 So, we will start this session on surgical treatment of locally advanced, localized disease and locally advanced RCC. May I have my introduction slide, please? My introduction slide, please? How many surgeons have we got in the room? Oh, quite a few. Great. May I have my slides? You just give us two minutes, please. We're just learning your slides. No, it's not this one. It's the other slide. It's introduction slide. This is the clinical cases at the end of the session. You have two set of slides. One is the introduction and the other is the clinical case. No, it's again, it's clinical case. So, basically, it was an introduction for seeing always in the audience surgeon, medical oncologist, nurses, pathologists, biologists, all over. And I wanted to show you some summary slide of clinical cases for having a vote before the presentation and a vote after. So, we will go to the presentation. It doesn't work. No, it doesn't matter. Let's go on the first presentation. Okay. We're covering four subjects this afternoon in the surgical series. The first is a debate about robotics. Does it have to be robotics if you're doing partial refractomy? The second is on ablation. The third on the surgery for advanced disease and then Jean-Jacques clinical cases to close the surgical session. Without further ado, then, I'd like to ask Christophe Fassan from Paris to come and make the case for everybody having a robot. If you don't have a robot partial refractomy, Christophe, make me want one. May I have my slides, please? That's the most difficult step. So, I must first thank the organizing committee for this invitation and to give me the opportunity to speak about this very exciting topic about robotic surgery. They completely changed the field of surgery in neurology and I think especially for the upper track. So, can I have my slides? Okay. Okay. Thank you. If it works. So, I think that first we will both admit the concept that partial refractomy must always remain the only goal of this surgery. And the way to do it will remain optional, of course. So, for those who are not surgeons, this is what robotic surgery looks like. The surgeon is sitting in a console, he's moving the instrument with joystick, he has a 3D view, so he's completely merged inside the patients. And on the other side, you have the patients with laparoscopic tubes that are moved by the surgeon. So, in my institution, we have a 10-year experience on robotic surgery. We do right now for more than 400 cases a year. And kidney surgery represents close to 150 cases per year concerning mostly partial nephrectomy, but also some kind of very large radical nephrectomy or patients for a living donor nephrectomy. So, which tumor will be accessible for this kind of surgery? Of course, the small localized periferic tumor, but also some larger tumor that you can see here on the solitary kidney that will be done with a selective clamping or this very posterior tumor and I like to do it in this case, laparoscopically, so you don't have to open the peritoneum. So, this is how the surgery looks like very quickly, so you have the external view and then we dissect the hillum of the kidney so we can clamp the artery and the vein and as soon as it is clamped, you can just remove the tumor. In this case, it was a 4.5 centimeter tumor. Then as soon as the tumor is, you can open, even open the cavity in this case, as soon as the tumor is removed, it's placed in a small bag and then you can just repair the kidney to make hemostasis and to avoid any perspirative bleeding, which of course sometimes can occur. So as soon as the kidney is repaired, you will be declaim the kidney and be sure the hemostasis is correct. So this was our last data from last year, so as you see, I do both trans- and retroperitoneal approach. If we compare tumor a little bit larger from trans-peritoneal and smaller from a retro, but we can go up to 8 centimeter depending on the patient. We always say that robotic surgery is longer. In fact, it's most of the time less than two hours and it's even quicker with the lomboscopic approach. With a very controlled warm ischemia, which is most of the time less than 15 minutes, and the hospital state, we will see a little bit later, that is the major advantage of robotic surgery is the hospital state. With also a very well controlled oncological outcome with a positive margin of 1.6 percent. So with, of course, observe a few complications, most of those will be hematoma, post-operative hematomas, and most of them were just under surveillance, few transfusions, and just one patient needed embolization of this bleeding. We also had one patient with a urinoma. So in our institution, we did compare the robotic partial nephrectomy and the open partial nephrectomy. So on 100 consecutive patients, we saw that the mean tumor size were not different between those two groups, and the only difference were the high complexity score, which was a little bit higher in the open surgery group. So we compared the operative time, of course, which are, which is almost the same between open and robotic partial nephrectomy, clamping time, 17.5 minutes, that was the first part of the experience. So it's why it's a little bit higher than the previous data that I've shown. So I think that right now, we go even faster with the robot, but then in open surgery. So the main difference was the length of stay, which is 3.8 days for robotic surgery and 6.8 days in open surgery. So the robotic partial nephrectomy was better than open partial nephrectomy in term of blood loss and hospital stay, and it has the same rate of complication, warm ischemia, and impact on renal function. So we could say that robotic partial nephrectomy is only accessible for small tumors. So in a survey in France, around six French academic center, between 2007 and 2011, we recorded 220 partial, robotic partial nephrectomy, and 54 patients had a tumor over 4 centimeter with intermediate and most of those patients had intermediate and high risk score nephronetry. So as you can see, the warm ischemia is a little bit higher, but we still have quite a normal operative time. It's a little bit higher also. It's turning around three hours, and the warm ischemia is 23 minutes. Complication rates. Of course, if you have larger tumor, you must see some more complications. So with nine complication, over 54 patients. Only three positive margins, which makes the outcome, oncological outcomes, quite similar to the open literature. So why robotic partial nephrectomy is all gold standard, at least in our department, just because also we completely switch from open to partial nephrectomy. This year, we are expecting to do more than 100 robotic partial, and only probably 15 percent of those will be open. We did 50 robotic partial nephrectomy during the first month of this year, and only six were open. So why also we choose to switch completely to robotic partial? Because we've seen the same oncological outcomes, shorter hospitals stay with a quicker recovery for the patient and less morbidity. When you see an open scar, and you have complication of that open scar, most of the patients don't want to go for that kind of surgery anymore. But nephron sparing surgery remains, I think, a challenging surgery, even open. And of course, it is robotically also. So I think it's the kind of surgery that should be done in a reference center with, I think, a high volume patient. Thank you. Thank you, Kristoff. Björl Lundberg is then using... Where is Björl? There you are. Sorry, Björl. He's going to make the case for sticking with the traditional technique, tried and tested over many years, rather than using new machines. Moderators and gentlemen, ladies, thanks for the invitation to this meeting. Well, it's a pleasure being here, and it's a challenge to be after such a nice presentation for the technique. But is a robot-assisted partial infractomy the new standard for treatment of small renal masses? Well it's a question for the patients to give an optimal oncological results. The renal functions should remain good. There should be few complications, low morbidity. And we know that the oncological risks are equal between radical infractomy and partial infractomy. Although small renal cell chesnomers can be local aggressive, metastasized also. But when we compare the data from partial and radicals, we know they give similar oncological results, but also smaller renal masses and for renal masses up to seven centimeters. The patients, they are not healthy. They have concomitant diseases. They have conditions that will impair or have impaired renal function already. And we know from a study of hanging at all for many years ago now, 2006, that even for patients with renal cell chesnomers less than four centimeters, having a normal contralateral kidney and normal creatinine serums, 26 percent already have impaired glomeral filtration rate of less than 60 milliliters per minute. And we can see that in the same publication that when they look at freedom from new onset of GFR less than 60. For partial only 60 for three years and for radicals only 35 remain free from GFR less than 60 centimeters of radical infractomy. And that's of