Welcome, everyone. The American Society for Gastrointestinal Angiostomy appreciates your participation in tonight's webinar. My name is Lauren Loading, Manager of Evidence-Based Guidelines and Documents at ASGE, and I will be the facilitator for this presentation. Our program tonight is entitled ASGE Guideline on the Management of Cholangitis. Please note that this presentation is being recorded and will be posted on GILeap, ASGE's online learning management platform. You will have ongoing access to the recording in GILeap as part of your registration. I also want to acknowledge the educational programming support from Olympus for the remainder of our 2021 ASGE Thursday Night Light Series. Before we get started, please note a number of features in tonight's platform so you're aware of the many resources available to you during and after tonight's program. Currently, you are all located in the auditorium. As you enter the lobby, you should note meeting information, which has tonight's agenda. There is also a satellite symposia section with recordings you can access. In the resource room, you will find a number of options, including video GIE Meet the Master videos, the history of endoscopy section, a gaming section, as well as access to ASGE guidelines and GILeap. In the networking lounge, you will find access and link to complete an evaluation survey for tonight's webinar. We would appreciate you completing this and it only takes a minute or two. And finally, I would like to guide you to the virtual exhibit hall, where there's a number of exhibitors providing information and resources, including an ASGE booth. If you have questions, swipe your virtual badge and a representative will get in touch with you. These features are available to you during the webinar and anytime following the program. There's a URL link, learn.asge.org, and that is where this recording will be located in a day or two. Tonight's objectives include a review of the guideline recommendation statements, discussion on how to implement recommendations into your practice, and time to answer participant questions. So please submit your questions through the Q&A box, and after each recommendation, we'll take a few minutes to go through those. Our moderator for tonight will be Dr. Bashar Qumseh. Dr. Qumseh is an Associate Professor and Associate Chief of Embassy at the University of Florida, and he is the Chair of the Standards of Practice Committee for ASGE. Presenting tonight's lecture will be Dr. James Buxbaum. Dr. Buxbaum is the Associate Professor of Clinical Medicine at the Keck School of Medicine at the University of Southern California, and he is the lead author on the guideline document being presented tonight. One quick final note, you do have full access to all of our guidelines through the GIE journal and on the ASGE websites at asge.org under the tab ASGE Guidelines. Now it is my pleasure to hand it over to our moderator, Dr. Bashar Qumseh. Thank you so much, Lauren, and welcome to the Thursday Night of Light by the ASGE. We're happy to present our guideline on the management of cholangitis tonight, and thank you for joining. This is going to be the first of a series of ASGE webinars in which we're going to present our most recent evidence-based guidelines, and we're very excited about this, and we hope this will be very helpful for you. We have many goals for tonight, including raising awareness of our new guidelines, fostering a better understanding of the evidence-based recommendation and process, and also to allow members and physicians to ask questions about the way these guidelines are developed and how the final recommendations are reached. The aims of clinical practice guidelines in general are to guide decisions based on the best available evidence, to standardize patient care, to improve provider performance, and to reduce variability in the practice. There are many studies that have assessed the benefits of clinical practice guidelines and adherence to clinical practice guidelines. I cited a few of them here. Guidelines can improve disease outcomes, lower mortality, and improve survival. They can improve the quality of care and lower the cost of health care interventions by improving cost effectiveness. And this is one of some of the few reasons why adherence to guidelines is very important and why we are here today. We follow a rigorous process in order to come up with these guidelines and recommendations. This involves systematic reviews of medical literature and a great methodology, which we will discuss further tonight and will allow you time to ask any questions. And all our recommendations are based on many considerations. Although looking at the scientific evidence is the centerpiece for these considerations, but there are a lot of other considerations that we think about, including patient's values and preferences, the cost of an intervention and cost effectiveness, adverse events related to the intervention compared to the comparison intervention, equity, feasibility, and acceptability. So all these factors work together in coming up with a recommendation and shape the strength of the evidence and the quality of the evidence. Please remember that guidelines are not a substitute for physician's opinion or on any individual patient, and that the final decision should be always based on local expertise and patient preferences. Without any further ado, I present to you Dr. Buxbaum. James, go ahead. Thank you, Dr. Bashar and the ASG. It is a great honor to present tonight on our guideline development. So as a bit of background, cholangitis is a combination of myeloduct obstruction with a superinfection. And historically, this was a surgical disease, and it was a disease of which there was quite a considerable mortality. During the past 40 or 50 years, there's been an evolution in treatment. First, there was the introduction of percutaneous drainage. This is from Bashar's home school of Florida, University of Florida, where they present the first major series of percutaneous trans-epidemic biliary drainage. And in the 1970s and 80s, endoscopic drainage came into the fore. An important study from Edward Lye's group in Hong Kong revealed that ERCP reduced the mortality of cholangitis from 32% to 10%, so a 22% reduction. However, there are questions in management, which we tried to take on and tackle in this guideline. One of these is whether percutaneous or endoscopic drainage is favored. Additionally, there's questions about the timing of ERCP. Is this something that needs to be done in the middle of the night, or should the patient be stabilized? We are also going to look at the extent of the initial therapy during that first ERCP. What's the appropriate level of intervention? These were guidelines developed using GRADE methodology, as Bashar described. There are no existing guidelines in the world literature for cholangitis management using GRADE methodology. And these guidelines were developed by a panel. This included the standard of practice committee led by Bashar, but also an independent content expert, Dr. Joel Munzer, a senior hepatobiliary surgeon, several interventional radiologists, and patient advocates. And the evidence for each of the major points in this guideline were subjected to systematic review and meta-analysis of pertinent quantifiable details. You