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Dr. Riccardo Superina: with the increasing amount of experience we have, we have increasing amount of confidence in our ability to fix the problem

Scott Webb: Lurie Children's is one of the only pediatric hospitals in the world, home to experts in the surgical treatment and care for children with a rare disorder in which a clot forms, blocking the main portal vein going into the liver. This condition is known as portal vein thrombosis. The cause of which in many cases is never determined. At Lurie Children's, two pediatric liver experts are able to help many children with this condition avoid a liver transplant, even when their families have previously been told that it's the only treatment. Today, let's talk with those physician surgeons, doctors Riccardo Superina and Caroline Lemoine. This is precision perspectives on children's surgery. I'm Scott Webb. It's so great to have both of you on today. We're gonna talk about portal, vein thrombosis, and a whole bunch of other things along the way. And as we get rolling here, Dr. Supera, what is portal? Vein thrombosis. And what are the symptoms?

It's so great to have both of you on today. We're going to talk about portal vein thrombosis, and a whole bunch of other things along the way. And as we get rolling here, Dr. Superina, what is portal vein thrombosis and what are the symptoms?

Dr. Riccardo Superina: Portal vein thrombosis is a name that we give to a variety of disorders that are all characterized by the lack of portal blood flow to the liver in a normal fashion. So the portal vein is a large vein that brings blood from the intestines and the stomach and all the nutrients that we absorb travel or absorb into the portal vein. And the portal vein brings blood to the liver. It's the main blood supply of the liver. And portal vein thrombosis refers to a condition where there's a blockage, essentially an obstruction to flow in a normal fashion so that the normal port vein, which is a large caliber vein, which brings a liter of blood per minute to the liver is broken up into smaller veins that try to accomplish the same work, but in fact do so under a great amount of pressure and in a very reduced amount.

So the symptoms are that the blood that normally should go to the liver is backed up as it were like a dam and it ends up going to other parts of the body, like the spleen and the stomach. So the spleen enlarges abnormally, the stomach develops abnormal blood vessels in its lining. And the symptoms are enlarged spleen and bleeding, esophageal and gastric varices, so these large veins in the stomach and the esophagus that can rupture and bleed and the spleen enlarges to very large amounts. And then, when the spleen enlarges, the side effect of that is that certain elements of the blood are removed prematurely, such as platelets and white blood cells. And so the body has to compensate and try to make up for and the platelet counts and the white counts fall, and those are the more alarming symptoms of what we call portal hypertension.

So portal hypertension is increased amount of blood pressure in the portal circulation that the gut and the liver have in this very close relationship where blood flows from the gut to the liver. And usually, that is a smooth flow under low pressure. But when the portal vein gets obstructed, as you can imagine, it's like a dam or it's like a traffic jam in the highway and the cars back up. And that's what happens to the blood. It backs up and it has to find other ways to get around the liver instead of going to the liver. And so there's a lot of things that happen that are not good. But the most dramatic symptoms are enlarging spleen, and this abnormal bleeding from the stomach and the esophagus.

Scott Webb: Yeah. And the analogies definitely help lay people like myself. And those symptoms are alarming to be sure. Dr. Lemoine, it feels like this condition is rare. But I want to ask an expert, is it rare? Am I right about that? And either way, who typically gets it?

Dr. Caroline Lemoine: It's actually a question that's not as easy to answer as one thing, because it seems rare if you look up on the internet or if sometimes families meet physicians and it's the first time that they might encounter that condition. But actually, it's probably more frequent than we think, but it's just underdiagnosed. So for example, one of the ways that you can get portal vein thrombosis is through something called an umbilical vein catheter. So when a baby is born, sometimes a baby is sick. And a way to get intravenous access to that baby, you can put a catheter in the veins of the umbilicus, of the belly button, what used to connect the baby to the placenta of the mother. Unfortunately, if that catheter is not placed adequately, or even if it is sometimes, it can injure the vein inside the liver, the portal vein inside the liver, and that may lead to thrombosis or cloting of that vein. So parents of babies that are in neonatal intensive care unit might be facing that problem or being made aware of that problem earlier or sooner than others.

Other risk factors could be if a baby has a bad infection when he's a baby or infection of the belly button that could track back all the way into the vein of the liver. But this may go undiagnosed and unknown to families and children for many years until they present with those very alarming symptoms, like Dr. Superina was explaining. In other part of the world, other reasons have been seen to cause portal vein thrombosis, like infections that are specific to those areas of the world, but maybe not as much seen in the United States or in North America, but with immigration or adoption, those are now recognized risk factors for patients that we see.

