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Giant Pituitary Tumors

William Couldwell

June 24, 2020

Transcript

- Welcome everyone and thank you for joining us for another session of the virtual operating room from The Neurosurgical Atlas. Our guest today is Dr. Bill Caldwell, chairman from University of Utah. He'll talk to us about surgical treatment of giant pituitary tumors, something that is very challenging. As you know, Bill, we have had many of those cases. When you go from the bottom through the nose, remove the tumor and they have an apoplectic event and hemorrhage and the vision gets worse, and then you go from the bottom and then go from the top, and it becomes an extremely challenging exercise. These big giant tumors are some of the most daunting cases we deal with. So if that's okay with you, I wanted to show you a video just to start to get our viewers engaged and then jump into your slides. So Luke, would you mind showing that video please? And here's the tumor, as you can see, it's pretty big. And I wanted to ask you maybe Luke, if you can stop the video right here. Bill, what are your thoughts when looking at this case, you know, very dense, not cystic, obviously a very large tumor? How would you manage that?

- So I would come in on this transnasally. This is an important point that I'd like-

- Yeah.

- and I don't think we look at the shape enough, of the tumor. So if you look at the superior border of the tumor, it's smooth. And that's an important issue, when I look at these tumors, because it indicates to me that the diaphragm sallae is probably not violated and it's being pushed up superiorly. And I'll talk about that during my talk, but basically the issue is, is that if we see that and the tumor's centrally growing up, and there's a fairly large opening in the sella, like you can see on that tumor, we would come in from below initially. And I agree that some of them, the consistency of the tumor may preclude the removal, but we would give that a shot from below first, absolutely because those ones are the ones where the diaphragm can be used to help push the tumor down, and I'll talk about that a little bit during my talk. So why don't we go back and look at the video then?

- Can you see it okay?

- Yep.

- Can everybody see that okay, please? So Luke's video had a computer almost passed out. So anyways, so here's the round shape that you talked about that you said we use the endonasal because probably the diaphragm's intact. So here's the opening of the sella. Obviously the wide opening is critical in these giant tumors, has to be from one cavernous sinus to the other. Any shortcoming in the exposure can be really a problem here, especially in the exposure of the sella. In this case, we opened the floor and opened the dura. And first the tumor appeared to be very soft. So we all felt, this is great news, this is something that's gonna deliver itself like a baby. And as we went ahead and removed some tumor, we were very surprised, that how this tumor can be so easy at the beginning and later so hypervascular. So we went ahead and remove more tumor as you will see in a second. And that initial tumor came out pretty easy, but the rest of it, and maybe we should have opened the dura a little bit more here. I came in as you can see, the first part of it was done by my fellow. And I said, "You know, this is definitely something where we need more exposure." And we came in and removed a lot more bone. I removed a lot more bone to be able to get that wide exposure that is so necessary. We used Kerrison rongeurs just to get more of the opening. How else do you do this differently, Bill?

- Yeah, I use a Kerrison rongeur. I rarely use a drill,

- Yes.

- usually use a Kerrison and remember that if you're careful and you stay extradural, you can expose the carotids and you come underneath the carotids in the cavernous sinus, just as long as you're careful with the distal tip of that, and make sure that you remain extradural. So don't be afraid to go further laterally and you'll see the cavernous sinus and you'll see the, the carotid impression. And you'll see also in a smaller tumor, you'll see the, the intervenous channels between the cavernous sinus and the cavernous sinus proper.

- Mm hmm, I agree with you.

- As you're doing, you get right up to the tuberculum on a tumor like this, because the way you get the roof of a house to fall, is you take out the floor and the walls, and so you gotta get an exposure that allows the tumor to descend. We do. We do, I started doing that a few years ago, actually, as a training exercise for the residents.

- Yes

- But helpful to you know, to sort of predict where the carotids are. You can usually see the bony landmarks of the OCR and the optic nerves and that type of thing in the carotids, but I find it very helpful as a teaching tool, and especially in these, especially in redos, we always use it in redos, because the anatomy, the bony anatomy has been distorted.

- I agree. So you use the CTA routinely

- Yeah.

- for CT skull-based stealth routinely for your cases-

- Right.

- Do you use ultrasound for the carotid localisation?

- We do, if there's any question, but usually it's not a mystery, you know. If your CT stealth is accurate and they usually are, it's not a problem usually recognizing it. If there's any question we'll, we'll Doppler it.

- Yes.

- Very helpful. Are you using a NICO or, or a CUSA like device there?

- No, we don't use either one, we're just using a suction and yeah, that's just a suction that is navigated. So in this case, you can see the exposure is a lot bigger, which is so mandatory for these big tumors. I believe the number one reason for sector resection pituitary tumors is inadequate sella exposure. It's just unless you get the sella widely exposed, it's impossible to get lateral enough to let the tumor drop down. So here you can see that we have much wider exposure. The tumor is coming easy and we felt that we're making good progress, but as we went more and more further, you can see that the tumor, it just becomes a lot bloodier. Bill, how often have you had issues with a tumor becoming hypervascular in these giant tumors?

- Yeah, it does happen. So one trick that I always use and my residents know this, is I always keep the head above the heart. And then a lot of this is venous ooze, and the arterial obviously you're not going to be able to change, but the venous bleeding you can affect by lifting the head and putting the head in the reverse Trendelenburg. And we'll do that routinely and try an reduce venous bleeding, it helps a lot. The venous bleeding is a little deceptive with a transplant surgery. This is going directly up your sucker and you don't have an appreciation of how severe it can be.

- All right-

- So getting the diaphragm to come down now, and that's good at 12 o'clock up there yeah.

- Right, So you remove tumor laterally then posteriorly, and ultimately superiorly, and often the diaphragm is extremely patchoulis and you can leave tumor in the areas that are within the blind spot. Is there any trick to remove the tumor in these creases of the diaphragm?

