We'll get things started with our EUS keynote presentation by Dr. Ken Binmuller. Dr. Binmuller is the Director of Interventional Endoscopy Services at CPMC in San Francisco, California. He lists three career-long passions, endoscopy, innovation, and teaching, and we know him well for all of these. Endoscopy is clearly the dominant passion, and it fuels everything else. He is a universal endoscopist with expertise in all aspects of interventional, and his daily practice inspires the innovation to improve outcomes for his patients and enable new procedures and products. He is the inventor of the Axios, or aluminum-opposing metal stent and delivery system that has been discussed and will be discussed throughout this course, and holds over 50 other patents for novel endoscopic technologies. He's recognized nationally and internationally as an authority and leader in advanced endoscopic procedures and EUS, and we can't think of a more fitting person to give us this keynote lecture on the evolution and future directions of therapeutic EUS. Ken, thank you for being with us. It's really an honor for me to give this keynote presentation at the New Frontiers in ERCP and EUS conference. I'm delighted to spend the next 45 minutes with you. I'd also like to take this opportunity to thank Klaus, our president, as well as Raju for organizing this, and also thanks to all of the co-chairs of this session. So I'm going to take you on a quick journey. I've got a lot of slides, so I'm going to go through these fairly quickly, and that really speaks for the amazing, remarkable progress that we've made in the span of four decades of EUS, and it all started as a imaging procedure in 1980 when de Magno first reported on endoscopic ultrasound. It was the first report in an animal model, and we used a radio-scanning echo endoscope. It was purely diagnostic. We had no capability for intervention, but that then changed. This was a huge leap, a paradigm shift now in the 1990s with the advent of the curved linear ray echo endoscope, and we could pass a needle now into our scanning plane. We could visualize that needle lengthwise, and we could perform FNA. And now in this millennium, this is where all the excitement is. We can perform therapeutic intervention. So of course, FNA was an extension of diagnosis, but now we can actually offer treatment for our patients, and this is without question the big new frontier for EUS. I really think of EUS-guided FNA as the birth of notes. It's using a natural orifice to now perform transluminal intervention. We have access to neighboring organs that surround the gastrointestinal tract, the mediastinum, the peritoneum, the retroperitoneum, the pelvis. We have access to lymph nodes. We have access to peri-intestinal masses and fluid collections. So we really have a large span of organs, almost all of the organs in our body that we can access with this unique window. FNA then evolved to FNI. We're switching out the A for I, and that I can stand for inject, or it can stand for implant. So what can we inject? Well, we can inject sclerosis, and we can perform celiac block. We can perform neuralysis. Most of the work has been targeting the celiac ganglia, but really we can target any nerve structure. That is a very exciting emerging area that we are advancing now. Oncologic therapy, we've been doing this for a while. The technology is fascinating. This is certainly very cutting edge. We can perform cholangiopancreatography. I like to call this EACP to distinguish it from ERCP because we're taking an anterograde approach to the A rather than retrograde, and we can perform transluminal amystomosis. So I'm going to spend time addressing each of these five categories. 1996, this was the first report of EOS-guided celiac plexus neuralysis. This is Moritz Wiersema. He was a pioneer of many, you'll see his name repeatedly now, of these early interventions. So he reported on endosterongic-guided celiac plexus neuralysis, 29 patients. He injected bupivacaine initially followed by absolute alcohol, and he used the bilateral injection technique. So he's going alongside the aorta on the right and left sides. And he reported less pain, medication requirement on follow-up, 24% at two weeks and 32% at four weeks. So this was that landmark paper introducing this therapeutic alternative to percutaneous celiac blocks. Next, we saw papers that looked at a comparison of the central technique where we're just targeting the knee, what I call the knee, where the celiac axis exits from the aorta, here the red arrow, versus the bilateral approach, you see that with the blue here, alongside of the aorta. And this was from Anand Sahai, a study that looked at the short-term effectiveness comparing these two techniques. Now, this was not a randomized trial, which actually a historical comparison, and that is important to emphasize here. He's comparing a early versus a later practice. And you see the results here. The patients that had bilateral injection had a significantly better response. So his recommendation from this paper was that patients should undergo bilateral injection. But now we see, and this is to emphasize how important it is to perform randomized controlled trials. This is a RCT comparing the central