 All right. Let's move on. This is a 57-year-old African American female who again presented with abdominal pain. She has a history of hypertension, sleep apnea. She had a heart attack back in April of 2012. She's never had surgery. Medications include metoprolol. She takes an aspirin. She takes drugs for her cholesterol. Her CT chest is negative and her laboratory studies are all within normal limits. And you can see here she's got a tumor that's basically completely inside the renal parenchyma here. And then she's got another tumor. You would think bilateral tumors are running rampant in Houston, but they're not. Another tumor present here in the left kidney. So first, maybe, Serena, could you just make a comment about the nephrometry score and how we use that and what the value of that is in terms of communicating about the complexity of tumors? Yeah. So the nephrometry score was developed actually by somebody I used to work with, Rob Huzo and his team. So it's a way for us to put a number on how difficult a partial nephrectomy is going to be or basically how complex is this tumor, which is really a great advance. Because up until then it was all description. Well, it's deep in the kidney or it's this big and there was really no way for us to have an objective number that you could translate that we would mean the same thing in Houston as it would in Chicago, as it would in Sri Lanka. So, but now we have that and basically it's a way of looking at tumor size, where the tumor is located in terms of how deep it is in the kidney. So the deeper it is, the harder it is to remove and the higher the risk of complications. For example, how close it is to the urinary collecting system, which you can't really see on these scans. But maybe later if we have some scans that have an excretory view we can show you. But for example, the right side of tumor, maybe Chris can point out with the mouse, it's probably contacting with the urinous collecting. And so that increases the risks of surgery a little bit. And then there's one more. Oh, and also how close it is to the to the hyalum, which is the, if you will, the heart of the kidney, right where all the blood vessels come in. So if you look at those five factors that you assign a number one to three in terms of how difficulty and then you add it up. So if a tumor has a complexity of six, it's not that complex. If it has a complexity of nine, ten, eleven, it's really pretty complex. Cameron, do you want to comment on maybe the role of ablation here? Would you consider ablating one or both of these tumors? I think the both can be done. I mean again, you need to think about the size and the location. So if both of these, they look like they both measure less than four centimeters. They're both on the difficult end of the spectrum. Similar to the nephrometry score, people have tried to establish criteria for ablation. And the same principles apply to ablation. How big is the tumor? Where is it located? How close is it to the center of the kidney? Both of these would have probably high score on that nephrometry score, if you will. But yes, they can be done. All right. Dr. Delacroix, how would this patient be treated in New Orleans? She would get a bilateral partial nephrectomies. Which side first? Left side first. Why? Because it's easier. It's got a lower nephrometry score. We would do a left side and we'd probably attempt that robotically. And then the right side would be an open partial. Okay. Dr. Chapin, how would you approach the patient? I agree. I mean, bilateral partials, I would do the left one first because it's easier. And if I know that I'm safe with the left kidney going to the right kidney, I don't feel as anxious about the difficulty level of the right partial. I would probably do both of these open. I actually wouldn't do these robotic or laparoscopic just because of the bilaterality. If the right kidney did not have a tumor, I might attempt the left one robotically, but that's also a matter of experience. And so the idea of choosing the easy one first would just help me out with that. What do you mean? Why? Nothing scientifically based. Again, it goes back. Surgeon preference. I can't point to. I think it's convention to some degree in the sense that the issue is preserving kidney. And so if you do the easy side, meaning there's confidence that you can preserve the kidney, then you're not putting yourself behind the eight ball when you go to the other side. And if you think there's a higher risk of having to remove that kidney, you know you've got money in the bank with the other side. That's sort of, it's a philosophical thing. It's not scientific really. But that's kind of what it is. It's really setting, I'm talking, saying yourself, but I mean the patient, of course, but trying to set the patient up for success in terms of kidney preservation. How long between operations? I mean I think that's also a point to be made of this complexity in which when you're choosing first. If you were to do the right one first and if you were to have a prolonged urine leak or if you really wanted to be clear of the one side being complete before doing the opposite side, I think your time between surgeries would be lower if you do the easier or less complex kidney first. So therefore if you don't have a prolonged drain and prolonged urine leak and issues that can come with doing a partial, it's more complex. So even if I were to do the left one first and the patient is a 57 year old, could relatively recover quickly, I would probably schedule the right side within four to six weeks. Okay. Of course, Dr. Chapin, we know you never have complications, so that will work out. Dr. Arar, would you ablate both at the same time or would you stage him and if it's so, how would