Liver transplants — Examining the evidence: Dr. Hernandez-Alejandro (2024)

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.