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Thank you so much to Colonel Professor or for delivering that talk. Unfortunately, professor or wasn't able to make it due to military commitments last minute. So she's more than happy for you to send questions in via email though, I'm sure. So you took the email down. I'll hand over to our next. It's a real honor and a privilege for me to introduce our next speaker today. Mr Pankus Chad is a Higher London Deanery transplant trainee and also a postdoctoral research fellow at the School of Immunology and Microbial Sciences at King's College, London, and the Center for Developmental Biology and the Institute of Child Health at U and Great Ormond Street. His scientific interests are machine perfusion of human organs for therapeutic intervention, regeneration and repair and complex pediatric transplantation. His research led to the first use of 3D printing for pediatric transplantation and also the first reported human model of antibody mediated rejection using war machine perfusion. He's also very active in public engagement in science. He was the Medical Director of the Netflix series, the Crown and has even acted in several episodes. He's made several short films for the Science Museum, the Hunterian Museum as well as the BBC NHS 75th anniversary in 2023 he was awarded the very prestigious Hunterian professorship by the Royal College of Surgeons of England. So without any further ado, I'm absolutely delighted to welcome Mr Pan Chan to the stage. Great. Thank you. Well, thank you for that very kind introduction and um thanks to Asset and all the committee members. Um It's uh it's a real pleasure to be here. It's my first um Asset Congress. Um I never came here actually when I was a trainee, but I regret that now. Um But it's really fantastic to see all the work gone in. Um And thanks for the invite. Um and also welcome to everyone online. Um So I was asked to talk a bit a little bit about um our work in complex pediatric transplants that we're doing and, and, and relate that to some of the research we've, that, that that's been going on and some of the journey that we've been taking. Um And to begin, I'm gonna take you back to um 1400 For those transplant trainees amongst you, you probably recognize this picture. This is um Saint Cosmos and Saint Damien. So, the idea of replacing a diseased human body part actually goes back many, many centuries. They're trying to replace the leg of this man with the leg of another man. They have no idea about immunology or about joining blood vessels, but I'm sure their hearts are in the right place trying to do this operation, forgive the pun. But then we come on to John Hunter, which Professor Colonel Linder or mentioned, I'm sure all of you know, John Hunter, um, very famous surgeon scientist and actually he was a polymath. Um, he started to experiment with xenotransplantation. Um, what he did here and this is a specimen from the Hunterian collection. Um He actually implanted human teeth into the head of a hen. Um and then dissected the specimen. Um and then observed that the blood vessels were going into the base of the tooth and the tooth was actually embedded inside the head of a hen. Absolutely amazing. Of course, he didn't know about immunology or, or, or, or the biology of blood vessels really. Um But it was under standing piece of observation and the first example of xenotransplantation, which is what we're doing now. Um And I'm sure some of you have read the recent report in the New England Journal of Medicine where they've actually started to put pig kidneys into humans. Um So that was extraordinary. That was almost 300 years ago. And then I had the great pleasure of meeting um Professor David Cooper. Um and we did this BBC world Service to commemorate the 50th anniversary of the first human heart transplant by Christian Barnard. And um if you think about it, that wasn't so long ago, that was only 50 odd years ago to basically open the chest about 15 centimeters to replace a human heart. And Professor Cooper was telling me that um he could sense the anxiety in the operating theater when Barnard removed the heart. And for the first time in human history, you're looking down at a human body which is alive, but there's no heart beating there. And you know, the whole world was watching, trying to put this new heart in and when it started to beat, that was really quite a moment. And as I say, it's only 50 years ago. And indeed, we can now transplant any solid organ almost. This is the uterus. I'm sure some of you have read which was successfully done a few years ago. Um But there are still challenges. So what are those challenges? Well, if we think about the transplant process, it's relatively straightforward. You've got a donor at one end, you've got the organ in the middle. And at the end of that process, you've got a recipient, it could be an adult, it could be a child and as transplant surgeons and a scientist, what we're trying to do is address some of the issues related to this process. So, for example, can we make the donor operations safer? That's quite important, especially if you're a living donor. Can we improve the quality of the organ? Now, this is very exciting and I'll come on to this later. Can we make organs better quality? Can we improve them, can we regenerate them? Can we repair them? And then of course, can we make the recipient operations safer? And that's the focus of my talk. Really. It's on Children. Now, Children are challenging to transplant, immunologically, metabolically and anatomically. And for the purpose of this talk, I'm going to focus on the anatomy. So here's a real case. This is um the first case that we did actually using complex 3D printing, which I'll come onto. But basically, this is baby Lucy um who was only 10 kg at the time of needing a transplant. And this is her father Chris, um 35 year old male who wanted to donate his right kidney to Lucy. Lucy. Lucy also had complex laparotomies for bowel ischemia. Um And as you can imagine, it's quite small. So how do we fit Chris's kidney and adult size kidney into baby Lucy? We'll come onto that later. But let's just think about this graph and I promise there won't be too many graphs in this talk. But this is an important graph from N HSP T which basically shows um the waiting list for pediatric patients. And as you can see it's basically increasing. So we need to get these Children a transplant as quickly as possible. And this is important because Children don't do well on, generally, don't do well on dialysis. Um And it's important especially for the smaller Children. You can see this, this, this is data from United States. This black line essentially represents Children from 0 to 1 years. And this lines here represent older Children, basically smaller Children have poorer outcomes on dialysis with longer duration. So it's important to get them a transplant as quickly as possible. And also it improves so many other things. Not just the actual fact that you're giving them an organ, but it improves survival growth, cognitive development for the child psychology of the child and the family. And indeed the quality of life and don't forget, although the child is just having the transplant, it's actually the whole family is involved, the siblings, mum and dad who are often the donors and of course, uncles and aunties. So it's a big, it's a big process really and it's a great privilege to be part of that. So we implant organs into Children. So as I say, the kidney will be the template for this talk, but of course, you can do liver and heart as well if you imagine we