Our next speaker, also from Europe, Czech Republican, Dr. Martin Lucas, a long-time friend of mine too, and he's a rising star, already a big star in terms of animal model for interventional IBD, and he's from the S-Care Medical Center at Prague, and then University of Prague, or Charles University. Martin, the platform is yours. Good morning, ladies and gentlemen, dear colleagues. First of all, I would like to thank Professor Bošan and Dr. Navanetan for the invitation. It's a real pleasure for me to hold a brief lecture about the development of animal models for intestinal stricture. Here's my financial disclosure. I don't have any conflict of interest. The hands-on training of endoscopic procedures is an essential part of the education of every endoscopist that has been a well-known and proven concept for many years. Training recommendations are incorporated into various international guidelines, such as ESGE guidelines for endoscopic somocausal dissection. When you start learning a new method, it is first recommended to gain a general and theoretical knowledge of the prospective technique and use equipment by self-study. Then it is recommended to visit a specialized center, which performs a significant amount of the procedures per year and thus has sufficient experience in all aspects, including potential adverse events and their management. After gaining the necessary basic knowledge, it is most appropriate to start training on models, mechanical or animal. Observation of an expert endoscopist is an expert center, and then performing the procedure by oneself on real patients, but under direct supervision of a skilled specialist, is the ultimate goal of the training procedure. The animal model provides the best condition for training of different endoscopic methods, including all essential pitfalls that can occur during the procedure, including movements, bleeding, or a tissue reaction. However, training on animal models has several limits. More than 66 different types of animal models were created in the past, but all these models were on small animals such as rats and mice, which are difficult to scope. All these models are widely available, but don't allow for endoscopic practicing. For these reasons, large animals are needed. However, the use of large animals is more expensive and is subject to more legislation. The most common animal model for endoscopy that we use is a mini pig. Endoscopic practicing in IBD-related complications is different from others, because most animal models for endoscopic training don't require the presence of a specific pathological condition. For stricture therapy training, it was necessary to develop a model mimicking the real pathological situation that frequently occurs in IBD patients. The anatomy of animals differs from that of humans in some details. In the case of a mini pig, it is the anatomical conformation of the large bowel. First, it was therefore necessary to overcome the technical challenges of the endoscopy. The modification of the classic Roux-en-Y procedure was done by surgeons with a small bowel segment connected to the oral rectum, as you can see in the left picture. This ensures proper reachability during endoscopy and also provides easy preparation before the procedure without the need of emptying the whole bowel. Second, it was necessary to induce an inflammatory stricture at the site of the anastomosis. This was achieved by a local application of two chemical agents, namely TNBS and liquid phenol. The application of chemical irritants must be targeted into the anastomosis site with the injections repeated at least four times in a two-week interval. Here you can see the result, the stricture of the anteroclonic anastomosis. This stenosis shows macroscopic and also microscopic signs similar to the Crohn's disease anastomotic stricture, as we can see in everyday clinical practice in our patients. However, I would like to point out that the animal welfare is utmost priority and must be very well taken care of. All procedures should be performed under general anesthesia and all procedures in our training facility are supervised by experienced veterinarians. The endoscopic courses are approved by the Veterinary Ethics Committee and care of animals is provided in agreement with international rules on the treatment of laboratory animals. It is important to keep in mind that animal welfare is always first. Why are pigs the preferred animal? The answer is simple. The pig has an anatomy and physiology very close to humans. In addition, the pig is large enough to be easily scoped with conventional equipment, so you don't need special instruments or modified scopes. The only anatomical difference is the special arrangement of the large bowel, which consists of a series of centrifugal and centripetal loops, so that complete endoscopic examination to the bottom of the cecum cannot be performed. However, this problem can be solved surgically by performing a modified U and epsilon bypass to create enterocolonic anastomosis instead of classical ileocolonic resection. Moreover, this anatomical intervention makes the bowel passage intact for digestion, even in case of complete obstruction of the anastomosis. The animals don't suffer from any clinical symptoms, such as the patients with the Crohn's disease with a very tight bowel structure. It is beneficial for our animals and in harmony with the animal welfare rules. Details of the model were recently published in last year's GI Endoscopy Journal, so you can familiarize yourself with the complete process of model creation in this journal. In this short video, I would like to present a practical demonstration of an endoscopic strictorotomy training. The video is from 2019, when we started practicing this method on animal morals before we transferred it into a common clinical practice. You