Welcome to ASGE Endo Hangout for GI Fellows. These webinars feature expert physicians in their field, and I am very excited for today's presentation. The American Society for Gastrointestinal Endoscopy appreciates your participation in tonight's event, Lower Motility for Practicing Gastroenterologists. My name is Michael DeLuttre, and I will be the facilitator for this presentation. Before we get started, just a few housekeeping items. We want to make this session interactive, so feel free to ask questions at any time by clicking on the Q&A feature on the bottom of your screen. Once you click on that feature, you can type in your question and hit return to submit the message. Please note that this presentation is being recorded and will be posted to GILeap, ASGE's online learning platform. You will have ongoing access to the recording in GILeap as part of your registration. Now it is my pleasure to introduce our moderator, Lavinia Viswanathan from David Grant Medical Center in Houston, Texas. I will now hand over this presentation to her. Thank you, Mr. DeLuttre, and thank you to the audience members who have chosen to join us this evening for this webinar entitled Lower Motility for the Practicing Gastroenterologist supported by ASGE. I'm Lavinia Viswanathan, and I'm an associate professor of medicine at MD Anderson in Houston, Texas, where I'm a neurogastroenterologist. I have the pleasure tonight of introducing our speaker, Dr. Baha Moshiri. Dr. Moshiri is a clinical professor of medicine at Wake Forest University and director of motility at Atrium Health. She is very unique in that she is a pan gut motility expert and has extensively lectured on and authored material on various motility topics. I'm eager to be not only a moderator tonight, but a very interested audience member as I always learn something new from her. Without further ado, I'd like to hand it over to the capable hands of my colleague, Dr. Moshiri. Thank you so much. I'm excited to be doing this talk, and thank you to the ASGE as well for having me to talk about this area of really great interest, I think, to many of us who manage these patients. So I'm going to pull up my slides here now. So this is really labeled as for the practicing gastroenterologist, but some of these diagnostic tests we'll talk about are things that are either available right now or will be available in the future. And I do have a conflict of interest with a lot of them. So Atmo Pharmaceuticals, we'll talk about one of their inventions. I have grant support from Biora, which is a capsule for small bowel placebo analysis, and then Medtronic, of course, and then I'm on part of the Gastroparesis Consortium now. So our objectives are to talk about the diagnostic tests that we have for lower GI, but some of them are also used for upper GI. As was discussed, we'll talk about a patient case that has constipation, severe constipation, slow transit. Then we'll talk about a patient that has small bowel dysmotility, and then we'll go into more of the capsule technologies and what interventions that can be done for those patients. So objectively, what we have available currently is, of course, colonoscopy is only for evaluation of change in bowel habits, patients with alarm symptoms, or of course, if patients are 45 and up. And then we've got our transit studies, small bowel follow-through is kind of an easy, cheaper way of evaluating small bowel transit, I would say. And then there's whole gut scintigraphy, which is only available in specific sites around the country. We only have that available for research, but that's not something that's widely available. Then there's the radio-opaque markers, which are, they're different types, ANX has one, and then the classic SITS marker. We'll talk briefly about the wireless motility capsule, maybe not so briefly, because this actually has been available now for 20 years, just recently got taken away in September. And then Atmel Biosciences, manometries, right? So we have anorectal, colonic, entral duano, we'll kind of brush on that, and then tests such as MRI, defecography for structural issues, and the lower GI tract, and then balloon exposure study will be kind of discussed. So when we discuss the diagnostic tests, obviously you start with a patient who has constipation. And usually by the time they see us as gastroenterologists, they're probably have weeded through, or at least over-the-counter agents, if not prescription medications, and they come to us to see, you know, how can we diagnose their disease? And so radio opaque markers compared to colonic scintigraphy and wireless motility capsules, they're cheaper, right? It's kind of standardized, provides some good results. It's more of a transit test. We used to say that if the markers are throughout the colon, it's more consistent with slow transit, whereas if they're rectal sigmoid area, they may be more consistent with someone who has dyssynergic defecation, but we find that that's not necessarily the case, because you can have it spread throughout the colon, and it could still be consistent with dyssynergic defecation, and there's a lot of overlap. It's widely available, so I think that's a positive. You don't really need specialized personnel, because it's just a KUV. It's convenient for the patient. You give them the capsule, you send them home, six days later, they get this x-ray. And then, yes, there's radiation exposure, but it's not a huge amount of radiation exposure. Colonic scintigraphy, we kind of touch base, but, you know, that's not really available everywhere. There are radiologists that can do this test over time. There is radiation exposure. The patients usually tolerate this very well, but they do have to drink a liquid substance. And then wireless motility capsule, which was given with a bar that the patient had to ingest, and this has, of course, been validated and standardized, not available since last year now, and then doesn't really, it's easy to read. Patients tolerate this test. There may be radiation exposure if the capsule is retained, but really, there's no radiation exposure just from the ingestion of the capsule, very similar to capsule endoscopy. And we had trouble, obviously, with getting a lot of insurances to pay for this test, which is why it wasn't really necessarily widely available. When you look at the utility of these tests for evaluating chronic constipation, you know, TSH, calcium, probably not that helpful, but of course, if a patient has diabetes, that's a risk factor for constipation, and a patient that has hypercalcemia, you should think about that. That could be a parathyroid issue or some perineoplastic process. So you want to be cognizant of those things, but those aren't tests that you want to do in every patient. Having a KUB is, there's poor evidence. This was a grade C recommendation based on this previous study in 2006. But really, if you have a patient with, I think, kind of these overflow diarrhea patients that fluctuate from constipation to diarrhea and vice versa, getting a KUB on a day of visit can actually be really helpful because you can show the patient there's excess fecal load on the KUB, and that may be somebody you could intervene in and maybe maximize their constipation meds if that's what, but that's what you need to do. And then barium enema is really for evaluating a mass diverticulosis, colonoscopy is more for evaluating mucosal disease. So that's a grade C. And then when you compare chronic transit, Sitzmarker study being one of them, wireless motility capsule, really the excellent grade was received by the wireless motility capsule. So we'll talk about how these new technologies hopefully will take a spot. And then anorectal manometry, Hirschsprung's is rare in adults, but we have seen them. And this synergic defecation is really what we use anorectal manometry to diagnose. And that's a grade B2. And impaired propulsion, which is another functional defecation disorder. And then balloon expulsion really helps us evaluate obstructive defecation, you know, this synergic defecation that received a good grade. And MRI defecography is not so standardized amongst radiologists. And it received a fair grade for that reason, and it is expensive, but it is a nice way to evaluate global pelvic anatomy. So now let's go on to the FDA approved capsules. We have wireless pH capsule, that's the gold standard for reflux analysis. We have the vibrating capsule that's vibrant. We'll talk about that for chronic constipation, not for IBS with constipation. The wireless motility capsule, there's several prototypes that are hopefully going to come about. This is for pan-regional testing. And then there's a gas sensing capsule that has been evaluated. And then there's others that test SIBO, et cetera. And then this other one, smart capsule bacterial detection system called Capscan. And then there's a capsule that goes through the small and large bowel, and that's for purposes of microbiome, bile acid determination, and metabolomics. So these are all different capsule technologies. So the first case is a patient of mine, 23-year-old military vet now, who has a history of encephalitis while he was in a military cap for practice and developed a tick bite and got infected really an extensive neurologic workup. At first had also altered mental status when all this happened, kind of ended up with megacolon on several KUVs while in the hospital, not really on narcotics at all. And CTs all were full of stool. He doesn't have any pain, doesn't feel pain actually, but strains to defecate constantly. Every laxative, every prescription laxative was tried on him, sometimes multiple ones along with over-the-counter agents, including just PEG. And it wasn't helping. Patient did state that they had some constipation when they were a child, but it wasn't severe and they were just eating a high fiber diet and it was fine or fiber supplementation. And that kind of just helped, but this is obviously very severe. These symptoms had been ongoing for a year by the time I saw the patient, patient had, you know, MRIs, they rolled out MS, you name it, LPs, everything was negative. We had performed an enorectal manometry, balloon explosion testing, and found that the patient also does have some dyssynergia, but we didn't think obviously that was the whole picture because there's probably an overlap since there was megacolon also. And then radio-opaque marker studies showed that all the markers were in the rectal sigmoid, so not really spread out throughout, which we would suspect. But the patient's going through biofeedback at this point and they're still not better. So what next? And so just to go over the past 20 years and advancement, right? So 20 years ago, if we had this kind of patient, we'd probably be giving them Tagacerod, which was probably the more common drug that we were using back then. That's for IBSC, that also is no longer available. We probably will be giving them Colchicine, that was one of our tricks in the old days. We used to use Colchicine for constipation because it side effect is diarrhea. And then all the over-the-counter agents