Betsy Post 0:00
Alrighty. So welcome. Welcome everyone. I’m Betsy post. I’m with COLONTOWN, and I’m helping facilitate this evening’s presentation with Dr Hernandez. And I also have, of course, our esteemed Mayor Lindsey and one of the folks on the cabinet with me, Julie, who are also running tech support, you know, kind of any assistance that you might need, you can definitely ping Julie Lindsey myself. I will try to help in any way. We’re not technical experts, but we’ll, we’ll do our best. But I’m going to introduce our esteemed speaker, Dr Hernandez, if you’re familiar with COLONTOWN liver lovers, Lane transplantation station, our various groups dedicated to liver Mets within the COLONTOWN community. I know that he is not someone that’s a stranger to anyone here, so we’re really honored and really thankful to have him with us this evening to talk to us about the new kid on the block, liver transplant for metastatic colorectal cancer and why that’s taking off. So just a little bit of background about Dr Hernandez and I have Julie go to the next slide. I’m not going to read to everyone, but this will be available in the recording as well. But he is the chief of the Division of transplantation at the University of Rochester Medical Center. Before that, he was in Canada. He has an amazing background and did extensive training and live liver donor transplantation in Japan. It’s really impressive. He has over 110 he probably knows the specific number peer review publications in liver transplantation and other hepatobiliary topics, and he’s on the editorial board of this esteemed Journal of surgery. So we’re super excited, again, flattered to have him here. There’s no one I think that knows more, I guess, arguably, in my opinion, about this topic of liver Mets for metastatic colorectal cancer than Doctor Hernandez, just a couple of housekeeping things, kind of in the in the middle, if you will. We do want to take your questions, so it’s really important that we keep this, you know, interactive. I would request that you please put the questions in chat. So we are going to monitor chat, and we are going to come back to it after the presentation and go back to those questions. We really want to try to answer every question that everyone has. So please put those in chat so that we can go through them. We’re again going to really monitor those, look at them, make sure that we do go back and ask all of those questions. So please put those in chat, and if you have any questions about how to do that, you can ping one of us will try to help you. So, Julie, you can go to the next slide. And so thank you guys so much for being here, and I’m going to turn it over to Dr Hernandez to start the presentation again. Please put the questions in chat. Say hello and chat. If there’s anything that you hear that you have questions about or you think is interesting, put it in chat. So we’re going to be monitoring that, and we’re all happy to have you here tonight, so take it away. Dr Hernandez,

Speaker 1 3:17
thank you, Betsy. Thank you Lincy, thank you, Claire, for this invitation. It’s always a pleasure to be in this group and to be part of it, once in a while, to be able to participate and guide patients I have dedicated the last many years of my career, a lot into this field of liver metastases, and I’m very happy and glad that we have been able to make progress in science, in medicine and surgery, and always try to push a little bit more the envelope to help more patients. And I like the title that it was assigned, that the new kid on the block. And I tried to find, I remember when I was younger, the New Kids on the Block. So I find this picture of them when they are 2022 they look a little bit older. They’re not kids anymore. And I think that’s exactly what happened to liver transplantation for colorectal metastasis. Is not a new kid, really. It’s new for a lot of us, but it already exists there for many years. So with this, I’m going to start. And last time, I don’t know how long ago was that, but probably a year or something like that, that I was invited by COLONTOWN to give a presentation, and I expanded a lot about colorectal liver metastasis, and then I talked about liver transplantation. Today, I want to concentrate much more in liver transplantation, but to being able to show the importance or why liver transplantation might play, or play a very important role, I want to talk. Back again, a little bit about all the background of colorectal liver metastases. With this, I want to show the this first slide, showing that you all know that is the third most common cancer. Colon cancer is the third more common cancer in the world, after prostate and breast cancer. So it’s not uncommon to have people like you or your beloved that has colon cancer, unfortunately, and it’s so common. But the good thing is that we make a lot of advancements in treatment, especially in chemotherapy, I would say, in the last 20 years. But unfortunately, there hasn’t been anything that is huge over the last 15 years for colorectal liver metastasis. We’re starting to do some changes, and I’m looking forward to, hopefully, within five to 10 years to be able to to have much more and more. But this slide is showing you impressively how colon cancer is increasing in these young population did from 20s, 30s and 40s. Look at the green part is showing how it’s increasing being the number of cases on this population is going up. When I train as a surgeon, as a liver cancer surgeon. I never saw these cases on younger population having colon cancer. We always look at the late 50s, 60s, 70s. It continued happening on them. But look at this. This is happening. Why this is happening? I think it’s difficult for to prove why I have my theories, and I think this will require another conversation, which I’m not expert, but I think it’s about what we eat. It’s the diet, I think so that plays an important role, the sugars. I think sugars are terrible and at bad. But Well, as I mentioned, that’s another topic. So cancer is increasing in the population, in the young population, and unfortunately, when we diagnose younger patients, the disease is more advanced, because we know we don’t have screening colonoscopies for patients who are this age. We were able to move it to 45 years old. The screening colonoscopies just recently, but before it was 50. So this is a population that is really affected, and hopefully we can make change. And recently, I was invited by the group of five colon cancer to go to Washington, DC for in March of this year for call for Congress. And you know that I am. A lot of you know that I’m a transplant surgeon, and I’ve been in the Senate of Albany, the capital of New York, trying to push for organ donation, for trying to increase the, you know, the sensitivity of the people to be organ donors when someone has brain dead, but that has been my only experience as a physician, trying to get into government and trying to push people from government, our congress people for moving into this but this time going to to the capital, it was, it was really impressive. It was taught you, for me, understanding being with patients, being with family, and listening to some of the politicians that are really helpful for this, independently of their party being strong, they saw it was very important and and I hope I can make more work next year, and I’m devoted to be doing this. It took me like to be three days out of work, two and a half days out of work, but I think it’s worth it, and I really enjoy and I want to continue working with them. So this was very important for me, and emotional. I want to continue doing this for for all of you. So liver metastases from colon cancer, we know that the vast majority of the liver metastases, unfortunately, are unresectable. What does that mean? That we cannot remove it with surgery. We know that surgery is the most important thing. It’s the only, only, only, and I repeat it, the only thing surgery that, at this moment, has been proved to be curative, is the only thing that can be curative, not always, but a lot of times could be curative. There hasn’t been any other thing that we can prove that could be curative. But the problem is that resectable, only 20% of these metastases are going to be resectable of the patients, and many of them are not resectable because there are multiple metastases, or the location of the metastasis in the liver, occupying some areas of the big vessels, the veins and the arteries and the bowel dogs or or the or the metastases are not responding to chemotherapy. We know that if a patient. Is not responding to chemotherapy, and we do surgery and we remove it, the chances of having recurrence early is very short, is very is very high, and the patient most likely will have recurrence very shortly, or sometimes. And I put it here in the bottom part, not an experienced surgeon or center, and that’s true, and that’s why I always ask patients to go for second or third opinions. When they come with me, I give them options. Even if they say, No, I’m comfortable with you. They said, Go. You can go with one of my colleagues here, or go outside. And I recommend people, because I want the patient to be sure of what they’re deciding. And I and sometimes there’s some centers that I have experienced that they said, You’re unresectable. They send it, they come to us, they find us, and they turn to be resectable. What happened with the patients who are unresectable and we cannot operate on them? This is not what I’m saying. This is what the literature is saying. The survival is around five to 10% at five years. What does that mean that if a patient cannot go for surgery, if 100 patients cannot go for surgery because they are unresectable, only five of them, or 10 of them, in the best case of scenario, are going to be alive at five years. So we’re talking about 90 to 95% 90% of the patients will die within those five years, perhaps of the one year, two years, three years. This is what the literature shows. And this is pretty well established and in a very high impact factor Lance, one of the highest impact factor journals when we do surgery, as I mentioned, these data coming from in 2009 from Memorial Sloan Catherine Center, where they have very good registries. This is these 60 months are five years. So to compare to the previous one that we say 5% at five years, this is around 40% at five years. So there’s a huge difference. Yes, you will say, Well, I would like to be cured. Well, you have perhaps 40% chances of being cured at five years, or maybe at 10 years, you have 25% percent, 25% chances of being cured. So most likely the cancer will come back, yes, but the thing is that we’re going to be looking very close to the cancer, and we can do other type of treatments. And this is we’re talking about resections at this moment. I’m not talking about transplantation, okay, I don’t want to mix things. This is what happened to patients.

Speaker 1 12:39
Many of the times when this is unresectable, the reason is because the remnant liver is too small. So a lot of patients come and we see that they have a lot of metastasis, perhaps in the right side of the liver and the left side is too small, or it has a small metastases. And I can say, okay, I can go and remove the left side and that little spot, and then remove the entire right side, and the patient will free of cancer. Guess what? The left side portal of the liver? Maybe it’s less than 20% of the size. So if I do that, that patient will have liver failure, and most likely patient will die. So we that will be on respectable as well, and and we know that many of the times those things happen, and there are some techniques that we can we can use, so other times, when the patient is on respectable is because of the multiple number of liver metastases. And this is where liver transplantation can play an important role. So I want to dedicate the rest of this talk about what are the outcomes of liver transplantation? What do we know about it? What is happening in North America? We know that this is started in Norway, in in the Scandinavian countries, and it has expanding faster in Europe, but there is data that I want to show about what is happening in the US, which is first time that I’m going to be showing this. I haven’t shown this data in any medical conference yet, so I’m glad that I’m going to be showing here at COLONTOWN. I mentioned to you before about the two stages hepatectomies, options that we have to do surgeries when you know, for example, in this case here, before doing transplantation, this patient, for example, has this large tumor here. So normally they will say, Okay, let’s remove the right side of the liver, and then the patient will stay with the left side, but if the left side is a small we can do a portal vein embolization. And I’m sure a lot of patients here are familiarized with this, and we can do this, we embolize the portal vein in the right side. So we put some glue and some coils here through interventional radiology, we wait around six to eight weeks. And we expect the left side of the liver, because now all the flow will come here will grow, or in this case where there are multiple we can go do surgery in the first stage. We remove the tumors in the left side of the liver. We clear the left side of the liver, which is smaller, and instead of embolizing, we can ligate will be the same effect, and then the flow will go to the left side. Will be a very similar scenario. This This one you didn’t operate. But in this one you operated. But in both, you will wait six to eight, six to eight weeks, and then the left side of the liver will grow to around 30% or more, and then you can go and operate. And that is called two stages. He protects. But what happened in this study of five US Centers, and you can see here, people from MD Anderson, people from Memorial, people from Hopkins at that moment. Tim poll, he was not in Ohio. He was in Hopkins. And these are our big centers in us, and they they were doing a lot of the two stages, hepatectomies, 16 years of data. A lot of these patients have hepatic arts in Fusion because they have a lot of tumor loads. The more than half of those patients of this have portal veneer, modelization. What happened to them? The morbidity. Morbidity means complications after the second stage was 50% so a lot of these patients have complications, expected two operations, and this is what happened, overall survival, those patients who had the two stage hepatectomy, compared to those ones who only went for chemotherapy because they couldn’t operate on them, there was a significant difference in survival. So you can see that these ones, at five years only perhaps 15% were alive, compared to almost 50% of the patients who went for the two stage patheta, means were alive. Now in this data coming from Rene Adam, you probably you know Rene Adam from Paul Bruce, very famous certain there. And this is from MD Anderson. And this is a systematic review. That means that this Dr lamb, he went and looked at the data from the MD Anderson, from Paul Bruce and from other centers. And they put all these papers together, 459 patients. And they saw that this population of patients, they survived 20% at three years. They did, sorry, not survive the disease free survival. So 80% of the patient the cancer will come back by three years. I think it’s something that is expected. Why? Because these patients had a lot of disease in the liver, and probably they have micro metastases that, as a surgeon, we cannot see and we miss them, right? The alt procedure, I think I have talked here about that is a very similar situation, but it’s quicker. It’s faster. It came here from from Germany. The Germans push this for doing this normally. There are more innovation coming from Europe. And then we start developing things here, because we have more regulations. That is complex to do things here, but they go and remove the left side of tumors. And then I gave the right portal vein, similar to what I described before, but the difference is, in the first surgery, we divide the liver completely. We divide like we open it like a book, and then the left side of the liver is small, but the right side of the liver, which has the cancer, is receiving blood supply from the artery still, so it’s alive, that portion of liver. And we went just 10 days, and in 10 days, the liver of the left side almost duplicate its size, and we go back and remove it. And with this surgery, we are able to operate more than with the two stage. He protected me. However, it’s very aggressive to do two major surgeries in 10 days of difference. And this was a case, as you can see, this is a small size. You can see there’s perhaps the CT scan is not the best, but you can see a tumor here, little two tumors here, tumor here, in the right side and the right side. And so this patient needs a hepatectomy of the right side, but the remnant liver was too small, and this is when we did Imagine we did an Alps. Look at this with the partition. It’s divided here you can see how the right side of the liver shrinks, and it’s impressive. Look at this. This is the left side. It was this part here. This looks like this patient was born with almost known left side, and now it’s huge. This was the first one that I did in my life, and I really thought this was phenomenal. And I continue doing in a very selective cases. This is one of the papers that I published where we can see that the survival of these patients with high two. Tumors we do Alps is very similar of what we saw in the two stage hepatitomies. It doesn’t change too much. Perhaps it’s around 30% that three five years of the survival and the recurrence is pretty high. We are able to operate more than the two stage hepatitis. But I think it’s just selecting the patient, because, honestly, I would do only this in a patient who is very healthy and in good performance status. Now, what happened to those patients who initially, we call them, you know, you’re unresectable. We cannot respect. We cannot use an Alps. We cannot use a two stage hepatite, a portal vein embolization. You are unresectable, so the patient just received chemotherapy, but the patient responds very well, and the patient, we call it conversion. Now we say, Oh, you responded very well. The tumors are smaller now we can go and operate. What happened to them if we operate on them and we remove the cancer, do they do the same as those patients who were initially resectable? Unfortunately, not. And the survival at five years is around 30% and around 80 to 85% of the patient, the cancer will come back five, about five years, so a little bit worse, and it’s expected. Why? Because some of the tumors that disappear, perhaps they are still there. We cannot see it in the CT scans. We cannot see them in the PET scans. We cannot see them in the MRI, but they are still there. So this is what, for example, this is a case in our in Rochester where this patient had look at these multiple metastases here in the right side and then in the left side as well. So this case was called on resectable on resectable disease. But look at this. Now, the patient received chemotherapy, and look at the response. I want you. I’m going to go back so you can see this. Look, the tumors are in the right side, multiple this one here, here, here, here, here. So clearly we do a resection. This patient won’t have it.

