January 25, 2021
- Dear colleagues and friends. Thank you for joining us for another session of the virtual operating room. Our guest today is Dr. Robert Spetzler from the Barrow Neurological Institute. He has been our most anticipated speaker. In addition, his sessions are all very much and very well attended, and that's obviously not as a surprised by any means. His expertise in microsurgery is second to none. So I'm so honored today Dr. Robert Spetzler to have you with us to talk about intramedullary spinal cord tumors, please go ahead.
- It's a pleasure to join again the Virtual OR. A big hello to all my colleagues and friends. My topic today is really management of intramedullary spinal cord tumors. This is a set of tumors that is really fairly infrequent. Intramedullary spinal cord tumors are between five to 10% of all spinal tumors and extradural spinal tumors are most common. The next ones are intradural, extramedullary and the least frequent are really the topic of today, which are the intramedullary tumors. The annual incidence is 13 per 100,000. For the intramedullary spinal cord tumors, really there is still a significant controversy as to what is the best treatment. External beam radiation, biopsy, is it subtotal resection, or is it complete resection where possible? And obviously the question will always be morbidity versus disease-free survival. Curing somebody of a benign intramedullary tumor, but leaving them a para or quadriplegic is not an acceptable outcome. And so the question really is, does the extent of resection impact a prognosis? Before we address these questions, we really have to define our tumors. And so what I've done is I've defined, I've categorized them into well-defined and diffuse. Ependymoma is the most common intramedullary tumor outside of cavernous malformations. Low-grade astrocytomas, cavernous malformations. And you might ask why I include cavernous malformations, because I think cavernous malformations and hemangioblastomas really are very, very similar in the sense that hemangioblastomas have three cell lines that make up the tumor and cavernous malformation only have cell line, which is the endothelial line but they both occur equally sporadically as well as familiarly. And then you have the intramedullary metastatic lesion, very uncommon and very rare lesions like dermoid and gangliogliomas. In the diffused category, the malignant astrocytoma is the most common. And then there's the much less common sarcoid or lymphoma. There are 285 lesions that we will be discussing and upon whose numbers my recommendations are made. So we had 116 spinal cord cavernous malformations, which is a topic that I will address only briefly in the sense of how we treat them and get to them as they are really a group that follows with the other cavernous malformation, a topic all its own. The most important category remained the 148 ependymomas and the 39 conus filum myxopapillary ependymomas. Then there are the astrocytomas, the hemangioblastomas, the gangliogliomas and metastatic or other lesions. Intramedullary ependymomas in our series ranged from 15 to 78 years with an average of 45 years with a male to female preponderance. They occurred roughly the same throughout the spinal cord, but considering how short the cervical cord is, it has a preponderance of lesions. How do they present? Well, first of all, they have symptoms for a relatively long period of time with an average of 31 months. In this cohort, the most common being pain, and parasthesias followed by weakness, followed by numbness and then bowel and bladder symptoms, but still each one of these insignificant numbers. How did we treat them? Well, we were able to achieve a gross total resection in 80% of our patients. 20% had a subtotal resection, seven had a subtotal resection with x-ray therapy and two of them with chemo at an outside hospital followed by gross total resection at the BNI. Four were treated initially at the BNI with subtotal resection or biopsy. Two with followed with radiation, and one then received a gross total resection a year and a half later. And this is really all a reflection of the comfort of operating within the spinal cord and the tolerance of the spinal cord as to aggress with the aggressive resection. Obviously follow-up has to be a long-term. And this was over three years, with 13 over five years and six over 10 years. And with the McCormick grading system from one to four. One being the best and four being wheel bore, a wheelchair dependent. So when we look at this data, we're gonna look subtotal and we're going to look at gross total resection. So if you look at presentation, if you start to look at one and two, you have 10 patients who presented with Grade I and II. And when you look at outcome, seven were in Grade III or IV, when only one was in Grade I to start off with that presentation. When you look at gross total resection, you had basically 41 that presented with Grade I and II and only six patients that were Grade IV and II at the follow-up, but two and one already presented that way. So that only three progressed during the follow-up period. And so this becomes very important because when you look at these numbers, there's absolutely no doubt that gross total resection clearly picked because you could pick them do that. But the gross total resection did much, much better long-term than subtotal resection, a point that can't be overemphasized. When we look at the fascinating myxopapillary ependymomas, these are fascinating lesions because when I test in rounds, I always say, "What tumor can present with hydrocephalus "or a subarachnoid hemorrhage or symptoms in the legs, "bladder, et