versus the bilateral injection technique. And this is from Indiana. This is from John DeWitt's group. And here now you see that when you compare the central and the bilateral, there really is not a significant difference between the two groups. There's no difference in pain relief, including onset and duration, and there was no difference in safety or survival. So based on this study now, if you randomize patients in a controlled fashion, there really is no difference between the two. So perhaps we shouldn't subject our patients to that additional injection. Next we have a randomized controlled trial that compares targeting only the ganglia versus the plexus. So we're comparing CGN with CPN. And this is a study from Japan. It is a 13-center trial. So they're comparing these two approaches in patients with pancreatic cancer pain. So this is for paleation, randomized, one-to-one. And the patients in the CGN group, and here you can see the needle targeting only the ganglia and injecting a small amount of sclerosin into the ganglia. The ganglia were visualized in 88% of the patients. And this is an intention to treat analysis. That's important. And CGN was found to be superior to CPN, 74% response versus 45%, and you can see here the results listed. So this study endorses a targeting of only the ganglia versus what we were previously doing, which is to just more diffusely inject the sclerosin in the region of the plexus. But then we have this study that was published two years ago by Michael Levy at the Mayo Clinic. Now, this is a little different. It's not strictly comparing apples to oranges, but it's a combined celiac ganglia versus plexus neuralysis. And this study found that the targeting of the ganglia shortened survival without any benefit compared to only CPN, plexus neuralysis. So 110 patients here, randomized control, double-blinded, 50 patients CGN, 60 CPN, pain control at three months, no significant difference between the two groups. In one, there's no difference in adverse events, but one patient in the CGN group actually developed paralysis. And the survival was significantly worse in the CGN group, and you can see here the graphs. So this, of course, now raises new questions, and at least I think we can conclude we shouldn't take a combined approach of CGN and CPN. So if you're going to do CGN, then only CGN. Now, the term block is often used interchangeably with the term neuralysis, and these should not be confused. When we perform a block, we're injecting an anesthetic, bupivacaine, followed by a steroid. Neuralysis is the injection of this fluorescent, ethanol. So the objective for neuralysis is to really kill the ganglia, and with block it's to paralyze the ganglia, but it will recover. So this is going to be temporary, and we want the neuralysis to be more durable. This is an important study. It's a randomized controlled trial. It was published back in 2012, and they found that the response rate in both groups comparing adding steroids versus not adding the steroid to the bupivacaine was only 15%. But importantly, the steroid added no pain benefit. So you can see the curves here. In fact, here below the patients who received the steroid, in addition, they had a worse outcome in terms of pain relief. So there was a shorter response. So in my opinion, we shouldn't be performing blocks anymore, and I still do see this being performed globally. Now here is the big transition to intervention and therapy. So the I now can stand for injection and implant, and I want to address next vascular therapy. In 1996, there was a report using the radio scanning echo underscope. This is Paul Falkins, and he was actually able to visualize the needle and cross section and inject a sclerosant to treat dilaphole lesions. So this was actually reported as far back as 1996, but it really wasn't until 2000 that Dr. Lee here from Hong Kong, he reported on EOS guided glue injection, and this is using the CLA echo underscope. And the concept here was endoscopy on demand. So doing it in the traditional way, endoscopy guided versus EOS guided, but really it's about repeating the injection until EOS confirms complete obliteration of the varices. So if you compare the EOS repeat group with the endoscopy on demand group, the outcome was significantly better in those undergoing EOS. Now, I want to emphasize that this is not a strict apples to apples comparison because of course the endoscopy could have also been with repeat injections until obliteration is confirmed. It's just that you can't directly confirm that obliteration endoscopically. In 2007, Rafael Romero Castro in Seville, he reported on the injection of glue for gastric varices targeting the feeder vessel. So this is the novel target here, the perforating vessel. This is proof of concept, five patients, and he reported great results. Now why did he target the feeder vessel? The goal was to produce a maximal blood flow blockage by targeting the feeder vessel with the least amount of glue. Now why would he want to minimize the amount of glue injected? Well, that's because he and all of us who have been using glue to treat gastric varices, injecting this of course in the conventional endoscopy guided approach, have seen complications related to