Adolescent Bariatric Surgery: Pediatric Obesity 2017

Welcome back everybody. We have had a fantastic show so far and we hope we won't disappoint you in the uh on the home stretch here. The next session is going to be about bariatric surgery, and today we have one of the world's foremost experts on Adolescent bariatric surgery. That's Dr. Tom Inge. Many of you know he's the PI of the teen lab study, and Tom is now the division chief and professor of pediatric surgery at the University of Colorado. Tom. Hi Mark. Hi Stephanie. Thanks, uh, so much for the invitation. I'm glad to be here. Um, just on the technical side, uh, is the audio OK? Is everything looking good? Yeah, everything looks great. Thanks. Sure. Um, and I will. Uh, venture to control the slide, wiggle and click, and you'll be good to go. OK. All right, perfect. So I think uh Excellent. OK. Um, all right. So I've, uh, I've been asked to give sort of an update, uh, about adolescent bariatric surgery. And I think, um, you know, this, this, uh, presentation will dovetail into Mark Mikowski's, uh, presentation. Uh, on, uh, on guidelines and, and bigger scale initiatives. But what I thought it would do is to start off describing some of the, uh, published long-term results in part because we really just have, uh, two papers that came out this month in The Lancet, uh, Diabetes Endocrinology, uh, which does provide some long-term estimates of outcome. And then I want to talk a little bit about how these uh studies in particular, um, might drive decision-making around uh the future uh work that we're gonna do in this consortium, the Teen Labs consortium, over the next 5 years. So, um, uh, without further ado, um, We certainly know what drives our thinking about pediatric obesity treatment um from the standpoint of, of aggressive treatment like surgery, and it's classically been described as, uh, as clinically severe obesity, where obesity is actually causing um uh some um health consequences or behavioral consequences, uh, impairments in quality of life for um teenagers. Um, but what happens when we, um, when we look at, um, the, uh, not just the teenager, but, uh, projecting down the road, projecting, uh, essentially even as few as, as 20 years, um, uh, or 30 years of age, we began to see, uh, that, uh, through these comorbidities, we began to see that there is a, um, a price to pay when it comes to mortality. So cardiovascular mortality. Really begins to climb um uh when you get into even the overweight range, uh, but certainly, uh, when uh you are in the ninety-fifth or above percentile for BMI as a teenager, uh, that plays out in a, um, a very, uh, definite increase, um, in, uh The probability of an early demise from cardiovascular disease. And so I think that these data from the New England Journal last year are really quite motivating for why it's important for us to take this problem seriously and in particular why it's important to take severe obesity very seriously. So one of the big questions I get in the clinic is, um, not just, you know, how was my, my son or daughter going to, uh, you know, gonna, um, uh, benefit from the surgery, you know, over 6 or 12 months. But what are the, what do we know about the long-term outcomes? And so, Um, the long-term outcomes, uh, really in bariatric surgery, um, are, uh, important to know and are, are very elusive because, uh, patients are hard to keep track of. But what I wanted to go over with you is long-term outcomes as documented in a small cohort from right down here in Cincinnati, Ohio. Um, uh, through the follow-up of adolescent bariatric surgery at 5+ years study and also some colleagues in Sweden, um, Gothenburg in particular, who conducted, uh, the adolescent morbid obesity study, which is a 5-year outcome and actually has some control group, um, uh, control groups to provide, uh, comparative estimates as well. So getting into uh these studies, what we did in Ohio, and I'm sorry, I'm trying to advance here, what we did in Ohio was to look back at, at our outcomes of gastric bypass for individuals who underwent surgery between 2001 and 2007. And we asked them um uh to come back to the center or to participate um in a field research visit between 2012 and 2015. And what we were able to achieve in this study is um about 81% of those who were eligible actually were findable and, and did participate. We hypothesized that the, the weight loss would be durable and that health would be improved and uh adverse nutritional effects would be, um, uh, mild again, based on what we knew from the adult world. Um, I won't walk you through all of this, but again, just to say that 58 out of 74 that were eligible to participate. Actually did participate mostly with full research visits in person, uh, or, um, uh, in person in the field, uh, with the research uh contractor that we employed to go to their homes, uh, 81%. So, um, you know, in, in, in distinction with a lot of the work that's been done with long-term outcomes where you might see, you know, less than half of those eligible. And you always wonder, well, what happened to the other half. Um, did they really, uh, do poorly and is that why