So I think without further ado, Fred, we'll have you come up and start us off. So, Michael, thank you very much, and welcome, all of you. So my talk this afternoon is on the management of recurrent and giant pituitary adenomas. Now, there's a number of controversies in pituitary surgery and pituitary, the topic of pituitaries. Diagnostic controversies. We now have a new WHO classification in 2017. We're not allowed now to use the word adenoma anymore. These are all now neuroendocrine tumors. The issue of predictive factors, the management of atypical, aggressive tumors, the management of cavernous sinus involvement, the role of radiotherapy, the whole issue of indication. Are there any indications of craniotomy? Then what is the best surgical approach to pituitary adenomas, endoscopic and microscope? There's still a little bit of controversy there. Management, of course, my main topic is going to be recurrent tumors and the management of giant tumors. So let me just quickly go through the issue because there's still a little controversy here on the issue of what is the best option. Now, there's a number of options for pituitary tumor. These are all generally transphenoidal is the root, but now you have, of course, the microscopic, sublabial, et cetera, and now we have the pure endonasal endoscopic approach. And transcranial, we still need, unfortunately, although in a minor situation, maybe 3 to 5% still need transcranial procedures for these tumors. Well, you can see the published reports of endoscopic pituitary surgery. This is up to just 2000. Significant growth of the literature with increasing reports. It's become very widely accepted. Some people would even say with unbridled enthusiasm. But, you know, if you look at the reports and, you know, look at the data, the issue is does it really make a difference? What is the advantage of the endoscopic approach? The major advantage is visualization. And, as you know, we are surgeons. We basically, the better we can see, the more we can do. It's simple as that. You get a very nice, excellent, wider illuminated field of view of the cellar, paracellar structures, closer view of the surgical target, better delineation of the tumor and gland surface and microadenomas. And some of the others here, as you see, basically I put question mark because the issue is more minimally invasive. Some people would say, no, this is actually more invasive, at least to paranasal sinuses, than the microsurgical approach. And then the issue of decreased hospital stay, I don't think that really is an issue. Cost effectiveness, we're looking at that. It may not. And better outcomes is question mark. We still don't have hard, hard data on this. This is our setup. And very briefly, we use image guidance in every case. Doppler is very important. And then we use a two-man technique, the driver, we call them. In the endoscopy, usually it's my ENT or my fellow and then the surgeon. So this is the view of an endoscopic approach to the cellar. This is that we brought in the microscope now in a hardy speculum. You can see the difference. It's obvious here. And when you try to then to bring in a drill and your suction, you virtually at least have a very, very wide. Now compare this to the endoscopic approach. Here we are, same patient. Look at the optic carotid recess, the optic nerve prominence, the carotid artery, the plenum, and the clivus. You get an amazing wide angle view. The key to this is no blind dissection. Those of you who have done microscopic approaches 20 or 30 years ago, and I've done many of them, the idea often of blind dissection laterally and so forth. There should be none of that, and there is none of that, in the endoscopic approach. And it allows you to deal with this type of tumor. And here's another one, a rather large tumor going laterally here to the medial wall of cavernous sinus and then superiorly over here. The endoscopic approach allows us to remove a tumor like this very relatively easily. Here's the dissection, the medial wall of the left cavernous sinus. And as we go on, I don't want to bore you with the entire thing. And anteriorly allows us to get this anterior component. And after the procedure, you can see you've got a nice view of the medial wall of cavernous sinus, left, right, anterior. And so you know that you've got a nice radical removal of this tumor. And postoperatively, you can see here, this is what you want to see, a tumor like that. And you want to see, maintain pituitary function if you can. Twelve years, and this patient remains stable. It also allows us extra capsule removal, not only in all cases, depending, but occasionally, if you get the right case, the endoscopic approach, again, because of visualization, you can see here after the exposure, and if you can find that plane. And here we are taking it off. Here's the normal pituitary gland, and we're peeling it off. This is a