Craniopharyngiomas in children: the pendulum moves again for an aggressive surgery. Late complications and considerations with a recent series of 26 patients treated in Lyon

Craniopharyngiomas in children: the pendulum moves again for an aggressive surgery. 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Late complications and considerations with a recent series of 26 patients treated in Lyon pierre-aurélien beuriat, alexandru Szathmari, federico Di Rocco, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5383509/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Apr, 2025 Read the published version in Child's Nervous System → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Craniopharyngioma (CP) surgery in children leads to high rate of recurrence, and morbid complications. Transcranial approach is the most frequently proposed surgical technique, but transsphenoidal endoscopic approach is also used. Pre and post-operative complications of the tumor are well known, but early multidisciplinary management could improve the long-term outcome of these patients. The aim of this study was to analyze the risk factors for pre-and post-operative long-term complications in a series of patients operated with an aggressive removal for CP. Methods: A retrospective study of 26 children diagnosed with CP was carried out. The surgical total removal was possible in 88% of cases after the revision of the post-operative MRI realized in the first 48 hours. Results: Children with hypothalamic involvement were more likely to have endocrine deficits and to be overweight or obese pre-operatively. They also had a higher risk of early post-operative complications, and late morbidities. Conclusion: Children with CP and strong hypothalamic involvement, have a higher risk of pre and post-operative complications but complete removal is associated with an high rate of cure with global good neuropsychological results. Early multidisciplinary post-operative management should be reinforced to improve the long-term outcome but surgery with total removal can insure definitive acceptable clinical results. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Craniopharyngiomas is a rare benign tumor developping from neuro epithelial remnants of the Ratkhe pouch that is a remnant of the primitive pharynx [ 1 – 5 ]. Gaining surgical experience in craniopharyngioma surgery is difficult and surgical results are characterized by a high rate of sequelae preventing patients from having a good quality of life with worsening of the initial clinical picture [ 6 – 8 ]. The sequels of surgery are characterized by visual and endocrinological disturbances, motor and intellectual impairment. Actually, the important improvement of diagnostic radiological tools with more efficient MRI; more efficient surgical tools, like the neuronavigation guidance system, the Cusa Cavitron , the endoscopic improved vision and overtime, the significant improvement of the quality of paediatric anaesthesia, have permitted the improvement of clinical results. With current progress, several different strategies have been possible: a complete surgical removal, a partial removal followed by radiotherapy, intracystic treatment with local chemotherapy or gamma knife irradiation [ 1 , 2 , 6 – 12 ]. Our own strategies for management of craniopharyngiomas changed over the past 20 years and we moved from a surgical aggressive treatment in the years eighty, to an intracystic chemotherapy with bleomycine, and more recently, with alpha interpheron for cystic craniopharyngiomas, reserving a surgical direct removal only for solid and calcified tumors or in cases of failure of the previous treatment. Of great importance is the multidisciplinary management of children with the diagnosis of craniopharyngioma for the management of hormonal, hypothalamic and visual sequels and for the surgical follow-up. We report the results of a last series of 26 paediatric patients with CP from Lyon, operated during the last 10 years with the aim to realize a total surgical removal. We analysed the factors influencing post-operative complications and long-term management strategies in patients treated with the pendulum of the surgical removal again oriented through an aggressive surgery. Material and methods Study design Twenty-six pediatric patients with CP who underwent a first surgical resection at the Department of Paediatric Neurosurgery of the Women Mother Child Hospital of Lyon (France) between January 2010 and July 2023 were included in the present study and retrospectively analyzed. Parents of children have been informed of the study by mail and could refuse to participate. The charts of the included patients were reviewed retrospectively. The study was approved by the Clinical Research Ethics Committee of the hospital (CSE-HCL – IRB 00013204; N°21_641) The study was conducted at the paediatric neurosurgery and endocrinology department, neurosurgical ward and histological results were reviewed at the Pathological department and patients' files were retrieved from the records departments in the Mother and Child Hospital in Lyon-Bron, France. The follow-up varied from 1 year to 11 years after treatment. Records of retrospective patients were retrieved. Inclusion/exclusion criteria Inclusion criteria All patients with confirmed diagnosis and admitted with craniopharyngioma in the Woman Mother and Child Hospital in Lyon during the study period Exclusion criteria Patients outside the above inclusion criteria Patient not operated within the Mother and Child Hospital in Lyon Data collection Preoperative data including age at diagnosis, sex, height, weight, Body Mass Index (BMI) and International Obesity Task Force (IOTF), clinical presentation, diabetes insipidus were considered. All patients had complete hormonal assays at diagnosis to evaluate if they have growth hormone (GH) deficiency (confirmed by IGF1 level <-1DS and inhibition of growth velocity or insufficient GH secretion after pharmacological stimulation), central hypothyroidism (Decrease free T4 level without an appropriate elevation of TSH concentration), central adrenal insufficiency (Decrease level of cortisol at 8 a.m.). In case of pubertal age, they have LH, FSH and sex steroids assays. MRI tumor characteristics (classification, maximal diameter, prior drainage of cyst, hydrocephalus) were collected. All pre-operative MRIs (with and without gadolinium) have been reviewed by an independent radiologist who determined the grade of the tumor according to the Puget classification [ 13 ]. All patients had pre-operative ophthalmological evaluation with visual field, visual acuity and the fundus of the eye. Treatment: surgical and medical data were also extracted from the charts Preoperative treatment, prior drainage of cyst, surgical route macroscopic total or partial resection were collected from the study of the operative chart and the study of the first post-opertive MRI realizated in the first 48 hours post-operatively. Patients with hydrocephalus first had VP shunt before the surgical direct approach. Patients with preoperative cortisol deficiency and thyroid hormone deficiency were supplemented. Two surgical approaches were realized: transcranial or transsphenoidal approach, according to the preoperative MRI observation. Follow up: the patients were followed up at 1, 6 months and 1 year, 2 years, 5 and ten years. Endocrine hormone assays, auxological data, and imaging examinations were performed at each follow up visit. Pituitary deficiencies, tumor recurrence were collected. The term CP recurrence refers strictly to the evidence of tumor on neuroimaging studies after the evaluation of the complete surgical resection with the study of the post-operative MRI and of the operative chart and the negative postoperative follow-up with MRI study. Neuropsychological assessments were carried out on the children at a distance from the surgery and collected in the article. Children under 16 years of age were tested with the WISC V scale of intelligence and children above 16 years of age with the WAIS IV. The same tests were used the verbal memory, the early memory system, the late memory and the late recognition, Attention test and quality of life questionnaire. Statistical Methods Descriptive statistics were produced. Frequency of interested data has been expressed in percentage. Results 26 patients were treated from January 2010 to July 2023 for a craniopharyngiomas. The age was comprised between 18 months to eighteen years old with a median age at the moment of the diagnosis of 6,8 years. The follow-up varied from one year to 11 years with a median follow-up of 5,2 years 11 patients were females (42%) and 15 were males (58%). Symptoms at diagnosis: 12 patients (46%) presented neurological symptoms of intracranial hypertension, 5 (19%) ophthalmological troubles, 8 (30%) presented growth failure and 6 (23%) had a clear obesity. In one patient, the diagnosis was an incidental discovery (deafness report). From endocrinological point of view, 17 children (65%) presented a growth hormone deficiency, 11 (42%) a thyrotropic deficiency, 10 (38%) an ACTH deficiency, 7 (14%) a gonadotropic deficiency, and 3 (11%°) had diabetes insipidus before surgery. According to the classification of Puget, the MRI showed 6 patients in type 0, 9 in type I and 11 patients in type 2. The pre-operative ophthalmological consultation showed an amputation of the visual field in 16 patients (53%) and an achievement of the visual acuity in 14 patients (53%). Six patients (23%) were treated before the surgical approach with intracystic alpha interferon, that was effective at the beginning for all patients, but after all, escaped to the treatment and surgery was decided. The median delay between the treatment and the surgical resection, related to progression of the tumor, was of three years varying from one year in three patients to five years in two patients. In two patients the surgical removal was realized after four years 25 patients (96,2%) were submitted to a surgical procedure by a trans cranial approach while a trans sphenoidal approach was realized in one patient (3,8%). 