Dr. Megan E. Anderson - Limb Salvage Therapy for Sarcomas

The University of Florida med school, so go Gators. Um. Uh, so, uh, anyways, um, thank you, Doctor Anderson, for being here and look forward to your talk. Thank you for inviting me and uh hopefully this will be entertaining and educational, uh, a little bit about the orthopedic side of the surgery world and what we do to try to save these uh not so perfect limbs. Um, So, um, the background is that really limb salvage surgery wasn't possible until a few things happened. One was that there was effective chemotherapy so that the kids who had sarcomas of bone lived long enough to have a limb that require a limb that would be useful in the full length. Um that happened in the 70s and 80s uh when effective chemotherapy was determined. Um, and then the other thing that was really important was that the imaging, uh, especially MRI, uh, came to the point that we could really determine the exact edges around the tumor, the exact anatomic details of it so that we could do a good quality limb salvage surgery that was a good oncologic surgery as well as a reconstructive surgery. And then, of course, um, it, it came along with advances in our bioengineering and our biomedical sciences to create prostheses and um implants that would allow us to rebuild these limbs. And then most of all, um, the willingness and the skill of the surgeons before me, before us, um, who were willing to, to try these operations, um, the patients who were willing to try that and, and following through the outcomes, most importantly. Um, We found that when we, as we sort of looked broadly at limb salvage versus amputation, the oncologic results are fairly similar. There's a slightly higher chance of a local relapse in limb salvage because obviously, if, if you amputate the limb, there's no limb for it to grow back in. Um, Function is possibly superior to amputation, but it's very much in the eye of the beholder and now that we use patient reported outcomes measurements, it may be that that's more our impression than the patient's impression. Quality of life is very similar. So, there are pros and cons in the quality of life of limb salvage, much like there's pros and cons in the life of someone who has had an amputation and you sort of, uh, pick your poison, so to some extent, Complication rates are vastly inferior to amputation. Patients who have limb salvage become in some ways, most often chronic orthopedic patients because the, the methods that we have to rebuild these limbs don't last as long as they do and so they require further treatment down the road. So that's sort of the, the general history. When, when do we do it? That's, I think, a very good question that is the, the big black box that a lot of patients come in with. They, I have an osteosarcoma in my tibia. Can you save my leg? Um, that really is the number one question and so I sort of look at the MRI with an eye to number one most important thing is the oncologic results. Can I get the whole tumor out on block with a clean edge of margin around it? Our definition of what wide is has changed. And I really think at this point in most centers and in the COG as long as there is no ink on tumor, we consider that to be an acceptable negative margin. The impact of pathologic fracture has also, I think, morphed and sometimes it goes one way, sometimes it goes the other. It used to be that that was a, a curse and you were doomed to have to have an amputation if you had a pathologic fracture. With, with some fairly large studies, one of which was a multi-center study between us and the BI and the MGH, um, It seems that it's not so much the local issues. Some can still have limb salvage. Um, some, it's just the tumor's too big or there's too much contamination and limb salvage is not possible. And so the, the local relapse rates aren't so much of a difference. It's more the, the overall survival and it seems that the kids who have pathologic fracture may have more aggressive tumors and so their overall survival is worse. And hopefully, as we're learning about the Genetics and epigenetics of these tumors, we'll, we'll know more about that biologic behavior. And then another thing that can affect our ability to do, to do limb salvage is, is biopsy-related complications. We drill into the residents' heads in orthopedics about the hazards of biopsy written by Doctor Mankin, bless him, he just passed away. We just lost Doctor Mankin about a month ago. Um, he spoke a lot about the risks of biopsy that can, can really make it so that limb salvage is not possible. Um, In, in terms of, uh, uh, incisions that cross over vascular structures, incisions that are horizontal and cross several compartments where too many compartments are contaminated, things of that nature. I think it, honestly, with the era of where most centers are, are doing needle biopsies, that's much, much less common but still can be a problem. So that's the oncologic side of it, which is definitely the number one side as I'm talking to families about can you save my limb? And then the other issue is, is what kind of a limb are