I'd like to present now Dr. Larissa Fujilao, who's coming to us from the Queens University Medical Group in Honolulu, Hawaii, to talk to us about updates in cholangitis. Thank you. Good morning. Thank you to the ASGE and the course directors for inviting me today to talk to you guys about the updates in the role of endoscopy in the management of cholangitis. This is my disclosures. So I'm going to use a case to review the diagnosis as well as the severity assessment for acute cholangitis, but I'm going to focus the majority of my talk on the treatment and the preferred endoscopic options for certain clinical situations. So the case is a seven-year-old female who I saw recently with hypertension and hyperlipidemia that came to us with fever up to 39 degrees Celsius and abdominal pain for the past eight hours. She had a similar presentation six months ago, but it was more mild and it resolved spontaneously. On physical examination, she was found to still be febrile and tachycardic. She had normal mentation and some mild epigastric tenderness. Her labs were significant for an elevated white count, elevated liver enzymes, her lactate was normal, her CRP was 1.9. If her CT scan showed a negative gallbladder and bile ducts, can you diagnose her with cholangitis? How about if the bile duct was dilated? So looking at the Tokyo guidelines of 2018, you have to have systemic inflammation. So that's either fever and or chills, as well as laboratory evidence of inflammation with either elevated white counts, low white counts, or elevated CRP greater than 1.9. Then the B is cholestasis, so either jaundice or elevated liver enzymes. And then C is biliary obstruction seen on imaging tests or evidence of an etiology such as stones or stricture. So if suspicion of cholangitis is if you have A and either B or C, and then a confirmed diagnosis of cholangitis is you have to have all three categories. So going back to my case, she did have a fever as well as an elevated white count. So that meets the criteria for A, and she had elevated liver enzymes. So if she didn't have any bile duct dilation, then she would have a suspicion for cholangitis. But in her case, her bile duct was dilated. And so she was, according to the Tokyo 18 guidelines, confirmed to have cholangitis. So next, you want to do a severity assessment. So going back to the case, what kinds of things do you want to look for in order to determine the severity? Of course, you want to look at their hemodynamics as well as their mentation, whether or not they have respiratory distress, get an ABG if they do. And then you want to look at the labs to look at their kidneys, their liver, as well as their hematologic and see if there's any end organ dysfunction. For moderate cholangitis, you want to make sure you look at their white count, their temperature, their age, bilirubin, and albumin. So this is the Tokyo guidelines, again, of 2018 of the severity assessments. Grade 3 or severe cholangitis needs to have evidence of sepsis-induced end organ dysfunction. So you want to look at their hemodynamics, whether or not they have any alternative status, whether or not they have any respiratory, renal, liver, hematologic dysfunction based off of their labs. And if they have any one of those, then that is considered to be severe or grade 3. Grade 2 or moderate cholangitis, you do need two of the criteria that is listed, including an abnormal white count, high fever, older age, elevated bilirubin, or low albumin. And then grade 1, mild cholangitis, is you don't have anything that was listed above. So in my case, she didn't have any of the criteria to suggest end organ dysfunction, but she did have an elevated white count as well as a high fever, so she was considered to be moderate. Why is this important? This is important because treatment is based on the severity. So if you have grade 1 or mild cholangitis, so again, you don't meet the criteria for moderate or severe cholangitis, then you can give antibiotics and general supportive care, but not everybody requires decompression. They suggest biliary decompression in patients that don't respond to the initial management. Grade 2 or moderate cholangitis, you still want to give antibiotics and general supportive care, but these patients are the ones that require your biliary drainage at an early timing. And then grade 3 or the severe require more urgent biliary drainage in addition to the organ support and antibiotics. So let's move on to the treatment. So this is the ASGE 2021 guidelines. They had three PICO questions that they addressed, and this is the first PICO question. This is addressing the role of ERCP versus percutaneous transhepatic biliary decompression. And they suggested ERCP over percutaneous transhepatic biliary drainage. And that's because there is a reduced overall length of stay and fewer adverse events. This one does not show, because this is the composite of comparative studies, but when they included non-comparative studies, they did show fewer adverse events, particularly in periprocedural hemorrhage. In