Function Tests & Pain Management: Pancreatic Disease

So I will cover in not too much detail the pancreatic function. A disclaimer on this portion is that we're only discussing direct function testing, and direct by definition means that you directly get the function from the pancreas right away. You are not relying on stool testing for fecal elastase and things like that. Um, and that's really the purpose of this talk, but I'm gonna use this as a chance to introduce our NASAAN, North American Society of Pediatric Gastroenterology, Hematology and Nutrition. It's going to have a one full hour CME activity that we're hosting on June 28th from 8 to 9 only to talk about exocrine pancreatic insufficiency. So stay tuned and register for that event. Um, you will learn much more. So they start with the poll question. Um, would you start PERTS, pancreatic enzyme replacement, to decrease recurrence of pancreatitis and pancreatic pain? And the answers are yes, no, or if you're unsure if you should do that. So there is exocrine pancreatic function testing that are either through endoscopic collection, drying tube method that has been strictly abandoned and replaced by the endoscopic collection, stool proteases. There is the indirect ones that deal with 72 hour stool fat collection and stool fat stain. And again for the sake of the direct function testing, we will focus on the first set of tests, mostly, so. You could really stage the disease from mild insufficiency to moderate to severe. This is the classic teaching of how the drilling method works. You have two kind of double lumen tube and one that sucks from the gastric fluid, so the suction is from the gastric fluid and the other one suctions directly. From it right in front of the ampulla bladder, which is the duodenal fluid, and um these are studies that have shown that bicarb concentration is lower when you have chronic pancreatitis compared to normal controls, and this is really the classic double lumen testing. And as I mentioned, it was really replaced by kind of the end of the 90s, beginning of the 2000s. Dr. Conwell and his colleagues, Tyler Stevens launched the endoscopic function testing and really it was a revolution that we could replace this kind of more sophisticated testing. Endoscopy and collecting fluids to measure either by carb or liases and compare them endoscopic and drying and they really showed comparable results. So the endoscopic hints after that really replaced the drying because the drying, the patient is awake, you're placing two tubes. It requires interventional radiology. So the endoscopic really became the standard. Um we have a protocol that I'm going to show here and run through really quickly, but it does show us kind of a trimmed version of what the adult colleagues have published. It has been published in previous pediatric studies in the 90s as well, where you stimulate the pancreas with either secretin, and this is the dose we use, 0.2 mics per kilo, or CCK cholecystokinin. And be aware that there are so many different trade names in the market 0.04 mics per kilo. You give it at zero time point and then you collect the duodenal aspirates using separate syringes every five minutes for three of them. We use an ERCP tapered catheter to collect those samples so that there is no no mixing with the gastric fluids if there was any gastric fluid that got into the scope while we're passing it to get to our location. Um, this is the lab we send it to. It's a Women's Children's Hospital. The lab has been validated for clinical use, and it measures the activities for 4 enzymes trypsin, amylase, lipase, and chemotrypsin. Um, and from there I'm just showing you pictures of post. Post stimulation, this is the brown kind of gravity dependent tissue where it's accumulating, and this is the ARCP catheter through which we do aspirate the fluid directly from the duodenum. I've been asked when I presented this before if we go to the ampula itself or the pancreatic duct, really just from the second portion of the duodenum. So, um, just kind of some pros and cons, uh, pancreatic function could be abnormal if you check it around an attack. Also, bear in mind we're dealing with kids, so there's a maturation process that happens over the 1st 2 to 3 years of life. And we're in the process of analyzing that and showing our experience with it and then we really need to validate further on a broader scale how we could use noninvasive functional testing of the exocrine pancreatic testing. So with that, I'm going to give the chance for Dr. Andrew Trout to kind of comment on what we do here with the MRPFTs. So what we're trying to do here at Cincinnati Children's with the MRPFTs or MR pancreatic function testing is to non-invasively accomplish or at least simulate what's going on with the endoscopic pancreatic function testing. And essentially what we do is we acquire identical imaging both prior to and following administration of secretin. So there's a question earlier about use of secretin and MRCP. This is our primary means of using Secret tin or the main reason that we use Secretin for MRCP, and we acquire identical imaging sets both prior to and following the Secretin administration. And then when you've got these two imaging sets, and I've labeled the left image here pre and the right image here post, and what you're looking for is that increase in enteric fluid, right? So you give the secretin, we know the exocrine pancreas secretes