can see here these are PICO questions. PICO stands for Population Intervention Comparator and Outcomes. This topic is on cholangitis, the population for all these questions was patients with cholangitis. The outcomes tended to be mortality, length of hospitalization, success of intervention. An individual three questions that we looked at was ERCP versus percutaneous drainage. The second was ERCP within the first 48 hours or after 48 hours. And the third was the extent of initial intervention, whether it should be ERCP with stone removal and therapy, or simply ERCP with decompression. The strength of our recommendations was based on several factors. This includes the certainty of evidence. So this has to do with quality, bias, imprecision, inconsistency, or indirectness. Do they compare the two groups directly? We look in papers with one or the other. And we rated these very low to high. Randomized controlled trials is the top level of evidence would start high, but then could be reduced if there is significant bias. Some observational studies, in contrast, start low. However, if there's a huge effect, if there's dose responsive relationships, then we raise these respectively. Additionally, we looked at the balance of benefit and harm. We looked at patient values and preferences and opinions, and we considered cost effectiveness. Our scale, which is standardized for all grade documents, is using the word suggest for conditional recommendations and recommend for strong recommendations. Now a conditional recommendation is the course that most patients would wish to pursue if recommended, but they're not the only course. There's also other reasonable options. That's fundamentally is what conditional recommendations mean. So on to our first question. So we looked at whether PTBD, percutaneous transoperability drainage, in which access is achieved via the liver and a drain is placed transopatically into the gut, versus ERCP, with stenting, should be done for patients with cholangitis. In regards to this, we looked at successful decompression, we looked at the adverse events which could occur, we looked at how long patients were in the hospital, we looked at mortality. In order to answer this question, we performed a de novo systematic review and meta-analysis. We looked through more than 15,000 citations, and we identified six comparative observational studies. This comprised approximately 1,000 patients. We also looked at another 89 indirect comparison studies. So these are studies that presented on either ERCP or PTBD, and the goal of these was to allow us to do sensitivity analysis, to stratify by severity. And this involved approximately another 10,000 patients. So from our direct comparative studies, the core, we found there was actually no difference in success for ERCP versus PTBD. There was a trend towards more adverse events for endoscopic versus percutaneous decompression. You can see the forest plot. This was limited by the number of studies. So we did look also to our indirect comparison, which I'll touch on in a moment. There was a significantly shorter hospitalization, however, for ERCP as compared to percutaneous approaches. Now we looked at our non-comparative observational cohorts. These general findings held up and were even strengthened. The total adverse events were higher for PTBD. There was specifically more bleeding and hemorrhage associated with PTBD than ERCP. And there was a greater length of hospitalization for percutaneous versus endoscopic approaches. The non-comparative studies did allow us to stratify, and we found, again, these same general trends, but they were more pronounced in patients with severe disease. However, the caveat is several of these outcomes stratified were informed by only a few papers. So in terms of the certainty of the evidence, there was significant bias in that these were all observational studies, albeit comparative. It was difficult to really assess if the groups were totally comparable. You could query whether the more severe patients were managed percutaneously or vice versa, the more severe were managed by ERCP. It was difficult to ascertain from what was available. There was also some inconsistency. I used the word I squared, which is a measure of heterogeneity for the conduct of the analysis. And it was fairly high for several of these outcomes. Other considerations, there was no direct cost-effectiveness papers. There is some data from the National Inpatient Sample of a quarter million patients with cholangitis. And for the most part, patients who require percutaneous drainage are more frequently, the majority are in the highest percentiles of hospitalization charges versus a more modest cost for those with ERCP. We did also query our patient advocates who were part of the panel, and they favored ERCP given shorter hospitalization lengths from our detailed assessment of the literature, but also from their own experiences with the discomfort associated with having the external catheter, which is part of a PTBD in cholangitis. Additional areas that need to be discussed is we did not feel there's enough evidence yet to weigh in on endoscopic ultrasound in cholangitis. There's certainly the issue of surgically altered anatomy for those, for example, who have had a Roux-en-Y gastric bypass, or post-liver transplant with an altered biliary anatomy, and PTBD may be favored in those patients. Just in critically ill patients, it was acknowledged by our interventional radiology colleagues that this can be achieved with very minimal sedation, whereas ERCP does require more extensive levels of sedation to achieve successfully and comfortably. So in summary, for patients with cholangitis, we suggest ERCP over PTBD. This was a conditional recommendation. The quality of evidence was very low. Thank you, James, very much. This is excellent. We'll see if we have any questions in the Q&A answers. I don't see any. If you do have any questions about this particular recommendation, feel free to ask at this point. So basically, to summarize, James, as you have done very nicely, we found some evidence of increased length of stay for patients with PTBD, increased bleeding adverse events compared to ERCP, although ERCP had higher risk of pancreatitis, and then also we had some patient values and preferences slightly favored ERCP compared to PTBD, and those were kind of the major drivers for this recommendation. Is that accurate? That's definitely true, Bishar, with the help of the whole great panel. All right. Excellent. I don't see any questions or something just came up. Okay, let's see. Is ERCP preferred over PTBD in all case scenarios? That was a question. Is ERCP preferred over PTBD in all case scenarios? James, you want to go back to that slide? We have a slide that James discussed. Certainly, I think it's not all the scenarios. James, you want to comment on that? I think you mentioned it here. Correct, Bishar. The comparative observational studies that we looked at to generate our recommendations were based on patients who had conventional anatomy and did not consider US. Based on the overall presentation of patients, we would recommend ERCP over PTBD, but again, there are these few possible exceptions where the data doesn't shed enough light. Those would be patients who, say, have a root limb, patients who