Speaker 1 22:17
So even here in the back part of the liver. And then the patient received chemotherapy. And you cannot see a lot of the tumors that were there. You can see this large one here, probably this one here, and even in the one that was here in the back disappear. And then you say, Oh, wow, we should go and resect. You know, maybe 10 years ago I would say, I can go and do an APR here, I can go and do an Alps in this patient, and the patient do very well. We will continue. Don’t forget about that. We’ll come back about that patient. So that is what we will call it a conversion. So what happened with those patients who has been heavily treated with chemo? Or you call it hepatic Arthur in fusion, you call it systemic chemotherapy or both. Because I know hepatic Arthur in fusion, they give both. They are never giving it alone anymore, because it was proof that it doesn’t work when you give it a loan. So in this paper, in this these are two papers, this is one and this is other one. In this paper, patients who have major treatment with a lot of chemotherapy for eight months, one year, year and a half, and then they go for a resection. 40% have major complications. When we say major complications that the patient require an intervention, a re operation for bleeding or a bile duct complication and a 10% mortality. One out of 10 of those patients die, and at five years, 13% were possible in cure. So we’re talking about that almost 90% of the patient the cancer came back in this other study of 47 patients who received more than 12 cycles. That is just six months of treatment. You know better than me about this with chemotherapy and when they went for surgery, 50% of the patient had major complications, and 20% mortality. Two out of 10 patients died. And at three years in this study, all the patients have recurrency. Cancer came back. I think they are. They did better than the patients who only received chemotherapy, definitely. But what I’m showing here is that we have to be very cautious in patients who have to have been heavily treated with chemo when we do liver receptions. And I witness of this as a search, I think some of you know I don’t do trans. Only I do a lot of reverse sections, a little bit that I want to talk about the paddy car three in fusion, because I have seen a lot of a few of these patients, I wouldn’t say like hundreds of these patients, but several of these patients will go for the particle in fusion. So in this paper, that it was probably a little bit off, because this is coming from 2007 but it was known that the hepatic artery in Fusion treatment alone, without systemic chemotherapy, is was not working. It shouldn’t be used. And they call it this the end of Panera, which is not because it’s coming back and they’re pushing and MSK is doing it, and nothing against them. I have very good relationship with them, and there were colleagues, and we have friendship communication with them, but I think we need to be cautious about this. In this study, where they did a trial of efficacy, that means how they compare hepatic artery fusion with systemic chemo. And if you can see here is these are patients. We’re not talking about surgery, we’re just talking about which one did better. Patients will receive a Patric Arthur in fusion with systemic or those ones who did systemic chemotherapy, and they were very similar in number of tumors and age of the patient, so there was no significant difference in those factors, and the only difference in survival of these patients, the patients who received only systemic chemotherapy and no surgery, they survived an average of 20 months because they were unresectable, and the patients will receive the fatty car in Fusion just four months more. Yes, there wasn’t a benefit of those ones who received hepatic art in fusion, not very impressive to see four months, and there were no survivors at five years in any of the two groups. So with that, I want to start mentioning about what’s new for unresectable liver metastas, and we call it the new kid on the block today, alright? And this, some of you are aware of this, and this is started, as I mentioned at the beginning. This is not new liver transplantation started in 2013 and and where is my friend here? PAL Dad, here it is. He’s the guy. He is the main guy. Pal dad, that his first name, his last name is like pal dad is the main surgeon. What is interesting about Norway? There’s only one center in that entire country, only one center that is doing liver transplantation in the United States. How many centers we have doing liver transplantation? Perhaps arrow, 180 maybe. Centers doing liver transplantation. It’s not socialized medicine here, over there is socialized medicine. So there’s no competition. Here is competition, right? So it’s very different. Every patient who needs a liver transplant will go to only one center in Oslo. So the the regulations and the main the way of managing things is much easier here. It’s if I want to do something different, I have 200 centers going against it’s very difficult to make progress with sometimes when we want to do something different. So they were able, and also, they have a short waiting list in their patients who have cirrhosis. They don’t have that many patients, and people donate a lot. So he said, Well, why don’t we start transplanting patients with unresectable metastasis? Because we can use this organ. So these patients, because the French surgeons in the 1990s they use those livers in patients with colorectal metastases, but the outcome was very good, but this was 30 years later, when they started using it now in Norway, and in 30 years, we have much better chemotherapy. We have much better immunotherapy for for patients who get transplant, because patients will receive transplantation require immuno suppression to medication for life to avoid rejection of the organ and and better techniques. So he started doing this, and this is what they saw. If you look at this graph, this is quite impressive. The red line is demonstrating the survival of the patients here in the bottom part is the years. So 60% of the patients who were transplanted with unresectable liver metastases were alive at five years. Wow. Even better that the patient who were resected with resectable disease since the beginning. Never seen that before. What was the problem? The problem this is recurrence. So at around two years, majority of the patient, the cancer came back, but they were alive. A lot of majority of them. So we’re going to go through that. What was happening, what was different? We. The recurrence compared when we deliver resection. I will answer that in, I think, in a couple of slides, probably. So then the Norway group, they start saying, Okay, let’s try to analyze these ones who did better. What were the main factors that created that they were doing better? And they found this as the new score. And they call it the Oslo score, if the two, if the largest metastasis is less than 5.5 centimeters, if the CEA a transplant at the moment of transplant is below 80, if the patient is not progressing on chemotherapy, and if the time from the diagnosis to the transplant is around two years. And if you have each one of these is four points and four points, the transplant will do very bad. If it’s three points, do better, two points or better, and zero to one points, all of the patients were alive. We need to be cautious as well. This is not like, Wow. Yes, this, this is impressive, but look at the number of patients. We’re talking about six patients, five patients, five patients. So we’re talking about small population of patients. So my I reviewed this paper many years ago, and when I saw that, I was really impressed. I was saying why we cannot do this in the US. Well, I was in Canada, sorry. Why? We cannot do this in Canada. It’s impressive, but, but I said, Well, we have to be cautious, because this is a small population, but this has been growing, and now the numbers are more higher and proving the same. Now this is a new thing that is happening, and here in Rochester, we’re taking consideration of this. We’re measuring this. This is the PET scans. We like to do a PET scan before transplant. And this data is showing, with a formula, we can calculate the amount of ability, abilities that the tumor takes this kind of contrast, which is

Speaker 1 32:02
the PET scan. You know, for example, here you see the the it’s highlighting here in yellow, and that’s the ability, if it’s not Avid, that means that it goes like reddish color normal. But we can quantify how much is highlighting and with this formula, if it’s below 70 centimeter cubics, it’s a good factor. If it’s above 70 it’s not a good factor, because those ones who have less than 70 centimeters cubics, they do much better. At five years, this patient has also around 80% survival. So this is a new data showing us that we can use it to verify which patients are going to do better. But it’s not always perfect. Okay. Now I mentioned to you about recurrence. What was the difference in transplant compared to liver resection, and this is so important, majority of the recurrence after transplantation, which is common, around 70% of the patient will have recurrence, but majority of them are in the lungs. But those ones who have in the lungs, they do much, much better and up in this data coming from Norway as well. At five years, all the patients were alive, they still have cancer, a lot of them, not all of them, because some of them, they were able to resect them. Those ones who have metastasis in the liver, their survival was short, but only around 5% of the patients will have recurrent in the liver. When we compare these to patients who have resection or recurrence, it’s pretty high. And I know that Dr Suarez, just a few weeks ago, presented, and he showed the data about the high recurrence after liver resection in this in patients who goes for liver section. Now this is pal that I asked permission for him to show these three lines of data, because his manuscript is under review that I think is going to be published very soon, the first study where they have the first in 2013 when they published, they continue following these patients and the five year survival, five years overall survival of 75% and 10 year, 10 year survival, 50% so we can, he can call that, if we are going to cure patients with Liver transplantation. He said that between 25 to 30% of the patients, if they are were selected, we can be curing these patients. That is pretty impressive. And to survive 75% at five years, this is something that we haven’t seen before. And as I mentioned, long recurrence. It’s very common in transplant. However, is. Is treated with curative intent. It can be resected, of course, if there’s multiple then perhaps chemotherapy will be the best option. This is data coming from the United States. This is your country, the first transplant for liver metastases in the new era, because there were old all transplants. So this is not the first one ever. Okay, no, there were other transplant that happened. Actually, Dr star saw the first Surgeon in the world that did the first liver transplant almost 50 years ago. He did colorectal metastasis liver transplant. So we’re not counting those ones. So those are the first patients who were transplanted for colorectal metastasis. This is the new era that we can call it. In this new era, the first case happened in 2017 and our programs are functioning around here, but you can see 17, 1819, how it’s increasing the interest in the in the United States. This is projection here, just with the way that is growing, and this is what’s until April here. But if we continue with the same projection, probably we will be in 30 just this year in the United States, very soon, probably one more year, we’re going to pass the numbers of Norway. But what is happening? I think what is happening. My point here is, in the United States is a lot of groups wants to do it, but they don’t have the it’s not about the surgical skills. It’s about the selection of patients and the follow up and the experience about being involved with colorectal liver metastases, because the unfortunately, here in the US, the surgical oncologist and the transplant surgeons are very separate. Where I was trained in Canada, I would do both. And I came here and I said, I only will move to Rochester if I’m able and continue doing both things. And I do liver transplant and liver sections, and we collaborate with our surgical oncologist as well, but I continue doing both things, and I think this is open opportunities for being able to to expand innovation in a lot of these spaces. If I wouldn’t be involved in both things, I wouldn’t be doing this. And why living donor? Initially, there were some centers that were using disease donor. Disease donors. I shouldn’t say this word, but I you know, because in transplant, they said that we should avoid saying cadaveric donation. But you know, when patients have brain dead, that’s the most common way of donating in the United States, the 90% of the transplants that I do are from deceased donors, someone who has brain dead our team flies go and retrieve the organ, bring it here, and we operate our patients who has cirrhosis and it’s very sick in the ICU, and hopefully we can save that patient. And we do living daughter in patients who are in the middle of the list that they don’t have too much access. For these patients, the fact that we’re doing liver transplant for those patients give us the skills for being able to deliver living donor liver transplantation in patients who have colorectal liver metastasis, because these are patients that they are not sick from the liver. They have cancer, but they are not sick to be able to be in the top of the list of liver metastases, of liver transplantation, to attract an organ, Cath, a coordinate. So that’s why the number of living donors is increasing for colorectal metastases. And last year, 80% of them of the transplants that took place in the US for colorectal metastases were done by living orders. I can tell you if I predict, well, 90% or more than 90% next year we’re going to see this line going probably around 90 or above. Now, this is the activity that I know so far, and I might be missing some centers. And this was, I think, for around three months ago. These are some of the centers that I know. They have done at least one liver transfer for colorectal metastasis. I put these hospitals bigger ones because they have been doing more. This is Houston, in Methodist. They did, I think four, but they are not doing more. Why? Because they don’t have a living donor liver transplant search, and at that moment, they were able to use some disease organs, because a lot of people around the area of fusion were not using some organs. They were saying, No, I don’t want to use this organ for my patient, because that organ is not very good. But this surgeon said it’s not that bad, and he used it, and he had probably good outcomes in those four patients and or in other patients. And. Okay, but now the allocation system in transplantation in the country change, and a lot of those organs now are going, I don’t know, to the north, so now he’s not having access. So now the only way that he can deliver transplant for these patients is with the living donor. So this is not going to grow unless here is, help me. This is San Luis, right, yes. And this Missouri, you wash you doing few of them that they have been using some calabari organ donation. Here is Cleveland, here is Rochester, here not here is Rochester. Here’s Cleveland, and here’s Pittsburgh. Those are the three other centers that has been doing a little bit more.

