up good questions. As you have seen, uh, you're really gonna have to understand the data that the reef that the questions them is presenting to you and understanding what they're asking of you in the question. What is the next best step in management for this particulary patient who has these criteria, whatever it may be, um, so perhaps we can we can move on from from gird on. Maybe Pascal can pull up the next question. Or unless again, there's this Q and a box on the bottom of your zoom. We would love Thio here from from you guys from the attendees. If you have any questions or concerns, this is why we are doing this. Uh, this is why we're crashing. Zoom inside and out to hear your question. So if you have anything, please please please ask us so we can answer them. But otherwise, in the meantime, Pascal, if you can let's pull up the next, uh, question or two I 37 year old man with the past medical history of long standing heartburn was one scene Your office, His peopIe I therapy was recently increased from once a day to twice today and h two blockers were added at bedtime. He denies other symptoms. He's been adherent to his good diet, is considering coming off of medications and is considering surgical options and e g. D. Shows a small hate, a hernia and normal dis philosophic Joe biopsies wireless ph study off medication percent time with pH. Less than four was 8% and a Dimitra score of 22. What should be done prior to innocents fund application in this patient? Barry. Yes, the nice thing about this question that easier than the other ones because they're telling you they want a Nissen fund. A publication to be performed on the question comes up. What do you do beforehand? And when a page kitchen has abnormal pH study of eight and a maester is greater than 14.7, give or take, so you clearly have abnormal reflux off medications. You want to know how the Paras topic function is because that's going to guide the surgery. Many surgeons, they're going to say, Uh oh, Mike and myself and whoever does Manama tree. Can I do a full wrap? Can I do it to pay? Do I have to be careful about post op this Asia? It's really a high resolution Manama tree in my mind would be the answer. C T scan of the chest and abdomen really wouldn't have much to do unless you thought the patient had a coll Asia with prosciutto. A Coll Asia Change of P P. I time after after meals, we all know it should be given prior to the meal, so it's unlikely that that's gonna help. Repeat E g. D and dilation of the esophagus. Uh, there's no evidence that the patient has a structure of this Basia and flew ticket zone, as we all know, is used more for you than for reflux. Um, any additions, Mike, that you think? No, I agree. I think this is right in the guidelines now from the American College of Gastroenterology Before you do anti reflux surgery. Given that it's much more widely available than it was just a decade or two ago. High resolution Manama tree is a must do before you spend somebody thio anti reflect surgery and perfect. And I think the important point there is that is there enough contraction of the esophagus to overcome the increased resistance at the L. A s from some sort of wrap. So, um, you know, interestingly things that I think we don't learn about as much as gastroenterologist, but as you is, you start to practice more. You see these things? There are different types of fund implications and, you know, the surgeon could tailor the tightness or the style of fund application based on how much contract Il Ity reserve is left in the esophagus. Eso certainly in a very important thing to do. Prior Thio fundo Great. Uh next question. A 65 year old woman with a past medical history of rain notes syndrome, scleroderma complaints of just Asia Barium swallow demonstrates a dilated, fluid filled esophagus and high resolution Manama tree is ordered. What are the most likely findings on this Manama tree study? Uh, Mike, uh, when I take a shot at this, sure, I think this really that, you know, it's funny. It's it's the it was. It's set in a much more simple way on the medicine boards because you have to determine, uh that you know the difference between a Coll Asia and scleroderma like esophagus. And I think here you've got a very This is just the G. I boards version of it right. You need to recognize the similar what's similar and what's different between those two major motility disorder Mana Metric diagnoses, right? In both, um uh, Ankle Asia And in scleroderma like esophagus, you have no ordered parastatals, presidents and a parasol tick esophagus. Um, it could take three different forms and high resolution Manama tree. But in none of them do you have effective Paracelsus. And in scleroderma, like esophagus, there is an absence of any kind of parasol, tick or even non parasol Tick appearing wave. It's just a blank section in the tubular esophagus on bond. The key. The key difference between those two conditions is what's going on at the lower esophageal sphincter, right? In this case, the I R p r integrated. Relax, ation pressure is what you have to know about in a coll Asia. There's