the fluid into the duodenum, into the enteric tract. That's what they're aspirating with the endoscope. Well, we can see all that with MRI using a fluid sensitive sequence, and so you can qualitatively grade the exocrine function based on the. of fluid that's secreted into the gastrointestinal tract, and this is a normal case. So on the left again you have prior to secretin administration and on the right you have following secretin administration with the yellow arrows. I've indicated the substantial increase in fluid both within the duodenum as well as within proximal jejunal loops there in the left upper quadrant, and so we see a nice qualitative response to secretin administration delay between pre and post. So we do the way our protocol is set up, it's about 15 minutes between pre and post. You give the amount, about 15 minutes for that fluid to accumulate. If we go to the next slide, this is a patient with an abnormal MRPFT test qualitatively again here I'm still talking. So in the upper right there I've shown you a. Maximum intensity projection or a MIP image from their MRCP exam showing a normal caliber bile duct indicated with the blue, blue arrow, and the abnormal pancreatic duct indicated with yellow areas dilated, irregular pancreatic duct. We don't see side branches at this point, but an abnormal pancreatic duct. And you can see again paired pre and post secretin images there on the lower part of the image how little fluid is actually secreted into the lumen on the right hand image indicated by the yellow errors compared to what we had in that prior case. And just quickly to go back to that prior case, note the substantial fluid volume versus the minimal fluid that's secreted into. The lumen in this abnormal case and again this is my qualitative assessment and at this point we are largely interpreting these in a qualitative manner. That said, the beauty of the way that these sequences are set up and what we're able to do by performing identical imaging pre and post secreting is we can threshold the images and we can actually quantify the volume of fluid that's secreted, so. You take your pre-image, you quantify your fluid on there, you take your post image, quantify your fluid there, subtract pre from post, and you have your secreted fluid volume in response to secretin. And the goal of this ultimately is to even go less invasive. You've gone from drying to endoscopic. Can we now go from endoscopic? To completely noninvasive, just an IV in your arm for the secretin and measure your fluid by MRI. So how well does your quantitative analysis correlate to Mysome's analysis? We are looking at that right now. That's, that's the big question. So we've done several steps to get ourselves on the way here. We've proven that we can accurately quantitate fluid. By measuring phantoms, so you can put phantoms in the MR scanner and you can prove that you can actually quantitate the fluid, right? So if we can't even measure it accurately in the first place, you're, it's a nonstarter, but we know we can measure it accurately. And we have some preliminary data in about 35 patients where we have been looking at the correlation between the secretin function, the endoscopic pancreatic function testing, some of the other function testing that they're doing that she said we're not going to talk about at this point, but we are looking at that correlation here. That's another key point. The other key point that we're working on as well, and we've got some grant support to do this, is looking at what's normal. Right, so we know what's normal in adult patients or we think we know what's normal, um, but even the qualitative assessment seems to be different between pediatric and adult patients, at least in my gestalt, and so it may be that there's a size dependency, a weight dependency, and so we're still figuring those sorts of things out, um, but right now this is the main way that we're using Secretin to sort of give a, it's at least an initial. Screening test and at least an initial assessment of is there really massively decreased or clearly normal exocrine function that maybe can help us guide therapy at this point. This may be a silly question, but your image was so pretty of the pancreas there. That the one you showed at the top right, I don't know, was that pre-secretin where you showed the irregular pancreatic, and that got back to my point before, right? So there was a question that came up about the secretin. Do you, do we use it? And in these chronic pancreatitic patients or these acute recurrent pancreatitic patients where they're having ductal changes, the duct at baseline is dilated and abnormal. So we are still unsure whether we really need that secretin to increase the conspicuity of the duct, because in many, in the vast majority of these patients in our. Experience you can really see that duct and you can see the course of that duct even without giving secretin. Does secretin help your imaging of the pancreatic duct? Does it, does it, so it does dilate the duct. I mean there are good data to demonstrate that it dilates the duct. The point is though, in a patient with an abnormal duct, does that dilation add anything? I get it. I think there is a subset of patients where it probably. Does and there's a subset of patients where it probably doesn't and that still needs to be teased and figured out so we're using it on a selective basis largely for the exocrine assessment. Um, the