Challenges and Innovations in Pituitary Surgery

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- Hello ladies and gentlemen. Thank you for joining us for another session of the Virtual Operating Room from The Neurosurgical Atlas. Today our guest is Dr Juan Carlos Fernandez-Miranda from Stanford University. Juan Carlos is an incredible surgeon. He is truly one of the most impressive rising stars in Neurosurgery. And I'm absolutely positive we're gonna hear a lot about his successful refinements of skull-based surgery in the next decade. Juan Carlos, I know you have been with us before, truly your contributions to skull-based surgery, endonasal surgery, technically and also neuroanatomical research projects have been groundbreaking. So it's an honor for us to have you again for pituitary surgery innovations and challenges and I know you have pushed the boundaries there and we're all excited to learn from you. Please proceed.

- Thank you Aaron. Is again a pleasure and honor to be with you again and continue our ongoing collaboration hoping to influence the next generation of surgeons in the field of skull base surgery, endoscopic endonasal. And today we're gonna talk about pituitary surgery. In particular, challenges and innovations in pituitary surgery. These are my disclosures, in particular, maybe relevant to this talk. The KLS Martin, Endoscopic Dissector Set Design, that you're gonna be seeing the use in these videos. This is my team at Stanford. As I'll emphasize today, it's so important especially for a pituitary successful practice to have a good Rhinology ENT team working with you. And to also have, very importantly, your Neuro-endocrinology team closely collaborating and working with you. This our beautiful hospital at Stanford, new hospital. And I'm gonna start by describing what I think are some basic principles of modern pituitary surgery that are relevant for me, important. Very important for me. First of all of course, is the importance of the use of a privileged visualization tool, which is the endoscope. And that makes a big difference and that made a big difference about two decades ago perhaps where the endoscope was introduced and substitute the microscope for the most part because the endoscope can provide this very wide angle view that the microscope cannot provide. Second very important principle, Pituitary surgery is actually a skull based surgery. And for long time pituitary surgery was like a reduced field and sometimes separate from skull base surgery and I think in my opinion as you will see today, that is not what modern pituitary surgery should be. It should be in the realm of a Skull Base surgery. As or admired Professor Sekhar say, "There is no place for occasional skull base surgery." Similarly I believe there is not place for occasional pituitary surgery. I firmly believe in super specialization in this field, in pituitary and skull base surgery and I personally, as you will see, why I discourage community hospital pituitary surgery for the most part and I encourage for centralization and referral centers for these complex operations because the outcomes are dramatically different. Please look, run this video if you could. So, a key principle of pituitary surgery elaborates is that this is endoscopic endonasal microsurgery for pituitary adenomas. We sometimes face very challenging tumors that in the past were inoperable through an endonasal approach and we had to do combine or exclusively transcranial approaches. But nowadays we can do really amazing work, working endonasally, using microsurgery-like techniques to remove these very complex tumors. There is this particular entity of subarachnoid invasion by pituitary adenomas that we always need to think about because these tumors do not respect the arachnoid and they are very challenging. Some people call them aberrant adenomas because they are just not the usual good-looking behaving adenoma. They behave more like invasive tumors such as Craniopharyngioma for example, are Meningioma and as such, they should be treated. Let's go to next please, look. Thank you. Along with that, it's important to use the proper instrumentation. So now for pituitary surgery we use this type of microscissors or we use the step of dissectors as explained before. In my dissectors there is only one ring curette which is actually not used very often but it has rhoton-like dissectors, it has angle knives. It's a different set than the traditional pituitary set that has, you know, 20 different ring curettes. We only have one and we have microdissectors and microscissors just like we do for microsurgery. Another very important principle is that we work with EMT and working as a team makes a big difference. The whole is greater than the sum of its parts. And I firmly believe in the benefit of working as a team and collaborating. For example, in this case, this is, oh, okay, well, I'll show this case at the end but this case illustrates, I wanted to say that the collaboration with EMT is so important, At multiple aspects, in particular for the approach and for the nasal care after the operation. But also because they provide superior operability because it drive the endoscope in a way that allows you to do a very efficient operation. And of course, the role in participating in Multi-layer Vascularization, Multilayer Reconstruction with Vascularized flaps is key. This is a case where there was no septal flap available and we used an inferior or lateral nasal wall flap. And their participation for this part of the operation is really, really relevant. Let's go to the next please Look. When we review or experiencing Pittsburgh long ago, this local paper. The view in the, the experience in Pittsburgh for a decade about 555 tumors, these were the outcomes we found. Ihis becomes better in most patients and rarely worse CSF leak rates at the beginning were about 5% now we drop it to about 2%. And of course there's always a risk of ICA injury. And there were two cases in that initial series with, you know, dramatically different outcomes, but we always would have ICA injury when we work in the pituitary region. My experience with this is being no injury to the ICA in the last 10 years and more than a thousand in the nasal cases. I'm always extremely careful with the carotid, but at the same time very aggressive to ruin tumor around the carotid. With this I wanna send the message that we can not take lightly working around the carotid. Very seriously but at the same time we can do very aggressive and effective work around it without injuries. And I'll illustrate that today. Also we found that the resection rates were highly correlated with the degree of invasion. And this is very well known of course. Not great correlates with the degree of invasion in the cavernous sinus and with the resection rates. But there are some things we can say and criticize about the NASCA grade. And that's another point I'm gonna make solely. But because of this invasive to the carvenous sinus, pituitary now become more difficult, more challenging. And that's why I had a long time interest on understanding the cavernous sinus anatomy. And how to do an operation safely within the cavernous sinus. As you know, when we talked about the cavernous sinus from a transcranial perspective, we talk about the superior wall or roof of the cavernous sinus. And when we talk about also the lateral wall of cavernous sinus can be accessed through transcranial approach. Even the Postial wall can be accessed through a transcranial approach. Now when we talk about endonasal approaches to the cavernous sinus, we talk about the anterior wall which is this one right here, anterior wall. But we also talk about the medial wall of the cavernous sinus here. And we don't see it here but