course a difference in renal function. What does that mean? Well, if you get reduction in the renal function, you also risk to be dead due to other causes. So have a risk for early cardiovascular events and hospitalization of any cause. So it's a risk factor having the kidney function reduced. We can see the same thing when we look at patients particularly treated for with partial nephrectomy and radical nephrectomy. So this is just that the cardiovascular events are larger in patients. Can I show it in something? No. You can see the upper curve is partial and lower and the red is a radical nephrectomy and they have more cardiovascular events and more overall mortality also. In Sweden we have looked at this data from compared with a population relative survival of patients with PTA renal cell carcinoma according to surgical technique. We can see in the total and higher Sweden that patients treated with nephron sparing surgery survive good as good as the population, but those treated with radical nephrectomy survive less good probably due to the other causes. So we know that nephron sparing surgery is good, similar oncological outcome. They say renal function, but as we heard it is technically more demanding, more time consuming and more complications, but it's recommended for instance by the EU. In Sweden we have used this nephron sparing surgery more and more during the coming years. That's depending on guidelines on the registration itself and educational efforts. We can see from 2005 the nephron sparing surgery increased from 20% in the population up to now 55% in the population. And that perhaps is the most important thing to have for these patients. So when the patients look at this, they wish to have negative margins. They wish to have a good oncological result. They want to have a short war machine year time. They want to have very few complications and they wish to have low morbidity. And that's a question then when you have different techniques. Could you do this in every hospital, every doctor, every situation? That's a problem. When we looked at data from the literature comparing robot assisted post nephrectis with OPEN, we can see it's very few really published comparative studies and no random study. This is some information. Lucas et al. This is from 2012, looked at only 27 robot assisted, 54 OPEN and they found that the operative time was better in OPEN, war machine year time was better in OPEN, but the blood loss was better in robot. And the length of stay was better for a robotic. And we look at the multi-center matched pair analysis from Italy. So also here that war machine year time was better for the OPEN, blood loss was better for robot and postoperative complications was better for a robot, but the rest of the factors were rather similar between the surgical procedures. In the more complex re-enlightened lesions we can see that mostly when compared the OPEN had higher pathological station size and operative time was in that comparison better also for the OPEN, but blood loss was better for robot and hospital stay was less with robot complications similar. When they have compared the situation for matched patients, matched tumors, they can see that robot offers comparable perioperative and earlier in the functional outcomes, but perhaps robot has the advantage of improved postoperative pain and shorter length of stay. This is a rather new publication from VU at all. They made a systematic review of what's published and they made a meta-analysis of comparing robot assisted partial effect miss versus OPEN and they found that the robot assisted partial effect miss had a shorter, longer postoperative time, but they have less post-operative complications, shorter length of stay and less blood loss, but other factors were rather similar. So what I mean is that even if there's interest towards robot assisted partial effect in minimally invasive surgery, the benefits of what we do must be waged against what we have for renal function, what will leave after us as post-immortals and recurrent tumors and bleeding and postoperative complications. On the other side also we must look at society's cost, the net cost for instrument, robotic platform and maintenance cost and that's another subject. And really the overall need for an optimal treatment of such a patient is to perform optimal partial nephrectomy. That's more important than the technique really. The conclusion is that for high level evidence-based data we need, we haven't that for these surgical techniques. We could do this single port surgery everyone, but possibly we can't do it. Each approach seems to have its advantages and disadvantages and we must compare these techniques to know what to do. We need randomized trials. So no robot assisted partial nephrectomy is not the new standard for the treatment of small renal masses, but it's an optimal treatment, optional treatment for patients with these tumors and nephransparency surgery is the standard treatment for patients with T1 RCC whenever feasible. Thank you. Thank you. Is there anyone in the audience who wants to ask a question? The message I got from you is that the tool matters less than the results. What you care about is the results, not necessarily the way you get there. Can I ask you a question, Christophe? Clearly beautiful surgery, amazing techniques, fantastic surgery. Which patients do you not do a brilliant surgeon? Which patients do you not offer robotics at the moment? I will say it's the very undefeated tumor or the very large cystic tumor because you cannot control the strength of the robot and I don't want to injure the cyst. So perhaps it's probably the only two. Single kidneys? No, it's not a problem. I'll show you two slides with single kidneys and I do it. For single kidneys I try to do selective clamping. So I just dissect a little bit more of the arteries. Just clamp the small arteries going to the tumor, do the tumorectomy and that's it. We didn't have any problem. Of course those patients are alert. In case of any problem, we will convert to an open surgery. Of course. I mean the result is better than the twos, you're right. In our hospital for the single kidneys we always cool the kidney, we chill the kidney. The big advantage to my mind of open surgery is that you can chill the kidney. You can absolutely make sure that there's cold ischemia. The kidney is definitely protected, there's no damage from warm ischemia and so in single kidneys we always cool. Do you think that's the wrong thing to do? I don't know because it's not something we do in our institution even open. So interesting. What do you do with single kidneys? Now because I work with Christophe, I was convinced that it was really only indication that was remaining for open surgery, solitary kidney but now I see that we can do a very limited length of clumping with early on clumping method and we have 8 or 10 minutes clumping and very limited consequences of renal function. I wanted to ask you one question regarding the cost, do you think that we compensate with a decreasing of length of hospital stay over cost of a robot when comparing open? I think so. It really depends on the number of cases you do every year because you have to buy the robot and you have the maintenance. So of course if you buy a robot and you do 15 cases a year that will be very expensive for patients but if you do 400 patients then the cost decreased dramatically and it's probably kidney surgery is probably the best indication for robotic surgery because the length of stay so short comparing to open surgery that I think we probably, it's I think on the financial aspect it's probably better for the robot than open. Okay thank you. So I think we should, that's pretty well done guys. I think we should move on. Oh a question. Sorry, not a question but a comment. I think it's not right to say robotic surgery is the best indication for the upper urinary tract but this is minimally invasive surgery. You can do exactly the same you told in conventional laparoscopy. Of course if you are one of the best surgeon in laparoscopic surgery I used to do my partial laparoscopically and there are some tumor which are a lot easier to do with the robot. That's a, and also I think that's the learning curve in laparoscopy is a lot higher longer than with the robotic especially now that we have the juice of the dual console the simulation and all that. So I think I'm very sorry also because I like laparoscopy but I think laparoscopy will disappear. There's no problem. Go on. Another question. Just a quick question. I just wanted to ask the panel what would your age limit, age cut off be for doing partial because in the older patients would it be quicker and if they have a normal contralateral kidney to go ahead and just do an aparoscopic nephrectomy? It's just one of the things that has to be borne in mind isn't it? I don't think there is an A or B age. It's just a factor that's built into the equation. I mean it seems to me there's a call for randomized trials but there is a randomized trial that says that nephron sparing surgery isn't as safe as radical nephrectomy. It's interesting we sit here meeting after meeting