advantage of doing it for exocrine is you do get it for the duct as well, um, but, um, but that's our primary use at this point. Still a lot to be learned there, um, but we're trying to push this forward. So cool, fantastic, um. And uh I think what we'll do because uh we do wanna get on to a few other issues before we finish up this session. So if I could have my slides up again, I'll just wrap up um sort of our management um of our case um and what we saw um with uh OK, yep, he's putting it back up. OK, um, so what we found from, uh, when we look at management of these patients, we look at their, uh, whether there's ERCP or surgical interventions that are helpful, whether it's nutritional interventions that are helpful and is, uh, um. My said already there'll be a nice talk um uh on NASPA about management of exocrine pancreatic insufficiency, so we won't go into details here. And then we'll also, um, I want to turn this over to Doctor Goldschneider in just a second to talk about our pain management because that's really a critical. Issue in our patient population and our center is really fortunate to have a very strong pain team component, both our anesthesiologists as well as our pain psychologists who work very closely with us on many of our patients with chronic and recurrent pancreatitis. So just a quick update on our last poll question. So low fat diet, so the low fat diet. So, um, if we show both the low fat diet where the answer was yes for almost 50%, right, um, and then for the per. For for Pert, it was, yeah, yep. So um if I can have my slide set back up, so unfortunately, the data doesn't hold true to that. So there have been multiple trials that have looked at a number of interventions to try and see if we can prevent recurrent pancreatitis episodes or pancreas pain episodes, and unfortunately, um, low fat diet, PET, antioxidants, and steroids have never been shown to prevent those. Episodes. Now they may affect some of their symptoms. Obviously if they're pancreatic exocrine insufficient and you put them on, they're bloating, their other GI symptoms may improve. A low fat diet is a healthier diet. Sometimes that is helpful with their symptoms as well, but there's no evidence that any of these interventions really prevent recurrent pancreatitis or pancreatic pain episodes. And just a quick follow up on the patient. Um, we did genetic testing. Um, he was PRSS1 positive. Um, he had a low fecal elastase on two occasions, and his endoscopic PFTs showed low amylase and lipase and borderline low trypsin and chimotrypsin, and his endocrine function, um, had a normal, um, hemoglobin A1C and a normal mixed meal test. Doctor Edel will be joining us later, um, from endocrinology, and she'll go over in more detail how we do, do the mixed meal testing. He did have ERCPs. He did show evidence of changes in his ducts, um, so he certainly has chronic pancreatitis based on his imaging and his ERCP findings. He continues to be pain-free and on PT treatment for the last several months. He's actually had, um, catch up growth, and so he's overall doing very well right now. I just saw him in clinic a couple of days ago, um, and so we're managing his enzymes and his nutrition right now and just following him very closely. But with that, I do want to pass it on to Dr. Goldschneider because I think this is a very important and key component to our management of our patient population. Well, thank you, Jeff. We're gonna start with a, uh, a poll question and just the basics to see where everyone's situated. Do you have access to a multidisciplinary painting? Yes, sort of, or unclear relationships? No or don't know, and we'll come back to that in a moment. We're gonna start with a case example to look at some of the um. Non-biologic or semi-biologic components which can really cloud the picture and make management much more complicated. We're going to talk about a 13 year old who had diagnosed annular pancreas, had chronic pancreatitis, and came to us scheduled for a Whipple procedure with the specific question, can you help make him comfortable to get him to surgery and then in the perioperative period. And so If we have time, if we've gotten enough responses pull up the uh poll, so what we have so far, it's still changing. People are still putting in their. But uh you have a good split there sort of no, sort of a no is the majority. All right, so there are there looks like a lucky few out there that that do have access. I'll tell you, I was confused by the term multidisciplinary. I'm going to cover that in 2 seconds, OK. I anticipated your question. I think I have the, uh, slides, uh, setback, please. Um, so the pain consult in our institution, if there is not physical, uh, disability, uh, it comprises 33 disciplines. One is a pain physician such as myself and my colleagues. We are responsible for overall medical and, uh, psychosocial assessment, medication management, and interventional, uh, management as far as celiac plexus blocks or other injection type therapies. We involve a psychologist, and this is 100% of the time. This is not an optional modality. This is part and parcel of what we offer, and they do an overall psychosocial assessment. They work on pain coping and functional and emotional impact assessment. So these kids going to school, participating in life activities, activities of daily living such as showering, helping with chores, doing their homework, going to family functions, and