Thank you, Sumit. Tough to follow cirrhosis with pancreatitis, but I am well caffeinated. Welcome back, everybody. I have the task of taking the next 45 minutes to go through both acute and chronic pancreatitis, and we'll talk a lot about the complications from both of those. And so if we start with acute pancreatitis, acute pancreatitis is an inflammatory disorder of the pancreas and the peripancreatic tissues, and it can have multi-organ involvement. And if you look at the CAT scan, you can see right into that red circle, there's a lot of inflammatory tissue surrounding the pancreas. Acute pancreatitis is a common GI cause of hospitalization in the United States, and the median length of stay is four days. And what we've noticed, this is actually happening more commonly, and there's no appreciable improvement in outcome. So let's start with a polling question. Which of the following is the most common cause of acute pancreatitis in the United States? Alcohol, gallstones, autoimmune disorders, or hyperlipidemia? Excellent, so I figured it'd be between these two. Let's take a look at what it actually is. So in the United States, gallstones just above alcohol, 33% to 27%, depending on the literature that you're looking at. Other common causes, iatrogenic, which is post ERCP, for example. Medications, trauma, autoimmune. Hypertriglyceridemia does happen. We talk about it a lot. It really only happens 2% to 5% of the time, and it's those patients that have super high triglycerides, not patients that are in the 200s or 300s. Pancreas devisum, which we'll look at. Hypercalcemia, hereditary pancreatitis, pancreatic tumors, cystic lesions. And then sometimes we just don't know, idiopathic. So if we look at choledocholithiasis, this is an MRCP image. So MRCP is a 3D image looking at the bile ducts and the pancreatic duct, and you're able to kind of rotate it around and really get a good idea of what's happening. This is obviously just a still image of it, but where that red circle is is the distal common bile duct, and you can see that there's some black filling defects in there, and that is a seven millimeter stone. Everything when we talk about the bile ducts is really plumbing. And so if there's a blockage, whatever is above it tends to get larger, and that's what we're seeing. So we're seeing some dilation of the proximal common bile duct as well as those intrahepatic ducts. And I explain this to my patients using the reference to a maple tree. And I tell them that big common tree trunk is your common bile duct, and where it starts to split off is your intrahepatic ducts, the right and left, and then it goes into the tiny ducts, which are all your branches and the leaves above. And so sometimes when you're trying to give them a reference point of where the issue is, you can use that analogy. And so this is an image of an ERCP. The dark black that you see coming across the screen is the ERCP scope. And then all of those red arrows are pointing to stones. This is a common bile duct that is full of stones. And here's another one just trying to show you different ways that we can see these. This is the coronal view of a CAT scan. And there's a dilated common bile duct with multiple filling defects there as well. If we talk about medication-induced acute pancreatitis, it's actually pretty rare. Less than 5% of all cases of acute pancreatitis are from medications. A lot of medications can cause it. And this is just an example. This was a list that I found in an article from 2019 that had kind of divided out what some of those agents are. Most commonly, we're gonna see it from azathioprine, furosemide, those loop diuretics, hydrochlorothiazide, estrogens, sulfosalazine, Bactrim. If patients have medication-induced acute pancreatitis, you really wanna stop the offending medication if you know that's what it was. You should not resume it. And these patients generally do really well. Pancreas devisum is the most common congenital malformation of the pancreas. It happens in about 3% of people. It's when the dorsal and the ventral pancreatic ducts don't fuse. And so if they're not fusing, the majority of your drainage, all of that pancreatic juice and the digestive enzymes are not gonna try to come through the minopapilla instead of the major papilla. Most commonly, this doesn't cause any issues. Over 95% of the time, people with pancreas devisum have it, they live their normal life, they don't have any complications. About 5% of people with pancreas devisum, though, may develop recurrent acute pancreatitis related to. Hereditary pancreatitis is really important to know because it's associated with a significantly higher lifetime risk of developing pancreatic cancer of up to 50%. The most common gene that we see with this is the autosomal dominant variant of PRSS1. You can also see it in SPINK1 and CFTR. Those are autosomal recessive, so naturally they're a little bit less common. If you have gone through the whole acute pancreatitis workup you haven't found an etiology, you're labeling it as idiopathic, start to think about, should we do genetic testing to make sure that there's not hereditary pancreatitis? Certainly if there's a family history, but even if there's not, it should be something that's on your differential diagnosis. In autoimmune pancreatitis there are two different types. I'm not gonna go into a lot of detail about this. Most commonly what we see in the United States is type 1, which is when we have IgG4 positive plasma cells. And so that's a marker for disease. The serum IgG4 will often be two times the upper limit of normal or higher. And you can also take biopsies and stain them for IgG4 from the duodenum and we'll often see elevation in those as well. Type 2 is actually characterized by granulocytic lesions. It does not have IgG4 positivity or systemic involvement. It can be a little bit more of a diagnostic challenge for that reason. And it can present with both pancreatic and or biliary manifestations. So autoimmune pancreatitis can be mass forming where you'll see oftentimes a prominent