Biliary Atresia-Case Presentation and Panel Discussion: Update Course 2014

OK. Uh, so we'll start with the case. There's a 10 week old boy who presents to the ED with failure to thrive and jaundice. He has iceric sclera and hepatomegaly. Um, labs are significant for cholestasis, and you can't see it here, but a mildly elevated INR as well. So he has acholic stools, and an ultrasound cannot visualize the gallbladder or biliary tree. Um, you suspect a diagnosis of biliary atresia. So we're gonna, we have quite a few questions in this one, so let's, let's keep it going. So the first one, what do you believe is the optimal age for performing a a successful Kasai procedure? Less than 30 days, less than 45, less than 60, less than 90, or it does not matter? All right, what do you think here? So definitely as possible, OK, so Ernie, what's your number there? You know, this paper is looking at 60 days and this paper is looking at 90 days, and the differences are not really that significant. In fact, the series, the first big series from Michigan we wrote up, the kids that did the best were done at over 3 months. Uh, I don't know why, but they did did the best. They had the best drainage and had the best long-term outcome. So I think, is there a bias there that they were diagnosed late because they most of it was like they may not have been, you know, I think they're different forms of biliary atresia and so you have to be careful about the patients selection, you know, when we saw them, we'd see them not as a newborn. Well, we wouldn't see them as a newborn. They'd be referred in, and a lot of them, we did, we basically, when they got referred in in a month, we'd do them, but some got referred in at a later date. Some were reduced. It's been a long time since I looked, but when we did all our studies in Denver with John Lilly, that was under 60 days, and no question that there was a difference in outcomes if you got them before 60 or to the point where, I mean, we would, if you were coming up on that day, you would do it on the weekend, and I mean it was an emergency, and that was we, we, we would do it at 60 electively, but there were a number that came in after that, and they, they did a little bit. Maybe they didn't have biliary retrieve. Yeah, that's always the question. Yeah, that's a, it's a pretty interesting spread on people and what they're putting up on the, uh, screen. But there's the whole spectrum there that describe that paper, Nick. That was, it's an interesting one for how they did it, which is what makes it. So, uh, the best paper I thought to illustrate this point is um actually a review of all the patients in France that have biliary atresia, and they have pretty decent follow-up, and you can see there. A significant correlation with survival with their native liver and having the procedure at an earlier age, and you can see, especially at the 5 and 10 year points, the children that had it at less than 1 month of age compared to the ones at over 90 days have nearly twice as high survival rate. And so it sure is hard, it looks like to put a date on it, but this was neat. It's literally every kid in France supposedly that had biliary tresia. They went back and actually dug out the old charts and tried to see just how they did. It just basically it's a pretty relatively smooth path, you know, as you move farther down the road. Don't you think the critical factor there is how much cirrhosis they developed in the liver? And some kids have cirrhosis earlier on than others. So it seems to me that if you want to get a little better data, it would be nice to see what the biopsy was at the time of uh Kasai, because it's, it's variable. It's not always directly correlating with the amount of time, you know as how old they are. Yeah, it kind of clicks to this next question that, you know, it's, I mean, like, and you were saying, Dan, is it, because when does it really start? We know it's not a It's some, it's starting at some point, but it doesn't start everybody at day zero. Somebody can start at day 20, and then they start to, and it's progressive. So, you know, Rich Ricketts, uh, I had written up a series from our institution, and, uh, he actually looked at 0 to 75 and then 76 days or older, and he had not statistically significant better results with 76 days or older. It's consistent with what I'm here, which is what you said. So, but it may be again, it's, it's if they're if they're presenting that late that you wonder, is that a different Is that what you're saying? Yeah, I mean that in that French study there's, they do have a nice review of all the, for many years they're all in there and it's the same deal. Some are a little bit outliers or sort of odd, but then you kind of look at it as a pattern and then it just kind of, there is some. I think we all believe it. There's the longer you