Hepatic Artery Infusion (HAI) chemotherapy for CRC liver mets
DocTalk
2021
Dr. Gholami
HAI
Liver
Stage IV
Surgery
Dr. Sepidah Gholami from UC Davis discusses “HAI Chemotherapy for Liver Mets: What’s Old is New Again” in this Doc Talk recorded in July, 2021.
Transcript
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.
DocTalk
2021
Dr. Gholami
HAI
Liver
Stage IV
Surgery
Dr. Sepidah Gholami from UC Davis discusses “HAI Chemotherapy for Liver Mets: What’s Old is New Again” in this Doc Talk recorded in July, 2021.
