Biliary Atresia: Update Course 2015

For the next few minutes we're going to talk about Billy Reresia trying to hit on some of the important points or some of the newer things that are going on. Um, there's a whole slide deck here. I kind of wasn't properly prepared and so there's way more slides that we can share with the group, however you guys want to use these down the road. But uh but you're going to be doing a podcast for us soon. Yeah, right, exactly. So again, so. Uh, if that clicker doesn't work because it might be out of batteries, just use the, uh, yeah, that or the forward backward arrow. So we will start with a case just to kind of frame the discussion. Um, pediatrician calls you about a 60 day old full term male with who is otherwise healthy but is noted to have persistent jaundice, and as you can see on the colors here, the patient's a little jaundiced, and I'm not sure if you guys can see the eyes, but it's clearly eeric, so. On exam, the patient is clearly jaundiced. He otherwise looks well. Like I mentioned, the sclera, his liver is a little enlarged, and his stool is clearly acholic. He gets routine labs. His bilirubin is up. Direct bilirubin is 5.8. AST and ALT are mildly elevated. He's dropping into his nadir from a hemoglobin standpoint. The pediatrician had gotten an abdominal X-ray that was otherwise. Remarkable. So as we start to think about the population of infants with cholestasis, it's important to think about things in terms of the anatomic and non-atomic, and I'm only touching on these just because biliatresia is well within the spectrum, but in this day and age, the frequency of idiopathic neonatal hepatitis as being the last diagnosis has actually shrunk tremendously. Years passed. If you actually looked at studies from the 70s and 1980s, idiopathic neonatal hepatitis would be about 70% of the patients. Now it's probably down to 10% as a whole series of forward steps have been made where they've recognized inborn areas of bile acid metabolism. The PFIs have been genotyped, and so a better understanding has been established. And so the point of this is how would you assess this patient and what studies would you want to think about performing. So again, this is an area where sometimes we'll be involved, sometimes the pediatricians will have already referred to a GI person. In this day and age, pediatric GI has expanded tremendously, so there's pediatric gastroenterologists at virtually every hospital. So ideally they will have started the workup. These patients, but on occasion you will still be in that position where you are one of the first line of responders in terms of the question. So what are the studies you're going to consider in terms of obtaining to establish a diagnosis of bilioresia in the order of them. Well, if they've had the biopsy, there was a paper published a year or so ago that said there's a scoring system, right? So if you have your biopsy and these clinical parameters, we are 99% accurate at diagnosing biliarreia, and that's before the ultrasound, I think, even so, so those would be the two things. Biopsy and an ultrasound. So of course Dr. Harman has jumped ahead of us because he actually hit one of the important things in the way we go about it at our institution. But of course not all institutions have the capacity to do percutaneous liver biopsies, especially in a 767 week old kid. So again from standard things we're going to be getting the biochemical analysis. One of the things I want to highlight here is something called the jaundice chip. The jaundice chip is a technology in which blood samples undergo a kind of a gene chip microarray analysis looking at the profile of molecular abnormalities within it. And within the gene chip are the PIC abnormalities PFC 123. Alpha 1 antitrypsin and the JAG 1 mutation. And so as a result, unfortunately it takes 4 to 6 weeks, so it still doesn't come back timely enough for us to be able to make a decision tree intervention from whether the patient has biliaryresia or not. But virtually all pediatric gastroenterologists, when they have a cholestatic infant in this day and age, if biliaryresia has been ruled. will do this jaundice chip because they'll get a diagnosis of these different PIs which then or allegs which then will help guide their decision making. And of course ultrasound and HIDA scan are still an integral part of the workup. A percutaneous liver biopsy is very much a part of many hospitals at this day and age, and intraoperative cholangiograms and biopsies, of course, are the things that we become responsible for. So a couple of questions. Well, the slide set didn't change. So I'm going to skip these things here just to point a couple of the slide set had some points about ultrasound. Ultrasound is obviously the first modality that we'll be utilizing as we explore the workup for these patients, but there are some considerations in terms of when you have the ultrasound and you look for the gallbladder. The absence of A gallbladder on ultrasound does not conclusively show biliary atresia. The corollary to that, of course, is the presence of a gallbladder doesn't exclude biliary atresia because the sensitivity of the ultrasound probes in this day and age are so much more sophisticated, so they can actually visualize even small shrunken down gallbladders that in years past maybe would not have been seen. Also, there is