 Okay, without further ado, I'd like to introduce my colleague, Serena Matine, who's going to talk to us about options for management of the small renal mass. Well, good morning, everybody. And thank you, Chris, and thanks for all the work you do with the Kidney Cancer Association. So I'll try to take less than my lot of 30 minutes and speak to you about options for managing the small renal mass. So things have changed a lot in the spectrum of options that we have for treating small renal tumors. It used to be that we did largely laparoscopic procedures and take out whole kidneys even for smaller tumors, but that really is not an option that we look at very frequently if at all. And in fact, more often than not, even when there's multiple tumors, we'll consider a partial nephrectomy. So really with the focus of what I'm gonna talk about today is gonna start with this kidney sparing operation, which is our standard. We'll talk about the robotic approach or laparoscopic approach, ablation with radiofrequency or cryoblation, and then also active surveillance, which is what I'll close with. So why are we so interested in preserving kidneys? All the options I just pointed out to you for treatment of the small renal mass are all kidney sparing. Well, what we've learned a lot over the past 20 years is that the cancer outcomes are the same when radical or partial nephrectomy is done. There is no higher risk of recurrence after we preserve the kidney. And so as a benefit, you not only get the same cancer outcome, but you have the benefit of more kidney tissue in your body. Also keeping in mind that depending on the scenario, about a third of these small tumors are gonna be benign. Now, if you're sitting in the audience, this probably does not apply to you. As many of you have been diagnosed with kidney cancer, but you may have friends or family that come to you in terms of their own scenario. And so when tumors are small, and that we classify that as less than three centimeters, maybe under four centimeters, depending on where in the world you are, in those cases, a large proportion of these may be actually benign. The other issue that we've become very cognizant about in the past 10 to 15 years is this concern about chronic kidney disease. And basically that means reduced kidney function. And what we find is that this can be a source of additional problems as we get older. Unfortunately, the kidneys don't regenerate like the liver does. Chris Woods and Mines and Jose Karam's life would be so much easier if kidneys did, but unfortunately they don't. And in addition, we lose kidney function as we get older. We're born with tremendously more kidney function than we need, but we lose it as we get older. And then when you add things like hypertension and diabetes, then that loss is accelerated with age. This is a very large, there are actually two large population studies that were done several years ago. And just the point of this being with this bar graph that you see is the percent of patients with chronic kidney disease in terms of what happens with age, and with increasing age, you can see that the incidence of reduced kidney function goes up. And so one of the things we have to be cognizant of is this issue of competing risks when we're looking at a patient who has a mass that may not be an immediate threat to their life. What do I mean by competing risks? Well, you basically have different variables that are threatening your life. One's pulling you one way, the other one is pulling you the other way. So the tumor on one hand could be a cancer, it could grow, it could grow to the point where it could metastasize and become incurable. It can also grow to the point where it destroys kidney function. On the other hand, the patient may have some comorbidities, some health issues that are risky in terms of what we do to intervene. It could be also that these comorbidities, these health risks, these health conditions may propose enough of a risk that the patient's survival is already shortened by them and not so much by a small tumor in the kidney. And the fact that there may be some baseline reduction of kidney function that could be affected by any intervention that we perform. So these are the competing risks which we're gonna come back to. But I wanna clarify this issue a little bit more and talk to you about how great this impact can be. Because whenever we hear the word cancer, there is a certain level of anxiety that bubbles up and overtakes everything else. Yet trying to convince an older, very obese patient who maybe smokes and has diabetes and hypertension that this risk plays such a minor role compared to their other baseline risks. That's a very hard thing to convince patients because the word cancer creates this anxiety and high blood pressure. You hear it in the news all the time. You kind of ignore it. Obesity, you kind of ignore. You don't think about all the little daily decisions that affect that, but they do. And that's what this graph is gonna, I'm gonna try to impress on you with this graph. This is a study that was done that looked at comorbidity scale. This is called the Charleston score. So basically the score of zero basically means a perfectly healthy person. A score of one or two means that they have one or two medical conditions. Let's say diabetes and high blood pressure. And then three or more, these patients have a fair number of medical comorbidities. And then here on this side you have the size of the renal tumor. The blue indicates the risk of dying from a non-cancer death. How much blue do you see versus red? Tremendously more. And especially when you look at the small tumors and even medium-sized tumors up to seven centimeters, especially in those who have multiple medical conditions, you can see that the