 All right, we'll make it work So good morning It's nice to be here and I appreciate all of you coming out and today I spent a little bit of time talking about kidney function after kidney surgery so obviously the kidney plays a vital role in filtering our blood and Whenever we talk about surgery like you just heard from dr. Chung Removing a whole kidney or removing part of a kidney may impact how well your kidney can work and filter the blood and We're just now starting to better understand the long-term implications of changes in kidney function after surgery so my disclosures, and I'm sorry the monitor is Zoomed here, but I have some grant funding from the VA from the Department of Defense and from the Parker Institute and And if if you've been to any of these conferences where I've given a talk before I always share this picture So these are my grandparents on the left at my wedding and my grandmother was diagnosed with bilateral kidney tumors after a fall and This happened for me at a time when I was in medical school And I was impressionable and this is really kind of shaped one of the reasons that I've been interested in kidney surgery Since that time she's now 91 and has no evidence of disease and is doing great so Ironically that says perspective up at the top left But this picture even with it being cropped Gives the impression that that I want to share So this is the a picture from the Cassini spacecraft as a past Saturn and this dot here down in the left is Earth and so it gives you a perspective That I think we can kind of apply the same framework looking back on what has been the history for kidney cancer surgery And that will help us hopefully moving forward so What I'd like to do is I'd like to share with you the impression of how much things are changing and how quickly they're changing for kidney cancer research and How this has been a phenomenon really of the past 20 years and Talk more than about kidney function how that fits into all of the work that's ongoing and then what we will be doing for Patients with who need kidney surgery in the future So this slide will come up quite a bit today 60,000 patients are estimated to be diagnosed with kidney cancer in the United States every year and Over 14,000 people patients will die from kidney cancer So that's the burden of disease the scope of the problem and one of the reasons that in the past 20 or 30 years Things have been progressing more rapidly is that we're diagnosing more and more patients with kidney cancer over time So this line here is the incidence of kidney cancer in the United States and over the past 40 years You can see that the general trend is that we're finding more and more patients with kidney cancer We don't fully understand all of the reasons for this part of it Maybe that we're finding tumors earlier just because we're doing more Imaging we do more CAT scans more MRIs more ultrasounds and so we find things by accident just because we have pictures to look But I actually think that there's probably something else going on and whether that's an environmental exposure Another risk factor that we don't understand yet. There may be something else that's kind of driving this increase in kidney cancer and so here I have a timeline and The way that I constructed this timeline These are all of the papers about kidney cancer that have been published in the New England Journal of Medicine so the New England Journal of Medicine is kind of a flagship journal and if you look over time in The early decades of the 20th century. There were almost no articles about kidney cancer and If you look I had to even shift the time scale so that after after the 1990s We went by five years and it's even hard to fit all of the papers in from the last few years But what you see is that all of the drugs that have come out in the past 10 plus years now for kidney cancer Most of those trials have been published in the New England Journal of Medicine And so they show up on this on this timeline and so you can see the new drugs When to use the new drugs and how to manage kidney cancer has really been a phenomenon Where this research has been coming out very recently so this is a rapidly moving field But today I'm going to talk about just the papers that are kind of still here in bright white And then the ones that are grayed out are all the other things that you're going to hear about from other speakers today But the main talk is about kidney function after surgery so that first paper that I'm going to refer to is from back in 1991 and This was a report in the New England Journal where they had taken a patient who only had one kidney They were born with one kidney and had a tumor in that kidney and they did a partial nephrectomy So you just saw beautiful videos from dr. Chung about a robotic partial nephrectomy and What they asked is what was the impact to kidney function over time in the patients that they did this type of surgery And their conclusion is that after they did the surgery the patient's kidney function remains stable over time So if you can preserve enough kidney function that you don't leave the patient on dialysis Then they're going to find a new baseline and kind of sit at that new baseline Hopefully forever and that they won't be at risk of kind of progressive decline of kidney function Like if you can imagine almost like a spiral where if we took out some of the kidney and the kidney function was worse Does that is that