they, they weren't locatable or, or didn't want to participate in a long-term outcome study or did they do great, you know, on the other hand, and, you know, I don't want anything to do with, with research. It, it was, it's always been a mystery, you know, um, and, and so we, we were really happy to see 81% back. At baseline in this cohort, um, uh, they were 70, uh, 17 years of age, 74, 64% female and mostly white, a very few Hispanics. They had a very high BMI of 57. On average, which is, uh, what we've seen certainly in a lot of adolescent series. And here's basically the, the long-term BMI outcome. What we see on average at eight years is a BMI decline of, of 29%. Um, now, within this, um, within this mean, there's a lot of variation, uh, as you can appreciate, and uh, that variation is actually shown here in the form of a spaghetti plot where you see some individuals that started at extraordinarily high BMIs in the mid-80s, for instance. They would drop down to the 50s and then have a very gentle increase. Some of the increases were not so gentle. Um, and, um, and again, on average, you see, uh, this, uh, remarkable, uh, durability of the weight loss response, um, many years, uh, all beyond 5 years after surgery, some out to 12 years. We were for the first time and with our data at least able to have enough uh individual data points to ask the question, um how does long-term BMI, how is long-term BMI affected by baseline BMI. And so what you hear or seeing um is the very strong correlation um uh RF 0.75 correlation between baseline BMI and follow-up BMI. And this is again just to make the point that when we are operating at baseline BMIs that are really in the uh very high range, um, that's very predictive of staying, uh, fairly high. And so just to simplify it. Um graphically, let's just say we're, we have individuals that started with BMIs in the 60s. Um, on average, we are going to get them to reduce their BMI by um not quite a third, but end up with BMIs that are still quite impressively high. Um, essentially over 40. Whereas, uh, in the individuals where we operated at BMIs that were in the more, um, uh, early range of uh severe obesity, that is BMIs in the 40s, uh, we saw them end up at BMIs that, you know, you might actually, um, uh, uh, uh see as more normal BMIs or certainly, uh, at BMIs where the predicted health consequences, um, might be few. But what did comorbidities do over time in this group as a whole? Uh, you see here, for the key comorbidities that we are able to look at, um, uh, relatively easily with clinical and laboratory testing, uh, we see that there were remission rates of 88% for diabetes, 64% for dyslipidemia, and three-quarters of those with hypertension, uh, resolved. Over that same period of time, for those who didn't have diabetes, dyslipidemia, or hypertension at baseline, but we saw incidence rates of none for diabetes, uh, 50% for dyslipidemia. But again, that's a very low number who didn't have dyslipidemia in the first place, so that they could be eligible for, for developing it over time. And then, uh, of the 29 who didn't have hypertension at baseline, about 3 of them developed hypertension. So pretty modest uh incident of disease rates. We did, um, want to also, um, uh, work with this data set to answer another question. And that's a question that relates to, uh, is there harm from, uh, only getting your BMI down to, let's say 40 or 50. Um, and what we, we did here is a, a regression analysis, um, which looks at baseline, um, sorry, not baseline BMI, follow-up BMI, body mass index at follow-up against the predicted probability of high blood pressure, for instance. And what you see is that there's a definite relationship. So where the BMI ended up matters. Um, and the higher the BMI ended up, The higher the predicted probability of hypertension at that follow-up time point. So again, this is asking the question, does it, does it really matter? Are, is everything gonna be, you know, peaches and cream or gravy or the bad examples, but uh uh uh bad things. But uh is everything gonna be good with your health, um, now that you've had surgery, no matter what your BMI? And the answer to that seems to be no. Those that ended up with BMIs in the higher range, um, did seem to have a detrimental effect. So, um, if you look at not just hypertension but dyslipidemia, uh, higher CRP values, higher insulin values, um, higher, um, uh, insulin resistance, uh, values, and lower, um, uh, concentrations of beneficial cholesterol, the HDL cholesterol, uh, we see that all of these outcomes, for all of these outcomes, the, uh, follow-up BMI. did predict um adverse um uh findings. Micronutrient status at 8 years was also examined, and what we found here in summary were low iron stores in a fair number of these individuals with anemia and parathyroid hormone elevations. Low vitamin D's in a substantial number of these individuals. And across the pond, um, in the Amos study that I mentioned, uh, previously, what we, um, uh, noted here in their paper is that similar age group, um, with BMIs that were in the greater than 40 range at baseline, uh, Tanner, uh, greater than 