EVLP_wakeam_06.24.24 (rev)

Hello and welcome to Behind the Knife. Today we're going to take a special focus on the highly complex and challenging field of end stage lung disease and lung transplantation, so taking a little bit of a divergence from your normal content, specifically in regard to how new organ preservation technologies have the potential to revolutionize the field and outcomes for patients with end stage lung disease.

If you're a student, resident, or fellow out there that's ever been involved with a lung transplant, you probably think of really long, arduous, complicated cases that happen in the middle of the night. And then always being on the lookout for issues and graft dysfunction afterwards for a pretty rocky post operative course for these patients.

But what if I told you that you could always book your lung transplants for a first start case at seven in the morning the next day? If that sounds like a pipe dream come true, or if it Doesn't sound like a dream of yours, but you just want to learn more about it. Feel free to go ahead and listen to this episode.

Machine perfusion of donor organs has certainly become kind of the hot topic in transplant innovation over the last several years, and

lungs are no exception to that. Ex vivo lung perfusion or EVLP. Is a novel lung preservation strategy that hit the scene for patient use back when it was approved by the FDA in 2018.

Today we're going to take a deep dive into the mechanisms of that technology, kind of a little bit of how it came about, how it's used today, and maybe what some of those implications of that technology are for the future of lung transplant. To have a conversation about the nuances of EVLP and lung transplant, of course we need an expert.

So luckily I'm joined by Dr. Elliot Wilke, who's a thoracic surgeon and lung transplant specialist at the University of Toronto. Toronto has a storied history of lung transplantation and is widely regarded as one of the busiest best lung transplant centers in the world and at the forefront of the field.

Dr. Wilke went to medical school at Jefferson Medical College in Philadelphia and completed both his. general surgery residency and thoracic surgery fellowship, including specialization in lung transplantation at the University of Toronto. He then joined the faculty at the University of

Michigan where within two years, he became the director of the lung transplant program there.

And in 2022, he returned to Toronto where he remains on faculty today, contributing to the center's one of a kind lung transplant service. Thanks for joining me, Dr. Rakhine. No problem. Thanks for having me. All right. So before we dive into kind of the intricacies of EVLP and organ preservation and things like that, and how it integrates into your practice, first, I'd love to talk more about just your story and how you became inspired to focus on lung transplant in the first place.

Where did you kind of first recognize that that path was right for you and what were the steps along the way? Yeah, sure. Well, my story, I guess, in thoracic surgery generally kind of started after I was an undergrad, I was living in Philly and I took a job, a research job in one of the pulmonary research labs, which was run by Partially run by one of the surgeons by the name of Larry Kaiser, who was a senior surgeon at the university of Penn at that, who happened to be a former

trainee of Griff Pearson at Toronto general.

But in any case he, I, you know, I kind of got exposed through some of the fellows to, you know, what it meant to be a general thoracic surgeon. And that was kind of what it, what started it in a way it was a little bit of chance, but I think, I kind of got interested in thoracic surgery and thoracic surgery research through that experience.

And then, you know, I went on to medical school and I came back to U of T and I knew you know, I was in the general surgery program. I knew I was interested in surgery, obviously. Um, And I was entertaining a few other things. I kind of thought I'd probably wind up doing thoracic and I wound up doing one of my intern rotations at Toronto general with one of my now partners, Tom Waddell, who, and I don't know if I've, I don't think I've ever actually told him this.

I should maybe tell him this. Maybe he would want to, but yeah I, he was doing an anterior approach to a Pankow's tumor. And to this day, it was one of the coolest things I've ever seen. And I thought, I saw him do that. And I thought, this is

what I'm going to do. And it was kind of all over from there.

I, my path to thoracic at that point had been sort of solidified. And I didn't get interested in lung transplant until kind of the end of my training. I knew I was going to be coming to the University of Michigan. And I, wanted to do more training. And so I, and I, so I wanted to do the lung transplant fellowship and You know, lung transplantation has everything.

I mean, it's just kind of like highly technical surgery. It's got ethics. It's got, you know, a lot of decision making. It's got critical care. It's got you know, it's got everything. I just really liked it. And I mean, TGH is, you know, I mean, it's a special place, I think, to do lung transplant because of the history, but also because of the present and.

You know, it was really like a special thing, I think, to get to train there. And and it just yeah, I don't know. It was all over after that, I guess. Very cool. A little bit of you know, right place, right time meeting the right

people. I suppose. I think that's always how it is. I think, you know, I think it's it's always a little bit of luck.