saying we need more trials and we do have a trial in this area and we choose to ignore it because radical nephrectomy is shown to be safer. It's odd how surgeons behave. Let's move on. So let's continue in many invasive techniques. The second debate is about small primary illa endophytic renal tumor. Cryos therapy will be defended by Roberto Salvioni. Good morning. Thank you for the invitation. I am an urologist. My interventional radiologist Dr. Carlos Prasikou is now in Berlin at the International Radiology Congress. Sorry. The cryo therapy is used to produce temperature decreasing in the tissues in the tumor between minus, then 20 degree and 15 degree. Okay. Thank you. The damage in the tissues is obtained by crystal formation, co-active necrosis, apoptosis and damage in the vessel. Efficacy, low morbidity and short hospital stay are required at the local therapy and cryotherapy. Now, cryotherapy is possible to have in two situations by laparoscopic approach from the urologist and in percutaneous approach by the radiologist. The difference in control of the tumor is the same in the literature, but percutaneous approach is superior in diminishing the comorbidity, like operativity and bleeding, transfusion, etc. For this reason, in our institution now we prefer the percutaneous approach. So, the argument of today is the eye and the feet is more renal mass. There are different definitions, but this problem is now about less than 20% of all renal mass in the tumor and in the renal. This is our experience and now this is the particular experience in eye and feet renal mass. Can you see this lesion is only 11% of the older cases, but it's important to see the good results in outcome, the control of the tumor. You can see the major complication on fistular atrovenosa and in shock and transfusion in one patient, but these are associated with the tumor size at the particular site of the lesion. It's important to see the normal renal function preserved in all the patients. Two cases. The first is one patient with a big, not a small, right kidney lesion. After the treatment, at the first contour, the CT scan shows at one mount the atrovenosa fistula. To repair this damage is necessary to embolization with radiological intervention. You can see the procedure. At the end of the procedure, the patient conserves the kidney and the renal function. The other case is a particular case who seen our institute with the proposal by the other center bilateral nephrectomy. This patient with TKI therapy and after the response, the patient was submitted to radical right nephrectomy and conservative left nephrectomy. But after 10 months, the patient elapsed in the solitari kidney and the problem is what do you do? They open or percutaneous corroboration or the other. We decide that they treat the patient with TKI and then with percutaneous corroboration. Now the patient is alive without tumor and with renal function conserved. Our conclusion, in particular case, in small renal, high-large renal mass, cryotherapy ablation is possible. Thank you. So let's move to radiofrequency ablation with Dr. Krokidis in small primary underfitting renal tumors. Thank you, Mr. Chairman. I introduce the organizing committee. I'm delighted to be here and be part of the kidney cancer association. So I'm going to argue in favor of the use of RFA in high-large underfitting renal tumors. I would quickly introduce the treatments that you all know about. It's very well known, the fact that Refrectum was introduced by Robson in the 70s and then evolved in laparoscopic techniques, robotic, we've seen, minimally invasive. And then laparoscopic ablation was introduced with the use of thermal techniques in aim for nephron sparing treatments. And this evolved percutaneous image guide ablation. However, if we think that we deserve the idea of treating tumors with ablation, we have to look at the history of medicine and think about Hippocrates and his statement 400 years before Christ that whatever cannot be excised can be cured by coterie or burned. And he was definitely ahead of his times. However, we don't really know what he meant by coterie. Was he really that ahead? Was he thinking of heat or ice? And was he thinking of the modern device that we have and the dilemmas that appear in the modern practice? Well, if we think about RF, we have to look at the technique and how is this technology resolving the tumor? Based on the use of radiofrequency waves that oscillate the ions of the tissue and this ionic agitation cause frictional heat and this motion energy is becoming thermal energy and it cooks the tissue. This is a very precise and repetitive cooking and it's very effective. It was introduced nearly 20 years ago in clinical practice in an interoperative setting by a Belgian group and then the first percutaneous case was done 1998 at the Massachusetts General Hospital. Since then a lot of series were published with fantastic results for small renal tumors with nearly 100% success rate in long-term results. If we see the cancer survival score, we will see that for up to three years we have very good results that excess 90% in multiple studies. So this is an established treatment for small renal tumors. Also for single kidneys we have seen in our experience, in Gaisens and Thomas, that after 56 months of mean follow-up the results were very good in terms of oncology control. The setting for RFA is very simple. We need a scanner, this is the scanner at Adam Brooks and we need the generator which is located here. The patient is usually anesthetized by local anesthesia or sconce sedation. He's positioned prone in the scanner. We need the monitor to identify where our needles are and if you see these pictures, this is an enhancing lesion. It's a typical RCC, intensive imaging. And then after calibrating and positioning the needle in the exact middle of the tumor, ablation is performed and as you may see there's no enhancement in the tumor and that indicates treatment. And that's how tumors look three years after being ablated. There's a scar on this picture that shows that there's no enhancement and this is a very good result. If you have problems in terms of other organs like in this case the bowel is dangerously near the tumor also in the prone position where the patient is positioned for his treatment and in this case we'd like to displace the bowel and we do that with a little bit of dextrose 5%, which is non-ionic solution and radiofringent ablations are transmitted and therefore we can ablate safely the lesion. Thermal ablation in our recent published meta-analysis has shown to be very effective. We have now long-term data, we don't have any randomized control trials but from the existing trials we can see that this is a technique that it is comparable to surgical techniques nowadays. Well, if we go back to Hippocrates, is that all? Is RFA perfect then? Well, we have to think about central lesions. What's going on with central lesions? And this is the argument of today's debate. So if we think about the location of lesions within the kidney the upper part we can say that it's clear RFA territory. We can ablate every lesion up to four centimeters of course. With a lower line is definitely an area where most of the radios would see it as a very dangerous area to treat. However, experts in the field have stated in the past that RFA is not influenced by the position and the location of the lesion. It has to be performed safely. And this trial has shown that in 41 patients, 41 tumors in 39 patients with endophytic location ablation was performed safely with very good results at approximately three years. But how can we ablate a central lesion? Well, we have to protect the pelvic and licell system the way we protect the bowel. And in this case we have to position urethra extent and perform cooling of the pelvic and licell system with the use of dextrose, which is perfused from the urethra extent. And in this case, a central lesion which is located here which can be considered as a challenging case with the use of a urethra extent and perfusion of the pelvic and licell system. We can ablate, this is our needle, that is in the center of the lesion and we can perform a safe ablation of this small renal tumor without damaging the pelvic and licell system. In similar case, in a more central location the urethra extent is positioned, pelvic or perfusion and our needle is positioned here and a very good result at one year. So RFA is feasible for central lesions. But this is better than cryo. Well cryo, we've seen that is based on a different principle. It's based on formation of ice. It's more controlled. We can see it with imaging modalities. Ice is usually performed extracellularly and the cells are killed by dehydration. And then intracellular ice is performed and coagulation crosses due to thrombosis of small vessels. The cryo ablation has been for a long time in the urological field. However, the first paecutaneous case was performed in 2001 and this is the publication and as you may see this is the ice ball and this is how pictures of cryo ablation look. Since then a lot of debate was on what would be the ideal ablation technique and a