so on. They provide cognitive behavioral therapy. And they look at school school and functional assistance and support to help the kids reintegrate if they've been out of those activities. And of course we could not function without our nurses who would do a little bit of everything and keep us organized because as you can see from the graphic that I have up, pains functioning. It's not just a matter of a physical sensation, it's an experience. And since this has so many different points of impact into life, that's the real reason for having a multidisciplinary group of folks to treat and evaluate the pain. So what did we find? Well, the physical exam, skipping to that was pretty unremarkable. Uh, the radiographic study showed an annular pancreas, and he had a history of, of chronic pancreatitis. But on our psychosocial evaluation, he had extensive psychiatric disabilities with bipolar disorder, attention deficit disorder, oppositional defiant disorder. He lived with his mom and her boyfriend. Now that sounds bad, except her boyfriend was the most wonderful person in the world and was very, very helpful. But he had very limited resources. They were in a rural area. They were very poor. He saw his father about every other week. There was a lot of school stress and family stress, and from the family history, Dad had pancreatitis, so his, any genetic predisposition, which at that point was untested, might have come from him. But oddly enough, whenever he went to his father's, he went off of all of his medical regimen components, so his diet was everything that had been recommended against. His enzyme therapy stopped. And as we probed into it, his recurrent episodes that would land him in the hospital were timed almost specifically with when he went over to see his dad, and then the following week. He also had a history of migraines, and this compounded things because sometimes, you know, it was hard to say whether he was staying home from school because he had a severe migraine or with belly pain with nausea or some combination. So all of the above had to be addressed. So here's the next poll question. How comfortable are you, uh, in discussing with the families the need for psychology for pain management? That's very comfortable, moderately comfortable, not very comfortable or flat out uncomfortable. And we'll come back to that. So from, from a psychological standpoint, there are a number of things that the psychologist brings to the interaction which are crucial. All right. Cognitive behavioral therapy is the standard, state of the art therapy for pain management, and that comprises anything from relaxation, uh, coping, biofeedback, a number of different pacing and management skills. Family intervention, and you can see how in this case that'll be kind of an important thing. They coordinate with psychiatry locally. They can't prescribe medications in the United States, but the psychiatrists can and do. And so having some guidance as those therapies are entered in can be very, very helpful. And in this case, supporting the mother was important. I mean, as I mentioned, the boyfriend was very, very helpful, but mom was feeling very caught in the middle between what the father's lack of interventions would be, what she was trying to accomplish, and the boy's psychopathologies. So let's see our comfort level in our audience about uh referring to 50% are yeah not very and that is and that is and that's not uncommon. That's actually um it's no different from our colleagues locally of course because we've been here long enough and been active long enough that are a little more comfortable, but raising that issue is still very touchy. There are a lot of social. Um, stigmas about mental health, mental illness, treatment for it. Um, there may be issues, um, in certainly in this country, but maybe others where paying for those treatments is, uh, is not robust or maybe absent completely, in which case they can't even get those services. So why bring them up? So it, it is a very touchy but very important subject. If I could have the slide back, I'd like to touch on, on medication, um. Now, we used a couple of sets of medications and this has been alluded to throughout the, the, the talks. Um, from the non-opioids I've used topiramate, which is commonly used for migraines, and this actually worked well and controlled his headaches along with the other therapies. And it may have a a a role for visceral hyperalgesia where the gut has become sensitized by, you know, repeated, usually inflammatory processes. We did use opioids and in this case we wanted something long lasting that was easy to take, um, and we used low dose methadone, and we won't have time in this session to get into the role for opioids, but I'll just say very simply that I look at opioids like any other medication or any other procedure. It's a tool to do a job. Um, you wouldn't pound a screw into a wall with a hammer. You wouldn't put a nail in with a screwdriver. You use the right tool for the right patient. We'll talk more about that later. He was on it for about 2 years, and weaning off was actually not a problem at all when the time was right for that. So opioids, let's just throw this out there. This is, this bothers everybody. All right, I don't think I've run into anybody besides my immediate pain uh treatment colleagues who are totally comfortable with prescribing opioids. They can be very, very useful, but you have to be