 Welcome you to the winter quarters program in the McLean Center seminar series on ethical issues and organ transplantation. We're just delighted that Dr. Gottlieb will be the first speaker in that series. As many of you know, Larry Gottlieb is professor of surgery, directs the burn unit and the complex wound center. And has been a faculty member of the McLean Center for Medical Ethics. After graduating from Penn State, Larry completed his general surgery residency at Yale New Haven Hospital and at the L.A. County USC Medical Center. His clinical and research interests include reconstructive microsurgery and patient care, and he serves as a program director of the reconstructive microsurgery fellowship here at the university. He's also active on many other tumor boards, melanoma board, head and neck cancer, pelvic health and the like. Today I'm delighted that Larry is returning to a topic that's been of considerable interest to us, and that is the topic of composite tissue allografts. Those of you who attended the McLean conference may recall that the first day we had two talks, Dr. Breidenback who did the first American hand transplant, an example of composite tissue allograft, and then Maria Siminoff from the Cleveland Clinic talked about doing the first facial transplant, another example of the vascular composite tissue allografts. Today Larry is going to talk about vascular composite allografts of the abdominal wall. It's a pleasure to welcome you and thanks so much. I have a little different perspective. Although I am positive towards composite tissue allografts, I think they gave somewhat of a skewed point. So what I'm really going to talk about today, rather than what it was originally billed as, is update controversies and thoughts on vascular composite allografts. In addition, we will have the abdominal wall part at the end, just because that's not an hour's worth of discussion. But this I think is, I have nothing to disclose. So what's a vascular composite allograft? As many of you know, it's a non-solid organ body part that may be transplanted from one person to another, just like a hand, a face, a larynx, that have been basically any part of the body at all. It needs to be harvested from a heart beating cadavers. It needs to be revascularized in a timely fashion. Warm and cold ischemia times are similar to solid organ transplants. So Mark used the term composite tissue allograft. I'm using the term vascular composite allografts. Anybody know the difference? There is none. But it's really important. And why was there a major push to change the name? Human cells and tissues and cellular tissue-based products are under the auspices of the FDA. Solid organs are covered by NONA under the auspices of HRSA. Composite tissue allografts, CTRI, are not designated. But it's anticipated in the near future to be designated either under the FDA or HRSA. The issues related to recovery, matching and allocation of the CTAs are similar to organs, as I mentioned. And they're not adequately addressed by the FDA. Defining a CTA as organs would give them coverage on the notar and oversight over HRSA, not the FDA. And the FDA is a panacea. Nobody wants to be under the regulations of the FDA. We ran a tissue bank years ago, and it was very, very cumbersome. Therefore, to avoid the confusion, less somebody might think composite tissue allograft was a tissue, and would thereby come under the auspices of the FDA, we wanted to remove the word tissue. If there's much debate, everyone agreed to change the name to composite tissue allograft. They tried other things, two vascular composite allograft. They tried CVA, but that had sort of a negative connotation. And putting everything together, this seemed to work best. So now the appropriate lingo is a VCA rather than CTA. So today's talk, I'm going to have basically four parts that are sort of interrelated. Abbreviated history, surgical history of how we got here. An update on the VCA from my perspective. A little abdominal wall 101 for those who are not surgeons. And then a little bit of abdominal wall transplant. So the first written recordings of surgery is way back 5,000 years. Anybody know the connection to the Edwin Smith pepperis to the University of Chicago? It was translated by Breston, who started the Oriental Institute in 1906. Reconstructive surgery, actually any written report, goes back 3,000 years to India to Sushita, who has these volumes and volumes on everything you can imagine. He's really considered the first father of surgery. Reconstructive surgery is the use of surgery to restore and form the functions of the body. Frequently involves transferring a transplant tissue from one place to another on the same patient. If you will, autologous reconstruction or perhaps autologous transplantation. Sushita was the first to record the use of skin grafts and flaps to reconstruct the nose. Everybody know the difference between a skin graft and a flap? If you do, I'll just go on if you don't know, explain it. Everybody explain it? A flap has a vascular kind of animal. Right, and a graft is just taken from one part to another. It could be skin, it could be bone, it could be tendon, it could be whatever it is. After the original papers of volumes in 600 BCE, other than the legends of cosmos and Damien, which we've all learned about in our ethics lectures, there's really no trace of reconstructive surgery in the literature until the 1400s. And the first one we start hearing about is this Branca family in Sicily in 1450. But they didn't really make it, and they didn't make it because they didn't write anything. And like anything else, if you don't write, your name doesn't go on it. And Taglia Cosi became really the founder of modern plastic surgery from his book that he wrote on reconstructing the nose. And this is the original picture from that book where he says, we repair and fix the body parts that were given by nature and taken away by fate. We do this not to please the eye, but to support the injured person's hopes and help his soul. His work was condemned by his contemporaries, and they regarded his operations as illegal and crimes against nature. He was eventually buried in unconsecrated grave. Getting back to CTA, there's a legend that he transplanted the nose from a slave to a nobleman. And allegedly, the transplant failed when the donor died three years later, and there's a statue of him holding the nose. Two hundred years later, the gentleman's magazine ran an article that basically reported the old ancient Indian technique. And Joseph Carpoux was the first European to practice this Indian method of rhinoplasty. In the late 18th and 20th century, there was an explosion of reconstructive techniques described, including, way back in 1864, the first growing flap for extra fee of the bladder. There was details of every artery invading the