This report is a review of findings on the diagnosis, treatment, clinical course, and prognosis of craniopharyngioma patients. Craniopharyngiomas are rare, partly cystic and calcified embryonic malformations of the sellar/parasellar region with low histological grade (WHO I°). A bimodal age distribution has been shown, with peak incidence rates in childhood-onset at 5–14 years and adult-onset craniopharyngioma at 50–74 years. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. If the tumor is favorably localized, the therapy of choice is complete resection, with care taken to preserve optical and hypothalamic functions. In patients with unfavorable tumor localization (ie, hypothalamic involvement), recommended therapy is a limited hypothalamus-sparing surgical strategy followed by local irradiation. Although overall survival rates are high (92%), recurrences and progressions are frequent. Irradiation has proven effective in reducing recurrences and progression, and timing of postsurgical irradiation in childhood-onset cases is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Anatomical involvement and/or surgical lesions of posterior hypothalamic areas can result in serious quality of life-compromising sequelae such as hypothalamic obesity, psychopathological symptoms, and/or cognitive problems. It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' clinical and quality of life consequences by experienced multidisciplinary teams.

Background: Hypothalamic obesity has major impact on prognosis and quality of life (QoL) in childhood craniopharyngioma.Patients and methods: For this study, 120 patients were prospectively recruited during 2001 and 2007 and evaluated after 3 years of follow-up (KRANIOPHARYNGEOM 2000). Body mass index (BMI) and QoL at diagnosis and 36 months after diagnosis were analysed based on the reference assessment of tumour localisation and post-surgical hypothalamic lesions. Treatment was analysed based on the neurosurgical strategy of 50 participating neurosurgical centres, the centre size based on the patient load.Results: BMI SDS at diagnosis was similar in patients with or without hypothalamic involvement. Surgical lesions of anterior and posterior hypothalamic areas were associated with higher increase in BMI SDS during 36 months post-diagnosis compared with patients without or only anterior lesion (+1.8 BMISD, P=0.033, +2.1 BMISD; P=0.011), negative impact on QoL in patients with posterior hypothalamic lesions. Surgical strategies varied among the 50 neurosurgical centres (three large-sized, 24 middle-sized and 23 small-sized centres). Patients treated in small-sized centres presented with a higher rate of hypothalamic involvement compared with those treated in the middle- and large-sized centres. Treatment in large-sized centres was less radical, and the rates of complete resection and hypothalamic surgical lesions were lower in large-sized centres than those of the middle- and small-sized centres. However, a multivariable analysis showed that pre-operative hypothalamic involvement was the only independent risk factor for severe obesity (P=0.002).Conclusions: Radical neurosurgical strategies leading to posterior hypothalamic lesions are not recommended due to the potential to exacerbate hypothalamic obesity and impaired QoL. Treatment should be confined to experienced multidisciplinary teams.

We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10–12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1–6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS at age 6–7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and independent impacts on the development of obesity. Patients with hypothalamic involvement (n = 48) presented lower ponderal index and BMI SDS at birth and higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual follow-up (P < 0.001) compared with patients without hypothalamic involvement (n = 42). From childhood (3.5–4 yr) to the time of diagnosis, growth rates were reduced for patients with hypothalamic tumor involvement. Patients without hypothalamic involvement presented reduced growth rates in early infancy (age 10–12 months) that persisted until diagnosis. We conclude that reduced growth rates occur quite early in history; BMI SDS increases occur later and are predictive of obesity. Hypothalamic involvement is the major risk factor for obesity in patients with childhood craniopharyngioma.