- Yeah, the way I do it is very systematic. And so I removed the floor completely, obviously, then work my way up laterally, and then CD arachnoid come in from the back, like it is here, and then keep working the gutters superiorly. That's the key, remove the gutters laterally because that's where people leave the tumor, and then ultimately you'll see the arachnoid come down and capitulate and bring the tumor down, and then you can take a up-angled curette and just gently work around. You're using a curve sucker there, I think that's fine. And but if you concentrate laterally and stay in the gutters lateral, I try not to remove the middle part of the tumor till near the end, because it allows, the heft of the tumor, allows the diaphragm to descend,

- I got you.

- that we use. And yeah you've got, looks like probably normal gland there coming down now, yeah.

- Yes, that looks like a normal gland Bill. And then I use a patty just not to put this suction directly on the diaphragm. So.

- And remember that, I think, remember that the diaphragm is your friend and the CSF pressure from above is your friend. It is your assistant, it's pushing the tumor down. So don't violate the arachnoid if you can, and the, the diaphragm, because it allows you to use the CSF pressure to push the tumor down. And obviously if you can have a tumor like this and we would try to preserve the diaphragm completely in this case, it just reduces the complication in your lives, if you don't have a giant leak that you need to close.

- Or what do-

- We use a couple of tricks. I've done that during my career. I don't use the lumbar drain, merely for the fact that I think the most effective thing is a Valsalva. And then adding as Ed Laws taught me, you add jugular venous compression, which is the big gun and just have anesthesia or one of your residents compress the jugular veins bilaterally, and that's like a Valsalva on steroids. And it works really well to bring the tumor down.

- How long do you hold down on both jugs?

- Oh you know, you're not doing it enough to stop arterial flow, so maybe 30 seconds and the same thing for a Valsalvo, we use it for 30 seconds to a minute at a time, and I've never had a complication with that. So what you're doing now is you're looking for through the folds to see if there's any residual tumor.

- Yes.

- And remember that the reason that you see it puckered like that, is where the stock comes through the diaphragm, it holds it up a little bit. And so you see a natural pucker point there, and that's where the stalk comes in. So that's where you're gland is gonna be, right there.

- Yes.

- Okay.

- So we use Hydroscopy as you can see in the fold, you see that? And you can see the stalk there and there's no residual tumor, but as you can see, it requires fair amount of patience to be able to see within the puckered creases and be able to make sure there's no tumor behind. And this is really the final product, and I think a piece of fat, most likely what's needed. You don't really routinely use a nasal septal flap for these do you?

- No, I, for routine pituitary surgery, I don't use a nasal septal flap its too much surgery on the nose. And it's, you know, all we need to do is protect that arachnoid here, you don't have a significant leak at all. And you know, you're using a piece of gel foam there, which I think is fine. We, we often just place a piece of fat in the, in the sphenoid,

- Yes. to close that. And the reason for that is 'cause if people use a CPAP mask or something, I don't want them pushing on the native arachnoid without, and then I always worry about them sneezing or having a jolt and then busting the arachnoid. So I think that looks great Aaron, you've had a good resection here.

- Thank you. We don't use nasal septal flap routinely for pituitaries either. For this giant case we felt that there is a reasonable risk. We may have to violate the diaphragm if there is tumor that we cannot reach. So that was more precautionary than anything else. But I agree with you for routine pituitary surgery it is unnecessary. Luke, let's go ahead and dive in into Dr. Caldwell's talk please. So I look forward to talk Bill.

