 So it's my pleasure to introduce Ben Chung. So Dr. Chung is an associate professor of urology. He, it's been a pleasure to work with Ben. We work very closely in taking care of our patients. He trained in Boston and then moved, did a fellowship up in Cleveland Clinic in minimally invasive disease. So Ben has brought to us the ability to do surgeries in a minimally invasive fashion. And he heads our laparoscopic surgical group here at Stanford and his clinical interests and research interests are really looking at developing new techniques in patients with minimally invasive disease. He does both our robotic kidney operations and prostate operations as well. And it's a pleasure to have Ben talk about what the surgical options are for patients with kidney cancer. Thanks Ben. Thanks for introduction. I'm gonna switch gears a little bit from kind of pathologic diagnosis to, what actually happens a lot of the times with these patients with patients who are diagnosed with kidney cancer. I have no financial disclosures to reveal to you. So kidney cancer was and is still a surgical disease to a large extent. In the past, before we had some of these technologic advances, we were doing a lot of these surgeries because of lack of technology through really maximally invasive means which will go through. Fortunately, over the past 10, 15, 20 years, we've actually made great strides in accomplishing equivalent safety and oncologic efficacy by using minimally invasive techniques which really benefits the patient to a large extent from a recovery standpoint. So we really rolled the clock back about 53 years to modern radical nephrectomy which was described by several people but in the literature by Dr. Robson and in Toronto, Canada. And the principles really are, well basically to make a very large incision in that time basically going through the rib cage all the way down here. And the principle was to really control the vessels to the kidney very early to prevent any sort of spread of cancer in tumor cells and then remove the whole kidney along with the adrenal gland and the surrounding fat to make sure the cancer was removed. At that time, the overall survival was not real great. 52% five year overall survival. Of course, this is an era before that preceded CT scan, ultrasound, MRI and any of those modalities. So really it was really hard to find these tumors until really they had spread. And of course, once they spread, there wasn't a lot that could be done that time to really check that spread. So really this was the gold standard for kidney masses at that time was to move the whole kidney. And that's how it was for several decades and we'll get into that. The thing about kidney cancer is that it can do interesting things, especially to the blood vessels that course through your body. So actually kidney cancer can spread through the veins of the kidney directly into the vena cava. And that happens about four to 10% of the time. And how that usually presents, in addition to other symptoms is that patients can have a deem of their leg. They can have a varicoseal, which is being portrayed here where the veins around the right testicle are enlarged. And they can present with a tumor that's spread into the lungs and having shortness of breath, the pulmonary embolism. There are a lot of ways to stage them, but this is a peculiar thing about kidney cancer that it can do such things to the point where it can go all the way into the heart. So we'll go through this real quick. A level on thrombus is simply a thrombus, tumor thrombus that's in the vein. And these usually can be managed with kind of minimally invasive methods. Oops, let me go back. The more extensive the tumor thrombus, the more difficult the procedure. So level two goes into the vena cava here, which is portrayed right here. Level three starts to go up towards the veins that drain the liver. Level four ends up in the atrium. And as you can probably imagine dealing with these types of challenges technically can be pretty difficult. With level four, usually a patient needs to be put on coronary pulmonary bypass, like you would have done for a bypass graft to the heart for coronary artery disease. Stop the heart, drain the blood. Kidney cancer can range from something that's relatively amenable to something with a robotic or laparoscopic approach to something that's really gonna be managed with multiple teams of surgeons to safely remove the tumor. Luckily, most patients actually do fairly well. So as you can see, the topic of this talk is kind of from the most invasive to the least invasive. And luckily, if patients did not have metastatic disease or metastases, then they actually did pretty well. Of course, we don't have a lot of data from the current era of tyrosine kinase inhibition. So we don't actually know how well these patients do. But in general, the feeling is that whether or not they have metastatic disease at this point, we try to take it out. We try to take it out. The thing about the kidney from a surgical standpoint, everyone has to remember is that no matter what we do to the kidney, it has a very avid risk of bleeding. And that's really because of its blood supply. So as you can see here, this is the vena cava and this is the renal vein and this is the right kidney. The kidney is located in a location that's really right next to the main blood vessels of the body, the aorta and the vena cava. And there's a lot of blood flow running through them. So no matter what we