Chapters Transcript Video Benign and Malignant Esophageal Disease: May 2021 Updates Mhm. If, yeah. Yeah. Yeah. Mhm. Mhm. Yeah. Yeah. Mhm. Yeah. Yeah. Yeah. Thank you. Hi I'm dr steven Hock. Well chief of G. I. And endocrine surgery and chief of our peri operative services at Roswell Park Comprehensive Cancer Center in Buffalo new york. It gives me great pleasure to welcome everyone to our Roswell Park cmi program focusing on benign and malignant south visual disease. I will be serving as moderator for this event. We have three excellent talks to be delivered by experts in their field. The first talk will be from Dr motion kook are discussing robotic approaches to surgery for a salvage of cancer. The second talk will be from dr todd Demi who will discuss advanced endoscopic techniques for the treatment of benign is salvageable disease. The third talk by our medical oncologist, Dr Mukherjee will discuss advances in systemic therapy for advanced the salvage of cancer. The virtual former. This program is relatively new for us. The need for this certainly has been driven by the recent and ongoing covid pandemic. We have missed the frequent discussions with colleagues that we have had with our peers in the community and with our colleagues at other institutions. We hope you will find this program informative and we expect you to please provide feedback. The three talks will occur one after another with the questions discussion to occur at the end. Questions however, can be entered and submitted as we go and will be collected and reviewed following the presentations again. Thank you very much for joining us today. Mm mm. Yeah. Hi, my name is Marcin cu car. I'm the associate professor in the Department of Surgical Oncology. I'm also the program director for the complex General Surgical Oncology Fellowship Hair at Roswell Park Comprehensive Cancer Center. Topic of discussion today would be the robotic management of gastroesophageal junction tumors. So what is the magnitude of the problem? 11 million cancer cases are diagnosed worldwide. Out of these gastric and esophageal cancer cases account for about 1.39 million. And as you can see this incident is actually more than the more common cancers like the lung cancer and breast cancer. Uh an estimated half of these patients, about 700,000 would benefit from surgery and have respectable disease. Uh unfortunately, the incidents of esophageal cancer is increasingly uh increasing dramatically in the United States uh annually. It's estimated that about 17,650 Americans will be diagnosed with esophageal cancer and about 16,000 people will die from this disease. So the five year survival is still about 20%. But the good news is that it's it's improving Uh the outcomes from surgical approaches. However, for esophageal cancers have significantly improved. So this is data from 1994. So this procedure has gone from a in the early 1900s where it was, you know, almost criminal to do this procedure where the mortality rate was very high. Two Recently in the late 1900s, where the this is a published data about 316 patients where you can see the operative mortality was 27%. So one in 31 and three patients did not make it after this procedure. Uh and over the course of next 20 years, I think we've made phenomenal progress with this operation. As you can see these are high volume hospitals. Uh and a lot of this is open surgery with a fairly robust sample size. And as you can see, the mortality rate has has gone down below 5%. So, if it's this is done in high volume centers, people that know what they're doing. I think it's a very acceptable mortality close to 1 to 2% at this time. So what are the approaches to soften your reception? It's it's a myriad of approaches whether it's done open hybrid, which means that part of the procedure is done laproscopic. The other part is done uh with an open approach are completely uh minimally invasive approach or robotic approach. So essentially there are 3 3 approaches to do this. One is you start in the belly, you create a tube out of the stomach and then you do the connection and the chest, which is called the Ivor Lewis approach. And that's our preferred approach. The second approaches where you mobilize the esophagus in the chest and then you create the tube in the belly and then you do the connection of the left neck, which is called them a Cuban IsAF ejecta me. That is being utilized for us that are slightly higher up in the esophagus, in the middle of the esophagus or more in the upper portion of the esophagus. And the third approach is what is called the trans title approach, where you completely eliminate going into the chest and you do the the section in the belly, make a gastric conduit, and then you pull it up into the left neck, so just from the neck and the and the chest and the belly approach. And I think the key to having a successful program is that the approach has to be tailored to the patients need. So one thing that we do well here at Roswell is that we're fassel with all of these three approaches and we really tailored to the patient needs rather than, you know, one technique that we're trying to fit to to every patient. So, so really patient factors to more factors, all these play a key role in us deciding what the what the correct technique is gonna be. So what is the data for minimally invasive? Self injectable versus open to self inject me? I think this is one procedure where common sense would dictate that instead of having a big laparotomy, open incision in the belly and a big incision in the chest, that patient may benefit from smaller incisions. Uh So so this is some of the randomized data that I'm going to discuss that supports the uh the minimally invasive approach for this for this procedure. So this is from Europe randomized controlled trial. You can see 56 patients in the open group, 59 patients in the my uh my group and they're fairly well matched. Uh and uh you can see the the pulmonary infections within the first two weeks or in hospital rate is significantly lower in the my group. Also, the hospital stay was significantly shorter, 11 versus 14 days. And the short term quality of life scores were also better in the my group. Uh The uncle logic parameters and the 30 day mortality were similar in both groups. So clearly a benefit in terms of having decreased amount of pulmonary infections and also hospital stay, which is favoring the minimally invasive self rejecting group. Uh This is another trial which compares uh the uh this trial computers Open us off rejected me with hybrid approach, which means that they did the belly part uh laparoscopically. But the chest part was done with a small incision open incisions. So that's a hybrid approach compared with a completely open approach, which means that both the chest and the abdominal portion. We're done with big incisions. And as you can see 100 and three patients were in the hybrid group and 104 patients in the open procedure group and the The total complication rate was higher in the open group 64% and also a higher pommery complication rate, which was 30% vs, 8%, And they have similar oncological uncle logic results. Three year old all survival were similar and the disease free survival is similar as well. This is the third trial which is actually comparing robotic assisted self eject me versus open a soft edge ectomy. And their primary endpoint was also postoperative complications. And you can see that the overall complications were less than the robotic assisted Asaf trajectory group, which was 59% compared to open this object me, which was about 80%. So their conclusion was that it was significantly lower rates of primary complications, cardiac, lower postoperative pain and better quality of life. Uh And their uncle logic, outcomes short term and long term were equal. So clearly good randomized data supporting a minimally invasive approach, whether it's robotic, laparoscopic or even hybrid is better than than an open approach. So how are we doing here? This is our data from published uh the uh lewis is a project amIS recently. Uh These were intra thoracic and esteem Asus. 11 unique thing that we do here is the site to site anastomosis. So traditionally the esophagus is joined to the gastric tube with an E. N. Est imuses and that gives you a diameter of 25 millimeters. What we do is what is called a site to site and esteem Asus, which gives you a diameter of six centimeters. And I think that certainly introduces at least in our experience the systematic leak and the stricter raid. So this is our data. 414 patients. As you can see, the pneumonia rate was