9 patients (34,6%) had a VP shunt for an active hydrocephalus before the approach to the tumor. The surgical resection was evaluated by surgeons and a radiologist with a post- operative MRI realized in the first 48 hours after the resection: it was complete in 22 patients (88%) and partial in 4 patients (22%). Genetic and molecular characterization All our cases were reviewed by a paediatric pathologist and all were of adamantine type. The genetic study showed in only four cases the expression of B-catenin and in two cases the mutation of the CNNBI coding for the B-catenin that is normally expressed in the adamantine form. Treatment after surgery Six patients (23%) were treated with proton therapy: two patients in whom the post-operative MRI showed a little residual nodule in the sellar region and four patients after a recurrence treated with a surgical resection, in two cases by a transphenoidal endoscopic approach and by transcranial approach in the others two. Short term complications After surgery, 88% of patients had GH deficiency, 96% had thyrotropin deficiency and one patient had ACTH deficiency (14%). Diabetes insipidus was present in 96% of cases. 17 patients presented in the post-operative course a tri-phasic hydro –electrolyte dysfunction characterized by an initial diabete insipidus, a syndrome related to a realising of antidiuretic hormone followed by a persistent diabetes insipidus [ 14 ]. 8 (30,7%) patients presented isolated and persistent diabetes insipidus and 2 patients presented a salt wasting syndrome with a further decrease in sodium concentration about 10 days after surgery. Three patients operated on for recurrence again presented with a triphasic syndrome similar to that following the first surgery. Long term evolution 6 (23%) patients had recurrence during the follow up and 4 had a rapid second surgery: the recurrences occurred 4months, 6months, 8 months, 1 year, 2 years and 4 months and 4 years and 6 months after first surgery. 4 patients had post operatory ophthalmologic complications. From the endocrinological point of view: one year after surgery, 25 patients (96%) had GH, ACTH and TSH deficiency, 10 (38,4%) had hypogonadism and 25 (96%) had DI. Overweight and Obesity At diagnosis: 27% were already overweight, 8% obese, i.e. 35% were overweight and obese. Six months after surgery: 17% were overweight and 33% obese (26 patients), i.e. 40% overweight and obese. After 1 year: 20% were overweight and 36% obese (24 patients), i.e. 56% overweight and obese; then after 2 years, 18% of the patients were overweight and 32% obese (23 patients), i.e. 50% overweight and obese after two years. So the number of overweight or obese patients increases after surgery at 6 months (from 35–40% at 6 months, then 56% at 1 year). At 2 years, there was a discret decrease from 56–50%; Neuropsychological evaluation 25 patients (96%) attended a normal or adapted school, while one patient was not yet of school age. 22 patients (84%) followed a normal school program and three patients were able to follow a normal program with assisted scholar help. 15 patients were examined and underwent neuropsychological evaluation between November 2022 to February 2024. They were tested with the Wechsler intelligence scale (WIPPSI IV (N = 1); WISC V (N = 13) or WAIS IV (N = 2) according to age to evaluate processing speed, fluid reasoning, verbal comprehension, working memory and global intelligence. All patients had index scores in the normal range. Patients were also given an attention test (ZOO map, BADS and Tea-ch (score! and sky search), which they all completed without difficulty. 2 patients had difficulty for BADS test. For the memory assessment (Children memory scale or RLRI 16 test (French adaptation of the Free and Cued Selective Reminding Test), 3 out of 7 patients had a deficit score (42%). These patients were also given questionnaires. Concerning anxiety (Hospital Anxiety and Depression scale), only one patient in five had a pathological score (20%). For quality of life (PedsQL Wellbeing) we received responses from 13 patients with good results in 75% of cases and 15% pathological for the overall score. 3 children out of 13 (23%) had pathological scores for psychosocial and psychophysical quality scores (2 only physical health, 2 only psycho social deficits and only one patient had both). For the fatigue scale (Peds QL Fatigue), 3 out of 12 patients had a pathological fatigability score (25%). With the Behaviour rating inventory of executive function (BRIEF), we found for 11 patients: 4 pathological scores for the emotional control subtest (36%), 3 deficits to start an action “initiation activity” (27%), 5 pathological scores for task control (45%). And 5 out of 12 deficits scores for metacognition condition (knowledge of one’s own competence and abilities) (41%), and 4 out 12 patients (33%), for flexibility (ability to switch from one task to another). Emotional control was also difficult for 4 out of 12 patients (33%). Discussion Treatment of CP still remains a challenge for neurosurgeons and especially for paediatric neurosurgeons. Results of large series published over the last twenty years showed visual troubles in 70% of patients, endocrine problems in 95%, neuropsychological troubles in 50% patients, and the incidence of recurrences in 25% of cases [ 15 ]. Thomson reported a ten-year survival rate in 69% of cases, an incidence of diabetes insipidus in 80% of cases, a rate of obesity and appetite disorders in 15% of cases, and a mortality in 10% of cases [ 16 ]. Thomson underscored better results before and after the years 1996 with the advent of major technological advances. For Zuccaro endocrine deficits were reported in 87% of cases, neurological complications in 4% of cases, and a mortality in 7% of patients. Of the 55% of patients with pre-operative visual disturbances, only 12% of cases had normal visual acuity after surgery [ 17 ]. While to-day surgery remains a very important step for treatment, their deep location and the presence of important anatomical structures such as the optic pathways, the hypothalamus and the carotid and basilar arterial system and the pituitary gland and the pituitary stalk are responsible for clinical sequelae [ 15 – 17 ]. Many surgical approaches have been proposed in the recent years but the main problem remain related to the pendulum of the surgical removal moving from a complete removal to a partial removal followed by radiotherapy to decrease the rate of sequelae. Many authors advocate a complete surgical removal [ 16 , 18 – 24 ]: a benign tumour completely removed provides the best chance of durable cure and of disease control with an acceptable quality of life [ 4 ]. A complete removal increases the survival rate on the contrary of an partial resection, mainly if the tumour size is giant as frequently in paediatric cases and also the presence of hydrocephalus or a VP shunt have a significant impact not only on overall survival but also on progression free survival [ 4 ]. After surgery lesions of the antero-medial and lateral region of the hypothalamus, controlling satiety and food intake, can cause hyperphagia and loss of the circadian rhythm of food intake increasing obesity or in some cases, loss of appetite resulting in refusal to eat, which can lead to the death [ 8 , 25 , 26 ]. The role of hypothalamus in determining cognitive and behavioural impairment has also been emphasized [ 8 , 25 , 26 ] and consequently to reduce hypothalamic lesions, has pushed to avoid a complete removal at all costs and to realize a more conservative attitude partial removal followed by radiotherapy. Many centres stressed the high rate of disease control with partial resection followed by radiotherapy apologizing results at least as good as those of complete removal in terms of survival but associated with a better quality of life [ 3 , 27 – 35 ]. Zuccaro reported that patients with total removal were able to attend school whereas only 62% of patients who underwent sub-total removal followed by radiotherapy were able to attend school [ 17 ]. Di Rocco stressed that all patients treated with radical surgical removal showed clinical improvement and that all of the 54 patients operated on, except two, presented a good quality of life [ 15 ]. In contrast, no significant difference was observed in 5 and 10 years’ overall survival and progression –free survival between GTR and STR followed by adjuvant therapy [ 36 – 38 ]. In cases of sub-total resection, the role of adjuvant radiotherapy is very important because a sub-total removal without adjuvant therapy ensures poorer overall survival and progression free survival than when combined with radiotherapy, with an associated high rate of recurrences as in 63% of cases [ 36 – 38 ]. The revision of our last series showed that patients were treated with an aggressive surgical attitude with a rate of complete removal in 88% of patients. The surgical approach was trans cranial in 96% of cases for the extension of the tumor and its volume; trans nasal trans sphenoidal endoscopic in only one case because the tumor was intra sellar and suprasellar strictly on the mid line. Complete removal, in experimented hands, permits the cure of this benign tumor with good results avoiding radiotherapy. This attitude of an aggressive surgical removal of CP was encouraged because, alternative strategies, that we have preconized like local intracystic treatments, with bleomycin and interpheron alpha, were not available because bleomycin is toxic for the CNS and the interferon alpha was no more available for intracystic use. Radiotherapy in treatment of Craniopharyngiomas Radiotherapy following surgery for treatment of CP has been recommended and many authors reported favourable results in 2/3 of patients [ 39 ]. Radiotherapy is not deprived of complications: paediatric patients present social and emotional functioning lower than a control group, difficulties for learning, difficulties for behavioural control and problems for controlling emotions and concerns for physical appearance as reported by Heinkes [ 40 ]. Radiotherapy become in the last years the standard of care in case of subtotal removal [ 38 , 41 ] and the new technologies have permitted to improve the dose conformity and to reduce the doses of irradiation to the adjacent structures: hypothalamus, optic pathways, the pituitary gland, the carotid arteries and the medial temporal structures. Conformational radiotherapy, proton therapy, intensity modulated radiotherapy and fractionated stereotactic radiotherapy have been used to reduce the risk of sequels [ 42 ]. The use of stereotactic radiosurgery for lesions of small volume has also been proposed with cautious because high dose applied in a single dose can be responsible of lesion of vital structures [ 42 , 43 ]. Only 6 patients of our series treated for a recurrence have been treated with a surgical resection followed by proton therapy to decrease the doses on nervous and vascular structures and it seems us better to avoid radiotherapy when a complete surgical resection is possible [ 32 ]. Molecular pathology In the last years also craniopharyngiomas have made the object of molecular