Open Fetal Surgery Overview: Fetal Surgery 2012

I'm grateful. We're going to be having a brief overview of open fetal surgery, sort of the current applications. Uh, that I know of, and then a discussion to follow. We're going to start more invasive and move toward less invasive as the day goes forward. That's actually the wrong talk. That's the next talk. And my open fetal surgery uh talk won't include myelomeningocele because I think that deserves an entirely separate, uh, talk and discussion that Scott Adzik will lead. So, um, once my Presentation comes up. OK, so this is a slide I borrowed from Mike Harrison about 25 years ago. I still like to show it just because it gives the big picture on what we're doing. Um, and it's really sort of a formidable enterprise if you think of it from that perspective, and you got to give Mike credit for having, uh, real cojones to, uh, start this field. Let's see, how do I advance these? Um, also click on that forward arrow, click on the forward arrow. You know. And I'm not going to do the big normal wind up for this, but basically, I put this up just to emphasize that, you know, most of the time what we do is to wait and treat the neonate still, but we do have a whole armamentarium of options for timing and mode of delivery, and still in a very few cases to with appropriate selection treat patients in utero. OK. These are Canada defects that uh really most of which were defined 30 years ago. I put them in different colors just to categorize them into things that I think are accepted indications for fetal surgery at the present time. Those include the yellow ones there, pulmonary airway malformations. I include a bronchial atresia in that, uh, as well as potentially chaos, uh, sacrococcygeal teratoma, and myelomeningocele. The sort of orange ones are. Anomalies that are still treated prenatally. They're controversial. They're treated in less invasive ways than open fetal surgery. Uh, but warrant consideration. And then the bottom one, CSF obstruction was one that was sort of taken off the list years ago and perhaps it should be reconsidered, and that'd be an interesting discussion to include a little later as well. So we'll start with CPAM, uh, congenital pulmonary airway malformations. And I think most of us in this audience anyway recognize that the prenatal history is variable with these lesions. They can grow rapidly in size. They can compress the heart and mediastinum, resulting in heart failure, and occasionally they can compress the lungs with secondary lung hypoplasia. We also recognize the majority of these lesions regress late in gestation and don't require any fetal intervention. So, prenatal classification, we're familiar with the Stalker classification that applies to postnatal CPMs. That's way too complicated for practical application prenatally, and basically, we talk about microcystic lesions that don't contain cysts and macrocystic lesions that do, and they behave somewhat differently and are treated somewhat differently. So it is a An important uh Um, Differentiation. I put this up there as another uh differential diagnosis that sometimes requires fetal intervention, or at least as a candidate for fetal intervention, and it's basically can look exactly like a microcystic secam. Uh, but you have very homogeneous lung parenchyma. You generally can see a dilated central bronchus or mucocele. And you have to be careful and document that a contralateral lung is present because lung agenesis can also masquerade as a microcystic seca. And again, they have different uh pathophysiology. So this just shows a brief Uh, Video cutting through a patient with bronchial atresia just to show you how impressive some of these lesions can be, and this is a Um this is a lower, uh, a, uh, upper lobe bronchial atresia patient. And you can see the massive distal lobar hyperplasia that exists in this patient along with associated ascites and ultimately hidrops. You can see the, the, the dilated bronchus and, uh, Centrally in the lesion that's the tip off of his bronchial atresia. Can you, uh, use the arrow and show me that? Show me what you're talking. So the arrow, where's the, where's his arrow? Does he have an arrow for this, Mark? Can't, can't use the arrow. OK, can't use. So I can't point it out to you, but if you see that white, uh, Um, dilated structure in the middle of the media site and we'll see more of them later. So let's move on to the next slide. OK. So, and obviously, uh, when CPAM evolves into eye drops, that's the sole indication really for consideration of open fetal surgery. And this shows a microcystic secam that's massive, and on the right side, you can see an MRI showing skin and scalp edema, uh, fetal ascites, etc. Gotta get my forwarding down. The rationale for fetal intervention with CPAP is to restore normal anatomy, restore normal physiology, and allow lung growth before birth. And when it, uh, actually works, that's what happens. And this is a complicated algorithm. It's gotten a lot more complicated over the years, but the blue circles are really to me the only pathway that justifies consideration of open fetal surgery, so you need an isolated CPAM. We use CVR, um, initially defined by Tim Crummelholm to estimate risk for CPAM of evolving into hydrops. This is particularly applicable to microcystic CPAMs. And you