Quality of life (QoL) and long-term prognosis are frequently, and often severely, impaired in craniopharyngioma (CP) patients. Knowledge of risk factors for long-term outcome is important for optimization of treatment. Overall survival (OS) and progression-free survival (PFS), body mass index (BMI), neuropsychological status (EORTCQLQ-C30, MFI-20), and psychosocial status were analyzed in 261 patients with childhood-onset CP diagnosed before 2000 and longitudinally observed in HIT-Endo. Twenty-year OS was lower (P = .006) in CP with hypothalamic involvement (HI) (n = 132; 0.84 ± 0.04) when compared with CP without HI (n = 82; 0.95 ± 0.04). OS was not related to degree of resection, sex, age at diagnosis, or year of diagnosis (before/after 1990). PFS (n = 168; 0.58 ± 0.05) was lower in younger patients (12 years of follow-up, patients with HI presented no further increase in BMI. QoL in CP patients with HI was impaired by obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and nonoptimal psychosocial development. OS and QoL are impaired by HI in long-term survivors of CP. HI is associated with severe obesity, which plateaus after 12 years. OS/PFS are not related to degree of resection, but gross-total resection should be avoided in cases of HI to prevent further hypothalamic damage, which exacerbates sequelae.

Background: Craniopharyngiomas are tumorous embryogenic malformations. As the survival rate after craniopharyngioma is high (92 %), prognosis and quality of life (QoL) in survivors mainly depend on adverse late effects such as obesity. Patients and methods: We analyzed 214 children and adolescents with craniopharyngioma. The records of 185 patients (86 %) were available for retrospective analysis of weight profiles and risk factors for obesity. Quality of life (QoL) was measured in 145 patients by the Fertigkeitenskala Münster/Heidelberg score (FMH) and in 77 patients by PEDQOL questionnaire. Results: Eighty-two of 185 patients (44 %) developed severe obesity (body mass index [BMI] > 3 SD). Obese patients were compared with 79 patients (43 %) who kept normal weight (BMI < 2 SD). No differences between obese and normal weight patients were found in terms of gender distribution, age at diagnosis and follow-up period. However, the BMI SDS at the time of diagnosis was higher (p < 0.0001) in patients who developed obesity than in those who did not. Furthermore, obese patients presented with bigger tumors (p < 0.05) and a higher rate of a hydrocephalus requiring a shunt (p < 0.05) and hypothalamic involvement (p < 0.05). The mothers of patients who developed severe obesity had a higher BMI (p < 0.001) at the time of diagnosis. Obese patients had a higher height-SDS at diagnosis (p < 0.05) and at the time of last follow-up (p < 0.05) when compared with normal weight patients. A prediction model for severe obesity after craniopharyngioma was calculated by logistic regression based on the risk factors: patient's BMI > 2 SD at diagnosis (p < 0.05; odds ratio: 16.4), hypothalamic involvement (p < 0.05; odds ratio: 3.4) and maternal BMI > 25 kg/m² (p < 0.05; odds ratio: 4.6). Significant increases in BMI (p < 0.001) occurred during the early post-operative period especially during the first three years after diagnosis. FMH percentiles correlated negatively with BMI SDS (Spearman r: - 0.37; p < 0.001). Children with craniopharyngioma rated their QoL more negative (p < 0.05) in regard to physical abilities, cognitive functioning and social functioning when compared with healthy children of the same age group. Severely obese patients with craniopharyngioma estimated their QoL lower (p < 0.05) for all domains except for autonomy, cognition and familial integration in comparison with non-obese patients. Conclusion: Hypothalamic