could, for some particular reason, need an US or been from the US, and also possibly the patient is critically ill and very, very unstable for sedation reasons. But using the totality of the data, yes, we found that ERCP would be favored over PTBD. Exactly. For the average patient, we want to start with an ERCP, but there are cases in which PTBD may be more preferred. Like you said, in critically ill or unstable patients, they require less sedation, and maybe in some patients with altered anatomy. We are contemplating a guideline on patients with altered anatomy, so stay tuned for that. We'll answer that in a different time. We got another question. Could increased length of hospitalization in PTBD be due to this being done in primarily critically ill patients who would spend longer in the hospital anyway? Very good question. James, what do you have to say about that? A consideration. Part of the reason we rated down our certainty of evidence was because it was difficult to ascertain whether the groups were totally comparable. From the limited studies, the six studies that were observational that did look at PTBD in ERCP, it looked like, for the most part, the factors were similar between the two. I think we'd still argue that there is likely some factor related to the intervention itself. In other words, PTBD may truly be associated with prolonged hospitalization. Again, these patients did appear fairly comparable, but again, it wasn't rigorously enough done that we can say this with great certainty. Did any of the authors adjust for any of these factors as far as you can recall? Unfortunately, they did not. Ideally, we were really looking for things like stratification. We tried to do this ourselves by doing non-comparative observational studies. This is when we looked at those 10,000 patients that either had ERCP or PTC and looked at by severity of cholangitis. What you can see is that unfortunately there's not very many studies, but if you look at the very severe patients, it does still look like the length of hospitalization when we did our quantitative pooling was greater for severe patients. If you're looking at severe ERCP versus severe PTBD, this is a stratified analysis, it still was quite a bit longer, 28 days versus 17 days. If you look at both severe groups. So the stratification would suggest that even despite the patient-related factors that there appears to be a difference, but again, this is based on just a few studies, so the certainty isn't there, but we did try to stratify for this. And I agree with you. I mean, this is an excellent question, something that we have discussed in the panel as well. But we do have data from, because we're looking at PTBD versus ERCP for other indications, not just cholangitis for other guidelines. And this is a common trend. We see that patients who had PTBD have longer hospital stays, whether it's because of pain management or peritonitis from leak or whatever it might be, this appears to be a real trend, not just related to the fact that patients who are getting PTBD may be too sick to get ERCP. So there's more out there than just that, but excellent question. Thank you so much for the questions. If there's no more questions, we will move on to the next PICO number two. Perfect. So this PICO really aimed at when do you need to come in and do the ERCP. So there's questions in regards to patient resuscitation factors of when an ERCP for cholangitis should be done. There's theoretically a risk of greater bacterial translocation if the ducts are still full of pus, and potentially the patients may do better if you do allow antibiotics to take some effect. However, the counterpoint is that there can be an accrual of adverse events if patients aren't decompressed. Maybe they develop hepatic abscesses, become more unstable, and end up having a worse outcome because of the timing. So this debate is akin to that debate about upper GI bleeding and timing of endoscopy. I show to the right here the very recent publication from James Lau's group. I'm showing there's actually mortality benefit and actually holding back a little bit in most cases and waiting a few hours to resuscitate. So we're trying to really get at this question for ERCP. Our outcomes were, again, successful decompression, but also the things like mortality, organ failure, and length of stay. Fortunately, there was an existing very recent systematic review and meta-analysis by Iqbal et al., which looked at more than 1,400 citations and included nine observational studies. And these, again, were comparative trials looking at less than 48 or greater than 48 hours. And what the group found was that there is a lower overall mortality for ERCP within the first 48 hours. However, there's no difference in organ failure or 30-day mortality. Additionally, there was a shorter length of hospitalization for ERCP within the first 48 hours. Now, the certainty, the bias appeared to be some, there was a moderate amount of bias doing that. Again, it wasn't entirely clear if there's comparability between these two groups of patients. These, again, while they were comparative studies that looked at the less than 48 or greater than 48 group, these were not randomized studies. So it was not entirely clear whether the patients were comparable in the groups. Additionally, there was some inconsistency. And again, this had to do with what we call the I-squared measure, which was how similar the studies are, especially for the key outcome of length of stay. Now, there have also been a number of other studies. We reviewed the entire literature as part of a systematic review that weren't part of the quantitative review. And these include a number of studies, including Amitabh Shah. It's the first paper in the area that showed that ERCP in less than 24 hours shortened hospitalization. This was also seen in the national inpatient sample. However, there's no difference in mortality in the groups. There's been several studies looking at length of stay and mortality over the weekend. There doesn't appear to be any difference in doing it by day of the weekend or waiting to basically till Monday. There is also a few studies looking at very early intervention, looking at non-severe cholangitis. There was no difference in outcome for less than 12 or greater than 12 hours. However, for patients who have severe cholangitis defined by actually cholangitis not responsive to fluid therapy. So these are patients who've had two liters of resuscitation who are still on pressor medications. So basically, intravenous medications to maintain blood pressure. In those patients, there was a greater mortality in those in which ERCP was delayed for more than 24 hours. Again, cost-effectiveness analyses on the topic were lacking. From the national readmission database, there was approximately a $5,000 benefit for doing the ERCP within the first 48 hours. And from the patient discussion, our patient representatives felt that they would prefer ERCP in the first 48 hours, given their wish to shorten hospitalizations as much as possible and the associated unpleasantries associated with being an inpatient. Other considerations, should ERCP be done in less than 12, less than 24, 24 to 48 hours? Looking at the totality of the literature, there didn't appear to be any significant mortality or organ benefit for