can see that a high risk CPAM that has a CVR greater than 1.6 is now treated with a trial of steroids. The majority of them respond to that trial, although occasionally we still operate for CPAM and eye drops. And if the eye drops persist, despite the trial of steroids at an early gestational time point, then open fetal surgery should be considered, at least if you have the capability. So here's a case report of a actually a recent case that we have treated by open fetal surgery, 23 week gestation fetus, left lower lobe, uh heterogeneous CPM, presented with a CPR of 2.7, uh without eye drops. And again, if we could just have the video. And again, just the images on this patient, you can see the size of this tumor. It was heterogeneous, but predominantly solid and therefore not treatable by a shunt. And we can go on to the next slide, I think you get the idea. And this was the evolution of the eye drops. 23 to 25 weeks. We treated with two courses of maternal steroids to try to prevent growth of the tumor and evolution of eye drops. In this case it didn't work. CVR increased to 3.4, had progressive polyhydramnia, skin and scalp edema and ascites, and had fetal surgery at 25. And a half weeks So, show a video of fetal surgery here. Can we get the video? Coming up. It's on its way. Here it is. All right, so just a few of the maneuvers. First, we relax the uterus completely with a deep maternal gaseous anesthetic. We map the position of the placenta. We put in stay sutures for hemostasis, make an opening into the uterus, and use a, uh, a uterine stapler that was designed by us in the early years, um, for, uh, opening the uterus. We start an IV just like you would on a postnatal surgical case. Put on a pulse oximeter. We're continuously monitoring the fetus with echocardiography. You can see the probe down below, and it's important to have a good view of the heart and monitor cardiac function and filling. We refill the uterus with a level one, infuser, a warm lactated ringer solution. You can see the thoracotomy there and the massive size of this tumor. And we often have to do a thoracoabdominal incision, actually, to allow us to access the hilum of the tumor and do, uh, the usual, uh, lobectomy because these tumors are so large. And, obviously, we have to close up the, uh, fetus. We've got to put the fetus back in the uterus. That's the, The key to fetal surgery is putting the kid back in the uterus and keeping them there for an adequate length of time for lung growth to occur. And we go through a multi-layer uterine enclosure and, uh, also in a mental patch, uh, which I don't think is shown here, um, to prevent amniotic fluid leak and to control the membranes, etc. and prevent, uh, postoperative complications. So, that's just the general overview of what an open, uh, fetal surgery looks like for a CPAM lesion. If it's a macrocystic lesion, we don't need to do open fetal surgery. This is a very large macrocystic CPAP with a CVR 3.6, treated by a thoracoamniotic shunt, and the CVR dropped actually, I think that's a mistake on the slide down to 0.8 or something like that, as I recall in this case. The fetus was successfully treated with the thoracoabdominal shunt. So this is the experience of CHOP just for general results of our interventions for CPAM. There's an armamentarium of approaches that we take. Very few patients are terminated. Some are delivered by exit if there's a residual very large mass at the time of delivery. Postnatal treatment is almost uniformly successful with very good outcomes, as we all know, often with thoracoscopic resection. Open fetal surgery is about a 60% survival, and thoraco amniotic shunts are around a 70 75% survival. So, uh, in general, I think a success story for CCAM compared to the natural history. Uh, bronchialatresia is a different story. Uh, this just shows our bronchialatresia experience at CHOP. Uh, we've treated three patients, uh, by fetal intervention, and one was a right mainstem, uh, bronchialatresia, and we actually had an intraoperative fetal death in that case. One was a left main stem bronchial atresia, and this patient, uh, for some reason that still remains somewhat unclear, had a hepatic necrosis following the operative procedure. You can see the postnatal film there with a liver calcification. There was almost no functional liver at the time of birth. It had almost had a complete hepatic necrosis and ultimately died. And then the third case is currently in our NICU, um, is a left upper lobe bronchial atresia that progressed to hydrops, had a left upper lobectomy, and it's had a fairly stormy course in the NICU, but it looks like we'll probably make it. So, we may have a survivor, but this is a much more difficult lesion to treat than the CAMs in our experience. Sacrococcygeal teratoma is another potential target for open fetal surgery. We all know that once a child is born with SCT in general, they have a relatively good prognosis with early postnatal resection. However, the fetal pathophysiology is multifactorial and often leads to fetal death by one mechanism or another. The one that we're most interested in from a fetal intervention point of view is the tumor vascular steel, leading to high output physiology and high output failure. So the idea was that you could potentially interrupt this arteriovenous steel from the low