wait, the riskier it gets. But what do you guys think? I mean, age of operation, or is it really how long you've been symptomatic? Yeah. Another way of looking at it could be, uh, who do you think would do better, an 8 week old that's had symptoms for 3 weeks or something like a 12-week-old that's had a week of symptoms, you know, came to the hospital immediately. But what, what do, what do you call symptoms? What are symptoms in Billy or treasure? Yeah, I would say jaundice, having pale stools. OK, but, but in most of the biliary trees, they're having that from basically the first week of life. So in, in, in the time you do it for referral centers, big children's hospitals is gonna, when they get, when you get referred in. Some pediatricians are gonna be much more aggressive in worrying about it and get them in early. Others are gonna wait. I, that's why I think the only thing that would be objectively uh uh scientifically more accurate was if you could correlate the results. Uh, with the, uh, biopsy they did at the time of Kasai and then correlate that with the age and then, you know, the, the outcome. Yeah, I think you're on target. Peter Altman used to, used to argue that, uh, you should do them between 60 and 75 days, and he had the largest series in this country, uh, from Colombia. Uh, so that's sort of what I followed. Uh, but as I said, some of, some of them did better later, right? And I mean, in, in every study, and every one of us knows somebody who got a Kasai late that did OK. And then, of course, did they really have biliary resia or how did it set out, they wonder. But the, can you, Todd, because I can't see the answer to that one. It looked like duration of symptoms people thought was a little stronger or something. Pop to the next one and see what people think on that duration of symptoms 57%. OK, so I guess fire away, read it up. Yeah, so going off of that, is there any age beyond which you would not offer to decide? Maybe you would just refer for liver transplant. Again we're gonna ask the next your question right after this, which is, you know, what would persuade you not to offer the cassa what liver symptoms, what biopsies. But does anyone just on age alone say forget it? Well, I think it depends on how, what degree of fibrosis they have in their liver. I mean, if they, if they've got very little liver fibrosis, even if they're 4 or 5 months old and it's been sort of a slow slide and you think that they've still got some element of preserved, Bowel drainage from the little tiny radicals or something that they have, you might be able to preserve that if you do it. You know, I, I, I, the longest survivor I have from 1974 had undergone an exploration and sort of a procedure at another children's hospital in Michigan and, uh, with no results and came up and I redid the whole thing and that guy's in his 40s, late 40s. Um, I'm sure he's just lucky in getting in, in draining, but, and he was. Clearly over 4 months. I don't remember the exact date. I remember his name, Angelo Daniels. Yeah, that's one you never forget, right? But I think there's some, but I think that, oh, I'm sorry. Sorry, I forgot about all the rules of regulation, uh, but, but I think that the, the message is that you don't really know whether or not you can get a good result and like redos, you know, you say somebody who knew what they were doing does the first billiary tree at the first cassa and they've done it right. If they don't get a good result, they'll go back in. But I think also there's an issue that we got to think about because we got a couple here for that for sure. Sometimes you can get a good result. So it's not like you have trouble finding any controversial elements with this one. So, um, about what this one is throwing again out of the question for people. And can we see the results as they come back we're missing. Hey, um, Stacey, can you or Jen, I don't know who's doing it, can you put that poll up? We're missing the one about, uh, the, the slide that he showed before about what, how many months until you would decide not to do a Kasai. We're still missing that poll, um, but now we have the poll result for this question. That's good. We, I mean, we have a million questions. So let's you want to do that one, sure. So anybody here, any thoughts of any of you guys at this day, would you say are the, what are the things that make you go, hey, we don't even need to do a cassa. Yeah, that, that reversal of portal flow makes me really concerned because, you know, I've I've had patients that I've done a cassa on have achieved good biliary drainage. They've got a normal bilirubin. But their portal hypertension then continues to ramp up because they've, you know, set this inflammatory, um, you know, sort of fibrotic change in motion in their liver, and they end up going on to need a transplant because of