Giant Pituitary Macroadenoma: Endoscopic Surgical Management and its Pitfalls Free

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- Colleagues and friends, thank you for joining us for another session of The Neurosurgical Atlas Virtual OR. My name is Aaron Cohen. Today, we have an incredible lecture, an honored guest, Dr. Siraj Belkhair. He is Chairman and Professor of Neurosurgery at Hamad Medical Corporation or Hamad General Hospital in Qatar. An incredible program, Siraj is truly a master surgeon. He established the only ACGME-accredited program that's really thriving in the Middle East, an incredible training program. I have come to learn their program very closely and have really learned about what they have done there. Today, he's gonna talk to us about management of giant pituitary adenomas and its pitfalls. This is really a difficult surgery, many pitfalls, many challenges, and really, would love to hear his perspective on this topic. So Siraj, thank you for joining us. I look forward to learning from you. Please go ahead.

- Thank you, Aaron, for the invitation. It's really an honor for me to present at The Neurosurgery Atlas The work that you guys done over the years is tremendous and it's well-known all over the world. So today, I'm gonna talk about the Giant Pituitary Macroadenoma Endoscopic Surgery Management and its Pitfalls. But before I start, I'm presenting from Qatar, which is one of the countries in the Middle East. It has been known recently for hosting the FIFA World Cup tournament in 2022. And the stadium was amazing and there was about half a million people who visited the country over a period of four weeks. Since I'm the chairman of the main academic neurosurgery department here in the country, I got to have some VIP seats in some of the games, and that was really a nice tournament that I attended. So to go back to the giant pituitary macroadenoma, these tumors are one of the most complex neurosurgical challenges in the medical field. Due to their large sizes, they cause mass effect on the optic apparatus and adjacent structures, like the cavernous sinus, hypothalamus, and sometimes, they do obstruct the cerebrospinal fluid pathway, and cause the patient to have hydrocephalus. They're are about 6% to 12% of all pituitary tumors, and we know that the pituitary tumors are the third most common intracranial tumors. So there are quite numbers of patients that neurosurgeons might have encountered during their career. And the challenge about these tumors, even though they are benign, is their invasiveness and their size. Histologically, as I mentioned, most of them are benign in nature. But when we talk about giant pituitary adenoma, there is not really a consensus in the literature about the terminology. The most common definition is by Symon and Jakuwoski. They described it as when the diameter of the pituitary tumor is more than four centimeter, which is 40 millimeters, it's called giant pituitary adenoma. Pituitary tumors that exceeds less than six millimeter from the foramen of Monro. Other definitions are pituitary tumors that are 30 millimeters above the tuberculum sella. And the last definitions among all of these definitions, the pituitary tumor have a supra sellar extension more than two centimeter in any directions, some of the authors describe it as a giant pituitary adenoma. But the definition that most of the neurosurgeons go with is when it's four centimeter in diameter or more, and that's when we call it giant pituitary macroadenomas. They usually present, as I mentioned, from their mass effect, but they're associated with the hormonal dysfunctions. Majority of these tumors are non-functioning, and they're associated with a decrease of the pituitary gland hormones. So basically, either partial hypopituitarism or panhypopituitarisms. We do check all the pituitary hormones profile in our institutions for any pituitary gland tumors, including a free T4 testosterone and insulin-like growth factors with the serum cortisol and 24 hours urinary-free cortisol. One thing that I want to emphasize on, sometimes these patients comes in with adrenal dysfunctions, hypoadrenalism. Like, their cortisol level, they appear to be normal because there is a random, but actually, when you check the morning cortisol and 24 hours urinate-free cortisol, they have a decrease in their levels and they need to have replacements. And this is something that everybody should be aware of. Clinical manifestations, as I mentioned, mass effects in the neighboring structures, mainly the optic apparatus, which are gonna cause a visual acuity defect and visual field defects, a decrease in the pituitary hormone secretions and sometimes, when it's invading the cavernous sinus, it's actually causing a mass effect and also, symptoms for the third, the fourth, and fifth cranial nerve and the abducent nerves. And when they extend more on the parasellar regions, patients might come with diplopia, ophthalmoplegia and ptosis. What we do in terms of radiological investigation for these patients, we do a CT for the sinuses, a CT angio to look at the carotid artery and an MRI of pituitary with contrast. And all of these investigations, we do it with navigation, so we can use it intraoperatively. One