going to accelerate? chronic kidney disease or worsening of kidney function over time and so then this So for a long time that meant that we were comfortable taking a whole kidney out Because we thought okay if we can take a whole kidney out and we don't put that patient on dialysis Then they're going to find that new baseline. They'll sit there forever and it'll be okay And then in 2004 another paper came out and this is from the bay area And they used a million patients in the northern california keizer system And all they asked was a very simple question. They take a million patients and they say what's your kidney function? And then based on your kidney function, what's the chance that you're going to get admitted to the hospital? Or have a cardiac event like a heart attack or stroke or die And If I asked you that question, I'm sure that you would be able to say, you know kidney disease is bad And if you're on dialysis, it's bad for you, right? And we all knew that as doctors, but what this paper was really Really helping us to understand is that even if you had slight decreases in kidney function You were more likely to have admissions to the hospital You were more likely to have heart attacks and strokes and you had a higher risk of death Even for small changes in kidney function that we would have blown off in the past and said that it'll be fine We'll take your kidney out. You'll have a slightly reduced kidney function, but you'll be okay because we'll be stable Well that paradigm started to change when we worried about these patients now These million patients in keizer didn't have surgery These are patients that just add their kidney function checked and maybe their kidney function was because of high blood pressure or diabetes or other things But this paper really shifted The surgical plan so that we would start trying to save kidney function whenever we could and so that meant doing more partial nephrectomies So i'm going to back up a little bit and talk about the history of partial nephrectomy So the first paper that I could find talking about partial nephrectomy When you didn't need to do a partial nephrectomy So this is a patient that's got two kidneys. You could theoretically take one of them out But you chose to do a partial nephrectomy anyway That first paper was from 1950 There was a series that was published in the 80s and then in the early 90s a series showing equal cancer outcomes for doing partial nephrectomy So this is really something that has been recent and accelerating So I know you saw videos from dr. Chang. I have one video in here. So I apologize if if You don't like watching surgery videos. This is what we do all the time So maybe we're a little bit desensitized to it But this is From a camera in the light of an operating room. So when we show videos from a robotic surgery We have a camera inside the patient. It's easy to show those videos This one is from the light overhead and this shows an open partial nephrectomy And a lot of the issues that you were talking about with dr. Chung Become relevant here. So The kidney's job is to filter blood if we're going to cut into the kidney We worry about blood loss and we have to do something to prevent it This is very similar to plumbing, right? If you're going to change a pipe or You know a toilet in your house you turn the water off to your house, right? So that you don't have this huge mess when you open up a pipe same thing that goes on when we want to cut into a kidney It's fancy plumbing So what we have here is a clamp That's squeezing the kidney So that some of the kidney still has blood flow going to it But we basically turned off the circulation to the part of the kidney that we want to work on And then with a knife we can literally carve the area that has a tumor Out from the rest of the kidney And so this is a process that is meticulous and very stepwise And this is obviously what we do in an open surgery and like dr. Chung said more and more of this surgery is being done robotically But these give you a nice picture of what the inside of the kidney looks like And how we can sew the vessels closed cut out a tumor feel confident that we're getting all of the tumor out And at the same time save some of the kidney Function by saving some of the kidney the mass And we have fancy things like this is an argon laser that we can use to cauterize the surface of a kidney And do other things to make sure that we don't increase the risk of bleeding But this is a more technically challenging operation than taking the whole kidney out Taking the whole kidney out To get back to plumbing is three pipes. There's blood flow going in there's blood flow coming out and there's their urine going down to the bladder And if you tie off those three pipes, there's nothing else attached to the kidney the kidney can come out of the patient To do this partial nephrectomy it's more involved because we worry about blood loss and we worry about bleeding from that raw surface of the kidney afterwards And because it's a more technically challenging surgery people weren't doing this very often until we had a reason to do it And this reason of saving as much kidney function as we can has really been what's Been driving this this field And so after we do all of our maneuvers to cut out the tumor We can put some fancy things on the surface to try to prevent it from bleeding We put our stitches in and then we can close the patient and be done