that we could. But now luckily we have these other ones. We have Lubiprostone, chloride channel activator, that was launched in 2006. Guanlycyclic C agonists we have, and this is probably the stronger of the laxatives that we have, I would say, in the 290 dose. Then we have Plecanetide, which works a little bit different than Lidoclotide. And this is the Guanlycyclic C agonists, drugs that start kind of working in the small intestine and then towards the colon and help with another secretogogue. Then we have the newest kid on the block, which is a sodium proton channel exchange inhibitor. And this one launched the most recently. And this is also something that we have in our armamentarium, which is nice. And this is all for IBS with constipation. Obviously, a lot of these are also approved for CIC. This patient has more of a CIC pattern, but we kind of do use these interchangeably. OK. And so, oops, sorry, going back. And there are studies with Jennifer Christie, who is the former ASG president here, and she looked at wireless motility capsule results in patients with slow transit constipation. These were patients that had diabetic constipation, pretty severe. Their primary endpoint using Luproprostone was weekly difference in number of spontaneous bowel movements a week. And this is the only laxative study using a whole gut testing, which for this study, it was the wireless motility capsule. And they looked at colonic transit time. And what they found was that Luproprostone improved that colonic transit time more than placebo did. And the delta for this was negative 12.9. So really, this is the only laxative at this point in time that we have with use of a test that evaluates gut transit, especially colonic transit. So when we look at the differential diagnosis, obviously, our patient did have a pelvic floor disorder also, and that's present in probably 40% of patients that have chronic idiopathic constipation. Then 20% of the patients have IBSC. Our patient is probably neurogenic, you know, bowel and ideology or some other ideology, but doesn't have any sensation. So it's not IBSC. And then you want to make sure it's not other agents such as anticholinergics, you know, something like, you know, diphenhydramine, especially during the allergy seasons, antacids. If you look at a lot of the antacids now, they're called antacids, but they're really other than just calcium, which can be constipating. A lot of them also have NSAIDs, NSAIDs are constipating. There's PERT therapy, you know, that's kind of controversial. I see a CF population, a lot of them are on PERT therapy, but you really have to give excess doses to get that fibrosin, colopathy that we used to think about and severe constipation. But then there's like narcotics, bilases, sequestrants. And then of course the GLP-1 agonists that now some of our patients may be taking. But really only 2% of the patients are true slow transit constipation and colonic dysmotility. So, you know, it's not the majority of patients that have this, right? So I'm really presenting the extremes, right? But in the normal setting, most patients are not the extreme, but that only takes 2% of the patient population. And so most of the patients are these other things, including pelvic floor disorders. And of course, everyone here probably knows the Rome 4 criteria for IBSC and CIC. There's not a whole lot of differences between the two, but abdominal pain is central for IBSC. And for functional constipation, you look at these other parameters and you have to have at least two or more of the following. But there's insufficient criteria for IBS that's met in the patients that have functional constipation. And so many patients, you know, will have kind of a spectrum, right? They may go between the two. They may have pain one time, but then not other pain another time. And so, you know, usually I try to just call it the IBSC CIC spectrum so that in my clinic, if I'm going to recommend one of the drugs, for example, Procalipride that's only approved for CIC, I've already said that. And so I can give these prokinetics with Procalipride, I didn't talk about on the other slide, is a prokinetic. It acts on serotonin and it works in the entire gut. You know, if I'm using it for constipation, then I've called the patient CIC. And so my poor nurses who are trying to get the prior authorization, they don't have as much trouble, right? Trying to get those things. And sometimes because of the different mechanism of action, obviously in studies, they're only going to study the drug plus placebo. But in real life, we probably would give a patient like this drugs from different mechanisms of action. And I think that would be okay to do. So comparing the radiopig markers to colon transit scintigraphy, there is a good correlation between the two. Of course, again, like we said, scintigraphy is costlier. You do have to have a dedicated radiology department that knows how to read these scintigraphies. And there is some protocols that usually we borrow from Temple University or Mayo Clinic and others, but this is really rigorous for patients that have to go through that. And then on the left, you have the radiopig markers and there's the Metcalf method. There's a few methods that have been used. And this is something that's more widely available, I would say, and most clinics could just get it. It's not super expensive. Okay. And then wireless motility capsules. So this was a nice tool when it came about. I was a fellow, we were actually studying Parkinson's at University of Florida, and this was used as a way to study whole gut motility in the Parkinson patients. And as you know, they have gastroparesis, small bowel dysmotility, and constipation in the Parkinsonian patients, including dysphagia. And so this is a nice way, if they're able to swallow the capsule and their dysphagia is not severe, of course, to really evaluate their entire gut. And so the green line here is the changes in pH that you see that tells you which part of the GI tract you're in. There's pressure waves that gives us like these motility indices in the antrum and the duodenum, and then those high amplitude contractions that you see on colonic manometry. And then there's temperature that tells you when the patient's ingested this, when it exits. And then there's variations in temperature as the patient sleeps and other things that can also be looked at. So this was kind of a nice tool. The reading is pretty actually easy for those of us that have read this, because the computer analysis runs you through all these and tells you when did the capsule exit, the small bowel, the IC valve, when did it exit the body, et cetera. So it's kind of like a transit and motility all in one, and the NIH adopted this actively as part of their many studies to assess gastroparesis patients. And then the joint European and American Neuromotility Society consensus document recommended this to assess gastric emptying time, regional whole gut transit times in patients with suspected gastroparesis, but then also slow transit constipation. So this was approved for both purposes, but it's different than, it's definitely different than scintigraphy, whereas this capsule is a foreign body, so it empties at a different time point. This is, when we look at the small bowel manometry, I can discuss this more, but this is more of a fasting state test, whereas the gastric scintigraphy is more a meal related emptying. So there are some nuances and differences between the two, which I think has been kind of a matter of controversy in ways, but the two tests do test kind of different things. And so when it's been compared to gastric emptying scintigraphy, the cutoffs at five hours have a sensitivity and specificity of about 87%, the R ratio was 0.73. And then at the five hour cutoff, the specificity is actually higher. The 87%, sorry, was the four hours and the 92% specificity is at five hours and sensitivity is 87%. And then that basically the FDA cleared this and ever since until September, we were all probably adopting this to evaluate gastroparesis and whole guts scintigraphy. And then when you compare wireless motility capsule to colonic manometry, which I know again is one of those tests that isn't available to practicing gastroenterologists, but just for you guys to see that kind of the history, right? When you compare the two, the wireless motility capsule is a moving target. So it moves through the GI tract. And so it has one continuous moving center, whereas the colonic manometry, whether it's placed by fluoroscopy or placed by endoscopy is stationary. And so they do test kind of different things because you can actually see these high amplitude contractions with the colonic manometry, whereas with the wireless motility capsule, that's a moving target. So there is some artifact patterns that happen, and then you don't know exactly which part of the colon you're in. Like with the wireless motility capsule, unless you get an x-ray constantly, you don't know, are you in the ascending colon or are you in the sigmoid or are you in the transverse or the rectal sigmoid, right? So if the capsule gets stuck in the rectum, then you're kind of not going to know that that's just all calculated as colonic transit, right? And I'm sure that happens to all of us. And then we're having to get x-rays to see where this capsule is. So different things are being evaluated by the two. And then these are just the normal values, just for you guys to know, there are some small bowel motility indices also that the wireless motility capsule provided. The whole gut transit was transit less than 73 hours. The combined small bowel, large bowel transit was less than 65. And then colon transit by itself was less than 59 is normal. And then for small bowel transit, probably by their parameters was less than six. We usually use less than eight. And then gastric emptying time less than five is normal. So this is a patient that has a slow colonic transit time. And it's compared here to the radio opaque markers. And for that, there is 87% agreement between the two tests that validated this test. This was a study that was published by Satish Rao, an expert in this field. And then this is again on colonic manometry. What that exactly is and does, this has done a lot more in pediatrics. So most of us in the adult world do not do colonic manometry. I've only done this myself very rarely because we had wireless motility capsule. And so this really looks at the contractile activity within the large bowel. You can see high amplitude propagating contractions which are normal. And then there's the specialized propagating waves that are high amplitude. And this is a nice way of evaluating meal related symptoms. You can see contractions during sleep, after sleep usually you'll see during arousal these high amplitude contractions as well. And then, you know, and it helps you with evaluating defecation disorders because this catheter is actually goes through the rectum throughout the whole colon. Again, this is a favorite for pediatrics. If they're ever gonna send someone for colectomy, pediatrics would