go by size. So if a child is greater than 20 kg, we normally implant the graft as you do in an adult operation into the right or left eye fossa, standard approach to the external iliac vessels. But if a child is very small by small, I mean, less than 20 kg, we actually do a midline laparotomy and put the kidney onto the aorta and the vena cava of the child. And as you can imagine that's quite a challenging operation, especially in very small Children. So the question you may ask is, is it safe to transplant very small Children? And I promise this this, I think the second graph I'm going to show this is data that we looked at over 10 years at Great Woman Street in Evelia. And I thank Nikos Karis for this my supervisor for this work, which was part of my phd. But basically, we looked at 420 patients, which is a very large cohort. And what we found is essentially, if you compare small Children to bigger Children, there's no real difference in kidney graft survival at latest follow up. And of course, we went on to look at UNOS database from the American database and we looked at over 14,000 pediatric kidney transplants looking at donor recipient mismatch. So how big the organ is compared to the child based on body surface area? And actually what we found was it doesn't really impact on delayed graft function or primary non function. But obviously, if you've got a bigger organ size, it's going to increase the survival significantly compared to smaller organs, especially in pediatric recipients. So let's go back to the challenges. What are those challenges? Well, we mentioned size discrepancy um placing an adult organ into a very small child. Um not only is it surgically difficult um but also um um it can affect the breathing of the child. How do you close the abdomen? Um what's going to happen to the perfusion of the graft once you increase the intraabdominal pressure. The second thing is a lot of these Children are actually born or develop abnormal vasculature. And this is quite important when you're thinking about implantation and where you're actually going to do the anastomosis, say normally we place them onto the aorta and vena cava even under normal anatomical circumstances, that's a challenging operation. Um But you can imagine this situation. Here's a child who um at the age of three, was born with congenital um abdominal aortic aneurysm and required a supraceliac to aortic bifurcation PTF E graft, which is here, this plastic graft here and then required reimplantation of the visceral vessels into that graft. And this child eventually um developed um um renal failure, had multiple laparotomies for abdominal injury. And you can imagine I've drawn around here the green which shows this meshwork of blood vessels in and around the graft. And this child presented to us for transplant and she was quite small as well. Relatively. So, and the mother was the donor, the living donor and she was immunologically incompatible to the mother as well. So, there's anatomical problems as well as immunological problems. So, how do we navigate around this problem? And indeed the aorta and the vena cava of Children can be thrombosed, there can be stenos, they can be occluded, they can be absent, narrowed, twisted, all sorts of configurations. And here's an example of a child, the same child actually, whose reconstruction on the last slide, there's no Vena Cava here, lots of dense collaterals developing in the pelvis going up towards the hemiazygous azygous systems. And the question really is, can we use some of these dilated veins as a, as a place where you can do the venous anastomosis from the renal vein? Um And we don't quite know until we open the child up and have a look inside ourselves. And here's a child whose aorta completely disappears, you can see no contrast going down there at all. So how do we transplant this child? Um We went on to look at some of this work and we developed a classification system. So essentially, it's based on whether your aorta or vena cava is present or not. Um If the aorta and vena cava is present, we've classified that as a four V four and if it's not, uh um um sorry if it's occluded and if it's, if it's presently classified as a one V one. So in the last child that you saw, this would essentially be an A four V four. So, um the entire abdominal vessels are occluded or absent or narrowed. Um That then that's probably the most complex situation that we're faced with. And of course, you can use this to go on to develop registry analyses to work out what the best outcome is. Um for Children with these problems. So we're basing our surgical approaches on conventional medical imaging. Now, this requires us to interpret a 3d structure on a two D computer screen and it requires a radiologist to interpret the anatomy and convey that to us. There's no tactile interaction really with the and you can't stimulate the procedure. So often when we're unsure whether we can transplant the child, what we do is we open the child up on the operating table to determine feasibility of implant, look at the vessels. And then once we've confirmed that we then take the donor kidney out which is usually mum or dad who's not yet asleep in the next theater. So that then as you can imagine requires some coordination with the implantation team and the harvesting team. But also it's quite a stressful situation. Actually, the child is under anesthesia for a long time. The donor surgeon now is under pressure to take the kidney out relatively quickly. Um And it's a live donor. So you can imagine there's lots, lots riding on the entire operation for this child. So what this led me on to think about how we can predict feasibility um of transplantation in these very complex Children. Um And at the time, um I attended a lecture on 3D printing in cardiac surgery. And it occurred to me perhaps that we might be able to use this for transplantation. So what I did was I tried to develop a proof of concept. And think about whether we can actually 3D print and model donor kidneys with babies abdomens as a retrospective proof of concept and then translate that into clinical practice to help de risk if you like or determine feasibility in those Children where the feasibility was uncertain. So I approached our medical physics team and what we did was we extracted anatomical data from CT scans and Mr scans. And then we developed this computer aided design as you can see here. And then we used our 3D printer here, which is based at ST Thomas's, it's a state of the art medical 3D 3D printer. And essentially we produced a three dimensional patient specific model using various software and materials. So here's an example of a baby's heart, actually a congenitally malformed baby's heart. Now, this is the segmentation part. Now this is quite an important part where the radiologist sits with the clinical team and the medical physics team. And we draw around essentially the important anatomical structures that we need to look at. And then it forms this rather beautiful computer rated design that you can see here. And then we translate that into a model based on oops based on um if this works here on this video, let's just have a look, doesn't work. But anyway, but what we were trying to do was this is a print head and it goes across like this and it lays down liquid plastic resin which then molds over 12 hours into a patient specific shape. And so I took this to the medical physics team and I said, can we do this for our case that we saw earlier with the baby that had a missing aorta. Essentially, this child was transplanted without the use of 3D printing. So I went back and