a failure of the L. E s to relax. That means there's, ah high I AARP in scleroderma like esophagus. There is absence of El es tone in addition to absence of parasol PSA. So there is a low i r p. So in this patient, where with the autoimmune history of Ray nodes in scleroderma on their this there's this Asian. There's a lack of tone on the Asafa Graham. You're expecting a low I R p and ABS and contract il ity consistent with scleroderma like esophagus. So the only choice here would be e um, Barry, Can you help us understand a little bit about I. R P. You know, Remember, we used to talk about, like, residual el es pressures and things like that. And so this is sort of a bit of an update to that old, you know, description. Mike would also agree the Chicago classifications really highlights each one of these. Uh, I r P is Relax, ation. We used to say percentage of it. The l es relaxed 50%. It was normal. Now we use not necessarily absolute value, but the number 15 millimeters of mercury as a porter line of up. So if you look at right here Hi, I r p me dysfunctional obstruction at the G junction. Premature contractions, when looking at was called the dlr distal agency would put you at some spasm in a way or likewise, you have premature contractions, so this automatically puts you to some type of spasm. Hi. Might end up being that you end up with what's called the type three a collage or spastic here when you have a normal, uh, I R P, which is different than the l es. It relaxes fine and hyper contract ability. You have to think of whether it's called Jack Camera or Nutcracker. So these really are basically the same terms for different terminology in Chicago classifications. And on my lecture, I suggest that everyone really almost memorized Chicago classification because if you have that, you'll have most of the answers. As mentioned by Mike. It will say, I've been taking my boards. I think about a a year ago. My research, at least the re certification exams give you access to up to date A. Za. Long as you understand how to navigate that Chicago classifications table, understand what the different categories are after? Memorize it all. But if you know how to use it, then knowing where to look it up on the boards, you could navigate these questions really, really well. It's really important to note that that you know Chicago classifications. It's on version 3.4 point Oh, is probably coming out end of this year, probably beginning of next year on gets a bit and evolution. So a lot of the times some of them were subtle diagnoses that you have to work your way quite a ways down the Chicago classification to get to are probably less likely to be are less likely to be shown on here. But if you you know, there's no doubt a Coll Asia versus Scleroderma is gonna be a question for you. It's just the form it takes is gonna be different. But Manama tree has come into the fold now. So understanding how to interpret a Manama tree study and what these key parameters mean is really crucial, right? All right, next question. All right, you're thinking 25 25 year old woman with past medical history of migraines and several upper respiratory infections in the last three years requiring antibiotics. She was sent to your office for newly diagnosed with the disease. She was told to start a gluten free diet and to see you for further management reviewing her records, you find the following. There's a five month history of diarrhea, stool studies or negative not taking any medication at this time. Well, I'm sure a positive I g eight and take laden a negative ttg and a positive h l a g q two e g d with small bowel biopsies were taken a shown on the left. Um, Lexie, can you kind of walk us through the biopsy findings. Um, yeah, it's a little bit, um, it's always a little bit subjective to determine whether the villas there is blunted or not, I would say it's a little bit more fat than normal and a little bit shorter, even though the tip of it, as you can see, falls over more specific for this kind of discussion. Here is actually the fact that if you see if you take a closer look to the feeling that the very surface at the very top of the slide, there's ton of these little blue dots. Those represent the nuclear of lymphocytes and there's many more than there should be. There should really be no more than one off those round blue dots or lymphocytes per five enter sites. And if you if you look closer in that and it probably would give you maybe an insight as well to highlight that there's many more than there should be. So we're talking about intrepid stealing the potatoes. Is there that, um, definitely increase more than normal? And I would say that there's a little bit of a disruption in the architectural that Phyllis it should be a little bit taller and thinner, and it's a little bit shorter and blunter, so there's also a little bit of architectural distortion as well. Um, the interview film for psychosis has a pretty broad differential, but coupled with the history and the the mild architectural distortion blunting that we see in the village, I would say that the physiologic