lot of publications were appeared. And in 2008 this meta-analysis has compared the two modalities in a very large number of patients. It's actually 1,375 patients. And patients were coming from a lot of institutions. Cryo ablation was performed mostly intra-operatively whereas radiofrequency ablation was performed percutaneously. And there was no true difference between the two modalities. So from the data that we have until now the two methods are completely comparable. Also in a more recent publication in 2012 regarding renal function in patients with already impaired renal function we have seen that there's no difference of the EGFR at one month and one year post ablation of both modalities. We need also to consider that cryotherapy is a little bit more demanding in terms of technical aspects. This is the setting and it's definitely time consuming to organize. It's definitely demanding in terms of technical knowledge and money. It's definitely more expensive than radiofrequency ablation. And it's not without complications. Well, we need to think that we have to position multiple needles and there's risk of bleeding. There's no track ablation, so there's risk of seeding. The cost is definitely significant as mentioned. It's time consuming and requires significant expertise and there's also always a risk of thermal injury of the skin. So if we have to compare between the two modalities we have to say that even though cryo is the new thing the number of probes, the multiple number of probes the significant technical effort and cost and the fact that we cannot ablate the track make this modality less appealing. Whereas RFA has established results the last ten years for small renal tumors it is feasible for central lesions and the cost is low and the technical effort is also not significant for an experienced operator. So if we go back to the hypothesis we can say that he would say today that RFA is feasible for central lesions. RFA is effective for small renal tumors. RFA is cheaper than cryoblation and RFA is more straightforward than cryo. So probably he would suggest that we could treat every lesion with RFA if it's smaller than four centimeters. We can reserve cryo and multiple probes for larger lesions. We have to use RFA if we want to be cost effective and if we want to treat challenging cases that cannot be treated in another way then probably cryo is the best solution. Thank you very much. We have time for a couple of questions. Is there any questions for the audience? I have one quick one, sorry. Just in terms of cryo and RFA in terms of patients at renal dysfunction what's the percentage of worsening that renal function? In our experience it's very small. In our 56 months of follow-up there was no patient in single kidneys no patient has gone to renal failure. So long-term data shows that renal function is preserved. And it's the same? In our experience only seven solitary kidneys all concern the function. Just a question for both of you. What is your opinion on cystic lesions and thermal ablation? Are you talking about Bosniaq type 2 cysts or non-definitive RCCs? Well basically anything where you think there could be a renal cell carcinoma behind a Bosniaq 3 or 4. We have these discussions very frequently at our institute and then there is this argument that maybe microwave ablation is more effective than these lesions, but we all have this feeling that once you stick a needle in it ruptures and it's something we don't want. Exactly. I don't have a large experience of cystic lesions. When cystic lesions become solid of course and it's within the limits in terms of size I would go on a blade. But I would prefer to follow up a lesion that is not definitive. And of course if it's too big probably in effect it may be the best solution. In our institution not treat the patient with the cystic lesion with the cryotherapy. In our institute not treat the patient with the cystic lesion with the cryotherapy but with the other surgery or the other thing. I think it remains a relative contradiction. Last question? I would just like to comment on the last slide which suggested to treat every lesion with RFA that is smaller than four centimeters. So there is a clear recommendation in the EU guidelines recommending partial nephrectomy for the PT1 renal cell, carcinoma or renal mass. And there is no recommendation to perform RFA or cryotherapy in such a tumor except the case that partial nephrectomy is not applicable in this patient. There is a great C recommendation for this situation where partial nephrectomy cannot be performed. The last slide did not say that every patient with I'm sorry for the misunderstanding up to four centimeters has to be treated with RFA. It says that RFA is very effective for the patients that after MDT would end up having an RFA. So every case has to be discussed. Every case has to be... It's multi-parametric. Not all the patient can be operated and the MDM and the MDT has to decide which patient would go anywhere. So in case the patient follows this pathway this modality is very good. So I'd just like to reply to this. So the guidelines are based on the data that is available on randomized trials or on the best data which we can refer to. So unless this data is updated by new data which supports your statement I think we should stick to the guidelines. Sorry. In our institute all the patients treated with ablative therapy are unfit to traditional surgery or refuse surgery. This is the selection of our patients. Very good. I love the controversy that the small renal mass generates. It continues to generate controversy and we need to resolve some of those. Great. Well done. The large renal mass. David, you're going to address minimal access surgery for some more complicated, larger T3, T4 tumors. Thank you very much. This talk is somewhat of a segue between minimally invasive techniques and small renal masses for which there is considerable controversy and the maximally invasive surgery which we'll hear next which I doubt there'll be too much controversy but it's the complexity of the surgery that's a fundamental issue. And I guess extending the minimally invasive techniques it's really whether these and specifically laparoscopic nephrectomy has a role in locally advanced renal cell carcinoma. Now, in looking at this we have to sort of define precisely what we're talking about when we discuss locally advanced renal carcinoma and I guess most of us would regard that these encompassed tumors defined as pathological T3 lesions with invasion into the peri-renal and renal sinus fat or where there is extension into the renal vein. Most surgeons however would regard that the locally advanced have connotations when they contain the features shown here in red. That is where there is a significant extension into the vena cava where there is invasion of adjacent organs or where there is gross lymphadenopathy. And as shown in this slide which is a full house of these adverse features there clearly are going to be cases where it's an appropriate contemplation that laparoscopic surgery be undertaken. Nevertheless, most of what fits within those definitions of locally advanced disease don't present quite such a challenge and I guess with these we then need to look at what is the purpose of the surgery and these tumors can be broadly classified into those in which a surgical endeavour is embarked upon with curative intent where maximal resection, radical resection and complete resection if feasible is the ultimate goal and I think as with partial effect to me it's not so much the method but the outcome that's important. A different group is the cytoreductive and where the principal purpose is actually just to reduce the patient's tumor burden and principally excise the primary lesion where the surgical goals in terms of cure of the patient are somewhat different. I guess now looking at what is reported in the literature everything in medicine pretty much everything can be done and certainly is reported and there's a large number of papers that report surgical success with the type of tumors that I outlined in the first slide. The issue with literature is that these are essentially anecdotal reports of surgical victories and also case series and the features particularly of the case series is that there is inevitably a component of selection reporting bias and that in many of the larger series there is a relatively small median tumor size of about 8 centimetres when they've reported it as a locally advanced tumor and the further feature is that the case series is largely bolstered by pathological upstaging where the patient is found to have a PT3 tumor but clinically it began as a T1, T2 tumor and so that does create a feature in the literature. Nevertheless there have been an analysis of these series and I'd commend the excellent publication by Grant Stewart now from Scotland who have the largest series relating to this particular topic and clearly based on their fairly extensive experience it's technically feasible and I'd highlight in selected cases and precisely the selection process is what is debated and certainly in those in whom it is undertaken comparing to similar