you stage him and what's the time frame? No, we would just stage him. We have treated occasionally bilateral tumors, but if they're very small and they're very easy to access. We do treat these patients under general anesthesia. It helps the procedure. The procedure can be long two to three hours, can be painful during the procedure. Although other centers across the country use moderate sedation without the use of general anesthesia, but I personally would not recommend it. I would stage it and it really doesn't matter. I don't want. Okay. So the patient unfortunately went to an outside hospital and was counseled to undergo a robotic assisted laparoscopic left partial nephrectomy, the quote-unquote easy side, followed by an attempted robotic parcel on the right. The surgeon apparently found the left tumor to be quote more complex and quote at surgery and that actually turned out to be a nine hour case. The pathology came back as unclassified renal cell carcinoma, firm in grade three. All margins were positive. Basically, they just chopped this thing out and all the margins were positive. So and just for the audience, margins means we look to see where we cut to be sure that there's normal tissue there because that implies that the entire tumor was removed. But if we look where we cut and we see cancer, the implication is that cancer is still left behind. So in this particular patient, all the margins were positive, implying that there could still be cancer cells left behind. So her surgeon after this nine hour case said, eh, maybe we'll just watch that right side for a while. Dr. Delacroix, do you agree with that? What would you counsel this patient? A second opinion would be good. And another thing, a nine hour robotic procedure. I mean, there's a point where principles of oncology need to preempt the way in which a procedure is done. If it's a nine hour case, you really need to be thinking about just doing it traditionally, opening the patient and doing what's right for the patient. Because completing this, obviously, robotically has left positive margins in this patient. It's going to be something that we'll have to deal with. So when you look at patients who have positive surgical margins, albeit most of them are microscopic margins, and I'm betting that this was grossly positive. Most patients who have microscopic positive margins after partial effectiveness for small masses will not recur. And you're talking 90 plus percent of them will not recur. So it is safe to watch them. The first thing I would do would be to reimage the patient. As long as I don't see anything in the operative on left kidney where she was operated on, I would go ahead and complete the contralateral kidney and just do a period of surveillance for this side. All right, so the patient comes four months after her left sided surgery, no interval changes in her medical condition, CT negative, labs are within normal limits. There's your repeat imaging. So just for the audience view, you can see here, here's the tumor in the right kidney still sitting there. And this is the area where the partial nephrectomy was performed. If you see that white stuff, that's contrast. That's where they injected the contrast into the vein. And it's excreted by the kidney. So she has what looks like a little bit of a urine leak in the site, where the partial nephrectomy was performed. But there's no obvious tumor present. No obvious tumor. Dr. Karam, what's in the abdominal wall? That nodule on the left side. Oh, this. Yes. That's nothing to worry about. That's a port site. Probably a port site on the robot. Yes. So I would love to see the same type of images that you have on the left, on the right side as well. So you showed the excretory, which is the late phase of the CT on the right side. But it would be nice to see the same view earlier on just to see if there's any enhancing elements or basically to see if there's any viable tumors still left on the operated side. There doesn't appear to be any evidence of viable tumor on the operative side. So in that case, we'll just proceed with the right side of operation. Okay, and that operation would be a right open partial nephrectomy with ultrasound. Okay. Dr. Mateen, what are your thoughts on this? No, I agree. I think, you know, you still want to give it your all for this. I have, you know, great concerns about follow up over the next six to two years, six months to two years and five years really. But no, I think I would I would do an open partial. Also, I'm sure at this point, she probably has no interest in anything robotic anyway. But you know, I think Delacroix, Dr. Delacroix point, you know, the it's nice to be able to do something minimally invasive, but it doesn't trump the need to do the single best cancer operation you can. So that's really takes priority. So are we all in agreement that we would do a right partial nephrectomy? Yeah, what about the left side? What will we do for that? You know, so just to clarify, in terms of positive margins, you know, so microscopic positive margins and kidney cancer seem to have very minimal implications. So if there's like a one millimeter positive margin, you know, those patients seem to do really well. The risk of recurrence seems to be probably close to someone who has a negative margin. Now, in this case, though, there's there, it's probably what we would call grossly positive margins, meaning visibly positive. And that's a totally different situation. Unfortunately, the truth is, there's nothing we can really do. You could go back and take out all of that tissue and not find any cancer. It does not mean that she would not have recurred. You could go in, take all of that tissue, and it does not mean that she, you know, that she that she won't recur. It