body without any x-rays or anything else by Mancho in 1889. And Wagenstein described the TFL flap in 1934, and then Bipedical Thoracal Epigastric flap by Webster in 37. The next main advance also we've seen and heard about at this conference, which is Alexis Carell also connected to the University of Chicago with his vasculinastomosis and is also auto transplantation of the hind limb, kidney and the scalp. The father of modern plastic surgeries considered to be Sir Harold Gillies, and he had all these principles, which there were about 16 that then got expanded to many more. And the most important one for this lecture was replaced like with like. In World War I, there was a new injury. It was these massive facial injuries basically because of trench warfare. They would put their heads up and get their faces blown off. And nobody knew how to deal with it at all. And so Sir Harold Gillies was commissioned to, okay, all of a sudden you're a plastic surgeon. Actually, he was an anti-surgeon at the time. He established the principles of modern reconstructive surgery, one of them being replaced like with like. He developed the tube pedicle flap, and this may seem gross to you. This is an intermediate stage, and the only way at that time to get tissue to the face or from one place to another was to make this tube in multi-stages and waltz it up and ultimately have it cover a nose, a mouth, a forehead, whatever it might be. And this was really revolutionary because before people would just walk around with the big holes. Nobody else knew what to do at all. He and his student Ralph Millard wrote the book on principles and art of plastic surgery. And Millard went on to write a famous book of principalizations of plastic surgery where he says, when a part of one's person is lost, it should be placed in kind, bone for bone, muscle for muscle, hairless skin for hairless skin, an eye for an eye and a tooth for a tooth. The problem with autologous reconstruction is frequently we don't have those parts available. The next major advance is Peter Medawar, who many of you know was a biologist who worked on skin graft rejection. And he discovered acquired immune tolerance, which was really the fundamental research that led to tissue and organ transplantation today. And he also won the Nobel Prize 30 years later. Joseph Murray, we've also talked about, he is that he's a plastic surgeon. And when he wasn't doing kidney transplant, he was fixing pressure source and abdominal walls. And in 1990, he won the Nobel Prize. The next major change, of course, was the advent of new immunosuppressives with cyclosporine and then all the new things we have now, which then led to the solid organ transplant world of really going forward. For the second half of the 20th century, we had an increased understanding of blood flow, an explosion of techniques and concepts of how safely to move tissue from one part of the body to another. Initially with Bacangian, with his delta pectoral flap, which was a flap going in one stage, rather multiple stages, from the chest wall to the head and neck. And then in the 70s, we called the anatomic revolution, whereby basically people were discovering or rediscovering how the blood flow to muscles and skin were that we can potentially move it, either as a pedicoflap or as a free flap. A free flap is basically taking a piece of tissue with the artery in vein, dividing it, hooking it up again with the microscope to a different area. Again, an auto transplantation. The next major, I think, change in our thoughts was from Taylor and Palmer in 1987. And they basically developed this concept of three-dimensional blood flow. And it wasn't just in one tissue plane, but it was the muscle, the fascia, the skin, the subcutaneous tissue. They called these angiosomes. And vascularized composite allograft is the latest in the advance of this long history of reconstructive surgery that dates back 3,000 years. Currently, almost all, unfortunately not all, VCA is done throughout the world, or in the auspices of an IRB or the equivalent. It still should be considered experimental. One of the main advances here, there's a lot of things you'd only want to think about when you really focus on is the first one, which is Dr. Lee, who was at Pittsburgh and now is at Hopkins. In 1991, he did these studies in rats that showed that the energeticity of a limb is less than any one of its parts of the tissues. So with metawar, and up to this point, it was always thought that the skin was the limiting factor of us transplanting. And the skin indeed is the most antigenic tissue in the body, the skin in the bowel perhaps. But when you add fat to skin and muscle and bone especially, you take a composite tissue, the antigenicity of the composite tissue is less than any individual and definitely less than skin. And this finding actually is pushed forward to allow for composite tissue allographs, because otherwise we were limited on being able to move skin. And there's no way we'd be able to hear and so face or other parts. Those patients that are best candidates for VCA have no acceptable autologous equivalence. Where standard means of surgery are either not feasible, not possible or contraindicated. Over here you have Isabelle Dignoire, who is the first partial face transplant. We can perhaps reconstruct a lower lip, especially, and we can reconstruct an upper lip. We can reconstruct both really. They won't look very good. We can usually do an upper lip and a male with a mustache and it'll look pretty good. But to do both lips and have them work is essentially impossible with autologous tissue today. And it won't work and look reasonable. Double hands, same sort of thing. There's really nothing we can do that can make that work like hands will. Throughout the talk there's double hands and single hands that we're going to talk about. In the United States, mostly single hands have been done. You have to think about the disability with a single hand versus double hand and think about the fact of, again, life long immunosuppression for a non-life-threatening problem, which is the whole issue that comes up. And in Europe, many countries have restricted hand transplantation to only double amputees. And they will not allow it on a single amputee because they say, well, it's a helper hand and it's not really going to do that much. C, with two hands, this guy can lift and do basic functions. And with a composite of the nose and double lips, you can see that we can reconstruct something that we can't do with autologous tissue. There's an international registry of hand and composite tissue transplantation. Unfortunately, it's not totally up to date and everybody doesn't put things on. But this gives you a general idea about the types of tissues that have been done and about the numbers worldwide. And these change because just last