All right and welcome back. This was that session was fantastic, pretty fiery. We want to keep it going. We're now going to bring it into session part two. Before we do, I want to invite everyone during the breaks to please visit the exhibit hall to look and see all the stuff that Cincinnati Children's is about and get more information about the hospital. Again, remember that they are the ones that have been providing these incredible educational events and we want to. Help support them and look at some of the stuff that they're talking about in their exhibit. So without further ado, uh, Jamie, I'm going to turn things back over to you for part two. Great. So we are moving on, moving on from acute pancreatitis, acute recurrent pancreatitis to now the chronic disease state, and how do we manage the chronic disease state? What are the implications from a genetic perspective for kids? How do we do pancreatic function testing, etc. etc. So I'm going to turn over to Joe Palermo, who's going to moderate this session. Thank you, Jamie. Um, If I can have my slides up, please. So what we'll talk about, um, uh, in this next session and hopefully we'll keep a lot of the interaction going because I think the first session was outstanding. Um, we'll go through chronic pancreatitis, um, and, uh, it's, uh, diagnosis, it's management, um, with the hope of, uh, sort of expanding, uh, on what you may already know, uh, and bring in again our phenomenal panel here to, to answer questions for you. Um, as one of the disclosures, Doctor Goldschneider, um, we'll be discussing off-label uses of some medications. So chronic pancreatitis, when we think about patients with chronic pancreatitis, we think about the, the, the pain as the main component that they often have, and then obviously they're going to have changes in their pancreas with calcifications oftentimes, as well as changes in their pancreatic function and exocrine pancreatic insufficiency. So our first poll question, um, recurrent pancreatitis and chronic pancreatitis are essentially the same thing. Yes, no, or unsure. So go ahead and answer that question and we'll go through a few more slides, uh, and get back to your answers. Um, so, chronic pancreatitis, as I said, we'll go through our definitions, um, we'll go through a case presentation, and then we'll, um, go through the diagnosis and management. So acute pancreatitis to recurrent pancreatitis to chronic pancreatitis, the natural history of this progression is really not known. And while we think that that's all patients go from AP to ARP to CP, it's not clear that that that that is actually the case. And a lot of what we're working on at Children's and along with the consortiums we're part of is to sort out what is the actual progression, especially in pediatrics. The main consortium we're involved with is the Inspire Consortium, and with this group we are looking at predominantly chronic pancreatitis and acute recurrent pancreatitis. We're trying to identify the natural history of the disease as well as what are possible biomarkers, and then hopefully the best therapeutic interventions to prevent progression of disease. One thing we do know from the literature is that if you look at all the studies that have been done for acute pancreatitis and looking at its progression, between 7 and 34% of pediatric patients will eventually develop recurrent episodes of pancreatitis, and you guys just touched on this in the first presentation. Um, but the definition for acute recurrent pancreatitis, um, is again two distinct episodes of acute pancreatitis with either complete resolution between episodes, um, or complete normalization of enzymes between episodes. Um, the exclusion for this would be is if they develop, uh, the sequelae of pancreatic pseudocyst, um, with their first episode. So then what is the actual definition of chronic pancreatitis? And so we do know that in chronic pancreatitis, the presentation again can be a little bit variable, but what we want to see is that it's a combination of both their clinical presentation as well as their imaging findings, and we see that there should be some abnormal imaging findings that go along with what you're seeing clinically, usually ductal irregularities, calcifications, or pancreatic gland atrophy. And we see these mainly in pediatrics by CT, MRCP, and ERCP, um, in adults, uh, and in some pediatric cases, uh, endoscopic ultrasound is used as well. Um, and, uh, we will be talking about EUS a little bit more in the third session, um, but those have both, uh, with EUS have both parenchymal as well as, uh, ductal characterizations, um, and depending on the number of criteria that you meet, um, uh, you may meet the threshold of uh diagnosis of chronic pancreatitis. Uh, in addition, as you'd expect, you'd have to have abdominal pain consistent with, um, a pancreatic origin, uh, or, and, uh, evidence of endocrine or exocrine pancreatic insufficiency. But what does this actually look like in the pancreas? And so what you can see on the left is a normal pancreas, and on the right you see the um the irregular fibrosis, loss of assinar cells, um, there's eyelet cell loss, uh, and there's infiltration by inflammatory cells. Um, but again, we generally don't get biopsies from the pancreas, and so we rely more on imaging. Um, and so these are just some representative slides to show, um, calcifications that you may see in the pancreas. As well as ductal changes, and here on an ERCP you can see there's a uh dilated um main pancreatic duct, as well as uh evidence of dilated side branches. And as disease becomes more advanced, you start to see um uh clubbing of the side branches as well. And. So if we can go back to our poll question and review our answers. So, it looks like 50%. Said answered no. Which is, you know, with, as you can see from what we were just talking about, there should be a progression. You should because patients can certainly have acute recurrent pancreatitis and not have the evidence of ductile changes or pancreatic atrophy or pancreatic function loss. And so, uh, what we don't know is What leads them, tips them over the