cetera?" And that is naturally the myxopapillary ependymoma. It can create a protein level that gives you hydrocephalus. They can bleed to give you a subarachnoid hemorrhage and not have any lower extremity symptoms at the time. So these are truly fascinating lesions. They range in age as depicted here with an average age of just less than 50. Male to female ratio, more common among females. And the unusual presentation as I mentioned already can include subarachnoid hemorrhage or hydrocephalus. And they are slow growing tumors. And therefore their a long duration of symptoms is very common with an average year of more than two years. Interestingly enough, almost all of them presented with pain as the primary initial symptom. But weakness, bowel and bladder and numbness obviously occur as the tumor gets larger. Gross, total resection was able to be achieved in 20 of the patients. One receive the radiation therapy afterwards. Subtotal resection, and five patients all received radiation afterwards. Two had had treatment prior coming to the BNI and the follow-up was not quite two years. When you looked at post-operative outcome, the immediately, there were five patients that were worse out of the 25. 20 of them were unchanged. For long-term too were better than their initial presentation. 20 were unchanged and three remained worse. So for that group of patients, again, I think we can be confident that the surgery is of significant benefit. How do we treat these lesions? Well, microsurgical technique is obviously the critical component using SSEPs and MEPs. Knowing your anatomy particularly the vascular blood supply as depicted in this little cartoon is critical and ultrasonic aspirator, and a laser have their use in certain selected cases. So what are the approaches that we utilized? There is the midline approach, which is clearly the workhorse. We have the dorsal nerve root entry zone, which is depicted here. We have the approach between the nerve roots, right along the dentate ligament, which is depicted here. And then finally we have the far lateral anterior to the dentate ligament, which is depicted here. We don't have an anterior approach because when you think about the blood supply that I have depicted in that cartoon, you have the circumflex vessels, which you can't interrupt without serious neurological . So if we look at these approaches, we have one, two, three, four, all of them getting us to the various areas of interest within the spinal cord. So let's look at a classic little cavernous malformation that you sitting right here in the midline. These are lesions that are associated with veins and here it is resected and this is what it looks like. You can see the veins being proagulated, opening the arachnoid peel membranes, and then going around the lesion with sharp dissection, making certain that you get everything. The secret of cavernous malformation is to spend a lot of time when you're all done going around the bed of the ABM and removing every little white fiber. Because when the blood is evacuated out of the little lesions, they can just be little white remnants that are collapsed capillary lesions which we want to remove to limit the risk of recurrence. Next. And here you see the post-op, no that's the, I showed that previously, but here is another lesion in a gentleman, which is now not directly in the midline, but off to the midline. And when you look at this here you can see why the dorsal nerve root entry zone is really the most reasonable. So here we are, we're cutting the dentate ligament. Here are the dorsal nerve roots, And now we're going just lateral to the dorsal nerve root, which is again, right here. We get to the lesion and then with fine sharp instruments, we remove it. And then these essential nonstick bipolars to get complete hemostasis. And then finally one that is even farther lateral. You can see how anterior to this here. And this is a businessmen. So here we're going to go lateral. You can see where the dentate ligament is right here. So we just ladder to the dentate ligament just right next to it, between the nerve roots, you have the dorsal nerve root here, and the ventral nerve root would be lowered. And then again, we remove the lesion and you can see by the different consistencies that these are different ages of hemorrhage. And then we see the post-op right here and the neuro exam was completely intact. And then finally, if it really anterior high up in the cervical cord, this is a young woman from England. She's actually an editor of the London Times. And you could see the lesions very anterior. In which case, what do we wanna do is to go completely anterior. So we cut the dentate ligament, which is this here, and now we're in front of the nerve roots. And this is the cervical medullary junction. And separating this lesion out of its bed. And you can see the different colors, the fluorescent orange, all depicting different times of when the lesion hemorrhaged. So I've really shown you an example of each one of these approaches. So what have you learned about cavernous malformations very briefly is really when they're accessible, they are resectable and they can be absolutely huge like this one in a ten-year-old that was severely incapacitated by this lesion. And remarkably is even though there's no visible spinal cord, the patient still had continuous although very impaired function, which was unchanged by removing this lesion. It's a pity that it was allowed to get this large. But so the point is when they're accessible, they are resectable with the appropriate approach, and we've published all this in journal of neurosurgery. So let's get to the