do a colonic manometry but that's really in specialized centers. And then they would do anorectal as well to make sure the patient doesn't have hirsprungs before they do any of those surgeries also. But it is kind of labor intensive, can take hours just to place. And they're not easy to place. So when you put the two on top of each other, obviously the wireless motility capsule is a lot easier than having someone do colonic manometry. Now, the wireless motility capsule does have contraindications. It's the same contraindications you would have with any capsule technology, with any capsule endoscopy. So if the patient can't swallow it, obviously you would abort it. Suspected strictures, fistulas, GI obstruction, GI surgery in the past three months, severe dysphagia to food and pills, Crohn's disease because you worry about strictures and severe diverticulitis is a risk. And then any implantable portable mechanical devices such as pacemaker infusion pumps is a contraindication. Although I would say I've had patients that we didn't realize had these things and we did the wireless motility capsule and it was fine. But those are contraindications. This is a patient of mine that had, it got stuck because the patient had a history of endometriosis, CAT scans did not show any adhesions, small bowel follow through was shockingly normal, but you can see this pinhole in their small bowel that was really, really adhesed and this capsule got stuck there. So it took about a few weeks before we could get the patient surgery and you can see this wireless motility capsule on the side. And obviously the patient is doing great now. And they kind of led to a discovery of the fact that they had severe adhesions and that was the reason for their pain and their symptoms. And so, yes, it got stuck, but it was kind of a good thing for this patient. So in that first patient, again, like I said, we had already exhausted all the laxatives on top of each other. I would say we also did Procalipride on top of linaclotide, Senna, Smooth Move Tea, every concoction we had, Marilax, et cetera. And so, this is a home enema irrigation system. The patient was undergoing biofeedback therapy at this point, because really this was a patient that had a bowel movement like once a month. And so this is added, the laxatives were added to this colonic system and this is FDA approved. You can use it for patients that really have neurogenic bowel or spinal cord injury. It's been studied in all these other disease processes. I think, again, pediatrics probably uses it more often, but it really liberalizes the patient in that they get to do this at their own house themselves. It's a nice irrigation, easy to use, it's labeled. We've even done this in patients that are blind. My APP was so smart and put letters on where the water goes in, where the flushing goes in, et cetera, that the blind patient could actually feel. And so this is something that the patient can do every few days and you do have to run through these hoops with insurance, unfortunately. They have a neurogenic bowel questionnaire that they'll have you use in clinic to be able to get this approved. But most third-party insurances will get some form of this kind of system approved. So it's just hard for if the patient has Medicaid. But this is something that is available to our patients. And I'm actually shocked that more folks don't try to get this for their patients, especially for these really severe folks that you don't really want an ostomy or a colectomy. So I'm gonna stop here because this was our first case and then our next one is mobile. So I guess any questions from the audience? Thanks, this is a really interesting case. I think you mentioned the tick bite in the history. Was that at all relevant? Did you find in the course of evaluation? Yeah, I mean, I think they kept thinking it's Lyme or some other weird encephalopathies. They never found out, they checked for so many things, like Babesia, I mean, all sorts of stuff. And neurology and infectious disease never found the source. So it's just like, he was really harping on the fact that it was right after that tick bite. But yeah, but we never found, yeah, we definitely never found the source of that. Great, and I think that your discussion and evaluation of this patient really highlights a very important point in many of the motility patients that I'm sure we're used to seeing, which is that motility disorders rarely happen in isolation. And so you may, the patient may present with constipation, but it's important, and I think that's the utility of the wireless motility capsule in that you should really assess for global dysmotility, where there's one defect, there's usually multiple. So in order to comprehensively work up and evaluate and treat a patient, I think it's important to highlight that aspect. Yeah, thank you. And then Ahmad here is asking a really good question. Can you combine like PEG, Docusate with other therapies such as Tenapenor and Buccalapride? And I think absolutely. Those all have different mechanisms of action, and sometimes we do have to. So I think the biggest, I guess, thing that I see is done in the outpatient practices sometimes from my referrals is that I think folks don't necessarily combine the meds. Like they'll be like, they'll start one, and they'll be like, oh, that didn't work. Or maybe it works, but partially. Then they stop that medicine, and then they try something else. Unfortunately, with insurances, you may have to do that sometimes, right? But I usually try to overlap them. So I say, okay, well, you already have this medicine. We already got this one approved. Let's say this is no longer working. Let me order this other one, and just, you combine them. So you can absolutely combine Tenapenor with Enlacotide, because those are two different mechanisms of action. You can combine PEG. I mean, for these kinds of patients that have neurogenic bowel, don't worry about even giving them Docolax, because most of the time, the important thing here is that this is not a patient with irritable bowel syndrome. Even for chronic idiopathic constipation, Vizicodile is on that list. You could give Vizicodile. And there's no tolerance to these things. This is different than a laxative abuser, eating disorder patient that's just abusing laxatives. But in this circumstance, they're probably not gonna feel the cramping from the stimulant laxatives anyway, because they have neurogenic bowel. And so these are nice options for the neurologic patients. So I do give that to the Parkinson's, or we have better drugs, I think, for those patients. MS patients get a lot of Vizicodile, Docolax suppositories. You can also do like Magic Bullet suppositories, glycerin suppositories, because really the markers were in the rectal sigmoid colon. So this probably still is a colonic inertia, slow transit patient, but they also happen to have dyssynergic defecation. And who knows, because this patient said that they were always constipated. So maybe they always had some dyssynergia, and now whatever happened, happened here with this whole fiasco with this encephalitis. And then now they have this megacolon, and we've got to treat the constipation. So I think those are absolutely easy. And then you should combine with some suppository before these devices are done, like these irrigation systems, clonic irrigation systems, because you actually can tell if the Magic Bullet or the glycerin suppository helps, then you know you're giving enough oral laxatives. You just need something to open the gate, right? So at the bottom. So I think combining these agents with that kind of agent, it makes it really helpful, I think, for the patient, and for you to sort out what you're going to give this patient to just help them. But usually in between one of these, you can save the colon from having to come out. And then of course, there's those extreme cases where, you know, patient has to get an ostomy, or if they can expel that balloon, balloon expulsion and things like that. You know, if it's normal, if the balloon expulsion is normal, they could get collected. And when you give this patient a home NMI irrigation system recommendation, what is your goal when you talk to him? Do you say, you know, kind of three times a week you should be having a bowel movement, or how often should they be titrating this to? Yeah, I mean, I think three times a week is a good goal. That's usually so, you know, because it's a lot for them to do every single day. And some of these, it can take them an hour to three hours to do this, you know, because they have to put water in the thing, they irrigate, and then they sit on the commode and it may take forever, I mean, long time for them to be able to really excrete everything. So yeah, so I usually will tell them, do it every other day, and let's see what results you have. If a patient has a fissure, like an active, obviously a thrombosed hemorrhoid, or a fissure, or rectal pain, this is not unfortunately an option, because this, you know, they have to insert this in, the probe, and then that they're going to have tenderness. So that is somebody you can do this in. Obviously, if they have proctitis, then these aren't something you could use, but hopefully without those things, then this is something they can do every other day. And usually the patient feels so much better and they can, you know, increase the volume as tolerated. Usually I'll start them with 500 mils and then increase it. They have, the companies that work with these systems have nurses that can also train you and your APP and your nurse, you know, because not a lot of it is me training anyone, right? Like I order it, I recommend it, I document on that neurogenic bowel questionnaire that they give you, and then it's really the APPs that are able to educate the patient with the nurse that works with the company. So, you know, it's not, the work shouldn't be necessarily on you guys as gastroenterologists who are busy, I know, and scoping patients. Right, and I think you brought up a great point that I wanted to highlight, which is, of course, it goes without saying that these patients should have a detailed rectal exam in your clinic as part of the evaluation, because as you said, if they have an anal fissure, that really needs to be addressed and you shouldn't even be inserting anything in the rectum at that point. Yeah, absolutely, exactly. And what do you feel, what do you tell patients or what's your thinking about Miralax use in CIC? Yeah, I think it's effective. You know, I think definitely there are patients that, you know, do well, it's easy, right? It can be taken as a powder. So some patients just prefer that to tablets. So I think these are good first agents that you could absolutely use. Maybe by the time they come to us, like I don't see any patients on Miralax anymore, because I feel like, you know, by the time they come to me, it's been already been tried and they're bloated or they had some side effects or it didn't work. So I think, you know, in the primary care setting, absolutely, those should be the first trials. It's probably, you