with the operation And so now you've kind of seen videos from the robotic angle as well as the open surgery angle I wanted to make one comment because someone talked about maybe a surgeon being in india Doing the procedure right with the robotic surgery and this this idea that maybe robotic surgery is misnamed Well, one of the interesting since we're talking about history of surgery one of the interesting things is darpa The defense department Funded the initial development of the robotic surgery platform here at stanford So the actual precursor to intuitive the company came from stanford and then went to the stanford research institute And it was funded by darpa as a way to have battlefield surgery So that the surgeon could be removed from the battlefield But the actual surgery could be done as quickly as possible for somebody who was injured And so it was really this idea of remote surgery the idea that maybe you could be in india and doing the operation that would that And there have been cases where there's been transatlantic and trans Pacific surgeries done The trick is you still need someone in the operating room with the patient and if something goes technically wrong You have to be able to do the surgery yourself. So it's never really developed as this remote surgical platform So instead we're 10 feet removed from the patient sitting in the corner of the room at our at our console doing the robotic surgery But all of this is really designed to facilitate doing this partial nephrectomy procedure to save kidney function All right, so I'll I'll share with you some some outcomes and some discussion about who gets a partial nephrectomy nowadays And what that means for their kidney function and these are all going to be data from the va So my practice is at the va And one of the very nice attractive things about doing research for the va is you have this large integrated healthcare system It's nationwide. So it's not going to be specific to what happens to patients in california This is over the whole country And people that use the va tend to stay in the va. So when we have kidney function measurements We can follow them for many years after surgery and know what happens to these patients So we looked at about 14,000 Surgeries in the va more than 4,000 partial nephrectomies more than 9,000 radical nephrectomies And our first question was well, who gets a partial nephrectomy? And I'm going to summarize these charts. I don't expect you to be reading it from where you're sitting seated But in the top left, that's the trend For the use of partial nephrectomy and you can see that it's going up more and more patients are getting partial nephrectomy And that trend is true in the va and it's true in the united states Basically anywhere you look that there's increasing numbers of partial nephrectomies that are being performed And if you think about who should get a partial nephrectomy You would think that the people that have diminished kidney function That are most vulnerable to having a kidney removed would be the ones to get a partial nephrectomy And what we found is that's not entirely the case So the bottom left Is the trend for people who gets a partial nephrectomy based on how good is your kidney function before the surgery And you can see that the group that's really had this rise this increased use of partial nephrectomy Is the blue line on the top, which is the people with the best kidney function to start with So what we have here is if I can extract extrapolate from this data is that we have a technically challenging operation That's being used more That maybe surgeons are are hesitant to do on older and sicker patients And I feel like that is As a result we're leaving some patients behind that we're not offering this benefit of a partial nephrectomy to all the patients that we possibly could It's not to say that we should be doing a partial nephrectomy for everyone. It's not a one size fits all There was a question earlier about how do you decide partial nephrectomy versus radical nephrectomy And there are factors about how big the tumor is Where it's located in the kidney how close it is to blood vessels and to other things That may make a partial nephrectomy very challenging and maybe unsafe But when we can offer it, I think we should offer it and we should be offering it to the people who need it the most And so that kind of idea that maybe this increased use is really helping the patients that are the healthiest going into surgery You can kind of see here on the right figure And so the yellow goldish line Is your chance of getting a partial nephrectomy? And when we first started looking back in 2002 when there were fewer cases being done They were really being done for people who needed it the most these people with poor kidney function And then about 2004 they started to flip and now the people patients with the poorest kidney function They're getting more partial nephrectomies than they were a decade ago But the other groups have kind of outpaced them in terms of the use of partial nephrectomy All right, so getting back to the va and how these patients do in the long term So we had these 14 000 surgeries And we were able to link it to almost a half a million blood tests of creatinine, which is our blood test to measure kidney function And so we can look long term At how the kidney function does over time And that's shown here in this plot where the red Line is the average kidney