tumor involvement and familial disposition for obesity are risk factors for the development of severe obesity in patients with craniopharyngioma. As weight gain starts early after diagnosis and severe obesity causes a reduction in QoL, early therapeutic efforts should be considered in patients at risk. To confirm our results the prospective multicenter study Kraniopharyngeom 2000 on children and adolescents with craniopharyngioma was initiated (www.kraniopharyngeom.com). Hintergrund: Kraniopharyngeome sind tumoröse Fehlbildungen embryonalen Ursprungs. Die Überlebensrate der Patienten ist hoch (92 %), so dass Prognose und Lebensqualität der Patienten von Spätfolgen abhängig sind. Kraniopharyngeome mit suprasellärer Ausbreitung führen häufig zu hypothalamischen Essstörungen und ausgeprägter Adipositas der Patienten. Patienten und Methoden: Im Rahmen einer multizentrischen Querschnittuntersuchung wurden 214 Kinder und Jugendliche mit Kraniopharyngeom nachuntersucht. Die Krankenunterlagen von 185 Patienten (86 %) wurden ausgewertet hinsichtlich des Gewichtsverlaufs und der Risikofaktoren für eine Adipositas. Die Lebensqualität wurde mittels Fertigkeitenskala Münster/Heidelberg (FMH) (n=145) und PEDQOL-Fragebogen (n=77) gemessen. Ergebnisse: 82 von 185 Patienten (44 %) entwickelten eine schwere Adipositas (Körpermassen-Index [BMI] > 3 SD). Die Gruppe der adipösen Patienten wurde verglichen mit 79 Patienten (43 %), die im Verlauf normalgewichtig (BMI < 2 SD) blieben. Zwischen beiden Gruppen bestanden keine Unterschiede hinsichtlich der Geschlechtsverteilung, des Lebensalters bei Diagnose und der Nachbeobachtungszeit. Patienten, die eine schwere Adipositas entwickelten, boten bereits zum Zeitpunkt der Kraniopharyngeom-Diagnose und im weiteren Verlauf einen höheren BMI-SDS (p < 0,001) und Körperhöhen-SDS (p < 0,05) als Patienten, die normalgewichtig blieben. Darüber hinaus waren die Kraniopharyngeome der adipösen Patienten größer (p < 0,05), zeigten häufiger eine Hypothalamusbeteiligung (p < 0,05) und machten häufiger (p < 0,05) einer Liquorableitung notwendig. Mütter adipöser Patienten hatten einen höheren BMI zum Zeitpunkt der Tumordiagnose als Mütter von Patienten, die normalgewichtig blieben. Mittels logistischer Regressionsanalyse wurde ein Vorhersagemodell für das Auftreten einer schweren Adipositas (BMI-SDS > 3 SD) bei Kraniopharyngeom anhand folgender Faktoren entwickelt: BMI des Patienten > 2 SD bei Diagnose (p < 0,05; Odds Ratio: 16,4), Hypothalamusbeteiligung (p < 0,05; Odds Ratio: 3,4) und mütterlicher BMI > 25 kg/m² (p < 0,05; Odds Ratio: 4,6). Der mittels FMH-Skala ermittelte Perzentilenwert für die Lebensqualität zeigte eine negative Korrelation (Spearman r: - 0,37; p < 0,001) mit dem BMI-SDS. Kraniopharyngeompatienten schätzten ihre Lebensqualität hinsichtlich physischer, kognitiver und sozialer Funktionen negativer (p < 0,05) ein als gesunde Gleichaltrige. Adipöse Patienten hatten im Vergleich zu normalgewichtigen Patienten eine niedrigere (p < 0,05) Selbsteinschätzung ihrer Lebensqualität in allen PEDQOL-Domänen außer für Autonomie, kognitive Fähigkeiten und familiäre Integration. Schlussfolgerung: Eine Hypothalamusbeteiligung des Kraniopharyngeoms sowie eine familiäre Disposition für Übergewicht sind wichtige Risikofaktoren für die Entstehung einer ausgeprägten Adipositas von Kranio-pharyngeompatienten. Da die Adipositasentwicklung bereits präoperativ beginnt und bei postoperativer Progredienz zu gravierender Beeinträchtigung der Lebensqualität führt, sind frühzeitige Interventionen zur Gewichtsregulation von Risikopatienten empfehlenswert. Die multizentrische prospektive Beobachtungsstudie Kraniopharyngeom 2000 wurde initiiert zur Bestätigung unserer retrospektiv gewonnenen Ergebnisse. (www.kraniopharyngeom.com)