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Ian Gralnek: Ian Gralnek Hello, everyone, and welcome to episode eight of ESGE's podcast, Endoscopy Unplugged. My name is Ian Gralnek, past president of the ESGE, and I'm your host. Today's podcast is titled All Eyes on Barrett's Esophagus, Part One: Expert Tips for Diagnosis. And my guest is Dr. Roos Pouw. Gastroenterologist at the University Medical Center in Utrecht, the Netherlands. Roos has a special interest in endoscopic management of Barrett's esophagus and is the senior author of the most recent ESGE Barrett's guidelines. Welcome, Roos, to the podcast. Great to have you here.

Roos: Roos Thank you, thank you for the invite, happy to be here.

Ian Gralnek: Ian Gralnek So you know, I think everybody knows who Roos Pouw is as an expert in Barrett's esophagus and endoscopy, but I don't think we know how did you get into endoscopy and how has that become the the main focus of your clinical practice?

Roos: Roos Hmm, that's a good question. We have to go back in time. And actually I always wanted to become a surgeon because I like to be practical and bit pragmatic and hands-on. And I was doing one of my internships at a surgical GI department where there were also a lot of gastroenterology patients. And I thought this GI stuff is quite interesting because you can diagnose, you can treat, follow the patients afterwards. So it's much more the whole package. And that really appealed to me. And that's how I started doing research in Barrett’s Esophagus already at that time. And that's how I sort of rolled into endoscopy. I never left because it's a very evolving and interesting field and there's always something new to explore.

Ian Gralnek: Ian Gralnek Well, we're happy that you chose endoscopy and you're also way too nice to be a surgeon. So sorry to all my surgical friends, I'm sorry, I'm sorry, but come on, you guys know that's true. Anyhow, let let's get to this. I think for this part one, what we're gonna really focus on today, Roos, is really defining and diagnosing Barrett's esophagus. how do you define Barrett's?

Roos: Roos Yeah, I define Barrett’s in patients who have columnar epithelium of over a length of at least one centimetre and their distal oesophagus stretching from the top of their gastric folds upwards. And then confirmed by the presence of specialized intestinal metaplasia when you take biopsies. So that's the diagnosis I adhere to, ESGE adheres to.

Ian Gralnek: Ian Gralnek So and 'cause there's a little bit of difference in terms of the definitions in terms of the length, right? Between maybe the American College of Gastroenterology, the British Society, and what the European Society says. So when I was growing up there was long segment and there was short segment, and now there are people who say ultra short segment. Can you give us a little bit of guidance about all that stuff?

Roos: Roos Yeah, I can. It's sometimes a little bit confusing when you look at the length. I think what we have to keep in mind that a lot of patients have a bit of an irregular z-line, but that doesn't necessarily make it a Barrett’s. We also know that about 30 % of healthy people have focal intestinal metaplasia in their cardia. Also doesn't make them a Barrett patient, because if you call someone a Barrett patient, that might be a patient who is at increased risk of developing esophageal cancer. And then you would like stamp a lot of patients with a diagnosis that's not correct. So in the European guideline, we really defined that you need at least a centimetre of columnar epithelium. In the American guideline, they also have a reference that if it's just very short, less than a centimetre, it might still be just an irregular z-line, just inspect properly, but don't necessarily take biopsies if it looks normal. And BSG guideline, also refer now to the one centimetre minimal extent. And I think that's a good thing because otherwise, as we also know from older literature, if you would include all those patients with ultra short segments, so less than a centimetre, you probably get a lot of patients with just irregular z-line or focal IM. They are not at increased risk of any esophageal cancer. So we should really leave those patients alone.

Ian Gralnek: Ian Gralnek So so sort of long segment, short segment out the window, it's basically now if you have a tongue of salmon coloured appearing mucosa of a centimetre or greater, then you should that's a suspicion for endoscopic Barrett’s. Is that correct what I'm saying?

