What is a Hepatoblastoma?

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Hi everybody, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, the Chair of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. And we are going to have a topic we have not had before on Butts & Guts, and that is, what is a hepatoblastoma? And we're very pleased to have two experts in the field, both members of our clinic staff here, Dr. David Magnuson, who is the Section Chief of Pediatric Surgery, and Dr. Stacey Zahler, who is a Pediatric Hematologist and Oncologist here at the Cleveland Clinic, in Cleveland Clinic Children's. So David, Stacey, welcome to Butts & Guts. Thanks for joining us.

Stacey Zahler: Thanks for having us.

David Magnuson: Happy to be here, Scott.

Scott Steele: So, to each of you, just give us a little bit of background about where you're from, where did you train, and how did it come to the point that you're here at the Cleveland Clinic. Stacey?

Stacey Zahler: I am from Cleveland, Ohio, actually born and raised on the East side of Cleveland, in Chesterland, and went over to the East coast to train at New York Medical College in Westchester, New York. I remained there for residency, as well as for fellowship, in Pediatric Hematology, Oncology, and STEM cell transplant. And came back to Cleveland, and to the Cleveland Clinic, because it was just the perfect job offer and opportunity to do what I love, which is treat patients with pediatric solid tumors.

Scott Steele: Chesterland, a great place to get Christmas trees and fruit pies. David, how about yourself?

David Magnuson: I grew up in Minnesota, in Minneapolis. I did all my surgical training, which included general surgery, an NIH trauma research fellowship, and a pediatric surgery fellowship in Seattle, at the University of Washington. Go Huskies. My first job out of fellowship was in Washington, DC at the Children's National Medical Center, and I came to the Cleveland Clinic 22 years ago, and have loved living and practicing in Cleveland over that time.

Scott Steele: And we share that, both training in Minnesota and Seattle for myself as well. So Dr. Zahler, I'll start off with you first. Anytime I see these big, scary words, I say to myself, "Oh my God, what is this?" And what is hepatoblastoma? What does that mean?

Stacey Zahler: So hepatoblastoma is a type of cancer that occurs almost exclusively in very young children. It is a cancer of the liver. And this is a very rare type of cancer that happens in very few patients in the United States, let alone across the world. So it can be difficult to study, but we've been able to do that, and we can talk more about that later.

Scott Steele: So David, we have a lot of patients, a lot of family members, a lot of parents out there that listen to Butts & Guts. Stacey talked a little bit about the fact that this is not too common, but something that we're going to get into a little bit about what is it all encompass and how do we treat these, but what are the symptoms? And how is it diagnosed? And probably more importantly, if this occurs in young kids, if I'm a parent at home, I'm thinking, "Oh my gosh, does my kid have hepatoblastoma? What am I looking for?"

David Magnuson: Well, I think the important thing for the parents who might be listening to this whose children do not have hepatoblastoma, is that it's something that they shouldn't lose sleep over. This is a very, very rare condition, and we certainly don't want them to have to be anxious about the need to survey or monitor their kids to make sure that there aren't any signs of a liver tumor occurring.

Basically, most kids that present with a liver tumor present either one of two ways. Either they present with a mass in the abdomen, that is discovered by somebody when they're holding the child or examining the child, so that could be the child's pediatrician, or it could be the child's babysitter who picks the child up and puts them on their lap and feel something in the abdomen. As is the case with a lot of children who have tumors, solid tumors in the abdomen, these things grow slowly, and they usually achieve a fairly large size before anybody really comes to recognize them. They change gradually, so it's not a sudden change that goes noticed. So often the first sign is that somebody will feel something.

Another potential reason is a child will just become sort of systemically ill, or sick, from the inflammatory effects of a tumor. And they'll go in and see their pediatrician, and they'll examine them or maybe get an ultrasound or check some lab tests. And eventually they fall to the diagnosis that there's a liver mass.