Another risk factor that also may not be known is a condition called hypercoagulable conditions, which are risk factors that make people prone to clotting. And sometimes families will know about this because mothers or parents or other family members may have those conditions. But again, most often, a patient will present with the symptoms, it's rare that you find the portal vein thrombosis first before the symptoms occur, because physicians are not as aware maybe of the condition beforehand.

Scott Webb: And Dr. Superina, is that your sense of things when we think about it being misdiagnosed or underdiagnosed, or just simply not diagnosed at all? Is it all of those factors and just basically that family physicians just don't have the expertise that experts like yourself do?

Dr. Riccardo Superina: That's certainly a factor. The parents of the patients who have this condition end up reading about it through social media and through mechanism like this podcast. They know a lot about this condition and often they end up self-referring or trying to instruct their doctors on what it means and what to do. So there is an increasing awareness among physicians and it's our job through education and papers and conferences to try to spread the word that this is a dangerous condition.

It really is completely unknown what the incidence of this problem is. I think with more and more babies being born prematurely with prevalent use of these umbilical catheters that Dr. Lemoine mentioned. There probably are a lot of patients who are really undiagnosed. And we don't even know if this condition actually leads to those symptoms every time. It could be that there are patients who are asymptomatic with this condition or who have minimal symptoms and who don't have those dramatic symptoms of bleeding and hypersplenism with the big spleen that I talked about. But with the increasing use of ultrasound for the diagnosis of almost anything, abdominal pain, for example, in the emergency room, or if patients get ultrasounds for any number of things, this condition is being diagnosed, I think, with increasing frequency. And one of the interesting things that we are trying to uncover is what is the state of the child's health before these dramatic symptoms actually occur?

So again, I'm going to use an example. If you have a hernia, let's say a child has a hernia, you bring the child to the surgeon before the hernia becomes incarcerated or trapped and needs an emergency resection. It's the same thing with this portal vein thrombosis. The portal of vein thrombosis, I think, takes a while before the actual clot or the actual malformation forms until the dramatic symptoms occur. So we are trying move that intervention back before the child presents with these dramatic symptoms. And one of the things that we are doing now is we're trying to discern what the symptoms are before the symptoms of bleeding and hypersplenism occur. In other words, what is the downside of having an impaired source of blood to liver? The liver does so many things that it compensates and the body compensates, but it's not normal.

So what we're trying to do now is we're trying to study the effects of portal vein thrombosis on the neurocognitive capacity of children. We know that these children can develop something called minimal hepatic encephalopathy, where they sometimes are diagnosed as having learning disabilities or neurocognitive disorders or attention deficit disorders. And one of the things that we're trying to do is to study the effects of restoration of normal portal blood flow to the cognitive function of the child. We know that there can be effects on the lungs, for example. You can develop pulmonary disorders because of things that aren't working in the liver and some children have presented to us with this as the presenting symptoms. So we're trying get ahead of when the child is actually vomiting blood, because that is like an emergency and very scary for not only for the family, but for the child themselves. So we're trying to get to intervene before that happens. Then with the increasing amount of experience we have, we have increasing amount of confidence in our ability to fix the problem than we did 20 years ago when this started. Because 20 years ago when this started, it was only those children with these dramatic symptoms that we were able to fix. But now, families are actually seeking us out at a much earlier stage of the game. And we get these patients coming to us who really, they're not that sick, but the parents want something done about it.

Scott Webb: Yeah. So interesting and complex really, I mean, not for yourself, but for the rest of us. I'm just trying to keep up with both of you. And just given how rare it is, how did you become the expert that you are, especially in terms of diagnosis, you know, what training have you done? How did you choose this specialty?

Dr. Riccardo Superina: The specialty chose me really. I started doing liver transplants 30 years ago and with that comes a familiarity and expertise with vascular disorders of the liver. And there's a few of us who have a friendship, a connection, across the world. And someone about 30 years ago really now first came up with this operation called the Meso-Rex bypass, which is correcting this interruption of flow into the liver. It was done in the setting of liver transplant. When I started doing liver transplants, I became aware of this operation. And then, when the first child presented to me here in Chicago, he presented after a open heart surgery and it turned out that the kid had portal vein thrombosis. Now, in the past, I might have done something else to correct this portal vein thrombosis. But because I was aware of this operation, we did it. Obviously, the parents were taking a bit of a chance. They knew that this was a first time I'd ever done it, but it worked out well. And so that was the first case.