pseudo-capsule of the pituitary. Pituitaries don't have a true capsule. It's just compressed pituitary. It allows us to get, and when you know that you've removed that, you've got a really nice radical removal. Nine years, no disease recurrence. And then it also allows us the paracellar. I'm not a real keen fan of cavernous sinus, going into cavernous sinus. I think it's a, but occasionally, if the tumor leads you there, I will follow it into the medial wall of cavernous sinus. And you see this tumor, very extensive vision issue, but in the cavernous sinus, and it allows us to remove this, at least in the medial wall of cavernous sinus, and, of course, decompress the optic apparatus. So it does allow you for some more lateral exposure. So the conclusion is we feel, and I've gone through, that really the endoscopic approach is really the approach of choice, the advantage that I just told you. But the question remains, and people talk about it, what about efficacy? So it looks all good, but what about outcomes? And this is, what is the data? This is our series, the first series, I think, of endoscopic pituitary, back in 2008 now, almost 10 years ago, 200 cases. You can see the gross removal rate's very high, 98% in those that were enclosed. Even with the supracellular extension, as long as there was no cavernous sinus invasion, we got, again, very relatively high gross removal rates. Cavernous sinus involvement, no patient that I feel like got a gross removal. However, obviously, we helped the patient decompress his optic apparatus, et cetera. And then when we looked at our series and the weighted average of the microscopic series, we were at least equal. In many cases, we felt we had better results. But, of course, look down here. Medium follow-up is very important in the pituitary, so you have to always keep that in consideration. So the issue now is, and I've presented this in a number of meetings, is endoscopic surgery has become the standard of care in 2019? Well, we've got to look at the definition of standard of care. And it's interesting, if you look in the literature, there's really no medical definition of standard of care. It's really based firmly in law and has medical legal implication. So if something is not done to the standard of care, you can be sued. And so if you look at the standard of practice in your surgery, it provides a framework and describes knowledge, technique, and skills that guide the daily practice of the majority of neurosurgeons based on best outcomes and results. So what can we say? And if you look in North America at least, 95%, at least in North American skull base society, are doing endoscopic surgery. But if you go to Europe, and I've gone to Europe, and still a third or so neurosurgeons do the microsurgical report. So what can we say? Has it become the standard of care? I'm not sure. We can say that from medical legal. But there's no question for the young neurosurgeons who are interested in pituitary surgery that it will become the standard of care, and you have to know the endoscopic approach. So these recurrent controversies, let's look at the management recurrent. Now, this is a patient I operated on in 2090, presenting with visual complaints, primary macrodermatosis, microsurgical approach, 27 years, no evidence of recurrence. We all would love to have all of our patients do this. Unfortunately, that's not the case. Here's another patient of mine, 1993, diagonal pituitary tumor, microscopic transphenoidal, gonadotropia recurrent in six years, repeat microscopic transphenoidal, then 10 years. This is the interesting thing about these tumors. You have to follow them because they can recur and delay recurrence. So then we did an endoscopic approach, 2007. Then went on, slow growth. Asymptomatic, conservatively, but then, 2014, further growth, a repeat endoscopic approach. Improvement in vision, et cetera. Now, small increase in the cavernous sinus. What now? Well, I'll tell you later. So recurrent adenomas are unfortunately common, and you see the incidence, time of recurrence can be very delayed, and this is why you have to follow these patients. They are difficult management problems, and there's really, if you look, there's no consensus on the optimal management of these. You know, what do you do? How many times should you operate before then you say, okay, surgery is not the answer, let's go to radiation? And there really isn't that, but I think everybody would agree that the management often requires a multidisciplinary approach. And if you look at the recurrence rates, this is under the microsurgical era, and if you follow them long enough, nonfunctioning up to 25% or higher, growth hormone, acromegaly, and our endocrinologists tell us about this. You follow these patients for 20 years and up to 80% will lose their remission. What are the factors? Of course, incomplete tumor resection is obviously, but other issues