did a proof of concept, retrospective case. And here's the computer R design and here's the actual model that we used. And we showed that there was geometrical correlation between all those three elements. We showed it to five independent surgeons who confirmed its value as a preoperative planning tool. And then we used it for surgical manipulation. So we then thought, can we translate this into practice? Can we do it for the next prospective case? Um And we published this work um and we did it in three different aspects of pediatric transplantation. A very small recipient, a child that needed a two stage procedure and a small recipient with, with vascular abnormalities as well. So coming back to Lucy and Chris, this was the small recipient case that we did. So again, we spent time with the physics team, we did all the um segmentation and then we produced this. So this is the first case that's described, it's now on display in the Science Museum in London. And basically this is the entire abdomen um that we 3D printed um of Lucy. So this is the pelvis which is a very hard material. And this is the liver, as you can see, two small kidneys the size of or nuts. And these are the blood vessels and these are the lateral abdominal walls. And the printer has the amazing ability to actually print the pelvis in a very hard material just like it would just like bone really. And this is the kidney from crisp that we used. And this is the right kidney. You can see the blood vessels just there. So we've got to try and fit this organ into this space. And don't forget, Lucy also had operations laparotomy. So we worried about scar tissue and adhesions as well. So we use this to plan our surgery in a multidisciplinary setting. Let me just see if this video starts. Yes, it does. So, um so this is what we did. This is Professor Mammo um um um using the actual models to plan the operation in a multidisciplinary setting. So, what we're trying to do here is to see how the vessels of the kidney line up with the aorta and Vena cava, the model gave us a sense of depth perception um because um we need to know whether we're going to remove the right kidney of the baby and he's going to point to that in a minute. Um And indeed, there we go, you can see the right kidney there and, and sometimes that's a decision we take into op but the model gave us an indication that perhaps would be ok to do that without sacrificing the right kidney. And of course, the lie of the blood vessels, the kind of you want to make and how the kidney would lie within the actual abdomen. And you can see our planning there actually coincided with what happened intra op and the blood vessels were also very similar size. So this was the first case that we did and this was work in progress. We then decided to test the model on another case. This was a 12 kg child who was born with bilateral renal artery aneurysms, but also an IMA aneurysm. So this child required and as you can see quite dysplastic kidneys here. So we used the model to plan a retroperitoneal bilateral nephrectomy prior to this child receiving a living donor transplant from their mum. And we also to deal with the IMA aneurysm that you can see here. There, there's the aorta, there's the cava and you can see the I aneurysm just here. So you can see some blue tag there where we practiced actually how to take the aneurysm neck off. But it gave us size dimensions. This is the kidney from mumps, the left kidney and it gave us the size of the vessels where best to place the anastomosis and how to deal with the aneurysm. At the time. Again, we plan this in a multidisciplinary setting to try and de risk this procedure, here's a child uh 14 kg um again, was deemed um very high risk transplant. And in fact, I think it was deemed untransportable at the time. The reason being um this is the aorta, this is the CAVA you can see there is a high bifurcation of the aorta completely twisted on itself. This is a called a trouser configuration. Um And what we decided to do was 3D, print it and then repres it to the MDT. There you go. There's the model itself. And actually, when we took this model back to the multidisciplinary team, the consensus was that this was, this was actually feasible. We took the model to there's a kidney that we used a living donor kidney from mum again. And we took the model to theater and we found that our anastomosis windows lined up with the model accurately. So there's the CAVA, there's the aorta and you can see there's the baby's Vena cava and there's the aorta bifurcating. It's a high bifurcation there. And we use that window there that we planned on the model to do the implant. We then went on to look at Children with complex pediatric renal artery aneurysms. So often what you have to do in this case is take the aneurysm out, remove the kidney, place it on to ice and then reimplant the organ back into the pelvis in an auto transplant. But what we did using 3D modeling was actually, and this was a 13 year old female who had a complex aneurysm was we proceeded to do in sit construction of the actual renal artery aneurysm with intraoperative cooling of the actual organ with ice. So we didn't actually take the organ out from its bed. And then we did the vascular reconstructions after we removed the aneurysms here without the need for auto transplant into the pelvis and reported that a couple of years ago and again, 3D modeling helped with that process. So what else is happening around the world? And indeed um coming to this country. Well, robotic transplantation in Children. Um This is Professor Pran Modi, um who helped um establish the robotic transplant center. Um Well, robotic transplant program at Guys Hospital. Um We did the first um U KS er robotic kidney transplant in 2016. And Professor MODY, who's got the most experience in the world of this came over to help us with that. And, and in fact, he's actually used the robot, the da Vinci robot to transplant Children. He's done more than 30 now, I think he's done probably 60. Now, this is slightly old data, but you can see the scars here. This is a child that you transplant, a very small scar here and a couple of laparoscopic port scars you can see compared to the conventional midline laparotomy that you would use or a Rutherford Morrison incision that you would use in a larger child and his data is very good at almost 90 100 per cent patient and graft survival. Of course, this requires a high level of technical skill because a smaller working surface. But Professor B had done almost three or 400 laparoscopic kidney transplants prior to this. But I think this is probably the way forward and this is going to come to the UK and we're looking forward to his published works to that. And the Children go home within about four days after a transplant, which is really, really good. So what we learned from these models that we're using is that they appreciate anatomy. You can translate them clinically. Importantly, you can simulate the procedure, but also you can have a personalized consent process for the family. I can take these models to a family and say these are the risks. This is what we need to do. Um because often you, you know, you use pen and paper to draw the diagrams and it's hard for them to simulate the risks and to understand it. So if I show them, this is your baby's abdomen, this is your kidneys, this is what we're going to do. It actually helps with the whole personalized consent process. Often these operations are fairly rare. So it's hard to give a percentage of risk. Um But these models certainly help to do that. And of course, you can develop an archive