about 9%. Which is which is very uh comparable to the other randomized trial. Probably even better. Uh The systematic lake leak rate was about 5%. Uh The chi leak rate was about 1.8% and the re operation rate was about 6%. The length of stay in our group was about eight days. Uh And uh we did not have any 30 day mortality with this operation and the and 2 90 day mortalities both from early disease recurrences. So that makes it a 90 day mortality rate of 1.8%. And as you can see, the stricture rate was also pretty low. This is 5% at a 90 day follow up. So this is one of the data is that we don't know about the the E. N. S. Thomas is what the long term stricture rate is. But I think this is certainly pretty good for the side to side stapled anastomosis. So it's not just about uh you know the the surgeon in this clearly as a high volume hospital uh I think it's uh it's just all the diversity of services. So you know it's the anesthesiologist that play a team approaching this dedicated oh ours ICU staff uh the interventional gastroenterologist and also the interventional radiologist. And then we have pathways that you know preoperative pathways, inter operative path inter operative pathways and postoperative pathways that we have that that we follow certain set of guidelines for all these patients that really help to streamline the process and improve patient outcomes. Obviously great help from our nurse coordinators in terms of navigating navigational problems for these patients. Uh and then, you know, truly utilizing a multidisciplinary approach where when these patients initially present, you know, everybody goes through the through the tumor board and we come up with a comprehensive patient centered plan in terms of the utilization of chemotherapy, radiotherapy and what the choice of surgical resection is going to be. And then if you can utilize a minimally invasive robotic approach and the management of these patients, which we're able to offer, I would say more than 90% to our patients. So we have been involved with laproscopic Dorcus copy cassava, Vietnamese for a long time. Uh My partner steve alcohol has been doing this for more more than a decade now and I did that early part of my career. But over the last two or three years we have sort of transitioned to the robotic approach. And I think of course the benefits of robotics in general, which includes three d. Visualizations, uh the very precise control of the instruments, you know ease of suffering on the inside and just the stability of the platform. That lets you do a little bit more than a typical laproscopic as a laproscopic surgeon. You can. So this has been a robotic experience over the last two or three years were actually up to 120 cases now. But as you can see uh 60-70 of those have been robotic. Ivor Lewis is a project to me some hybrid cases which is when we were establishing our program uh and based on this data which which the manuscript is under uh is an a preparation. You can see that there were no abdominal conversions, only two chest conversions, which means that we started robotically and then we had to convert to open. Uh There were no 30 day mortality. These uh there was 1 90 day mortality which was a patient that record had a brain metastases in a massive pulmonary embolism. Uh And only two contained an s demotic leaks which makes our uh secret to be about 3% at this point. You know? And both these leaks did not require take back to the operating room. They were very small. One was just managed conservatively but just nutrition, good nutrition and uh N. P. O. For a little while. And the other one required an endoscopy and a clip placement. Uh and one colleague that did require take back to the O. R. So overall, I mean, considering that this is a learning curve, even though we're pretty well established laproscopic laparoscopically, I think this is this is pretty good results. So how do we compare to the to the national other high volume hospitals? This is a part of the Netscape collaborative nightscope is a is a collaborated by the American College of Surgeons where more than 500 hospitals report their data to. Uh And as you can see this is our sausage ectomy data and uh we are exemplary uh in most of the categories including morbidity. Uh the bone infection rate which is the S. S. I. Had returned to the operating room readmission rate and the ns demotic leak rate. And this puts us into the into the top sent tile as compared to other high volume hospitals. So certainly very favorable data. Hair. Uh We have published a lot on this topic, steve Hock. Well and I published this text book which includes uh every single minimally invasive technique for forgot malignancies for esophagus and and gastric uh malignancies. Uh And then we have extensively published all our techniques and our experiences with all these videos. And these are resources that are extremely helpful for training our fellows who are expected to sort of go through these and and before they come to the operating room. So all of this, all of the day, all of the stuff has already been published and is available for review. So I'm going to show a little bit of this robotic video and how we do the site to site stapled anastomosis and also the ease of inter corporeal suffering with the robotic platform. So this is the video in the in the chest. So just to give you a perspective, that's the gastric conduit which is being pulled up into the chest so the patient's head towards the top of the screen feed or towards the bottom, You can see the gastric conduit and the left hand is now going to be grabbing the, so these are the robotic arms that are moving in the right side and there's a bedside assist that has a laproscopic instrument that's helping. So you can see the esophagus that has been stapled above the tumor. So the left hand is grabbing the esophagus with the N. G. Tube that's coming out and that's the stomach tube. So we're going to be making an opening into the stomach there. Uh We make an opening with Elektra katari and then we use an instrument to a large that opening and then we will introduce a stapler And that's the linear stapler. Uh which is what we're talking at the six centimeter stapled anastomosis. So you can see one job, the staple are going into the stomach tube, the other jaw of the stapler is going to go into the esophagus there and then and these two get approximated. And then that gives you a a six centimeter site to site stapled, esophageal guest Rostami. We're just making sure that the any momentum is not into the stomach there and there you go. That's the that's the anastomosis right there. And then the other thing is as you can see where the openings were. The solution is extremely easy with the robotic platform. So now we're gonna be putting some searchers there. So that's that's a silk suits are too close what is called the common channel and you can see how easy it is to be able to tie knots. Ah And the visualisation of of course it's a three D visualization which is which is obviously makes things a lot easier for us and there you go, that's sort of tying the knots and we can put multiple suitors and then we can excise Excise this channel as well. So that's what gives us the six cm site decided, stapled anastomosis. So in conclusion anytime there is a suspicion or a diagnosis for an esophageal malignancy uh referral to a high volume hospitals should be made. Uh These patients should be discussed at a multidisciplinary tumor board where there are other surgeons, radiologist, pathologist that we can come up with a uh tailored approach to that to that patient. Most importantly what modalities treatment modalities will be used, including radiation, chemotherapy and what the sequence of these therapies would be. Uh And then also determining what the extent of the surgical resection would be and what the the approach would be. Uh And then in the end utilizing M. I. S. And robotic approaches to to achieve the best patient outcomes. This concludes my talk and I would be happy to take any questions at the end. Yeah. Hello, I'm Todd Demi. I'm professor of oncology at Roswell Park Comprehensive Cancer Center. Today I'd like to speak about the poem procedure for accolade asia, which is a disease of progressive neurologic dysfunction of the esophagus which presents with multiple types, at least two dilation of the esophagus. I'd like to speak on the history and indications for procedures to treat this disease. The various techniques, some results and then also our local experience. Now I'd like to start with human story of an old argument which actually