the roof of the Cavernous sinus will be there, deeply. All those can be approached endonasally. We took a great interest in studying the dural layers of the celebrium. Everybody knows that we have two layers in the pituitary area, outer layer medial periosteal layer. And inner layer, medial layer. This periosteal layer continues laterally here and forms the anterior wall of the cavernous sinus. One single layer right here. This medial layer of the cavernous sinus, this one right here, in red now goes around and forms the medial wall of the cavernous sinus. It completely surrounds the pituitary gland, that is the medial wall. While the anterior wall is this area right here. Now there is bifurcation of these two layers that happens right here at the floor. This bifurcation is what forms the cavity of the cavernous sinus. The envelope of the cavernous sinus that contains the wheels blood of the carotid and the cranial nerves. Now, based on these knowledge of the dura layers, we had studied carefully the meningeal layer on the, or it forms the medial wall of the cavernous sinus and we found all these ligaments, we call them the parasellar ligaments, and these ligaments go from the medial wall of the cavernous sinus to the other walls of the cavernous sinus from the carotid itself. They are not between the pituitary gland and the medial wall. They are between the medial wall and the, all the walls of cavernous sinus. So they are inside the cavernous sinus. Okay, so there were other authors in the past that were pioneers on or understanding of the medial wall of the cavernous sinus and its relevance for pituitary surgery. In particular, Dr Oldfield with his unique and amazing experience with Cushing's disease. He described the occasional occurrence of tumors in the medial wall of the cavernous sinus and actually nested it within the medial wall of the cavernous sinus and he discovered the need to remove it, and so in phenomenal results. Similarly this Japanese group of the Pro Gemara, they published this paper some years ago with extraordinary results in acromegaly, 85% remission based better than ever before reported. And they showed that there were 18 cases where they remove the medial wall of cavernous sinus. 16 of them being positive histologically. And they don't really describe the anatomy or really the technique to remove the medial wall but they show this picture and the medial wall is being removed here. So also their plenty of work needs to be acknowledged. Because we stand on their shoulders and we continue understanding this better and develop this more accurate understanding of the anatomy. And when we looked at these, we found that is a very constant and a strong ligament which is called the carotido-clinoidal ligament, CCL. CCL is a continuation of the medial wall of the cavernous sinus, of these meningeal layer. It goes like this and then it goes in this direction. And this forms the superior anchor of the medial wall of the cavernous sinus. You can see in this cartoon, this is the CCL. And the CCL is direct posteriorly to attach to the under surface of the anterior clinoid.. But it also surrounds the carotid, anteriorly as you see right here. It goes in front with some attachment and goes around it. It forms like a collar around the carotid artery. This CCL is what we call the ventral aspect of the proximal dural ring and is the superior attachment of the medial wall of cavernous sinus. And it actually defines the clinoidal segment or paraclinoidal space, or carotido clinoidal artery. This is the carotido-clinoidal artery right here. So when we look at the CCL from an axle perspective, you can see it has this trajectory, usually from the middle clinoid,, goes, a bit in front but mostly behind the carotid to go to the anterior clinoid. And it can have multiple fibers. There are many variations here, sometimes you only have these fibers. Sometimes you have all these other fibers here. And they can be all continuous forming a firm roof or discontinuous with holes that connect clinoidalous space and cavernous sinus. Importantly, the fibers of the CCL then close the coralade with the interclinoid ligament. The ICL goes from the anterior clinoid to the posterior clinoid is a well-known ligament because he forms part of the oculomotor triangle, but the CCL is located infront of it. So this is, here, CCL and then all the way back you're going to find the interclinoidal ligament. To the point that I know that all the carotido clinoidal ligament has been removed or transected when I actually look and find the interclinoidal ligament. That is my key landmark. Different than the ICL, the carotido-clinoidal ligament is free of standing here. You can cut it. But the ICL is a stuck to the dura. You can trim it but it's stuck to the dura that forms the roof of cavernous sinus. Okay. So, based on that knowledge, we are revisiting the anatomy of the clinoidal space from an endonasal perspective. And of course we always need the carotid open an endonasal perspective. So endonasally here, we can see this is the CCL right here, thick ligament and it goes underneath the carotid, a bit infront but mostly underneath throughout to the anterior clinoid process. The space that is leaving above, this space here, is the clinoidalous space that contains the clinoidal segment of the choroidal artery. Okay the space below that contains the carotid here, that is the cavernous sinus segment of the carotid. Okay. As I will show you, tumors can selectively more often go into the cavernous sinus but sometimes can actually embed the clinoidal space. There's a very important consideration that I found in recent cases. So when we look at the anatomy from an open perspective, you know, here we're lifting the roof of the cavernous sinus. I'm gonna find the ICL, interclinoid ligament, and there's a little fiber right there, we're starting to see fibers of the CCL. You remove all these dura, we can see CCL in this case. There is a big hole here, meaning this CCL is not very complete. But this is CCL, this is ICL. And this anatomy again defines the clinoidal space. And we can compare it again from a above from below. These are the fibers of the ICL going in this direction and attaching to the carotid in front and behind. And then this is the interclinoid ligament here. Again everything above this space is Clinoidal, everything below is or cavernous sinus. Okay so, with that in mind I'm gonna show you this first case. Case example, small tumor based in middle-age with the prolactin levels elevated. Present with sexual dysfunction and he tries medication but he's intolerant. And this is coming up more and more often in my practice and in the practice of others where patients are not tolerating the medication well. They have especially increased irritability, increased depression and this cabergoline or bromocriptine medication really has some side effects in patients that appear to be subtle but not so much. So we have a stronger consideration for surgery sometimes in these cases. Especially as we become more confident with our surgical skills and outcome. So this is the tumor right here. And the location of this tumor, you know between the carotid here and the pituitary gland here, it is very suspicious for a location into the clinoidal space. Look, can you play this video please? This is the MRI, you see the tumor? How it's bracing the carotid? So this tumor, when I look at it makes me think this tumor is invading into the clinoidal space. Okay, let's go to the next please look. So this is the challenge of selecting curable PRLomas. By this, what I mean is let's play the video please look. There are PRlomas that are incurable with surgery because they are twin based. But others, we can actually cure and make a big difference