Vascular malformations: Update Course 2015

Todd has asked me to talk about vascular anomalies in 20 minutes. So this is going to be a rapid fire sort of cases that as practicing pediatric surgeons that you may see. So we'll start off with the first slide. Child 28 week premature infant NICU for feeding and growing started to develop multiple hemangiomas. In total you can count at least 8, and within every sort of few days the new one pops up. Um, on exam, the systolic murmur, palpable liver edge, um, the NICU rightly did a, uh, AFP and hyper and then showed elevated AFP and hyperbilirubinemia. Also had an elevated TSH, um, and started on Synthroid, and so there's no coagulopathy there. This is sort of pictures of what you may see on the baby. Um, so just quickly, um, this sort of a poll question at this point in time, when would somebody screen for internal hemangiomas and where? So there's been a paper and we've actually reviewed our own data that if there's more than 5 hemangiomas, the likelihood of having internal liver hemangiomas, which are the most popular, is more common. So we screen any child who has more than 5 hemangiomas as well. If there is a palpable liver edge in a child with less than 5, it's something to consider. 87% got that right. There you go. So this is the MRI. So initially we screen with an ultrasound and then proceed to an MRI. On the MRI you see multiple focal hemangiomas here. At this point in time, um, the decision to treat the liver lesion or not becomes sort of the, the big question. Um, I don't know if anybody in the panel um has any thoughts on that, or so looking at the images, and at this stage I would be still monitoring as long as the patient's not symptomatic, we'd probably be, probably be patient um and see how she progress the baby progresses. If they start to have more symptoms, then interventions might be considered. So the only thing that would push us to treat this one was actually the elevate the TSH. So these kids can become hypothyroid because there's a consumption within the liver hemangioma. So for this baby we actually treated. And the standard of treatment now is propranolol. We can go up to 3 mg per kilogram of propranolol if the child is sick. We can actually add corticosteroids to sort of jumpstart it. So I don't want to mess up your flow, but I want to make sure I understand. First of all, they checked an AFP level. Why and when do you check an AFP level? So they checked an AFP level because there was a liver mass. On ultrasound or they felt the liver edge, just because of the liver edge they checked, OK, but it wasn't because of the hemangiomas. No, we do follow AFPs on our hemangiomas, so sometimes you'll see them elevated, if it's elevated, we'll follow the AFP until they go back down to normal. We'll also follow the hemangiomas until they completely disappear because we've seen late change into angiosarcomas, and we've had two patients that has happened. So we actually follow them until they're almost completely gone and we'll do a screening ultrasound when they're 5 years of age to make sure they are gone. When you treat them with beta blockers, do you follow the thyroid hormone? We do. So the thyroid, so these kids, a normal synthroid dose is not enough. They sort of need an exaggerated Synthroid dose, and we have our endocrinology folks involved. The actual hyperthyroidism resolves once the hemangioma improves, so they get treatment for both. So if we go back to the slot, so, so most babies tolerate it quite well. We start at a low dose. We start at 0.5 mg per kilogram and escalate up to 3 mg per kilogram sort of as our max dose in these babies. We escalate within two or three days as long as their heart rate, blood pressure, and their glucose stays stable. Most of our kids will tolerate very well. We've only had maybe one or two who couldn't tolerate it, not because of blood pressure, um, but because of hypoglycemia. Because they're bad, bad feeders and so if you become hypoglycemic, we have to bring down the dose. So Belinda, when do you start worrying about malignant transformation or how do you how do you monitor for that? So we monitor with ultrasounds every month initially to make sure that our treatment is resulting in decrease in size of the hemangiomas, and then once they're stable or almost gone, we'll do it every 3 months. And then if it's completely gone, we'll do sort of a screening ultrasound at 5 years of age. Is there a role for MRI at all? So we do an MRI after there's the hemangiomas are noted on the initial ultrasound to give us better characteristics. It also helps our liver surgeons if we need them in the future for treatment. When would you ever think about intervening from a liver standpoint? So we do that as a collaborative discussion, at least in our institution. So together with our vascular team and our liver team and depending if there's cardiac failure issues, we use our vascular team includes an oncologist as well as a surgeon. If there is significant heart failure, if the lesion is growing, if there's any concerns with regards to that and there's no response to treatment, then we would consider intervening. Intervention now, you know, we, there's a lot of talk about embolization and, uh, surgery. Um, I know that within our sort of, um, scope at our, our institution embolization is not as common anymore, uh, more because it results in necrotic tissue, um, and then the child still needs surgery eventually. I don't know if you have anything else to add to that, Greg. Yeah, I think the point is that you want to limit the liver interventions because