 Good afternoon, everybody who is on the line to watch this grand round. Today we have two speakers, and Dr. Daniel Maloof, MD, Professor, Department of Surgery, Director, Program of Transplantation, University of Maryland School of Medicine, and also Dr. Chandra Bhatia, MD, Professor of Surgery, Director of Liver Transplant and Hepatobiliary Surgery, University of Maryland School of Medicine. They are going to talk today, Living Donut, Liver Transplantation, and Role in Transplant Oncology. Doctors, you may begin now. Thank you very much, sir, for the presentation. Let me know if you can see the screen there. Yes, I do. Wonderful. It's an honor for us to be here. For some of you that don't know me in the region, I joined University of Maryland in July 2020 in the middle of the pandemic. But previously, I was Director of Liver Transplant University of Virginia. Before that, I was in BC June Richmond, and we've got very lucky to have and bring with us Dr. Chandra Bhatia, that will be the speaker after me. He just arrived as the Director of Liver Transplant, and he was trained also in UIC, but he also came from BC June Richmond. So we have some common paths in the past. But it's an honor for us to be the speaker today. I will try to give an idea of the liver transplant process, especially my area of expertise is Living Donut Liver Transplant, that we started recently here in Maryland, and then Dr. Chandra Bhatia experienced in liver cancer, so it would be a great combination of expertise. We're going to try to leave 10 minutes at the end for discussion. But that's my intro. As you know, liver is kind of a unique organ, as you all know, has been spoken from the past, the capacity of liver regeneration. And that is being used in great advantage from our centers, but other many centers for Living Donut Liver Transplantation in patients that cannot wait enough to get the liver. And I will go some of the challenges that we have in that matter. In general, Living Donut Liver Transplantation, I was, when I was finishing my fellowship in the year 2000, there was a lot to talk about Living Donut Liver Transplantation. One of the guys that trained in BCU at that point was faculty, Dr. Marcos Amadeo was kind of one of the leads in the country in Living Donut. And we saw a significant increase of the number of transplants by Living Donut then. I remember that for the year 2001, we did 64 Living Donut cases in BCU. It was one of the largest in the country. It was not the largest in the country. But then there was a kind of event that happened in New York City when a donor died. It was kind of a very public and publicized debt that really pushed the whole idea of Living Donut and down to for the following decade, really. And as you can see in the year 2006, 2009, there was really a very small amount of Living Donut happening in the year, not because people will get great benefit out of it, but there was a lot of concerns about doing this and what the challenges are if some donor will have a complication. Since then, and obviously when you start balancing what's the complication of doing Living Donut, but also the complication of having people sitting in the waiting list for a long time, the numbers start growing again and the kind of people start understanding the reason benefit and being a little more tolerant to the risks that you were taking. And you can see that the numbers have increased to the last year was the first year that I think that we surpassed the one that was in the year 2000, about 515 cases of Living Donut. Several institutions have become kind of, or are trying to become specializing in the area of Living Donut and kind of being guided by our colleagues in Asia and here in America by the Toronto Group. And the main reason that we need to develop Living Donut is because we know that even if you go on the list, the chances to get the liver transplant is not that high and that is because we don't have enough organs or donors or organ donors to supply all the amount of patients that are in need of liver transplant. And this is not just in liver, I will say in general in all organs, but here obviously with focus in liver. So recently we can see that the amount of, and this data a little bit old 2018, but you can see that the number of patients receiving liver transplant via Living Donut was about 4.8% then when up to 5.8 in 2019. I think this year is about 6.4%. So it is slowly growing. The number of deceased donor also is becoming more and more challenged. We have about 10% of the organs that are recovered that hasn't discarded. And the main reason as you will know, is obesity and all the fatty liver complications related to the donors. But we know that if you go on the waiting list the planning of your blood type, you have about half 50% of chances to receive a liver while waiting for the liver transplant. So 50% depending on the blood type is kind of a risk that really need of increasing the volume of organ for transplantation. In fact, looking at some of the proposals and some of the prediction models show that if there's not any change in the term of organ allocation or quality improvement in organs with the increasing epidemic of obesity and alcohol and NASH, the amount of organs in the future to be able to transplant probably will even decrease making even more complicated and more difficult the chances of a patient that going to liver failure to receive an organ. But there is not just the issues related to organ availability. It's also a reality related to the population age. We also know that we have increased if you look at the numbers today for units the number of donor has increased but a lot of this increase is related to what is called this DCD organs or donor after cardiac death that we know that sometimes are not as good as you can have with the brain dead donor. And also there's a lot of regulatory oversight or transplant centers would really put a lot of pressures for those patients to do very well because when you have poor outcomes really reflected in the units and there is a lot of pressure on those and centers to have a risk aversion strategies. So when we look at specific why we have challenges receiving organs for patients receiving organ for transplant we know that donor age is a big issue. It's a significant