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What is liver cancer and what typically causes it? What treatment options are available and what is on the forefront of liver cancer treatment today? How much of your liver can you live without? Federico Aucejo, MD, explores these questions and many more in the latest episode. 

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All About Liver Cancer with Dr. Federico Aucejo

Podcast Transcript

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

Welcome to another episode of Butts & Guts. I'm your host Scott Steele, the Chairman of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. And in an effort to explore all of the digestive system, today we're going to talk about the liver and, specifically, liver cancer. I'm very pleased to have Dr. Federico Aucejo here with us, who's a staff hepatobiliary surgeon, and a liver transplant surgeon. He's the Director of the Liver Cancer Program, also an Associate Professor of Surgery at the Cleveland Clinic Lerner College of Medicine here in Cleveland, Ohio. Federico, welcome to Butts & Guts.

Federico Aucejo: Thank you so much, Scott, for your invitation to this wonderful podcast that you have developed here at the Clinic.

Scott Steele: One of the things we'd like to start off with is getting to know our guests. So, tell us a little bit about where you're from, where you trained and how to come to the point that you're here at the Cleveland Clinic.

Federico Aucejo: Thank you, Scott. I am originally from Argentina. I came to United States 15 years ago to train in abdominal organ transplantation with focus in liver transplantation and liver surgery for liver cancer. I initially performed a year of training in Mount Sinai Medical Center in New York City. And then I moved to Cleveland Clinic and completed my fellowship, my training here, and I've been staff surgeon here under general surgery, performing hepatobiliary surgery and liver transplantation since 2006.

Scott Steele: Let's start from a 10,000-foot view. Tell me about the liver, before we jump into what we're going to discuss most today, a lot of our listeners or patients out there, they know they have a liver and everything, but what does the liver do and what is its purpose and function?

Federico Aucejo: The liver is like a chemistry factory and it has several functions. We could not live without a liver. So, it's involved in detoxifying toxins, it's involved in the metabolism of sugar, producing clotting factors. So, again, it's a vital organ that is involved in many, many different functions that are vital for us.

Scott Steele: I get what a liver does and everything like that. And today we're going to focus on liver cancer. So, a couple of quick questions. How common is liver cancer?

Federico Aucejo: Liver cancer is now about the third leading cause of cancer-related mortality worldwide. The reason why is multifactorial. Number one, the etiology study cause liver cancer. For some of them we have a potential cure, including surgical interventions, medications and local regional therapies. But for other etiologies we're still behind. And the other problem is that most of the patients, when they are diagnosed, will present with advanced stages. The potential curative options still remain surgical options, won't be possible at that point in time. So, there is a problem that we have to solve around screening these patients, the patients who are at risk, so they can be seen by the physician at the early stage. They need to be aware that they are carrying the risk factors, so they get and see the doctor, and if they have the cancer, this can be caught at an early stage.

Scott Steele: We're going to talk a little bit later about how we diagnose it, what symptoms patients have and then delve into the treatment and the frontier of treatment for liver cancer. But, again, just sticking with the very basic overviews, how does liver cancer present, even more than that, what really is liver cancer?

Federico Aucejo: Liver cancer, primary liver cancer, we're talking about hepatocellular carcinomas, a malignant tumor that arises from a liver cell, from the liver. It originates there, because tumors can go to the liver by they originate different organs, so they metastasize. This is originated in the liver. And there are two types of primary liver cancer. The most common one is hepatocellular carcinoma. The second primary liver cancer is cholangiocarcinoma that originates from the bile ducts. Usually when it becomes symptomatic, again, is at advanced stages. And the symptoms will not be very specific, but the patient may present with right upper abdominal quantum pain, jaundice and symptoms associated with what we call cirrhosis or chronic liver disease or end-stage liver disease, because, 90% of liver cancers present in patients with background of chronic liver disease.

So patients can present again with abdominal pain, jaundice, ascites, recent history of bleeding from viruses, from the gastrointestinal tract and cephalopathy. There is confusion, memory problems, because the liver is not being able to clear the toxins. So, the broad spectrum of potential symptoms, but again, when a patient becomes symptomatic, usually is an advanced stage and potentially curative options at that point are not possible.

