I'd like to invite Luca Regli, the chair in Zurich, who's going to no better place to talk to us about the 50th anniversary of the bypass of Yazd, well 51 now, but Luca, tell us where bypass surgery was and is taking us into the future. Well, thank you very much Jacques, thanks, it's a great pleasure to be here and an honor. So yes, let's try to run through this. So really, well, I mean, everybody knows that it was now 50 years ago, plus one, so in 67, Yazargil did his first bypass, and actually it was a Marfan syndrome and complete MCA occlusion. Interesting enough, in 72 he did also the first Moyamoya bypass in a kid. Really it's, why did this happen? And really it was about the interest, Kraembull and Yazargil kind of had this interest in microscope, and then from there, having this new visualization tool, he developed his vision and turned microsurgery into kind of a standard. Oops, sorry. Now that was the golden area, but we all know that already in the 85, there was a decline because of the bypass study, and so really it's not going to be about technique today, but much more about indications. So where do we stand today? You know, it was established, and it's used worldwide still, so what are the indications today? And that's the present then. Well, we can start, first of all, to separate what Fadi, Fadi Charbel very nicely coined kind of the role, the purpose of the bypass is really two things. It's either flow preservation when you sacrifice a vessel and you want to maintain the flow, or it's flow augmentation in patients who are suffering from any kind of hypoperfusion. So if you want to replace the flow, it's flow preservation. If you want to restore flow, it's flow augmentation. And then if we look now at the indications, once you separate those two purposes, those two roles of the bypass, well, its indication for bypass can be cerebral aneurysms to preserve flow or cerebral tumors or intracranial tumors, actually. Now for the bypass in aneurysms, there really is no big randomized study, and I think there never will be a study just because the disease, these kind of aneurysms that need to be bypassed are so complex, so different from one patient to the other that I really don't think that we'll ever have it. So the evidence that it is useful to bypass patients to preserve flow when you treat an aneurysm is really based on case series, but it's still used, and it's probably the highest indication for bypasses, which are not flow augmentation. It is for aneurysms. And the key element there is to match the flow to the vessel that you're going to sacrifice. Now tumors, sorry, my iPhone, my Siri is kind of waking up, sorry. And then for intracranial tumors, well, I think we can go very quickly through this. I think this is based on even smaller series. It's really just some case reports. And the risk-benefit of treating an intracranial tumor with sacrificing the vessel really is shifting now with also radiotherapy and chemotherapy and complementary. So I think this is an extremely rare indication. I haven't bypassed a patient for intracranial tumor since several years, so I think this is really very, very small indication. Now that's about all for the flow preservation. Now what about flow augmentation? So there really are two indications. One is Moyamoya, and the other one is atherosclerotic disease. And if we look at the Moyamoya, the ischemic Moyamoya also there. There are no randomized studies there, but there is no treatment for Moyamoya except to revascularize and assure and prevent ischemic complications. So it's extremely useful. And for the ischemic Moyamoya, although we do not have randomized trials, the evidence that it is useful and the recommendation out of it really is pretty strong based on a multi tute of case series and also studies of cohort studies. So surgery is recommended for children and adults with ischemic symptoms and compromised cerebral hemodynamics, and to the opposite of that, if it is asymptomatic and if the cerebral hemodynamics is normal, well, careful observation will be the way to go. And that is what is kind of the main accepted attitude for flow augmentation in Moyamoya ischemic. Now, the athero, which really is mainly carotid occlusion, which actually was one of the main indications in the past, there are two things. And we all know the studies of 85. We all know the cost. Still, these patients do not have a benign natural history. So patient with atherosclerotic carotid occlusive disease do not have a good natural history. So there still is the need to ask the question if it is useful. Nevertheless, we all know the cost study, and the cost was not negative in the sense that it was worse with surgery, but it was futile. So really, the results were not any better with surgery. And two important things just to remember. The one thing is that the stroke rate in patients who were bypassed was in the very early period, so actually in the first two days, pretty high, and actually a little bit higher than in 85 study. And the other thing was