increase in the population aging. The mean age in the US is about 77 to 81 years old depending in the female or males but you can see we frequently get calls for organs offered that are 75. We just last week we transplant one patient with the donor from 74 years old and did very well but we know that those organs if they are exposed to call ischemic time longer call ischemic time or any challenge during the operation those organs that don't have the capacity of regeneration like you have in other organs. The same we as you probably know Nash prevalence 10 to 30% I would say that now it's more than 30% and we frequently go and look at organs that eventually end up to be fatty livers. We know some tricks how to use those organs better with this pump proficient now for liver transplant that has been proved to be improvement but we still face it with about 20% of the liver that we actually go and we look we cannot use because we know the consequences of that. So that's another big challenge with that obviously diabetes and obesity is increasing especially in the Southeast but in general across the entire country. And as you know alcohol has really significant increase in recent years especially with COVID pandemic have really kind of skyrocketed in recent times. So we frequently have more people coming into the list for alcohol related disease but at the same time we have more donors that are not known to be alcoholic but really have impact in the quality of the organs that we are receiving. So transplant program has a risk aversion related to regulatory oversight, consequence of the poor outcomes sometimes programmatic priorities and this has sometimes to do with the fees and the payments related to liver transplant, the public view of using living donors and the cost of transplantation. The cost of liver transplantation I'm not gonna go in detail but as you know as you are using more marginal organs and we are using more marginal recipients patients stay longer in the hospital that correlate with the expenses in the liver transplant and as you know especially here in Maryland that we have a cap payment for liver transplant if patient don't do well frequently we end up losing money for liver transplant and that is something that happened really across the entire country. So the question is how we can help patients that have that are sick but are not to be put on the top of the list and I'm sure that's the majority of you are very familiar with what is called the what is the male score the model for end-stage liver disease but the male score that go between six and 40 and we know that patient that has very high male score usually get an offer and the liver transplant pretty quick but if you have a male score with less than 30 and above 15 or below 15 and you have complication of cirrhosis patients struggle significantly to identify or to receive offer for liver transplant and that's really the area that I think that we can serve better via living donor and that's the area that we focus to to help these people to help those patients to do better. Now in terms of how we can expand the organ pool and one of them obviously is living donor that I will explain next but we have used all these other technologies and techniques to increase the donor pool and we use pump perfusion, we use I-A-G donors we use donors with hepatitis C, donor with hepatitis V fatty livers, donor after cardiac date or DCDs some type of cancer patients that die and we can use the organ pool and some other technologies such as bi-artificial organs and senotransplantation those two are in process and there's a lot of progress made on that but we're still not ready for prior time in the clinical practice so at this point either you get the DCS donor or you get the living donor and in terms of ex vivo normothermic perfusion some of you may be familiar we're not gonna expand on that but we are being kind of one of the leaders along with other centers in the country in terms of these two pump perfusion machines that can be used in the US TransMedic recently got FDA approved and also Oxford machine that had been used and what they do is they perfuse those organs with warm and normal human blood and allow you to extend the survival of that organ of that organ and I'm gonna go and expand much on this but this is a huge area of research today and in the clinic and also clinical research the group in Switzerland already developed a machine that can support is called liver for life and what they do is add dialysis machine to this and other management biomarkers and they have extended the survival of the liver outside the body for more than seven days that's obviously will change the entire reality of transplant as you keep the organ out ex vivo and perfusion Bible you can really act on that organ and treat several diseases and several fatty issues but that's gonna be a topic for another day of discussion in term of living donor for those that know a little bit we can either transplant right low we can transplant left low and when pediatric cases usually we can transplant just the left lateral segment of a potential donor and what is the rationale to do living donor? Number one, this started in countries where living where disease donor is really not an option Asian countries like Japan or Korea or Turkey where disease donor is really kind of not the good options the minority of those patients receive liver transplant via disease donor so they need to come up with some options and living donor so that is they started now here in the U.S. we have a significant change in the donor and the recipient characteristic we see donors increasing age, increasing obesity increasing alcohol, recipient being older recipient have more obesity recipients to be more prone to have complications as you all know hepatitis C is really not the lead cause of liver transplant anymore so now we have a lot of Nash older people with Nash obesity and alcohol and sometimes those cases get very complicated but having the option of living donor is always a good thing and then more organs are needed for transplantation clearly living donor clearly increase the organ pool the outcomes are good now described to be even better than the disease donors and the donor surgery over time has become a safe operation as you can