Chapters Transcript Video Pancreatitis in Children and Adolescents: Who, Why, and What We Can Do About It Without further ado, it's my pleasure to introduce our speakers for today, uh, who are, uh, Michelle uh Slosterman and Doctor Emily Farito, um, starting off with Michelle, uh, she completed her undergrad at UC Davis in Dietetics, followed by a Master of Science in nutrition science at San Jose. She also did a dietetics residency at Johns Hopkins Bayview Medical Center, after which she completed her pediatric NP training at UCSF, where she continues to practice today. As for Doctor Emily Perrido, she completed her undergrad degree at Harvard, followed by medical training at Columbia, she completed her pediatric residency at Columbia University Children's Hospital in New York Presbyterian, uh, and then she joined us here on the West Coast, uh, doing her pediatric GI fellowship, followed by a transplant hepatology fellowship at UCSF. Currently, she serves as a co-director of the pediatric pancreas Program. As well as an associate medical director for the pediatric liver transplant program at UCSF. Please join us in welcoming Doc uh Doctor Perito and Michelle. It's all, it's all you guys. Great, thank you. We're really excited to join you today. Thanks so much for having us. Um, we're gonna talk today about pancreatitis in children and adolescents, who, why, and what can we do about it. Um, and I'm really pleased to, to be here presenting with Michelle. Um, here are my disclosures. By the end of this presentation, hopefully you will be able to classify categories and causes of pancreatitis in children and adolescents, identify complications of pancreatitis and their management, and then understand treatment options for complications of acute recurrent and chronic pancreatitis. We should give you a little bit of history about how why when you come to UCSF do you see so many children that are affected by pancreatitis. So back in 2015, we noticed that there was an unmet need for coordinated expert care for children with chronic pancreatic diseases. So not just pancreatitis, but some other pancreatic diseases that we will talk about on a different day. The goal was to coordinate and elevate the multidisciplinary expertise provided at UCSF. In the past, we took care of kids with pancreatitis all the time, but it was a little bit more disjointed, a little bit more just consulting with the experts here and there. Now we really try to have a core team, a bunch of different experts, and then with that also fulfilling the UCSF mission and vision to Drive innovation, improve care as we move forward, find curative options, and train and mentor, of course, the future of our clinical experts in this field. Um, we also wanted to mention a network that we're really fortunate to be a part of. It's called the Inspire Network. Um, as you can see, there are many sites across the country and across the world actually. Um, this has also been running for several years, um, has is a prospective research study, and you will see a lot of the data from that today. We We now have more than 600 kids and teens across the network with acute recurrent or chronic pancreatitis enrolled. Um, and we've been really fortunate to have NIH funding to support this. So I think what we know now about kids with acute recurrent chronic pancreatitis is a lot more than we knew 10 years ago, although also, as you'll see as we get towards the end of the talk, there's a lot still to learn and a lot we could improve. Um, we always like to start by just reminding folks, you know, what the pancreas does, and in our sort of simplified GI understanding, there's two main functions of the pancreas. Um, the endocrine function of the pan. which is performed by the cells in the islets. Um, and those are primarily the insulin producing cells as well as those that produce um counter regulatory hormones to help control your blood sugar. Um, the other part of the pancreas, which is all, you know, mixed into the pranoma and this part along the ducts, is the exocrine part of the pancreas. Um, those are the asinar cells that secrete pancreatic enzymes into the pancreatic duct, um, down into the duodenum to aid absorption, particularly of fats and proteins. So when we think about the pathophysiology of pancreatitis, um, we actually talk mainly about the exocrine side of the pancreas, which, because it's sort of disruptions in that part of the function that seems to trigger um and really set pancreatitis, both in kids with acute, acute recurrent and chronic pain. Pancreatitis. Um, when you have something that triggers pancreatitis, and we'll go through a little bit more what that looks like in kids, um, the sort of main bad actor that we think about is trypsin, which is designed inside your intestine to, um, to cause proteolysis, right? To break down proteins so that you can absorb them. But when it gets activated for any number of reasons inside the pancreas, it starts to digest the protein it finds there, um, causing both edema, necrosis and hemorrhage of the pancreatic parenchyma, as well as activation of a cascade of other enzymes that can also cause damage. So causes of acute pancreatitis in children. When I first started working in healthcare and took care of adult people, excuse me. We used to think that, oh, if you just drink too much alcohol, you get pancreatitis. But how many of us know 4 year olds that are drinking alcohol, right? We, we don't. And so as we've done data collection, we go through the process of figuring out, well, what is the epidemiology. So in some kids it's just obstructive. There's gallstones, biliary sludge, maybe a choliocal cyst, um, maybe there's an anatomic variant in the pancreatic anatomy like pancreas divisum, and ultimately things cannot drain in the way that they should, and then triggers that cascade that Doctor Parito is just speaking of. Other causes that may be more common that you would see a one and done type episode. There's trauma. They were riding a bike, they flipped over, they hit the handle their abdomen on their handlebars, and that caused an injury, an acute injury that hopefully in time will get better and they won't get it again. A viral infection. We've seen plenty of kids who, this story, they come in, they were sick, they get pancreatitis, or they had COVID, they get pancreatitis. It resolves, and we also hope that we will not see them again with pancreatitis. Um, there are some that have medication-related pancreatitis, Tegospirogenase tends to be a frequent, a frequent one that we see in our hospital, um, azathioprine or 6MP, some anti-convulsants, some other medications that we're discovering along the way. Idiopathic, our fancy word for we just don't know. Uh, we've looked at all these other possible causes, we can't find them, so for that moment we just don't know. Hopefully as we do more research, we'll start discovering other reasons. Metabolic