Our next speaker is Dr. Tim Gardner on chronic pancreatitis. Dr. Gardner completed his training at Dartmouth-Hitchcock Medical Center and Mayo Clinic Rochester. He's a professor of medicine at Geisel School of Medicine at Dartmouth, and he focuses on therapeutic endoscopy and clinical pancreatology. Welcome. Well, thank you, Jonathan, and the organizers, and really the ASG for being here. Thank you, again, all of you for coming here early on a Sunday morning to listen. My talk is going to dovetail, I think, nicely on Dr. Casey's talk about the need for indication and the importance of indication, and, again, my focus is going to be mostly on chronic pancreatitis with the title being When to Get In and When to Get Out. So no disclosures. So the treatment of painful chronic pancreatitis really, which is what we're focusing on here today, follows generally a path of least aggressive to a more aggressive approach, and if we go through this, everyone, I think, in this room knows this. We try to get rid of the offending agents. We use analgesics, and then we can go and do interventions, modifying neural transmission, decreasing pancreatic pressure, and, finally, removing the pancreatic parenchyma. And all of you here are probably very interested in endoscopy, as I am, and this is where we can intervene. We can intervene when painful chronic pancreatitis, doing ciliac plexus blocks, and we can also intervene when there's periods in areas where there's ductal obstruction. So it's really, really important to recognize that these are areas in which, as therapeutic endoscopists, we can really intervene to benefit our patients. So I'm going to focus on this talk in regards to ductal obstruction. Another really important caveat that I want to make, and I think, again, this follows up what Brenna just says, is during your training, you learn how to do the procedure. Really, in the first several years, you're out of training. You learn when to do the procedure, and I think you spend the rest of your career learning when not to do the procedure, and I think that's a really important message to get, and I'm going to focus in, and that's going to color a little bit what I'm saying here today. So the first half of my talk is why endoscopists are told to get out. Why, as therapeutic endoscopists, are we told not to go and intervene on stone disease or on strictures and chronic pancreatitis, and it really comes from several trials performed by the Dutch and same group that Brenna referenced, and there were two trials. The first one was in the New England Journal in 2007. The second was a follow-up extension trial in gastroenterology in 2011, and it was really the same group of patients, so it was only 39 patients total, and these were all patients who had painful chronic pancreatitis with stones in their duct. The duct was of varying sizes. If the duct was greater than 7 millimeters in size with stones impacting, those patients underwent ESWAL and subsequent pancreatic ductal stenting. If they were in the surgery group, they underwent a lateral pancreatic augenostomy, or PUSTO, procedure. So the first trial was published in the New England Journal, and this was the first really good comparative effectiveness trial between surgery and endoscopy for pancreatic duct stones. So let's just review that first trial. So these were the outcomes. Again, this was at two years of follow-up following the procedure, and what you can see here is the Zbikie pain score, which is the validated pain score we use for chronic pancreatitis pain. That's on a scale from 0 to 100, and if you look at the surgery group here as opposed to the endoscopy group, the surgery group had much less, significantly less Zbikie pain scores after two years. So as far as that goes, better for surgery. Pain relief as far as complete, partial, or no relief, the surgeons did better. The surgeons did better than the endoscopists. Interestingly, technical success was much better with the surgeons as well. The average number of ERCPs in this procedure to complete ductal clearance was five, okay? So technical success was much better. So furthermore, the endoscopy showed over time, this was the mean Zbikie pain score, that this was a durable process over time. So at baseline, at six weeks, it was better, and as you brought this out to 24 months, that durability of pain relief continued. So the authors concluded that surgical drainage of the pancreatic duct was much more effective than endoscopic treatment for patients with stones in chronic pancreatitis. Subsequently, they published their data, just as they did in the tension trial, they published their data several years later. So the average time was about six or seven years with these two groups, and they followed these groups out to see if there was durability to their pain relief, and this is what I want to call your attention to. If you look several years out from their procedures, 80% of the patients who had surgery versus only 38% of the patients who underwent endoscopy had durable pain relief. And most strikingly is that they did a cost-effectiveness analysis, and the absolute numbers are not important, but the relative numbers are, and what they found, and this is in U.S. dollars, that doing surgery up front as opposed to endoscopy was more cost-effective than doing endoscopic treatment. And they concluded that in the long term, that surgery was better