know, but it's not inexpensive necessarily, unfortunately, but I think that is something that we should resort to first and then go to these prescription medications if it's not helping. But of course, abdominal pain, bloating doesn't get better. You know, it doesn't help all the symptoms of an IBS patient, but for CIC, absolutely. You have a limit of how many capfuls per day before you say this isn't working? Well, the dose that's supposed to be is once a day, but I've used it twice a day in many patients. I think by three times a day, they get a lot of bloating, you know? So even in the CF patients, those are the ones we push just the most because it's very hard to get the other agents, to be honest, approved. And they're most, the CF patients have constipation all their life and the pulmonologist have put them on Miralax as they get to, you know, the first one. So they're very used to that drug and are not scared of it and it doesn't have drug-drug interactions, right? So that's, you know, those are patients I will push it sometimes three times a day to prevent any constipation side effects, you know? I'll like diastolic idiopathic obstruction syndrome, but for most patients, I don't think I go above twice. You know, I think by that point, you should, we have so many drugs now that we can choose from. Luckily for the lower GI, now for the upper GI tract, different story. For small bowel, different story. But yeah, for colon, it's like, oh, good. Right. Yeah, those are wonderful practical points. Thank you. All right. Okay, so I'm going to move on to the second case. Okay, the second case also rare. You know, you guys are probably not really going to see these things, but I want to show you the more extreme. I feel like the more extreme you see, your other cases will be really easy. This is a patient with prune belly syndrome and I'll talk about what that is later, but severe constipation, explosive diarrhea also, fecal incontinence. And then, you know, this patient actually played sports in the special Olympics. I know this is like Olympic time, and I'm sure all of us are like zoomed in to that every night. And then the patient doesn't actually have upper GI symptoms, no nausea or vomiting. From the records I had, you know, they had an upper endoscopy in 2008 that showed retained food, chronic gastritis, a gastric emptying study that showed 10% emptying at four hours was fine, but they only ate like one egg and some water, so it wasn't standardized. Small bowel series showed dilated loops of small bowel. And so there's been lots of CTs that keep showing small bowel distension and then anorectal manometry. This patient came to us from Wake Forest and had had evaluation there, which is our like sister hospital at Winston-Salem, Brett Atrium Health in Charlotte. And they had a positive rare, so that's good. They had the recto-anal inhibitory reflex. It wasn't Hirschsprung's. And then there was some weakness of the external puberectalis muscle that was noted, but not the synergia that was read there. And then they had tried a lot of therapies, azithromycin, erythromycin as tablets, which were ineffective. And I write that as tablets because if you're using the motillin agonists for any gastropathic patient, they're not actually helpful in tablet form. You have to give them a liquid form because that's really, they need to bind the motillin receptors. And there are motillin receptors in the small bowel, the antrum and the colon. And so you would want to give that as liquid form. So that's usually a really common thing that I see that people are like, oh, she's aspirating and has gastroparesis. I'm going to give them azithromycin tablets. I mean, it's a great antiviral and it's a great antibiotic, but not for this purpose of motillin agonism. And then Reglan, which is metoclopramide, and that worsened the patient's symptoms. So to go through, I mean, no one, the small bowel dysmotility patients are, their symptoms are all over the place. They can have diarrhea and constipation. They have bloating and distension. You know, a lot of times they'll have burborygmy and they'll comment that their belly makes a lot of noises. So they really come like a lot of our mixed IBS patients, but they're very obviously distended, right? So the physical exam is very different, but there's no way based on symptoms that we can differentiate these patients. So if we saw them on a virtual appointment, there's no way we'd be able to tell like what this patient has, right? So these are patients you really need to see face-to-face. You have to examine them because, and then there's, yeah, the CAT scans, small bowel follow-through is usually show these air fluid levels, but it's not an obstruction. Obviously you want to rule out obstruction, but this is all in the absence of an actual obstruction. So again, you know, you can have obstruction in a patient with pseudo obstruction also, right? So every, unfortunately, every episode where this is, there's a flare is important to analyze because it could be an obstructive episode. They can get all the things that everybody else can get, but there's many different types of this. So there's different types of small bowel dysmotility. There's sporadic and there's familial. The familials are the ones that people come to us in the adult world from pediatrics and they're already diagnosed. So these are the visceral myopathies and the neuropathies. That's easier because they already have a diagnosis. The idiopathic ones that are due to systemic illnesses, that's 60% of the secondary cases. And those are neuropathic. So diabetes is one, perineoplastic syndromes, amyloidosis, which is something I see commonly here because I'm a referral center, and then Parkinson's disease. And then there's these post-viral infection patients that they got some kind of virus and then develop pseudo obstruction. The myopathics are the connective tissue disease, Ehlers-Danlos. There's a type of Ehlers-Danlos that has this alpha actin deficiency subset. And some of those patients can present with small bowel diverticula. So you may see diverticula in their small bowel when you're scoping them. And then also small bowel distension, dysmotility. And then there's these other patients that have ICC abnormalities, mesenchymal origin. And so we'll talk about that. But when you look at both the small bowel and the stomach, usually we say that they're missing interstitial cells of Cajal, which are the mesenchymal pacemaker cells. If they have less than 10 per high power field, that's what the pathologist will comment on. But you have to ask them to do staining for ICCs. So if you do full thickness biopsies, which is the only way you'd be able to see the full thickness and see the ICCs, that's the only way you'll be able to diagnose these patients. But some of them have gone through surgery and may have a small bowel specimen. And you can, hopefully if they still have that surgical specimen, you can tell the pathologist to look and see if there's under electron microscopy and other staining, if they have ICCs. So the ICCs can be in the smooth muscle, they're in the submucosa, they're between the longitudinal and the muscle layer. All those layers have ICC cells. And so they all may have different functions, but we don't actually know what functions all of them have. Some of them help with motility, others may help with the immune system of the gut. You know, there's these macrophages also that communicate with them that, you know, so it's very complicated, but basically these patients with pseudo obstruction may be missing some of those. And then these are some of the other causes. So there's congenital Hirschsprung's disease which is one of these that causes CIPO. There's mitochondrial diseases. Meninges is the mitochondrial neural intestinal encephalopathy that sometime we see Duchenne's muscular dystrophy. These are the things that are again, rare. Celiac is an autoimmune cause. So some patients with severe celiac can have small bowel dysmotility. Lupus, obviously dermatomyositis and scleroderma. Those are ones we see in the connective tissue world and they have small bowel dysmotility and then Lyme disease, others, you know, Chagas disease and just cancer, like perineoplastic syndrome cancer can cause pseudo obstruction. So, you know, those are patients you can send anti-HU antibodies, ANNA antibodies to make sure. But of course those patients will have a lot of weight loss. Now it's rare. So chronic intestinal pseudo obstruction is rare. It is heterogeneous. There's no FDA approved treatment for it. The radiologic feature is either a dilated small bowel or large bowel with air fluid levels. And usually the symptoms have to be at least present for six months to make that diagnosis. You can also do MRI in places that have Sine MRI. I'll show you some pictures of that. It's actually a nice way to diagnose patients. And then really the prognosis depends on the cause. The estimated prevalence of this is one to 0.8 cases per 100,000. And it's actually the same in females and males. So it's not more common in one gender. And then it's really, the diagnosis is made on the exclusion of other things and drugs. So GLP-1 agonist, just for you to know, also slowed down small bowel motility. So they're not just isolated stomach, it's also small bowel and colon. And then there's other agents, narcotics included in Clonidine. So Meninges, which a lot of attention goes to, this is an autosomal recessive and homozygous mutation in the thymidine phosphorylase enzyme. And these patients present with peripheral neuropathy that have GI dysmotility. Usually we're not the ones diagnosing them, they get diagnosed in pediatrics, but I've had some patients that we diagnosed in adulthood and they have progressive external ophthalmoplegia and they can have leucoencephalopathy. So they usually present between the ages of 10 and 40. And so that is something that you may have to rule out, but this requires genetic testing if you really have a patient with these syndromes. They may have dysphagia, vomiting, the labs that you can check are CPK, LDH and plasma lactate levels, they may go up. And so those are nice ways, easy and cheaper ways of evaluating these patients without genetic testing. And then on brain MRI, they'll have cerebral leucoencephalopathy. So our patient was actually evaluated for this and this was ruled out, that first patient represented. So the small bowel issues, they can be evaluated with small bowel antral duodenal manometry. This is probably, although it's not standardized and it's not widely available, this is probably the best way to evaluate small bowel motility. I know we do have wireless motility capsule and that has some parameters, but that's really a capsule that goes through the small bowel, it's not static. So this is probably the best way we have. We used to use it for a lot of other things like refractory gastroparesis, refractory overgrowth and things like that. We don't, I think, need small bowel manometry for that. The sensors are now not the one I'm showing here where it has sensors in the antrum and the