mass in the head of the pancreas on your imaging. These patients may have mild to moderate abdominal pain and they may have evidence of pancreatic duct strictures. Also could have patients that come with more of an obstructive jaundice and intra and extra hepatic stricture picture. And so this is an example of a common bile duct stricture. This is a patient who had type 1 autoimmune pancreatitis. He had that high serum IgG4, and this is the ERCP film where that red circle is right inside of it. You can see that there's a very, very narrow caliber of common bile duct and above it, you can see the white is that dilated proximal common bile duct. Regardless of etiology of acute pancreatitis, the most common presentation is that sudden onset of epigastric pain. This is one of those pains that's, it's really deep seated. It's moderate to severe. It typically will radiate to the back. Gets worse with oral intake. You'll often see these patients when you walk into the ED room or the exam room, and they're kind of tripodting. They're bending forward, and they really have a tough time straightening out for you. Or if they're lying in bed, they tend to be kind of curling up into the fetal position, and that's because that does sometimes help to relieve some of that severe pain. Pain with acute pancreatitis can last for days, can go for weeks or months when it's really severe, and it's often associated with nausea and vomiting. On physical exam, we can look at systemic signs. So patients with acute pancreatitis will often have fever or tachycardia, and they may have hypotension. We start to think about SIRS criteria in these patients. And then the abdominal exam is gonna be that epigastric tenderness. Oftentimes they'll have guarding and rebound pain, and they may have an ileus. It's pretty common to have an ileus during the acute pancreatitis. So if you're listening to their belly, you may not hear bowel sounds, or they may be significantly less active than typical. So which of the following laboratory tests is most commonly used to confirm the diagnosis of acute pancreatitis? So the answer is lipase. An elevated lipase three times the upper limit of normal is the most common diagnosis of acute pancreatitis. So the lipase is gonna be the most diagnostic. If we look at the revised Atlanta criteria for diagnosis of acute pancreatitis, we really want two of three criteria. So abdominal pain that's consistent with acute pancreatitis, that epigastric pain radiating to the back worse with oral intake. Elevated serum amylase or lipase more than three times the upper limit of normal, and characteristic findings of acute pancreatitis on imaging. Remember all that peripancreatic edema in the first CAT scan image I showed you. And when we're evaluating acute pancreatitis, just some common labs that we'll often look at. So LFTs are super helpful, not only because you wanna look at the impact of the liver, but it helps us to identify biliary pancreatitis, or pancreatitis that's related to a colodogolithiasis. You'd expect that if you've got some kind of biliary obstruction that's causing acute pancreatitis, those gallstones that are sitting there, your LFTs are gonna go up as well. Fasting triglycerides are important. Remember that you typically will not get pancreatitis unless you have triglycerides that are very high, not just a little bit high, but important to look at that. IgG4 for that autoimmune pancreatitis, your B1 and creatinine, so that we can see what their hemodynamic status is, then their hydration status, calcium. Also looking for hemoglobin and hematocrit. We'll talk about that as we go through the management. And then their white blood cell count can help us when we look at severity and prognosis. And so I kind of divide these into two different areas. How do we identify the cause of acute pancreatitis? And then what are those predictors? And I really just put this here for your reference when you go back and look at the slides. As you're seeing these patients though, always remember those Sears criteria. Patients with acute pancreatitis can get real sick real fast. From an imaging standpoint, ultrasound is really good to look for CBD stones. Sometimes when patients come in and they've got garden and you're worried about their abdomen, a free air series can be helpful. In acute pancreatitis, I wouldn't expect to see much more than an ileus, but it does help you to rule out other causes. Chest x-ray, also looking for pleural effusion, which is a marker of severe pancreatitis. We typically don't need abdominal CT scans or MRIs unless you need it to help you to evaluate the cause of pancreatitis. It's really only needed for kind of specific indications. Oftentimes we'll do CT scan later. And if we were to look at severity to kind of classify it as mild, moderate or severe, mild tends to be a length of stay of less than three days. There's no organ failure or local or systemic complications. Moderate, you have this transient organ failure less than two days, or maybe some local complications. And severe pancreatitis is persistent organ failure for more than two days. It could involve one or more organ systems. These patients tend to have a length of stay of a week or more and may require ICU care as well. There are prognostic scoring systems. They can be somewhat limited though. They have poor sensitivity and specificity. They also require a lead time and they actually have pretty limited predictive value. So I listed a few here and I think it's important to know about them. They can be helpful. Depending on your health system, you may or may not use some or all of these. But I think that one of the big challenges with acute pancreatitis and probably one of the reasons why we see our actual prognosis has not improved over time is that it's really difficult to predict which patients will present with acute pancreatitis and develop a severe course with that multi-organ failure and which patients are gonna present and they'll do okay. And it ended up being just a mild to moderate and they'll go home