systemic embolization of the glue. This is our dreaded complication because the glue can embolize anywhere in the GI tract. And if the patient has an open foraminal volley or AV shunts, it can get into the arterial system and go to the brain. And I personally had one case of a patient that became hemiplegic after glue injection. So I put a moratorium on my use of glue following that, and I started thinking about how we can reduce this risk of systemic embolization. Raphael in 2010 reported on the use of coils for obliteration of gastric varices. So let's just eliminate the glue entirely, just use coils, targeting the perforator vein with good results. But it required a large number of coils to get obliteration, in one case, 22 coils. There is this study, it is a retrospective non-randomized trial, but they are comparing in this study EOS guided glue injection versus EOS guided coil implantation in both subsets of patients. They are targeting the feeder vessel. So that is similar. And with the glue, a mean of 1.5 milliliters. And they obtained CT scans afterwards, and they found that there were lung emboli present in nearly half of those patients. So that's very impressive in terms of a high embolization rate. When they used a coil, coils, it was a mean of six coils per patient, 18% of those patients still needed glue. Now here's what's noteworthy, none of the patients had evidence of lung embolization on their CT scans, including this 18% that still needed glue. So glue still did not embolize. And this led me to wonder, well, perhaps it's placing that coil first, acting as a scaffold to retain the glue that might reduce, ideally eliminate the risk of systemic embolization. And the coil itself will fill and reduce flow in the varicose veins, and that too can reduce that risk of embolization. And here in this proof of concept ex vivo model, you can see that I have planted a coil followed by glue into this jar of heparinized blood, and you see the glue attached to the wooly fibers of the coil. So at least in this model, it appears that a coil with its wooly fiber strands can prevent systemic embolization. So we started doing this in our unit, and in 2011, we published our first series of this hybrid approach of coil and glue for gastric varices. 30 patients, great technical success, all EUS guidance, as you can see here, you can see a 50 millimeter coil being placed inside of a gastric varix, and that is immediately followed by injection of the glue, the glue attaches to the coil. And here on six-month follow-up, you can see the glue adherent attached to the coil, again confirming that the coil is fulfilling its role as a scaffold to retain the glue in place. We had re-bleeding in four of these 24 patients, and, but of which only one of the patients had a variceal bleed, no complications, no systemic embolization. This is the new frontier that I think we're going to be hearing a great deal about in the coming years, and that is EOS-guided portal vein and geotherapy. A key advantage of EOS is that we have direct access to the portal veins, this is in contrast to percutaneous, where the radiologist does not have direct access. And these are three potential areas for application. The first would be a portal pressure gradient measurement. I'd say that this is already here, because the device has now been commercialized so that we can perform this. So I think this will take off, and will replace the radiological approach to obtain portal vein wedge pressures. Portal systemic shunts, a TIPS in theory, can also be performed. We'll see if this, and it's only be done in animal models, whether this enters into the clinical sphere. But this is an area that I'm particularly excited about. It's called EPIC, portal injection chemotherapy. And here you can see in the diagram, by the way, how with our EOS scope positioned in the proximal stomach, we have direct access to the portal vein. So this is a study that was published by Doug Fagel in 2016 on EPIC. Now this is only in the Porcine model, and we are anxiously awaiting a clinical study in the future. But the goal here is to optimize liver levels of the chemotherapeutic agent while minimizing systemic toxicity. That, after all, is the holy grail of chemotherapy, that we can minimize that systemic toxicity. So for chemotherapy, they used a delayed release chemotherapeutic agents that are bound to albumin or drug eluting beads. And they then injected this directly into the portal vein. And they found, you can see here, paclitaxel, doxorubicin, arenotecan. For all of these, the hepatic levels were significantly increased, whereas the systemic levels were significantly decreased. So a great proof of concept. I think for doxorubicin, it's very impressive. We know about the cardiac side effects, a 30-fold decrease in the cardiac levels of the chemotherapy. Oncologic therapy. Now, I could show you many, many slides here because there's been a lot of very fascinating research that's been done. Let me just move this one down here because it's meant to be shown afterwards. But here you can see a spectrum of what has been done. We've performed sclerotherapy using ethanol, injecting that directly into tumors. Chemotherapy, especially paclitaxel, has been used. Immunotherapy, there's