collection of training for future surgeons. So where where are you going to be in a few years time? So the next part of research that we're looking at is actually organ regeneration and repair. So we're working quite closely with Professor PK, who's NIH R, professor of pediatric surgery woman street, Professor David Long at the Institute of Child Health, Professor of Developmental Biology and Nichols Garis. Um he's one of the senior pediatric transplant surgeons. And what I'm trying to do next is develop models of regeneration repair, using organoids and different types of cells. So, here's a, here's a liver, um a human liver and they've completely decaris it um and then you can start to use um different types of cells um um to try and, and repopulate that. And of course, you could try and um use machine perfusion technology to try and um model some of those disease processes. So, um what I mean by that is you place an organ on a, on a bypass machine. Um You give it warm oxygenated blood and this is already in clinical practice and the indications for this are really viability testing of organs prior to transplant, you can manipulate them. And of course, you can put stem cells in and develop interventions for bioengineering. So, here's a kidney that was rejected by all UK transplant centers. Um because as you can see, it's quite mottled and there's not very good blood going through it. We subjected to one hour of warm perfusion and this kidney became transplantable and was eventually used in a recipient. And we were part of a trial published last year in nature medicine, looking at the effects of cold storage and comparing that to machine perfusion. And we found that actually it's a safe and feasible procedure to use for clinical transplant. Um This is a circuit itself um very quickly to go through this. Um um This is the kidney on the rig. You can see it's making urine outside the human body, which I always think is an amazing thing to see. You can often have hearts there pumping away. Um You can have the liver making the bile. Um but you can see it provides a fantastic experimental translational platform for intervention. So you're going to get it red cells, you get all these nutrients, here's the venous reservoir, you pump it using the centrifugal pump, you oxygenate it, you heat it and then you send arterial inflow back into the organ and venous outflow. So it's a closed system. And of course, the idea is that it regenerates ATP as I say, it's used for clinical transplants now and also used for experimental transplantation as well. So it's mostly used for adult transplantation. Um But I think it's got great benefit for pediatric uh transplantation as well. And it's something that we'll be looking into and of course to model um 3D 3D um printing uh bioprinting. Um and also disease modeling. This is work that we did um from um our phd um and published a couple of years ago. Now, we modeled uh for the first time actually human um er transplant rejection. So we actually deliberately rejected kidneys on this bypass system. And the next part then is to try and put drugs into that kidney to prevent rejection and repeat the process and see if it works. And so this is called organ precision medicine, moving away from systemic treatment. And of course, you can also model fibrosis and other things. And this may have relevance for pediatric transplantation as well. So just to end, really, this is um baby Lucy. Um you can see her, she's grown up now. She's a real ambassador for UK transplant. She's absolutely amazing. She lives in Belfast. Um and this is her handing her models over to the Science Museum um which is fantastic. And um as I say, she's, she's really doing very well. Um And you can see her there on the BBC in full glory with a picture of her kidneys on at shirt there. Um So just to end really, um we professor um Linda Ross spoke about inspiration and, and, and research. So um for me, there are, there are, there are two people really who have inspired me in my journey. One is Joseph Lister. Um And um he always said that there is only one rule, put yourself in the patient's place, a very powerful aphorism really for any uh clinician, there's a wealth of technology innovation that we can do. But I guess the center of oo of this is really isn't gonna be beneficial to the patient. And that's the most important thing. Um This is Professor MODY. This is a very um important picture actually which we're trying to get on to Time magazine if we can. Um these three Children are quite, quite special, Professor MODY. Um as I say from India, he went to harvest um three organs from a child that had died um almost 200 kilometers away. He drove himself, harvested the liver, the left and the right kidney came back and transplanted all three Children in 24 hours. He gave this child a liver transplant, this child, a kidney and this child, the other kidney um all in 24 hours. Absolutely extraordinary. And I think it really exemplifies the aphorism of um of Joseph Lister there. This is a, this is a choir. I set up with BB BC Children in need. These are all Children that we've transplanted from Evelia Great Woman Street. And they in the BBC studios a couple of years ago just before Christmas, which was absolutely amazing. So, they're all real soldierss really, they're absolutely fantastic. And just with the one quote from a scientist Michael Faraday who was my other inspiration, still try for, who knows what is possible. And I think certainly when I started this work, a few years back. I didn't think where it was all going and how it was going. The questions were out here, we had a lot of problems with funding, et cetera. But if there's a will, there's a wave and I think Michael Faraday's ayr there is very powerful for any scientist. So there we are, that's my funding bodies and my team and I thank as it again. Um There we go. Thank you very much. I think we can all agree that that was an incredible and inspiring talk um from Mr Chenk, but in the interest of time, if that's ok, we're just going to defer Q and A for now and I'll hand over to ba who'll introduce our final speaker. Thanks as well. So, our final speaker for this particular session is Professor Dominic Thompson. So it's my honor and privilege to invite pro Thompson to our surgeons at the cutting edge plenary session. MS Thompson is a senior pediatric neurosurgeon in the Department of pediatric Surgery at Great Ormond Street Hospital and an honorary associate professor at the Institute of Child Health in London. He is the current president of the European Society of Pediatric neurosurgery and harbors special interests in the surgical management of congenital and acquired disorders of the pediatric spine, in particular cranoc cervical junction, anomalies, spinal dysraphism B spina bifida basically in spinal tumors. But you may have seen on the news that most excitingly, he's performed the first in utero closure of spina bifida in the UK. So this is absolutely phenomenal and we're very, very privileged to have him speak for us today. So without further ado, I like to hand over to Professor Dominic Thompson. Thank you very much indeed for the uh introduction and uh welcome er everybody to the er morning. It sounds like it's been an amazing program so far and in the interest of time because I know we're running over, I'm going to, uh, to, to, to crack on, uh, as you gather, I'm a pediatric neurosurgeon. Um, so, uh, interested in disorders of the central nervous system of, um, of Children. Uh, but for the purpose of today's uh, talk, um, I thought I would say elaborate on what you've just heard about the