Biliary Atresia Part I

Stay Current is a multimedia publication designed to keep healthcare professionals up to date on standards of care and new emerging ideas. This chapter is created and edited by Todd Ponsky, Alex Kassar, Alex Gibbons, and Ray Henke, and is recorded and produced at Cincinnati Children's Hospital in Cincinnati, Ohio. Welcome to Stay Current in Pediatric Surgery. This is Ray Henke. Bileary atresia, the leading cause for liver transplant in the U.S., is a complex disease. Each patient requires expertise of a knowledgeable multidisciplinary team. However, the management differs around the world. So we gather experts from Japan, the U.K., and the U.S. to share their practices and debate the literature. We split this topic into two parts. In part one, we have three surgeons discuss the differential diagnosis, workup, and surgical management of biliary atresia. In part two, we add the gastroenterology perspective with an exciting insight into the future evaluation for biliary atresia, followed by debate on postoperative management and complications. Now let's dive into the discussion. Who do we have with us today, Todd? From the United States, we have Dr. Greg Tiao, who is the director of general and thoracic surgery at Cincinnati Children's Hospital. He's the Fred Reichman chair in pediatric surgery. He's the surgical director of liver transplantation, and he's the program director of the pediatric surgery fellowship. Greg, thanks for joining us. Thanks, Todd. We also have Dr. Atsuyuki Yamataka, who is affectionately known by most of the world as Yama. And Yama is professor and head of the Department of Pediatric General and Neurogenital Surgery at Jantendo University School of Medicine in Tokyo, Japan. Yama, thanks for joining us. I'm happy to join you. Thank you. And then we have Professor Mark Davenport, who is the head of the Department of Pediatric Surgery at King's College Hospital in London, and he is the immediate past president of BAPS. Mark, thanks for joining us. Thanks for the invitation. So let's dive right into this. And just for everyone listening, we are going to dig right into the clinical aspects of the management of biliary atresia. I think we're going to find that regionally there are some differences, and we'll try to get to the bottom of what are some options that we have in the management of this sometimes very difficult disease. Hey, Greg, let me start off with you, and let me give you a typical presentation of biliary atresia. So a 50-day old male presents to you with jaundice and clay-colored stools. That's all I'm going to give you right now. So talk to me about how you evaluate this patient and what might suggest biliary atresia and what's in your differential. Sure, Todd. Thanks. So for a patient who's presenting with jaundice at that age, biliary atresia would be very high on our differential diagnosis. Of course, we'd want to find out more history when the jaundice was noted, what was the perinatal course. And typically here in the United States, we would have had a hepatologist involved in some of the care. That said, for us, when we see a patient at that age, biliary atresia would be high on our differential. But of course, the many other causes of neonatal cholestasis would have to be considered. Can you explain to me what a stool card is? I would actually ask Yama to do that because that is really something that came out of the Far East. It's been spread around the world now. The Japanese have a stool card in which they have seven different colors of stool and they also have stool consistency on that card. And they send it home with families right after birth so that the families can track this from early on. And if the baby changes their stool color, that can translate to a earlier referral for workup and evaluation. I believe our Japanese colleagues use it also afterwards. But again, this is where I would defer to Yama to describe it more. Yama, do you use the stool card? Yes. Most pediatricians and pediatricians use the stool card because this is very effective when we are talking to the parents. Because when I say to the parents, your baby has a clay colored stool or yellow stool because they don't know the degree. So when we show the stool card, you know, they can understand what we are saying. So when we're talking to the parents, stool card, I feel very, very effective. Where can you get these? Well, I have copies of them because they're on the internet. They're widely available. They're widely available. And there actually is now an app. What's the app called? It's like a poop app where they actually have... I think it's exactly that. It's a poop app. Yeah, it's a poop app. Poop app. Yeah, where you can actually on your smartphone download it. It's actually done for families so they can actually track this. So the social media being applied, familiar, Tricia. I mean, we're thinking of integrating it into our post-op care process. So from a standpoint of workup, we would typically obtain a biochemical profile, CBC, liver function tests, a urinalysis. From there, depending on what those studies reveal, we would begin considering other