So, welcome Dr. Matisson from the Karolinska in Stockholm, Sweden. We are eagerly awaiting your counterpoint. So, thank you very much. So, I have to change my affiliation, though. It's University of Copenhagen, not Karolinska. It was close, though. So, thank you very much for inviting me. And I don't think it's really appropriate to talk about which technique is better because, as Andre so cleverly and ethically said, it's not about that. It's about the results. And I think we can have good results with either. How do I advance there? Okay. So, sorry. I think what we really should concentrate on is on what we don't know on the topic, which are the gaps of knowledge. And I think there is a gap of knowledge regarding immediate treatment morbidity from microsurgery, both regarding surgical outcomes, neurological, and even more so neuropsychological outcomes. We should know more about return to previous life and quality of life. And there is a lack of knowledge about recurrence after treatment, seeing as a lot of the series are short-term, as Andre was also saying. We lack knowledge on natural history, and we certainly lack knowledge, relevant knowledge, about late epilepsy. Looking on the literature, there are a number of papers on endoscopy and, of course, also on microsurgery. And I think there is a problem with many of these papers because it's very common to find normative conclusions. And dealing with rhetorical papers looking for shorter, for low morbidity compared to literature, no surgery for recurrence, that's endpoints that are not completely relevant. And frequently with a conclusion that endoscopy should be the primary treatment modality. And the comparison is made to microsurgery with morbidity from older series. Typically, if we make a meta-analysis, it will cover all published series, and there are a lot of complications out there, both in endoscopy and in microsurgery. I'm not sure whether all of these are reproducible in modern series. We saw from Andre's series that the morbidity was much lower than you can find in some papers. There are endoscopy benchmarks, and most of the series show that we have a very low proportion of complete removals of the cysts. And question is, what are the implications? It's very common that the papers argue that even though there is a cyst residual, it doesn't matter because during a one, two, three, or four-year follow-up, the patients were not reoperated. Now, Andre didn't say that, but a lot of the literature says that. Also, many of the papers report mortality from endoscopy, memory deficits. This is not what Andre had in his series, but if we would make a meta-analysis, we would find bad outcomes. A typical paper on the significance of cyst remnants after endoscopy, there were a number of patients with no cyst visible on post-operative MRI, of whom 7% had recurrences. So I think this is a problem. Neuropsychology, not very much available in the literature. And as with endoscopy, I think with microsurgery, it is very probable that the technique matters. We have a number of surgical steps that we use where one of the important issues is to use a wide, sharp interhemispheric dissection, not to sacrifice any bridging veins, and go through the corpus callosum, not through the cortex. Just illustrating the interhemispheric dissection. It's nothing fancy, but it's bimanual and it's sharp and it's preserving all veins. So we free the veins in order to be able to dissect between the hemispheres and reach the corpus callosum. We make a small opening in the corpus callosum, not cutting the fibers, rather trying to split the fibers. When this is exposed, I'll show the callosotomy of this patient, which usually makes for a fairly small opening initially, and pulling it gets a little bit larger, but again, when looking at the post-op MRI, it looks really small. So look at the next case where we are, sorry, dissecting the cyst a little bit closer, again by manual, slightly shaky, sharp dissection, mobilizing the veins in the ventricle, and using the same technique that Andre was describing for the endoscopy, really going around and gradually decreasing the size of the cyst and getting complete removal. I think we need to move on. I would like to show some benchmarks, because I think from the gap of knowledge, there is a lack of benchmarks, and there are two different series that I wanted to show you here. First is an institutional series with five different surgeons operating between 1991 and 2006, and this has been published. Three surgeons did a total of 60 operations, and they had some temporary complications, mostly temporary short-term memory deficit from clinical follow-up, and some cognitive affection and decision-making problems, again, temporary. Two surgeons did three operations and had three permanent complications. So there is a huge difference between these two groups, and I think this also shows