relates to this new problem of the proper place of the poem for the ankle asia. This goes back to a thoracic surgeon named belle Z. And equally famous dome easter who were arguing when I started my career about whether or not you need to do an anti reflux procedure, approaching it from the abdomen. Doctor did Mr had to do it for the cause. Patients had disabling uh GERD symptoms. But when approaching it from the chest to get down to the esophageal gastric region, it would not disrupt all the anatomy and the natural anti reflux mechanisms that go along with that anatomy. And therefore uh Dr Bell's, he did not need to add an anti reflux procedure and this will come. Uh We'll learn more about this as we go on with the talk. The treatment for actual asia is one of palliative in. We never treat that. We never cure the disease, but we're treating the symptoms and a good way to judge the patient's symptoms is through a scaled score system as such as this eco score Which looks at the domains of weight loss, does facial pain and regurgitation and scores one scores each one with a maximum score of 12. This is an old slide showing the old ways of measuring the pressures. In the esophagus. On the right is a mega sarcophagus filled with food. You can see in the center that the pressures of the esophagus with actual asIA show that there is a high pressure zone at the lower esophageal sphincter because as the esophagus lose loses its nervous function. Not only can it push the food into the stomach, but the nerves which opened up the sphincter, the bottom, go away, leaving this this victim the sphincter in a high tone state. Now we do this manama tree with a multi sensor catheter which gives a beautiful longitudinal wave. Uh And this is a normal reading that you can see here on the screen in a patient with Akhil Asia. In this case one with type two, actual asia where there's a pressure banned from top to bottom. With each swallow uh is typical. You can see the upper gi and the left showing that bird beak appearance of the low pressures of the high pressure zone at the bottom. And you can see that that line at the bottom of the screen, it stays relatively constant compared to the previous slide where it tends to open up the swallow to let the food into the stomach. Now we can actually measure that pressure zone while we're doing our operations, whether it's a hell or through a poem procedure by using a low pressure balloon uh and a device called an impedance Catheter that can measure the amount of compression there. And show us as you can see here the hourglass appearance before in the straight appearance afterward after we treat the uh and opened up the muscle at the bottom of the esophagus. As a general timeline, the operation that we which is considered the gold standard. The hell of my anatomy, began back in the early 1900s. Uh, interestingly, there was a procedure, endoscopic Lee to treat this that actually was published in 1980. I'll talk more about that in a second. But the poem procedure which we're doing today grew out of research research in the early 2000s. The first clinical case was in Japan in 2008. And by 2015, over 1300 procedures were performed. The anatomy of the G junction and this high pressure area is demonstrated on this slide. And if the muscle fibers that kind of tighten that junction between the esophagus and stomach are cut, allows him to costa to pooch out. And the slide or the panel on the far right shows attacking the stomach behind to create a sort of speed bump, to keep the acid from going back up into the, into the esophagus to prevent reflux when this is done laparoscopically. Now the best results for a hell of my automated done if the patient has had no previous uh, procedures to treat their actual asia, if their symptoms have been shorter, they haven't developed a sink trap deformity. Uh, and if there's high pressure there, and if you treat this disease earlier, before they develop those secondary changes, the patients get better long term results With up to 80% success at five years. Now, I like to use this analogy when I'm counseling patients, patients generally have blown up a party balloon or the balloon that you can make animals out of and they know how hard it is to start and I tell them that this is important that we treat this disease before it becomes easy to blow up that balloon. Because if you can do that, not only does the balloon not become easier to distended with as the disease progresses as time goes on, but also the balloon doesn't lengthen. The esophagus doesn't lengthen. If the esophagus lengthen, it's got no place to go and it creates a sink trap, which further makes it difficult for the patient's esophagus to empty. Now, this was thought uh this is an old slide 1980 a surgeon in South America would just take a simple endoscopic knife and cut through all the layers of the sophos include esophagus, including the mucosa, the g junction, and this really didn't catch on because everyone thought it was crazy. Most doctors thought this was crazy, creating what would amount into a Borzov syndrome. But now looking at it whether what we're seeing today, this shows that there probably is a fair amount of safety and that even opening the mucosa with the natural if you had sufficient tissues around that would prevent the patients from um uh developing a major leak or infection situation. And we have to consider these these days are probably more valid than we thought at the time. The use of the poem, procedure terminology is kind of grouped in these different areas. I'm going to talk mostly about the panel on the left, which is the poem on the lower esophageal sphincter, but they're also poem procedures on the pile or is to treat diseases like gastro paralysis and problems with stomach emptying after other surgeries. And a newer opportunity which is treating Zenker diverticular um or it's also called a deep coma diverticular poem, which I'll show a couple of cases at the end. But this these are now the major groups of this poem uh terminology. Now this will show a movie of the esophagus is now the scope in the distal esophagus and this esophagus is much dilated. It should only be about a third of the size and you can see going through the sphincter into the stomach, how the scope has to be pushed hard to pop in. And then the scope can be turned back on itself to look back up at its entry into the stomach. And that's the retro flex view. And you can see how tight that sphincter is around the scope. Now, after the poem procedure, the scope goes in. And when it does the retro flex move and pull back. You can see how much wider open uh the esophagus is you can actually see the z. Line the junction of the esophagus and the gastric mucosa. But you can also see here how patients could be prone to get in reflux after this procedure. So because there's a much less effective check valve there. So they're really the indications for the poem procedure or any disorder of the esophageal muscle causing pain or compression, that it would be the different types of actual asia or the other types of esophageal disease where there's high degrees of spasm. Uh There are only a few absolute contraindications listed here. One that is that one that is uh sometimes difficult to uh to predict is the patient's response to previous radiation in that area. That confuse all the layers together and make it difficult if the patients have an inflammation of the esophagus or a lot of bacteria overgrowth at the time, it may be a relative uh dissuasion for the surgeon to make a hole in the because a tunnel into uh to deal with the spastic muscle. There might be special circumstances where the poem is actually better, such as situations with patients have had a previous failed. Hello, my Autumn E. Or patients who are frail or elderly or the spastic disorders now. Uh I think it's important to realize that these procedures are not mutually mutually exclusive and many times patients have failed. One can have the other in this particular diagram shows how uh one could consider if the patient has an early failed or an incomplete my ah to me how they could go through a repeat surgical procedure. If it's been a longer period of time when there's more scarring, then there's the options of doing a re to surgical procedure or pump in case you. Some of these patients will go on and need the esophagus to be removed. Which can also be done laparoscopically or endoscopic lee. We prepare our patients by giving them antibiotics the day of surgery. They have to have anti reduction. Acid reduction has already demonstrated the