really that the natural history of the patients medically treated was better than what was expected, which obviously also reflects the improvement in medical treatment. So it was futile. Another interesting thing in some of the studies that came out after, still from the cost data, was what I just mentioned before. Well, first of all, again, as in the first study, the patency rate is extremely high. It's really very good. And also, the principle of bypassing works. So we do have an influence on hemodynamics. However, the stroke rate perioperative was too high. And again, obviously, we cannot do that. But if one would take out those first two days, the stroke rate afterwards was clearly better for patients who were bypassed. So again, we definitely learned how to select very fragile patients for surgery. But we also saw that once you survive the surgery without complications, your natural history, well, it's not natural history, but your stroke rate did decrease. And so that also kind of puts the challenge on, you know, we should put in efforts to find how we can reduce perioperative risk. And obviously, perioperative is not only the surgery itself, but it's preoperative and postoperative in the first period. So nevertheless, we can turn it all the ways we want. The studies did show that for atherosclerotic steno-occlusive disease, especially carotid occlusion, and there's, you know, there's more than one study, there was no benefit. So there is evidence, really very, very strong evidence, that that indication, the cost indication, is not an indication to bypass the patients today. So where are we going from there? And what we can try to look is, so what is, what directions do we go in the future? And although the hemorrhagic moia moia, maybe it's not, it's wrong to say future, I put it in here in the little bit future perspective, because there are these two more recent studies. One is from 2014, which is the GEM. So it's the Japanese adult moia moia trial. And actually, very interesting, it's some sub-analyses of the GEM trial, which came out in 16. So it's a little bit more recent, and it's always nice to take this opportunity to repeat this data. So indication for moia moia, and definitely for hemorrhagic, is very well established now. And I think that's a category of patients which will increase. The indication for bypassing moia moia patients with hemorrhagic presentation, due to these two very good studies, which actually really is one study, but with a sub-analysis, is strong. So adult patients within one year after hemorrhage with good modified rankings, so with independent for daily activities, which also means absence of major brain damage. And that's extremely interesting. With a posterior hemorrhage, have a very strong indication, and have a big difference in evolution if they have surgery or if they will not have surgery. And this is just this sub-analysis of the pre-specified from the GEM trial. And just very shortly, essentially, there's details how they separated anterior and posterior hemorrhage. But extremely interesting, it shows that if you take the anterior, and actually just primary endpoint and secondary endpoint, the difference in a short summary is that the primary endpoint was almost any kind of stroke. And the secondary endpoint was only re-hemorrhage. So but for both, there was a clear difference. If we take anterior hemorrhages, you see that the difference between surgical and non-surgical is way smaller than if we take the posterior hemorrhage. And this is not only interesting to see for this kind of presentation, but it shows that if we don't select the patients correctly, we may actually be discarding a treatment which may be very good for another category or subcategory of patients. And that is extremely important. So we have to improve our understanding of the disease. So again, very, very impressive results for the bypass in posterior hemorrhage in presentation for Moyamoya patients. Now that was, so again, it's actually present. It's not really future. But in the future, in the close future, this will be a category of patient which is increasing for the indication of flow augmentation bypass. And then, and this is a little bit on a more maybe provocative level, I think that there may be some indication for emergency bypass for acute stroke, which actually really is despite maximal medical treatment, if the patient has one of the two situations, either ongoing hemodynamic symptoms despite best medical treatment, and this does not correspond to the cost definition or cost indication. So it has to be ongoing hemodynamic symptom despite best medical treatment. And you can also think about acute stroke and persisting penumbra when any other possible revascularization procedure failed, well, you could think about revascularizing. And really, I mean, also the endovascular studies proved that the concept of penumbra, which essentially is salvageable tissue, does make sense also in a clinical setting. And there may be a very small, very highly selected