So, next, it's my great pleasure to introduce Dr. Jennifer Christie. She is the current president of the American Society for Gastrointestinal Endoscopy, a professor of medicine and division director for gastroenterology and hepatology at University of Colorado School of Medicine, and she will be giving our keynote. Let's give a warm welcome to Dr. Christie. Okay, well, thank you, course directors, for organizing a wonderful program today, and of course, ASGE staff, as well as all of our presenters, and then, of course, you for being here. This is very exciting for all of us and for me and my role at ASGE. So, I'm actually going to do something a little different. I mean, I do have a passion around colorectal cancer screening, particularly as it applies to underserved communities, but I also have a passion for GI functional disorders. I know. I know. Everybody's like, what? Yes, I do, and I want to talk about them as it relates to endoscopy, and I know it sounds like an oxymoron. However, despite what we, where we practice, how niche our practice is, how many advanced procedures we do, this is something, this is an area in which we all have to face and do the best for our patients that we possibly can. So, how do I? Okay. So, here are my disclosures. All right. So, our three major objectives for this talk are to, number one, understand the current role of endoscopy in common functional colorectal disorders, two, to review the utility of future endoscopic technology and assessment of these disorders, and then, lastly, to discuss the potential role of endoscopic technologies for the management of functional GI disorders beyond our current practice. So, you know, what the indications for endoscopy in our patients that present to us with functional GI disorders, sometimes it just can tell us what it is, and oftentimes it can tell us what it is not. We know that endoscopy allows us to evaluate the mucosa, just to rule out IBD and other pathologic disorders. Endoscopy helps us to guide therapy, and then also to administer therapy in these patients, and I'll give you an example of how I've used that in my career. And so, in keeping with the theme of this course, I want to talk to you about how we use endoscopy today, how we may use it tomorrow, and then how, potentially, we can use it beyond. And it's going to require all of us in this room to apply the gaps in our current knowledge and gaps in our current technology to be able to advance this specialty. So, as I mentioned, functional GI disorders are very common. In fact, one in four adults experience functional bowel disorders. And when you look at prevalence data, there's about 29 to 32 percent prevalence for functional bowel disorders based on Rome IV criteria. And in fact, if you look at GI practices and GI clinics, there's more consults for functional GI disorders than any other disorder or class of GI disorders. And so, we'll talk about, again, the current role of endoscopy focusing on three major disorders, fecal incontinence, constipation, and then irritable bowel syndrome. So, I want to just give you a set the stage with an example of a patient that I've seen in my practice. This is a 49-year-old woman who presented with diarrhea, and she labeled it as diarrhea because it's embarrassing, right, to come into the office and say, I have fecal leakage. But in fact, that's what she had. And I, you know, couldn't elicit that without asking additional questions about this diarrhea. And then she reported that she has several accidents commuting to work. She has to wear a pad. She has to carry a change of clothes because she doesn't know when it's going to happen. And obviously, it's impacting her quality of life significantly. She's married with three kids and has had two forceps-assisted vaginal deliveries. And of course, we know that can be very important from a physiologic standpoint. And then just when she came in, her labs are absolutely normal. Going the wrong way. So, as I mentioned, people don't offer that they have fecal incontinence. But today, it is a silent affliction. And it is the release of fecal contents against one's wishes. And it affects more of the population than we could ever imagine. And in fact, this is the main reason why a lot of elderly people are admitted to nursing homes because their families just can't manage it. And it is more common in women because of obstetric injury. So, it does result in isolation. It has a significant impact on self-confidence because as an individual, you think, I'm the only one dealing with this and I can't talk to anyone about it. You develop a negative self-image and it is associated with anxiety and depression. And so, as I mentioned, obstetric injury is one of the main causes of fecal incontinence. However, oftentimes patients who have diarrhea for any etiology have this problem in addition to having some obstetric injury. And we see this sometimes in patients who present with irritable bowel syndrome and certainly IBS and other disorders that affect absorption. Another common etiology is neuropathy. And then sometimes that neuropathy is idiopathic, affecting the pelvic floor. So, what are the most helpful tests today in evaluating patients with fecal incontinence? So, depending on if that patient is age appropriate for routine screening or has diarrhea, certainly endoscopy, either by FlexSig or colonoscopy has been shown to be very effective in terms of diagnostically. And there's good evidence for that. You want to rule out inflammation, strictures, tumors. Then also importantly is anorectal manometry. And then, so selfishly I had to put that in there because I love talking about anorectal manometry as well. But it allows us to look at sphincter pressures, compliance, and also sensation. And then, of course, endoscopic ultrasound is very effective at looking at sphincter integrity. And