patients are done supine under general anesthesia. Uh and we use carbon dioxide to blow gas into the space to create this tunnel in which to work. And the CO two is turned down to a low flow while we do this to prevent the gas from finding its way into other body cavities. Here is some of the tools that we use a needle to inject the uh saline underneath the surface to create a starting point. A knife that's able to cut through various tissues that goes through the endoscope and a cap showing an upper left hand corner which is attached to the end of the scope to create it to create a viewing space. And I'll just show a couple of the basic steps here. This is making the cut in the mucosa with that knife. It also can be done with a needle that this particular knife has an injection port in it that can kind of create a bubble for allows us to open up that mucosa. Now, this allows this entry into that space underneath that inner layer and there are some variations on how surgeons like to do this. The 1st 500 cases done in Japan were done at the 2:00 position to bring them. I ought to be down close to wait would be done laparoscopically, but they've got sent switch to more of a five or six o'clock position and this has kind of done, I think more or less, 50, 50, various various centers, there are various advantages to doing them at a different location, particularly if they've had in my ah to me before on the opposite side. And this is a view going into that tunnel going through that whole, demonstrated making that you can see the muscle bars, the circular muscle bars on the right side of that movie and the floppy mucosa with the little blood vessels on the left. And that Takes one then to the next step, which would be cutting the muscle. Doesn't know whether or not your tunnel is far enough down the stomach. Uh There are various ways of doing that. You can see if the blue dye has made it down to the point in this particular case, surgeons actually introduced another small scope into that tunnel to show that it's actually made it onto the stomach. Can actually see the light coming back on the retro flex view there. Once the tunnel has been made, that same knife that's been used can be done here where I'm cutting the circular muscles. It's interesting that many times the circular muscles are cut. But the longitudinal muscles are not very strong and they typically will open up and you'll see in some of the some of this movie actually peering into the media spinal tissues there. That's actually the pleura on the right. And generally that keep that that those tissues around the esophagus are sufficient to keep the gas from or the operation to enter any other part of the body. Once we're done, we're able to close up the whole with metal clips here to allow ceiling that that entry point. And those those clips will stay on for about uh several weeks to sometimes several months after the procedure. Post operatively we send the patients home with liquids. We sometimes during the operation have to vent some of that gas that may build up in the chest or in the belly bleeding. And infection can be problems. We have not had a major infection and we've had one episode where patients lost a little bit less than a pint of blood were able to control that without a bigger operation. Now, the results and other centers have been very consistent and that the Poem procedure has achieved very similar improvement in symptoms compared to the laproscopic. Hello my. Ah to me. And the other thing though, is that because there's no anti reflux operation. The Poem procedure has also had consistently higher level of gastroesophageal reflux. Whether this is a problematic in the long term is too early to tell based on our experience with this. Currently our experiences actually up to about 35 procedures of the poem. 34 pop procedures and several of the diverticular poem procedures And looking at our internal results on the 1st 25 cases. And there's been no advert major adverse events since that we've seen that there has been a a improvement in the anesthesia time down to that of the major centers. Um the Bolas has been minimum by and large. The patients have gone home the first day afterward and there's been no deaths in only one case where we had to abort the operation because the patient had preoperative radiation for previous cancer. And it kept us from being able to do the procedure. Just like the other centers. We've seen a significant improvement in the patient's Eckert scars before and after. And a few of the patients have need to go on one uh to have ballooned or something, have balloon dilation, is to stretch out the esophagus and some to actually have an anti reflux procedure. And if the patients are appropriately counselled, many of them do prefer this. Uh this uh uh decision to have the anti reflex procedure done if needed, uh if they have severe symptoms versus having it being done on every single patient whether they may need it or not. These are just some of the examples of our first patient here, before and after barium swallow images showing a nice opening compared to the pre op one on the on the left side of the panel. And this is patient number three were similarly opens up well and you can see a little indentation on the circle on the forest right side screen where the actual clips went on creates a little bit of a mucosal regularity there. This is kind of midway during that first evaluation against similar patients. 16 and this is now the interesting deep homes. This is an epic, frantic diverticular that put pouch there indicated by the arrow caused by a distal relative obstruction because of spastic disease at the lower esophageal sphincter. And even though the poem procedure doesn't cut, remove that diverticular one can see how it is starting to regress in the immediate post operative home opera Sasha graham by simply improving the outflow of the esophagus. And finally, the Z poem operation where we see an improvement in the in the pouch, particularly. This might be useful for smaller. Zanker is diverticular, which are difficult sometimes to do uh trans orally. And you can see how that a couple months later, how the particular reserves after you take care of the muscle bar. So, um seems to be a growing in popularity procedure for ankle asia. We still do not know its long term results. Uh we don't know if there will be more complications than long drawn, but similarly we don't know whether or not it may actually be better by not actually creating an anti reflux obstruction, which is necessary. It's kind of counter goes counter to what you're trying to accomplish doing an anti reflux procedure because you're closing it up after opening it. So we don't know if it may actually be better. Uh We think it may be preferred for certain pathologies or for frail patients. And thank you very much again for your attention and uh well now we will answer questions later on this topic. Thank you. Yeah. Hello everyone. My name is Doctor shortage Mukherjee. I'm an assistant professor of oncology at Roswell Park Comprehensive Cancer Center. The focus of our talk today is recent advances in its official cancer. With a special focus on targeted therapy and immunotherapy. This is an exciting year for us who are treating its official cancer. We have had several recent approvals particularly in the field of immunotherapy. So for this talk we will focus mostly on advanced is a vigil cancer. So let's start with the case. So we have a 58 year old female patient who has metastatic hard to negative pD. L. One positive metastatic stable is official adenocarcinoma who prisons to you for an initial consultation. She denies any other comorbidities and retains a good performance status. What would you offer chemotherapy alone? Chemotherapy plus immunotherapy, immunotherapy alone or D assessment for a clinical trial will come to this answer at the very end of our talk but let's review some background information about this vigil cancer first. So what's the current standard of care in S. A. Vigil cancer in 2021? So if you look at the NCC and guidelines you will see for hard to negative metastatic are un respectable. Is a vigil cancer. The first line treatment is through a pyramid in oxalate platon and Nivola map for Pd L. One cps card off credit the nickel to five. Remember our patient Had. AC. score of one. Um There is another potential standard option which is floral pyramid in with oxalate platinum pain buddhism for those who have a PD L one cps greater than or equal to 10. Now you could use chemotherapy alone and you could use uh cis platinum instead