in a couple of days. So if we talk about severe acute pancreatitis, you're looking at really local regional complications. Is there evidence of pancreatic necrosis? Do they have other sequelae of disease? Also systemic complications. Again, that SIRS criteria, multi-organ system dysfunction commonly will involve renal failure. Do they require ICU care? These patients have a high morbidity and mortality and they really need to be in a treatment center that has excellent supportive care, right? It's ICU, it's management of the SIRS criteria, drainage of fluid collections when and if needed, prevention of infection. So if we look at the management of this, we do have some guidelines and I list them here for your reference. So this is from AGA in 2018. We also have the ACG guideline which came out back in 2013 actually. Typically these patients will be admitted to the hospital especially if it's the first episode of acute pancreatitis. They should be on pancreatic rest, meaning nothing to eat or drink and IV fluid hydration with goal-directed fluid management. Acute pancreatitis is very painful and so controlling their pain is important with analgesics. Oftentimes these patients will require a short course of opiates. Antiemetics for their nausea and vomiting. You really wanna monitor the urine output, the hemoglobin and hematocrit, BUN and creatinine and their vital signs. If they're not able to tolerate oral intake within two days, consider enteral nutrition. It's always best to feed the gut so typically avoid using TPN. Then depending on the cause of pancreatitis, they may need some further intervention. So for example, ERCP if they have cholangitis and CBD stones or discontinuing a medication if it's medication-induced. For nutrition, nothing to eat or drink initially, NG tube only if there's ileus or vomiting. Eating typically with primarily carbs. These are gonna stimulate your pancreas less than protein and fats. In mild disease, once their pain starts to improve and those markers of inflammation are improving including your lipase and your white blood cell counts getting better, you can start to feed them. Usually that's happening within one to two days. In severe disease, you want to make sure that they're getting some food within a week. It's a high catabolic process. If they're not able to take oral intake themselves, particularly we're talking about those severe cases in the ICU, then a nasodegenerative tube is preferred. When you place a nasodegenerative tube, you're bypassing the duodenum so you're not stimulating the pancreas further and they're still getting that nutrition. And IV fluid resuscitation is super important. This was the Waterfall trial. And so this was published in 2022. It was a randomized controlled trial. They ultimately only enrolled 249 patients. It was actually stopped early. The goal of this was to look at aggressive IV fluids versus moderate IV fluid resuscitation and to help determine what is the ideal resuscitation volume. The reason it was stopped early is because they saw that there was an increase in fluid overload in patients who got aggressive IV fluids without any significant impact on the clinical outcome. Meaning patients who got aggressive IV fluids had more likelihood of fluid-related adverse events such as anisarca, pleural effusions, pulmonary edema. And they didn't actually have any reduction in the incidence of moderate to severe or severe pancreatitis. And so the recommendation when we take a look at this is really that goal-directed fluid therapy. It's making sure that patients are still getting an initial bolus and they're still getting moderate IV fluid resuscitation, but you're adjusting it depending on their own personal hemodynamic status. And that's going to be a combination of looking at that urine output, the hemoglobin, the hematocrit, really being able to pay attention to the patient themselves. They also kind of concluded that the patients who become fluid overloaded can get diuresis with something like IV furosemide to help to take away some of that and still continue the fluid resuscitation which is required for management of pancreatitis. Prophylactic antibiotics are not recommended in acute pancreatitis but they are needed in some conditions and so the most common one we probably see is that biliary sepsis or cholangitis. If you have biliary obstruction from choledocal lithiasis, it's not uncommon to present with cholangitis. Also, if they have any intra-abdominal sepsis, if you suspect that they may have an infection and you've taken, you know, you've pan cultured them and that's pending, then empiric antibiotics certainly could be warranted in that case as well. When do we do ERCP in acute pancreatitis? Certainly for choledocal lithiasis cholangitis when there's documented stones or very high suspicion. You can also use ERCP if there's a suspicion for pancreatic duct disruption or leak. We talked about this briefly yesterday but if you have that pancreatic duct disruption and leak and you start to develop a pseudocyst and you can kind of get the smoldering acute pancreatitis picture. So sometimes doing an ERCP with a pancreatic duct stent to allow that to heal will help them to recover and completely resolve the pancreatitis. It really should not be used as a routine procedure in all patients with acute pancreatitis. It's certainly not warranted for many of them. It does not reduce the pancreatitis severity or duration which is also important to know. Once you have acute pancreatitis that course is going to run its course but ERCP is going to help with all of the other things including infection, biliary obstruction, things like that. Surgery traditionally had been used for necrosectomy and debridement. This has now almost entirely been replaced by endoscopic fluid collection management. It still may be invoked if patients have boluschemia or you know other catastrophic diseases but it's pretty rare. Cholecystectomy is indicated in patients who still have a gallbladder in situ and who have gallstone pancreatitis. Oftentimes