Next, it's my true honor to introduce our next speaker, whose name has come up quite a bit throughout the whole course today, Dr. Vivek Kumbhari. He's the adjunct associate professor at Johns Hopkins and the director of advanced endoscopy at Mayo Clinic in Florida. Today, Dr. Kumbhari will be going over endoscopic management of weight gain after bariatric surgery. Thank you for being with us, Dr. Kumbhari. Hi, good afternoon, everyone. It's certainly a pleasure to be part of the ABE, ASG, and TOSS endobariatric symposium. I think this virtual platform is certainly very suitable for the current climate. So I'll be speaking about the endoscopic management of weight gain after bariatric surgery. I'm currently an adjunct associate professor of medicine at Johns Hopkins and I'm due to start my faculty position at the Mayo Clinic in Florida in the coming weeks. Several disclosures that are related to this talk, I'm a consultant for several companies in the interventional endoscopy and endobariatric space, and I've received some research support with respect to endobariatric therapies as well. So just to provide some context here, if we look at the ASMBS data, so this is data from our centers of excellence across the US, between 2011 and 2018, you can see that there's a growing number of bariatric surgeries performed in the US. And it's interesting, if you go back to 2000, between 2011 and 2013, you can see that by far and away, the predominant bariatric surgery performed was the gastric bypass. And this is relevant because as we look at sort of therapies to address weight regain after bariatric surgery, a lot of the data is based around patients who've had a gastric bypass. Although, as you can see, you know, trending from 2013 and 2014 onwards, the predominant surgery starts to become the surgical sleeve. And so I think there'll be, there's growing data and emerging data on weight regain after the surgical sleeve also, but I think we'll be seeing that in the subsequent years. What's also interesting is that if you look at the percentage of revision bariatric surgeries performed in the center of excellence, that also is increasing over time. And some of that is managing sort of complications in the true sense of bariatric surgery, but there is a significant proportion of this that is also revision surgeries because of weight regain. So certainly one option to treat weight regain after bariatric surgery is for revision surgery. But certainly one would consider that endoscopic procedures, endopharmacotherapy, which I know you heard about earlier, might be a superior alternative in view of its minimally invasive nature. But certainly the burden of disease is significant. Now, without going to sort of the issues around stigmata here, surgical failure is common. As you might've heard, you know, patients who have bariatric surgery lose a considerable amount of weight. You know, they almost described the weight as melting away within the first year with minimal effort. And then, you know, several years later, the weight starts to creep back. And this is an issue because patients who are initially taking photos of themselves every week, you know, people around them are congratulating them on this tremendous life change. They get out there, they become very social, and then suddenly when the weight gain comes, they become a little bit more reserved. They tend to stay away from social activities, increases their sort of, you know, cognitive and psychological syndrome, which can cause weight regain, et cetera, et cetera. And so it's a very difficult clinical problem to treat, which is certainly multifactorial. And so the term surgical failure is really here to stimulate thought. But how do we define an inadequate outcome? You know, the definitions are varied, but some would say that if you lose less than 50% of your excess weight after your original bariatric surgery, that's a failure. So let's look at this. If, say, you're starting BMI is less than 50, right, only about 20% of patients, you know, reduce their weight such that their BMI becomes less than 35. And if you take patients, sorry, 20% of patients actually maintain, you know, weight with a BMI below 35. However, if you take patients with BMI above 50, only around 35% are able to reduce their weight to a BMI below 40. So you can see here that, you know, getting to normal weight is certainly, doesn't appear to be the goal. It's very few patients would get there. This is an old data, but important data, which basically shows that weight regain is common, regardless of the bariatric surgery type you have, and even occurs in patients who undergo gastric bypass. So you can see here, most of the weight loss is within the first year, you know, or one year to 18 months. And you know, most patients actually regain at least 30% of their lost weight. And there's even, you know, up to 20% of people regain all of their weight that's lost. This is a very new data that came out in January of this year, which I think is somewhat stimulating and maybe a little off topic, but once you look at the, this is a randomized control study with 10 year follow-up of patients with, with who underwent bariatric surgery compared to medical therapy. And sleep gastrectomy is not part of the study. It's biliopaircritic diversion and gastric bypass where two bariatric surgeries performed. But look at the, the weight loss scene was significant, you know, with over 30% total body weight loss early on, which essentially seems to have persisted over time in this particular cohort. But the image on, on the bottom right, I think is, is sort of really hypothesis generating. So despite weight maintenance being seen in this study, there certainly was a recrudescence of a disturbed