week there was another hand done in England and there are things that are done that are sometimes not reported for a couple of months or even longer. But you have dozens of abdomens and almost 30 faces and a bunch of hands and then more single digits for mostly everything else. If you take a look at this list, which one do we not have either autologous or prosthetic possibility for? Ones. Anybody? There's only one I can figure out. It's uterus, right? That is, we might have a prosthetic. So obviously we have hand, a knee, we have prosthetic knees, and a larynx. We have provoxes or electrolux and things where people can talk. Now which ones do we have no good autologous reconstructive options in an otherwise intact body? That's basically, again, the eyelids and the lips, long segments of the trachea and the tongue. We reconstruct the tongue all the time but we're really just putting a piece of tissue there to baffle the sound or to allow for swallowing but it doesn't move. We don't know how to make a tongue that moves and works. The rest are really balancing the morbidity of recipient autologous donor site versus immunosuppression. So the uterus I found really interesting. Actually in 2000 in Saudi Arabia, they did the first uterus from a live donor. Unfortunately within three months it failed presumably from some vascular accident and they ended up removing it. Subsequently, there's been 10 years of research in different institutions, mostly in Turkey and Sweden where they've looked at mice, rats, sheep, pigs and non-human primates and showed that all these animals could accept uterine transplants. All the animals except the non-human primates, it's not clear if it wouldn't know that you didn't want to give it the time to do it because that was the last one they did they needed for their IRB before they could do the adults or the humans and they gave birth to healthy offspring. I think Karel did uterus also as part of his original series. It's actually pretty straightforward. I mean it's basically just a couple of vessels and it's not a technically hard thing. So last year, a Turkish group transplanted a cadaver uterus into a 20-year-old female, not gotten pregnant yet. Basically the protocol is they usually wait a year, make sure there's no menstrual cycles and everything is going okay and there's no toxicity. The other justification they had here is the number of patients that are on immunosuppression for kidneys or otherwise that have gotten pregnant may need some modifications of it, but that's not been a problem with those fetuses or babies later on. A Swedish group did two living-related donors from mother to daughter of uterine transplants. One was a 50-something-year-old to a 20-year-old and I don't remember the ages of the other one. Their protocol is to wait a year and then do in vitro fertilization and if a baby is produced, they'll then stop the immunosuppression and perform hysterectomy. Well then they would do another year. So they said one or two is what their protocol is. They're allowed for two. They're allowed for two. Get twins. So who could be candidates for uterine transplant? It could be women who have uterine factor infertility which is this new term I learned about. They've had hysterectomy for one reason or another or they have congenital absence of deformity of the uterus. It could be transgender women. A man that's now officially a woman. It could be a man. It's limitless. Ethics talks, it doesn't have answers, it just raises questions and eyebrows. What are the alternatives to women with uterine factor infertility? Adoption or surrogacy? And they're unique. They're unique because they're temporary to a few years of immunosuppression. Anybody know that some other transplant that is currently done throughout the world, mostly in St. Louis, that is also temporary immunosuppression? Somebody in the back should know that. So what do we need just a limited amount of time to have immunosuppression? It turns out nerve grafts. So we have a very large nerve graft. You can put it in, get the axons to grow across, the axons for the cell body and you have the sheath, and then you can stop the immunosuppression later and the nerve works. And people that either don't have or it's a very large nerve that you need, it works very well. Susan McKinnon from St. Louis has pioneered that and we've done most of the work on it. Interesting one is transplanting the penis. And in China, six years ago, they reported a case report of a penile transplant. 42-year-old male sustained traumatic amputation of the penis. They don't say how. The donor was a 22-year-old brain-dead male. It's not clear if the brain death was after the amputation of the penis or some other reason. This is from their article. And you can see, here's the donor, it's now intact, acutely, had some vascular congestion early on and then pretty much was recovering by two weeks. Allegedly, it was removed in day 14 because of severe psychological problems exhibited by the recipient's wife. And the surgeons swear that it was not rejecting and it was just fine otherwise and they have a pathology of the thing which shows no evidence of rejection. Get back to hand for a minute. The first hand transplant was in 1964. Again, there's the early time of immunosuppressives which were not good enough for the composite tissue allografts. And it was rejected since that time. Essentially, all the tissues of the hand, tendons, nerves, skin, whatever it may be, have been individually transplanted as well with success. The international registry started looking at quality of life in people that have been out for five or 10 years and they found that most of them are able to eat, drive, grasp objects, ride bicycles or motorbikes, shave, use the telephone and ride. Most people can't do those things very well without a hand. They all developed protective sensation and then more than 80% developed discriminatory sensation that is fine touch and be able to really use your hand well. They had eight-year follow-up on their first transplant and although protective sensation they had on everybody and the discriminative sensation they had on the hands, but anything more proximal did not. So they just had protective. There are now reports of bilateral arms, mid-upper arms, actually at the shoulder. It's a major, major issue is what happens with the nerve regeneration and whether or not the muscles that ultimately need to get renovated are going to be renovated because if it takes more than a year, those muscles lose the motor end plates. Composite transplants, there's an increased instance of acute rejection which we don't really know why except maybe we're just seeing it very well. It's also easy to detect, easy to treat because you see it right away. You see a change in the skin which is one of the controversial things which I'm not going to