careful, uh, more careful than my typing was apparently, um, so. You have to do a lot of risk. You do risk assessment. We do mitigation. We have a whole protocol that we use in our state, in the state of Ohio. We have to get informed consent for the use of opioids for chronic purposes in minors. That's a relatively new law about a year ago, and that may be different to your own locality, you got to observe your own laws. We have them sign a controlled substance agreement, so we lay out what the rules and expectations of therapy are. That's really important. It's not medically legally worth very much, but as far as an understanding between you and your patients, having a set of rules where you know what to expect from one another is really, really helpful. We track your prescription history. We're lucky to have an automated way of doing that where we can see if a patient's bouncing from us to several other doctors, getting opioids from each of them for the purposes of some sort of misuse. We use the lowest effective dose, and the choice of opioids we'll talk a little bit about in the 4th session, I think, for time purposes, but there are a variety of choices. What was the outcome? Well, for a couple of years this young man's pain resolved without any surgical or endoscopic intervention. He came off of all of the pain medications. He went back to school. He enjoys fishing. He likes playing with his friends. We worked with the family dynamics so that the interventions that would happen when he saw his father were no longer. Having a bad influence on his medical condition and surgery has been deferred indefinitely and so this is one of those cases where by stepping back and using that multidisciplinary approach we actually saved him from a major surgical procedure which if he needs in the future, obviously we would all reserve the right to reconsider it, but for now he didn't need it. So with that, I think we're gonna wrap up this session. Let's see we have any last comments or questions. Uh, one quick question that I just comment that Mira Menon said that in community practice, yeah, I, I'm shocked about that, Mira, but that, uh, in, in community practice recommending psychotherapy in the setting of actual pancreatitis is would buy a lawsuit. In other words, you're, you're, you're, you're saying you're, you're crazy. Uh, and so, yeah, we, that's it, yeah, um. It, it would invite, you know, if I were to come out and say, look, you need a, you need a psychotherapist because, you know, I, I, there's nothing going on, this pain is out of proportion, uh, you know, your behavior is unreasonable, you're just drug seeking. I wouldn't worry about a lawsuit so much as about getting smacked in the face. All right, that's, there are ways of communication that can be tactful, um, and we spend our visits tend to be kind of long, and we spend a few minutes just talking about some of the neurobiology, neuropsychology of pain. And I have a number of anecdotes and images that I use and sort of just fun folksy kind of images that bring forth the relationship between emotions and thoughts and pain. And if we have a moment, I use a paper cut. You get a paper cut opening a million dollars lottery ticket. How much does that hurt, right? You get that same 2 millimeter cut opening up, um, say an overdue bill or in the kid's case, a bad report card example. So this is so much more than the pain of a paper cut, right? So the interplay between our emotions and our thoughts would be that much more important. And so since we're treating a whole person and not a hurting body part, yeah, those are some of the ways that that we use because otherwise we would get hit with the same kind of. They would feel like they've been disrespected. You can't say we have nothing to offer you. Go see a shrink. I'll tell you what, go see a psychologist. That, that really puts people's backs up, and it's not therapeutically helpful. What I like about it is Rich Falcone, uh, did a podcast and he said that for patients that come in, come in, you're suspecting, um, a child abuse. OK, uh, we, we. Most places sort of they hear things they suspected so they say we're going to call child services here they do it on everybody. So if you do it across the board, then you don't have to worry about, you just say, look, this is what we do for everybody, then you don't, you're not singling someone out and saying you've got some issue going on, correct? And that's what I said it's it's, it's a nonstarter to say, well, you're going to come and see our pain management group and not see the psychologist, right? It's just part and parcel there. I love it crucial member of the team. And we've changed some of the way we've approached some of the inpatients who come in with abdominal pain while we're still working them up to see if they have pancreatitis or whatnot, and have psychology see them very early on regardless of the end diagnosis, because it doesn't matter whether it's put it in quotes, organic or uh psychophysical, as as a colleague of mine like I think it's call it. We are whole people and so we've taking care of them is what gives you a good outcome. That's great, great. With that, we'll wrap up session two and we'll head to the more interventional endoscopic surgical components of pancreatitis, uh, after a quick little break. So we'll take a 5 minute break. Does that sound good, Mark? Yeah. All right, we'll be back in 5. Thanks. Great session.