- Great. Great, well it's an honor to be here, Aaron, and to talk about our experience with this. So this is The University of Utah. We live in a beautiful place and we had a long history now of pituitary surgery over a hundred years, and these original pictures of Max Rodell, of Cushing doing the tumor. And Cushing wasn't too innovative at this, he used Halsted's submucosal technique and sub-labial technique, and then this bivalve speculum. It was interesting that Cushing started off with his career and did a lot of pituitary surgery, but then backed off because he shouldn't, he said he couldn't decompress the optic nerves as well because he wanted to come in and at the same time promulgate his approaches, open approaches, from above to the suprasellar region. It was, it was Edinburgh or Norman Dott and Edinburgh that really kept doing the transsphenoidal surgery when Cushing had stopped doing it in the 1920s, and he taught the operation to Gerard Guiot in Paris, and then who really trained Jules Hardy. And Jules, who grew up in Montreal, he's French Canadian, and he went and trained with Guiot after his residency, and then came back to Montreal and its these two men that really repopularized and brought the operation back to America, and then perfected it, and Guiot was an amazing person. So here's a picture of Guiot when he was young, he was very innovative. Did craniofacial surgery, did stereotactic surgery. And he also was the first person to take a pituitary tumor out, using the endoscope in 1962. And I just wanted to give a shout out to Jules Hardy because I went to medical school in Montreal, and Jules was one of my mentors, and he was at the peak of his career at that time. And he, he and I recently wrote a paper on Guiot because of Guiot's contributions. And Jules is almost 90 now, but as sharp and I talked to him and he's an amazing person, and he's still very active. And here's Guiot and Hardy. And these were the two gentlemen that really brought, the operation into the modern age. They brought the operating microscope in. They used illumination, which allowed the surgeon to differentiate between the tumor and the pituitary gland. So really brought the whole age of functional pituitary surgery, where you can remove a Cushing's tumor, or a growth hormones creating tumor and preserve pituitary function. So let's talk about giant pituitary tumors. So the way we'll define them in this talk will be tumors larger than four centimeters in diameter. They account for approximately 10% of adenomas and 0.5% of all intracranial neoplasms. As you know, pituitary tumors are very common. If you look fine enough at an autopsy study, about 17% of them, people have a pituitary tumor at autopsy. And the reason that these adenomas are challenging is that they're hard to get out, there's vascular encasement often with cavernous sinus involvement, and pituitary dysfunction, and also a apoplexy and I'll talk about that. So this is the most common presenting symptoms. They involve visual disturbance, endocrine dysfunction, neural compression and we treat all prolactin secreting tumors with Cabergoline, and only operate on those tumors that failed to respond to Cabergoline or the patients cannot tolerate Cabergoline 'cause of nausea, vomiting, or also movement or mood disorders. 'Cause some people have a real alteration in their mood balance with the dopamine agonists. So this is a slide from Atul Goel, my friend in Mumbai, and he likens this to a finesse delivery of a baby. And I think it's a good analogy because what you're trying to do, is you're trying to remove a very large and complex tumor, through a sort of a narrow opening. And you have to tease the tumor and then use all techniques to try and get the tumor to drop as we've talked about already. It is remarkable in my mind that you can have a tumor. This is a five or six, I think about a five centimeter tumor that is producing dramatic compression of the pituitary gland. I see this, I always look for where the native pituitary is on these tumors, and it's often just a thin rind and here the tumor, just like the one that Aaron showed you, but you can see the remnant of the stalk, and the pituitary gland and remarkably, he had normal pituitary function at the end. So it's a very, very resilient structure, and I think it's important to remember that. You stun them when you remove these tumors and they have DI and that sort of thing, but it's amazing how much the patient have endocrine function, that you can have. So, as we've talked about, you need to open up widely from below. So this is the original description from Guiot and Hardy, but what you wanna do is open the dura. Now I do not open the dura this way, I open the dura in this way, or else I remove the face of the dura. And the reason for that, is you can get to the corners much better by using an X instead of a cross. And so it's important to get right out to the, the medial wall of the cavernous sinus here. And you can recognize that adjacent ruddery impression, or you'll see blue staining through the dura, from the venous structures. And then you can also remove the dura if you wish, as well. So we've talked about, a little bit about this already. I do not use a lumbar drain and the reason that I stopped using it is because when you put a lumbar drain in, you automatically create a leak from below, which it reduces your ability to use Valsalva, et cetera. Now you can inject, you can inject saline. I appreciate that, but we've gone away from doing that. And we remove the floor and the walls, as I said, and then work your way up laterally, and then work your way posteriorly and watch the arachnoid fold come in. The diaphragm will be like a arachnoid and it's just a fold coming in as you saw in that case and keep working the interface between that diaphragm, herniating down, and the tumor, and then work the lateral walls, work the gutters. I save the middle part for last, and it's hard for the residents and fellows because they want to grab the middle part. But if you leave the middle part in tact, the heft and the weight of it, helps bring down the arachnoid. So I remove that part at the very last 'cause it's easy, and as they say, it's low hanging fruit. So we'll routinely use Valsalvo with the anesthesiologist, and then the big gun is this bilateral jugular venous occlusion. So what are your options for removing these giant tumors where you can use a single transformative approach, and if we believe that we'll be successful at that, we'll use that. We can use a single transcranial approach and I'll show you that, in some cases, sometimes seeing the interstellar portion can be more difficult if you're using a frontal temporal approach, which you can use an endoscope there as well. You can do a combined approach. I've done this occasionally with these tumors. The one concern that I have, and it hasn't been born out of my experience, is that you're using a clean, contaminated approach from below, and then you're adding a clean approach from above. And I'm just wondering whether it increases the risk of infection from the transcranial approach when you've got the nose open, but we've done that routinely, and I do that routinely with skull-based tumors and I haven't seen too much of a problem with it. And it is an important method to use to get the tumor out properly, and I'll talk about the importance of that. So if you look at the experience of, of mortality in these giant adenomas series, it's remarkable how high the mortality is in these series. You've got my picture Luke, over part of the slides here. But the point I like to make is that this is not a benign disease, this is a dangerous disease. And you can see, even in the most recent large series here where they combine some of the cases from the literature, it's still a 4.5% mortality. And early on, it was very high. And the extent of resection is often low because of the fact that the tumors are so invasive, and I'll talk about that in a moment. So this most recent study looked at 250 patients, near total was achieved in 74% of patients. I don't know what that means, that means your tumor is left in the cavernous sinus, so it's not a total reception. And then mortality was still 4% and morbidity was 14%. So if you compare the transcranial versus endoscopic or microscopic, you'll find some interesting results. Let's talk about the endoscopic results. So there's a little bit better resection with the endoscope. That's intuitive as you'd expect because the endoscope enhances removal by being able to see the residual tumor in the lateral margins. And we usually use the endoscope for these larger tumors from below for that reason. So I'm gonna talk about my own personal series that is just being published right now, but I wanted to review a contemporary series with the best endoscopic and microscopic abilities, to be able to look and see what the current mortality and morbidity is, in people with experience. I've done over 3000 pituitary tumors and I wanted to show you some of the results that we've had. So what we did is we went back and we wanted to go back and find over a hundred giant tumors. And so we looked at 741 patients over the last 15 years, and these are only ones that we had follow up in MRI on and endocrine follow up as well. And I'll show you the results, in our hands of using endoscope, microscope and transcranial approaches. These are the demographics and they're, as you'd expect, it's a disease in middle and older age. 13% of them are presented with apoplexy. I just wanted to show that, preoperatively, these are the tumor sizes and the Knosp grading system, and you can see the majority of them are higher Knosp grades. Okay. So that's an important fact because I'll show you what the Knosp grading system entails. And basically it means that the cavernous sinus is definitively invaded