It's a little bit of, it's a little bit of who you are and it's a little bit of taking advantage of the opportunities that come your way. But Yeah, no, I feel very lucky. And and yeah it's, you know, that's how it's worked out, I guess. Excellent. So lung transplant probably more so than other solid organ transplants that are done nowadays is definitely fraught with a lot of challenges and, you know, some disease specific complexities that may surpass other transplanted fields.

What do you see as the largest hurdles to lung transplants? being more successful and having better outcomes in addition to increasing in frequency? Well, I think those are two very different things. So I think, you know, optimum, like, like what are the challenges and then increasing frequency, although the low frequency is a challenge, but I think you know, I would say the biggest challenge overall is

probably the incidence of chronic Rejection for what's what we refer to as collateral chronic lung allograft dysfunction, you know, the overall survival rate of of lung transplants is probably between, you know, between 50 and 60 percent at five years, if you look at the overall kind of global data from the ISHLT and obviously there's groups that do better in groups that do worse.

But, you know, overall that that's like a major problem. And most of those deaths, not all of them, but most of them are driven by CLAT. So if I was going to change one thing about it, that that's what it would be. And that is being changed slowly. You know, we're, kind of evolving in our immunosuppressive efforts, surveillance efforts.

You know, what the role of you know, like how the replay with reflux disease. There's all kinds of different things that are always evolving, but I would say that's probably the biggest challenge if I was a recipient today. Now the other element of that is, is the short term part.

And certainly that I think has changed dramatically. I mean, if you talk to some of my senior partners, Shaft and Tom, who are, you know,

doing this in the very earliest days, I mean, Shaft talks about. being a resident and having to sleep in the room with the patients because they were so unstable that you just couldn't you couldn't leave their side.

Right. I mean, otherwise they would die. And I think we've come a really long way in, you know, learning how to preserve lungs. And we can, we're obviously going to talk a little bit more about preservation in a second, but. You know, how to preserve lungs and how and the critical care aspect of this, of how to, you know, treat and manage graft dysfunction and all the other kind of issues that, that these patients have so that, you know, our residents don't have to sleep in the ICU rooms anymore.

And in fact, the patients do relatively well, at least, you know, at our place, they seem to be doing better and better. And we're kind of pushing the limits on who we're transplanting and the lungs we're using and everything. Just because we've gotten so much better at kind of the, on the preservation side of things.

So let's talk about organ preservation. So, you know, I think traditionally in the world of transplant

and, you know, this is not necessarily unique to lungs, but any solid organ transplant the, Standard historically has just been putting the Oregon in a cooler and transporting it to where it needs to be and then going in and transplant it.

Nowadays, there seems to be way more options out there and in terms of preservation strategies. So I'm curious to hear what you have to say about the options for Oregon preservation and how some of those are becoming more historic and some of those are becoming more contemporary and what you see in that.

Sure. Yeah. So I think I would just start by saying You didn't say this outright, but just by making a distinction between, you know, machine perfusion, EVLP for lungs and preservation you know, our current preservation method. As you allude to, you know, the one that's probably still the most widely used, although it does seem to be changing rapidly in the last couple of years.

But the classic one is preservation at what was thought to be four Celsius on ice. Although it's not really four

Celsius, because when you put them on ice, you really have no control over the temperature. And sometimes it's sub zero. Sometimes it's zero. You just don't really have good control, but that was the classic way that we did it until more recently.

You know, some data from one of my partners, Marcello and others who have followed have, you know, shown that maybe not only can we do. You know, longer static preservation at 10 Celsius, but they may actually even help the lungs recover in the bucket and do better when we put them in. And that's actually based on it's an old idea, actually.

Some of the earliest work on the, what temperature lungs should be stored at. Like from the 80s and early 90s actually showed that 10 Celsius was better and for some somewhat unclear reasons, people just preserve the mud for and that was the end of it. And until he kind of revisited this it wasn't really a thing, but, he's shown that there's I'm not an expert in the biochemistry of it, so I can't totally get into all the details, but basically, you know, there's emerging data on the function of the mitochondria,

and that the mitochondria in the cells may actually recover sooner, and they may actually do better.

And this is gonna, I think, will spread to some other organs. They've, we've started it in heart. I've seen some data in heart and there's some people who are interested in liver. So, you know, it may be something that is beneficial in other organs, but in lung, You know, certainly the preclinical data that he's produced to shown that it's better.

We've we use it all the time. Our clinical data shows that it's certainly non inferior, if not, maybe better. And so, you know, our standard is now 10 Celsius preservation and you can probably store the lungs up to all, 24 hours that way. And so, yeah, so, certainly we use it liberally, 24 hours still makes me a little nervous, but it, you know, definitely, definitely have, I've done it many times and so, so that's how, I mean, when we talk about like trying to sort of create like a semi elective practice of lung transplantation, it's really the fridge

that allows us to do that.