the consequences can be so significant. We have certainly seen patients who've come with hemangiomas that were embolized that actually were more consequential from the embolization rather than the treatment. And so I think the critical component is the symptoms of the infant if they have heart failure, if they have a. Of the coagulopathy, that's when we'll be more aggressive in terms of treatment. Going back to the slides, you know, I just, there's 3 of MRI pictures at the bottom, just sort of the differences and the categorization of hemangiomas now is sort of into 3 groups focal, multiple, and diffuse. It's mostly the multiple and diffuse that cause troubles with Steve Fishman's group in Boston. They've developed a registry. Um, and the focal liver hemangiomas actually behave more like congenital hemangiomas or rapidly involuting congenital hemangiomas where they actually go away quite quickly on their own. The multiple and diffuse are the ones that actually usually require treatment. So second case um is a segmental face hemangioma. 6 week old who comes to the office, was an ex-preemie, um, initially had some bruising, um, and then within a couple weeks had a rapidly increased, um, in size. The eyelid, eyelid component, um, grew quickly and, uh, the baby was unable to open the eyes, the sorry, the, the eye. So this is a picture of a segmental hemangioma of the face which you know some people would say well maybe it's a strawberry um capillary malformation but with the story you'd have to think that it is a hemangioma and so. I brought this case to talk about treatment once again, but also to think about the other things that can be involved with the segmental face hemangiomas. So there's something called face syndrome. I'm not sure how many people have heard about face syndrome. So this is the baby after they've been treated, propranolol. So the thing. That whenever we see hemangioma like that, that we would actually screen the child for is posterior fossa anomalies, arterial anomalies, cardiac anomalies, eye abnormalities, and developmental issues. So these babies actually end up getting an MRI when they're a little bit more stable to look at their posterior fossa in their brain and the vasculature to the brain. They all get a screening echo, um, and they get eye exams. Any of the kids who do have abnormalities, um, we follow quite closely with developmental. Their development because they can develop significant developmental issues and learning disabilities as they get older. So. Um, and Todd actually brought this up, um, earlier as we were sitting here, whether if you had an imperforated anus and a, um, a hemangioma, and there's something called pelvis syndrome, so there is a syndrome where you can get imperforate anus, hemangiomas, and irregular abnormal, um, vasculature in the pelvis, um, mostly you'll see them in, in babies who have, um, sort of the perineal fistula, the fistula that extends up the. This one actually has a normal anus, but we've seen children with with imperforated anus as well. The biggest thing about these ones is that you do have to screen their spine because a lot of them have intraspinal abnormalities. And so initially if they come to us early enough they'll get a screening spinal ultrasound, and if anything is significant they'll get an MRI. And this baby actually had a tethered cord that they actually operated quite quickly on because it was quite significant. I had a patient once who um was born with a red little hemangioma in the in the um the sacrococcygeal area. I would, and they got an ultrasound and it was an SCT underlying it which so those are very ominous those those spinal hemangioma so you know the pediatricians now will ultrasound almost anybody, but it's really the lower sacral midline hemangiomas that you have or even a vascular malformation so all our capillary, all our sort of abnormal vasculature on the back we'll, we'll screen. Great. So this is a baby with a prenatal fetal MRI. We have an active fetal center and so we see a lot of fetal consults with a mass on the forehead. And so, um, it was questionable whether this was a vascular tumor at the time and, um, the, the child was seen by us immediately, um, postnatally, and this is what we found so this is more consistent with what we call a congenital hemangioma. So congenital hemangiomas are the ones that you see at birth or you can with now prenatal screening, um, that you can see them on prenatal imaging. There's sort of 4, sort of 3 types that we look at the riche, the niche, and the piche. So, uh, RISH stands for rapidly involuting. Um, niche is, um, non-involuting, and piche now is a new category which is partially involuting. So this baby underwent, um, we actually waited for a while, but because of the significant tissue expansion and the lesion that was there, we, we proceeded to, um, have surgical excision for that. So we're going to jump from hemangiomas now to Consideration when you biopsy these, what are the, what's the immunohistochemistry that you guys think about staining for? And are there markers for us to understand? So, so the riches or the niches and the peaches, so a hemangioma, when you look at it under microscope, the biggest marker that we're looking for is glute 1 staining, and in congenital hemangiomas they're glute 1 negative. So that that is what differentiates it. As well, it's differentiated by its, um, natural history, so an infantile hemangioma, if you wanna call it that, um, does not usually present at birth. Um, the congenital hemangiomas, you'll also have a halo which the, the, um, uh, infantile