come into play. The biology of the tumor, some of these are more aggressive, the silent corticotropes adenoma. Of course, the experience of the surgeon is critical, and duration of follow-up. The options for recurrent are the same, basically, as they are for the primary. So here's a patient, that 51-year-old male, had persistent cushings after a previous microsurgical approach. And here, this was the original exposure. This is now our exposure with the endoscope. And then you can see here now, that was not the tumor, by the way, that I'm taking out. This is the tumor. Look at that beautiful little adenoma that Jules Hardy was the first to talk about that. It allows us to remove this adenoma nicely. Here's the medial wall of cavernous sinus that we can take it off nice and cleanly. And again, just very quickly, here we are after the removal of this adenoma. And then look inside here, the medial wall of cavernous sinus. You can actually see the carotid artery looking through. And so you know you've got a nice radical removal of this patient. And she postoperatively urinary free cortisol for normal. She remains in remission 11 years. Here's a patient, again, microsurgical approach. Here's a sort of conchal, really a type 3 cella. Very difficult to get at. They had obviously persistent. So we basically you have to do a transclival approach, upper transclival approach, that the endoscopic allows us to do that, drilling off the clivus. Then, you know, you can get a nice exposure. And this is after the removal. And this patient, again, postoperative remission. What about this patient? Transfenoidal microscopy in 2017. Look at the problem. Kissing carotids, true kissing carotids. How do you deal with that? So we basically, with the endoscopic approach, it gives you, again, because of the visualization. And again, I'm going to go very quickly here. See the previous exposure. And here's now our exposure that we can do a much wider exposure. And I just want to go back to show you here. This is where the carotids are. This is the carotid. This is the carotid with Doppler. So you basically go above the carotids to allow us to get into that tumor. And we were able to decompress her. The patient was really vision. This patient, you can see, we did not get a total removal. Decompresses. And now we're following this patient. This is a 66-year-old patient. Was lost to follow-up. I did an endoscopic approach. Then she, for 10 years, now returned with this large recurrence. And even, you can see, with a recurrence, we can go in. And then we are taking a nasal septal flap that allows us, if there's any issue with CSF leak, and allows us to go and do a nice, again, radical removal in this patient, and then the repair. This is this patient you can see here, three weeks, so it's just three weeks postoperatively. So we've done about 1,800 endoscopic pituitary adenomas. The question is, has it really improved our ability to deal in terms of outcome? Because again, we can look at outcomes. This is, again, published back in 2012, almost seven years ago, 39 patients. You can see the demographics here. If you look down here, 43% had frank cavernous sinus invasion. So it's a problem already. That's why they obviously recurred. And what we found, basically, the problem was exposure. That in the previous one, there was three-quarters of them, really, the sphenoidotomy was not adequate. And in two-thirds, the cellar opening was not adequate. And our results, as you see, overall growth was 54%, which doesn't look all that high. But in fact, for recurrent tumors, that is quite reasonable. 66% in the non-functioning. As long there was no cavernous sinus invasion, the functioning is, again, 75% in the Cushing's and 44% in the growth hormone. So overall, the reports, the results of the endoscopic are, I believe, as good or superior to the microsurgical approach. And then I can go in the literature. There's another one, 30 patients similar to us, but with 50%. This is from Cavallo's group in Naples, important of, again, about 62% overall. So back to that case that I showed you. So this patient is two microscopic, two endoscopic. What do you do now? Well, I think it's time that surgery is not the answer here. So we sent this patient for radiation therapy. This patient, two years and almost three years with stable disease. So there's no question that the radiation has a role to play in recurrent pituitary adenomas. And the issue of which type, I think, as we'll see, there's not really a major issue depending on if it's feasible to use gamma knife, but not always, because it's sometimes too close to the optic nerve, would usually need at least a millimeter, millimeter and a half. But conventional radiation is also good. And if you look in the literature, in fact, there's, the results show good control rates at five years, 86%. And then for the functioning adenomas, you can see here, 40 or 