studies with the aim to find targets that could permit a tailored effective medical treatment that could represent an alternative to surgery in the next future. Two different subtypes of craniopharyngiomas have been described the adamantinous (ACPs) predominant in paediatric cases and the papillary craniopharyngiomas (PCPs). The average age of incidence is regulated by two pic of age, one between five to twelve years old in children and another, in adult patients, between 50 to seventy years old [ 7 ]. Papillary CP occur rarely in paediatric age and account for 11–14% of CP and the average of diagnosis is between 44 +/- 15 years and have a better five years’ survival rate and a less aggressive disease behaviour [ 44 ]. The genes involved in the pathogenesis of the tumor and that can be conditioned by medical treatments have been studied. In ACPs the Wingless pathway (WNT pathway) activation seems to be regulated by the gene CTNNB1, encoding B-catenin that are activated in more than 2/3 of tumors in recent studies [ 45 ]. In other patients also the MAPK/ERK pathway has been demonstrated opening novel therapeutic strategies with the suppression of this pathway with chemical agents like MEK inhibitor trametinib [ 46 ]. In PCPs the sub groups BRAF V600E mutation has been found in 90% of cases [ 45 , 47 ]. The BRAF system is a proto-oncogene encoding serine-threonine kinase involved in growth factor signalling and regulation. Its mutation results in an active form that promotes the cell proliferation and tumor growth. These mutations in PCPs pushed to treat some patients with targeted therapy in cases of recurrences or for reducing the volume of the tumor [ 47 , 48 ]. The expression of the Beta catenin was present in four of our patients and in one the mutation of the gene CNNBI that code for the Beta catenin. The genetic studies can be useful for cystic types to reduce their volume or for papillary types in case of huge recurrences in adults but, until now, there are no treatments effective for the cure of paediatric craniopharyngiomas Intracystic chemotherapy We reported our experience with intracystic chemotherapy for craniopharyngiomas [ 49 ]. At the beginning, the treatment was realized for cystic recurrences and successively, after the good results obtained,also for primary cystic form of craniopharyngiomas. Bleomycin, and successively, interferon alpha were injected locally after the implantation of an Ommaya reservoir [ 49 ] The implantation of the reservoir was realized with a direct approach because the aim was to remove the tumor at the end of the treatment disposing of the way already open. Successively with the good results obtained, the surgical removal was judged useless and consequently the reservoir was implanted with endoscopic or stereotactic technique. The endoscopic technique was realized in presence of large ventricles while the stereotaxic technique was more useful in cases of slit ventricles. The first drug used was bleomycin, introduced by Umezawa in treatment of cerebral cystic lesions [ 50 ]. The first report with treatment of cystic craniopharyngiomas with bleomycine was reported by Takahashi in 1985 with good results in 7 patients [ 51 ]. Broggi and Lapras and Mottolese also reported preliminary good results.[ 49 , 52 ]. The toxicity of bleomycine for the CNS needed a watertight closure of the Ommaya system before to start the treatment. The action of the bleomycine was at level of the lattico-deidrogenasis system blocking the duplication of the DNA and consequently inducing the death of the cells [ 49 ] with satisfying results [ 24 ]. We reported a severe complication with the injection of a toxic doses of the drug responsible of blindness in a patient and we stopped its use and, after the experience of Di Rocco [ 15 ] and Cavalheiro [ 53 ], we started the use of interferon alpha. Interferon alpha is not toxic to the central nervous system (CNS) but its effects are limited in duration. However, the treatment is sufficiently long enough to delay the need for surgery, which subsequently delays the worsening of pituitary insufficiency and the onset of post-surgical complications. Preserving endocrine function can be a medium-term goal, as it helps to reduce the pressure on neighboring nervous structures. However, reversibility of the existing signs of pituitary insufficiency has not been observed. We have treated 7 patients with cystic craniopharyngiomas with interferon alpha. The median delay between the treatment and the surgical resection, related to progression of the tumor, was of three years varying from one year in three patients to five years in two patients. In two patients the surgical removal was realized after four years. The mechanism of action of the interferon alpha seems to be mediated by an inflammatory reaction [ 15 , 54 ]. The variable efficacy and the limited effect in time of the drug represent a matter of reflexion and could be related to different genetic tumoral constitution responsible of a programmed inflammatory reaction conditioning the response to the drug. Actually the interferon alpha is no more available for intracystic administration and consequently we were obliged to come back to a surgical removal of craniopharyngiomas. A subcutaneous injection of the peginterferon alpha-2b [ 55 ] has been proposed but we have no experience with this drug but we believe that, the possibility to dispose of more effective drugs, in the future, could completely change the strategy for treatment of craniopharyrngiomas. Surgery The surgical resection of CP is a challenge for experimented paediatric neurosurgeons. The rarity of the lesion (two new cases per millions per years in US and in France [ 56 , 57 ] and, on the other hand, the deep localization with close relationships with nervous and vascular structures make at risk the quality of life of patients. Many surgical approaches have been proposed for surgery: sub frontal, pterional, fronto temporal, sub-temporal, interhemispheric, trans callosal each of them with specific advantages and disadvantages. We prefer the sub frontal pterional approach that permits, in our experience, the exposition of the four basal triangles whose exposition is imperative to remove craniopharyngiomas mainly when they are of great volume as frequently in children. The four triangles are the opto-carotido, the retrocarotid, the interoptic triangle that, when the optic nerves are long and chiasma retro fixed, give a very large space for the dissection. The fourth triangle is delimited by the carotid bifurcation and is very interesting for removal of the upper portion of very huge tumors.(Fig. 1 ) The trans- frontal trans-ventricular approach, for craniopharyngioma resection, through the third ventricle has for us limited indications because craniopharyngiomas of the third ventricle are very rare, only 4% of cases in the series of Yasargyl [ 58 ], and because craniopharyngioma growing upwards raised the floor of the third ventricle exposing the floor to damages for the removal of the tumor. The transcallosal approach proposed by Yasargil for intraventricular tumors was used in our experience only in eight cases [ 24 ] and in no case of this last series. The opening of the lamina terminalis represents a good door to approach craniopharyngiomas when the chiasm is ante fixed in presence of short optic nerves. The dissection of CP at level of the optic pathways represents an important step of the surgical removal and the experience of the surgeon is important to preserve the functionality of the optic pathway. In our last series of 26 patients 16 patients (63%) before the surgical procedure had visual problems while after the surgery only 9 patients presented visual troubles (35%) translating the fact that in 7 patients (27%) the decompression favourited the visual improvement, while in the others patients, the decompression, cannot be effective to recover deficits appeared from long time. (Fig. 2 A and B) The lesions of hypothalamus with repercussions on the hypothalamo-pituitary axis and on behavioural troubles with difficulty to control the thirsty, the hunger, the aggressiveness, and memory and school difficulties represent also a critical problem. (Fig. 3 A and B) The lesions of the hypothalamus are not only related to the surgical dissection but also to the ischemic lesions related to the occlusion of the perforating vessels originating from the posterior communicating arteries [ 24 , 58 , 59 ]. The CP is an extra-arachnoid tumor and respecting the extra arachnoid plane of dissection it is possible to avoid problems with the dissection of posterior portion with the basilar artery trunk. The perforating vessel of the basilar trunk are headed back, in a plane posterior to that of the tumor with a posterior direction through the mesencephalon and consequently can be spared. The endoscopic approach has permitted to reduce the exposition of nervous structures for craniopharyngiomas removal favouring a great enthusiasm for it. Surgery of CP with endoscopy in children, in our opinion, should to be addressed only for lesions developing on the mid line and that remain exclusively under the diaphragm sellae without lateral extension and without the need of extended opening of the skull base and consequently it has been realized in only 4% of our cases. For huge tumors and for tumor with a lateral development the endoscopic technique is not indicated for the difficulties to close the skull base in children when an extended endoscopic approach is necessary for the high risk of infectious complications with an important rate of mortality for fulminans meningitis responsible of 8% of mortality [ 60 , 61 ]. Mazzatenta has reported a pediatric series treated with endoscopy with a rate of peri-operative mortality in 4% of cases and a rate of recurrences of 19% [ 61 ] In this last series we have treated only a patient with an endoscopic resection for a primary treatment and two patients for an intrasellar recurrence but, for us, endoscopy is very important after the microsurgical dissection to explore the operative field to discover pieces of tumors left in place that removed increase the rate of complete removal, reducing the rate of recurrences. We recommend the endoscopic exploration in each case at the end of the microsurgical resection. Recurrences The recurrences rate after the total surgical removal of craniopharyngiomas have an incidence varying from 4–30% in literature [ 21 , 57 , 62 – 65 ]. Historical experience reported a rate of recurrence after a total removal of 11% (Matson & Crigler in 1969 [ 66 ]), of 25% (Sweet in 1980 [ 67 ]), of 16% (Hoffman in 1986 [ 21 ]), of 4% (Symon and Sprych reported in 1985 [ 68 ]), and of 16% [ 24 ]. Osborn showed a proportional relationship between recurrences and the volume of the tumor: for tumor with a diameter inferior to 5 cm. the rate of recurrences was of 20% while for tumor with a diameter > to 5 cm. the rate of recurrence increased to 80% [ 69 ]. In our last series, the recurrence rate after a total removal was of 20%. 