actual intramedullary ependymomas, this is a classic picture of a lesion. What do we wanna do is we wanna go utilize the midline raphe approach. I will frequently spend a lot of time moving a large central vein, separating it from its arachnoid attention, so that I can have access of the midline raphe without sacrificing the vein. And you can see how you wanna extend the opening of the spinal cord beyond the inferior and superior edge of the lesion, since you don't wanna retract to the point where you can hurt something, you can very nicely see the top of the lesion, and you can see the bottom, which I just showed you here. And then we go along the side, separating it from its minor attachments. The majority of the blood supply comes from anterior, from the anterior spinal artery. So we wanna lift it up and bipolar each one of these little vascular pedicles. At one point in time, I did close the pia with panel sutures, but I really don't think that that makes any sense and have abandoned that after that. And so here you see the post-op MRI scan, the top, the bottom, the edge, and there was no change in the neurological function. They can be associated naturally with significant syrinx and here you can see the various components of taking out the tumor. Again, very similar to what we did before, elevating it out of its bed. You can see that this tumor is also partially hemorrhagic, and then you can see the post-op where the syrinxs have shrunk basically to nothing. This is a patient as an example of the recurrent ependymoma. This was first operated by a chairman at the University of Michigan. One of my old professors had ran the lesion, which was subtotally resected recurred. He referred the patient to me, and this is what it looked like. You could see the evidence of the previous surgery, the classic and enhancement of an ependymoma. So they did a beautiful job at surgery because could see how clean it is. Even though we're reopening the old incision, the spinal cord is not tethered, and the dura was able to be freed effectively. Now reopening their old incision become down to the classic appearance of the ependymoma syrinx. And you notice in the syrinx the old hemosiderin, the yellow. And despite the previous surgery, we're really able to get a good border of tumor from spinal cord. And that's really what we need in order to gain complete resection and the fine border between tumor and spinal cord. And here it is out. You can see how there's just this thin membrane to the front of the spinal cord. And he didn't turn a hair. And he said, no recurrence with a long follow-up. And then finally with spine ependymomas, you can also have an exophytic component. And so this one is a 44-year-old female long-standing progressive symptoms, and then clumsiness of the left arm. And this is what it looked like. You can see here on the cross section, the tumor right here, and you can see the extent of the tumor, the length of the tumor here. So here we are lateral, and now we're using a little CO2 laser to separate the tumor from the edge of the spinal cord. You can see the nerve roots draped over the tumor. And so I'm working between the nerve roots and I'm using the laser both as a cutting tool and a dissector. And then just like with the intramedullary one, you wanna get to a nice border and then try to obtain a gross total resection. And here's the post-op. You can see the tumor completely removed. Intramedullary astrocytomas, they're really come in two kinds like this one with an exophytic component. You can see the extent the x-rays of the tumor, but you can also see a sharp edge of the tumor so that you can resect this with favorable astrocytomas. And here is somebody that is very dear to me, she's an elderly lady patient. When I saw her and she had trouble walking and an age of the 69, she had a diffuse astrocytoma. And because of her symptoms, when we explored it, it was clear that resection would result in a very unacceptable result, we did a duroplasty. We gave her a lot of room and look at this. Between this interval, she is still walking with a cane and she was 92 years old. And every year, she was an entertainer. She insisted that Dr. Shapiro, my neurology colleague at the time and I would join her for dinner. But again, decision, it really comes down to decision-making. Here's a case of a tumor with this appearance on MRI scan. Surgery was uneventful with very sharp edges, as you can see. Completely clean cavity. And the question is, what is the diagnosis? Well, I was hoping that it was an ependymoma, but if you look up here at this MRI scan, those are very concerning enhancement pattern. And naturally what this turned out was to be a GBM and that patients succumb to this disease within a year. How about this? This is a patient with significant symptoms, and you have at least two lesions that we can discern. You can see a significant adenomatous response on the MRI scan. So what is the diagnosis here? Made easier by the fact that she has an lesion in her temporal lobe and a history of breast cancer. And this was a rare intramedullary metastases. What about this here? This is a patient with progressive symptoms. You see a diffused enhancement, mild enhancement of the spinal cord and the nephew of a colleague and friend. As we look at these, it's hard to be definitive, but this was sarcoid. And actually this gentleman after we discovered this diagnosis ended up doing well. A patient with progressive symptoms had a carpal tunnel decompression and an MRI scan, which demonstrated this lesion with enhancement was operated on. And you can almost see the sarcoid exploding. As we open the arachnoid membrane, we