findings are consistent with silly activity. Pascal, can you add some more to this? What are your thoughts? So? So The one thing that the questions them seemed to highlight was the fact that this patient had upper respiratory infections in the last three years, and so, coupled with the diarrhea respiratory infections, you have to consider other things within the differential. Namely, what they're leading to is a common variable immune deficiency or C v I d. Should be entertained. Um, just wanted to point out that they made a point that, yes, there's intra epithelial lymphocyte. Assis is obviously some villas, actually, that they were trying to point out, but also a positive e of plasma cells in Lebanon. Yeah, now again, I took my boards a couple years ago, too, but looking at this closely and thinking of the question stem. Um, that is not consistent with celiac when you're not finding when you're finding that there is Ah, what they described here is a possibility of these plasma cells. Um, taking that into account, we see that there's some discordance between the anti Glidden antibody and the TTG once positive and one negative. And we know that from the talk that lead and has less sensitivity and less specificity. And so if we have to think that this may be a false positive here in this patient and that the negative t t you get a diagnosis of Syria, Um, with that being said, um, looking at the questions and this patient obviously is already on a gluten diet gluten free diet. Rather so referring to a dietitian, would it make sense here? Checking and and unusual antibody tighter. What? We already have the best test here. A ttg So repeating that again. Would it make sense here, um, and said Use can come with. Obviously there's there could be like an answer to do vcenter apathy, but it wouldn't explain the complete clinical scenario, especially when they're highlighting this upper respiratory infection and HIV, you know the path here doesn't It is not consistent with that. And in the clinical history. So they're really leaving you towards C, which is the checking immunoglobulin levels. And in patients with C V I. D. Uh, they're going to have low i G i g m and G A on. So they really wanted to thio to look at other diagnosis other than celiac here and and knowing that there could be some overlap between this and other types of ideologies that could also cause it interrupt with Olympus psychosis. Do you think that would really ask you to identify this as a positive plasma cells? I mean, it's a very low power. They won't. They wouldn't. I think the whole point here is that if you're not, I mean for me, I'm looking at the path, and when you're on the boards and you any questions and you I mean, you look at it to see if there's obvious things. You got to see obvious blue things there like you were saying the the lymphocytes. But, you know, I would be looking at it closely for lack of plasma cells. I think they were trying to lead you towards, um, the main clue here was the upper respiratory infections that were three years that in the overlapping, um, diarrhoeal illness. And what about the age of the patient? What about it? Um, are they e guess they're still in the in the, um, age appropriate for silly idea. Yeah, they can. And you can actually have patients who are diagnosed with celiac, you know, in their in their sixties as well. So there is Obviously, it could be mostly a disease diagnosed. And younger adults, obviously in Children. Um, but you can see older adults with celiac disease as well. We call those latent, um, celiac. Silly hackers. Yeah. I mean, I like this goes to the point I think you're making When you first discuss the path is that there is a differential on all of these findings. Are there certain features of this that what would be more conclusive for celiac based on the biopsies? Because another is different marsh classifications. And would you consider this sort of just, like, suggestive of celiac arm or diagnostic? Um, well, again, I mean, it's low power, so I can't see the absence of plasma cells, but that's something that you should look for, So I'm guessing that if they show. And then he said, I don't know if they would ask you guys to identify the lack of plasma cells, but if they showed you in instead of the lamb inappropriate that would that would. That would probably what they'll be, what they would be going for. Um, so yeah, I guess back to the point is that there is a broad differential for interpret killer lymphocyte. Oh, so that includes things like See, the I. D. Of course, as well as select is, of course, other immune disorders. H. Pylori infections. Some medications like and says so. That list is very long, Andi, I guess that's part of what the question is getting at. What are the other causes of interpreting photosynthesis? Um e mean? I think if they want maybe to show a classic see like they would show something a little bit more flatter. And already I was. I was saying that this vote is not as flat as a Zaken get in select disease or fully fully expressed Cilic disease. It already is. You know, it's still it's still