of oxalate Platen. But sally platini is generally preferred because of lower toxicity at Roswell, we generally use oxalic planting more commonly than CISplatin. Now this epidemiologic study, along with some other epidemiologic studies actually looked at the survival trends in is a vigil adenocarcinoma and for the found that we have had a modest improvement in survival and this could be related to advanced surgical techniques, chemotherapy and or radiation techniques. However, if you look at the overall outcome, it is still very poor for patients with cervical carcinoma, adenocarcinoma, which means that we need to do better. So to find better treatments, we must understand the biology a little better. And this particular paper actually looked at the molecular classification of gas stories of vigil cancer. So what they found was s official square muscle cancer, which is the predominant histology worldwide, was genetically very different than is a vigil adenocarcinoma, which is the predominant histology in the United States. So next generation of clinical trials should focus on separating these two entities together. Now, for this official adenocarcinoma, we learned that patients with MSC high status and those who have an E. B. V. Positive tumor tend to do better with immunotherapy. So the question is for the majority of our patients who present with other genotype like C. I. N. Or G. S. How do the fear when they are treated with immunotherapy? And there are several studies that try to answer that question and that led to some recent approvals. So check mate 649 study actually looked at the addition of immunotherapy on chemotherapy. So they enrolled patients with both gastric G junction as well as its official adenocarcinoma. And patients were all hard to negative. They randomized patients to Naval Plus E. P. A combination of two checkpoint inhibitors or Naval plus chemotherapy or chemotherapy alone. The present did the data at is more 2020 annual meeting. Um Just looking at this uh to Nevo plus chemo compared to chemo alone that dwell primary endpoints were overall survivable and progression free survival. In patients who had Pd L one cps cut off of greater than equal to five. And they had several secondary endpoints. They looked at overall survival and progression free survival in all randomized patients. They looked at over a response rate as well. Okay, so this slide actually describes the baseline characteristics of our study participants. And you can see that Castro's official junction adenocarcinoma and s official adenocarcinoma comprised about 30% of the whole patient population. And as expected, EMC high represented only a very small subgroup and fall fox and C locks were given in equal proportion in both the experimental arm and the control arm. So the study made its primary endpoint. Um they found that the overall survival was significantly improved and this was both statistically and clinically significant in patients who had a Cps Cut off grade nickel to five. However, the study was also positive for all randomized patients and those who had a Pd L one cps credit than Nicole to one. However, the benefit was a little less prominent in all randomized patients compared to those who had a higher Pd L one cps cut off and same thing was absurd with progression free survival. So there was a 32% reduction in the risk of progression or debt with Nivea plus chemo versus chemo in those patients whose CPS cardiovascular the nickel to five two. This actually led to the FDA approval of Naval UMA in the front line setting. Now coming to the adverse events, you can see that adverse events were pretty similar, especially the severe adverse events were pretty similar between these two groups. Um, great three or four treatment related adverse events occurred in less than 5% of patients and there were no grade five events. Similarly, a keynote 5 90 study actually looked at the addition of liberalism app to frontline chemotherapy in the cervical cancer. Now There was a slight difference in the patient population here. This study actually included patients with both metastatic is official adenocarcinoma, as well as its official square missile carcinoma and type one G junction adenocarcinoma. So patients of course were treatment naive. So this was the first line study and patients were randomized to chemotherapy plus pm realism versus chemotherapy plus possible. And dual primary endpoints were again overall survival and progression free survival. They had multiple endpoints. Their secondary endpoints included overall response rate as you can see here. Um The study made its primary in point. So for those patients who had a pd L. One cps cut off of greater than equal to 10. Um they had a clinically and statistically meaningful uh survival gain. And they saw similar survival gain in its official squamous cell cancer patients. And in all patients we saw that both for overall survival as well as progression free survival. But as you can imagine, the benefit was much more in those who had a higher cps cut off. So this study led to FDA approval of Federalism app in the first line setting for s official cancer patients. Now, talking about adverse events, you can see that most patients tolerated this pretty well and grade three or higher adverse events were just slightly higher in patients who received Kimbrough and chemotherapy compared to chemo alone. Overall this was fairly well tolerated and this is uh consistent with what we have seen with other studies that combined chemotherapy and immunotherapy in the front line setting. Now for hard to positive is official. And local cinema or G junction adenocarcinoma patients. There has been an interesting trend towards combining targeted therapy and immunotherapy with chemotherapy upfront. Um So we have had two studies that looked at the combination of chemotherapy with targeted therapy trust is um and immune checkpoint inhibitors and the response rates were impressive. And this led to bigger phase three studies. And most recently just a few days ago FDA actually granted an accelerated approval for chemotherapy Plus trust is um plus pain realism app for patients with gastric or G junction adenocarcinoma who expressed hard to now. The next part of our talk is going to focus on some of the novel targets and some emerging data. So one of such targets is clouding 18.2. It's a structural protein expressed at tight junctions broadly expressed in various cancers including biliary duct, pancreatic gastric and milks in as ovarian cancer. Um there are very specific for cancer and uh this new anti body I. M. F 362 is a primary cai gUO and backbone antibody which is highly specific for clothing. 18.2. This was actually looked at in combination with chemo in metastatic gastric or g junction cancer. In this global phase two study, the primary point of this study was overall response rate and the study met its primary endpoint. However, I wanted to show you that even the progression free survival and overall survivable were improved with the addition of this antibody to standard front line chemotherapy. And when when they looked at the clotting expression, they found that when the clotting expression was high, this benefit in PFS and always were much more prominent. So they are currently using this anti body in the frontline clinical trial that is open globally, including our side at Roswell. Um If you look at the adverse event um the adverse events were pretty similar between these two groups. However, those patients who received this experimental antibody had higher incidence of severe neutropenia and vomiting. So so far we have talked about the frontline treatment of his official or G junction at no carcinoma. But there has been some excitement in the refractory setting as well. So this study Destiny Gastric One study looked at her two positive G junction or gastric cancer. Um They used trust is um of direct stick and or T. D. X. D. Which is a drug antibody conjugate with an antibody against hard to and a payload. Uh that is a top i somewhere is one inhibitor. So in this phase two randomized study, they randomized patients with advanced G junction or gastric cancer who were hard to over expressing to receive T. D XD versus physician's choice chemotherapy. All these patients were heavily pre treated. They had progressed on at least two prior lines of chemotherapy and I will just point out towards the overall survival and progression free survival. Here you can see that overall survival was significantly improved with use of D. D. XD. And progression free survival was improved as well. How