Speaker 1 40:44
In our experience, we have done 10 cases, which to my understanding, where the center could have been doing more. And we published with the group from Cleveland and Toronto, this paper that perhaps some of you are away. Are aware, and this is confirming the data outside Norway. It’s a short follow up, because not all of all our patients from that we we have four patients from Rochester, four patients from Cleveland, and two patients from Toronto. Not all of them has five years arrested follow up or more than three years. So we look at three years survival, but looking at this survival, looking at almost 80% of the patients were alive at three years in this patient, and 60% recurrence free survival, that means 40% of patients have recurrence. So that as a pretty similar scenario on Norway, perhaps even a little bit better. But I don’t want to be feel like so excited, because we have to wait to see a little bit more. I will show more data there, specific from Rochester. In Rochester, as I mentioned, after 2000 it was 2018 passing that we started our protocol, and this is our protocol, and I’m gonna go for HD Cal, we go for an Oslo score below two. But to be honest, this is what we have in our protocol. But when we analyze to because we’re writing a paper right now, all our patients has been one or zero, and probably that is one of the reasons that we’re having an acceptable outcomes in our patients. And this, you know, this is the ultra score that I mentioned. But to me and to our group, there are two important things here in this ultra score. I don’t think it’s necessarily to be below 80. I think it’s more important the trend, yes, below 80. Perhaps it’s a marker that the group from Norway found. But imagine if a patient goes from 80 to 40 to 20 to 10, but then it goes from 10 to 30 to 50 to 60 to 70? Is it below 80? Yes, but that’s not good. It’s going up continuously, and closer to 80. That’s something that is not going good there, and probably that trend plays a more important role than the fact that it’s below 80. And the other point is progression of disease. Progression of disease is a bad marker that we know for liver resection, if a patient received chemotherapy and is not responding and progress those patients, we know that they have very high recurrence in transplantation, probably it’s happening. Would happen the same if we translate the data from resection to transplantation, so doing a salvage transplant, probably no, no, it wouldn’t be the ideal. And there’s sometimes that is a little bit difficult to take a decision, because you cannot prove that is progression, and it might not be progression because of the when you measure the the size of the tumor, some of them could be bigger, some of them could be smaller. And then it’s difficult to call it if it’s progression or not. But in other than that, when it’s clear that a patient is progressing, I think transplantation should be avoided. So far in our institution, we have more than one quality 140 referrals. We have a dedicated navigator that is a key member of our team, and Kayla do phenomenal job trying to be in contact with all our patients, responding as soon as possible and reporting to our nurse practitioner and to our coordinators that play a very important role, and to me and we look after there’s a lot of work that we do, bringing all the images and looking at details of patients we have to review sometimes 4050, images in our tumor board. And our radiologists are tired. They say, Well, this image. Is coming from others. CD for mother center, but we review in detail all of these things. Of those, 140 patients, only 10 has rich liver transplant. Wait a moment. There are several, at least eight or more that are still in the process of potential candidates that I think they could be candidates on 24, probably. So that’s huge number, huge number. Hopefully, the eight reached that. But to be honest, probably of those eight, maybe six or five, were reached despite that, that’s still a very big number for the next six months, majority of the patients who were who didn’t reach transplant was because there was evidence of extra particle disease, disease outside the liver. Many patients were potential candidates, but developed progression during the follow up treatment. Because we follow the patients from distance, we look at the imaging device, which sometimes we have to do biopsies to prove either a positive lymph node or lung metastases. Few, probably a handful of the patients who were sent to us for transplantation turned to be resectable. And I was, Wow, really, this is resectable. So we talked to the patient said, you know you’re resectable. You want to come to register? I can do the resection, but probably I can call one of the surgeons close to you, and maybe will be easier for you to go there. If they want to come with us, they’re welcome to come and we do the resection here. But it has happened that sometimes we find that they are resectable. If you went for third or fourth opinions, which is completely okay, because the most important thing is the patient needs to feel confident that where that patient is going is going to be the right place. I think we have all the opportunities to go and say, Okay, we I can. I want to go and see four or five centers, or four or five surgeons, and then I will decide. But when you decide stick to that, that that would be the best thing, because that creates a much better management that’s my advice. This is the data of our 10 patients. This is not the paper that we published, because remember, the paper was Toronto, Cleveland and Rochester, here is only Rochester, and this is what we’re finding out. The shorter recurrence, around 70% survival at three years. So this is pretty impressive, that it was going to change most likely because our there’s new patient that has a very short follow up, only one of our patients, of our out of the tent, has died after having some recurrence. All our nine patients, the rest of the nine patients are alive. Another patient had recurrence, unfortunately, and is getting treatment with chemotherapy. Now here, this is what we’re doing. We have a trial that we’re going through that known as the patients. Doesn’t have to go through the through, through the trial, but we registry these things here because it may cause a more creates more credibility when when you publish things for this, what we found, this is what we’re working this is my research fellow, Mariana Chavez, where these are 14 cases, 10 cases from Rochester and four cases from Cleveland. I’m not showing which one is which one. And this is so interesting. These are each patient, each patient. This is a cartoon of the when they were diagnosed. The number of metastases in the first column. In the second column is the number of tumors prior to liver transplantation. This is after the patient receive a lot of treatments, RFA, so ablation, y 90, Paddy car three, in fusion, chemotherapy, surgeries, etc, etc, right? And then this is what we found when we remove the liver in pathology. And what is impressive is that 60% of these patients, 60% in in where the pets can set. There’s no cancer here. There was cancer. So the disappearing liver metastases that I’m mentioning, they were still there. I think this is the first time, because this is the first time in the history that we have the entire specimen of the liver out. Normally, when we do live resection, we live, you know, part of the liver for the patient to survive. But this is the first time that we remove entire and we can analyze entire liver, and this is what is happening. We’re finding, clearly, with all the evidence that there was still cancer, there are 60% of time even that it’s disappear. It does not

Speaker 1 50:02
some tips and tricks that we have learned. And this is when I go to give a talk. I think I spend a lot of time with the surgeons talking about this, because they want to learn more about this, the timing from colon resection, because a lot of the patients come okay, I still have the primary side. Can I go for a transplant? Well, yes, you can go for transplant, but we have to remove the primary at some moment, or the patient goes, Hey, my colon cancer is gone. They cannot see it. What is the evidence if we go and do a liver transplant and we don’t touch the colon? I haven’t done that, but I wouldn’t, I. Am sure if we give immuno suppression, there might be some cancer cells in the colon, you will come back. So we have pushed for removing it. There’s one patient that I know that we could transplant that we remove a portion of the column for it was tattoo the cancer, and there was no cancer. But there were other two that apparently disappeared, and when we removed the portion of colon, there was still cancer, so it’s better to remove it, and we don’t want to do experimentation here in large lymph nodes. That’s a big question. What should we do? So we use endoscopic ultrasound, sometimes through the stomach, to be able to biopsy the lymph node to be sure if that’s a positively if not. If it’s a positive lymph node, it’s not a good prognosis. And we use Final aspiration, or sometimes the interventional radiologists use percutaneous biopsy. Or few times we do a laparotomy. We have to Okay. If everything looks good, but we have high suspicious we open the abdomen of the patient before or the day of the patient is coming from outside, let’s say if the patient is coming from far away from, I don’t know, Kansas City and the patient and the donor here, but we have suspicion of that. We start the operation with a recipient. Normally, we start with the donor. Normally, that’s when there’s a donor, a living donor. We start with the donor, and then we bring the recipient to the operating room. But in these situations, we don’t want to put the risk of the donor if we are not sure if we can transplant the patient, so we start with the recipient. We open, we take a biopsy of the lymph nodes there. If it’s negative, then we do, we do the transplant. If not, we have to stop the transplant. Long nodules. We have to review the two more board these what they are very dedicated, and that I’m proud of my team, that they review every single thing, and our coordinators take notes about this so and this is on top of their normal work with all the cirrhotic patients, because I’ve been able to have, in my case, a lot of resources from the department of surgery and the institution to be able to set up a team dedicated for this. But a lot of the other coordinators who are not fully involved with these, are very supportive of all of these. We talk about immuno suppression. We try to bring it down as soon as possible. We have learned more about immuno suppression because we have been trying to change some patients that probably they don’t tolerate it very well when we try to switch them. And we’re learning a lot of those things. And this, I think, a new area that I call it HEPA oncology. We have hepatologies. We follow that follows liver transplant patients, and we have oncologists that follow the patients with cancer. This is putting both things together. Our hepatologist with oncology, and I personally call it our hepato oncologist, and this is what we’re trying to develop here. I think, what time is it? Okay? I’m Hurry up. Betsy. I’m sorry for the same criteria for recipients with the Paducah pump. Just 111, more. Note about the Patriot pump. We have the same criteria for as you can see, the patient is a candidate for transplant after the pump. However, it’s very clear to tell the patient there’s a way higher risk in the transplant. Why the pad three pump creates, unfortunately, damage in the paddy Carter. You cannot use it for transplant. And without the paddy car three, deliver one work. So we need to bring the artery of the spleen, or put a conduit from the aorta from a cabaret daughter. We call it graft or conduit, the portal vein, a lot of the times, is very inflamed because of the pump, and also because of the chemotherapy of the pump in that area, and, you know, a lot of the patients capillary damage. So the risk of transplantation is way higher. We do it, but it’s way higher. The only thing that I see for me is, I think there’s a place for the palm a place for transplant. I don’t think it’s a five more, but what I would say more is, if a patient is responding to systemic chemotherapy, why changing the game? If the patient could be a transparent candidate, continue for one year, complete the year, and probably the patient will be a transplant candidate, if the patient is progressing on systemic chemotherapy, okay, the patient is not going. To be a transplant candidate. Let’s give the pump, right? And if it comes back to conversion and respondents, they doing well and well, then find surgeons who want to play hard ball and do this transplant. But if not, I wouldn’t change them the positions here, I think I will stop here. These are the areas where I think the patients are probably four areas that I call it transplant, transplant categories, those patients who we see these since the beginning were unresectable, and they still have the primary inside you, patients who have multiple metastases, but they have multiple treatments, surgeries, ablation, pump, etc, etc. And I call it more burnout, cancer burnout, liver patients who are unresectable because they have recurrence, and probably this is an area where it’s going to be extending those ones who were unresectable and converted to resectable. Perhaps transplantation will benefit this patient. And to finalize, I told you about this patient, right? Look at these metastases, this patient, and then this patient responded. And some surgeons say I can resect that, the patient decided, and we did a liver transplant because we were sure there were more metastasis. Sorry to show you this, but this is the liver. And look at the metastasis. This is the left side of the liver. Should, sorry to show you these, but 12345, here. This is the left side which I’m showing it here. 123, and this is proven that there’s cancer here. So we would do a right hepatectomy for that patient that here, they said, Let’s do a right hepatectomy only to remove this part. We will be removing this part. We will live in all these cancer. So I think we did the correct thing. This is another patient. Look at this amount of disease. Of course, this is unresectable, and this is the amazing the same patient, I promise you. It’s impressive. The response that the patient had. Look at this amazing patient came here for transplantation. This is their lovely donor. We remove the right side of the liver, a beautiful left side of a liver, enough for the donor. And this is the right side of a liver where we use it for reconstructing it. And you can see here, once the blood came into the new liver of the of the recipient, and it looks pink and beautiful. I know probably you don’t feel that this is beautiful, but it is, and this is what we find in the explant. The pathologist look at these spots of cancer. It’s suppose that here it almost disappeared minimal disease. But when we go and see in the pathology multiple spots of cancer, they’re still there. That’s what I want to show you. Another case. Look at lost those liver metastases. Patient responded so well, you can see these calcifications. And, you know, I, I’m part of these. So if, if you would bring me this patient when I was in Canada, when I didn’t have an idea that we were I was going to be doing liver transplantation, I will take this patient to the operating room and try to do resection or Alps, or two stage protections or something. We did a liver transplant, and there were multiple metastases still in the liver, as you can see here, 234567, here in the back of the liver, we’re taking a lot of this tissue as well, with the consent of our patients, that we consent them into my lab, and because we’re trying to analyze more of the biopsies to understand more about the immune system that is playing a role in this cancer, to hopefully, in the future, being able to find markers and decide which patients are going to respond better. And in conclusions, surgery is the goal in metastatic colorectal cancer and surgery, I include transplantation. There are favorable results with chemotherapy, and we have gone far away, and that’s what is helping us for being able to do liver resections more aggressively. Patients should have the opinion of different treatments modalities to explore second and third opinions. I think the field of liver transplantation is evolving quickly, and we need to be cautious about this. I don’t I hope not a lot of surgeons taking us the new thing, the new toy, and not selecting the patients correctly, the multidisciplinary team, the experience, is very important, and we should keep fighting and moving forward. These are frequently asked questions, but probably the people I would like really that people ask questions and feel comfortable to open your your camera, your screen, ask questions. There are no dumb questions. There are important questions, and I’m here for you, and thank you for this invitation. Again. You.

