Thank you. Thank you, Dr. Peterson. Hello, everyone. My name is Rahul Banala. I'm at Mayo Clinic in Arizona. And on behalf of my course co-directors, Dr. Kumbari and Dr. Pryor, I would really like to welcome you to this ABE annual course. We've put together a really superstar faculty from all parts of the world and focused on pretty much everything that's current and looking forward into the near future in endovariatric. So we're really hopeful that you will enjoy this program. We've broken it up into three sessions, as you would see in the agenda. The first session is on gastric and small bowel devices. And we'll get that started. So first, I would like to introduce Dr. Shelby Sullivan. Dr. Sullivan is an Associate Professor of Medicine at the University of Colorado in Denver. She'll start off by giving us the current landscape on gastric devices. Dr. Sullivan. So I'll be talking about gastric devices, the current landscape. These are my research disclosures. So obesity is highly prevalent in the United States. About 108 million Americans have a BMI of greater than 30. And about 24 million Americans have severe obesity. That's a BMI of greater than 35 with comorbidities or a BMI of greater than 40 with no comorbidities. And this is a problem because we have an estimated only 213,000 patients who undergo primary bariatric surgery. This is numbers from 2019. And we only have about 1% to 2% of patients who are treated with obesity pharmacotherapy per year. This means that effectively, we have less than 5% of patients who are actually treated for obesity per year. So along with this, we have significant obesity related disease burden and cost. So we've got about 84 million Americans who have nonalcoholic fatty liver disease, about 88 million patients who have prediabetes, about 34 million people with diabetes, and about 18 million people with cardiovascular disease. All diseases that are highly, that obesity is one of the driving risk factors for. And this has cost to it. So we have the cost of a new diagnosis of nonalcoholic fatty liver disease is $8,400 versus $2,298 for control patients in 2010 to 2014 dollars. We have the cost of prediabetes per year $6,837 per year in 2010 to 2012 dollars. And the incremental cost of obesity is $9,600 per person per year in 2017 dollars. This is above and beyond what is normally spent on the average patient without diabetes. And the annualized cost of cardiovascular disease is about $18,953. That was based off of a Kaiser study, and that was in 2000 to 2005 dollars. So significant expenses associated with obesity. So I'm going to now kind of switch gears and really talk about what I was tasked with talking about today, which is the endoscopic gastric devices. And we have lots of different devices now that some of which are in practice in the United States, some of which are not yet and are under evaluation. And my talk is going to really focus on the space occupying devices, the intragastric balloons, and the non-intragastric balloon gastric devices. So first talking about the gastric balloons, we have a number of different types of gastric balloons across the world. We have the endoscopically placed balloons and the swallowable balloons. And then from there, we can subdivide into fluid-filled, air-filled, air and fluid-filled. And for the swallowable, we can divide into gas-filled and fluid-filled. For the fluid-filled, we have the Orbera balloon and the reshape balloon that have at one point at least had FDA approval in the United States. The SPATS balloon has been studied in the United States, the Silymed balloon and the Medsil balloon. For air-filled balloon, there's the Heliosphere bag. For air and fluid-filled, there's the N-Dallas, N-Ball, and then the Easy Life gastric balloon. And for the gas-filled balloon, there's the Obalon balloon system, that's a swallowable balloon, and the swallowable fluid-filled balloon, which is the Ellipse intragastric balloon. Both the Orbera balloon and Obalon balloon still have FDA approval in the United States. SPATS balloon and the Ellipse balloon have undergone evaluation in the United States and are currently under FDA evaluation for approval, but have not been approved yet. And the reshape dual balloon is no longer approved in the United States, although that isn't for any adverse events. It's because the device is just no longer marketed. So talking first about the Orbera balloon, this is a single balloon with transoral delivery under direct visualization. And you can see in the animation here how the balloon is filled. And we fill it, the instructions for use are between 400 and 700 milliliters, although most people typically do 500 to 650 milliliters, using methylene blue to dye the saline. It's considered off-label use, but most people do it because it helps us determine if a patient has a leak for the balloon. It's removed at six months in kind of a reverse process. There's a catheter that is inserted into the balloon, the fluid is removed, and then the balloon is grasped and pulled out of the patient's stomach. And it's FDA approved for patients who have a BMI of 30 to 40. The Obalon balloon is a swallowable gas-filled balloon system. The balloon is folded in a capsule and it uses electromagnetic localization, looking at the dynamic capsule transit into the stomach. And that's the video that's playing right now is an image from this. And we just saw the capsule go off of the midline and now turn on its side. That means it's actually popped into the stomach. And then you'll see that on the video, there'll be a deep breath taken so you can see it's in the stomach. It goes down with the breath and then comes back up. This is filled with 250 milliliters of a nitrogen-mixed gas. Three balloons are placed or administered over six to 12 weeks. And it is FDA approved for patients with a BMI of 30 to 