that you cannot just compare methods. You have to compare how the different surgeries are done. Then I worked up a personal series of 65 patients that were operated between 1991 and 2013. There is some overlap between these two series. I have not put the last 15 patients after 2013 into this series, but it's not cherry-picking because the results appear to be the same. With transcallosal transforaminal subcoroidal microsurgery, no post-operative shunting, no recurrences, again, like Andre had some learning curve. We had three 1- to 2-millimeter large coagulated residuals in the earliest cases with 12- to 15-year follow-up, but none of these has progressed and nothing has recurred. There are no permanent neurological complications. We had four bone flap infections, which I think is a lot. All returned to previous life except for two who were admitted in coma and only went back to part-time work. We did cognitive workup on 29 patients here, and we used NKSU, which is a Swedish version which is very similar to the MOCA, for comprehensive cognitive screening. This was done by an occupational therapist, so it's not as comprehensive as a formal neuropsychology exam. And we had follow-up after surgery. Of the patients that were studied with NKSU, four were urgent acute cases with major hydrocephalus and symptoms of high ICP, and none of those had a Glasgow coma scale of 15 when admitted. And 15 were elective cases. The early outcome in the urgent cases, even in the urgent cases, one was normal at the screening. Nine of the urgent cases had moderate to severe memory deficits. Seven had moderate to severe problems with arithmetics and construction, and five had moderate to severe attention deficits. Of the elective cases, we had some minor and one moderate and two moderate, sorry, and one with moderate attention deficit early after surgery. Late outcome, the elective cases were almost completely recovered. The mild case, we don't know what it was, how he was doing before, but looks like decent results. Also, the urgent cases are much better, but not as good, and some have remaining neuropsychological problems. So with the elective cases, we have some early problems with neuropsychological issues. We had no deteriorations late, and of the urgent cases that were undergoing life-saving surgery, all improved after surgery and during follow-up. The typical cognitive complications in patients like this would be memory deficit, probably temporary and permanent memory deficits from injury to the fornix or medial temporal lobe, or executive dysfunction, which is probably more related to dorsolateral prefrontal cortex, cingulate cortex, and I would guess could be connected to bridging vein problems, sacrifice of bridging veins. And of course, we had patients who had herniation, and they had problems with memory, with arithmetics, with construction, and with attention, which I think is what you can expect. So what can you expect from residual cysts in endoscopic series? We published in 1993 on patients that had only undergone aspiration, and we found that after more than 10-year follow-up, all of these patients had progression or recurrence. So aspiration of a cyst is not a good idea. We see from the endoscopy papers that many of the papers describe residuals. And as Andre was showing, the mean radical resection rate in endoscopy was less than 60%, and in microsurgery was more than 98%. So I think it's clear from literature data, from our observations, that safe subtotal surgery is wishful marketing. You really need to take out the complete tumor. And unless you can do it with endoscopy, you have to be prepared to convert from endoscopy to microsurgery or go for microsurgery right away. The modern results for microsurgery, and there are not too many papers, it's our data from this one, Hernesime published in 2008, and Shapiro published, I don't remember the year, I'm sorry about that. But clearly, there is less than, I think there was one, sorry, there is radical removal in all patients, and there is less than 0.5% permanent morbidity in those three series. And looking at, actually I think I agree very much with Andre, is what we should look for is relevant outcome criteria, which would be the neurological morbidity. We should look much more on cognition, and we need to look at the extent of resection. And unless these primary outcome criteria are perfect according to modern benchmarks, the secondary don't make sense. That's surgical time, hospital stay, and health economy. So looking at our data, I think we have remaining gaps of knowledge. Regarding permanent morbidity, though, I think that surgical and neurological morbidity is completely avoidable also with microsurgery, and should be expected to be zero, although there may be a remaining problem with bone flap infections, which of course takes meticulous respect for tissues, including veins, and of course