I guess case matched open cases the local recurrence rates time to survive, time to recurrence and also long term survival are equivalent with open surgery. It's not just important to consider what is in literature we also have to look and be aware of what may not be in the literature. An important factor is that the series are often reported when there has been a very specific selection bias or referral pattern that is not representative of the true world to quote an oncology presentation this morning. There's also the issue of catastrophes and these tend not to be reported in the literature but nevertheless are a well recognized phenomenon with laparoscopic nephrectomy with locally advanced renal cell carcinoma. I personally am aware of currently four active medical legal cases in England alone over the past 18 months of patients who have died as an intraoperative early post-operative death related to a locally advanced renal tumor related to vascular disaster and this is where surgery was undertaken with gross lymphadenopathy where bleeding occurred related to use of clips as a result of the lymph node enlargement precluding the application of a clamp and in two cases, perium-esoteric artery was divided because the large tumor bulk obscuring the anatomy. Other catastrophic events are known with duodenal and visceral injury and also the consequences of protracted surgery including gradodomialysis. These are all cases that I suspect most surgeons are aware of not necessarily a personal experience but by rumour and the fact that they are not reported but nevertheless clearly there is a safety issue in our case selection process. Certainly to drift into the sort of more I guess technically challenging and this is the group in which there is renal vein extension and with careful selection pure lap is probably feasible in a number of cases with level one tumor thrombi. This is those within the renal vein and not into the venercava prior occlusion of the artery will often result in some retraction of the tumor and with use of slings and other devices application of stapling devices feasible but again this does come at a potential price with their reported incidents of positive margins at the safety at the stapling line having been occurred. Obviously the more adventurous cases of those at level two and three and certainly there are individuals who have reported isolated success but again with hand assist and open completion being necessary. And the largest series where this was undertaken as an endeavor this was a Chinese series only 30% of those embarked upon laparoscopic ultimately prove feasible and so even with determination in a group we can see that only a subset ultimately prove feasible. So thus with laparoscopic nephrectomy for locally advanced disease there clearly are major technical issues which provide limiting factors and need to be borne in mind because this is clearly an issue of case selection and the factors to consider are the large tumor or really it's actual overall specimen size rather than actual tumor itself perinephric fat is a major consideration. Cases in which there is profound or marked lymphadenopathy which often obscures the vascular anatomy where venous congestion is present with hematuria and non-functioning kidney being hallmarks and this is often index of tumor thrombus in a vein and venous infarction of the kidney and where multi-visceral resection is required except with the possible exception of distal pancreas and splinic involvement as these are standard procedures performed by general surgeons. I guess other potential considerations are large right-sided tumors because of the small or short renal vein limiting application of vascular staples safely and perinephric infarctional though usually the pneumo perineum does not result in this being a substantial problem but certainly it's a factor to consider. Sider-reductive nephrectomy is a different issue to someone who you're contemplating a curative procedure margins become less of an issue and so therefore we're not attempting or necessarily needing to achieve the radical resection of a curative resection. Recovery and morbidity are an advantage with laparoscopic surgery where this is feasible and this will allow the early introduction or reintroduction of systemic therapy. Building on that topic with Sider-reductive nephrectomy my anecdotal experience is the pre-operative medical therapy does not increase the prospects of laparoscopic approach and based on experience with free agents generally in trial settings, pizoponib and acetonib are preferred if feasible if initial medical therapy is to be undertaken with a plan to subsequent Sider-reductive nephrectomy and this relates to the intense desmoplastic reaction that frequently occurs with a student and can make the section identification of anatomical planes very difficult. So in conclusion I think if we're looking at the topic of the talk and that's locally advanced renal cell carcinoma I think it is a clinical reality which just does relate to the pathological upstaging of tumours that were initially identified radiologically as clinically T1 and T2. It is applicable in selected cases with clinical T3 disease but again this is dependent upon careful case selection with considerations of patient safety and also the surgical margins which one can realistically achieve and this is obviously an individual surgeon decision and I think it's advantageous when feasible and again I stress feasibility and safety in the Sider-reductive setting in that it won't allow more rapid recovery and the reintroduction or induction of systemic therapy depending on the clinical decision in terms of longer term management. Thank you. Thanks David, that was terrific. Would anyone like to ask David a question? Hi, I'm from Glasgow. Do you think radical node dissection is appropriate in these patients and if so do you think we should be encouraging surgeons to do these cases open to facilitate that? I mean the whole issue of node dissection is one of considerable controversy. I think if we're wanting to or believe in a node dissection it's actually far more extensive than most of us would imagine and it's actually something akin to what we perform for a radical or an entrepreneurial node dissection for testis cancer. In my hands I don't believe that it is feasible to undertake a true node dissection laparoscopically because of the extent of dissection required and that includes the inter-autocable lymph nodes with a definite instance of crossover to the other side and so I think there are considerations. Most people when they say they perform a lymph node dissection in reality perform a lymph node sampling which is a staging modality and I think if that's what you're wanting to achieve it would be acceptable. It is difficult isn't it when success is reported and failure is covered up? It is difficult to know where we are with procedures when it's only the successes that get published and the failure is done. The people who are not from the United Kingdom will probably not know but it is now mandatory for surgeons in the United Kingdom to report every nephrectomy that they do since 2012. So there is mandatory reporting of nephrectomy across the whole of England, not Scotland. And we hope because of that that we'll start to understand the safety of some of these operations much more clearly. In 2012 there were 34 people who died following nephrectomy in the United Kingdom and it will be very interesting to do an analysis of those deaths and see why people died. But it is now mandatory in our country that nephrectomies are reported. I think that's the only way we'll judge whether certain techniques are safe and how common catastrophes are. It's actually in the public domain as well. Patients can look at the results of individual surgeons. David, that was great. Oh, I'm sorry. I'm really sorry. I was wondering if I could ask any of the speakers who would care to comment whether you would make a different decision about ablation versus the laparoscopic or robotic technique in the case of someone who has a genetic cause of kidney cancer like VHL or HLRCC or BHD. Where there's risk of subsequent tumors. Shall I answer that? We have quite a big BHL practice in our hospital. What we tend to do is tidy up the kidney with a maximal tidy up the first time we do it. So all the solid lesions, we follow the NIH guideline of operating when things get to three and when they get to three we do an open multi-partial and tidy the kidney completely up and then if tumors recur then we tend to use the ablative techniques for second and third goes. That's what we've tended to do. We haven't had anyone die in the 15 years I've been managing that service because of tumor recurrence. No, I guess the issue that I was concerned about is the amount of scar tissue that some of the ablative techniques leave behind and then if you do have to do an open surgery or something later on it's much more difficult to do dissection. You're absolutely right. I think that's an important point. I don't think cryo radiofrequency ablation is a half way house for partial infractomy that if they fail the fallback