 Next speaker is Dr. David Cronin. Dr. Cronin is a transplant surgeon who has just recently moved to Colorado where he's at the Port of Transplant Center. He has both a Greenwell Fellowship as well as have been a McLean fellow and on our faculty. Dave will be talking today about too much too soon. Dr. Cronin. I want to start my thank yous now because we'll run out of time later. Thank you to the McLean Center and for facilitating this very unique opportunity to have clinical medical ethics. Thank you to Mark specifically, but that is just not even the beginning and the list would be too long and I would exclude people and feel bad and I have had a very unique opportunity to be part of the University of Chicago and in particular transplant at a time when I would say arguably it was the best transplant center in the world. The innovations that occurred here are taken for granted now and have formed the practice and it's not just the surgical innovation, it is the ethic interweaving of the practice, the contemplative way that things are done here, the challenge to every concept without fear of being stifled and I think that that has passed in medicine, unfortunately, but I'm so happy that I benefited from it. And Dick thank you because your program and Frank Stewart's program was really something that I use every single day. I even I think sent you an email thanking you for doing kidneys the way I did when I was a resident because I do that for residents now. Okay, the talk, too much too soon. Well, I think we've now moved from too much too soon to too little too late in the practice of adult to adult life donor liver transplantation and my comments are very specific for the United States because I think Asia has eclipsed us exponentially. So as we've seen by other speakers, this was really the paper that started it and this paper set out the rules. Everything I'm going to say after this paper really is in this paper. And then it was in the next most read paper as soon as the transplants were done. And this is the template and the narrative to introduce surgical innovation and this is the template and the narrative to introduce anything that had to do with life donor liver transplant. Unfortunately, 89 wasn't too long ago and we will see that the suggestions here were missed. So when Mark and I and Mike Millis contemplated the adult to adult transplant, you see this was the state of affairs. The red is the adult recipients of life donor. It really began around 1997, 1998, although the first adult to adult life donor liver transplant was in 1991 at the University of Chicago and it wasn't really published. It's buried in a deeper manuscript. But this took off and it disseminated rapidly and widely. And I was rather outraged because many of the programs that were doing the adult to adult life donor transplant, a lower order of magnitude, much higher in risk and complication was primarily being done by people who had no experience in pediatric liver transplant and no experience in life donor pediatric liver transplant. So we published our paper in 2001. Now what had occurred before we went to press was a donor death and this was in 1999 and it got very little attention and why was that? Because the donor and recipient pair were just common folk. They weren't newscasters, they didn't work for a media outlet, they weren't celebrities. And this donor death basically went unknown. There were a couple of publications. This one here on CBS News in 1999, that was the only one I could find. The donor who died, his name was Danny Boone and his wife launched a crusade for donor safety. And I know her personally and the door was shut everywhere she went for donor protection. She wanted an explanation, door was shut, donor protection, there weren't any. Someone to talk to, none. Someone to adjudicate this, none. Someone to help her put her, her only child through college, none. So, Mark, you really are a prophet. Because it was all there. And, you know, I don't know who that is in the background, but okay, so we were fortunate enough to get a paper that was submitted and then rewritten by the New England Journalists. I found out they do on every paper and it was great because they're so much better at writing. We looked at the time of our publication and we called for guidelines, policies and regulations and we warned the transplant community, and I am being a little self-serving, that if we didn't control ourselves, someone would step in and control us. And at the time in 2001, when adult life donors were disseminating widely, nobody, there were no policies, no regulations, no controls. Because you-know's is primarily concerned with deceased donors, as we've heard. They stay away from the life donor business by and large. We were so disturbed by the lack of criteria that people should at least master before they take a healthy volunteer adult and take out 70% of their liver that this paper, I don't know if you remember this, Mark, we were sitting in a bar at a meeting in Europe, I think it was Italy. And this very accomplished group, I'm the lightweight in the group, we sat down and constructed with Max Milago's Apple laptop the rules and criteria to enter into life donor liver transplantation for adults. Here is where the next donor death occurred. And this one was very public. And this was at Mount Sinai. And this was very public because the donor who died was in the New York media. So you can see that our paper came out in 2001 and this was the peak of the adult to adult life donor business, about 475 cases. And there was that very public donor death and everyone was outraged. And there was a scramble for punishment and blame and accusation. And the life donors for adults plummeted. And poor Charlie Miller suffered this fully