we saving? You have to, of course, have vascular and nerve supply into the lower part of the limb. If you don't, you may wanna think long and hard about um whether that limb should be saved. Yes, we can bypass segments of the arteries and the veins, but nerve bypasses don't really work. Um, so you gotta really consider that. Is there gonna be enough muscle left to power the limb or is it just gonna be sort of this structure that is attached to you but you can't move and you can't use? And then the other issue with our young patients is whether the limb length inequality is just gonna be too severe, that there's no way we could make that up with any reconstructive option. When we talk about the different types of resections, there are some general categories. The most common one is intra-articular where we are going into a joint. The joint's not contaminated by the tumor and we remove typically a metaphycele tumor. There are extra-articular resections as well when the tumor grows into the joint. A very, most commonly seen in the knee joint, but also that can be seen in the shoulder and the hip. Um, and so the whole joint has to be removed, the whole capsule, the, the, the bone above, the bone below to get all the, the tissue out if that's contaminated. Sometimes we're lucky enough that the, that, that the joint and the fiss above and below the tumor can be spared and you can do an intercalary resection and intercalary reconstruction. It's, there's absolutely no doubt that if you can save the patient's native joints, that's gonna function better than any joint that we rebuild. And then sometimes the tumor extends across the whole bone and so the whole bone must be removed and reconstructed. So, I'm gonna go through some of the general categories of our reconstruction options. The, the resection is basically just like any tumor resection in general surgery or orthopedics. Remove the involved areas. Um, some are trickier than others and, and get it out with a cuff of normal tissue preserving the critical structures. The reconstruction is sort of where we, we get more orthopedic on, on you and, and talk about the, the different options and what's best for each patient. Um, we've long been sort of an allograft center here, and I think, um, as the years go by, we probably change more and more to metal, but we still, there's still lots of times when allografts are, are really a good idea. It's, the pros are that you can reconstruct a really large defect and it's bone. So we're, uh, some, there's this thought that bone is better than metal. That may or may not actually be true. Um, bone probably has a slightly higher Failure rate, rate than metal metal because that transplanted bone is not typically a vascularized bone and so dead bone doesn't have the same material properties and modules of of elasticity as living bone and so it's prone to issues from that. The one big advantage in my mind of an allograft, especially if it's a joint, uh, an intraarticular, the, the, the joint has to be removed, is that the neighboring bone phss is not injured. So if you're doing a metal implant, often, you have to do something that bridges across the joint and you may injure the fiss of the bone that's next to it. With an allograft, thankfully, you don't do, so if, if you have a proximal tibia, you would replace the proximal tibia, but the distal femur would still grow at the same rate and that's a big advantage cause a lot, most of the growth of the limb comes from the distal femur. The other big advantage of allografts are the soft tissue attachments. They're far better than with metal implants. Getting a tendon to, to attach patellar tendon, abductor tendons, um, the, the rotator cuff to attach to metal is next to impossible. They're, they don't really work. You either have to use flaps or you use an allograft where you attach it to the allograft tendon. And even though that tendon is dead, that attachment actually heals. Tendons healed a dead tendon pretty well and can still work really well. The best results though for allografts are the intercalary ones where you don't have to involve any part of the joint, and that sort of makes sense. The negatives of, of the allografts are the, the really long healing time. Um, they, they, you, you have to put these patients in a immobilization for a really long time. And I think um in some ways, my, my mentor Dempsey Springfield always said that that was actually an advantage cause the child, the child learns to sort of protect this delicate limb, whereas when you put in a metal prosthesis and you say, go work hard, do your therapy, they're, they sort of learn to abuse it and they may not treat it as well. Um, I don't know, every kid's different. Um, again, the majority of it remains dead and so there are permanent activity restrictions. These kids, we don't say should do any high impact activities, walking, hiking. Um, a little bit of like playing hoops but standing in position, but, but mainly, uh, non-impact sports and that's a big deal for these kids. Fracture risk is pretty high. It's up, it's 20%. Infection is up to 20%. That's really