reasons, so hypercalcemia can trigger a cascade. Of events within those cells, and then we think also trigger pancreatitis, hypertriglyceridemia. Now we're speaking of levels of above 500, um, not the 100, 200 levels, although we would encourage those kids to make different changes in their life. Um, those aren't the type of levels we think of in terms of causing pancreatitis, and then autoimmune. So as we go through the diagnostic workup, this is the reason why we do some of these checks. So was there a history of trauma? Were they sick before this episode? What medications have they tried? Were they just on some medications? And then what do we need to look for? Um, are they actually having signs of pancreatitis on imaging? We may do an ultrasound or if we can see the pancreas, but looking for something more dangerous or acute, um, before we may move to cross-sectional imaging. Checking their LFTs, maybe there are gallstones or some sort of obstructive cause, and we would see that in their LFTs, a lipid panel, calcium, and then looking for signs of severity, so CBC inflammatory markers, electrolyte imbalances. We'll go through more of this as we move on. Um, we're not gonna talk a ton about acute pancreatitis today, um, but we wanted to just give a little more information, and these, I think are helpful references for you. When I have, um, a kid who comes in with acute pancreatitis, I still look back at these two sets of guidelines. Um, to just help remind me about the different steps in management and workups. So both NASpagan as well as the European Pancreas Club, um, have guidelines for the management of pediatric pancreatitis that are helpful references to know about. You will find that. The sort of like strength and grade of the evidence is unfortunately relatively limited. So I think of these more as like consensus guidelines, as well as an indication about, you know, there's a, there's a lot of evidence basis that we could still build up over time to, to improve how we care for these kids. When we think of acute pancreatitis, we do think of categories. So this first picture on the top is interstitial edematous acute pancreatitis. There's acute inflammation of the pancreas and surrounding tissues. Excuse me, I don't know why I'm losing my voice. This is a coronal CT image of interstitial edematous pancreatitis here, and this is actually in an adult, but it's easier to see than some of our smaller patients. Um, this is a 34-year-old man with acute onset of epigastric pain for 12 hours. This one in particular was due to gallstones. And these arrows where you see the arrows pointing show it's heterogenogeneously enhanced with indistinct margins due to inflammation of the periopancreatic fat, and there's some stranding and minimal fluid where you can see. Emily, I don't know if you can move the cursor so they can see the other arrows or where we're where I'm talking about, but um and then that's also present in those pictures. And then the next figure below is acute necrotizing pancreatitis, and we have pancreatic parenchial necrosis alone, and this is an axial CT image in a 38 year old man. This is 5 days after the onset of symptoms, and the tail and the body of the pancreas are non-enhancing. That's what the arrows are pointing to and slightly heterogeneous in appearance. Excuse me. And I, you know, I would say not every kid that we see with mild acute pancreatitis, who has like pain and an elevated lipase but normal vital signs necessarily needs to get cross-sectional imaging. But when they're sicker with vital sign abnormalities or severe pain, um, or electrolyte abnormalities, then differentiating between these two things can help you kind of see a little bit about what their potential complications are and what the course may be in the, in the coming days. Which speaks to the severity of acute pancreatitis. So there are some risk factors for complications. Um, obesity, we think for severe acute pancreatitis, um, there also may be more complications, systemic complications, some more more uh severe local complications and increased mortality. Mhm And if you have a kid who's been, I say, languishing for days before we see them, assess them, and figure out what's going on, that also may increase the risk for complications because things are happening, things are changing, and they're progressively getting worse, and we see them sort of late. Um, some other comorbidities, whether that be kidney disease, diabetes, um, previous, you know, other comorbidities that they had and they're coming in with this, uh, cancer, for example. Organ failure is especially persistent and worsening over 48 hours. That's obviously a, a bad outcome or a bad complication of pancreatitis. And we don't see them as often, but it does happen and kids can get very, very sick, um, with pancreatitis. Necrotizing pancreatitis, of course, has increased severity that's an increased severity, uh, of pancreatitis and Has some downstream effects. Some of those kids end up being insulin dependent, um, for example, or some of them may eventually need to have their pancreas removed. I'm getting ahead of myself, but the point being that there are increased factors that may increase the risk for complications, and it's important to think about those as you're assessing a kid with pancreatitis. It's not just, oh, they're just in pain, we just give them some pain medicines and they'll get better in 24 hours. We really have to think about what else might be going on. Um, and I, you know, necrotizing pancreatitis, the adult population reports up to 17% mortality. We, this is extremely rare in kids. Um, most kids get better even from severe necrotizing pancreatitis, but, um, it is something that, you know, families may be thinking about if they have experience with it and that we're thinking about again to just make sure that we're protecting kids and kind of um being aware of of when their other organs start to see um effects also. Um, so we're gonna go a little bit now into some of the complications that can develop after a severe episode of acute pancreatitis. Um, and, you know, in the first sort of week or two after an episode of severe acute pancreatitis, differentiating between these two can be very challenging even on cross-sectional imaging. But as you sort of go through the course and try to help understand what um What the trajectory for the child might be and what interventions you might need, it can become more clear, particularly with the help of your radiologist. So, um, on the left side, and kids that get interstitial edematous pancreatitis, um, they can develop acute perippancreatic fluid collections. You can see the arrows in this picture pointing to the like lighter gray fluid that is outside of, but next to the parenchimal tissue in the middle. That can develop into what we call a pseudocyst, which initially is like a um not well-defined sort of fluid