duodenum. You have to go past the ligament of trites. The sensors can be a centimeter apart with the high-resolution manometries that we now have available. So this can really give you good pressure waves. And what we look at are these phases of contractions, which we call the migratory motor complexes. So these are antral contractions, you know, contractions during the fed state, the fasting state, and then this beautiful antral activity fronts we call that develop into MMCs, which are these migratory motor complexes that go through the small bowel. And usually we should see an MMC every 90 to 120 minutes. So they're not like often. So this test has to be done over like six hours, eight hours, depending on the lab. And so everybody kind of does their own thing. This is not really standardized, or we ask other experts who've done this and we just follow their protocol. Some do provocative testing where they give tegacerod, truchalopride, octreotide, you know, motillin agonists and other agents to see, you know, usually this is more often done again, also in pediatrics patients. And so this is the way we evaluate pseudo obstruction. And then in this study by Casilli, which now is a long time ago, back in 2008, they superimposed the small bowel manometry. So they did that, and then they did wireless motility capsule at the same time. And you could see that the results are exactly the same. All the contractions lie over each other. And so yes, the wireless motility capsule can also look at this, but again, it's a moving phenomenon. So you may miss one of these phasic contractions, whereas manometry is static, but it is helpful. And not a lot of people love to do small bowel manometry. I mean, that catheter, I mean, esophageal manometry is hard, but small bowel manometry is like 10 times harder because you have to get it past the ligament of triton. It's like eight hours, right? Whereas esophageal manometry is hopefully less than an hour. And then these studies have looked at, small bowel hyperactivity based on the MRI studies and MRI transit studies. So they're kind of nice ways of looking at small bowel motility and of course less invasive, but they're expensive. And when you look at CIPO patients, they actually have most of the postprandial symptoms when they're not CIPO. And then this is a wireless motility capsule that looked at this patient had small bowel transit. So their small bowel transit, the gastric transit was four hours, 48 minutes. That's when the pH is like about two. And then all of this area is small bowel transit. So that's from five hours to 19. So it's about 15 hours, this capsule was in small bowel. So that's very slow. And then you can kind of see the red lines, the motility indices in the colon, they're amazing. They're like high amplitude contractions in the colon, which is like here. But in the small intestine, they're low amplitude contractions. And so this is somebody that has isolated small bowel dysmotility. And so, yes, you can use this as a way in some of these patients to diagnose this. And then just to reiterate, there's been a lot of attention on this. Most recently, I would say in the past few years, that when you have a patient with severe constipation, usually they're not enrolled in gastroparesis studies. So in the gastroparesis consortium studies, they looked at their patients that came in with upper GI symptoms. And 32% of them actually had delayed colon transit. Again, these patients weren't recruited based on lower GI symptoms. They were recruited based on upper GI symptoms. But like we were saying, the symptoms can be very confusing. So patients can come in with nausea, vomiting, but their colon transit is so delayed and we've got targets for that, right? So we have treatments for colonic transit issues and constipation, but not so much for gastroparesis. So some of this was pointing towards treat the constipation and maybe the upper GI symptoms will get better. So just for you guys to remember. And then these are all the studies that have been done looking at role of constipation in gastroparesis studies. And the Medtronic one is highlighted here and patients even with functional aspexia can have delayed colon transit and vice versa. And so these are kind of looking at all the studies that show that there's upper GI symptoms, but you may have delayed small bowel or colonic transit. And so again, whole gut scintigraphy, whole gut testing with wireless motility capsules or whatever tool you have could be really important. And I think this is kind of saying almost the same thing. Okay. And so we've taken patients that are part of, this is not published yet, but we've taken patients that were part of the gastroparesis consortium enrolled with upper GI symptoms. And this is 56 patients, 47 of them were female who had wireless motility capsule at the time and scintigraphy at the same time. And these patients were given different treatments. They were given laxatives, diet, prokinetics, antiemetics, neuromodulators. So the expert physicians that recruited these patients, really gave them different medications depending on the results of the tests. And so if they had laxative that they were already on and a change in laxative was made, those patients were recorded. And so what we found was that the patients that had delayed colon transit, when those patients were given laxatives or their existing laxative was upscaled, they actually had improvement of their upper GI symptoms. But the ones that had normal colon transit and just had symptoms of constipation, those patients being given laxatives didn't necessarily get better in terms of their upper GI symptoms. So that's kind of like the conclusion here is that it's still with a patient who has upper GI symptoms, it's still good to know if they have delayed colon transit because those are patients you may be more aggressive with giving constipation meds because chances are you may improve their upper GI symptoms. Now, of course, in the setting that you guys are in in general GI practice, and in our setting even now, we don't have wireless platolet capsule, right? So I think it's just good to always ask patients, really, how many bowel movements are you having if they're presenting with upper GI symptoms? And then if they're not having, if they're having less than three bowel movements a week, maybe those patients are ones that you could be more aggressive with giving laxatives because that's a target we have, whereas for upper GI stuff, other than dietary interventions and things like that, we don't have a whole lot of FDA approved drugs, right? We only have medical overmind for gastroparesis, right? So I know that's like a lot. All right, now we'll go into some of the fun stuff. So please don't photograph this. This is gonna be submitted at ACG. These are the ATMO trials. And so this is a different than wireless motility capsule, but in this study, this is the validation study where in several centers around the country, patients had both wireless motility capsule because this study was done basically the last four months of us having the wireless motility capsule still available where we could do the correlation study with the gas sensing capsule. And so patients had both this gas sensing capsule and wireless motility capsule superimposed. And these patients had constipation, gastroparesis, mobile issues, recurrent SIBO, all sorts of just GI symptoms. And that's how they were recruited. They underwent these two transit studies at the same time. It was 213 patients from 12 sites. And we paired their results of the two testing, the gastric emptying time, which is what we look at with both the wireless motility capsule and this gas sensing capsule. And there was overall agreement between the two, 83%. For the colon, there was agreement 84% of the time. We don't have the small bowel results, but interestingly, 7% of the patients had small bowel dysmotility. So again, quite a bit of these patients, I mean, that's not a little bit of patients, right? This was only a study. This wasn't a study in pseudo obstruction. This was just a study in GI symptoms and 7% did have delay small bowel transit. So multi-regional delay was seen in 18% of the patients. And I think this is nice because now we kind of may have another tool and this is now going through the FDA to see if this device can also be approved just like wireless motility capsule was so that we have more tools where we could look at whole gut transit issues. And then this is another one. So this is kind of cool. This is the ANX device. It's a magnetically controlled capsule. So you put the patient on a machine, the patient swallows a capsule and then you control it with a magnet. You move it around so that you can see the fundus, the cardiac, the stomach. You can see contractions as it goes through the pylorus. They took patients with gastroparesis and functional dyspepsia. These were patients that don't need to get any sedation because they're just ingesting this capsule. And it's Navicam is the name of that company. They also give them like a sham meal. So they saw the contractions as the patient ate a meal and is like laying down and then they kind of validated that. And when it was a very small, this is a very small study. So it's yet to be determined. It was presented at DDW this year, but they looked at the frequency of and waves of contractions. And they saw that there's actually lower contractions were seen in the functional dyspeptics and the gastroparesis sham meal versus the control. So both patients, both functional dyspepsia and gastroparetics who had had a scintigraphy before and were diagnosed with gastroparesis formerly, they both had abnormal contractions in response to a meal. So again, these are kind of cool things that we may have as tools in the future. And then this one is the poor man study. This is kind of like the blue muffin. We use this to study patients. This is Dr. Dolman, who's a zebrafish expert. She studies autism spectrum disorders and neurodegenerative disorders. And then Andreas Jimenez, who's a pediatric neurologist and then myself. And so we were literally looking at a way that in an adult or children with autism, we could give them a transit test that they were willing to eat, because the scintigraphies, nobody wants to eat that egg sandwich that has these issues. And it's not appetizing and I don't blame them. And then the GBT has spirulina. And so all the kids were like, no, it looks so nasty and it kind of smells. And then there was this, right? So we decided to kind of take a study that was done in patients who actually were being evaluated for short gut, and they were given this blue dye as a transit test. And so we made these muffins that were the exact same calories, protein, like micronutrients as the gastric emptying test, which is the 256 calories. And we put a blue dye in it. And then we had the moms and the parents really tell us when the patient first ingest this meal, and then when they see blue poop in their diapers or the toilet. And so that was our cheap method for knowing what their gut transit is. And shockingly, it was actually