been a lot of work in this space using activated lymphocytes. Even gene therapy, various vectors for gene therapy, adenovirus, herpes simplex virus, TNF-alpha. So just a wealth of research that's been done, mostly in the animal model, but there have also been some clinical trials. Thermal ablation has been another area that has been explored using laser, using cryotherm modalities, using radiofrequency ablation. Here's the bottom line. I think as exciting as all of this is, I consider all of this still experimental. We have no proven survival advantage. And unless we have that proven survival advantage, in addition to just anecdotes of our ability to perform this, so we may have the impression that our patients benefit from this, but we really need proof in a randomized controlled trial that there is a survival advantage. Of course, when we're dealing with cancer, there usually we're dealing with something that's often systemic, and that's a significant limitation in terms of local treatment. But there's no question we're going to continue to see advances in this area, especially for patients with local disease. Pancreatic cyst ablation is in my opinion, a one area that I believe we're going to very soon see an application for EOS guided treatment. This is the CHARM trial that was performed, a randomized controlled trial comparing chemotherapy with and without ethanol. So the issue is the ethanol, because it can cause pancreatitis. And if we can eliminate the ethanol, this really makes chemotherapy a more attractive option for treating pancreatic cysts. And in this CHARM trial, ethanol added no benefit over just chemotherapy alone, paclitaxel and gemcitabine. So here you can see the results. So we've seen an evolution here from using ethanol alone, then adding chemotherapy to ethanol. And now I think we're going to see the application of just chemotherapy making this approach much safer, but this certainly has not entered the mainstream yet. Let me move on to cholangiopancreatography, what I call EACP. And this was reported by Moritz Wiersema in 1996. So he performed the first EOS guided cholangiopancreatography. This is something that just seems obvious to us today, but back in his time in 1996, this was truly revolutionary that we could now anterogradely approach the bile duct, the pancreatic duct, and inject contrast to get a cholangiogram or a pancreatogram. So 11 patients, and they fielded only three patients to obtain cholangiopancreatography. So at this stage, this is still diagnostic. Here you can see the approaches. We're going gastrotranshepatic from the upper stomach to approach the hepatic ducts. We can approach the distal bile duct transduodenal. For the pancreatic duct, we can go directly transgastric, or we can go transduodenal depending on the part of the duct that we want to approach. Moritz actually called this EGCP, so an EOS guided cholangiopancreatography, but I like EACP better. So what we're seeing now in 1996, we're seeing a convergence of EOS and ERCP. So here you can see the evolution of ERCP. You see the evolution of EOS, and now they converge at this point with Moritz's paper. And next we see from the University of Minnesota, Sean Mallory and Marty Friedman, reporting on the rendezvous technique. So this is where, in addition to injecting contrast, now we pass a guide wire through a needle. And this guide wire now gives us access for intervention. In this rendezvous technique now, the guide wire is passed across the ampulla, and you can see it in these cartoons here, how now we can switch to the duodenoscope, and we have access to the bile duct retrogradely or the pancreatic duct retrogradely. So this was a landmark paper reporting on the rendezvous technique. It was something we were doing, the rendezvous, but we were doing that in partnership with our radiologists who passed the guide wire percutaneously. Now we can do it ourselves. In 2007, Olympus had actually developed this front-viewing, forward-scanning echoendoscope. And I wrote an editorial titled Optimizing Interventional EUS, the Echoendoscope in Evolution. This has been slow to disseminate, but it gets us closer to that true hybrid echoendoscope that allows us, with one scope, to perform diagnosis and therapy, both inside and outside. So I wanna show you this video, and it's already a bit dated because I did it back at the time, so over a decade ago, but in a 78-year-old male with jaundice, post B2 with long afferent limb, CBD cannulation had failed with the pediatric colonoscope. So now I went down with the forward-view echoendoscope, and you can see here our underwater image, which I like, and you can see the CBD here and the PD. And now under ultrasound guidance, we can directly cannulate the bile duct. So this is a true convergence of these modalities, and we're doing this with one scope. So you can see the guide wire being passed into the duct. So here are the pancreatic duct and the pancreatogram, and now the CBD. So we've selectively cannulated each of these ducts. Here's the cholangiogram showing the stone, a big stone in the duct, multiple stones, in fact. And then we perform sphincteroplasty, and again, this is through that forward-view echoendoscope, all with this instrument. So