this is being done during the admission itself and so this was a couple studies actually that have really looked at it and they concluded that cholecystectomy within 24 hours of admission reduce the number of ERCPs patients needed also reduce the time to surgery and the 30-day length of stay. Same admission cholecystectomy has been shown to reduce the 90-day healthcare system cost and patients with a severe acute pancreatitis obviously may not be a candidate for same admission cholecystectomy. You would want them to recover and to be able to go through surgery when they're a little bit stronger and so in those patients you should perform it as soon as possible after the initial event. If we talk about complications of acute pancreatitis there are obviously a lot. The most common is going to be your pancreatic pseudocyst which can happen in up to 25% of patients. Pancreatic necrosis, multi-organ failure, pancreatic duct strictures, pancreatic duct obstruction, biliary obstruction, duodenal obstruction, malnutrition, pleural fusions, pancreatic ascites, all of these. And so this is a CAT scan which is looking at pseudocysts and you can see there's two here and as we were scrolling through the images they likely connect to each other. Hard to appreciate on this image but that dark gray is really looking at those fluid collections. The one that's really more towards the top of the belly you can see that well-defined capsule around it. How do we manage these? If they are asymptomatic then really it's just observation and you can follow them up with imaging with a contrast enhanced CT scan or MRI. If it's symptomatic and this varies depending on the patient but it tends to be abdominal pain, biliary obstruction, or infection then we're looking at drainage. Most commonly it's a step-up approach where we start with endoscopic drainage and then if that were to fail or if it's not able to completely access and drain a collection then we look at percutaneous and kind of lastly is the surgical drainage. This is indicated for those rapidly enlarging infected symptomatic pseudocysts with a success rate up to 95% but a fairly significant recurrent rate. And this is an example of a transgastric endoscopic pseudocyst drainage. So the first picture shows that there's this large pseudocyst up to 13 centimeters in one direction going in endoscopically into the stomach. Doing an ultrasound you're able to locate the fluid collection and then create a tract from the stomach into that pseudocyst. A axia stent is placed and then a double pigtail plastic stent and that allows that drainage to go into the stomach and ultimately they pass it through the bowels. The second image is looking at four weeks after that cyst gastrostomy and you can see that it's significantly drained and then if we look at the last image it's nine weeks after. Right in the middle of that residual fluid collection is a bright white kind of like a rainbow shaped object that's actually the plastic stent that's there. So you can make sure that it's still sitting there in position this looks like it's in a good spot it's continuing to drain. There's still a lot of discussion about what the optimal timing is to remove these stents. A lot of times especially if they had a really significant episode of pancreatitis we leave them in for months. Let the pancreatitis completely resolve so that that chance of reaccumulating the fluid collection is much less. So now shifting to chronic pancreatitis by definition chronic pancreatitis is fibroinflammatory syndrome of the pancreas and it's in individuals with genetic environmental and or other risk factors who develop a persistent pathologic response to parenchymal injury or stress and so the incidence of this is up to 12 per 100,000 persons with a prevalence of 50 per 100,000 persons. The causes of chronic pancreatitis you can think of Tiger O. So toxic or metabolic that's like your alcohol, tobacco, high calcium, high triglycerides, medications. Certainly idiopathic is always going to make the list. Genetic your CFTR and SPINC1 mutations that hereditary pancreatitis which can be acute. Multiple episodes of recurrent acute pancreatitis can cause chronic so genetics on the list. Same with autoimmune recurrent and severe acute pancreatitis and then obstructive things like pancreastabism or pancreatic duct obstruction for other reasons. Chronic pancreatitis is going to present with a similar type of pain but generally more mild. These patients will still have kind of that mid-epigastric pain. Tends to be more of a constant dull ache or episodic severe pain. Still can radiate to the back and their pain can last for many days. Of patients with chronic pancreatitis about 75 percent will actually present with pain the first time that they come. More than 85 percent are going to have pain at some point during their disease course. These patients can also have evidence of digestive insufficiency. So things like postprandial bloating or abdominal cramping, those fatty stools, weight loss. It also can be asymptomatic though. Early chronic pancreatitis sometimes we see evidence whether it's on a CAT scan or an MRI or endoscopic ultrasound and they really don't have any symptoms yet. If we're going to diagnose chronic pancreatitis certainly we can do imaging. It's the least invasive of the options. Cross-sectional imaging such as CAT scan, MRI or MRCP. We also could do endoscopic ultrasound. More invasive but it is more sensitive for the diagnosis of chronic pancreatitis. The pancreas function tests are typically not done. They're not very easily accessible. These are more complementary tests as well. And so it's looking to say do we have evidence of pancreatic insufficiency and if so why do we have pancreatic insufficiency and then you start kind of going backwards to look for evidence of chronic pancreatitis. So if we look at CAT scans and chronic pancreatitis the most common thing that we're going to see probably the easiest thing to see is pancreatic calcifications. You can see one calcification on the scan to the