resistance tumor and prevent the evolution or uh progression of high output failure. These patients are the most closely monitored of all of our fetal anomaly patients, and basically we do a very detailed analysis of echocardiographic analysis of blood flows in various chambers and chamber sizes, and we follow them for evolution of high output physiology. If that evolves, then one option is to perform a surgical debulking procedure, and this is a quick and dirty operation to remove the arteriovenous steel and the bulk of the tumor without doing a coccyxectomy or prolonging the procedure. This is Uh, our most recent case of a fetal SCT resection, it's also our most successful case, I would say. It's a 22 week gestation, predominantly solid type 1 SCT. Lots of blood flow to it. You can see the massive size of the tumor there. Um, and between 22 and 23 weeks, uh, had clear evolution of high output cardiac failure, and you can see the, uh, the parameters on the slide. At that point we proceeded with an intervention, and this is the video. And you can see us bringing the legs of the fetus out. All of that is tumor on the lower part of the screen. Again, we start IVs, we put on pulse oximeters, we monitor the fetus. And in this case, all we do is score the skin, preserving the interectal complex circumferentially around the tumor. We place a tourniquet around the tumor, tighten it down, and remove the tumor using a harmonic scalpel to seal the vessels. We slowly release the tourniquet and over-sew the bleeders. And uh then we close the uterus. You can see that uh those tumors can be incredibly big, highly vascular, and it's um Uh, you really just struggle to. To get them resected without too much bleeding. In this particular case unusually went on for 11 weeks in utero, was delivered as a stable newborn, underwent definitive resection soon after birth, and that's the picture of her at 2 years of age. Her bottom's not pretty, but it's functional. And uh she's essentially a normal kid at 2 years of age, except for that scar on her bottom. This is the results of surgery for SCT at CHOP. As you can see, we haven't done a lot of cases, and it's an extremely rare tumor to begin with, and the controlled progression to hydrops is an unusual progression, so that the majority of our candidates our patients never are true candidates for fetal intervention. And this is sort of an overview of that. Um, our last analysis, basically, uh, you see, we've seen followed quite a few patients, very few of them have qualified for fetal intervention. And we recently looked at the mortality in our series, which is reasonably high, um, And a lot of that mortality occurred at 27 to 32 weeks. So that tough period between prematurity and adequate maturity for delivery. And when we analyzed that experience, we really came to the conclusion that watchful waiting can be very hazardous if you wait for the mother to go into preterm labor or the fetus to evolve significant high output failure and just allow nature to take its course, and the majority of those kids will die. And so we've taken a very preemptive approach. This is our new algorithm, the CHOP or more recent algorithm. In which we deliver these patients prematurely either by an emergency cesarean or the exit procedure, depending on the maternal status. We deliver them anytime after about 27 weeks at the slightest hint that the fetus or mother are decompensating. And with that protocol, we've now had 5 kids and the results have been remarkably good without going into a lot of detail, surprisingly little morbidity from prematurity and basically relatively good outcomes. So I think this may be an important component of management of these patients in the future. So the future for fetal SCT, physiologic and metabolic assessment, we need better methods to predict which kids will evolve high drops and need fetal therapy. Minimally invasive ablative technology has been used. These slides are flipping around on me for unclear reasons. Things like RFA technology on these tumors thus far, I don't think there has been a safe abl of technology identified that doesn't induce a lot of collateral injury and bad outcomes. And so I don't recommend this at the present time. Hopefully in the future at some point. A safer and more focused ablative technology will be available to treat these tumors. And then early delivery either by cesarean or the exit procedure, I think will play a role in salvaging some of these kids. Finally, the exit procedure. I'll just run through this. It is a spin-off of fetal surgery. It uses fetal surgical techniques when done correctly, fetal surgery and anesthetic techniques as well. And initially it was developed to remove the tracheal clips after tracheal occlusion for CDH. Since that time, it's been applied to a number of applications, and I'll just run through those quickly. Cervical teratoma is the most common of those applications. The essential components of an exit procedure are maintenance of utero placental blood flow, you need complete uterine relaxation, which means you need an anesthesia team that's tuned in to the maternal issues related to that. You need to maintain intrauterine volume, uh, keep the uterus from contracting. You need maternal homeostasis and hemostasis, control of the membranes, and avoid the placenta and the