and was exiled to practice in Palermo until he was returned now to the Cleveland Clinic. This also was a media frenzy and Denise Grady spoke too many times. And the New York State Department of Health and so everything is politics are all local. So in New York it's a very controlling state government and the New York State Health Department came in and closed down the program and launched into an investigation and they levied fines. And they came with a conclusion that although everyone was skilled, the patient didn't get the best care possible and simultaneous with that finally, finally the professional organization in the NIH funded an adult to adult life donor cohort study. And nine programs applied or were selected and these are the representatives that populate this national study. This group has published at least 33 publications addressing adult to adult life donor transplant. It is the best data source for the U.S. experience although some of the publications although in very great journals are scientifically, they could have been done better quite honestly. But what have they talked about? They've talked about the outcomes for finance, for psychological safety, for the bile duct complications, recipient and donor morbidity and mortality, physiologic and anatomic responses of the donors and what happens when you use it for cancer and hepatitis C whether there's a higher risk or a higher rate of recurrence. The New York State Health Department also convened a council. And although we got no credit for this, if you look at the council's report, it mirrors the two New England journal papers, the 1989 and the 2001 too much too soon. And in this report they use a phrase that was not in the literature before we gave it to them which is called it's not just informed consent, it's informed understanding. So I give the informed consent but the recipient has to give me informed understanding and I think that that relationship between the doctor and the patient is a minimum for this process to move forward. Their report and guidelines and regulations were updated in 2004. Now if you get this report, this report is the basis for what eventually comes as the government rules, the UNOS rules for adult to adult transplant. So this is the landscape to 2006 and you see that at its peak, adult to adult only contributed about 10% of all the transplants performed for adults and at its nadir it was 3%. Now it's bouncing between four and five. Well, it's relatively flat in the early 2000s and we've started to have an uptick. Now what's interesting about this is this uptick has occurred in spite of two more deaths. Both in 2010, they're a couple months apart. And you can see with these two deaths there's really no response in volume. And in fact the media frenzy that surrounded the second death of 2002 really did not occur here. One death was at the Leahy Clinic in Boston. The publication is, the death was in 2010 but this publication which is a good review is really in 2014. There is some fighting in the media about controlling the media and maybe this should have been more publicly disclosed but it wasn't. And the second death occurred in Denver at the University of Colorado. So as we're percolating along doing this operation and as pretty much anybody can do it for any indication OPTN and UNOS, the government agencies for transplant are pushed into regulating a field that they weren't originally charged. So they were originally charged for deceased owners but because there's really no other organization they've now tried to address live donors. And kidney was first and the data is very good and so are the regulations. But here's the OPTN bylaws. And in these bylaws there are rules, minimum criteria for what constitutes a live donor liver transplant surgeon. Well that's 20 liver resections in five years, seven of which have to be live donors. That's it. You can be certified to be a live donor liver transplant surgeon. Unfortunately when you go to the centers that perform this operation and there aren't many as a fellow I would be hard pressed to find any fellow that does seven live donor liver transplants. They may be in the room and they may be holding the suction machine but the thinking and planning and operation is primarily done by the staff but the rules aren't that granular. Likewise we have the liver donor policy statement which is very, very large and it goes in excruciating detail. Unfortunately when you're done reading all of this I did not come away with any greater sense of safety for the donor. This paper which is an editorial really calls out a very critical part and that's disclosure. When a catastrophe occurs, death being the most notable but 30%, 30% of adult donors have significant morbidity from the operation, 30%. Healthy people walk in, 30% chance of having a chronic problem. That information is not really captured and we never understand the near misses or the ambiguous threat as it's called in the safety literature. What could happen that we should be planning for so that when it does happen we can mediate it or we can avoid it occurring? So where am I going? This I adopted this from Amy Edmondson. In liver transplant for adults there's a knowledge spectrum and if we start with the standard of care that's pretty straightforward. That's what everybody does. There's easy to give informed consent. It's all predictable. It's the skill is a commodity. It's the same in one hospital or another, maybe a little different. And the risk benefit analysis is easy to define. When we move into surgical innovation this is done with the informed consent of the standard of care procedure. The innovation occurs in real time in the purest sense and the innovation occurs to address a problem that has occurred in real time