hemangiomas don't have, um, and the, the congenital hemangiomas usually don't grow after they're born. They usually start in ballooning quite quickly. So now we're jumping. So we're gonna do vascular malformations now in 3 minutes, so. And I brought these the the couple of cases that I thought would be interesting to talk about are ones that have prenatal diagnosis because I think that's when we get involved, um, and you know when do you talk about debulking and when do you talk about surgery versus when do you talk about sclerotherapy and, and more within the last sort of 7 to 8 years, you know, medical management now with rapamycin and serolimus so this is an MRI of a baby that had a did I. Um, a prenatal diagnosis of a vascular lesion of the thigh and hip. That's pretty dark. There you go, so you can see that, um, this was her post-op imaging. The fetal imaging wasn't great. So the post-op, um, sorry, the postnatal MRI showed a very complicated phno lymphatic malformation with significant overgrowth and bleeding into the lesion. When the baby was born. Her actually her right foot was by her ear because her hip had dislocated from the, the mass of the lesion. So the baby was seen in our NICU, initially managed with an observation. We did not start her on steroids right away because a lot of these babies, once they're born, will have a significant amount of swelling and bleeding into the area which will resolve within the first few few days to weeks and then we sort of expectantly treat the symptoms. And our goal in treatment of the malformations is to preserve function and to treat any complications. So this baby actually had compression of her bladder as well as had compression of her rectum, so had difficulty with stooling as well as voiding. She ended up getting a a vesicostomy for voiding issues, um, and as long as we kept her stools soft enough, she was able to stool OK. There's just a picture of her. um, this is about a month after she was born. So this baby at 2 months of age because of how poor her leg looked and the dislocation of her hip, we actually started her on Cerulimus and so Serulimus was one of those medications that was, um, sort of a last ditch effort in one of our, um, patients and and our medical director Janice Adams started using it in a KHE lesion. We've now applied it to a lot of our vascular complicated anomalies. This is her MRI with just medical treatment alone and a couple of rounds of sclerotherapy. You can see that her hip is back in place and she's actually very functional and walking on it. But Belinda, can I ask you before you get there, this is a newborn child's born with this large exophytic mass. Do you, do you feel the need to biopsy it, or do you know by certain criteria by MRI imaging and looking at it clinically, we usually don't biopsy if there's any concern. So the ones that we think may be, so Kaposiform hemangio endothelioma, we will biopsy, but if it looks like a complicated veno lymphatic malformation, we won't. It's very bloody if you do. So we have, we have a whole group that sits and we have a very dedicated radiologist, actually two radiologists, an interventional radiologist and a radiologist who will look at prenatal and postnatal imaging, and there are certain criteria they will look at. Um, to, to help us diagnose them and then just looking at the baby, um, if there's, if it doesn't behave normally, then we'll biopsy, but if it, it looks straightforward, like, well, straightforward as it is, a, a venous lymphatic malformation, we won't biopsy. So she was treated actually for 2 years with rapamycin. She's very functional. She walks, she dances, she runs. Um, the biggest thing about her, she's got a little bit of excess tissue on her buttocks and her thigh which doesn't allow her to wear jeans, um, so we actually ended up doing a debulking of just a very limited segment. So this was after 2 years of rapamycin and you can see that um it actually looks pretty good functionally. The amount that we actually ended up debulking was very minimal compared to if you were to do it at birth and the amount of debulking you would have to do at birth. Belinda, there's a question from the audience about what agents you use for sclerotherapy. So depending on what is in the malformation, so it's a venous malformation. Will you Use a soap, so sodium tetradiyl sulfate STS. If it's lymphatic, we'll use doxycycline and people also use bleomycin, so the two of those. bleomycin we are a little reluctant to use a lot because there's potential issues with pulmonary fibrosis, however, You changed my management by I was way under frequency. I was using it seldom, and I think you do it sometimes you'll leave an indwelling and do it twice a day or once a day or twice a week or I don't remember what your frequency was. We will, we can, no, we'll sclerotherapy probably every 3 to 4 weeks, but I had a child once that had a catheter in. And instead of, so we'll leave it in there overnight, so you'll do the, is that what you're asking? How often do you give the doxycycline once every several weeks. OK, yeah, so, so our interventional radiologist does it, but what he will do often is inject it, leave it in overnight, leave a catheter in, and pull it out the following day. When you do sclerotherapy after the first week, the thing will swell up and get hard and look horrible, and we always warn the family that it's going to look worse before you get better. It looks better, and then usually within 3 to 4 weeks you'll sort of see the results of it. Our management of um these complicated lesions has really changed I