This is an automatically generated transcript.

Betsy Post 0:03
I’m really excited to have Dr. Hernandez from the University of Rochester Medical Center with us this evening for tonight’s DocTalk on liver transplants. I think there’s truly something for each one of you that are here, because Dr. Hernandez is going to talk about some of the basics about liver transplants. He’s going to address everything from who makes a solid candidate to get screened for a transplant. And then he’s going to talk a lot about some of the evidence that we’ve seen in the last couple of years for transplant, including, I think a lot of people are really excited to hear him talk about the information that was just released at ASCO in June 2024, just a couple of weeks ago. So we’re very excited to have him here. And I don’t know if he’ll tell you this, but he was up all night doing a transplant last night, came home, took a shower, had a little snack, and went back to work. So we’re so happy to have him here tonight. Really, I want to be really respectful of his time. Let him get through his presentation. At the end, he will do Q and A with us. So at this point, I’m going to turn it over to you, Dr. Hernandez.

Dr. Hernandez-Alejandro 1:25
Well, thank you.Thank you very much. As always, it’s a great honor to be in front of patients and caregivers. Thank you very much, Betsy and COLONTOWN for this opportunity. I like to see that there’s a lot of names that I don’t know, and hopefully we can have an impact, and we can help and guide patients and caregivers here. That is my objective. While Betsy was making the introduction, I was able to see some names. I know a few of them. And two big names from the West Coast that make me smile a lot. Over the next several minutes, what I’m going to be talking about is just the specifics about the role of liver transplant for colorectal metastases, and show some of the evidence of what is happening nowadays, especially in our country and what do we know about new data? Because probably people want to know new data, and I think hopefully this helps patients and caregivers for decision making. I want to be clear and disclose that I’m a liver surgeon. I do this procedure that I’m going to be talking about, liver transplantation for colorectal metastases. I do liver resections. I do many other treatments I don’t want to cover in that aspect right now. It’s going to be concentrated into liver transplantation. With that, I’m going to start and again, I will share my screen. And thank you very much for this Betsy. I want to know if my screen is perfect?

Betsy Post 3:16
Yes, it’s perfect. We can see full size.

