 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 maximum 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 define as pathological T3 lesions with invasion into the perirenal 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 inappropriate contemplation that laparoscopic surgery be undertaken. Nevertheless, most of the 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 the surgical endeavours 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 effectiveness, 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 and like 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 eight centimetres when they're reported as a locally advanced tumor. And the further feature is that the case series are 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 of the literature. Nevertheless, there have been an analysis of these series and I'd commend the excellent publication by Grant Stewart and Al 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 again, 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 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 or early postoperative 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, perimesanteric 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 grabadob myelosis. 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 tumors from by. This is those that are within the renal vein and not into the vena cava. Prior occlusion of the arterial 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've reported isolated success but again with hand assist and open completion being necessary. In the larger series where this was undertaken as an endeavor, this was a Chinese series, only 30% of those embarked upon laparoscopic the 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 local 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 tumors fromis 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 splenic involvement as these are standard procedures under performed by general surgeons. I guess other potential considerations are large right-sided tumors because of the small or short removane limiting application of vascular staples safely and perinephric neovascularization although usually the pneumopyrite neum 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 cured procedure. Margins become less of an issue and so therefore we're not attempting or necessarily needing to achieve the radical resection of a cured 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 three agents generally in trial settings pizoponib and excitonib 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 sutant and can make the section identification anatomical plane 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 and this just does relate to the pathological upstaging of tumors 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 the longer term management. Thank you.