doing ERCP at 0 to 24 or 24 to 48 hours. This appears that 48 hours is a reasonable cutoff for these really hard outcomes. There was some conflict whether less than 24 was 24 to 48 decreased length of stay. The exception, again, was the studies of patients in septic shock who were on processors. These patients, it may be a consideration to do the ERCP within 12 to 24 hours. So for patients with cholangitis, we suggest the performance of the ERCP in less than or equal to 48 hours compared to 48 hours. And again, this was a conditional recommendation with a very low quality of evidence, again, given the nature of the observational studies. All right, excellent, James. So to summarize, we found some evidence for a decreased length of stay, lower mortality, maybe a cost benefit to performing the ERCP within 48 hours, and also patient values and preferences favored doing this sooner than waiting. The real question here was, if you get a call on Friday evening about a patient with cholangitis, do you have to come in and do them over the weekend or could you stabilize them and do them on Monday? And I think the answer here is yes, you should do them over the weekend, even though you don't have to do it within 12 hours unless they're in septic shock and on processors, in which case you should do them sooner than later. But if you get a case on Friday, you should probably do it on the weekend. If you get it on Saturday or Sunday, it can wait until Monday. Does that sound accurate to you, James? Yeah, that's very nicely put, Bashar. I mean, the data basically strongly suggests 48 hours that cut off the key things of mortality or even length of hospitalization. For the period before then, there's no clear benefit except for the sickest patients. However, there's quite a bit of strong data not to go beyond 48 hours, so both for mortality but also some of these other things like readmission that we saw from the systematic part, which is the non-quantitative part. So like we said, if you get it on a Friday, you should do it over the weekend. If you get a patient who is relatively stable later on and gets admitted on Saturday or Sunday and they're stable, it's probably safe to wait until Monday when you have the rest of your crew. We got two questions about what one says. If septic shock is not responsive to fluids, then ERCP in less than 12 hours versus PTBD. James has stepped out, so I'll answer that. So this question was not comparing the timing of ERCP versus PTBD. Again, this is just what is the timing of the ERCP, and if the patient is in septic shock and not responding to fluids, then the data would suggest that you should definitely do them within 12 hours of admission. So again, you get this on a Friday evening. You should probably do it the next morning. The next question is, if the patient does not respond to fluids, should you do them within 12 hours? James, I'll leave this question to you. It says, if the patient does not respond to fluid resuscitation, should you do them within 12 hours? Yeah. So this is an excellent question. Probably the best study in this area is a Carvelis paper from 2016, which was an AP&T. And basically, this study did look at the 12-hour cut point and also 24-hour. What they found is if you don't do it within 24 hours, there is certainly an increased mortality. So I think the answer to this is yes. If they're not responding, and they're basically giving them a great deal of fluid, and they're still requiring pressure medication, those are the inclusion criteria in the study, then you should go ahead and proceed with the ERCP. OK. Excellent. Drs. Kumsey and Buxwell, we do have another question in the chat box. Any data on stabilizing with antibiotics and reassess? Go ahead, James. So we thought about antibiotic as a potential PICO question, but this is actually part of another ASG guideline. And it is recommended, again, that based on the ASG guidelines in this area, that patients should receive antibiotic therapy of cholangitis. But again, since all of them are already recommended B on antibiotics across the board, that generally our guidelines should apply in terms of the time resuscitation. So again, this is you're talking about the very severe patients, that those that maybe aren't responding at 12 hours, that they should probably go ahead, we should go ahead with the ERCP. But again, that's not really part of our quantitative guideline looking at the general overall approach to cholangitis patients. Thanks, Loren. Another question is for a patient on vasopressors in the ICU with cholangitis with the native anatomy. Which is better, ERCP or PTVD? That kind of takes us back to the first question, James. Go ahead. So based on the literature in our system analysis, it would be ERCP. If there's unusual situation where they're not stable on multiple pressors or declining, that's maybe a little gray area. But based on our inclusion criteria, again, it would be ERCP. Yeah, this kind of takes us back to PICO number one, which we said that if somebody is really sick, i.e. you think you cannot safely sedate them, they may, you know, they're hypertensive to the point that you cannot safely sedate them, then maybe PTVD is the way to go because they require less sedation. But if they can be sedated for all the reasons we talked about before, if they are stable enough to be sedated, then definitely ERCP would be the study of choice if you have staff availability. Now, when we think about these guidelines, these apply across the board, not only to a cadet. A lot of the people who write these guidelines are in academic centers. So in some community hospitals, this, you know, you may not have physician availability, staff availability. And so, you know, that it may be better that they do have IR. So it may be better in this case, if you feel like you don't have the availability to do it, to have PTVD. So that is a different, if you have the availability and you can't do it, then you should do the ERCP. All right, excellent questions. So far, you know, please, we encourage you to ask more questions if you have any. We'll also take questions at the end about all of all of the presentation. But let's, James, let's see what we have to say about the third PICO question. Our final PICO question that we address in this guideline was really this kind of age-old debate of whether endoscopic therapy should be performed during the initial ERCP versus decompression alone. So you just place the stent and get out. The concept is that sphincterotomy, lithotripsy, and removal of stones may worsen cholangitis and make the patient more unstable. The outcomes that we looked at were successful decompression, again, adverse events, mortality, length of stay. To address this topic, our team did perform a de novo systematic review and meta-analysis. We looked at more than 10,000 citations on this topic, identified eight observational studies in one randomized trial comparing decompression alone, which was in 418 patients, versus decompression combined with other forms of endoscopic therapy, a total of 485 patients across the nine studies. We also did stratify this meta-analysis by severity to try to add some nuance to our decision making. So, again, one of the main outcomes we did find was that there was a shorter length of hospitalization if endoscopic therapy was performed