left and then you can see multiple throughout the pancreatic body and tail on the one to the right. On MRCP you may also see some irregular dilated pancreatic duct. This is happening because of all the scar tissue and parenchymal changes that occur during the chronic pancreatitis course. And so this is typically going to happen in generally a localized area of the pancreas and then it can expand further. So in this patient you can see it certainly throughout the body and tail. And in the second picture you can see a calcification and that's actually causing dilation of the pancreatic duct itself. So it's probably blocking the duct to some extent. Secretin enhanced MRCP. Secretin is going to stimulate the release of biocarbonate from pancreatic duct cells. And so it allows for better visualization of both the main pancreatic duct as well as those side branch ducts. And it helps you to really quantify the degree of filling into the duodenum. It's not 100% clear whether that's got a great correlation with the severity of chronic pancreatitis or with exocrine pancreatic insufficiency however. It's also expensive and it's not widely available. If we look at the endoscopic ultrasound images in chronic pancreatitis you can see that there's fibrotic foci on the image to the left. It's kind of got that hazy appearance to it. And then you can see some stranding. And so it's a little bit tough to see but the arrow is pointing right to one of those kind of brighter strands of the pancreatic parenchyma. You can also see some lobularity. So the head of the pancreas can become a little bit more bulky, doesn't have quite that smooth contour as usual. And then a dilated irregular pancreatic duct on the right. Endoscopic ultrasound, if you meet up to 0-2, probably unlikely that you have chronic pancreatitis. If you have 3-4 criteria it's indeterminate. And if you have 5 or more then it's a high probability that there is evidence of chronic pancreatitis there. You also have the Rosemont criteria for endoscopic ultrasound diagnosis of chronic pancreatitis. And this looks at parenchymal features, which are those top criteria, and then the ductal features, which you'll see on the bottom. And if we're going to make a diagnosis of chronic pancreatitis you want to have at least one major and three or more minor, or one major A, one major B, so hyperechoic foci with shadowing or main pancreatic duct stones with lobularity and honeycombing. And so again this can be helpful from an endoscopist standpoint to be able to take a look at it and give you the probability of chronic pancreatitis. And so back to our polling questions, which of the following is a key differentiating feature between acute and chronic pancreatitis on imaging? Diffuse pancreatic enlargement in acute pancreatitis, calcifications, presence of a pseudocyst, or atrophy. Perfect, yeah, so you know it's a little bit tricky because all of these things can be shown in chronic pancreatitis, especially if you're somebody who's had recurrent episodes. But calcifications typically are going to happen more in that chronic state. It's not something that you're going to see in acute pancreatitis, so that is the correct answer. So when we talk about chronic pancreatitis, we're really looking at the probability of developing some pancreatic insufficiency, and we want to look at pancreas function in these patients. Chronic is there, it's long-term. You know, I look at it kind of like cirrhosis, like Dr. Twani was just talking about. If you start to get scarring of an organ, then you have to start to look at function. It doesn't mean that you're always going to have malfunction of the organ. You can have compensated chronic pancreatitis, just like you can with cirrhosis. But we do have to start to think about that, and I explained to my patients that our whole goal is to protect as much function as we can and prevent it from getting progressively worse. So we have a few options here. I'm going to start with the two in the top. Those are hormonal tests, so CCK stimulation test and secretin stimulation test. These are both not widely available. They also are quite expensive and difficult to perform accurately, but they are looking at direct stimulation of those pancreatic cells to see how much activity is happening. If we look at the bottom ones, those are the non-hormonal tests. And so the most common tests that we do are the two right in the middle, the 72-hour fecal fat and the fecal elastase. The 72-hour fecal fat is gold standard for anybody who has to take their boards. It was on my boards when I retook them recently. This is the gold standard for pancreas insufficiency. It is very difficult to get a patient to collect their poop for 72 hours. It's very difficult to get them to do it for a full 24 hours, but certainly for 72. So accuracy is a huge concern with this test. The most commonly one that's actually used is the pancreatic fecal elastase, the fecal elastase 1. This is universally available. It's one bowel movement. It's not invasive. It does have some limited sensitivity though. If patients have diarrhea, it can be falsely low. And so when I have patients who I want to check a fecal elastase, it's my test of choice for sure. I do ask them to make sure that their stools are formed. If they consistently have loose stools, which you can have in pancreatic insufficiency, I'll actually have them take Imodium and bulk them up and then do it. Because if you have a secretory diarrhea, it's going to look like it's low. It doesn't mean it's related to this. So if we do it on a formed stool, we definitely have better specificity. Then if we look at our complications of chronic pancreatitis, exocrine pancreatic insufficiency is going to happen before endocrine pancreatic insufficiency. With the exocrine pancreatic insufficiency, when you get a good portion of your pancreas not functioning, you start to get digestive symptoms. We actually don't get endocrine pancreatic insufficiency until about 90% or more of the pancreas is not functioning. They can still develop