consideration about those tumors, especially when they're expanding in size, sometimes the sella are well-preserved and the tumor is expanding superiorly. And when you see that dome of the tumor superior, it means that the diaphragm is intact. It's actually when you see the snowman appearance, it's when there is a defect in the diaphragm and that the tumor is extending beyond it. So this is one of the considerations. It's like looking at the shape of the tumor, whether it's multilobulated, multi-compartmental or uniform in shape, as the one shown in this photo. Sometimes they invade the sella, and they go into the sphenoid sinus, but this is not usual, but sometimes it happens. In terms of the management of the giant pituitary macroadenomas, first of all, if the patients have a hormonal dysfunction, then you need to replace the hormones that's being deficient. But in case of there is a prolactinoma, which is a rare identity, and they're causing a giant pituitary macroadenoma, the first management is a medical management. But otherwise, a surgery is the mode of choice for those tumors. As I mentioned, most of them are non-functioning and mode of surgery has been evolved over the years. Like, over the last 20, 30 years, we went from a transcranial approach to microscopic-assisted trans-sphenoidal approach, to the extended endonasal approach. And I think most of the neurosurgical centers who deal with this very often, they adapted the extended endonasal trans-sphenoidal approach for its effectiveness. As I mentioned, rarely that those tumors can be due to prolactinoma, and in that regard, the treatment will be a medical treatment, in terms of dopamine agonist therapy, but this is very rare. The goals of surgery, when it's non-functioning, it's to make a pathological diagnosis, to decompress the neural tissues and for complete resection of rare functioning giant macroadenoma. Sometimes, these patients comes in with a secretory adenomas and reduced growth hormones or ACTH, in terms of the cushings and acromegaly, and in that regard, it's gonna be a challenge, because any small piece of that large tumor, if you leave it behind, then it will continue to secrete and will then cause symptoms to the patient. And that will add another challenge for the surgeon to remove the tumor totally, without leaving any residuals. The ultimate goal is maximum safe resection without jeopardizing the patient's health. The challenges of the surgical treatment, why these kind of tumors are challenging, and not many surgeons have an experience with those and there is a learning curve for those. And you need, really, to be first comfortable with the endoscope, doing the skull-based approaches and going with microadenomas, then macroadenomas, and with the learning curve, with the time and experience, then you can challenge those cases. So the challenges, as the surgeon experience is very important, sometimes, total resection is difficult, and occasionally, sometimes dangerous, due to the invasiveness of this kind of tumors and encasing the carotid arteries. Also, due to the tumor size and irregular margins, and sometimes, it's multi-compartmental, so it's difficult to have total resections. The problem is when you have a subtotal resection alone, it's associated with recurrence and it's up to 80% of the time that the lesion will regrow. But the main risk is when you do a subtotal resection and leave a considerable residual behind, there is a risk of intratumoral bleeding, and that will cause, really, apoplexy and might lead to a neurological morbidity, including blindness and panhypopituitarism and thalamic dysfunction, and you want to avoid that. So we've come to what I'm gonna be talking about in how you'll treat these patients surgically and what's the mode of surgery. As I mentioned earlier, I believe, in this era, the way to go with this kind of surgery, with these kind of tumors, is endoscopic endonasal extended trans-sphenoidal approach. And the reason for that, it avoids retraction of the brain. In comparing to a transcranial approach, it avoid the retraction of the brain and optic nerves, presents minimal risk of injury to the brain and vascular structures with an experienced hand. Also allow rapid recovery of the pituitary function and visual impairment that the patient had. I remember, more than 20 years ago, when I was a resident, one of the retiring neurosurgeons was arguing about these cases, that it has to be done transcranially, but actually, this is not an argument anymore. With a developed endoscope and the expertise and the training that the new generation neurosurgeons are having, which I strongly believe, and I will show you in a few minutes some of the cases that we've done, you can have a cure for the patient with just doing it by the extended endonasal skull approach. When we say it's extended approach, what does it mean? It's like we're going through the nose, through the sphenoidal sinus, but taking more bone, and actually, taking more bone is based on the location of the tumor and the direction of its growth. So basically, you tailor your bone resection based on the size and location of the tumor. So there are different names, for the residents who might be watching this, there is different names