versus decompression alone for cholangitis. This was strongly significant. Interestingly, we also did find that there was a trend, actually there was significantly more adverse events, though, for ERCP with therapy versus decompression alone. And this was driven by more bleeding in patients who had ERCP with therapy versus those who had ERCP with a stent placement alone. We did stratify our meta-analysis by disease severity, and the same general trends were seen, but they were more apparent. The higher rate of adverse events was a stronger magnitude, anyway, with more severe patients, particularly the bleeding, which was 8.4 for the odds ratio. However, we did delve deeply into the literature, so the question is really whether they're looking at just the very first ERCP or whether they looked at the subsequent ERCPs required to perform therapy. And looking at individual studies that compare the two approaches, in most cases they did not report the adverse events for subsequent ERCPs, so they would really just report that first ERCP. And so it's difficult to say what the treatment rate of adverse, what their adverse event rate would be for the whole course of treatment in most of these studies. We also looked at how they define bleeding and how they manage bleeding. So among the 32 bleeding events, these were defined either as overt bleeding or drop in hemoglobin greater than two. And actually, in 75%, these were simply managed by conservative therapies, so some of the patients got blood or just monitoring. 25% did require endoscopic therapy, and one of the patients did require IR interventional radiology with embolization. None with this surgery. So the level of certainty, there was one RCT, but it was unblinded, so it was rated down for bias. There's also some worry about comparability. It wasn't clearly, we weren't clearly able to ascertain whether there was some type of differential assignment based on coagulopathy or biochemical parameters in the observational studies. And again, there's also inconsistency with the length of stay outcome. In regards to patient values and preferences, so the patient advocate on the panel did describe there's a strong desire to reduce hospitalization and have less procedures. Additionally, the group did discuss, the GRADE panel, that the decompression may be fair for some patients. So if a patient's very unstable and they wouldn't tolerate a hemorrhage, or if they're highly coagulopathic, or if they have to continue on anticoagulation, for example, a patient with a mechanical mitral valve, for example. In regards to costs, there was no formal cost effectiveness analyses, although from the available studies, they reported approximately a median of one less ERCP for those that did receive combined therapy, that is ERCP with stone removal and other interventions in addition to decompression. There's also less hemorrhage during the index procedure for decompression. However, again, the overall rate of adverse events for the two groups could not really be interpreted, because it was really only reported for that very first ERCP, and it wasn't described, for example, subsequent procedures. So the GRADE panel discussed that the rate of hemorrhage, of course, is low if you decompress alone without a sphincterotomy, but these patients, many of them, the majority did have stone disease and likely would require sphincterotomy and other interventions of subsequent time. Unfortunately, the adverse event rate of these subsequent procedures was not available for analysis and discussion, and so it's somewhat biased in favor of decompression alone, and that we don't really know what the final adverse events were in those that had decompression followed by a follow-up ERCP versus those that just had the ERCP up front. And we did note that in most cases, the bleeding could be managed conservatively. There was no surgery. So our summary statement was that for patients with cholangitis, we suggest that biliary drainage be combined with other maneuvers such as sphincterotomy and stone removal versus stent placement alone without attempted stone removal, and this was a conditional recommendation with a low quality of evidence. Thank you, James. Excellent. So to summarize, the real question here is you go in, somebody with cholangitis, again, this may be the weekend or may not be the weekend. Should you do a sphincterotomy, try to do stone extraction, do as much as possible, or should we just go in and maybe leave a stent, don't do a sphincterotomy, bring them back another time when they don't have cholangitis and take care of it at that time? So that was kind of what we wanted to try to answer. Is that accurate, James? That's absolutely correct, Vishwan. Absolutely. Basically, what we have summarized here is that we found some evidence that there is decreased length of stay if you do intervention the first time you do the ERCP. There was increased bleeding. Obviously, when you do sphincterotomies, you're going to see more bleeding compared to that if you don't do sphincterotomy. However, we felt that these patients who have stone would still need a sphincterotomy next time they come in and the rate of bleeding would likely not be different than if you consider the second or the third ERCP that they had to get. Of course, again, patient preferences play the role and decreased number of interventions because you go in the first ERCP, you try to clear the stones, maybe you clear all of them, maybe you don't, the next time you do and then you're done. Versus if you do it the first time, they may need two more, maybe three more to get rid of all of it. So it can decrease the number of interventions. So based on all of this, the panel felt that we should recommend or suggest that you do it at the same session. So we'll take some questions now. We have two in our Q&A box and we have one in the chat box that we'll go back to. So the first question here says, does antithrombotic use impact this decision? Use of anticoagulants may be obvious to defer sphincterotomy. James. Yeah, so again, there was a sort of lack of evidence whether these groups were stacked differently in terms of who was on antithrombotics and who was on anticoagulants. So, you know, it's difficult to fully weigh in on that without a totality of data. Not necessarily from this guideline, but in other areas in terms of the ASG guideline on the management of antithrombotics and anticoagulants. If the job can be done without a sphincterotomy, sphincterotomy, then probably. So in this circumstance, this specific group, most likely you maybe should just, in those patients, it may behoove you just to place a stent. So that's part of our discussion of those, you know, for example, a mechanical mitral valve patient or a patient who has to stay on these anticoagulants at the time when you're doing it. And again, those patients probably just a stent alone are the exception to the rule, rather than looking at the bigger group of patients. Exactly. I agree with you, James. So to answer this question, you know, you come in and this patient has cholangitis, they are on anticoagulation, Plavix or whatever they're on, and you have to do it. You cannot wait for them, you know, to be off of the anticoagulation. And then in this case, the best case may be to not do the sphincterotomy and just do the