around the pancreas, but can develop into a more well-defined walled off collection. But about 4 to 6 weeks after an episode of severe acute pancreatitis, most of these resolve spontaneously actually. And in kids who may have this, if they're not symptomatic, we may not know, and then it may go. Way. Um, and you generally try to avoid intervention unless they're really symptomatic. Um, it does often form right next to the stomach. You can see the stomach in this picture with the air fluid level sitting right above the pancreas. And so, if they cause, um, a lot of pain or difficulty eating because of some partial gastric obstruction, those are usually the times we need to intervene on these, and we'll talk more about how we do that later on. Um, on the other side, if a patient does have necrotizing pancreatitis, um, then they are at risk for getting necrotic collections that can include both the area next to and inside the pancreas. So in that picture, you can see the arrows pointing to, um, lighter, a lighter area that takes over some of the space of the pancreas that sometimes can communicate with the pancreatic duct, causing an ongoing leak from the duct into that collection. And these usually contain both necrotic pancreas and fluid. They're not, they look, they can look sort of simple on the CT scan, but they usually are not simple fluid that drains out easily just with an interventional radiology puncture. Um, eventually they can develop in what we call well off pancreatic necrotic collections, which again may um may resolve themselves, but can also cause problems. Here again is what look, these look like after they, what we call mature or after there's time, um, where the pancreatic inflammation itself has calmed down, but sometimes these fluid or other, or tissue collections remain. Um, on the left side, again, you can see a picture of the, of a pancreatic pseudocyst. Um, the arrows are pointing to a well c scribed fluid collection that's outside the pancreas, sort of above the pancreas and below the stomach. Um, again, they often resorb spontaneously, but if the child comes back with fevers or symptoms of obstruction, then they may need intervention to help with that. Um, walled off pan pancreatic necrosis, you can see on the right side where there's actually a walled off collection that is replacing some of the pancreatic parenchyma. Again, these can communicate with the pancreatic duct and lead to ongoing fluid accumulation. They can both become quite large, um, in some cases over time. And again, these also can sometimes absorb. ous ly Um, and actually in adult studies, it's been shown that mortality is lower with delayed intervention. This is not always possible, but if the child is sort of human dynamically fine, symptomatically improving, um, then just seeing a fluid collection doesn't mean you need to intervene on it. It's really driven by symptoms and their clinical status. So what do we do if we need to intervene and once that pseudocyst has matured enough to to do so, there are some endoscopic therapies for pseudocysts. Um, at the top picture you can see this is a transgastric endoscopic pseudocyst drainage where they can cut. With, uh, within the gastric or duodenal wall into the pseudocyst, and then place a double pigtail stent or a straw in between the two to let it drain directly into the stomach or to the small intestine. And then this this picture below that, the surgical cyst gastrostomy, is when the pseudocyst is in part of the pancreas that adheres to the stomach, and they can surgically go in, but actually then still put um put a hole, try to drain it, um, and then there's also percutaneous drainage, which you can see on the right hand side. Where they take a needle and they insert it through the gastric wall, and then the catheter is placed under fluoroscopy. And again, another double pigtail stunt is sometimes placed, um, to help facil facilitate drainage into the stomach. No worries. That's OK. Um, and You know, over time, eventually what you see is decompression of these pseudocysts and we'll repeat imaging to see, OK, is that catheter still in the area that we originally had it? Do we need to either do an exchange or removal or, you know, it's not just sort of a one and done thing, it does have these serial imaging and serial care after these procedures. Um, uh, for kids, even the smaller kids, the endoscopic treatment is by far the preferred first approach. So if you have a kid with this kind of complication and they're not yet at a center that can provide um a cyst gastrostomy or advanced endoscopy option, it is definitely worth talking to somewhere that can. Um, the interventional radiology, um, is usually reserved for kids who are so sick, um, like I see you kind of sick that they need something more immediate or they're, they are not stable enough to go to endoscopy. The surgical cyst gastrostomy again, usually reserved for when this is a chronic problem, but, um, the Endoscopic drainage is by far the preferred first approach, um, because you can establish um the leakage of that pancreatic fluid that has, as we said, the activated enzymes in it back into the intestinal tract, sort of where it belongs. So that's the place to start if you're able to. Um, one of the sort of complications that we need to be watching for in this in these kids, it's what's called disconnected pancreatic duct syndrome. This usually develops in kids who've had necrotizing pancreatitis, and with that necrosis, you can have necrosis of the pancreatic duct epithelium itself that causes disruption of the main duct and then ongoing leak into a fluid collection. And again, this is pancreatic fluid, so it has proteolytic enzymes in it. It's very hard for that to heal over. Unless it's drained, um, usually diagnosed weeks to months after the initial pancreatitis because of persistent symptoms. With all that sort of necrosis and inflammation, even a few weeks after these episodes or within a walled off pancreatic, um, necrotic collection, it can be hard to tell um if this is there on imaging. These folks do, you know, sometimes after initial drainage, have recurrent pancreatitis or persistent collections, and again, often require treatment to allow for drainage and try to let this heal up over time. Same interventions that we use with endoscopic stenting being by far the preferred approach. So, something wonderful that is coming out, come out of the Inspire data and group is defining what acute recurrent pancreatitis and chronic pancreatitis is in kids. So on the left hand side you'll see acute recurrent pancreatitis is by definition, at least two distinct episodes of pancreatitis. So, When we talk about the lipase level, it would be elevated, normal, elevated, or complete resolution of pain, greater than or equal to 1 month pain-free interval, or normalization of amylase and lipase and resolution of their pain before the subsequent