Roos: Roos Yeah, well, if it really extends into the esophagus, it is, yeah. And then of course you should inspect really well. We know that we're not good at differentiating gastric mucosa from Barrett’s mucosa. So you really should take your time and measure if it's indeed around a centimetre.

Ian Gralnek: Ian Gralnek So when you're inspecting, are you routinely I mean in in a patient who you have no idea whether they have Barrett’s or not, let's say, are you routinely doing these endoscopies with a clear cap to try and better visualize?

Roos: Roos No, I'm not. No, because so if I know that they have Barrett’s or they had Barrett’s and they were treated and I really want to do meticulous inspection, I have a low threshold of putting on a cap. But otherwise I always start without one because the cap also has disadvantages. You can touch the mucosa, it can bleed, takes away bit of light. And actually without a cap you can also quite nicely inspect. And if you have areas where you find it difficult to go to with your scope, or if you have an area that you want to inspect in more detail, I think it's very easy to just go back, put a cap on, and go back in. Also keeping sustainability in mind, of course, and green endoscopy.

Ian Gralnek: Ian Gralnek so something you also touched on is you talked about from the top of the gastric folds. So can you explain to our listeners how let's say in a patient who has a hiatal hernia, maybe a small hiatal hernia, how you're supposed to deflate and measure from those folds? Because sometimes that can be confusing to people.

Roos: Roos So what I usually do, so when I'm inspecting a Barrett’s, I want to measure Barrett’s, I use the Prague classification system, which is very easy. So usually I go first start cleaning the esophagus, then clean out the stomach so there's no more fluid and air there. And then make sure that you have not over-inflated the stomach, which is something you can easily do if you want to inspect well. But if you over-inflate the stomach, you may over-inflate a hernia, and then all the folds get stretched and it may appear as if the patient has Barrett’s. So usually I try to deflate the stomach, then pull back until you can clearly see the diaphragm. It's usually quite easy to find because it goes up and down with the breathing of the patient. That's your first landmark. And then from there, pull back slowly, centimetre by centimetre, and just see where. So you will see gastric folds, see where they end and where the esophagus becomes more straight. And if I'm not sure if I'm at the correct place, I play a little bit with the in- and desoufflation. And then usually you can sort of see where the folds start and when they come back, and that's then the top of the gastric folds. And then from there, you can pull back and see over how much centimetres you have columnar epithelium, in case of Barrett’s. How long that segment is circumferentially and maximally.

Ian Gralnek: Ian Gralnek So that's the Prague classification. Okay. Good. So we should be standardizing how we report that in our endoscopy report. What scope should we be using today in terms of, you know, high definition white light, et cetera, use of some type of, you know, NBI or I scan or BLI. What what should be the standard today?

Roos: Roos I think the standard should be a diagnostic scope with high definition white light endoscopy. And nowadays they all have some sort of virtual chromoendoscopy, either narrow band imaging or blue light or eye scan. And I also prefer a scope with a water jet because cleaning is very relevant. Just get rid of the saliva and any mucus. Then you can inspect properly. think sometimes you have to wait for diagnostic scope and you settle for a therapeutic one, for example. But there is really a difference or an older version of a scope. But then if you're using high definition wide light scopes, it really improves your visualization. The lighting is better. The view of the mucosa is better. And if then there is an area that you would like to inspect in more detail and you can switch to virtual chromo to inspect the mucosal pattern, vascular pattern, it gives you so much more information. And inspection really is key, I think, when you're looking at Barrett’s and looking for neoplasia.

Ian Gralnek: Ian Gralnek Are you using some simethicone to clean the esophagus when you're using your water jet? Do you add anything?

Roos: Roos Yeah, yeah, that's an excellent point. think we always give the patient some simethicone to drink before the endoscopy. I think that's quite helpful. And if there's still a lot of bubbles, I ask the nurses for a bit more and I just flush it down my scope and you immediately see the bubbles disappearing and it's very helpful because they can be in the way. And it's a very easy and cheap method, I think, to improve your visualization a lot.