then some of these other tests we really don't use as much anymore because the evidence is weak, such as EMG, prenatal nerve terminal modal latency testing, and then deficography, which is most helpful in constipation. So, in terms of colonoscopy, today it's important to do a colonoscopy in your patient who is above the age now of 45, right? And so, they may have an increased risk of colon cancer. And what you want to do is reflected in this image here is, well, A, do a rectal exam. That's number one. But also, in endoscopy, sometimes you can see a mass that's infiltrating that neuromuscular bundle right at this anal canal and that sphincter, and that may be triggering incontinence. So, that is very important. And then also allows you to get random biopsies in your patients who have diarrhea. And of course, someone who is coming in with bleeding and other alarm symptoms, you want to go to endoscopy for them. Also allows you to look at the mucosidum to make sure there's no proctitis or even radiation injury in someone who has had radiation for prostate cancer or cervical cancer. And then also, again, allows you to look for strictures. Maybe that patient has overflow incontinence or a mass right there at the anal canal. So, in terms of high-resolution manometry, that's usually we proceed to that if endoscopy is otherwise unremarkable. And I personally think these images are beautiful. I think they're just as sexy as the ERCPs, but that's me. And but just so that you guys know what you're looking at. So, this is an image of a metametric tracing. This is the proximal sphincter. This is distal. And that probe, that manometry probe is sort of straddling the anal canal. And so, this is the resting pressure, which usually is around 40 millimeters of mercury. When you ask the patient to squeeze right here, it goes up. It gets hotter. It's red. And you expect for them to be able to hold that for about 30 to 45 seconds. This image right here is a patient who has some injury, right? So, here's your resting. They squeeze, but then it drops. They squeeze, and then it drops. And so, oftentimes, that can be very helpful in assessing these patients. Also, we can look at sensation. We ask them to simulate defecation to see what happens to those muscles when they simulate defecation. But also, we can assess some reflexes that can be important. So, in terms of correlating the metametric tracings with endoscopy, the endo, that's where your endoanal ultrasound comes into play. And the two together can be very sensitive in terms of predicting what is happening with your patient and what to do for him or her. So, this is a normal anatomy in which you have the, here's your ultrasound probe. The internal anal sphincter is usually hypoechoic, so this is your little line here. And then your external anal sphincter is sort of a mixed echogenic picture, kind of salt and peppery. And then in patients who have dysfunction or some sort of injury, you see that your external anal sphincter is disrupted here. You have this tear. You're not seeing that nice sort of heterogeneity that you see over here. And then, and this panel over here to the right, you see that there's disruption of the internal anal sphincter, and you don't see that nice hypoechoic band. And so, this is actually an image of the patient that I started with in which this is the ultrasound here. Again, you see this defect. You see it's not that salt and peppery right here in the anterior. This is the anterior side, right, which is where we normally see these defects because of, again, the obstetric injury, and you probably have episiotomy here, comparing it to the normal. And then I'm showing you the same manometric picture in which you have the normal resting pressure. You ask the patient to squeeze, it drops. So, again, external anal sphincter weakness injury here correlating with your defect on the ultrasound. So, it can be very effective. And so, how do we manage patients with fecal incontinence today? Today, of course, we encourage general care, pads, caregiver support. If they're having overflow incontinence, we want to get them on a good bowel regimen. And most commonly, if all that, and then we say fiber as well if they're having some diarrhea. More often than not, we recommend biofeedback for these patients, which can be very effective depending on the motivation of the patient and then the expertise of your therapist. But then also, there's these anal injection therapies that I want to talk to you about. So, NASHA is this dextronomer that's in the stabilized hyaluronic acid, and it was approved back in 2012. It's a little bit difficult to get just because of insurance coverage, but it can be very helpful. And it's indicated for patients who have failed some of the medical therapy that I just told you about. And then based on your assessment of them, they have intact but deficient anal sphincter. And this is usually done in the office. You give the patient four quadrant injections, and this is done via anoscopy just above the dentate line. Patients don't typically feel it unless you're in the wrong spot, but it can be very effective. And over time, what this dextronomer does is it forms these, this gel, these microbeads form a gel that help bulk up the anal canal. So, this is a patient that I injected. This was based on a study that we did. And so, endoscopically, this is what it looks like. You see that nice little bulge there, and it creates this cushion that typically may help in terms of preventing incontinence episodes. And then this is an ultrasound from one of my colleagues at Emory showing, and I hope you guys can see this from the back, that little nice round bulge here where it enhanced that anal canal. And then the panel on the right here, you can see it sort of a little bit better with these little, it's supposed to be four, but maybe