high. So think about total joint arthroplasty is a, an infection risk of less than 1%. at at some centers or maybe 2% in a, in a center that does complex surgery. So 20% is ridiculously high. Um, and even when patients have been kept on antibiotics, like some people keep patients with allografts on antibiotics forever and ever and ever, it has no effect. It probably just breeds resistance. The other issue that can happen is that the um The junction between the allograft to the native bone sometimes doesn't heal and creates a non-union. Um, healing means that the bone crawls across it like a fracture healing, and it takes a really long time because one half of that bone is totally dead. It, it will cause some living bone then if, when that happens in the top, say centimeter, but that's as far as that goes. Non-union is as good as 20%. So if you have an intercalary allograft, it's 20% at the top junction, 20% at the bottom junction, so it's a very high rate of non-union. The other thing that can happen is joint wear. So the, the, the donor bone grafts are frozen and so the, the cartilage is not healthy living cartilage. Sometimes they do really well, surprisingly well, um, but sometimes they really wear very, very quickly, and I, someti I don't know that I have a rhyme or reason for it. I feel like when you can get better joint congruity where the match of the anatomy is better and when there's less sloppiness in the joint, it tends to wear less, um, but that's not even always the case. So I would say in general, allografts have a higher early complication rate than metal prosthesis, but, but fairly similar late complication rate. So this is an example of a patient who had a very large osteosarcoma in her diahocele region of her femur, but thankfully, the, the bone above, a short segment of her femur above, and a short segment of her femur below were spared, so the fiss and the joints were spared. So that's a really good reason to do an intercalary resection. Here's her vascular structures and her sciatic nerve is somewhere over here, so, uh, definitely a candidate for limb salvage. Her muscle can be spared. Good, good candidate for limb salvage. So, did a big femoral allograft, and she's so little. These are the best plates that I can fit into her tiny bone to fix this. There's not one long enough that can span the whole thing. The, the, she's too small for a nail to work. So this is what we did and then about a year later, the the distal junction is healing. You can see there's a bit of a spot weld here, so this is healing. It's not healed, but it's healing. But the upper junction is really nothing going on and probably we don't have enough stability. And so she's windshield whoppering enough to break one of her screws. Never good to have a broken screw and allograft. So, then, if she wasn't having any pain, she had to have thoracotomies done. So, cause she had a late solitary pulmonary nodule relapse. Um, so, 2.5 years after the original surgery, the distal junction looks great, but the proximal junction is still terrible. And now She's broken another screw. So this is just losing, we're losing ground. However, she's now grown a big enough femur proximally that I can get in better hardware, so we exchange that to better hardware. And then this is only about 6 months after that operation. She's, she's actually healing this really nicely. I think she just needed more stability. So I think that's the The trial and tribulation, you, you, these kids have to go through, usually a fair number of operations to, to get these things to heal, but then once this heals, she's gonna have a better long-term result cause she has her own hip, she has her own knee. Her, she's gonna have a reasonably long limb that's similar to the other side. So this is a win, even though it takes a lot to get there. So moving on, the another option is metal prosthesis, really commonly used all over the world and, and here. They're modular so you don't have to have them custom-made for the most part unless it's something complicated, uh, like a pelvis or something. Um, so it means you can have it ready, ready off the shelf for whatever size and length you need. Um, the, the advantage is that it's a much more stable joint. Patients Feel that stability, the leg underneath them, um, just is, has more stability to it, it's more reliable. It's a much quicker recovery, much quicker weight-bearing than with allografts. Um, a lower early complication rate than allografts, but as I said, the late rates are about the same. The cons is the risk of fatigue fractures. So like, you know, if you cycle a paper clip over and over and over again, it'll break. Similarly with a metal prosthesis, if you play soccer with your distal femur replacement, it will break and um no matter how much you, you tell, some kids are just gonna do what they're gonna do, but it just, it means they're gonna have more surgery and they may end up with an amputation down the road. We try to, to counsel them to change to other sports that are non-impact rowing crew. Cross-country skiing, hiking, and then, you know, when you're 40, you