episode, irrespective of the time interval. So at least two of the three, and distinct periods of time in between. As, as compared to chronic pancreatitis, you know, we sometimes learn that chronic just means it's greater than a certain amount of days. So if it's 90 days or more, it's chronic. It's different in pancreatitis for kids. It's actually the abdominal pain is consistent with pancreatic origin, plus imaging findings suggestive of chronic pancreatic pancreatic damage, and exocrine and or endocrine pancreatic insufficiency. Um, as promised, we're gonna, uh, share some of the data that the Inspire network has been able to collect again over the last 10 years or so. And, you know, both acute recurrent and chronic pancreatitis are relatively rare conditions in kids. We see a lot of them at UCSF because I think we sort of collect kids um from a relatively large geographic area. Um, but it's really taken this, this multi-center network to be able to start to understand, um, you know, disease trajectory and, and get towards more evidence-based treatments for these kids. Um, so when we think about chronic pancreatitis in kids and adolescents, this starts early. In these kids, actually, the median age at first attack is 6.8 years. Um, there is definitely a range. We've seen it in babies and in adolescents. Um, and it really is a painful chronic disease, often requiring frequent hospitalizations. It's a huge burden on the child and the family. Um, in the Inspire cohort, 57% report constant pain. Um, between 1/5 and a third of the kids develop pancreatic exocrine insufficiency from ongoing damage to their exocrine system with pancreatitis flares. And initially, um, around 6 to 8% have diabetes. Both the EPI and the diabetes do increase over time in these kids and, um, you know, we're just sort of starting to understand the trajectory of that and then Um, hopefully in the next generation of Inspire um developing more effective treatments to help with that, but I think, um, we have a lot of work to do on that. In terms of what causes chronic pancreatitis in children, um, uh, a lot of these kids do have underlying genetic mutations. We'll talk a little bit about what those do in the next slide, but essentially they affect the function of the exocrine pancreatic system and the drainage of the pancreas. Um, often they have more than one mutation, um, in addition, sometimes to other Things where, you know, often in pediatrics, we think about like there's usually one thing that causes a problem in kids. And actually, we find in, in acute recurrent chronic pancreatitis that there's often like 2 or 3 contributing factors that seem to sort of tip kids over into this. So it is really important even after we find one genetic mutation to complete the whole panel and the rest of the diagnostic workup to see if we can figure out all the contributing factors. We think about pancreas divisum or other anatomic things blocking drainage of the pancreas, um, and then in more rare cases, autoimmune pancreatitis or medications. Um, this is a flow chart that shows you sort of the, for the common genetic mutations that contributes to acute recurrent chronic pancreatitis where they affect the trypsin pathway. Um, the press. The press one mutation, which is probably the most common causes early activation of tripsinogen to trypsin, usually inside the pancreas, which shuts off the cascade of inflammation and damage. Um, the other, um, commonly seen, uh, mutations, um, will affect the pancreas's ability to control active tripsin and tripsinogen. Sospink one is probably the second most common and causes um a problem with trypsin inhibition, such that if tripsin is prematurely activated, um it tends to stick around instead of getting appropriately inactivated inside the pancreas. And just um another comment about this. Since we started, or since I've started in this role over the past 10 years, the genetics have changed and evolved as well. There's, you know, we started with a 4 gene panel, we're looking for the 4 most common genetic mutations. Now there's 61 that's not pictured on our slides I've noticed is the CFTR mutations that are not your classic CF but CFTR related disorders or CFTR metabolic syndrome, there's a different um sort of constellation of things that go along with that as well, but it's definitely evolving. And then also important to know about these, which is kind of unusual is that at least press and often spanker autosomal dominant mutations. And so it often is, um, you know, if you get a family history where one of the parents has pancreatitis and one of the grandparents has pancreatitis, and somebody's had pancreatic cancer, um, Then thinking about these mutations is important. The, um, the, the sort of phenotype can be different in different generations, um, but it is, um, you know, it is autosomal dominant and so, um, it's not quite as rare as some of the more recess as more some of the recessive mutations. So what do we do when we see the kid with pancreatitis and we hear about the family who has multiple generations with pancreatitis, um, or we've seen a kid who has multiple episodes of pancreatitis. So initially we, we say consult GI, yeah, get us involved. Um, we might think about doing an ultrasound initially, although oftentimes, I don't know if we've looked at this data, but how many times can they actually see the pancreas? It seems like it's gallstones, right? Yeah, the gallstones and to look if there's anything, uh, very sort of acute and dangerous going on. Um, is there a thrombus? Is there a pseudocyst that you might be able to see that's bigger? So it's not necessarily to look for the pancreatitis itself. Um, we do a lipid panel again, looking for those triglycerides. Get that history. Are their family members? Does it sound suspicious that this has been going on for generations and generations? Um, if they've had more than one episode, or if it's our first time seeing them, but they have that family history, then we'll say it's worth trying to get genetic testing. And again, uh, I, I'm sorry, I didn't update this, that there are more genes to add to this, to this list, but there are pain. Panels from genetic companies where you can say pediatric pancreatitis panel and Vita happens to be the one that we use just because they have, uh, a panel, but we don't endorse them. There's tons of other places that have different panels. Um, even if their CFTR gene comes back without any anomalies, we still do, do, we still do recommend. Doing a sweat test because some kids, there are mutations in the CFTR genes that will still alter their proteins without showing up in their genetic testing. So this is the gold standard to see if they do have an alteration in their sweat test, um, as well as their history and exam. And IgG 4 as well as a total IgG, but the IgG4 specifically looking for IgG4 mediated autoimmune pancreatitis. There are two types, one