And then, once a child has a diagnosis of a liver mass, whether it's discovered by somebody feeling it or a general workup for a child who is systemically ill, usually things at that point kick into gear pretty fast, because unlike most adults who, when they do have a liver tumor, the vast majority of those are benign. In children, when they have a liver tumor, the majority of those are malignant. So about three fourths of kids with liver masses will be found to have a malignant tumor, and that percentage is higher the younger you go. So as Stacey said, these hepatoblastomas almost exclusively occur in young children, and when young children, meaning infants and toddlers, have a mass in the liver, the chances are pretty high that it's going to be a hepatoblastoma.

Scott Steele: So, Stacey, one of the scariest things is to feel a mass on your own child, especially when they're extremely young, and then now you've got to go to the doctor and you got to deal with it. So, walk our listeners through, parent, child comes in to see you, what are they going to experience? What type of tests are you going to order? Does that involve anything that they got to grow under anesthesia, or invasive tests, or just on the diagnostic part, and then we'll jump into treatment afterwards.

Stacey Zahler: First of all, yes, you're absolutely right Scott, that this is a very scary time for families who come to meet me and my colleagues because we are cancer doctors. But what is almost always the case is that the child has this tumor that's been found by either a family member or the child's pediatrician, and so I always tell patients and their families, "Thank goodness that you're here because you are the one that got your child to medical attention." So that's first and foremost. And so yes, when they do come to us, oftentimes some type of imaging study may have already been done either by the pediatrician or by the emergency room. So that may be, for example, an ultrasound of the liver, which is where they put the probe on with some jelly, and are able to look inside the belly and see the liver, and see that the liver tumor there.

This is a less detailed type of imaging, and so in order to really characterize what the tumor looks like in the liver and how extensive the tumor is, and also if the tumor has spread anywhere else, we need to get more advanced imaging. There will also be blood work that needs to be done. There's a very important lab test that we do called an AFP, or an Alpha-fetoprotein, and this level is often extremely high in children who have hepatoblastoma. Less commonly, you'll have very low or normal levels, but most of the time the AFP level will be very high. So we call that a tumor marker, and that's something that we get at the beginning, and then we can follow throughout treatment, to sort of see how we're doing with treatment.

And the advanced imaging studies are more than likely to be an MRI, so Magnetic Resonance Imaging, and/or CAT scans of the chest, as well as the abdomen and pelvis. Because again, we need to see if the tumor has spread anywhere else. And oftentimes for these advanced imaging studies, because these kids are so young, usually infants and young toddlers, hepatoblastoma really isn't diagnosed after the age of four, very, very rarely is it diagnosed after the age of four. So yes, these children will need to undergo anesthesia just to have the scans done, so that they can lay very still so we can get adequate pictures.

Scott Steele: So I know there's a lot of variation, depending on the extent of the tumor, is it localized, is it small, has it spread somewhere? Again, I don't want to get beyond the scope of what the podcast is, but just in kind of very basic general terms. When I think about cancers or lesions, and I think, okay, we got chemotherapy or maybe hormonal therapy or radiation therapy or surgery or something like that. So on the medical side of the house, Stacey, what are the common types of medical ways that we have to treat hepatoblastoma? And then David, if you'd follow that up with, what are the surgical things that we have to treat hepatoblastoma?

Stacey Zahler: So I'll start with the medical piece. You're absolutely right that hepatoblastoma is treated with both medicines, called chemotherapy, as well as with surgery. And I'm going to just say right now that the most important part of the treatment in hepatoblastoma is the surgical piece, because in any type of solid tumor, including hepatoblastoma, we have to have what is called local control, which usually means surgery or radiation. So surgery is the most important part of treatment, but chemotherapy is also very important to kind of clean up all of the cancer cells that might be floating around that we can't see on imaging and that are not removed by the surgery.

So, we usually start with a couple of cycles of different types of chemotherapy. It depends on whether or not the patient is considered low risk or high risk or intermediate risk. So there are different chemotherapy regiments that we would use. And actually that's an area of study that we can talk about in a bit, trying to both enhance what kind of chemotherapy treatments we give for patients with high risk disease, and also to back off on giving so much chemotherapy to those patients with lower, intermediate risk disease, so that we can avoid some of those late effects and toxicities. So that's in general how chemotherapy works, and then the surgery will happen at some point in the middle of chemotherapy. And then we give at least two more cycles, and sometimes more, of chemotherapy after the surgery.