40. The video below is during balloon removal. Endoscopic removal occurs at six months after the first balloon is administered. It does require a six to eight millimeter injector needle with a converter in order to hook up to suction. And a 15 millimeter rat tooth alligator forceps or larger is needed in order to grasp the balloon and pull it out of the patient's stomach. So looking at the current landscape for intragastric balloons in the United States, we do see that we have higher effectiveness in clinical practice than what we saw in the FDA trials, in particular with the FDA studies. And you can see that very clearly in this first, in the first column here, or in the first section, we see that we have sham controlled trials for both reshape and ovalon. And those have lower weight loss compared to the Orbera balloon, which was an open label randomized controlled study. However, you see in the registry series in this part of the graph, that weight loss is pretty similar. That is also true for the post-market study, although ovalon's post-market approval study is not yet completed. When we look at 12 month data, even for the FDA trials, despite the fact that especially ovalon compared with Orbera had, was a randomized sham controlled study, we see that six month weight loss is, or 12 month weight loss is very similar between the two balloons. And that is also true for the post-market study, which has similar weight loss that was seen both in the randomized controlled trial for the Orbera balloon. And it's also very similar to the 12 month weight loss in the ovalon randomized controlled trial as well. And again, post-market data is not yet available for ovalon, but will be soon. When we look at serious adverse events, there are some differences between the balloons in both the FDA pivotal trial and the post-market approval studies for reshape and Orbera. We see that there's a serious adverse event rate for these fluid-filled balloons between 7.5 and 10 percent. The gas-filled balloon, the ovalon balloon system over here on the right, has a lower serious adverse event rate. So lower serious adverse event rate pretty consistently for the gas-filled balloon, both in the randomized sham controlled trial and in the registry series compared with the current fluid-filled intragastric balloons that are endoscopically placed and endoscopically removed. But I want to have everybody keep in mind that the majority of the serious adverse events that are associated with the fluid-filled intragastric balloons are accommodative. That means they're related to nausea, vomiting, and dehydration, and are very easily managed. Looking at cardiometabolic risk factors, there have been, this was a meta-analysis that looked at intragastric balloons. And we can clearly see that when we look at these diseases that we talked about in the beginning, prediabetes, diabetes, cardiovascular disease, the cardiovascular risk factors in fasting plasma glucose and hemoglobin A1c do decrease with weight loss seen with these devices. We can see this in the top two lines here. We also see that there is a decrease in diastolic blood pressure. And of course, compared to the control arms, there was 5.9% more weight loss with the balloons than was seen with the lifestyle therapy groups. We have also seen in a study of paired liver biopsy, there was 21 patients that started the study, 20 patients with paired both pre and post liver biopsies in this series. We can see that there was improvement in intragastric balloons, BMI, weight, hemoglobin A1c, fasting plasma glucose. And one thing that's really important on this is that there was a significant reduction in the, and I'm sorry about these slides, they seem to be going forward by themselves. There was a significant reduction in fibrosis in all of these patients. So there was a shift in the stage of fibrosis that was seen on biopsy from the higher stages, especially those that were at two to three or up to two to three, really shifted down to either normal or mildly elevated. This is really important for patients. And recently, Orbera intragastric balloon has been given breakthrough device designation from the FDA for the indication of treating NASH in patients with a BMI of 30. What this means is that they will be undergoing a study to specifically evaluate the effect of the Orbera intragastric balloon on non-alcoholic standoff hepatitis. And if they see a benefit, they will be approved for that indication. The Ellipse balloon is a swallowable gas filled balloon. This is a thin polymer that's again, swallowed in a capsule filled with 550 milliliters of saline and itself deflates at four months and then passes naturally. There has been a trial in the United States, that data is not yet available, but there was a multicenter European registry that included 1,770 patients across 19 centers. Most patients were able to swallow the device, but they do have a stylet assistance. This is a stylet that goes into the catheter so that you can push it into the patient's upper esophagus if they're not able to swallow it on their own. Most of the time it passes out in the stool, but it is important to tell patients that sometimes patients vomit the balloon up. It occurs rarely, but can happen. So we want to warn patients about that. There were some patients that required endoscopic removal, and there were four patients that required surgical removal. Weight loss in this series was 4.2% total body weight. The Spatz intragastric balloon has also been studied in the United States, not yet approved. This is a silicone balloon. It has variable fill between 300 and 900 milliliters plus methylene blue. It has a 10 centimeter retractable stretchable silicone inflation tube that allows for inflation or deflation while the balloon is still implanted in the stomach. It's placed endoscopically and removed endoscopically at 32 weeks. It is also endoscopically, like I said, endoscopically adjusted. In a multi-center open label randomized controlled trial, there were 288 patients with a BMI of 30 to 40. 