imaging analyses. So talk to me about when you mentioned other causes of non-surgical jaundice. Just in brief, what are some of those things that might be on the differential? The things that we worry about most in that time period in terms of the differential are allergial syndrome, alpha-1 antitrypsin. Less common disorders include the progressive familial intrapatical estasis syndromes. There's now four of those classified and they continue to evolve. When kids are diagnosed or come to our attention a little bit earlier, sometimes we'll be worried about the infectious etiologies that can occur in utero or soon after diagnosis. So that's when we're thinking about torch titers, things along that line. So those are the viruses that can trigger some of these changes. Okay. So Greg, you want to start off with some blood work. What are you looking for on the blood work? Primarily, we're looking at the breakdown of the bilirubin. So obviously, at a 50-day old, the likelihood of having jaundice as a newborn would be highly unlikely. But you're going to want to see the breakdown of total bilirubin versus direct. We typically want to see the GGT because a high GGT is going to be more consistent with an obstructive process. Also going to guide you towards eliminate some of the P-fix. And so that's where the AST-ALT will also be elevated, but it's not as diagnostic. So you said that at a 50-day old, by that time, you think that jaundice would be normally unlikely? Well, from a jaundice to the newborn, the physiologic jaundice is going to have resolved. Have resolved by then. So that's a key point. Okay. Mark and Yama, would you agree that the first step is blood work? Yeah, absolutely. The key thing is to show that you've got a conjugated hyperbilirubinemia. Okay. And if you've done that, then all else flows. And Yama? Yeah, I'm also focusing on the degree of direct bilirubin level. And also, I'll ask parents when, you know, the baby started a clay-colored stool, immediately after meconium passed. Or initially, if the patient had a yellow stool, I think outcome is better than, you know, comparing when the patient had a clay-colored stool immediately after meconium. Okay. So, Yama, just to clarify what you're saying, if they started off with yellow stool and then it became clay-colored, you think that is a better prognosis? Yeah, much better than the baby had a clay-colored stool after passing meconium. Got it. All right. So, Greg, you go ahead and you get your blood work. And how do you proceed next if you have a high conjugated hyperbilirubinemia? At that point in time, we'd probably think about an ultrasound to differentiate between potentially a biliary atrecia versus cystic malformations in the biliary system or a colidocal cyst. So, we typically would go to an ultrasound at this stage. All right. And on your ultrasound, other than looking for presence or absence of a gallbladder, do you look for anything else like the triangle sign or the chord sign? We're fortunate in Cincinnati that we have an excellent ultrasound team and they will look for a triangle chord sign, but we really don't find that to be too consistent. We'd be looking for just the presence of a gallbladder or if they had a dilated biliary tree, we'd be thinking more of a colidocal cyst. All right. Mark, do you agree with that? Is there anything else that you like to look for on ultrasound? No, the ultrasound itself separates out the other surgical issues. So, we haven't mentioned inspecated bile syndrome. You can have a spontaneous perforation of the bile ducts. All of those should have ultrasound positive features. Boreo atriso itself is largely, on the ultrasound at least, something to exclude later on. They've usually got an atrophic gallbladder. Some of them have a mucose seal when it's difficult to differentiate. We also are a bit skeptical about the value of the triangular chord sign. It's not something our ultrasonologists really appreciate or think it's particularly discriminatory. So, once they have ultrasound features suggestive which is, as I say, by exclusion, then we would sort of move on after that. Yama, anything to add? Yeah. My way for approaching is similar to Greg and Mark, but I will more focusing on the presence or absence of triangular sign if the gallbladder is absent. Okay. So, some variability, but it sounds like there's some question about the accuracy of that. So, Greg, you have the ultrasound and the ultrasound shows absence of a gallbladder, no visible ducts, and that's all you see. How would you proceed now? Again, here in Cincinnati, I'm privileged to have a really strong hepatology team. And so, we would proceed to a percutaneous biopsy at this stage. Our pathology team is quite capable. They participate in the children's network. And so, our senior most pathologist is the lead pathologist in that network. So, as a result here, we would typically go straight to a biopsy. Some teams might consider other diagnostic evaluations a high-to-scan, but that's not something we've done probably in the last 25 years here in Cincinnati. Okay. So, for the listeners, I think this is where we're going to hit a point of