function for patients who had a partial nephrectomy And the blue line is the average kidney function for people who had a radical nephrectomy and this is after surgery So you can see the red line is higher than the blue in other words partial nephrectomy saves some kidney function And if you have a radical nephrectomy you have lower kidney function afterwards But gets back to this idea that we saw from that first paper the 1991 paper in the new england journal Which is the kidney function over time looks pretty darn stable And so there is this idea that will after surgery if we do a partial nephrectomy will save some kidney function And we don't expect that it's going to accelerate any kind of decline in kidney function over time And the other question that we wanted to ask is When do patients progress to have chronic kidney disease after surgery? So if you are in a group that does develop kidney problems after surgery When does that happen? Does that happen right after surgery? Does it happen five years down the road? 10 years down the road and what we found is it happens right after surgery So the average time to chronic kidney disease if you were going to have it Is five months. So it's in the first half a year after surgery We know if there's going to be a problem with kidney function and after that it's pretty rare To have somebody progress to have kidney problems So if you've had kidney surgery we monitor your kidney function over time we check it every year But the chance that you progress to have worse kidney function over time is actually pretty low After you've made it through that first year. So that's good And these graphs here on the bottom these are just the number of months And patients that had this progression. So of the 8% of our cohort in the VA that progressed You can see it's almost all within that first year. Yes Ah great And this is a tricky one So when you have that blood test you'll have a creatinine blood test Creatinine is a protein that's made in your muscle That normally has turnover. So your muscles doing their normal thing will leak creatinine into your blood supply and your kidney's job is to filter it out So if your kidney is doing a good job, you'll have a low creatinine Because it's filtering it out and putting it in the urine and as you have worsening kidney function that creatinine blood test will go up So then they take that creatinine blood test and they have a formula To convert it to something called the gfr the glomerular filtration rate And that is based on your age your race your sex and that estimates how well your kidneys are filtering and so They then take that gfr and they have categories. So if you're above 60, they say you're normal or near normal That's good And as you get down to less than 15 Your end stage renal disease you're at risk of something like needing dialysis or a transplant And so that's the definition and for this study We were asking how many people got to a gfr less than 30 If they started below so that we interpreted as being significant kidney disease And we also looked at people who started with really good kidney function at the beginning and how often they got to a gfr less than 45 So those were our definitions But these are things that are different and if you look at different papers people will define kidney disease differently And it brings up this whole idea of Is a chronic kidney disease measurement a gfr of 45 after surgery is that really a disease if it's going to be stable And then maybe this isn't we were mislabeling it as a disease It's just the way that your kidneys work afterwards And if we are careful and you don't progress it may never affect your quality of life when you eat anything else That's true They're separate by a little hesitant to say no correlation because what we do see is that people that are on dialysis For other reasons so before surgery Actually do have a slightly higher risk of kidney cancer And we don't know if that's because we're taking more pictures of their kidneys and they're You know they're interacting with the health care system more so we find it more Uh, but we do think that there is a link at least from that direction If you have kidney disease to start with you may be at higher risk of kidney cancer But I don't see it going the other way Yeah, if that makes sense Part of the part of the kidney How much can you how much do you take right where do you get to the point where you say I might take the whole thing Right and the other question is Tell them It doesn't retain To our radical doesn't retain to the size of the opening So I mean whether you take A radical is just taking the whole kidney Correct correct right right right Correct correct correct So the first question was you know how much kidney can you take with a partial nephrectomy Before you just decide to take the whole thing out or what does partial nephrectomy really mean in terms of how much kidney you're taken out So the way I think about that is these kidney tumors often grow And they push out on the kidney So the normal kidney kind of gets pushed out of the way as this tumor grows And because we only take a small margin of normal kidney around that tumor A typical partial nephrectomy doesn't take that much kidney mass out So it may take 5% or 10% of the mass of the kidney if we're taking a tumor that's relatively small The bigger the tumor the more kidney we take out. That's true And there is a point where you say