talk about as to whether or not it's appropriate to transplant to a blind person who cannot see that and if they don't have somebody all the time ready to be able to tell because the only thing you really see is sometimes is this change in color. There seems to be a decrease in incidence of chronic rejection. This has not been reported very much. Almost none in any of these patients. With hands or face. And it used to be thought there was no vasculopathy with the VCA's and vasculopathy seems to go with the chronic rejection until actually this year 2012 just a few months ago using advanced imaging techniques the Louisville Group actually demonstrated vasculopathy in one of their patients. They then went back and biopsied some minor vessels in a number of their patients and found that actually it is there. We just haven't seen it yet. World experience, the US has about 19. The world is probably about 60 now. 34 singles, doubles and then also only in China to do a single finger and put somebody under suppression the whole life for a single finger is pushing it in my mind. There are about 10 hand transplant programs in the country and about 24, 25 in the world. One of the concerns was was this really going to affect donors and we're going to get donors. But almost none of the programs have waiting lists and there's more donors than patients. Of the 10 hand transplant centers in the United States two have done none. They just advertise we want to do it. One has done five and one has done six. Louisville has done 99. Maybe off by one or two. Most programs have done only one or two. So the question is why? Why so few? This is the first many United States get a hand transplant by Bradenbach and this is the first double hand transplant Pittsburgh by Andy Lee. Class of question. This versus quality of life. It's a tough one especially if you talk on single hand. There are many improvements in prosthetics and if you have resources to buy the best that it's hard to justify. I have a number of in my practice of four limb amputees that would never even think about it because they're doing just too well with their prostheses. The amount of time it takes for rehab which is five or six days a week for six or eight hours a day for a year at least and if they don't put up with this rehab very aggressively nothing's going to work. It's like the old data of any hand surgery. You're only as good as the compliance of your patient because if your patient doesn't go to hand therapy you can be the best surgeon in the world it's not going to work. And then there's the funding issues. So it's about two million dollars lifetime for any of these about $350,000 right away and then $25,000 a year it comes out to about that. So the Department of Defense has bankrolled most of the transplants you've seen. Definitely the faces. Institutions have done it. Why do institutions put out that kind of money? Anybody know? The PR they get is hundreds of millions of dollars they translate to. I mean they cannot get that kind of PR. Now that's sort of changing now though first they made us fortune. Boston then. So as new programs come up it gets to be less novel so it ends up being less of a cash cow from a PR point of view. And then you have the problems of insurance dealing with experimental stuff and something that's expensive and most of the time they're not covering it. And thereby they're not covering the medication not just the acute surgery. Then there's the patient selection which is compliance and psych issues. You know I see in the burden unit we said you know there's always there's an occasional true accident but there's frequently some issue that goes on that leads to somebody that has a major loss. I'll point out in a little bit the two main patients the Cleveland's patient there's a gunshot wound and the Hopkins patients clearly a self-inflicted gunshot wound nobody talks about but that's just the classic finding. So you know are they pushing with this psych issues or not? Is it appropriate? I don't know the answer to that. But one of the most interesting things is that Louisville screened 600 interested hand transplant candidates and they transplanted 607. They had 600 people wanted it but they could only find 607 that would meet their criteria from a physical and psychological and resource point of view. So Lowryx was done first in Cleveland Clinic then the only other place that's really been done is in Columbia and it's not clear exactly how many are larynxes, how many are segments of tracheas, it's hard to say. One of the problems with larynxes is that the um if you didn't notice this, the the nerves don't really regenerate and it's true if you cut the nerve as we've heard in our ethics section before and you put it together right away or if you transplant it. Initially for years they said well why is it working on a transplant? It doesn't work at surgery. Well these nerves for whatever reason it's not clear when you put them together the muscles don't work they're not coordinated and even the 1998 patient still has a trache but is able to use his larynx to a certain degree but as a chronically open mid-level larynx. And then so you have to say okay so the nerves don't really work but if you want to be on chronic immunosuppression why don't I want a larynx versus a trache? So what do you need your larynx for? Well you can speech or you can have an artificial speech what else? Some of the things we don't think about you can't you're swallowing, right? You can't smell if you can't bring the air by if you have a trache that's bypassing your oral nasal you can't smell whereby you can't taste very well. And then the other thing that you wouldn't think about it's hard to lift a cough and strain right because these are things that you have closure of your pharyngeal sphincter or making a valsalva you can't do that with a trache it's all open so it's limited to what you can do then I've seen written that it's really hard to kiss as well obviously people can move their lips and I just saw a patient the other day and I was in my clinic and I was asking him about it he said tell me about all the things you can and can't do kissing he said he's been married for 30 years he doesn't kiss very much anyone so he couldn't he couldn't sell me but it's really pretty miserable for people which they don't always tell us the most we talk about it we tend not to talk about it too much there's been a number of studies done the impact on the offerings on people to function as a society and many of them end up being reclusive and depressed but when they come to clinic they're you know have a smile on their face and want to keep doing what they're doing and when asked in this paper whether they would give up 10 years of their life whether they would take the risk of emotional suppression to be able to be normal the answer is yes and