this is not a duodenoscope, this is not a colonoscope, it's a forward-viewing echoendoscope, and we're doing it all with one scope. All right, now, last is transluminal anastomosis, and of course, I've kept the best for last. So this too had, we've seen a long evolution, and it starts all the way back in 1992 with cyst enteroscopy, so pseudocyst drainage. And now it's, we're, in 2015, we've seen reports of gastrogastrocystin, I'm gonna comment on that in just a moment a little more, but this is really the exciting new frontier. And in 2011, I reported on the use of the lambs, and this has greatly facilitated our ability to create transluminal anastomosis more safely and more expeditiously. I'm Peter Hamburg, working with Nibsandra in 1992, and we published this as a case report. We had just received a new CLA echoendoscope. We, up to this point, this time, had only been using the radio scanning. So this is from Pentax with small channel, two millimeters, but using a self-fashioned diathermic needle, this continuous needle, inserted through a five French Teflon catheter, I was able to visualize the cyst under EUS guidance and pass the wire into the cyst. Now, at this point, we switched out for a duodenoscope, leaving the wire in place, and then we placed through a duodenoscope, the 10 French Plastix 10. But this was the first true therapeutic application of EUS guidance, and now we're applying the Solginger technique. It's the over-the-wire technique, and we're borrowing this as we borrowed so much from our interventional radiology colleagues. And this is just to acknowledge Sven Solginger, the Swedish radiologist who described this in the late 1950s, the Solginger technique of needle puncture, followed by placing a guide wire, dilating the tract to then enable a therapy such as placement of a stent. So in 2001, Mark Giovannini reported on the first Colodoco enterostomy. So he's extending this from pseudocyst drainage now to drainage of the biodect, reports this as a new technique, also as a case report. So same application of the Solginger technique, transduodenal CBD puncture, placing a guide wire. You can see this nicely in some of the pictures. He then performed over-the-wire Bougie dilation and then exchange for a duodenoscope, and then placed in the 10 French plastic stent. But he notes, and he emphasizes this in his paper, the main problem is the risk of leakage of bile into the peritoneum. And a year later, in 2002, pancreatic enterostomy was described, was multiple authors here. And this is more of a challenge because when we go through the pancreas in a patient with chronic pancreatitis, the organ is indurated, of course, it's difficult to penetrate. So here they used a cystotome. So they're using cautery to facilitate puncture through the pancreas to gain access to the pancreatic duct. But using this 6.5 French cystotome, they were able to access the duct, place the wire, and once again, Solginger technique, and place a six or seven French plastic stent. And in their discussion, it's noted that special devices are needed, such as a diaphragmic sheath, which provides the only means of entry into the pancreatic duct after passing through fibrotic pancreatic parenchyma. So we're seeing how these technologies are all coming together and enabling us to do things we couldn't do before. Todd Barron then, in 2007, reports on the first cholecystointerostomy working together with Mark Tobazian, the ultrasonographer working in partnership with him. And in this case report, patient with acute cholecystitis after placement of ability SEMS, they had tried to drain the gallbladder by ERCP transpapillary, it was not successful. And then they performed transduodenal gallbladder drainage, again, using the Solginger technique. Now, when we start draining a structure like the gallbladder, obviously a structure that is not adherent normally to the gastrointestinal wall, this is very different from draining a pseudocyst that usually is adherent. And that makes us more aware that transluminal therapy is really an intentional perforation. We are perforating, but we're doing that intentionally. You can see in this ultrasound, this very bright layer sandwiched between the gallbladder, the gallbladder is distended. It is pushed up against the duodenal wall, but these two structures are not adherent. When the gallbladder decompresses, it's going to move away from the duodenal wall. And here in a patient of mine who ended up having to go to surgery because of a massive bile leak from the gallbladder when I attempted this, you can see the plastic stent interposed and sandwiched in between those two cavities, the gallbladder and the duodenum. So really what we need or needed, because we now have, I think, the tools, but it was the tools, we needed tools to prevent drainage, sorry, leakage. We could drain these, but we couldn't prevent leakage. And there are two tools that I had been, basically spent the last decade working on. And I think that these are truly making the procedure much safer and easier. And the first is the transluminal stent, what we call LAMS today. So it is covered and self-expanding and seals off the tract. It's luminoposing. But most importantly for me, it provides support for transluminal