Craniopharyngiomas are rare, benign epithelial tumors that typically arise in the suprasellar area of the brain, extending to involve the hypothalamus, optic chiasm, cranial nerves, third ventricle, and major blood vessels. It represents a special challenge for the physicians treating it; these physicians commonly include neurosurgeons, neuro-ophthalmologists, neurologists, endocrinologists, and pediatricians. Curative surgeries are extremely difficult due to their location and infiltration into the surrounding structures. Further, the quality of life is compromised due to the development of multiple complications, including panhypopituitarism, visual problems, obesity, and mental disorders.
Professor Hermann Lothar Müller is giving a lecture on “Craniopharyngioma”, don’t miss it!
Thank you very much for the kind introduction can you all hear me yes okay that’s great so my talk will focus on graan Anda as I am a pediatrician I will focus on pediatric granifera but as already mentioned we we know main up to now almost 800 patients
And most of them are adults right now so as you all will know Craner Ina is a nonm an low grade um Mal embryonal malformation located at the skull base and here you see an intraoperative Imaging and only in very rare cases this tumor can be radically completely
Resected you can see here the optic nerves and you can see the pitutary stalk and the reason for for this rare events is the fact that this tumor frequently involves suell areas as you can see here and second L most of these tumors show also when you look at the
Hystological Imaging of these patient they show protusions in the neighboring tissue so whenever you have a complete reception many of these patients they suffer from relapses due to this um neighboring tumor parts of these tumors accordingly when you look for nonradical reception and you don’t risk a HEPA type
Thalamic D D AG you will have to do a second treatment which is mainly IR radiation however most of many of these patients they show a significant increase in bmis yes they develop obesity and when we when we when we started almost two decades ago 20 years ago first of all we were
Interested how frequently does obesity occur in these patients and these two graphs show you the BMI SDS at the time point of diagnosis and in at yearly intervals after diagnosis of childhood gruma patients and as you can see approximately half of all patients they kept normal weight and the other half of
The patients they developed severe obesity as you can see here and what we also saw is that the most critical time period for the development of obesity and for the increase of body weight was the first year after diagnosis and the first year after surgery in this period there is a steep
Increase in bmis SDS which levels up after the following years and what was really interesting was the fact that we could see and detect that patients who were at risk for obesity that were patients who were already more obese or had a higher BMI SDS at the time point
Of diagnosis which means before treatment when compared to patients not at risk for obesity so from this results we speculated that the pathogenetic risk factors for the development of obesity in these patients should be effective already before diagnoses and what we did we looked at the symptoms and history of these
Patients and here I show you our analysis of the records of these patients and indeed many patients had symptoms in history before diagnosis in terms of headache visual impairment growth retardation neurological symptoms weight gain po Y and disturbances of pual development as you can see growth retardation and weight gain and you see
These numbers which are the interval between the first detection of the symptom and the diagnosis is pretty high for growth retardation and weight gain so these data are actually biased because it’s only based on what is written in the documents and not everything is written in the document
And not everything is documented so we ask the question do we have reliable data on weight and height development before diagnosis in these patients and indeed in Germany we have these data we have a national health survey which this does measurements of height and weight
On each newborn at the time of birth at the first day of life and then at defined time points we call it U1 to u9 and as you can see these time points are up to five years of life and what we did is we analyzed how height and weight in
Almost 90 patients who later on developed the childhood onet graan fora and we look for their height and weight development before diagnosis and this shows you the data for growth before and after diagnosis of childhood granena shown are the height SS scores and you see here U1 is at Birth and then
You can see beginning with U6 there is a steady and significant decrease in height SDS which means means those patients have decreased grow growth velocity and here you see the diagnosis is at the median age of eight years and then further on you see these data until
Last visit and you have to imagine when it starts at U6 then it starts at the at the end of the first year of life so that’s a pretty early symptom years before diagnosis of the tumor which is usually diagnosed in this coword in between between six to eight years of
Age so five to six years before diagnosis these patients tend to grow less and we also looked at the development of weight before and after diagnosis of childhood CLA and I’ll show you here the bmis SS once again at U1 at you at diagnosis at 8 years and then
During followup and this data you know already this deep increase but we were able to show that in these patients the increase in weight occurs pretty um pretty close to the diagnosis which means only two to three years before before diagnosis these patients tend to increase their weight to a certain