only three are left. So, I did okay, but there's three little bulges here. And this patient actually did much, much better after these injections. So again, utility of endoanal ultrasound in managing these patients. Now the pivotal studies looking at this show that if you see here in the figure on the right, it showed that at six months and even up until 36 months, that a little over 50% of patients had a 50% reduction in fecal incontinence episodes. That doesn't sound like a lot, but in someone who's having fecal leakage, it can be substantial. And then there's an okay proportion of patients that actually had a 100% reduction of fecal incontinence episodes. So what about tomorrow? So now we're using endoflip to assess a lot of our patients who have esophageal disorders, right? Achalasia and other problems with EGJ obstruction. But what about using it in patients who have incontinence and other disorders of the pelvic floor? So the endoflip, as you know, it's a catheter, it's a two-lumen catheter, it has about 17 electrodes along it, and it allows you to measure the electrical impedance. And then using the electrical impedance and correlating it with the pressure bag that's at the end of the probe, you calculate the distensibility index. And so the distensibility index, when it's high, then that suggests that the pressures are lower. So the Leroy and colleagues did a study looking at whether endoflip can be diagnostic in patients who have fecal incontinence, and they correlated it with manometry. This is just an image looking at a patient who doesn't have incontinence, looking at their endoflip images. And this is at rest, and then this is during voluntary contraction, so it's a little bit narrow. That distensibility index is likely lower. And then this is a patient who has fecal incontinence. As you can see, this correlates to a distensibility index that is higher, and the resting pressure is lower. And when they looked at it comparing to manometry, it actually showed like a 70% correlation. So it's still probably not ready for prime time compared to anorectal manometry, but maybe tomorrow it will be. So let's talk about constipation. So today, there's really not a significant role to do colonoscopy in patients with constipation without alarm features. However, in theory, there's some theoretical concern that patients who have slower colonic transit, they may have more contact of carcinogens along the colonic mucosa, and that this may increase the risk. However, over 10 years ago, and there's been multiple studies to confirm that there is not an increased risk of colorectal cancer in patients who are constipated without alarm features. And this is a meta-analysis by Powers and colleagues that show that the odds are lower than one. And then more recently, in 2022, Stahler and colleagues published this case control study of about 41,000 patients with colorectal cancer compared to over 200 controls. And they were looking at those who had a history of constipation, and about 4,000 of them did. And initially, when they did the analysis, it did show a modest association with increase of colorectal cancer risk and constipation, but then when they did this comparison with, the match comparison with siblings, that association disappeared. So again, without alarm features, no indication for colonoscopy, but certainly if they're age appropriate. Also today, what is the diagnostic yield of colonoscopy in patients with irritable bowel syndrome? So this recent meta-analysis, this was actually done this year, and published in Neurogastroenterology and Motility, they looked at a meta-analysis of 12 studies with 28,000 patients with IBS. And when they looked at the prevalence of colon cancer, IBD, and microscopic colitis, you can see that the pool prevalences are not high. They're probably the most, the highest prevalence was in microscopic colitis in this group, and this is for patients who were younger than, or older than 50, as well as younger than 40. So, and then also looking at the yield of colonoscopy in patients with IBS, they looked at patients with alarm symptoms and those without. Of course, patients with alarm symptoms like bleeding and had chronic diarrhea, there was more IBD in these patients compared to colorectal cancer and microscopic colitis. And then certainly when they looked at subtypes of IBS, patients with diarrhea had more IBD, as well as more microscopic colitis. So that's not surprising. So this is what I found really fascinating. So, you know, we see this all the time. We see this layer of yellowish, greenish mucus on the colon. We think, wow, that prep is not great. Well, maybe it's not, but then also this study with Baumgarten, they looked at these, what they're calling mucosal biofilms, right? And we all see these, we wash it, and they just sort of peel off as we're using that water jet. So what this group did is they looked at, they took, it was like 1,400 patients, and they did biopsies of the cecum, as well as the ascending colon and the terminal ileum in these patients that had biofilms. And more patients who had symptoms of IBS actually had these biofilms compared to those who didn't have symptoms of IBS. And some proportion of patients with IBD had them as well. And then they biopsied the mucosa. And you can see in this panel up here, this is the patients who had these biofilms. This panel below, they did not have the biofilms. Then they did scanning electron microscopy on these biopsies. And what this pink illustrates is these, sort of this inherent conglomerate of bacteria, right, when they looked at it, compared to those who did not have these biofilms. And then they also did, they stained it with this blue dye. They did in situ hybridization on this. And I hope you can see it in the back there, that this blue here that's outlined in red, again, these are these conglomerate