stent. So I hope that answers the question. Excellent question. Second question, in a patient with septic shock, should you decompress and come back to finalized treatment after septic shock? James? Again, I think, you know, the kind of exception to our rules would be patients that wouldn't tolerate adverse events. I guess the question by septic shock is how unstable are they? Are they hypotensive and tachycardic, but otherwise, you know, they don't have coagulopathy, you know, renal failure, things like that. And you may argue to go ahead and do the sphincterotomy. You know, we saw in like a number of the papers, although it's not part of the quantitative pooling, is that it does appear that there's a more rapid, more accelerated normalization of the liver test and the destruction of the sphincterotomy is done, which is an interesting thing. It deserves really more prospect and more randomized studies. It's a very interesting phenomenon. So I'd say overall, I would still do the sphincterotomy if the patient is septic. However, if the patient is so sick that they're not coagulopathic and their INR is three and their creatinine is two, then again, that patient might not tolerate a bleed or it may be catastrophic. And then that would fall in the group where they most likely then should have a stent. So I'd say overall with these patients, from what we found and from the guidelines, it probably behooves them to have intervention. The other nuance is that we did end up combining sphincterotomy and stone removal and intervention in general in one area. That's basically the way the literature lied. It'd be interesting whether maybe sphincterotomy plus stent should be compared to stent alone compared to the full shebang of treatment. That might yield some interesting results and someone needs to do that study. It would be really critical to really inform us further. But yeah, I would say sphincterotomy and intervention and stent, unless they're, would again, would not tolerate a bleed. Definitely, exactly. And when we certified based on severe cholangiitis, we still found the benefit for therapeutic intervention compared to just doing the stent. Those are excellent questions. And they point to the fact that these patient scenarios that we come up with, there's so many variables that can be happening at the same time. And clinicians should always use their best judgment and our guidelines should be used to hopefully help them make those decisions. One more question here. It says, how much weight is given to patient advocates in deciding the guideline? While it is understandable from their standpoint, complications procedures are higher when patients are sicker, an advocate may not be aware of such nuances. James, I'll let you comment on our panel and how it works. This is a terrific point. Because again, part of the nuance of this great panel is how much do you weigh each individual aspect? You know, the greatest factor that gets, that goes in these grades, again, is the benefit versus harm, but Shark can comment more than anybody else being the chair of the SOP committee, but it always comes up at the end, is there a greater risk or greater benefit to all patients as a final decision? So I do think that the real risk of complications does really trump everything else, maybe even some of the detailed, you know, quantitative pooling, all the other fun stuff that we do. The advocate is part of the voice, but so is cost, and so all the other things. But again, the benefit of harms versus benefit is the overall standard. Bashar, maybe speak more to that. Yeah, so thanks, James. Again, this is an excellent question. The way we use patient advocates are more of a supportive role, right? So very commonly when we, an old way of doing guidelines, there was no patient representation, and now what we try to do is get a patient advocate and in this case, somebody from an advocacy group or maybe a patient who had cholangitis and had these interventions, and we asked them for their opinion and how they think about it. Ideally, we'd like to find literature about this. We'd like to find that this has been studied and reported, but unfortunately, frequently, we don't find available literature on what patients feel. It's very important because ultimately, we're doing all these things to patients, but we don't really know how they think about them. So we like to include them. They are in the panel. They tell us what they think. Normally, they have a supportive role. Ultimately, we take votes on how a recommendation is gonna go and patients do not get to vote and patient advocates are not part of the voting on the final recommendations. But again, their opinion is very much valuable to us, but that's kind of the extent of what we consider them and during the panel. Excellent question. Another question just came up. Perhaps we should look for volunteer physician patients. Sure. I mean, the problem is with having physician patients is we sometimes know a bit too much or we have our own biases. So we'd like to normally, we like to, as I said, the first thing we'd like to have is to have studies about patients' values and preferences. And we encourage all of you in your respective fields, whatever you're doing, to consider studying patients' values and preferences. Certainly, I'm just studying patients' values and preferences in treatments of baritissophobies. Those are things that can be studied relatively easily and would make excellent publications for us to use. The next best thing we use is a patient advocate, which is usually a group of advocacy group that deals with patients who have a particular condition. A lot of times you see them in patients who have cancer, cholangiocarcinoma and esophageal cancer and stuff like that. So we can find a patient representative that way. And the third kind of tier is actual patients. Next question is, would you comment on patients with PSC and also those with non-primary issues, prior procedures, those with stents, underlying tumors, coming with cholangitis, James? So other patients other than stones, PSC, existing stents, tumors, and cholangitis. Yeah, so the source literature wasn't, for our meta-analysis on these three big topics, was not restricted to specific types of ideology. So they're the broad swath of cholangitis. It's not, I don't think it was in my talk, but we actually have, in the actual paper, you could see what, for the different meta-analyses, what the breakdown was by cancer and versus stone versus other things. So it does apply to the cadre, the full group of cholangitis. So I would say that this should apply also to PSC and patients with malignant tumors and those that have stents as well, in terms of timing and intervention. Yeah, so I agree with you, James. So basically, this was not specifically meant for cholangitis with stones, although the majority of cholangitis cases we see are related to patients who have stones. But there were other patients who have cholangitis, like you said, people who have stents, prior procedures, PSC, and the recommendations that we made today for any of those cohorts. Another question just came up, is 48-hour optimum time starts day of presentation to the hospital or start time of symptoms? So basically, they're asking, when does the 48-hour window start, James? It's from the presentation