president still there, So it's If anything, it's only mildly, um, blunted. Andi that raise again. The differential of interpreting for us, it was a very long one. All right, again, for the absence of plasma cells, I don't know if they would actually show you an inset off. It does look a little bit empty in retrospect, but, I mean, the recognition of the the the absence of plasma cells would have required an inset of higher magnification to see that all the cells in the lab inappropriate lymphocytes rather than plasma cells. And I don't know if that's something that would have been appropriate for you actually to ask e think there'd be a lot to ask for us on the boards. Questions from the audience is, uh, Pascal would be common for patients with C C V i d. To have a positive G a glade antibody level. So if they have like a concurrent illness, it could cause a false positive. But again, um, usually, that's why you would double check it to make sure that it's low, Um, all around in terms of gm. Perfect. Um on. Then is there another question? Uh, Pascal, um, this is the last one of the slide set up on the slide said Okay, great. Um, a couple of questions. Just ask other members of the panel here that are more clinical. So Myrna and yeah, we and I think it's something that's been evolving a little bit. It seems like the PP I re category may have changed. Can you comment on that a little bit? Yes, indeed. So as much as we try to push the p p i r e as an entity for a few years now, we are doing exactly the reverse. We're trying to eliminate it from everyone's mind. What happened is you had these patients that, um, had symptoms similar to e findings on endoscopy and biopsy similar to E and, uh, they. But they responded to high dose of P p. I so peopie I twice a day, and the question became, Why are they responding? Could they have been severe reflux? That's mimicking a uh, but they really didn't meet the reflux criteria. So they were classified in this gray zone off PPR responsive Santa Geo Yoshino Philia. That's what p. P. R. E stands for. Aziz. You can tell from the spelling of it It's just a descriptive term. So it was These patients were in the gray Zone because they were responding to P. P I. And then more studies were found, uh, some of them clinical and some of them lab based or research based, um, when patients were responding to a p p I and they decided to come off the P p I and go on a diet that is specific for you, even they were responding to that as well. And then from a research standpoint, when several groups took some of these cells, uh, self jail cells and culture them, uh, in the lab in the presence of allergic side kinds. And, um, they added the PP I so here you don't have the acidity involved at all because it's literally in a Petri dish. What happened is you aggregated the secretion of the attacks and three, which is an important molecule that is important for us and fill recruitment survival. So then we could see that there was an effect of the P p I on these patients and eso and that, along with several other small, um, clinical, is well as research studies. Then I think as AH group of international e physicians and researchers. We put out a new guidelines that were published at the end of 2000, uh, 18, where we decided this is it. There's no p p r e thes thes are patients who have you e but they are responding to hide those peopie i, but a mechanism that we really still are all looking into Thio to figure it out. In the meantime, from a clinical standpoint, who cares if they respond to a P p I and they're doing great clinically as well as in this comically and histological E, then that's their treatment. It may be safer than an experimental, um, those of a topical steroid or a diet that the patient may not be interested. Thio end Tony, I like to ask you then, to follow up on that, you know? See, we all see plenty of patients with just asia. Um, you know, is your approach. Would you often like a young patient, that alarm systems, which you just drop them on the PPE empirically? Are you now kind of moving right to endoscopy to sort of further establish the diagnosis? Sort of. What's your approach well in the old days, we used to start them on PPR and see what happens, because this is how we all learned it. But I think what happens is that now you're going to miss Those peopIe are responsive patients, So if you have a young patient with this if Asia there's really no heartburn. There's a history potentially of food imp action. Um, and there's some history of 80 p that's almost classical, your patient. So in that case, it's better to scope them initially. And no, Do they have E o E or not? Before you give them a P P I because another reason to do that is the PPR response is about 50%. So it's not small. And while you may say well, if they respond to a PP I if it's reflux or yo, I may not care now, but on the long run, you're deciding what to do with their PP I they come back to you and say, What do I do now with the high dose? Can I go down to a lower dose? Can I stop the PPE? And of course this management is a little bit different for a