Dr. Hernandez-Alejandro 3:19
So Betsy mentioned who I am and what I do and where I work, in Rochester, New York. Many of the slides that you will see if you have seen other presentations, not many, but several are in already-presented and I have shown. But for me, this is very important and I want to show this because this reflects the impact of the topic that we’re talking about, and I will try to make it more clear here. Remember for some that maybe some people are familiarized with graphs. Others are not. But if you see here, for example, the yellow line, or the purple line or the green light line, here you see that with the years it has been going down. So this is a population of 85 years old, 80s, 70s, 60s. The incidence of colorectal cancer, it’s decreasing in this population up to the 50s. Why? Because we are the countries doing a good job on doing colonoscopies nowadays, even in patients of 45 to above. But look at these numbers here. These are going up. All these younger people who were not used to have cancer. When I was in my training, I didn’t see colon cancer in this population. It was very uncommon. Nowadays I see a big majority of my patients that I assess for liver metastases from colon cancer are within these ages, from 20s, 30s, 40s, early 50s increasing. It doesn’t mean that doesn’t exist in the 60s, but it is happening. But it’s the incidence is decreasing. Less people having this because we’re doing colonoscopies, removing polyps. But this population is disadvantaged. I’m not here today to fix the healthcare system about who should be having colonoscopy or not, but there’s more than 150,000 patients, people in the country each year, in the US that there are diagnosed with colon cancer, and we know that probably half of them will develop liver metastases. So this is a big problem, and that’s what we’re talking about. What does it mean when we talk about unresectable colorectal metastases, as the majority of you know, and the caregivers as well, surgery would be the best result. And what does that mean, if we can go and remove the cancer, the tumors in the operating room leave enough liver to survive, because the liver is going to regenerate, but if we are able to remove all the tumors, then the patient will have the best prognosis. Chemotherapy helps, but it’s not going to cure patients. It’s a help. I want to see that a lot of the things here are “friends” – they shouldn’t be competing. They are friends. The importance of this, of a team, when you see a doctor or a physician, an oncologist is someone who really creates good allies with the other specialties and is able to think a little bit out of the box, especially with those patients who have metastases, multiple metastases in the liver, like these cases, where we see a lot of metastases here in this liver. What happened with these patients who have unresectable that we cannot go on remove it, because if you see in this case, if I remove all the spots of cancer, I’m going to leave this patient without a liver, and you cannot survive. So what do we do? The only treatment normally for this patient will be chemotherapy. Maybe you can say, “Okay, I’m going to give that Y-90 as well.” Maybe we can do some ablation. But all of these are too much disease and it probably won’t work doing other local, regional therapies. Probably the only option will be chemotherapy or the pump in this patient and what happens with these patients from 100 patients, only five or 10 will be alive at five years and with cancer, So the outcome is not very good. But what makes chemotherapy of advantage, not only giving a little a little bit of survival to these patients, because if we compare chemotherapy with nothing, chemotherapy gives an advantage, but I see that chemotherapy allowed us to identify which patients might be the ideal candidates, or better candidates for going to other treatments such as transplantation, because it give us a chance to understand the behavior of the tumor, what we call ‘tumor biology’, and I would like all the patients and caregivers to understand what this is. When a doctor talks about tumor biology, it’s the tumor behavior. How we know how the tumor behaves, if it’s very aggressive or mild or moderate is if we give chemotherapy, we see how it responds. It allows us to evaluate how bad or aggressive it is, and then we can make decisions on how can we treat these patients. This data that I’m showing here is very important. This is from 2023. I was showing for the first time, a lot of new data coming. This is from LiverMet Survey (2023). This is from Europe and this is in patients with liver resections. I’m not talking about transplantation here. A lot of the information that we know and we use in transplantation, we adopted from liver resections for colorectal metastasis. And this is telling us that: number of metastases matter. Patients who have resection and have metastases between one and three and they go for resection, their survival of five years is around 76%. In this group of patients of 27,000 patients in Europe, when they have metastas between four and seven, look at this, how it drops to 16% at five years, and if they have more than seven to 7% that five years. What is this telling us? If we have a lot of metastasis, our outcome, even with surgery, is not very good, probably better than only chemotherapy, probably better than non-treatment. But we want to do something different for these patients, because this is very small amount of benefit of this patient. And again, this is just showing in a different way, the survival of these patients who have one to three, four to nine or more than 10, that clearly tumor burden matters – how many metastases and what are the size of those. So, look at the date of this paper. This is 1990 1991 so in the late 80s, Austria and France, they started doing liver transplants for colorectal metastasis, and they published this paper in this journal, which at that moment, it was important, but nowadays, it’s not an extremely important journal, “Transplantation Proceedings” in 1991, and they showed what I want to show is here. It is the patients who have had a liver transplantation. Here it is – the dark line here is liver transplantation. They compared patients who have advanced liver disease that they transplanted, compared it to patients who have had chemotherapy and some type of hepatic artery pump. It’s not the same pump of what we use nowadays. It’s not the same that what the patients who go to MSK and get this pump, you can’t get this pump. It’s different. It was a different chemotherapy, but it was intra-arterial so they compared this patient with transplant, and the ones we did that pump at that time, and they saw that the survival of this patient was better, but really, at five months, around 20% of the patients were only alive, and the vast majority of the cancer came back. So clearly, in the entire world, liver transplantation was decided that it’s prohibited. It was not an indication. It was a contraindication. So everybody abandoned the few cases that started transplantation. So we’re talking about 1990; so we’re talking about we’re taking 25-30 years later. Now there’s a lot of things that have changed, and this is how we understand that tumor biology that I was telling you, I showed you that size and number of tumors matter. Now we can measure better with tumor markers, with the CEA. A lot of you know about Signatera, or Guardant 360 that we can use to measure the circulating tumor DNA. We can understand – I was mentioning this – for me, this is a very important one. How would the patient respond to chemotherapy? When patients do not respond to chemotherapy, normally, the outcome is not going to be good if the patient has disease outside the liver. Not always. It’s very important – it depends where it goes. Sometimes, if it’s in the adrenal gland or in the lungs, is different than if it’s in the peritoneum, which is the layer of of tissue that covers all our organs, in the abdomen, the presence or not of lymph nodes around the liver or in the retroperitoneum, which is the area which is behind the organs, more into our back. This is very important as well. And I always talk to my patients, we need to understand more about the tumor genetics. So what mutations exist? Very few people have BRAF mutation, but that could be pretty aggressive, or the KRAs and RAS TP53 etc, etc. The more mutations apparently, we know that the prognosis is worse, but it’s not the only thing. And now we know that the presence of tumors in the right side or left side, the prognosis is different. When patients have cancer of the primary tumor, the colon cancer in the right side, we need to be more cautious, because the cancer normally is more aggressive, and tumors in the right side of a colon are associated not always, but are associated more with mutations. So what have we done up to this moment over the last 25 years? So we have chemotherapy agents you might identify, many of you. What are these? FOLFOXIRI is a combination of FOLFOX and FOLFIRI. These are two different chemotherapies, kind of the same families, but they are different. One uses oxaliplatin with normally patients, there are some patients that are very strong, that they tolerate many months of FOLFOX, but they develop some neuropathy. It’s very common to have that, but the response is pretty similar. A lot of the times we start FOLFOXIRI, then the OX, it gets removed, and then we continue with irinotecan, which is FOLFIRI, which also has some bad side effects of GI symptoms. We also use some biologics, depending if what type of tumor it is. You can use all of these, which are bevacizumab, cetuximab, panetumumab. There are some generic names that we know. We can nowadays, there’s some oncological centers where they’re able to give biomarkers driven approaches to patients who have RAS mutations, BRAF mutation. I remember a patient from Australia who got a trial on BRAF and did extremely well, hopefully she continued doing well. And also local regional approaches, which are resection. It’s a local, regional approach, ablation, the pump, the Y-90, and now the histotripsy that I’m not going to be talking about that. Another day we can talk about that, because there are very interesting things that we’re seeing. And the only sentence that I’m going to say here is, it’s not a silver bullet, but I think histotripsy is a good tool and bridge to be able to get, perhaps surgery, to get perhaps transplantation. It’s a bridge that has, that’s the way that I’m seeing. There’s not too much data, but this is pretty interesting. Another day we can talk about that. Everybody knows that this new era is not that the Norwegians started doing liver transfer for colorectal metastases. You saw that the French and the Austrians started doing this, but the Norwegians said, “All right, let’s do this again” after 25-30 years later, and then they started doing it. And what was the difference? Remember, only 15, 20% of the patients were alive, and now 60% were alive. What happened? Well, we are better in science. We’re better surgeons. We’re better in selecting and understanding the tumor biology. I’ll repeat it again, and they were able to see this outcome. Now, the majority of the patients in that trial have recurrence at two years, and these were only 21 patients that were treated in Norway. But instead of dying, many of them, 60% were alive at five years. That is a big thing. I remember reviewing this paper, and I was so impressed. In 2013 they created this Oslo score, which I think is very clinical. It works very well at my institution. We follow it in some ways, but not all. We’re a little bit more strict in my institution, but it helps. The more points that there are, the better, the higher points, the more complex or more difficult outcome, the less points, the better. So if someone has zero or one, apparently their survival is much better. And we see here that this is only six patients who have a score of zero or one, and all those six patients were alive at five years. If the patient has a score two and three, around 70% of those five were alive at five years. If you have four and you get transplanted, your outcome after three years, nobody survived. So it was pretty clear, the more points you have, the worst the outcome, and these are the size of the tumor, the largest tumor in the liver, the level of the CEA, if the patient is progressing on chemotherapy, and the survival from the moment of the patient was diagnosed with liver metastases to the moment of transplant. This is something that we have been doing more and more in Rochester with some of our patients, and we are practically adopting to do these, the MTV criteria. It’s a specific formula where you, as a surgeon or physician or oncologist need to work with the nuclear medicine department, because this is a specific formula that they have to do a study in the this nuclear medicine physicians, where we do a PET scan, but they measure with a formula, the uptake, and if it’s more or below, higher or below 70 cubic centimeters. And we know that if patients have lower than 70 cubic centimeters, that means that the cancer is less active, and the outcome of those patients is very good. If it’s more than 70 you can see here that majority of the patients will have recurrence, and their survival is shorter. So it’s a tool that help us now we need to be cautious, because when we do a PET scan for MTV, for calculating this MTV, and we do it after a run of chemotherapy of the last few days, then the the results are going to be alternated, because it might be negative, but it’s false, because the chemotherapy put the tumors to sleep, and then the results that we have might not be very reliable after the Norwegians started. This is an explosion. Look at this in these are, if you PubMed is a way to try to find a specific topic on surgery or medicine, something that you want to search. And this is where all the doctors, when we publish our names, are going to go there. So you type liver transplantation for colorectal metastasis, and you see what has been happening over the last year. There is a boom of number of publications. And this is impressive, because it has been like more right now, maybe like 900 articles, publications, and you will say, “Oh, my god, who’s doing that many? It’s quite impressive.” Probably in the world there are 200 or 250 liver transplants for colorectal metastasis only. So a lot of these are letters. A lot of these are just repeated things that are happening. But this is opening the flood gates, and more importantly, after Betsy mentioned, this is Dr Rene Adam, a good colleague and friend, presented in ASCO, the randomized control trial, which I will talk about that later, but that is going to be this is opening the the gate now, when the paper gets published, hopefully soon, this is going to make a big revolution in that. Let me talk about North America. My country is not here Mexico, which is North America, because in Mexico they don’t do liver transplants for colorectal metastasis. There are two centers or three centers in Canada doing that, and much more centers in the US. You maybe of many of you might be familiarized with this paper, that this was the first paper in North America on liver transplants for colorectal metastasis. Here you can see some of the surgeons at work in my institution, people from Cleveland and people from Toronto, and we saw here clearly that there was an advantage and overall survival. But these are only 10 patients between the three centers. As you can see, 10 patients, seven to zero. So at three years we the survival was close to 80% so that was pretty good, similar of what the Norwegians showed. We’re not the only ones. This is ? for Abhi Humor and Chris. They published this paper where you can see the overall survival. Again, this is at three years showing around 80% – similar of what we were showing with the three centers before. Now Kazunari Sasaki, is my good friend in Stanford. They are not doing transfer for colorectal metastasis yet, but he was working in Cleveland. He’s a good friend. We worked together, and we published this paper. We analyzed, there’s a registry where you have all the transplants in the United States that are happening, kidney, liver, pancreas, face transplant, hand transplant, anything that you want, you need to have a special access. But so we requested access, and we analyze how many transplants had been done in the United States from December 2017 which this the new era to March 2022, we published this, and it was published here in Surgical Oncology at that moment. We’re talking about more than two years ago, 46 liver transplants and 50 centers. And you see the outcome here. There were some done with living donor some of them with deceased organs. These are cadaver organs, and you can see that the living donor has a much better outcome compared to the diseased donor. I want to be cautious here. I’m not saying that living donor is a better organ than diseased organ. What I’m saying here is we need to understand what type of organs were these. How come these patients got these organs? Is this a marginal organ that nobody wanted and it was transplanted in this patient and the patient accepted? This is a fatty liver. So because probably the outcome of this organ, which is not as good as the living donor, is because of the quality of the organ, not necessarily because of the cancer perspective of the patient. So this is something that we are investigating, and we want to learn more about it, but this is new data. Until March, two years later, and I haven’t published these and I worked with Kazu again, but I want you to see here, this is the amount of cases. There’s 10, 20, and 30 per year, transplants for colorectal metastasis. Look what happened last year. Last year, we did more than 30. It’s probably 35, so you know what’s going to happen in 2024 and you know what is going to happen in 2025, this is just going to go up. And now with the paper of Rene Adam that maybe gets accepted, this is going to change. The medical oncologists are going to be referring more patients for transplantation. But I want to show something interesting. Here is when we are divided. I’m going to go back. These were, this is organs, and these were living donors. The green: a little bit more activity with living donors in the US. Here is the overall survival of all of the patients that were transplanted, 65% at three years, not as good as we would like to see, like the Norwegians that they have, right? They have this number, but at five years. So at three years, they will have much, much better. So why is this? So when we divide between living donor and disease donor, here is a very important gap. The overall survival of living donor went up, and of course, this one go down. So that’s why it was 60 something percent and now 74 and 54. Why is this? Why the patients who receive living donor do better, or the ones who have disease organs do worse? I don’t have that answer. We are trying to investigate, and I need to be very cautious with the message here. We need to see what type of quality, the quality of that organ that patients are receiving here, or the selection of patients. Maybe, maybe the selection of patients is not ideal. Maybe these patients are not fulfilled the criteria, but we’re working on that. And unfortunately, it’s a srtr, it’s a transplant registry and it’s not an oncological registry, so we don’t have the details. Remember, when I talk about tumor biology, if I want to analyze and all these patients in the US srtr database to analyze the tumor biology, I don’t have the data, unfortunately, so we’re working on that. There’s a lot of things that we’re doing. I want to share our protocol in Rochester. As I mentioned to you, we’re a little bit more aggressive in the aspect like, for example, these two criteria from the Oslo score. We don’t follow them. If a patient has more than 80 of CEA, even if it’s the only one, even if this is zero, this is one, zero and zero and it’s only one, we won’t do the transplant. We believe, and I personally believe, that a CEA above eighty is bad, and it’s even worse if the CEA start coming up, you know, from eight to 12 to 15 to 32 to 42 and then you do a transplant going that way? I don’t think it’s a good idea. And even if it’s only one point progression of chemotherapy, that is a contraindication for us. So we really look at: we ask for the patients to have a colonoscopy if there’s a year interval between the colectomy, the surgery in the colon or rectum, and the date of the transplant, as you know, in our institution, we just living donor only, and the primary has to be removed more than six months prior to the planned living donor. As I mentioned, the CEA less than 80, if the patient has BRAF, we are extremely cautious. That would be normally a contraindication. But if the patient has double mutations of KRAS and TP53 we’re going to observe the patient a little bit longer. This is just to justify why we don’t do transplants when a patient has progression on chemotherapy. This is showing in liver resections, when a patient got a liver section while the patient progressed on chemotherapy. Look at the outcome the when we compare to the patients who respond to chemotherapy. It’s pretty bad. Now imagine in liver transplantation, putting a donor on risk when we’re going to have very few advantages in the recipient. I don’t think would be ethically justifiable to do that or to take a cadaveric organ. You’re taking an organ from another patient who could do better. So I think there’s a lot of things that we have to be cautious the more mutations, the worse the outcome in liver resection. So we are adopting these in transplantation, and we are very careful. In my practice, what we do is if the patient has a lot of mutations we do not necessarily say no transplant, but we observe the patient for a longer period of time to understand the tumor biology. This is when patients have metastasis in the lymph nodes. The outcome is worse, even when we do resection. So you can imagine liver transplantation is going to be worse. So when there are positive lymph nodes around the liver or around the retroperitoneum we don’t do transplantation. In Rochester during this period of time since we started our open donor program, we’re talking about five years, at that moment, until May 2024 so we’re talking about a little bit more than a month. We evaluated 225 patients from around the country. Of those ones, 23 were transplanted only. There were several patients, few patients still on the workup and we have two that we’re going to go for surgery in July, and hopefully, hopefully one or two in August. We have the appropriate follow up of 20, and then this is what I will show you in some data. One of our fellows did that study here, you can see. Red is going to be the recipients that we have, the donors that we have, and the referrals from different places. These are the referrals from many – I think there are 35 states where we have assessed patients. We do a lot of these things from telemedicine, a lot of them located in the East Coast, especially in the northeast, but many here, a lot of patients that we have seen from Georgia and some of them here in Texas as well. These are the donors, who have donated, for those recipients who receive a transplant. You can see there’s three of them coming from Canada, from Ottawa, Toronto, Vancouver, and we have a lot of other patients coming from different parts of the country. And the red are the recipients where they got transplanted. And we try to follow up them as much as possible, and as well to follow them with support from other teams. Sometimes that works in those areas. For those, I mentioned 23 patients, but 20 patients, we have continued having these very detailed follow up, and I want to share these that three year overall survival of 90% so the outcomes are pretty, pretty, pretty good.