then when you tell them well the nerves don't really work the risk of the emotional suppression they say well maybe the best candidates for face we're going to get back to have no acceptable autologous equivalence we can't otherwise reconstruct with a reasonable aesthetic result we've talked about this lady already so the technical part we really figured out I think you've all seen that in the news we can keep the tissue alive we've pretty much figured out the immunology part I mean we're so far the ones that have been done years ago are doing reasonably well and the ethics of restoring the face for quality of life has been pretty much agreed upon by most so why is it still experimental and not standard of care because there are a lot of unanswered questions typically we compare composite transplants to solid organ transplants specifically kidney as far as the data and we say okay we use that for the immunosuppression that was initially used and we because we don't have our own data same risks, opportunistic infections, metabolic disorders diabetes, skin cancers for liverative diseases and most labs are working on minimizing immunosuppression the Hopkins group is on one drug and other ones have different the Boston group has a tolerance program and everybody's looking for this holy grail of tolerance which we may or may not have a get to probably most likely to be minimal tolerance if you will or just one or two drugs since lifelong immunosuppression is thought to decrease lifespan by 10 years at least the old stuff that we've had the typical face transplant candidate is asked would you give up 10 years of your life for a new face so you can function in society and they all say yes the one thing they're not necessarily told is that my understanding is that the 50% of the non-living related kidneys will be lost in 10 years due to rejection intramole proliferation arterial occlusion so not only are they just shortening by 10 years but they're actually limiting their life to 10 years and this leads to one of the biggest controversies in face transplants today what is the exit strategy what happens if it doesn't work so kidneys patient goes back on dialysis patient if it's a liver or heart lung if the patient dies but it's a life-threatening illness already or they get back on a transplant list in the face it's not a life-threatening reason why they got it can we just take the face off are the conventional donor sites left if you've gone through all your reconstructions before and will the patients survive it's really really complicated if you look at the first transplant there's a partial face right nose and lips so if we lose that what happens she gets back to what she was pretty much not so significant maybe a little gin skin is missing but pretty much this is what she would be like if she ended up losing the transplant as experience grew it became clear that partial face transplants were improvements but not great gentlemen this actually is vitiligo from an acute rejection phenomenon and all of a sudden everything just turned white these are clearly improvements from before but you see seams, you see difference in the skins especially you see these people close up and they're not quite as good as you might want them to be or as people want to think you think that they should be and that's why the Boston group and others started thinking about full face transplants even if it meant removal of normal skin and it's really really interesting because it takes a lot of guts if you look at this kid here all those diseases down here and they're replacing everything here and this is because this guy they had a normal chin they left it and they put all the face around it and the only thing that's abnormal is his chin the problem is they've taken normal stuff is that although the skin full face looks good you really want it to look good you really want it to hang right in order to droop and everything else you take the bone and it's pointed as one piece a little bit cheekbone, a little bit of maxilla, a little bit of chin this is the latest Baltimore Edward Regas University Merlin Merlin group and they took you can see this is the guy that had the self-inflicted gunshot wound he's had a bunch of reconstructive surgeries and his cheeks are not bad his eyelids aren't bad his neck isn't bad and they wanted to hide his seams so here's the seam for his transplant here's the scalp all the way down and they threw everything else away but in addition they took mandible from about here to there they took maxilla and they threw all that away and then they put this on and tongue part of the tongue now what happens if this fails is this guy going to be able to survive did they really talk to him about that what happens if he rejects what happens if he develops a tumor three of 23 face transplants have died already weren't from China only because they weren't given enough medication and went to a rural place and ended up not taking their immunosuppressants a known problem in France, Lentieri who's done most of the face transplants in the world actually had a major burn patient who when he was a burn victim had pseudomonas sinusitis he was a couple of years out already and there was no evidence of any infection they do a face on him and hands by little hands same time the question was was it the antigen load or exactly what the story was but he got septic from the same organism from a couple of years before and ultimately one of their trips back to the OR rested and died so our last month at a meeting actually in Chicago at the SRT this guy from Spain who tells us oh cancer patients if you want five years out you fine let's say I had a patient actually it was a friend of his who had head neck cancer, laryngeal cancer actually 12 years before no evidence of disease so he said oh can we do your face? it recurred with the immunosuppression and he died from it so Lanteri tells his patients if it fails you will die he is absolutely convinced of this they get septic, they get sick you can't get the medication off fast enough you can't get the face off fast enough there's no way that you can keep them alive especially the more we're taking out the more bones and everything else because you have this giant raw surface that you're leaving somebody with in a failed transplant so the next question is are there any conventional donor sites left and the next question is if you have somebody that came in let's say with a self-inflicted gunshot wound or some other trauma and you know from all your experience and the world's experience that you can't do a really great job and you're going to end up with one of these things should you skip trials and just go to a face transplant right away and then you have the real problem of consent because then you have somebody that has this terrible deformity where you didn't even try