controversy, a point of difference in management. I think historically, a high-to-scan would be a common next step. But as you just heard, in Cincinnati, they would go straight to biopsy. So, of course, now we're going to turn this over to our other two experts. Mark, how do you do things there in the UK? Very similar to Cincinnati, you'll be surprised to know. I am surprised. So, our biopsy is the key. So, if you've got a pathologist experience, confident, et cetera, almost 90% of these can be diagnosable on the biopsy findings. We don't use a high-to-routine. The only real indication that we use a high-to-routine for typically pre-to-be babies that have parental nutrition, long history, that kind of thing, and there's a question mark over the actual sort of pallor of the stools. Then we might get a high-to-scan to try and prove that it's not really easy. But like Cincinnati, we gave that up a long time ago. Okay. So, Yama, do you get high-to-scans there in Juntendo? Yeah. We do liver sintagram. We call PMT sintagram, probably similar to high-to-scan. Okay. We will check the scan first. Then, you know, in the most majority of the cases, we don't do biopsy. Right. Before we get to that, let me ask you a question. For this, I'm assuming it's a nuclear study that you do there that's similar to the high-to-scan? Yes. Similar. Okay. Very similar to high-to-scan, yes. Do you pre-medicate them with phenobarb first? No. No. Okay. I know a lot of places, just to make sure that we hear all the different options, will obtain a high-to-scan and will pre-medicate for several days with phenobarbital to increase the liver uptake. And so, it sounds like that is not done there in Japan, or at least at Juntendo. If there's excretion into the cyst, that is likely to be cortical cyst. If there is no excretion into the cyst, it's likely to be biliae atrasia. I feel liver centigram is so important. Okay. So, you don't get biopsies routinely. Tell me then what would be your next step after you did your high-to-scan and there was no excretion. I would do laparoscopic investigation. You said laparoscopic investigation? Yes. Without biopsy, going to laparoscopic investigation. And tell me what you do during that investigation. To see the size of the goldbladder or we can proceed to cholangiogram. And you do that laparoscopically? Yes. I want to quickly ask you how you do that technically. I'm assuming you put a port and put a catheter in through the right upper quadrant and you clip it into the gallbladder? I will, you know, through the umbilical, I put the troca for scope. Then there's another troca on the right subcostal troca. Then I can grab the gallbladder with the forceps. And then deliver through the troca side. I can deliver the gallbladder. Even the gallbladder is very, you know, atrophic. We can stop pneumoperytonium. Then we can deliver atrophic gallbladder. Then we can see the lumen. If there are sometimes, you know, if the lumen is tiny, we cannot insert the, you know, tube for cholangiogram. At that time, that patient is very much likely to be in atrasia. The most of the cases, we can do cholangiogram. Just one observation about HIDA. I think HIDA is certainly utilized. The NASSIGN guidelines actually right now are saying its value is a little bit equivocal. Just as Mark alluded to a second ago, it's helpful when you're not too suspicious of bilatresia and you're really trying to rule it out rather than rule it in. And so, you know, the NASSIGN guidelines, which is what most of the North American pediatric GI people are going to, in theory, follow, actually recommends not to get a HIDA scan because there's always a concern, especially in a 50-day-old, that if you tried to load the patient with phenobarb, you delay treatment by potentially five, six days. And that starts to push you closer and closer to the windows in which the efficacy of the CASAI is going to continue to deteriorate. So that's where, at least in North America, the guidelines are to not obtain a HIDA scan. Thanks for explaining that. So let me go back to Davenport. So Mark, so you have this patient, you did your ultrasound, you're suspicious for bilateria atresia, and at your place, you would go straight to percutaneous biopsy. And so you then wait several days for those biopsies to come back? Yeah, no. So we can typically get, certainly in a 50-day-old baby, get a diagnosis in approaching 90% of them. If there's still clinical suspicion, bale stools, et cetera, we then go to an ERCP. Wow. So we use ERCP for about 10% of our babies. Wow. So you're able to get a side-viewing ERCP scope into our BGA-old. They're not made in America. Don't worry about that. It's a Japanese scope. It's only the very best. Very, very impressive. So you would do, your next step would be an ERCP. Before we get to the ERCP, Mark, tell me what you look for on the biopsy results to suggest bilateria atresia. Okay. Well, I pay someone to look for it for me. Okay. So we're talking buctylar proliferation, typically. And bridging fibrosis? Those aren't diagnostic of bilateria atresia. So a proliferation, a small cell infiltrate, that kind of thing. So they've got their