the end-stage results of having such profound portal hypertension. Yeah, and so, you know, that to me is a very concerning. It is hard because you, we all, like we were just saying, you know, the ones that, well, does everyone just deserve a shot, you know, because maybe it'll go because you have that anecdotal thing. But is there a point where you're just truly But I think it's more than a binary. It's either gonna work or it's not going to work because I think if you can buy them time, and how then you increase the donor pool potential. And so, uh, I think in several institutions where I got in the OR, had a horrible looking liver, and had the transplants come and look, they're like, do it anyway because if even if you buy us months, that helps, helps, yeah, some of those, they can limp on. I mean, the thing is like it technically becomes an easier operation. It's less. Of hepatic artery thrombosis, and I mean, you know, the ones that don't get a casai then are just managed by the hepatologist and go on for some time. I mean, the hepatologists can actually limp these kids along. They're not nutritionally in a great place, but they can get them out to be, you know, a year in the absence of a cassai and the absence of a transplant. And so by then, you know, the donor pool is far expanded, and then, you know, they're a better candidates. So you're saying don't do anything if you have, yeah, they, I think if they've got signs of end stage. Um, liver disease, you know, you know, so profound portal fibrosis, you know, or profound fibrosis and reversal of flow in their portal vein, I don't know that you're really gonna make anything better with a cassa. In fact, you may put them through a worse thing by stressing them with the operation. And if the hepatologist can limp them along and get them, you know, to a size adequate for a liver anyway, then. Right. Maybe that's a patient to, I mean, it does go right to your point, and I don't think we have the data yet to say definitively, but I think that's what people are trying to maybe the way we can get our biopsies better, you know, if the patient hasn't developed severe portal hypertension, which then makes the operative procedure a little more risky in terms of bleeding, etc. The operation itself is not a big deal, you know, it's not a technically demanding operation with a lot of technical risks. So if you're not sure, why not go back in? And I've done that a few times, and sometimes it works, and you get a flow and the kid goes for a fairly long time. But do you think, but, but do you think that that's because, I, I mean, it's hard to know if your second operation got it to work or if it was just sort of limping along and then eventually worked because there are some of these that, you know, it's almost like um a race between regeneration of hepatocytes and progression of fibrosis. And so, If, you know, I, I've had a patient that I didn't redo, and I thought surely the thing was a failure because the bilirubin remained elevated, and then at 5 months post-op, the bilirubin dropped to normal. So, you, you know, and how do you explain that? Well, it seems like that somehow, eventually the scales tipped in favor of liver regeneration and they were able to, you know, start clearing things. So, but even if you get liver regeneration, you still haven't done anything to the drainage procedure, the cassa. So why would you assume, do you think that the bilirubin went down simply because the liver regenerated, because you still need, you need bile drainage too. And so if you don't go back in to operate on it, how do you get better bile drainage if it wasn't working before? Well, I think it's a question of whether or not The fibrosis is reversible. Yeah. Yeah. Let's move on challenge and pop the next one they would do. Yeah. OK. So, do you alter your workup based on the patient's age or duration of symptoms? Um, would you expedite your workup for older patients or would you forego anything like, um, I don't know, using phenobarbital for a HIDA or getting a liver biopsy before going to OR. In, in the interest of time, we have a few, so that's clearly where we're going to lead is, is there a reason that you changed speeds? Do you get HIDAs, things like that. So a quick answer to this, we get what you say. Um, it's 50/50. Well, it's changing, but, but right now 60% say they would not, not anybody else think they change it, but it's grinding back to 50/50. It keeps, I think I tend to, I, I think we do tend to change. I do think we do tend to change it, change the workup and stuff a little bit. I, I tend to drop the Haida. Yeah, because especially the go ahead to the next question. So we get a liver biopsy, and if that is suggestive of biliary, then you don't need a bunch of other stuff. I mean, it's interesting is we never used to, you know, it's like, I don't know, I