because you see tumors surrounding the carotid in anything three and four, you'll see tumor mostly around the carotid. So that's the real feature that I use because you occasionally get a pantalooning of the menial cavernous wall, and it looks like the cavernous sinus is invaded, but it's not. And that's an off grade two or one. Operative management, this is what we've used transsphenoidal in most cases and combined in is some, and both come from above and below, but I'll show where I've come to because I want to summarize it by showing a couple of cases. You can see the complications that we've had, CSF leak in three patients are normal. Pituitary series is about a 1% complication risk of CSF leak. So this is higher than that. And this is because you're opening the, the bone from below much more. You can see the recurrence we've had in months. These are slow growing tumors, and we've radiated some of them, and we resected and radiate some of them as well. We had a couple of complications that I'll discuss with you. This is an interesting case. This was sent to me as a cystic lesion. This was a 30 year old, but he presented with acute headache and diplopia. And you can see here, the cat scan doesn't show blood, but there's no enhancement of the lesion. And we looked at that and we said, "Is that a cystic lesion or is this pure apoplexy?" And I think it's important to remember that apoplexy represents a spectrum from hemorrhage to necrosis, and you can have a purely necrotic tumor presenting with apoplexy because it's swells. So this young man had bilateral 6th nerve palsies. We operated on him emergently, with a six centimeter tumor, and it was all dead tumor. And here's the post-op scan. So remember that you need to look for apoplexy in the presentation of these tumors, and may not have overt hemorrhage, but we'll be able to see infarcted areas and areas of the tumor that don't enhance. That was quite a dramatic example. So the classic indications for transcranial approach, and you saw the number of cases that I use transcranial approach on. I use it a little bit more, of the giant ones, and parasellar extension, it's the big one, if it's going laterally, and you don't think it's gonna drop down from the midline. Tumors that are fibrous, sometime we'll start from below and if we don't think we can get it out that way, we'll abort and we'll, do a transcranial approach. This is a relative one, active sinus infection, adjacent aneurysm or kissing carotids, carotids are very close to each other. And then this is one that I wanted to specifically discuss. So what do you do with a patient that's already got a cranial or palsy and a giant tumor in the cavernous sinus? So here's a 57 year old woman, cognitive decline, six months, a hundred pound weight gain. And you can see she presented with hydrocephalus and she's got this tumor that's large in the sella, and this is a sign for the younger people that I use, I always look at the size of the sella to see if it's primarily enlarged. 'Cause that's a good indication that the origin of the tumor is within the sella, on these large tumors. And this was the case and it's growing up and it's growing over. Now, this was a few years ago. I probably would do this different now, but I did come from below, and cause I thought, I'd see what I could get out from below. And we used an endoscopic approach, and I used curve curettes. I got everything that I could out from below. This was not a prolactinoma and prolactin was 14. And we routinely used dilution techniques in our lab. This shows you an example of what you're able to get out. I couldn't get the thing to drop and I've removed maybe, maybe half, maybe two thirds of the tumor, but the superior part is still there. And so we came in and did a transcortical approach very, very shortly after that approach and were able to get it out. Look at this case. Here's a case, 42 year old man, cognitive decline and headache. So we came in from below and it was soupy, the tumor was soupy and this is the point that I wanna make. So this indicates that the diaphragm, this indicates that the diaphragm has been violated here, this part here, because it's a bud off the original tumor. So that may not drop down like you saw Aaron's case. You need to be aware of that. And so he had a transsphenoidal approach from below, and it was very soupy, and I wasn't convinced that we got the majority of the tumor out, and his CT scan is here. You can see it's a giant tumor. It goes all the way up to the frame, put 'em in row there. And he had post-op deterioration. He was fine immediately, had deterioration and what you see here now he's got acute hemorrhage in the residual tumor and it looks like the mass is just as large as it ever was. So this is a problem and he was devastated by this. So this is a complication of partial resection of these tumors. It's in up to 13%. And I think it really, I'd like to emphasize if all the we can really emphasize today is the important thing is, to try and control the mass of the tumor, to try and avoid apoplexy and a residual component. So what do you do with this tumor? So, you know if you come from below, you'll get the center part of the tumor, but I wouldn't realistically expect this to drop. And so what I'll do in this case, and I just wanna remind people that you can come in transcranially, and get the sellar component. And so, here's the tumor, it's very tall. It's up past, it's into the lateral ventricle. So we'll come down the axis of the tumor and remove it. And you can also remove the sellar component. If you come down the long axis, you'll get down to the sella and I'll show that in a video in a moment, and you can see we've preserved the stalk, and the pituitary. And I don't think people appreciate that you can do that. So let's go to the videos now, Luke. And so the first case, I'll show you with a case with a lot of sub tunnel attention. And so what do you do? Do you come from above? Do you come from below? I didn't think that I could get it all out from above because of this lateral extension. So we'll come in transcranially and do a complete removal transcranially here. And I think that's the important point, is what I've learned over the years, is that you can do a more complete resection transcranial. So it's interesting when we opened up the dura on this case, we used a frontal temporal approach, there's hemorrhage. So this tumor has already had apoplexy and hemorrhage. And so we'll go ahead and identify the carotid, then remove the sub frontal tumor. And the importance here, we'll open up the fissure, is we want to dissect out the tumor that's encased in the anterior cerebral and anterior cerebral complex. So we identify the bifurcation, and the tumors, there's a cleavage plane of the tumor around the anterior cerebral. So we'll continue to bring down the rind of the tumor capsule from the sub frontal region and remove the rhine, and then leave the vascular structures intact. And we could never do a complete resection like this coming from below, because you just wouldn't have the ability to manipulate the vessels, and you'd have to open up sub frontally so much. This is just simpler and more practical coming in from above. And you can see that we'll just remove the tumor and then dissect out the region of the anterior cerebral here. Now it's important when you go back, this is the last part of the tumor, and you want to recognize the normal pituitary gland. I've seen people leaving and what I've done here now, is I, now I'm finding the rind of the pituitary gland and you can feel it just like you can, I mean, from transnasally, you can recognize the pituitary. What I'm doing is, I'm seeing the posterior aspect of the tumor. I'm bringing it out of the suprasellar cistern and anterior to the basilar there. And what I'll do, is I'm feeling for the pituitary gland and trying to find the, the zone of emergence of the tumor from the pituitary. And there's the pituitary now that I've identified and we're finished the dissection. And so we'll go ahead and do a postoperative scan on him. He was confused for a few days with all that sub frontal dissection, but he did quite well and ultimately had a great resection. So we were able to unnecessary, to come in a transnasally on him. I think I've got post-op images, yeah. And you can see the pituitary is still intact in that case. So could we bring up the next video, Luke? Great, we'll go to the next one here. And this is an important one. Each one of these videos is chosen to emphasize a different point. This is a woman with a recurrent pituitary tumor, primarily in the cavernous sinus. She had radiation 35 years ago, and now she's got diplopia, and she's got a lateral rectus palsy, and you can see the tumor here, in the cavernous sinus on the right side. Most of it, there's tumor in the sella, but there's also cavernous tumor that's really the predominant amount of tumor. And so what do you do with this? She's got a sixth nerve palsy, do you come from below? Do you go under the cavernous side from below, do you go lateral to the carotid? We've certainly have done that. We published that many years ago, but this is a unique case. And I'll show you why. And hopefully have you think about this because, I thought that if I came from below and the sixth nerve was identified and injured and unable to be repaired, then, then I wouldn't help her. So my goal was to help her with the six nerve palsy. So this is a, you can see the frontal approach from 35 years ago, and I'm coming now, extradural, middle fossa, a dual link approach, and that was something that Hakuba Dolenc demonstrated to us many years ago. That's the middle meningeal artery, we're in the spinosum. And I'm exposing the entire trigeminal nerve. Now remember this is a pituitary tumor. So it's going to push the nerves laterally. It's going