4 patients with a residual volume after the first surgery were treated with a new surgical procedure in two cases by a trans-sphenoidal and with a transcranial approach for the other two, to obtain a complete removal followed after by proton therapy. All these cases did not show a new progression after a median follow-up of 3 years. In our last series 19 patients have been treated with only surgery: the complete removal of craniopharyngiomas can be the aim of surgery because a complete removal of a benign lesion permits a definitive cure of patients also if associated with endocrinological, visual and behavioural troubles. The good neuropsychological evolution of our patients with surgical complete resection confirms that also large craniopharyngiomas can be treated with only surgery. Lesions of hypothalamus can be prevented with the respect of the perforating vessels of the posterior communicating artery [ 24 ]. A meticulous atraumatic dissection at level of the hypothalamus and of the optic pathways reduce the risks of post-operative clinical aggravation. The respect of the arachnoidal sheaths guarantee the protection of vascular and nervous structures favouring a good quality of life after surgery. In our series, the high number of patients with a normal life, attending a normal school program (20 patients, 76,9%) are witnesses of the progress attained with surgery. In 15 out 20 patients, we observed a contrast between the results of their performances obtained with the neuropsychological tests, and the difficulties they encounter in daily life. The majority of these children are in great social distress, leading to withdrawal and even, in more severe cases, dropping out of school. While the main hypothesis was to explain these difficulties by cognitive deficits resulting from the children's brain damage, the data obtained suggest more socio-psychological difficulties. Indeed, children suffering from hypothalamic damage that has a direct impact on their quality of life (eating disorders, obesity, etc.) can also affect their psychological well-being. Our study also demonstrates the shortcomings in the psychological follow-up of these children and their families. Improving the follow-up of these children through group therapy, in-depth psychological monitoring, and monitoring of diet and weight management would be relevant to their care. With better care, these children could more fulfilled in their school careers. The overweight and obesity can be better taken in care using better protocols of monitoring avoiding unnecessary food intake with better social and educative programs not only for patients but also for their family. For this reason, we can be accepted that the pendulum of the surgical removal can move again, in experimented hands, towards an aggressive surgical resection until, advances in biomolecular studies, offers the possibility to switch to medical treatments based on drug administration, at the condition, to avoid serious toxicity and complications related to radiotherapy mainly in very young children. Endocrinological considerations The consequence of surgery for craniopharyngiomas is dysregulation of the hypothalamo-pituitary axis which affects 97% of patients. An early post-operative complication is triphasic syndrome. The incidence of triphasic syndrome was more frequent in our experience than in others [ 70 , 71 ]. A great deal of clinical experience is needed to avoid this phenomenon, which in the post-operative period requires to avoid very severe fluid restriction at the outset, to compensate for water loss, and which needs the cautious use of antidiuretic hormone to avoid the conflict with SIADH syndrome, which can be very dangerous for the clinical evolution of patients. We emphasize the role of paediatric endocrinologists in collaboration with the intensive care physicians in limiting the incidence and effects of this syndrome. It is true that the relationship between the tumor and the floor of the third ventricle as well as the large volume of the tumor, are significant factors in the appearance of this syndrome. The number of overweight or obese patients increases after surgery at 6 months (from 35–40% at 6 months), then at 1 year (56%). At 2 years, there was a decrease from 56–50%; The role of the multidisciplinary management (dietetic follow-up, adapted physical activity instructor, psychologist, pediatrician, pediatric neurosurgeon) introduced in our department 8 years ago seemed very important to control the overweight and obesity. (Fig. 4 ) Conclusions Craniopharyngioma remains a difficult tumor to treat in the paediatric population. The role of surgery is still a topical issue in paediatric craniopharyngiomas. It is always difficult to decide intraoperatively whether to completely remove the tumor or to stop resection and proceed with partial removal followed by radiotherapy. Surgery requires special expertise to respect nervous and vascular structures, which represent the main risk factors for sequelae and sometimes the cause of catastrophic results. Our latest cohort shows that complete resection is possible, even if associated with endocrinological (96%) and visual sequelae (23%) but with good neuropsychological evolution. Surgery in experimented hands can be the treatment of craniopharyngiomas also if the extent of resection should always be related to a pendulum that shall move in relation with the experience and the expertise of surgeons, the extension and the volume of the tumor, the possibility in the future to find effective pharmacological treatments to preserve the aggravation of function already affected when tumors are discovered. Declarations Fundings : all authors declare no conflict of interest. This work has not been funded by any means. 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16:09:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1773035,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5383509/v1/c468a5c3-cb4d-44de-b906-818b79b37e4e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Craniopharyngiomas in children: the pendulum moves again for an aggressive surgery. Late complications and considerations with a recent series of 26 patients treated in Lyon","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCraniopharyngiomas is a rare benign tumor developping from neuro epithelial remnants of the Ratkhe pouch that is a remnant of the primitive pharynx [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Gaining surgical experience in craniopharyngioma surgery is difficult and surgical results are characterized by a high rate of sequelae preventing patients from having a good quality of life with worsening of the initial clinical picture [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe sequels of surgery are characterized by visual and endocrinological disturbances, motor and intellectual impairment.\u003c/p\u003e \u003cp\u003eActually, the important improvement of diagnostic radiological tools with more efficient MRI; more efficient surgical tools, like the neuronavigation guidance system, the \u003cem\u003eCusa Cavitron\u003c/em\u003e, the endoscopic improved vision and overtime, the significant improvement of the quality of paediatric anaesthesia, have permitted the improvement of clinical results.\u003c/p\u003e \u003cp\u003eWith current progress, several different strategies have been possible: a complete surgical removal, a partial removal followed by radiotherapy, intracystic treatment with local chemotherapy or gamma knife irradiation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur own strategies for management of craniopharyngiomas changed over the past 20 years and we moved from a surgical aggressive treatment in the years eighty, to an intracystic chemotherapy with bleomycine, and more recently, with alpha interpheron for cystic craniopharyngiomas, reserving a surgical direct removal only for solid and calcified tumors or in cases of failure of the previous treatment.\u003c/p\u003e \u003cp\u003eOf great importance is the multidisciplinary management of children with the diagnosis of craniopharyngioma for the management of hormonal, hypothalamic and visual sequels and for the surgical follow-up.\u003c/p\u003e \u003cp\u003eWe report the results of a last series of 26 paediatric patients with CP from Lyon, operated during the last 10 years with the aim to realize a total surgical removal. We analysed the factors influencing post-operative complications and long-term management strategies in patients treated with the pendulum of the surgical removal again oriented through an aggressive surgery.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eTwenty-six pediatric patients with CP who underwent a first surgical resection at the Department of Paediatric Neurosurgery of the Women Mother Child Hospital of Lyon (France) between January 2010 and July 2023 were included in the present study and retrospectively analyzed. Parents of children have been informed of the study by mail and could refuse to participate. The charts of the included patients were reviewed retrospectively. The study was approved by the Clinical Research Ethics Committee of the hospital (CSE-HCL \u0026ndash; IRB 00013204; N\u0026deg;21_641)\u003c/p\u003e \u003cp\u003e The study was conducted at the paediatric neurosurgery and endocrinology department, neurosurgical ward and histological results were reviewed at the Pathological department and patients' files were retrieved from the records departments in the Mother and Child Hospital in Lyon-Bron, France. The follow-up varied from 1 year to 11 years after treatment. Records of retrospective patients were retrieved.