do, unlike other organs that say like the liver, believe it or not, which can be controlled with minimally minimal effort, the kidney's not that way. And it can be a very unforgiving organ to operate on, which we can get into on future slides. But for example, if the vena cava is invaded with a tumor thrombus, really need to make sure that you get control of the vena cava before you pull the tumor thrombus out. So again, this is not a trivial thing. And again, we're going from maximally invasive to minimally invasive, but these are the ways that kidney cancer can present in a very aggressive fashion. And as I mentioned, if the tumor thrombus is more extensive within the vena cava, then you're gonna need to control every single blood vessel that enters into the vena cava, that point, open up the vena cava, and pull out the tumor thrombus. And again, just like Dr. Kyle's talk, if there's any questions, feel free to interrupt me. This should be an interactive, informal type of forum. So, and you can see from this curse works too well, but you can see that little yellow-ish kind of knob pushing out. That's actually the tumor thrombus, and actually that's pushing out of the renal vein, the main kidney vein that drains this kidney, which I think is the left kidney because of the length of the vein. And typically, that's what kidney cancer looks like. It's like this bright yellow-ish-looking tumor, which is very characteristic, grossly. I don't know if Dr. Kyle went into that. And as I mentioned, when tumor thrombuses get really extensive within the vena cava, then this is what we need to do, which is drain the entire blood volume out of the body, cool the patient, pull out the thrombus, open up the heart, close it, otherwise the patient would bleed to death. There's just too much blood flow running through that area. So, we can pass on this slide. So, again, we start from maximally invasive, and we're gonna start the progression down the timeline of minimally invasive surgery. So, like lots of surgical techniques, kidney surgery has not been an exception as far as evolution from something that was rather morbid from a patient standpoint, to something that's a lot better tolerated. And that started in the early 90s. Dr. Klayman, who's now at UC Irvine, I think he was at Wash U at that time, described the first laparoscopic nephrectomy, removing an entire kidney through laparoscopic means, through small incisions, not that big incision, which I showed you from that original description from 1963. And then, 1993, started talking about taking out part of the kidney through laparoscopic means, through small incisions. Whereas before, the concept of even moving part of the kidney was not really that well-established. People said, well, take the whole kidney, you have two kidneys, why not? You have another kidney, you should be fine. That's not necessarily true, we'll get into that. And as the 90s went along, people recognized that and realized that saving the kidney, if at all possible, was beneficial to the patient for a variety of reasons. So, people started trying to do this laparoscopically, which was of great benefit from a patient morbidity standpoint. And then, people started putting their hand in there to facilitate laparoscopic or minimally invasive techniques. And in the 2000s, we have robotic platforms, which we can get into now. This is actually a robot, right? So, it's not like, if I were gonna do robotic surgery, I kind of go to my office, push a button, leave, have a cup of coffee like this. I wish, that would be fantastic. And now I could just go, I don't know, surf the web or watch YouTube or whatever, watch the Olympics, have a cup of coffee. Oh, it's done perfect, I can come back. No, that's not how it works. I wish, maybe Sunday. But robotic surgery really is really a refined laparoscopic technique, where your instrumentation's a lot more sophisticated and your visualization's three dimensional and high depth. So, it's not that there's some automaton doing your surgery, not yet at least, I wish. So, laparoscopic techniques, these have been around, as you can see for over 20 years. How is it compared to open techniques? Well, all the data thus far to date over that past 20 plus years has shown it's equivalent. So, there's no disadvantage of doing it this way, where in the beginning of that learning curve, at the beginning of that era, people said, well, you shouldn't do it that way, it's not proven, et cetera, et cetera, well, I think it is proven. Unless you have a good reason to do it open, then there's, you don't have to because of a cancer control aspect. And the, right, so the aggregate data, again, confirms the safety of this type of approach. And again, the difference is in incision are significant. So, the kidney for a variety of reasons is kind of under the rib cage, so to get there is actually not that easy. And I don't know if any of you have broken a rib, that's not all that comfortable either. So, to get through there and get into that space with enough exposure is not easy for anybody, especially the patient. And a lot from a laparoscopic approach, we're putting small incisions, probably the biggest port is gonna be the width of the tip of your thumb. So, there's gonna be a lot less pain and a lot less hospital stay and a shortened time to recovery. Now, patients always amass me this. So, when you take a radical defect, you may take the kidney out, right? What do you do with the kidney? Just leave it in there. No, I'm