risk of kidney cancer death is dwarfed by the risk of death from non-cancer causes, okay? So again, this may not be applicable to you, but for friends and family or people that you know who present with a small renal mass, it's a different scenario. And so these are one of the things that we have to keep in mind as we're counseling patients. So now on to talk about these different treatment options because now we have a context for talking about why we may offer different options to different patients. So the partial nephrectomy we consider the gold standard. It's the reference standard that we measure everything else by. When we did a large-scale study at the American Neurological Association about six years ago, what we found looking at publications with thousands of patients spanning decades is that it's got really good results, 98% efficacy at greater than five years. And what we've basically concluded is that it's an excellent option and it remains the single number one option for small renal tumors. Now, things have evolved with these other options that I'm gonna talk to you about, the other ones. And so we do still do this quite a bit and particularly we look at it whenever we want to do any complex type of resections or if the patient has really poorly functioning kidneys and we really wanna be, for example, very fast. And one of the things, one of the other misconceptions is basically what we used to do, which is these huge incisions back in the day, to really what we do now, which are really these mini flank incisions. And so the truth is, if I really wanted to convince a patient to have something minimally invasive done, I would try to overemphasize the incision, but the truth is that we really don't. This would also, the other thing that I'll show you and I'll show you a couple of more specimens. This is actually a specimen from a partial that I did about 12 years ago. Shows you the classic clear cell renal cell carcinoma. There's a hefty margin here. What you'll notice over time is that this margin has gotten smaller and smaller. And basically what we found is that the size of the margin doesn't really matter like it does with some other cancers as long as that margin is negative. In fact, there are some practitioners out there that routinely just shell these out and leave basically a millimeter or less of a margin. And even those cases, the patients do fine. Just sort of as an aside there. So here's an example of situations where we might do an open partial. This is a patient that was referred to me. Has, it was born with a poorly functioning left kidney. You can see it's quite small compared to the right kidney. There's also happens to be a large tumor in the right kidney. And it's in a tough spot. This is the renal artery, the main artery to the kidney. And basically this patient was not felt to have a salvageable kidney. And as with many cases that we get sent here, we looked at it, we thought we would be able to do it. And in fact, what we did was partial nephrectomy. Here's the healthy part of the kidney. This is the ureter tube that carries urine down. The tumor is right here. This is a hefty margin. Again, if I had to do this case over again, I probably wouldn't even leave this much margin. And then this is the kidney after the tumor's been resected. And then basically we have to reconstruct these areas of cut across blood vessels, of cut across the urinary collecting system. And so we need to reconstruct all that and then reestablish the blood flow to the kidney. Now as it turns out, that tumor was benign. Now I'm not sure we would have done anything differently had we known that ahead of time. It was a pretty big tumor. But the bottom line is the patient did beautifully. No dialysis and kidney function remain completely stable. Another similar situation of a patient will highly desire preservation of the kidney. And was sent to us for this consideration in a very difficult location. It's completely buried within the kidney. The yellow arrow points to the urinary collecting system highlighted in white here. The tumor is the gray part outlined by the blue arrows and here's normal kidney. Here's another view. Tumor, you can see it's surrounded by the urinary collecting system. And in this picture, the red arrows indicate are the arteries that are surrounding the tumor. So quite complex. And basically some of the shots from the operation showing what we do is do a very careful ultrasound examination of the kidney. This way we could basically it's like X-ray eyes. You can look inside the kidney. See exactly where the tumor is. Even though we have absolutely no surface landmarks here. But with ultrasound we can do a lot more than we could before in the days of ultrasound. Here's that urinary collecting system. You can see it's very similar to that MRI that I showed earlier where it's straddling the tumor. This is the edge of the tumor that we're seeing as we're dissecting it out. I've stopped the blood supply to the kidney so you can see the kidney is pale now. Cutting across the normal renal tissue. We can actually at every time we make a little cut in the normal kidney assess whether we can go closer or further. And that's one of the advantages of doing it by stopping the blood supply. Which is that we can be very precise every second of the operation. And make adjustments as we need to. Here's the tumor with some margin of normal kidney being lifted up. Here's some of the blood vessels and other things that we've divided off and tied off. But this is basically the kidney. And then after we reconstruct the kidney together then we reestablished the blood supply and you can see it's nicely pinked up. This is what the specimen looks like. You can see there's a hefty margin here. This is basically the tissue