was always trained that there's no need to do the preoperative liver biopsy for hepatology, but now we're in an era, everybody, everybody gets one, and it's, you know, it's like they consult us after they've done the liver biopsy, and we don't do that here. Well, coming up shortly will be, do you combine that with now. Uh, cholangiogram, percutaneous cholangiogram. Anyhow, this one is you order hya for suspect biliarresia, and if so, do you use pheno? Do you think phenobarb is important? If you get a hideout, I would do phenobarb. It increases the accuracy theoretically. I would say no because, you know, if, if the question is getting them to the OR sooner, now you're going to delay by, you know, however many days, you know, while you're inducing them with phenobarb and If the, if the question is really like we want to get this done as early as possible, then why wait for a week? It is the way that spins it because if you go do your tube clicks for it, just that's the quick height. Can I ask you a question? You mentioned getting a cholangiogram. How many times with a real biliarytri have you been able to get the cholangiogram? Has the gallbladder been patent? question. We'll hit on that in just a second. It's not very common. No, so describe this for me. Yeah, so this is just a study looking from Children's National Medical Center actually looking at how accurate a HIDA with phenobarbital is, and it's a pretty good test, you know, high sensitivity. What year was that? What era it was from 1990 to 2011. So it's 20 years. Wide range. The thing about it is when you look at that, um, Their description of an effective HDA is at least 5 days of phenobarb and a level that's high enough. And that's a big commitment to, to get there. If you're doing it in a 2 week old, that's one thing. If it's a 4 month old. Yeah, so it makes it, I think the data, when you look at it together, at least when we were going through this, yeah, it looks, I mean, the Haida with phenobarb looks like it's the way to go, um, but it's, it's costly in time. It's a big, there's a big time commitment. Well, you know, has anyone done, I'm asking you guys because I don't know, has anyone done the study where you look at, you know, you do the HIDA scan without. And then do the HIDA scan with and see if it changes the results. Has anyone done that? There's this study actually has where they did it and then repeat, did it with, without or got a negative amount then, but there was a misplaced, you know, they didn't have enough. The phenobarb wasn't at the right level. Then they went back and about a third of those, if I remember the numbers right, I'm not going to get them right. But uh, you know, a significant number then showed up as biliary atresia because they. Did the what they considered a full phenobarb route when they repeated it. But now you're probably 89 days into this workup too. But they absolutely had a, a pretty good number. I, I can check it in a second, but it, it was impressive to me anyhow reviewing it that the phenobarb clearly changed it, but it was a very costly time amount. Uh, liver biopsies, we talked about you guys, everybody get one in percutaneous, does everyone do a percutaneous somewhere? Yeah, we don't order it, but it comes, it comes up front. We get the results that will pop up yet. That's uh, but, but the question you're raising is a good one. Do you need a liver biopsy before you go in and explain the kid? The answer is no. Yeah, well, there was just a, just a paper published in the last month, I think it came out as, uh, one of the apps that suggested reading papers that, that was a big group published in gastroenterology that looked at biopsy plus other clinical parameters, and they had a scoring system that they developed, and the ability to predict, yes, biliary tresia, no biliaryresia was almost 100%. Using the biopsy plus these other parameters. So going back to what we said earlier, I think it's changed. I think our, our pathologists' understanding of what to look for is different now than it was 20 years ago. I think also the ability to get a percutaneous liver biopsy safely, you know, our interventional radiologists, they do it all the time. It's a, you know, nothing, right? It takes a day. I think that's a big factor. I agree with you. Anybody have this where they're at? I can't see it. Yeah. I can't imagine it's like if you, I mean, I, I couldn't imagine doing that because if they really had biliary atresia, they're gonna be mucking around in there so much trying to something that doesn't exist. I mean, the number, if you look at your, your, everybody look at his series of bili atresia, how many that you did had a patent gallbladder. You know, I'm just thinking at the top of my head, it's super rare. So why even bother trying to do it? I agree. It's interesting though. I know in, in Jensen in