Degree as you can see here and then we looked at the same data of body mass index SDS before and after diagnosis for two different cohorts of our patients these were the patients without hypothalamic involvement and these were patients with hypothalamic involvement and as you can see what I’ve shown you
Before this steep increase in BMS shortly before diagnosis and definitely after diagnosis this was observed almost exclusively the cohort of patients with hypothalmic involvement of their cran droma so many Quest many P many patients ask us whether the duration of History has any impact on the prognosis and they
Expect larger initial tumor size that diagnosis when the duration of history is pretty long so we looked at the duration of history and tumor size and indeed there was no significant correlation between these two parameters we had patients with large very large tumors and short duration of history and
Patients with very long duration of history and very pretty small tumors so no correlation no reason to to have fear about late diagnosis but when you look at the correlation between duration of history and the diagnosis we definitely saw a correlation in a way that the younger the patients are the shorter the
Duration of history is okay this was already mentioned that over the years we have recruited many many patients in our multicenter study and I have to say that right now we have over 800 patients with this very very rare disease in Germany we expect approximately 15 to 20 new diagnosis per
Year in our in our population and what we did is we we analyzed these patients in in several studies and I now want to focus on this study which was a study which only included patients who were diagnosed before the year 2001 these are long-term survivors and we were able to
Analyze 280 of these patients and we look for the survival rates overall survival and progression survival and we look for quality of life and psychosocial status in one and eight patients of this Co and this first graph shows you the 20e survival RS for these patient that’s overall survival that’s progression free
Survival and first of all we were surprised to see that in this disease also after very very long followup period there are still events happening in terms of progressions relapses and also fatal events occur in these patients looking now at 20e survival rates with relate with regard to H
Diagnosis we saw that overall survival there was no significant difference with regard to H diagnosis however looking at progression free survival we saw that the younger the patients were you see the patients Bel lower younger than five years of Agia diagnosis they had the lowest progression free survival the
Most frequent events in terms of progressions and relapses when compared to older patient at the time of diagnosis and you also looked and that was pretty a pretty important finding for us we looked at 20 years survival rates and the degree of surgical reection and as you all know when you
Look at very old textbooks there is the hypothesis that this a a curable disease by by surgery and that there are no no no events when you do complete reection and in this graph you we could show when we looked at progression free survival in patients after complete reection and
In patients after inmp complete reections these curves were not different which means there was no advantage of complete reection during longterm survival uh during long-term followup when you compared radical and non-radical surgical approaches and we also looked at the impact of hypothalamic involvement and we could show for the first time that in
This non-malignant disease hypothalamic involvement indeed has impact on overall survival that means when patients have hypothalamic involvement the the death rate and the the rate the overall survival is decreased in these patients significantly when compared to patients without hyperic involvement so we also looked at the the
Causes of death in these patients and there we saw in these 23 patients which we could evaluate that almost um 25% of these patients died due to acute adrenal insufficiency and I would speculate that also in this co-ord of patients where there was no documented cause for death
That many of these patients had also endocrine problems in form in terms of and of adrenal insufficiency and we were not surprised to see that many of these almost all of these patients were on endocrine medication but we were really surprised to see when we asked them and how
Whether they were treated or t with any endocrinology took care of them only two3 of these patients said they were in endocrin endocrinological care and almost 10% of these patients said they have no medic medical attendance at all and then you look at the frequent fatal events during long-term followup this is
Something which really um makes us surprised and uh yeah okay let’s have a look at these two patients one patient with suprasellar extension she developed Cal obesity and this patients with a tumor confined to The Cellar area both had complete reection and she perfectly kept her normal weight and we also
Looked at the very long-term followup in these patients we looked at once again at the patients with hypothalamic involvement and without hypothalamic involvement and this time we looked at bmis SS at very long ter for at diagnosis and open boxes 8 to 12 years and more than 12 years followup uh with
A median follow up 16.9 years range from 12 to 36 years and once again this you know already that these patients have a significant increase in bmis during the first years but we were surprised to see that there is a certain stabilization and there’s a certain plateau of very
High BMI SCS during longterm followup so we analyzed quality of life and psychosocial status and these one night patients and we used the following instruments ERC quality of life m mfi for assessment of fatigue we used the questionnaire of Psychosocial status and we were able to analyze one of their
