Liver Transplant Procedures to Treat the Effects of Colorectal Cancer

Podcast Transcript

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

Welcome again, everybody, to Butts & Guts. I'm your host, Scott Steele, the Chairman of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. Always great to have a repeat guest here on Butts & Guts. Very happy to welcome Dr. Federico Aucejo, who is our Surgical Director of Cleveland Clinic's Liver Cancer Program. Federico, welcome to Butts & Guts.

Federico Aucejo:  Thank you so much for having me, Scott. Thank you.

Scott Steele:  So today we're going to talk a little bit about something that's, in my mind, a little bit more cutting edge. That's this concept of having transplantation in the realm of treating liver metastasis for colorectal cancer, and also just about liver transplant in general.

So give us a little bit of a high level about what liver metastases are, and how they're formed for colorectal cancer.

Federico Aucejo:  Yes. So there are different types of tumors that would affect the liver we can talk about. The primary tumors are the ones that originate in the liver, such as hepatocellular carcinoma and cholangiocarcinoma. Then we have the secondary liver tumors, which are the metastatic disease. The most common one is the ones that originate from colorectal cancer.

The organ that is mostly affected from metastases is the liver. We know that the best therapy for this is associated with surgery. We know that the five year survival of these patients when they're affected by liver metastases, when we can apply surgery, is in the order of 30 to 60%. When we compare that to the alternative treatment, which is systemic therapy, despite the emergence of more evolved systemic therapies, the five year survival is on the order of 10, 20%.

So it is very important to emphasize that surgery has a crucial role to treat these patients. Within that, we have the liver resection, and we have transplantation, as part of the surgical options.

Scott Steele:  So we're going to get to each of those in a little bit, but let's take a step back. I want you to cover a few things for our listeners that may not have as much of a medical background. What's the liver's function? Why is it that colorectal cancer goes to the liver? Then, is this a big problem? Is this common for these diseases, these cancers, to go to the liver?

Federico Aucejo:  Yes. So the liver has a number of vital fundamental functions; helps us clear toxins, helps us produce proteins, enzymes that are vital, contribute to the coagulation. A number of things that makes it an organ that is vital. We cannot live without the liver.

In terms of metastases originated from colorectal cancer going the liver, about half of the patients with colorectal cancer at some point in time will develop metastases that go to the liver. Some of them will be diagnosed at the same time, of the diagnosis of the primary colorectal cancer. Some of them will be diagnosed posteriorly afterwards.

Why is that? Because of the connection between the veins, and lymphatic tissues, that connect the bowel with the liver, that these cells go through. They go through the liver, and they stay there and develop and they form metastases.

Scott Steele:  So when you talk about, something you mentioned earlier is that, we talk about that there's now metastatic disease, that the primary tumor has escaped and gone elsewhere, and in many cases there's a need for chemotherapy. So when does surgery come into play? Maybe asked a different way is then, when wouldn't you do surgery on somebody that has liver metastases?

Federico Aucejo:  So the role of chemotherapy, when a patient is first diagnosed, it's important to us because we will have the opportunity to evaluate the tumor biology. That is how the tumor responds to the chemotherapy. We will give us time to evaluate whether the patient has evolving metastases in other parts, not just the liver. Because of that, it is very important to complement surgery with chemotherapy; before, or after, or both.

One caveat with chemotherapy; when we have a patient who is a candidate for liver resection, is that we know that chemotherapy can be toxic to the liver over time. So we don't want to overdo too much chemotherapy, and create toxicity that then won't allow us to perform surgery on the liver, number one.

The other issue is that metastases, especially if they're small to begin with, they can disappear on chemotherapy. So then you won't be able to find them, if you would like to do surgery, which is the mainstay therapy. So we don't want to do chemotherapy to the point where the metastases disappear, or to the point where we induce toxicity to the liver. We want to do the right amount of chemotherapy, which is the amount that allow us to perform the resection and be able to remove all, or if not everything that we can see that is visible, the macroscopic disease in the liver.