some evidence that there is this thing. Called the triangular cord sign, which is something that again you have to be working with a radiology team that's pretty darn experienced where they can look for the fibrous plate, in essence above the portal vein here demonstrating where the bile ducts were supposed to be and how there's now an inflammatory fibrous scar occurring and as a result actually has radiographic characteristics that are a little bit different. So again, this again is stuff that our radiology teams are working with and again depending on the experience of the hospital and center you're working at is a consideration in terms of your workup and of course a HIDA scan is still a standard part for many centers at our hospital we actually don't use HIDA scans and in fact if we order a HIDA scan, Dr. Ballesterri, our senior most hepatologist, looks upon it quite poorly. And will yell at the GI people fairly significantly because one of the challenges with the HIDA scan is these patients, it is beneficial to have a 3 to 5 day load of phenobar phenobarbital, and as a result you can delay your intervention into a time period which theoretically could be detrimental to the outcome of the Kasai. But this is just the standard kind of normal hepatobiliary scan where Start to see uptake in the liver pretty quickly. It concentrates into the gallbladder and then gets into the GI tract in a 15 to 30 minute period and sometimes it takes up to a day to absolutely make sure. In contrast, here's an abnormal HIDA scan in which you can see contrast being taken up in the liver. There's no localization within the gallbladder and even after a day there's no contrast getting into the GI tract. So from there, actually Dr. Harman preempted this, but do you routinely obtain a liver biopsy? And that really is kind of where many centers have moved to at this stage, which is, should you get a liver biopsy at this, at this point in time. And again I think it depends on the institution. What do, what are you guys doing in Akron? It depends. So in, oh, in well, so I was at Rainbow first, and at Rainbow we did a, uh, we, we would do the liver biopsies in the operating room, and then, uh, at, in Akron we get the liver biopsy ahead of time at the same day we start the phenobarb because we do do HIDA scans and that by that time, the time your biopsies are back, you can do your HIDA scan. And so that actually is one of the questions that you have to ask yourself, which is what is the capacity of your hospital institution in terms of getting that biopsy. At our center, of course we have very experienced interventional radiologists who are routinely are doing biopsies in kids as small as 3 or 4 weeks of age without any complications. But again, not all institutions have that. We also have our gastroenterologists will do biopsies in that age group percutaneously on their own, although they've become somewhat much more cautious. Other teams will consider a biopsy at the time as a separate procedure. Then you're talking about two anesthetics, and of course some people will only do the biopsy at the time of the changiogram. But the point of the biopsy, and this is again what was just mentioned a second ago, is on the biopsy again for those people who are very interested in chronic liver disease, what we're really looking for is this is the normal hepatocytes over here. Here's your portal triads with significant bile duct proliferation. And then this is a pathognomonic finding where you're actually seeing bile plugs within a bile duct. And if you see that, the confirmatory, I mean the likelihood of it being biotresia is well over 90+%. It's very rare that you will have a misdiagnosis at this stage. And in this in this regard, then the intrepid changiogram becomes a little less necessary. if we see it, if we go in and we will always review our biopsies before we actually take the patient to the OR with our pathologist. Just, just because these will have been obtained preoperatively and we'll have a chance to see it and it makes our sometimes sometimes intraoperative decision making a little easier because we have a very high likelihood of it being biresia if they see this and some of you ever not do the chang that's what I was, so um we almost do it more as a routine thing for for education purposes, but the reality is sometimes you do a chalangiogram, you can't even you can't get anything in anyways and so the point is its role is not. Beneficial in a population of patients in which we're fairly confident that the biopsy is consistent with biotresia, and we're also looking at for the gross appearance of the liver where it's green, it's got telangjectasia. Those are the things that we'll be looking for on, you know, at the time of exploration. But that's great because you can waste a lot of time in the operating room trying to convince yourself on the cholangiogram that there really isn't anything there. I, I, oh my gosh, I don't know. I can't be. So confident or you can look, yeah, or you can get into this kind of circumstance back to the slide here where you actually have the, you know, the distal patent cystic duct and common duct and no contrast going up into the gallbladder and so up into the hilum and so in this kind of picture, yeah, you have to sweat allegs pretty significantly as being well on the differential, but if you, if for us, if we've seen