It's really 10 Celsius preservation that allows us to do that. It's not really evlp per se, evlp obviously has a role in that we can talk about what the role of evlp is or that we use it, the clinical role anyway, but really the fridge has totally changed, you know, how we, how we approach this and it gives us so much more flexibility.

Logistically, but also for other things like, you know, when our, I don't know, when there's other testing and things that have to be run on the recipients, like we take organs from different O. P. O. s and they don't always run all the testing that we want. Well, it takes three or four hours to get a COVID B.

A. L. done and if we have to bring it back. You know, you can't really start the case right away. You have to wait anyway. So it allows us just a lot more flexibility. And I think the real reason to do it is actually because I think that the patients do better. I think the reperfusion is smoother.

Their post op course is smoother. The graft rates, the graft dysfunction rates seem to be a little bit better and they're at least non inferior. So. I think

the advantages in terms of doing it in the daytime are clear and there's clear data to show that it's safer to do these kinds of cases during the day and it's better for the patients.

Absolutely. Yeah. I think it's so amazing that, you know, such a complicated entity that is lung preservation and transplant seemingly has a relatively simple solution, which is. 10 degree storage in the fridge that is allowed for more tolerable cold ischemia times. And, you know, I think the extension of that flexibility results in these things that you're talking about, which is, you know, being able to start a case with more personnel around having, you know, Yeah I would just add to what you're saying though.

And I would caution you a little bit. It's not just 10 Celsius, right? I mean, we, you know, there's an entire technique that's taken 30 years to develop, including the preservation solutions, the way that we're flushing the

lines, I mean, there's a randomized trial going on right now to know of four Celsius versus 10 that we, and some other centers are running.

So we'll know for sure if it's safe in a randomized way. Certainly the, our current clinical experience would suggest that it will be fine, but we'll know, cause we're going to randomize, we're randomizing people to this trial. But you know, 10 Celsius can't fix all the problems. I mean, I think if the lungs aren't preserved properly, you're going to have a problem.

And so, I think we were already pushing the limits. of preservation before 10 Celsius came around, right? And so I think it's just a bit of caution. I don't think, you know, I think people need to be careful a little bit about how we're adopting this because it builds on 35 years of research into how to properly preserve a lung.

And that's like a critical part of it. You know, how to flush, what to flush with, all kinds of different things that that really get us this like really high

quality preservation. And I think that's a really important point, actually. I think, you know, most of the new research has focused on, well, just putting them at 10 Celsius and you can wait as long as you want.

Well, you can't really do that. And it still requires a fair amount of certain judgment on which lungs are going to be appropriate for prolonged preservation and which lungs aren't. So anyway, just a word of caution on that. Yeah that's really insightful. So let's talk about how EVLP kind of fits into the equation of the ex vivo time period for.

Donor lungs. So it may be just for, you know, folks that aren't quite as familiar with machine perfusion, can you kind of give us the basic nuts and bolts of EVLP, what the technology is and how it fits into the handling of donor lungs? Yeah. So EVLP is an acronym that stands for ex vivo lung perfusion, and that's exactly really what it is.

You're taking a

lung and you're hooking it up to a circuit. that perfuses the lung with a solution. There's different options for which solutions we have ours that we use, but there's different ones that exist and it's hooked up to a reverse oxygenator, a pump and a ventilator. The lungs have to be ventilated.

That's sort of, I think, a unique thing about lungs versus other machine perfusion for different organs. You have to ventilate the lungs and You know, as I said, I can speak mostly to our version that we use here, but there are different systems there's different approaches, they have pros and cons you know, our approach has been a cellular perfusion solution.

So in other words, not a blood based perfusion solution, there's different advantages and disadvantages to that. And then a in the original, um. Iteration that of the Toronto EVLP system, which was from like 2008, you know, the components were separate. So they were, you know, like an ICU ventilator, the separate pump, a separate reverse oxygenator with a reservoir well, You know, in the dome, that's like the classic dome and has now been kind of

combined into the system that we're using, which is from TRIFAROX, a company called TRIFAROX, and it's sort of like more compact box, but it's basically all those components among other things.

And and it allows you to sort of sustain the lung outside the body for a varying amount of time in the lab, we've done it for, I don't know what the max would be in the lab, but certainly we've done it for. You know, longer periods of time. Clinically, we use a minimum of three hours. Sometimes we stretch it to four hours.