And from there, it just grew slowly at first, because it was only in those patients who presented with these dramatic symptoms. But it's the liver transplant training that makes us able to feel comfortable with this kind of operation. And for a while, I think we were the only center in the United States that was actually doing this. And so the small cohort of patients who had children affected by this disorder, you know, they were drawn to us, like word of mouth really spread. Like I said before, it was the parents themselves who sought us out. Some people just happen to have those symptoms and be in Chicago, but other people, that we've had patients coming from basically every state in the union and many different countries now to get this operation. So like word of mouth, honestly, that spread the word among parents who are clearly the best advocates for their children.

Scott Webb: No doubt. I try to be for my kids as well. And Dr. Lemoine, let's talk about the treatment for portal vein thrombosis. I'm sure it's complicated, but if you could give us sort of the broad strokes.

Dr. Caroline Lemoine: I think it depends a lot on when the child presents. So for example, if the child presents with that catastrophic symptom of having a bleeding from the mouth, obviously the first thing to do is to stabilize the patient and make sure that they're okay before considering any next steps. Then, it also depends on if there is underlying disease to the liver. So right now, we're really focusing more on children that have normal livers. But like Dr. Superina was saying, you can have portal vein thrombosis after a liver transplant, for example. But that may be like a different category of patients. So right now, I'm talking more about the patient that would not have a liver transplant.

Once the patient has recovered from a GI bleeding or, for example, the patient presents to a doctor and has a big spleen, then as part of the investigation, we make sure that they don't have liver disease. And then, at our institution, they get referred and then we evaluate to see if they can be a candidate for the Meso-Rex bypass, which is really when possibly doable, the best surgery, because it really puts the patient back to a state of normality where there's normal blood flow feeding the liver and allowing the liver to grow and recover.

Now, this is not going to be possible in all children. In our experience, we're able to successfully perform a Meso-Rex bypass in children about 80% of cases. Maybe Dr. Superina will comment. It's hovered between 70% and 80% of patients that came to see us to get that surgery. And there are specific reasons why a patient can or cannot be a good candidate for a Meso-Rex bypass. And part as a workup that we do here at our institution, a very important study is a study of what the vein looks like inside the liver. What we're creating with a Meso-Rex bypass is a bridge. It's a bridge over a roadblock like Dr. Superino was explaining. So you have to make sure that you have a good starting place for your bridge and a good arrival place for the blood also from that bridge.

So the vein outside the liver is usually okay, the vein that feeds the bypass, which is usually the vein draining the intestines, the superior mesenteric vein. But very importantly is what is the status of the vein inside the liver. And in many other institutions, patients or their families may be told that their child is not a candidate for a Meso-Rex bypass, because the other teams based themselves on a CT scan or an MRI that is not able to see the status of the vein inside the liver. And it's only that specific test, which is an interventional radiology test, where we go backwards into the liver to see what the vein inside the liver looks like that tells us the real story. And we're often very happy to see that the vein actually is open. But then, it's what quality of the vein it is. Is it a grade A or is it a grade E for example? Is it a very good-looking vein, a very normal-looking vein or not? And that helps us in counseling the families in trying to tell them what is going to be the chances of a successful Meso-Rex bypass for their child. So understanding that it's not a hundred percent of patients that may get that surgery, we still want to help the children. And if a child has had, for example, bleeding or has very low platelets, we still can do surgery to treat those symptoms and those signs.

So our usual plan B is called a distal splenorenal shunt, which is another type of surgery. It is very efficient in treating those symptoms of the GI bleeding and the big spleen and the low platelets. Unfortunately, it does not bring back blood to the liver in the same way. It does not bring it back to the liver like the Meso-Rex bypass does. So it does not completely bring the child back in a state of normality, but is very efficient of treating those dramatic symptoms. So those are usually the surgeries we present to families with portal vein thrombosis. And obviously, there are exceptions to those two and there are other options that we can offer. And I'm sure Dr. Superina wants to add additional things to this topic.

Scott Webb: I'm sure. Yeah. Dr. Superina, would you like to jump in? And also if you could touch on what's the recovery like from this surgery? How do most children do from these respective surgeries?

Dr. Riccardo Superina: Well, the Recovery is usually pretty uneventful. It takes about a week in hospital. It's usually characterized by pain control at first, which is kind of the common denominator in every operation. And then, we do ultrasounds and CT scans to make sure that the flow is going in the appropriate direction and an appropriate speed. There are things that we monitor such as platelet counts. Often children are put on a blood thinner, like an anticoagulant for the first few months after the surgery in order to make sure that there's no clots that form that would interfere with the blood flow through this newly constructed vein.