a biopsy that is so convincing that it's An obstructive process because Ali Gel's patients don't have the same bile duct proliferation. They won't have the pathonomonic finding of a bile duct plug, and so that's where it's actually very helpful to have a liver biopsy, but it does require you having a pathologic team that's confident and capable of reading it. And so you need experienced pathologists on top of the ability to obtain the biopsy, you know, at the DC update course and actually our Interventional radiologist was trained in Cincinnati and she did, we had a kid that had a frozen abdomen from a meconium cyst. She did it percutaneously and it's, so I, she trained there, so I'm assuming the others do that, but that blew my mind. I had never seen that before. And then at the update course in DC, uh, or the, uh, the fellows review course. There were all these people saying, oh yeah, our centers, we do percutaneous changiograms. Well, people are doing percutaneous changiograms. I'm not exactly sure what the benefit or role of that is because the reality is with a liver biopsy, you know, a reasonable history, you pretty much are steering. So for our center, our workup is actually limited to a biopsy, labs, and at that point in time and an ultrasound, and then we're posting the kid. What if it was a negative biopsy? How confident are you? So we certainly have had those circumstances where the biopsy is equivocal and then we'll watch them. And again it depends on the age. In this particular case, it was a 60 day old, so we're facing a little bit more of a compressed time frame for some things that we'll touch on here in just a second. But those are the patients where then we sometimes will be doing a more careful cholangiogram at the time and exploring with the intent with uncertainty in terms of the workup or the plan to proceed. So back to the slides here, I just want to point out one thing here, which is making sure that people are all cognizant of the way you think about a biliary atresia hilar dissection, where the ideal circumstance is at the minimum to get above the portal veins, but this is what the Japanese will call an extended dissection, where they'll go to the first bifurcation of the vessels. This is actually the proper way or the way Kasai. Described it and this is also one of the reasons that when we look at the results for Kasaientostomy done in the United States versus those done in Japan, why their outcomes may be better might be because they have a more extended dissection performed uniformly, and I'll touch on that just in a second here and then we'll flash through a couple of pictures here, but this is just what we mean by the. Extended dissections where you go beyond the bifurcation of the branching, the branching of the patic arteries on the right and left. Normally everybody thinks about the portal vein as being the hallmark for where the dissection is initiated and where you end, but for the extended direct dissections because this is where there are small bile ducts coming into the hilar structures in terms of your fibrous plate. So the same depth but going out going out more lateral and this has implications for one of the things we're going to touch on towards the end and I'm so sorry that Mark's not here, but in terms of the laparoscopic side. So anyways, um, just a couple of pictures for those who don't haven't seen this before, but this is a polysplenic polysplenia syndrome patient where they'll have these multiple splenic nodules and of course in this population of patients you will also find these patients with pre-duodenal portal veins, and these patients are the ones who are most difficult in terms of actually. Doing a cassai because a lot of times there is no bile duct remnant. There's not a bile duct connected to this area. It's all above it. And so this is really oftentimes a population of patients where you almost can't do a cassai in that population because there's no obvious target in terms of where to go. And then just another one to show one other slide here which is this is a patient where we actually had a cystic variant of a biliary atresia where we're actually in the gallbladder doing it. This patient actually got diagnosed in utero in utero with a cystic mass in the hilum. The differential at that point in time was a cholidocal cyst versus a cystic variant of biliaryresia, and unfortunately the patient got lost to follow up and so showed back up at 40 at 6. odd days, 50 odd days, and at that point in time had a liver that was starting to get firm, so she went to the OR and so this is actually what we saw, which was a cystic mass in the hilum with bile duct remnants going out both sides here and this is a patient who we actually ended up doing a cass or what would be called a correctable variant of biliaryresia, but we intervened at too late of a point in time and there's some data that came out of England here from a few years. Mark Davenport wrote up the experience where in these patients if you intervene before 30 days they have a better outcome. And so again for those patients in which you're getting in utero consoles for a cystic mass, you always have to differentiate a cystic variant of the bilioregia versus a choliidocal cyst. Choliocal cyst patients will still have pigmented stool. The cystic variants will actually become a colic, and so it's a simple clinical way to try