can see that the endoscopic images are very similar to what can be found in humans. In this case, we practice a horizontal type strictorotomy. Peristaltic movements, respiratory movements, and the presence of bleeding are essential aspects mimicking real clinical practice that can hardly be simulated in a non-lift model. Because the animals continue to live after procedures, it is possible to perform a follow-up examination and to monitor the condition of the anastomosis over time. In November 2018, we organized the first postgraduate course for endoscopic strictorotomy training in our facility. The course was attended by Professor Kovchar from Pittsburgh, who was the main lecturer and demonstrated a sample strictorotomy procedure. He then supervised each individual participant during their turn. In the following slide, I would like to show you a short video directly from the course, which has original audio, so you can get a better image of how the course went, and especially how important it is to learn a new method from an expert. This is almost like in a real life that the scope is not in the same, what we call it, N-fast position. It's not looking directly at the anastomosis, so it's at an angle. So, you have to find a good spot. Like anything else, keep the knife closed. So, open the knife. I like to keep this black out close to the scope. So, I'm just going to see if in a longer position I get a better look. And I might get a better look in the longer position scope for it for me. And then, because I can't get a circumferential cut, I'm going to cut a deeper cut. And we've got a nice deep cut there. And now, since I can see, so the safest direction is this direction. The lumen is here, right? So, this is the thickest point. So, this is where my first line cuts were in this direction, not be in this side. Toward the side of the lumen, that's the safest. So, I would like to thank Professor Kovchar again for his excellent demonstration. It was very instructive and educational. Unfortunately, current worldwide situations don't allow us to continue with these courses. We are still waiting to see what happens in the upcoming months or years before we reopen these courses. So, the next short video is from our real clinical practice. After performing several procedures on animal models, we started to apply the endoscopic stricturotomy in real life. Here, you can see the horizontal type of stricturotomy using a needle knife. The presence of tin septum between large and small bowel is an optimal option for cutting in one direction. But it is important to place a clip on the bottom and on both sides of the cutting area at the end of the procedure to prevent delayed bleeding and microperforation. Well, what else can be done with our model and how could it be used? In addition to endoscopic stricturotomy, it can be utilized, for example, to practice standard balloon dilations or a stent placement. When complications such as perforation occur during the procedure, solutions can be part of the practicing. So, this animal model also opens up space for developing or modifying methods which are currently used in other indications. Here, you can see the short video from Hotaxia stent implantation, for example. Insertion of this type is very simple and quick and usually does not require x-ray control. In the literature, you can find some small key theories about the usage of this type of stent in patients with Crohn's disease stricture. In this video, you can see another type of stent placement. It's a Tiwong stent. NTS is the full-covered self-expandable metal stent dedicated for colonic stricture, but not specifically for Crohn's disease. Implantation is easy as in the previous case, but the extraction could be more challenging, especially due to the length of this stent, which is at least six centimeters. In addition to NTS stents, we can use Hanaro stents in Europe. These stents include a model dedicated specifically for colonic localization, as you can see on this short video. However, the results from stenting are still not consistent and not convicting. Unfortunately, no perfect stent is yet available for patients with Crohn's disease. There are also no recommendations on which kind of stent, what stent shape or length should be used. We are currently testing various types of stents, and we are cooperating with pharmaceutical and biotech companies to customize unique stents for patients with IBD. Here is another example of model's usage. Modified distal procedure, which we performed last week. Double incision and SNARE resection method is established for resolving Sankars Diverticulum in the esophagus by cutting the cricopharyngeal muscle. We tried to apply the same method in enterocolonic anastomosis and resect the large part of the fibrose ring in the stricture. First, we cut the septum into two similar directions, as shown in the green arrows, and then we cut the middle part as a pseudopolyplesion between the cutting areas by SNARE. After the SNARE resection, we place two clips on both sides of the cutting area to prevent delayed bleeding, as in the case of endoscopic stricturotomy. Dear colleagues, let me conclude by saying that training on animal models has been showing to improve the learning phase of new endoscopic methods and its routine use can facilitate spreading of the new methods in a clinical practice. A specific model of Kranz-like stricture for teaching of endoscopic stricturotomy has been available since 2018. However, there is no recommendation for its routine use in a training kit. When the worldwide situation improves, we can renew our courses for hands-on endoscopic stricturotomy training and offer them to more endoscopics. Thank you for your attention.

animal models

endoscopic procedures

intestinal stricture

inflammatory bowel disease

hands-on training