list of criteria. And particularly, we can, in a 50-day-old baby, the problem is, therefore, the biopsy itself is taken too early. If it's something like a 10-day-old baby, 20-day-old baby, then they will have a problem about making consistent diagnosis. But by 50 days, all of the features should be established. The other pathognomonic finding for bilateria, as opposed to some of the other obstructive processes, is you'll see bile duct plugs in those bile ducts that are proliferating. So yes, as Dr. Davenport said, you do need an experienced pathologist because depending on the age and the progression of the disease process, the findings will vary. And so you need people who are quite experienced in terms of looking at that. You did hit on something that I think is helpful, which is if you see significant fibrosis on a biopsy, that may guide you down the road in terms of how you want to proceed because it is another piece of information that reflects the disease progression. So let me rephrase that. Yama would do lab work, ultrasound, a nuclear imaging study similar to a HIDA scan, and then proceed with laparoscopy for a cholangiogram. Mark would do an ultrasound and then a biopsy, and if it's suspicious, would then proceed with ERCP. If it's suspicious but not diagnostic of it. Ah, okay. Suspicious. If the biopsy is usually positive and then we just go on to a laparoscopy plus or minus cholangiogram. If they've not managed to tick all the histological boxes. Okay. Got it. I still think it's a possible diagnosis we will do an ERCP. Okay. Greg, have you used ERCP? No, we haven't. We are aware of the literature and it's actually pretty interesting consideration. I think our European colleagues have embraced that a little bit more than we in the North America. That said, our endoscopy team here is willing and interested in integrating that into the paradigm. And I think what Mark said was very true, which is if you don't hit every one of the pathologic parameters that guide you towards the diagnosis, I think an ERCP is certainly a way to avoid exploration. That said, because they're all infants, an ERCP is going to require general anesthesia. So the benefits of it in terms of precluding an exploration is the technical aspect of it, but they're still going to require anesthesia either way. All right. So Greg, talk me through after you have your biopsy that is highly suspicious or diagnostic of biliary atresia, how do you proceed? We would then proceed to exploration. We would, we almost always try to do a cholangiogram just as a kind of a concept. And because it's a teaching institution, we want to make sure our fellows know how to do that. So we would proceed with a cholangiogram. So we'd make a small right upper quadrant incision, find the gallbladder, put some sort of typically angiocath into the gallbladder, secure it, try to take a picture, see if you get any flow. In the complete biliary obstruction where everything has sclerosed, then you won't get much of a picture. But it is helpful in terms of trying to get some idea of the distal patency of the bile duct and also the cystic forms of biliary atresia. It can be quite interesting more for us than for the patient. I think now the patient has been, let's say, determined to have biliary atresia. Mark, how do you proceed with, and you've done your cholangiogram, so you have your, I'm assuming small right upper quadrant incision, and now you're going to proceed with your CASAI. Can you talk us through that operation? Okay. This is one of the last remaining examples of a maximally invasive operation. We extend it across to the left. We extend it down to the sort of flank. So it's a big incision, and the way we do it is to exteriorize the liver. So we would be dividing the falciform ligament. We would be dividing the left triangular ligament, and that enables you to deliver the liver onto the abdominal wall. So that makes it open like a flower and is the best way of actually trying to dissect into the port of the abatis. And so we've been doing that for probably now 40 years, haven't really had any issues from it, and many people do do that. There are still some that clearly try and lead the liver in. But if you regard the philosophy as trying to actually achieve the best possible dissection, this is one of the ways to try and improve that. Let me stop you there, and then I'll get to Yama last since the operation was described there. Greg, tell me, do you exteriorize the liver? Do you pull it all the way out? I've done it both ways. There are times when if you're trying to visualize the hilum, and for other reason, it just doesn't, the baby's body habitus is not allowing it, I wouldn't hesitate to exteriorize. On the other side, I think you can do it in a reasonable fashion with the liver in. But as Dr. Davenport said, you need a pretty generous incision to do this either way. The exteriorization makes it very, very clear cut to see everything. And so it is a nice way. Because I'm a transplant person, I've seen some of the consequences of that, where you just seem to see a little bit more dense adhesions. And again, depending on the stage of the