Scott Steele: David, can you talk a little about surgery?

David Magnuson: Sure. I'd be happy to. So I would say that surgery and chemotherapy are probably of equal importance and I'll explain why. But back in the days, let's say starting back in the 1960's and 70's, it was considered surgical dogma, or oncologic dogma, that if you're a child and you had a cancerous liver tumor like a hepatoblastoma, that it had to be resected right upfront, that you had to operate immediately. You had to try and resect the entire tumor, and even these huge tumors where resection was very hazardous, you had to make a surgical go of it.

That had a couple of consequences. One, the surgical mortality was high, and the perioperative mortality was high, and unsuccessful surgery, meaning the inability to actually remove the entire tumor and having to leave a significant amount of tumor behind, was high as well. So the results for hepatoblastoma back in the early days were very poor. What changed the equation was the change in attitude and philosophy that surgery didn't need to be done immediately. That if you could make the diagnosis, the medical oncologist could give the child chemotherapy, usually based on a drug called cisplatin, that was very, very effective in shrinking the tumor, and that after a couple of cycles or maybe four cycles of chemotherapy, those tumors, which presented as enormous challenges, sometimes shrunk to the point where they could be safely resected, and completely resected by surgery.

And that has completely changed the game in terms of management of hepatoblastoma. So when chemotherapy is given upfront, we call it neoadjuvant chemotherapy. And that was a strategy that was, I think it was probably adopted first in Europe, and kind of adopted and accepted maybe later here in the United States, but it's sort of derogare now, it's the standard of treatment now, and it's made an enormous impact on the prognosis in kids that have liver tumors. So I would say they're of equal importance, and I think if we had to go without upfront chemotherapy in a lot of these patients, I think we would all find the management of liver tumors a lot more daunting. So they go hand-in-hand now.

Scott Steele: So, Stacey, you had mentioned that there's maybe some changes in terms of chemotherapy. So a couple of questions that often come up, how long, what type of chemotherapy, what are the side effects? Is my hair going to fall out? How do you deal with all those questions? And I know that there's probably variations between this, but in general, what are the responses there?

Stacey Zahler: Yeah, so, these are all very important questions because it has to do with quality of life during treatment for these kiddos. And, so yes, everyone asks these questions and they're important to talk about. Yes, with this chemotherapy regimen, so as Dr. Magnuson mentioned, cisplatin is one of the main chemotherapy drugs in the treatment of hepatoblastoma, and it is a toxic one. So, even now in the current clinical trial that is being run, it's an international trial that is being run across the world, where we're trying to decrease the amount of cisplatin that we give, even in those regimens, yes, children will lose their hair. And what I tell parents is that if it's their infant child, hopefully they don't have too much hair to begin with, and yes, when we're done with treatment, it will always grow back. And sometimes it's fun the way that it does grow back because it might be curly, whereas you might not have had curly hair before.

So yes, hair does fall out, and yes, there are side effects during treatment that we have become very good at managing. And so we give other medications during chemotherapy treatment to try and ameliorate, or get rid of, or minimize as much as possible, the side effects of chemo, such as nausea and vomiting. We give medications before chemo even starts to try to make that as minimized as possible, and then again, throughout treatment, we continue that.

There are other effects of chemotherapy, for example, a big one is on the bone marrow. So your blood counts, your white blood cells that fight against infection, whose normal job is to fight against infection, will be low, because of the chemotherapy affecting not just the tumor cells, but also some of the good cells in our body, including the cells that fight against infection. So we have to give antibiotics to decrease the risk of infection sometimes. And we take fevers very seriously, any fever over 100.4 degrees Fahrenheit or more, we consider that an emergency that has to be dealt with right away.