Scott Steele:  Is everybody that has liver metastases a candidate for surgical resection?

Federico Aucejo:  Not everybody. First of all, if... We see many patients, especially young patients for some reason, cancers tend to be more aggressive I would say, compared to other patients who have both lobes of the liver affected in a very extensive way. Because we need to leave at least 30% of the entire liver volume in the patient so the patient can survive. If we cannot do that, then that patient would not be, at least up front, a candidate for surgery. I'm saying up front because there are techniques, surgical and interventional radiology techniques, that we can apply. So that the future liver remnant, that volume that we will live without disease, can reach that level of 30% that we're looking for.

Scott Steele:  The so-called staged procedures that you do, can in very basic terms, can you outline a little bit of what that involves?

­­Federico Aucejo:  Right. So what do we do to make that future liver remnant big enough to reach that 30%? We can do something called portal vein embolization. So the portal vein is the main vein that drains the blood that comes from the intestines into the liver. The liver has two lobes, and when it gets to the liver it divides into one for each lobe.

So let's say we have a patient with most of the disease located in the right lobe, but the left lobe is only 15 or 20% of the entire liver volume. So we need that left lobe to grow. So the interventional radiologist, what they would do is they would occlude the portal vein going to the right side-

Scott Steele:  The diseased side.

Federico Aucejo:  The diseased side, right. Typically a few weeks, two to six weeks after that, the left lobe would grow to the 30%. At that point then we are able to go in surgically and remove the right side.

There are more advanced techniques if we need to increase more, in a more aggressive way, the lobe that we're going to leave in the patient. That is with combination of embolization, not only of the one side portal vein, which is the in flow, that is the blood going into the liver, but also the blood getting out of that lobe, going back to the heart. And that is the hepatic vein. There is recent data that shows that blocking both vessels at the same time, or sequentially, can induce a more aggressive growth of the side that we are going to leave in the patient.

Scott Steele:  The body senses that it needs a little bit more liver, and it's able to grow it back. So let's go now to something that I think is really kind of unique, and that's this historic new transplant protocol that your liver team here at the Cleveland Clinic has developed. Can you walk us a little bit through that?

Federico Aucejo:  Yes. So liver transplantation for liver malignancy can be then for different scenarios; that includes primary liver tumors, hepatocellular carcinoma, cholangiocarcinoma, and metastatic liver tumors.

Scott Steele:  Just for people who don't know exactly what a transplant is, can you just give even more generalizations?

Federico Aucejo:  Of course. So when we talk about liver transplant we mean that we remove the entire diseased organ, liver, of the patient, and that is replaced by a entire organ, or a partial, a piece of organ, from a live donor or a deceased donor. That is what transplantation is.

So there are different scenarios for transplantation for liver malignancy. For patients who present with primary liver cancer, called hepatocellular carcinoma, or cholangiocarcinomas, or metastatic cancers affecting the liver; which is neuroendocrine tumors, or colorectal cancer liver metastases to the liver.

When we go back in time, we see that in early '90s there was an early experience in transplantation for patients with metastases from colorectal cancer, but the outcomes were not good. Because of that it was deemed a contraindication for transplantation.

So what changed from then to now? Number one, when we look at the data from that time, we appreciate that a lot of, almost half, of the bad outcomes were related to technical aspects of transplantation. Because transplantation, technically speaking, was in its infancy. Not then because of oncological reasons so much.

And the other thing is that now we have better systemic therapies, and locoregional therapies, that help us keep the metastasis limited to the liver and observe therefore over time how that this is behave. Again, having a better idea of the tumor biology. So overall we are able to select patients better than we used to for transplantation today compared to back in the early '90s. And technically speaking, we have learned and evolved compared to those times.

So those are the reasons why the concept of transplantation for colorectal cancer liver metastases has been revisited by a pilot study published from Oslo University in 2011. What they observed, this was a 21 patient pilot study, what they observed was that patients who presented with metastatic disease that was not amenable to resection, because of extensive involvement of the liver, they were offered transplantation. They observed that most of the patients would develop reoccurrence of their cancer, and that within the first or second year after transplantation.