intervention. I want to extend the reach of the endosynographer. So you can see some of the patent drawings here way back in 2005. So these ideas have been germinating over a long time. And we also need a transluminal stent delivery system that eliminates Seldinger, the over the wire exchange technique, something that was very valuable to us at one time, but we really need to evolve further because our needs are different from the radiologists who can work from a sterile environment. We can't work from a sterile environment, we're creating an intentional perforation. So we can access our target lumen with a stent-loaded catheter. So in 2011, I reported in the Porcine model and spent a lot of time placing the lambs in animals to finally come up with the configuration that would work if holding two lumens in apposition. Essentially, the functional equivalent to surgical anastomosis, it seals in the tamponades, and it creates a port for transluminal endoscopy. You can see the endoscope being passed through the lambs into the gallbladder in this Porcine model. And we have a cystogram and a cholangiogram. So here, you can see that we achieved durability of the placement of the lambs. Then working with Takao Itoi in Japan, couldn't do this in the US, so we went to Japan. And we were able to create the first lambs' anastomosis in patients, patients with pseudosys, patients who needed gallbladder drainage, great technical success, and no complications. Stents were removed without complication after a medium of 35 days. But some patients refused to have their lambs removed because they were so grateful to have relief of their symptoms. And gastroenterostomy, again, this is a Porcine model published in 2012. But this is the introduction of the concept of the electrocautery enhanced cautery system. You can see the hot puncture being performed here into the small bowel. So when you go into the small bowel, that is the most mobile structure, far more mobile than the gallbladder. And here, it is critical that you be able to deploy your lambs immediately. So the Sonygier technique is not applicable, in my opinion. It would be hazardous to use that when you're trying to perform a gastroenterostomy. So you can see the distal anchor, the proximal flange here, and here we've created the gastroenterostomy. Here, necropsy, you can see the stomach with the distal flange and the proximal. I'm sorry, the proximal flange and the distal flange and the jejunum. So we see that the lambs' applications falls into three different buckets, if you will, categories. We have the pancreatic obiliary, pancreatic cyst enterostomy, pseudocyst or wands, gallbladder, cholecystoenterostomy, bile duct choledocal enterostomy. I suppose we could also add pancreatic duct. That certainly may also be a possibility. And we're starting to see some first reports on that. Enteric would be small bowel, the gastroenterostomy, but also the bypass stomach, creating a gastroenterostomy. And ironically, we're now seeing luminal applications of the lambs. None of you was guided, of course, for bridging pyloric stenosis and short strictures, mostly anastomotic. This editorial dates back to 2006. And the title is, does the advent of endoscopic ultrasound sound the death knell for ERCP? And actually, I think the author is correct, that it is sounding that death knell, that EOS-guided will, over time, replace ERCP. We're starting to see papers like this in 2019 from Bertrand Napoleon's group. Endoscopic ultrasound guided biliary drainage, a change in paradigm. We're no longer approaching this with ERCP. In this paper, also, EOS-guided biliary drainage versus ERCP for first-line palliation of bulimia disobiliary obstruction. So we're seeing that we are moving in the direction of EOS-guided as first-line therapy. But of course, this is just a prediction. We'll have to see what studies show. But there is one subgroup of patients who will always benefit from ERCP. And those are the patients who are post-gastric bypass. This is the EDGE procedure. And I love this procedure. We perform this routinely. It's disseminated. And of course, with a large population of patients who are post-gastric bypass, this is a literal godsend that we can gain direct access to the bypassed stomach, to the remnant stomach here. And we can take the shortcut and then pass our duodenoscope directly to the ampulla to perform ERCP. And we don't have to use our double balloon scope to try to gain access. And usually, the cannulation is unsuccessful anyway after all that work. So this is the first report by Michelle Kahela, five patients post-gastric bypass placing a 15-millimeter LAMS for gastro-gastrostomy or jejunal gastrostomy. And I think this also deserves underscoring because it's a great example of how, when we endoscopists are given tools, we come up with ways to use those tools for the benefit of our patients. And so this is a wonderful illustration of that. This is my last slide. And this is what it's all about, expanding our reach. We want to expand the reach of therapeutic EOS. Who would have thought that the day would come when we would go beyond the gastrointestinal tract? We were literally caged in in the GI tract. We could do wonderful things, but now our reach