in these patients. So we are doing a wide exposure. We are surrounding the tumor. You can see the tumor protruding through the dura. And next to the clinoidal corusegnal of the coronary artery. So what we're doing is finding the pituitary gland. And then I'm gonna find the clinoidalous space. This is the dura that separate the Suprasellar arachnoid. This is the carotid in the clinoidal space right there. So now I'm opening below into the cavernous sinuses space. Now I'm gonna enter into the tumor to debulk it some. To make it easier, it's removal. But just debulking it is not enough because it has all these attachments where there is tumor. So I'm working in the clinoidal space, detaching, cutting those fibers of carotido-clinoidal ligament. And that allows me to join the paraclinoidal space from the cavernous sinus space. So I need to get a picture that is from this to this picture. Okay again, I wanna get from this, the tumor is invading this area right here. What I wanna do now, cutting in surgically the attachment of the posterior region so I can mobilize the carotid more. We're doing at this level is opening now below the CCL. We're opening right here. And now we're cutting through the CCL. Look at the beauty of those fibers. Those are fibers of the carotoid-clinoidal ligament. The same fibers as these that you're seeing right here. And the tumor is growing along these fibers. This is something I'm finding more and more often, how tumors use the fibrous tissue to grow within. Embedded in that tissue. So I have to go below, find the clinoidal in the cavernous sinus here. And then I found both sides of the carotido-clinoidal ligament. So I can transect it above and below. You can see the ligament right there. Now we'd love to just get a clean cut on this ligament but it's stuck to the carotid so I'm going to coagulate it and then cut it, trim it progressively and remove all the tumor and whatever it is left I'm just gonna coagulate. So that's the residual attachment of the tumor and all the way back. I'm seeing that interclinoid ligament, we will seen right here, which we see right in there. Keep the anterior clinoid process, interclinoid ligament, you see beautiful fibers on the interclinoid ligament right there that tells me I removed all the CCL. So that is an interesting resection involving clinoidal space and cavernous sinus. I haven't, I'm not aware of any other publications reporting tumors invading the clinoidal space absolutely in this area. So we are preparing, you know, our next paper on this topic. Let's go next, please look. Now when we go more inferior within the cavernous sinus, along the medial wall. We find the inferior parasellar ligament right here. And this ligament had attachments to the carotid and to the anterior wall of cavernous sinus commonly. You can see it right here in the cartoon. And it's a very relevant ligament because it is the first one we find when we opened the cavernous sinus wall at this level, we're gonna find this ligament. Now this ligament is anchoring the carotid to the medial wall. So if I wanna remove the medial wall, or if they wanna get my way towards untill the posterior clinoid process, I need to transect this ligament right here. So once you transect it, remember that behind you will find more often, most often the inferior hypophyseal artery. And that artery is at risk when you do these operations as I will show you in some case examples here. So remember the IPL, Inferior Parasellar Ligament, important reference for the inferior hypophyseal artery. There are other ligaments within the cavernous sinus with significant variability that we are trying to understand better but this is what we found in our initial studies. These were published in this article and then we had a second part. So with that anatomical knowledge. We design this step-by-step anatomically based technique to remove the medial wall of a cavernous sinus entirely. And this is a technique that I've applied multiple times with, you know, excellent resources I shall share with you. For example, here in this case, the tumor has been removed. And then our next step is to find the right opening point to separate the medial wall from the anterior wall. And then we can start modulation the medial wall, the cavernous sinus, the inferior parasellar ligament be transected. Next we nedd to transect the artery. We transect the CCL, coagulate the artery and at the end you get a picture where you see the posterior clinoid ligament, interclinoid ligament that tells you you have to remove the whole medial wall of the cavernous sinus. I always look for these two landmarks, posterior clinoid, interclinoid ligament. Of course, inferior hypophyseal artery, post . There is so much important element here to remember. The first 50 cases we did, we did at the University of Pittsburgh. And our initial results were, you know excellent with no ICA injuries. Four patients, 8% develop a transitional palsy. Probably secondary from some of the packing material we use to control the bleeding. Histologically confirmed invasion 86% of the patients. So excellent results. Biochemical remission rates were super high but this was very short follow up. I'm sure there have been several occurrences since then. But now when I joined Stanford in the last two years, we've been religiously following and documenting our outcomes and registering our cases. Excuse me. We've done 120 pituitaries in the last two years. And if you can look at the numbers there are 105 primary tumors and 15 recurrent adenomas. Globally, we have removed the medial wall in more than half of these tumors. So imagine these are routine pituitary practice. Mine is not routine of course it is referral-based biased but in my pituitary practice, more than half of the patients require medial wall resection, cavernous sinus surgery. That's why this is not just conventional pituitary surgery, this is skull base surgery. I've done this, you see in all recurrent adenomas, 15 out of 15, all of them require this medial wall resection. Which tells you why these tumors recur because they are in the medial of the cavernous of sinus or within the cavernous sinus. Inspite of the complexity of these cases we had, again no ICA injury. Only two patients got transient diplopia. There were no permanent morbidity in this series. Very remarkable, we've been looking at the frequency and patterns of invasion based on cell lineage. And if you look at this data, we can see that Somatotroph Adenomas stand very much from the other cell types as the one that invade the most commonly, most frequently, the medial wall of the cavernous sinus. In 87% of the cases, 21 of 24, I removed the medial wall of the cavernous of sinus in a Gonadotroph Adenomas. Well this was an only, in you see 32, 38, 57% of the cases of other tumor types. And you can see the correlation with histology how often they histology confirm positivity of the wall. Now, I know, I am convinced there are false negatives here because for example, some of these tumors are very difficult and there is a lot of coagulation artifact and maybe you are losing the cells when you're sending to the pathology so there's not a hundred percent accurate. But many of them are being confirmed and you can, for example see a slightly how 10 out of 10 of the non-functioning gonadotroph adenomas had positive in the, confirm with histology. Now we focused on acromegaly patients. Now we have 30 cases here because we have 24 plus Plurihormonal Adenomas plus double adenomas that also cause acromegaly. That's why we have, you know this mix adenomas that produce acromegaly. When we put all the acromegaly cases together, 30 cases that I've done in the last two years and we look at the correlation between medial wall invasion, histologically