But when they look at the overall survival, they observed that at five years about 50 to 60% of the patients would be alive. If you compare that to systemic chemotherapy, which is the standard treatment for that stage of disease, again the five year survival is in the order to 10, 15%.

So that's how we again, started looking at this option with more interest, then we adopt it here at the Cleveland Clinic. There are other centers that are interested in looking into this throughout the US, as well. We have the early experience, and so far it's going well. We have to, I think, learn more about the selection criteria. That's very important. The one thing looking into the future that we have a very important role, is the discovery of biomarkers; liquid biopsy and similar interventions, to select patients better.

Scott Steele:  Yeah, that's a great point. So obviously this has been the first time a liver transplant surgery for colorectal metastases has been performed in the US, to my understanding. Congratulations to you and your team on that.

So let's talk a little bit more about that last thing that you talked about. So this new transplant, now that we're starting to look into this, what really is the next phase of your team's research into this? Or the next step in the evolution of this process?

Federico Aucejo:  One thing that we have recognized, although if you think about it rudimentary, element to evaluate how the patient would respond. But very important, very effective, is the test of time. So we see that the patients who receive many interventions to keep the metastases limited to the liver, because that's the most important inclusion criteria, if the patients have metastasis somewhere else, not only the liver, unfortunately they're not candidates for transplant.

So all the interventional radiology interventions, embolizations, radiation, and surgery, surgical resections, that we can apply to that patient. So we delay the time for transplant, and so therefore we have more time to observe how that tumor behaves in response to all these treatments. In addition, how this tumor responds to the chemotherapies they have been offer. That tells us an idea of how is going to be the outcome after the transplant, and what are the chances of reoccurrence of the cancer after the transplant.

So looking into the future, for us it will be very important to achieve total disease control before the patient gets to the point of transplant. With interventional radiology tools that we have today, we want to see that there is no evidence of active tumor, radiologically speaking, before we consider the patient to transplant. Or not evidence of microscopic disease, if we are treating the patient with a surgical resection. That is very important.

Another very important element is to observe that the tumor responds to chemotherapy. Transplant in somebody who is progressing on systemic chemotherapy is perhaps not a good idea, because the problem would be the patient will have aggressive recurrence after transplant.

Scott Steele:  Is there any thoughts around the fact, if a patient did get a liver transplant, would they continue to need chemotherapy after that liver transplant?

Federico Aucejo:  That is a very good question to answer. I can't answer that, because there is no studies that show the benefit of that. There are trials in Europe looking into that right now. We are not prescribing empiric chemotherapy after transplant, so far. We're observing the patients. We're trying to keep the immunosuppression at the minimum, and we're using some immunosuppressants that can have some anticancer effects in the immunosuppression protocol.

Scott Steele:  So walk me through; I'm a patient that has liver metastases, looking out there, wanting to explore different options. How do they get in touch with you? And what can they expect when they come to visit you in your office, with either you or one of the members of the transplant team?

Federico Aucejo:  For these complex evaluations there are a lot of patients coming to me for consultation out of state, and so I try to set up, take advantage of our digital platform, through the virtual visits. So it's a very nice way to talk to the patient face-to-face through the computer. They have by that time already submitted to us their lab work and imaging studies. We had the chance to evaluate all that. So that way we can have an idea whether the patient is a potential candidate or not, and they have the opportunity to address the questions that they may have. Essentially I look at everything, and essentially they have to be patients who surgery cannot be performed because of the extensive involvement of the liver. There has to be no evidence of extrahepatic disease. There has to be response to chemotherapy, as I have explained.

There is some genetic mutations that we don't consider for transplantation, specifically the BRAF mutation because it's associated with a very aggressive tumor biology behavior. So we don't consider those patients for transplantation.