metabolic profile, you know, seen here when looking at glycated haemoglobin, you know, you can see here that there's a rapid reduction in HbA1c. But despite the weight being maintained, certainly the HbA1c tended to rise over time and certainly it did not hit pre-procedure levels, but there was a disproportionate increase in HbA1c as compared to weight loss. And you've certainly got to wonder why this happened. And certainly this again alludes to the weight independent benefits with bariatric surgery, but also there could be some, you know, weight independent factors that are contributing to, you know, some of the syndromes that we see post-bypass. So what Regan has mentioned, multifactorial could be because of a change in the neurohormone or milieu. There could be dietary non-compliance, the microbiome is altered. And then there could be anatomical factors at play here, presence of a gastrogastric fissure in gastric bypass patients, dilation of the gastric pouch in a bypass or even the stomach after a surgical sleeve, and dilation of the stoma or gastrointestinal asthmosis in patients who had a gastric bypass. And, you know, we'll discuss most of this talk around the endoscopic management of weight Regan and endoscopy is really focused at targeting anatomical changes as opposed to sort of the other neurohormonal changes that occur at bypass. So you know, this is early data, somewhat controversial, but it appears to suggest that an increase in gastrointestinal stoma diameter does correlate with the risk of weight Regan over time. And similarly, the increasing diameter also correlates with the risk or prevalence of uncontrolled eating. And so, you know, what can be done for patients who've had weight Regan? Well, you can do a surgical revision, you know, transect the pouch, make that smaller, redo the gastrointestinal asthmosis to make it smaller. You can increase the length of small bowel malabsorbed by distalization of the bypass, you could abandon your bypass, or you can convert to another surgery. So what are the endoscopic options available? Well, there's the over-the-scope clip, radiofrequency ablation using the Barrett system, there's placation using the Rose system, there's ablation using argon plasma coagulation or cryoablation, and then the most common technique, and we'll focus most of the talk today on endoscopic surgery, more of the transoral adlib reduction procedure. So as part of the initial assessment, I think we should look at the nutritional physical activity assessment, do a medical assessment, obviously check the anatomy with either an upper GI series or endoscopy. My preference is to do an endoscopy and upper GI is sort of two-dimensional and can sometimes, it can be difficult to interpret. And then I think it's very important to discuss the expectation, you know, patients often think that when you intervene, they're going to lose as much weight as what they did with their original bypass or original surgical sleeve. And so I think the expectation needs to be set, you know, and what I would say briefly is that, you know, our procedure is part of the entire process of therapy. You will, it's highly likely that you will stop gaining weight and you are likely to lose weight with the right sort of dietary and lifestyle modifications. So just briefly, the over-the-scope clip approach, you know, there was a study in 94 patients where, you know, clips were placed to a post-size of gastrointestinal anastomosis and this study, no ablation was performed and immediately post-procedure, the anastomosis was successfully reduced in calibre down to eight millimetres, technically not a difficult procedure to be performed and you can see how it can, you can successfully reduce the diameter. The results, you know, were promising. When you look at the BMI reduction, it was almost just over a five-point reduction in BMI over 12 months, was relatively safe. What about radiofrequency ablation using the BARRIC system? So in this study, there were 25 patients that had a gastric bypass, had weight regain, radiofrequency ablation was applied to the gastric pouch and gastrointestinal anastomosis. There were multiple ablations performed. The procedure was repeated at four and eight months and at 12 months, you can see there was a mean of 18% excess weight loss at 12 months, which translates to about 31 pounds. So that's not insignificant and I think this was a reasonable strategy because it allowed therapy to the pouch as well as the anastomosis and particularly if someone is not familiar with placation techniques, this could be a reasonable option. Now, one of my concerns with this technique is that radiofrequency ablation was designed to be superficial. It was initially used to treat intestinal metaplegia of the esophagus. It wasn't designed for deep thermal injury and subsequent tissue remodelling. So, you know, I wonder if further optimisation would be necessary before this really achieves a significant effect. The other technique is this ROSE system using the incisorless operating platform. This is where full thickness placations are placed using this sort of snowshoe type anchors as seen in this image at the pouch and the gastrointestinal anastomosis. In a large study of 116 patients with BMI of 43, there were six anchors placed. The mean gastrointestinal anastomotic reduction was reduced by 50% and the pouch was also reduced by 44%. This is a potentially technically challenging procedure for some. The pouch is a small place to work in and there's a somewhat large device that's placed there. There's often not a whole lot of room to move and it takes some expertise to get this going. You know, at 12 months follow-up, there was around 6 kilo or 15% excess weight loss. The anchors were seen