So, firstly, I would like to thank the ASGE, Paul, and Shabana for this kind invitation to participate in what I think is going to be a very exciting webinar, and also to thank Mike and his colleagues in doing all the technical and administrative support work. So, I guess I have the privilege of giving the first talk, which entitles me to talk about some of the historical aspects of this and the very basis of what the other speakers are going to talk about. So, just by way of disclosures, I'm a consultant to Medtronics and get research support from A&X Robotics. My objectives are to inform the audience of the history of capsule endoscopy, to provide a framework for its role, and to describe the essentials of performing a VCE. So, let's step back in time. Some of you might even remember there was a film called The Fantastic Voyage, starring a lady by the name of Rachel Welsh, where the film's theme was to reduce a submarine to a capsule size that could be injected into a blood vessel containing the investigators, and then this would move through the bloodstream and dissolve a clot. We haven't quite got there yet, but we're getting close. But in reality, anything in the small intestine, diagnostic, therapeutic, before 2001, was extremely difficult. And it was really, by 2001, it had become a sort of moribund area of investigation because of difficulties of access. We simply had an upper endoscopy, we had colonoscopy, we could poke both of those scopes in a few inches into the small intestine, but not very far. Pediatric colonoscopes came with an overtube. We can make a little bit better progress, but not a whole lot. And then this medieval instrument, the SOND enteroscope, was introduced, and I'll show you a picture of that in a moment. We've had angiography for a long time, but that has a very limited application in the small bowel to acute bleeding and perhaps delineating tumors in one way or another. Laparotomy and laparoscopy have been around for a while, not really very helpful unless you've got a very specific target. Interoperative enteroscopy has sort of come and gone and come back. There are some much easier techniques that can be discussed later in the day to do interoperative enteroscopy than has previously been the case. And barium studies have really been useless in this arena. And here is that medieval instrument, the SOND, which is nine feet of fiber optic cable. It has a balloon on the tip. It has no up-down controls. So the device is passed either through the nose or the mouth and either fluoroscoped or directly with an endoscope placed into the duodenum. The balloon is inflated, and then over an eight-hour period, the balloon allows peristalsis to slowly drag this instrument down the small intestine. And then you deflate the balloon, and I say there's no therapeutic channel, but you can put some water through it, and then you drag it back. And then, as you all know, that if you put an instrument deep into the small intestine, it doesn't come back in a smooth fashion. It's pretty herky-jerky, and this is particularly true of this device, so you need to video what you were doing. But the pain on patients and the operator was so great, this fairly rapidly fell out of vogue, and it's now on the history shelves. Where it really got started was in 2001 with this group, Gabriel Aydan, Gabby Meveron, who was the businessman behind this, and Paul Swain, who was an English gastroenterologist and engineer. And they got together and purchased some spyware, which was available over the counter, and created a capsule. I first saw this in a focus group, and having worked in the field of obscure bleeding, now small intestinal bleeding, for years in a very frustrated state, saw the immediate potential of this device. So I talked to what was given imaging at the time, and the day the FDA approved it on 25 August, under the guidance of Blair Lewis, I was able to get it in St. Elizabeth's Hospital in Boston, and had the sandbox to myself for a couple of years. And it unleashed an extraordinary panoply of pathology, which really nobody had ever seen before. So this allowed us to build up a big library and develop a lot of techniques. And this is a montage of the evolution of the various technologies, started again with the hardware. We started with the thing called the M2A, which had a remarkable sensor arrangement with a heavy recorder, a D2 battery packed with five batteries, which patients had to carry all around. And that morphed then into what's much more familiar with the battery pack and recorder, and even a real-time viewer, all built into one pack. And then the latest iteration is with the NaviCAM system, which provides a magnetic control of the capsule. And the hardware has similarly evolved. This was the original capsule, the SP2, the mirror cam, the double-ended pill cam, and the capsule cam with four cameras. So the evolution has been patchy. It was frenetic in the first five years when Gibbon put out a lot of small grants and allowed us to do some very interesting research, and then there was no competition. So the whole area kind of languished until about 2015, when suddenly other manufacturers appeared on the scene. And since then, the whole field has exploded, and really there's some very large grants being awarded for capsule technology for all sorts of applications, which you're going to hear about later in the day. Similarly, the software evolved from very fuzzy little images, and then to the standard M2A, and the very earliest versions of it. And then you could get two images, then you could get four, then you could get a mosaic. And the remarkable thing now, I think, is the high resolution of all the systems are able to visualize individual villi, which is really an extraordinary achievement and allows us to pick up on all sorts of details in the small bow, which was never previously possible. I know people are going to talk more about this, but there's a couple of things I'd like to mention. The frame rate has become variable, field of view in general is in the sort of 150, 160 range, except for the capsule cam, which carries four cameras. And because of that, that is not capable of transmitting the information or the data. So you have to recover that capsule. All the other ones are either radio frequency, human body connections, such as the Merocam and so on. Battery life is getting better and better and better. Some are equipped with an RT viewer, real-time viewer, but only one system so far is equipped with artificial intelligence. So the technology has come a long way. We now have a