Scott Steele: Let's delve a little bit more into some of those risk factors that you talked about. Just to unpack that a little bit further. You talked about cirrhosis. First, tell us a little bit about cirrhosis and then, when I hear the word "cirrhosis" and many people either think about drinking, do you have to be an alcoholic or anything to have cirrhosis? Are there other causes of having underlying liver disease that can lead to primary liver cancer?

Federico Aucejo: Cirrhosis is one the histology of the liver, the components of the liver are replaced by fibrosis, fibrotic tissue, so the liver becomes hard, nodular and shrinks. It gets smaller. There are different etiologies that, over time, can cause chronic inflammation on the liver and that, therefore leading to cirrhosis. Those etiologies, the most common ones include hepatitis C, so viral etiologies, hepatitis B, of course, alcohol cirrhosis, obesity, causing fat deposition in the liver over time. That creates chronic inflammation and, therefore cirrhosis and then potential formation of cancer. There are auto-immune diseases that affect the liver that can evolve into cirrhosis and hepatocellular carcinoma. And then toxins are less common that can cause cancer as well. In terms of the prevalence of the different etiologies that can cause cirrhosis, that varies according to the geographic areas.

For instance, in Asia and South Africa, hepatitis B is the leading cause despite the fact that these days we have vaccination for hepatitis B. In the Western world, such as the United States, hepatitis C continues to lead the cause of cirrhosis, and therefore hepatocellular carcinoma. However, now with immersion, very effective medications we are expected to see hepatitis C declining in the near future as a cause of cirrhosis and hepatocellular carcinoma. And we're going to see obesity again being the most common risk factor for hepatocellular carcinoma in the Western world specifically in United States as we have an epidemic here.

Scott Steele: Can you get liver cancer, and again, I appreciate you bringing up the fact that what we're talking about here today is primary liver cancer, not different types of malignancies such as colorectal cancer or something else that can go to liver. So we're talking about primary liver cancer, but can you get that primary liver cancer in the setting of non-primary liver disease or non-cirrhosis as well?

Federico Aucejo: Yes, you can in about 20% or 10% of the time, there are known risk factors. And those cases require mutations lead to cancer formation in the river.

Scott Steele: So, how is liver cancer diagnosed? Is gallstones a risk factor for liver cancer? And if you've had gallstones or if you have some of the symptoms that you mentioned, are those factors related, and how is liver cancer primarily diagnosed?

Federico Aucejo: Gallstones typically are not related to liver cancer. They can be related to gall bladder cancer and stones be associate with my bile duct cancer, but patients who have metabolic syndrome, are obese, patients that are known that they carry hepatitis B or hepatitis C or some auto-immune disease that can affect the liver. Patients who have chronic alcohol abuse, those are patients who should know that these conditions are associated with hepatocellular carcinoma and potentially can lead to the formation of liver cancer and therefore, are the ones that should be investigated for.

The diagnostic elements that we have these days are a combination of imaging and laboratory elements. Within the imaging tools, we have ultrasound that typically we would use for patients who have no established cirrhosis. For instance, hepatitis B chronic carriers. For patients who have established cirrhosis, we would prefer to do a CT scan or an MRI, cross-sectional imaging. And alpha-fetoprotein is a specific protein that is released by liver cancer in about 50% of the time. And when it reaches certain values that correlates quite specifically with hepatocellular carcinoma. So, combination of ultrasound or CT scan and AFP or alpha-fetoprotein is what would lead to the diagnosis of HCC.

Scott Steele: One of the things that we do in colorectal cancers, we have a screening program and there's national guidelines and about this and we don't hear much about screening. You talked a little bit about the surveillance for those people who have high-risk factors, the alcoholic, the hepatitis viruses, but is there a screening program and if so, who would you recommend that for? Is that for everybody?

Federico Aucejo: Again, not always easy to recognize that these risk factors exist, and there is no reason to screen for liver cancer if you don't suspect any risk factors. When you do a hepatologist or liver doctor should be the person conducting all these screening tests to detect liver cancer.

Scott Steele: I am somebody that, for whatever reason, I had the jaundice or had the pain and I got worked up and I got an ultrasound or a CAT scan and was diagnosed with a liver mass. Take me through the next steps as a patient and then we'll discuss a little bit about treatment.