the primary endpoint of the study was overall response rate and needless to say that was much better in the TD extra group compared to physicians choice chemotherapy. And this study actually led to FDA approval of D. D. XD in metastatic gastric or G junction cancer patients who have received at least one prayer line of treatment and whose humor is hard to over expressing. So based on our discussion, I think it is clear to us now that targeted therapy and immunotherapy are making an impact on this field. And this was only made possible because of these clinical trials that patients participated in and physicians and several other clinical stuff around the world where consistently working on their four N. C. C. N. Believes that the best management for any cancer patient is in a clinical trial and participation in clinical trials is especially encouraged. Therefore coming back to our patient if you see a patient like that who is otherwise motivated to participate in a clinical trial and does not have comorbidities, please always consider referring them for a clinical study. If you have them at your side, that's great. If you do not then please consider referring them to a tertiary care center at Roswell. We have several clinical trials including first line clinical trials for S. Official and Castro's official junction cancer patients. Now I'll just end my presentation with some safety risk later and off label uses on drugs that are approved and not yet approved but might be approved in future. I'll in my presentation right there and I look forward to talking to you all. Thank you. Thank you for joining us. Those were three excellent talks. We're ready to start our live question and answer session, which will kick start off with a pole. You should see the poll on your screen. Now The question I have is which of these patients with this phase Asia Eckerd Score seven and otherwise suitable, imaging is most likely to be an appropriate candidate for poem. Is it one Type two, a Kel Asia by Manama tree in a 55 year old patient who was healthy despite requiring radiation therapy for lymphoma as a child is a choice too diffuse esophageal spasm in a frail 80 year old patient with a medium sized epitaph Rennick diverticular. Um Or is it choice three, Type one, a Kel Asia in a currently compliance 65 year old alcoholic patient with spline Omega Lee. So while you're answering the poll, we're going to get started with some questions that the audience has provided to us. And so the first question that I have here is uh dr Mukherjee, I think this is the best uh opposed to you. What is your preferred new adjuvant therapy for the treatment of the South ago cancer? I guess in order to answer that, can you elaborate a little bit on what stage patients you think might be best appropriate for a new agent therapy? Sure. So, um you know, this is an excellent question and you know, we always determine the best pre operative or data driven approach after an M. D. C. Discussion where we make decisions together collectively with the surgeons, radiologists, radiation oncologists, pathologists. So we all make these decisions together whenever we see a patient at Roswell. Um So basically depends on two things first the stage of the patient and uh secondly what the patient's preference is or the and also the physicians preference is. So number one if the patient has a high tea stage or in stage bye hi T. Stage I mean that T. Three or higher and if the patient has a positive lymph node um then those patients are most likely suitable for a multi modality treatment approach. Um So uh if the patient is a surgical candidate, the preferred treatment option is chemo radiation followed by surgery. However um there is a long standing debate for G junction patients and you know, some G junction patients um could also be treated with preoperative chemotherapy. Um So, you know, we always make these decisions together in a multidisciplinary setting. Okay, choices of agents that you would use in the preoperative chemo radiotherapy strategy. What would you recommend? So, you know, since the cross trial is published in New England Journal of Medicine? Um Many people across the United States have been using carbo and Taxol on a weekly basis. But there are some newer studies that looked at other combination chemotherapy regiments as well. And some centers have been using Fall Fox um during chemo radiation. Um So Fall Fox basically consists of far before recovering and obsolete platon. In my personal experience, I have seen that Carbon Tax Soul is tolerated a little better. Um I also take into consideration the histology. If the patient has a squamous histology, I prefer um carbo Taxol a little more. Um But again, um you know either of these regiments can be used from a patient. Tolerably perspective, we tend to use more carbon and Taxol. Now we also have a study um in this particular setting um where we're using um some novel induction chemotherapy followed by chemo radiation. So we always look into that as well. If the patient could be a potential clinical trial candidate. And and if you were going to give just preoperative chemotherapy, what regimens would you use for that? So since um the flawed trial was presented, uh we have been using triplet chemotherapy for patients who can't tolerate it. So that essentially consists of three drugs. One is five if you um And along with that comes to covering obviously planning and the tax seen. Now this is something that is associated with toxic cities as well. So, you know, if the patient has in a multiple comorbidities or they're elderly, um then we also use Fall Fox in that setting where we essentially take out the tax in part and use five if you look over in and actually planning dR motion. Can you explain to us a little bit about most of these tumors were seeing or at the g junction or distal esophagus? Most of them are adenocarcinoma. Is that we tend to see. So can you go through a little bit about the staging of the tumors at the T junction and what you are thinking in terms of what treatment approach based on the g junction type. Thank you doctor talk? Well, I think that's a very important point. I think from a surgical perspective, it is critical for us, especially at the preoperative planning stage, to really determine what the origin of this tumor is. Whether this is an esophageal tumor going into the G junction, or is that a gastric tumor going into the uh, you know, the involving the gastroesophageal junction. And and that's very important, not just from surgical planning purposes, but also the choice of neo adjuvant treatment that we're gonna be choosing. So I think a key component to this work up is a good endoscopy with careful attention to the landmarks. Uh, we do often see endoscopy where we have, you know, it's done and we have a tissue diagnosis, but there's not mention of the landmarks and and we don't get a good sense. So we are very liberal in terms of repeating our own endoscopy here before starting any treatment. Then we also utilize a combination of a good quality cat scan with contrast of the chest, abdomen and pelvis. In combination with the pet scans and all of these are reviewed that our um our board uh to really get a good sense of what the again what the landmarks for this um are are the extent of, you know uh you know, neural involvement here. And what kind of treatment regimen we're gonna be using. And then what definitive surgical surgical resection are we planning for these patients? Uh And then we selectively use uh laparoscopy where you know, you put the patient to sleep small incisions in the belly and take a look around. And uh we use that approach for patients that have either needed feeding access before they start need to start treatment or in patients that have bulky tumors. T. Four disease. They have long segment disease or they have high normal burden that you're these are the patients that are high risk of having potential disease. So we utilize the diagnostic laparoscopy. So you're utilizing a combination of all these techniques, we get a good sense of what the origin is and what the extent of the disease is and then what surgical resection is going to entail down the road. So are you trying to think about this in terms of type one, type two, type three G junction? In terms of trying to think about what treatment they should embark upon. So, right. So, so I think in our practice at least in the Western world, Type one tumors which are the tumors that start in the esophagus and go down into the gastroesophageal junction. Type two tumors are the ones that start in