diabetes, but oftentimes that's not caused by the pancreatitis. It's for other reasons. Opioid dependency is a real concern in chronic pancreatitis. These patients do have pain, it's real pain. And so we'll talk about ways to manage that. Osteoporosis and osteopenia, pseudocysts, any kind of biliary or duodenal obstruction, pseudoaneurysms, and they do have a higher risk of pancreatic cancer as well. I think the management of these patients is always best in a multidisciplinary, multimodal setting. And so really being able to involve pain management, primary care, nutrition, surgery, palliative care. I tell my patients I like parties, and so we're going to get the right people involved. Medical management of chronic pancreatitis is really multifactorial, and I call this medical, but it's kind of medical and lifestyle together. And so if we look at nutrition and lifestyle first, we're looking at really needing to have a good diet. And with that, the majority of patients actually need to increase their calories, but they need to lower their fat. A lot of these patients are going to be fat soluble, vitamin deficient. So vitamins A, D, E, and K supplements. If they have an alcohol history, they may need some thiamine. Pancreatic enzyme replacement therapy, if there's evidence of exokinprankatic insufficiency. So if that fecal elastase is super low, less than 200, and you've already bulked their stools up, putting them on pancreatic enzymes. Dietitians certainly are invaluable in being able to help to counsel these patients. Alcohol and tobacco cessation and complete avoidance. And there's been some literature to suggest that antioxidants may be helpful, although it's not really determined what quantity, what amount, and how do we actually get these formulated so it's easy for patients to take. So for exocrine pancreatic insufficiency, if we're looking at our enzyme replacement therapy, typically the starting dose is gonna be 500 units per kilogram per meal, or 250 units per kilogram per snack. It's really important to counsel patients that this should be taken with food, and a lot of times I will emphasize this by saying I want you to sit down, I want you to take your first two bites of food, then I want you to take it. Because what happens is they are so used to us counseling on other things, like PPIs for example, where we say take them at least 30 minutes before meals. We want you to make sure you have that time before you eat anything, that they'll kinda just take it with a PPI. So I really wanna emphasize this has to be with food. I want it in the stomach at the exact same time as your food. If they're taking multiple capsules, it can be helpful to have them space it, particularly if they're a slow eater. So take one capsule at the beginning of the meal, one capsule when you're halfway through, for example. They should be told not to crush or chew the capsules, it can cause a lot of irritation to the oral mucosa. If they can't swallow the capsules, then you can open these, and you can sprinkle the beans in a small amount of applesauce, and you can take it that way. The second most common thing after that digestive insufficiency is pain. And remember that over 85% of patients with chronic pancreatitis are going to develop pain at some point during their disease course. And so looking at this, if they have ductal obstruction, so stones or strictures or interpranchymal hypertension from fibrosis and edema, you can also get pain from pseudocysts causing compression on adjacent organs. Fibrosis is a very common symptom. So compression on adjacent organs. Fibrosis is going to reduce the ability of the pancreatic parenchyma to distend. You can get neuropathic pain from it. And then there's a lot of inflammatory mediators that are going to contribute to this. And ultimately patients can develop kind of that centrally sensitized pain state. Alcohol and smoking cessation are really important. It can contribute to the progression of chronic pancreatitis that also increases the risk of pancreatic cancer. And so counseling on that is really important. We also know from some of the recent literature that your endoscopic and surgical interventions both are less effective in patients who smoke tobacco. And then again, limited data on antioxidants. Maybe it helps to reduce the oxidative stress. Maybe it has an anti-inflammatory effect, but not something that I've ever recommended mostly because the regimen and the dose is really not clear. So if we look at analgesics, oftentimes we look at this kind of World Health Organization analgesia ladder and start with mild pain, anti-inflammatories, your acetaminophen, your NSAIDs. If they have mild to moderate pain, you may have to go to some opioids, maybe some tramadol. And then certainly if they have moderate to severe pain, being able to do something like morphine or oxycodone, hopefully short-term. I look at this as a spectrum and as they start to progress to it, integrative medicine's playing a bigger role now. And things like acupuncture, cognitive behavior therapy, massage, all have actually been proven to be quite helpful in this population as well. So this was a study from four years ago that was published in Clinical Translational Gastroenterology. It looked at 30 adults with chronic pancreatitis and they were randomized to internal organs with chronic pancreatitis and they were randomized to internet cognitive behavior therapy versus none. They had five sessions over eight weeks and it was really about thought-challenging relaxation activities. 