Federico Aucejo: When somebody is diagnosed with a liver mass, there are characteristic features from the CT scan or the MRI that can tell us that that's hepatocellular carcinoma. So there is no need for performing a biopsy as opposed to many other malignancies, to confirm we're dealing with liver cancer. The very first question that we ask ourselves when we're dealing with a patient with liver cancer is whether the patient is a surgical candidate or not. Because, as I said, currently surgery still remains the mainstay therapy and potentially curative. And there are two different types of surgeries that we can perform.

One is liver resection, that is removing the liver cancer, but preserving the native liver of the patient. And the other option is a liver transplant. That is, we change the whole organ that includes the cancer. And how we decide which surgical option we pick is based on the liver function, and how advanced liver cirrhosis maybe in the particular patient. Patients who have advanced liver cirrhosis and complications from cirrhosis prominent with bleeding, ascites, jaundice, low platelet count, those patients will need to get their livers replaced, because the liver doesn't have enough reserve to tolerate a resection of it.

The patients who present with what we call well compensated liver function, early-stage cirrhosis, or no cirrhosis at all, but they have the liver cancer, those are the patients that we would pick for liver resection. When the patients are not candidates for liver resection or a liver transplant because the tumor is too advanced and there are some certain criteria we'll look into to determine if somebody is a candidate for liver transplant, we know that the patients are beyond these specific criteria, they will very likely have recurrence of the cancer after a transplant. The outcome will be dismal. In those cases, these patients are not surgical candidates.

And then we have to look into the so-called local regional therapies, which are non-surgical interventions that include transcatheter chemotherapy or radiotherapy to the liver, microwave ablation, which is a needle-based therapy that is inserted into the tumor and creates a microwave energy and kills the tumor. And sometimes the patients are not even candidates for these local regional therapies and only just candidates for systemic therapy. And those are the patients in whom the liver function maybe too deteriorated. But these also, most of the time, don't even tolerate the medical therapy. So the patients who have disease that has spread outside the liver, so they have metastatic disease now, those are the patients who would be candidates for systemic therapy, in a general way.

Scott Steele: How much of your liver can you go without? How much should the liver, when you look at it, do you say, "I can resect this much," or how much do you have to rather leave behind?

Federico Aucejo: In a general way, somebody who has a normal liver, somebody without cirrhosis, we could take up to 70% entire liver volume. In those cases where we are doing resections in patients who have some background of liver disease, we have to be more careful and we'll have to leave let's say 40%, 35, 40% of the liver volume. But these determinations are made based on how much liver we have to take and that in combination with a performance status of the patient and some parameters that tells us how bad or how not so bad the liver is functioning.

Scott Steele: I know we're going to have another podcast about transplant and so we're not going to cover all of transplant. We'll do that on another podcast, but can you give us a kind of a few tidbits and an inside look into liver transplants? How difficult is the procedure? How long are these patients on a wait list? And then, what is postop life like after a liver transplant?

Federico Aucejo: Liver transplant is a wonderful option that has evolved over the years. And is a safe life-saving option for many, many of these patients that entails removing the whole liver of the patient and putting a whole new liver from somebody else. And also, it could be half of a liver, we call it a split liver transplant or live donor liver transplant. Unfortunately, the issue with liver transplantation is that the demand for organs is much higher than the offer that we have. So just you have an idea, the United States, we have about 16,000 patients on the wait list and we get to do about six or 7,000 transplants each year. That's the dilemma we have to deal with, but when a patient is lucky enough to get a transplant, these days, because of improvement in surgical technique and postsurgical and perioperative management and new anti-rejection medications, the outcomes are really, really good.

We're talking about 90%-plus survival at one year, five years, 70, 75% overall survival specifically for hepatocellular carcinoma, if the patients meet specific criteria. Currently, we are under the so-called Milan criteria, which is one tumor up to five centimeters or up to three tumors. Each one of them no larger than three centimeters. Those patients have a five-year survival in the order of 70 to 80%. The recovery after a transplant depends on how sick the patient was before the transplant. Some patients had less complications from liver cirrhosis, and those are the patients who do better, because they're less sick going into transplant. But, overall, for the standard postop period, we would say that it's expected that a patient should be in the hospital about a week or two. And the recovery time can vary. But we're talking about four to six, eight weeks. Other patients who are really, really sick, and these are actually very common, can stay in the hospital for months.