not going with transcortical trajectories. Regarding neuropsychology, I don't know. Maybe some mild neuropsychological deficits are unavoidable with craniotomy, and if this is true, this needs to be studied. If this is true, this may be a problem, and this needs to be studied, because if there is a difference between endoscopy and microsurgery, I would certainly argue that we should go for radical endoscopy instead. But this we don't know at the moment. So I think this gap remains, and neuropsychology is grossly understudied with these patients. We should look at whether the patients return to previous life and quality of life, which I think can be expected with our benchmark of microsurgery. Recurrence after treatment is highly important, and I agree with Andrei that unless surgery is radical, it shouldn't be thought of as a golden standard. Natural history is not fully studied, and epilepsy remains a gap of knowledge. In our patient, in our complete material of 80 patients, we had one case with epilepsy a couple of years after surgery, where a bridging vein had been sacrificed. But I wonder how this compares with the transcortical access in endoscopy, and that needs to be followed up on long-term. There are data in literature that just putting in an external ventricular drain carries a 5 percent epilepsy risk. So taken together, I think it's not a question of endoscopy or microsurgery. I think it's a question of getting complete removal of the cyst without neurological morbidity, and I think we really need to follow these patients much more meticulously with neuropsychology, and we should follow them long-term for epilepsy. Thank you. Thank you so much. Any questions for Dr. Mattisson? Yes, sir. I think that when we look to our personal experience to the series, large series of the literature, and also to what we have heard now, it seems that there are maybe some more morbidity with open surgery and maybe less with the endoscopy. However, the problem of endoscopy is the removal, the quality of the removal of the cyst and the recurrence. So my question for both speakers, when you see a case, when you see patients, for the first speaker, are you deciding just to go by endoscopy? Or the second one, to go by open surgery? Or both of you have some criteria to make the choose. Can you tell us these criteria? Because it would be important to know how to make the decision for one of these two techniques, because the results seems not the same as it's said in the literature. I have mentioned it briefly. If a patient comes with a cyst, I will start with endoscopy. But what I tell the patient is that I will also be prepared to convert to microsurgery, because what I tell the patient is I want the cyst to be out. The cyst should be removed. And with my personal experience, I feel more comfortable starting with endoscopy. If it wouldn't work, but in the whole series, in the beginning, yes, we had to convert it. But now not. Then I would, of course, do the transventricular approach. You use the same approach. Then I don't go transcalosely. So that would be a difference then. And that's, so for me, I start, and especially now with the transcarotid technique, even if it's not a huge hydrocephalus, I will do that. So, André, how often do you convert? Well, the last conversion was in 1997. So that's once in 25 years or what? 21 years. No, but listen, in the beginning, and that's interesting, I said, I haven't mentioned that, the eight that I only aspirated, seven of them still have that cyst inside and only one had a recurrence. That's also one of the frustrating parts. The very first case I did in July 1990, he still has a very, very prominent 12-millimeter cyst inside and perfectly fine. So this is also one of the tough things we have to experience. In the initial phase, there was, of course, also instrumentation. We had no way, the same possibilities as we have now with our modern endoscopes and much better instruments. And then you get this dangerous thing, as they say, just going with the grasping forceps and just quickly pull it out. Of course, that is not surgery. That has nothing to do with treating these kind of cysts properly. No, I think actually, well, of course, I don't start with endoscopy because I don't have 25 years of this excellent experience. I would prefer to do microsurgery because I can go transcolosally, which I think on the long term should be much better. But, again, I think the question is not endoscopy or microsurgery. The question is to be able to do bimanual dissection and complete removal of the cyst and to have zero neurological morbidity and, again, to be able, actually to be able to make meaningful neuropsychological work up to because we need to find out more. We see so many patients who undergo craniotomy for different indications who do have memory deficits and things like that for months after surgery. We don't know