edge, what takes them from having acute recurrent pancreatitis to actually then developing chronic pancreatitis. It may be the ongoing inflammation, but there may be other factors, and we'll get into some of that a little bit later with regard to genetics or other ideologies that may predispose them to chronic pancreatitis. So, uh, oh, I'm sorry, I went too fast. So, um, the next poll question, uh, does low fat diet decrease recurrent and chronic pancreatitis? So yes, no, or unsure. And while you're answering that, we'll go on to our case for chronic pancreatitis. So this is a very interesting little boy. So he's a 10 year old male who was previously healthy by all accounts, um, who presented to a local emergency room with acute onset of abdominal pain, nausea, vomiting, and lethargy for about one day. He was seen at the local ED. He had a normal CBC, a normal CMP, and a normal lipase, and they did a CT scan to rule out appendicitis. And I'll bring in, uh, Andrew Trout to discuss his imaging findings. So what you can see right off the bat on this CT scan, it's a little surprising, at least from our perspective as a radiologists, that this patient would have been symptom free. The right lower quadrant was normal in terms of the appendix, but what you can see looking at the pancreas, and I've got on the left an axial image, this was done without contrast at the outside hospital, without intravenous contrast. There is oral contrast on board, and then on the right is a coronal image. Of the same scan, and what you can see is extensive calcification throughout the pancreas involving everything from the unsnip process out to the tail. The pancreas is atrophic, so it's decreased in volume, and the contour of the pancreas is abnormal. We don't see any findings on this set of images right now that suggest that there's an acute attack going on, but there are clear findings here of a chronic process in the pancreas. And then following that, still at the uh local um institution, he had an MRI. And so this, these two cases side by side show a little bit the strengths of MR versus CT, and what you see here on the MRI, the yellow arrows again indicate the pancreas like they did in the prior set of images, and what you can see is again the gland is atrophic, but all that bright signal, those branching bright signals throughout the pancreas, this is a fluid sensitive sequence. You can tell that by fluid in the gallbladder as well as in the spinal canal, and what you see. Throughout the pancreas, all of these branching structures are the dilated ducts, and you really could not see those on the CT. That's the strength of MR compared to CT is visualization of the ductal anatomy of the pancreas. The blue arrow here indicates an intraductal filling defect that is one of those calcifications. So there's a stone here in the duct. There is some dilation of the biliary tree, and the gallbladder here is quite distended, but MRI really does give you a much better look at the ductal anatomy than CT does, and CT does in general. A better job of highlighting those parenchymal calcifications that you'll see in cases of chronic pancreatitis. Do you see any calcifications on the parenchyma on this MRI? So what we can see on this MRI is that the signal of the pancreas is lower than what we would typically expect it to be. Again, it's not as obvious as on that CT, but some of these punctate fossa, I know the cursor is small here, but I am indicating a punctate focus of lower signal than the remainder of the pancreas reflect. Those calcifications that we saw on the CT, but it certainly is not the same level of conspicuity that you get on the CT, though that patient, you would have seen those calcifications on a radiograph, right, and they're so extensive. Wow, I wonder, Joe, if you could comment on this, the concept of calcifications in kids. I mean, you know, those are pretty, this is pretty striking. I mean, right, we don't, we don't generally see this degree of pancreatic calcifications in kids compared to adults, especially during their first, at their first presentation. Um, when we do see it in. It's usually after we've been following them for a while where they've had, you know, recurrent episodes that we've sort of documented, and they generally develop, they can develop them over time, but in a 10-year-old who was previously healthy, this is, this is a very atypical finding, but it certainly shows that with chronic pancreatitis, these patients, if you're not thinking about it, you know, had they not gotten the CT scan and they had just treated them as a viral gastroenteritis, we would never have known what was going on with this case. Um, so a little further history because, you know, again, this was very atypical. He'd never had any previous pain or vomiting episodes. There was no family history of pancreatitis that we know of, that the family knew of, and the only really relevant bit of history that we could find is that he had had poor growth and actually very recent over the last 3 or 4 weeks, decrease in oral intake. Due to his and the onset of vomiting, but if you look at his linear growth over time, you can see that when he was younger, 3 or 4 years of age, he was around the 50th percentile for his height. But at the time of his presentation, he'd already dropped down between the 5th and 15th percentile. So obviously there had been something going on for a longer period of time than than than his symptoms bore out. Um, so the next step, thing that we want to talk about, uh, and go through are sort of how, what is our diagnosis and management strategy in our patients with chronic pancreatitis. Uh, we'll talk about the etiology and I'll bring in Doctor Haja to talk about some of the additional testing, um, and then, uh, assessing the extent of disease, um, and then parts of the management issue. Although I will let you guys know some of the management issues will be put off until, um, the, the, uh, the next two sessions. So this is a a summary slide from our consortium which looks at what were the etiologies of our patients with acute recurrent and chronic pancreatitis. And unlike in adults