to push, obviously the fifth nerve laterally, it's going to push three and four laterally but we don't know where the sixth nerve is. So this is like doing an acoustic tumor. So we're going to sort of debulk the center of the tumor and then bring the capsule of the tumor in. And I'm looking for the 6th nerve, because I presume it's traversing the tumor and you'll see what happens here. Is there I find the sixth nerve in two different pieces and there's part of it, there's the anterior part. And so you can go back now to the framing, and bring it out of Dorello's canal, and freshen up the end, and do an end-to-end anastomosis. Now, this is the single reason that you should think about a transcranial approach in a case like this, because at least in my hands with my skills, through the nose, I could not do this level of repair. And so I believe that this is an indication for a transcranial approach, if you've got cranial neuropathy and remember that the cranial neuropathy also gives you somewhat of a hunting license to be able to go ahead into the cavernous sinus and repair these nerves and try to get a good resection. Because normally I don't leave, like to leave somebody with a new cranial nerve palsy with a benign pituitary tumor. But this woman already had a 6th nerve palsy, and you'll see the post-op scan here, that demonstrates a good resection, and she's had a excellent resection and we've merely followed her. There's fat in the cavernous sinus, but we've resected the tumor well. So we'll go to the, the last video, which has demonstrated it, which I wanted to use to demonstrate, indication for another approach. In this case, I wanna call out to Chandrasekhar Deopujari, a good friend of mine from Mumbai. And we did this in Mumbai together. This is a young man, who'd had two previous surgeries for this tumor, with visual loss and the tumor was growing straight up. And so what was happening here, is the tumor was growing up in this area, suprasellar tall. And when they came from below, they weren't able to get anything because it was too firm apparently. And they also came frontal temporally and couldn't get the tumor. So what we're doing here, is we're coming in transcallosally. So I pick purposefully the axis of the tumor that needs to be addressed. So I'm coming from the top of the tumor and we'll go right down into the sella, you'll see this. So what we'll do again, same technique. It's like doing acoustic tumors. We're going to debulk the center of the tumor, and then come around the periphery of the tumor and gently dissect it from the surrounding . So, center of the tumor debulking here. And then what I'm looking for is that plane, that plane between the margin of the tumor. I'm using soft cottonoids to dissect and retract the tumor from its margins. You can see continued dissection and lifting the tumor out, and then using the ultrasonic aspirator to remove the center of the tumor. And there's a soft cottonoid. So I put a soft cottonoid there, so I don't have to redo that area of dissection and keep the case moving forward. We'll find the anterior cerebrals here, and we'll just move this along. And now we're moving the last bit of the tumor. Now we were in the floor now of the sella, you'll see this, this is the sella itself. We didn't use image guidance for this, but now I'm down in the sella. The tumor was extending into the cavernous sinus on the left side. So we stopped at that point, since the patient had no cranial neuropathy. This little trick, I use a little bit of gel foam and fibrin glue to try and seal off the hole into the ventricles to avoid hygromas. And you can see the resection, here's the tumor in the lateral wall within the cavernous sinus. So we've come down the axis of the tumor, right to the sella. He ultimately had radiosurgery for the portion within the cavernous sinus that were growing. Luke, can we go back to the yes, very nice. Thank you. So just a few other tips, I want to leave you at the end. Often these tumors have these hairy tumoral cysts, and it was Ann Osborne, who's is one of my colleagues that, that demonstrated this to me, and we wrote a paper on it. It really helps with the dissection plane. It's basically trapped arachnoid, sequestrated arachnoid cyst around the tumor. So it aids in a dissection plane around these tumors. The other thing is, is that you want to see how the tumor grows within, and then beyond the cavernous sinus. This is a very important point. The third nerve runs within a cistern prior to entering the cavernous sinus proper, and you can see it in the cistern here, and I want to show it to you here. You can see the third nerve running in the cistern of the, the oculomotor cistern. And you can use that as an indication of whether the tumor is invading this ocularmotor cistern, and ultimately it can herniate out, and grow out into the suprasellar cistern. But remember, this is from the roof of the cavernous sinus. This is not from the suprasellar arachnoid in the midline. And so if you do a transnasal approach, and the arachnoid is not violated, you'll never see this component. You can see this also on the, on the medial, or on the AP views, as you see in these right-handed images. This is a cartoon, but the idea is that the supra- suprasellar component is growing through the oculomotor cistern to reach the superciliary component. So you'll never see that through a transneural approach. It's important to recognize that. Here's a case in point. This is the man who I saw, he had visual loss, and here's his pituitary gland at the top here. This is a pituitary gland, but this is the portion that's grown out of the roof of the cavernous sinus. He had a cavernous sinus invasion. And so when you remove the tumor from below, you will never see that, and so unless you specifically open up and look laterally. So needless to say, this is what happened on this case. He had a fat graft here in his resection cavity. We did a good resection, but he had apoplexy in this lateral component. And I don't know what I'd do differently on this case today, but I had to go back in trans-cranially to remove that tumor 'cause it was growing right around the third nerve, and I was worried about the function of the third nerve. And so we went in and decompressed. We were able to remove the tumor subsequently. This is a little trick that we just published, but you might consider this in some cases. This is an extension of the idea of using the jugular venous compression or a Valsalva to get the tumor to squeeze down. We call this the toothpaste technique. So you can have a tumor that's in the cavernous sinus with a bit of middle fossa encroachment here. And normally you would say from the transnasal, unless you came in through the cavernous sinus and gave her cranial nerve palsies, you're not going to be able to remove this unless you specifically go after it. And as I said, my motto is I don't actually try to create a cranial palsy to get tumor out with the initial approach with a benign pituitary tumor, unless they have a deficit already. So what you can do in this case, is you open up underneath the carotid as if you're going to do a lateral extension of the transneural approach. And you can use this window here, in the carotid loop, and lateral to the carotid in this area, use it to try and retrieve tumor. So you get them to give a Valsalvo or a jugular venous compression during this resection, and you can often squeeze tumor down. And this is what you see in this case. So you can see we've removed most of that middle fossa component. And so we've actually reduced the amount in the middle of fossa. She ended up having radiosurgery for her residual component. So indirect tumor removal is feasible. Ongoing controversies. What do you do with this? You remove the tumor, which you've got tumor in the lateral wall of the cavernous sinus, much bigger case here. Do you primarily go after that or again if the patient doesn't have cranial neuropathy? I prefer not to. And that can be a point for discussion. Just to give you a heads up with acromegales, they can have large carotid arteries. Initially there was a journal group that published a paper where the carotids canals were closer together in acromegalics. I think it's due to this enlargement. And what you can have is, you can have fusiform enlargement of the carotid in the cavernous sinus, but the importance of this, is that it affects the resection and it puts the carotids closer to you, so you don't have much room to work between them. This is one such example on a non secreting adenoma like carotids in an acromegalic. So are you always use it as a fair warning? That we did a little study that shows that it's, it's greater than five millimeters in at least 30% in some up to 50% of patients. The cavernous carotid can be significantly dilated, increasing the risk of injury during surgery. It can be a real impediment. And finally, I'll leave you with this. This is a man I operated on in Eastern Europe. You can see how tall he is. I think he's the tallest man on earth. And he had a tumor, a growth hormones creating tumor that was within his third ventricle, and none of the instruments would reach it. So we had to use instruments from, from other surgeons to be able to reach it, but endoscopic and exposure is important, and you have to be able to use all the tools available to you, to be able to reach some of these tumors because they can be real treacherous. His carotids were quite close to one another as well. So mortality has improved. Complete resection is not possible in most cases 'cause of the cavernous sinus invasion. Large functional tumors, the growth hormone especially can be problematic. And I'd like to emphasize to control the mass, to avoid apoplexy, and multimodal treatment is, is necessary in most cases. So I'll leave it at that. And thank you very much.