We tend not to go much beyond that. But you can and it's really neat. It's a it's a, you know, the perfusion solution has, different components, antibiotics, steroids, glucose, other things. And and we can get all kinds of parameters like You know, ventilatory parameters like compliance and airway pressures and we can do x rays and bronchoscopy and You know, you can take gases you can look at function.

It actually measures the glucose I shouldn't say the solution has glucose in it, but it does Accumulate glucose as the lung is perfused and then you know It accumulates lactate as well because the lung makes

lactate you can measure all of these things And you can measure the compliance, as I mentioned, and you can sort of, you know, measure the text, like the physical texture of all along.

Are they getting boggy? And all these other things that help you make your decision. Not only does it perfuse and ventilate the organ. It also gives you a whole host of avenues for diagnostic tests and things like that. Yep, exactly. And so, you know, we, the way we use it are, is sort of the parameters that I just mentioned, but there's, I think a whole, you know, a big possibility of other kind of, you know, biochemical perfuse eight and other things that we could do that we are really just scratching the surface of.

So how do you decide? And I think you, you hinted at this. this topic earlier, but how do you, as the transplant surgeon decide this is a pair of lungs that would benefit from EBLP versus this pair? Maybe not so much. Yeah. Yeah, yeah, sure, sure. So the way I

use EBLP and this gets back to, the original, you know, thing that you said, which is, well, maybe EBLP can help us start our transplants at 7am.

I don't use it as that way, although you can use it. For logistics. We sometimes do that. We use it really more as a, like a diagnostic. At least that's how I use it. If I'm not sure, well, there's a question about whether a set of lungs is good enough. I check them using EVLP. So situations like might be, you know, for example, if they see the lungs seem good on the clinical assessment and we go to assessment lungs and all of a sudden the gases are no good.

And I can't figure out why the gases are no good. And I'm just not sure, you know, the donor operation, there's a lot of variables. Sometimes the PO two's aren't good for. Reasons of hemodynamics or other problems unrelated to the lung, but I don't feel that I can just sow this lung in right away. Mm-Hmm, , we'll check it on an EVLP circuit.

DCDs are a great example. If you're worried that the DCD that the patient might have aspirated during withdrawal, you won't necessarily, you know, you might not necessarily see

it at the time of bronchoscopy. Obviously you put the bronch down and their green bottle in the airway, well, okay, fine, they've aspirated, but you could aspirate a little bit of saliva or even some stomach content and it really doesn't take much to get a terrible.

Aspiration injury, and it might not be super evident on the bronchoscopy because the solution, the secretions that they're aspirating are clear. So, you know, we'll check a lot of those lungs on EVLP, particularly if it's like a prolonged withdrawal, prolonged diagonal time, excuse me. That's a very good example.

And then, you know, I think the holy grail of EVLP is can we use it? Fix lungs. I think there's. Not that many situations where I would be hoping to fix a lung per se. I think this is really the potential of EVLP more so than the current reality. If you know, we have the lungs outside the body, can we do something to fix them?

The best example that I can think of that we're doing currently would be like would be like for PEs we can, we'll thrombolyze PEs readily. So, so, so that allows us to use a lung that

if you don't have the capacity to thrombolysis a PE, you might bring them home and put them on UVLP and give TPA.

So we do that readily. I'm trying to think of other things that we might be able to fix. I mean, I think currently, you know, it's a, it's more of at least the way I use it it's to help give me confidence that the lungs are going to be okay. Or if there's a unilateral problem and I want to try to salvage the other side, that's another indication where I might say.

Okay. You know, I'm not sure they're good. The other side is good to use, but if we put them on EVLP, we could try to save both. One side goes down. You can clamp out one side or the other and use the other side. So those are kind of the main indications I would say. Interesting. So it's, it tends to be scenarios where there's some sort of, at least in your practice, some sort of ambivalence as to whether or not that donor lung or pair of lungs is Immediately ready to go into a recipient.

Yeah. I think it's a diagnostic check. Generally speaking is how I would, is how I would use it. Right.

So, trying to think of some other scenarios, you know, if there's some, if there's something about it that I'm not sure about. And I just don't, I just don't know that it's safe to put into a recipient then I would put them on EVLP.

I think that's the general idea. I see. Do you think that that allows for you and for the institution or even on the large scale of transplant programs nationally or internationally, do you think that that allows for potential for more donor lung use? Do you think that? A lot of those lungs that you decided upon EVLP for the reasons you described would be lungs that you would have passed otherwise.