percentage of patients which may fail any kind of revascularization or best medical treatment and still have either penumbra, salvageable tissue, which is a threat depending on the time that you let by, or ongoing ischemic symptoms. And we showed in a consecutive series of eight patients, again, this just shows how small and highly selected category of patients these are. And again, I'm not going to go through the whole protocol, but essentially, it's extremely important to say that this would be like a last resort and keep these patients on acute stroke, had to fail any other kind of revascularization procedure, and still show the concept of salvageable tissue, penumbra, and symptoms, ischemic symptoms. So they had to be with fluctuating symptoms, which we say see. But really, the hypothesis is, if we believe that the penumbra exists, there may be this highly selected and small amount of patients. And this was an acute bypass patient. A young lady who had a dissection and trauma embolic closure, which was not able to be revascularized and reopened. And the concept is, if you have this kind of mismatch between the perfusion and the stroke, we do sometimes bypass these patients acutely. And this was just to show the other part, the ongoing symptoms. This was a 50-year-old patient which had a carotid occlusion. This was like in January of 2015, not so important, but in January. And despite best medical treatment and attempts to revascularize it, he continued to have symptoms. And then we didn't bypass him acutely in the stroke phase. He had a stroke in January, but continued to do badly. And so we did bypass him in February. And this was the PET also showed clear stage 2 compromise. And I also would like to take the opportunity to show that we have to continue to study these patients and find better ways to maybe also understand the hemodynamics. And this is an example of BOLD-CVR with cerebrovascular reactivity with BOLD. And you really see that the PET and the BOLD, which BOLD is much more clinically accessible through the EMR, kind of really show a very good match between the two things. And actually even more so, it shows that the contralateral hemisphere, you could see before that there was some compromise also in the contralateral hemisphere. And we were able to show in a recent paper that the correlation between PET and BOLD was extremely good for stage 2 insufficiency. So this patient was bypassed. And this is also extremely interesting then. Three months later, he was not, he still had some tears going on. And actually the BOLD, again, three months later, and the PET did show some improvement, but not really a major improvement. There still was, even in the posterior fossa, there was a little bit of diaschesis. I'm not going to go into that detail. But you see that his hemisphere was not, although the region of the bypass already did show some improvement in cerebrovascular reactivity. And he didn't have a stroke, but he still had some ischemic symptoms despite the bypass. And if we look then, the same study 12 months after the surgery, we could see, I mean, there was a really major improvement in the cerebrovascular, or at least in the hemodynamics of this patient, with a normalization of the contralateral hemisphere and clear improvement over the whole hemisphere. So what I'm trying to say there is that we, it's not just bypass in, bypass out. We have to understand the disease. There may be the hemodynamics, I'm finishing, the hemodynamics of what happens after bypass, we don't, we haven't really sorted out. The bottom line of the bypass is to avoid a stroke. And if it takes time maybe, and if it protects, and maybe the bypass shuts off and the natural will take over, that's fine. So we don't know enough. And that's my take-home message is indications, well, there are some indications. Many of the indications are recommendations which are not based on highly level one evidences. But again, tumors, very low aneurysms, we all agree and feel that it's a strong indication. Moyamoya is probably the best indication if we look at grades of recommendation, which B for ischemic, probably B, C, and B. Non-indications for atherosclerosis right now, and a little bit more provocative, and maybe all the way down to today, just really just a 102K series for some ongoing persistent ischemic symptoms. Now future directions, I really think that we have to learn to select better the patients. That's what Moyamoya and hemorrhage shows us. That's what endovascular colic showed us with stroke. Had they not highly selected their patients, all the studies would have been negative. And we have to improve the understanding of the evolution of the cerebral hemodynamics. So very important to develop clinically more accessible, like bold CVR methods to understand how it changes after we bypass. And last but not least, we absolutely have to reduce the risks in the perioperative period of these patients because they are extremely fragile, which actually shows that the disease is not benign. So