that you see in the literature. It's basically, you name the bone that you're taking during the procedure. So when you take a tuberculum, you call it trans-sphenoidal trans-tuberculum. When you take the trans-sphenoidal, it's the same thing. When you go anterior up to the cribriform plate, which is rare to have it for pituitary macroadenomas, usually, we do it for the meningiomas. Trans-sphenoidal trans-clival, when you take the clivus bone. And sometimes you go laterally, taking the pterygoid bone when the lesion is extending in the enfractum . That's basically the CT scan showing the bones that you might resect, in addition to taking the floor of the sphenoid. So we come to what's the advantage of doing the extended endonasal endoscopic approach to the microscopic assisted trans-sphenoidal approach? The difference mainly is you'll be able to see. Using the endoscope, you're gonna have a panoramic view of the sphenoid and then inside the sella itself, and you will be able to see on the supra sellar area. With the microscope, it's actually, you're gonna be curetting the tumor blindly when they are extending into the cavernous sinus or into the supra sellar area. And this is really a recipe of disaster, curetting the tumor without seeing what you are curetting, using just a microscope, it's not really acceptable, and you expose the patient to a risk of bleeding, mainly from the carotid artery, or injuring any of the neurological structures around the sella. So the endoscope will provide you a better visualization and a safe resection of the tumor. You can use the microscopic-assisted trans-sphenoidal for the limited microadenomas that's in the sphenoidal sinus, with limited extension to the retrochiasm, but in my opinion, going laterally with the curette blindly, or up into the supra sellar area just using a microscopic-assisted trans-sphenoidal approach, it's a recipe for disaster. There are multiple case reports in the literature showing the difference between the microscope and the endoscope through the trans-sphenoidal approach, and that's through that time when people were converting from the microscope to the endoscope. And it's well-known to everybody by now. So with all these literature that's published over the last 20 years, especially for the large tumor, more than three centimeter, the endoscope will provide much better resection, in comparing to the microscope. This is what I usually just explain to the residents. It's like going with the microscope... And I've faced both eras, I've done it both ways, with the microscope and endoscope, with pituitary macroadenomas. This is during my recent trip to India. I was invited to Dandy neurosurgical meetings, and this is one of the Maharaja's palaces. When you go inside the sphenoid sinus, it's like going into this hallway and trying to remove the tumor from that far side door, without seeing, really, on the sides or up, and doing it blindly. But when you go with the endoscope, you'll be having the panoramic view of the sella with the supra sellar extension. And with a 30 and 45-degrees endoscope, you will be able to see details in the corners that you will not be able to see just going from outside. So how we do it here in our hospital, this is my picture during one of the surgeries. I'm the right-hand surgeon. I stand on the right-hand side of the patients. We do it in collaboration with our ENT colleagues. So the ENT surgeon will stand on my left side, and he will put the endoscope on the upper part of the right nostril, and my surgical assistant will be opposite to me. And so he will be handing the instruments, while the ENT surgical assistant will be on his left side and he will be handing the instruments to him. So that will allow an easy flow in the operating room. Between us, we put the navigations, and in case if we need to, between me and the surgical assistants on the top of the head of the patient, we put the navigations, and we use a neuro navigation in all of the cases just to orient about the anatomy, in case if the tumor is embedded into sphenoidal sinus, and also to help during the intraoperative resection. So this is basically our setting in the operating room, and it works best for me, and every surgeon can modify the way that his team can stand, based on the way that the workflow of his operating room and the size of the operating room. The technique, we do a bi-nostril technique, as I said, with the ENT. The endoscope is on the right nostril, in the upper part of the right nostril. And I use both nostrils. So I put the suction on the right nostril and the instruments that I would do a resection with is on the left nostrils of the patient. And that will avoid crowding and scissoring effect of the instruments. With the giant pituitary macroadenomas, I do posterior septectomy and wide sphenoidotomies, plus/minus posterior ethomoidectomy, and that's to give a wide exposure inside the sphenoid sinus. So it allow me to handle the large tumor without having an obstructions from the bone. We enlarge the surgical corridor by taking the middle turbinate on the left side, and that will allow us to pass the instrument easily inside the sphenoid sinus, while we're keeping the other contralateral middle turbinate intact. As I mentioned