Dr. Hernandez-Alejandro 33:10
This is 60% of the patient at this moment will have recurrence. But they some of them, they have recurrence only in the lungs. Sometimes we just observe. I know one of our patients recently went for surgery and it was removed, and he’s of chemotherapy, and hopefully he doesn’t have more lung metastases. And I think this patient probably had that lung liver metastasis that was not resected before, and then now it got resected. I hope he’s got no evidence of disease. Now, Matt Byron, one of my research fellows, did this study when we evaluated only 162 patients. But this is very interesting. I want you to – hopefully I can explain this well. These are 20 patients transplanted, who were transplanted in our group, and these are 13 patients who came to see us virtually, or something like that, and they were candidates for transplant. They were candidates, if I would have a liver in my hands, I will transplant them. But they themselves decided I don’t want to go for transplant. They decided I’m going to go to get more pump, or to get pump, or to get more chemo and ablation and whatever. This doctor is saying that he’s going to go do some robotic thing and cut here and resect here and do ablation, and, you know, a little bit of of everything. So because they were our patients, we are allowed to follow their records. So we compare these 20 patients who were transplanted, who would feel the criteria for transplant, and compared to those 13 who were candidates for transplant, but they decided to go to other place. In this short period of time of following up after they decided, 70% of them progressed. That means the cancer progressed, even that they went to more chemo ablations, Y-90 Etc, from the 20 patients, right, only 25% had recurrence during this follow up. This is, clearly, this was just accepted in JAMA Surgery, which was the highest impact factor journal in surgery, and we published this graph over there, which is, I think it’s very important, and it’s telling us that transplantation, at least in this study, has better outcome in patients with very advanced disease compared to other options. This is the same graph, and now you, many of you, are away about this. This is something that we study in our patients, that shows that when we remove their liver after transplant, 64% of the time, there were more cancer, more metastases that were we were able to see in their images, CT scans or MRIs, so there’s hidden tumors in the liver. So I think that is when we go and do resections in patients who have high tumor load, and we do resections, that’s why six months later, 12 months later, eight months later, they have recurrence. I don’t think it’s recurrence. I think it was disease that was already there that we couldn’t see. Now we have been talking about three years outcomes. Five years outcome. Is there data that has long term outcomes? Well, the only ones can have that is their Norwegians. And here it is the Norweigans. This center here, they’re looking at more than 10 years, and they have close to 40% survival at five years. But wait a moment. These are the patients, all the patients in Norway that are like 70 something patients where they were initially treated. But many of those patients, I want you to know are the ones who were not a very strict criteria at the beginning. So there are some ones that have an Oslo score of three there for of course, probably they will have very good outcome when they do these at 10 years. For only patients who have an Oslo score zero or one, their outcome goes as high at 10 years at 60% so that is pretty impressive. That is very similar of the outcome when we do liver transplant for cirrhosis, liver transplant for other type of primary liver cancer in the liver. So this is where colorectal metastasis, when it’s well indicated the patients do well. Now, timing. This is a slide that, you remember when I mentioned about the Oslo score, the Norwegian guys analyzed it again in this long term follow up, and they were able to see that if, when they analyzed from the diagnosis of liver metastasis to transplant, if it’s one or two years, there was no difference. The biggest difference was if it’s more than three years. But as I mentioned to Dr. Paldacline, I said, “Well, if I from all the 24 patients that we have done. If I would only take the ones who have more than three years, probably of those ones, I’m going to be only doing two transplants or three”. So I think having that one year, it’s what we adopted in our institution. Of course, if there are mutations and more complex things, we observe more than one year, maybe one year and a half. I mentioned to these that the recurrence in the liver after the liver is transplanted. It’s very small compared to when we do liver resections. I have the opportunity of being invited to the ihpba, which is the largest center of liver cancer in the world this year, was in Cape Town, South Africa. And I give, and I was have the honor to give their give three state of the art lectures, one each day. And I give the state of the art lecture of worldwide activity. So I needed to not only present what I’m showing you in Rochester and in Norway, I needed to find out what’s happening in the world, and I did a survey, and I contacted these surgeons that I know, surgeon from all over the world. You know, Europe has been pretty active, and there’s a lot of centers in the US doing liver transplant. So the 45 Respondent of the International Group, around 36 The rest were from the US and and when we asked them, How many transplants you have done for colorectal metastasis, look at this. The purple is the 97% of the programs they have done, less than five. So very small experience, only 3% have done more more than five, between five and 10. When we ask them if they use a tumor board. interestingly, 20% they don’t use a tumor board if they follow the Oslo criteria. 1/3 of the people who responded, they don’t use those criteria. 26% they didn’t use genetic testing, or they don’t do a laparoscopy, or laparonomy to see the lymph nodes. So that was pretty impressive to me to see those things. I think it’s it’s a little bit concerning that part what is happening in many places of the world, so routine treatment with chemotherapy after liver transplantation. There we asked that, and very few people are doing that, nine out of 30. But the ones who responded, and they were saying that they expect to have five year overall survival between 54% between 50 and 74 and more than 75% at five year survival, 35% I think we personally, we should target this, because that’s what is justifiable with other diseases that we do liver transplantation. Now, this is Rene Ada, and this is the highest level of evidence. Briefly, what is a randomized clinical control trial is the highest level of evidence. Let’s pretend that we, I don’t know quite example, I can say, imagine that we are going to do one randomized trial. And if I, if I tell you, if you use helmet when you jump into motorcycle, your chances of being alive at higher. I am sure all of you will say, Yes, that’s true, right? But someone of you can come No, no, no. There’s no randomized control trial. We need to do that. We need to do a randomized control trial to see the perfect statistics and to see if it’s true or not. So why would you do you’re gonna get 100 people and you’re gonna tell them you’re gonna go on your motorcycle from here, from Rochester, New York to Atlanta, in your motorcycles, 50 of them are going to be wearing helmet, go and hit the road, and 50 of them are not going to use helmet. Now we’re going to see what happened, who has an accident, who survived, who doesn’t survive, and you know what most likely will be the outcome? Right? That is a randomized control trial. You probably knew what’s what’s going to happen, but this is going to be the highest level of evidence. And in medicine, in oncology, in transplantation, a lot of people want to know the result of randomized control trial, because the highest level of evidence the Norway people show us that transplant, they do, do well, Rochester people show you, show you that, right? But now the French came and with Belgium and Italy, they have, there were very few patients from here. Majority were from France, and they did this. They have 94 patients. Half of them were for chemotherapy alone with unresectable liver metastases. And 47 received chemotherapy and then went for liver transplantation. And what is very interesting is the chemotherapy for liver transplantation. 81% achieved to get liver transplant, because there are some of them who progress Unfortunately, while they were on the list, nine patients have tumor progression, which were those ones who were here, who didn’t reach but what do we call it intention to treat? So even if these patients, not all these patients reach transplantation, but they were in this arm of liver transplant, plus chemotherapy, five year survival of 50, 57% compared to 13% this is a huge difference at five years, but with the benefit of the patient who have liver transplantation, If I am here, I want to liver transplant, because I have 57% chances to be a light at five years. Compare if I have 13. And these are very similar populations, but now those ones who reach transplant not intention to treat 73% compared. To 9% is huge. This is we knew that because Norway show was that, but this is the highest level of evidence. Now, what now? This is really opening the gates. Now, the medical oncologist, the day that he was show in ASCO I started getting a lot of emails from my colleagues saying, “Oh, we’re so happy that we’re working with you now.” They are trusting and believing that this is happening. And let me show you, this is the outcome that it was happening. This is intention to treat that. I show you the data. These are the patients have chemotherapy. You don’t need to be an expert in stats. You just see the difference between the red and the black, the black is chemotherapy alone, and this is chemotherapy followed by transplantation. Here is, again, the intention, the overall survival once you get transplanted. And it’s huge. Look at this gap. It’s impressive to see that. And this is the progression-free survival. This is patients, a lot of them probably here in France. What is happening is around 80% of the patients will have records at some moment here in the chemotherapy. Of course, they they have progression of disease and they die at some moment. But this will probably 20% are cure on this population of patients, but many of them, as I mentioned, they have only lungs or only other things that can be treated. Now, what happened when we convert when do we decide that the patient is unresectable? So this patient, clearly, here, is unresectable. Lot of metastases. There’s no free liver that I can live. But what about if we give chemotherapy and look what happened to the same patient? Oh, my God. Patient responded so well to chemo or to a hepatic artery infusion or something like that. What does that mean? Based on what we have learned, patients who have this response, they will have very high recurrence if they go for surgery. And many of you know that I’m telling you the truth. That is true, because those disappearing liver metastases, they still exist there. And this is what I show you with that paper from Rochester, that 64% of the patients have more cancer of what we can see in image. This is a case that looks similar. Look at the amount of cancer, multiple cancer, you cannot resect these. Patient received treatment, and look at this very it’s the same patient. The calcification got smaller. You can say, maybe we can tabulate these, or if you want to use histotripsy, or you want to do whatever you want to do, and then what happened? The patient have more metastasis when we did the transplant that we were able to find that we were not seeing in the CT scan. I show you that. And this is just kind of showing. I put this like, where are we at this moment? The places who are doing a lot this is all the country together, in the US now, 65% at three years. Only, not because we don’t have too much data to get to five years Norway, which there are champions, five years, 60% and then at 10 year and 10 years, they go like around 40% five years overall survival in the data from Rene Adam in Paris, 73% that is pretty good. Rochester, we’re here. We have 90% I don’t want to show off, but this is three years. This is not five years yet. Hopefully we can continue doing well, which, that’s my expectations. I think we are very cautious, perhaps on patient selection. Maybe in the future, we’re going to be more open, and maybe we can lose our criteria. But in this moment, what we’re doing is good for patients, and we follow them very closely. And you know, I want to be sure here that the message is, you know, life after transplantation is not that everything is perfect. There are some patients that is have a beautiful and amazing life, but there are some patients that, especially the first month, they have some bio leak, some complications, some bleeding, or they have to stay longer. Here are they coming from far away? I feel so bad for that, but I know that long term is for them, majority of them, I cannot guarantee everybody for me, just to conclude this liver transplantation can provide a substantial survival benefit in patients with colorectal liver metastases, it’s very important that we reflect all the parameters of tumor biology, as I mentioned and the concept of technical resectability that we can remove in high tumor load where there’s a lot is not by itself, valid exclusion criteria for transplant. What I’m trying to say with this and this sentence, I took it from Rene Adam in France. He clearly said here that many patients will have a lot of tumor load, and even if we can resect them, he believes that they will benefit for transplant, and I agree with him. The multidisciplinary management including transplant oncology, which is what we’re doing, might improve outcomes in selected patients. The question is not resect or transplant, it’s to choose between partial or total resection. Total resection is a transplant. Partial resection is just a resection. So with this, I want to finish. I will stop sharing, and I would like people to ask questions, please.

Betsy Post 50:57
Great. Well, I have questions for you in the chat, are you able to hear me?

Dr. Hernandez-Alejandro 51:05
I I can hear you, perfect.

Betsy Post 51:07
Okay, so your first question is, if someone has the NRAS mutation, is that person eligible for transplant?

Dr. Hernandez-Alejandro 51:18
That person could be eligible for transplant? Yes, I will be more I will be more cautious. I will analyze more things and everything. But that patient could be a candidate for transplantation for sure.

Betsy Post 51:29
If a patient has stable extrahepatic mets. Does that automatically make you not a candidate for liver transplant?

Dr. Hernandez-Alejandro 51:41
Alright, I know you’re recording me, so the answer is, you have a traumatic disease. I would say no, but if you tell me, the patient have metastasis in the lungs, one or two and they were resected, and if the patient comes and see me one year later and there’s no evidence of disease, it will be hard for me to say no, so probably that would be a candidate, right? So I think it depends on how it’s treated. But in the moment, if you tell me I have disease in the lungs that I can clearly see, and the patient needs transplant, the answer will be no, because there’s the evidence of extra-hepatic disease. If it was treated and it’s removed and there’s no evidence of recurrence, then I would say yes.