Patients and the main factor which we’re interested in which we were interested in was hypothalamic involvement and this shows you the results for the functioning domains and we could see that in patients with hypothalamic involvement especially physical functioning and emotional functioning was self assessed significantly lower when compared to patients without hypothalamic
Involvement and these show the symptom scales which was also a certain surprise this we expected already that the patient said a higher rate of dispa and we speculated and hypothesized that that was due to the severe obesity but these patients very frequently have also gastrointestinal problems in terms of
Diarrhea that was something newe we could show and that always applies for patients with hypothalamic involement when compared to to patients without hypothalamic involvement and this are the data for fatigue you measured by mfi and once again patients with hypothalamic involvement had more significantly um findings for physical fatigue and reduced motivation when
Compared to patients without hypothalamic involvement and what about psychosocial status this compared patients with and without hypothalamic involvement and you can see that in patients with without hypothalamic involvement the rate of marriage and Partnerships was higher and that’s also that we expected that the driving licenses were significantly highend patients without hypothalamic
Involvement because in this Cort they had frequently visual disturbances due to the close close proximity to the Kaya okay there are some challenges in treatment which you all know we we asked a question for the outcome and development of sever hypothalamic obesity after diagnosis and treatment whether this was
Related to initial initial presurgical hypothalamic involvement at the time of diagnosis which makes before treatment or whether hypothalamus sparing surgical strategies had significant effect on surgical hypothalamic lesions and we ask the question whether primary hypothalamic involvement has prognostic impact whether surgical hyp determine the outcome and so the main
Question was what is the effect of surgical thic lesions an outcome in cruma patients with severe pre-surgical hypothalamic involvement and in order to understand what how we did the the grading of hypothalamic involvement this graph shows you the memary bodies and this are the posterior areas of the hypothalamus
And whenever the tumor or the leion involved the memary bodies in this area we called it posterior leion or location if the anterior parts of the hypothalamus will were involved be in front of the memory bodies we called it anterior involvement or anterior leion when there was a leion and all others
Had no leion at all and this shows you some examples that’s a patient with a tumor confined to The Cellar that’s presurgical grade zero and this tumor was removed the hypothalamus is perfectly intact that’s no hypothalamic leion that means hypoth lean crates here when you have a tumor like here and you
Still can identify the memary bodies and the anterior and the posterior parts that’s an anterior involvement a great one and if parts of this anterior tumor are reected and the other parts are intact we call it anterior vision and this is the worst case a large very large tumor involving the anterior and
Posterior parts of the hypothalamus and this tumor was completely removed so that’s a great two involvement and the posterior grade two complete reection and what we did is we analyzed patients who all had these very large tumors with involvement of anterior and posterior part of the hypothalamus and
We have different ways to treat them surgically yeah there is a patient who had only a cystic trage he had no this patient had no hypothalamic surgical lesion after surgery this patients had a reception of part of anterior um parts of the tumor that’s only anterior hypothalamic leion and that’s the worst
Case which you have already seen that’s a complete reection with anterior and posterior hamic lesions and we were able to analyze 169 patients and uh we found in these 100 in 109 of these patients we found pre-surgical anterior and posterior hypothalamic involvement so these are the patients who present with very very
Large tumors at the time point of diagnosis and 21% of these patients were operated in a way that they had no postsurgical hypothalamic lesions 27% of these patients were found to have anti hypothalamic lesions all these assessments were done by reference neuroradiological assessment in Germany by one person who did all the Imaging
Evaluation and 52% half of these patients had anterior and posterior hamic lesions after surgery and what we did is we analyzed overall survival in these patients progression free survival bmis SDS quality of life self and parental assessed by petall questionnaire and functional capacity assessed by FMH scale so these are the patients
Characteristic once again actually we saw no differences between these patient cords without anterior and anterior posterior hpic surgical regions in terms of gender AG diagnosis agent study followup years and also tumor size what we found is and that was expected that in patients who had incomplete reception
Um this this in these patients with incomplete rection we had the highest rate of patients with our hypothalamic lesion and that in patients with complete radical reection there was the highest rate of anterior and posterior hypothalamic lesions and also as expected the rates of irradiation were higher in patients
Without hypothalamic lesion these were patients with residual tumor who needed irradiation and as you can see in our cord the treatment with proton therapy was higher okay this shows you the data for procession free survival after these different strategies of surgical treatment actually when we look at progression free survival in the
Patients with anterior and posterior that’s the worst case in patients without hypothalamic leion and interior leion there is no significant difference nevertheless there seems to be a tendency that patients with anterior plus posterior hypothalamic lesion these are the radical rected patients seems to have less frequent relapses and progressions which did not reach