to differentiate what the patients are doing. And a couple of of just quick operative questions, which is what's the length of the rear limb that you routinely use and are there still centers that are considering anti-refluxing valves for limb. Uh Not 40, 20 short. What, what reaches right? OK, Jason, 20 to 30, 20. OK, so just so you know, 20 is not good for a transplant team because almost always you'll lose 5 to 78 centimeters of length on your root at the time of the hilar dissection. Yeah, so our, our, our target 30 to 40, yeah, our target is 30 to 40 because if you shorten your roo. And the transplant team, again, one of the few advantages of doing a transplant on a biliotresia patient is you have a pre-existing root so that you don't have to recreate it. There's nothing more of a nuisance than actually having to go back and recreate a second root because the first root, and again we can't predict ahead of time how many patients are going to lose roe length because of adhesions to the hilum. And then the anti-refluxing question again, this was done long ago and there are still some centers that do it, but the value of this is really has been not proven to be effective. And so really the point is a 30 to 40 centimeter ro and then bile drainage. Almost, well, yeah, just we'll finish up because we're, yeah, so I'm just going to just come to a to a couple of observations, some of the newer things. One consideration is how many surgeons do you guys have in your practice who's actually doing cassa. We're all doing them, which is not right, but. our place David and I, OK. And then in that respect, how many casais do you actually do a year? Well, so we always have two surgeons, OK, so for that reason you get double. So, the point of that is there is actually data that came out of the UK, and this is from almost 15 years ago, and the United States hasn't been able to adopt this for a whole slew of different reasons, but it's pretty clear cut that when they localized or focused on the group just 3 centers doing their biliatresis, that the 3 centers that did more than 5 cases a year had. Much better outcomes than those who had less. Now this is not, I mean, it's statistically different. It was like a 20% difference, but this is as a result led to the British health services focusing all Casa at those three centers, and they're the only ones who actually can get paid to do that. And then just the last thing I'm going to touch on here before, since we're running short of time, is the use of postoperative corticosteroids. Yes, and that Dan told me not to. Journal Club. All right, so the data for corticosteroids in biliotreia, actually there are two studies that came out of Europe, one from the King's Group in which they used low dose steroids, and the steroid dosing was actually only 2 per kilo here. Klaus Peterson and the German group then used 10 per kilo for 5 days. Neither showed benefit. The Children's Network, which is the national biliotreia Research Consortium, did a multi. Center trial in which they had about 70 patients enrolled in two different arms and they showed clearly that there was no improvement of drainage in terms of corticosteroid use between those who got it and those who didn't. And there's actually a slight increase in the adverse offenses, adverse events in the patients who got steroids, although this wasn't really surgical complications. It was more medical issues that arose. And so from this one might conclude. That steroids are not beneficial. The reality is though, as we studied studied biliotresia more comprehensively, there's a profile of patients with biliotresia who actually have an inflammatory milieu in which they actually have a gene profile in which steroids might actually prove to be beneficial. So even though we ran the study and are very careful about it, and the conclusion was that it was not beneficial, there are still times when steroids can be considered. All right, I think for that we'll stop just because there's a, oh, you ended on, so there's questions for you and because we're short on time, I'm gonna give you my phone and have you text your answers here about MRC role of MRCP and measurements in a chalangiogram to determine hypoplasia. I don't know if you unless you want to give a quickie. So we don't use MRCP. We've actually explored um the role of ERCP, but again for us since we have a a fairly high capacity pathology team. We don't need to go that route. I think there are certainly reports out there in which MRCP is being done. And then in terms of allos, ages is still the most difficult diagnosis, and I think it was actually done on a national, a national experience during a laparoscopic procedure for Kasai, for Casais in which they actually were doing it on an alls patient. If you cassa and Alis patients, you will shorten their natural. History of that liver staying with them and they will be transplanted sooner. That's actually fairly clear cut. So this is where the JAG 1 mutation works for patients in which you have cholestasis and you're not certain about the diagnosis of biliotresia. This is when we'll get an echo to rule out pulmonary pulmonic stenosis. We'll get X-rays of their spine to rule out butterfly vertebrae, and they'll actually do eye exams on those patients, all in an effort to try to understand if they're allergies. Uh, Thank you, Greg. Any comments or questions?