- Thank you so much, Bill, really very illuminating, very thoughtful. I cannot emphasize the disappointment I'm left with when I tackle these giant tumors, very giant tumors. And then you work so hard from the bottom, you feel like you get a good resection. They still have reasonable vision before surgery, after surgery, they wake up with relatively okay vision, but then deteriorate. You do a scan, they have apoplexy, they're blind. You go back in from top and bottom and their vision never improves. I think that is sort of the, something that we all struggle with and people who say it doesn't happen, probably not doing enough of these cases.

- Yeah. If you ask any experienced pituitary surgeon, they've had this event, and it's a very humbling thing because usually pituitaries is sort of the easiest part of your practice. The patients are, are healthy, they're grateful, they do well, but these giant adenomas are treacherous cases, And you need to remember that. And so I really want to emphasize you need to control that mass. And so you have to pick an approach, or a combination of approaches and do them within short time period, to be able to get that mass out to avoid these complications.

- Yeah, I think that's a critical point. You know, some people often say, well, we went from the bottom, it wasn't safe to take out more and use the safety method. We wanna be safe, and leave a lot of tumor behind, patient becomes apoplectic, which often happens in these tumors where there is residual left. And in this case, where it's a large mass, the mass effect, obviously become significant with a clot, and it can be really a problem, and the vision never improves, and they are left with legal blindness. So these are critical aspects that people have to know about and minimize the complication, which you so eloquently mentioned. So that's a number one major pitfault of a major transsellar surgery. What would you say is the second major pitfault Bill?

- I think, I suppose it's CSF leak for the reasons that we mentioned. The CSF leak rate is higher in these cases. I think, you know there's many different ways to close and I, it's beyond the scope of this talk to address that. But I would say that, you know, use all elements at your disposal to be able to do that. Just by nature of the fact that the amount of skull-based removal is so much on these cases, you risk the patient of having a CSF leak. The fat graph can shift, be careful with fat graphs. I've seen several cases where people put the fat graft in too aggressively and you take out a pituitary tumor, and you give them a lipoma, and you can have visual loss from that as well. So, and then we use lumbar drains post-operatively. I don't hesitate to use a lumbar drain if I'm worried about the closure. And we use nasal septal flops when we need to. As I said, for routine pituitary tumors, I think it's too much surgery, but for, but for these big tumors, as you showed, I think that's very reasonable and that's a great asset to help with the CSF leak. So lumbar drain, fat graph, nasal septal flap, If you want to go that route, I think that's great.