work we've been doing in spina bifida and particularly the fetal surgery for spina bifida. Why? Um, because I think it is contemporary and topical and I think, as you've just heard from the last, er, speaker that actually surgery needs to be moving all the time. And I think certainly the last 1015 years I think, have seen an absolutely extraordinary explosion in the use of the integration with technology and surgery, um, which I think is unprecedented uh, in, in, in the past when I was training, all the major developments were really on the medical side. But I think we're seeing huge advances in, in surgery now and some of you may have seen it. You just heard that uh horizons showed a, a documentary related to our first case of spina bifida in, in uh treatment in utero. Why? Why do I think this is a good talk again for a particular trainee audience is because I think it's an excellent example of the use of translational research in surgery. I think again, and I can't uh um exaggerate this er, more the importance of collaborative treatment. You know, all the big names that you've just heard about Hunter Lister Faraday. All those, you know, those are people that often did work in isolation in the past. But now the real progress has been made in, in teams collaborating across specialities. And of course, this makes for a pretty exciting uh speciality and it's important to maintain your excitement as you go forward, I think in your career. So, what I want to do is give you a little bit of an overview of uh spina bifida. What is it? And what's the conventional treatment? What's the rationale behind trying to treat this in utero before kids are even born? Uh and demonstrate how that's been translated into routine, pretty much clinical practice now and possibly some observations on the future. Just to take you back a little bit to some basic embryology and how the central nervous system develops. You remember, just within a few days of fertilization, we have a bilaminar disc of epiblast here in blue and hypoblast in yellow it's the epiblast which is on the dorsal aspect of the uh embryo that within a couple of weeks develops a polarity with the um er primitive er streak down the er center, the er notochord defining um the rostro chordal access of the um er embryo and as the notochord regresses, it leaves behind the primitive streak regresses, it leaves behind the, the pale blue here, which is the neural plate. Yeah, we've now got a three layered uh structure of an ectoderm mesoderm and endoderm. So gastrulation has completed that outer layer of ectoderm. You can see now folding over meeting in the midline here and this now zipping up top to bottom finally with closure of the anterior and the posterior neuropore, you know, within 2 to 3 weeks of fertilization. And of course, it's the problem of closure of this bottom uh neuropore which leads to the issues of spina bifida and its related er problems. Sometimes these are put together uh in under the under the term that spinal dysraphism. And uh don't worry about this here. I'm just trying to put it in context but that this is a rough schemer of the developmental basis of dysraphic abnormalities. All the clinical ones that I would see are on the bottom there and the um supposed and it is very much supposed unproven in many cases, embryological basis above that. But it's really in relation to open neural tube defects that we're gonna speak today. That's basically open spina bifida, myelomeningocele, the more severe variant, this is what it looks like when kiddies are born and basically they're born with central nervous system exposed on the outside. It's apparent you can see it. Hence the term aperta spina bifida, aperta, as opposed to spina bifida occulta. When the neural tube is hidden under um under skin, what do we do to normally treat um uh spina bifida? Well, you'll see in this little video and I'm gonna move along, uh just selecting relevant cases in uh relevant bits of this uh video just showing you, er, what happens in terms of the surgery, the surgery is typically carried out within the 1st 48 hours or so of life. Er, this is typically what it would look like, almost like a blister. And in the center there you have the uh neural tube and then, uh, that's the pea, the placode, er, surrounding that you've got some rather dysplastic meninges and then you've got normal skin and above and really we start by exposing um the underlying fascia through an incision in the normal skin and then we elevate some of that surrounding skin. So, trying to separate it away eventually from the, er, neural uh placode, we do that at both ends as you can see here. And the next thing is to take a sample of CSF A for you because we're looking to check for any infection that might have, uh, have gotten, which is pretty unusual. And then you can see I'm just manipulating the neural plateau there. That's the bottom end of the spinal cord. Yeah. And now we want to, uh, we've got the placode completely mobilized, replaced back within the spinal canal. And now the important thing is to reconstruct the layers around the outside. Here's the, er, dura new dura being made, you can see there's the um bottom end of the spinal cord now, back inside the uh uh spinal uh canal and er to um er er finish, we then close the er dura as you're seeing here inflate the dura to check for any leakage. And then finally the skin is er closed er over the top um in a continuous manner and then the kidney goes back to the ward. So that's the sort of if you like typical um er means of er treating er postnatally hydro um uh spina bifida. Now, what are the problems that kiddies with spina bifida have? Well, they have problems with CSF circulation because fluid is being lost from the bottom of the spine. The normal pathways that develop uh to absorb CSF, they go wrong. And so when the baby's born, they, they don't have an ability to absorb spinal fluid and so they can build up um er er their um er they can build up fluid inside the brain, the condition of hydrocephalus and that will often need them having to go on and have a shunt in about probably up to about 80% of cases. The other problem they get is this phenomenon of chiari malformation. You can see here because of the big sac or the sump of fluid at the bottom. Yeah, the the under surface of the brain, the hind brain starts to sink into the upper spinal canal. And that gives us the so called chiari two malformation and that can cause breathing, swallowing problems, even death. Uh in, in babies. Of course, the other problem that kiddies get is problems with development of bladder and bowel control. And many of these Children have neurogenic sphincter impairment and require augmentation, cystoplasty, intermittent catheterizations, various things in order to protect their renal tract as they get older. Uh And finally, of course, because the lower part of the spinal cord is affected, they get limb weakness and that weakness is worse. The higher up the spinal cord that this problem is, is, is affected. So it's a pretty significant um condition with massive comorbidities. I think one of the interesting things and I think worth remembering this in, in, in the the audience that yes, we're gonna talk about some of the sexy research that's happened in this. But it's important to remember that from 3040 years ago, we have a cure for this condition which people often forget in the and the enthusiasm and the publicity. Yeah, it's a cheap cure. Yeah, it's called folic acid Yeah. And if women were taking this prior to getting uh uh pre pregnant, then um, the risk of um spina bifida of this type of open spina