just kidding. Yeah, I say that most of the time. Either they laugh or they're kind of aggastic. What? How do you leave? Well, no, no, of course not, you know. So, we, yeah, you know, you roll around the bed at night and you feel like a little bump. That's okay. It's normal. Just kidding. So, we kind of put into this bag inside the body and there's a little straw string on the bag and we pull it out. So, so in case you were wondering, you know, I mean, you could put your hand in there, but you know, putting your hand in there can manipulate the tumor and your hand is bigger than this bag. If you put it in a bag, you can really safely entrap it, safely contain it and then pull it out throughout the smallest incision possible. Well, you know, what about tumor size? You know, can we, what can we do from a, you know, minimally invasive standpoint? Well, the tumor, as you can see, is marked out by that yellow arrow and it's taken up about half the kidney, which is kind of the limit of what you can expect to be able to save the kidney. You need to save about half. Anything less than half, generally the kidney doesn't do all that great. But, you know, there's really no limitation from a laparoscopic standpoint, as long as it's feasible. And a lot of time, you know, if the tumors are really large, which we don't see that much of anymore, to be honest with you. We do still, but, you know, the, and we'll go into this, you know, with the proliferation of CT scans, MRIs, ultrasounds, you know, we're finding these earlier and earlier stages, which is a benefit to the patient. So fortunately, we don't see a lot of this, but you know, these can still be approached, you know, through a minimally invasive approach if feasible, you know, and you've probably seen some scans, but again, this is a, you can see the tumor pretty clearly on this cross-sectional imaging study marked by the yellow arrow. Again, these can be accessed through a minimally invasive approach. As you probably know, or I've talked about, one of the things that kidney cancer insidiously does is it, you know, recruits blood flow. Like cancer, you know, and that's the basis of all these medications we have, really. I mean, not the immunotherapies, but the TKIs is really to stop that process of recruitment of blood flow, you know, and I'm not in Southern California, so I can probably say this. It's like stealing water from the Delta for Southern California, right? It's like buying an island in the middle of Delta and trying to get a pipeline to whisk it off to someone's lawn in Orange County. Okay. When I said in Southern California, I didn't get a very favorable response. They didn't appreciate that. I guess they really want to water that grass, but anyway, that's my, you need to divert blood flow and actually through a laparoscopic approach because what you're doing is you're actually filling the entire belly with carbon dioxide. All those little arrows, arrows point to all of these little vessels which have been kind of insidiously recruited to feed this tumor and actually the laparoscopic approach by insufflating the abdomen with carbon dioxide actually exceeds the pressure of those, a lot of those blood vessels so the bleeding is gonna be less. So it's a side benefit. So, you know, it's always good to see a video because otherwise, and I think it gets kind of boring. I mean, not you guys, but you know, sometimes I'll give a talk and people start falling asleep saying, oh, I don't wanna hear about talk. I don't wanna hear about facts. I just wanna see some videos, right? I mean, it's a YouTube generation, so. But anyway, so this is a video of a tumor thrombus that's kind of in, I can repeat the video, that's kind of encapsulated by, well, first of that vessel loop, but we'll go back through that again. So basically the principles as Dr. Robson described for, for kidney cancer or for kidney removal is to really control the blood vessels. And back then, you know, controlling blood vessels meant in an open surgery, like tying them off with suture. Actually, we don't have to do that anymore. We can use things like a stapler. Now, you know, when people think of stapler, it's like, well, you know, I put my Christmas lights up with a stapler, you know, how's that remotely safe from a vessel standpoint? Well, they're titanium staples and what happens is they, the stapler throws six rows of staples and then there's a little blade that cuts in between. So there are three rows of staples on each side. And actually it's very secure. I know it sounds kind of weird. It's like, I staple my papers, you know, I mean, what, and it doesn't work very well, you know, if it's really thick, I can't staple it. Well, of course, right? So I mean, those considerations are germane here too, but at the same time, you know, this is actually a very safe way of dealing with it. So again, the deal with the kidney had the first stop, the blood flow of the artery, which is what we're doing with the stapler. You can see kind of that pulsation down below. And then there is a tumor thrombus in this, you know, a kidney vein on the right side. And you can kind of see that yellowish thing kind of above that reddish vessel loop. And the stapler actually is a very efficient way of dealing with this. And you can see the staple line on either side. So again, you know, dealing with pictures and diagrams and figures and cartoons can be somewhat abstract. It's kind of better just to see what it'd like in real life. And we don't