patient with the O. E than a patient with guards. Mhm. That's definitely a dramatic change. You know, the way I practice for a while and I'm curious to hear what other people in the panel do is I often with started PP I there weren't any alarms and it was so obvious. Slam dunk triggers for like that makes you think you we and then if the endoscopy is normal, you sort of call it GERD. Um, you know, Barry, Mike, Tony any other? What are your thoughts on this? Or have you adopted this new guideline or new approach? I think you have to think about the presentation of the patient. And, uh, you know, if the patient presents with the food impact Shin and you go in there Andi, there's a really nasty imp action. You're not excited about taking biopsies at that time, or your colleague takes something out in the middle of the night and is not in the SAF Ecologist or has not participated in this board review course. Um, that, you know, at that point you may not wanna wait and bring them back and go through the time delay. There because they may impact again. You know, dysplasia is one thing, and if you get them in relatively quickly for the scope, it's there. But if there's an acuity of the situation and you're trying to calm things down quickly to minimize a really adverse outcome, you know that that may be a time that you have to sort of buck the system and go with the PP I first. But I wouldn't I would agree that if you're able to get the men in a timely fashion and do the buyout, do the biopsies off PPE. That's really helpful just to get yourself a baseline. And you know, even if you do end up in this scenario, where you really stuck and you have to treat them. So um, in that, like in the case that you mentioned Michael, I think it's important that you follow them over a period of time and see what they do and what kind of symptoms they have, because you don't want to keep them on a high dose. B P I for too long. Eventually, you want to go down to once a day and see if they respond about 70% of the PPR. Responsive patients will also do well on a low dose after being on a high dose twice a day, PP I so eventually it's good to monitor when you even when they come off the PP, whether they do it on their own or whether you try them off because you're not sure what the diagnosis is and you're not sure what to commit them to on the long run. That's when it's really important that this is when I face many of the patients where, um, they've had the treatment and now they're not sure what to do. And then we deal with it on to diagnose it eventually. In retrospect, which is not a big deal if the patient has been under control all this time. Uh, Tony, any any thoughts like, how are you approaching, you know, sort of young patients without an obvious Yui background or history, Um, to me, it's really still the guy go by. Our upper endorsed BCG guidelines, which is the key to me is dysplasia. Uh, we see tons of people in private practice, young people that have reflux disease, and then in my mind, there's no reason Thio scope them all unless they don't respond to a PP I but one. Somebody has this aphasia. Then you have to raise that Congress you know, concerned about whether you we you know, especially in a young man, Benjamin dysplasia Ah, yeah. I think that, you know, the two reason I do is I want diagnostic certainty in that car. And I also want to get an idea of how if there is any structural damage to the esophagus. So I always tell these patients I'd rather know that you have this now than learn about this at four in the morning and emergency room when you've got a food imp action. Yeah, that makes sense. So if you could get them in a timely fashion that you're not even starting on the T p I a follow up question, let's say that you have diagnosed a patient with you. We you select your therapy of choice, whatever that may be. P p I who destiny died or some sort of elimination diet, and they feel better. Um, in the age of IBD, where we're all about mucosal healing and that's our target. Um, is that where we're headed with e o e. Should we be doing a follow up endoscopy at some point Time to confirm that those s NFL's are gone? Or is this the clip the target of I'm feeling better. Is that enough for us to just manage them clinically? Well, I think we did not go through this dilemma that waas that the IBD I experts went through Where, um do we now look at the mucosa? I think what happens is that from the get go, everybody followed up you e clinically endoscopic lee and histological E. And I think that this will most likely still be the case, since in many patients and the younger the patient, the more you see this that there's sometimes disconnect between symptoms and histology and eso patients will feel better. And, um, a a lot of times it's not that obvious as to are the really better ah, 100 percent or they kind of half way better If they're having intermittent food infections, for example, well, and they've adapted to a little bit of this facia the so we What we do is we look and see if the U. S and Ophelia is gone Now you might argue. Why would you want to do