see Korea and Turkey and Saudi Arabia are the three leading countries where we get a lot of information and improvements in living donation and we know also that in general the population is willing to donate in the U.S. about three every four people that have been asked are willing to donate for the loved one and when there was cash in the middle and the in this is even more than that so we have experience accumulated the Asian countries are really great experience in leadership in this area here in the U.S. we have the H2L Consortium we want to continue to be the lead in North America now Pittsburgh also has become an important program as well as other programs we think that there's a little more increased acceptance in the U.S. medical community and for the first time last year it has been proved that the three years survival outcomes here as you can see in Yunus is higher the three and the five years survival is higher when you receive a living donor than when you have a deceased donor and Peggy can I ask you is this an hour because in my schedule appeared 30 minutes is this an hour talk? Yeah, yeah. Yes, okay, so I don't need to rush that much because I have few more slides I didn't want to rush it so for the first time last year the report of the Yunus report identified that the three and five years patient and graph survival is better if you receive a living donor compared if you receive the disease zone so it's clearly now become a great and safe option for those patient in need of liver transplantation University of Maryland has a great reputation I think that you can see here if lower the better and you can see that in term of volume we are not the largest center in the country but we clearly in term of outcome is one of the top centers in terms of good outcomes compared with other institutions all across the country. In term of donor risk for living donor some people obviously talking with patients patients they're very concerned about the risk the mortality continue to be very low continue to be 0.4 and 0.1 percent depending on right love or left love whatever donation is and this is just for donor obviously it's not for the recipient just for the donors but as the center get more experience the mortality has dropped there's not recent any dead in donors and we have become more expert to identify what donors we can use and which one we can't the complication rate in terms of more complications about 30 percent but serious complications like areas of necrosis or light bilid requiring some cases that are recovery transplantation is about 2 percent. The H2O which is this group that was created in the U.S. in the early 2000s has a long term follow-up of 760 donors. The majority of them they write love and some of them left love and they came up with this rate of complication that you show here and they also show that 85 percent of them really resolved pretty quick. So there are a few patients that have complications but when that happens it's very concerning for the patient and for the institution. Internally we look more around the world and there's a different obviously perception of what the complications in the way that the complication is accepted or not. There is about 23 cases in the world now of almost 12,000 cases of donor death and the majority of them happened at the beginning. It's recently been described but if you I think a couple dead in the last few five years but still the risks are there we know that and we always present that to the patient several times so they are very aware of the potential risk of complications. Also has improved the depending of the need is depending of the risk that you're willing to take. As you can see this was presented where they have a triangle where in each of the point you have donor safety, the need and the recipient outcome expected and depending of the area for example in pediatric we know that the need is high the donor is safe because the area that delivered that you really take is very small and then the recipients outcome are very close. So you can see that in pediatric there's no doubt that this is probably the best option leaving donor for pediatric patient that need the liver transplant. If you can see when you use a level of you can see that it's very safe for the donor because you are using the smaller part of the liver and but you but also you cannot accomplish all the needs that you you're supposed to cover so you can transplant less patient and the risk outcomes have been excellent too. When you use the right love you are taking a little bit of risk on the donor side but you in case you can cover more needs you can transplant more patients and even when the outcomes now have proven to be excellent and I will probably at this point put it up here still the outcomes in general for the right love is excellent. The only thing that you are taking a little bit more risk on the donor obviously. And the last thing I want to mention about our donor champion program we developed this donor champion and we are not unique several other programs have developed that but what this is really is education and training and education for patients to understand two things the need of transplant and the challenges that they face if they do not have a living donor. And we talk about whether this mortality complications for those patients that receive transplant with the male score is very high and we try to go over that. What we observe that if you educate those patients they really you really see a significant improve increase in the volume of patients willing to donate for liver transplant. And like I always said I think a lot of our patients come to to being evaluated for transplant it is a complete lack of understanding what transplantation is and what they can expect from this. So any education is good but what we observe that if you do education for living donor you see increased significant increase in the number of family members that are willing to donate. So I will kind of stop here so we have some time for for discussion later after Dr. Barry finished but I will say that living donor is the best or a good option to alleviate the organ shortage that we're facing and especially good for those patients with the male score between 12 and 30 or 28. I put 28 there because all H