really helpful because some patients never saw blue, but a lot of them that have GI distress, it was able to kind of differentiate the patients from each other. So the most severe transit patients were the ones with the more severe symptoms. And for the nonverbal kids, obviously this is something very hard for parents to be able to tell, but these were kids that were gesturing or drooling a lot, or kids that were not eating, they were failing to thrive, things like that. So I do do this in clinic now for some patients because I can't get wireless motility capsule, but I'll just ask them even in not autistic patients to make these blue muffins and then use them as a way, McCormick's blue dye, mix it in and see if you can see what gut transit is. But again, I call it my poor man's way of testing gut motility. Hopefully we'll have better technologies in the future. And then there's these other, so we do have to think about disadvantages of having these machines. So this one is this tele-GI, which is just the concept of having these capsule technologies. The patient comes in a room and they're asked to ingest these capsules and then you can evaluate them with all sorts of different tests. They're not invasive. There's no sedation required for these. The operator doesn't have to necessarily be a physician, use minimal space. There's a financial incentive to do this and some centers are actually adopting this. And then it has AI capabilities. So some of these in the future may be able to just read themselves. And then there's advantages and disadvantages, which the disadvantages, you can't get same day results as you do with endoscopy and you can't really biopsy. So if you see something abnormal, you'd have to send the patient for endoscopy with these capsule technologies. And then of course, always the capsule could get retained. And then this is the creation of these capsule devices that I think will help our motility world in the future. But really the patient gets the box with the capsule, you do tele-visit, the patient ingest the capsule, it gets delivered to you when the patient finishes with the study. So obviously they're gonna wear a receiver. And I think this is probably gonna really change, hopefully the future of GI motility too, where space in hospitals and endoscopy centers tends to be an issue. And then this one is a whole gut monitoring, which is more like an EKG, but it's like an EKG of the gut. And so Brian Lacey presented this a while back. It measures electrical gut activity and it's through this Bluetooth device. There's an app that the patient fills out their symptoms and you're really looking at six days myoelectric activity through the gut. And so when they looked at this, it was able to evaluate nausea, vomiting in patients with functional dyspepsia. And those were patients that had less activity. And so I think this will be something really cool that we'll have in our armamentarium, maybe even for small bowel, colon and upper GI because the device goes over the whole GI tract. So it's really, the purpose of this is also for the whole gut motility, but they do need to associate this with symptoms. And then just to note that, really anything helps these patients. So diet is probably number one for patients with whole gut transit issues. Neuromodulators help pain, but they may not help the transit or any of the other symptoms. And then prokinetics along with neuromodulators, this is Dr. Hassler's study, can be very helpful. And then of course, if they have symptoms of constipation, you'd want to give them laxatives because we don't have a lot of treatments for gastroparesis itself. And so I kind of showed this too. Now, of course, most of the patients we'll see will be IBSC. One size doesn't fit all. The symptoms will be distension, but really even in the IBSC population, 2% of the patients could have a motility disorder, right? So you do want to do further testing. If they're severe, if they're not responding to the good drugs that we have now for IBSC, then I think that does warrant sending these patients forward. And all the IBS guidelines now say that. So they say, you know, if the patient has refractory constipation, not getting better, has symptoms of a pelvic floor disorder, send those patients for anorectal manometry and balloon explosion testing. So that's just to point out, you know, motility disorders can be seen in patients with IBSC, you know, but these are the other, I guess, pathophysiologic mechanisms. And then the vibrating capsule, this capsule has kind of revolutionized in a way, right? This is a new treatment that's not drugs. And it goes, travels through the whole gut. The quality of life of these patients improved. At eight weeks, it was better than placebo. Three different phase three studies have been done now. And they had more complete spontaneous bowel movements with this capsule. Some of the patients can feel it as it goes through, but you don't want to do an IBS patient that has a lot of visceral hypersensitivity because that patient may have a lot of pain with this capsule type device. And there is some data that there's even enteric nervous system kind of gets activated. And so gastric motility may be stimulated also, even though it actually acts on the colon. So maybe it stimulates the gastrocolic reflex or some of those things. And we do hear that sometimes when patients get wireless motility capsule, that some of the patients who have had severe constipation, all of a sudden the capsule comes out in 24 hours. And those may be patients that this really, you know, activates their gastric stimulation and that's why that's happening. So I think, you know, there's going to be many of these versions of these capsules that will come about, but these are kind of tools that you also have for some of these patients without dysphagia. Okay, and now bloating, right? Because some of the patients that come, they just come to all of us with bloating. So this is a differentiation of the gastric, you know, what we think about, okay, is bloating coming from the stomach, the small bowel or the colon, right? So if it's during or within 30 minutes after the meal, it's probably gastric, you know? So usually the associated symptoms are epigastric discomfort, fullness, nausea, that's functional aspects here and gastroparesis. Then for the small bowel, it's usually 30 minutes to several hours after the meal. They usually will say they pass a lot of gas, they may have abdominal pain. These are the other conditions that are in the differential diagnosis. And then there's the colon ones that a colonic bloater usually is not associated to any meals. So they'll say it's unrelated completely. Their symptoms are mostly the hard stools, difficulty evacuation, incomplete bowel movements. And so those things should make you think IBSC, CIC, or pelvic floor disorder, or again, rarely slow transit constipation. And so I have just highlighted here the algorithm for abdominal bloating and distension. This is in the center. We noted that some of these patients who have alarm symptoms may have small bowel dysmotility. And so those are patients that need extensive motility testing, perhaps in specialized center. But pretty much the rest of these patients don't. And they may be carbohydrate malabsorption, celiac disease. You should think of abdominal phrenic dyssynergia. And these are the therapies that may help them. I don't wanna go through this extensively, but some of these patients that come to us may have transit abnormalities, but they just come in with abdominal bloating. And so these are the testings that can help. And then of course, pelvic ultrasound can be helpful for the patient that is post-menopausal, perimenopausal, and you do have to think about ovarian cancer. And I think there's been some new studies that have come out saying that ovarian cancer is now happening at an earlier age. And so just be cognizant, especially for your female, obviously for the female patients, because those may be at highest risk for that. So just the concept of abdominal phrenic dyssynergia. So these patients can sound exactly like pseudo-obstruction, like small bowel pseudo-obstruction. They'll come in, they'll show you photos of how distended they are at different points in time, sometimes male-related. As the day progresses, this usually gets worse for the patient. And so normally, normal abdominal accommodation is that the diaphragms usually can ascend and the abdominal muscles contract, the intercostal muscles. In a patient with abdominal phrenic dyssynergia, the diaphragm actually descends and the intercostal muscles actually expand and they relax. And so the belly just kind of protrudes out. And these patients have anterior wall relaxation and feel like they're very distended and they'll tell you they feel pregnant. And what helps here is diaphragmatic breathing. There's EMG biofeedback that can be helpful, sometimes low FODMAP diet, and then central neuromodulators and hypnotherapy. But this is very different than the concept of obviously pseudo-obstruction, where in pseudo-obstruction, imaging actually shows distension of the small bowel. There's air fluid levels and all sorts of stuff. In these patients, they're very symptomatic, but imaging doesn't show any of that. The small bowel is not distended, it's really just their abdomen. So there is a way to differentiate the two. And then I guess lastly, the next few slides are really just about, who do you refer for pelvic floor therapy, anorectal manometry and balloon expulsion. It's not every patient, but again, if they have severe constipation, they're not getting better on oral laxatives and oral prescription laxatives. Those are patients you may want to send forward. And then specific symptoms, if the patient says they're using digital manipulation to have a bowel movement, they're excessively straining, they have fecal incontinence, 30% of patients with fecal incontinence, it may be due to retention of stool. And so those patients may benefit from having anorectal manometry also. And then rectal prolapse, you know, a rectal seal. So let's say the patient had an MRI defecography, a rectal seal that's over four centimeters is usually what's concerning for our urogynecologists and our colorectal surgeons. Those are the ones that they'll intervene in. And then complicated vaginal deliveries would be a patient that you would think about a pelvic floor issue. And then of course, someone who doesn't have a bowel movement for a whole week, despite laxative use, you'd want to send forward. And then other patients where we get sent anorectal manometries or BET are just ostomy takedowns who are gonna get surgery. Usually you want to do that within six months of the ostomy and prove on a balloon expulsion that they're able to pass the balloon before they get takedown and put together. And then these catheters have all evolved, right? So these are all the different catheters we now have. We have high resolution, we have a 2D probe and a three-dimensional probe that's available. The three-dimensional is nice to evaluate the fecal incontinence patient