separate it, and it's a very, very bloody tumor. It was able to be completely removed. And I suspect that most of you are thinking that this is probably a melanoma. This is what the histology looks like. This is what the post-op looked like. Patient did very well, but the diagnosis was a melanocytoma. Melanocytoma which is a benign tumor, it's found throughout the CNS's axis that the intrinsic melanocytes and a nice review in 2004 by Turhan. And the advice is gross total resection, which was very straightforward. And the unusual presentation. This is a patient with subarachnoid hemorrhage and neck pain. You can see the subarachnoid blood here. You can see pooling of blood at the cervical medullary junction. An angiogram was performed on the suspicion of an aneurysm, especially down in the posterior fossa. Andrew grandma's completely negative, including vertebral arteries injections to rule out the cervical ABM. But an MRI scan with and without contrast demonstrated a enhancing lesion that you can see here. And the abnormality and this you can see on the-- video, you can see all the hemorrhage that was present along the nerve roots. And then this was a classic ependymoma that had eroded through front and presented with a subarachnoid hemorrhage. And his was removed and this was well tolerated. Next. So now we get down to the myxopapillary ependymomas and you can see just a classic appearance of a mix of myxopapillary ependymoma right down the coldness and down below. And you can see in between the nerve roots, the diffuseness of it all. And here at surgery, you can see the tumor sneaking out through the arachnoid. Video. Yeah. And so just opening, you can see the nerve roots, there are separate blood supply. So it's really key to separate this sharply from the nerve roots. And from the colonus in order to get a complete resection, very tedious, time well spent. Four hands are sort of nice when you have a good fellow resident or a colleague so that you can gently irrigate at all times and separate the tumor from the nerve roots. I'm cutting the file on both ends and taking out the tumor. You can see, you can get really complete resection while preserving all the nerve roots and just inspecting the cavity. And then the pulse stop lesion gone. They're not all as clear cut as the last one. Here is another example of one, and this is the sticky variety. You can see the lesion. It looks like it really shouldn't be easy to resect. And here we're opening between the nerve roots and there's the tumor. And this one is just a lot stickier. Again, you wanna use sharp reduction, I mean, sharp dissection. Some sections are very straight forward. Others like here are much more difficult, but you wanna preserve all the nerve roots. When the bulk of the tumor gets in your way, then obviously ultrasonic removal of the bulk of the tumor will aid in your visualization to allow you to remove the rest of the tumor, but you can see how it's attached to the nerve roots, but we wanna spend all the time that's required to preserve every nerve root while still getting rid of the tumor right at the edge. I'm using the basket of forceps because they grip those tiny little fragments much easier. And then again, spending time with the non-stick bipolars and making sure that we've gotten as gross total resection as at all possible. And here you can see the bed afterwards and the tumor gone. So some of these are rather complex, and this is a relatively young man who has been biopsied elsewhere, and a diagnosis of glioma was established and he was scheduled for radiation. He then saw me for a second opinion. This is what his scan looked like, probably from the disease that he had inside a spinal cord. He also had a spinal deformity. This is where they operated on to get the biopsy. And I requested a MRI scan with and without, and this is what we saw. Previous surgery, obviously very, very abnormal spinal cord with multiple cysts or syrinxes. But with contrast, we saw this, and this is why it's so important to really completely review a scan because that is not diffuse appearance of an astrocytoma. So what is the diagnosis of this enhansion of lesions? Well, we took him to surgery and it becomes immediately obvious when you look at this because you see big blood vessels and that classic color. You see all the cyst formation and what causes cyst formation and has that orange beautiful color? Well, it's the hemagioblastoma, and it's only this little lesion that was responsible for everything that we saw here, all these cysts. Nothing else was done, this was removed. And when we see the post-op and then my spinal colleague came in and performed this instrumentation, but the tumor is gone. And when we look at it pre-op, and then we look at it post-op one month, you can see all these cysyts all the way down to here have contracted remarkably and his neurological exam actually improved. And he ended up walking independently. So hemangioblastomas is a fascinating lesions because they can be familial or sporadic. I've had one patient who I've operated on 11 times in the spinal cord for her lesions. This is a 27-year-old minimal myelopathy and had this lesion. This was an old angiogram that was done. And this is why they were sometimes confused with ABMS. They're brightly enhancing lesions, and they have to be treated like ABMS because they are so vascular. And if you get into it, then the problem is that it's very hard to visualize what is going on. So here we're taking it out. You can see this was through a transfer vasectomy. My colleague, Dr. Dickman did the exposure for me, and then we're working underneath the spinal cord to remove this