and you talk about a course of situation where oh I can give you the world if you take this drug if Lanteri is correct do we have to worry about this back up because if indeed we're talking about if it comes off you want to be able to have something that you can close the wound with who's the correct candidate psychological physical patients with malignancies how long is it safe there's a bunch of talk about this how bad a malignancy does have to be is it a basal cell, is it a cervical cancer, is it a lung cancer, is it a pedocyclic cancer which you're doing fluid transplants for children right you do kidney transplant in kids face transplant in kids then there's a conflict of interest the DOD money is a big one grants a big one competition giant ego even higher assuming that we have all the resources available and we construct almost any aesthetic unit of the face with conventional autologous techniques reasonably well what can we not do reasonably well with conventional techniques there's basically two both lips which we talked about and the other is both eyelids we know how to do the forehead, we know how to do the nose, we know how to do the cheeks we know how to do the neck, we know how to do all the other stuff and we can get pretty reasonable results enough that you would not subject somebody to life-long immunosuppression now if you have tolerance it may be different at this meeting a month ago there's the American Society for constructive transplantation this guy from France presented this mind-boggling case that drove me and everybody else nuts patient was missing his lower lip no question reconstructable and in order to have ideal function and an aesthetic unit he decides he's going to take both lips off and give them a unit like Isabella face transplant maybe even a little nose problem was PTLD post-transplant pulaviric disorder and chronic rejection the only treatment available for his lymphoma was to stop the immunosuppression whereby you take both lips off and you've given them a non-reconstructable problem he didn't tell us what they were doing and this was sort of just an intimate update but it was just where this concept of IRBs and some oversight and some ethics and some control of ego really came to light at this meeting domino wall 101 you know surgery is basically principles and concepts and anatomy I'm going to do a little bit of anatomy and then talk about principles and concepts talk about the concept of domino wall and then get into domino wall transplant there's a theory that don't know there's a bunch of muscles of the abdomen there's rectus abdominis external oblique and the abbasin between and then there's different layers there's antero erectus sheath there's a sheath in bobbin below internal oblique and transversalis this little girl on your right never had repaired we're now dealing with her and actually we have another patient like this and worse who all the guts are outside we're going to talk a little bit about loss of domain which is when the guts are outside and the inside gets smaller well if you're normal development and then also you do have a hernia or a trauma and you eviscerate all your guts your body was big enough at one point if you never had your guts inside it's not like re-putting it back in you're not stretching things out you really got to make some space really a major, major challenge then we have the acquired defects which are from tumors, infection, radiation, trauma, hernias everybody in general surgery have seen these and we've dealt with them we deal with the size and location so the big midline hernias we pretty much know how to deal with pretty well liver transplant or liver surgery whether you have a Mercedes kidney transplant hernia is a real, real problem and when we have both the Mercedes and here this is a real problem because not infrequently incisions come down here and denovate part of the abdominal wall so the layers we have to deal with are all of them, the skin fascia, muscle, fascia again and peritoneum and then we have to think about are these full thickness defects are they true losses or are they just separations can we get things back together or are we missing tissue, we're missing muscle that is there a loss of domain so again the abdominal cavity is unable to fully accommodate the abdominal contents within its fascial boundaries basically the abdominal cavity shrinks because there's nothing there pushing on it and the closure of the fascia if done too tight will compromise the circulation of the organs or transplant if there's one in there and fascial dehiscence is we see a lot usually from things being too tight and poor tissue or get abdominal compartment syndrome as a result of that so the indication for abdominal wall reconstruction is loss of structural integrity exposure of vital structures loss of skin integrity and contrived abnormalities one thing to remember because I get sent to all these giant hernias the small hernias are the ones that are dangerous small hernias have to come through and strangulate these giant hernias may be uncomfortable for the patient but generally they're not dangerous and so the risk benefits are very very different if I have an 80 year old with a small hernia I'll more likely do it than a 30 year old who's not very compliant patient with a large hernia hereby I have to think about all the comorbidities and all the things that you want to individualize as to whether or not it's going to cause a problem or not cause a problem so there's a guy who actually had a whipple what's his survival going to be and you know you get him to get in shape, you give him a year he's doing pretty well, he's still pretty miserable he's sent by the chairman of the surgery so he got to sort of do something here he is when he's lifting his legs leg raises to see that hernia come out here he is when he's asleep on the table really really good sign for us because this is scaffold it's depressed, it's not everything's not bulging out so I don't have to worry about stuffing things in I can just sort of manipulate and get those things closed and then we do it just define all the abdominal wall layers and ultimately close it that's what eight months is pretty good shape and he's back doing everything with no restrictions so open wounds that can't be closed acutely due to swelling they're usually temporized we'd had one of these the other day and a begota bag this guy that was resident in Bogota, Columbia called it that, basically a piece of plastic IV2B or something that we put in just to hold everything in place and you can see through it so you can see if the valve is live or dead or a temporary mesh frequently vicaral again to hold things in place vicaral mesh goes away loses strength about six weeks a little granulation forms and then either we can close it or usually when you have this chronic