3, excluding, um, uh, monogenic and syndromic obese obesity, um, in particular. And primary outcome, weight loss, uh, and weight, uh, stability over time. A lot of uh important secondary endpoints as well. And what these investigators found is that, uh, for individuals that were uh severely obese and didn't undergo surgery, uh, they essentially gained weight, uh, very gentle weight gain, but BMI of 42, uh, going to about 45. After surgery, Adolescents that had gastric bypass had a, uh, a dramatic and similar decrease in BMI, uh, with a stable BMI, um, at 5 years after surgery. Um, again, BMI is going from about 45. a 3 reduction ending up at about 30. That was very similar to the adult control group that they uh matched to their uh teenagers um uh for outcome of the gastric bypass in adults. They actually did a neat overlay here. This is the often quoted and often shown uh SOS results from, uh, also from uh Sweden, of course. And what you see here is that the teenagers uh who underwent bypass, uh, did remarkably like adults in this, you know, widely published, uh, cohort of SOS participants. And those who gained, um, so didn't undergo surgery, um, actually gained more than the adults, uh, as you see here. And this dotted line is just those, uh, uh, handful who underwent surgery that randomized themselves out of the control group, in essence, and underwent uh gastric bypass surgery during that two, beyond that two-year follow-up. They also noted um a uh resolution of diabetes as well as resolution of pre-diabetes. Uh, they noted 83% resolved their dyslipidemia. Again, very comparable to our data from, uh, Cincinnati. And uh they also found uh the uh very uh beneficial and um And now, uh, rather expected rise in good cholesterol levels. Blood pressure resolved in 12 of 12 that had high blood pressure and uh inflammation uh resolved in 3/4 of their patients. As measured by high sensitive CRP levels. The one, I guess, um, uh, the drawback of their study, uh, was that they were using a technique at the time, um, of enrollment, uh, which actually didn't close mesenteric defects after, uh, or at the time of laparoscopic gastric bypass. Um, and I think that, uh, we have, uh, uh, been Teaching for some time that these defects have to be closed or they will lead to uh internal hernias and incarceration and uh general misery. Um, and so, Um, they did have to re-operate on a fair number of, of patients for that. Um, and then they, uh, took out a, a, a number of gallbladders as well. Um, and in, in contrast, in the non-surgical controls, uh, they found that 25% of them had to have surgery as well. They had to have weight loss surgery. Uh, similar to the Cincinnati data, they noted, um, low vitamin Ds in more than half, uh, notably, uh, the controls also had low vitamin D levels. This was a, uh, a population, of course, that's significantly higher in latitude than, uh, the Cincinnati cohort. Low vitamin B12 levels, um, and iron deficiency anemia was also, of course, found. So how does that, um, uh, uh, what does that tell us about the future, these small samples, they had 81 teenagers, we had, I guess 58. Um, what does that tell us, uh, we need to be doing? Um, and, um, and I, I have to say that as, uh, one of the architects of the, the, the new phase of Teen Labs, um, I did take these data into consideration. Um, Teen Labs is the multi-center study, prospective outcome study for adolescents undergoing bariatric surgery in the United States, funded by DDK. 242 were recruited initially. And they were all less than or equal to 19 years of age. Um, we studied them at baseline and now annually, um, to determine major benefits and adverse effects of, uh, surgical treatment. At the time of enrollment in the study, we were able to enroll 161 bypasses, 67 sleeves, and 14 bands because those are the relative proportions of operations that were being done at our centers, um, 5 enrolling centers. Um, the age, uh, mean age at the time of surgery was 17. And current age of the cohort median age is 24 and you see how the distribution uh looks now with some approaching, you know, uh 30 years of age and really none in the, um, in the, um, uh, well, all, all of them now adults by the definition of age 18 being adults. Visit completion by time point here. Uh, you can see that out to 5 years now, Teen Labs has 203 that have completed a 5-year visit. Uh, the color scheme here shows that, um, 72% were in-clinic visits, 17% were field visits where again we send a research contractor, uh, to their home. And 10% were missed visits. One was a telephone visit. Um, so we have pretty strong numbers here at 5 years. Uh, those strong numbers continue at 6 and 8 years too for um solid data that we're going to be having from this cohort. Um, so what are we, uh, collecting, um, and what, what's the, what are the new aims for the, the new grant cycle? Um, as we see here, I'm sorry. Um, the first aim is to really get 10-year outcome data. So we have again 45 out to, um, 45 individuals out to Uh, 8 years, let's see. Can I get that slide up? There it is. OK. Um, what are the new research questions? What's the ten-year durability and