cord. This is our uh exit team at CHOP. Typically, you can see it's a cast of multiple, multiple people, each with their own role, uh, multidisciplinary team that is required to really do this in an optimal fashion. And then post delivery, sometimes we'll take the baby to an adjacent operating room to complete the operative procedure. Sometimes they go down to the NICU following delivery, but you may need a second operating room team to do the definitive procedure on the baby. You may need ECMO, and obviously you need a maternal care team. So it's not a minor undertaking and requires a lot of coordination between services to do an optimal exit procedure. I have the video. This is a video I used just to show the, uh, the difficulties you can have with an exit and why exits are necessary and life-saving in many circumstances. This is a massive cervical teratoma. And one in that an airway could not be achieved from above. We couldn't pass a guide wire. We couldn't pass intracheal tubes. We ended up having to dissect the tumor out of the thoracic inlet. To reach the trachea, we tried to retrograde cannulation of the trachea with the guide wire, etc. and couldn't feed anything that way. We tried to advance the tube integrating the trachea, and ran into the carina, which had been pulled up into the neck by the tumor, and then we had to literally stabilize the ET tube with a surgeon's finger and transfer the child to an adjacent room and resect the tumor. So that was about an 11.5 hour hour procedure, all on placental support, maintaining good blood gasses throughout, and ultimately a successful outcome where otherwise there was no way that child would have survived. Other indications for the exit procedure include the congenital high airway obstruction syndrome babies. This is also a potential indication for prenatal surgery. And this is what chaos looks like. Uh, you can see the marked diversion of the diaphragms, the ascites, the thoracic, um, uh, uh, abnormality in the ribs, etc. And, uh, this was a laryngeal cyst and the first survivor of chaos actually delivered by the exit procedure. So, It can certainly result in salvage of these kids. They have to grow into their ventilatory mechanics. There can be a lot of morbidity associated with treating chaos at birth, and it's really a lesion that I think there's a strong rationale for treatment prenatally and if you have the appropriate patient. Epiathous oropharyngeal teratomas is another indication for the exit procedure that we've seen. This is a massive oropharyngeal teratoma. The child's head's under the tumor there. He's been delivered by the exit procedure. She has, uh, with a tracheostomy in place. I'll just show you other views of this. That's the tumor from the side. You can actually see tumor coming out of the nostrils on this kid on each side. There it is from the top, so you can see the massive tumor that was present and the difficulty you might have trying to intubate this baby without an exit procedure. And I basically debulked it, and then our ENT colleagues did the resection of the hypopharyngeal tumor. It had an origin at the nasopharynx, and basically this child is alive and well and normal at about 5 years of age, 6 years of age. And a few more indications, mediastinal teratoma. You can see that massive tumor and the compression of the heart downward and laterally by the tumor. And in this case, we did a median sternotomy with an exit procedure, and we actually had to pop the sternum open before the endotracheal tube would advance down the trachea. That's how much pressure was in the chest. And here's the tumor. It was actually quite easy to resect um after uh getting the exposure, so. And then recently, we had this pericardial teratoma that's compressing the right atrium, causing eye drops. You see the big left pleural effusion in that image and the massive tumor within the pericardium distorting the, the heart. And basically did an exit procedure with our cardiac surgery colleagues. Uh, it was attached actually to the base of the aorta, um, didn't need bypass, and, uh, had a good outcome. So those are various indications for the exit procedure. I think the future in fetal surgery are clinical trials, reduction of maternal and fetal risk, and that may make open fetal surgery obsolete in many of these anomalies. We need better imaging systems that give us not only anatomic but physiologic information. And I think tissue engineering approaches again to make open fetal surgery obsolete will ultimately be a component of it. And just to, to acknowledge my fetal surgical and obstetrics colleagues at CHOPP that uh participated in all these cases. So, that's all I have for the general overview. Um, And maybe we can open it up to our, Expert panel, I never realized how colorful CHP was. It's beautiful, isn't it? It's just a gorgeous place. Um, well, Alan, that was great, and we actually have some questions for you before we get to the questions. Let's bring on our virtual faculty. Um, can we, uh, hi, Doctor Farmer, how are you? If we can invite, have all of the faculty, go ahead and turn on your Yinka. Hello, go ahead and, uh, turn on your webcams so we can see you, uh, and, uh. Then we'll, uh, start, start opening this up to panel discussions. First of all, while we're waiting for, uh, we have on the phone line for this