earlier, it's very important to understand the anatomy, to start with small cases, where the tumor is confined to pituitary sella, where you see the anatomy. And then, with the time and experience, you can advance your surgical skills to tackle such challenging cases. What we do, we remove the floor of the sella from one cavernous sinus to another. As I mentioned, we use a navigation and also a Doppler ultrasound to check where the location of the carotid artery. And the wide resection of the bone, taking the whole bone, from one cavernous to another cavernous sinus, is really key here. Removing the bone, avoiding any obstruction of your vision to remove that tumor. Also have a wide opening of the dura is essential. We use navigation at different stages during the surgery, when we open the dura and also when we are resecting the tumor. I usually open the dura on a cross-shaped fashion, but sometimes, when the preoperative MRI indicate that it could be that normal pituitary glands is on the floor of the sella, at that point and only that point, I will do a U-shape. And as I show in this picture, doing the U-shape opening of the dura, in my opinion, that will enable us avoiding injuring the tissue underneath it. And that way, on the right-hand side pictures, is like pushing the normal pituitary glands upward and removing the tumor below it. And that's in case of the preoperative MRI indicating that there is normal pituitary glands between us and the tumor. We use different angles, as I mentioned, zero degree, 30 degrees and 45 degrees. Reconstruction of the postoperative dural defect and the skull defect after the surgery. Traditionally, and this is what I want to share with you guys, something that we've done differently here at Hamad General Hospital is, but traditionally, we used to put the fat graft in the sella and reinforce it with the Onlay DuraGen or fascia lata and then reinforce it with the fibrin glue and put the vascularized nasal septal flap over it and then put the nasal pack in. And this is basically what most of the neurosurgeon around the world is doing. But for vascularized nasal septal flap, it's very important. One thing that I'll touch base on before we go to show you what we are doing differently is when you make a cut for the nasal septal flap, we have that flap here, two things we do, we don't use a obi to trying to avoid injuring the blood vessels that's supplying the sphenopalatine vessels, that's supplying the flap, and also preserving the mucosa of the flap. So we only use a knife or a scissors plus we make the cut just above where we think is the blood supply is coming to that flap without going superiorly early to injury the olfactory nerve branches. So this is what we do in terms of the flap and then we put it in the nasal pharynx to preserve it and avoid injuring it during the resection of the tumor. So we develop a noble technique here for reconstruction of the postoperative dural defect. We as, as I mentioned, traditionally we use a fat graft that we remove either from the incision in the abdomen or from the thigh plus the fascia lata. And that's exposed the patient to another incision that's in my opinion is unnecessary. What we use, what we did differently, we start using the onlay dural substitute called ReDura, putting it instead of the fat graft and the fascia lata and we overlay it with a vascularized naso-septal flap and then buttress it with Surgicel and tissue glue called Tisseel and followed by mechanical compression using a nasal ball, which is coming from Stryker into the nasal cavity to put the pressure and keep the flap in place. And we put the lumbar drain for all our patients with a dural defect. And there's a couple of randomized trial showing if you put the lumbar drain, there is less CSF leak than no lumbar drain. And we keep the drain at draining 10 cc's per hour CSF for five days continuously than we remove it. Why we are putting a Redura. The Redura is a novel substitute in terms of it's originated nanofibrous for the dural defect repair. And this is coming from a German company, it's called Medprin. And we start, actually, we came to to know about this ReDura during the, the COVID-19 outbreak where there's a shortage of supply for DuraGen and this is a, this substitute is a, is a FDA approved. And as per the manual from the manufacturers fully degradable and absorbable and one year after implantation, what we found is we were using this in the intracranial surgeries, we removing a tumor and there is a dural defect, we put the ReDura and then we had a series of cases where the patient develop an intens fibrosis and granulation tissue on the area where the area where that ReDura was put in. So we stopped using it, we publish it as, as something that other neurosurgeon around the world should be aware about it. But then I thought with myself, why don't we use this for the, when we do an extended endonasal approach that will enable us having the thick fibrotic tissue that we would like to have it to seal the defect that we are having during the procedures. And since then over the last two years, we start using it instead of the fat graft and fascia lata with the way that I showed you. And we did not have any CSF leak, zero. And we have about