have to really get into this because we've talked about this. Now what about patients with metastatic disease? Unpresentation, you know, should we take the kidney out? Well, the general consensus is we should. And if there's, you know, if the kidney is removable, we should take it out. And if there's a solitary site of metastasis, should try to take that out as well because there is survival benefit. Now, I don't think we have all the data yet to guide us, you know, through this. And I can, we can go through that. But, you know, back in 2004, what we know is that, and this precedes kind of TKI's because they came out probably about 05, 06. We know that patients did better if you took the kidney out from a survival standpoint. This is in the interferon era, which we don't think we ever use interferon anymore, or IL-2, which we rarely use. So I think that, you know, the consensus still, you know, and we don't have randomized data yet. I don't think Sandy, like the Carmina trial, I don't know when that's coming out. Probably the next year, probably. Yeah, we're gonna have randomized data soon to guide us with respect to, is there a survival benefit taking the kidney out in patients with metastatic disease if they, you know, in today's era of TKI's? But the data we do have to date suggests that it is a benefit. And, you know, back then, what they found was that, you know, there was a small survival benefit, but definite benefit, and those who did best actually had the best performance status. They were the healthiest, or they had better prognostic features of their cancer. It wasn't as aggressive appearing, or they had metastasis only to the lungs, which is the most favorable site. As far as, you know, when we talk about minimally invasive approaches, I think if you can do it minimally invasive, you should, because the patients actually can recover faster to get back on medication, to get back on therapy. So if you can, you should do it that way. Talked about this. So these are the trials that are ongoing, that are designed to understand, you know, is this truly helpful when patients who are getting SUTEN, for example, you know, taking out the kidney first, or SUTEN, right? I mean, both of these trials are designed to answer the question about SUTEN, which was the first line treatment when the trial was started, probably in 06 or 07. So we'll know soon, but again, the data we have to date, which is not randomized, suggests that it is a benefit to remove the kidney. If at all possible. I can skip this. And we talked about this. Now, let's talk about kidney cancer and how it's being diagnosed. And, you know, I think I touched on this. So, you know, back in 1963, when kidney cancers were being diagnosed, they were being diagnosed because people having blood in their urine, they're having, you know, their intern has felt something on their abdomen, they had pain, you know, and we didn't have CT scans. We didn't have MRIs. We didn't have any of that stuff. You know, I remember, how many of you have seen The Exorcist? Yeah, so I saw The Exorcist, like for the first time in the theater, like in 1999. Scared the, you know, what out of me? But back then, you know, this is a movie from the 70s and they're trying to diagnose the possessed girl with some kind of brain thing. But all they have is angiograms. I mean, they're just basically cannulating an artery and just shooting contrast to see if there's anything abnormal. That's the only way you could find kidney cancer at that point. You were shooting a, you know, contrast into an artery near the kidney and seeing if there's something that lights up. I mean, basically what you're doing is you're opening the patient up and looking for a kidney tumor. It's very, it was very, very crude, obviously. You know, so obviously things are different. And as you go through this timeline, actually the incidents of kidney cancer is going up. And it's going up mostly because what we're finding is tumors less than four centimeters in size. You know, so people, they go to the ER, they have pain, they get a CT scan, they find a tumor, you know, or whatever. You know, they have something. And then, oh, you got an ultrasound. Oh, you have a kidney tumor. Luckily in those situations, for the most part, they're less than four centimeters and, you know, four centimeters or less. That's a stage one for the most part. They're not gonna present with widespread disease. So things have changed from a paradigm standpoint. And because of that comes the concept of, well, why take the whole kidney out, right? And we're finding a lot of tumors that are small. Why can't we just save the kidney? Well, it's a good question, right? So, you know, people have looked into this probably from about 15, 20 years ago to now. And it's clear that there's no difference in cancer control whether you take the whole kidney out or not. In a tumor that's less than four centimeters. So you really should try to save the kidney if at all possible. There's no difference in cancer survival. Of course, there's, okay, so the other thing is that it might be that these smaller tumors have a higher incidence of not being cancer, which is controversial. That data is mostly from the Mayo Clinic, which suggests that if you have a small tumor it may not be cancerous. So you probably, again, should try to save the kidney if at all possible, because you may be removing a benign tumor. And not surprisingly, if you're taking the whole kidney out, your kidney function