\u003c/p\u003e \u003cp\u003eInclusion/exclusion criteria\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eInclusion criteria\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eAll patients with confirmed diagnosis and admitted with craniopharyngioma in the Woman Mother and Child Hospital in Lyon during the study period\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eExclusion criteria\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePatients outside the above inclusion criteria\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ePatient not operated within the Mother and Child Hospital in Lyon\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePreoperative data including age at diagnosis, sex, height, weight, Body Mass Index (BMI) and International Obesity Task Force (IOTF), clinical presentation, diabetes insipidus were considered. All patients had complete hormonal assays at diagnosis to evaluate if they have growth hormone (GH) deficiency (confirmed by IGF1 level \u0026lt;-1DS and inhibition of growth velocity or insufficient GH secretion after pharmacological stimulation), central hypothyroidism (Decrease free T4 level without an appropriate elevation of TSH concentration), central adrenal insufficiency (Decrease level of cortisol at 8 a.m.). In case of pubertal age, they have LH, FSH and sex steroids assays.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMRI tumor characteristics (classification, maximal diameter, prior drainage of cyst, hydrocephalus) were collected. All pre-operative MRIs (with and without gadolinium) have been reviewed by an independent radiologist who determined the grade of the tumor according to the Puget classification [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAll patients had pre-operative ophthalmological evaluation with visual field, visual acuity and the fundus of the eye.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTreatment: surgical and medical data were also extracted from the charts\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePreoperative treatment, prior drainage of cyst, surgical route macroscopic total or partial resection were collected from the study of the operative chart and the study of the first post-opertive MRI realizated in the first 48 hours post-operatively. Patients with hydrocephalus first had VP shunt before the surgical direct approach.\u003c/p\u003e \u003cp\u003ePatients with preoperative cortisol deficiency and thyroid hormone deficiency were supplemented.\u003c/p\u003e \u003cp\u003eTwo surgical approaches were realized: transcranial or transsphenoidal approach, according to the preoperative MRI observation.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFollow up: the patients were followed up at 1, 6 months and 1 year, 2 years, 5 and ten years. Endocrine hormone assays, auxological data, and imaging examinations were performed at each follow up visit.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePituitary deficiencies, tumor recurrence were collected.\u003c/p\u003e \u003cp\u003eThe term CP recurrence refers strictly to the evidence of tumor on neuroimaging studies after the evaluation of the complete surgical resection with the study of the post-operative MRI and of the operative chart and the negative postoperative follow-up with MRI study.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eNeuropsychological assessments were carried out on the children at a distance from the surgery and collected in the article. Children under 16 years of age were tested with the WISC V scale of intelligence and children above 16 years of age with the WAIS IV. The same tests were used the verbal memory, the early memory system, the late memory and the late recognition, Attention test and quality of life questionnaire.\u003c/p\u003e\n\u003ch3\u003eStatistical Methods\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eDescriptive statistics were produced. Frequency of interested data has been expressed in percentage.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e26 patients were treated from January 2010 to July 2023 for a craniopharyngiomas. The age was comprised between 18 months to eighteen years old with a median age at the moment of the diagnosis of 6,8 years. The follow-up varied from one year to 11 years with a median follow-up of 5,2 years\u003c/p\u003e \u003cp\u003e11 patients were females (42%) and 15 were males (58%).\u003c/p\u003e \u003cp\u003eSymptoms at diagnosis: 12 patients (46%) presented neurological symptoms of intracranial hypertension, 5 (19%) ophthalmological troubles, 8 (30%) presented growth failure and 6 (23%) had a clear obesity.\u003c/p\u003e \u003cp\u003eIn one patient, the diagnosis was an incidental discovery (deafness report). From endocrinological point of view, 17 children (65%) presented a growth hormone deficiency, 11 (42%) a thyrotropic deficiency, 10 (38%) an ACTH deficiency, 7 (14%) a gonadotropic deficiency, and 3 (11%\u0026deg;) had diabetes insipidus before surgery.\u003c/p\u003e \u003cp\u003eAccording to the classification of Puget, the MRI showed 6 patients in type 0, 9 in type I and 11 patients in type 2.\u003c/p\u003e \u003cp\u003eThe pre-operative ophthalmological consultation showed an amputation of the visual field in 16 patients (53%) and an achievement of the visual acuity in 14 patients (53%).\u003c/p\u003e \u003cp\u003eSix patients (23%) were treated before the surgical approach with intracystic alpha interferon, that was effective at the beginning for all patients, but after all, escaped to the treatment and surgery was decided. The median delay between the treatment and the surgical resection, related to progression of the tumor, was of three years varying from one year in three patients to five years in two patients. In two patients the surgical removal was realized after four years\u003c/p\u003e \u003cp\u003e25 patients (96,2%) were submitted to a surgical procedure by a trans cranial approach while a trans sphenoidal approach was realized in one patient (3,8%). 9 patients (34,6%) had a VP shunt for an active hydrocephalus before the approach to the tumor.\u003c/p\u003e \u003cp\u003eThe surgical resection was evaluated by surgeons and a radiologist with a post- operative MRI realized in the first 48 hours after the resection: it was complete in 22 patients (88%) and partial in 4 patients (22%).\u003c/p\u003e\n\u003ch3\u003eGenetic and molecular characterization\u003c/h3\u003e\n\u003cp\u003eAll our cases were reviewed by a paediatric pathologist and all were of adamantine type. The genetic study showed in only four cases the expression of B-catenin and in two cases the mutation of the CNNBI coding for the B-catenin that is normally expressed in the adamantine form.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTreatment after surgery\u003c/h2\u003e \u003cp\u003eSix patients (23%) were treated with proton therapy: two patients in whom the post-operative MRI showed a little residual nodule in the sellar region and four patients after a recurrence treated with a surgical resection, in two cases by a transphenoidal endoscopic approach and by transcranial approach in the others two.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eShort term complications\u003c/h3\u003e\n\u003cp\u003eAfter surgery, 88% of patients had GH deficiency, 96% had thyrotropin deficiency and one patient had ACTH deficiency (14%). Diabetes insipidus was present in 96% of cases.\u003c/p\u003e \u003cp\u003e17 patients presented in the post-operative course a tri-phasic hydro \u0026ndash;electrolyte dysfunction characterized by an initial diabete insipidus, a syndrome related to a realising of antidiuretic hormone followed by a persistent diabetes insipidus [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e8 (30,7%) patients presented isolated and persistent diabetes insipidus and 2 patients presented a salt wasting syndrome with a further decrease in sodium concentration about 10 days after surgery.\u003c/p\u003e \u003cp\u003eThree patients operated on for recurrence again presented with a triphasic syndrome similar to that following the first surgery.\u003c/p\u003e\n\u003ch3\u003eLong term evolution\u003c/h3\u003e\n\u003cp\u003e6 (23%) patients had recurrence during the follow up and 4 had a rapid second surgery: the recurrences occurred 4months, 6months, 8 months, 1 year, 2 years and 4 months and 4 years and 6 months after first surgery.\u003c/p\u003e \u003cp\u003e4 patients had post operatory ophthalmologic complications.\u003c/p\u003e \u003cp\u003eFrom the endocrinological point of view: one year after surgery, 25 patients (96%) had GH, ACTH and TSH deficiency, 10 (38,4%) had hypogonadism and 25 (96%) had DI.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOverweight and Obesity\u003c/h2\u003e \u003cp\u003eAt diagnosis: 27% were already overweight, 8% obese, i.e. 35% were overweight and obese. Six months after surgery: 17% were overweight and 33% obese (26 patients), i.e. 40% overweight and obese. After 1 year: 20% were overweight and 36% obese (24 patients), i.e. 56% overweight and obese; then after 2 years, 18% of the patients were overweight and 32% obese (23 patients), i.e. 50% overweight and obese after two years.\u003c/p\u003e \u003cp\u003eSo the number of overweight or obese patients increases after surgery at 6 months (from 35\u0026ndash;40% at 6 months, then 56% at 1 year). At 2 years, there was a discret decrease from 56\u0026ndash;50%;\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eNeuropsychological evaluation\u003c/h2\u003e \u003cp\u003e25 patients (96%) attended a normal or adapted school, while one patient was not yet of school age. 22 patients (84%) followed a normal school program and three patients were able to follow a normal program with assisted scholar help.\u003c/p\u003e \u003cp\u003e15 patients were examined and underwent neuropsychological evaluation between November 2022 to February 2024. They were tested with the Wechsler intelligence scale (WIPPSI IV (N\u0026thinsp;=\u0026thinsp;1); WISC V (N\u0026thinsp;=\u0026thinsp;13) or WAIS IV (N\u0026thinsp;=\u0026thinsp;2) according to age to evaluate processing speed, fluid reasoning, verbal comprehension, working memory and global intelligence. All patients had index scores in the normal range.\u003c/p\u003e \u003cp\u003ePatients were also given an attention test (ZOO map, BADS and Tea-ch (score! and sky search), which they all completed without difficulty. 2 patients had difficulty for BADS test.\u003c/p\u003e \u003cp\u003eFor the memory assessment (Children memory scale or RLRI 16 test (French adaptation of the Free and Cued Selective Reminding Test), 3 out of 7 patients had a deficit score (42%).\u003c/p\u003e \u003cp\u003eThese patients were also given questionnaires. Concerning anxiety (Hospital Anxiety and Depression scale), only one patient in five had a pathological score (20%). For quality of life (PedsQL Wellbeing) we received responses from 13 patients with good results in 75% of cases and 15% pathological for the overall score. 3 children out of 13 (23%) had pathological scores for psychosocial and psychophysical quality scores (2 only physical health, 2 only psycho social deficits and only one patient had both). For the fatigue scale (Peds QL Fatigue), 3 out of 12 patients had a pathological fatigability score (25%).