epatocelular cancer patients get the middle of 28. So until there if they don't have ACC anyone between the middle of 12 and 20 struggle for a long time to receive an organ. So that is what living donor kind of do the best of the best good. Liver transplantation required a time of committing the individual with the expertise that we do have and we have also committed physician advocate to advocate for for living donor some of the outreach and education that we're doing here but also with patients that we do webinars the patient can every month we do webinar where the patient can come up or the physician can come up and we have discussion about the stage of the waiting list the risk and the benefit of using living donor we're doing some community partnerships with some schools and other entities to promote living donation and clearly you have to have a clear institutional support to remove all the barriers for those donors that are willing to donate and ethical issues that have been discussed in this in this case we have been discussed this and having quite a proven and the understanding of the the better good that we do with living donor is clear to our institution it's up to us to bring it to colleagues like yours and your institution to make that very clear for the patient as we present the patient and I will stop here thank you very much for that attention I'm happy to stay so we can answer any potential questions thank you Dr. Malik there was one question for you in the chat what percentage of liver is excised from the donor and most commonly from which lobe thank you that's depending the if we do right love or left love donation we in you know right love is as you know is 60 percent so we can either take 60 percent 50 percent or 40 percent of the liver if you do right or left we because we have more experience in right love we tend to do right love donors but we never go above 60 percent even what we know by surgical expertise you can transfer you can excise up to 70 percent in the patient safely but we try to never go above 60 percent at the same time I will say that also depending age we know that if somebody is less than 30 years old you can go and take 70 percent and the believer will do very well when you get to do above 45 or 50 years old then you become more challenging so depending but in general we try to stay in the 50 percent range of of resection and start that's a bad thing start right away is your question the end I didn't I didn't asking questions sorry the can I answer a question ask a question yes yes of course um what uh this the living donor procedure involves uh taking the patient to the operating room yes and uh what percentage of patients the fail uh the criteria for living donor in the operating room so that's a great question and we know that about every four patients that uh proposed to be living donors we end up with one so in general from the phone calls to being in the order is about 10 to one from the patient that goes through the evaluation is about four to one so and that when you go to the order with the technology that we have today is very rare at the beginning was described about between three and four percent patient that you go to the order and you find something that you didn't see in the MRI and you will stop I would say that never never happened to me but I'm sure that sometime may it may happen saying unexpected thing like an arterial was not seen in the so it's all about the anatomy but you know with new technology we use these medias which is the 3d uh software that really kind of help us so I would say between one and three percent they say don't go when you go to the order it's very rare well uh excuse me but I'm what I'm talking about is the um the situation where the patient uh when he's taken off the ventilator in the operating room continues to breathe or that has signs of life and is unable to be declared dead you're talking about dcd then James right so you're talking about donor after cardiac and not about leaving donor correct okay yes so the dcd you're right so in dcd it's about patient that they are extubated I will guess it's about 40 percent of them that end up to be donors and it's about half that they will never don't arrest or they arrest too late to be used as a donor but that's you know that disease donor correct okay got you thank you one more question and then we can switch to doctor body what are the most common complications for the donor so the most complication for the donor I will say we see three three things frequently um complication is is uh hernias obviously like any surgery hernias frequent uh few times we see bilics and most of them can be resolved by ERCP some patients you see jaundice post post donation we see some patients especially when you go about 50 percent resurrection that you see that the billy rodent go up to four or five and the patient gets a little bit yellow and then after three or four days go away um but most of the complications are those that happen the first two weeks um after two or three weeks as you know the liver regenerated especially in young people pretty fast we have seen leavers almost go back to normal size in about six weeks so once you go through the first two weeks uh complications are very very rare okay they're getting lazy for them all right well we can get dr body to start and then uh we can still get more question at the end I will be here anyway good afternoon everybody my name is Chandra Bhatti I'm one of the transplant surgeons at University of Maryland I'm a surgical director of liver transplant and hepatability surgery um first I would like to thank everybody for giving us an opportunity to talk about uh liver transplantation and particularly transplant oncology world which is relatively new and emerging um and if I have if you have a questions please let me know um and I'll answer at the end in this talk I'll discuss mainly about transplant oncology world what is coming up what are the various indications for transplantation and Dr. Maloof has already covered the living donor part and I'll talk a little bit more what is the living donor role in these patient population so in today's talk main discussion about non-HCC patients as you all are aware that the hepatocellular carcinoma is a main indication for liver