50%. And again, this is by Loeffler looking at the radiation therapy. And again, high success in controlling tumor growth, up to 90% in most series. And then medical therapy, unfortunately, I don't have time to go into this, but this is very important. You have to have very good endocrinology that we work with. And sometimes a combination of the, are now being used even for non-functioning adenomas. They can use dopamine agonist combination with, even for the non-functioning adenomas. Okay, the management of giant. Giant adenomas, like recurrent, are a real problem. The incidence is about 5 to 14%. These have increased incidence of endocrine dysfunction. Their capacity for aggressive growth, they are surgically challenging. The growth tumor rates are usually less than 50%. Some would say even less, about 30%. And the optimal management, again, is not clearly defined. This is our series that we presented back, again, in 2014, in our patients. We looked at the definition. Sometimes in the literature, it's a little unclear. Generally, greater than three centimeters is large, considered large. Greater than four is considered giant. We used a volume-based, which we felt was a little bit more accurate in terms, as opposed to a diameter-based. So, we used 10 centimeters or greater, defined as large or giant. This is the clinical parameters we did. And what we looked at was outcome of resection and the predictors of outcome of resection, shown here. So, we had 73 patients, 12%, usually the same as the series. Here's the demographics. I don't have time to go through this. But just here, about 20% had already prior surgery or radiation. The presentation, of course, the majority of them were vision here. The treatment for giant are the same, basically. Options are the same as for recurrent. So, here's a patient with a giant adenoma. If this thing is going to play. Here we go. There's a tumor, you know, giant adenoma. We consider this. And what we do, I'm not going to show you. But in these cases, we will do a middle turbinectomy. I actually, most of the time, do a routine middle turbinectomy for exposure. But in the giant, I generally do. And in all the giants, we take a nasoceptal flap. These giants have a higher rate of CSF leak. And the nasoceptal flap really gives you that assurance to prevent that. And then, basically, the bimanual technique was your septectomy. And then, the nice exposure that you can get here. And then, here we are taking it out, like I showed you sort of before. And again, I won't bore you with the video. And the key was you want to be able to ultimately get the lateral medial wall of cavernous sinus and anteriorly. And here we are. And what you want to see is this diaphragm come down. And you know you've got a nice radical removal of that tumor. This is repaired with braces and the nasoceptal flap. It just covers that very nicely. This is another patient, 58-year-old patient, bitemperal amyotropia. Here's another lesion, large lesion, superior lesion. This is good for an endoscopic approach. And again, I'm not going to bore you here. Was that the same? Was that the same one? There we are. No. So, this patient, as you can see here, postoperatively, one year, nice removal. This 70, 40-year-old patient, again, just showing the ability to get a nice radical removal in these large, large tumors. And again, there we are taking it off. And that's after the removal. This patient is six months. Now, these are complex pituitary tumors that probably previously might have done a craniotomy. Because this anterior, the endoscopic approach, at least the transmineral approach would allow for this, but not this. Now, with our ability to do extended approaches, what we use sometimes for craniopharyngiomas and small meningiomas that I do, so allows us to deal with these tumors here. What we do is a trans-tubercular transplant approach that allows us to get anterior here. And as you can see, again, as I come quickly over, this is the component in the cell, which is easy to remove. But it was the other component that has not come down. And this is where we do a transplant or trans-tubercular approach that allows us to quickly go over the tumor, as you can see here, and bring it down. And at the end, we know we've got a nice removal because we've gone above it. Here's the optic chiasm, and shown here with a pituitary stalk, which of course did not work. So this patient is 11 years postoperatively. Here's a 34-year-old patient, large adenoma, multiple, as you can see here. Initially, it was prolactinoma. We knew that this was not a prolactinoma with a lesion that size. Prolactin should be in the thousands. It was treated with dopamine agonist. But after six months, no change. What do you do now? What is the best approach in this patient? Well, again, this for us, we would do now an expanded endoscopic approach. You can see here. But because of this, and over