\u003c/p\u003e \u003cp\u003eWith the Behaviour rating inventory of executive function (BRIEF), we found for 11 patients: 4 pathological scores for the emotional control subtest (36%), 3 deficits to start an action \u0026ldquo;initiation activity\u0026rdquo; (27%), 5 pathological scores for task control (45%). And 5 out of 12 deficits scores for metacognition condition (knowledge of one\u0026rsquo;s own competence and abilities) (41%), and 4 out 12 patients (33%), for flexibility (ability to switch from one task to another). Emotional control was also difficult for 4 out of 12 patients (33%).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTreatment of CP still remains a challenge for neurosurgeons and especially for paediatric neurosurgeons.\u003c/p\u003e \u003cp\u003eResults of large series published over the last twenty years showed visual troubles in 70% of patients, endocrine problems in 95%, neuropsychological troubles in 50% patients, and the incidence of recurrences in 25% of cases [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Thomson reported a ten-year survival rate in 69% of cases, an incidence of diabetes insipidus in 80% of cases, a rate of obesity and appetite disorders in 15% of cases, and a mortality in 10% of cases [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Thomson underscored better results before and after the years 1996 with the advent of major technological advances.\u003c/p\u003e \u003cp\u003eFor Zuccaro endocrine deficits were reported in 87% of cases, neurological complications in 4% of cases, and a mortality in 7% of patients. Of the 55% of patients with pre-operative visual disturbances, only 12% of cases had normal visual acuity after surgery [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile to-day surgery remains a very important step for treatment, their deep location and the presence of important anatomical structures such as the optic pathways, the hypothalamus and the carotid and basilar arterial system and the pituitary gland and the pituitary stalk are responsible for clinical sequelae [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMany surgical approaches have been proposed in the recent years but the main problem remain related to the pendulum of the surgical removal moving from a complete removal to a partial removal followed by radiotherapy to decrease the rate of sequelae.\u003c/p\u003e \u003cp\u003eMany authors advocate a complete surgical removal [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]: a benign tumour completely removed provides the best chance of durable cure and of disease control with an acceptable quality of life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA complete removal increases the survival rate on the contrary of an partial resection, mainly if the tumour size is giant as frequently in paediatric cases and also the presence of hydrocephalus or a VP shunt have a significant impact not only on overall survival but also on progression free survival [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAfter surgery lesions of the antero-medial and lateral region of the hypothalamus, controlling satiety and food intake, can cause hyperphagia and loss of the circadian rhythm of food intake increasing obesity or in some cases, loss of appetite resulting in refusal to eat, which can lead to the death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe role of hypothalamus in determining cognitive and behavioural impairment has also been emphasized [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and consequently to reduce hypothalamic lesions, has pushed to avoid a complete removal at all costs and to realize a more conservative attitude partial removal followed by radiotherapy.\u003c/p\u003e \u003cp\u003eMany centres stressed the high rate of disease control with partial resection followed by radiotherapy apologizing results at least as good as those of complete removal in terms of survival but associated with a better quality of life [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR28 CR29 CR30 CR31 CR32 CR33 CR34\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eZuccaro reported that patients with total removal were able to attend school whereas only 62% of patients who underwent sub-total removal followed by radiotherapy were able to attend school [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDi Rocco stressed that all patients treated with radical surgical removal showed clinical improvement and that all of the 54 patients operated on, except two, presented a good quality of life [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, no significant difference was observed in 5 and 10 years\u0026rsquo; overall survival and progression \u0026ndash;free survival between GTR and STR followed by adjuvant therapy [\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn cases of sub-total resection, the role of adjuvant radiotherapy is very important because a sub-total removal without adjuvant therapy ensures poorer overall survival and progression free survival than when combined with radiotherapy, with an associated high rate of recurrences as in 63% of cases [\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe revision of our last series showed that patients were treated with an aggressive surgical attitude with a rate of complete removal in 88% of patients. The surgical approach was trans cranial in 96% of cases for the extension of the tumor and its volume; trans nasal trans sphenoidal endoscopic in only one case because the tumor was intra sellar and suprasellar strictly on the mid line. Complete removal, in experimented hands, permits the cure of this benign tumor with good results avoiding radiotherapy. This attitude of an aggressive surgical removal of CP was encouraged because, alternative strategies, that we have preconized like local intracystic treatments, with bleomycin and interpheron alpha, were not available because bleomycin is toxic for the CNS and the interferon alpha was no more available for intracystic use.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eRadiotherapy in treatment of Craniopharyngiomas\u003c/h2\u003e \u003cp\u003eRadiotherapy following surgery for treatment of CP has been recommended and many authors reported favourable results in 2/3 of patients [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Radiotherapy is not deprived of complications: paediatric patients present social and emotional functioning lower than a control group, difficulties for learning, difficulties for behavioural control and problems for controlling emotions and concerns for physical appearance as reported by Heinkes [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRadiotherapy become in the last years the standard of care in case of subtotal removal [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] and the new technologies have permitted to improve the dose conformity and to reduce the doses of irradiation to the adjacent structures: hypothalamus, optic pathways, the pituitary gland, the carotid arteries and the medial temporal structures. Conformational radiotherapy, proton therapy, intensity modulated radiotherapy and fractionated stereotactic radiotherapy have been used to reduce the risk of sequels [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe use of stereotactic radiosurgery for lesions of small volume has also been proposed with cautious because high dose applied in a single dose can be responsible of lesion of vital structures [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOnly 6 patients of our series treated for a recurrence have been treated with a surgical resection followed by proton therapy to decrease the doses on nervous and vascular structures and it seems us better to avoid radiotherapy when a complete surgical resection is possible [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMolecular pathology\u003c/h2\u003e \u003cp\u003eIn the last years also craniopharyngiomas have made the object of molecular studies with the aim to find targets that could permit a tailored effective medical treatment that could represent an alternative to surgery in the next future.\u003c/p\u003e \u003cp\u003eTwo different subtypes of craniopharyngiomas have been described the adamantinous (ACPs) predominant in paediatric cases and the papillary craniopharyngiomas (PCPs). The average age of incidence is regulated by two pic of age, one between five to twelve years old in children and another, in adult patients, between 50 to seventy years old [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePapillary CP occur rarely in paediatric age and account for 11\u0026ndash;14% of CP and the average of diagnosis is between 44 +/- 15 years and have a better five years\u0026rsquo; survival rate and a less aggressive disease behaviour [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe genes involved in the pathogenesis of the tumor and that can be conditioned by medical treatments have been studied.\u003c/p\u003e \u003cp\u003eIn ACPs the Wingless pathway (WNT pathway) activation seems to be regulated by the gene CTNNB1, encoding B-catenin that are activated in more than 2/3 of tumors in recent studies [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In other patients also the MAPK/ERK pathway has been demonstrated opening novel therapeutic strategies with the suppression of this pathway with chemical agents like MEK inhibitor trametinib [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn PCPs the sub groups BRAF V600E mutation has been found in 90% of cases [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. The BRAF system is a proto-oncogene encoding serine-threonine kinase involved in growth factor signalling and regulation. Its mutation results in an active form that promotes the cell proliferation and tumor growth.\u003c/p\u003e \u003cp\u003eThese mutations in PCPs pushed to treat some patients with targeted therapy in cases of recurrences or for reducing the volume of the tumor [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe expression of the Beta catenin was present in four of our patients and in one the mutation of the gene CNNBI that code for the Beta catenin.