overall globally is gonna be a lot worse. And that's no surprise. You know, so what? Why is that a problem? We'll get into that. And again, as I mentioned, robotic surgery, you know, I showed you that one little picture. Here's a couple more. So again, it's not some, you know, automaton. It's not a self-driving car. You know, not that I have a self-driving car, but it's not a self-driving car. You have to control every movement. Kind of the nice thing is that as a surgeon, kind of the nice thing and not nice thing is that you're not actually sterile. You're not actually scrubbed. You're not actually next to the patient. You're actually in this little console. That's in the same room. Doesn't have to be actually, but it's in the same room. And you're operating kind of hand controls and pedals that actually control every movement of the robot. So it's not the traditional surgery where you're actually next to the patient, you know, your hands are on the patient. No, actually you're, you know, five, six feet away. They're even assisting who's changing instruments, but you're not actually there right next to the patient. So, you know, you could check text messages and I'm just kidding, but it's a different paradigm with regards to this. Now, what I tell patients and they're very surprised about with regards to moving part of the kidney is that it's actually harder than moving the whole kidney. You said what? I mean, why? Well, I'll show you why. So when we remove part of the kidney, we have to stop all the blood flow to the kidney. So we have to put these clamps on the artery and vein to stop blood flow. We have to cut the tumor out accurately so we don't leave any cancer behind. And then we got to suture the whole kidney back together. So in other words, you know, as I mentioned, the kidney has a very robust blood supply. So let me repeat this. So, again, you have to cut the whole tumor out and you have to suture it all back together. The kidney blood supply is so robust, if there were no clamps on the kidney at this point in time, the patient would bleed to death. It would just be a torrent of blood. And, you know, if you were not to repair the kidney, the same thing would happen. It would just be a torrent of blood. I mean, the patient would probably bleed out their entire blood volume in about one minute. So because of that, you have to be extremely careful about what you do. And actually the robot gives you that flexibility to do so. So, you know, because of all the suturing that's involved, you know, to repair the kidney, the robotic instruments, because they're quite facile and articulating and all that can actually help you do this in an accurate fashion. Because in the past, you know, what you were doing was using laparoscopic instruments and that the, you know, the technical facility was somewhat crude. You know, this is a lot better to be able to do it in a controlled, controlled, accurate fashion. Another thing about partial nephrectomy is that, you know, just like your finger, if you put like a clamp on your finger for a long time, your finger would fall off. So you can't actually just, you know, take your time and say, okay, well, you know, see you later. I gotta, you know, run to the restroom. I'll come back. You know, basically you have about 30 minutes worth of time until the kidney starts to deteriorate functionally. So you're kind of under the gun from a, you know, technical standpoint, but also from a time standpoint. You really just can't, you have to act expeditiously because the kidney, you know, it's like your heart, right? Your heart attack, you gotta revascularize, you gotta get blood flow back to the heart, or otherwise the heart will die. Same thing with the kidney. And, you know, basically, so as far as outcomes between robotic and laparoscopic, because, you know, people are doing laparoscopic partials before they start doing robotically, you know, what's the difference? Well, actually, warm up scheming time. So what's that? That's how long the kidneys clamp for. Again, it should be less than 30 minutes. It's actually a lot faster doing robotically for the reasons you can see. I mean, it's just a lot easier to do these suturing maneuvers. And the blood loss, a little bit less too from a robotic standpoint. So, you know, I think, you know, actually for someone who is actually doing a lot of laparoscopic partial effectiveness, you know, it could be done, sure. But it can actually be done better if you have a, you know, better platform. It's like, yeah, I mean, you could drive, I don't know, you go. You can drive, you can't drive very fast. You could redline the car, you know, trying to get on the freeway and get re-randed. Or you could drive, I don't know, take your pick McLaren, who cares, whatever, something. Something really expensive, right? Hey, it's better. I mean, it is. It's more expensive. And the robot is no different. It's about one and a half million dollars. But it's better for the patients. Yes? Yeah, radical and effectiveness can be very variable in blood loss, really depending on how big the tumor is. Mostly because of those parasitic vessels. So sometimes you can just lose a lot, a lot of blood, you know, during a radical. If it's a smaller tumor, not generally not. So, and actually we have updated data, but, you know, robotics, you know, that as far from a partial, from a kidney standpoint, really started taking off around 0607. Now I would say that in 2016, what percentage of partial