transplantation but we'll discuss mainly non-hepatocellular carcinoma today so when we talk about the transplant oncology um as you all are aware that the the hepatocellular carcinoma patients who are within the Milan criteria get an exception point as Dr. Maloof discussed before about um um meld score they get an exception point and that meld goes to close to 27 28 based on where you are there's additional criteria which are UCSF and there are a ton of more other criteria including Toronto criteria as on criteria UCSF and other criteria where you don't get exception point living donor liver transplantation is an important tool to get these patients uh offered what is the best treatment for them and uh these patients can be offered living donor liver transplantation since they're not eligible to receive extra point from you know we discussed about uh liver metastasis from neuroendocrine tumor we discussed a little bit about colandrocarcinoma and we'll talk about two different kind of a colandrocarcinoma one is a intri-patic and one is a extri-paticolendrocarcinoma means what we're talking is a is a claskin kind of a tumor a little bit talk about your batic epitheloid hematoma and the most controversial topic in today's discussion will be colorectal metastasis as you all know that this is relatively more emerging field and I will tell you what is the current data and who are eligible for liver transplantation going back to a little bit of what Dr. Maloof discussed that as you can all see that we we have about 10 to 12 thousand patients currently getting currently listed for liver transplantation and only 67,000 patients get liver transplantation so there is a huge gap between demand and supply and that's what the living donor plays an important role in providing additional donors the number of living donor transplantation has been pretty stationary and a relatively few centers across the countries are doing it this is the next slide sorry the next slide shows about the the current weight list mortality as you can all see that at about 100 patients who got listed in 36 months about 18 percent of the patients die while waiting for liver transplantation just because of the discrepancy between patient listed and organ available so now we talk about cancer development and as you can see this is a timeline for development of these patients who receive liver transplantation 1996 was the era when Milan Monsofaro from Milan basically discovered that the patients who have three lesions less than three centimeter to much better in comparison to any patients you you transplant and that's where the Milan criteria came in and these patients were considered for additional point otherwise they would never receive a liver transplantation when we move forward in 2005 that's when the Mayo Clinic came up with the mayor protocol which we'll talk a little bit later on about those patients that the patients who have a class in tumor receive a particular dedicated protocol and they do reasonably well after liver transplantation in comparison to providing them the section then in 2007 again from the Milan group they came up with the patients who have a neuroendocrine tumor metastasizing to the liver and again they showed excellent outcome will again discuss what are the indications and contraindication towards later part of the talk in 2013 that's when the colorectal metastasis came in a play and group from Norway came up with the idea that these are the patients can be served with liver transplantation as long as as long as pick the right patients and we'll again discuss a little bit later on Toronto groups of question who came up with the idea of doing the same thing with intra hepatic cholangio carcinoma which has traditionally been considered a contraindication for liver transplantation and it still is considered for contraindication but there are selected criteria where you can offer the middle of a transplantation similar patient was re-emphasized by Houston Methodist group from Lunsford and she did similar kind of a transplantation in those patients let's talk a little bit more in detail about cholangio carcinoma as you all know cholangio carcinoma is a melignin tumor of ability system about 10 percent of hepatability melignins present as a cholangio carcinoma second most type of a tumor after hepatocellular carcinoma when we talk there are three different types intra hepatic which is present inside the liver perihylar means present in the dot just outside the liver mainly in a hyalur plate the third one we talked about the distal cholangio carcinoma where the ripple operations play a more role and it's more towards we're talking mid common bile duct as well as a lower common bile duct when we look at their outcomes after surgery their outcome five year survival arranges from 25 to 45 percent which is not great the multiple risk factor which has been sort of said that they could cause as more risk of cholangio carcinoma particularly PSC colidopulocyst and stone formation with multiple parasites present in the liver now we talk about the perihylar which was again published in 2005 2006 in the form of a Mayo protocol mainly coming from Mayo and these are the criteria which they used it these patients were undersectable the tumor was present above the cystic duct they had no extra hepatic disease and there was nothing present inside the liver they received a sandwich sort of a treatment were in the form of neo adjuvant treatment but they received external beam radiation and a 5FU they received brachytherapy and a 5FU until the transplant was done when they were ready for transplant they underwent exploratory laparotomy confirmed that there is no extra hepatic disease once they confirm extra hepatic disease they underwent another transplantation the first data was published in 2006 where they did 19 they put the 19 patient under this protocol only eight patients were only 11 patients completed the protocol and received transplantation and as you can see the median follow of 44 months and they had all patients alive they did a follow up study where 71 patients were put into the study and 38 patients underwent a transplantation and you see 3 in 5 year survival is 82 to 80 80 to 80 percent after liver transplantation which is in comparison to we are talking about 