now about 80 cases. We're gonna publish our experience with that hopefully in the next few months. But since we start using it, we did not have any CSF leak doing the way that we are doing it along with the lumbar drain and vascularized naso-septal flap. It's either we don't apply too much ReDura it's only one or two layers on the defects. And that's it. And I will show you a couple of cases that we've done that and the postoperative images to show how we did it. Again, we use this for any dural defect and we don't use more than two layers maximum trying to avoid any abnormal reactions from this dural substitutes. So our experience with giant pituitary macroadenoma in Qatar. Hamad Medical Corporation is established in 1979. We are non-profit healthcare provider. We have nine hospitals and 20 primary care facilities and we are the only neurosurgery academic neurosurgery center in the whole corporation. So all the cases comes to us and that consolidate the experience of the neurosurgery team working with me. Hamad Medical Corporation is the only organization outside United States that has JCI accreditations for all of their hospitals. So that tells you the amount of cases that we are receiving from all over the country and the population is about three millions and that really expand our experience with all the rare diseases including the giant pituitary macroadenomas. Case number one I'll discuss with you is a 51 years old lady. She's a local patient. She had a left eye blindness for two years, progressive right eye visual loss over, over a few weeks. And then she presented to the ophthalmology, the vision examination and visual field, which shows visual loss of the left eye, with a significant loss on the right eye. MRI showed this large tumor that is expanding on the supra sellar and going into the spino sinus up to the foramen of Monro and that's a severe compression of the optic chiasm. The lesions joined the pituitary macroadenoma by definitions is more than four centimeters and it's invading the sphenoidal sinus and also going laterally but not invading the cavernous sinus. And as you see in this image, it's really causing a huge compression on the optic chiasm. I'll show you the video to show you the challenge of these cases when they are in venous sphenoidal sinus, you'll not be able to see much of anatomy. So we'll start with doing the naso-septal flap on the right nostril putting it in the nasal pharynx and taking part of the middle turbinate on the left side, to allow the axis of the instrument to resect the tumor. And then we do a posterior cystotomy and taking the vomer bone with the mucosa of the sphenoid sinus. But as you see here, this is inside the sphenoid sinus, there is no anatomy at all, there's no normal anatomy. You see the tumor is in front of you along with the mucosa of the sphenoid sinus. The bone is still there. So you have to resect the sphenoid symptoms that's remaining and you have really to create anatomy. This is the challenge case when you will use everything possible in your hand to avoid going into a structure that a vascular structure or a neurological structure that you might injure. So I'm here inside the sphenoidal sinus, resecting the tumor in the sphenoidal sinus within the sphenoidal sinus, I'm aggressive because I know there is no carotid artery there and I can resect the tumor in a fast speed. And also what I did is try to develop my anatomy. I remove the tumor first in the sphenoidal sinus without going into tunneling inside the sella area. And then once I resected the lesion from the sphenoid sinus aggressively with removing the remaining part of the mucosa. And then I followed the tumor into the dural defect because obviously this tumor has penetrated the dura and went outside toward the nose. Once you reach the dural defect, and that's when you come a little bit more cautious and also using a navigation with the Doppler ultrasound, it'll help you avoiding injuring the carotid artery plus the removing the lesion has to be in a systematic way. What we do is taking the inferior part first, then the central part that we do a decompression, then we go to the lateral part of the tumor because you want to avoid premature descending of the diaphragm. And that will really obstruct your vision from resecting the tumor. And then inside the sella itself, then I advanced my scope to see on the sides and also on the supra sellar extension. So I will just fast forward this fast one this for the sake of time and I just wanna show you at the end of the procedure putting the ReDura substitute, which is I said the dura substitute. It's called ReDura laid over the diaphragm. We had a dura that have a defect that causing CSF leak. And then I just laid over it in a way that's just obstructing that hole from having the CSF. And what I do differently also with these tumors, I don't remove the capsule when they are adherent to the surrounding structure. In my opinion and the experience that we are having here, removing them might cause a complication in terms of the perforator that's attached to it or a carotid or or a major blood vessels and might cause an injury. Leaving the capsule alone after devascularizing it from taking the tumor, with time, this capsule will go