why are we doing this riskier surgery if we're only leaving 10% of the kidney behind But for the most part we can leave patients with 50% or 75% of their mass kidney mass After a partial nephrectomy in almost all cases So we this is really talking about trying to leave the majority of the kidney behind if we can And obviously there are other factors if you start with bad kidney function Your surgeon is going to be more aggressive about trying to preserve the kidney if they can And then that second question is you know, it does a radical nephrectomy Is it any different if you're doing it laparoscopically or robotically through small incisions or through a big incision? And it's the same That term really just refers to taking the whole kidney out part. That's part one Part two is if there are any lymph nodes removing those at the same time And so the surgery is the same no matter which approach what they do on the inside of the patient You know, whether it's with the robot or the open So can this is oh, sorry Yes So we can do that. We don't always do that So the proof is in the pudding so to speak after surgery We can look at your blood test and we can do those same measurements to estimate your gfr Back from the creatinine blood test But if you have two kidneys Then it may not be possible to know how much your left kidney is contributing to that number versus your right And so the way that they can get to that information Is there are nuclear medicine scans sometimes they'll be called renal scans Where they'll give you a radioactive tracer and they'll take pictures of the kidney and they'll say okay This kidney filters out this much of the tracer this kidney filters out another so they can give you a split function 65 percent 35 percent numbers like that with the renal scan And the other way to do it that's kind of the poor man's estimate of that is you can actually measure the size of the kidney So how much kidney is left on a CAT scan or some other test that you have after surgery? And that can give you a decent approximation of how much each kidney is working But there are ways to do it, but we don't always feel like we need to if your blood tests are looking okay After surgery then there may not be anything we would do different so we may not order that renal scan test on everybody Yes, I mean yes, yes, yes So the answer to both is yes So the staging for kidney cancer First started in the 50s and 60s And at that time we didn't have fancy CAT scans in MRIs And so the way that you staged kidney cancer was you did an operation And what you saw during the operation was the information that you used to give the stage So you can say this tumor was only in the kidney or it had spread to the things next to the kidney There were lymph nodes involved and that's the way you would know And so the first staging system for kidney cancer was exactly that what do we find after surgery? And over time as imaging has gotten better. We've adapted that same approach to what we see on the pictures Whether or not you can have surgery So stage one if you can imagine is going to and so I'll back up a little bit to hopefully explain things there are Different categories for the staging system So you may hear things like TNM the tumor The nodes and metastases And that's a common framework for staging any cancer And so for kidney cancer, there's a T stage based on the size of the tumor So it's T1a if it's less than four centimeters It's T1b if it's four to seven T2a is seven to ten more than ten centimeters is T2b So that's the idea of these breakdowns of staging And then when you when you hear people talk about overall staging for cancer like I have stage four cancer What that usually means is it brings together those TNM different categories to say that Stage four means that it's outside of the organ where it started So it's spread and stage one and two usually mean that it's in the organ where it started to different degrees And so stage one kidney cancer will be the small tumors that are only in the kidney and stage four means that it's spread outside of the kidney Yes Right Would you say that the original staging was incorrect? Yeah, it has to be But this is one of the things that kidney cancer does that has kind of evaded us Just like it's evaded your body's ability to clear cancer kidney cancer can sometimes be dormant and come back Years after the surgery with no signs of cancer in between So kidney cancer can do these things that we don't fully understand and we don't know where those cancer cells are Hiding but they were there before So somehow in that case where somebody had a stage two cancer They had surgery and it comes back years later. The stage was wrong We just didn't have a way to know that the stage was wrong at the initial time if that makes any sense So there are a percentage of patients where just like you said, we do a surgery. We think that we got it all That still will have the cancer come back And that's why even when we think we got it all we'll do those annual follow-ups We'll do lab tests and imaging as a way to as a surveillance strategy so that if it does come back We know about it as soon as possible. All right, so I'm gonna I'm gonna wrap up here So getting back to the pictures from Cassini In the past and this is not This didn't pass this is 20 years ago The vast majority of patients would have their whole kidney removed and everybody was treated the same if you had something seen