lesion. We wanna get to the vascular pedicles. And it's actually nice to use ICG with this as well, because you can see where the apedicle is. That's maybe down below, not so much in these lesions that are so well-defined, but if you're dealing, for example, with a giant hemangioblastoma in the cerebellum or in front of the brainstem, then ICG can be helpful. But here we're looking anterior to the spinal cord, separating the lesion from the anterior spinal artery, and then just rolling it out. And whenever we see a pedicle that has some blood supply, we get and here's the very last pedicle bi-polar and cut and the lesion is out and this young man did beautifully. More difficult are lesions like this here. This is actually one I was called into to help a colleague who got into a little bit of trouble or who when he saw this, he thought he was dealing with a hemangioblastoma, but obviously that was not the case. And here, when we came in, we looked at this and at the typical appearance of hemangioblastoma and all these vessels. So the key with this surgery is to define the plane and keep going and try not to make the tumor angry so that it's swells a lot. So we can get to this interface right here between tumor and spinal cord. And then I like these spencer dissectors, they're sort of round, but very sharp. So they can be used to retract as well as remove the tumor. And here it is completely out. Here's the lesion and the post-op. Very similar. You see classic appearance of the hemangioblastoma, it's virtually diagnostic. And then naturally this very, very sharply enhancing mass that looks like it really take up the entire spinal cord. And this patient was still very, very functional. So here we are, looks like an ABM. Here's an ICG and you can see the epidity of the minas filling just like a spinal AVM, utilizing ultrasound to see if we can find an edge and then just carefully and gently identifying and separating the edge of this lesion from the spinal cord. Once we have that plane, we then just meticulously go around the lesion, separating spinal cord from the tumor. You can imagine this, if you make this tumor angry, you're gonna have a much bigger problem getting down to the bottom where we need to go. And now the interface between the anterior portion of the spinal cord and the tumor bi-polar cut. Everywhere you see those cysts that are associated with these fascinating tumors. And finally out with beautiful preservation of the spinal cord. This has been vivo testing, and this is in vivo confocal microscope, and this is actually live tissue. You can see the flow and the spectacular pattern of these vessels within. And this is what the histology looks like as we all know. And here's the post-op. And you can see already the resolution of the cysts, even so far away from the actual tumor, which was sitting right here. So what have we learned? Well, here's a gentleman who ended up becoming a very good friend who has this lesion, Triple A Personality runs his own company, is a national water skiing competitor and actually makes the skis that are the most commonly used for this. His name is Mr. Goode. And this is done with this permission. So he is minimally but progressively symptomatic, and he wants to know what to do. He went around the country and finally made the decision to have surgery so here he is. Minimally symptomatic opening the midline raphe, getting down to the tumor and then carefully resecting the tumor through this small incision. And it's always using the sucker which has a teardrop opening in it so that when your finger is off of it, there's absolutely no suction going through it. You can use that as a channel retractor, as well as a section and it's malleable so that you can fix it. So it has the best angle for your approach. And here, the lesion is out. In the cervical area, that's what it looked like after it was out. And with permission, two years post-op, he got another first place in the national water skiing championship, and he feels his performance and physical performance is better than ever. So what do you do when you have somebody who is a pianist, has NF-2 and presents with this lesion? In NF-2 naturally ependymomas are more common. Because of what we have learned, we offer the gentlemen surgery, you can see the expanded cervical cord. So I include this. You can see this going right down the median raphe, median raphe is right here. So we've cut this one branch, and now we've moved the vein from the median raphe so that we could maintain its launch intuitional integrity. So just taking off the branches and preserving it's continuity. So moving the vein way off the midline, which is where we're making our incision. And then getting down to the tumor, using every trick that we have learned separating the spinal cord, and just gently, gently, little bit of retraction each time, a little bit further with every step, always counter pressure. When the tumor is too big, debug it, but this separation here it's just so critical to see the normal spinal cord really until it is completely gone. So what have we learned? I think complete resection of intramedullary, ependymomas hemangioblastomas and cavernous malformations improves neurological outcome and prolongs disease-free survival. Myxopapillary ependymomas should be resected when possible with minimal risk to the nerve roots. Radiation for subtotal resection remains a viable option. And astrocytomas and other rare lesions may benefit from total resection or subtotal resection. Our whole goal is really to further neurologic intactness, avoid complications and keep our patients walking for as long as possible. Thank you and best wishes.