confirmed and knosp grade, we are finding something that is striking. Which is that knosp grade is not useful to predict invasion of the medial wall of the cavernous sinus. It is not at all for growth of the adenomas because we find in 29% of grade zero and 57% of grade one, that there is actually invasion of the medial wall in the cavernous sinus right here. And this is again, quite remarkable and new knowledge we are providing. Grade twos, a 100% of them. All of them invade the medial wall of the cavernous sinus. If you compare these with non-functional adenomas. Right here, you can see that for example, grade twos on functional adenomas, all of them invade the medial wall. You look at the non-functional adenomas, just a few of them invade the medial wall. Grade three we know not always non-functioning tumors Grade three invade the medial walls. Sometimes they are just compressing the medial wall. However when you have a functional tumor, in our experience they always invade in the medial wall. So there is something about the biology of these tumors that made them more invasive. And therefore Knosp Classification cannot be applied similarly for non-functional and functional adenomas. In particular I would say that it's not useful to predict cavernous sinus invasion in functional adenomas. So at least not as useful, not as reliable. Okay, so I'm gonna show you a case that is, please look all ahead. And this case, it was very interesting because you know, that's a Grade zero or a Grade one, if you will, Knosp adenoma. I think it's at zero. But in this case it is with acromegaly. You know, you will not expect that it's invasion of the medial wall of the cavernous sinus. I'm not sure what the video quality, doesn't look that good. Maybe it's the connection. But we do a wide exposure and then we are going to focus on removing the tumor from the sellar first. And this the usual whitish soft growth from a pleomorphic adenoma. But when we look at the medial wall of the cavernous sinus, we see these two implants right here. And this cannot be really taken with pituitary, with curette. They are stuck for the wall. So what I do then, is I map with a doppler the anterior wall. I find this spot to separate medial wall from anterior wall. I open it, pack it with Floseal. With, you know hemostatic agents and then I start peeling the medial wall off the anterior wall and the carotid. So what I need to think here now is inferior parasellar ligament and behind, I need to find the inferior hypophyseal artery. So I found those, coagulate the artery, cut it and then once I do that, I start cutting the dural of the medial wall along the posterior clinoid process as you see right here, The posterior clinoid process is the point where the medial wall becomes a posterior wall. So that's my landmark, posterior. You can see the implant on the medial wall. Then my super limit as I to do this resection, as I told you is the carotido-clinoidal ligament, which I need to cut and I cut it all the way until I find the inferior, sorry, the interclinoid ligament. So you see this technique is totally anatomically based. Every step is based on the knowledge of the anatomy of the cavernous sinus to do this successfully and safely. Now then we send the sample to the pathologist and they will do H and E and they will also do immunohistological studies to confirm the invasiveness of the tumor into the medial wall. And this is at the end of surgery. So there we go. So you saw that case that a Grade zero or one is invading the medial wall of the cavernous sinus strikingly. Now as the tumors grow and become a Grade two or Grade three more invasive, more extension into the cavernous of sinus. We need to start understanding the concept of the compartments of the cavernous sinus. And something that I still am trying to understand is, you know, there are tumors that grow within the structure of the medial wall the cavernous sinus. And then they expand and extend into the cavernous sinus compartments but they're still contained within medial wall and fibrous ligamentous structures. However there are some other tumors that completely break through the wall. Destroy the wall entirely and they invade diffusely in the cavernous sinus. Why one thing happens and so the other? We don't know it yet. I don't know if it's the tumor characteristics. I don't know if he's the medial wall structure, characteristics of the patient. Maybe both but those are both our findings. But before we had the knowledge that tumor adjusting into cavernous sinus and you need to go there and just suck it out. But we find more and more often, very frequently that tumors actually are containing the wall. And that fibrotic tissue makes it more difficult to be, you know, entirely removed. So this classification of the compartments of the cavernous sinus is different than Knosp classification in the sense that Knosp Classification tries to predict the invasiveness into the cavernous sinus based on its Grade and to relation with their carotid lines. But all anatomical classification of the compartments is based on anatomy ofcourse and it aims to help understanding the patterns of tumor extension into cavernous sinus. We have a superior compartment above the carotid. We have an inferior compartment below the carotid. We have this component that is often forgotten and is so important because it's an area of residual tumor very often, is the posterior compartment behind the of the carotid just above the sixth nerve. Now I'm gonna show you an example of this, again another prolactinoma but in this case, this tumor was a resistant tumor with very hydrosoft cabergoline the tumor continue growing. Yes you can do radiation for this but I think surgeries are more effective and an experienced hand. Hands safer option with less side effects, at least in my experience. With no ICA injury and no, no permanent injury to the cranial nerves. Radio surgery has a risk as we will see there are about 4% injuring, permanent injury to cranial nerves and about 25% injury to the pituitary gland function. So that's the rationale behind being more aggressive with the surgery. So in this case we need to understand the Superior compartment anatomy and this another of the superior compartment. There are three structures we need to remember. One the interclinoidal ligament, as you see right here and then that interclinoidal ligament defines a compartment above or a triangle, the clinoidal triangle with the clinoidal ICA, clinoidal space and the oculomotor triangle here with oculomotor nerve. So clinoidal and oculomotor and in between the interclinoidal ligament. Key landmark and reference during surgery. So in this case, that's the prolactinoma, we're going to go and what you're gonna see is that this tumor that appear to be completely built into the cavernous sinus you think you can go there and just suck it out you will see that's not the case. So within the cavernous sinus I can see the carotid very nicely. And then look at this, this is the medial wall of the cavernous sinus. Right there, medial wall. So the tumor is displacing the medial wall and invading into it. So to remove this tumor you not only have to remove the tumor soft part of it but you need to remove the attachments because the tumor is growing into them. And that makes the operation significantly more challenging. Again you can see the CCL that is a carotido-clinoidal ligament where tumor is extending. We are cutting the atonomy of posterior legino where the inferior hypophyseal artery is. And then we are cutting the dura of the oculomotor triangle because the tumor is embedded in that dura. And as we cut the dura, we find the supra, the interclinoidal space. But remember this is our interclinoid ligament right here. And if we