And then, usually, children go home and I think that's when kind of the surprises start because, at first, they're just happy that the operation's worked. But then, it's the parents who really noticed the small things that happen after the surgery. Not only do they not have to have concerns about bleeding anymore, but they see the spleen come down, the bellies of the children usually become flatter. Whereas before, they had this big protuberant bellies from their big spleens.

And then, they notice sometimes that their childs grow more quickly. So one of our research studies was in order to try to figure out why these children grow more after restoration of blood flow to the liver. And it's really the parents who pose these questions to me. And I didn't know the answers to them. So that became the food for thought and for research project. One of the things we looked at is the relationship between restoration of blood flow to liver and growth hormone, how growth hormone may function more efficiently in the presence of a normal blood supply to liver. Then, parents would come to me and say, "Oh, my child was in these special, I don't know, classes after school or in some sort of special program for children with learning disabilities. And now, they're out of them." So that kind of prompted the research into how neurocognitive functioning changed after this. And it's just wonderful to see these kids thrive, grow and develop more normally. And the parents are so grateful. Now, that doesn't happen in all the cases. Sometimes the kids are already functioning pretty well, but the bleeding stops, the spleen goes back to a more normal size.

And it's really interesting to me to see how some members of the medical community really are still skeptical. And one of the things that we encounter is why do you think that this operation works better than any other operation? Dr. Lemoine mentioned another operation that was done for this when we can't do the Meso-Rex bypass, it's called the distal splenorenal shunt. And that's a much easier operation to do and I think more surgeons are capable of that or have the expertise to do that. And of course, you know, I think you try to promote what you know or what you feel comfortable with.

And one of our tasks is to actually try to prove what seems intuitively to be common sense. If you can restore something to normal, wouldn't that be better than simply doing an operation that palliates some of the symptoms? So one of our tasks is to really try to prove what seems to be apparent to the casual observer that you would think wouldn't need to be proven, but in fact it does. And we want to also be sure that we're on solid ground when we are promoting this operation and trying to really say that it's the best possible treatment for portal vein thrombosis.

Scott Webb: Yeah. And not surprising that, you know, being at Lurie Children's that you're really listening to patients, obviously the children, but really the families as well. And I think we touched on this earlier, but I'm sure it's very gratifying that not only, you know, as you say, some people just happen to live in Chicago, but you have people and families coming from all over the country and all over the world. And you mentioned it is probably or mostly word of mouth, but I wondered if you could just kind of talk a little bit more about that, maybe just how gratifying it is to know that your center there at Lurie Children's is kind of the place to go for portal vein thrombosis.

Dr. Riccardo Superina: I think it's become the focus of the liver center, which has a lot of things to offer, among them liver transplants, resection of liver tumors. But one of the main cornerstones of the liver center is this center for the correction of portal vein circulatory disorders and Meso-Rex bypass is only one of them. But we believe that the team is very important. The patients come to see us as surgeons for the correction of this disorder. But we count on a lot of other people to help us with this. We mentioned the interventional radiologists who are incredibly important in not only trying to map out the problem, but then in terms of helping us tweak some of the things that can go wrong after the bypass, in terms of correcting stricture or blockages or things that will optimize flow.

There are people who cannot come here to the United States. Obviously, it's not often easy for people to come and see us because of insurance issues, distance and that's something that we're trying to overcome. It's really hard to know how to handle it because we want to reach out to as many patients as possible who want to come and see us, but there are certain things that have to be overcome in order to do that. And the cost associated with the operation is one thing that is a problem for some families, particularly if they don't have insurance who are patients from out of state who want to come here, who may have Medicaid. Our hospital is very good at trying to advocate on behalf of these patients so that they can come here to get the treatment they deserve.

And from an international perspective, Dr. Lemoine and I are going to Brazil to try to teach surgeons there how to do this operation, because it's very difficult for people from South America to come to North America. And we've had patients from Europe come to see us. But what we really need to do is set up a learning system so that we can teach others how to do this operation. And one of our goals is actually to set up a Meso-Rex registry so that we can all learn from each other. There are a lot of good surgeons all over the world, and we're trying to get a registry so that every patient who has a Meso-Rex bypass is in this registry. And we can do studies that are more than just our center, but we can collate the experience of a number of centers that we can perhaps all learn from each other.