Milwaukee's been working on this stuff for a pretty good. It's the only place I saw where there's really a significant numbers with success rates, and they basically, they just combine them when they do them. They do, and if they, it's there, they try and get it in. And they get numbers that pretty quickly can give you an answer. To me it's like, wow, how many of those kids had biliary atresia? This is anybody who had cholestasis. This, I don't have to give you the number. So, so I don't, to your point, how many of them are actually possible when you actually have biliary atresia. It just means you can technically, you can get a needle in a patent gallbladder. Yeah, exactly. I mean, I think that's a good way of putting it. I mean, I think it's rare to have a patent gallbladder with real biliary atresia, but if the basis studying is cholestatic jaundice, it's a different patient population, and you get that mixed up. Uh, I, we, we never did any, but the hook is to the core. The flip to it, Dan, is, I mean, if you can't. Visually, when you keep, you're gonna have to operate you can't, but if, if when you do the percutaneous biopsy and you shoot something in the gallbladder and you're done, you're not even getting a call. I mean the kid is the biliarresia is off the off the map. So if it's not dangerous, you know, it's, well, you get the call for the one required surgical intervention, right? So 1 out of 1 out of 46, yeah, and that may be it. So if you do the ultrasound and there is a gallbladder, then it may, and if, if, if it was safe enough, it may be a reasonable thing to do to rule it out, but it would be that plus a HIDA scan that's negative. You have to, right, that shows no secretion because in probably in most of the kids who have a gallbladder, you're going to be able to show secretion with a HIDA scan, you know, this brings up a little side thing with the gallbladder and the ultrasound is, you know, they do a prenatal. Uh, ultrasonography to see if a baby has biliary tresia, if they're worried about it, and they make that diagnosis on the basis of not seeing the gallbladder, and that's totally dependent on what angle they went on and one of my closest friends overseas, grandson in utero, was they were told it was biliary tresia. They were considering an abortion. On the basis of a very experienced pediatric uh uh radiologist, and they called me and said, don't do that. The kid turned out to be perfectly normal. So the, the prenatal ultrasound with with this particular disease is a very important thing too. So I think we need to wrap this up. Do you have any final comments? Uh, how about this last one, steroids. OK, you guys use them. Who uses steroids? Post-op steroids. It's been studied, right? It's been studied studied. That's so nobody's using them. I should not be done. I still am. Really, really, you do. The Japanese, by the way, the Japanese are still using them. Last year at the big 50th anniversary of the Japanese Society of Pediatric Surgery, they presented the Japanese experience, you know, they get every patient in Japan registered, and they were still recommending steroids if they either routinely, even before they saw that maybe the drainage went down, or when there was drainage decrease, they would put them on steroids. The, the most important thing with Billy atresia right now is what's happening in Japan with the way they're doing the operation. And if you want to see a couple of nice papers, September issue of Pediatric Surgery International has a couple of papers from Yamataka, you know, who's the one who's replaced, uh, Takeshi Miyano at Juntendo University, and they have looked as, and as they can do there at where you should start doing the Kasai procedure. And they go much wider than Dr. Kasai did. And in addition, they claim, I don't know how they prove this, that they make the stitches much more superficial, so they don't damage any little ductules. And at 10 o'clock and at 3 o'clock where the normal bile ductuals would would bifurcate would go, they don't put any stitches, and they put the stitch on either side of that. Now looking at that and then looking at the cassai, the classic casai there, they. Claim they've got better results. The numbers aren't statistically valid, but they seem to be better, uh, and they are now they're trying to prove and refute IPEG's recommendation to not do these laparoscopically by showing, and this Yamataka is the one that's doing it, that if they do it laparoscopically, their results are just as good as open. So, so it's yeah, I mean I mean. is iPad. So yeah, I know it is. I know it is. So, uh, I, I wanna wrap up here. Um, I know you have more questions and you guys, everyone can see the questions on the, if you download the files, you'll be able to get access to that and see the bibliography. I think today has been a fantastic day.