of bacteria that kind of hide on the mucosa covered by these biofilms, which is extracellular matrix that protects it and allows it to grow, right, compared to those who did not have the biofilm. And then H&E, same thing. You can see this conglomerate of mucus and what's thought to be bacteria there. And then when they looked at the density, this is reflected down here, the patients who had the biofilms had a higher density of bacteria in general. And the diversity of those bacteria was much, much lower as well. So we want high diversity and fewer bacteria, actually. Okay, and then the other thing, let's talk about beyond quickly. So you can't talk about anything beyond without an endoscopy or even medicine, without talking about artificial intelligence. So this group by Tabata and colleagues, they were looking at, they created this model, this AI model using a code-free model. And I think they used this Google platform to do this. So you don't really need a lot of knowledge around machine learning. And they looked at a few thousand patients, actually, but they took about 117 of them, and they did biopsies. And basically what they wanted to do is see if you can predict whether they have some microscopic or changes to the microenvironment that were more common in IBS patients. And they separated the groups into four groups, the healthy controls, and then the patients with different subtypes of IBS. And they looked at how this model could predict. And as you can see in this panel here, that actually the area under the curve was about 95%, which suggests that that model was good about 95% of the time. And then they also looked at the precision when they intersected the recall as well as the precision model, and it was actually still very high here. And they used a reliability threshold of about 0.5. So again, there's still work to be done here to see if we can use AI to create images or look at models and see changes that we can't see with the human eye, but yet predict patients with IBS, and then maybe help determine therapy for them. So also, when we're talking about BEYOND, again, there are a lot of gaps in terms of how we can use endoscopy in patients who have functional bowel disorders. But I think it's really important for us to continue to partner with each other. ASG invites you to partner either through grants or through innovation applications so that we can better understand this. But we certainly need to further develop endoscopic AI systems to assess sensation, motility, and also the mucosal microenvironment as it relates to our endoscopic images. Also, it would be interesting to be able to use endoscopic pressure measurement systems that allow you to kind of do both. And then also, 3D functional luminal imaging may be helpful in these patients as well. So a key takeaway is endoscopy has a role in assessing mucosal integrity and obtaining biopsies in patients with functional GI disorders, but the history is key. Endoscopic ultrasound is helpful in evaluating and directing therapies for these patients with fecal incontinence. EndoFLIP may be helpful in determining anal disensibility, but currently it modestly correlates with anal manometry. And then again, beyond, mucosal biofilms and artificial intelligence may have a role in evaluating patients with functional GI disorders. So again, thank you for your attention. And another little plug is a lot of this stuff, and I think Dr. Patel had mentioned this earlier, GIE, IGIE, VideoGIE, always looking for really interesting technologies and ideas, because they're coming out in these journals every month. So I encourage you to continue to read and work with us to advance these technologies. So thank you for your attention, and enjoy Vancouver. Thank you. Thank you. Thank you, Dr. Christie, for an insightful talk on a very challenging topic. Every time I see fecal incontinence, I'm like, okay. So we had a quick question, actually. Sorry. Yeah, so from the audience, not just yet. What do you think about increasing soluble fiber intake to help increase stool diameter and improve diarrhea in patients with pelvic floor injury? Injury, yeah, yeah. I thank you for that question. See, it's functional bowel disorders are important in endoscopy, okay. So I think in terms of increasing fiber, I mean, that's always helpful, and not necessarily just for pelvic floor, but just constipation in general, and sometimes diarrhea, too, because we know when we bulk the stool, it helps to stimulate colonic transit. And so when you say injury, I assume that that may be some surgical or physical injury. It's unclear what that is, but depending on what the underlying etiology is, it can be very helpful in transit and improving constipation in these patients. Thank you. What do you think is the role of MR deficography in constipation or fecal incontinence, or does it not have a role? MR deficography does have a role, and mostly in constipation. And it's really important because it allows you to, number one, look at the pelvic structures and how the bladder, the uterus, the rectum, the distal bowel is functioning when a patient defecates. It can rule out structural disorders like a rectal seal, intussusception. And it also allows us to assess whether patients can actually empty the contrast out of the rectum, or is it just a heightened sensation of distention, and perhaps it's more around improving sensation. But it can impact whether you decide on deficot biofeedback in these patients. Thank you. So that ends the second session. Again, thank you all for being here. I know we're all hungry, so lunch is just outside the door. And we'll reconvene back here at one o'clock for the second half of the day. Thank you.

Dr. Jennifer Christie

American Society for Gastrointestinal Endoscopy

keynote speech

gastrointestinal disorders

endoscopy

functional GI disorders