ineffectiveness had been done robotically? I would say it's about 65, 70%. So, you know, it's kind of showing that, you know, the technique is better. And it's better for the patient and it's kind of, you know, people recognize it's better, you know, on all fronts, you can skip this. Now, finally, what's the last thing, you know, well, you know, we've been, oh, sir, go ahead. I'm sorry. So, stage two would be difficult because you're talking about tumors that are, you know, upwards of seven centimeters, you know. In other words, the larger the tumor, the less chance you'll have to save the kidney. But, you know, there are patients who you can try to move up to seven centimeters. If it's in a location that's amenable to that, you should, if you can. Just sometimes it's not. Just not going to be located and you take out a seven centimeter or less tumor or six centimeter, let's say, T1B. The kidney doesn't work very well and you just end up taking the whole kidney out. And again, since I guess tumor growth can be asymmetric, if it winds up going past the centerline, probably you might, I guess, take the whole thing out because it's wound up being periphery. Yeah, I mean, the best place is really on either the very top or very bottom because you can kind of just chop it off. Once it gets in the middle, then that becomes more complicated because all the blood flow's running through the middle and the more reconstruction you need to do, the more a potential compromise of blood flow. And the other thing inside the kidney is that, you know, yeah, there's blood flow, there's also urine. And there's like, you know, urine collection. There's a urine collection system. And if that gets violated, you know, that could just, you know, leak. So, I mean, there's a kind of a risk stratification that has to occur, right? I mean, if you're 88 years old, you know, probably shouldn't be trying to do something like this. If you're 28, yeah, you should. So, I mean, I think you have to, you know, think about it sometimes individually in the context of the patient. So, you know, we've been talking about cutting things out, you know, but there are other ways to deal with this and that would be ablation. So what does that mean? Well, it means either freezing it or burning it. And here's a still picture of a freezing procedure where there's a probe stuck directly into the tumor and it's frozen. And the accepted techniques for doing such are either percutaneously or through the skin, you know, usually it's an interventional radiologist putting a needle into it under CT guidance in the tumor and freezing it. Or burning it, which is radiofrequency ablation. And you could do it laparoscopically as well, you know, put a probe in under direct vision during a laparoscopic approach and freeze it or burn the tumor. And there are newer things like microwave ablation or Haifu or high frequency ultrasound, which are not quite there yet as far as accepted techniques, but you know, they're expanding the gamut of these types of things. Now, you know, that sounds great, you know, just freeze it. Why cut it out? What's the difference? Well, there's a difference as far as cancer control. So basically, I mean, this paper was from several years ago, but basically between, where is this? Yeah, so the risk of local occurrence was about seven times higher with freezing it at that time. So, you know, if you can, so basically I think the bottom line is if you're gonna freeze or burn something, that's fine, you know, but it has to be again, kind of measured to the individual context of the patient. Now if someone's 89 and they have a small tumor and they really wanna treat it, well, you could do something like this, you know. If they occur, okay, fine. Their life expectancy is probably less than 10 years. If it occurs, they're probably gonna die of cancer. If they're 28, you shouldn't be. You shouldn't be, you just have a long window which you have to have confidence in. We just don't have that data, don't have that data. But in certain patients, it's actually a very good thing to have this type of technology available, which we do here. And I'm highly reliant on my inventoryologists and these kind of patients who are not great surgical candidates and doing this type of thing. And finally, there's surveillance. So, in other words, you find the tumor, you just watch it. Why would you do that? Well, we generally know how fast these things grow, which is actually not that fast. It's like a couple millimeters a year. And when tumors are small, like less than three, four centimeters, their chance of spreading is actually quite low, quite low. And we have very good imaging modalities as we've alluded to to follow these things. Again, it's not appropriate for someone who's in their 30s or 40s. But patients who are much older and they have competing risk, let's say, heart disease, stroke, whatever, you don't necessarily have to treat them. These tumors, you can watch them and if any hand gets forced, you might freeze them or burn them. But these patients are not great surgical candidates. There's no reason to really diminish their quality of life by trying to do something definitive. So I think in conclusion, surgical options, as you can see, are continuing to evolve into less invasive techniques, which is great for patients. And continuing advancements technically really lead to increasing safety for doing these things, which again are beneficial for patients. Hopefully the trial data on removing