the gastroesophageal junction. And type three tumors are the ones that start in the stomach and actually go up to the gastroesophageal junction. So type one and type two are treated as a soft edge of cancer And type three is typically treated as gastric cancers. And as dr Mukherjee was eluding type one and type two with these official cancers. I think our preferred me evangeline treatment is based on the cross trial for type three gastric gastroesophageal junction cancers. We utilized peri operative chemotherapy, typically the flight regimen, which is a triplet therapy but based on the patient's condition, sometimes we end up using a doublet regimen there. Okay, okay. Um this next question uh appears to be toward for dr Demi. Uh The question is that what progression of symptoms should a patient be referred for salvageable disease? I think I think the question probably pertains to their symptoms, may be related to a dysplasia or swallowing disorder, potential that they have. But what when were they, Should they be referred? Yeah. Right. So the patient should be referred for consideration of an intervention uh when they have symptoms that are disruptive to their daily life for for patients who have symptoms that are potentially life threatening. For instance, patients who come down with pneumonia from the dysplasia symptom pathology. Um, most these patients have a significant disruption. That's how the disease is picked up. And the other thing I covered in my talk is that patients who were caught early before esophageal dilation that occurs both readily and also distension, that causes the esophagus to also become a sink trap or a a um an obstruction just because the esophagus is not well aligned with the stomach. Those are reasons to try to get the patient to consider surgery earlier because they have a much better long term uh improvement of the symptoms if they can avoid that, an atomic change that it can occur. Okay. And since you're doing now, these advanced techniques and poem is a is a relatively novel technique that can be used to treat uh, kel asia but has of course, its pluses and minuses. What do you counsel a patient before embarking on Poem in reference to possible reflux disease that might occur. Right. This is a first thing I tell patients, is that they are never going to have a normal swallowing compared to a person without these diseases and it's really just trying to palliative their symptoms. One has to see what their main symptom is. Uh try to uh see if you can come up with the techniques to control some of the symptoms. Pathology. Without surgery, for instance, there are not less permanent interventions such as pneumatic balloon dilatation, occasionally Botox. But these less or shorter procedures sometimes have side effects of scarring, which can make the the long term result of poem less effective. So it's really getting to develop a relationship with a patient. Because oftentimes these patients will come back for the other procedure if they started with the hell, or they might need a poem later on, vice versa, and ultimately they may need an isaf ejecta me one day if the esophagus is so damaged and so poorly functional and also dilated so that they can't really have any suspected esophageal drainage. You use an asian all to determine which patients and patients should be treated with a poem or not. Or is it based on a lot of other factors besides age. So we'll age is becoming less and less of a concern for any type of our surgical procedures, including the minimally invasive itself, reject me because age does not really affect how patient heals. It does affect a patient if they have a complication. So generally the trans oral approach, which doesn't leave any external incisions, is pretty well tolerated with pain afterward. And so it's generally a much better option for patients as far as the concern of complications related to post operative pain, We don't know yet if there's going to be any downsides to it because they do have more reflux with us compared to others. Sometimes the patients don't experience the reflux because the esophagus is so dilated, the juices cannot quite make it up to their mouth. But they then require surveillance to make sure they're not developing any occult burning or damage to their distal esophagus. Afterward, I think we'll get back to the poll results. So in reference to our question that we asked um And also to uh what that movie Dr. posed in his question regarding the role of immunotherapy uh for the treatment of respectable salvage ill cancer. 100% of responders said that yes, immunotherapy could have a role for the treatment of respectable salvage of cancer. Dr. can you elaborate on that please? A little bit. So we recently had a check made 577 study published in the New England Journal of Medicine. And based on the results we saw there was a significant improvement in disease free survival for is a vigil cancer or type on you know, some G junction cancer patients who did not achieve a complete pathologic response to their initial chemo radiation. So those patients were treated with a german naval map after surgery and they saw this significant improvement and this is pre survival. So based on that data patients can now actually get a juvenile volume app if they do not achieve a complete path pathological complete response. And in our clinic we have already implemented that and we have some patients who are already being treated that way. Now those patients who do not undergo chemo radiation and co period operative chemo. Um the question of immunotherapy is not still very clear, but there's currently some studies that are ongoing and hopefully we should have an answer within the next few years. So just as Summers, you routinely will offer immunotherapy following resection of the software cancer if there is residual disease. That's correct, yes. And in the absence of residual disease, if there's a complete pathological response, what do you typically recommend? We typically take a surveillance approach in that situation. So patients come see either us or you know, they're surgeons and we basically follow them long term. Uh doctor I think this is best for you. Is there a role for maybe different than what we talked about in your talk But is a role for a radio frequency ablation after E. M. R. Resection for high grade dysplasia. Well um yes there there is uh that you know that technique that we're using for poem can be uh changed in bed. We can actually resect the whole superficial layer of the esophagus which is makes which makes the diagnosis of whether or not the patients have a disease or esophageal cancer that is penetrated deep enough to increase the concern of nodal metastases. That can help us with that decision point. It's not every patient who has a small adenocarcinoma of the distal esophagus requires in this art project. To me, they can be effectively monitored referring to doing endoscopic sub mucosal dissection or E. S. D. For and then you can do that to remove the area of concern, right? And then so if we remove the whole area of concern, it's high grade dysplasia. And you have negative margins. Would we typically offer radio frequency ablation after that or just observe the patient typically? Okay. Radio frequency ablation to to treat the vulnerable because uh such as various barrett is considered appropriate therapy. Now that therapy would also make it difficult to treat some of the things in that area uh in the future. Like if the patients have that type of therapy, they may not be eligible for some of the things I was talking about the benign approaches such as the natural orphans surgery. Okay. The poem. Okay. Uh this is best for dr koop card as this question is. What is your thought process with determine a patient's candidacy for a salvage ectomy, fitness comorbidities, tumor location etcetera. So what are you thinking about to take uh the audience through that? Yeah I mean I think it's uh it's obviously assessing the patient as a whole. Risk factors. You know they're comorbidities. You know are they smokers? What their cardiac status or palmeri comorbidities are. But I think in general what has been a game changer is is the is the minimum remains of a soft reject me. Where we're doing these procedures with small incisions in the belly and then small decision in the chest. So I think the pneumonia complications or respiratory complications post operatively for these patients. The time they spend in the I. C. U. Is is minimized. So so we can certainly offer this to a lot more patients. Now even potentially that were considered