know that's the ligament right here the third nerve is gonna be here. This is clinoidal triangle. Okay. So superior clinoidal carotid Right here, this is Pecam. And then the whole superior compartment has it been accessed and the tumor removed from there with the identify of the third nerve, Clinoid segment, occulomotor segment. And this is a postop MRI of the video where we can see the the postop MRI here and the postop MRI with a complete tumor resection and normalized prolactin. This patient is six months out of surely with still normalized prolactin without any medication. Okay so, that's an example of going into the cavernous sinus superior compartment. Now we also need to understand of course, very importantly the inferior compartment of the cavernous sinus. Has the sixth nerve running just below and lateral to the carotid. We find sometimes find a sympathetic nerve and it's important to understand the surgical of the carotid artery. And then when I listed these with a few cases. So when I look at MRIs, I look at the inferior compartment right here. You know below the carotid. And that tells me that I need to work in that compartment. The posterior compartment is behind the carotid. It's just here. So it's this area right here. I know that at the floor of this compartment I have the sixth nerve and I'm gonna talk to you later about how to find this sixth nerve effectively but the key is this one right here. Finding what we call here petrous apex. That is often the Petrosal process of the sphenoid bone and this shape is where the sixth nerve turns and goes into Dorello's canal. I found that dura that is curving as my landmark to find the sixth nerve behind the carotid artery. And that is an extremely effective way of finding it. So Posterior compartment, where tumors like this for example, are invading. Posterior, Inferior, Superior. So let's see this case. This is a young female patient. Non-functioning adenoma invading the cavernous sinus. Likely based on imaging. You see there's tumor here that tells me superior compartment. Right here superior compartment but also posterior and also inferior. So let's do this operation. Now, young patient. So we just do it conservative. Leave tumor and then do radiation. I know many students advocate for that. I believe that you have the chance of curing this tumor, you should try if you have the ability to do it safely. It's always be better than adding Radiosurgery to the mix. You can remove it all completely. So we are opening the dura of the sellar. We are taking removing the tumor in the sellar. You see a nice clean pituitary gland here. And now we start seeing the tumor that is going to invade in the cavernous sinus. So I open the entry wall of the cavernous sinus widely because I need to see the tumor inside and I need to see the carotid artery. So this is a soft tumor that makes it easy. We see an inferable CRG branch we're coagulating. We see another one. Sometimes there are two well branches perhaps. So we need coagulate that one too. And then I always thinking about landmarks. So I'm thinking about I need to find the interclinoidal ligament. And here this, interclinoid ligament right there. You see it very nicely. And whatever is above is clinoidalous space. That is clinoidalous space right there. Whatever it is below is oculomotor triangle that's what my third nerve is gonna be like. So now I'm working in the inferior compartment and this is medial wall, what is left of it. In this case, it was not all destroyed. This is medial wall, still here with tumor on it but it destroyed other parts on it spreads through the cavernous sinus. So we are cutting this medial wall and then we're slowly gonna get access to the carotid right here. So I keep opening the anterior wall of the cavernous sinus. This is that Cartool stimulator that helps me to confirm the location of the sixth nerve. It really doesn't find the sixth nerve for you, it confirms the location. So as I see the carotid, I go slow. Another sixth nerve is gonna be right here. And that is my sixth nerve right in this area and now I can stimulate it. And that is useful to predict whether the sixth nerve is gonna be functional right after the operation or not. And in this case the patient had an excellent outcome with no sixth nerve palsy after the operation or whatsoever. Working in front of the carotid, working behind the carotid. On the inferior and posterior compartments and finding the sixth nerve on both areas. And now I'm working again into the superior compartment. working around the interclinoidal ligament towards the Oculomotor triangle. And you see the carotid has been fully scrutinized. The medial wall has been completely removed what was invaded. Compartments have been explored. That's proving that the third nerve is intact also. There is still a bit more of medial wall that is invaded so I'm removing it and this is at the end of surgery. Whatever remains I can coagulate to assure that the tumor will not grow and then you're sucking from the residual on the suprasellar space arachnoid and a nice clean resection. And this young patient has the better chance of not having a recurrence ever with this more aggressive type of operation. Again no complications that could refunction and an excellent outcome. So and this is the postop as you can see. And it's probably two years postop at this point. So oh let me go next. So this is the postop. So another case, this is also a non-functional adenoma and this lose more complex. Superior, Inferior, Posterior made a bit of lateral compartment. But also look at the carotid, it's very loopy. So these are more ugly tumor. Okay and this one, I guess when I jump to a later area here. So that's a beautiful view of, let me ask if you guys go back a little bit, because I wanna show you a couple of concepts here. First is the carotid extending into the anterior compartment. Taking tumor from there. We're gonna find the sympathetic nerve right there. That is sympathetic nerve that joins the sixth nerve. You stimulate, It will stimulate the sixth nerve right there. So sympathetic nerve. Now I keep taking tumor and I'm gonna move towards the posterior compartment. But as I take tumor and I go to the posterior compartment, I coagulate and I'm gonna find Dorellos canal and you're gonna see this is Grubers ligament. Petrosphenoidal ligament that covers the sixth nerve posteriorly. So the sixth nerve is just infront of it. And then I find arterial bleeding and that arterial bleeding is a bit scary because it's right on the ball of the carotid artery and that's the area we need to be extremely cautious always. That's why I like to identify the anterior and coagulate it early on. But with good bipolars you can coagulate the injury right at the exit and be done with it. So you need to be very comfortable managing arterial bleeding from branches of the carotid artery. And ideally make sure you don't avulse them from the wall of the carotid. Look at how loopy is this carotid. So you need to have always a three-dimensional configuration of the carotid artery within the cavenous sinus when you are working in this area. Okay so, maybe there is a postop for this patient. Let's see this is the postop. And again this patient has a complete tumor resection. No residual, no recurrence. Now another challenge, this is a functional tumor patient with severe Acromegaly. Look at the extent of extensions. Uses a Knosp three, Needs three Knosp three B, it would be called. Superior compartment, inferior compartment. Inferior compartment here is clearly invaded. Now, what I wanted to film with this case is two things. One, how this tumor, I'm gonna show you that is not like the others that are fullly built into the cavernous sinus. This tumor is completely contained within the