 Thank you so much for this opportunity. I very much enjoyed Dr. Boll's talk and I'll try to stay fair and balanced just like Fox News when I talk about metastatic RCC. And it is indeed true while we're waiting for the true randomized trials from the URTC and Kermina we should not really hold our breath too much because some of them are really accruing quite slowly and we may not have the results for a while. I do miss 2001 when the approach was quite simple. We have a tumor, we have a study, it shows we have two studies, it shows advantage to the cytoreductin nephrectomy, and we go ahead and do it. And a decade later we have this very helpful diagram as one would call it, but nevertheless let me focus on this very area on the left of the diaphragm. When we look at this beginning of our progress and the beginning of our decision-making relapse in stage four or medical or surgical and unresectable disease these are different patients. We start our treatment paradigm with a very mixed bag of fruits and oranges and apples and I don't even know what else is in there and I can assure it's not a pumpkin there will be some very angry oranges that we need to pull out out of this group. And we do have prognostic models, we do have a very nice MSK-CC prognostic model by Dr. Mothra and Danny Heng has done a great job with his group with the International Consortium, but one thing we need to see is although these patients are well separated into the Greece groups these criterias were not designed for patients with synchronous metastatic RCC. And I think it is very important as much as we lean on these criterias we cannot necessarily stratify patients by synchronous metastatic RCC. If you look at this very table the time from diagnosis to targeted therapy in years was 1.4 years. We don't have 1.4 years in patients who present with synchronous RCC. Take a look at the data again by the International Consortium and those patients from the treatment to less than one year the median overall survivors is only 14.7 months. We do not have 14 months to start. Take a look at Alex's back to study. These are all in the form of the abstract in ASCO. Poor risk is 8.5 overall survival and we have only 15 months before these patients die. And I'm very happy that this is truly recognized by the medical oncology colleagues because as we can see here the recent paper by Mothra and the BJC shows that those that were treated less than one year 7.4 patients had a median month of progression free survival and only 16 month again consistently prior to abstracts I just showed before they die. So if we do not proceed with something fast and if we do not commit early I think we may be losing a little bit of a time because on patients who have eight months to leave if we subject them to a trial of the drug first we may not have the time to recuperate. And let us take a look at the group from MD Anderson 10 years data and his group and take a look what we have. 50% survival these are outcomes of patients with metastatic RCC treated with targeted therapy without cytoreductomy. Granted many are half are intermediate half are poor risk factors and take a look here. We have less than a year for these patients to leave. So what do we do in a targeted era if we give them the drugs first less than a very few patients have 30% or more in response and while it correlates with the overall response it is certainly not enough to make our say that let us use the targeted therapy first. If we look at those patients and proportion of those will present with the IVC thrombus the level of the thrombus is much more likely to increase rather than decrease in the area of targeted therapy and then we're truly taking somebody sick and subjecting them to a much more challenging surgery. A little bit of a basic data while we have some very interesting studies from several institutions including Harvard Eric Jonas's group recently showed a rapid angiogenesis onset after discontinuation of sonitinib. So what we have here is the proliferation of endothelial cells and those patients one we stop sonitinib as they the group described maybe there is some sort of a rebound effect of endothelial cells and maybe indeed our angiogenesis is just taken out of control are we really doing anything good. Babuza yesterday gave a fantastic talk and he suggested to put things in boxes and unfortunately I can't fit my patients in boxes but if we try it we will look at tumor factors we will look at location number of mats, patient factors, markers and we will have to decide how we're doing with the site reductive nephrectomy and again these are tumor markers we're looking at the we're looking at the site of metastatic disease at the patient factors at the other things and I will not have enough time to go over all the data where we try to look at the prognostic criteria. Indeed we do know that the tumor burden is indeed important and Dr. Bauer appropriately pointed out that as patient with the tiny renal mass and a large metastatic burden should not undergo site reductive nephrectomy but we do know indeed that the more tumor we removed with nephrectomy the better chance that they will do well and it has been shown in several studies. It is very important to appreciate the work by Shuk and others from UCLA that the ECOG is a very important prognostic factor and this ECOG is study after study and the conoptic performance status is study after study that it's very important problem one of the best and most predictive things and again if one is sarcomatoid then perhaps there should not be operated. The issue is if you look at over 400 patients done at MD Anderson we cannot adequately and preoperatively with the needle biopsy state whether or not they have sarcomatoid RCC and in fact less than 10% of patients were adequately and appropriately diagnosed with metastatic sarcomatoid RCC unless we do a saturation biopsy of the big mass. So here's the study that is supposed to help me out and I thank Tony Chawari for putting it in and having it published that we have a site reductin nephrectomy on survival of patient and indeed patient with site reductin nephrectomy appear to the wall. While I was at the NCI we actually wrote an editorial that the median time to treatment in this group was five months and some patients treated as late as 17 months after surgery just because this patient had site reductin nephrectomy these are not patients with synchronous metastatic disease and unless we understand the behavior of synchronous we will not be able to do too much of a progress and this is a courtesy of John Leppert who presented this data yesterday and indeed they know site reductin nephrectomy have done worse than those with site reductin nephrectomy but take a look we're indeed a very different patients and our selection bias is quite strong and it doesn't matter that we do propensity score analysis and I can take as many square roots out of the sick patient I am not going to take a sick patient a healthy patient by subjecting them to mathematical methods. We should not forget a very important and a very practical scoring algorithm by LiboVitch and a group from Mayo. I think it is very practical because it minimizes all the other things that we look and continues to look for and this is in 2005 and it really gives us a very good stratification and I truly wish that we would use more of these algorithms in designing of our trials and take a look at the very nice stratification and again every other factor that we can see from pathology or from patients performance or symptoms at performance we can at presentation are very helpful. So the group from MD Anderson have appropriately brought up a question can we better select patients with metastatic disease synchronous metastatic disease for site reductin nephrectomy and they have performed this very eloquent multivariate analysis and again looking at the number of risk factors we can stratify those. What I'd like to point out that patients treated with medical therapy only are a almost in a very very bottom so it tells me two things it and it can be interpreted by two things number one is that we're just so good as doctors in selecting patients for surgery and indeed we have the Gestalt we'll look at everything we'll look at all the boxes and we say you shouldn't have it and that's why we're just so good. It can also argue that those patients that were deprived of site reductin nephrectomy have truly done poorly. I know that the truth is probably in the second in the first that we're just selecting patients appropriately but I'm sure that a proportion of patients could have benefited from site reductin nephrectomy and denying everybody site reductin nephrectomy upfront may not necessarily be the right thing. If you look at the diagram from the public relations and this is my last slide if we look at the decision-making in a medicine I think the public relation knowledge is actually quite good. This is a continuum what we're not talking is black and white as Dr. Bowles alluded and if we look at a truth we will go to persuasion, a storytelling and obviously the seed and if I had to use these four things as well I would say that indeed a young healthy person with a no CT4 and few meds and a ECOG-0 should probably or definitely or absolutely undergo site reductin nephrectomy upfront. The old frail person with a CT4 and numerous meds and different spots including the brain should probably not be offered site reductin nephrectomy but I do think that as we do gain some risk vectors as these patients do get sicker I do think that more patients than not would likely benefit from the site reductin nephrectomy upfront although it certainly should not be black and white. I thank you all. This is a picture of a Syracuse and our department. Thank you.