Yes. And no, I would say. I think it does two things. I definitely think that having a backup of EVLP, if there is uncertainty at the time of the donor operation allows you as a sort of gives you a little bit of a backstop, gives you the confidence to go out and look at a lung that you might not otherwise

be too sure about.

I think and I think what happens is half the time you go out, the lungs are fine. They actually don't need EVLP, but I think it gives you a backstop and the assurance to just be a little more aggressive about what you're doing that. I think, you know, that's a little bit program contextually specific.

I mean, I think, you know, our program, if we didn't have EVLP, we'd still be very aggressive, but I think, you know, for example, when I've been in other hospitals, like, I think it, it just gives you a little bit. More assurance that worst case scenario, if I'm still not sure after the procurement, I can put them on EVLP and check them and make sure that they're safe.

So, so I but the reality is half the time you go out they're fine. Right. I mean, I think you know, we know the donor use rate is very low and that's because we're really not looking at that many lungs. You know, and I don't we didn't really talk about at the beginning, you know, how to increase the frequency of lung transplantation generally, you know, the overall use rate for donors is like 20%.

It's very low for lungs. It might not even reach 20%. It might be sub 20%.

And, you know, one of the ways that we need to address that is just by, by like, Going and looking at more organs because the way that we currently assess a donor is very subjective. It's very fraught with Uncertainty and you really don't know until you go and look at it and so I think one way that EVLP helps is by sort of Giving you the confidence to have an attitudinal change in your approach, which is you know, what there's adalactosis on the CT There's this on the report.

There's that there's whatever we're just gonna look and maybe they'll be okay when we assess them and you know half the time or more You go and they're fine. They're just fine. Interesting. They're just fine. And you can just put them right in. So I think EVLP changes your attitude in that way because it gives you a backstop.

So, and then does EVLP allow you to salvage some lungs? I think it definitely does because I think, you know, when you talk about things like, I don't know, a DCD that you're not sure aspirated PE that you're not sure, you know, can you use it or not?

You can bring them, you can check them on the circuit, and sometimes they're not good, but sometimes they are good, and those people, those donors, may have had to be declined because you just aren't sure they're safe.

You know, maybe it provides you some comfort in that decision making, and they make you, like you said, Go look in the first place, you know, my own limited experience in the donor space, I do sense that there's a lot of hesitance to even go in the first place, if there's any shadow of doubt that those lungs are going to be usable.

You know, the topic of kind of. You know, how do we increase the use rate of donor lungs is a major challenge. And I think EVLP plays a part in that, but I think a lot of it is also surgeon education, you know, encouraging programs to take those risks. I mean, I think, in the U S particularly, I mean, I don't know so much about.

You know, the allocation and the regulatory environment of places like, like in Europe or Australia or other places or Asia where they're doing, you know, where they're doing lung transplant, but I think in, in, you know, in the United States,

there's a lot of sort of pressures that are being put on the programs, which pushes them to say no very readily.

I mean, it's always easier to just say no. Right. And some of that is the regulatory pressure, you know, So some of it is just that. There's low volumes. And so even one bad outcome can kind of screw up all your statistics. But the other is just that it's a huge resource investment.

And I think, you know, it takes real commitment on, on the part of of an institution, not just of a group of surgeons, but of an institution to really commit the resources necessary. To do this, to go send teams, to look at organs that might turn out bad and to kind of, you know, incorporate that into the, you know, the, with the interruptions, like just the unpredictability of it, the interruptions to the elective schedule, the operating room, the ICU, et cetera.

It really requires like a real institutional commitment to be able to do that. But I think, you know, the shortage of donors could be addressed if we just got a lot more aggressive. And I think, you

know, EVLP factors into that. But I really think just trying to, just trying to evaluate more lungs directly would go a long way.

One of our research fellows recently looked at our donor use rate and our donor use rate in the greater Toronto area is something like 50 or 60 percent. Wow. Right? Nationally in the U. S. it's like sub 20. So like, you know, and there's a lot of reasons for that. I mean, all, a lot of the things. That I just said to you, institutional commitment, resource commitment.

I mean, all these things you know, we have, and it's really It's a testament, I think, to, to the system that's been built, but not by me, but by my senior partners, I came kind of, you know, trained in it and kind of walked into it, I'm a beneficiary of it. I think it's amazing, but I think it I think it's it's really translated into, you know, into what I think is a model for what other centers could do to try to increase that, that, that use rate.

It kind of makes me think about is that there seems to be at least around here, a

higher. Movement of local procuring teams, and then the organ comes the recipient rather than, you know, sending a whole team from your hospital. Do you think that that's something that may become not only just feasible in lung transplant, but acceptable by lung transplant programs?