80% of patients said that the program was highly acceptable. It was something that they could do that they were happy to do. Only 64% completed all four lessons. But of those 64% that completed all four, they had a significant improvement in their pain intensity and also how much their pain was contributing and interfering with their daily life compared to those in the control group. Neuromodulators and antidepressants can also be really helpful. So this is when we come to that kind of central pain processing. Pregabalin induces moderate pain relief in these patients. There was a randomized controlled trial that looked at pregabalin versus placebo. And after just three weeks of treatment, there was a pretty significant improvement with pregabalin. And then some of your neuromodulators, tricyclic antidepressants and SNRIs. Oftentimes when we talk about pain and chronic pancreatitis, we start with a starting point and then I may increase the dose a little bit, but I always have the conversation with my patients to say, pain can happen for a lot of different reasons. And we may have to target this in different ways in order to get the best effect for you. Medical cannabis is also something that we are seeing more and more, I think in all specialties, but certainly within GI. And so this looked at 53 patients who were on chronic opioids for chronic pancreatitis and 34 of those were enrolled in a cannabis program. Of those who received cannabis therapy, they had less daily opioid use as well as fewer hospital admissions and fewer ED visits. And then when we get to a combination and you're looking at it from a multimodal standpoint, you're treating their pain the best you can with dietary modifications, maybe some pharmacologic therapy, maybe some neuromodulators. There is a role still for endoscopic management of chronic pancreatitis. And there's several different things that we can do. Certainly they're all done for a different reason. Endoscopic pancreatic sphincterotomy will typically be done if there's some kind of obstruction right at the beginning there, or you can do this of the minor papilla in patients who have pancreas divism to open it up and try to dilate it and stretch it a little bit to reduce the impact and the frequency of acute pancreatitis. This has a success rate of 98%. With 4% complication rate, most common is going to be causing pancreatitis. There is a restenosis rate of about 14%. And this is just looking at the ERCP. So again, that big black is the ERCP scope. And you can see that that catheter is being passed through into the pancreatic duct itself. And then the second image shows that pigtail stent in the pancreatic duct. So what's the efficacy of endotherapy for treatment of chronic pancreatitis pain? This was a meta-analysis. It was about 1,500 patients, 16 studies. And it looked at pancreatic sphincterotomy, pancreatic stent placement, pancreatic stricture dilation, and lithotripsy if there were stones within the pancreatic duct itself. And it showed 88% efficacy of endotherapy with 67% efficacy for long-term pain relief. And long-term was defined as three or more years. The most common adverse events were acute pancreatitis, stent occlusion, and stent migration. US guided pseudocyst drainage. We've talked about this a couple of times, but this is really for those symptomatic walled-off pancreatic fluid collections. High success rate. Recurrence rate, I think, is starting to decrease over time as these endoscopic techniques are being refined a little bit. Celiac, plexus, block, and neurolysis are also options that can help to manage the pain in chronic pancreatitis. They are temporary. We know that eventually this is gonna wear off and either have to be repeated or you'll have to pivot to some other pain therapy. Endoscopic ultrasound guided celiac plexus block is when you're taking that local anesthetic with a corticosteroid and you're injecting it. And it can be repeated as often as every three months. It's obviously invasive. It requires you to go in and do an endoscopy. About half of patients will get pain relief from that. Celiac plexus neurolysis is actually injection of alcohol or phenol. This has a more permanent effect, but certainly has more significant side effects as well, including irreversible paralysis. And it really doesn't increase the pain relief much over celiac plexus block. In our practice, we typically will entertain celiac plexus block, but we reserve neurolysis for patients with pancreatic cancer. And then there's still an indication for patients with surgical therapy. So if patients have intractable pain and you've already gone through your lifestyle, your medical, your endoscopic therapy, or if they have non-resolving, we'll do a homobile doctor duodenal stenosis. A lot of times we'll put endoscopic stents in there. We'll try to dilate them if they're not responding to that. And certainly if there's a suspicion for malignancy, if you have somebody who has chronic pancreatitis and you're worried that there might be a malignancy there or a proven malignancy, then surgery therapy still may stay. And depending on where your pathology is really helps you to decide what the appropriate surgical therapy is. So in the head of the pancreas, we have the Whipple, Frey, and Beegersted surgeries. If it's in the tail of the pancreas, you're looking at distal pancreatectomy. If there's obstructed ducts, you can do a hepaticogenostomy and essentially bypass it. And then total pancreatectomy and islet cell transplantation if there's disease throughout the whole pancreas or if there's hereditary pancreatitis. So remember in hereditary pancreatitis, this can happen in young people. The lifetime risk of developing pancreatic cancer is approaching 50%. And so there are benefits to total pancreatectomy not only in being able to reduce the number of acute pancreatitis episodes, the only way we can actually stop that is by taking the pancreas out, but also in being able to prevent that development of pancreatic cancer. And so this is the Frey procedure. Just for awareness purposes, I wanted to show quickly what it was. This is basically when they're doing a partial resection of the head of the pancreas and they're draining the duct. So if you have a dilated pancreatic duct with an abnormal head of the pancreas, this actually has a pretty high probability of providing some long-term pain relief. And the bigger procedure is a little bit different. This is more transection, resection, and then a Roux-en-Y anastomosis with bile duct reconnection. And this can provide long-term