why. This is completely understudied. So maybe that would make a difference. I don't know. But at the time being, I think I can do safe microsurgery transcolosally. I don't think it would be ethical of me to practice something else. And I don't think that the differences are clearly so big that I should send the patients to someone who does yet. Maybe they become like that, but not today. Please. Comment and concerns. The comment is the craniotomy. I think the essence of going the interhemispheric route is the preservation of the cortical veins that drain into the sinus. Yes. I think if we can take care of that, I think the craniotomy should not cause any problem. That's the comment. The concerns are I think I would not like to handle the surface of the brain. So putting an endoscope is you're handling the surface of the brain, the cortex. Going transcolosal to my mind is far, far safer in the long term. So there's no question or no doubt in my mind that in transcolosal microscopic technique would be better. That's the first concern. The second is that you're working at a depth of almost eight or nine centimeters or 10 centimeters from the surface. And to do that with the endoscope, I would be a little scared to do it. I would prefer the bimanual technique with the microscope. Two concerns. Can I just close one thing? If that's the operation you're doing, that you're really expanding the fissure and open it up and dissecting, that's the microsurgical operation too. And I don't know where the idea that's doing it with the endoscope is less morbid than do it with the microscope. It's the same morbidity. So what you discharge them next morning, we do discharge them next morning too. That's the idea that the endoscope is less invasive or less morbid. It doesn't count. The morbidity is what you're dissecting down there. If you could achieve the same results, then the microscope is still safer because you could handle a problem that would not make you convert to the microscope very fast. No? But one other question and final one. Urgent cases, obviously sicker. Yes. Obviously, but sicker because of the hydrocephalus, not because of the presence of the cyst. Yes. But obviously they had a lot worse cognitive function. Yes. Well, it's probably because of the hydrocephalus largely. You mean the cognitive function is coming from just that an hour or two or three of acute hydrocephalus? It's a longer process. I think looking at our cases and looking into literature, I think it's a myth that the hydrocephalus and headaches and coma come out of nowhere. These patients have usually they have at least a month history of headaches and things like that. And they have definitely more than two days of worsening. So it doesn't come out of the blue. Sorry? Before they are, yeah, before they deteriorate. Since Dr. Omefti touched upon this topic, we have a few minutes additional to spare. And we didn't talk about this emergent issue. So your moderator has prepared a couple of cases. So both for Dr. Mathisen and Dr. Grotenhaus and everybody else. This is a patient, 19 years old, with two weeks of severe headaches, presented at 2 o'clock in the morning to the Copenhagen ER, comatose, decerebrate. What would Dr. Mathisen do? Two o'clock in the morning, your residents are all at the review course in Belgrade. Oh, this is a very serious case. No, I mean, this is, I mean, two o'clock in the morning, bad condition. I would put a ventricular drainage and see if the patient recovers. And if I see neurological improvement, I would do a surgery the next morning. So the patient improved. She woke up in the morning, and this is the condition. She woke up. She's talking to you in the emergency, in the ICU. When is the next surgery, and what kind of surgery? Well, now it's not that urgent. I would do surgery within a few days. If possible, I would do it same day. And I would do a transcancer removal of the tumor, of the cyst. All right, thank you. I think Dr. Kalkanis has another question. I would not, if you place an external ventricular drainage, instead of the external ventricular drainage, I would put in an endoscope and take the cyst out. And even at 2 a.m., even if it is a Sunday night, Tuesday night, it doesn't matter. With patient herniating? Yes. You treat hydrocephalus immediately. In the ER? Like you do with an EVD. No, you go to the OR, you place the endoscope inside, you release, of course, the pressure, and then I will take out the cyst. I have done a few of these acute cases with excellent results, as you have shown now also. Is comatose in the emergency room? Yes. You go immediately to the OR. How long is your OR, Dr. Grotenhaus? How long do your nurses need to prepare the OR? Because if they come in comatose, it takes us about 10 minutes to be ready in the OR. Wow. This is unbelievable. Yes. 10 minutes at 2 o'clock in the morning? Absolutely. Oh, my goodness. You