Betsy Post 52:33
I think I’d like for you to expand a little bit, because I understand, because I’ve been studying transplant with you for a long time. But I think it’s important maybe for folks to understand why, if you have disease outside the liver, the problem that presents for transplant. Why is that a problem for transplant?

Dr. Hernandez-Alejandro 52:56
In transplantation, we use in immunosuppression. Immunosuppression are drugs that bring your immune system down to avoid rejection, even if your sibling or someone donate part of their liver to you, even if there are a lot of genetic similarities, the action of our bodies is to reject what is not ours, so they’re going to go and try to fight that. So that’s when we started using immunosuppression. 50 years ago, the life of patients with liver transplantation and kidney transplantation changed completely, and immunosuppression is extremely well tolerated. It’s not chemotherapy. It’s not like dialysis is very well tolerated. But the problem is that if the patient has active cancer and you give immune suppression, we are just enhancing and pushing the cancer to spread quicker. And that is very, very, very dangerous. And so that is a reason that we don’t do liver transplantation with patients who have extra hepatic disease when they have metastasis in other places. Did that explain it Betsy?

Betsy Post 54:15
Yes, and I think that’s important, because I know we might have newer people that don’t know too much about transplant at this point. So I thought it was important to clarify that point.

Dr. Hernandez-Alejandro 54:25
Can I expand something here? There have been some patients that have connected with us at my institution asking for an assessment for transplant, a few, perhaps a handful of patients who, perhaps they are not candidates for transplant, because they’re exactly what you’re describing. There have extra hepatic disease. However, when I saw the images I was I was like, wow, I think I can resect you. I cannot do a transplant, but I can resect you. We have to push the envelope and try to do something, and maybe we can go and remove that metastasis that is in the peritoneum, in the abdomen, or something like that. I think that is more justifiable because you’re not involving a transplant, you’re not involving a donor into this. And you can push the envelope a little bit in some of these patients. So there has been a handful of patients who they have the sad news, no, you’re not a candidate for transplant for our team. However, we can consider resecting you. You probably won’t have the amazing outcome, but probably you can have a good outcome if we resect you. So with the message here is there might be opportunities, and you just need to explore teams that are willing to do more for patients.

Betsy Post 55:47
Thank you. There’s a question about, is there anything we can do to have more livers available to cancer patients so we don’t have to rely on living donors? That’s

Dr. Hernandez-Alejandro 55:57
A great question, and we’re working on that. One of my colleagues who works in University of Cincinnati, he brought the bush for trying to get — in transplantation, you receive an organ when according to a score that is called male score. And this we’re talking about patients with cirrhosis and those things, the meld score, the higher you have it the word, the more sick you are. A patient who have cancer have a normal liver function, so their meld score is going to be very low. So what they are trying to do is to if we list these patients with colorectal liver metastasis, they will get 15 points at least. I think with 15 points is nothing, because it’s until 40 I don’t get, I don’t transplant anybody with the meld score of 15 in New York State. But I think it’s a good start. At least they go to the list, they get extra points. And I think the next step is, okay, let’s push and get more. But what we have to do is, as a country, we need to show good results. If I when I show you the data from the US overall, the outcome is not very good, as you saw with deceased organs and that and that and living donor is helping that data overall to get better. But if you remove the living donor, the deceased organ, the Calibrate organ comes down. Why is that? I want to learn why? Why their outcome is not that good, because the organ probably is not the ideal, or maybe they are not selecting the recipient the most, the best way. But there’s much more to work on this and understand.

Betsy Post 57:44
Thank you. Do you foresee transplant becoming a first line treatment for patients with low Oslo score and high disease burden? Or do you think response to chemo is an equally important factor in determining eligibility?

Dr. Hernandez-Alejandro 58:00
Well, I would say both things are true.

Dr. Hernandez-Alejandro 58:04
Chemotherapy is helping us to decide who could be a candidate, according to the response, that’s very important. And definitely, I think what we have to do clearly here, the message is, if you have a low Oslo score and you have a high tumor load, like a lot of two cancer and there’s no evidence of your body disease, you should potentially be a candidate for liver transplantation. Definitely.

Betsy Post 58:29
If you don’t qualify for liver transplant today because of a high Oslo score, because of disease progression on chemotherapy or pre transplant, CEA as too high. Do you have a recommendation on a path to get on track for a transplant qualification?

Dr. Hernandez-Alejandro 58:49
I Well, it has to be case by case. Analyze it patients. Needs a doctor who thinks and it’s transparent with the patients, and let them know we can do this. And sometimes the patient to me, they push me. And, you know, there’s, I don’t know, there’s a patient who recently came and was progressing, not doing well, got the pump progressing. So we know that biology is very bad. And the patient told, can you do? Is to trypsy. For example, I cannot transplant. I can do another resection. This patient is not going to do well. But the patient asked, Can you do histotripys. And I said, Well, why is the reason of doing histotrypsy. It’s not going to help you to get into something right say, let’s give it a try. The insurance approve it, and we treat it. And we didn’t cure him, but tumors get reduced inside. I don’t know if it’s going to help him to survive a little bit longer or not, but it was very interesting to see that, and probably it happened in some Patients, not in all the patients. But I think what we have to do as healthcare workers, oncologist surgeons, transplanters, or whoever we are, is to try to offer options to patients. There are some things that there’s not that many, but we have to think about, how can we help? Because, when I knew you guys know better than me, because you are the patients or the caregivers, when patients have these diseases is bad, they they want to have options and have hope, and that’s what part of our big part of our job.

Betsy Post 1:00:40
How long do you have to be off chemo while you wait for transplant, and what happens if CEA increases or disease progresses while you’re waiting? So basically, like you’ve been approved, but then that happens while you’re waiting, and you’re off the chemo waiting.

Dr. Hernandez-Alejandro 1:00:57
Oh that’s a great question. So this is what happened in France. In France is not Norway. You don’t have the access of transplant like in Norway. In Norway, if you’re in the transplant list, you get transplanted in a month. It doesn’t matter your meld score, boom. You get transplanted with cirrhosis or whatever. Now in France is more like in the US or in other countries, where you only transplant the sick patients who have a high meld score. So how does that those patients in the trial got transplanted? Because it was an agreement between the opios, which are the organizations control organization in the country, in Belgium, Italian France, and the opios said, All right, we commit, with this trial that patients who are listed for colorectal liver metastasis in this study, that is just 47 patients. We’re going to get them an organ within two months, within two months, no more than two months. Guess what? There were some places that you cannot guarantee that, and they have to wait three months. What happened to those patients? They progressed and they lost their chance to be transplanted. Are there some that even were two months waiting, and when they open, they have progression so clearly, to me, that’s why I think living donation works very well, because you don’t have to wait, especially in this country, you don’t have to wait. And then we can plan it, we can continue to give in chemo, chemo, chemo, chemo, chemo. Patient is tired, but it’s going to get transplant, all right, two weeks, three weeks before the transplant, stop the chemo, but we know there’s an organ, and we’re going to do it in the best way. And it works when you Okay, get listed, and you’re waiting for be transplanted or cadaveric organ. We don’t have that access here, you’re waiting to get an organ which probably is not the ideal organ, or extended criteria organ, or something like that. Especially if you have, of course, you will have a kind of score. That’s why we want to, at the end, be able that our patients with colorectal metastases In the future, they can get exemption points, right so they can get a good quality organ, but in this moment, is, it’s difficult, and I show you the results that they are a little bit of questions there,

Betsy Post 1:03:32
Does utilizing the HAI pump complicate eligibility for living donor liver transplant?

Dr. Hernandez-Alejandro 1:03:41
Definitely, definitely true. Definitely true.

Dr. Hernandez-Alejandro 1:03:46
We have done four transplants after the pump. One was miserable. This is one of the few times in my life as a surgeon that I said what I am doing here. You feel like even though there are 25 people in the operating room, you feel that you’re in the middle of the desert and nobody’s around you. It’s It’s pretty bad. But that patient survived and did well. We were four surgeons and operating, and it was very bad because of the bleeding, the inflammation and those things, the artery, what gets very damaged. But I’m fortunate to have an amazing team, one of my colleagues, her disease expert with micro vascular anastomosis, when you put together the arteries, and we were able to do this type of complex liver surgeries and reconstructions of arteries. So it is doable, but there’s going to be more technical complexity, but it’s doable.

Betsy Post 1:04:50
Can you talk about some of the things that disqualify people from transplant when they’re in the review process?

Dr. Hernandez-Alejandro 1:04:59
The number one. Is presence of extra hepatic disease. This is outside the liver, which could be lymph nodes that are positive around the liver, under the retroperitoneum, multiple metastases in the lungs, in other places: that would be one. The other one would be progression, when the patient is progressing, even if there’s no disease outside the liver, even if it’s contained, but it’s progressing, and we’re giving chemo and the patient is progressing, that is a bad sign. And as I show you, the data, progression under chemotherapy is a bad prognosis for resection, and even if it’s bad for resection, even worse when transplantation. So progression, evidence of extrahepatic disease, are the most common way of Not, not to be a candidate. So those, those should be the major ones that happened here. One of my colleagues, of my researchers, analyzed from all the 200 and something patients that we have. Probably we already have assessed 300 from all these patients. If you analyze which ones have more chance to get to transplant compared to which ones didn’t. There was an something interesting here that is the timing for referral. So when the patient came to see a transplant center for analyzed transplantation, if they come very late, the chances of getting transplant is small. If they come earlier, they have better chance. And perhaps it’s because the communication of the transplanter with the Oncology Center is okay, let’s do this. Let’s continue chemo. So there’s a very good feedback back and forward, and they can treat the patient when there’s when transplanters get late, or the referral is late, then patients have less chances to get into transplant.

Betsy Post 1:06:54
That’s one thing that I really work hard on in COLONTOWN, is just trying to educate patients that are unresectable in air quotes, you know, by a good liver surgeon with a tumor board or more than one, I try to talk to them about this as an option, not as a Hail Mary at the end. And, you know, to follow that process. So I think that’s definitely something that, you know, we’re it’s just going to take education anyway, right?

Dr. Hernandez-Alejandro 1:07:23
Yeah, early referral is the best. And some patients come and say, Why do you want to see me if I still have the primary and we have to remove it? So because we want to make a plan, we need to create a good connection here, a good relationship between physician and patient, and then work together into this and follow up. I prefer to generate that communication without my patients.

Betsy Post 1:07:52
Next question, if looking within my own circles for a possible donor, what are some things I should look for whether the person would be a good candidate or not to waste our time with.

Dr. Hernandez-Alejandro 1:08:06
You know, I think I can. I will tell you something that happened with this. A lot of the times, there’s some patients, and I know you’re talking about colorectal metastasis only. I’m talking about many types of of diseases, cirrhotic and those things. And sometimes patients come and say, How come I don’t have a donor? You know, all my friends are telling me that they’re calling you and you’re not answering or sometimes, probably my team is busy, but I doubt it. But it happened. It could happen. So I’m not saying that that’s not an option, but many times people tell us, I’m going to do this, and they don’t do it. And we cannot go and tell you as a patient, a this patient call and now he’s not responding. Or this patient call, we send them the questionnaire, and he’s not responding. We for HIPA regulations, we cannot say that we cannot go and tell you your your patients, your people, are not responding, or someone is telling you, yes, I I call. And that’s not true sometimes. So what type will you need to have someone who really wants to do this for you, who really is invested, who really is open for for doing this? Of course, it has to be a healthy person, someone who is, you know, if it’s someone who drinks a little bit of alcohol or something, they can stop drinking and they can prepare and get their liver better. Is if someone who has a little bit of overweight then, okay, hit the gym. There’s going to be time. We have two, three months for for getting better, and people can change a lot. Within three months, there’s a lot of change, things that can change in a donor. And there’s a risky operation. It’s a big operation, but we are. We’re fortunate to have pretty good outcomes with all our. Donors, people who are the same blood group that’s ideal, or at least being compatible, right? But someone who’s between our criteria is between 18 and 60 years old. I saw a patient today that is a patient that is going to turn 60 in the next weeks, and it’s going to be a donor for another person in the fall. So that’s amazing, and it’s a super healthy, beautiful woman. And I think, I think it’s going to happen, hopefully, so people who are willing to take the next step, to put their life on risk, someone who is willing to to to help and not necessarily needs to be a family member. No, there’s a lot of people who come with friends or friends of a friend, or sometimes, you know, people use social media, and it’s impressive to see the results that that social media creates people you know, your high school friend that you haven’t seen in 20 years come and say, I want to donate to someone. And some of the patients said, Okay, I want to donate to that person. That person doesn’t know that I want to donate. Please do my work up, but don’t tell that person that I’m willing to do this, and we need to respect so we cannot tell you that. We can mention there’s a potential donor, and that’s it. We cannot see more. So it’s a very interesting concept. And our, you know, our program, and I’m sure there’s other programs, our coordinators in the best try to invest time and education with the patient and the family that needs a light on.