sounds like I said the same thing, but actually trying to make a different point. But someone with grossly positive margins, he really is at risk for recurrence. And I think it's like a seven fold risk of them developing it and dying from it. So I would I would watch her very carefully. This would not be a case where I would follow with the CT in two or three years. I would be following her much more closely. Any role for just taking out the left kidney and eliminating as a risk? Why don't I give one of the other guys a chance to answer that? I have not not at this point, I mean, I would want to see what happens with the right side to make sure that the partial nephrectomy was successful with negative margins and with preserving of the right kidney. But it is worrisome that the patient has the unclassified type of kidney cancer. Basically, like Dr. Metin mentioned earlier, about 70 or 80% of the kidney cancers are clear cell. And the rest are papillary or chromophobic. Unclassified is probably less than 5%. And when the pathologist says it's unclassified, it means it doesn't fall into the other known categories. And these are typically aggressive tumors for the most part. Okay, so the patient under... Sorry, Chris, but to answer your question, I think this is one of the things that's difficult for patients to accept is the problem with taking out, just going in and taking out everything on the left side is you don't really know what to take out. The scar tissue feels like cancer. You're not going to be able to tell by looking or feeling. And you don't really know how much spread there's been. And then the other thing is, you don't know if... You don't want to make things worse because you don't know where things are or how to differentiate cancer from scar tissue. So the last thing you want to go in is that insult to injured by going in. Does that make sense? I don't know if I'm expressing myself well. But you and I have been there where you've sensed the frustration of the patient wanting to do something and you want to do it, but it's usually not a good idea to do that. Any role for biopsy? Would you try maybe biopsy on that left side? The sampling is going to be a problem. You don't know where to put the needle. What about targeted agents? Dr. Keneer, any role for targeted agents? No, as we said earlier with no. All right, let's move on. It's a funny idea, you know that... I mean really what we're talking about is in terms of agents, I'm sorry, probably being a little overboast, but it's kind of interesting. Don't answer that. You know, you would think when you see a lesion, a metastatic lesion, you would think that if a drug works for that, that it should work better for when it's microscopic and you don't see it, right? I mean, you would think, but it doesn't work that way. Because that's really when you're talking about additional therapy, you're talking about microscopic disease that's cybernating somewhere that we just cannot detect. I mean, that's why patients with breast cancer don't just have surgery or just don't have radiation. They have chemo, radiation, surgery, hormone therapy, because breast cancer does that. It tends to spread very easily and there's microscopic disease, and for them, thankfully, there's agents that work for that. For kidney, there isn't. Why is that? Can you give us a follow-up on what happened to that lady? She underwent a right partial infractomy. There was an unclassified tumor, margins were negative, kidney did fine, and then she's being observed on the left side. And Nazar, why don't you comment on why it is that maybe these targeted agents are not very effective or we believe they're not going to be effective in the setting of micrometastatic disease? Well, you know, because probably there is the way these drugs work is most of these target therapies we're talking about are angiogenesis inhibitors. And it requires a metastatic phenotype with advancing progressive disease where these drugs can work. And maybe when it's still in the primary tumor, the milieu is such that it doesn't really help as much. Although we have seen, you know, your trial, you will probably, I'm sure there will be some cases where you have a trial with a drug that's called Exitinib that you have seen, unlike we saw with the previous target agents, where we didn't really see significant tumor shrinkage of primary tumors in the kidneys with this second generation tyrosine kinase inhibitor, as we call them now. You have seen more than you would have expected with significant shrinkage in maybe two-thirds or three-quarters of the patients. So I think it's the jury is still out. I don't think we can say that these drugs don't work in the adjuvant setting. The trials are out and we will have the results in the next two or three years, at least with the first trial, the largest trial and the short trial. We will see if these drugs do have value in the earlier stage disease than in the advanced stage disease. But you know, this concept of drugs working in a metastatic setting, not working in the earlier stage setting, is not just in kidney cancer. In prostate cancer, for example, chemotherapy works very well for patients with advanced castration-resistant prostate cancer, but when you give them early on, when the patient still has disease in the prostate, they don't work. So that is a concept that is not just for kidney cancer, for many geniturinary cancers. I think the point needs to be made that these drugs target the vasculature. They're not anti-tumoral. They don't attack the cancer cell. They attack the blood vessel that supports the cancer cell. And in the setting of micrometastatic disease, do we even know if these cancer cells have a vasculature? So it may not have any impact on them at all.