don't usually play those sports anymore, so we just gotta get you through the adolescent period. Um, loosening where the stem that fixes the prosthesis into the native bone loosens happens about 20% of the time and that's um a little tough to deal with cause it means revising the implant. Infection is much lower than allografts, it's 5 to 10%, still higher than regular joint arthroplasty, but better than allografts. And so the most recent data we have is that 80% of patients at 5 years have their original um joint implant if it's a meta if it's a metal prosthesis. Um, and then, so 20% have lost it due to infection, due to loosening, due to local relapse, um, all of those issues, mechanical complications, but only about 60% at 10 years. Um, I, patients always say like, how long is this implant gonna last? And it's really difficult to say. I usually tell patients if, if you're gonna behave and follow the rules and not go play soccer and run, um, we expect the implant to, to last about 20 years. Um, and then we have to just do a simple replacement of some of the bushings, which is not a huge ordeal. The, the disadvantage too is that you, you, you have to have something that goes on the other side of the joint that, that affects the ability of the other, other bone to grow and so your limb lengths, you have to take that into account. And then again, the poor soft tissue attachment, not like, not like allografts, the soft tissue attachment is not very good in metal. So this is a um really sweet patient who presented with this sort of ill-defined, very almost difficult to perceive lesion in his distal femur, but certainly he has a marrow replacing process with extension out of the bone. The nerve is here, the vessels are here, they're totally fine. He's 16 so no worry about limb length inequality at that age, so we did a distal femur replacement prosthesis. And really got a nice fit. This is a, a stem that's fit in by fitting it in very, very tightly called press fit. And the idea is that then his bone grows into this um trabecular sort of pattern that's on the stem. It encourages bony ingrowth and then you never have to revise the stem again. So you have to really get this thing tapped in very, very tightly. Um, and I even put a little wire on it so I could really pound and get the stem in fixed tightly, but here he is about a year after and he's done with his therapy, and he's getting all this funny bone down here. He's having pain. So I, I've, I, he had to be loose. Unfortunately, it didn't really look like it, but other than this funniness here and the fact that he was having pain. So, unfortunately, in the operating room, it just came right out. It wasn't fixed at all. So I revised him to a much bigger stem and then you can see here how this is a year or so after that revision stem where the, the bone has just sort of glommed on to the stem and it's even changed its shape because of some stress shielding, but that's great. That stem will never have to be revised. Um, but even with our best efforts, you know, if we don't conquer the disease, we're never gonna win, and he had a local relapse, distant relapse, and, um, things didn't turn out so great. So, some of, a newer option. In the development of all these prostheses are the prostheses that can be lengthened. This is, this, the idea is that you can do some sort of mechanical extension of a tube within a tube to basically get the limb to grow and match the other side. Um, the original versions of these were ones where you'd have to make a little incision and then unlock it, crank out like a worm gear type of device, and then lock it back up again. We have a newer version now that's made in Stanmore, England, where that there's a motor in the prosthesis that can be turned on with just an electromagnetic coil that's an external device, and so you can lengthen. Or turn, reverse the polarity and shorten the device, the, the length, uh, with just an external magnet. You don't have to make any incisions, so that's really nice. Um, it gives you a stable joint and a quick recovery just like a, a, an another implant. It's, um, the, the, the disadvantage is I think that people are tending to use these when you don't really need to use them. You, there's a very narrow Uh, indication, uh, uh, for ages, like if the child is 12 and she's female, you don't need this. She's gonna end up with like a maybe a 2 centimeter limb length inequality. 