kidneys and metastatic disease will be out soon, so we can talk more about that next year. And there are non-surgical options, there are blative options which really have to be weighed in face of the individual patient context. Thank you very much. This doesn't relate directly to surgery, but perhaps you could address it. And that is originally my cancer was found incidentally with a clot. So then what happened was as I was therapeutic on Warfarin and I still wound up getting another clot. So they went on and said, well, what's going on? They found this out. So they wound up getting the cancer out, but still I'm taking anti-coagulants and I've actually thrown another clot. Why? I mean, it turns out that cancer is gone. What's going on? I don't know if Sandy, you wanna start with that? I mean, basically sure. Having cancer can render one more prone to have a clot. It might have just unmasked some sort of underlying tendency you had already. And unfortunately, you know, I don't know if there was residual clot there or whatnot, even something structural that's persistent that's causing that. So I didn't really get it from the presentation, but why exactly is a radical removal more the consensus instead of like partial nephrectomy? Why is radical movement more easy? More what? More preferred than the consensus. More preferred? So why is radical removal compared to partial? Okay. Oh, well, again, I think if you can't say the kidney, you should. But in instances, you can't, then you have to remove the whole kidney. And part of that has to do with the overall global kidney function, which again, in the past, back in the 60s, 70s, like, well, you have two kidneys who cares, just take one out. That's why you have two kidneys, right? Well, sure, right? I mean, it's better to have two kidneys than one. I mean, that's true, right? And I mean, you don't have two livers or two spleens or two whatever. But what we found recently is that, sure, right? I mean, people who have, let's say, donated a kidney for a transplant, like to a relative, they actually do very well. And why is that? Well, because those patients are very heavily picked out and screened. You're not gonna take a kidney out of someone who's kind of on dialysis range kidney function. You're gonna pick a kidney out of someone who's actually very healthy and who's gonna maintain health throughout their entire life. So those patients actually do very well. It's the patients that come in with a diagnosis of kidney cancer, who already have, let's say they're in the 60s or 70s, they have high blood pressure, diabetes, and that's pretty common. They're not gonna do as well if they have compromise. And not only from a kidney function standpoint, where they could end up going on dialysis, which is not good for anybody, but actually we find that people who have diminished kidney function are also at risk for a variety of cardiovascular risks as well. So I think things evolve to the point where there's clear evidence to suggest that the more well your, the better your kidney function is globally, the better off you are. But sometimes technically for whatever, not for whatever reason, usually cause the tumors are too large, you can't save the kidney in that situation, then you have to take the whole kidney out. Why not do surgery on a stage four patient if the tumors are very defined and? You mean if it's doable, why not do it? Yeah. You should. Unless for some reason the patient's so ill that doing it would risk their life. And sometimes you find, I mean, once in a, because people are getting scanned all the time, we'll find patients that say they're 95 or something. They have a tumor that could be resected, but they have so many other issues that you could actually kill them doing the surgery, then right. It's like, how much are you really buying here? Cause we don't know actually how much the survival benefit is. It might be like from that paper from 2004 from the New Lane Journal, it was about three months. It might be more. There's other side benefits to that obviously, because these things can bleed and then that can cause a lot of issues, but right. I mean, if you can and if you can, you should. And sometimes you can't because of other issues that come into play. But that's the most controversial thing, right? I mean, we think about patients who have breast cancer that's left the breast and gone to the bone. There's no great added value of removing the primary. I think kidney has just been so unusual in that, removing the kidney has resulted in an improvement in longevity. And so that's why it's been done. But you know, the last 10 years because we have had such good drugs to treat kidney cancer, it's come into question as to is there any value added by removing that kidney? And as Ben said, we are awaiting the randomized trial, but I think our strategy here at Stanford is we individualize it. We look to see what is the extent of tumor outside the kidney and should we be doing drug therapy first, followed by kidney removal or should we just take directly get the kidney out and then proceed to drug therapy? So a couple of questions about the surgery. So if the cryoablation and other types of ablation are advancing very quickly, is Stanford kind of the primary research center or advancement center of cryoablation relative to say Kaiser if a patient was in Kaiser or something or is it mostly the same everywhere? It's not. I mean, it takes a, it's just like anything, right? The more of this you