is ultimately an infractomy rather than a partial infractomy. So I think having treated someone with cryo RFA precludes the possibility of a subsequent partial in the majority of cases. Thank you. Go ahead. Also dealing with multiple lesions it's definitely more challenging technically and the risks are increased of bleeding and also of sepsis. So multiple lesions increase the technical difficulties of the procedure. Great. I'm really looking forward to the next talk over coffee. I was talking to Chris Wood and I felt I'd had a really busy year in London and I'd done 100 major renal resections and I asked Chris Wood over coffee how many he did last year and he said 350 and I felt rather intimidated. Chris, tell us about some of the 350 you've done. Well, thanks to the organizers for the kind invitation. This is actually my third time in Dublin and I've fallen more in love with the city with each visit. And I'm happy to talk to you today about the surgical strategy for the management of patients in free vena cava invasion. When I first made this talk I had something like 100 slides. I didn't realize there was so much to talk about but because of all the coffee I've been drinking from jet lag and the two points I tossed back in the afternoon I think my bladder is going to make this a quicker talk than it originally was. So what I'm talking about, this is a patient actually that I recently saw at MD Anderson, locally advanced tumor involving a right kidney with the IVC thrombus extending up into the right atrium. Now you can see the locally advanced tumor in the right kidney again and on cross-section. These cases are probably one of the most daunting cases that urologic oncologists face, probably this in post chemotherapy retroperitoneal lymph node dissection for testis cancer, probably the two toughest cases that we face in our practice. Venous tumor thrombi are found most often with clear cell renal cell carcinoma but they can occur actually with all types of kidney cancer and it's not just limited to kidney cancer, a variety of other different non-renal urologic tumors will form tumor thrombi. I quote patients that the incidence of venous involvement is somewhere around 15%, you can see it's anywhere from 4 to 36% in the literature, but IVC extension and subsequent atrial extension is obviously much more rare. The vast majority of these patients will present with blood in their urine or flank pain, but you can see that almost 20% of patients that will actually be in incidental finding with no symptoms. With regards to evaluation, probably the gold standard for evaluating a tumor thrombus remains the contrast enhanced MRI although with the developments that have been made with CT scanning, I often use CT scanning for my patients to try and identify the thrombus, the extent of involvement and so forth, but the MRI undoubtedly does give more information than a CT scan can and you can see here the differentiation between the actual tumor thrombus which is vascularized and the associated IVC bland thrombus and the venous collaterals associated with IVC occlusion. It's very important to get updated imaging before taking these patients to the operating room, the tumor thrombus can progress rapidly so frequently I'll get scans within a week of surgery. The further staging of the patient is for any other advanced clinical mass, for those patients that have near occlusion of their IVC or have presence of bland thrombus, we often recommend anticoagulation. I can't tell you the number of times I've been called in the community by well-meaning urologists who want to transfer a patient with an IVC thrombus and they tell me don't worry, we put a filter in the vena cava so the tumor thrombus won't move. Please don't do that. There have been some papers in the literature on the thickness of the IVC or the thickness of the renal vein to try and predict wall invasion. This is an important preoperative evaluation because it may give you some indication as to whether or not you're going to do IVC replacement or whether you'll need a vascular surgeon on standby although this still remains a imperfect science. There are a variety of staging systems that have been reported for characterizing tumor thrombi with regards to height of ascent. I think the vast majority of us use the male system which is highlighted there. This is a summary of our experience where we've noted patients who present with tumor thrombi the vast majority of them are level one and level two with a significant minority of patients having tumor thrombi extending up to the hepatic veins and then on into the atrium. Unfortunately, a significant percentage of our patients present with metastatic disease either distant metastases, nodal metastases, or both. We had a significant or about 20% of patients were managed with preoperative embolization. This was largely before I came to MD Anderson and I'll talk a little bit more about that and the troubles it may cause later on in my talk. So with regards to surgical technique preoperative embolization for intracardiac or keboatrial thrombi used to be the standard at our institution. It was thought that perhaps it may decrease preoperative blood loss and may cause thrombus regression particularly if it's vascularized but we rarely use it anymore because of the complications that are associated with it. The tumor can be approached through either a midline or chevron incision and the real key to this surgery is early arterial control. We use ligature for collateralizing vessels and virtually all our patients are monitored with transesophageal echocardiography both to confirm the location of the thrombus and monitor for the devastating complication of thrombus embolization. And obviously sternotomy can be used for selected level 3 and 4 thrombi although I find more and more we're actually able to manage these through a transdiaphragmatic approach without opening the chest. So it's critical to assemble an experienced team that may include surgeons that are familiar with hepato-billiary techniques obviously vascular surgery and when it goes to the heart cardiac surgery. It's important to operate on the vessels first to ligate the renal artery to isolate the venous structures and remove the thrombus and then the cancer operation begins with removal of the kidney and the lymph node dissection. I borrowed this from Brad Lipovich. This basically describes the management of the inferior vena cava during thrombus resection. In group A if there's no evidence of any clot within the vena cava you do a simple cavotomy extract the thrombus and close. If you have distal tumor thrombus in the iliacs frequently we'll put in a green field filter or a dewey's clip to prevent subsequent post-op embolization. For those patients that have partial or total IBC occlusion frequently we'll just staple across the IBC or actually physically interrupt the IBC again to prevent post-operative embolization. Again a word about pre-operative embolization as I said it used to be the standard of care in our institution before I came there but in this study you can see that in patients who underwent pre-operative embolization it was not associated with decreased blood loss it was also increased complications and mortality. In the multivariate analysis there was a five-fold increased risk of pre-operative death in those patients that were embolized pre-operatively. With regard to technique level one and level two thrombites were relatively straightforward. Frequently we'll mobilize the caudate low off the vena cava tying off those short hepatic veins and then it simply involves including the left renal vein the vena cava below the thrombus and above the thrombus and also securing the lumbar vessels and then extracting the thrombus becomes a bit more complicated with level three thrombite there is a procedure to it first again renal artery ligation making sure that you get all the renal arteries going to the kidney with the tumor mobilizing the liver to allow retro-epatic and super-epatic IBC access and then you include the left renal vein the distal IBC make sure to get all the lumbars in that area you do a Pringle Maneuver to cut off hepatic inflow and then finally ligate or not ligate but include the super-epatic vena cava to remove the thrombus. Frequently after extraction of the thrombus you can get control of the vena cava below the liver and allow return of liver blood flow by releasing the Pringle. With regards to level four techniques veno-veno bypass has been described I've never used it we use cardiopulmonary bypass rarely with hypothermic circulatory arrest although reported advantages of hypothermic circulatory arrest are resection in the bloodless field. The problem is after the arrest is over it's anything but bloodless but it does allow you a significant period of ischemia time to extract the thrombus. There was a study done by Brian Souk that demonstrated the hypothermic arrest was associated with a longer overall survival and a significant reduction in perioperative mortality but that has really not been my experience. Just a word about the devastating potential complication of tumor thrombus embolism. This