- Yeah and do me a favor, one of the reasons for these giant tumors, I definitely have the nasal septal flap ready is because we often have to resort to a transtubercular approach. And what I have then is that I see the tumor is not coming down. There's a big mass left, it's a point of no return. If I take the patient, close up, they get apoplexy and they are blind forever, and I'm stuck, I don't wanna make dangerous moves. So what I do in that case is, I remove the tuberculum. I expose the base of the frontal lobe. I get transneural and go over the diaphragm and I pushed the diaphragm down with one device and I removed the tumor with suction. So essentially use the extradural or intradural technique to push it extradurally. Have you ever tried that before?

- Yeah, I've used that technique. The real, the risk with that, and I think it's another technique that you can use 'cause, so instead of staying in the center of the tumor, like we traditionally do and have the arachnoid come down, or the diaphragm come down, what you're doing is you're doing an extra capsular dissection. And I showed that with these open cases that I was doing. The risk with that, you need to just be aware of this for the young people, is that if you come from tuberculum and you come extra capsular like that, obviously you've gotta worry about the vascular stroke supply. You know, the vascular and the intracerebral, A1's, bilaterally and the optic nerves. But the other thing is, you need to be able to recognize when you're coming onto the normal pituitary stalk and pituitary, because I've seen people do hypophysectomies that way. Is they come around and the pituitary gets taken out with the specimen.

- I agree. In that case, we cut the diaphragm parallel just in the middle until we get to the stalk.

- Yeah you want to be able to, and it's a consistency issue, and I was trying to show it with that first video that I showed, is you can feel the tumor and it's just like doing it from below. You need to understand the consistency of the stalk and the gland in comparison to the tumor.

- Right, it's such a fine line Bill, as you very well mentioned, between trying to do the minimal invasive approach and do endonasal, and then suddenly you're trapped not taking a lot of tumor out, and now you're worried about blindness because apoplexy after surgery. So it's almost, as I said, it's point of no return because now you're handcuffed. What am I gonna do? And that's been, our second strategy, may not be the perfect solution, is there listen, we can do transcranial right now. We could have apoplectic event and lose vision. Why don't we go to the second strategy and open up the diaphragm, extra capsularly and remove the tumor. So those have been the things that we have used in the past, but I really like your technique. I think the transcranial approach is not unreasonable in these giant tumors, because if you don't have a lot of experience, like you have Bill, this can be very dangerous to go endonasally when you're not able to remove a lot of tumor. And then you're really placing the patient at a significant risk of blindness.

- Right.

- Even beside blindness, these patients can bleed into the diencephalon

- Right.

- because you may have injured- you may have injured the the diaphragm during the case. Now there is a connection to the nervous system's nervous tissues, and then they get interthalamic hemorrhage, blindness, hemiplegia, it just looks very messy.

- Yeah don't, you know, there's no, there's no harm at all in telling the patient that I don't know if I can get this tumor out from below. And I routinely tell them that. I say, "You know, let's try from below, we'll see how it goes." If it's soft and it comes down, that's great. If not, I reserve the right to be able to just, you know, stop that, pack it off, and then open the head from above. And the patients are usually very reasonable. and if you explain them the difficulties that you have with these tumors. So we routinely will consent somebody I just did one last week. I just routinely consent somebody to do from below on a giant tumor, but be able to convert it to a transcranial if necessary. And I would like, I like to do it at the same time now, 'cause I don't want to really have the risk of having that intervening apoplexy once that's happened to you once, you never forget it, and it's a lifelong lesson.

- I agree. Let's go ahead and address some of the questions. Some of them are very interesting. Somebody asked, "Why did you put fat in the cavernous sinus in that dual link?"

- Yeah, good point, probably not necessary. I completely agree. I use it as, I mean fat, I use it to close dead space and to avoid venous hemorrhage. That's the only reason you could probably fill it with liquid gel foam. I have no problems with that. It's going to melt away. And the reason I like the fat, I used to close the nose with like, you know, inserts and I've used MedPore and more like smash and such. I don't do anything like that, everything I use is biodegradable. And so that when the fat melts away in the sella or the suprasellar area, then you've got a perfect MRI and I don't have any artifact. So people have used titanium and all that kind of thing. You can't see small tumors recurring, if you've got artifact from, from foreign body. As well, I've been burned in a couple of times in the past with pituitary abscesses after surgery. And when I went only to a fat, I use a surgecell sling technique, and we publish that, to hold the fat in the, in the sella or the sphenoid. Once it melts away, there's nothing there. It gives you a perfect MRI scan to follow, that's the reason, but you could put anything in for hemostasis in the cavernous sinus. I have no problems with that.

- Gotcha, there's a couple of good, a few good questions. What do you think is a learning curve for endoscopic pituitary surgery, especially for giant ones? How many do you think you should be doing before you tackle a giant tumor through the nose?

- Yeah, that's a good question. I mean, these sort of techniques that I've evolved to over the years have been a career. It's been like 30 years of doing, you know, over a 100 tumors a year, kind of thing. So it's, it's a, it's a lot of experience. And as you know, this is a humbling business and we're learning our whole careers. In fact, I tell our residents, that's the benefit of being a neurosurgeon, is that you don't, you never get complacent and bored because you're always continuously humbled and learning from things during your career. And I think that, that's one of the wonderful things about our specialty is that we've still got a long way to go. And so I think probably you need to be doing a lot of routine pituitary surgery. And before you start doing the big ones from below, because of the risk that we talked about, you know, I'd like to see probably 50 tumors, just regular ones done before somebody did a giant one, that was gonna require a lot of technique to get it down.

- When you go transcranial Bill, how much do you aggressively manipulate the tumor capsule? If it's adherent, I assume you leave it behind. Is that correct?