because you can see if there's a sphincter defect, but otherwise the two-dimensional probe is fine and can be used. So these are the solid ones. Again, a rectal exam, like Lavanya was saying, is really important to do because if a patient has a fissure, you can see that this probe may cause a lot of tenderness. So you may want to use the other smaller probes for the patients. And these are really nice devices that we can use for evaluating. And this has been standardized. So just like the Chicago classification, this is the Satish Rao protocol up here that was published by ASNM and ESNM. And so this is one protocol you could use. The one in the bottom is a modified version of that, that really cuts this test short, tells you for the nurse, especially, like I just print this for the nurses as the protocol. And so they do it exactly this way on every single patient, no matter what, you do want to check the cough reflex, which is inserted on this one, whereas we don't have it in the top, but sensory testing, it tells you how to do all those. And this is really the London protocol that is the standard. Now we're in the first version of this, there are gonna be different versions of this that will come about, but hopefully this is something that will be further developed. And then just to reiterate the functional defecation disorders, you have to have two out of three tests abnormal to call it these. So the choices are balloon expulsions, cause I know there's studies that are like balloon expulsion is enough. You can just do point of care testing and you don't need to do manometry. So maybe in places that don't have manometry, you could do that, but really anorectal manometry is a physiology test. And it's a lot more helpful than just balloon expulsion by itself. Cause you can have an abnormal balloon expulsion because of structural issues. And the anorectal manometry is just more about muscles and coordination and this synergia patterns and impaired propulsion. So they're really providing kind of different tests. And both of those have to be abnormal to call it a functional defecation disorder. If you don't have one of those available, you could do an MRI defecography or a barium defecography. So, and they have to have symptoms at least six months, just like all the other, you know, the Rome criteria. And then you have the two different ones are inadequate defecatory propulsion. So it's the force of the contraction and then the synergic defecation patients. These, the pelvic floor muscles inappropriately do not relax when they're supposed to. And so this is like, you know, the standard, how we do it in our center. We just follow that London protocol. And then this is a patient that has good squeeze, but during the push maneuvers, they did not relax the sphincter muscles. And so this is somebody who has this synergic defecation, their balloon expulsion also failed. They did have rare. So they had normal relaxation of the internal sphincter muscles. And then this is a patient that has fecal incontinence and during the push maneuvers really had poor propulsion and the sphincter muscles didn't really relax well. So, and this patient during the rest had very weak muscles, external sphincter muscle. And so this is a patient with sphincter weakness, impaired propulsion. You would send both these patients forward to physical therapy, because that would be biofeedback would be definitive therapy. And so the types of other therapies you could do for this synergic defecation are diet, exercise, fluid, habit training, sit on the toilet when they feel the sensation to go. And then specific treatments, you could do botulinum toxin injection, especially for the pubertalis patients that have levator ani syndrome or pubertalis dysfunction. Biofeedback therapy, cognitive behavioral therapy can be helpful. And some patients may need myectomy and surgery in the hands of an experienced surgeon. But colostomies rarely should be indicated. So I didn't talk about that case that I presented, but that patient has small bowel pseudo obstruction. The agents of choice for that would be octreotide, which is sandostatin. You know, this patient did have SIBO, gets refractory SIBO all the time, needs cyclic antibiotics. I had that patient also on procalipride, which also works on the small bowel. There's some small studies using capsule endoscopy that show procalipride also promotes small bowel motility, same as tegacerod. But unfortunately, tegacerod is not available. So we did procalipride plus octreotide plus azithromycin in liquid form, because you can't just give octreotide alone. It does promote, in low doses, it promotes small bowel motility. In high doses, it's for short gut, 100, three times a day. But in low doses, it actually promotes small bowel motility, but it actually delays gastric motility. So if you just give it by itself, you need something that's a prokinetic for the stomach to not delay the stomach, because otherwise they won't be able to tolerate the meal. And so that was kind of our tool. And then we had to do cyclic antibiotics and sometimes antifungals, because the patient had refractory SIBO as a result of having small bowel dysmotility. And so, you know, that's, I know a very tough case, that you would probably send that forward. But again, if you know what to do with tough cases, then the easier cases are just like very easy. All right, very good. And I'm done. I want to hear from you guys now. That was a very complex case, but I think very useful in terms of reviewing many different differential items and how best to look for them. And I think it really highlights the fact that bloating is a symptom of a disease. So a lot of patients come in with bloating as their main symptom, but it's really much like an onion. You really have to peel away the layers because it's very often an innocent bystander of really something else that may be causing it, like constipation, like gastroparesis, like SIBO or SIFO. So we're really great that you included that in this case as well, that this patient had SIBO. Thank you. Let's see if we have any questions from the audience. Please feel free to ask. I know, I hope I haven't confused you more. I hope I haven't lost the audience. So Dr. Moshiri, what do you feel about the use of MR deficography and when it would be useful? I know this isn't ubiquitous, it's not at every center and it needs specialized radiologists who are trained in doing this, but when would you perhaps refer to an outside center that has MR deficography in which patient with what features? Yeah, great question. So I do MRI deficography in patients who have rectal pain, because you can actually look at rectal intussusception. I've had a few patients where we've caught that rectal intussusception that we didn't necessarily see it on the day that they had their manometries. So yeah, I think rectal pain, rectal spasm, these levator ani syndrome type patients, proctalgia, feedbacks, I think it's helpful in that patient setting. Obviously you have to do a rectal exam first and make sure there's no costa denia, pudendal neuropathy, things like that. So that patient population, I think is helpful. And then anyone with digital manipulation who may have a structural. So if they have like, if they say they have urinary issues and they have constipation issues, like urinary retention, things like that, then usually I think, okay, this is like a multi-organ issue in the pelvis. And then I wanna see, are they able to on MRI deficography empty the contrast in their bladder? Do they have prolapse of the bladder? Our exams, when we do the exams, we don't do pelvic exams, right? Like when we're examining them on their left lateral, they're not like they would be in a GYN exam where rectal seals can actually really be examined for better. I think we do miss rectal seals. So I think if I feel a rectal seal on my exam, when I'm doing the rectal exam, then I usually think it must be bigger than I think. And prolapse, you have to really have them squat on the floor. And I don't think many of us do that when we're doing rectal exams or even afterwards. So I think we absolutely probably miss them. And in the patient with complex pregnancy history, vaginal delivery, lots of pushing, lots of straining, forceps and things like that, I usually like looking at structural issues. And then of course, obstructive defecation issues, like where they say, I feel the stool comes down, but I can't get it out. I have to use my fingers or I have to change my position in the toilet. I think things like that. I think anorectal manometry is very helpful, but if there's a structural issue, I don't think I know how to read that on manometry. So I usually go back after the MRI is done and I'm like, oh, that must've been the rectal seal or something. So I think there's more patients that probably need it than we think need it. I probably order it less on men, I would say, because men less often have rectal seals and these prolapse issues than women. But yeah, but I think those are probably the patients I think about doing MRI defecography on. Right, and also, especially women who have had pelvic surgeries before, I think would be great candidates to look at MRI defecography on. Yeah, yeah, absolutely. I've also seen intussusception on 3D HRM. Yeah. So sometimes that can be a useful way to pick that up. Yes, no, absolutely. Yeah, I think the few times I've seen it has been on 3D. I don't think I've seen it on the 2D. But, and then same with prolapse. I mean, you can see prolapse on manometry easily, but yeah, but I feel like, you know, unless it's very severe, you may not see it. Right. And going to gastroparesis, which you touched on in this past case, what are your feelings about metoclopramide? I know a lot of people can be nervous about using it. And I think recent analysis has actually showed that it might have been an overstated risk of tardive dyskinesia. Could you speak to that? Yeah, I'm not a fan of metoclopramide because I have had patients that have had it, you know, and it just didn't go away. But that was also before we had these agents that are now available to reverse the tardive dyskinesia. There's like two approved FDA agents that we can use. So, you know, maybe that was part of the issue I had, but really I, because we can't use it for more than three months anyway. And all the patients I see with gastroparesis have symptoms for much longer. I mean, by the time they come to me, everything's been tried, you know, Botox, everything, dilations of the pylori. So I think, you know, I have a very skewed view of the world. I think it's absolutely okay to use it in hyperemesis gravidarum, gastroparesis that's idiopathic, and we're hoping it's going to get better. I think that's fine. Inpatient, I think is fine. Anything that's going to be lasting longer, I think than six months or so. If they're responding, I try to decrease their dose. You know, I don't stop them, obviously. I don't want anybody to vomit. I decrease their dose. I like the ability to use the intranasal format of the metoclopramide. So I think that adds a benefit because, you know, if