Significance what about the development of bmis STS during followup of these patients once again these are all these patients have severe hypothalamic involvement before surgery at the time point of diagnosis but they are treated different ly without hypothalamic s surgical damage with anterior lesions and with Anor and posterior lesions and
First of all all of these patients when you look at BMI and BMI diagnosis and one years after diagnosis all these patients have an increase in bmis SDS however the most significant and clinical relevant increase occurs in patients with severe hyper theine lesians as you can see here and what was
Also a surprise to us was that in patients who suffer from anterior hypothalamic leion the de weight development in these patients was pretty similar to patients without any hypothalamic lesions that was really a surprise and you also looked that’s a very busy slide for Parental and self assessed quality of life in these
Patients and as you can see that’s self assessment after one year threee parental assessment at one year and three year and as you can see during the first year quality of life there is no difference between patients with anterior anterior posterior no hypothalamic lesions however looking later on after three years there are
Indeed differences in self assessment and also parental assessment in a way that patients with anterior and posterior hyp lesions they have lower or not not not good self assessment in terms of social functionality the higher these vales the lower the self assess quality of life is in physical functioning and also in emotional
Stability in autonomy and you see here this social dysfunction is also self assessed by the patients themselves after three years okay you know about this we we have seen this this is a high rate of relapses after complete and incomplete resection and we asked also the question
What might be the the risk factors for this High rates especially during the first years after diagnosis and this is also the time period when growth amone substitution is usually initiated and we included also growth Amon substitution in a risk analysis for this progression fee survival curse at
Least 170 patients and as you can see we were really happy to see that degree of reection irradiation and so on they had all influence on these curves but Glon substitution therapy had no significant impact on the rates of progression and and relapses in these patients so from
This data we very early on could could conclude that grosson substitution is pretty safe in these patients and nowaday we also start this substitution pretty early almost sometimes also during the first year after diagnosis okay from this I would conclude that posterior hypy spering surgical strategy does not result in
Increased relapse and progression rates improves quality of survival and ameliorates the development of severe obesity also in TR fora patients at high early risk for hypothalamic obesity due to primary presurgical anterior and posterior hypothalamic involvement however oh we could also includ that anterior surgical hypothalamic lesions do lead to
Similar weight development like non hypothalamic lesions on no no hypothalamic lesions and seem to be acceptable with regard to risk for hypothalamic obesity however we also had data on neuros pychological C which seemed to be related to anterior hamic damage especially when we looked at oxytocin and what we did is we analyzed
34 cranor patients and 73 healthy controls and we measured oxytocin concentrations in saliva and urine before and after standardized meal that was a standardized breakfast and the assessment of the oxytocin was done by enzyme imun assay and we look for associations with gender radiation and greater hypothalamic
Involvement and this graph shows you the oxytocin concentrations in saliva of 3 34 patients with and without hypothalmic involvement and in 37 73 controls before and after breakfast this is before breakfast after breakfast and that’s the Delta the change of oxytocin concentrations and as you can see see we
Were really disappointed to see that there were actually no differences between controls gruma patients without hyperic involvement and Craner Anda patients with hypothalamic involvement however you know that we can great hypothalamic involvement as I’ve shown you in the slides before and looking at different grades of hypothalamic involvement that’s no
Involvement that’s anterior involvement and that’s anterior posterior involvement there we could see that patients with grade one that’s anterior hypothalamic involvement had significant lower um oxytocin levels before standardized breakfast and you see the data after breakfast and the change other datas we looked for was irradiation there was no the change in
Oxytocin was not related to the the fact that the patients were irradiated that the patients had their diabetes incipits and there was also no significant difference in change of oxytocin with regard to jeda however what we saw is that the change in oxytocin concentrations in our patients and
Controls especially in the patients was significantly correlated with bmis SDS with the degree of obesity which means the more obese the patients were the less significant was the change in oxytocin when look before and after standardized breakfast okay we also did based on this we did an analysis we looked at neurosc
Effects of a single administration of oxytocin in 10 of these patients and we administered 24 units oxytocin in a single nasal Administration look for oxytocin concentration once again in saliva urine and this time we use radi Muno essay we analyze neuros pychological Effects by using an instrument perception and identification