wall of the cavernous sinus. You have to find the ligaments, cut the attachments. Peel it off directly from the carotid artery which is an increased level of complexity. Second, you see how low this tumor goes right here. This is the level of the Foramen lacerum right here. If I really wanna get a clean margin of tumor resection here, I need to expose the Foramen lacerum. And that's what I'm gonna do in this case. So we talked about it from the lacerum anatomy. This is the paper we published. I think this is very important anatomy complex to understand to me. Long time to understand as well but the most important concept I want you to take with you is the anatomy of the Pterygo-Sphenidal Fissure. Okay the Pterygo-sphenoidal fissure is this picture right here. And it's a fissure that goes between the floor of the sphenoid right here and the pterygoid bone right here. Okay between pterygoid and floor of the sphenoid there is a fissure right here. Pterygo-sphenoidal fissure is formed of fibrous tissue ofcourse. You can see this in the CT scan. You see this right here. There is that line. This is the line. And this line forms a confidence with these other lines which is the Vidian canal, which is right here. So this vidian canal comes like this. This fissure comes like this. They join at this level here which is called the Pterygoid tubercle. This is the name of this area right here. Pterygoid tubercle. They both convert. This is a triangle. This triangle takes you directly to the Foramen Lacerum. You follow with your nerve, which is the classic that Professor Cacambas found many years ago. But I found that if you also take this key landmark in consideration, the pterygo-sphenoid fissure. This takes you directly to the inferior aspect of the Foramen Lacerum right on the carotid. And the way to expose this is by drilling the floor of the sphenoid here. The pterygoid here and you'll keep following this drill takes you directly following the fibrous tissue as you see right here. Takes you to the Foramen Lacerum. To me this is the most difficult part to expose, the carotid. But using this technique, this has become much more simple. And now you see confluence of the fissure bigger nerve. And here is where the pterygoid tubercle was located. When you remove it, you're directly on the carotid artery at the Foramen Lacerum very important technique. To some extent that some of my fellows started calling this the Miranda triangle. And last time we talked Aaron, we talk about naming some triangles but I don't mind as long as this helps people remembering this triangle because I think it's very important triangle for me in doing this operation. Vidian nerve, Pterygo-sphenoidal fissure, they formed this triangle. And these are two triangle as you see right here. And the apex of this triangle takes you directly to the Foramen lacerum. Now remember that this triangle is not a perfect symmetrical triangle because vidian nerve is above, the pterygo-sphenoid comes like this from inferior to superior and you need to find it deeper. So it's more like a pyramid in a three-dimensional in a three dimensional perspective. But again, key landmark technique to find the foramen lacerum. Because if you find the Foramen lacerum right here. You see this is the lateral and inferior compartment and it can be expanded all the way down here. And this is the posterior compartment right here and often this posterior compartment is extended and rolling the bone all the way down here. So you need to have control of the carotid. You're gonna do an aggressive resection in terms of controlling the carotid right here. So from here you can start exposing on the way and working behind, infront et cetera. That I found to be very safe and very effective. And in fact, this Foramen Lacerum exposure is key for many operations. Not just popping through the dermas but for many skull base tumors because this ventral foramen lacerum is a cross road. From the Foramen lacerum you can extend, you know, towards the Petrous apex, along the carotid canal there was the middle fossa and Meckel's cave towards the jugular tubercle and hypoglossal canal and in theory, laterally towards the jugular foramen. And in fact So it takes you to so many areas and that's why it's so important to understand how expose these areas safely and how to work around it. Okay so we go back to our case, this complex acromegaly. You know, this exemplifies very well, why these cases are true skull-based operations. So in this case, this patient again had severe acromegaly. And the first part of one, my first move is to find the Foramen Lacerum before I, you know, take any tumor out. And I'm drilling the floor of the sphenoid and the pterygoid This is the stamp of the vidian nerve. I look at the fibrous tissue, I found it and once you find the fibrous tissue I follow it and remove the bone, the pterygoid cubicle and I find the carotid right on. Use the doppler to check it and this is my carotid artery. So the beginning of the operation I have the carotid controlled at the most difficult part which is the foramen lacerum. Then after this I just need to have my inferior and just need to start opening the Cavernous sinus and you will see this is all soft fibrous and it's completely stuck to the carotid. And this is stuck to the carotid because of these ligaments. These ligamentous attachments. So you have to sharply dissect and transect those. And you see as I pull a little bit on this tissue, you can see that the tumor is growing through that wall, but it's still embedded in that fibrous tissue. So I detach it superiorly from the clinoidalous space and superior compartment. This is Inferior ligament which I'm transecting. That's Inferior hypophyseal artery which I'm coagulating. There are several attachments along the whole lesion disectional the cavernous carotid. I need to coagulate, cut, coagulate, cut, coagulate, cut until I get all the way back to the posterior clinoid. This is as much posterior clinoid, which for my key landmarks I said before. And now we are in the interior compartment. Taking these attachments, separating from the carotid artery, finding the sixth nerve and then again detaching the last bits of tumor from the carotid artery. Opening the inferior compartment and finally detaching this from the Foramen lacerum carotid artery almost. And then we cut it. Coagulate and cut. And then this tumor has been, now look at the ligaments of the fibrous tissue that contains, embeds the tumor. And now we have removed the tumor. Look at this fibrous piece of tumor. This would never come with bipolar with, with suction. And now we're looking at any residual, well explore again clinoidalous space. Superior compartment clinoidalous space here. The whole carotid having a skeletonized completely and this s an aggressive resection for an aggressive disease. His idea of one or two months postop is already normalized with a possibly one with more zero point one. Which is equivalent to our excellent prognosis in the long-term. Let's go to the next page look. And finally we have also lateral compartment. Lateral compartment, key hypophyseal compartment are the inferolateral trunk. It's not about the throw hypophyseal anymore it's about the inferolateral trunk here. It talks about the Proximal dural ring but now on the other side, the carotid oculomotor membrane which you see right here, So artery here. Oculomotor membrane here, which you can cut to mobilize the carotid more and then all the nerves along the lateral compartment. And we do this in this operation in this compartment, more selectively because the risk of injury to the nerve is higher. Unfortunately, at least in my experience I don't have that many of this very high Grade Knosp four, going lateral to the carotid. But