in 92% of cases so this is a durable placation technique and it looked like those who had a smaller stoma had more weight loss. What about argon plasma coagulation? So this is, you know, a very simple technique using thermal ablative technology to cause tissue injury. You essentially, you know, want to create a circumferential injury such that a circumferential ulcer is formed and the ulcer then heals with scarring and this causes a reduction in the aperture of the gastrointestinal stoma. And so, you know, the settings, just be wary as you read the literature, when you use different generators require different settings and so just keep that in mind, but if you're using the most common generator, the Irby generator, it's around 50 watts, so you can use straight fire or circumferential fire here. And there's sort of a touch and no touch technique that people describe, but I think a non-contact technique is probably the best way of doing this. So the initial report was a case series of 30 patients, they were able to successfully use the gastrointestinal anastomotic aperture when they did serial ablations over an eight-week period. As you can see in this image here, the total body weight loss was reduced by 16 kilos and the aperture was successfully reduced to less than four millimetres, which is arguably a target. You know, some would want an aperture as small as eight millimetres, but I think 12 is reasonable depending on the starting size of your stoma. The beauty of this technique is that it's just technically simple. Most of us have this technology in our endoscopy units, it's a sedation procedure, it takes about 10 or 15 minutes and it's covered by the insurance payers. And so when you look at a percentage reduction of anastomotic diameter, you can really get to where your target is after two to three sessions. Now as with any technique, you know, stenosis is a potential concern and I'll go through some other data which really highlights stenosis later on. This is a large retrospective study of almost 600 patients across Brazil and the US, and you can see that most patients had a median of two sessions. There was a reduction in the aperture of GJN anastomosis by about 10 millimetres using this technique. So again, simple, relatively safe. But what you can see here is if you follow patients over time, even with this technology, you can get weight regain. So you can see at 24 months, you see around 11% total body weight loss, but at 36 months it's up, it's sort of dropped to 5%. So you know, in the case of bariatric surgery, weight regain is a problem. Even in the case of endoscopic therapy, or the similar indication, you will also regain weight if you follow patients for long enough. And with the bench rate, we're relatively low, but you know, stenosis is possible, ulceration is possible, and as a consequence of ulceration, you can get bleeding too. You know, we published a study looking at the cryo balloon, which is, you know, made by, initially by C2, and then PET-TACS acquired it. This technology, in a similar way to conventional radiofrequency ablation, has been used to treat Barrett's esophagus. It's a single standalone system with a hand controller and a balloon which fires some of the therapy. The nice thing about this as compared to other cryo ablation systems is there's not a whole lot of gas entering the stomach, everything's restricted towards this balloon. And you can see here, you can treat the gastrogen, you can look through the balloon itself and you can treat the gastrogen and elastomosis, as well as the gastric pouch. So that can be nice. It's a fairly efficient technology and very simple to use. And you can see here, you can get quite a significant reduction in anastomotic aperture size in as early as eight weeks. In a study of 22 patients, we did a short study, eight-week follow-up, the anastomosis was reduced by 34%, total body weight loss was reduced by 8%. And it seemed that the more the aperture reduced, the greater the weight loss. But there was a significant adverse event rate, you know, 14% that was really bleeding. So what about suturing? There is level one evidence using any sort of previous endoscopic suturing system. But there certainly is, this is not experimental, there's randomized controlled data available. So with this technique, you use the agonoplasma coagulation to do a full thickness circumferential ablation of the outlet. You can see here, if you want to reduce the patch, you can, and you can choose to mark it and then basically take your endoscopic suturing system here. And you can run a suture pattern around to reduce the aperture of the anastomosis. And I'll show you the end result here, something along those lines. So you can reduce the patch, the outlet is buried in the middle there. This is the best data to show you, in my opinion, from Cy and Chris Thompson. Basically large series of patients followed up for five years. You can see here that again, most of the weight loss, if not all, is within the first year. And then there seems to be a weight plateau from one to five years. So very similar to what we see with bariatric surgery. And it does seem to be, you know, in their cohort where they quite effectively follow up patients year on year, there seems to be some weight maintenance as well. But if you've got the net weight loss, you know, you're talking 10 kilos. This is not the same as having a revision surgery. And just showing you again, data in a number of formats. So without getting too technical here, you know, which suture stitch pattern is best, I believe that the drive home, the message that doing a simple interrupted technique is not particularly helpful. There was a randomized control study published comparing endoscopic