than endoscopy for the treatment of pain in chronic pancreatitis due to obstructive stone disease. So that was the conclusion. There was a wonderful editorial written by Grace Elta at the time, and I just want to highlight here what she said, which was, surgical drainage in patients and introductable stones gives better pain relief, but the key thing is it depends on patient preferences. It is so important to get to the indication, the patient preference, and that's an important message I think I want to leave you with here today. This is a critically important thing that we're going to have to decide when we offer these patients these choices. Subsequently, the Dutch Acute Pancreatitis Study Group did the ESCAPE clinical trial, which was published in JAMA in 2020, and this was a slightly different group. This was patients with painful chronic pancreatitis, 80% of these patients had stones, 20% or so had strictures, and they randomized these folks to either early surgery, which is an upfront pousteau or occasionally a fry procedure, which is a resection of the head in addition to the pancreatic or jejunostomy, versus an analgesic first approach, and if that didn't work, going with endoscopy. So about 80% of these patients who were in the endoscopic group had ESWAL and then subsequently had drainage. That determination was made on if the stone was greater than 7 millimeters. So they randomized these patients, 44 in the early surgery group, 44 in the endoscopy first group, and what they found over time was that early surgery had a lower pain score than did endoscopy. And if you look at this over time of 18 months, you see that from the beginning, the endoscopy first approach looking at the pain score was not as effective as early surgery. So again, we show this again. So patients who had complete pain relief here, this is the early surgery group versus the endoscopy group in the dark green, they did better overall. So the conclusion again was in patients with chronic pancreatitis, early surgery is better than endoscopy and lowers pain scores in this group of patients. So this is why as endoscopists, we're told to stay out. If you have a patient with chronic pancreatitis who's got a stone and dilated duct, you should talk to them or at least offer them surgery upfront. So when to stay out, if we look at the evidence, one of the things that we all know in this room is that a stone is not necessarily stone is not necessarily stone, nor is the endoscopist not necessarily an endoscopist, not necessarily endoscopist. A lot of this depends on the scope of your local technical expertise. And if you're at the University of Indiana and you're doing 3000 ERCPs a year, you probably have a great deal of expertise compared to other centers that are doing this 20 times a year. You have to make sure that you're really following your local expertise. And one thing I think that we don't do, or at least I don't do well, is that we really have to get at the tolerance of our patient. We have to talk to that patient and really do a good informed consent and tell that patient doing five ERCPs is expensive. Are there transportation issues, pain thresholds, need for sick leave, et cetera. We really have to perform this informed consent and can't just have these patients drop in for an ERCP. Pancreatic stone disease is tough, and I think we have to recognize when they're speculated, embedded, panductal stones, those are harder to get out. And finally, if the patient has failed endoscopy previously somewhere else and they come to you, you have to recognize that that's a risk factor for not being successful. So again, there's a lot of data that says to us as endoscopists, stay out, stay away from these patients. What I'm here to tell you, though, I think there's a lot of reasons to get in, okay? So obviously, in chronic pancreatitis, things like ductal disruptions were very effective and ciliac plexus blocks were somewhat effective, but there is a role for us in stones and strictures, and that's what I want to talk about. So let me just present two cases. So 65-year-old male with chronic calcific pancreatitis, alcohol-as-a-mediology, having intermittent severe pain attacks, and here you can see on the CT scan there's a small stone obstructing the distal pancreatic duct. Contrast that to case two, which is basically the same patient, but having chronic severe daily pain, and these are the same stones in that duct. And I think all of us here can look at this and say, who has the better chance of success? Who is probably going to do better with an endoscopic approach? And it really is case one, the patient with the smaller stone in the distal duct, and I think we can get out very easily. So it's really important as you consider whether or not to offer surgery or endoscopy, whether or not this is feasible. I think you really have to pay attention to the symptoms, if this is a chronic daily pain issue or is it pain that becomes intermittently, the so-called AMAN Type 1 pain. And then you have to talk to your patient about endoscopy and be realistic about the number of ERCPs they're going to have to go through, surgery, et cetera, and really have that informed consent discussion. But there definitely is a role, I think for us as endoscopists, to get in on these certain patients. There's lots of different ways to do this, and I'm not going to go through the minutiae of how to get