has extended outside. We can pass our endoscope directly into structures neighboring the GI tract. And the GI tract really runs the length of our body and gives us access to virtually every major organ in the body. So we're going to see the continued development of dedicated EOS devices, neurological to denervate and stimulate and oncology. We'll be seeing a movement towards precision ablation. So this is the advantage of EOS, the higher resolution, our ability to more precisely intervene and to customize that intervention for our patients. And I think immunotherapy, just as we're seeing in oncology in general, we're going to see applications under EOS guidance. Vascular, this burgeoning area, we're going to see, I think thrombolysis, seeing reports of portal vein thrombolysis, patients who have portal vein thrombosis, because we can access the portal vein again directly under EOS guidance. Drug delivery, we talked a little bit about that. And I look forward to studies like EPIC going into patients now. And shunts, we can perform these shunts. I'm just not sure I want to be called at three in the morning to do a tips though. Anastomosis, well, basically if you can see it, you can drain it or you can anastomosis. So a real exciting future ahead. Thank you very much again for this great privilege of presenting the keynote lecture. Ken, thank you. That was really a fascinating, amazing lecture. And I think it was a beautiful demonstration of your dedication to this field and how much we have to learn. Also sort of a real reminder that we need to get back to basics in order to understand how we can progress forward. I do have a question for you actually related to this last slide and your process and innovation. How important is it to now kind of work in more of a multidisciplinary fashion with oncologists, with our surgeons in order to understand the implications of these therapies that we're, you know, not only the implications actually to start with the needs, the unmet needs and then the implications of what we'll now be able to enter because we're going far beyond just GI. Wow, that, Amrita, that is just a wonderful question. It's so important that we really start, we've been talking about this for a long time. There are so many pioneers of the idea, let's start with Peter Cotton, with the idea of a digestive disease center bringing radiologists and surgeons and endoscopists together and working as a team. So, and then obviously Dick Kozarek at Virginia Mason, also an advocate for this approach that makes obvious sense. And Shyam, of course, you are benefiting from that model that Dick created. We have to see this really disseminate more and I almost feel it should be a prerequisite. And we have a interdisciplinary tumor board now every week and we have everyone sitting at the table to discuss these cases. The days are over where you propose a treatment in isolation. So when we develop these devices, firstly, we should benefit from the opportunity to adapt technology from other specialties. And remember, surgery is also evolving. It's becoming less and less invasive. So we have so much that we can learn from our surgical and our radiology colleagues. And that's one thing I learned with Nipsey Hendra. I remember the Cherumo wire, that didn't start with us, the Glidewire, he borrowed that from the radiologists. He spent a lot of time working in radiology or observing because he saw the wealth of innovation there. So, so critical really, as we think about devices, says, first of all, we need to identify where the need is. And really there's no need to invent something if another specialty can do it well with great outcomes. Why should we try to reinvent the wheel, so to speak? So let them take care of it. But if there is something we can do less invasively or with a better outcome for our patients, then we should innovate. And we should take advantage of the wealth of experience that already exists in these other specialties. That's great. And maybe also to challenge you a little on one of the things you mentioned about EUS taking over from ERCP or getting rid of it. Do you think this applies to both malignant and benign disease, or is there still a role for respecting the anatomy when we don't necessarily need to alter it? Well, again, this is an area where I think we have the right tools that allow us to now approach benign disease. We never want to burn bridges. So one of the big open questions about cholecystoenterostomy, so draining the gallbladder internally under EUS guidance, the big question is, well, how would that impact a cholecystectomy? Should the patient need one? So we have to have that question answered. If there's a way that we can do this and it will not impair a possible cholecystoenterostomy, I'm sorry, a later cholecystectomy, then yes, we can start thinking about using this beyond just situations where the patient's a poor surgical candidate or percutaneous drainage is not a good option. Certainly for patients with malignant disease, let's say pancreatic cancer and bile duct obstruction can be done EUS guided. But we don't want that anastomosis that we've created to in any way impact, negatively impact a Whipple operation, for example, if the patient needed surgery. So