situation like this we'll just put a skin graft on it the problem is we'll put the skin graft right on bowel how do you get that off? well if you wait four to six months the swelling goes away this looser, realer layer sort of develops and actually you can just lift the skin graft right off the bowel even though it's put right on the serosa and it's pretty straightforward and there's a couple of spots that may be adherent to the skin graft there's this guy before, just look at what happened in the swelling he's trying to do a sit-up or a sit-up so again we find the fascial edges bring them together and get them closed here he is two months post up with the sit-up again the whole thing is centralizing the muscles, he didn't lose muscle there wasn't a problem so then what happens if we can't get the edges together there's two basic things passing incisions we can do to bring things together or we have to fill a gap fill a gap is a problem Oscar Ramirez in 1990 described this thing called component separation which has been a big craze the last number of years and component separation is basically this is the rectus muscle rectus muscle, here's the external oblique internal oblique and incision is made usually we're in the belly already right here usually through the fascial portion to separate this from this the nerves to this come in this next layer so down here so if you don't go through the internal oblique you're going to be okay how much time do we have are we supposed to be done? okay I'm going to go real quick then and basically you get things closed that goes to 130 alright this is component separation and here's the certain limitations its defect size I'll just go through it quickly here's a double kidney transplant multiple problems large fascial defect here's a Mercedes type incision so I'm not sure why he because he had all these infections would treat it with a tensor fascial autograph and end up closing I'll go through quick this is a disaster that many people will see the main reason I want to show you this I'm just going to go through just look at the pictures this disaster belly here we use in the alloderm mesh unfortunately it not infrequently gets infected it's left open then we went to a thigh and ultimately able to close this wound with a thigh flap because we didn't have, I'll go through that and here we have the wound closed and able to actually close the donor cell with another flap this is a different patient and I show this patient again to show the difference we need all this tissue these are the donor sites that we need versus if this was a transplant patient we could take that from somebody else and not bother with the legs at all so two classes of patients one without immunosuppression and the other ones with immunosuppression they're getting transplants anyway here's a guy that came to me who had a kidney transplant with massive complications and the question was should he get autologous reconstruction or a CTA there's the repeat liver transplant patients all develop abdominal wall hernias and the question is would it be reasonable to harvest a part of the abdominal wall when we get in the next liver so a tiny bit of separate time although you could do it separately there's no donor cell mobility there's no increase in immunosuppression and you minimize subsequent surgeries the main stumbling blocks of CTAs is the cost of immunosuppression and the controversy of immunosuppressing non-life threatening problems and then choosing the appropriate recipient and donor availability if we're taking somebody that's on immunosuppression already we don't have to worry about the cost we don't worry about the ethics of using immunosuppression considering this I got an IRB to transplant abdominal wall actually any BCA in somebody that's on immunosuppression already there's a guy who comes to me with a complaint about hernia he's hypertensive, he has CVA he has asthma, chest pop phase apnea and end stage renal disease until he got his double kidney transplant with a complicated post-operative course so in 2008 he had this he had a problem with his airway right away he had a wound to hissins soon afterwards with evisceration as all his guts came out at the bedside and he kept doing that wound to hissins same thing, this was the last one actually a different surgeon operated on him and still got the same thing and he was ultimately got some allograft on that granulation tissue as a temporary thing and then autographed and then he was actually sent to me as a possible abdominal wall transplant and then I realized I gotta deal with this loss of domain before I do that because if I can't get all this stuff in I can't build a abdominal wall that's that big this is his CT which shows basically all his abdominal cavity it started to grow and it was clear that there was a lot of ascites sent them to nephrology and liver they did liver biopsies, they did portal pressures, they did everything and nobody could figure it out everything was negative so I made a presumptive diagnosis and I made it which is called the site's attraction of cites that is all that the evidence can pull down and so it's for inflammation and it's doing it so if I was right, reducing it we corrected the cites so we drained it a little bit didn't really change the size of the hernia and we set up this crane in the OR which we draped then hang things up so that we can have some control ultimately go real quickly we were able to stuff everything in but couldn't stuff it enough that we can get fascia closure so we had a bridge it so we bridged it with some porcine stuff temporarily closed it but I knew that porcine stuff was going to go away a little bit of graft here with the kidney allograft underneath it so six months later I was planning to remove the acela dermal matrix same setup, went in wanted to get rid of the scar had fascia to fascia and ultimately was able to do that and here he is six months post up four years after his kidney transplant and we didn't need a abdominal well transplant so most of these are relatively straight forward almost done these Mercedes can be really really complicated though they always develop abdominal well hernias and they're upper in this area so again we have this loss of domain issue I'll move through this problem with decreased volume of intradermal contents you can wait for the bowel demons to subside or you can transplant a smaller organ or you can make the envelope bigger component separation prostheses otologous fascia or abdominal well transplant the problem is not enough abdominal well tissue for repeat livers, multivisceral besides misdemeanor transplants traditional techniques don't take care of this immunosuppressive preprosthetic mesh and non-best waste tissue at a high risk for infection otologous tissue requires a donor site on the recipient which I just