Before we move on to any further talks, we actually have time for our Q&A scheduled next. We have several excellent questions that have come up in the in the Q&A here. So I believe Cyril, you've already identified a couple that you wanted to address live. We can start with some of those. If you want me to start, I can start off. First one on the list, when would you recommend performing PH Bravo testing? Would it be after failing twice daily PPI therapy for four to six weeks? I mean, there's a lot of ways to go about doing that. You can certainly have them stop the PPI and see if they do have reflux before even starting them on the trial. Starting them on a PPI trial is not wrong either. So if they don't respond to twice daily PPI, it's a good idea to take them off, do EGT with Bravo and see what is going on. Alternatively, we can put a PH catheter down there to see if their current symptoms are really reflux, non-acid reflux, or whether we see symptom coordination-wise. Kind of in association with that question, does a patient need an EGT or a PH study before making an official diagnosis of GERD? Are clinical symptoms, daily or frequent symptoms, enough to make that diagnosis? I think it's enough. I mean, if they don't have any alarm symptoms, I think it's okay to start them on a PPI trial if they have typical symptoms. We can't ideally do endoscopy. It's not a good way to diagnose or not diagnose parents unless, obviously, they have right COD, esophagitis, or lung segment burns. Then you can make the diagnosis of GERD. Yes. Yes. Good. It's got to be pretty severe to pick it up on an endoscopy, right? Yeah. Yeah. You're basically looking for those complications of GERD to make that diagnosis. Exactly. Yeah. It's a good way to put it to me. Another question dealing with PPI therapy. What would you recommend for patients who have osteoporosis and severe GERD symptoms who are resistant to the idea of going on PPI therapy? Yeah. That's a hot topic. I think the study's coming out of Canada. I don't know if they show really much increase in bone fracture risk, but most of these patients have some bone fracture risk, but most of these patients are so set because of what they read. I often tell them there might be an association between PPI and these things, but not direct cause and effect. Most of the study was done, and looking back, those patients could have been sicker, had more heart disease, and diabetes, and just happened to be in a PPI. We can't really truly say. On the flip side, the risk of esophagitis and peritsis, that's what we worry about. That's how I sell it to my patients. When you have that discussion with them, what triggers you to bring in, for example, endoluminal antireflux therapies that might be available, et cetera? Yeah. We talk about that and talk about the potential side effects of the antireflux surgery. It's basically a good discussion to have about really what's the lesser of the evils here, and PPIs tend to be bad if you look at all the potential side effects. Speaking of which, do you run into payment-related issues? I guess I should say coverage issues are getting blocked from coverage when you seek those endoluminal antireflux procedures? There are. I rarely send people for antireflux surgery unless they have a parasubdual hernia, they have obstructive symptoms, but for some of the newer ones, we do run into some insurance issues covering that. There's always that tough side of it, right, where what gets done is what gets paid for, let's be honest. That dovetails with talking about all the plethora of those biologicals that are out there. You saw the list. It's unreal how many different ones there are for IBD. So many times the answer is, well, what's actually available to any given patient is what's covered. Yes, unfortunately, there is sometimes a limitation there. Going back to, I guess, patients more with maybe milder symptoms or infrequent symptoms, do you have a threshold for when you decide to recommend daily PPI therapy as opposed to just on-demand therapy? Yeah, that's a great question. I don't know if I have a specific reason to use one or the other. I generally use H2 blockers for breakthrough nighttime symptoms rather than kind of twice a day or once a day. I just find it works better for nighttime symptoms. I tend to go to PPI low dose in the morning and see if that works if they don't have any alarm symptoms. Let me ask you a question about that. I mean, physiologically or pharmacodynamically speaking, does it make sense to use PPIs for sort of as-needed therapy? Doesn't that stuff take a few hours to take effect? And H2RAs are quicker, right? Quicker, right. It generally takes a few weeks to be in your system. Like you said, H2 blockers are quicker. What is your experience with the new PCAB, Vaquenza? Sorry, Vaquenza. Yeah, that's a great question. I have a lot of difficulty getting it covered. So I probably have two patients on that. It's a coverage issue for me for now. I mean, it's promising, especially healing esophagitis. It's a once a day dosing. And it's not so picky towards a meal. But hopefully with time, it will become more available. So taking it with or without meals kind of is less of an issue than with the traditional PPIs. In the meantime, when we're having patients that are not responding well to