was a review in one of the thoracic surgery journals where they looked at nine patients who presented with pulmonary emboli in addition to IBC thrombus. They did an aggressive surgery which included pulmonary embolectomy. It's always the question of whether or not that embolus represents bland thrombus versus tumor. In this particular very limited series of patients nine and all the vast majority ultimately went on to recur and die and I'm suggesting that the thrombi were in fact associated with tumor thrombi. In contrast we did a retrospective study looking at our patients who presented with pulmonary emboli and we noted absolutely no difference with regards to recurrence free and cancer specific survival when compared to those patients who did not present with a pulmonary embolus so I would not suggest to you that all patients who present with a pulmonary embolus should be assumed to have metastatic disease because they don't. What about the robot? Is there any role for robot surgery in the management of IBC thrombi? This was one of the first series that was published with regards to management of IBC thrombi using the robot. It was by Ronnie Abaza who used to be at Ohio State and now is in private practice. He reported on five patients and alluding to the comments that were made before we haven't heard about the disasters that he may have had. But in those five patients he had very respectable blood loss, very respectable operative time and the mean length of stay was 1.2 days. Presumably these patients are highly selected. He went on to report partial nephrectomy with associated venous tumor thrombus. Again reporting on four cases. Of note, two of those four patients developed metastatic disease in less than one year. So it is technically feasible. Doesn't mean just because you can do something, you should do something, I think the jury is still out. This was a review that was published by Indy Gill and he noted that there were a total of 78 minimally invasive IBC thrombus cases reported in the literature. You can see that the vast majority were level one and to date only nine robotic cases have been reported. So is it possible yes, should we do it, I'm not sure. This is our experience with management of patients with venous tumor extension. We reported on 605 patients who presented with venous tumor extension and had a follow-up of two years. Only 45% of our patients had no evidence of metastatic disease and you can see the difference between the two. These are very challenging operations. You can see there are medium blood loss was almost the leader. Hospital stay was six days. Complications do occur with this surgery. We had 25% within the first 30 days, 10% within the first year. Almost 60% of our patients went on to receive a transfusion and the 30-day mortality rate was 2.6%. If you don't have metastatic disease, the outcomes from this surgery can be excellent. We did an analysis trying to predict which patients would have complications and in our multivariate analysis we noted that those patients who were older than the age of 60 and those patients who underwent preoperative embolization were far more likely to have complications. This included major complications and embolization was also associated with an increased incidence of minor complications. 12 patients died. One was intraoperatively. 10 were within the first 30 days postoperatively and we did have one late death from a massive PE at three months out from surgery. We looked at a variety of different predictors of overall survival. Those predictors are listed there but in our multivariate analysis these were the factors that predicted outcome for patients who had IVC thrombi. Clear cell subtype actually provided a protective phenomenon whereas those patients who had non-clear cell histology and venous tumor involvement had a worse prognosis. Patients who had high grade sarcomatoid de-differentiation, perinephric fat invasion, nodal metastases or distant metastases all were associated obviously with an adverse outcome. Graphically here we noted that those patients who had involvement of tumor thrombi up into the atrium had a significantly worse prognosis than those patients where the tumor was located to the IVC below the diaphragm. Our results are comparable to numerous other ones that have been literature historically where patients who don't have metastatic disease can have a significantly better outcome than those patients who present with metastatic disease at the time of presentation. This is another study that was published out of Europe where they noted that any involvement of the IVC not just limited to atrium involvement but any involvement was associated with a worse prognosis. In their multivariate analysis they noted that IVC invasion, tumor size, fat invasion and metastatic disease all were associated with an inferior outcome. These are data that again, Bradley, let me borrow, where they noted that the head of the thrombus and also perinephric fat invasion was associated with outcomes. So here you can see this is a level zero thrombus limited to the renal vein. Patients who had fat invasion had a worse prognosis than patients who had only venous involvement and then you can go on from there where if you had fat invasion with a level zero thrombus your outcome was the same as if you had IVC involvement and if you had IVC involvement with fat invasion your outcome was the same as those patients who had a level four thrombus and then T4 disease in this series did the worst. And the factors that predicted their outcome in this particular series included TN and M stage, grade, sarcomatoid features, the presence of histologic decrosis, performance status, fat invasion and histologic subtype. But by and large as I stated over and over again patients who don't have metastatic disease can be cured by this operation and I quote patients that without metastatic disease there's a fifty to sixty-five percent five-year disease for survival but those patients with metastatic disease obviously do worse. So we looked at some of the factors that predicted outcome in our series of patients who underwent IVC thrombus resection. We looked at 270 patients who had noance of metastatic disease at the time of surgery and we noted a very surprising finding. Nineteen percent of these patients actually had cancer invading the wall of the vein at the margin of resection. Positive margins were more likely in patients who had a higher level tumor thrombus and also in those patients who had a higher tumor grade. And you can see here that the risk of the local recurrence was significantly higher in those patients who had a positive vein margin and also the risk of metastatic progression. Initially this led me to believe that we should be sending frozen sections at the time of surgery to rule out the presence of venous patients. So we looked at some of the factors that we thought were likely you can see from these data that that probably is not going to impact outcome. The vast majority of these patients present with metastatic disease or local and metastatic disease and it's actually relatively uncommon to just have a local recurrence. So from my perspective, invasion of the vein wall is more a depiction of the tumor's biology rather than poor surgical technique. I did mention that histology played a role in predicting urology and the bottom line is papillary histology with venous involvement is a death sentence. In our series all of the patients who had papillary histology were dead at five years. There are other studies that look at tumor thrombus consistency. This was one retrospective study that demonstrated that those patients who had a friable tumor thrombus when compared to those that had a solid tumor thrombus had a significantly worse outcome. In a more recent series looking at that they actually looked at some of the markers that might predict for a solid versus a friable tumor thrombus. They noted that there was increased expression of the cell adhesion molecule you can hear in and also increased collagen in the solid tumor thrombi and in fact they noted that in their multivariate analysis the only factors that predicted for outcome were the friability of the thrombus as well as the presence of tumor necrosis. Okay, I've told you what can happen if you do operate. What happens if you don't operate? Well these patients do dismal. This was a retrospective study that looked at patients who were resected versus those that were treated with quote-unquote conservative management and you can see that the survival for the no-surgery group was horrible. And this is a retrospective study out of UCLA that basically demonstrates the same thing be it just renal vein involvement or IBC involvement. So in the time that I don't have left I'm going to talk to you just briefly about the role of targeted therapy in the management of tumor thrombi. We've all seen these retrospective studies, the anecdotal studies that have demonstrated these remarkable regression of tumor thrombi associated with targeted therapy. So perhaps we should be giving this to all patients who present with locally advanced disease with venous tumor thrombi to get