panel, um, Doctor Harrison, uh, and his group at UCSF, uh, Hae Min Lee, uh, Yinka Olutoye, uh, Doc, uh, Doctor Moldenhauer, Doctor Adzik, uh, Doctor, uh, Doctor, uh, Gladios is trying to get through, and Muelli is in the OR, will be calling in soon, uh, when he gets out of the operating room. Uh, so, uh, let's just make sure there. Doctor Harrison, can you hear us? We see, OK, we'll try to get Dr. Harrison back on the phone. He's on. He's on and he's present. We're, yeah, we're here. Hey, hey, Mike, how are you? Thanks for joining us. How are you? Uh, just go ahead and turn on your webcam, um, and then Hanman Lee, uh, Dr. Lee, are you there? Yep, we're all, we're all here. Oh, you're all there together. Perfect. OK, uh, we're all here. OK, perfect, perfect. Uh, and, uh, and, uh, Dr. Adsik, are you there? Yes, I'm here. Perfect. So if you guys can go ahead and turn on your camera by clicking that button at the top of the screen so we can see you and we'll start opening this discussion. There's questions from the audience about, um, if you could clarify CVR. Uh, there's been a few questions about how you calculate the CPAP volume ratio or what is it, and yeah, the CPAN volume ratio is, uh, based on. Measuring the CPAM tumor in 3 dimensions, 3 maximal measurements in 3 dimensions, and applying a formula for an ellipse to those numbers. Um, and that's, so it's basically the volume of the CPAM as estimated as an ellipse over the head circumference. And so, that standardizes for gestational age. And that that measurement has actually been quite reliable. It's been assessed retrospectively and prospectively. We've continued to use it for many years with our large CPAM experience and found it very reliable from the perspective of predicting. Patients' risk for eye drops, particularly with microcystic lesions, determining how often we do surveillance on the patients and just for their management and counseling in general. There was, you had mentioned about the trial of steroids first and then you may have mentioned and I missed it. When do you consider failure of, of steroid therapy? How long do you wait? Well, uh, a failure of steroid therapy is progression of eye drops, right? So. What period of time? Uh, well, it depends how fast it happens, OK? So, if you have a, if you have a patient that you treat with steroids and has rapid progression of eye drops, you know, you need to act in one fashion or another. Now. Once a week you check an ultrasound or. No, no, you do it two or three times a week. Two or three times a. On every other, every other day or so, um, because things can change rapidly. Um OK. I think there's a, there's a lot of experience with steroids out there among our panelists. Uh, they may want to comment. There's a UCSF group. Hey you guys. Um, Diana's on the bottom. We've got most of the people now, and I think there's been a, a large experience at UCSF. They actually started the, the first study, I think, with steroids. Um, I know Cincinnati's published on steroids. Uh, we certainly have. So, any comments out there? Do you guys still do open fetal surgery for CAMs? Um, I, I don't remember the last time we've done a C cam, um, over here. It's, it's probably been 5 years. Since that 5 years ago. When I first started. and we would have said the same until about 2 months ago when we had to do one, but So, uh, I think in our two centers that's one case in 5 years. So, um, not that many. Yeah, so, so for microcystic CPAM, I think it's, it's clearly the right thing to do even though we haven't done the randomized study on it. It's had a dramatic impact on the number of these cases that we do. Um, I don't think the same can be said with respect to response of macrocystic C cams, at least that's been our experience, and we haven't had much luck with bronchial atresia patients in terms of preventing eye drops with steroids. So would you guys agree with that? The theory that when we um when we um looked retrospectively at it was, uh, was that, um, by Sam Hogood, who is a neonatologist, now our dean, he thought that the steroids, um, drove lung development and made the microcystic, uh, CPA tissue. Uh, invalid or mature a little bit more completely unproven, uh, and hard to prove, but that was sort of the theory, um, although Tippy, uh, do you wanna maybe put some speculation into that a little bit, which is always good for some speculation. Go ahead. You trained, you trained her. Well, one of the things we're studying in the lab is uh whether the preterm labor, uh, that you see in hydrophic patients is secondary to a maternal fetal immune response. Um, Uh, and potentially the steroids may be ameliorating the maternal immune response against the fetus. That is pretty speculative, but we look forward to you, to you proving it. Alan, you should point out that this is a very happy story for fetal intervention in general, right? Absolutely. It's a very happy story. Uh, uh, we have, uh, do you, do you wanna bring up any questions to the, uh, panelists in specific, or do you want us to Ya's got some, can you hear me at all? OK. Go ahead. Someone had a comment. Ya. Yes, you hear me? Yeah. Oh, excellent. If I can just make a quick comment, I, I think steroids probably have a role, but one thing we've also found is we have. Always use eye drops as a means of defining who has or, or who, which