Of emotional expression in voices and M multidimensional mood question there and that’s a busy slide which only wants to show you that these patients were pretty comparable to the large coord of the other patients in our registry of these 200 patients they were in a way representative for this coord
Of patients with hypothalamic lesions which we usually have and these are the 10 patients which we analyzed and I want to show you not all I don’t want to interrup it all the data but I want to you to focus on this we had four patients who had grade one hypothalamic
Involvement and you know grade one that’s anterior involvement of their tumor uh and these were the patients who had in the previous study lower oxytocin levels and we had also six patients with grade two involvement these are anterior and posterior involvement and first of all what we did
Is we looked at the concentration in urine because we were afraid that when you administer this oxytocin via nasal application and then you measure it in saliva you could possibly only detect a contamination of the SLA by your administer oxytocin so we wanted to know whether this oxytocin is really resorbed
And which whether it’s follow it is followed the administration is followed by an increase of oxytocin in urine and indeed it was could be showed that this medication was really resor over the nasal epithelium and this shows you the data and whenever you do 10 patients before
An after Administration you cannot do uh statistical analysis but you can do only descriptive analysis and what is shown here in solid lines are the data of before and after um standardized breakfast for patients with anterior involvement and the dotted lines are the patients with anterior and posterior
Involvement and from this data we that was a first hint to say that maybe also these patients where we could show that they have a lower oxytocin concentration that these patients with anterior involvement they might benefit from an an ministration and it you I have to to point out it’s only a single
Administration that’s not long-term treatments we gave it to them and then we measured their neur neuros pychological behavior in these tests 60 minutes later so from this I would like to conclude that cran anduma patients continue to treat oxytocin especially when interior hypmic areas are not involved or damaged and oxytocin may
Have positive effects of emotion perception in these kifa with specific lesions of the anterior P hypmic area and granifera patients improved assignment to negative emotions after oxytocin these data have not shown but I have mentioned that okay irradiation nowadays in Germany almost all our patients who need irradiation we
Are treat them we are treating them by proton beam therapy and the reason for this is with this technique you can actually spare neighboring tissue and you the the effect is similar but we hope that during long-term followup we could reach a lower rate of second malignancies and also the the
Neighboring optic nerve and the optic system might be and more or might receive less irradiation with this modern Technique we also looked the effects of irradiation and in this study we looked at the patients who received immediate irradiation after inob rection of brain foma and compareed this BFS rates to
Patients with residual tumor who received irradiation at the time of progression of the residual tumor and as you can see there was a very really clear significant difference in a way that patients who received immediate irradiation they developed no more events in terms of progression and relapses whereas these events occurred
In the patients who were only later on irradiated this um actually leads to the conclusion that irradiation is effective in preventing relapses and uh progressions okay this slide you know already um it’s a very rare case of a complete reection and in many of these cases you have large very large cystic
Tumors and in many of these tumors you you insert a catheter and you remove the fluid you decompress the cyst and you hope that that might solve the problem but in many cases the cysts reappear they refill so that you have to do it repeatedly and sometimes even not even
Repeated drainage does not lead to a good result so Interra cavitary therapy was suggested using sclerosing agents years ago bomy was used which is um very highly toxic neurotoxic so nowadays others agents are preferred first of all you have to prove that your system is
There is no leakage and you have to do imaging of the system and install a contrast medium to make sure that there is no leakage and then utab bottles almost 10 years ago published first her her treatment strategy using interr Alpha um over four weeks with four cycles and pyes 60 36 million
Units and early on she promised very she published very promising results with a very good response and very good toleration of this therapy and also recently there was an international multicenter evaluation which could show that the disease at that time to decrease the disease progression was really longer when you installed this
Intracystic interal Alpha when compared to patients without intracystic interr therapy and it was very very tolerated there was indeed very low rates of deterioration of androgine and other sick feeling however and that’s very really a Pity INF Alpha is currently not available on the market so you have
Problems to get it when and hopefully in the near future it will be available again hypothalamic syndrome that’s a very special area where we are also doing research and there are many theories what is the reason for hypothalamic syndrome and especially hypothalamic as the main symptom of this
Syndrome and um that’s one hypothesis that’s vagally mediative hypers insulinemia an autonomic imbalance reduce sympathetic tone reduce sensitivity to endogenous leptin altered energy expander which we have also analyzed and also other other contributing factors such as reduced melatonin levels increased daytime sleepiness and neurological defects and visual failure and also decreased