Scott Steele: In general, for liver cancer, do all patients need chemotherapy and if so, how long they are on the chemotherapy for?

Federico Aucejo: Indication for chemotherapy currently for unresectable liver cancer. The first medication that was approved by FDA in 2007 here in the United States, it's called Sorafenib and this is a medication that targets the vascular formation of vessels by the cancer among other mechanisms. Again, the indication is when we cannot remove or transplant the tumor surgically. Unfortunately, with this first-generation of systemic therapies, the response rates is in the order of two to 4% and the survival benefit, compared to placebo and the initial studies, were only three months survival advantage. In the therapy, what we were unable to remove surgically the tumor, there are no studies that have shown that this medication could be benefit to prevent the recurrence of the tumor.

Because one thing that we need to be aware of is that the patients are at a very high risk in the order of 70 or 80% chance of recurrence after resection because most of these patients have something underlying in the liver that caused the cancer initially. I suppose with transplant in which the recurrence rate on patients who meet the standard criteria to undergo transplantation with liver cancer, the recurrence rate is in the order of 10 to 15% only. There are new generations of systemic therapies including immunotherapy that recently have been approved for liver cancer, have been approved before for other types of cancer, and the response rates are in the order of 13%. So, they are more evolved, better, more effective therapies compared to the first generation of medications that came into the market such as Sorafenib. So, we'll see what happens next.

Scott Steele: Speaking of that, particular things that are happening here in the clinic in terms of either liver cancer treatment or in regards to transplant.

Federico Aucejo: I am very excited and proud about the group that we have developed here at the Cleveland Clinic. We have a state-of-the-art Liver Cancer Program that has put together clinical arm and a translational research arm where a group of surgeons, hepatologists, interventional radiologist, oncologist, that work together through the liver tumor clinic, see all the patients in the same setting at the same time, we discuss about the patients all in the same setting through the tumor board. And then, our research arm is super exciting. We work with a number of scientists from our Learner Research Institute through which we're working on different angles of research oriented to liver cancer.

Currently, every single patient that comes to the liver tumor clinic gives bio specimens to us for research purposes, including saliva, blood, breath exudate, tumor tissue. So what we're doing is we're trying to find molecular signatures, gathering all the information from the vial specimens, along with the clinical information, to be able to, in the future, work towards precision medicine and be able to determine for a particular patient, what are the expected outcomes, what are the expected responses to the therapies? So this is very exciting. I hope that we continue to make progress in this direction and why not come up with drug discoveries or therapy discoveries that can take us to the cure of liver cancer?

Scott Steele: Well that's absolutely fantastic and exciting stuff. Federico, we'd like to end up with some quick hitters to get to know our guests a little bit better. What's your favorite food?

Federico Aucejo: Favorite food? I come from Argentina. In Argentina, we eat Mediterranean foods. So, yeah, obviously steak and pasta, pizza, those are the three on the top 10.

Scott Steele: What's your favorite sport?

Federico Aucejo: Tennis.

Scott Steele: Tennis?

Federico Aucejo: You should play, you play tennis too.

Scott Steele: I thought you play soccer, so.

Federico Aucejo: And soccer too, soccer too.

Scott Steele: What's the last fun Book that you read?

Federico Aucejo: The last fun book that I read, that was about history, Argentinian history.

Scott Steele: And tell us something you like about Cleveland.

Federico Aucejo: I moved into Cleveland, I'm from New York. After being here for over 15 years, I love Cleveland. I think it has a great combination of a great town to raise a family. And from a career standpoint, well, working on the Cleveland Clinic I think is a fantastic opportunity. So, Cleveland, it's a great place to be.

Scott Steele: Well, we're sure glad you're here. So, to learn more about liver cancer, please download our free treatment guide. Visit clevelandclinic.org/livercancer. That's clevelandclinic.org/livercancer. And to schedule 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 so much, Scott, for having me.

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

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Butts & Guts

A Cleveland Clinic podcast exploring your digestive and surgical health from end to end. You’ll learn how to have the best digestive health possible from your gall bladder to your liver and more from our host, Colorectal Surgery Chairman Scott Steele, MD.
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