relief also in over 90% of patients. A pancreatic otogenostomy is the modified Proust-O procedure, which is also called the longitudinal pancreatic otogenostomy. And so what they're able to do with this is basically splice open the pancreatic duct and then use part of your small bowel to connect to it and drain it. This will cause great initial pain relief, but it does look like this decreases over time and becomes less effective long-term. And then the WIPO procedure, if there's pancreatic head inflammation, concern for pancreatic head malignancy, if it's causing any kind of compression on the common bile duct resulting in biliary obstruction, this would be the surgery of choice for that. This causes 80 to 100% post-operative pain relief. The long-term relief is about 2 3rds. And the morbidity, unfortunately, is still relatively high because it is a really significant surgery, resecting the head of the pancreas, the first portion of your duodenum and the distal common bile duct, and then reconnecting it all. Total pancreatectomy, again, if you have intractable pain, impaired quality of life, particularly patients with hereditary pancreatitis and you've failed other surgeries. This does cause reduced narcotic use. However, there's a rate of insulin dependence at 10 years of 20% and a rate of partial graft function about 30%. So how do we decide endoscopic versus surgical drainage if you have an obstructed pancreatic duct? This was a study that was published a while ago now in the New England Journal of Medicine, but it showed that surgery was better than endoscopic drainage at the end of two years, and it was pretty significantly better. Patients who are receiving endoscopic therapy required more procedures, and the complications, the length of stay, and the changes in pancreatic function were all similar. The Xscape randomized controlled study, which was just done and published in JAMA in 2020, looked at early surgery versus endoscopy. And so patients who had chronic pancreatitis with a dilated main pancreatic duct, and they were not yet on chronic opioid use, ended up having complete or partial pain relief, 58% with surgery and 39% with endoscopy, and surgery, only one surgery versus three endoscopies, again, with similar rate of complications. There's a lot of challenges in chronic pancreatitis management, however. So these patients tend to have a higher incidence of alcohol addiction, opioid addiction, independence, and psychosocial issues. And I put those in red because they're things that we really don't wanna overlook. They are difficult conversations to have with patients, but they do help to guide and really direct us on how we need to tailor our therapies and individualize them. Neuropathic pain is also a problem, as well as that self-perpetuating pain as well as that self-perpetuating pain process. And these patients can also develop extra pancreatic pain. And so when we see a patient with chronic pancreatitis, it's difficult because we know chronic pancreatitis causes pain often, but we don't wanna forget about other things that can cause it. Make sure you're always thinking about peptic ulcer disease, GERD, H. pylori, other causes that could be concomitant. And then pain relapse is a real challenge, whether it's from endoscopic or surgical therapy, as well as determining the appropriate time for therapeutic interventions. We can't talk about chronic pancreatitis without at least talking about the risk of developing pancreatic ductal adenocarcinoma. The incidence has been reported in up to 4%. There have been several large groups that show that this is independent of age, sex, and cause of pancreatitis. The risk is also higher in patients with tropic pancreatitis and then certainly the highest with hereditary pancreatitis. There is no randomized controlled trial or systematic review or meta-analysis that supports pancreatic cancer screening in the absence of genetic mutations or family history in this population. However, we know that that risk is higher, so you should still be thinking about it. And if you're imaging your patients for other reasons, pay particular attention to the potential development of precursor lesions. So to summarize all of that, the incidence of acute pancreatitis is increasing. Management remains a challenge. Early diagnosis, goal-directed fluid therapy, prevention of multi-organ dysfunction, and necrosis are your goals of therapy. The prognostic scoring systems are tedious, but they're there. Probably the one that's the most useful and the easiest to use is gonna be the SIRS criteria. CAT scans and antibiotics for specific indications only in acute pancreatitis. Entral nutrition is critical. If they can't eat after two days, start to think about feeding them nasodigenal. Non-invasive imaging with endoscopic ultrasound and MRCP is recommended when needed. ERCP in specific cases, such as cholangitis, choledocholithiasis, pancreatic duct strictures, maybe pancreas divism if it's recurrent acute episodes, you wouldn't do that the first time. For chronic pancreatitis, exocrine pancreatic insufficiency and chronic pancreatitis typically require a combination of testing, such as fecal elastase imaging clinical presentation. Think about, look for autoimmune pancreatitis, particularly type one with the IgG4. Endoscopic ultrasound can be helpful looking for small and early tumors, but it does still have its limitations. Pancreatic enzyme replacement therapy for your management of patients who have EPI. Address pain management and quality of life. Remember that a lot of these patients can develop or already have alcohol or opioid dependence. And then think about endoscopic and or surgical management in these patients, specifically if they have evidence of a dilated and obstructed pancreatic duct or a big bulky head of the pancreas that's causing some biliary complications.

acute pancreatitis

chronic pancreatitis

diagnostic criteria

management strategies

gallstones

pancreatic insufficiency

multidisciplinary care

pancreatic cancer risk

individualized treatment