Physical activity which also Le leads to increase in weight in the next slid I want to show you when we have recently summarized the current options for medication in these patients to treat hypothalamic obesity and um these are many many data which I want to summarize before I show them all
In a way that none of these uh reports show you data based on a randomized control trial these are only as you can see very very small cohorts which mainly also report on very um different results on the one time you have reduction in continuous making and
In some cases you have also increase and you can see at the data for dextramine that’s an Central stimulating agent which usually causes very good effects on activity and also leads to a reduction in BMI at least based on these reports and also other Sy stimulating agents are used nowadays as meth
Fate and as but you can see very very small co-ords and actually a weight gain or beneficial effect on weight but no control study actually we have now some more information and results and on gp1 receptor Agonist exid lurde and um actually with using these agents we realize that they are very
Well tolerated and the patients lose weight know a way that they tolerate it and that they can stand it and um we have the problem in the German Health System that’s an off Lael use of these medications so you need the approval of the the authorities to to get the
Permission to to use this and that’s sometimes really difficult but we are we hope that currently there is a trial in Northern America analyzing this in a in a control trial U randomized control trial fashion and whenever the result are out we hope that this medication also becomes available in our health
System okay what about bariatric procedures you can do lab gastric binding in these patients and actually we very early on did a report on these patients and when we started it was very difficult for us to believe that that might have an impact on on their their
Well-being you said the problem is in the brain whenever you do surgery in the on the the stomach there will be no result and no effect and that will all will be even a greater problem for your satiety problem but what we saw in these our data our data of our four patients
We saw that in all these patients actually they lost weight after this um gastric banding but when we looked further on after many years of followup they all regained weight but actually none of these patients was was disappointed or they all said they had a great benefit using this me method and
They all decided to to remove this gastric Banning and to go on to other procedures such as gastric SLE gastrectomy which many of these patients then experienced and also here you see that there are small cords who all all said that’s nice but others also had complications and side effects which were really
Severe and the most effective perc procedure is gastric bypass this was also analyzed in the multicenter study where we could show that that had the most and the most significant impact on the the weight development however I’m a pediatrician and my patients are minors and there are no adults and this is an
Irreversible procedure and I think um on legal and ethical based on legal and ethical considerations I I don’t recommend gastric bypass as a non-reversible bariatric procedure in these patients who are non- adults and kids obesity and nutrition and physical activity that are also very old data where we looked at energy intake in
These patients with intracell graany foma with hypothalamic graa and with in healthy controls and we were surprised to see that actually there was no significant difference in and energy intake and these data have been confirmed by other studies those patients don’t eat much more than other patients and then healthy controls and
And then these controls are BMI matched that’s clear physical activity we did Exel ometry and there we found that healthy and then what we did is we for patients with cran controls in open boxes are the very severely obese patients above for standard deviations of BMI 2 to four standard devation and
Normal weight patients and as you can see looking at nine time melatonine especially in very severe obese cran J hypothalamic esosa patients the nighttime melatonin concentrations were significantly lower when compared to BMI match controls and the similar finding was was observed for morning melatonin so these patients had melatonin shortage
And we also treated these patients by melatonin and experience very good effects in Improvement of daytime sleepiness and when you have these patients with daytime sleepiness you usually do poly sonography and we did this in these 11 patients and what we expected was that they have a sleep OB
That they had an obstructive sleep ATA due to the severe obesity and we were surprised to see that actually was only the case in very few patients most of them had hypersomnia and secondary NYY and that’s a disease which actually can be treated and is treated by using Central stimulating
Agents so the last question I would um want you to think about how many do you think how many of 567 long-term survivors of childhood grila had no problems in terms of relapses progressions neuroendocrine deficits or visual function after five years followup after diagnosis in our cohort we did this
Analysis and we were also really shocked to see that only in five patients of 567 that’s below 1% these patients had no problems at all in these terms in these criteria and based on this data I would like also to conclude that these patients have a many
Of these patients have a chronic disease which keeps them and the treating Physicians busy for years after diagnosis and treatment because many of them experience side and late side effects so let me conclude child Adon is can be diagnosed or can be suspected when the growth rate is very
Early on decrease so that’s an early symptom of this disease which usually which normally can also cause by many other diagn by many other diseases but in our code it was symptomatic for patients with hypothalamic involvement that they had a very early decrease in height velocity combination of growth