to the hospital based on the source data. It's just, it's very hard to, for the individual authors, I think it's very hard to establish when patients actually, the symptoms develop. So that was how the papers went. So it's time to presentation to the hospital. Excellent question. So, and definitely agree with you, James. So this starts by the time they show up to the hospital, to the emergency room, and that's when the 48 hours start. All right, let's see. We had one question in the chat box. One question says, does the timing matter if it's native papilla versus post-sphincterotomy? Given some theoretical understanding of the spontaneous drainage and decompression of duct when it gets pressurized through a sphincter, which is open. Is there a difference, James, in our recommendation? I think this is talking about the timing, so back to PICO number two. If it's native versus status post-sphincterotomy. Yes, again, it's a very good question. Look at the source literature. It allowed both native as well as patients who'd had interventions before. My group did one of the papers as an aid in the meta-analysis by Iqbal on, and we included both. You know, while my modify opening the sphincter may allow better drainage, I think that the counter argument to that is if they had such good drainage, how do they develop cholangitis anyway? So I don't think it necessarily applies. Excellent. All right, one more question. We love those questions, and this has been very interactive, so that's great. The next question just came up in the Q&A question is, so for now, you'll suggest a door-to-scope time of less than 48 hours, to use a cardiology metaphor. James, what do you have to say? Yes, I would agree with that. It looks like that's sort of the magic number, not just because that tends to be the number in most of the studies, but looking at those that have stratified by 24, 24 to 48, there didn't appear to be a lot of really hard outcomes in those shorter times. Certainly beyond 48, it gets worse if you go to 72 hours. So it does look like that 48 hours is a magic number, at least based on what we have in the literature right now. Yeah, and for practical purposes, if you work in a hospital, if you're in a community hospital, you don't think you have, we don't do advanced all the time, but you do some ERCPs, you're not gonna be able to do it over the weekend, then you should transfer the patient to a tertiary center. That's perfectly acceptable, as long as they, and with the understanding that they will do it over the weekend. But to answer the question is, yes, we would like, if somebody comes in, it has to be done over the weekend and within 48 hours. Usually if this comes in during the weekdays, that's not much of an issue because most of the time, James, you can add them to somebody's schedule the next day, correct? Correct, correct. And even here, I'd say if they come in on Sunday morning and you're still resuscitating, it's probably fine to do it on Monday. Just don't wanna, as Bashar alluded to, the current Friday, you don't wanna wait days and days. That's where you get the cruel, these adverse things happening. Exactly, okay. Another question from an anonymous attendee. He says, assuming we can do ERCPs within 12 to 24 hours, is guideline essentially eliminate the need for ERCP at night? Is this a first statement we can tell to the resident slash hospital administration? It's a bit of a loaded question. Go ahead, Dave. I'd, of course, qualify it. It's limited studies on the areas. It's not known for sure. Our uncertainty was high, obviously, but yeah, it does look like that. You know, when we talked initially about Jimmy Lau's study with bleeding, you know, it does look like we're kind of in that general direction that probably some resuscitation may improve outcomes. And clearly, going in really, really early doesn't appear to have any big benefit, either mortality or even maybe of length of stay. So that would be correct. Yeah. So I agree with you, I think. Yeah, I agree with you. I think in most cases, a patient comes in in the evening, they can wait 12 hours, even if they're in septic shock, you know, we'd like to do them in 12 hours. Let me ask it differently, I guess, James. How many times, and you do a lot of ERCPs, and we do as well, but how many times in the last year did you have to come in overnight for a cholangitis case? Probably one or two times. You know, both those times, I think we were all a little frustrated to always hear they'd come in at seven in the morning and resuscitating all day, and now they told us at like midnight that they needed to go in. Yeah. So it's a common problem that we have is sometimes, you know, like you said, somebody comes in and maybe the team is pushing to have the patient done, you know, as soon as possible. I mean, there are some people who think that, you know, we should do ERCPs, you know, within hours of us being consulted. Certainly, we don't have a lot of evidence that that's helpful, even in severe septic shock. You want to resuscitate them first, stabilize them first. If they're completely unstable and you think, I don't know, you can get them intubated and do it, or suggest PT, PD, if that's the case. But, you know, most of the time, in these cases, we're not doing them, as James said, overnight. Most patients can wait till the morning. Any recent studies in the COVID times, James? Of course, you know, this guideline was done. We met, we had the panel meeting in March, right before COVID hit. It was the last implicit meeting we had. So this was definitely, the literature searches preceded the COVID times. Have you seen anything regarding patients with COVID and cholangitis? And if we need to be doing anything differently? No, not that I've seen yet that that's compelling. Now, of course, we've all done patients with COVID positive that have cholangitis. You know, I've done a number of those and you have to wear the PAPR and all that kind of thing, but we still handle them just like every other patient. You know, with the exception of if they're hypotension and other things you're due to COVID directly, then you have to tease out what the real problem is, whether it's a biliary problem or the lung infection, that part. But if it's a COVID positive patient, that's not all that symptomatic and has cholangitis and just treat them like any other patient, you know, based on our guidelines, you know, applying our guidelines. Exactly. So while we obviously did not address COVID in this guideline, I agree with you, James, and we should treat patients with COVID just like anyone else. Obviously, we have to take the right measures to protect ourselves, protect our staff, protect everybody who's involved. So, you know, maybe somebody comes in with cholangitis on the weekend, on a Saturday, and you have more resources to do them on Monday and they're stable. Certainly, this guideline would support that you can wait until Monday and do them in your regular setting, where you have your equipment, where you have your staff, where you're more comfortable. So that would be preferable. So I don't think COVID specifically has affected our recommendations in any significant way. Our anonymous attendee says that he has to do at least one to three per month at night. And if he doesn't do it, he is in the hot seat the following