has IgG4, 1 does not, but we, we still look at that. Um, their endocrine and exocrine sufficiency testing, so for their endocrine testing, we can check a fasting glucose, a C peptide level, and we may or may not do an oral glucose tolerance test, depending on where they are in their course, but once they've had chronic pancreatitis, we'll at least do this once a year, once every 2 years, and then adjust that frequency depending on their symptoms. And the fecal elastase. It's not affected by taking exogenous enzymes, um, so we do recommend checking a fecal elastase to try to get an idea of how well is their own native pancreas making their endogenous enzymes and do they need supplementation. Or what's going on there? Is it progressing? Is their disease progressing and affecting their exocrine function? An MRCP for cross-sectional imaging, we prefer that over CT if they're stable enough to to withstand the MRCP just because of the radiation, and then maybe an EUS and endoscopic ultrasound and or an ERCP depending on what's going on and what intervention may or may not be needed or be helpful. Um, we wanted to give you a little bit of a sense of what chronic pancreatitis looks like in children. These are both ERCP images, so, um, it's fluoroscopic, um, contrast injected directly into the pancreatic, um, duct during an endoscopic procedure. You can see that big thick black line in both of the pictures is the endoscope that goes, um, sort of through the mouth into the stomach, down into the duodenum. Um, in the upper corner you can see what a normal ERCP image looks like. So the PD is the pancreatic duct. Um, it is sort of pretty smooth and thin in caliber, um, and then you can see it comes down to join the common bile duct, the CBD, um, and they dump into the intestine at the, um, major pilla. Um, these are ERCP images from two of the kids that we take care of. Um, you can see that the pancreatic ducts are quite dilated, that there are, um, some strictures here and dilated side branches. Sometimes these filling, uh, the filling defects over here um represent actually stones, so concreted pancreatic secretions that form inside the pancreatic duct. Um, on the left, it was a 9 year old who had SpiNC 1 and CFTR mutations. Her first pancreatitis was at age 6. On the other side, the right side, a 3.5 year old with press 1 mutation. Our first pancreatitis was aged at age 2.5. Um, and so this can start early. It can be really hard to pick up in these younger kids. They are often in and out of the ER a few times with like Vomiting or just not feeling well, and somebody sort of finally checks a lipase. Um, and the 315 year old with the press 1 mutation, actually, um, her mom was subsequently diagnosed with press 1. She had had a history of pancreatitis, but press 1, which was the first, um, mutation known to cause hereditary. Pancreatitis was actually only identified in the late 80s. And so a lot of the parents who had pancreatitis when they were younger, um, were, were not very genetically tested. And, um, when they were adults actually, and would go to the, or even teenagers would go to the ER bound to have pancreatitis and accused of just being alcoholics and not admitting it. So this is not always something that the family already knows about, um, but, you know, we, we do sort of reverse diagnose a fair number of folks. Her baby brother actually was also um subsequently diagnosed with pancreatitis, and we um have the privilege of following them both. Um, but as you can see, even in, uh, you know, from these pictures, I think they illustrate that even in younger kids, this can really cause significant damage to the pancreas, um, uh, in terms of strictures and, and stones and, and these dilated pancreatic ducts. If you happen to find a press 1 mutation in one of your patients, it's, it's really important that you do counsel their first degree relatives, um, because of the risk of pancreatic malignancy and that specific mutation with pancreatitis. So just a point to make. So there are major challenges, you know, for of chronic and acute recurrent pancreatitis for children and families, um, and for the healthcare team, and so these are kind of the, the things that we're thinking about in terms of taking care of these kids, um, you know, it's a lifelong burden with chronic disease, often chronic pain, and I think what we've found one of the hardest things for families. That you can get the disease often sort of under control with not having daily pain, but then this threat of like unpredictable painful flares where it comes back and they end up in the ER is is really hard for a lot of of of families and kids. It's scary and um and is is one of the, I think things that weighs most heavily on them. Right now, we do not have a cure for these. Um, we do worry about, as Michelle was sort of talking about screening for with ongoing chronic damage, these kids are at significant risk of developing exocrine and endocrine failure, and they do, the press one kids in particular have a risk of pancreatic cancer in adulthood. Um, I cannot say that we've seen pancreatic cancer related to any of these hereditary pancreatitis genes in childhood or even adolescence, but later in adulthood, they have a clear high risk. This is a stressful and often, you know, repeatedly traumatic disease for the child and their family. As we mentioned, um, it can be hereditary in this dominant pattern, both the like sort of impact on multiple family members, but also for the family knowing that like it came from one of the parents can be sort of stressful with the family dynamics, so we try to think about that with them and address it too. And then it certainly has an um you know, a risk of impairing quality of life and family functioning. So the goals of treatment for pancreatitis is pain relief, improving their daily function. We focus on that a lot, preserving their pancreatic function, that's exocrine and endocrine, minimizing those emotional effects as much as possible, minimizing trauma, preventing narcotic dependence, and overall, the most important goal that includes all of the above is improving their quality of life for the child and their entire family. Um, we're lucky enough to have a therapist and a social worker as part of our program who provides so much emotional and support and therapy for all of the trauma for both the child and the family, and I can't say enough about how helpful that is for these families. Oh, I got ahead of myself. You can say more about it. I can say more. So, um, we have specialists that help with mental health support. They, they are a therapist, social worker. We also have child life specialists within the hospital. It's such a painful condition. They are in and out of. The hospital, um, a lot of stigma, sometimes we'll get patients who are in their later teens, they've never been diagnosed. They've been accused of many different, you know, drug-seeking