risks? Uh, are there differences between bypass and sleeve gastrectomy? Another huge question that we're getting in the clinic, of course. Um, and, um, is there a detrimental effect, um, on the bones? I mean, I think that, uh, when you look at the Cincinnati long-term data as well as the Gothenburg long-term data, you see these signals for low vitamin D levels, high PTH levels, and, and up to half of these gastric bypass patients. So this is a key signal I think that we've got to take seriously. So the conceptual framework for the next 5 years of the consortium's, uh, research. is to, to say, you know, we, we know this. We know lean uh is healthy. We know obese and severely obese are uh less healthy. But what happens when we, uh, when we have now a severely obese individual uh taken postoperatively. Um, back in, in, in BMI, what is the range of their 10-year outcomes for health gonna look like? Um, and, um, and so that, uh, was a nice little infographic there that we used to sell this, uh, grants, uh, third funding cycle. Um, I'll have to take credit for that actually. Uh, so, when it comes to the first research question, 10-year outcomes, uh, we're gonna be following them, uh, closely with 4 visits, uh, over the next, uh, period of, of time. And we're gonna focus on, uh, the main efficacy and uh safety measures that we've collected in the past. And we're gonna do some other things. We're gonna ask them specifically about infusion therapy or blood transfusions for iron deficiency anemia. Rensnet. Uh, we're also gonna ask them about fractures and hypoglycemic events, um, other new diagnoses that, uh, we might not have been charting in the past. Uh, we're gonna ask them about, um, psychiatric problems and substance abuse, uh, problems, uh, suicidal ideation, um, and of course, we're gonna be collecting information about that. Since there has been this major shift in procedures though with uh really a domination of the field by the vertical sleeve gastrectomy without a lot of good long-term data, I might add, um, certainly, a very sparse long-term data for teenagers, um, we wanted to use teen labs as a platform to ask questions about comparative effectiveness. And so, Um, what you see here is, um, what sort of power we would have for comparing sleeves, uh, to, um, bypass if we only had our original 67 patients or if we added a few patients and got to 80 or 100. And I think what you see here is that, uh, with the addition of just another 33 or so patients. We're able to get the 80% power um to look at important outcomes, um, uh, with confidence. That is, uh, blood pressure, parathyroid hormone, HDL cholesterol, a body mass index. Um, these, these important outcomes that really people wanna know and we wanna know, um, is there a difference, uh, between sleeves and gastric bypass. So I was very pleased to see that with only 34 more. We would be able to um answer some of these important questions or at least give some solid estimates on these outcomes. Excuse me. Um, we will do that, um, with patients that exist that, uh, actually came through our centers immediately following the closure of enrollment of team labs. And so it won't take us forever to get the, uh, the data, the long-term data from the new sleep patients. So in wrapping this up, um, I, um, I wanted to, to show you a graphic hypothesis, uh, pertaining to the bone density work that we're planning. And that is to remind everyone, um, that When we show age in years, um, across the bottom, and these are 1020, 30, 40, 50 years of age, and plot that against bone mass in our bodies, what we see um is uh this rapid accretion of bone mineral density and then a plateau phase where we gently lose it. Um, and, uh, until we get into our sort of pre-retirement, uh, years here, um, where we're actually kind of appreciably losing it and, and, and can be termed osteopenic. Um, and in the presence of certain conditions, we might even, um, uh, dip down into an osteoporotic range, um, with a bone mineral density that's, you know, 2.5, uh, standard deviations below the, the norm. Well, if that's what happens normally, and what happens in those that we're operating on. So the severely obese patients, um, have a greater bone mineral density, uh, because in part of loading consequences. You load the bones with more mass and they have to respond physiologically by becoming more dense, or else there will be an excess number of, of fractures in the weight-bearing joints. Um, so, Um, so that's, uh, the estimate there. Um, what happens though in the presence of bariatric surgery? Do we get to some homeostatic level that's more normal, uh, when we drop, um, uh, body mass rapidly, and we know we've dropped bone mass, um, uh, in early studies that we and others have done, we know that the bone mass drops, but will it stabilize is the question. Um, or will we have, uh, uh, what can be termed bariatric bone disease, where, uh, this curve really just continues to drop. Um, that's a question that we will be readily poised to answer because as I told you, in this next, uh, 5-year cycle, Team labs patients will all be in this, um, you know, sort of 25 to Uh, 30 year