\u003c/p\u003e \u003cp\u003eThe genetic studies can be useful for cystic types to reduce their volume or for papillary types in case of huge recurrences in adults but, until now, there are no treatments effective for the cure of paediatric craniopharyngiomas\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eIntracystic chemotherapy\u003c/h2\u003e \u003cp\u003eWe reported our experience with intracystic chemotherapy for craniopharyngiomas [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt the beginning, the treatment was realized for cystic recurrences and successively, after the good results obtained,also for primary cystic form of craniopharyngiomas. Bleomycin, and successively, interferon alpha were injected locally after the implantation of an Ommaya reservoir [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe implantation of the reservoir was realized with a direct approach because the aim was to remove the tumor at the end of the treatment disposing of the way already open. Successively with the good results obtained, the surgical removal was judged useless and consequently the reservoir was implanted with endoscopic or stereotactic technique.\u003c/p\u003e \u003cp\u003eThe endoscopic technique was realized in presence of large ventricles while the stereotaxic technique was more useful in cases of slit ventricles.\u003c/p\u003e \u003cp\u003eThe first drug used was bleomycin, introduced by Umezawa in treatment of cerebral cystic lesions [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. The first report with treatment of cystic craniopharyngiomas with bleomycine was reported by Takahashi in 1985 with good results in 7 patients [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBroggi and Lapras and Mottolese also reported preliminary good results.[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe toxicity of bleomycine for the CNS needed a watertight closure of the Ommaya system before to start the treatment. The action of the bleomycine was at level of the lattico-deidrogenasis system blocking the duplication of the DNA and consequently inducing the death of the cells [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e] with satisfying results [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. We reported a severe complication with the injection of a toxic doses of the drug responsible of blindness in a patient and we stopped its use and, after the experience of Di Rocco [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and Cavalheiro [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e], we started the use of interferon alpha.\u003c/p\u003e \u003cp\u003eInterferon alpha is not toxic to the central nervous system (CNS) but its effects are limited in duration. However, the treatment is sufficiently long enough to delay the need for surgery, which subsequently delays the worsening of pituitary insufficiency and the onset of post-surgical complications. Preserving endocrine function can be a medium-term goal, as it helps to reduce the pressure on neighboring nervous structures. However, reversibility of the existing signs of pituitary insufficiency has not been observed.\u003c/p\u003e \u003cp\u003eWe have treated 7 patients with cystic craniopharyngiomas with interferon alpha. The median delay between the treatment and the surgical resection, related to progression of the tumor, was of three years varying from one year in three patients to five years in two patients. In two patients the surgical removal was realized after four years. The mechanism of action of the interferon alpha seems to be mediated by an inflammatory reaction [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe variable efficacy and the limited effect in time of the drug represent a matter of reflexion and could be related to different genetic tumoral constitution responsible of a programmed inflammatory reaction conditioning the response to the drug.\u003c/p\u003e \u003cp\u003eActually the interferon alpha is no more available for intracystic administration and consequently we were obliged to come back to a surgical removal of craniopharyngiomas. A subcutaneous injection of the peginterferon alpha-2b [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e] has been proposed but we have no experience with this drug but we believe that, the possibility to dispose of more effective drugs, in the future, could completely change the strategy for treatment of craniopharyrngiomas.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eSurgery\u003c/h2\u003e \u003cp\u003eThe surgical resection of CP is a challenge for experimented paediatric neurosurgeons. The rarity of the lesion (two new cases per millions per years in US and in France [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eand, on the other hand, the deep localization with close relationships with nervous and vascular structures make at risk the quality of life of patients.\u003c/p\u003e \u003cp\u003eMany surgical approaches have been proposed for surgery: sub frontal, pterional, fronto temporal, sub-temporal, interhemispheric, trans callosal each of them with specific advantages and disadvantages.\u003c/p\u003e \u003cp\u003eWe prefer the sub frontal pterional approach that permits, in our experience, the exposition of the four basal triangles whose exposition is imperative to remove craniopharyngiomas mainly when they are of great volume as frequently in children.\u003c/p\u003e \u003cp\u003eThe four triangles are the opto-carotido, the retrocarotid, the interoptic triangle that, when the optic nerves are long and chiasma retro fixed, give a very large space for the dissection.\u003c/p\u003e \u003cp\u003eThe fourth triangle is delimited by the carotid bifurcation and is very interesting for removal of the upper portion of very huge tumors.(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe trans- frontal trans-ventricular approach, for craniopharyngioma resection, through the third ventricle has for us limited indications because craniopharyngiomas of the third ventricle are very rare, only 4% of cases in the series of Yasargyl [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e], and because craniopharyngioma growing upwards raised the floor of the third ventricle exposing the floor to damages for the removal of the tumor.\u003c/p\u003e \u003cp\u003eThe transcallosal approach proposed by Yasargil for intraventricular tumors was used in our experience only in eight cases [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and in no case of this last series.\u003c/p\u003e \u003cp\u003eThe opening of the lamina terminalis represents a good door to approach craniopharyngiomas when the chiasm is ante fixed in presence of short optic nerves.\u003c/p\u003e \u003cp\u003eThe dissection of CP at level of the optic pathways represents an important step of the surgical removal and the experience of the surgeon is important to preserve the functionality of the optic pathway. In our last series of 26 patients 16 patients (63%) before the surgical procedure had visual problems while after the surgery only 9 patients presented visual troubles (35%) translating the fact that in 7 patients (27%) the decompression favourited the visual improvement, while in the others patients, the decompression, cannot be effective to recover deficits appeared from long time. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B)\u003c/p\u003e \u003cp\u003eThe lesions of hypothalamus with repercussions on the hypothalamo-pituitary axis and on behavioural troubles with difficulty to control the thirsty, the hunger, the aggressiveness, and memory and school difficulties represent also a critical problem. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and B)\u003c/p\u003e \u003cp\u003eThe lesions of the hypothalamus are not only related to the surgical dissection but also to the ischemic lesions related to the occlusion of the perforating vessels originating from the posterior communicating arteries [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe CP is an extra-arachnoid tumor and respecting the extra arachnoid plane of dissection it is possible to avoid problems with the dissection of posterior portion with the basilar artery trunk. The perforating vessel of the basilar trunk are headed back, in a plane posterior to that of the tumor with a posterior direction through the mesencephalon and consequently can be spared.\u003c/p\u003e \u003cp\u003eThe endoscopic approach has permitted to reduce the exposition of nervous structures for craniopharyngiomas removal favouring a great enthusiasm for it.\u003c/p\u003e \u003cp\u003eSurgery of CP with endoscopy in children, in our opinion, should to be addressed only for lesions developing on the mid line and that remain exclusively under the diaphragm sellae without lateral extension and without the need of extended opening of the skull base and consequently it has been realized in only 4% of our cases.\u003c/p\u003e \u003cp\u003eFor huge tumors and for tumor with a lateral development the endoscopic technique is not indicated for the difficulties to close the skull base in children when an extended endoscopic approach is necessary for the high risk of infectious complications with an important rate of mortality for fulminans meningitis responsible of 8% of mortality [\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMazzatenta has reported a pediatric series treated with endoscopy with a rate of peri-operative mortality in 4% of cases and a rate of recurrences of 19% [\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn this last series we have treated only a patient with an endoscopic resection for a primary treatment and two patients for an intrasellar recurrence but, for us, endoscopy is very important after the microsurgical dissection to explore the operative field to discover pieces of tumors left in place that removed increase the rate of complete removal, reducing the rate of recurrences. We recommend the endoscopic exploration in each case at the end of the microsurgical resection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eRecurrences\u003c/h2\u003e \u003cp\u003eThe recurrences rate after the total surgical removal of craniopharyngiomas have an incidence varying from 4\u0026ndash;30% in literature [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan additionalcitationids=\"CR63 CR64\" citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistorical experience reported a rate of recurrence after a total removal of 11% (Matson \u0026amp; Crigler in 1969 [\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]), of 25% (Sweet in 1980 [\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]), of 16% (Hoffman in 1986 [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]), of 4% (Symon and Sprych reported in 1985 [\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]), and of 16% [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOsborn showed a proportional relationship between recurrences and the volume of the tumor: for tumor with a diameter inferior to 5 cm. the rate of recurrences was of 20% while for tumor with a diameter\u0026thinsp;\u0026gt;\u0026thinsp;to 5 cm. the rate of recurrence increased to 80% [\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our last series, the recurrence rate after a total removal was of 20%. 