Scott Steele: And David, the surgery side of the house, and that sounds pretty scary. Can you live without your liver? Are you taking the whole liver? I mean, tell us a little bit about what this involves, and is there a role for liver transplant in all of this?

David Magnuson: Yeah. Well, so, liver surgery is a complicated affair, and you can live without a large part, or a significant part, of your liver because your liver is really the only organ we have that's regenerative. It will regenerate after you take a part of the liver out. That doesn't happen in any other organ. So when we remove a part of a liver with a liver tumor in it, the complexity of that operation really is based on where the blood vessels are located inside the liver, and when you take a part of the liver out, you can't interrupt blood vessels that are going to the part of the liver that's supposed to stay behind, so it takes a lot of preoperative planning. But generally, if you have to remove a liver tumor, or the portion of the liver the tumor resides in, you can usually do this in a fairly straightforward manner if you have to remove half the liver and leave half the liver behind. If you have to remove more than half the liver it's a more difficult surgical procedure, but it can be done.

The other thing that you mentioned is, what can you do about patients that have liver tumors where you can't really resect the entire tumor and leave behind enough of the liver where you can survive, and that's where transplantation comes in. So sometimes when we have multifocal liver tumors that occupy various portions of the liver, so that have to remove all of it, would leave behind no meaningful liver tissue, we have to think about doing an upfront transplant in a situation like that.

There are also smaller liver tumors that just happen to be located at a very strategic area, in what we call the hilum, or central core, of the liver, where removing that tumor would interrupt all the blood vessels to the rest of the liver. So in a situation like that, the tumor might not be massive, but it might just be very inconveniently located, and that might also be a situation where transplantation is a better option than resection. But as Stacey said a long time ago in this podcast, complete surgical removal of the tumor at some point is necessary for survival. So whether that's resection or transplant, they can both be effective mechanisms to achieve a remission.

Scott Steele: So in other tumors, especially like rectal cancer, we're starting to see similar to anal cancer, that chemotherapy has evolved to the point, and maybe even a mixture in that case with radiation therapy, that surgery in very select patients may be avoided at all. Stacey, are we seeing any of that in hepatoblastoma? Or David, is his surgery still, as you said, the way that all of these patients have to go?

David Magnuson: Well, at the present time, surgery is still an instrumental or a central part of the management, and we don't really see hepatoblastoma patients that are candidates for non-surgical therapy very often.

Stacey Zahler: Yes, I would have to agree with that, Dave. Radiation in such young children can have side effects and long-term effects that we try to avoid in very young children. And on top of that, you know, as Dave said, surgery really is the staple here.

Scott Steele: So to both of you, is there any other research on the horizon or things that we're doing here at the Cleveland Clinic regarding the treatment or evaluation or surveillance of hepatoblastomas?

Stacey Zahler: Yeah, Scott, so we are, what is called a COG institution. So COG stands for Children's Oncology Group, and it is one of the largest collaborative pediatric cancer groups across the nation, and including other countries in the world. And so we have open here, through the Children's Oncology Group, many clinical trials to treat all types of pediatric cancer, including hepatoblastoma. And the current COG clinical trial is actually collaborating with multiple other collaborative pediatric cancer groups across the world, in Japan, in all of Europe and in Germany. And so together, we have come up with a clinical trial that risk stratifies patients into the very low risk category, the low risk category, intermediate risk, and high risk categories. And it depends on, again, how much of the liver is involved and how much the tumor has spread, if at all. And it also depends on what type of cancer cells you can see under the microscope, as far as what kind of treatment is offered on this clinical trial.

One of the main objectives is to, obviously, increase survival. In the last 40 years, as Dave mentioned earlier, we have really improved survival because of the combination of both that neoadjuvant, or chemo before surgery, as well as improvements in surgical techniques, as well as differences in chemotherapy techniques. And so, some of the goal of this trial is to obviously improve survival even more, but also to decrease the toxicity that we have seen in the late effects of chemotherapy that we have seen. And so that's, sort of generally what this trial is studying.

Scott Steele: Exciting stuff there. David, any final take home messages for our listeners regarding hepatoblastoma?