suturing with APC alone. And the findings showed no real difference. And I think that's because the suturing pattern they used in that study was an interrupted pattern. And so if you're going to do this properly and use the purse string or running suture pattern, there was a study that actually showed that when you compare the two techniques, you in fact get superior total body weight loss at three and at 12 months with the purse string pattern. So really, I think that is the way to go. We sort of tried to modify this technique and did a double purse string pattern. So I thought, well, why not go around twice and really reinforce the semastomosis to reduce the risk of expanding over time. And so we take a large outlet, like you see in the top left, do aggressive ablation to get the dark brown color, then do a double suture pattern until you get, so you run two purse string sutures to get the aperture about six to eight millimeters, as you can see in the top right. And the bottom left, you can see that what the appearances are at eight weeks, a beautiful nice stenosis, exactly what you want. But interestingly, look at the bottom right, one year later, the anastomosis is as big as what it was. And so what you can see here is that even with endoscopic techniques to reduce the aperture, it can increase again. And our data showed a similar thing to what some of the APC alone data showed, that you seem to get your weight loss over sort of six to nine months, maybe a year, and then there is a risk of some weight regain. If you don't aggressively follow this up, like the Chris Thompson group does. And this I thought I'd show you because it's intriguing, you know, the way this works, I think, is that you do the ablation, create tissue injury, and then you suture, and you basically suture the anastomosis in a fashion such that you want it to scar in that position. But as early as eight weeks after the procedure, you can see that the sutures have de-hissed, they're there, they're dangling, but they're not particularly effective. And so I bring all my patients back at eight weeks just to see what's going on and to see if there's any opportunity to do another, just ablation only, to help with weight loss. And sort of we, you know, we've done this, as mentioned, this is a double suturing technique. You can see in the top right, there's two sutures running, we can use a balloon to size the anastomosis. And basically, you know, this technique I thought would really cause a nice, robust anastomotic aperture. But unfortunately, what we found was that there was a very high stenosis rate. So you know, we had a 13% rate of stenosis, which is higher than the usual two to 5% seen in other studies. And I think maybe doing the double purse string suture, just using two running sutures was maybe a little more than a little too aggressive. What's also interesting is that when you get a stenosis, it's not a simple thing to fix. You know, 60% of the stenosis did respond to balloon dilation, but 40% required a stent. So remember, this is multiple procedures now you've required to fix a problem, you have to put a stent in, take the stent out, etc. You know, what about if you don't have suturing or you do have suturing, you know, how do you decide whether a patient could have APC alone or they should have APC in suturing? This is nice data from Psy basically saying that if your gastrointestinal aperture is less than 18mm, there doesn't seem to be a whole lot of difference between APC alone and APC plus suturing, but if your aperture is greater than 18mm, then certainly suturing is preferred. Just to wrap up here, what about sleeve gastrectomy? You know, often people believe they've regained weight because their stomach has started to stretch over time. You know, there was some data to suggest that the larger the stomach, you know, the greater the French, the less the excess weight loss, and there was some data to suggest that, you know, the volume of the stomach as well, if that increased over time, that contributed to weight regain. The initial data on endoscopic placation or doing a revision ESG on a patient who's had a surgical sleeve was somewhat poor, with sort of total body weight losses that were reported around 10%, although there's been emerging data here. You can see this data from Brazil, where they did, you know, basically a sleeve gastroplasty of the stomach using the Apollo overstitch system, where they did a revision and made the stomach smaller over time, and you can see here that really regardless of overweight or obesity class, there was a substantial reduction in total body weight loss over six months, and again at 12 months, you know, with numbers, you know, as high as 18 to 20%. So this does appear to be an effective tool to manage weight regain after surgical sleeve. And this is other data from really the US and Brazil, which again showed around 16% total body weight loss at four months, so also promising data with this very difficult patient cohort. Just to wrap up, you know, there's growing evidence of endoscopic techniques to manage weight gain after bariatric surgery. You know, I believe weight stabilisation is valuable, even when there's only minimal weight loss. There's multiple modalities available and really you can choose what's at your disposal. Comparative data is not particularly available yet. Endoscopy is one part of a comprehensive management strategy and I reinforce this to patients. And I think there's really further study of endoscopy, you know, plus medications or some other tailored therapy, you know, based on individual patient profile. Thank you very much.

endoscopic management

weight gain

bariatric surgery

anatomical factors

neurohormonal changes

realistic expectations