PPIs, do you try to change to alternative PPIs? What's your approach there? And do you have any guidance that we may use in terms of PPI efficacy when you have a patient that's not responding? Yeah, I think one change is okay. I generally start with omeprazole. And then I will go up to esomeprazole. But really, if they have breakthrough symptoms on twice a day therapy, I would wonder, is there something else going on? Makes me think about doing a PhD in a study on therapy. You talk a lot, Sorrel, about the bioavailability deltas between the different PPIs and it being important to consider which ones to try next and so forth. Yeah. And I can share this. There's a nice graph on a paper that talks about the PPI equivalency. So for example, if you take pentoprazole 20 milligrams, it's only about 4.5 milligrams of omeprazole equivalent. And I can share that. I rarely use pentoprazole. I generally start with omeprazole, then move on to esomeprazole. Then it really becomes a coverage issue whether we use dexamethasone or the new PCAP. Yeah, that resource that you mentioned, we've found to be really an excellent source to help us guide when we're changing our, if we have to change PPI therapy. So I follow the same general rule. I start with omeprazole. If that's ineffective, try to move up to esomeprazole. I rarely use pentoprazole except for the patients that are discharged from the hospital, because that's what's on formulary at the hospital. And so those patients are usually discharged on pentoprazole if they need ongoing PPI therapy. But I have the same experience as you do. Shifting a little bit more towards the Barrett's esophagus, there are a few questions here on Barrett's. Have you encountered some challenges, any challenges with Barrett's esophagus with regards to the intricacies of histologic interpretation? Do you have any scoring symptoms or anything to guide interpretation and then subsequent surveillance? Yeah, I think the big question in my mind is, is this truly Barrett's or not? And is it about a centimeter above the G-junction or not? And does the biopsy show intestinal aplasia? I mean, I would probably ask for a referral for a second opinion if there's any question or an expert pathologist or a second pathologist to look at the biopsy slides to see if it's truly Barrett's. I oftentimes see referrals for a second opinion regarding Barrett's. It's really hard to undo that diagnosis once it's done. Yeah, I think the understanding the definition and understanding the nuances of the definition as they are in the American societies compared to maybe some international societies, the requirement for that one centimeter length of salmon-colored mucosa and both endoscopic and histologic diagnoses, characteristics to make the diagnosis. What's your experience? Do you have any experience using TissueCypher? Yeah, I've actually been using TissueCypher a lot. So, it's a company that, you know, we sent the slides to them. It takes about a month to get out there. And they give you a risk score of the progression to high-grade or cancer in five years. So, it's a low or higher risk score. It helps me in, especially on folks that want to come back three years or shorter with a short segment of Barrett. It helps tends to calm them down and say, well, here's your risk of getting high-grade or cancer in five years. And I've seen most of them come back so far as 0.3%, 0.5%. I've not seen a high-grade. How do they do this? Is this AI driven? Yeah, I believe it's all AI driven. Yeah. And what does it cost? I don't think there's any cost for the patients as far as I know. I think the company is covering that. I hope that will play out in the future. I'm not sure. Yeah, it's interesting. So, that's my understanding as well that the insurance or that the company is covering the cost and it's all AI driven. But we have started to utilize it much more frequently here in the last year or so for our patients as well. Let's see. There was another question here about tobacco use or history of tobacco use as a risk factor for Barrett's. Would you like to address that? Yeah. I mean, I would always think about your nicotine relaxing the sphincter. Could there be increased risk of esophagitis in Barrett's? Do we know it causes Barrett's? I don't think so. Is there a risk of Barrett's progression? I think there probably is with tobacco use. We worry more about, you know, squamous cancer of the esophagus in tobacco use. That's kind of my take if you... Yeah. Yeah. I think it's evidently clear that there is an association. I don't think anybody's implying cause and effect and it probably is multifactorial. There really aren't too many things where tobacco helps. And I think it's becoming clear that this is one where it not only doesn't help, but it hurts. And that's not surprising. Do you counsel these patients on tobacco cessation or at least encourage it? Or do you not mention it at all? What do you do? It's actually, it's part of kind of pre-ordering when they see us if there's a tobacco history, they order the negative teen dependence clinic here. Now, if everybody follows up, I don't know or think so. But that's pretty aggressive compared to, you know, days of yore. Sure. I mean, I think it's becoming increasingly recognized that it's an important service to the patients to