day. I think, James, you can use our guideline to show people who are putting you in the hot seat that this evidence would suggest that most of these patients who are stable don't have to be done overnight. And you might even argue that akin to bleeding, you may be causing increased morbidity by rushing in the middle of the night and doing it to those that are criticizing. Also not having your own staff and things like that. What do you think, James? Certainly, there's a lot of data outside of the ERCP that if you do things over the weekend, you don't do them as well. What do you think about that argument? That's absolutely correct. And again, there probably is important to resuscitate these patients, again, because you're going to sedate them and you can drop their blood pressure and give in a bottom. It has been studied, but again, probably that first short period of antibiotic therapy also is important in terms of the LPS surge and things like that. All right, excellent. Those, I think, are all the questions. I haven't seen anything else. Can you move to the next one? We have one more question in the chat function. Okay, let me take a look at that. Thank you, Lauren, for that. Okay, acute pancreatitis with cholangitis. When and just drainage or sphincterotomy. So this is talking about cholangitis with acute pancreatitis. We didn't specifically address this in this guideline, but we have addressed this previously. James, go ahead. Yes, it's a tricky question because it's hard to really tell whether it is cholangitis or pancreatitis. In someone that has pretty significant pancreatitis, from necrosis and edema, they'll have high bilirubin. So is it really cholangitis or pancreatitis? So we took this on actually in our stone guidelines. And so in general, again, based on the stone guidelines from 2019, we recommend that if the bilirubin is greater than five, then to proceed with the RCP. And again, specifically whether you should do the sphincterotomy or not in this specific scenario hasn't really been looked at, but the meta-analysis we did do looking at combination therapy versus stenolone did include the whole range of causes. So it should apply that you could go ahead and do the sphincterotomy and some of the therapy then. Exactly. So we did talk about this in a previous guideline about choledocolithiasis, but the answer is normally if somebody has a galson pancreatitis with no evidence of cholangitis, then you should wait until kind of the pancreatitis cools down. This does bring up a good point, James, that I would like you to kind of briefly talk about our BILE criteria, because part of talking about and creating this guideline was a significant effort that we put in and that you personally put in about what exactly does cholangitis mean? And, you know, we've talked about patients with cholangitis in every question here, but we really, we need some better ways to define it. So do you want to maybe, and this has been published in GIE as a commentary, if you will, to go along with this guideline. So we encourage you to read about it, but we came up also with a criteria called the BILE criteria. So James, do you want to kind of maybe briefly tell us about a confusion we have a little bit about the definition of cholangitis and what we suggest to use in this situation? And this is not, again, part of the guideline, but this is just a work that we have done to go along with the guideline. So part of the dream that Bashar had as long, as well as Sachin Wani, our good friend and colleague, who was a former chair of SOP and myself was to also try to figure out if there's enough evidence to really define cholangitis. And given the lack of evidence and clarity, it wasn't something that we could include in the guideline, but we did look at the entire world literature on diagnosis, which is in a companion paper to the guideline from last month's GIE. And what we did find is that there appeared to be a few core criteria, which we call the BILE criteria. And so that included abnormal mobility imaging, infection with other Y count cultures, lab abnormalities and the exclusion of pancreatitis and exclusion of cholecystitis. And so the last question does kind of bring that up. So we, and to have a high probability of cholangitis, it really has to have all four criteria. So Bashar has subtly alluded to that last question. If someone does have fairly severe pancreatitis, they wouldn't really meet the full definition of cholangitis based on this paradigm that we looked at with the BILE criteria, but it's a critical area for future work. And I encourage you to take a look at that paper if you're interested in this topic of nailing down the diagnosis of cholangitis. Thank you so much, James. Yeah, we encourage you all to look at that criteria and consider using it and studying it and tell us how it works. Certainly we need better ways to, and easier ways to identify patients with cholangitis. All right, this is just a summary. I know we're about to wrap up. We'll just go over the recommendations for patients with cholangitis. We suggest ERCP over PTBD. It's a conditional recommendation. For patients with cholangitis, we suggest that you perform ERCP within 48 hours compared to waiting more than 48 hours. Again, a conditional recommendation. And for patients with cholangitis, we suggest biliary drainage should be combined with other maneuvers such as sphincterotomy and stone extraction versus stent alone. Again, a conditional recommendation. So we hope that you found this webinar useful to you and we hope that this will help you take care of your patients and save some lives. Thank you, James, for an excellent presentation. And of course, for your very, very hard work in doing this guideline, we really, really appreciate it. Many thanks to all of our SOP members who worked very hard on this guideline as well. And of course, our panel members, including our patients advocates. Also like to thank our ASGE staff who are doing an amazing job to helping us in doing all of this. Lauren, who's here with us and Billard. Feel free to contact us if you have any questions. Here's my email address. As the chair of SOP, I'd be happy to answer anything. Lauren is our staff liaison and she would also be happy to answer any questions. Thank you so much for being here. And we have our next webinar in two weeks in which we're going to discuss our guideline about malignant titer obstruction. And we hope you join us for this and let us know if you like this format. And if you would like us to continue, we certainly enjoyed it. Thank you so much. Thank you. Thank you, Dr. Kumse and Buxbaum. Awesome presentation and great discussion. Participants, before you log off, we'd really appreciate if you give some feedback on tonight's events. Just go to the networking lounge and complete the evaluation. And as a reminder, you can access a recording of this webinar. You just go into GILeap at learn.asge.org. You don't have to be an ASGE member to access this. Our goal is to provide information and education from these Thursday webinar topics as an open resource. So this does conclude our presentation. Thank you again, everyone, and have a good night.

ASGE

webinar

cholangitis management

Olympus

Thursday Night Light Series

webinar platform

evaluation survey

ERCP

percutaneous drainage

Q&A session