4 patients with a residual volume after the first surgery were treated with a new surgical procedure in two cases by a trans-sphenoidal and with a transcranial approach for the other two, to obtain a complete removal followed after by proton therapy.\u003c/p\u003e \u003cp\u003eAll these cases did not show a new progression after a median follow-up of 3 years.\u003c/p\u003e \u003cp\u003eIn our last series 19 patients have been treated with only surgery: the complete removal of craniopharyngiomas can be the aim of surgery because a complete removal of a benign lesion permits a definitive cure of patients also if associated with endocrinological, visual and behavioural troubles. The good neuropsychological evolution of our patients with surgical complete resection confirms that also large craniopharyngiomas can be treated with only surgery.\u003c/p\u003e \u003cp\u003eLesions of hypothalamus can be prevented with the respect of the perforating vessels of the posterior communicating artery [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. A meticulous atraumatic dissection at level of the hypothalamus and of the optic pathways reduce the risks of post-operative clinical aggravation. The respect of the arachnoidal sheaths guarantee the protection of vascular and nervous structures favouring a good quality of life after surgery.\u003c/p\u003e \u003cp\u003eIn our series, the high number of patients with a normal life, attending a normal school program (20 patients, 76,9%) are witnesses of the progress attained with surgery.\u003c/p\u003e \u003cp\u003eIn 15 out 20 patients, we observed a contrast between the results of their performances obtained with the neuropsychological tests, and the difficulties they encounter in daily life.\u003c/p\u003e \u003cp\u003eThe majority of these children are in great social distress, leading to withdrawal and even, in more severe cases, dropping out of school.\u003c/p\u003e \u003cp\u003eWhile the main hypothesis was to explain these difficulties by cognitive deficits resulting from the children's brain damage, the data obtained suggest more socio-psychological difficulties. Indeed, children suffering from hypothalamic damage that has a direct impact on their quality of life (eating disorders, obesity, etc.) can also affect their psychological well-being. Our study also demonstrates the shortcomings in the psychological follow-up of these children and their families. Improving the follow-up of these children through group therapy, in-depth psychological monitoring, and monitoring of diet and weight management would be relevant to their care. With better care, these children could more fulfilled in their school careers. The overweight and obesity can be better taken in care using better protocols of monitoring avoiding unnecessary food intake with better social and educative programs not only for patients but also for their family. For this reason, we can be accepted that the pendulum of the surgical removal can move again, in experimented hands, towards an aggressive surgical resection until, advances in biomolecular studies, offers the possibility to switch to medical treatments based on drug administration, at the condition, to avoid serious toxicity and complications related to radiotherapy mainly in very young children.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eEndocrinological considerations\u003c/h2\u003e \u003cp\u003eThe consequence of surgery for craniopharyngiomas is dysregulation of the hypothalamo-pituitary axis which affects 97% of patients. An early post-operative complication is triphasic syndrome.\u003c/p\u003e \u003cp\u003eThe incidence of triphasic syndrome was more frequent in our experience than in others [\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e]. A great deal of clinical experience is needed to avoid this phenomenon, which in the post-operative period requires to avoid very severe fluid restriction at the outset, to compensate for water loss, and which needs the cautious use of antidiuretic hormone to avoid the conflict with SIADH syndrome, which can be very dangerous for the clinical evolution of patients. We emphasize the role of paediatric endocrinologists in collaboration with the intensive care physicians in limiting the incidence and effects of this syndrome.\u003c/p\u003e \u003cp\u003eIt is true that the relationship between the tumor and the floor of the third ventricle as well as the large volume of the tumor, are significant factors in the appearance of this syndrome.\u003c/p\u003e \u003cp\u003eThe number of overweight or obese patients increases after surgery at 6 months (from 35\u0026ndash;40% at 6 months), then at 1 year (56%). At 2 years, there was a decrease from 56\u0026ndash;50%; The role of the multidisciplinary management (dietetic follow-up, adapted physical activity instructor, psychologist, pediatrician, pediatric neurosurgeon) introduced in our department 8 years ago seemed very important to control the overweight and obesity. (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eCraniopharyngioma remains a difficult tumor to treat in the paediatric population.\u003c/p\u003e \u003cp\u003eThe role of surgery is still a topical issue in paediatric craniopharyngiomas. It is always difficult to decide intraoperatively whether to completely remove the tumor or to stop resection and proceed with partial removal followed by radiotherapy.\u003c/p\u003e \u003cp\u003eSurgery requires special expertise to respect nervous and vascular structures, which represent the main risk factors for sequelae and sometimes the cause of catastrophic results. Our latest cohort shows that complete resection is possible, even if associated with endocrinological (96%) and visual sequelae (23%) but with good neuropsychological evolution.\u003c/p\u003e \u003cp\u003eSurgery in experimented hands can be the treatment of craniopharyngiomas also if the extent of resection should always be related to a pendulum that shall move in relation with the experience and the expertise of surgeons, the extension and the volume of the tumor, the possibility in the future to find effective pharmacological treatments to preserve the aggravation of function already affected when tumors are discovered.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFundings :\u003c/h2\u003e \u003cp\u003eall authors declare no conflict of interest. This work has not been funded by any means.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ePAB, AS, FDR, CM perfomed research and surgeriesLB and CV reviewed all endocrinological dataSC reviewed all MRI dataMV performed neuropsychological testingPAB and CM wrote the manuscriptAll authors reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAli ZS, Lang S-S, Kamat AR et al (2013) Suprasellar pediatric craniopharyngioma resection via endonasal endoscopic approach. 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Horm Res Paediatr 76:22\u0026ndash;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000324115\u003c/span\u003e\u003cspan address=\"10.1159/000324115\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5383509/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5383509/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Craniopharyngioma (CP) surgery in children leads to high rate of recurrence, and morbid complications. Transcranial approach is the most frequently proposed surgical technique, but transsphenoidal endoscopic approach is also used.\u003c/p\u003e\n\u003cp\u003ePre and post-operative complications of the tumor are well known, but early multidisciplinary management could improve the long-term outcome of these patients.\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to analyze the risk factors for pre-and post-operative long-term complications in a series of patients operated with an aggressive removal for CP.\u003c/p\u003e\n\u003cp\u003eMethods: A retrospective study of 26 children diagnosed with CP was carried out.\u003c/p\u003e\n\u003cp\u003eThe surgical total removal was possible in 88% of cases after the revision of the post-operative MRI realized in the first 48 hours.\u003c/p\u003e\n\u003cp\u003eResults: Children with hypothalamic involvement were more likely to have endocrine deficits and to be overweight or obese pre-operatively. They also had a higher risk of early post-operative complications, and late morbidities.\u003c/p\u003e\n\u003cp\u003eConclusion: Children with CP and strong hypothalamic involvement, have a higher risk of pre and post-operative complications but complete removal is associated with an high rate of cure with global good neuropsychological results. Early multidisciplinary post-operative management should be reinforced to improve the long-term outcome but surgery with total removal can insure definitive acceptable clinical results.\u003c/p\u003e","manuscriptTitle":"Craniopharyngiomas in children: the pendulum moves again for an aggressive surgery. Late complications and considerations with a recent series of 26 patients treated in Lyon","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-11 14:10:33","doi":"10.21203/rs.3.rs-5383509/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-05T17:35:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-04T16:54:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"45011628022682540552006420475589696603","date":"2024-11-24T21:42:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-22T18:38:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-08T12:14:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-08T12:14:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Child's Nervous System","date":"2024-11-03T19:59:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9ff6bc12-b6f3-4961-ac25-e47b03c8021f","owner":[],"postedDate":"December 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-28T16:02:57+00:00","versionOfRecord":{"articleIdentity":"rs-5383509","link":"https://doi.org/10.1007/s00381-025-06815-3","journal":{"identity":"childs-nervous-system","isVorOnly":false,"title":"Child's Nervous System"},"publishedOn":"2025-04-26 15:57:59","publishedOnDateReadable":"April 26th, 2025"},"versionCreatedAt":"2024-12-11 14:10:33","video":"","vorDoi":"10.1007/s00381-025-06815-3","vorDoiUrl":"https://doi.org/10.1007/s00381-025-06815-3","workflowStages":[]},"version":"v1","identity":"rs-5383509","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5383509","identity":"rs-5383509","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}