where you see predominantly alcohol as the cause of chronic pancreatitis, with up to 70% of patients with chronic pancreatitis being caused by alcohol, the main risk factors for our patient population were were genetic, and then the second most common risk factor was an obstructive process or an anatomic process. Um, and so I will let uh Doctor Hadjael go ahead and talk a bit about what we do for our, uh, genetic workup, uh, and then our, um, pancreatic function testing. OK, so, um. Again, a very hot topic with the expansion of genetic testings and what's available commercially and non-commercially, so I'll cover it in a few minutes and keep the questions coming. So since 1996, there was a revolution in chronic pancreatitis when Dr. David Whitcomb found an association between familial clustering of chronic pancreatitis cases um and. A gene called PRSS1, which is the cationic trypsinogen gene. It is a gain of function gene, so when it's activated, it sets the fire up. Pancreatitis keeps happening over time with unknown or limited triggers, and then the patient would have chronic pancreatitis and even pancreatic cancer. Since that time, what we used to call really idiopathic is no longer idiopathic because we know it's linked to some genes, and I hope to show you some of that data. Oops. So the first gene discovered, as we said, is PRSS1. So it is the classic definition of hereditary pancreatitis. It is an autosomal dominant disorder. It causes acute pancreatitis in 80% of people who have the gene, chronic pancreatitis in about half, and pancreatic cancer in more than 40%. And that of course goes up with age. Spink 1 is the next one that was discovered on the blog, and it's the trypsin inhibitor gene. It's more of a modifier gene. It is an autosomal recessive, but we have seen cases where even one copy could result in a disease. So it is a risk factor and in combination with other factors, it causes chronic or acute recurrent pancreatitis. We do have also cases of heterozygous patients with SPINC1, even in our own registry and through the Inspire as well. Cystic fibrosis aging is very well associated with pancreatic diseases in general, so the extreme or the severe we want to call it mutations, which is the classic delta 508, causes exocrine pancreatic insufficiency, EPI. even a term we hear now when we're driving to work on, you know, marketing. People are just more aware of this condition, so exocrine pancreatic insufficiency is caused by this gene. However, if the patient is sufficient and have CF mutations, they would be at risk for pancreatitis and then chronic pancreatitis. CTRC is a relatively newer gene, so maybe in the last kind of 3 or 4 years, and it's been shown through even functional studies and essays that it's very linked to development of chronic pancreatitis and acute recurrent pancreatitis. The story still is unfolding. There is more and more that comes, so I'll show you just from our own data when we looked at 50 patients with 34 of them have acute recurrent pancreatitis and 16 of With chronic pancreatitis, 85% of the acute recurrent patients had extensive gene mutation analysis for the four most common genes, and 100% of the CP patients got this extensive gene testing. So we tested them for CFTR, PRSS1, CTRC, and SPINC1, and the data was striking that 55% of the ARP patients were positive and 68% of the CP patients. We positive. So that's really, really a high likelihood. There is no other testing, I think, when you say before testing it that it's going to be positive by almost 70% to the patient. When we showed differences in this table just highlights phenotypic features of those patients. The ones who had chronic pancreatitis really were diagnosed earlier with the first attack. They had more additional attacks and they were more likely to be exocrine insufficient. And this is a busy table, but I'm just going to highlight from it two points that the CFTR gene was more commonly found in the chronic pancreatitis patients compared to the acute recurrent patients, and you are likely to have two genes affected compared to one. So always test not just for one gene at a time. Try to get more bucks for your money and test for more. In the last 2 years, actually 6 more became known to be associated with ARP and CP, so on top of the 4. So we really need to keep up and we really need to overcome the challenges that are associated with the relatively long and inefficient essays. Sometimes we send to commercial labs at different ones and We really wait 4 or 6 months to get the patients back to the, to get the info back to the patient. We have designed to overcome these challenges a next gen platform here in our institution that combines target genes into one efficient and timely essay. We have validated up to this point and strategically designed it at a very low cost, and we called it the Pancreas panel that will be launched in October. So we're very excited because it will improve diagnostic algorithms to identify etiologic diseases in children and adults. We use next gen sequencing and these slides will be saved for later, but to tell you this is. One of the most efficient techniques in rapidly replacing the previous technology, it sequences the entire genome and once you custom platform it, that's the most, that's the most kind of precise and accurate testing you can get and compared to whole exome sequencing, for instance, someone might say why just not send whole exon. You get lower coverage actually with the whole exome and you could deal with incidental findings that you won't be able to interpret to your patients. So affordability, focused analysis, and the short time for the report are the reasons why you want to use a custom platform. We use what we call True, Trueeek custom Amplicone. I list here the genes that we test for, so the pancreatic. The panel would be the most inclusive and it will have calcium sensing receptor gene and all the ones that I mentioned and the clodin 2 and CPA1 amongst others and then we also have a pancreatic insufficiency panel that when you get a patient with Cura, for instance, you get also a good screening whether