liver disease patients, those things can become quite vascularized. I've actually always wondered that, Greg, from a transplant surgeon's point of view, it creates a great deal more adhesions doing that. It can. Again, it varies. I mean, we just did a transplant on a Kassai baby of Dr. Reichman's from 21 years ago. And his liver was frozen up there. And Maria and I were kind of laughing. I said, I wonder if Fred actually exteriorized this liver. Yeah. So that's a great point. Yama, do you exteriorize the liver? When I have to do open surgery for billiard treasure, for example, the baby is less than 2 kg, 2 kg. I externalize. But for externalization, we need big incision. Because with a small incision, and externalization can cause kinking of a hepatic vein. You mentioned when you do open surgery. Talk to us about what you do in babies that are over 2 kg. If the baby is more than 2.5 kg, I do always laparoscopy. Because my impression is that most of the cases is diagnosed by cytoscan and blood test and ultrasound. That's why I don't do biopsy. So after ultrasound and hydro scan and blood test, if there is a strong suspicion of billiard treasure, I proceed to laparoscopy investigations. And laparoscopy investigations clearly show the diagnosis of billiard treasure. Because we can directly see the gallbladder. Gallbladder is very atrophic. Sometimes I omit cholangiogram. If the gallbladder is big enough for cholangiogram, I do cholangiogram. Then if the diagnosis is the billiard treasure, I proceed to laparoscopy casai. I remember that IPEG, I think it was in Argentina, I'm not sure, there was a moratorium placed on doing a laparoscopic casai because of poor outcomes. Yet I know there are people like yourself and Marcelo Martinez-Ferro that are still doing the laparoscopic approach. Talk to me about what your feeling is about laparoscopy versus open casai. I feel there is room for us performing the laparoscopic casai because in our center, and I think the outcome so far is the same as the open casai. But the latest data shows liver function might be worse than open surgery for the patient who had a laparoscopic surgery in the midterm pull-up. But still, I feel there's room for us to perform laparoscopic casai. For the audience, I think that right now there is still a lot of trepidation about that operation, and it's only probably recommended that people that are performing that are either doing it in a prospective trial or have demonstrated equivalent outcomes. But I don't think it's yet considered to be an operation for the masses. I think it's still recommended to do this open. Yes. But recently, I think from Asia, I found several papers who recommend laparoscopy casai. Okay. So, Greg, let me ask you, and I want to eventually ask Yama this too after we hear from you and Mark. I know I've seen Yama's videos from Professor Kasai showing how to do the operation, the depth, what are some tips and tricks that will give you a better potential outcome. Greg, talk me through your technical thoughts of the operation and the major steps and what you think pretends a better prognosis. I've seen Yama's laparoscopic videos, and he does an excellent job. And he does cut the hilum to the same depth as perhaps we might do open. So, you know, if you are a very experienced laparoscopic surgeon, I think it is a consideration. But as you said a second ago, Peterson ran that prospective randomized trial and stopped it. You know, there's been other examples where people were doing the procedure and realized it was an allogials patient. So, I think the idea of offering laparoscopy on a consistent basis is something that still, as you described, should be done only in the context of a well-controlled design study. I think the question for all of us when we do that is the only chance this kid has to avoid transplant early on is a well-done casai. And so, that's where I think you really have to be thinking about the patient's best interest when you consider this. And if you're not a seasoned laparoscopist, then it's really hard to justify offering it. And I think in the past, people would do it, and perhaps they say, oh, I got 40% drainage rate. That's pretty good. And that's the problem with casai is even open, that because the drainage rate is not so ideal, even in the best hands, it's only 70%, 75% long-term. It's an operation in which people can try other things and claim, even if it's a little bit worse, okay responses. To your question of doing the procedure, for us, we'll have wide exposure of the hilum with the liver out or the liver in. And we can set up retractors where you've exposed the hyalur structures pretty well. We take the gallbladder down, we use it as a handle. Sometimes the gallbladder and the common bile duct or the bile duct remnant are not in continuity. That's always interesting. But generally, you would be able to use your gallbladder as a handle to track down whatever remnant of the common bile duct that is still present, and then take your dissection up into the hilum. And of course, what we try to do is quickly get onto the portal vein, because that's the safest landmark for us to track. And of