25 to 45 percent which is almost more than double they found some prognostic factor in these patients that the older patients who have received gallbladder surgery before and see a 99 more at the time of transplantation were known to have a poor outcome further studies were done using the same protocol U.S. multi-centric study published in 2012 12 U.S. different centers 287 patients 5 year disease free survival was 65 percent again way better than having a 25-30 percent patient two other studies which confirm the similar kind of outcome and as you can see the overall 5 year survival rate without Mayo was 21 percent with the Mayo 60 percent and similar with the liver transplantation 64 percent versus the resection 18 percent so as you can see the transplantation offer much better chances of survival in comparison to patients who are receiving a just pure resection or any sort of a chemotherapy now we talk about intriapatical angiocarsinoma as I mentioned this is more controversial and they do not receive extra point from you know still the patients with the with the very high of the angiocarsinoma do receive extra point from you know and they get same point as HCC while these patients do not receive extra point and there is a reasoning behind it because we have done retrospective studies in those patients where liver transplantation was done with the thought process that they either have a PSC or hipatocellular carcinoma and they were found to have actually a clangiocarcinoma and we noted the outcomes are much worse that's why it was not favor to do a transplantation in this patients two studies one from the large Spanish studies again they showed that the disease free survival five year 27% not great but still there the Toronto study which again confirmed that these patients have if they have a very early intriapatical angiocarsinoma less than 2 centimeter the five year risk of recurrence is 60 18% in comparison to 65% they again showed that the very early intriapatical angiocarsinoma have a five year survival of 65% again we're talking that this is a risk this is an area which is developing we're not there where we can say this is as good as this there but still 65% is way better than the patients who are having outcomes in 25 to 40% now let's discuss a little bit about the metastatic neuroendocrine tumors I'm sure you all have seen large neuroendocrine tumors studied in a liver with multiple symptoms patient keep receiving Lentrotide on a monthly basis and they have multiple symptoms these patients typically have a bilobar disease and cannot receive a resection these patients could be served with the transplant patient again the patients most of the patient who are present is about 10% of all hepatic neoplasm 25 to 90% of the patients who have a neuroendocrine tumor do present with some kind of a liver metastasis disease and we'll be talking about five year survival in patients with liver metastasis is only 40% so that is something which we can offer to these patients and increase their life expectancy there are some prognostic factors which are described in a literature who the tumors which presumes hormone tend to do worse the degree of tumor differentiation poorly differentiated tumor will do worse again number of hepatic lesions also has a role in how much how well they're going to do it or not when we look at the studies which are published there are two major studies one was ELITA which is a transplant organization Europe which collect all the data similar like UNOS they published in 2013 they showed the five year overall survival is 73% again much better than what we were talking 30 to 40% here they they selected patients and they selected patients where the hepatic involvement was less than 50% those patients did much better similar from the Milan group which we talked about presented the data which initially they did in 2007 followed by in 2016 they had 42 patients who received liver transplantation and we can see 97% survival five years and comparison to 51 almost double so the liver transplantation do offer a significant role in their overall life expectancy based on these studies UNOS has come up with some guidelines that any patients who is less than 60 have resection of primary disease or we don't know where the primary is well differentiated or moderately differentiated cancer mitotic rates less than 10 and less than 20% key 67 if these patients fulfill those criteria they can be considered for liver transplantation the most important part which is important here is that the metastatic part is still less than 50% if it's over 50% they are typically not considered and I think that's where the living donor plays a role if they are more than 50% they still get benefit but they could not get a point and I think that's where the living donor plays a important role now we talk a little bit about the colorectal cancer which is again most controversial topic most of people don't even know that we can offer liver transplantation for these patients just to give a little bit of idea third most common cancer worldwide 1.3 million cases diagnosed every year almost 700,000 patients die from colorectal cancer 25% of the patients presents with synchronous metastasis and about 50% of them will develop liver metastasis whether at the same time or later down the stage this is just the overall brief what is the treatment options as any as you can see the transplant is not part of it and hopefully with the time going along with more and more studies become available there will be transplant at some point so when we look at the outcome after surgery and as you can see Fiker survival is 47 to 60% after curative hepatitis sometimes we do liver surgery in patients who are not a curative intent but sort of a deep can give a chemotherapy if we can make them receptable but if you look at the curative hepatitis outcomes there are only 45 to 60% almost 40 to 75% patients do get recurrence out of which 50% do recurrence in liver and the liver section is only visible in about 40% of the patients so most of the patients who present present with advanced disease where it's not receptable so I want to give you an idea that this is a new kind of a surgery which we can offer in the patients where most of the people think that it's not receptable because