try to help them with some of these more extraneous yet controllable factors that contribute to disease and progression and severity and so forth. Absolutely. We do have some questions with regards to dysphagia. So we'll move on to some of those as well. What are some key questions or physical exam findings you try to use to differentiate oropharyngeal dysphagia from esophageal dysphagia? I just, you know, basic question for me to ask, and do we have trouble with actually when you can chew the food and you have trouble moving it out of your mouth into your esophagus, a simple basic question, especially in the allergy. Nasal regurgitation is things I look for, coughing, choking. Physical exam is really not much other than looking at tongue movement or maybe uvula. But physical exam is not very helpful in dysphagia, but that's what I look for anyway. And with oropharyngeal, which we can also call transfer dysphagia because it's dysphagia related to transferring the oral bolus into the esophagus, right? If there is malfunction of that type, then there are symptoms related, often symptoms related to aspiration resulting from that, right? So you would ask about coughing when they're eating or swallowing, right? Yeah. Yeah. While we're on the topic of oropharyngeal dysphagia, one question here is that, can CVA patients develop achalasia? And we know CVA patients are at risk of oropharyngeal dysphagia. Do you see any association for achalasia with CVA? I have not. Yeah, I think they're unrelated. That's not to say that just because you had a stroke, you can't get achalasia. I mean, they're different and you can certainly get them, but there's no association or relatedness between the two that I am aware of. Great. One question with regards to interpreting esophagrams. So I see a lot of tertiary wave contractions in addition to dysmotility noted on esophagram. Should that lead one to pursue a manometry exam and are there any specific treatment recommendations? Yeah, that's a great question. We oftentimes see that on esophagram. It really depends on how, if they have symptoms. If they have, you know, solid and liquid dysphagia, I would pursue a manometry. If they don't, then I would not do anything in my practice. I think it's very, and the radiologists calling tertiary contractions, I think it's very idiosyncratic, right? I mean, some radiologists call it more frequently than others. And I think the bottom line is the sensitivity and specificity of barium esophagograms, which are very subjectively read tests. You know, the sensitivity and specificity is not high. That's not the reason that we get those studies. And so I think we treat the patient, not the radiogram, just like we treat the patient, not the blood work when push comes to shove, yeah. And I'd also have to ask why that barium esophagogram was obtained. If all that's found is tertiary contractions and nothing else is seen, I'd want to know what the clinical symptoms were that elicited that study. That would also play a role in where we would move next. Yes, definitely. We do have a few more questions going back to PPI therapy. I'll try a clinical scenario here. We have a patient who's being treated for H. pylori infection. We've stopped the PPI after two weeks and put the patient on an H2 blocker. And we're planning to wait four weeks after treatment, so with the bismuth for retesting for H. pylori. But what if the patient still has significant GERD symptoms? Is it safe to restart the PPI? Should we leave them on the H2 blocker? How does that affect our subsequent testing, our follow-up testing for H. pylori? You want to take that one? Yeah, and I'd appreciate your thoughts on it too, because I think there isn't a right or wrong about this. I think the way I would manage it is, yeah, I mean, you do need to stop the PPI for a couple of weeks to a month, a month's on the long end of things, before you retest to make sure that you've eradicated the HP regardless of the modality you're using to do that. That being said, I think whether to put the patient back on the PPI or not, largely depends on how, A, how dependent the patient is from a GERD symptomatology standpoint. Do they need the PPI in order to get rid of their GERD symptoms, or are their GERD symptoms mild enough that the H2RA that you had them on is effective? If the H2RA wasn't effective enough, well, I mean, from a pharmacotherapy standpoint, the PPIs are about the only thing that's covered by the insurance company that you're going to be able to give them. So if they want relief of symptoms and they're not getting that from the H2RA, then they either need to go back on the PPI or they'd have to have something that's treatable mechanically, such as with endoluminal therapy or surgery, right? There's only so many options available. And I think that's the options that are available and whether the patient's symptoms are severe enough to warrant going back on the PPI and meaningful enough to the patient to go back on the PPI are, I think, what drives what to do. It always, you know, to me, it always goes back to a discussion with the patient and the patients so appreciate that. They want that dialogue. They love the association with their provider and that therapeutic relationship is something I think both of us enjoy so much about the work that we