behavior or, um, alcoholism or any of these things. So they come with a lot of that sort of Experience, negative experience that we're working through, as well as how, how it affects the siblings, the family dynamic, um, people's jobs, all of the above. We have an amazing pain team at our hospitals and also in the community there are pain pain members, we cannot say enough about how important it is to consult them early. We're very successful at preventing narcotic dependence with their assistance and helping with chronic pain. Of course, getting endocrine involved or GI involved for both exocrine and endocrine function, trying to do things that we can to preserve any of those functions, or keep monitoring them to make sure that they're intact or doing healthy things like if you have a comorbidity of obesity, well, maybe we need to work on that more so because we know you're at higher risk of these other comorbidities as related. To your pancreatitis. Um, of course, advanced endoscopists, I think, I know personally, I probably take it for granted because I'm here at UCSF. We have access to this, but nationally, it, it is very rare to have pediatric advanced endoscopists. So it's important, like Dr. Perrio said earlier, try to get people involved sooner than later so we can try to help if something is needed. And genetic counseling, of course. So once we have these genetic tests, we have the benefit of getting them done, but what do we do with that information? Do we give the families the basics? I'm not a geneticist, let's refer them to our colleagues to try to get more information. What are the implications for their family members? What are the implications for the kid as they get older? Um, child life, of course, helps prepare for procedures, hospitalizations, espe especially repeated procedures, ERCPs, anesthesia. The more time goes on, it goes one way or the other. Some kids say, Great, sign me up. I felt so much better. Let's just do it again. And then there's other kids who are avoiding even telling their parents they have pain because they're so scared and they don't want to come back to the hospital or come back for that procedure. Um, and I, I just wanna try call out by name our, um, child and family therapist Demitra Pharma, who we've been extremely lucky to have on our team. I think it's a pretty, it's a unique model, um, for even within our hospital system, and we were able to obtain her help and support it through a philanthropic gift to the program. Um, but she again is a licensed child and family therapist. She works part time with our team, and she's been working with us for several years, so she really knows this disease. She's able to meet with kids both in person and virtually inside and outside the hospital, um, and also to talk to their families and sometimes their siblings, and sometimes their schools, um. Less on the sort of diagnostic side of mental health and really more on the like helping with coping strategies, with um functioning, with thinking about how to deal with chronic pain, and that sort of embedded person who really knows this disease trajectory and is able to provide some of that emotional support. Um, without all the barriers that I know a lot of us all run into with trying to get our, our families connected to good mental health support, um, has been just an incredible privilege for us. And I think a really important resource that has added a lot to our team and I hope can be a model for other programs as well in terms of, I hope everybody has that opportunity. It makes a huge difference for our kids and their families. Um, there are, you know, treatment options that we think about for kids with acute recurrent and chronic pancreatitis. Um, they, there are not as many tools in our toolbox as we would like to have for these kids, given the burden of disease, but we'll walk through some what those are. Um, you know, it, on a really interesting more recent development that will show a little bit of data on the CFTR modulators. These are currently limited for, um, to kids who have what we think is CF related disease. Um, and the idea with CF causing pancreatitis is that the, those like thick secretion. That cause the obstruction in other organs like the lungs also cause obstruction in the pancreatic ducts and seem to, to lead to pancreatic obstruction and, and increase the risk of, of pancreatitis. Um, so there's a little bit of data coming out that will show you about CFTR modulators to potentially help with this. Um, we use pancreatic enzyme replacement therapy and a lot of these kids. There are not yet trials on efficacy in children, although we're working on this now and inspire. Um, but about a third of kids with acute recurrent or chronic pancreatitis, uh, do report using pancreatic enzymes. We use these in our practice. The idea is to try to take them before you eat, even in kids who are pancreatic sufficient to prevent activation of the pancreas. And reduce the secretions that their pancreas, pancreas tries to excrete but then gets stuck inside the pancreas. Um, we find that some patients have a great response to this, and it really seems to help. Not everybody does. It's usually not strong enough to like halt the the progress of press one pancreatitis, which are really, you know, more aggressive cases, but is a relatively low risk adjunct therapy that can be helpful. Nutrition support is really important. Um, we actually really encourage an age-appropriate balanced diet, diet, and we try to avoid overly restrictive diets that could impair growth or development. I think a lot of people have gotten advice that they should be on a super low fat diet. We find that there's not really very effective. We'd rather use pancreatic enzymes to try to avoid, um, pancreatic secretion, and it can really affect kids, you know, growth, and we worry about like cognitive development and other things over time. So we try to avoid overly restrictive diets, although folks have often gotten this advice previously, I think. And then pain management and mental health care, I think we, we talked about already. Um, we wanted to just briefly share a little bit of very recent evidence about how CFTR modulators impact pancreatitis in patients with CF. Um, on the, the right side, actually, there's a small case series of CFTR modulators in kids with cystic fibrosis, um, that suggested that this might actually increase the risk of getting Pancreatitis, and I think this is something we have to think about. The idea is that in these kids who had been measuring pancreatis insufficient, if you give them CFTR modulators, which in some kids enables their pancreas to start secreting digestive enzymes, if the drainage is not great, it may predispose them to getting acute pancreatitis flares, and that is a concern and something you have to watch for. However, on the left side, you can see um a much larger um uh database um uh