colon capsule, which is the colon capsule two. The first one was a bit of a disaster, but the second one's become very good. And I'll come back to that later. Now, training in video capsule endoscopy has languished in the United States. The ASGE was a very big supporter in the early days and put on a lot of courses, rather like this one, hands-on. I vividly remember visiting the McDonald's University in Chicago on several occasions, and that got the whole field really underway. But the training has sort of fallen by the wayside, at least in this country. Europe has got ahead of us, and so has Canada. And they're not truly guidelines, but they're really recommendations at this point for training for capsule endoscopy. And a site where training occurs should have a minimum of doing 100 capsules a year, at least a faculty member with 500 VCE reads under his belt or her belt. Technology obviously has to be available. The individuals are capable of teaching the indications and contraindications, understand what the pathology is all about. And perhaps in a way, a very important component, if not the most important, is the generation of a report with the capsule endoscopy standard terminology. And then most physicians have absolutely no idea what they're looking at. So management recommendations are absolutely paramount in terms of communicating what you've done. And then in terms of the actual training, the exposure to upper and lower and push enteroscopy is an important adjunct. The training can either be during a fellowship program, and that's quite variable from institute to institute, or it can be done through a CME-endorsed national or international society production. The training involves didactics and real-time viewing capsules by the trainee and completing at least 25 capsules and their interpretation. However, metric-based competency, I'm not sure what that really means at this point. But the Europeans have provided a good framework for how we should be teaching capsule endoscopy. So reading a capsule again, I know people are going to talk more about this, but just a few crucial points. Make sure you have time available, read it early as possible in the day before you get tired. What I'd personalize you is to identify the landmarks, particularly the first gastric, first duodenal, and first sacral. Mark those and thumbnail them just by clicking on the appropriate places, and then that gives you an idea of how long this is going to take, because then you can allocate that time. Choose the speed, and other people are going to talk about more details on that. And we have the option, as I mentioned, reading one, two, or four frames per second, and then you can subsequently review the thumbnails, complete a report, and then upload it into your local EMR. So actually reading a VCE, there are a number of options, really, from 10 to 40, but somewhere in the range of, particularly if you're using a four-frame system, I like to read at 22 frames a second. The beauty of the four frames is that the actual dwell time of each image is longer than if you do it in a one- or two-frame arrangement. A couple of pearls, and then we have the ability to do it in a one or two frame arrangement. Couple of pearls, bleeding site is the most proximal site of fresh bleeding. Multiple sites in general do not occur. They may occur on different days, but generally there is only one bleeding site at a time. And don't forget bleeding is intermittent and don't forget to check the sacrum and the right colon because a significant percentage of bleeds do occur and originate in that area. Preparation remains controversial. This site is I think the most recent meta-analysis on this whole arena. My preference at UMass was not to do a prep other than keep people NPO from dinner the night before. The Brigham uses much the same system where I'm currently at. The meta-analysis demonstrated that really there's no increase in diagnostic yield, no improvement in visualization, completion rates are the same and there's no effect on transit time. So we put patients through an awful lot. So why put them through an unnecessary prep? Preparation adjuncts, again, very little support, but I'm sure other people are gonna talk about this in more detail. The one comment I would make is that if you're doing capsules with the patients who are bleeding acutely, that is they come in with melanin through the ED and you drop a capsule early on, out of the nearly 200 patients we've done capsules in this setting, we have never seen food in the stomach. So you don't have to wait eight hours before you drop the capsule. Location remains the, if you like, almost the final frontier. A lot of very smart people, much smarter than I am, have spent a very large amount of time trying to work out how to sort out or develop a, if you like, pedometer for a capsule. We've got quite good systems that give you 3D information, but in clinical reality, they're not used. So what I use is a, record the time at the pylorus and the cecum, split the small bowel up into quartiles, and then give a best guess estimate as to where the lesion actually is. Sometimes we're pretty accurate, sometimes not so accurate. On, at least on the Medtronic's device, the percentage time provided by the software is probably the least reliable assessment. Now, why do we want to locate the capsule? Really the answer is because if we're going to do enteroscopy, which is an essential adjunct to doing capsule enteroscopy, we need to know whether we go from the top or the bottom. So, essential piece of information. And then for push enteroscopy as a pearl, you by and large can't get beyond 30 minutes from the pylorus. We did a small study many years ago now, looking at this, it only got to abstract form, but 30 minutes represents about as far as you can get with a push. The other essential tool is the patency capsule, which consists of a, the body of the device, which is a plastic sheath filled with a barium lactose mix and two biodegradable plugs. Those plugs start dissolving after about 30 hours. And at 60 hours, pretty much the entire contents of the envelope have disappeared, leaving just a shriveled little plastic piece and a transponder in the middle. So, this device is useful for those where you suspect there might be a stricture, Crohn's disease, radiation, NSAID use, and so on. And this has been a useful device to keep you out of trouble with dropping capsules in an inappropriate setting. Again, just one slide on the enteroscopy in general. The tools available are the push enteroscope, either a dedicated