when I do the tumor is amenable. I can do some aggressive disection as you see in this pre, postop. Now to summarize all this anatomy and technique I've shown you, you know, Endoscopic Endonasal Cavernous Sinus Surgery is about, it's all about disecting the cavernous carotid artery. Understanding very well, you know segment by segment, ligament by ligament, compartment by compartment so you can do an effective operation here. And things I've learned along the way is that key landmarks on each compartment, which actually did not describe this on the original paper on the compartments and this is something that has come more recently as they get more and more experienced is that for the Superior Compartment, my key aspect is the clinoidalous space and CCM. Inferior compartment to access it the foramen lacerum is key. Posterior compartment, I need to remember the Petrosal process which I'm going to explain to you in a minute, it's right here. And the lateral compartment is about Maxillary strut which is right here and optical storage here. We need to expose from here to here to have good exposure to all the lateral compartment here. Okay so, so we look at the significance of our results by analyzing our 30 patients with acromegaly. Does this technique in anatomy make it any difference. So we look at the post-op growth hormone levels more series. The mean on 30 patients is 0.9. And this is, you know, better than reported by excellent pituitary students with great experience and it's better because our techniques are more aggressive and more involved and I believe we can we can get better results, not only in the early growth hormone levels but also in the remission rates acromegaly. These are based on meta analysis between 40, between 50 and 60 percent. And in our series, we have a remission rate at this point of 93%. All 30 patients except two were in remission. The two patients that are not in remission are not in remission with adjuvant treatment. One with the surgery and the other one with just medication. And we have three of these patients that needed six months to normalize it, I only have one. So I advice being sometimes patient. If the patient have no symptoms or no acromegaly, wait because maybe it takes a bit longer for the AA1 to normalize. This has also been described and known before. But these results are you know, at this point the best ever reported for surgical remission in acromegaly patients. And just remember as we said, you know, Radio surgery is of course an option. One of my patients got Radio Surgery, but just one because Radio Surgery has a new risk of endocrinopathy of about 26%. New cranial neuropathy, that is a permanent one. Not the transient we get with surgery sometimes patients get better in weeks to months. This is a four percent of complete palsy and permanent. So Radio surgery is not safe of complications. Now to finish I'll show you this last case. This is a patient with Cushing's disease and this tumor illustrates so many different things. So let me stop the video here because I wanna show you some anatomy about this case before. So, there you go. So this case has invasion around the Foramen Lacerum on both petrous apex's as you see there. You can see carotid to some extent. Anatomy that is key we need to understand here is the petrosal process of the sphenoid bone right here. Why is this important? Because the sixth nerve is going to run like this just above it. So you can find with, you expose the carotid, so the carotid runs in the bone right here. There's the carotid runs. If you find the carotid, snip behind it, you can find this boney slope and you tell that, you can see that that's where the sixth nerve is located. Again the technique, the carotid is being mobilized. I can find this boney slope and that's where the sixth nerve is located. And even more, if you have tumor around the sixth nerve and you have to manipulate the sixth nerve, it's always best to drill this bone. It's difficult. Sometimes you have to use this ultrasonic bunker because it's a very narrow space. But if you remove part of this bone, the sixth nerve is more free and you can work around it with less risk of injuring the sixth nerve. So another key detail on this case, this case all so many complexities. You see that the tumor has a bubble here. And we described this. You look at this carefully there is a line right here. This line goes from the clinoid anterior is the interclinoidal ligament. What is happening is this tumor is breaking through the Oculomotor triangle. We described this some time ago, how to go through the oculomotor triangle to follow tumors. You see interclinoidal ligament here. The tumor growing through it. Third nerve here. In the past we had to use transcatheter approaches to get to these tumors. But nowadays we've learned to just go endonasal, this way, and we just follow the tumor and we can remove it completely. All in this one single approach. The anatomy again, remember the intercranial ligament, the posterior petroclinoidal ligament and anterior petroclinoidal ligament. This is the oculomotor triangle. They break through this posterior part more often and they display the sixth nerve medial and superior as you see right here. Okay I think we are ready now to see this video. We have all the anatomy we need to understand this. And this video puts together all this anatomy. Previous operations three years ago somewhere else, never got in remission. Severe Cushing's disease. Young patient. As you know this has extreme morbidity, this disease. So first we go into the foramen lacerum. We follow pterygo-sphenoid fissure. Find the carotid of the foramen lacerum starting the paraclinoidal segment. Again you saw the fibrous tissue the pterygo-sphenoidal fissure using the Doppler always. Great agent for surgery. We can extract the carotid from inferior to superior, afterwards the cavernous sinus. Now we are removing all the abnormal bone. Here we are transecting the pterygo-sphenoid fissure. And this is done to get access to the jugular tubercle behind. That is bleeding from the petrousal sinus. We drill abnormal bone and I'm right now finding with my dissector, this local the petrosal process. I'm cutting the dura and now I'm working on the left Cavernous sinus. Opening the cavernous sinus wall, removing the medial wall. Carotid all exposed. Bleeding from the carotid directly from a branch, but I can coagulate it effectively. No problem. With good by prone technique. You just saw Dorello's canal. This is the sixth nerve. Again petrosal process and sixth nerve with tumor around it. And this becomes at times, you know, if I remove part of the petrosal process So I can mobilize the sixth nerve if I work around it more safely but this invading dorello's canal. So now again, back into the cavernous sinus. I'm working on each side of the CCL, joining the clinoidal segment with the superior compartment of the cavernous sinus, transecting the CCL, accessing the superior compartment. Identifying the interclinoidal ligament right here which I'm coagulating, transecting and getting me access to the oculomotor triangle and I find the tumor that is getting into the Oculomotor triangle, through the oculomotor triangle. We actual the lateral wall of the cavernous sinus, all tumor is removed. Now we go to prosterior. This tumors as we started this talk. This tumor has subarachnoid invasion. This is a higher level of complexity. There is no respect for subarachnoid plains. You need to be extremely careful because the tumor is incasing micro vessels. It is stuck to the nerves, stuck to the arteries. Difficult to remove. We can see the carotid bifurcation. The anterior circulation. Dipped the corpus in the hemispheric fissure. The pituitary stock right here. And you can see the third