Headache and vision and also diabetes inhibits is something very typical in the history of these patients we recommend treatment in a way that that this treatment should be um performed in a hypothalamus bearing strategy we know that the prognosis of these patients is impaired du to neuroendocr especially
Hypothalamic obesity what I have not mentioned is that there should be further research in targeted therapy and and also molecular finings in these patients which opens up New Horizons for treatment and I think what’s really important is that all treatment teams should be EXP experience and also multidisciplinarity of these
Teams should also be the case I would like to thank you for your attention and I would like to thank the patients and that’s before the pandemic situation they met every year at a place at a very very quiet and nice place and you can see here that in such a meeting
Sometimes over 100 patients met and they want to know what’s new in the area and they have important questions and many of our Publications they are based on a question which was asked during such a meeting and then we said we will analyze it and then two to three years later we
We gave them the answer and that that is something very very um satisfying when when patients have problems and you can solve or can answer the problems and can help them so once again thank you very much for your attention and uh I’m happy to answer your questions thank you Oh thank you sir for this great lecture it was uh very informative and I think that this is one of the best lectures that I have heard for cral fora you you have given us very uh wide view about the treatment and symptomatology and uh I really thank
You you’re welcome so uh before uh going to ask the uh questions from the participants I I would like to ask myself one question um do you think that this proton beam therapy is the future of the of the uh treatment of this car foras because not every country has a high
Economy like Germany for example in Bulgaria there is no proton beam therapy what should we do should we send these patients to Germany or we should beam them in uh countries in lwi income countries I I have to confess that let’s say five years ago we had also no
Opportunity to to treat all these patients because in Germany we have we had only three three hospitals who could provide this treatment and it was very cost intensive and there was not enough space nowadays we have more places let’s say and almost 20 years ago when we had very
Severe cases where everybody said this should be treated very very precisely then at that time we sent them to Boston and we sent them to Paris that that was okay but nowadays we have the the following attitude we think that we want to analyze this scientifically we want to know the the
Answer that of your for your question when you ask what is better do do we recommend proton beam therapy then you have to analyze it so what we do we think we treat these patient now and we hope that we can give the answer during the next years whether there is an
Improvement in prognosis on the other side not everybody is we recommend treatment in this proton beam facilities but we have patients where based on social and economical um reasons we we say no it’s not necessary to treat it by protom therapy because the irradiation effect is 100% similar when you do Photon and
Proton the the the effect on the tumor is similar but we hope that we could show after 10 years or 20 years that the rate of second malignancies for instance is lower and that maybe the the the the damage of any Optical functionality might be improved but that’s that’s an
Hypoth hypothesis which should not lead to the conclusion that everybody should know use proton be therapy I think there are some cases when it’s really it’s really useful to think about using it and then you should think about sending the patients to somewhere else some other places but not every patient needs
It and most of the patients are also very sufficiently treated by Photon therapy by the conventional phot thy thank you very much sir uh so I I will start to uh ask the questions from the participants yeah please can you add your uh names and hospitals please so first nit
Tambay uh he says it was interesting and good good presentations congratulations so he has contribution beas augus he says thank you very much Professor Miller for sharing your important and excellent work with us another contribution from Gela Ramirez she she says thank you for amazing lecture Professor Miller
Okay I will wait a little bit for our participants to write down their questions perhaps I I have a question uh in Germany we we have a problem which I I don’t know whether it’s an international problem in Germany we have many many hospitals and the system is not centralized
So and that’s that’s not bad you know I live at aldenberg when when when when in Germany only patients could be treated at Munich or Berlin all these patients have to travel huge distances and I think in in Turkey it would be even far longer distances so I want to know how
Many centers are taking care of these patients have you centralized the surgical service or or do you have in in special for each area a hospital or is it localized treatment I think that Professor suju can ask the better question can answer Professor suu I think that he’s not here selin are you
Here yes I I couldn’t find uh his name okay I think that you are the next best person who can answer this question it’s okay no problem problem no problem uh I can give an example because I live in Bulgaria yeah I’m not in Turkey so in Bulgaria we have very big
Problem because we don’t have uh one national uh children hospital so it is like in Germany the same so patient comes in one hospital for surgery he goes in another hospital for uh in the in theologist he goes in third hospital for radiation so it’s the same there is no