showed you the solution is in the late 1990s actually in 1995 when corona was here we went to the Erie cafe for steak cigars and discussion of abdominal well transplant and I presented to him the concept of doing this this was about 10 years before they did it in Florida and primarily in then Lawrence Schecter who was my resident we decided he was planning this out so we went to Woodlawn tap for this plan and this one we discussed how technically we do it do we need to perfuse it we don't perfuse free flaps I don't know why they perfuse vascular composites what do we do if the patient is unstable after the liver transplant what's the limit of cold ischemia will be our recipient vessels didn't know any of that stuff and then I had a little epiphany this is for my old general surgery days and that's mostly fashion we really don't need skater in most of these situations we just want to keep all the guts inside and that I was making a hypothesis that the posterior rectus sheath had at least a secondary blood supply from the phallus form ligament this was actually brought out in 2004 in a radiographic study that showed that the artery from the right hepatic artery or the hepatic artery goes to the phallus formage that goes to abdominal wall meanwhile in 2003 Levi in Florida did a bunch of abdominal wall transplants these were for small bowel transplants so when you transplant small bowel everything is totally swollen most of these people have had disaster bellies to start with there's no way you're going to close them so they have most of the problems with prosthetics and a group in Italy did the same thing with microvascular techniques the immunosuppression was the same basically they just took all this out and took the vessels underneath since there was nothing inside because they took the small bowel they were able to close the belly without a problem and they have this report in 2003 they had 23 month follow up 6 surviving patients no problems with wound healing and 2 deaths with sepsis with intact abdominal walls interestingly you would think that one would be a sentinel of the other of rejection and there were 2 acute intestinal rejections with no involvement of the abdomen and there were 2 of the abdomen with no involvement of the intestine go figure interesting in his paper he says all his small bowel transplants were done under the IRB but he felt that just taking the abdominal wall didn't really need a separate one and so this was considered to be okay so he did not get an IRB for that so the problem again is lack of fascia and in 2010 we proposed a new thing which was the posterior rectus sheath liver CTA at the time and we reported a case report along with Dr. Miles and Harlan and then went back and did 2 of them and reported these 2 in the same journal this past year so the concept here is you have the liver, you have the pedigree and mains and you have phalliform ligament and that goes and supplies a perinealized live piece of fascia in the posterior sheath here it is in site here and so we have this nice healthy piece of fascia that should withstand infection here is the vessel we have done 6 of these in 5 patients one patient lost their liver and we had to do another one and we did that right after the same sort of thing one patient died of pulmonary sepsis his abdominal wall was intact all of them have had some sort of complications except for this last moment 16 year olds was actually done superbly well recently went home the ages were 12 16 but not necessarily correlating with the donors so we put a 20 year old liver in a 14 month old here is the ischemia time and the cold and warm ischemia time we timed how long it takes to harvest this and we start at the beginning before anybody starts and it's about 35 minutes it's not long there's basically 4 different categories of the 4 different groups so let's go through this quickly so this is for the multi-organ transplants we have 2 cases 1 and 6 there's number 1 we had the liver and 2 kidneys and there's no way the abdominal wall is going to tolerate that on a little baby who's had multiple surgeries and the other one was a liver and a kidney so here's a size mismatch we have a recipient's 14 month old donor's 20 year old needs a liver so split the liver they split the liver and keep the pores attached and then we have so this kid now has a half part of a liver from the 20 year old and it's almost his entire post-directed sheath which we can drape over everything and basically close, patch, reinforce the entire abdominal wall with live tissue we've had no complications of the abdominal wall biopsies, multiple biopsies so there's no rejection first patient died from sepsis everybody else alive and the immunosuppression was not altered do this so immunos, the single artery and vein that they use for their liver transplant proposes this thing, keeps it alive and in contrast to abdominal transplant described by Levi we don't have to do anything special all we've got to do is keep it attached to the liver so it can be used for a bunch of different things organ mismatch, multi-visceral transplants and just when you're with a hostile abdomen and you can't get things closed and we want to close it with a live tissue rather than either otologous dead tissue a donor site for the patient or a prosthetic the key about it though, it only works if you think about it at the time of harvest because you can't go back and get it unless you're getting another liver so just in summary the central difference between otologous transplantation and allotransplantation one has no immunosuppression the transplant is usually one big surgery multiple reconstructive surgeries for the otologous I didn't put them in here, it takes too long with a massive dog bite kid that ate his face I'm still operating on him seven years later no donor site scars for the allot donor site scars and potential mobility for the otto cost of surgery and life-long immunosuppression cost of multiple surgeries and we compare that case actually with Maria's first case seminar from Cleveland that it comes out about equal if not, if I have a major complication it actually puts us over there's limitation of our donor sites though not only number but type if we need hair-bearing skin and a scalp is gone patient doesn't have hair-bearing skin anyplace else so it's a significant amount that we can make a scalp and other examples are the same thing one of the theoretical things again if we get down to this minimal tolerance level is off the shelf surgery so you need something, it's not very risky immunosuppressives and we just take it from somebody else it's basically a change in thought process from reconstructive surgery which is doing our best to make things as good as possible to restorative surgery basically really replacing parts of the way they were made thank you very much