And does, yeah, yeah, that's such a good question. That's a really good question. And I think, you know, some of the barriers are because things are the way they are. I mean, the way that we do this, where we send a plane full of people to go to another state rather than having like centralized sort of organ banks, I mean, all these things, I think, maybe in the future, you know, you could say, I mean, shaft kind of taught has a talk where he, you know, kind of goes over what the future of this might be.

It may look a lot like blood banking. Where we have kind of central banks of, you know, of organs that can be redistributed. And maybe we'll look back on this in 20 years or 30 years and think

about how crazy it is that we go send a bunch of surgeons to fly across the country in the middle of the night to go get an organ.

Like that may seem like a really crazy thing to do in the future. In some way, it is a really crazy thing to do. On the other hand, I will say, and I think there's a solvable problem, but it is a problem. I know that my team. Can salvage lungs that other donor surgeons cannot salvage. And I think that the expertise and that subjective judgment about.

Whether to use a lung is really important and and it takes a long time to develop that judgment. And so, you know, currently when I can, I want my team to go because I know that particularly if I'm looking at kind of a marginal organ, I just can't. I just can't, I just can't trust anybody.

And I think I think EVLP has a role here too. You know, if I'm having a donor surgeon who I don't know, procure an organ for me all often, if not every time, put them on. EVLP to check that they're preserved properly.

So, cause it's just so subjective and I think that gets to the need for a general kind of increase in educational quality around lung transplantation.

I think for a long time, lung transplant has been kind of a sidebar of heart transplant. I think that's part of the reason why we used to store our lungs on ice because that's how you store a heart. And there was not a lot of thought given to how, how to make, you know, how to optimize it for lungs because it's been kind of a sideshow to heart transplant.

And I just think, you know, we need to kind of, you know, increase the our sort of dedicated efforts to teaching people how to do lung transplant, teaching people how to. for cure lungs. And I think it's happening slowly. And I think it's something that we'll get better at. Yeah, it's interesting. The blood bank for organs concept is a interesting thought process.

I just think about how much more complexity and higher stakes there are when you're talking about Banking and Oregon versus banking packer of blood cells and things like that. And yeah, sure. I mean, I think that's, I mean,

that's I can't speak to how that would work per se, but I think it's important for us to maybe think about, you know, think about how this could be done a bit better because it is kind of crazy the way we do it now.

So it certainly sounds like you're kind of circling back to. the nuanced decision making around utilizing EVLP for the donor lungs versus not. It sounds like at least in your practice and maybe the group's practice at Toronto, it is a bit of an individualized decision. Do you perceive that EVLP use decision making is variable across institutions?

Are there some that are very standard about their approach to it that have kind of like protocolized systems? Protocolized systems for Selecting who they're going to put on, which lungs they're going to put on EVLP, or which lungs they're going to take off EVLP, or what. Maybe both, you know, prolife system, say every donor that's above this age and has these things goes on

every month.

There might be, you know, there, there might be. And we have some kind of general guidelines. I think I don't know the practice of other centers, so I really don't, I can't comment on that. But it is an individualized decision and it's about surgeon comfort and it's about the organ and it's about how they're preserved and it's about who's preserving them.

And it's about. All of those things. And so it's, it is really, I think I think it's not really possible to say, well, every single lung of this kind should go on EVLP it, you know, it's an individual decision that the surgeon has to make, I know we kind of talked about this a little bit in a broader topic of donor utilization, but maybe we can focus a little bit on the concept of centralizing EVLP use.

I know that it, there's kind of been this advent of. quote unquote, EVLP centers where lungs are procured, they're brought to a location where EVLP is available, and then those lungs may be brought to a recipient hospital that's elsewhere. What do you think about the benefits

and drawbacks of centralizing something like this where marginal lungs that would benefit from EVLP and further assessment kind of cluster into certain locations and then disperse from there for centers.

Yeah. I think that's a bit contextually specific. But I think there, there have, there are a few places like lung bioengineering and others. I'm not familiar with any, like an academic medical center who will like do it for the state. Although I do recall when I was at Michigan, there were some discussions as to whether, you know, we were going to set up one at Michigan that would be sort of the EVLP provider for the state or where that was going to be or whatever.

So I mean, I think there's a lot of discussions around that just to give you a bit of sort of background about our context and how we do this. You know, we. Have a separate kind of almost an, it's not really an operating room, but it's kind of a a two room operating suite that is set up just for organ perfusion.