all of that does need to be addressed. So personally, I think we're going to get there. But it depends on having the right trials to verify that we indeed are able to do this responsibly and we need better tools. Great. And there's a question actually related to the long-term placement of LAMs, particularly in anastomosis and the effect that you're trying to create. We know that surgical anastomosis is different than that created by pressure as the LAMs does. What is your typical practice and suggestion with regards to longevity of leaving that LAMs in place? And what's the next step afterwards? And where do you see the future of that perhaps? Well, you have to individualize. So this is the era of precision medicine, right? Customized medicine. And that's how medicine always should be approached even without coming into this new era. So what's very interesting is if you look at the paper I published with Takao, I think three patients just refused to have their LAMs removed. They said, look, I'm elderly. I want to have quality of life. It's not about the lifespan anymore. It's about the health span. I want quality of life. I don't want you to remove this stent. So there you make an exception because otherwise we were removing the LAMs after a month. So there are a subset of patients. I have a few patients who opted against having a cholecystectomy and they could have undergone cholecystectomy. They were in fact candidates, but they wanted to have internal drainage of their gallbladder as a treatment for their gallstones. And they have the LAMs in place now two, three years later, and they're doing wonderfully. And they come back for an annual surveillance and I check it out. It looks great. I probably could remove it. Maybe the fistula will stay open after being in so long, but the patients don't want that. And so I don't know what the answer is. I think the way you approach this is you have guidelines in terms of what we know is safe. And for example, right now we're following the three week rule for drainage of pseudocysts and LAMs. And I think that's fine. We follow that rule, but there are going to be a subset of patients where the patient may benefit from having it left in place longer, but we're going to be more vigilant about the potential complications like bleeding. So customize, individualize. Great. And maybe one last question and comment from you. There was actually a comment from one of our attendees commenting about having different rotations, such as a rotation in IR and surgery to really help with their interventional GI fellowship and knowledge. What are your thoughts about that? And particularly in respect to innovation as your career has been about? Yes. So when I arrived, this is the anecdote. I don't think many people know this. When I arrived in Hamburg, I went to Hamburg because Nip Sahindra, I considered him the grandfather of ERCP. There's so many devices in ERCP named after him. There's reason for that. He pioneered this field. And ERCP was my love. I was married to ERCP. So I went to his center to refine my skills in ERCP. And at that time I was taking over a position from another doctor, Horst Grimm. And he was leaving and he did endoscopic ultrasound. Now I had no background in ultrasound at all. In fact, I wasn't interested in endoscopic ultrasound at all. Nip Sahindra told me that if I wanted to do ERCP, I would also need to pick up endoscopic ultrasound to carry on that program in his department. And I was disappointed by that, but I agreed. So he sent me every morning to learn ultrasound in the Department of Medicine. We were in the Department of Surgery to learn that with Frau Dr. Rudolph. And she trained me at six in the morning for an hour every day, every morning. She taught me trans-abdominal ultrasound. And today, as I look back, I feel that was so important, that learning process, spending time there. So that's just one example. And I also, because we already did so many, we were part of an interdisciplinary department. And again, Nip Sahindra is also protagonist for this concept in his department. It was called interdisciplinary endoscopy. We spent a lot of time with the surgeons and I was in the operating room a lot. So I think it should be a requirement, actually. It's not just an elective. I would say, if you want to go down this path of becoming a, what does universal interventional endoscopist mean? Well, it's not just universal in terms of our procedures. It should also be understanding how these basic techniques, coaxial catheter trick techniques now are used in other specialties. Well, Ken, thank you so much. This has just really been a wonderful conversation with you. And thank you for all of your contributions to our field. I think everyone on today really sees you as a mentor and we continue to look, we look forward to your continued contributions as we go forward. So thank you so much for joining us and for sharing your experience. Thank you very much. It's my pleasure. Enjoy the rest of your Sunday, Saturday. Thank you so much, Cheyenne.

Dr. Ken Binmoeller

endoscopic ultrasound

therapeutic endoscopy

evolution of EUS

Axios stent

diagnostic and therapeutic tool

multidisciplinary collaboration

individualized medicine

future of EUS