course, we take great care not to damage any of the hepatic artery branches, because I think that is one of the other critical elements that sometimes people have to be careful about, because sometimes the artery branches can be quite small, but still critical. And if you take any of those branches, you can exacerbate the underlying liver disease process. So we'll dissect up to the bifurcation of the portal vein. We'll roll over the top of it, taking down some of the perforating branches that come right between the right and left branch. I don't loop the portal vein to pull it down, but I will completely mobilize it to the back side so that you can really see the beginnings of glisten's capsule beyond the hyalur remnant posteriorly. Then we'll take the dissection out laterally to where the arteries have really started to split into the major segmental branches. And that's kind of where we'll stop. There have been occasions where we'll see a tiny perforator coming off the bifurcation of the artery heading up into segment four. And sometimes we'll take that, but even there, we'll try to preserve it. Then what we'll do is once we have the fibrous mass completely dissected, then we'll put stace sutures a couple millimeters in on each side as traction along with a gallbladder coming out in the center and use those three as the mechanism to cut across the fibrous plate, leaving glisten's capsule intact. We do not dig into the liver. I think Dr. Neo wrote a paper just a few years ago where he described the different depth of the hyalur plate transection. Fred spent time with Dr. Kasai back in the 90s, and so he had a pretty good sense on the depth at which Kasai cut the hyalur plate. So that's where we do not cut into the liver itself. In the Children's Network, we actually had this discussion in the surgical committee, and maybe a third of the centers actually cut into the liver. The rest of us do it right at that millimeter, two millimeters of the fibrous remnant, and then that's where we then pack off the area and then go make our room. Mark, anything that you do different? The level itself, this is the sort of key distinction between an open operation and Yama's operation. And Yama actually replicates what Kasai did, which is not the kind of Kasai's which we do nowadays. That's more of a product of later Japanese surgeons. He left kind of distinctive remnant, an ovoid remnant in the middle. And Yama tries to do that laparoscopically, and to say he does that on the basis of what Kasai did. He seemingly gets the same kind of results. But most of the open people, particularly the Japanese people, are much more radical in trying to size all of the biliary remnants. As Greg says, it's a beautiful thing to see, the surgical plane. You can almost strip it off. And the idea is there's nothing left. And certainly those people that dig into the liver, that's a very unstable interface, and that's never had good results. I'm sure that any kind of biliary ductules that transgress that just simply scar over. I've never seen any kind of pro-coring of the liver that's achieved anything in the literature. So I'm surprised there are people in North America that would advocate that. And in terms of the width, we will do add the isthmus that goes from segment two to four. And so I'm just to open up that rex fossa, get a little bit higher into the umbilical fossa. On the right side, you should be demonstrating the bifurcation of the posterior and anterior right-sided vascular pedicle as well. And we take all of that into our root loop. So it's really quite a wide sort of draining operation. As far as your anastomosis, how long is your rule in? Ah, 40 centimeters. Again, that's been standard for a long time. It's in all the textbooks. Yama will tell you that's too much. He deliberately does a shorter root loop. Before I ask Yama, Greg, do you do 40 centimeters? We just take a silk suture and measure it out. It's 45 centimeters, so someplace around, you know, 35 to 40 is where we usually transect. And what suture do you use for your anastomosis? For these sites, kids, we're typically doing a single layer anastomosis with sergelon, which is another kind of a braided nylon. Some people will do it with micro. I don't think the rue anastomosis makes a difference. For the hyalur plate anastomosis, the quarter anastomy itself, we use 6-0 maxons and we try to leave all the knots on the outside. Which is a absorbable monofilament that lasts for a while. Okay. All right. Yama, how long do you leave your rue in? I've never measured. I think it's written in my papers, my rule loop. I think it's shorter than maybe others because I don't like a redundant rule loop. For anastomosis for Kassai, I use a 6-0 PDS C1 needle or BV1 needle. Join us for part two of our discussion on biliary atresia, where we add the gastroenterology perspective with an exciting insight into the future evaluation for biliary atresia, followed by debate on post-operative management and complications. We hope you enjoyed this episode and stay current. You can listen, watch, or read all content anytime by downloading the Stay Current app. We'll see you next time.