old range and uh we'll be able to see them beyond surgery in the teenage years, where did they end up? Did they plateau or did they not? Um, and for those who, who did not plateau, for instance, what might be, um, the factors associated with that? Um, so technically, we will be getting, uh, wrist, um, hip, and, uh, lumbar spine, uh, DEXA scans on, um, uh, these individuals, as well as a BMI similar non, uh, surgical control group. So with that, I, I think I'll um do a quick wrap up and say um in summary that severe pediatric obesity is rarely reversible. I think we've seen that um prior to the, the Amos study, but certainly the Amos study has 81 severely obese teens that, um, that point to weight gain as a consequence uh over a five-year time frame. I think we can expect poor health outcomes as well, uh, for these individuals as we've seen from the Israeli data that I presented with excess cardiovascular mortality, um, accruing as early as 10 or 20 years later. I think we've also begun to appreciate now with the, these longer-term studies that have been published, uh, that bariatric surgery does appear to result in durable weight loss, at least with small numbers of individuals um uh that are now in the literature. Um, surgery allows the BMI to both decrease and remain reduced. Um, and also in work I didn't go over from the AMOS study enhances, uh, quality of life and reduces depression. It corrects diabetes, hypertension, dyslipidemia, to name a few of the metabolic, uh, medical consequences of, of obesity. But the, the larger studies are needed. Uh, the power of team labs, I think, will be to give us estimates from Um, you know, upwards of 300 individuals, uh, that, uh, will be undergoing surgery and that the team lab's numbers combined with the Amos numbers combined with the FBS 5 numbers will, you know, give us an excess of 300, um, uh, data points to much better answer some of these important long-term questions. Surgery certainly um is not without risk. And uh we um, believe that the, the complications that we've seen uh certainly can be serious. Some of them like internal hernia is preventable. Um, uh, it's the nutritional consequences that I think, uh, really have the limelight here. Um, and we want some solid estimates around that. We want some, uh, uh, ways of predicting, uh, those and, um, and, uh, and preventing them. Uh, we're gonna look at bone health, um, with an eye toward again, using, uh, data for patient's benefit. Uh, if we can advise them about the risks, I think that we may be more successful in convincing, uh, individuals to actually, uh, use the, the tried and true, uh, supplements to prevent this. I also think that there's reason to believe that sleeves, uh, may have, um, a fewer consequences of this, uh, type, at least from some preliminary glimpses of the data. And I'll end by saying that these current data do suggest that there's a window of opportunity to reverse severe pediatric obesity when we operate late, that is when we operate long after the diagnosis of severe obesity has been made. We end up with higher residual BMIs. Uh, the FAS 5 study had a residual mean BMI of 38, which is very nearly still severely obese. So most of those individuals were less than 40, um, but, a, a large number still remained severely obese at 8 years after surgery. So certainly, surgery earlier after the diagnosis may end up with fewer um that are still severely obese. Um, and the other thing again that I, I, I pushed our analysts uh with the FAS Five data on is, is this res residual obesity, uh, metabolically harmful? And um when we, when we looked at it, we did find significant um uh numbers of them that's, that had uh high blood pressure, had uh lipids that would put them at long-term risk. So I do believe um it's, it's not. Uh, we say, we often say it's not all about the weight, um, but it, it is about the weight, and I think that when we can get them to these, to the lower BMIs, perhaps by operating, uh, uh, earlier after the diagnosis of severe obesity, uh, the better they're gonna be long term. So with that, I'll just um again, thank, um, uh, the, the organizers here but also thank uh the individuals involved with Team labs and, and, uh, who have been collaborating, uh, over the years uh for this team science. Um, and we'll be happy to, happy to stick around and, and take the rapid fire. It sounds like a, a, a fun way to, to finish up a, a session. Uh, uh, great, great, great update, Tom. Uh, just a quick question, what's your, what's your time frame for, for getting those sleeve patients in and when you think you'd start getting some data out of this? Yeah, we, we're pretty confident that we can get them in within the year. Again, these are patients that had surgery at consortium sites and um and the clinical follow-up should be ongoing, uh, but from a research standpoint, we should be able to go get them and enroll them. So within a year we'll have the 33 and we'll be able to start doing some long term comparisons. Yeah, no, that, that's, that's really awesome. I, I, I, I do have some other bariatric surgical questions. Maybe we'll just save them for the rapid fire.