where the standard of care does not give a satisfactory outcome. So you're in the middle of an operation and the anatomy is slightly different and you have to innovate. And you're doing it for the benefit of that individual patient at that individual time. So the consent process carries over. You can't stop, wake them up and say hey you have an abnormality here and we have to do something a little different. The risk and benefit analysis here is intended to benefit that individual at that time. The informed consent here is interchangeable. The problem is in experimentation and it's only a problem when it's not identified as experimentation and here informed consent's difficult because I don't know what the outcome is. There's high variability in the process and it's very difficult to assign risk and benefit and the application is still under definition. So if the risk and benefit you can't really inform consent. So what do we have? We have adult to adult live donor liver transplant and the indications are not really solidified nor is the surgical procedure at this time and I will not show you but I will tell you. We're moving now from using right lobe donors to maybe preferentially using left lobe donors in adult to adult transplant. Not because the left lobe is better for the recipient in point effect it's probably worse but people are trying to get away from taking out 70% of the liver and only giving 30 or 40% because it's technically an easier operation. Well the consensus from Vancouver tried to put constraints on the practice and they established that the live donor should only be used for standard of care procedures. There was analysis of what the live donor volume is and the conclusions that were made is that colostatic liver disease was a good indication and used and malignant neoplasms not hepatocellular cancer so here's where we get into a little weeds. We're using live donors for indications of malignancy that are not permissible using deceased donors because the outcomes are not acceptably good enough and their conclusion here and this is really what we said that there are some situations in some geographic areas for some diseases that adult to adult may be necessary but they truly need to be defined. So let's talk about hepatocellular cancer because this is the one that I really want to address. On the left side is, oh the hell with the left side, let's go to the right side. That's where I want to go. On the right side, so this is deceased donor transplant in the United States and the top two bars are male and female so just make it one bar. We'll be non sexually discriminating here. What it's saying is if you have a hepatocellular cancer in the United States and you will have a higher rate of transplant using a deceased donor. Now that's because we rigged the system intentionally so this criteria called malan criteria which is restrictive and it came as the standard because when you transplant a patient in malan criteria for liver cancer their outcome is equivalent to basically everyone else on the list. So we're looking at outcome equivalents for this indication and what happened in 2002 when malan criteria was invoked we had to give exception points for hepatocellular cancer and we found in five iterations we kept giving too many exception points. So patients with hepatocellular cancer were transplanted at a higher rate than anyone else on the list even though patients with hepatocellular cancer were healthier and could stay on the list longer. So this has been modified. Prospective data analysis, consensus, public discussion. And in fact we have enough data that we can retrospectively model the entire transplant system for hepatocellular cancer and we find out that probably the most equitable allocation would be to impose a nine month waiting period from the time you're identified and only give exception points after the nine months. But it's public forum and public discussion so what we came down to is we picked the middle one, we picked the six month. So this just went into effect in 2015 to try and level out access. We have just two publications looking at hepatocellular cancer and adult live donor liver transplant. So this first part is in the first phase. It's all retrospective, not a very good data set and look at the numbers, 58 live donors and 34 dead donors. And the waiting times, critically important. If you got a live donor you waited 160 days. If you got a dead donor you waited 469 days. The rate of cancer recurrence in live donors is extraordinarily high. They revisit this in 2012. The numbers show that the waiting time in both groups has gone away but your hazard ratio for reoccurrence is still high in live donors and there's no survival advantage. Now this is my last three slides. That's what you're telling me, right? Yes. So this is a double equipoise paper which Liz Pomfrit wrote but I think she missed our concept of double equipoise. And what the entire paper goes through is to say that the decision to use a live donor is a utility argument and if the donor and the recipient agree you should move ahead and do the transplant. Not only did I find this problematic but so did Dr. Volk who I agree with as abdicating this autonomy, sole autonomy argument abdicates our professional responsibility. So here's what we said in 2001 and the yellows are still true today. I'm sorry to say I don't think as a profession we've progressed. We have to use live donors. I would like to know specifically in what cases when you use live donors for this operation there will be death but it would be nice if best practices were shared throughout the profession and rather than organizations policing themself when they have a donor death that we have an objective third party come in and share the findings.