- Great videos, just amazing outcomes, pushing the boundaries and making miracles for patients, something you have done all your career, Dr. Spetzler. You have really made all of us to be better. Many generations of neurosurgeons have followed you, including myself, and you have truly made all of us better. You have made neurosurgery better. I have a few questions for you. Number one is, which I'm sure it's gonna ask frequently is the use of monitoring? As you know, these are intramedullary tumors, the monitoring may change, and you have to be very judicious in terms of responding to the changes and not necessarily abandoning the procedure. Would you please comment on that?
- Yeah. I consider monitoring a feedback system, just like monitoring your heartbeat and respiration. It doesn't mean you're not going to continue the surgery. For me, it creates a pause. I look at the surgical exposure, see if by chance there is a party or something that may be squeezing on something or something else that's wrong. Check with the anesthesiologist, whether the blood pressure is okay, were there any other symptoms. And if I do not see any cause for the change, most commonly obviously with the motor evoked potentials, then I will continue the surgery if I'm at a point where I think that's judicious. I think what is the most important for a surgeon is to gain the maturity, to say, I don't know whether I'm gonna be doing harm or not, and back out and come back again. And I tell each and every patient that I never apologize if I have to come back and do another operation, but I will very much apologize if I hurt the patient. So by having them prepared that you may come back for a second operation, it really has never been a significant issue, a disappointment, but never an issue. But with a spinal cord tumor, if I don't see anything else that's going on, I will continue the resection.
- Right, that is such an important point to emphasize that if you have done everything, you know, remove the retraction, bumped up the blood pressure, irrigated, relieved all the physical details that you think are affecting the potential or revoke potentials and you should still continue unless God forbid you have completely lost the potentials, which I think is a different situation. So I think it's just, as we have said before for a spinal cord AVMs or carvenomas, is that it's only piece of the puzzle and not the entire puzzle in terms of the monitoring aspects of these procedures. The other issue that comes up is that it is so critical, the experience in terms of how aggressive you should be. I think you have beautifully illustrated the idea that, these hemangioblastomas can really look like very vascular or high grade tumors, and you really have to persist, find the planes, remain in the gliadic planes to provide the patient with an effective outcome. If I may ask you, if you were exposing the tumor, looks like a perioperative ependymoma you do the midline raphe dissection, you see the tumor but its very adherent to the surrounding spinal cord. The pathologist says, I think it's an ependymoma, I can't be sure, but the tumor is still looks pretty adherent. What is your strategy in that case? Yeah, it's one of those scenarios that you really can't answer adequately without being there. But first and foremost, I go back to the fact that my overriding goal is not to hurt the patient. So if I think there's a risk of hurting the patient, I'm not sure whether this is a different pathology, because sometimes the pathologist has significant difficulty with being certain as to what kind of a tumorous. And I think I'm gonna hurt the patient by trying to dissect that out of the spinal cord. I will debulk and wait and get further studies and get a final pathology. And then depending on that final pathology offer the patient either radiation or going back or whatever.
- Makes sense. And in reverse, if you're removing a tumor that has great plains during surgery but pathologist says, well, this looks like a high grade tumor or diffuse glioma or grade three anaplastic astrocytoma. I think at that point, you have to really obey the plains and continue to section because I have rarely seen that the pathologist can be wrong or frozen, and therefore interoperative judgment of the dissection planes would override with the frozen section results, do you agree with that?
- Okay. Very good. Well, again, I cannot thank you enough for sharing your immense experience that continues to guide us every day. And again, thanks very much.
- You're welcome. My pleasure.
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