do, the better you're gonna be at it. And I've, I didn't get into this, we can get into this now. I mean, I've actively been pushing the envelope to our interventional radiologist from cryo standpoint. Generally the feeling was that if it was three centimeter or greater than three centimeters of tumor, then it wasn't really that approachable with some sort of ablation. But I've been sending them patients, because they're not great surgical candidates for a variety of reasons, five, six centimeters. And they've been successfully treating these. So I think it has to do with your level expertise. And I think level expertise of our radiologists, interventional radiologists here are very high. I don't, I can't speak at other places, but I know that I've seen patients sent here directly from other interventional radiology practices to do such things. So it's, I think it's just again, about how much you do. And we see quite a bit of that here. And that brings me to another question. Since we're finding small and smaller tumors, how come the paradigm just doesn't adjust to the point where at age 40 there's a routine MRI or CT scan, you find really small one centimeter tumors very early, just cryo plate them and the person goes. Yeah, I wish. So. And the sequence be in that order. So, you know, because we deal, we're dealing with dollars and cents at that point. And we start talking about that. And we start talking about policy. We start talking about healthcare, money. We start talking about Medicare. We start talking about deficits. The problem is actually when you look at the data, it's not cost effective to do that. In other words, kidney cancer is not common enough to make it worthwhile from a global, not global, but national health standpoint to advocate screening, unlike breast or unlike prostate, which is controversial as well, or unlike colon. So, and you know, the Japanese actually probably were the last people to look at this and they found that it was not cost effective. So that's why it's not being done. It just really from a dollars and cents standpoint. You know, other countries, people just get scanned from head to toe. I'm not saying that's what you should do. You know, and you know, that's not necessarily the answer, but that's the reason why. It's unfortunate for us, I guess. But then third and final question is, if we say cryoblation doesn't have the same decisive removal as a laparoscopic PN, but there's a lot of drugs coming out. And if somebody's young, is it maybe a good idea to just cryoblate a two centimeter tumor and then go on drugs because it's minimally evasive and you won't lose the kidney or even part of the kidney? Well, I mean, doing a two centimeter partial is very, you know, it's very straightforward. Going on drugs is not without side effects. So you don't want to, first of all, it's not an indicated, it's not indicated to give someone drugs for a two centimeter tumor that's been cryoblated. Plus you wouldn't want to necessarily assume the risk of side effects for what's the end point. It's probably lifelong. You know, when do you start, when do you stop? So, you know, again, if you're young, you should really go with the gold standard from a cancer control stamp. When you could go with cryoblation, the problem is that the risk of recurrence is higher. If it does recur, then we start to run out of options to a certain extent. So, you know, from a, which I didn't get into this, but you know, it's just like anything. When someone else has been there before, trying to go back in there is gonna be more difficult. So with cryoblation, there's gonna be a certain amount of scarring that occurs around the kidney. It's gonna make saving that kidney downline much, much more difficult. So, you know, until we have data that shows or suggests that cryoblation is equivalent, which we don't have yet, then we have, you know, for someone who's young and healthy and has a long life expectancy, we should really stick with the modality that has the best cancer control. Yep. Yeah, I have a very basic question. When you're talking about cryoblation, you're talking about going in there, you're freezing the tumor. Is the tumor then taken out? Is it left there? By freezing it, you kill the cancer cells, or it stays frozen forever? Could you just explain to me? Yeah, it's like you get frostbite of your finger. Eventually, their fingertip falls off. You know, that's the idea. So, you know, they'll put a probe or two or three how many they need to cover the tumor. And actually, cryoblation, in a lot of ways, is preferred to radiofrequency ablation. So freezing is preferred to heating it. The reason is that because when you freeze it, you actually see kind of an ice ball forming around the tumor, engulfing the tumors. You can actually objectively see that it's being treated. But what's going on is when you freeze something, it bursts the cell, it kills the cells. And that's the idea, just kill the cells. You don't take it out afterwards. What you do is you're going to continue to monitor it to make sure there's no sign of it coming back. And that follow protocol, surveillance protocol, will start, for me, I started three months, three months for the first year, then six months, and that looks fine then every year. So that's the idea. You don't want to really go in there and take it out because if you were, then you should have just done in the first place. Other questions? Great, thank you Ben. Thank you so much for taking your time.