Ian Gralnek: Ian Gralnek And what about are you using anything else with like a spray catheter like acetic acid or indigo carmine or methylene blue to assist you in trying to figure out if if there's Barrett's mucosa there?

Roos: Roos Actually, I don't. I think with the current high definition scopes and virtual chromo, I personally don't think there's a need for any dye-based spraying. It only makes the procedure a bit more complicated and messy. I don't have anything against it. I just don't think it's necessary.

Ian Gralnek: Ian Gralnek Okay. I think all these th these tips and tricks is are extremely helpful because when we go to conferences, we oftentimes don't get into this type of minute detail. And I think there's a lot of people want to hear these types of things of how experts such as yourself do this. So this this is fantastic. So so let's say you have a patient, you're scoping them and you're suspicious you see some type of a tongue that's there that you think is a couple centimetres in length. How do you go about then taking your biopsy? Do you take it just from that one area or do you do like the Seattle protocol or is that just for surveillance and already diagnosed Barrett's patients? Tell us about that.

Roos: Roos Yeah, so if I see a short segment, I'd always do a very proper inspection, in a retroflex position, because that's very easy way to assess that junction in more detail. And then if I see tongues of Barrett's mucosa, of course, inspect if the mucosa is regular, but if I don't have any suspicion on neoplasia, I take the random biopsies according to Seattle. And I have to say that if there's a tongue of about one to two centimetres, I biopsy the tongue, but I also take random biopsies of the junction just to have like four quadrants. Just because I think if you do it and you take the biopsies anyway, it's easy to take a few more. And if there's a longer segment Barrett’s, I also start at the junction taking four biopsies in four directions and then move up every two centimetres. But I only start doing the biopsies once I'm sure that I finished my inspection properly.

Ian Gralnek: Ian Gralnek And you put those in separate pathology bottles, correct?

Roos: Roos I do Yeah.

Ian Gralnek: Ian Gralnek I think that's very important. You don't want to combine these all together. You wanna be able to well mark what let what level you took the biopsies at and put them in a separate path bottle.

Roos: Roos This is sometimes a point of discussion. Also, my fellows ask this a lot, but sometimes you have just have this case, or when we get patients referred and there's high-grade dysplasia or even cancer in a random biopsy. And it's quite helpful if you have a little bit of an indication where in the segment the biopsy was taken, especially in the long segments, because of course you inspect everything, but then you know that somewhere halfway you have to pay a bit more attention for example. So personally I think it's still very helpful to put it in separate jars.

Ian Gralnek: Ian Gralnek any special use of biopsy forceps or a type of biopsy forceps like large cup or s regular size, does that matter to you?

Roos: Roos No, I just use a regular size that fits through a diagnostic scope. I'm always quite particular on my biopsy technique. So I put in my biopsy forceps, ask the nurse to open it and then pull it back in my scope. And then I steer my endoscope towards the area I want to biopsy. And I actually push my endoscope into the mucosa, then suction, apply suction so the mucosa goes into the forceps and then have it closed. So I don't push out my biopsy forceps, but I really get the tissue inside the forceps.

Ian Gralnek: Ian Gralnek Do you try and rotate the scope around so each of the four are at six o'c the six o'clock position when you take those biopsies?

Roos: Roos Sometimes I do, but sometimes it's easy just to go depending a little bit on how wide and floppy the esophagus is. But if I can manage to get good contact, just for example, so 12 o'clock, that's okay. I sometimes do start at the nine o'clock position because that's the area where the blood pools. And if you save that for last, it might get a bit more difficult to see if you have good contact. So you start at nine and again, nine, 12, three, six. But if it's like 10, two, four, seven, it's like, it's random anyway, but that's sort of how I approach.

Ian Gralnek: Ian Gralnek That's a nice tip. I've never thought about it like that. I just learned something myself. Okay. That's good.

Roos: Roos Yeah. Good.