2 centimeters is fine. Just put a lift in the shoe. But it, but people are using them over and over again and then they're not, they get broken because they're maybe in teenagers who shouldn't have them, they're abusing them. Um, there's a need to revise it. At the end of all this expansion, you wanna convert that to an adult type prosthesis so you know that you're, you're making them again this orthopedic patient. Um, it does mean multiple operations, more so than even your standard, um, orthopedic implant because of these multiple lengthenings and that affects the kids too. Um, and then I think because we're doing them in kids who are like age 8, age 10, you can't make them do the therapy and so their joints are really contracted and tight. I've had so much difficulty with that. So, that's the negative of these. I think the, we're still really learning more about them in our, we only have about mid-distance, midterm results uh uh where maybe 1015 years follow-up and they, they, they're good mechanically, it's just some of the other issues that come up. So this is a young patient who has retinoblastoma and then developed an osteosarcoma when she was about, I think, 8. Um, she, unfortunately had a fracture through her osteosarcoma, so put a little plate on so she could get through her chemotherapy with a stable femur. And then she really did not wanna do rotationplasty or amputation, so did limb salvage with this, um, Stanmore extendable device. And this is some flu shots of where it looks, um, pre and then post-expansion, where you can just see sort of a tube sliding on a tube to lengthen it. And, um, and, and it, and it did well, um, uh, for her, unfortunately, uh, you know, the disease being what it is, we, we don't have tremendous follow-up because we, we always, we lose some patients to the disease. Uh, but for, for the time that she had hers in, uh, it worked very well for her and, and kept her limb lengths very nice and equal. So then what about putting allografts and prostheses together? Does it give you the advantages of both? Yes, but it also gives you the disadvantages of both. It's much, much more stable than an allograft joint, so that definitely is, is a better functioning joint. Than just allograft alone. It gives you the soft tissue advantages of an allograft, probably maybe slightly better function, particularly with things like the abductor tendon and the hip joint, uh, and, uh, patellar tendon attachment and a knee joint. So it gives you some of those advantages. It's, the difficulty is that it's a little more technically demanding, so it takes a little more time in the operating room. There's more recovery and healing time than metal alone, similar to allograft rehab. Um, and then you, you're trading a higher risk of infection than when you use metal alone. So this is an example of a child who was 7 when she had her osteosarcoma. The tumor extended too high into the femoral neck to be able to save the head of her femur. So we did a resection. And this is the allograft. You can see, even with a very small adult donor, it, it still looks large for her, but it, it did fine. Thankfully, over the years, her acetabulum grew well. That can be a problem where the acetabulum doesn't develop because it doesn't like the metal implant or it's not, not the right forces in it. So this is her now at the end of skeletal maturity. You can see she has a limb length inequality. She had to have some, um, she ended up with a sort of a valgus posture to her knee, so we had to sort of stop one of her, half of her faces from growing for a little while. And she had to have the other side, um, an epiphysodesis to, so that it didn't grow too long. Uh, but instead of, so she's comes from a very tall family. She probably was projected to be about 6 ft, so she's, you know, 5'10, which is ridiculously wonderful. So, all, all came out fine for her and she just wears a lift to correct the limb length inequality. She rose crew. Um, so here's some other options. That we sometimes employ, um, vascularized grafts, and most often we think of a free fibula transfer. It's a great option because it's bringing vascularized healthy living tissue into the mix. It's a disadvantage because it's really labor intensive. It doubles your operative time, it doubles your, your risks. You've got risks at the donor site as well as the recipient site. And, um, so it, it adds a lot to the, to the procedure. So we often use vascularized grafts more as a backup if we've got a non-union problem or if in an area that we just know is never gonna heal. Um, Joint fusion, we rarely use anymore. Um, certainly, if there's a tumor in the spine, that's, that's always employed. Um, some people have used in the past for hip, shoulder, um, where it can be done, but you usually have such a big gap that you're having to heal then with an allograft in between or you're shortening the limb a lot. It's just not a good, it's probably your like 8th choice, um, and we really wanna fuse a knee. It just doesn't do well to walk with a peg leg. And Special considerations in the spine. The, the problem is not so much the reconstruction, it's really getting negative margins. There's always that pesky cord in the way of trying to get the whole tumor out on block. And so often we're doing an intentional intralesional excision at part of the margin and that's where we also employ sometimes some protons or things like that to try to um get better margin control. That being said, the risk, uh, the, the general outcome from spine. Osteosarcoma in particular, but also Ewing's is just far worse than other locations. In a distal location like a hand or a foot, we almost always favor something like amputation, but in a wrist, um, you, you, you could get away pretty well with a wrist fusion and even with a big chunk of