do. And the patients appreciate that so much. We're not going to be replaced by AI. AI is going to be a helpful tool for us, but they're still going to want their provider. Thank goodness. We're still employed. We still have work to do. Yeah, yeah. It's great work too. Couple more questions. If a pH study shows non-acid reflux, do you recommend continuing PPI after that diagnosis? Yeah, I think so. If it treats their symptoms, I guess I would want to know how much symptoms they have off of the PPI. But like I tell my patients, right, we can give you PPI, but it's not going to prevent the stomach contents from coming up. It's just going to block the acid. So perhaps if they have significant non-acid regurgitation, especially in the setting of the hiatal hernia, obstructive symptoms, pneumonia, then I would think about referring them to be seen by a surgeon. Good point. In those patients that were stopping PPIs, how long does a rebound acid reflux effect typically last for patients? I'm not sure we have evidence for this, but I typically ask them to stop it over two weeks. Take it every other day for the first week and every third day for the second week and stop it. They can use some H2 therapy for symptoms there. But I have seen it probably a couple of weeks. And I take it you don't immediately reduce that prescription in case they need to go back on daily. I've seen some suggest that it may take as long as six weeks, but I haven't had that clinical experience. Usually it's that first two to four weeks in my experience. Great. Another Barrett's question. If a patient had, I think you might've sort of touched on this earlier, but if a patient had an original EGD that showed Barrett's and then subsequent endoscopies were negative, how would you recommend surveillance thereafter? Yeah, like I said earlier, it's hard to undo this original diagnosis for Barrett's. I think we're stuck. I mean, potentially refer them for a second opinion to really see if they Barrett's, if they have Barrett's. But once you make that diagnosis, it's really hard to undo for patients. They are, it's, so it's difficult. Not a great answer for that, but. That's true of so many diseases, isn't it? I mean, you know, if you did a breast biopsy and it was positive for CA and for whatever reason, somebody biopsies it again and doesn't see CA, are you not gonna treat it? I don't think so, right? I think once you have an abnormal diagnosis, you can't go back and erase that because maybe the next, the second time when it was not positive, you just didn't get a bullseye. You know, you biopsied a different area. That doesn't undo the fact that the biopsy was positive the last. Yeah. I tend to follow them if they have a diagnosis with true endoscopic appearance of Barrett's and the biopsy is initially. If anything, you could always send it to a second GI expert pathologist to review that original specimen to see whether it was truly intestinal metaplasia or not. Right? Because columnar mucosa alone, that's not intestinal mucosa, does not Barrett's esophagus make. Isn't that right, Cyril? Yeah. We have a couple of minutes left, a couple of questions left. I think these are with regards to infectious esophagitis as might've been mentioned previously. Would an EGD show HPV on biopsy or culture? And as for testing for HPV, if you want to examine for that, is there any specific tests that you would suggest or recommend? Yeah, I mean, these infectious esophagitis, I mean, although they talk about them a lot, they are rarely seen in clinical practice. As regards to HPV specifically, I know there's a risk for squamous cell cancer, but would you see it on sampling the esophagus? I don't know. I can certainly research that a little bit more. CMV, I'm sure we can stain for that or culture for that. HSV, but- Yeah, I think the HPV, the association in the upper GI tract is, the known one is in the oropharynx and the hypopharynx. I don't know about the association with the body of the esophagus and in the oro and hypopharynx, that's the realm of otolaryngology and not medical GI like us. That being said, I don't think that the type of HPV that we're talking about here causes endoscopically or laryngoscopically identifiable papillomas. I think what you see is the cancer once the cancer takes a foothold, right? That's my understanding, not being an ENT person. So this isn't like going into the colon and seeing a polyp that over the years turns into a cancer. I don't think it's like that. I think it's more like an HNPCC, which is a cancer from the get-go before you see anything else visible on examination. But that's the best guess from a couple of medical GI guys that are not ear, nose, and throat surgeons. Yeah, I'm not aware of any esophageal testing for HPV specifically, or I was thinking along the lines of a squamous cell carcinoma or squamous papillomas that we might identify endoscopically, but I'm not aware of the exact association with HPV or testing for HPV. I think that concludes the esophageal questions that we had in the Q&A. We are a couple minutes early, but we were planning to take a break at three o'clock with a plan to reconvene at 3.15 for the home stretch. So I hope you all enjoy a 15-minute break.

GERD

Barrett's esophagus

PPI therapy

PH Bravo testing

TissueCypher

esophageal dysphagia