down and will disintegrate. I know that some neurosurgeon will advocate about opening further the dura and try to take the capsule and resect from the surrounding structure, but it's really, in my opinion, this is not necessary. This is the MRI of the patient three months later, as you see, the capsule has completely disappeared and as you see, the ReDura that we had that we put on the defect, it's caused a fibrotic tissue that's really occluded the defect and obstructed the defect of the CSF, the defect in the dura and the skull that we have from the surgery and made like a mattress preventing a CSF leak. This is a post-op MRI three months later, this is the images and also showing the normal pituitary function, the patient has a normal pituitary function, no CSF leak. She was still left blind on the left eye and the right eye has a significant improvement. Nine months later, her right eye becomes six over six in terms of visual acuity and start seeing a left eye counting fingers at one meter. And this is the nine months MRI, as you see here, that ReDura develop more fibrotic tissue that sealed the defect on the skull base and the patient has no complication from removing this large tumor. The second case that I wanna discuss with you is another patient with a giant pituitary macroadenoma. She has bi-temporal hemanopsia, with the more deficiency on the visual, on the left eye than the right eye. The lesion was, was going lateral three for the left side and it's invading the carotid, the invading the cavernous sinus. And this is a visual field defect that the patient has. We did the extended endonasal approach. What I do with these cases, all the giant pituitary macroadenoma, I remove the sella and I also remove the tuberculum sella. It is part of the procedure because going into the supra sellar extension without taking the tuberculum sella or , then you will not be able to see the supra sellar extension fully. At that time we were still using the fat graft and this is the fat graft that closing the skull defect with the naso-receptor flap. And this is the post-op MRI six weeks later showed the complete resection with the fat graft in the sella. Six months later the patient's visual field was done and it shows a significant improvement. Third case, another patient with a giant pituitary macroadenoma. Again, same thing, it was referred to us by ophthalmology. As I mentioned earlier in the presentation, these patients are having none, most of them non-functioning tumor. So they don't present with hormonal over secretions. They mostly coming with a visual field defect. And this patient can had a history of 10 years of headache and gradual deterioration of visual field. Again as a giant pituitary macroadenoma is reaching to the third ventricles. We did an extended endonasal approach in his visual field shows almost on the left eye visual, there's no vision at all. And the right eye has a hemianopsia and optic nerve shows atrophy as he has a 10 years of gradual deterioration of his vision. We did the extended endonasal skull base approach through the transsphenoidal. And again, we put the Redura and as you see this is three months after the surgery showing it that the skull defect was basically most of it has been covered by the ReDura and the regeneration of fibrotic tissue that evolved over the skull-based defect. This case, I will also show you the surgical video. This was a patient was referred to us from . It's one of the countries in the central Asia. He is 49 years old and he came in with headache with a significant deterioration of the left eye vision. He has a high prolactin with a high growth hormone levels, but the prolactin levels, when we did the full workup, it's says more like pituitary stock effect. And he came in with acromegaly clinical features. Looking at the MRI here, this regions occupying the sella and the supra sellar extension into the floor of the third ventricle. You might expect this is an easy surgery. This is an cystic lesion, once you open it, you might have a fluid, but actually it turns out during the surgery, this is a firm thick tissue and probably due to taking a cabergoline in his home country before coming to us for a couple of months that might made that difficult to us. But anyway, the preoperative assessment shows the patient is really having an acromegaly with a high growth hormone like most factors. And as you see here, the tumor is compressing the optic eye as more on the left side than the right side. And he basically having a more visual field effect on the left eye. As shown in these pictures, we did an extended intranasal transphenoidal approach, again, having the nasoseptal flap using the knife and the scissors, preserving the blood vessels and also preserving the mucosa of the flap. I'll just go fast on this. And then removing the vomer and the floor of the sella, showing the sellar floor using the navigation here just to identify our landmark. Usually this part is being done by my chief resident with our ENT colleagues. Then they remove the floor of the sellar and we go from one cavernous sinus to another cavernous sinus. One thing that I want to show you really, and this the dura after removing the floor of the sellar and in this case we did the