not improving our treatments really does hurt those patients. So yes, absolutely, we still have to continue to do bypasses and to teach micronastomosis. I think it's a technique. And unless you haven't done some micronastomosis, I don't think you know how to handle delicately tissues. But also, we have to see that, especially for flow augmentation, maybe it has to be very highly selected referral centers because these are so fragile patients and they need the best skills. And as my prior speakers, I also would like to announce that we are trying in 2019, so everybody has still time. But I think we should mark, because it really has been a very important step in neurosurgery, the micronastomosis and the bypass. And we would like to do a kind of a special anniversary edition in Zurich and followed, if possible, with a think tank about where cerebrovascular surgery goes, maybe associating in December some nice places in Switzerland. Thank you for your attention. Thank you, Luca. Thank you for this nice get-together of the bypass concepts. Any questions from the audience? Thank you very much for your nice presentation. In the last, in your pyramid, we make education for resident for neurovascular surgery. So this part of skull-based surgeon should be in the same. Do you think that after training of microsurgery, which is easy to teach to the resident, vascular surgery, because when we are in the vascular, there is no tumor, so the anatomy is respected. But when in tumor of sela turcica, for example, everything is modified, no cisterna, no visible arteries, so it's more difficult to teach that, to operate the skull-based tumor and to make education for resident to vascular surgeon before, in the beginning? Yes, well, I'm not sure if there was a question, but yeah, I agree that, and how I say here, I'm just, what I can say is I see it not every day because not every day we have new residents, but every time the resident goes to the micro-anastomosis course, they come out like they discovered something new, and they have this feeling, now I really understand what microsurgery and delicate handling of tissue is. For the second level of the pyramid, it's, you know, I think we all agree that today, even in tumor surgery, the highest complication rate is vascular complications. And so I think you cannot be a tumor surgeon if you are afraid of vessels, and you should realize what it means, and so on and so forth. So I think it's definitely a skill we have to preserve and cherish in our specialty. Luca, can you comment on the couple of details from the COST study, which is, you know, why it was criticized in some way? Well done study, but still, the average, the mean time to randomization was 72 days. By definition, that means all those patients who cannot sit up in bed because they go ischemic were not entered in a trial. And those are the patients we see, those are the patients we're bypassing. We can, it's just a disservice, unfortunately, to cancel all those operations based on very powerful level one data. Well, Jacques, I think it's fantastic how you're presenting this, and that's exactly the point. You know, we should absolutely not try to criticize the study for what it did study. But we should be critic about what it did not study. And so we should not be operating a patient who has a carotid occlusion 70 days after he had his carotid occlusion, because that COST showed that it's not useful. But the same way, I think it's wrong if you have the neurologist that presents you a patient with a carotid occlusion who has ongoing symptoms, and you can call him those hot patients. I mean, that patient deserves a treatment. And the other thing that's still... Because this slide is still up, the one thing I do plead for is that there should be some referral centers for that. Because if we all start, you know, kind of bypassing one or two patients, then we will never have the truth. Agreed. Another just brief technical point, average clamping time during the COST trial was, for the patients who had a stroke, was 55 minutes. For the patients who did not have a stroke, was 45 minutes. No statistical significance. I'm still puzzled how high it is. I mean, I don't... I mean, and these were, you know, the best centers, and I still honestly don't have... Not that that was shown to explain the outcomes, but still, these are long times for a, quote unquote, simple STAMC. Right. Well, I think you're probably referring to the challenge that we have, that if a technique decreases in indications, how can you keep up also the skills? So you know, it may be a reflection of a skill in doing something on a very regular basis. And you know, you could say if you have done 500 of those, probably you will never forget how you do it. But if you do five a year, your training, your skill, and your speed will need to be refreshed every time you do it. So that's probably what you're alluding to. Yeah. Thank you, Luca, for this.

bypass surgery

neurosurgery

indications

Moyamoya disease

cerebral tumors

acute stroke