overlying the tumor. It really was not preservable. And then the rest of it you can see we kind of shelled out. And then left a margin some other places. Out of that patient do. Great. Six years later this is her CT scan. No recurrence. Beautifully functioning kidney. So a partial nephrectomy is an excellent option. Especially in someone who's got the technical expertise to be able to do it. Being able to do it minimally invasively adds a benefit in the short term recovery for the patient. Because that flank incision is small as we've been able to make it. It's still not the nicest incision for patients and there can be some issues with it. So we used to do laparoscopic partial nephrectomy. We've gone away from that and now we do it robotically which is just another way of doing laparoscopic surgery for those of you who are not familiar. Basically it's two components. There's a console where the surgeon sits into and looks into a stereoscopic view. It's a three dimensional view. The surgeon's hands control these instruments. And these master's as we call them, flight controls if you will, control these instruments that are attached to the actual robot. So this robot is wheeled up to the patient that these arms are put in through these ports. And then what one can see is the tips of the instruments working and they basically have seven degrees of motion. It's basically like having a mini wrist inside. So it gives us a lot more dexterity. And we can use different instruments, needle drivers, scissors, cotter instruments, graspers, et cetera. So this is an example of a partial nephrectomy. What we're doing here is stopping the blood supply to the kidney. We've already exposed the kidney, exposed the tumor, done the ultrasound. And now we're ready to do the actual partial removal. So again, we're gonna stop the blood supply. These are just temporary clamps that we put on. This is fat that's covering the tumor. You don't even see the tumor because I've left a bunch of fat covering the tumor. It's sort of insulation, if you will, and it allows me to grasp things without even touching the tumor. We're cutting into the normal kidney tissue. This is the robotic scissors that I'm controlling. This is the grasper that I'm controlling. Down here is a suction instrument that's being used by my assistant. For the little bit of blood that oozes, you'll suction that up. Here's the margin, looks perfectly healthy. I'm looking at it as I'm cutting it out. I'm happy with it, we look at it. Everybody decides that looks fine. And then basically we suture these areas. If we don't, it's gonna bleed or leak urine. So we suture all this up and when we're done, we then take those clamps off and reestablish the blood supply to the kidney. And this is what some of these specimens look like. Part of the other reason I wanna put this on, it's one of the things that we kind of forget to talk about at these conferences, but patients ask us all the time. We come out, we talk to the family and the first question we get is, Doc, what did it look like? Well, the truth is we don't know most of the time. What we see is this, because the tumors are covered by normal renal tissue usually. We try to keep them covered. As I told you, we keep it covered with fat whenever we can. So this is what it may look like to us, but when it goes to the pathologist who starts processing it, one of the first things they do is measure it. They cover it in ink. They then start slicing it up. Then they start seeing what's on the inside. Usually they're doing that while we're talking to the family or sometime after. So this is what a typical clear cell renal cell carcinoma looks like. This canary yellow color. This is a partial nephrectomy I did. Again, what you see is sort of all normal tissue surrounding it, but when the pathologist cuts into it, they see this. They have to do microscopic studies. And then what we find is that it's a papillary RCC. And then this is an anchocytoma. And the reason I put this in is because even when sometimes we see the edges of it, we can't really tell. It's not that we're lying to the patient or we don't want them to know. We really can't tell with our eyesight. Because as you can see, this and this look very similar. And what the pathologist has to do is we do a pretty careful exam under the microscope. Sometimes they have to do chemical stains, six or eight or 12 different chemical stains to actually figure out if it's cancer or not. Or what kind of cancer. That's besides the point. Just a couple of tidbits for you. So one of the things that we get referred a lot about are these tumors that are in the kidney high limits in a very difficult location in the kidney. And these kidneys are not thought to be salvageable. So a lot of times in the community, they may just be removed. And what we can find is that quite often we can do it. So here's an example of a tumor immediately adjacent to the major blood vessels of the kidney and the urinary collecting system here in white. Several different examples of these locations. Every single case, we were able to do a partial nephrectomy, negative margins, salvage of the kidney, okay? And in many cases we did these minimally invasively. So it is possible to do it, but what it requires is a knowledge of the anatomy and a thorough knowledge of the technical strategy needed to approach these. This is an example of these in what we call Heiler micro dissection. It basically means being able to do vascular, micro vascular surgery to the kidney before we actually remove the tumor. Here's a tumor in the upper part of the left kidney. The blue indicates the vein to the kidney, which is crossing right over the tumor. There's a couple of arteries right next to the tumor. And then here's the urinary system. This film is sped