Ian Gralnek: Ian Gralnek Let me ask you another question. a patient who is referred to you with a prior diagnosis of Barretts, but there's never been intestinal metaplasia documented. You've seen this patient in the clinic, let's say. What do you do? I mean, do you accept that that this is what it is? This patient has Barrett’s. Do you plan to re-scope that patient and do rebiopsy and sort of reevaluate? What what do you do in your practice? Because we see those patients a lot. I mean, I see patients like that and there's no histologic evidence of specialized intestinal metaplasia. Yet as you said earlier, they've been stamped or labelled as a Barrett’s esophagus patient.

Roos: Roos I think those are very interesting cases because we do see them. And then if I have good pictures from the referral centre and there's actually, I think well endoscopically this is no Barrett’s and there's no IM, then I don't see them in the clinic. I just say, I don't think this is a Barrett’s. There's no indication for surveillance. But if there really is sort of an endoscopic picture of columnar lined epithelium in the distal oesophagus and there's no intestinal metaplasia depends a little bit on the age of the patient. If they're like 75 plus, don't bother. But if they're young patients, I tend to re-scope them, inspect and take a new set of biopsies. But I am a little bit more reassured because we know from NICE data, especially from the UK, where they have followed patients without intestinal metaplasia for a long time, that really patients with just gastric metaplasia or cardiac metaplasia, they have a really lower risk of progression than patients who actually have intestinal metaplasia. But if there's endoscopic evidence, I do re-scope and take new biopsies.

Ian Gralnek: Ian Gralnek What what are your what are your thoughts about biomarkers or molecular assays today in terms of helping us to predict risk of patients progressing, let's say, to dysplasia or to even malignancy?

Roos: Roos I think that's really a very exciting area. So when I started my Barrett's research in about 2006, this was already the holy grail everybody was searching for. Because we know that just the histological interpretation is just difficult, especially if there's some inflammation going on and everybody was looking for the biomarker that could predict progression. And there's been quite some progress made. I don't think we actually have the Holy Grail yet, but there's a lot of different approaches and there's some very promising markers available, mostly a combination of markers. To keep it very simple, I think there's really nice evidence that P53, just very easily available, not very expensive. It's very good for pathologists to, for example, diagnose if there really is low grade dysplasia, yes or no, so it decreases inter-observer variability. And we also know that patients with p53 positivity really are at a bit increased risk of progression. And then there's like the more complex essays like the tissue Cypher TSP9, which is available in the US, that you can also apply on a biopsy that looks at morphology and a set of different biomarkers. And it's also very reliable in predicting patients with low risk or high risk. And I think we might just need a bit more data and it has to be a bit more practical, but I think especially differentiating low from high risk patients will be very valuable in the future.

Ian Gralnek: Ian Gralnek Should we be asking our pathologist to check these biomarkers in patients where we're sending pathology for to rule out Barrett's?

Roos: Roos Yes, I think that for the more advanced TSP9, I don't think it would be ideal if it was possible, but I think that's a bit too complex just yet. But P53 is quite easy and it's not very expensive. I think if the pathologist is very sure that it's not dysplastic or it is dysplastic, but especially for those indefinite cases or where they’re not sure, I think it should, it should be done because it's just very helpful.

Ian Gralnek: Ian Gralnek Okay. You know, you mentioned something. I I should have asked you about this earlier. The whole issue of if you're scoping a patient and there's actually endoscopic evidence of active inflammation. So they have reflux esophagitis, whether it's LA grade A or LA grade B, or even even worse. I was always taught you you don't take biopsies at that time if you're worried about Barrett's, if you see a potential segment, because that can confuse the pathologist in terms of whether they're calling inflammation or dysplasia. I was taught that you need to put these patients on PPI, send them away for eight to twelve weeks, explain the situation, then bring them back once they're usually healed, and then reevaluate and potentially take the biopsies at that time. Now is that is that what you're also doing?