these stones out. A lot of this has to do with your local expertise and your practice patterns. We have balloons, we have baskets, and there's all sorts of lithotripsy devices, and there's been many studies comparing single ESWALs versus single ESWAL plus ERCP versus Holmian lasers versus EHL, and I'm not going to dive into that except to say that if you're playing with the stones, make sure you're very expert on the technique that you use. I personally like to use the EHL because I think it's simple and it's under my control, but a lot of people use ESWAL, and that's okay, too. It's just a matter of what's within your armamentarium for your local expertise. So when to get in on stones. Patients do better when they have intermittent pain. When they have chronic, daily, severe, almond-type B pain, they're generally not going to get better with your intervention. We like to do this in dilated main pancreatic ducts because that suggests obstruction. Smaller stones in the right pancreas do better than the larger stones panductally. Make sure you get good informed consent from your patient, and most of all, make sure you have the technical expertise to get this done. So let's switch base a little bit here on strictures. In those two pancreatitis studies that I showed you earlier from the Dutch, about 15 to 20 percent of the patients had strictures and did not have stones. Point is, is that patients with chronic pancreatitis do get strictures. Isolated strictures causing pain are a little less likely than you'll see with stone disease. So again, similar type of presentation, 65-year-old with chronic calcific pancreatitis, intermittent pain, stricture in the neck causing upstream dilatation. Important to recognize that not all strictures are inflammatory in chronic pancreatitis. So you have the post-inflammatory strictures. Don't forget about the underlying threat of malignancy in chronic pancreatitis. You have malignant strictures that you've got to deal with. And more and more we're recognizing these autoimmune strictures, particularly in type 2 autoimmune pancreatitis. So really important to recognize what type of stricture you're dealing with because the treatment's very different. For post-inflammatory, it's stenting. For malignancy, obviously, resection. For autoimmune, it's corticosteroids. So important to remember that not all strictures that you're going to see in chronic pancreatitis is necessarily an inflammatory stricture. So how do we deal with these? Well, there's multiple different stent types that we have. Generally, we have the plastic stents versus the self-expanding metal stents, both of which have been studied. Both of which are good. I'm going to show you a little bit of data about that. But basically with strictures, you generally don't need to dilate the strictures. You don't want to keep these stents in for too long because you can get iatrogenic stricturing at the stent sites. And be really careful of this stent misdeployment. So these are two stents. One's marked with a black metallic mark to tell you exactly when that stent is going in. Because what you want to make sure is that you don't misdeploy the stents. And for those of us who have been doing this a while, we have spent all of us probably a great deal of time trying to pull out stents that have been placed too far into the pancreatic duct. So be really careful of a stent misdeployment, which is a pretty devastating complication. So just looking at evidence. The best evidence for stricture therapy, there's a paucity of data. There's really no good randomized controlled trials. But there are a few meta-analyses that we have. This is just looking at self-expandable metal stents. This is a meta-analysis showing that self-expandable metal stents are about 93% effective in relieving the stent, excuse me, relieving the stricture. So they are very good at relieving strictures. When you compare them to multiple plastic stents versus the SEMS, basically they're pretty equal as far as pain improvement, because that's really what you're doing. You're trying to improve the patient's pain. So for pain improvement, these work quite well equally. The problem with the SEMS is that they migrate. So there tends to be more of a complication of migration. So in my opinion, if you're going to be using these for strictures, you should use multiple plastic as opposed to the self-expandable metal. Just because there's equal efficacy, but less risk of complication. So when to get in on the stricture? When it's post-inflammatory, you're going to use multiple plastics. If they have a strong pain response to your intervention, remember, just because the stricture goes away does not necessarily mean that their pain is going to improve, and that's where it gets to the indication. And really, there's minimal surgical comparison studies between these groups. So final takeaways, generally, surgery is the best option for complex stone disease. I hate saying this to this group, but I think that's true. But you have to pick your battles, and you really have to know your indication and your expertise. Endoscopy, I think, is probably the best option for strictures, especially the multiple plastic interventions. And more than anything, local expertise trumps everything. Thank you very much.

chronic pancreatitis

therapeutic endoscopy

pancreatic duct stones

strictures

surgical and endoscopic treatments