David Magnuson:

Well, I think the take home message is something that Stacey alluded to in what she said last. And that is that these are extremely rare tumors. You're a colorectal surgeon, Scott, so I think I remember seeing that there are, what, 150,000 cases of colorectal cancer a year in the United States, or something on that order. Even the most common solid tumor in childhood, which is called a neuroblastoma, there's only 700. And for hepatoblastoma, there's like 70. So think about 70 tumors, hepatoblastoma tumors, in the United States per year. No institution could perform any research, or try to move the needle at all on management, if they acted alone. And so, really the most important feature of children's cancer management is the fact that institutions participate and collaborate in these large cooperative groups in the United States Stacey alluded to it, the COG, Children's Oncology Group, and their collaboration with other oncology groups around the world.

And it's important to find an institution that participates in these groups because it's the only way that an institution and the people who practice there, and render care there, can stay really on the cutting edge of what's offered in terms of efficacy of therapy and reduced toxicity of therapy. So I think that's a very important thing for people to take home. And I think it offers a lot of hope, where a lot of these tumors that are very serious, very difficult and complicated tumors, and would normally have a very poor prognosis, in the setting of a collaborative treatment group, kids can get the best kind of therapy and have the best kind of outcomes.

Scott Steele: We are so thankful for the both of you and your continued efforts against not only hepatoblastoma but diseases such as these. So, we always like to wind up with our guests, especially our new guests, some quick hitters to get to know a little bit more about each of you. And just because there's two of you, Stacey, I'll have you go first, and David second. And so, what's your favorite food?

Stacey Zahler: Gosh, I love food, but I grew up on Italian food, so I'd have to say Italian.

David Magnuson: And anything I'm eating where my wife isn't watching. But if I had to pick, I love Italian food and French food, but for me, nothing beats a well-prepared steak.

Scott Steele: All right. All right. What is your favorite sport to play?

Stacey Zahler: I was a gymnast growing up. I don't do that now. I'm too old for that now, but gymnastics, I would say.

David Magnuson: I play the age appropriate sport of golf.

Scott Steele: Fantastic. Both of you, now listen up here, what is the last non-medical book that you've read?

Stacey Zahler: I would say, I have three children at home, I was most recently reading the book, No Drama Discipline.

David Magnuson: So I'm a new grandfather, for the first time, and I would say that the most recent non-medical book I read was Good Night Moon, to my new grandson.

Scott Steele: That's a classic right there. And then finally, to the both of you, tell us something, you're both Clevelanders now, what is something that you were able to enjoy about Cleveland that you think is a highlight of the area?

Stacey Zahler: Well, Scott, I was born and raised here, and I chose to come back here after my training, and I'm so glad I did. The four seasons, I would say, are just incredible here, as well as the people. Having trained on the East coast and then coming back to the Midwest, to Cleveland specifically, it's just a lovely place to be.

David Magnuson: So I grew up in Minnesota and I found myself here in mid-life, and I have to say that my entire family has been very happy living here. There's a tremendous exposure and opportunity to do things in the fine arts and in professional sports and spectator sports. It's a really vibrant community. And unlike a lot of the other places we lived, the people who live here can actually enjoy these things without having to stand in line for nine months. So I like living in Cleveland because there's access to world-class cultural and sporting events and we get to enjoy them.

Scott Steele: That's fantastic. Well, so to learn more about cancer treatment options at Cleveland Clinic Children's, please visit clevelandclinicchildrens.org/cancer. That's clevelandclinicchildrens.org/C-A-N-C-E-R. And to make an appointment with Cleveland Clinic Children's please call 216.444.5517, that's 216.444.5517.

In times like these it's important for you and your family to continue to receive medical care. Rest assured, here at the Cleveland Clinic we're taking all the necessary precautions to sterilize our facilities and protect our patients and caregivers. Dr. Zahler, Dr. Magnuson, thanks to you again, so much for joining us here on Butts & Guts.

Stacey Zahler: Thank you, Dr. Steele.

David Magnuson: It has been a pleasure, Scott.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.