Betsy Post 1:11:48
If a stage four patient is currently NED, but at a high risk of recurrence, would they be eligible for transplant? Or must there be a recurrence first?

Betsy Post 1:11:59
Again, if a patient has stage four, no evidence of disease,

Dr. Hernandez-Alejandro 1:12:07
okay, so late treatment, right?

Betsy Post 1:12:10
So, for example, this patient, if the patient had a liver resection, was no evidence of disease, negative ctDNA, but high risk of recurrence, would they be eligible to start the process of transplant, or do they need to have a recurrence first?

Dr. Hernandez-Alejandro 1:12:29
Okay, what’s going to happen if I do the transplant and the patient had a bad outcome, and then in the pathology things comes and there was no cancer? Can you imagine that? So, yeah, there’s always risks, right? That could happen. So the way that I would do these, if the patient has resection, if I see recurrence, this is where I will say, Okay, let’s go for transplant, let’s ablate it, let’s give chemo. Let’s have a control, and in a few months, we do transplant,

Dr. Hernandez-Alejandro 1:13:06
I think at this moment, if I don’t see evidence of disease. So this is is very different if there is disease and you treat it with chemo and it disappear, than if the patient go for resection, thinking the patient go for resection, there is a chance that that patient could be cured a little one, but there could be a chance. So I will have the I will give the benefit of the doubt. So if patient have resection, no evidence of disease, I will wait for recurrence to think about transplantation. If the patient has disappearing liver metastasis from that disease that wasn’t resectable, then I would say that patient should be transplanted.

Betsy Post 1:13:51
Okay, so if a patient’s been on chemo for over a year, overall, really good response. You know, tumors decreasing, but there’s one liver lesion that progressed but was ablated successfully, no evidence of any other progression. Would this be a disqualification for transplant?

Dr. Hernandez-Alejandro 1:14:11
No in my problem that patient. Of course, I will have to read and do all the detailed work up on that patient. But I think, you know, there’s in this moment, there’s no evidence of progression, right? There was progression. You hit it, you, I would say, Okay, you have been on chemo. You have been responding, except one now, and the other one is treated. Let’s observe it for a few months, while you and then if, and then we can do the workup of a donor. And if it’s okay, then we do the transplant.

Betsy Post 1:14:43
Are there procedures you prefer for patients not to have done if their goal is to have transplant? Y-90 specifically but any others?

Dr. Hernandez-Alejandro  1 1:14:58
Again, I didn’t understand the. Question. Betsy,

Betsy Post 1:15:01
sure, so the patient’s asking if there are any procedures that you would prefer patients not to have done, if their goal is to have a transplant. So specifically, like Y-90, would you prefer a patient not to have Y-90? Or any other procedures you’d prefer a patient not to have if what their goal is, is to seek transplant.

Dr. Hernandez-Alejandro 1:15:23
Who did that question? I’m gonna I want to know, that’s a very smart question.

Dr. Hernandez-Alejandro 1:15:33
Well, you know all the questions I think I presented here a slide I remember a long time ago where I put the Arc de Triomphe and just trying to put the streets together, and, you know, trying to get to the the center. And it doesn’t matter if there’s traffic in one street, you take one street parallel and go up, etc, etc. So I think that is the goal of having Y-90 ablation, pump, resection, and trying to go into transplantation, if you are candidate for that, right? So, but if there’s something that I would like not to have is I have two one answer that is very clear, and another one that I will leave it in the air. (So don’t pay too much attention.) The first one is, if you are a patient who are responding to systemic chemotherapy and wants to go for transplantation or resection, why changing to the hepatic artery pump infusion, if you respond when you can continue in the systemic chemotherapy without opening your abdomen, without putting a pump in your artery, just continue with chemo, and then we do the surgery or the transfer, and the life will be easier and less complex. Now I think pump can be used in patients when it’s progressing on systemic chemotherapy, and you might come back for being a candidate for transplantation. So that will be one of the things that I would say, if a pump could be avoided, go ahead, avoid if you are responding to systemic chemotherapy, that will be one of my things, which I don’t know if I would be talking to my colleagues from MSK, with Dr Kingamara or or probably Dr D’Angelica or Dr Charnic, and they will be debating me, and they could be mad, but well, we need to respect each other, and I like them. They’re my friends, and I have dinner with them, and they respect that. I’m not against a pump period, not against the pump. The pump is very good. Patients responded very well. They they do very well. But a lot of the time it’s long term, these patients are going to have biliary complications and problems of the artery. It’s very common. I see those patients happening. So that would be and now, now also is that in the data that we’re trying to publish now, my research resident Matt found that those patients who have Y-90 have less chances to reach transplant. So we have to be careful, because are we gonna see bad things about Y-90? I don’t think we can see bad things. Probably that group of patients were the ones who were having more progressions, or they were exhausted of chemo, and that’s why they went for Y-90. So that will be understandable. So not necessarily the fact that they not necessarily the Y-90 did worse. I have operated patients in the resections and transplantation after Y-90, and I haven’t seen a big problem, but I think this is an area that we have to understand more in the future, if there is one or other of the local, regional therapies that might get better outcome or worse outcome as a bridge for transplantation,

Betsy Post 1:19:13
What does recovery time look like for transplant patients that don’t live local to Rochester, but I think it would apply to any you know, what’s recovery time look like, generally for the patient.

Dr. Hernandez-Alejandro 1:19:26
So, you know, we, we normally tell our patients, you know, you’re going to be here for, you know, the donor comes here. The donor gets discharged on day six or sometimes five or seven, and they we want them to stay in Rochester, if they are not from Rochester, for another two weeks. Majority of the time they leave on day nine or 10, because normally they do very well. Our donors now the recipient is different, because if you get to have a very good outcome, and you don’t have any body leak, and you don’t have any one. Their problem. There are patients who in after three four weeks, they leave and they go back home. But there’s a good amount of patients that they have a complication. Some of the times, this can be managed long term at their home hospital in the West Coast, in the East Coast, in the center, Midwest, whatever. And we have the connections, and I personally know a lot of people around the country who do a living donation or something. We don’t need, not sometimes a surgeon, we just need a GI doctor who put this stent or remove it, or they or they need a drain. But this is, this is a little bit sometimes exhausting and frustrating for patients when they have a complication, but I can tell you that long term is going to be good. There was, I remember one of our patients still here from, I think, one month, two months and a half or three months probably, and I know that. I think he is listening to me here and and I understand he’s doing very well, but it happens sometimes that they have to stay longer.

Betsy Post 1:21:05
Okay, we don’t have too many left, so thanks for hanging in there. How long does all the eligibility testing take?

Dr. Hernandez-Alejandro 1:21:17
I meet with the patients few times before that, I like to meet with them. I do a lot of zoom meetings with them, like this one. What we’re doing now with this course, we learn I introduce part of my team, and when things are getting ready, like the timing of observing, and it’s a candidate we bring for the patient for evaluation, and all the team is like any other transplant there, either psychiatrist, social worker, etc. And sometimes the biggest complaint and painful thing is the insurance, as many of you know, but I think we have been able to do a lot of work, and then we we’re having less complications, like less problems with insurance. We have a patient recently from California who was ready to go for transplant, and insurance didn’t accept and they said that the patient needs to stay in California. And I said, Well, California is not doing any Center in California has done one of these cases yet. Then we contact one of my colleagues there saying, Okay, we might be able to do it, and the insurance didn’t accept it. So I am worried about that patient, like, who’s going to transplant this patient? There’s nobody doing this there. I will be happy if someone is doing there, because they’re very good surgeons, right? Probably they don’t know the details of the of the of the protocol, how to do it. We can guide them. I have helped a lot of other programs to try to set it up, but if the patient is not getting access, I think insurance should be able to give opportunity to patients to go out of the state and go where they wanted to go on and find opportunities for them.

Betsy Post 1:23:02
So we’re down to our last three questions, what happens when there is recurrence in the liver after transplant?

Dr. Hernandez-Alejandro 1:23:10
Good questions. And apparently the outcome is worst. When there’s recurrence, it can progress faster. But I remember, I haven’t had a case where we have to do anything on that but the only case that I remember having metastasis in November is one of our first cases. And this is our a single patient who die after transplant. But I know that

Dr. Hernandez-Alejandro 1:23:36
is it Norway? I think so they did some liver section in a couple of patients after that. I wouldn’t do a liver resection. I will wait to see, you know, give treatment chemotherapy, trying to do ablation or histotripsy or something like that, try to control and if things are key, and there’s no more rigorous later on, then I will go and do surgery, but normally it’s not associated with a good outcome.

Betsy Post 1:24:15
And then does this portal hypertension complicate transplant?

Dr. Hernandez-Alejandro 1:24:23
Depends. That’s going to be a funny answer. Depends on your surgeon. So remember, I do liver transfer for cirrhotics patients. That is the worst portal hypertension, the portal hypertension that a patient with a lot of chemo. Any of you cannot compare with the portal hypertension of a cirrhotic patient. The cirrhotic patients, they have this massive case that I did last night. It bled a lot, and it was portal hypertension. So I. Certain transplanters, we know how to manage portal hypertension, so it won’t disqualify you. That won’t be the answer.

Dr. Hernandez-Alejandro 1:25:12
That’s okay. It’s going to be complex, but it’s going to be okay.

Betsy Post 1:25:16
Think there was one question I saw, but I feel like you answered this one. It was, when can someone be a candidate for transplant after colon and liver resection if there’s a reoccurrence? But I think you answered that one already. I think that came in after we had already answered that one.

Dr. Hernandez-Alejandro 1:25:34
Yeah, once, once you have recurrence. You know, I have seen some of these patients say, okay, hold on, let’s control it. Let’s have systemic treatment or something. Let’s control it, and then start thinking about transplantation as an option, and we can work on that and and hopefully the patient is stable and get a donor into the transplant data.

Betsy Post 1:25:54
And we have quite a few of those patients in COLONTOWN, you know, that went the transplant route after recurrence or after multiple recurrences. So definitely you can ping me to the person that asked that question, ping me, send me a message, and I can definitely talk through that with you, or connect you to some of those folks. So at this point, Dr Hernandez, there’s just a lot of love and thanks for you in the comments. So people are just thanking you so much for your great DocTalk and all of the time all of the great answers that you took the time to give. I think you have several patients here, so definitely they’re also, you know, thankful for you and happy to hear the survival information and all of the information that you boiled down for us from ASCO I know, I learned a lot this evening, even though I feel like I try to stay up to date on transplant, I still learned a ton of things.

Dr. Hernandez-Alejandro 1:26:54
My pleasure. I wish I could answer all the questions. Thank you for the comments. I saw some people that I know. Thank you very much. I send hopes to all the patients and the people around there. Thank you Betsy, and thank you COLONTOWN.

Betsy Post 1:27:11
Thank you so much, and we’ll see you again soon. And thanks everyone for coming. We really appreciate your time, your attention, your great questions, and thanks a lot for all the love in the chat that means a lot talk to I know it means a lot to me, and I know it means a lot to Dr. Hernandez too. So thanks everyone. Have a great night.

Dr. Hernandez-Alejandro 1:27:30
Have a good night. Thank you.