cruciate incision for the ReDura. But what I really wanna show you in this case is what you're gonna be seeing next after opening the dura and then the tumor is appearing. But actually the opening of the dura was not really enough. Also the bone, as you see here, the edges of the dura is there. They're trying to remove the tumor. The tumor is like thickened tissue, thickened consistency. And then this is when I came in and I resect, I opened the dura, I calculated the edges and I opened, I took the tuberculum sella as it shows in this by my mouse here. So I removed the bone tuberculum sella, I removed the edges of... Also up to the cavernous sinus and I coagulated the dura. And this is what you see with the exposure. So good exposure is very important in terms of removing the tumor, inadequate bone removal and opening the dura will not make you achieve the total resection of the tumor. So here I dissected that the tumor from the surrounding tissues and very carefully. And then going into the cavernous signs on the left side, as it looks like the tumor was invading there, up to the floor of the third ventricle. It's very important not to pull anything inside the sella using a pituitary rongeurs as this might be dangerous and might be attached to the carotid artery. So you have to dissect it, remove it, and then dismantle it from the surrounding tissue. Here you see there is an opening of the diaphragm with the CSF coming out, but using a third degree endoscope showing that the lesion has been totally resected. Again, covering the defect using the ReDura, which is the dura substitute that I mentioned earlier. I put one layer on where that defect was and then another layer overlaying it to close the defect on the skull base. And this is post-op MRI showed the complete resection of the lesion. And the patient has growth hormone, has dropped significantly from the day one. Case five, which is the last case that I wanna show you, is 46 years old patients with, coming with ptosis of the left eye with the third, fourth, and sixth grand nerve palsy. And he has an opthalmoplegia on the left eye. Again, the tumor is expanding to the cavernous sinus, invading the lateral wall of the cavernous sinus and encasing the carotid artery. What we really did here, is again extended the nasal approach and we opened the cavernous sinus following the tumor laterally. So what I wanna really show you here is once you resect the tumor and follow it into the cavernous sinus, if the tissue is soft, you really don't need to open lateral to the carotid artery. But sometimes you do need to do that in case of the tumor is thick and a adherent to the carotid artery to avoid injuring it, especially if the tumor is is functioning. So here we opened the dura, we resected the lesion, and we follow the tumor into the cavernous sinus. And we achieved a gross total resection of the tumor. And again, we did our way of closing the dura defect and the skull-based defect. The pitfalls very quickly going through it. Sometimes giant macroadenomas, pituitary macroadenomas is thick and might prevent diaphragma from falling down after decompression. Don't try to pull it down and it might be adherent to the nearby blood vessels and neurological structures. Just leave the capsule, it will come down by itself and disintegrate. And you don't need to expose the patient to risk of vascular injury. Morphology of the tumor can significantly affect the technical difficulty of the resection. If the tumor is really multi compartmental or going laterally into the sylvian fissure, a second stage of transcranial approach might be an option or doing a radiosurgery or just follow the patient closely with a serial follow up. When the anatomy of the sella is distorted, you really, you need to use a navigational ultrasound to avoid injuring the blood vessel and the nearby neurological structures. Generous opening of the dura from one cavernous to another cavernous sinus is essential for pituitary macroadenoma surgery. Do not attempt to do a total resection for multicompartment giant pituitary macroadenoma, especially when they are extending into the Sylvian fissure, as it's beyond your reach, and you might cause an injury if you are trying to curette the tumor blindly or pulling it. Second stage pterional craniotomy might be an option or as I said, adjuvant radiation therapy. Intra cavernous carotid artery might be in direct contact with lateral edge of pituitary macroadenoma, but sometimes it's separated by venous spaces, which would give you an indication that the carotid artery is very close when you start having a profuse bleeding from the venous plexus. Blind tumor resection is dangerous and might lead to perforator avulsion. Inadequate extent of the bone removal and also inadequate dura opening might subtotal resections and that might cause a further complication of the patient by having the tumors having a tumor apoplexy inside the region. The inferior and central portion of the tumor should be debulked first, then followed by the lateral portions. Otherwise the diaphragma sella will descend into your surgical cavity and that will obstruct your field of view. Do not attempt to resect all the tumor if it's encasing or adherent to the neurovascular