here, look at the significant residual in the cavernous sinus and going posteriorly. What do you do now? Do you go above? Do you go above? Some people might consider a craniotomy. Our issue that we are, we use fractionated radiation, 50 gray, a stereotactic three-year stable disease. So this is our series. The gross removal rates was 24%, near total of 16, so about 41% total removal. Yeah, the interesting thing was the predictors of the extent of resection. Of course, size is very important. Hemorrhagic component, invasion, of course, was all predictors. I was surprised a little bit of the non-significant parameters, including prior surgery or prior radiation. I thought that surely that would be, but it wasn't in our case. And interesting, also tumor biological characters, MIBs and so forth, which again we thought would be a predictor, were not. The post-operative visual, we're pleased with that. As you can see, three patients, however, were worse. Complications shown here, CSF leak rate was still 10% despite our, you know, use of nasal septal flap. So that still remains a concern. This is a patient that, our complication, a major complication. This did not, it was after our publication, so it wasn't included in that. Sixty-one years of age, look at this tumor, posteriorly, what is the best approach of this? You know, some people say, well, you should do, you know, maybe a combined approach to this and then this, do it all from below. We did a craniotomy, at least a transphenol approach. Post-operative, you see blood, patient was hemiplegic, and his vision was worse. Virtually finger counting. And look at what happened, obviously, a perforator, thalamic perforator. This patient has remained basically with finger counting, no improvement, one year later. And we're basically at this stage following that. There are limitations of transphenol approach, large invasive adenoma lateral, significant lateral extension, the middle fossa, multiple compartments, and vascular encasement. So this is a patient that I operated on, if you look here, a very long time ago. Blind in one eye, what approach? Well, this is not a good approach for an endoscopic approach. You're not going to go out there. And it's dangerous, as you can see here, the vessel. So this patient, I did a craniotomy, a bifrontal endomyspheric. Here's the tumor, and here's after the removal. You can get a nice removal. This patient did not change in his blind eye, of course, but improved in his right eye. Full replacement, and this patient, I think, is about 10 or 12 years out. So let's look at the results. I don't know how much time I have, Mike, but I'm just going to finish off. This is from the endoscopic approach, as you can see here. This is from the PISPR group, showing, again, resection, a near total of 36%, which is realistic. It's very difficult in these giant adenomas. Here's the factors limiting. Again, as we found, basic lateral extension, complex multilobular shape, and the complications that you can see here, very high for new pituitary dysfunction. This is a systemic review that tried to look at endoscopic versus open, but as you appreciate, these systemic reviews are sometimes comparing apples and oranges, and you have to be very careful when you're talking about any case. The endoscopic here, it came out higher. It's 47 versus 9, but as I said, very careful with these. So what is the conclusion, basically? First of all, when you have a conclusion, you'd like, in our era of evidence-based medicine, to have some evidence, and if you look in terms of giant adenomas, unfortunately, all the evidence we have, the best evidence is C and D. There's nothing, you know, so we have to make it under those auspices. So what can we say? Well, that the endoscopic approach can obtain an extent of resection equal or higher than cranial approaches for giant adenomas. I believe that it's safer and more effective in alleviating the symptoms, particularly the neurovascular symptoms. However, transcranial approaches are favored for tumors extending significantly laterally, and radiation therapy has a definite role to play in controlling residual disease for recurrences. So final conclusions, recurrent enlarged pituitary adenoma remain a significant surgical challenge regardless of the approach or technique. The pure endoscopic approach, as I said, can provide, I think, an equivalent, at least in my mind, better outcomes than the standard approaches. However, recurrent and giant pituitary adenoma require a multimodality approach with adjuvant radiation and or medical therapy to affect long-term control. So you really need a very good endocrine team of surgeons, medical therapy, and radiotherapies to deal with these very challenging lesions. Thank you very much for your attention. Thank you.

pituitary adenomas

neuroendocrine tumors

surgical approach

endoscopic approach

recurrent tumors

multimodal approach