up, just so I didn't have to edit it very much. So it's going at about twice the speed. Here's that vein, which we see here. There's a branch of it going up to the kidney. I'm gonna isolate it. We're gonna clip it, divide it. And what that does is unhinges, it starts to unhinge the tumor away from the normal part of the kidney. And instead of just having to blindly cut through these things, we can do it upfront and get them out of the way and do a much more precise resection and in a way that also preserves the kidney in a much better way. Once I've done as much as I can, then I clamp the vessels and then we start the actual resection and then we'll suture it up. Now I'm not gonna do that. I'm not gonna show all that just for the interest of time. The time we had the kidney clamp was 22 minutes, 22 minutes, perfectly respectable, minimal blood loss. It turned out to be a fairly aggressive type of kidney cancer with negative margins. Patient did fine on follow-up. This is another example and I'll just show a few seconds of it. But same idea where we do this heiler micro dissection, this sort of vascular dissection on the kidney. And you can see in large part, I've been able to actually separate this tumor before even getting to the formal resection part. And you can see it's hard to tell what's going on. This is covered by fat. There's normal kidney covering a lot of this tumor. You can't really tell what it is. 14 minutes is schemia time, two days in the hospital, negative margins. It was a clear cell RCC. So that summarizes the options in terms of partial nephrectomy. It's open and robotic. So I'll speak with you next in the next few slides about ablation. So this is basically when we use energy to kill the cancer without removing it. And pretty much any form of energy you can think of has been tried. Cold, heat, electrical. There's a newer one, non-thermal electrical called electroporation. You may start hearing about it. Everybody's gonna get very excited about it and then they're not going to. Only because I actually did some of the work on this about four years ago. And decided it was not something that was worth testing. But we'll let everybody else investigate also. Photodynamic therapy, radiation, all these things have been tried. The fact is, what's really the most standard of all these options is cryoablation and radiofrequency ablation. And that's what I'll briefly talk to you about. Cryoablation basically means freezing the tumor. We do it either percutaneously, right through the skin using a CT scan, or we can do it laparoscopically. Most of what we do these days is percutaneous because it's basically much nicer for the patient if they're able to approach it that way. We puncture the tumor with these specialized probes. And then when you turn on the machine, it creates this ice ball. And it gets really cold. And you have to get it really cold, really fast in order to effectively kill that tissue. And we actually do that twice. And then basically the patient recovers usually goes home the next day. This is what it looks like before surgery. Here's a kidney. Here's the tumor in the left kidney. One month after, you see it's kind of bigger, but the key here is that there's no blood flow. All the white you see in the kidney is actually blood flow to the healthy parts of the kidney, but there's no blood flow. And it looks bigger because we treated a larger area than the tumor in order to make sure we get it all. We get a margin, same as we do with surgery. But then over time it shrinks. And then at six months, you can see that it's shrunk down even more. And more importantly, there's no blood flow. Radiofrequency ablation instead of using cold uses heat. Again, we can do it percutaneously or laparoscopically. And just like cryoblation, it's really ideal for the smaller tumors. This shows the different manufacturers and the configurations of their probes. Here's what it looks like when we do it percutaneously. Here's a small tumor in a patient with a solitary kidney. The patient now is laying on their belly. And then through the back, one of our colleagues in interventional radiology pushes this specialized probe right through the skin, through the muscle of the back, into the tumor. The ablation is caused right at the tip here. Then afterwards at one month, again we see area without blood flow that over time shrinks. What we found when we did our analysis with the AUA in terms of ablation is that it was pretty effective, but not as good as surgery. So I showed you open partial was 98% effective. This is only 88 to 90%. And that was in the short term. There was no five year follow up at the time. So results don't get better with time, they get worse. So it's something to keep in mind. And it's a reason why we don't offer this to everybody. Because it is less invasive, you know, patients leave the next day, recovery's pretty quick. Why wouldn't we? That's the reason why. So we do reserve this for patients who present a risk, either they're elderly or they're high surgical or anesthetic risk, or for the patient who basically refuses the standard of surgery. But there's a little bit of a ball and chain in the sense that you can't just do it and forget about it. We do have to do a biopsy first to make sure that we're actually treating cancer and that we know what happens down the line should it not do the things we expect it to do. We do imaging here at our center because an outside radiologist doesn't know what's going on. They read that as basically, they read it erroneously as progression of cancer. And sometimes we even do biopsies afterward. One of the things I wanna spend just a couple of minutes talking about is this very interesting concept of what happens when we treat tumors and leave them there for the body to