bifida goes down by about 70%. So it's a, it's a significant uh uh uh uh ef effect. But of course, what I'm talking about today is really the why we would go and think about even think about operating on this so called congenital malformation even before uh Children are born. Well, one of the reasons for that is it became apparent that yes, it is a congenital malformation. Clearly, you're born with it. But actually in the latter stages of pregnancy, there is worsening of the neurological condition. So there was ongoing loss of fluid leak from the bottom end of the spine. The baby is banging up against the uterine wall as you've just seen. And of course, as pregnancy progresses, the uh amniotic fluid becomes increasingly toxic uh and damages the er neural tissue. So, in essence, we've got two components. Yes, we have a primary abnormality of neural tube closure. So yes, of course, there is definitely some underlying uh neuro developmental failure, but also we've got some secondary damage due to trauma and to the toxic effects of the um uh amniotic fluid and so forth. And this led to the concept of the so called two hit hypothesis that yes, you have a primary congenital malformation. But then there are additional problems that worsen the prog prognosis, er, for the um er, for the, for the, for the child in the future. And this really led to the um to some really elegant basic research. And it began with a phd student being asked by his supervisors to, could you generate an animal model um of, of spina bifida and what he did, he used sheep as you can see here. And uh during pregnancy, the pregnant ewe the uterus would be opened. A hole was made in the back of the spine, a slit in the spinal cord. And when these lambs were then, then they'd close up, wait for the mum er, to give birth. And when these lambs were born, if they'd had this surgery, they had the very typical appearances of spina bifida. So weakness of the legs and um uh incontinence of, of urine. However, what they then went on to do is they made the lesion in the spine and then a couple of weeks later, they reoperated in utero to close the hole that the they had made. Yeah. And then, uh, lo and behold, what they found is that the neurological function of those lambs when they were born was actually better. In fact, some of them were able to walk and uh they did all sorts of electrophysiological studies showing the efficacy of this uh treatment. So this was a really major advance. Yeah, that you can actually have a neurological deficit in that could then be rescued by surgery before um, the, the animal was born. So, of course, the question, and here's one of the, er, I images from uh uh more recent um, er, surgery in, uh, and the question of course, is really, can you translate that into the human situation? Is it possible to actually operate on the human fetus and improve um uh clinical outcome? And this, as you can imagine was quite controversial in the early two thousands. Um, because it was being carried out in a rather uncontrolled fashion. And of course, there was then clearly a need to try and examine this on a trial basis. And so, uh, it was agreed that there would be a moratorium, everybody, particularly at that stage. A lot of it was going on in South America and in the US that, that surgery should stop pending the results of a trial. And so a randomized controlled clinical trial was set up, um, of, uh, fecal surgery versus normal postnatal treatment as I showed you earlier. And the outcome measurements were the ones really, I've just been talking about how many ended up needing a shunt, how many of them got the chiari malformation and, and how many of them ended up walking, uh, uh, at a reasonable age after, after birth. And this, as you may have, um, heard it was called the mum's er trial and was published in the journal of medicine about 10, sorry, sorry, years ago. Um, now, and what they found was that prenatal surgery led to significant improvements in the outcome of the these babies. And in fact, this occurred across all the parameters in terms of hydrocephalus. Yeah, you can see that in the standard postnatal group, the vast majority required shots for hydrocephalus. Whereas in the prenatal group, it was around two thirds of them, the chiari two malformation, the so called hindbrain hernia. Again, almost all of the postnatal group have that but only just under two thirds of those in the prenatal group. And then importantly, and this became quite a, a big headline of the uh trial that under Children that had had the fetal surgery up to almost a half of those were ending up walking independently by 30 months compared with only 1/5 of those having postnatal surgery. But in fact, the trial was stopped early because these results were looking uh looking so good. So what's involved in the, in the fetal uh surgery itself? Well, I think the first thing to say is there are important um selection criteria, not every mum who is found to be harboring a baby with spina bifida is eligible. So don't worry about the list down the the the left there, but there are significant inclusion and exclusion criteria as you can imagine. So for example, multiple pregnancies would be clearly an obvious uh uh example of that other comorbidities in the infant. So Children who've got multiple congenital abnormalities. Again, that would be uh an exclusion. And and of course, there were some maternal, maternal ones as well. Part of the initial screening process is of course, also important to rule out any of those other forms of spinal dysraphism that I showed you in the earlier slide. This is an example of something called limited dorsal myasis, but this is a form of spina bifida, occulta, it's the closed form. And of course, this would not be appropriate for spina bifida because these kiddies don't for prenatal surgery because these kids don't get the hydrocephalus, the hindbrain herniation and the motor probe prognosis for them is significantly better. It's quite exciting now because obviously, having been a pediatric neurosurgeon for many years to then start uh working with um er um surgeons who were from a different uh speciality. So um working in er with and fetal medicine surgeons really opened your eyes to a whole new world of, of interventions. So you can see briefly, I'll show a little bit of a video in a moment as the actual surgery itself. But obviously, mum has basically has like a Cesarean section to expose the uterus. There's then quite a lot of ultrasound done to work out a where the placenta is and B obviously where the back of the baby is. So that when the opening is done uh in the uterus, that the fetus can be uh uh easily seen for the for the surgery and uh you can see the uterus is obviously stapled along the edge during the um er procedure um in and then obviously allows the, the surgeon to get in and do the, the operation. So th th this is a video of the procedure because we do this in collaboration. We've been doing it between London and Leu and Belgium and that's where the NHS um surgeries get done. Er, currently. Um and you can see what I was just showing there's the um exposure of the uterus and you can see now the ultrasound happening cos clearly it's important when the uterine incision gets done, that has to be well away from the placenta. And then of course, the baby has to be manipulated so that the back of the baby is exposed through that hole in order to uh to operate on. So once the obstetricians have made the uterotomy, um you can see the stapling device going in er there and then uh once all that's er sorted, then obviously it's time for the er neurosurgical