high risk because in the past they may require a big laparotomy, a big incision on the valley, a big incision in the chest. So they may struggle with their recovery. So it is uh it is rare that we have to, you know, deny patient curative, potentially curative operation based on just the co morbidity is uh but you know, happens you know once a year. But I think in general looking at those factors and then as I said before in my talk, you know, the tumor location really getting a good sense of what you know, is this going to be, is this going to be in a soft eject me which is a type one versus type two tumor or where the gastric conduit is. You know, we can create a gastric conduit, it's a usable conduit or this is more like a gastric cancer that needs to be treated with a total gastrectomy in a formal Linford ectomy, you know, along the celiac axis and the you know, the splenic artery and stuff like that. So I think that determination is made pre operatively. But I think being able to do this in a million ways of fashion, I think really helps us to broaden and offer this to treatment options to a lot more patients and then just to follow up with you and dr Demi to what's your preferred approach if we're seeing are typical patient with a salvageable adenocarcinoma in terms of location of the nasty nemesis and the preferred approach for doing the minimally invasive resection. Yeah, I think in general, I mean if the most of the patients that we see are tumors around the G junction so we can. Our preferred approach is is what is called an Ivor Lewis technique where you create the conduit in the in the abdomen and then you do the N est imuses in the chest, which with a thorough lymph connect me both in the in the in the belly and the chest patients that have tumors that are located higher up, which is close to you know where the carina or above the carina. Those patients may be best served by anastomosis in in the neck and I think part of you know, having a successful program is that we should be fast. All of the surgeons should be fascinating. All of these techniques, whether it's total gastrectomy, approximate gastrectomy and the self inject me with the chest and estamos is that our neck anastomosis based on the location of the tumor and the patient factors to if the patient we've certainly offered patients transfer title subject may not have preferred approach. But if the patient has bad lungs, bad COPD and a relatively skinnier patient low B. M. I. Uh we can easily accomplish this without getting into the chest cavity at all, although the normal dissection is debatable. But again, weighing the risk and benefits, you know that that potentially is probably the best approach for that patient so that the doctor Demi No, I think I think it's right. The I think the only thing else I would add is that some of my patients that come see me at a cancer center for benign disease. You know, they learned after a while that that we have the systems in place to not only treat the patients but treat the side effects. Was many patients who have any kind of assault rejection, even though we've gotten more scattered around. There's a relatively high complication rate that we have to adjust for. And having the case density here allows us to take care of that and also take care of people with serious but benign esophageal conditions as well. Okay, Okay. We're gonna get back to the second poll question that we uh had put out there, which was regarding the patients with this V Asian equities score seven. Um, so 29% of the audience said a was the correct answer. The type to a call Asia by Manama tree in a 55 year old patient who was healthy despite requiring radiation therapy, 28% said uh B was the correct answer saying diffuse esophageal spasm. These are appropriate patients for a poem. Diffuse esophageal spasm and frail 80 year old patient with a diverticular. Um and then 43% said, see so the majority of the, Of the audience that see that poem was most appropriate for Type one Nickel Asia and a currently compliant 65 year old alcoholic patient with spline Omega Lee. What do you think dr Demi? Well, I structure this question to just to bring awareness to the audience that any of these answers could be appropriate options for these patients. If they had additional tests, answer A and answer C should set off some red flags to the referring position that there could be problems for for answer A And this happened to one of my patients, all the layers of the esophagus we refused together because of the mantle radiation. So that patient couldn't have a poem procedure answers. See uh certainly patients can have spent a medically for other reasons. But in a in a patient with a history of of uh of alcoholism, they certainly could be pulled a portal hypertension and and embarrasses. And those are very difficult to manage if you get bleeding from a barracks during the home procedure. So none in the middle answer. Even though the patient's frail as we discussed, the frail patients really can tolerate an anesthetic free. Well if there's no incisions or pain when they wake up and the diverticular disease is as we're running more is actually seems to be a very good indication, a very good indication for doing the poem procedure. Because the diverticular does not have to be resected, it tends to wither away from both the cervical cervical diverticular on the bankers as well as the epa frantic diverticular and the prophetic diverticular um usually occurs in a patient with a lot of hyper motile spastic disease of esophagus and and a long my autumn. It can be done actually more readily with a poem procedure because the whole esophagus is basically available to the surgeon. Whereas with a soft object me from an open surgery or even a laproscopic. With orcas coptic, you have to deal with the location esophagus is in the left chest, down below, it's in the right chest in the middle and it's in the neck for the upper third. So those are those are the reasons that I think that the letter B the middle answer is the better option here. Just briefly, I mentioned the introduction that some of your advanced techniques can be used potentially for either benign disease or the treatment of we talked about taking care of patients with complications after South rejected me. So how can you use your advanced and discomfort techniques potentially after a self rejected me to help patients maybe with trouble with stomach emptying for instance. Right. The treatment the G. Poem or the uh Now it's a pop per oral pilo maya. To me is a treatment that can help patients sometimes with diabetic gastro process that can help about half to two thirds of those patients. But if the patients has had a vigata me which all patients with soft reject me for cancer generally get unless there are some ways of spirit. But in general for cancers we see the vagus nerves have to go. The politic valve may not open. And there's controversy about whether or not we should cut that valve during the surgery because that can lead to problems. Now with the ability to do a pop procedure, we can have the option to not do that the the floor drainage procedure at the time of surgery and then allow us to do that later uh to allow the conduit to drain better uh and reduce the patient's symptoms of reflux and dysplasia. That can sometimes happen after a minimum based on the sop project to me. Okay, very good. Any closing thoughts? Otherwise we feel it's probably reasonable to wrap up at this time. Yeah. You know, I will just mention that, you know, as I mentioned during my talk that um you know, enrolling or considering patients uh you know, to be involved in clinical trials is you know, one of the strengths that we have at Roswell. So, you know, if there is an appropriate patient was motivated, you know, we always are open to, you know, uh you know, consider them for clinical trials, whether this is in a potentially respectable setting or advanced setting. And I think another strength here at Roswell for us is our multidisciplinary approach where we have all the experts from different fields and we make decisions together and we tailor it to patients needs. Um so, you know, these uh two things should be considered multidisciplinary approach as well as participation in clinical trial for any patients with the cervical cancer. Since this is uh an aggressive disease, wonderful. Thanks again for three wonderful talks and for the audience for for listening and for submitting your questions and for participating. So once again, thank you. Yeah. Created by
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