nerve. And the third nerve and the tumor right here. This is tumor that is growing through the Oculomotor triangle. Now in this case I'm now seeing the Oculomotor triangle, Dura from above and from below which is a pretty unique perspective. Showing removing this tumor that was extending through the roof of the cavernous sinus. I was at first trying to limit the dural opening because of the reconstruction challenges we have in this case. But the tumor was so invasive that I had to continue operating the dura to get better access to the entrance of the nerve into the oculomotor triangle. You can see there is still some more tumor around the oculomotor triangle dura. But after I cut this Dura I can mobilize the third nerve a little bit better. Get better access to the dura I'm cleaning it effectively. This third nerve, as you see it right here was completely intact after the operation. Not even ptosis. You can see the basilar bifurcation. Beautiful third nerve all the way and then we go back to the sixth nerve in dorello's canal. And drilling tumor around dorello's canal. And finally the challenge with reconstruction. This is a lateral septal flap. Previous operation unfortunately destroyed the septal flap. That is very unfortunate because it increases the risk. In fact this patient got a CSF leak and meningitis that would repair with just a septal flap but you know, remember previous operation always carries significant risks. So that's why important coming back to the first message Pituitary has to be a specialized because you can ruin, you know the future of a patient and the next operations can be more and more challenging. So this patient, let's go to the next page look. I wasn't even expecting to be able to get a remission in this patient but putting all of these techniques together and all this anatomy together, this patient crash, her cortisol levels were two, possibly one and possibly two and so was taken to in replacement. As I said intact third palsy not even have minimal ptosis and left cranial sixth palsy that actually has already four weeks out, or I don't know how much but maybe four to six weeks out has completely improved. No sixth nerve palsy any longer. So in conclusion, I wanted to illustrate what I believe are some of the basic principles of modern pituitary surgery. The concept of Subarachnoid invasion makes these tumors very challenging sometimes and it's key to Microsurgical light dissection for these Aberrant adenomas. Where we can remove them all. Clinoidalous space, Carotido-clinoidal ligament, Superior compartment, Medial Wall Resection and the differential frequency and invasion based on cell lineage is new knowledge and constantly have been acquiring recently. The concept of cavernous sinus compartments and anatomical classification versus regular classification and how Knosp specification fails with functional adenomas. Also the same key concept, cavernous sinus floor, foramen lacerum access to superior, sorry inferior and posterior compartments and finally even access to the the roof to get to the Oculomotor triangle when the tumor extents to those areas. So as you see from the lab to the OR we can definitely improve emission rates and outcomes for pituitary patients. Thank you very much for your kind attention.

- You know impressive, really incredibly well done techniques. It's next level in pituitary surgery there's just no question about that. This just shows really a true mastery of skull-based surgery through the endonasal approach. Juan Carlos I really wanna congratulate you because your work in this area has truly been pioneering. It's never been done before. It requires a certain courage, talent and knowledge. I think all of those you have truly mastered. I just wanted to ask you a question which obviously comes to mind of anyone doing the, trying to do these operations which obviously requires a complete level of technical talent, is if there's evidence of an injury to the carotid, it appears that using the bipolar first, if the injury is very small and potentially a perforatory's evolse, you just go ahead and coagulate the wall gently. If that doesn't work, obviously then use either. I use a thrombin soaked piece of ENT cotton, shredded cotton and I just cover the carotid. Obviously use the adenosine freely in that time because as you know the flow can be so extremely overwhelming and using adenosine even without a pacer. Just pacer, a cardiac pacer is very safe in patients who don't have a significant cardiac history and gives you just enough time to see what's going on. Can you give us other pearls in terms of managing a carotid artery injury Juan Carlos?

- Sure, thanks Aaron. Thanks for your comments and for having me again and for the opportunity. Yes I think you mentioned very well. So if the injury is just a hole and you saw. A small hole from the artery, Bipolar is extremely effective but you need to have a little stump, I think to be able to coagulate that. It's like sidewall bleeding. Now if you have a real injury, that's a different scenario. I always comes to mind, you know, muscle parts ofcourse. You know crash muscle, a big chunk of muscle against the carotid, keep it pressed there with patties for a few minutes might make the trick if the injury is not too big. I also always have you know, as I said, I've been very lucky, I'm very careful not to have major injuries to the carotid but I've been part of involved in a good number of those. But I always have a tray in my cases that is not open but is immediately available with an aneurysm clip applier. It's a single self aneurysm applier. Because if you need to get proximal control or proximal and distal control, usually the goal is all nicely exposed, you can try to get that too. And even you can try to do sidewall clipping of the carotid or put a little cotton and clip the cotton with the clippers you know. So some sort of clip technique can also be used. I haven't done it but I've seen that done and being successful with that technique too.

- Yeah. I think one of the first things you wanna do is just take a deep breath because as you know the floor is so extremely brisk, especially the nose and the endoscope. It really overwhelms you. And I think the best thing is just pack it with some cottonoid or patties and just take a deep breath because really gentle pressure controls that bleeding so effectively. So there's nothing to panic about. Panicking is the last thing you wanna do. Even though everybody panics, believe me even the ones who are calm in fact may be feeling differently underneath. But the first thing is just to pack well, take a deep breath. Don't do the first knee-jerk response and just after it's packed, find, you know use idenos if you need to. It's very safe again to do things relatively clearly known by anesthesiologist, and then as that's working for 30 seconds to a minute, you will remove your patties, you inspect the area relatively well and then really the shredded Teflon or shredded cotton with thrombin soaked with a gentle pressure can do incredibly amazing work. There's been times I've had carotid injury, I've put on there and continued resection. Obviously we don't wanna advise that. That may be a little bit too carboish I would say, but I have done it in the past. And then obviously you have to do a angiogram afterwards. Roll out a pseudo aneurysm, do stinting if that's required but you will be absolutely amazed how many patients do well. So with that in mind, Juan Carlos, I wanna again thank you for being such an incredible contributor to this series. Such an honor to work with you and we're so impressed by your incredible contributions again. Have a good evening.

- Thank you Aaron.

- Bye.

- Bye bye.

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