and surgical team to get in to begin the er surgical repair. And you can just see now there's in fact that sac you can see is the bottom end of the spine of bifida. What we're doing now is starting to immobilize the spinal cord away from the surrounding skin of the fetus. And obviously, this is a lot smaller than it was in the video. I showed you of postnatal. So typically, you know, these kids may be 5, 600 at least um grams at the time you're operating. So, a pretty generous baked potato would be a good uh good analogy. So pretty small. But in essence, what we're doing is what we would do in postnatal surgery, mobilize the spinal cord, mobilize the muscles around the outside and then do a layered closure. Um so that the spinal cord is protected inside. And of course, that the fluid leakage is then stopped. You can see mobilizing the muscles um here on either side. So that then we can suture the muscles uh closed. Um And once you've got a nice watertight closure across the muscles, the next thing is to try and uh close the skin in a watertight er manner as well. And you can see the skin being closed here now and once that's done, the baby's popped back into the um uh uh uterus, the uterus is uh filled up with um, er, er fluid to recreate the amniotic fluid cavity. Um And then the um er obstetric team then go on and close the um uh uterus and then bump goes um back to the ward remains on some tocolytics to stop contractions and then we will deliver by a Cesarean section a little later. So, in essence, in the, in this is known as the open fetal surgery technique because obviously the uterus is opened and the surgeon operates directly on the back of the er, fetus. And most of the time, probably 80% of the time we can get what's called a primary closure where it's skin to skin apposition as you can see in these uh pictures uh here, um, now, occasionally the lesion will be so big that it's not possible to do primary closure. And in the postnatal case, we would get the plastic surgeons to give us a hand if we needed to move skin around. Of course, you can't do that in a fetus and in the fetus, what we sometimes have to do is to sew in a patch of tissue. Um This is a durable patch which sometimes used in, in the management of burns. Um And uh it doesn't give you obviously quite as cosmetic a result. It looks a bit ugly uh for the first few weeks, but gradually skin grows into that and it heals over leaving a uh you know, an intact cover over the underlying neural tube. But of course, wherever possible, this is what we're after. This is a couple of case of babies who were born that had had uh primary uh closure and as you can see, they can heal up very nicely indeed. So how do we think the surgery works? And, and, and that really is still a bit of an unanswered question, I think from the neurosurgical point of view, I think there were probably two explanations. The first is it's a simple hydrodynamic problem. And there we are uh basically closing off the tap of fluid that is leaking into the to the um amniotic fluid. And I think by stopping that fluid leakage, it's that what's allowing the um hindbrain to return to its normal position. So reversing the chiari malformation and it's allowing the kicking in if you like of the normal CSF circulation. So there's one aspect that's hydrodynamic. And I think the another that's neuroprotective, as I said before, the fact that the neural tissue is exposed to the uterine environment, it's been damaged in the last few weeks of life by covering it with hopefully normal healthy skin. One protects some of that ongoing damage. So you're not really reversing anything, you're simply hopefully preventing a further secondary damage. As I told you, I know after the mom's trial, clearly, there was then enthusiasm for that to be done. We then decided we worked with uh colleagues in Leuven and we've been down to uh South America where they've already got a good established programs because there's a lot of Children born with spina bifida in South America. Um And now there is a National Health Service Commission Service. And as I was saying, we split the UK between those that have their surgery to the north of England, they go to Leuven and have their surgery and to the south of England, they come to us at UC H and then we follow them up basically um um through a um coordinated follow up at uh Gyn Spina Bifida Clinic at Great Ormond Street. And um this is a uh selection of the mums from AAA year or two down the, er, line with their, their various babies and in fact one of them, uh one of the uh, er, mums, er, sent me this little, er, er, video of um her kid and this was literally a few, just a few days or a few weeks after her taking her first uh steps. And so, you know, I say she's obviously having to get used to her walk at the moment. But uh you know, this is clearly a significant advance for these uh for these kids. Now, is it all, is it all rosy? Of course not. Are there downsides? Yes, I mean, mum has to have a Cesarean section to deliver following the open procedure. There is a risk of the uterus dessing or at least thinning. And that's one of the reasons why they have to have not only a cesarean section in this pregnancy but also in er subsequent ones, there's a risk of premature rupture of the membranes. Um and thus potentially implications for future pregnancies. From the point of view of the fetus, there's uh fetuses who are being operated on prenatally are very commonly born slightly prematurely and of lower birth weight. Um, and of course, not all derived benefit. Yeah, the majority get an improvement, but that's not necessarily guaranteed across the board. There may be repair site complications. So the baby may be born with some leakage of fluid through the uh wound or the tethering of the spinal cord that may require subsequent neurosurgical in er interventions. And so far, we're not convinced that the surgery is changing the prognosis in terms of bladder and bowel control. The, the evidence on that is some papers are saying yes, it's improving that others are, are saying not. So I think the jury is very much, uh very much out there. Um, uh, and as you can see, uh, he here that compared with postnatal surgery, um, uh gestational age and birth weight are both that somewhat compromised. But when we've looked at this in terms of all the patients that have been operated on, the degree of prematurity is moderate and that doesn't seem to have confer any bad neurocognitive uh implications uh uh for the, for the Children. So, what about the future? Well, as you well know, particularly in surgery, everything's going minimalist and technology uh based and uti um fetal surgery for spina bifida is no different. Um, perhaps one of the most uh known is the possibility of doing this endoscopically. Um And uh certainly that is now a well established uh technique. This was not the technique used in the Mons trial and it is not the technique that we have been using so far. But my colleagues at Great Ormond Street. Um and certainly uh in, in uh also at King's College Hospital in London, people have been doing the FOSC, er, er, technique. Um, er, and so this is um differing, as I say from the, from the open er version. Um now, er, why pursue FOSC topic really for the sole purpose of improving matters for the mother? Nobody at all is suggesting that the surgery gives you a better fetal outcome. In fact, if anything, some of the fetal uh um parameters aren't quite as good as with uh with open. But the main thing is it is better for the mothers because they don't necessarily have to deliver by Cesarean section. And the implications