analysis of adult CF patients. Actually, I think this is adults and children, um, and a very large number looking at patients who had received a CFTR modulator, and they found actually a significantly reduced overall prevalence of acute pancreatitis with reduced hospitalizations in CF patients who did start CFTR modulators. There are limitations to both studies that I won't sort of dwell on today, but um it is definitely something that um we are thinking about that may be helpful to patients over time, but I think that needs to be trialed on a case by case basis for now. Um, this actually is the most recent report from the Inspire database and has inspired some work on a trial that should be hopefully coming up. Um, the question is, you know, I showed you that a lot of patients, including our patients are prescribed pancreatic enzyme replacement. Um, to try to reduce pancreatitis episodes and the postprandial pain that some of them experience. Um, this is a retrospective analysis of data collected from the Inspire cohort, looked at 356 children, 17% of whom were on pancreatic enzyme replacement therapy. All of them were pancreas sufficient. And you can see in the graph that whether it's um acute recurrence and chronic pancreatitis, just the chronic pancreatitis kids or just the acute recurrent pancreatitis kids. The number of episodes they had after starting PET, which is the, the smaller boxes, was lower than before they were on them. And so this is sort of a signal that averaged over all kids, this may be a helpful therapy. So we're currently working on designing a clinical trial to look at this in a placebo controlled way. This is just a picture, uh, Doctor Prato kind of went over this earlier, but in terms of treatment options, and this is an ERCP, so the scope that's past past the pyloris just butts up against the exit of the pancreatic ducts and the common bile ducts, and you can can they, the advanced endoscopist can cannulate the pancreatic ducts and or bile ducts through an ERCP. And during these ERCPs there's different interventions. So this again is just to show you the dilated duct. You can see the wire faintly inside of the pancreatic duct on that top left picture. Um, they can place stents, they can make little cuts in the sphincter that is the place where the pancreatic duct empties into the small intestine, the little muscle that's on the outside of the um The major papilla, and this is just to see what the scope view looks like when you see the um stent in place. I'm trying to speed up because I think we're running out of time, but Anything you wanna say about that, Doctor? No, no, I think, you know, the goal of using ARCP is an is a more invasive procedure. We worry about it triggering an episode of pancreatitis, but the goal is really to try to use it therapeutically and I think um for some kids it can help a lot. Um, you know, and when we look in the Inspire data, about 40% of children in Inspire, um, have had an ERCP, um, and children with obstructive factors, so who have Pancreas disease some, a history of gallstones or coal cysts were more likely to get an ERCP, but only about 20% of centers even that have pediatric gastroenterology offer ERCP for children with pancreatitis. So it's not something that they're sort of equal access to, particularly, um, from a pancreas standpoint, it's much more common to do ERCP on the biliary liver side for something like gallstones. The number of folks that have experience on the pancreas side is lower. Um, how helpful is the RCP delivered therapy in kids with pancreatitis? You can see here again. Um, evidence from the Inspire cohort, and you can see across the bottom the different, um, interventions that people do. So the idea of ERCP overall is to try to improve drainage from the pancreas. You can do a sphincterotomy of either the biliary or the pancreatic side to try to open up the, the sphincter between the organs and the intestine. You can put stents in to to facilitate drainage. You can also dilate strictures and sweep out those stones. Um, and in about half of kids who have these procedures, they are found to be helpful by the family. Again, we definitely see this in some kids where they have less flares, they go from having constant pain to rare pain, um, and do better after relieving these obstructive factors, but it doesn't work for everybody, and it sometimes sort of works for months to years, and it is not a necessarily a long term cure. If the family, the patient is not able to respond well to medical or endoscopic management, and they continue to progress in their disease or have impaired quality of life, there are different surgical options. The one that we have really focused more on over the past 10-ish years is something called a total pancreatectomy with auto eyelet transplant. Which is where they remove the pancreas, they remove part of the small intestine that's immediately next to the pancreas, um, the spleen and the gallbladder that share the same blood supply. They take the pancreas. Greg Zo is our amazing scientist who can we say, will milk a rock, even though the pancreas may be really sick and really atrophied or very scarred and fibrosed. They blenderize it, they harvest the eyelets out of that, and then re-inject them into the portal vein that feeds into the liver, where they eventually established their own blood supply in their new home, and ideally will end up making their own native insulin, um, sometime. Kids will need to be on insulin forever, but, uh, many of them can come off of insulin, but regardless, even if they're on insulin, they don't have acute flare-ups anymore of their pancreatitis. Their pain is dramatically improved, their quality of life is dramatically improved, um, compared to where they were before that type of surgery. When we talk about the goals and indications of TPIT, it's a very big surgery, so we're pretty candid about Is this right for you? Is this right for your family? The main goal is to improve their quality of life, so minimize their pain, decrease the amount of times they're missing school, their life activities, playing, go to birthday parties, um, but preserve their insulin function, so even if they end up on insulin, still prevent the liability of diabetes if they were to develop that. And then wean from narcotics if they're on them, and decrease their risk of malignancy if they have one of those genetic mutations that increases their risk with chronic pancreatitis. We do consider TPIT in kids that are frequently hospitalized, they have signs of chronic pancreatitis on imaging, their inability to function. Many kids are missing school or they've eventually dropped out of school and gone to home hospital or independent study. Um, they have silent signs of eyelet destruction, so whether their hemoglobin A1C is going up or their OGDT is suggestive that they're having impaired function. Um, the lack of improvement despite