in your kidney Whether it would look like a complex cyst if it looked like a tumor it didn't matter The the approach was the same and that was that we'd take the whole kidney out And we have increasing numbers of approaches now of things that we can do And one of our motivating factors is to try to save kidney function wherever possible So now in the future we're going to be doing more and more partial nephrectomies whenever we can Dr. Chung mentioned ablation. So that's another strategy that saves kidney Function if we can just treat the one area of the kidney by freezing it or heating it We're observing more and more patients So many patients that have a small mass that we think is a kidney cancer We may watch it before we decide to do a surgery. That's the ultimate way to preserve kidney function Is just you don't kick the beehive. You don't go in there and mess with the kidney unless you have to And then I'd say that there are future things that I think will happen That may also be a way to preserve kidney function and one of those that I think has made a bit of a resurgence There's no long-term data for this yet Is doing radiation for tumors that are in the kidney where in the past that was not effective But with some of the new ways to do radiation like cyber knife one of the things that Was developed here at stanford. We may be able to radiate That section of the kidney and kill the cancer and avoid the need for surgery And so in the future there, I think we're going to have an increasing number of tools in our toolkit That we can use to try to preserve kidney function. Yes It's very close. So if I what I tell patients, let's say they The example is a two centimeter mass is ablation as good as surgery I tell patients that the success rate for a two centimeter tumor is roughly 90 to 95 percent Being able to get it all in one treatment and with surgery. It's 98 to 99 percent If you're 85 and you get diagnosed with a two centimeter mass and you want to do something about it that 90 percent 95 success rate starts looking really good because then you avoid a general anesthesia You avoid a long operation Much quicker recovery and if you're 35 That difference between 98 percent and 90 percent may be meaningful enough that you would take the risks of surgery So those are kind of extreme examples And the other thing to think about is when you're freezing. So cryo ablation or you're heating a tumor. So microwave ablation What you're really trying to do is get the temperature in that part of the kidney to the proper temperature Cold enough or hot enough that you kill the tumor And so the location in the kidney matters if you're near a blood vessel Then you've got Body temperature 98 degree blood running right by that tumor. You may not be able to freeze it Cold enough to get it all and so the location of the tumor for some of these ablation strategies Matters and if the tumor is right next to the ureter You may not want to cook that portion of the kidney because you worry about damaging The ureter which is right next to it and so all of these things kind of play into that Risk of what is the likelihood that we can treat you with one treatment and get all of a two centimeter tumor ablated But roughly it's actually pretty good and as the tumor starts to get bigger That's when those numbers drop off because it's harder to get that much of the kidney to that correct temperature For the ablation, but that's exactly what we think about with all of those questions So again, I appreciate your time and uh, I'm glad that you all could make it and I'm happy to take any questions Yes, sir Yes Yes, so I just There seems to be very little additional right right right so the question is when When do we're going to be able to regenerate a kidney to make an artificial kidney instead of doing a transplant Where you wait for a donor we that we could manufacture a kidney and preserve kidney function in that way So I was actually just this year Asked to be what they called a provoker Where I followed dr. Atala the esteemed researcher who's done all of this work on stem cell and organ generation And my lead slide was a picture from the Jetsons Where I said dr. Atala, where is my flying car right? This was you know the 1940s 1950s they had flying cars and cartoons then I want my flying car now Why can't we have these kidneys? And the challenge has been that you can do these things on small scales and have partial success And these things become far more complicated when you're going to put it back into a complex person Or when you're going to try to do this at scale where we're going to generate kidneys for lots of people And so these are where all these problems are they've done some of this work But the trials where they've made new organs or new, you know, blood vessels and put them into patients These are usually on the order of five to ten patients in the trial And we're very early on so even though he can stand at a ted doc and and show you what he what can be made This is still I still think we're in the Jetsons future Area era where it's it's unfortunately not as quick as we want it to be I would guess probably 20 I mean this is this is a ways away. Thank you so much. John. Thank you for your time I think we are going to take like a 15 minute break You know, there are restrooms at both ends if you want to go ahead and use them We are a little bit behind, but I'm sure we'll be able to make up time as we go along