- Absolutely. Yeah, if it's adherent, there's no point, it's a benign tumor. You've got other techniques that you can add over time if it's a problem. But oftentimes if it like in a lot of pituitary surgery, we just were entering, emptying the tumor out. We're not doing an extra capsule or dissection. We know we're leaving residual microscopic disease, but we follow those patients. And if the patients are reliable, I think that's a very reasonable thing to do, and then we can add either further surgery or radiation, if it continues to grow down the line.

- And these giant tumors that chiasm can really descend, have you ever done for any type

- Yeah. Yeah. I get asked that and somebody showed me a case the other day about this. I must admit it's rare, rare, rare. And you know, we see, I mean, you showed your case. There's a huge defect once the tumor has been removed and it's remarkable how infrequently you have to do anything about that. And you see the tumor, you see the optic nerves can be bowed down, they can scar down, but if you do an extra, a capsular or intracapsular dissection of a tumor where the diaphragm herniates down, and the diaphragm has not been violated, I've never seen that in those cases, because I don't think you're in the sub-arachnoids space and your creating scar. The cases I've seen, it has been where the tumor has been stuck and the diaphragm and this arachnoid's been opened, there's been CSF leak at surgery, and as it scars down, it tends to herniate down. And I've gone in once and done a . But it's very rare. I know it's been published in the literature. I just, I must admit, I just don't see it like that.

- I agree, I have not seen it either. Last question, Bill. If somebody presents with third nerve palsy, big tumor, no visual field deficits, do you have potentially apoplexy, do you operate or not?

- Yeah great, great question. Apoplexy, and we should probably talk about that sometime Aaron, because it's, it's an interesting and nuanced business. So my personal feeling is that apoplexy occurs more frequently than we recognize it and I have cases, and I've published a series of cases, a very small series where patients have had a headache. They've had a scan and been followed in the community 'cause we serve a very large rural community, and they had apoplexy in a small tumor, and it was unrecognized. And then subsequently over the next week or two, their headaches got better. And then we scan them three months later and the hemorrhage has gone and there's, it looks like an empty sella. So, so I think it happens more frequently. It's probably mild grades of apoplexy. And I will tell you that if it's a prolactinoma and they've got a cranial nerve deficit, except for visual loss, for visual loss, we always operate if they've got acute visual loss, but if they've got just ocular motor deficit and it's a prolactinoma, we'll just put them on medical therapy because I've seen that third nerve get better quickly with that. If it's a nonfunctional tumor, I would probably operate.

- Okay. Excellent. And it's, somebody asked about apoplexy after resection. Can it be residual tumor and cavernous sinus versus intersellar? I think both, I have seen apoplexy happening with residual tumor in cavernous sinus causing blindness or intersellar. Do you agree with that?

- Yeah, I do agree. I think it's probably harder to tell, that one case I showed you, with that knob that got apoplexy in it afterwards, that was coming out of the roof of the cavernous sinus, and I never went near that thing and I, it just must have changed the dynamics of the whole thing. And so it must've started bleeding in the cavernous sinus and extended up into the tumor in the suprasellar cistern.

- And the very last one. How do you really feel like intraoperative MRIs necessary for between pituitary surgery?

- Great question. Great question. I'm glad somebody asked that and I appreciate your thoughts on this Aaron. So we have, we have intraoperative 3-T magnet at our shop, and I must admit I use it very infrequently, and the reason for that is a practical reason because it takes all day, and also, I'm not sure that with, with experience with great endoscopic techniques. And if there's any question, you know, we can do an MRI, but I have not used it routinely. I have used it for the complicated cases with multi-lobular suprasellar extension, that I didn't know whether I was going to achieve getting every labial emptied. And so I've done it in those cases, but very rarely, and I don't use it routinely unless it's a very unusual tumor.

- Gotcha. You know, for us Bill, and again, I'm sure it's the same for you. We have developed so much experience with our ENT colleague, we have worked with the same person over 10 years and with endoscopy in 45 degree angle and extended transsphenoidal approaches, we have felt pretty comfortable that without intraoperative MRI, we can remove the tumor effectively. We also do believe that using intraoperative MRI extends the operation time significantly. And it can be a challenge because by the time you do initial MRI, remove the tumor and other MRI, the extent of tumorous time of operation is so significant that we have not seen any significant benefit if we have a good selection criteria of who to use for endoscopy. So we do not use that.

- Yeah, the other point that I've made and I've made comments about this, is that I think if you have an MRI, I think you're more conservative with your resection initially, because you're gonna check yourself. Whereas I think if you don't have an MRI, then you're gonna just take a look and don't hesitate, take a look and see with the endoscope and see if there's residual tumor. So I'm wondering where you stopped short a little bit when you have an MRI. So we and I think that nobody's looked at the, the morbidity of doubling the anesthesia time for a case with an intraoperative MRI on a case that could be done without it so.

- I agree. Well, Bill, I wanna thank you. Excellent discussion, amazing material, huge experience. Obviously you have been a mentor for me, so many other people, with your vast technical expertise and so many people across the world, really look up to your expertise for taking care of their patients. All of those mean so much to us. And again, thank you for taking the time today from Hawaii, where you're not even working today, for being with us. That means so much, so much you have done for neurosurgery through your huge legacy Bill. And thank you again for your time.

- Thanks. I just wanted also just mentioned that, you know, it's really an honor, I've had fantastic mentors and we all have, but it's really Hardy, when I was a medical student, that really got me interested. And then I trained with Marty Weiss and he was amazing, amazing person with a huge experience with pituitaries. And so it's something that you just build on and we should always, always recognize our mentors.

- I agree. We stand on the shoulder of giants, no question about it. And you know, Bill, we have had over 300, we just about 300 people all the way through the lecture with you. And I think that's truly a, a demonstration of your contribution to neural surgery. So thank you again.

- Thanks Aaron. It's an honor to be here. Preciate.

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