all of the things we've tried medically. So enzymes, endoscopic therapies, um, gabapentin, whatever it might be, it's not working anymore. And then we are definitely more proactive with kids who have a hereditary cause because we know despite medical intervention. They're probably still having parentchimal disease that we can't necessarily intervene on. Um, this takes a very multidisciplinary team to do. Again, it's not something that we enter into lightly with the family, um, and we really rely on a, um, on a lot of our different teams, both inside and outside the hospital to help guide this. Um, just to wrap up, we wanted to go back to our 9 year old with chronic pancreatitis. She did OK with endoscopic management for a little while, but again, was really having intensely impaired, um, quality of life and frequent hospitalization, so ended up going through TPIT at age 11. She had a really good eye yield. She spent about 3 weeks in the hospital, and everybody gets started on insulin, at least temporarily afterwards. She came off of opioids. She came off of tube feeds, which we used temporarily because of gastroparesis after the surgery. She went back to school, she came off of insulin, and this actually needs to be updated again. She's in high school now, right? Um, but did really well. So this is In the in the kids for whom this is the right treatment, we really see it like a great um improvement in quality of life, and we see them much less often in the hospital afterwards. Um, thank you guys for being here with us today. Thank you in particular to our team that makes this possible, um, and I think we have a couple minutes left for any questions that folks might have. Perfect. Thank you guys so much. Thank you, Doctor Perera, and thank you, Michelle. Um, perfect. You have this slide up on the end as well. Um, we have a few questions. Uh, we only have 5 minutes left for them, so I'm gonna ask if we can be a little bit brief with them so we can try to get through most of them. Um, we have a great question from an anonymous attendee who asked, um, In terms of when you would want to re-image and have clinical suspicion for an acute recurrence pancreatitis or chronic pancreatitis, are you looking for similar symptomatology as just regular acute pancreatitis as well, or is there other additional findings that we should look for and additional lab testing we should do as well? Yeah, usually we're looking for this again in kids who come back with a 2nd episode, or who have a super strong family history, or who just like have an episode of acute pancreatitis and then are not recover their pain isn't going away over time. Gotcha. And this sort of leads us into another question an audience member had about uh how can you really tell the difference between a functional, a chronic functional abdominal pain? That was triggered by a pancreatitis versus like, this is a chronic pancreatitis now that the definitions are out there. Great question, Michelle, you wanna take that? It's difficult. Um, I can say, of course, enlisting a pain expert is always ideal because they will help tease that out, not just with their uh medical providers, but also their psychologists or their alternative medicine, um, professionals, but I will say just anecdotally, you kind of get a, a good gestalt of what's going on with families as you get to know them. I cannot speak enough to continuity of care for these families. Um, I think it can be a very challenging illness to take care of because it feels like it's just pain, pain, pain without a fix, and we all kind of go into healthcare because we hope to fix things and help people become better. So that continuity of care allows the provider to really tease out, OK, what might be affecting your pain. It's not just physical pain, but what's going on in your environment, um. And what is influencing this sort of flare up of pain. Now, there are other things we can do, of course, if they still elevate their lipase level, if they have imaging findings that are consistent with acute pancreatitis and that's a flare up. If we've ruled out other things that suggest, OK, no, this really is this. Organic disease that's happening, well, then we might get into the differentiation between is it acute on top of your chronic pain? Um, I could talk about it for hours, but I hope that answers the question. But it's something we see a lab, right? And, and the other thing we have to do is acknowledge that it can be both at the same time. And that you often need to think about treating both and not trying to like say we'll get your pancreatitis totally under control and then we'll treat your chronic pain. We have to do both at the same time. Visceral hyperalgesia incredibly common in these kids. Um, and so again I think having them multi disciplinary approach, continuity, um, and kids will tell you, you know, they, they know if it's their pancreas pain or not often, so, so I think listening to them is really important too. Is there a space for uh repeat lab work, repeat imaging, like the fecal elastase? Is this something that PCP should be looking at and following up and trying to uh help along the course as well, or is this purely GI led and you guys are the ones managing all of this? I think the PCPs are really important partners in this also, um, these are, I, they're often like we're involved both directly with the family and with the PCP as support, um, and we're more than happy to do that cause they're just really complicated, really hard cases, um, but yes, monitoring with labs, imaging, fecal elastase over time, both depending on disease activity and just as part of routine surveillance is is a big part of our practice. Great, I think we have time for one more question. Um, apologize, apologies if you have already answered this. What's the racial or ethnic breakdown of the genetic, uh, ideologies or the genes that have been identified so far, or do we know any of that so far? You want me to say that I, I was gonna say, do you have the inspire data with you? Yeah, I, I don't have the data, but I will tell you we see this across races and ethnicities, um, and, um, there. There, I'm not sure we've like broken it down by both with a focus on that, but you will, it it definitely um is seen across races and ethnicities, doesn't necessarily cluster in any given like um sort of group in terms of, of where they're from or what their background is. So if you see a kid who has findings of chronic pancreatitis or multiple episodes of pancreatitis or um You know, or a strong family history, then it is important to do genetic testing, cause you, I don't think you can predict. Gotcha. Perfect. Well, thank you guys so much. Uh, I think this was very pertinent and this is something that all of our residents as well as our community docs are gonna be thinking about throughout the week as well, so appreciate it. Thank you. Thanks for having us. Created by