addition, with the patient values of not requiring an external drain and the overall reduced length of stay, the recommendation was a suggestion of ERCP over percutaneous drainage. But there are some clinical situations when you want to consider percutaneous drainage, and that's in people with an inaccessible papilla, such as altered anatomy or duodenal obstruction, or if they're unable to tolerate deep sedation. The second PICO question addressed in this ASGE guidelines is the timing of ERCP. And they specifically used 48 hours, because that's where most of the studies focus on. In addition, it also accounts for the weekend ERCPs. And they suggested the performance of ERCP within 48 hours as compared to after 48 hours. And that's because there is a reduced inpatient mortality, 30-day mortality, a shorter length of stay, and also potential cost savings and patient values. Some caveats for the timing of ERCPs. Urgent ERCP is considered less than 24 hours after admission. Several studies have shown no difference in inpatient mortality, 30-day mortality, or readmission rates. It could have a possible shorter length of hospital stay. In one retrospective analysis of patients admitted to the ICU with cholangitis due to stones, they did show that if an ERCP was performed more than 24 hours after admission, there was a higher 30-day and one-year mortality, respiratory adverse events, longer ICU and hospital stays in that group. Delayed ERCPs considered to be more than 72 hours after admission. In one retrospective analysis, it did show that delayed ERCPs were associated with higher rates of the composite clinical outcome, including death, persistent organ failure, and or ICU stay. And then how about specifically distal malignant biliary obstruction? There was one study that showed that urgent ERCP, so less than 24 hours within admission, was associated with lower 30-day and 100-day mortality in these patients, which is particularly important in this patient group where their overall survival rates are lower in general. This was in particular for patients with primary distal biliary obstructions and moderate to severe cholangitis. So let's move on to endoscopic techniques. Before I do that, I just wanted to mention that the Tokyo guidelines do say that if biliary drainage is performed, bio-samples must always be sent for culture. So that's a step that you want to do and you want to collect some of the bio before you inject contrast. There are several institutions that have shown their data, if they routinely collect bio-aspirates for patients with suspected cholangitis, and the bio-aspirate cultures are positive more frequently than blood cultures are positive. And in patients with a prior sphincterotomy or a prior biliary stent placement, it does increase the risk of things like VRE. And over time, this university showed that there's a decreased sensitivity to Cipro, so they actually changed their antibiotics that they use when they're faced with a patient with acute cholangitis. So they say that doing these bio-aspirates can help to tailor your antibiotic regimen to the resistance patterns in your location. So going back to this case with a 71-year-old female with moderate cholangitis, you plan to perform ERCP within 48 hours. During the ERCP, would you consider biliary sphincterotomy, stone extraction, stent placement, or all of the above? So this is the third PICO question from the ASGE guidelines, and their recommendation was that for patients with cholangitis, they suggested biliary drainage to be combined with the other maneuvers, such as sphincterotomy, as compared to just decompression alone. So why is this even a question? And this is a question because earlier studies showed a higher risk of biliary sphincterotomy in the patients with acute cholangitis. The mortality rate was up to 8%, and a lot of studies reported an increased risk of bleeding in this patient population of acute cholangitis with biliary sphincterotomy. The risk of bleeding was up to 12%, and the landmark New England Journal of Medicine article on the risk of biliary sphincterotomy did say in a multivariate analysis that active cholangitis was a risk factor for bleeding. Even in the ASGE guideline, they did show an increased risk of bleeding of up to four times, particularly in the severe group as compared to the non-severe group. So why is it that their recommendation suggests that a biliary sphincterotomy be performed? So their arguments for a biliary sphincterotomy is that it was unclear if the overall bleeding risk occurred during the first procedure as compared to any procedure performed in this group, unable to account for the endoscopist, more likely doing decompression alone in sicker patients. It was unclear if the risk overall was higher in this group as compared to other indications for biliary sphincterotomies. Some studies may have included patients with severe cholangitis and a coagulopathy, and majority of the bleeding adverse events were mild. However, both the ASGE and the Tokyo guidelines say that a biliary