allograft donor bone, dead bone in there, the, the, for whatever reason, the wrist usually heals actually pretty well and if you don't have wrist motion, you actually can make up for it pretty well with just your hand motion. In the foot, and the distal tibia are, are ways of reconstructing the ankle joint and the soft tissue coverage problems with that lower part of the limb are, are challenging and so most patients do better functionally as well as quality of life without having a multiple operations by doing uh below the knee amputation or ring amputations. There's some locations where there's no reconstruction necessary, uh, and those are always wonderful. The clavicle, proximal fibula, mid-shaft fibula, ulna, and the patella. It's rare to see them in that location, but you don't have to do any reconstruction at all in those locations. When children are very young, like under age 6, that's when we really push more towards amputation or rotationoplasty. It's just too difficult to try to reconstruct the limb that's not gonna be so different in length compared to the opposite side. Pelvis is a challenging location as well. Usually, tumors in the pelvis are, have a far worse prognosis. Um, even if they're non-metastatic, for instance, pelvic osteosarcoma patients only have about a 20% 5-year survival rate, which is compared to a patient in a femur, for instance, it's, it's like 75% 5-year survival rate. Um, and it's really difficult to rebuild parts of the pelvis, particularly the, the acetabulum. That's really the most challenging. We have the option of just doing a flail reconstruction where you're basically are dealing with just soft tissue repairs and then the leg shortens quite a bit to where they have to wear, um, a lift on the outside of the shoe which no teenager likes. Allografts, um, are reasonable to put in to redo the acetab and you usually have to put a joint replacement on top of that, so there's failure rates with all of that. Um, and then I'll show you an example of what we're doing now more, uh, is a, is a trend of, of doing metal prosthesis that we match exactly the patient's anatomy by using 3D printing techniques. Then the key with the shoulder girdle, much like the, you know, the shoulder is the pelvis of the upper extremity, you, you really, it's not so much the shoulder itself that's important though in, in this location. It's really the hand. You wanna keep a good functioning hand and so even if the shoulder isn't all that great, as long as your elbow and your hand work, you can use, you're very functional and it's really important to keep, keep a good hand. This is an example of a patient of ours who had a very, very, very large osteosarcoma involving his hip joint and his ischium. And so, this is one where I asked, uh, there's a particular company we use most frequently to help me design a replacement. And so, we, we do a CT, we build this model using basically AutoCAD software and I tell the engineers where I wanna cut. So I'm gonna cut through the sciatic notch and just below the AIIS and the whole last tabulum is gonna go, most of the pubis is gonna go and almost all the ischium is gonna go. And, and so I, they just do that with AutoCAD. They take it out and then using that software, they build me a model of this part based on his normal anatomy on the other side as well. So taking away the tumor shape. We add some flanges to give me screw holes and plates to fix to the rest of the Um, pelvis that we can save and we plan then a, a replacement that has the acetabulum as well as the screw fixation that matches exactly what I'm taking out and then we put it in with a hip replacement. And I think what this does is it, it, because it matches the patient's anatomy so exactly, it decreases your operative time by like 5 hours because you don't have that futzing around trying to make things fit that don't fit. It, we also plan cutting guide so that the, the, the guide, the way we set it up, it's just done and so you, you decrease all that fiddling around and so the, again, the operative time is decreased. What we don't know is long-term is the function of this just as good or better than some of our other options, but, um, again, the survival rate being what it is for pelvic sarcoma, we don't have a lot of long-term data cause not many patients make it long-term. But in the short term, uh, what it does is allows patients to recuperate. Much more quickly than a lot of our other options. And it's a reliable and stable reconstruction, very fast. So, this young man at, uh, a year after the surgery, walked the entire Jimmy Fun walk, which is 26.2 miles uh all without any assistive device. So, it was, it's pretty, I think that's pretty telling of how functional it can be. And then, I can't leave, of course, without some tribute to rotation plasty. Uh, it, it's sort of an in-between, right? It's not an amputation, but it's, it's not, it's not, uh, it's not limb salvage either. It's sort of a, a, a nice in-between. It's a really good option for children who have a lot of growing left, so they're 4 years old, they're 6 years old, and so, the people are