thrombus to regress. Well we recently published a multi-center experience with UT Southwestern in Wisconsin looking at patients who are managed with the venous tumor thrombi with targeted therapy, the vast majority receiving synitinib. And you can see from these data that the vast majority of these patients had little to no response in their venous tumor thrombi after being treated with targeted therapy. We recently updated this looking at an experience of 48 patients who were treated with a tumor thrombus in place. And again the same story, the vast majority had little to no response in their primary tumor suggesting that targeted therapy is not a way to get the tumor thrombus to regress and make the surgery easier. So if there's no evidence of metastatic disease, the preferred option for these patients is surgical resection receiving, reserving systemic therapy only for those patients who are not really surgical candidates. And just the word about Bud Kiari syndrome Bud Kiari syndrome relates to hepatic venous outflow occlusion, which is associated with abdominal pain, ascites, epitomegaly, lower extremity edema and abnormal LFTs. In our hands the in-hospital mortality rate for taking these patients to the surgery is in excess of 80%. So we no longer operate on patients who present the primary syndrome but instead perform angioma embolization and if they have regression of their tumor thrombus and reperfusion of their liver and reversal of their symptoms then we take them to the operating room. So in summary, radical nephrectomy with IBC thrombectomy is a technically demanding surgery that can be associated with significant morbidity and mortality. In the absence of metastases nodal disease, sarcomatoid de-differentiation and invasion into the perinephric fat or vein wall appear to predict prognosis. Minimally invasive approaches are described but patient selection clearly is critical. And pre-surgical treatment with either embolization or targeted agents does not appear to be helpful and in fact may worsen prognosis. Thank you very much for your attention. Wow, that's kaleidoscopic. Fantastic. Is anyone in the audience want to ask Professor Werder a question? I just want to ask a little more about embolization. You don't think there are confounding factors? The embolization were performed earlier in the series before you started with the surgery and it might be a selection of patients and when did you do the embolization the day before the surgery or earlier? And otherwise what should be the reason for the bad performance of the embolization? So you know when I was a fellow the person that did these before me did embolize and I was honestly never impressed with I don't think it decreases blood loss I think it does make the surgery more difficult there's some question as to whether or not the edema that it causes may help you with the surgical planes but quite honestly I think that the problems it causes are not worth any potential benefits I never saw any dramatic regression of our tumor thrombus never saw our approach change so when I joined the faculty after the first few cases in the old way because that's the way I was taught decided this is probably not the way to do things you know I think that with embolization you basically can operate at two different times you have to operate within 48 hours because after 48 to 72 hours the tissue is basically like wet Kleenex trying to sell or you operate three months later and so our approach with patients who have Bud Kiara syndrome we embolize them, we wait three to four months re-image them and if they have reperfusion of liver and resolution of their symptoms then we treat them with surgery but if they don't then we treat them with systemic therapy but I just have not been impressed with the potential benefits of embolization and I think that the side effects and the potential for increased morbidity and mortality are significant Bill, you had a question and now I had the answer to Sven this made a systemic review of the literature finding that there's more bleeding and complications after embolization so that's in the guidelines here, your guidelines also yes, I know that but all patients that are embolized are selected patients they are not randomized serious comparing embolization that's not that one observation I would have about embolization is that it means different things to different radiologists and I think the cases I've done that have been embolized it's extraordinary it's made things a lot easier or it felt like it's made things a lot easier and there are many cases where it seems to have made no difference at all or made it worse I think I'm not sure there's a standardized technique of embolization that has been described which can produce a consistent result within the kidney what do you think about first of all are we all talking about renal embolization because I think talking also about the liver embolization for the bat kiari renal artery embolization I think the best way to do it is go and embolize with a couple of coils in the main renal artery to reduce perfusion and this is the way that what we're aiming is to reduce vascularity but not cause an immediate ischemia so from my experience this has been the feedback it's the best way of treating high vascular lesions I think the problem is at least what our problem was when we embolized the artery our thought was okay the artery is controlled we can go after the venous structures when in fact many times it wasn't controlled and so then you're opening up the vein there's still artery going into the kidney blood's going everywhere it's just miserable I agree with that I'm going to ask you a question the cases I really struggled with were cytoreductive big venous thrombus is it the right thing to operate there are some metastases it's going to be complicated how do you make your mind up in those situations whether to do complex venous surgery I mean 55% of your patients have metastases so how do you make your mind up about surgery to people who already have metastases because many of them may never get the TKIs if they get a complication that's true but I think complications can happen with any surgery the group from UCLA published on this and reported that patients even with IVC thrombi and extensive nodal disease can still safely undergo cytoreductive surgery and I think that the complications of a thrombus that progresses and causes hepatic outflow obstruction lower extremity edema and so forth those are not insignificant and we've already shown in a couple of slides that targeted therapy is not going to impact that thrombus it's going to continue to grow, continue to cause problems so I think if you can get the you know I'm not advocating this to be done out in the community but if you can get the patient to an experience center who has a lot of experience with IVC tumor thrombi management those patients can get through surgery relatively well Tim, can I ask Christopher what his indications or strategies with vascular replacement of the caver with resection the Marsden we tend to be very aggressive in terms of resection even the absence of obstruction not just with these but also R-pill and D and many of the retroperitoneal sarcomas just resect at the patients generally experience leg edema for about 3 months but by 12 months they've largely got pretty much some normal lower limb function right and that's basically our experience we do try to rebuild the convenia cable if we can typically using bovine pericardium again prior to my coming there some of the vascular surgeons were using teflon and cortex that doesn't work it clots off so basically if we can reconstruct with either a tube graft or a partial graft with bovine pericardium we'll do that and put the patient on aspirin after surgery but we've also been in scenarios where there's still flow through the vena cava but we had to resect a portion of it and just left it resected and I agree with you those patients are miserable for about 3 months but they develop collateralization and subsequently a lot of those symptoms will go away Jean-Jacques do you want to bring things to a close? No, no Just a question do you think that there are some predictive factors in metastatic disease that could help for selecting both patients who are going to benefit from surgery? I mean, yeah, I published a few articles on it but I don't think it relates to IVC thrombus I mean I think that the factors that you have to look at are, you know, presence of liver metastases presence of CNS metastases presence of nodal metastases those are all predictors of bad outcome extensive bone metastases poor performance status absence of clear cell histology presence of sarcomatoid those are the features that we use to select patients for for cytoreductive nephrectomy but I think just the presence of a tumor thrombus is not in and of itself a contraindication Okay, thank you So we are out of time now and I will close this session I thank all the speakers of this session and we are I think a good cover of all the the mini-invasive treatment of small benaltimone also the practical approach for locally advanced disease Thank you very much