We have like a staff of people who do nothing but EVLP

with three main guys who are kind of alternate on call with research fellows who come and help them. And, you know, they've pumped over a thousand lungs. I mean, they really know what they're doing. And and they're on call for that 24 hours a day.

And so, you know, that's the kind of institutional commitment you're going to need to make this work at an institutional level. The reality is that's probably not feasible for most academics, thoracic surgical groups. I mean, certainly, you know, when I was at Michigan, we tried to do this and, it's just not.

possible if to do it easily if you the surgeon yourself is going to have to sew the lung onto evlp and put the lung on evlp and kind of you know tend to the lungs and make sure they're okay and whatever and it's really just not that feasible for groups of academic surgeons who have other things that they need to be doing like for example the implant and then you know their clinics and their general you know whatever their oncology practice and all these other things to also be maintaining an evlp lab And so I think the centralized

model works really well for that, actually.

Because, you know, you can send the lung to lung bioengineering where they have their own teams of guys who do nothing but that. And so they do it well, and they are on 24 hours and, you know, and they do a really good job. And I think that's a lot of a lower bar than trying to set up, you know, the way we've set it up.

That, that being said, it's not impossible, but I think you know, to do, to sort of do it yourself. I think. You need a certain volume to stay competent, which has been a struggle, I think, in a lot of academic places that have tried to do this, that it's just, you just have to keep doing it. And it's hard to do, but there are places that have done it, you know, there are places that have done.

So it's possible to do it either way. But I think the centralized model makes a lot of sense. Yeah, I guess in one sense, it almost seems like a potential solution to the catch 22, so to speak of if you're a low volume center, you're probably more conservative with your donor utilization for fear of adverse outcomes and those effects.

But if you're a low volume center,

you may not have the benefits of kind of that safeguard of having something like EVLP at your disposal. So now you're even more conservative because you can't take those chances maybe quite as easily as a center that is higher volume, has more experience with those technologies, has those at their disposal, whether it's at their home institution or elsewhere.

Yeah, I mean, I think, you know, the theme of trying to increase. donor utilization and look at more lungs and convert more donors to successful transplants. How to kind of leverage this technology to do that. I think the centralized model helps immensely with that. I mean, I think The other thing that you get with that is also is I know lung bioengineering does this.

I think the other companies probably do this too, is you get some amount of consultation also with people who do a lot of EVLP. I think the mentorship aspect is quite critical. Because the volumes just by their nature are not high. I mean, for

us, you know, we're doing, we did 219 lungs last year, which was the most we've ever done.

I think probably the most that anybody's ever done. And that's only 219. Right. I mean, if we were a cardiac program, we would be like the lowest volume cardiac program around. It's like nothing. Right. I mean, the scheme of surgery, that volume is not high. And so when you talk about, you know, how to, you know, like, and how many lungs went on EVLP lecture, I don't know the number, but.

It's it's not super, super high volume. And so, if you're doing 30 a year, your volumes are going to be even lower. And so I think that's, I think that's a perfect application of where, you know, you, you might be able to get the expertise of people who do a lot of EVLP, you could start to look at some, maybe what you used to consider marginal donors.

Put them on EVLP and and check them before you put them in. I mean, I think that's definitely a way to gives you a bit of a safeguard when it comes

to trying to expand the donor pool that you're considering. Just shifting gears a little bit. What do you think? We talked about how resource intensive lung transplant overall is in terms of critical care capacity, specialized personnel.

Logistics and travel resources, especially if we're sending our own donor teams out. What are the, what are some of the cost implications of, EVLP, part of the financial calculation of lung transplantation. And do you think that to some degree, those cost implications may weigh into institutional or individual decision making and use of the technology?

Oh, for sure. Yeah. Yeah. I think the cost implications are huge. I can't quote all the costs, but they're high. And that's generally, I think not the personnel costs on top of like the equipment costs and it does factor in. And I think that's why, you know, being really. thoughtful about what lungs you're putting on EVLP is important.

That being said, you know, the idea is you're going to hopefully, you know, the access to EVLP gives the surgeons more confidence to go look at more lungs. And may increase your non EVLP transplant volumes just by nature of that. I think that's why it's been it's a little complicated of an argument to make from a business standpoint because you know, you're definitely putting on some lungs that you would have discarded.

So from that standpoint, it's easy because those lungs would have gone in the garbage. And so instead you're transplanting them. So that creates revenue to the hospital. So. There is a business case from that standpoint, but I think it's a lot harder to measure the attitude change that comes with that.

That also helps you to increase your volumes. But yeah, I mean, you know, I think the cost issues are significant, but I think the cost issues of, you know, having a patient who either gets a lung that didn't go on EVLP that should have and winds up in the unit for a month or

dies you know, what's the cost implication of that versus.