sort of blown away by like, you're gonna do what? Um, we always refer them to our little video that we made where you, you, pictures always worth 1000 words. So you take out the centerpiece of, of the bone, the femur, the tibia, then the whole knee joint goes away. So it's a really good tumor operation. Then you connect the tibia to the femur and so your ankle joint is now your knee joint, but it has to be turned backwards because your ankle bends this way, your knee bends this way if I'm looking at myself. So, that, that's the rotation. Um. And, you know, kids do really well with this. So this is some wonder, when we made this video, um, some of our kids wanted to show off what they do for sports, and not every child who has rotationplasty ends up doing sports, but a lot do. This is Mark's Gebhardt's, like, I think, very first patient he did rotationplasty on. When he was like, just out of fellowship, and he owns his own landscaping business. This is him when he was a youngster and he was a ski racer. You can't even tell which leg he had operated on, right? It's amazing. Um, so they can achieve a much higher level of function because they don't have any orthopedic implants, right? It's all their own normal bone, their own joints, and so they do a little better functionally. And this is one of our female patients who chose this option because it would allow her to still be active and do the things that she wanted to do. Some kids choose it because they have to. The tumor's too big or they're too little, they're too young. Um, uh, and then there's that rare child who chooses it because it lets them do the active things that they really, really wanna do. Um, and it's almost like the procedure chooses them. They don't choose the procedure, so that's the, the rare case of that. Uh, and then some of our patients even play football with, there's this little rotation plasty prosthesis. That's all I had. Thanks for your attention. Well, Megan, it's great to have this very nice summary of what the options are for, for kids these days. I know that um Saving the, the limb has a major psychological effect on the, on the kids and their families. Um, on the other hand, I think you, you very nicely expressed at the start what the issues are, and they, they are not insignificant as you, as you point out, and particularly when the kids are in the midst of their ongoing oncologic therapy, if they've got multiple surgical procedures that have to get wedged in and disrupt their, their therapies. It's not a Not a good thing and the oncologist particularly get distressed about that. We both know. Um, there have been some studies, I think, done as far as, um, Particularly for the rotation plasty, about the different energy expenditures that are, are required when the kids are out doing athletics and sports, it might be uh of interest for you to, for you to mention to the audience. Yes, so kids with rotation plasty, you have the same sort of oxygen requirement when they're being athletic as someone who has a below the knee amputation. Um, when the alternative is a, is a high above knee amputation, which is usually the case cause we're mostly doing this for distal femur tumors that are fairly large or in a small bone. So the, the high thigh amputation is a fairly high oxygen requirement and it's just really difficult to motor a prosthetic limb when all you have is that much limb to use to motor it. So the, the, the increased length and having your own joint, even though you're, you're using an ankle as a knee, it actually works very similar to someone who's had a below the knee amputation. And so most of the kids walk without a limp. Um, they, they, they run differently. You can tell when they run often that there's a, a difference, uh, but the oxygen requirement is like below the knee. And then the other question that always comes up is when you, when you do the uh limb saving procedure, are you putting the kids at a higher risk of, of recurrence than if you do a, do a formal amputation? Yeah, the, I think the best data comes out of the COG and it, and it's fairly old data though, and it was about 7% risk of local relapse compared to amputation. I would love to look at that again. Um, especially now where we're, we're, we're, we're pretty close on our margins, you know, we're, because of MRI we gotta save that, you know, superficial femoral artery, uh, you know, we're, we're intending our margins to be close in very critical areas, um, but we're still saving the limb. It, it would be good to really look at that. Um, now, with the modern era of the surgical techniques, the drugs haven't changed, unfortunately, as you know, there's no new, new drugs for osteosarcoma. Uh, nor for Ewings, but the, the surgery has definitely changed. It would be good to look at that again. It's particular concern since often recurrence uh equals mortality for kids since we don't have any. curative chemotherapy for them. Additional questions for Doctor Anderson. Doctor Jennings. Uh, Rusty Jennings. So I've, I love the talk. I loved about your approach. You have all these. Externally designed. Things that