would say in the last you know 5 years, whereas surgery I think was a mainstay for debulking and excision. Um, it's sort of used in conjunction now with serolimus and sclerotherapy because we'll all target the macrocystic lesions with sclerotherapy first, um, and then we'll use the the serolimus and then we sort of do the clean up work afterwards. At what point would you say that you've maximized your sclerotherapy approaches? So I think if there's, there's no more macrocystic lesions that you can target or if you're not getting a significant result from it. So just sort of some background on there's just one slide. This is the only slide with words really, the use of Cyraimus ambassador anomalies. So we've done phase one and phase 2 trials at our institution in conjunction with multi-institutional trials. It's because there are. Kinase somatic mutations in these anomalies that we've identified and the MTOR inhibitor, so rapamycin tar is downstream of of that PI3 kinase. There's been multiple case reports and trials, um, and we use it in conjunction, like I said, sort of as a collaborative approach. Um, and we've used it in almost any vascular anomaly you can think of, so it's, um, been quite effective. I don't think it's a be all and end all because when you wean it off or you take them off, the lesions actually become more symptomatic, um, so there's more in the works for that. From here, you know, so rapamycin is used commonly in the transplant population. Do you guys monitor levels and do you target certain levels? So we target a level of 8 to 10 usually and we were targeting 10 to 15, but then we found that they actually have effect with a lower level. When we do maintenance dosing, it's even lower than that, and they go to once a day dosing as opposed to twice a day dosing. Have you guys had any From the trans We don't actually start Or at least a month after the transplant because of the delayed wound healing effects when you're considering is where myself and the surgery people argue with our medical and oncology people because they support that there's some study in rabbits where there is no wound effect issue. But we will hold it before and after if we're going to do a debulking, so I don't hold it a month. There's no anastomosis or anything that I really have to worry about, so I'll hold it for a week or two after surgery. Belinda, what do you, you may be going on to discuss this, I'm not sure, but what do you do with those large cystic lymphatic malformations in the abdomen that are totally asymptomatic but have been identified on scan because the child is distended but otherwise doing great. So it depends if we think it's a lymphatic malformation, we'll actually sclero them or we will excise them. Depends on the symptoms and what's going on. If they're asymptomatic, if they're asymptomatic, sometimes we even leave them alone. It does. I mean, I had the, the one I called you about. It was excruciatingly painful for the child. Um, we had to stop just because we couldn't, we didn't want to do a general anesthetic what we do now. I mean, it's, we just tried to do it. We left the indwelling in. We did it under anesthesia, left it, and we had to pull it out because it was just so we do it under general anesthetic because it's painful. I mean, but you leave it in dwelling, right? Well, you leave it in dwelling, but they get admitted and. Yeah, maybe it was just this one kid, but it was terrible. We've also had those kids who present with a very large retroperitoneal solid lymphatic malformation. There really isn't much to do, and you just hope that it doesn't continue to grow. So I mean if they're solid, they're usually the microcystic type and so if it's causing any functional issues, then those are the ones that we'll try erolimus with, um, and you can some of them, I mean. The complicated lymphatic malformations, probably upwards of 70 to 80%, will get some sort of response or stabilization. You don't get complete disappearance. You get stabilization and potentially a small decrease in size on erroimus or just naturally on erolimus. Yeah. Um, we're running out of time for my portion. Do you want to skip, I guess. Let me ask you this. You just spoke to us about a lot of different things. Put you on the spot here a little bit, but can you recall maybe 4 key takeaways, cliff notes? What are the key things that we should take away from what you just told us? So, so as a surgeon, I think the things that we see most commonly are hemangiomas. So you know. It's not always a operate now anymore I think now it's a think about the different sort of types of management because there's one thing to take things off and leave a scar there's one thing to treat it, um, so at least for hemangiomas with propranolol now you have, we have amazing results, um, it takes away from our business, of course, but I think, I think without a scar and if it can disappear and I just have to touch up and do some laser afterwards, the family's much happier. So propranolol laser, propranolol laser, those sort of things, I think for hemangiomas, I think you need to differentiate between a congenital hemangioma and an infantile hemangioma because they're very different. And then with lymphatic malformations, I think the biggest thing now is we need collaborative multidisciplinary treatments of them because once again surgery is one thing, but now we see people with scars with post-op issues with Recurrence of their lesions with surgery. So the sclerotherapy plus the rapamycin plus the surgery, I think benefit the patients much better. Great, thank you very much.