instrument or a pediatric colonoscope, single balloon, double balloon. You can, instead of using balloons, you can use a spiral device built onto an overtube with soft flanges. Works about as well as the double balloon and the sad story of the power spiral enteroscope. Great technology enabled, under the right conditions, to go all the way through the small intestine. But unfortunately, the company withdrew it because there were a couple of deaths, probably because of people who didn't understand how to use it. It does require a real significant amount of training much beyond this double balloon because of its potential lethality, but it did provide a extraordinary way of looking at the entire small bowel. Sorry, let me go back a bit. So enteroscopy, about as efficient and accurate as VCE, but obviously has that therapeutic overtone. The downside is that, particularly the double balloon, which is probably the most widely used, is quite time-consuming and physically laborious. And anybody who's doing capsular endoscopy needs to find a buddy who's doing this, either in the same institution or locally, so you can provide a therapeutic option for the patient. I'm just going to take you through some of the normal variants. On the left, there's obviously some rather poor dentition and papillae on the tongue. This is something you do not want to see. If you have a elderly patient who has trouble swallowing it, get the patient to spit it out and place the device endoscopically. There are anecdotal stories of people swallowing the capsule, getting it into the bronchus, coughing it up, and then being given it again, and then having to go in with a bronchoscope to pull it out. So don't do that. The pylorus, many of you will know what this is. The white discoloration, if you like, is the pressure of the antral mill peristalsis in the antrum pushing on the microvasculature with the capsule just before it pops through into the duodenum. And this is a retrograde view of the pylorus, what I like to call the dark side of the pylorus, quite commonly seen because you have no control, obviously, as to which way it goes through. The papilla is seen about 5% of the time by a single-camera capsules, up to about 40% with the double-ended capsules. Beware of bubbles. They can be very misleading. Try not to read anything through a bubble. Villi, you can see this is actually a rather old one, but here you've got these white folds. Again, there's no luminal contents. This is a physiological device, and if there's air, you see a very different image to what if there's no luminal contents. So this is just the normal mucosa with pressure on the folds. Vessels, quite variable in appearance. And then cholesterol deposits within the mucosa, characterized by very fine blood vessels running across the surface. Some people may have seen these bleed, but I have never, in the many years that I've been doing this, seen these as a site of origin of bleeding. They're very common as patients get older. And then lymphectasia can be quite useful, in fact, as a marker as to where a pathological lesion is. These are entirely benign. Again, don't bleed, and quite decorative. Phlebactasia, again, quite common. This type is particularly common. This one is more advanced. And then this can morph into the concept of portal hypertensive enteropathy. And then debris, rather frequently found. Some of you may have seen this. These are actually tomato skins that have rolled up, and this particular patient had them throughout the small intestine. Looked very interesting. Pills can create debris, just as you see through a regular endoscope. And this is really what you don't want to see as a second capsule, which has been retained. I'm going to make a couple of comments about the colonos, the colon capsule. It started in 2006, became the 2002 colon capsule. I'm sorry, the 2009. Then the Crohn's capsule. And at the moment, for those of you that ever read a colon capsule, it's a shortcut to a headache because you've got two video screens to look at, or streams to look at. There is a colleague of mine has developed a very efficient AI system for reading it, but it's not yet available. Now, why do I bring this up? Because it's not really available in the United States, thanks to our insurance industry. So I'll come back to that in just a moment. So the current indications by the FDA are for incomplete screening, if you can't get your colonoscope to the CECM, for assessing IBD activity, and if a patient is unwell enough for colonoscopy. And in the rest of the world, it's starting to be used quite extensively in under-resourced areas. And I think that's really very interesting. The colon capsule now in its current iteration is capable of producing remarkable images of large and small polyps within the lumen, another polyp here and a tiny one here. And numerically, its sensitivity and specificity compared with colonoscopy is getting up to pretty high levels. So it's a competitive tool. And if I am gonna come back one, to say that the advent of remote reading has allowed various individuals around the world to develop kits so that they can send off the capsule, a sensor belt and a transmitter via a local community clinic to patients in isolated areas. Patients can do the colonoscopy, capsule colonoscopy on their own. And then the transmitter in the kit will transmit the data to the cloud where it can be read from anywhere in the world. So for under-resourced areas, this is gonna be a very interesting series of development. And in England, they're using, or they've just completed a trial of 11,000 colon capsules to look at its utility in, again, a general population that has comparatively little access to colonoscopists. So we are in, at least in many parts of the States, we're in a sort of elitist situation, but there are vast areas of the United States without a gastroenterologist. So this is gonna be an interesting area to watch, and it's gonna put a lot of pressure on the insurance industry to start to reconsider financing this technology. So in summary, this is a relatively new technology. It's a non-invasive or minimally invasive technology. You can see most of the small intestinal mucosa. We've talked about the rapid development up to 2005 and accelerating development since 2016. And then speakers later in the day are gonna talk about all these really exciting adjuncts to the original concept of capsule endoscopy. Thank you very much for your attention.

capsule endoscopy

small intestine

imaging advancements

patency capsule

minimally invasive

global application