that? What's the big deal? Um, the persistent yes, and Ophelia is so far based on research potentially associated with fiber cinematic disease. So yes, NFL's do release the, uh, many fiber optic molecules under Granules, and that could contribute thio potential structuring or this motility so or narrowing of the esophagus. So that's why we try to chase the Santa Julia Soon Ophelia as well as the symptoms. Also, I'd like to comment on the previous question Is that you know, if you had a patient with this Asia, it's an a straightforward, um, scenario where you would be more likely going for an endoscopy before you initiate treatment. But I'd like to draw the attention of the attendees here to the patients with persistent heartburn, despite PP I therapy. I know for the boards. I don't know if they're now starting to incorporate yo you when they list potential reasons for that. But yeah, we should be considered, you know, persistent heartburn, despite PP, a therapy. Uh, you have to think you're in the right clinical context, especially it is more common in women to present that way than in men. It's more common to present that way with African Americans than in white um, Caucasians. So this is the category that 15% of patients with the that that are more likely to be missed. So we always used this fake Asia, and we're doing a great job diagnosing these patients. But I we should think about the heartburn patients. Persistent heartburn. I want to ask one last question before we end up end here to Tony If you can comment a little bit on drug regimens for H pylori, Um, in that, you know, we used a lot of people and still use the sort of, you know, press pack. You know, Let's hope resolve box of Silin. You know, p p I, um type regimen. Um, is there a general shift to move towards a four drug regimen up first line because they send them, So you conflicting guidance? Well, when I think you look at the three major criteria that guidelines have been published, the Toronto Concessions the A C G contentious consensus. Excuse me in the masterplan from Europe, they're all recommending forward drug regimens, meaning three antibiotics plus P p. I for 14 days rather than seven. Um, and I said before the major driver of this is, of course, drug resistance clothes or mice and resistance being so prevalent and having such a bad effect on the outcome of H. Pylori eradication. And really, you wanna have your best regimen first? Because if you start treating within effective doses than you're less likely to be successful with alternative regimens down the road, um, the So I. I am a big believer that we should be doing for drug regimens. The only reason I my mind not to do a three drug regimen if you happen to know for some reason which no one does, that you're in an area of low closer mice and resistance. But that data is like I said, not available. And we have to assume that you're in an area. Put surmising resistance in the United States, and it's based upon the sparse data that we have. And, um, you know, the only other argument you can make is patient tolerance, and I think it's just who's you to make a major effort when you sit down with the four drug regimen to sit down with the patient and go through. Specifically, I give them pre written instructions. It's an office is a just to discuss the treatment. I don't do that over the phone. I find that increases the compliance level. Sure. Do you have a couple of like I go to regimen you tend to use or do you try to base it on recent antibiotic use and other historical factors? Yeah, I think we can antibiotic use as important. I think, in the slide of my talk, we showed how in the Korean study that just having history of private college, um, is in, uh, use in the past couple of years reduced the likelihood of success of a three drug regimen. Clever myson, based by about increased by about 100% chance that you're gonna fail for about 15% to about a 30% failure rate. Um, and then, really, I think the standard these days unless your patients a pan allergic is to go with the amoxicillin Metron Aysel Clue horizon combination, if only for the fact that it's very hard to get touch. Recycling is not routinely available unless you have one of the pre op, you know, like the the pile, Eric one. It can also be hard to get. There is some data to say that doxycycline is equivalent tetracycline, and so if you can't have it, you go that regimen. But that's probably what ways me in the favor of doing the amoxicillin cloth or my son regimen before the business one. So after the antibiotic regimen, when they get C diff, we'll talk to Ari at a future webinar about fecal microbial transplants. So I want to thank all of our Panelists and and thank all of our attendees for joining us. Sorry for the little technical glitch we got booted by by the zoom gods, I think partly because they didn't like Mike's answer to the question, but who knows? But anyway, thank you all for joining us. We have our next webinar believe in a week and just keep an eye on your emails and take a look at our website where all of our videos were posted online. Thanks again