beat all American centers. It depends. I mean, such a patient is announced. Somebody is bringing the patient with an ambulance. They are found comatose at home. So you are prepared. They are scanned, and sometimes they will, from the scanner, they will go immediately to the OR, and that would be like in the other side of the hall here. How far do you live away? I mean, you now raise too many questions. Patient is herniating. Her pupils are blown. You are at home. They are calling you from the OR, ER. Yeah, okay. I live a walking distance from the hospital. So that's my advantage. Or if I really, really have to hurry, I take a bicycle. Okay. I think Dr. Kalkanis has another question, and we'll move on. That's tough to beat. My question is on the other end of the spectrum. For either of you to comment on the incidentally discovered asymptomatic lesions, what is your threshold for operating? And when you do, we're living in a precision medicine era where there's lots of molecular genetic testing. Is there any evidence, either anatomic, biomarker, or otherwise, to predict which of these will stay stable for 17 years, like I believe you showed, or are at greater risk for enlarging? And how would you advise the audience to deal with those? Well, I think there are two issues. One is that we shouldn't be that convinced that the asymptomatic cysts are asymptomatic. You showed nice data that they may be neuropsychologically compromised. I operated a patient with an almost 2-centimeter cyst who was completely asymptomatic, and then when he came back for the follow-up, he said, Thank you, doctor, I no longer have headaches. This is the case, basically, of that asymptomatic patient in the emergency room, has occasional headaches, he's freaking out, and would you operate on him? Would you watch him, Dr. Mathisen? This is the case where is the cyst? Here you go. Oh, yeah, okay. So I don't think this cyst is symptomatic. We have patients with occasional headaches who don't have cysts also. I would send this patient for a neurology workup for the headaches, and I would recommend follow-up MRIs. I think in our experience, I didn't show those cases, but in our experience, the small cysts that we consider asymptomatic with a 10-year follow-up seem to be growing in approximately 10% to 20%. And I don't think we have any way to predict who do. However, your radiologist says that she has a mild hydrocephalus on this right scan here. Far right. Okay. Would it change your mind? Well, again, I would work up the headaches properly. If I could think of looking at the CSF flow, if I would be convinced that this is symptomatic, of course I would operate. But it's really a matter of seeing the patient and discussing the symptoms with the patient. I think that's the best way to get an understanding of it. I just made it up. This patient had severe headaches, and he had growing hydrocephalus in the follow-up scan. So we did operate on him, but this was just for the purpose of discussion. Who is using the colloid cyst risk score that has been published two years ago? By the way of hands, Dr. Grotenhaus is asking who is using colloid cyst score. I see at least one hand. Maybe you published it. No, but to be honest, I think we have to study that. I would add to that score also neuropsychological testing. That is what they do now with so-called asymptomatic patients because they sometimes are not so asymptomatic. At least they present with something like headache, and sometimes really an incidental loma because they have a completely other indication for the MRI scan. But that is it's seven millimeters, hydrocephalus yes or no, the so-called risk location. So if it is more posterior on the third ventricle, they have lower points. And then also the black dot, so the black on the T2 has a higher risk of growing. So you come to a certain point, and if you have more than four points, they say that should be a surgical indication. So I think we should go maybe also that direction. Thank you very much. I would like to add on that. We raised a question regarding the era of personalized medicine, and I think we cannot just look at different objective predictors. We are dealing with patients. So we have to talk to the patients and see what kind of risk they would prefer. Even if we have established a surgical indication from a score, this does not mean that 100 percent of the patients either benefit from the surgery or do badly from not being operated. No, but then they showed that the lower the score, there was hardly, let's say, a chance of any growth of becoming asymptomatic. It was also not that it's a surgical indication, but then you can discuss with the patient if he should undergo surgery, yes or no. And that is essential. Laura, thank you. We have to move on.

cystic colloid tumors

patient outcomes

microsurgery

neuropsychological outcomes

epilepsy

endoscopy

complete removal