this is Schwachman diamond or CFDR or other genes that could be causing that. So here, do you want me to cover that, or yeah, let me ask before, before we move ahead to pancreatic function testing, could you comment a little bit on uh penetrance issues with some of these genes, right? I mean, you know, is every patient with PRSS1 going to get rip roaring chronic pancreatitis that's going to be completely debilitating? Yeah, or same for sink one and maybe also comment on. Uh, combination disease process, so genetics and pancreativism. Yeah, actually, uh, Jamie, you ask a very interesting question because both together yesterday we saw a patient in clinic and her kid who has chronic pancreatitis, um, really a debilitating and complicated course, her younger son, and they have a PRSS1, she said, Should I go? Of course I am going to go gene test him. And our response was that you probably don't want to just test for genes, just for testing. He was never diagnosed with an attack of pancreatitis. So there is a penetrance issue where it shows on different phenotypes show differently, um, like we showed from studies by Dr. Whitcomb, the PRSS1, for instance, half of the patients would get chronic pancreatitis, not everybody, so it becomes more of a counseling issue. Do they want to know and um. I think If I, if I covered that first part, what was the second one? I just want to make sure because. This sort of answers the other question. Specifically CFTR, does heterozygosity also predispose you? Yep, and you know, the, the paper that I just showed that got out from our center and also the Inspire publications show that if you have in, in kids, I'm speaking strictly about kids, if you have one gene copy of the CF and you're not homozygous, you're heterozygous, um, by itself it increases the risk for chronic pancreatitis. Um, with another gene, it's, there's like this pink one in CFDR. It's almost 800 relative risk of having chronic pancreatitis. So we want to really extensively gene analyze these patients because the combinations, this is going to be the beauty of the future. It's going to be personalized medicine when you know the patient has this combination of genes, this is what their disease is going to look like in 5 years. This is how it's going to look like in 10 years, and that helps you because, because. Really, the patients want to know what's going to happen. I have my first attack and second attack. Am I going to have cancer? Am I going to have, but you can't do well, but you can now. So you have to remember the CF Foundation actually has a very extensive pipeline of small molecules that they're using for patients that that optimize CFTR function. And so this is especially true for some of the atypical mutations. And so a combination of both knowing what their mutations. Are, are there going to be therapeutic interventions, and this is the first pipeline, the most active pipeline, because these, these are already in production for the CF population. And so for the CFTR mutations, then there certainly may be some options. We may see some differences because the number of patients are already on some of these medications and so we may start to see differences like they're seeing in both their lung disease and their liver disease. We may may be able to start applying this to patients with. CFDR mutations and pancreatic disease and then hopefully down the road as we identify what these, which combinations of mutations are more problematic and understand more about how they, what the interactions are, we may have other therapeutic options down the road, but until you really understand the true phenotype of the patient and their genotype, you're not going to be able to identify which patients are going to be, are going to be able to be enrolled into a trial that can then show whether there's a benefit or not. Got it. And I didn't mean to interrupt you because then so Jamie's second question, um, concept of, you know, throw in pancreativism, the genetic disorder. Yeah, because we know we see patients with pancreas ivism that don't have, we see it in, we find it incidentally, quote unquote on cross sectional imaging studies, right? So there are patients running around with pancreas ivism that don't develop pancreatitis. Yeah. And so is it a two hit process where these are where the division patient who has a gene mutation is the one that develops pancreatitis. Do we know? I love this discussion because we're really jumping ahead of the game. So Dr. Lin through the Inspire consortium, which has now 400 patients, I think you and Dr. Och are looking at this question of divisum and genetic mutations. That is correct. And so there is, as we all know, there are different schools of thought when it comes to pancreas disease, and there's definitely Evidence out there supporting that the majority of individuals who have pancreas and know the risk factors for pancreatitis have have no type of health disease related to the pancreas their entire lifetime. But then there are other individuals who have pancreas and will develop acute recurrent pancreatitis and develop to chronic pancreatitis as well, and it goes back to the idea. As Dr. Trout was kind of mentioning, somewhat of a two hit hypothesis or more than one hit hypothesis on having one risk factor and then an additive additional risk factor, does that increase your propensity to develop and progress to those, those chronic disorders, and uh our general thought is yes, and, and the early evidence that we have right now is, is also supportive of that. Great. Alright, here's a question from Luis, Luis Figueroa, who I think, Luis, I think you're from Colombia, uh, and his question is they have a patient who they want to do genetic studies on. Is it possible to send the studies to Cincinnati Children's? That's the question. Yeah, that's a great question. Absolutely. This is going to be an international available test once it's clinically available for use. Actually, it's validated. The platform is designed. We're just really in the process of setting all the Requisitions and just really protocols for a matter of, you know, practicality. So hoping by the end of September, again, as I said, the World Congress is our deadline to launch it. So hoping if everything goes in line, keep your patients promised, and we will run the test, yep, for the 10 genes together. OK, 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, and that's really the purpose of this talk, but I'm going to use this as A chance to introduce our NASAGAN North American Society of Pediatric Gastroenterology, Pathology 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. That event you will learn much more. So they start with the poll question. Would you start PERS, 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 drying 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 right in front of the ampulla bladder, which is the duodenal fluid, and 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 using 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. 