Scott Webb: It's always very heartwarming and gratifying and encouraging to hear world-renowned experts saying, "Hey, you know, we can all learn from each other. There's other great surgeons out there." And wouldn't that be great, right? To travel around the world, teach everybody, have that registry and contributing and collaborating. It's very cool. And you mentioned your research a little bit there and what drives the research there at Lurie Children's. Maybe just talk about the future. What does the future hold? Where do you see that research going? What will be the results of that research? If you can look into your crystal ball a little bit.

Dr. Riccardo Superina: You know, certainly understanding the effects of this on the brain, I think, is one of the most important things that we can do. And other circulatory disorders of the liver that are associated with shunting of blood. So this is what happens when the portal vein is out and you get these varices in the stomach and the esophagus. It's really a shunting, because the blood is shunted around the liver rather than going through the liver. And this has a deleterious effect on the brain's function. It also has an effect on what's going on inside the liver. So some patients develop liver tumors because of this. As I said before, there are effects on the lungs. So these are all important research questions that I don't even know how to formulate the question or let alone answer it. But we certainly are working very hard on trying to characterize the neurocognitive defects. And from a parent's perspective, I think this is one of the answers that they want the most is how does this affect our child's learning and our child's brain. And so one of the things that we're thinking of doing is looking at the brain with MRI scans to see what changes happened before and after the operation that will accompany the improvement in neurocognitive functioning. Caroline, do you have any other thoughts about the research?

Dr. Caroline Lemoine: Well, I think you've spoken about the big areas that we're focusing on. When we create that bridge, we have to use a vein, and it's often the vein of the neck of the child that we use, that we harvest and that we put to connect the veins outside the liver and inside liver. Sometimes we use veins from inside the abdomen when we can. But wouldn't it be great if we could grow veins or get veins without having to do an extra part of the surgery on the child's neck? So I think if we could grow vessels and that'll be part of learning how to grow organs also for transplantation, that would be very useful in that specific surgery. But that may be the next frontier of research for our team.

Scott Webb: Well, it's all really amazing. You know, I have the pleasure of being able to host these and I hear about the future, well, really the present in a lot of cases, whether that's robots, sonar, lasers, you know, growing vessels, growing organs, it's all just amazing. And it's really mind blowing to be honest. Dr. Superina, I'm going to finish with you here. What gives you hope for children with this condition?

Dr. Riccardo Superina: Well, the success rate of the operation is very high. And I think that the main impediment to any more progress, as far as I'm concerned, is trying to rebuild the portal vein inside the liver. So one of the things we're trying to do is to promote less use of umbilical vein catheters in newborns which we think is one of the problems associated with the formation of a portal vein thrombus. But I think the main hope for us is to spread awareness of this condition, get earlier interventions and really be advocates for these children whose parents are desperate for answers and who really want to believe in us. So we want to reward their faith and belief with results. And that's what really drives us to do this.

There's nothing more gratifying than a child 20 years later saying, "I understand what you did now thank you so much for it," and it affects the whole family. So I think the restoration of normalcy to a child who is really disabled in some sense is the thing that gives me the best hope for the future that we can continue to reach out to these patients.

I think one of the things that is impressive to me is that some of these children come to us for a second opinion. Some doctors, some centers would say, "Okay, well let's just replace the liver," which is not an easy task to do. I mean, not only does it mean you have to have a liver transplant, but then that means lifelong immunosuppression. So we're trying to say, "Okay, no, you don't need a liver transplant for this kind of thing. You can do this, you can do that." And clearly, 80%, 85% of kids who come to see us can have a successful restoration of portal blood flow. The 15% who can't, then those are the question marks, you know, what happens to those who do not have that, who have the distal splenorenal shunt, or who have some other palliative procedure. Those are the kids who really need help in the long run. And it could be that some of those may require liver transplants in the future.

Scott Webb: Well, I want to thank you both for your compassion and your expertise. You've said here today that, you know, it's really about getting the word out, about education. And so we hope in a small way, this podcast helps to do that. I feel like we could talk forever, but I'm sure you have patients and surgeries to perform and so on. So thank you both and you both stay well

Dr. Riccardo Superina: Okay. Thanks very much, Scott.

Dr. Caroline Lemoine: All right. Thank you.

Scott Webb: And visit Luriechildren.org/livercenter for more information or to learn how to make an appointment. And if you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you.

Scott Webb (Host): This is Precision: Perspectives on Children's Surgery, the podcast from Lurie Children's Hospital. I'm Scott Webb. Stay well.