Or what's the cost implications of having, you know, a super sick patient and respiratory failure who should have got a lung but didn't and is either really sick in an ICU or dies, you know? So I think I think it's probably cost effective, but I'm not an expert in that, so I can't really tell you.

Sure. But the cost implications are the cost implications are real. I mean, and they have to be reckoned with for sure. Yeah, definitely challenging to suss out. I'm sure, you know, especially when you're talking about these kind of like abstract concepts of potential, you know, life outside of ICU or life inside of ICU.

So broadly speaking, last real question about. All this, what do you looking into the future? What do you envision not just in the context of BVLP, but maybe in the context of donor utilization of lung preservation, what do you envision are the next big steps? Over the next five to 10 years. And how do you predict that

the lung transplant landscape at large may change in relation to that?

Yeah, that's a sort of a multifaceted question. I think what we will see is I think 10 Celsius is taking off like crazy. And I think that's going to, you know, that's going to, I think that that will supplant ice based preservation if it has not already. I think there's going to be somewhat of a duel between all the companies to sort of position themselves and who's going to sort of, who's going to dominate in the 10 Celsius preservation world.

But I think, I do think as a concept you know, it will help us do better for the patients. I think the potential of EVLP to try to start really maximizing the therapeutic aspect of it as opposed to just sort of the diagnostic aspect of it. And I think this is kind of what, you know, certainly You know, my partner shaft and Marcelo have been working on for a long time what that's going to look like.

I'm not an expert on, so I won't go too much into it, but I do think, you know, obviously that is an

untapped potential. And I think in kind of a less like, for lack of a better word, sexy way, I think, you know, lung transplant is relatively new, right? The first really successful one. It was done at TGH in 1983.

It's only about 40 plus years old. I mean, that's not really that old when you compare it to stuff like first esophagectomies being done in 1907 or the first Whipple operation, which was, I don't know when, maybe in the 20s, I think, but like a long time ago. We don't know so much about it. And I think, you know, one of the focuses for me anyway is like, You know, how do we start making this better in the same way that we've made cancer surgery better and safer, which is studying maybe more mundane things like, you know, what's the rate of VVT, PE, atrial fibrillation, all of these things that we've been able to address in these other populations.

We've never really tackled in lung transplant. So I'd like to see that kind of come of age a little bit. And I think that the donor utilization question is,

has dogged us for a long period of time. I think we have a way out of it, but I think that it's, I would like to see that change a lot. I mean, I think we're just not really using organs that we could be using and there is not really a good reason for it except that we just don't want to go look.

Well, sounds like an exciting time to be a lung transplant surgeon. I think it really is. I mean, I think we're doing more transplants. We're doing them better. We're doing them more safely. I think the patients are doing better. You know, if we could tackle chronic rejection, I think we'd be laughing, but I don't know how to do that.

I'm not a respiratologist or a pulmonologist, as you would call it in America, but you know, that's a major problem that we have to fix. But I think, you know, I think it'll allow us to, and we're already sort of expanding the indications, but you know, we're transplanting older patients now, like we're transplanting

patients, 70 plus.

very readily. You know, we're, they're doing, you know, reasonably well, at least the same kind of the same as our other patients from what we can tell. So we're transplanting more people with more donor organs. And we're doing that in a way that's safer. And I think some of these new, you know, technologies, EBLP technologies and things will be able to help keep pushing that farther.

So, yeah, it is. Awesome. Well, Dr. Rakeem, thanks so much again for taking the time to chat and for an incredible conversation looking into the nuances of organ preservation and lung transplantation. And yeah, I think the speed at which the innovation is happening is really Interesting and exciting. And I'll certainly be interested to see what things look like in the next five to 10 years.

So real appreciate your time. Yeah. Thank you so much for having me. It's always great to talk about this. You know, it's something I'm really passionate about, but I think I would be remiss

if I did not also. Shout out my senior partners who have pioneered a lot of this stuff that we've been talking about and who have been working for since maybe before I was born, I'm not that young, maybe, maybe, maybe slightly after, but for a really, really long time to get us where we are.

And so, I mean, credit goes to them for kind of like seeing the way and. Awesome. Thanks, Dr. Joaquim. And if anyone has any questions for Dr. Joaquim or is interested in lung transplant or anything we talked about here, you can reach out to us at behind the knife as well at hello at behind the knife. org and we'll put you in contact.

Thank you so much for joining us. That concludes this episode. Once again, thanks for listening and as always dominate the day.