0.4 mics per kilo. You give it a 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. 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. 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. Um, 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 noninvasively 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 Secretin 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 volume. 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 secrettin administration time 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 area, 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. Illumine 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 secretta 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. Um, 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 points that we're working on as well, and we've got some grant support to do this, is looking at what's normal. 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. 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. Can I, 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, because 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. And uh I think what we'll do because uh we do want to 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. Mysam said already there'll be a nice talk um uh on NASPA about uh exocrine 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, 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% um and then for the per. For, for PET, it was, yeah, yep. So um if I can have my slide set back up, so unfortunately, um, 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, um, recurrent pancreatitis episodes or pancreas pain episodes, and unfortunately, um, low fat diet, PETs, 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 PET, they're bloating, their other GI symptoms may improve. Um, a low fat diet is a healthier diet. Sometimes that is helpful with their symptoms as well, um, but there's no evidence that any of these interventions, um, really prevent recurrent pancreatitis or pancreatic pain episodes, um. And just a quick follow up on the patient. Um, we did genetic testing. Um, he was PRSS1, um, 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 chimarypsin, 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 this, do the mixed meal testing. Um, he did have ERCPs. He did show evidence of, uh, 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 um 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, 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 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 so get 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 do have access. I'll tell you, I was confused by the term multidisciplinary. I'm going to cover that in two 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 functions, 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 do a little bit of everything and keep us organized because as you can see from the graphic that I have up, pain affects 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. The radiographic study showed an annular pancreas, and he had a history 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 genetic, 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, 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, uh, state of the art therapy for pain management, and that comprises anything from relaxation, uh, coping, biofeedback, a number of different, uh, 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 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, um. And it may have 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 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. 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. Um, that's a relatively new law about a year ago, and that may be different to your own locality, you've got to observe your own laws. We, 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 a 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. Now 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 you know we would all reserve the right to reconsider it, but for now he didn't need it. So with that, I think we're going to wrap up this session. Let's see we have any last comments or questions. Uh, one quick question that I just comment that Mira Mennon said that in community practice, yeah, I, I'm shocked about that, Mira, but that, uh, in, in community practice recommend 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 about getting smacked in the face, right? 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? You get that same 2 millimeter cut opening up, um, say an overdue bill or in the kid's case, a bad report card a great example. All right, 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, 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, correct. Then you don't, you're not singling someone out and saying you've got some issue going on. So correct. And that's what I said 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 is 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 psychophysical, as a colleague of mine like I think it's call it great. We are whole people and so we 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 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.