fetus is going to get into trouble. And the definition of high drops using fluid in body compartments is that inference that right heart failure results and you see fluid in extra compartments. We have actually been a little more specific using the. Cariographic assessment of the heart directly as a main indicator of whether this fetus is developing heart failure or not. We've seen several fetuses now with, you know, massive ascites and maybe some mild pleural effusion, but as long as the cardiac function remains intact, we actually wait. Now whether it's the, you know, we started doing that even before steroids became quite popular, and we've been given steroids as well, so. I think until that randomized study is done, it's not going to be clear whether we've just gotten a little bit better in assessing those that have true heart failure from cardiac dysfunction or those that have some ascites due to either impingement of the cyst chili or distortion of the IVC, etc. that's contributing to this fluid in the extra compartment. Well, in the interim here, Tim joined us. Hey Tim. Well Tim, uh, are you still doing fetal surgery there in Denver, Tim? Tim, uh, Doctor Kho, if you could call into the phone line, we don't have you on the phone. Oh, we have, so, uh, call the phone line and then we can hear you. Although Alan's very good at reading lips, so Uh. Doctor Farmer, do you have any comments about what's been said? No, I think I just to reiterate Mike's comment and Alan's overview, I think it's a great example of the evolution of fetal intervention and that just, just when we get one problem apparently solved, it's not a reason to stop doing investigation and stop pushing the field forward, and I think that's true of all the disorders we're going to talk about today. Still can't hear you, Tim. No, he's still calling in, I think. We can see Tim, but we can't hear Tim. Dr. Adzik, do you have a comment about what's been said? Just two things. One is that the CCAM volume ratio, which Bev Coleman and Tim Chromoho devised years ago, has been a very good way to not only counsel families but also to determine the The pace or the tempo in which we follow up if you have a dish with a high C volume ratio, you might want to follow her 2 or 3 times a week, for instance, and then we've learned as well. I don't know if that Dr. Kholm, if you could mute your speakers, it's causing a feedback. Great. Sorry, Dr. Hadson. Go ahead. One of the things we've learned by really following literally hundreds of sea fetuses now is that The growth rate can be quite abrupt, between 18 and 26 to 28 weeks gestation, and then tends to plateau. So that's useful for counseling as well. And then my bias as far as the effect of steroids is that some somehow through maturation of elements or whatever, the steroids put the CCca further along that growth curve in terms of gestational age, and that might be an explanation. I'd also like to comment that uh we have some pretty well-dressed presenters here. Um, I, I can see that uh Doctor Otoya has some sort of peculiar blue background there. I'm. Uh, that's this guy in Houston. He's a It looks pretty good. Uh, diner, of course, looks wonderful. The UCSF folks look like UCSF folks. Alan Flake, uh, you know, I, I can't recall the last time Alan Flake has looked really so good. It was actually, it was actually my last webinar. It was. So Tim, are you on board? I am. Are you still doing, are you still doing fetal surgery there in Denver? We sure are good. We've done about 30 cases this year since I arrived. All right, so, so I'm glad we brought you on board as a panel member. Want to make sure you were still qualified as a fetal surgeon. So, so what's your view on steroids, Tim? You've done uh a fair amount of work on that. Well, I, I agree with everything that's been said. Um, we, I agree that if they're most effective in the, the microcystic, the solid forms, but we tend to use them even in cases, uh, where there are type 1 and type 2, because all of those have some degree of solid component to them. And the, the intent is trying to arrest the growth of that component, recognizing that it's not going to be as efficacious. And In the experience we had in Cincinnati with about 56 cases. Um, what we found was that if, if you were treating for cambine ratios above 1.6, which were the high risk group, uh, literally 100% survival did beautifully. Uh, in once Hydrops was established, uh, even in that setting, we had a 49% survival and good response. Um, If they did not respond to one course of steroids, the second course of steroids would salvage about 2 out of the 6 who got the two courses, and the others went on to fetal surgery. So, um, So, so, so that raises some good questions there. And so, do, do all of us, uh, agree with prophylactic treatment for CVR is greater than 1.6? Is that what we practice, um, even in the absence of high drops for the first administration of steroids? Anyone who disagrees with doing that? Well, uh, as you know, um, uh, we did try to look at that, um, but I think there was an equipoise to go forward because I think everybody basically, uh, gave steroids in that group, um, and I think it's still somewhat of an unresolved, uh, question. And will anyone, does everyone give a second dose. Well, they treat with two courses of steroids versus one.