Roos: Roos Yes, so if there's just grade A or B reflux, it's okay to take the biopsies, but then do put in the report for the pathologist that there's presence of little bit of esophagitis, so they can take it into account. But if there's really a grade C or D, I think you should inspect properly to see if there's no big, well, evident tumour. But if that's not the case, then really explain that they need high dose PPI and then see them back in about six to eight weeks to properly assess because then you can actually see if there is a Barrett’s, yes or no. And if you take biopsies, it's not hampered by all the inflammatory changes that you would otherwise see. So you get a much better diagnosis. if there is a little bit of high grade or low grade, like six to eight weeks isn't going to make a difference for the prognosis of the patient.

Ian Gralnek: Ian Gralnek So so the takeaway here is even if you have a mild esophagitis LA grade A or B, you can actually go ahead and take those biopsies, but notify the pathologist about that. Is that correct? Okay.

Roos: Roos Yeah. Yeah. Yeah.

Ian Gralnek: Ian Gralnek Okay. So I think we've done a pretty good job of defining and in diagnosing Barrett's esophagus. Because I think this is a nice teaser to say we've covered the waterfront here on defining the diagnosing. And in part two, we're gonna talk about okay, a patient comes back, you suspected Barrett, it's it's it's true by biopsy, by histology, and now how do you do surveillance and and what are the endoscopic standards?

Roos: Roos Yeah, I would agree. I think this is a nice diagnostic part one.

Ian Gralnek: Ian Gralnek Okay. This was this is I think very helpful. As I said earlier, I think there's many of us, including myself, who wanna know this minutiae sort of tips and tricks, and we don't always have the opportunity to ask experts such as yourself. So this I think has been absolutely wonderful and it it's been great having you. And I look forward to part two, we're gonna where we're gonna delve into okay, what do you do now in terms of surveillance and following up these patients, and what are the current evidence based recommendations, the international recommendations at this point in time?

Roos: Roos Looking forward to it also.

Ian Gralnek: Ian Gralnek Well listen, before I let you go, I wanna know and I think everybody out there wants to know, what what do you do when you're not in the endoscopy suite when you're not scoping Barrett's patients? What do you like to do?

Roos: Roos What I'm doing or what I like to do. Those are two different questions.

Ian Gralnek: Ian Gralnek Okay.

Roos: Roos So usually what I'm doing is usually, well

Ian Gralnek: Ian Gralnek Working.

Roos: Roos no, just being at home, chilling with my kids and my cat and my husband. And what I like to do really to sort of relax and unwind is running. trail running, just through the woods

Ian Gralnek: Ian Gralnek really? Okay.

Roos: Roos or sand or whatever. I think it's a very relaxing way of clearing your mind

Ian Gralnek: Ian Gralnek How often do you run?

Roos: Roos about two to three times per week. About 10 to 15 ks

Ian Gralnek: Ian Gralnek Wow. That's not that's not a short run. That's fantastic. Any anything else you do besides trail running? Do you do mountain bike or anything like that?

Roos: Roos I've done so, but a few years ago broke my arm and I fell off my bike. So I've become quite cautious because as an endoscopist, a broken arm is a very annoying thing to have. It's very frustrating. But like reading. I do always read in English somehow because I think it's a good way of also keeping my English skills up to par and I usually ask people who I know are readers as well if they have any recommendations. But I like a very diverse type of books.

Ian Gralnek: Ian Gralnek Well, I think your English is better than mine, and I'm a native speaker, so that that says something.

Roos: Roos That's a compliment, thank you.

Ian Gralnek: Ian Gralnek No, very I it's very sincere compliment, Roos. Okay. thanks again for being here. It's been great and we'll see you back in part two.

Roos: Roos Thank you too. Bye bye.

Ian Gralnek: Ian Gralnek Thank you for listening to this episode of Endoscopy Unplugged. If you found this podcast useful, please subscribe wherever you get your podcasts. And remember, they drop on the third Thursday of each month. To find out more about the European Society of Gastrointestinal Endoscopy, for example, to browse our scientific publications, visit our website at esge.com. And of course we'd love to hear your feedback. What would you like to hear more of? Send your thoughts to podcast at ESGE dot com. Thanks for listening and join us next time.