187 of those patients got device. There were downward adjustments in 15% of patients, and there was an increase of weight loss with upward adjustments by 4.7%. Weight loss at 32 weeks was 14.9% compared to 3.6% in controls, and weight loss maintenance of more than 40% of the weight lost at 56 weeks was 75%. Again, we see a lot of weight loss maintenance with these patients as well. Serious adverse event rate was 5.3%, and there was 4% of patients that had ulcers. Our next therapy is the Aspire Assist System by Aspire Bariatrics. This is similar in concept to a percutaneous endoscopic gastrostomy tube. It's placed during an endoscopy with the same technique as PEG tubes. Patients aspirate gastric contents about 20 minutes after a meal, two to three times a day, and it removes about 25% to 30% of the calories consumed at that meal. It accounts for 50% to 80% of weight loss, and the other weight loss is really related to lifestyle and mealtime behavior changes. Patients are eating less with this therapy. Patients also tell us that anecdotally, food choices improve. This is an important point. We sometimes think that actually seeing the food come out is not a pleasant thing. For patients, it really helps with positive and negative reinforcement. Unhealthy foods do not look good coming out. Healthier foods really look very similar to how they went in, other than looking a little chewed up, and this really reinforces healthy food choices and helps patients avoid unhealthy food choices. There are components that are implanted. Those are seen in panel A. The A tube and the skin port are placed and are implanted semi-permanently. They can be removed. The things that are used only during aspiration are the components that are in the bottom panel, the companion, the reservoir, the connector that connects to the skin port and opens it, the patient line, and the drain tube. This is approved for patients with a BMI of 35 to 55. We recently published a PIVI meta-analysis on the aspirocyst. This included four studies at one year and three studies that went out to greater than one year. What we saw is that we had weight loss of 17.8% total body in those who completed one year, 16.6% total body weight loss in the intention-to-treat analysis at one year. For those patients who continued aspiration therapy, we saw 18.3% to 19.1% total body weight loss from years two through years four. There was a serious and other adverse event rate of 3.8%. Buried bumpers occurred in 2.2% of patients. That occurred mostly at one site and may have been related to the skin ports being placed too tightly, but it's unclear exactly why that happened. Those were treated just by removing them and placing a new tube. Peritonitis occurred in 0.5%. Severe abdominal pain after placement in 0.5%. A prepyloric ulcer occurred in 0.3% and a device malfunction requiring replacement, which did not have any long-term complications and really just only required the replacement occurred in one patient. We also looked at metabolic comorbidities in these patients as well. You can see that there is an improvement in hypertension in both systolic blood pressure and diastolic blood pressure. Hyperlipidemia, there was an improvement in triglyceride and low-density lipoprotein and high-density lipoproteins. Hemoglobin A1C dropped by 0.13% hemoglobin A1C and signs of NAFLD or ALT and AST also improved. The last device that I'm going to talk about is the transpyloric shuttle. This is a device that has been approved by the FDA but has not yet been commercialized. This is a device that is placed through a sheath and an over tube that is placed endoscopically and the device is assembled in the stomach blindly. It has a silicone sheath that's filled with a coiled cord of silicone that's tethered to a small weight. It intermittently blocks the pylorus and remains in the stomach for 12 months. We're seeing here in this animation that silicone cord being coiled into the transpyloric shuttle. The end-obesity 2 trial has been completed. It includes both randomized sham-controlled patients as well as 32 patients that were included in an open label section. The age percent of female patients body weight and BMI were similar to the other intergastric balloon device studies. This is a picture of the device actually in a patient stomach. You can see that it isn't that big. It's not taking up space. It really is working by intermittently blocking the pylorus. In the end-obesity 2 trial, we had a percent total body weight loss of 9.5 percent at 12 months in the patients in the active arm and 2.8 percent total body weight loss in the control patients at 12 months. There were six patients that had serious adverse events. There were some serious adverse events that overlapped in patients. All of the adverse events did resolve after treatment. There was one patient with an esophageal rupture and pneumothorax that was repaired, upper abdominal pain, gastric ulcer, and vomiting. There were four patients that had device impactions. Those overlapped with gastric ulcer and vomiting as well, but those were all treated by removing the device. In summary, obesity affects over 40 percent of the population and is associated with significant disease burden and high cost. There are multiple gastric devices, intergastric balloons, aspiration therapy, and transpyloric shuttle, which is again approved by the FDA but not yet marketed. These therapies are safe and effective therapies that improve cardio-metabolic risk factors through their weight loss. Thank you.

gastric devices

obesity treatment

endoscopic gastric devices

intragastric balloons

non-intragastric balloon devices