sphincterotomy should be avoided in patients with severe cholangitis complicated by coagulopathy or recent use of antithrombotic agents. So what are some other options? Endoscopic papillary balloon dilation is where you can inflate a small balloon with a diameter of up to 10 millimeters without a biliary sphincterotomy. In this Cochrane review that was not only on patients with acute cholangitis, they did show that the papillary balloon dilation was associated with a lower risk of stone removal during the first attempt. It did have a higher rate of requiring mechanical lithotripsy. It had higher post ERCP pancreatitis that we just heard about, but it did have a significantly lower bleeding and infection risk. So the clinical use of this endoscopic papillary balloon dilation, you can consider it in people with a coagulopathy and acute cholangitis due to small stones, so stones less than 10 millimeters. Since it theoretically preserves the function of the sphincter of OD, you do not want to do it alone and you have to always put some form of decompression with it. And you want to avoid it in patients with a biliary pancreatitis. So how about large balloon dilation? So this is in larger balloons, 12 to 20 millimeters. It's useful for the removal of large or multiple stones, but in this perspective, observational study of 68 patients with cholangitis that had multiple complex stones, they had a group A that had the sphincterotomy and the large balloon dilation performed in the same session and group B that had it in two sessions. So the sphincterotomy first and then the large balloon dilation second. There seems to success rates between the two groups and the need for mechanical lithotripsy, but there was a lot more adverse events in group A that had it in the same session, including severe adverse events like death, significant bleeding, and moderate pancreatitis. And so if you are considering to do the large balloon dilation, you want to do it in two sessions. So biliary drainage, this should be performed in most patients. It might not need to be performed in patients with mild cholangitis. Other options include the endoscopic nasal biliary drain placements or biliary stent placements. Overall, there's no difference in technical, clinical success or adverse events, but you might not want to consider the nasal biliary drainage in somebody that might remove the drain, like if they have dementia or delirium or due to patient preference because they're going to have the nasal biliary drain. If you are doing a biliary stent, there's no recommendations on what type of stent. You can use a 7 French, 10 stent. There's no difference in those straight plastic, straight or pigtail plastic stents. Fully covered metal stents, unclear role at this point in time, but you can consider in patients with cholangitis related to malignancy or in patients at high risk of bleeding or where they have hemodynamic instability, so bleeding may pose a risk for the patient, or if they have multiple complex stones. So going back to the case of the 7-year-old female with moderate cholangitis, ERCP was performed within 48 hours. During the ERCP, there is actual purulent fluid draining, sphincterotomy, stonous logistraction, and a stent was placed. I'm going to briefly talk about U.S.-guided biliary drainage. This should only be done in places with local expertise. In this study of two tertiary care units with moderate to severe cholangitis where the ERCP either failed or was not feasible, there is different ways to do it, hepatogastrostomy, colodocal duodenostomy, antigrade stent placement, or rendezvous. There's overall high technical success, clinical success, biliary drainage, and there was a decent adverse event. So again, that should only be performed where there is local expertise. So overall, in summary, in mild to moderate cholangitis, you can do a single session with biliary sphincterotomy and removal of any stones. With severe cholangitis, you want to consider decompression. Not all patients should have the sphincterotomy and stone clearance. If somebody has an inaccessible papilla, then you either want to consider percutaneous or U.S.-guided drainage. If somebody is unable to tolerate sedation, then you want to think about percutaneous drainage. In patients with malignant biliary obstruction or ICU patients that do not respond to initial resuscitation, you want to do more urgent ERCP within 24 hours. In patients with coagulopathy, recent use of antithrombotic agents, or they need to go back on antithrombotic agents within 72 hours, or if they're hemodynamically unstable, you want to do a decompression without a sphincterotomy. In somebody with a coagulopathy and a small bile duct stone, you can consider the endoscopic papillary balloon dilation, but you have to place a stent. And then in patients with large or multiple stones, then you can consider doing the endoscopic papillary large balloon dilation, but you want to do this in two sessions. Thank you.

endoscopy

cholangitis

severity assessment

biliary drainage

ERCP