it's a bi-loba disease where what we can do is a two-stage operation what we call it's a liver partition and a portal wing ligation where this just to give you an example that the lesions if you look at that there are four lesions in the right lobe and two lesions on the left lobe if we take the right have to take maybe don't have enough volume to take out all the tumors in this situation we can go ahead and do the surgery take out the lesion in a left lobe will I get the right portal wing let the left lobe without any tumor grow and then go back in and do the right hepatectomy this is becoming more and more common in patients who have a bi-loba disease now we talk what are the outcomes why did we start thinking that the colorectal metastasis could be a potential case for liver transplantation we did liver transplantation for colorectal metastasis in early years as early as 1963-1964 when we looked at the data between 68 and 95 there were about 50 cases and as you can see 5-year survival wasn't great only 18 percent again and looked in the euro similar kind of a database the 30-day mortality was 30 percent and 5-year survival was 12 percent so that's why we thought it's probably not a good idea to do a transplant in these patients because that's not an optimum use of liver transplantation this is the same data 5-year data 5-year survival 18 percent from european liver transplant registry that's when this study and this trial came in from Norway Norway is strange in a little bit different situation than what we have in the United States that they have more donors than they can transplant they started transplanting selected colorectal patients they came up with the idea of 2006 they did an open trial at Norway they had average weight period of less than a month so they could do these kind of things which we typically could not have done it they included the patients where there's a primary tumor is gone 6-week of chemotherapy is received they have a non-receptible liver metastasis confirmed by two group of compatibility surgeon patient is an excellent excellent performance status they all end up in the staging laboratory to make sure that there's no tumor outside the liver frozen sections were done when they confirmed that there's no tumor outside they underwent a transplantation so they presented the data in 2013 and they had 25 patients in a trial 21 patients underwent a disease donor liver transplantation with the median follow-up of 27-month and you can see five-year survival is 60 percent we're talking in comparison to non-receptible cancer where the five-year survival is less than 10 to 15 percent we are achieving 60 percent of survival again the biggest concern was the recurrence was achieved and the recurrence occurred in 90 percent of the patients but all of them were alive and most of the patients were able to receive a second treatment for those recurrent tumors again it was a small study first today's first study which actually was done as a randomized trial so there was a follow-up study from multiple European center and they also showed that if the right patient were used five-year survival is 50 percent again all patients were alive without any cancer recurrence up to almost four years that's a great achievement again those patients would die typically within a less than a year so they are current they did the second part of a study where they broaden their horizon and included more patients into this again these are the various indications I'm not going to go into detail but typically it says the patients are by low bar disease non-resectable have a CEA less than 80 not very surgically complicated and lesions no lesions less than 10 centimeters and no more than 30 percent lesions they did 15 patients with the median weight period of one month and as you can see they had a patient's lesion up to 100 metastasis in one patient and if you look at those patients they come up with various score called Fung score and Oslo score and their score were low and their outcome 36 month follow-up 5 year survival 83 percent as you can see gain a great improvement in an outcome in a patients who are going to die within less than 12 months again the disease-free survival was not great 30 percent of the patient recurred in three years but again the patient survived 85 percent patient 83 percent patient survived five years that's a big achievement and survival after relapse means some kind of a recurrence are kept still four years is 73 percent which is which is tremendous improvement in their outcomes these are the two comparison between two trials as you can see they won't become more aggressive in SICA two trial then they were in a SICA one trial where they had a limited deliver lesions where they were gone more aggressive and there were more patients in there they come up with the idea that these are the prognostic factors which will define their outcomes tumor diameter less than 5.5 C a less than 80 time between liver transplantation and a colorectal resection should be ideally more than two years and a stable disease if disease progress while they're on a chemotherapy they should not undergo a transplant these are current ongoing trials various trial happening throughout the world again looking into various patients which are the ideal candidate these are the two scores which we talked briefly about Oslo's scores and Pong's scores again less the score better their outcomes are so this is what we are currently trying to sort of go more in detail and trying to come up with the best score which will be ideal for these patients now we get into ethical dilemma that the current weightless mortality in these patients about 17 to 20 percent how do we justify that we transplant those patients where there is a recurrence rate and overall survival is as good as other patients so we are not there where we could use these disease donors because we have to consider those patients who have a primary liver disease not secondary to the cancer other than SCC so that's where the living donor liver transplantation you saw the outcome 85 percent if you have a loved one who has a liver cancer and they can survive five years 80 chances of five years of survival is 85 percent I'm sure a lot more people would be interested so this is where I think the living