they can't take oral and they're vomiting so hard, and I actually think for cyclic vomiting, it may not be a bad option. I know that's not FDA approved for that reason, but I think for cyclic vomitors, it may not be, you know, because that's in remission. You know, so I think, I feel like I think of, if you're a gastropedic that's relapsing, remitting, it's fine. But if they're chronic symptoms all the time, every single day, I think that's when I start thinking about other agents and other things I can do. Right. Yeah. Right, and I agree that there's only a three month indication. I personally get around that by giving them a brief drug holiday in between and then restarting, which can be an option for those who are responding to medical opramide. Yeah. No, absolutely. And then I have the Domperidone IND, and I know others that have the Cicipride one. But so I think for those of us that have that, I think we probably go to our IND more than anything else because it has less risks. But of course, with Domperidone, you do have to worry about cardiac risk. So there's always something you have to worry about, but I find that the patients, if they're getting better on Reglan, they're also better on Domperidone. So it's kind of like, I try to switch them. Right, and I think it speaks to, I think the previous, one of the previous questions asking about using multiple drugs. Yeah. I mean, very seldom do I find that IBS patients or motility patients are just kind of cured by one medical drug. It's almost like IBD in the sense that you're sort of constantly titrating based on the patient's reactions to certain drugs. And if it's working, great. If it works at first and it isn't, don't be afraid to revisit the issue and try something else because we really do have a lot of, a lot more options now than it used to be. No, absolutely. And then just like IBD, right? Diet is important. So I feel like for the, especially the upper GI patients, small frequent meals, small residue, not necessarily low fiber is probably very helpful. Right, and I think, you know, people who are labeled as IBS, either with C or constipation or diarrhea, who may not respond to low FODMAP diet, it may be helpful to biopsy them for disaccharidase levels, which is something available to all of us. We can all do a simple EGD and take duodenal biopsies. I know you kind of talked about everything except for this. It's hard to find one case that's going to encompass all the things that you spoke about, but something to think about if a patient is not responding to a low FODMAP diet. Totally, yeah. And even the bloaters, you know, especially the patients that comes in with bloating, right? So I think that's easy. You know, I would say I'm one of them because I'm lactose intolerant, but I never had disac testing, but that would have been nice, you know, like to have the disac testing and you're right. We have it available. Why not test patients? I think it's very satisfying. If you just tell someone stop eating dairy, they, it limits a lot of really delicious foods, right? But if you say, okay, well, your lactose enzyme is bad, just take lactate, you know, we checked it when we did the upper, I think it's nice for the patient to know. Right, and it's about a close to 40% prevalence of of course lactase deficiency, which is very common, but, and the most common disaccharidase deficiency, but I think pan disaccharidase deficiency happens in about eight to 9% of the adult population. So it's more common than one might think. Yeah, absolutely. And there's treatments. So that is, again, like these are things that we check for, but then we also have treatments, so it's nice too. And then I see someone in the audience asking about autonomic testing. Yes, so if the patient has pan GI dysmotility, we send them to, you know, one person that we found that is willing to do autonomic testing for autonomic dysfunction. Unfortunately, it's not widely available. I know it's more done in research settings and it does take an arm and a leg, like a lot of convincing for the cardiologists and the neurologists to do this for us, but yeah, but I think it's why not, especially if they're sweating, they're having these other symptoms, cardiac symptoms getting syncopal, pre-syncopal, right? I think absolutely. It's just that the treatment, you know, they'll give them Florinef. But one thing I would say that they do differently now that I've seen recently is they do try phytostigmine, which is Mestinon. Some of the cardiologists I've seen in neurologists will put them on, you know, a pan gut agent, which we use also as a prokinetic more often than not. Like this has been kind of a pattern I've seen for the past year, actually. So that's kind of nice because I think those are cholinergics and so they can help some of these patients. Yeah, enterovirus testing. Yeah, I used to do that. You know, I did. Yeah, yeah, exactly. So we used to do it after COVID. This is about enterovirus testing in some of these people with GI dysmotility. Well, after actually it was Zika virus. After the Zika virus, we published on this a long time ago and then so has Dr. Patricia. But, and some of those patients we gave IVIG to. Now IVIG is being studied for these patients with autoimmune type of gastropathies, autoimmune related, you know, gastropathies. But at that point in time, we were just checking for these enterovirus and did staining that we had to send to California. Zika happened and then we were sending our biopsies actually at that point to the CDC. Then, so there was a hall after Zika and then COVID happened and obviously that all got shut down. But I think some of these patients it's some kind of virus, right? So I think it could be helpful. And there are patients I think that would benefit from IVIG. Those were the patients at that point that were doing IVIG. And, you know, with COVID, a lot of patients were getting IVIG inpatient, it's expensive, you know, there's a lot of other issues with that. So I like that question a lot. A couple of really nice practical questions. So what's your primary therapy for OIC for inpatients? Yeah, great question. I usually go to lupiprostone. I know we have metal naltrexone and things like that. Also naloxegol, we have available in our patients. It's actually what's on formulary, but we have to first go to lupiprostone, which is what I use first. And then, yeah, and then I go to the PAMORAS, you know, one of the PAMORAS that's available. But we do have them. I mean, I think we need to be able to treat our patients. And again, a lot of times they'll also need other laxatives on top of that. Yeah. And where do you place Vibrant in your constipation treatment algorithm, that the vibrating capsule? Well, they only have to have failed one other agent, which is surprising, right? But in self-pay, I haven't done, but I think that would be, there is an option, it's expensive. I don't know how much it is, but it is expensive. And then they do use the one pharmacy to get this approved. So if you go on the website, it'll tell you like how to do it. But usually I have now done it in all the patients that have failed everything, you know? But I wonder if that's not the right patient, you know? I mean, I think we'll all get that experience here, but I think we're just not used to it. So we're not doing it first line. And I know I'm one of those people. And if they have pain, I'm not gonna do that in patients who have IBS, you know, just in the CIC, that's what is approved. Right. And it's really a device, not a drug. So it goes by a different prescribed mechanism. Absolutely. And then there are patients that will tell you that they don't want to take drugs. So I think those are maybe patients that this would be beneficial, you know? Like if they don't want to take medications. So that's another patient population. Right. And another great practical question. Can you recommend resources to learn ARM interpretation and normal values? Yeah. I mean, I think a good resource would be, there's ANMS, the American Neuromotility Society, has some online things that they've done. Jason Baker has taught a lot of it. They've done it for APPs, but they're also for others. So there's little modules on there. Some of them are on YouTube. So you can go on there, watch them if you like them, say you like them, because it helps the ANMS do a lot more of these courses online. And they're usually once a month, like those courses. But other than that, I mean, obviously coming to the meeting there's also a book, several books on anorectal manometry interpretation and things like that. Some of them are from the Cedars-Sinai group and others. So you can look at that as preliminary. Normal values, the normal values are published. So Satish Rao has a few, we use his Augusta values. You know, he's in Augusta. So I use his normal values for 3D and 2D because my patient population in North Carolina is probably more like the Georgia population. You know, when I was in Miami, I was using the Mayo Clinic one, you know, from the Mayo Clinics in Jacksonville, because I was like, okay, well, I have those. I never had my own normal values. So I kind of do the patient population that I think I'm more similar to. All right. And there's different normative values for women versus men. So that's also important. Exactly. Yeah. Yeah. So they have those published and those. Right. I think there's a lot of societal resources. All the GI societies have online access tools to prior lectures. And there are, I think that would be a great place to start. And honestly, I think you can learn anything these days on YouTube. So it's a great resource. Yeah. No, absolutely. All right. Thank you to our moderator, Dr. Viswanathan, and to our content expert, Dr. Moshiri, for tonight's amazing presentation. Before we close out, I want to let the audience know to check out our upcoming ASGE educational events and to register. Visit the ASGE website for the complete lineup of the 2024 ASGE events. Our next end of hangout session, Approach to Fistulas, Leaks, Perforations, will take place on Thursday, September 12th from 7 to 8.30 p.m. Central Time. And registration is open. At the conclusion of this webinar, you will receive a short survey and we would appreciate your feedback. Your experience with these learning events is important to ASGE. And we want to make sure we offer interactive sessions that fit your educational needs. As a reminder, ASGE trainee membership for fellows is only $25 per year. If you haven't joined yet, please contact our membership team or go to our website and sign up. In closing, thank you again to our presenters for this excellent webinar. And thank you to our audience for making this session interactive. We hope this information has been useful to you. And with that, I will conclude our presentation. Have a wonderful night. Thank you, everyone.

GI motility

diagnostic tools

treatment strategies

Michael DeLuttre

Lavinia Viswanathan

Baha Moshiri

radiopaque marker studies

wireless motility capsules

ANX device

Atmo gas sensing capsule

functional defecation disorders

multidisciplinary approaches