for mums in terms of future um pregnancies and so forth are are better. One of the problems at the moment is that everybody doing fos scopic surgery is using a slightly different technique, whether they use one patch, two patches, no patches, um whether the uterus is exteriorized or whether it's done fully percutaneously. So that's making it a little bit difficult to work out the stat statistics at the moment. Um And even with the fos scopic, there are still problems of prematurity, there are problems of premature rupture of membranes which is slightly greater than with the open technique. Um And it's you're more likely to require some neurosurgery to the baby once the baby is born. Um Well, following the endoscopic versus the open technique. What we have done in the last couple of years since we started is to move to the mini hysterotomy. So initially, we were operating through a seven centimeter incision, which is what I showed you in the video earlier. Now we're doing it through a 3 to 4 centimeter incision. And that's been shown to have significant improvements in terms of the health of the uterus. Longer term. Of course, it makes things a little bit more challenging from the neurosurgical point of view. As you heard in the last, er, er, er, talk, er, this morning robotics is absolutely on the horizon. And, er, robotics will most definitely. And I think, and in fact, has already been used in Canada to do, um, intrauterine surgery and there's all sorts of technological developments being done there. So I think that's pretty much, uh, the end of what I was going to do take you through a little bit of a journey of a very, um, obviously niche area of pediatric neurosurgery. But the one I, the one I think hopefully has demonstrated the translation from basic science all the way through to delivery of an established clinical service. And, uh, I, as I said, at the beginning, you know, I, II think, you know, surgery and I'm obviously at the other end of my career to most of you. But, um, uh, you know, surgery is, is absolutely astounding. I would never have done anything different looking back on my time. Uh And I think some of the things that I've learned over time is that surgery is very much a dynamic and in fact, an increasingly dynamic speciality and there is plenty of room for innovation. Yeah, collaboration, I think is absolutely the key. None of this is I would ever have even conceived of doing it on my own, but actually joined together with some of these amazing people, Palo de KPI, the PPL and many others uh has been a real, real privilege. And at the end of the day, you know, yes, we hope we do a hard job a lot of the time, but uh important to continue to enjoy it as you go forward. So I hope that's been of some interest to you. Um uh And uh just as I say, to reflect that collaboration, just a list of my colleague who have been involved in this amazing journey. So thank you all very much and I hope you really enjoy the rest of your weekend conference. Thank you very much. Thank you very much to Pro Thompson for delivering such an inspirational and quite a unique um talk. We've thoroughly enjoyed it in the interest of time. So there is lunch being served at the minute. So if you do want to go and grab some lunch, you can, but we will allow a little bit of time for some questions if that's all right. So if you have a question equally, please just pop your hand up and then we will endeavor to answer you. Got any questions or? Yeah, got one question. We got a microphone, rhyming mic. Do we, do you want to ask your question and speak up or do we have a roving microphone? Oh, there we go. Perfect. Thank you very much. I was just uh wondering is there is the fetus anesthetized at all during the operations? So a good question. So a lot of the, the, the fetal um from just by virtue of the mother and on placental circulation, they, they end up um er, getting uh so some of the um a anesthetic. But in addition, they're given a uh muscle relaxant and morphine as an injection just before once the fetus is exposed, that injection goes straight into the bottom of the uh fetus before we start the actual er, surgery. Great. Any, any more questions and any questions for um Mr Chanda as well, please? Hi. Thank you very much for these talks. Uh It's a question for Mr Chan. Um with these were, were you transplanting an adult kidney into a pediatric case? Is there any reason why you can't do a partial nephrectomy to fit it in easier? There's no question. It's a very good question. But no, we generally don't tend to do that because if you do a partial nephrectomy, firstly, it's another procedure and secondly, there's a high chance of leak and bleeding from the raw surface. So we generally just go for the whole organ. There's nothing better than giving as much Nephron mass to the baby as such. I mean, for liver transplants, you can do the left lateral segment of the adult living donor liver which is fine when the liver regenerates and grows. But for the kidney, we don't tend to do that at the moment. Any other questions, please? In the hands? Oh, we've got another question just here, right? Uh Is there an optimum age for the fetus when you perform the surgery for spina bifida? Like how early do you normally do it? Thank you. Yeah. So the the short answer is the earlier, the better. Um of course, it takes time for the diagnosis to be made and all the necessary genetic and exclusions to be done. Um So, uh but it definitely has to be done before the end of the 26th week. So that, that's the cut off that the mum's trial established and that's what NHS England are, are currently imposing. And the reason for that is if you leave it beyond that, you, you start to, there's no evidence, you get the same benefits. Well, at the other end of the spectrum, even if we could uh get the Children into the or the months into the operating theaters at 2021 weeks, it becomes a very different. I mean, tissue handling does change down at around 23 22 21 weeks. So typically the vast majority are done between 24 and 26. Another question you just there. Thanks. Yeah. Um, is one of the um, exclusion or inclusion criteria, the level of the defect? Because you did mention that the higher up it is um, the worse functional outcome becomes. Yes, that's right. So the higher up the spine goes, obviously, the more of the spinal cord has been affected. And so these Children, you know, by the time you're up in the thoracic level, um, then typically you often have a lot of spinal deformity, which is an exclusion criteria. And then obviously the, the, you know, the, the motor benefits drop off simply having a lesion in the thoracic lesion is not in itself an exclusion because there's still the potential advantage of reversing the chiari malformation and avoiding a shunt. Um, but, uh, um, certainly the, the advantages become much less as you go, um, higher up the, uh, spine. So the majority of our cases are, are mid to low lumbar and of course, by the same argument, uh, if they're so low. So if you're below, um, er, er, s one again, because the prognosis for those Children is relatively good, even if they've operated on postnatally, uh, we exclude those as well. So there's that spot really in between where you're most likely to get the advantage. Thank you. Any, any other questions? No. And if there aren't any further questions. I'll wrap this session up. So, thank you so much for attending the session. Thank you to our speakers today for giving some absolutely incredible talks and I hope you enjoyed hearing more about the cutting edge of surgery. So, another round of applause for. So what?