Then these are the main, and obviously it has to be a relatively young patient, and they have a good performance status. So the level of energy and function ability has to be good. We are offering up front for most of these patients a living donor liver transplant, for these patients is more difficult to obtain a deceased donor. That's because there are many other standard of care indications for transplantation. They have to compete with these other patients that are on the list. So we're prioritizing living donation.

Scott Steele:  So just to be clear, you still, your primary surgical treatment for these would be to resect the metastases like you've been doing for a long time. So this is almost what somebody who has a little bit too much disease, but not too much disease that they don't even qualify for a transplant.

Federico Aucejo:  Right. I mean, as long as everything is limited to the liver, they will qualify for transplant. But if it's resectable, if we can remove surgically all the disease that we can see, that would be the first approach. The transplant would be the very, very last resource. So when there is so much disease that we cannot resect, or because the liver has been damaged from all the treatments that we have applied, including the chemotherapy, the resections, the locoregional therapy. So the patients can develop cirrhosis, and they become really sick from liver failure, and still have active metastatic disease, extensive or low volume. Those patients would be candidates for transplant.

Scott Steele:  So any of the things our listeners should know about the transplant program? Or the liver team in general?

Federico Aucejo:  I'm very proud, very lucky to be part of a wonderful team. That we have wonderful colleagues from all the specialties, oncology, hepatology, surgery, interventional radiology, who have the luxury of being able to develop our multi-discipline Liver Tumor Clinics. So patients comes one stop. They get to see everybody, so they save their time. The use of their time is more effective that way.

So again, the first step would be through a virtual visit. Then if things look like a patient is a candidate, then we have a formal visit through the Liver Tumor Clinic. They get to see everybody, and then we have a formal presentation through the Multidisciplinary Tumor Board. Then we have a connection with the transplant coordinators, and we initiate the formal process of evaluation that way.

Scott Steele:  Well, that is certainly exciting stuff. For listeners of this podcast, you know I like to end up with the Final Five. For our repeat guests here we're going to change them up, the questions, a little bit. So first of all, do you play music in the operating room? If so, what is it?

Federico Aucejo:  I like music, but I have a special interest for classic music. Something that I enjoy in the OR.

Scott Steele:  Soothing music in the OR. So number two; what's the best trip? What place is the best trip that you've ever been to?

Federico Aucejo:  This year I actually took my family to Spain; Barcelona, Monterey. There's a lot of common points with my culture. I'm originally from Argentina.

Scott Steele:  I thought you were going to say Argentina. I wasn't going to let you go home on that one. Number three; if you could go anywhere in the world going forward, where would that be?

Federico Aucejo:  I haven't been in Paris. So that would be my next desired stop.

Scott Steele:  Number four. We know the food that you like. What's the food that you hate that you just won't eat?

Federico Aucejo:  That's a tough one. I like to eat anything. I'm very open-minded with that. I don't think I have anything that I wouldn't eat.

Scott Steele:  That's fantastic. Number five; if you could go back and give yourself advice on your first day of internship, what advice would you give yourself?

Federico Aucejo:  This is an advice that I would like to extend to all our general surgery residents, and that has to do with the opportunity to have an open mind to observe surgical cases. I know that there is a tendency towards that if they're not actually hands-on, doing the operation themselves, they don't getting engaged, they think that they're not going to learn. I really think that looking retrospective, I should have been more mature. I used to think that way. I think you learn a lot, even if you're not doing with your own hands, but scrub as much as you can, and a second assist, observe; you will learn a lot that way.

Scott Steele:  Sage advice and wisdom there. So for more information about liver tumors, liver cancer, and liver surgery options here at the Cleveland Clinic, please visit clevelandclinic.org/livercancer. That's clevelandclinic.org/livercancer. L-I-V-E-R-C-A-N-C-E-R. To make an appointment with a Cleveland Clinic specialist, please call (216) 445-8389. That's (216) 445-8389.
Federico, thanks for joining us on Butts & Guts.

Federico Aucejo:  Thank you.

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