Centralization the hypothesis is that when you centralize it as it is done now in the Netherlands they have only one one hospital for treatment of all patients with with tumors and brain tumors and then it’s centralized it’s high standard but the it it also has problems for the quality of life of the
Families because uh they have to yeah they have to move they when it takes two years the treatment or one year they have to move one year for another place and that’s not that easy to to to accomplish for All Families yes there is one question from unidon he says thank
You very much for your great lecture how you can make your total or incomplete ex exision can you decide before surgery or you decided in surgery are you Pro for gross total or not actually um I I’m not a neurosurgeon I I always have to depend
On the the opinion and the advice and recommendation of the Specialists and the Specialists are the neurosurgeons but based on our data I think in in Germany and and and in the in people who who read this data they come to the to the conclusion that it’s really and
They’re doing it’s really important to have a special look at the Imaging before you start surgery to know whether this is a patient with high risk of hypothalamic damage when you do a radical reection and based and beside this and I know this and everybody tells me the final decision how to do
Operation and how much to resect is always taken intraoperatively there are so many things which you cannot see on the Imaging which you experience during surgery in in the during surgery which you have to reflect and that’s based on this you have to decide when to stop surgery and
How to progress with the the the reection I’m in I’m um I’ve seen many patients with wonderful Imaging after surgery there no no more tumor could be seen and uh the problem is that the Imaging is very nice and if it is a malignant tumor that’s a very good result because in a
Malignant tumor when you have removed all tumor MKS then the patients have a better prognosis but in Craner Juma when you have a beautiful Imaging MRI after surgery showing no more tumor at all and the hypothalamus and theut is gone then the patient has lifelong problems and uh then then that’s no
Not yeah that’s a that’s a Pity that in spite of such beautiful Imaging the prognosis is very bad so I’m in favor of a responsible procedure in terms of reection especially in patients where we know before surgery that they have an involvement of the hyp
Thus thank you for very much sir and I would and uh I always say when there is a residual tumor you should wait whether this residual tumor grows again and when it grows again and you have no no no opport or you have no chance to remove it completely then do
Irradiation really then do irradiation that’s better and tolerable for the patient and the prognosis thank you very much uh n he says please Professor is it possible to send me the support of this presentation to my inbox you can write to the professor Miller email and yeah
Um did you find my email that’s no problem just send me an email you and I will returnin it with with these slides they you can even send them on email they are not such big that you need a Dropbox or so yeah uh there is answer to your question Professor Miller
From what I also can do perhaps one of you when I send it to one of you and you can distribute it to to your colleagues you know who might be interested interested in it yeah okay thank you very much Professor there is a answer to your question actually Professor Miller from
Beus he says the problem is the same in Turkey yeah there are a lot of centers taking care of such patients the biggest Center ISE Children Hospital yeah um it’s I think in any case in Germany I I realized that it’s difficult when these patients come and they have
Hydros they have headache they they’re in really bad condition then it’s a also it’s in terms of emergency that you you don’t have the time to to say let’s transfer these patient so mainly they come and they get operated during the same day or night um but and we we have
50 recruiting centers and 51 operating centers so that’s a huge amount of and when we know that we have only 20 new cases per year then it’s clear that in these 50 Neurosurgical hospitals they will operate only one patient in five years or 10 years one kid with Granny F
Juma and uh whenever you have so low case numbers then it I think the question is not you can ask the question whether then the experience is always the same when you do it every month you have more experience when you do it once in five years I think everybody will
Will agree with this yeah personally I I agree with you I will not touch our patient with CR for I would send him to a better surgeon than me yeah but on the other side you know in Germany people say they they need to do education they have to learn
It and they need it also for their examination they have to prove that they have done surgery in in so so many cases so many many you have to say when when we send these patients away to other hospitals we lose our our capability to educate and uh
That’s also an argument you know I can understand that the boss of a hospital he also needs to to to be yeah successful yes War C is very important concept that we have to keep in mind I agree with you yeah okay I I do not see any more questions in the
Chat part so Professor suju he’s on the road I think that he has no internet ah he’s back I see him trve safe yes yeah Professor suu I would like to give you the final words s you Canute unmute him I couldn’t find him he’s here hi okay okay
Yes I want to thank you again soin said I am still driving thank you so much thank you was it was a pleasure to to give a talk and uh yeah okay sir thank you it was very nice to have you here and we would like to
Hear more from you about the treatment of CR CR for in the future would be happy I would be happy to do this okay thank you very much stay healthy bye-bye why why