donor liver transplantation play important and a huge role Dr. Maloof covered all these parts so I'm going to skip the living donor liver risk and the start liver which Dr. Maloof has already talked so here we are going to start doing those patients I'm coming from VCU where we did these transplanted we have transplanted these patients the patients we transplanted we have current 16 month data with zero recurrence and we are going to include exactly the same protocol which is an Oslo protocol which says 18 to 70 year old has a clinical approval colorectal liver metastasis we do biopsy if there's a questionable piece will be the various tumor characteristic features pretty much based on all the trials saying the same thing what we have discussed there and we're going to include those patients in this study anybody who has wild type Keras wild type mutant wild type they will be included but their Oslo score has to be less than three we will exclude any patients who fail our transplant evaluation or have a barf positive tumor pregnant and other substance abuse typically who's not candidate for liver transplantation would not be a candidate for this otherwise most of the patient would be considered for liver transplantation to conclude my talk liver transplantation colorectal metastasis is evolving while it is getting it is established for colandrocarcinoma and I think we are not there in terms of when we are talking about intriapatical and your carcinoma as you all can see initial results are encouraging with survival over 50% and a recurrence rate is high but still survival is 50% even after recurrence rate typically in these patients as you know the recurrence rate the survival was less than 10% five years my biggest question to all we when we talk among ourselves that we are transplanting the best tumor characteristics among the worst patients what if we choose the best tumor characteristics in the best means like when we do FCC we pick three tumors less than three centimeters but for colorectal metastasis we are picking the patient who have bilaua disease everywhere what if we did the similar kind of a treatment where okay three tumors less than three centimeter and see their outcome but right now we don't have undermitted supply so we cannot do it so that's why we are offering to the patients which are typically not a candidate for any other treatment and this is sort of a resort treatment for them role of transplantation in a resector liver metastasis as I said we have to be determined living donor are the most important pool for these cancer patients which typically would not get a point and that's where Dr. Moulou's previous talk is important that any patients who have a liver disease should be considered for liver transplantation and these patients if they don't get a transplant from the list they should be able to receive transplant form the living donor liver transplantation I'll stop my talk here we'll take any questions if you have can I ask two questions sure the first is phogia survival one or two years' survival that's important but could you comment on the quality of life with this extended survival that would be the first question and the second question when you do a staging leperotomy and determine that there's no further cancer it would seem to me that the patients who have recurrence after transplant do have this micro metastasis that were somewhere but were unable to be picked up with the staging leperotomy so how can you be sure that a staging leperotomy is completely accurate so those are my two questions so the first question the quality of life is excellent the first patient which we did before I moved from VCT here is a school teacher she's back to work she's going doing as every other transplant patient will be doing it so the quality of life is pretty much normal there is no difference in comparison to anybody else except they need to take some immunosuppression and other medications other than that there is no difference in that quality of life when we talk about the patients who had some kind of a recurrence even their quality life is very good we have a lot of data published about quality of life in these patients who got the recurrence and they all are are still living with the lung metastasis some of them had a research for the dissections or my revelations but their quality of life is excellent when we go to the second question unfortunately you're very right that the staging leperoscopy or leperotomy is not the ideal way to know whether they have a recurrence or whether they have extra hepatic disease or not but we have to do what we have what we have to do what we have available right now and the only way to find out about those macromatastasis is by staging leperotomy there is clearly no way to find out about those micromatastasis that's why we are using a very strict criteria in these patients that the patients if they progress while they're on a chemotherapy they are not eligible for transplantation so there are some ways by which we are checking those patients but there is no physical way to confirm that there is no micromatastasis present in the body having said that there are more and more tests coming up which are based on tumor DNA and in a cancer world and I'm hoping in the coming future those tumor those tests will become more and more prevalent and we should be able to incorporate those tests into our selection criteria if these patients have those high tumor burden of that DNA is present then we should not transplant those people or we are not there yet thank you if we don't have any more questions thank you for thank you to everybody for attending this weekly grand round and especially I want to thank Dr. Daniel Malouf MD and Dr. Chandra Bhatti for the information lecture and we will appreciate if you have any more topic we can sign up more thank you and I'm writing my email address and my cell phone if anybody has any questions about liver cancer patients or have any patients feel free to reach out to me directly thank you thank you very much thank you everyone for being and also Peggy Dr. Chandra number is there and if you need us Peggy always can be in contact with us and we don't mind to share the email or the phone number so thank you everyone thank you very much thank you bye bye