you're utilizing to reconstruct. But there are two things I just wanted to ask, um, what's the potential for using cadaveric vascularized bone grafts? Can you just harvest some femur and keep the blood vessels and put it in? The second. Um, What about using everybody's using 3D printed customized this and that for everything. Um, and I don't know if that matters one bit to that this particular field. But does it? Well, I'll answer your second question first. The, the 3D. Um, What basically what works for us is that you, you use the CT scan to build a 3D model from your model that allows you to make um a mold. And so then your mold then makes you a metal implant that's exactly matching the patient's anatomy. I really think the it's, it's one of those things where it sounds really fancy, but in reality, the, the only areas that we really need it are for places that it's the uh the anatomy is really complicated, such as the acetabulum part of the pelvis. So any pelvis reconstruction that involves the hip joint. Um, we have done one talus, um, across the street, my partners, we did a talus for, it was a post-traumatic problem. Her talus basically was spit out of her body and didn't make it, so I gave her a metal one. so, so I think it's, it's, it should be applied judiciously because, uh, you know, it's sort of like a last resort in some, in some ways because, but, uh, then again, in the pelvis, I think the advantages are huge because of the The matching the anatomy exactly and uh giving the patient a quicker rehab than any of our other options. And then the first question was about vascularized. So the problem is logistically, that um by the so you would, you would harvest, you would have to do the transplant sort of right away um because the bone only lives for so long um in the donor. And, and the problem is, is that our kids have to have their surgery at certain times based on the chemotherapy regimen, so the timing would just be extremely difficult to work out. There are some situations where we take like half of a condyle of a femur from a, a living donor and, um, you know, the heart goes, the liver goes, all the important organs go, and then they let us take like um a half of a condyle that still is living at that point with its blood vessels. The patient has to sort of be on call. This is, they're usually used for patients who are fine from a tumor standpoint, it's sort of a, a reconstruction option down the road. It probab it really is great because the, there's no doubt that a living bone with living cartilage on the end of it is gonna do better, um, but it's just hard logistically to organize it. And, and sort of an, an offshoot of this 3D printing with stem cells and bioabsorbable. You know, all this stuff they're they're coming out with, which is all has some impact in some areas, at least it's starting to show. Any future for that in, in your field? I think, yes, the, the, there's always this fear that kids with cancer and you use anything that's made with a stem cell, you're gonna reactivate their cancer, and so the FDA is very stringent about it. However, if you're talking about taking stem cells and then growing them. Some of their own cartilage on a, a model of a femur bone that they, that's their tissue that you then implant back into them. That's really where I, hopefully, the future is, is in that type of tissue engineering. We're pretty far away from that. Um, One of our, one of our researchers in orthopedics, Martha Murray, is using basically sort of that similar concept to just get an ACL to heal, to heal. And it's been like a 25 year process to even just put a little sponge by an ACL to, to get it to heal instead of replacing the ACL. So it's probably not in my lifetime. And my, my last comment is a general comment to surgeons in general, I hear this all the time. Gee, we need to do, we don't wanna do this operation, we're gonna do this other operation cause it's too much time in the operating room. It's gonna take 5 extra hours to do this operation, which is superior, but we're gonna do this other one cause it's gonna save time. I always get nervous when I hear that, cause I, if it was my kid, I want the longer operation. I want to go to somebody who's gonna be committed to spending that extra 5 hours to the better outcome. And, and what do you, how do you do that? I think really what it comes down to is that often those longer operations are not necessarily any better. That's the problem. If, if it was certainly, I spend 12-hour cases a lot of the time, and if it would vastly improve the function, we, we would absolutely do it. But I think some of the advantage of these, like this, for instance, the pelvis 3D implant is that it not only decreases OR time, but it is a better functional implant as well that works better for the patient. You're right, you have to have both. Additional questions for Doctor Anderson. No, Megan, thank you so much for a great summer. I appreciate it. I forget her name. OK. Yeah I. Thank you thanks so much I know it was so bad this morning. I know I was like almost. It was like, yeah, they were talking. Yeah. Yeah