structure. Residual tumor is okay. You can just follow the patient closely with a serial images and in case it shows growth, you can do radiation therapy. A recovery of visual function from our experience is even if there is an optic atrophy at the time of presentation, they still, patient might recover. Yes, it is a predictive factor for visual functional recovery, but it's not determined. So patient might recover and have some visual improvement afterward. Recovery in the visual function might be evident immediately after the surgery. But in about 50% of the patients takes three to six months to have a significant visual improvement. Our surgical experience over the last five years, since I joined here at Hamad Medical Corporation coming from United States in 2007, there's a steady increase in the number of the cases that we do, or major cases in general. Over the last year we've done more than 1000 cases in our department with a study increase in the number of the giant pituitary macroadenomas. And as you see, 2017 we just had the 16 cases, but right now, on average we are doing 34 to 40 cases per year. So it's almost every two weeks we have a giant pituitary macroadenoma that we operate on. This is coming with the efforts of many people and it's a team that dedicated to patient's care showing the good outcome safety of the patients. We start having patients coming from the neighboring country for us to treat them. And over the years we are having more and more patients coming to us and we're having successful surgery, thankfully. And that's basically by following the basic principle of extended endonasal scallop based approach without having a major complication. I would like to thank you. This work is is not just myself, it's a team of resident, junior faculty, and senior faculty who are all dedicated to treat those patients. Ready for any questions.

- Very well done. Very much enjoyed it, Siraj. I think one of the important facts that you mentioned that is critical is exposing the dura from one cavernous sinus to the other and also exposing the dura over the tuberculum sella because even though you may not open it, it gives you freedom of movement with your instruments to be able to remove the tumor. One of the bigger pitfalls in big residual tumors after surgery is because of inadequate bony removal. And I wanna repeat that again. The number one reason for subtotal resection and a bad looking scan post-op is inadequate bone removal first from one cavernous sinus to the other and second from anterior removal for giant tumors over the tuberculum sella. So I really appreciate what you mentioned there. If the tumor gets super giant, one of the tricks I've used is open the duro under the tuberculum and really just work intradurally and push the diaphragm down and be able to remove the tumor. It works really well. Most of these tumors have already eroded through the diaphragm, so you'll be working intradurally anyways. But I do believe to avoid a transcranial operation and a stage approach, which we have, I don't believe within the past 10 years we have done a transcranial operation for pituitary tumor is the idea of going above the diaphragm, removing the bone over the tuberculum, really having a very expanded view and try to be aggressive to dissect the tumor from the arteries. Do you have any other pearls or thoughts about the comments I just mentioned?

- Actually we'll mention what you're saying, this is a recipe of successful surgeries following the principles, and the principal as you will say, it's wide exposure to the bone, opening the dura and don't do the surgery while you're not seeing the tumor. You have the endoscope, you can advance it, you can see the tumor and you're resect it safely. One thing I really want to mention, and this is from experience that I had here, is not chasing the capsule. And I know some neurosurgeon will disagree about that. But really some of these capsules, especially the patient that we are seeing here, there most of them are expat and they're coming from other countries and they have this tumor for a long time. And it's not like pituitary apoplexy it is a giant pituitary macroadenoma. Those capsules are adherent to the nearby blood vessel and the perforator, if you try really to dissect it and cut it, you might be lucky not to injure the perforators, but you might injure the perforator, injuring the perforator is same as injuring patient you never know this perforator would supplying and what would be the outcome of the patient. So what we did and what we are doing is resecting the tumor, while leaving that capsule devascularized and I showed you a couple of the cases that that capsule would disintegrate and come down with time. I know it's sometimes the capsule might remain, but most of the time it will go away and you will have an excellent post-op images.

- Well said, well said. We really appreciate it. Beautiful lecture, Siraj, great work. Your leadership in your program, really great to hear how successful that program has been. Very proud of it. Look forward to having you with us in the near future and thank you.

- Sure. Thank you very much Aaron. Thank you everybody.

- You're welcome. Thank you.

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