process. On a separate track, what we've noticed and known for many, many years is that white blood cells, our immune cells actually are attracted to kidney cancer. They go there, they recognize it. But once they get there, they're totally incompetent. And what we think is going on is that the cancer basically makes those immune cells unable to function. They're there and you can see them on the slide. And the question and something that many people have been interested in is, can you activate these immune cells to actually start fighting the cancer? So what we've noticed when we do ablation, and we've seen this happen twice in our patient population, is that tumors can regress after ablation. It's a rare event. We don't do it for that reason. We don't do it for the reason of getting regression, but we've noticed that it happens. There's a patient with a large tumor in the kidney. They had a metastasis in their bone. Because that was causing a lot of pain, we treated that first. Actually, I think this was Eric Yonash's patient. And then when I saw the patient right before surgery, I said, you know what, it's been a couple of months since this scan. Let's get another CT scan, make sure there's no surprises. There was a surprise, but it was actually a good one, which is that the tumor had shrank and there was no blood flow to it. Kind of weird, didn't expect it. We went ahead and did the surgery. What we find is that there was absolutely no viable cancer in the kidney. Patient did have a biopsy before all this that showed viable cancer in that kidney. So something happened. And what we see is that there's a tremendous amount of immune cells within the dead cancer. Now, there's some other data to support this concept. And especially now that we have drugs that can activate the immune cells, if you will. What they're really, they're doing is removing that inhibition that the cancer does. They're able to block that. These are called checkpoint inhibitors. I think we're gonna be hearing about them in a couple of lectures. So I'm not gonna go into it very much, but this is an animal study that combined one of these new drugs, anti-CTLA-4, with cryoablation. And when you combine the two, the cryoablation and this immune checkpoint inhibitor, you can see that the tumor growth in mice is significantly slowed down. And that these mice also do better in terms of survival. Now, we've cured a lot of mice of kidney cancer. We haven't done the same with humans. And so one of the things we are getting ready to do and to open up this trial, it's actually approved by our IRB. We are just waiting for the sort of logistics of the trial to get going, is this concept of taking patients with clear cell RCC, performing ablation of a metastatic site. And the idea there is that we're priming the immune system, we're getting it revved up, okay? And then within a day or two, we give them this anti-CTLA-4 drug that basically takes the brakes off the immune system. Say, sir, you're revving up the engine, then taking off the brakes. And then what we're hoping to do is basically to effectively activate the immune cells to start fighting the cancer. We'll remove the kidney afterward, which has basically so far been untreated except for the drug. And then if we see a benefit in terms of patients, how they're doing, then we can actually continue the drug therapy. So we're very excited about this. And we're hoping it'll be opened up within the next couple of months. I'm gonna close up with active surveillance of small tumors, something that we've been very interested in and basically a lot of data suggesting that this is a safe thing to do for the very small renal mass, particularly in elderly patients. This shows data that we looked at back in 2012, when we had about 246 patients in our registry. This is a waterfall graph. Basically it's the change in size of the tumor over the course of 30 months. This means that some tumors shrank. This means that some tumors didn't change at all. This shows you that some tumors grew a little bit and this shows you that some tumors grew a lot, but not very many of them. Most of them remain fairly stable. And multiple other publications that have shown the same thing that the average growth rate is actually quite small for these small renal tumors. I don't have a lot of the time to go over all of the data with you. So just to summarize on one of my last slides here, that the growth of the tumor doesn't tell us if it is cancerous or benign. A common misconception. Doc, my tumor's growing and must be cancer. Nope. Actually kidney cancers can remain completely stable and we can see the oncocytomas grow. So very interesting as to why or how that happens. For these small renal tumors, the risk of metastatic disease occurring is very, very low, less than 1%. And again, where there's hundreds and hundreds of patients from throughout the United States where that data has been published and supported. We're unlikely to lose the opportunity for doing a kidney sparing operation later. That does not really seem to happen very often. And it's not something we want to offer to a 30 or 40 or 50 year old very healthy patient, but for someone who presents with some competing risks who we have the risk of injuring, then we may want to do this for a while. Chris, how am I doing on time? Okay. I have some slides on biopsy. I can withhold these and basically we can get to them later if we need to. And what I'll do is just summarize by telling you that we have a lot of options. It's been great for us because now what we can really do is individualize patient care, depending on not just the tumor factors and our technology, but also look at the individual patient factors and really try to provide personalized care as much as possible. Thank you. Thank you.