Oxytocin in survivors of childhood-onset craniopharyngioma.

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Fusiform dilatation of the internal carotid artery in childhood-onset craniopharyngioma: multicenter study on incidence and long-term outcome.

PURPOSE: Fusiform dilatations of the internal carotid artery (FDCA) represent a vascular complication following surgery for suprasellar tumors in children. Incidence rate and long-term prognosis of FDCA in terms of survival rates, vascular complications, and quality of survival are unknown for patients with childhood-onset craniopharyngioma. METHODS: Magnetic resonance imaging (MRI) results of 583 patients with childhood-onset craniopharyngioma, recruited from 2001 to 2015 in the German Childhood Craniopharyngioma Registry, were reviewed for FDCA. Risk factors for FDCA and long-term outcome after FDCA were analyzed. RESULTS: Fourteen of 583 patients (2.4 %) developed FDCA based on reference assessment of MRI. FDCA occurred ipsilateral to the surgical approach and was not related to degree of resection, hypothalamic involvement, or irradiation. The median time interval between first detection of FDCA and initial surgery was 0.79 years (range 0.01-5.56 years). During a median follow-up of 6.47 years (range 1.2-21.9 years) after first detection of FDCA, no bleeding or cerebrovascular events were observed in any patient. Irradiation was not related to FDCA. Survival rates and functional capacity were similar in patients with and without FDCA. Clinically the FDCA was unapparent in all cases and not treated. CONCLUSION: FDCA is a rare complication related to surgical treatment of childhood-onset craniopharyngioma without major impact on prognosis and clinical course of the disease. CLINICAL TRIAL NUMBER: KRANIOPHARYNGEOM 2000-NCT00258453; KRANIOPHARYNGEOM 2007-NCT01272622.

History before diagnosis in childhood craniopharyngioma: associations with initial presentation and long-term prognosis.

OBJECTIVE: Childhood craniopharyngiomas (CP) are often diagnosed after a long duration of history (DOH). Tumor size, hypothalamic involvement (HI), and obesity are associated with reduced overall survival (OS) and functional capacity (FC). The effect of DOH and specific symptoms in history on presentation at initial diagnosis and long-term prognosis are unknown. DESIGN: Retrospective analysis of patients' records and prospective longitudinal follow-up. METHODS: Histories of 411 CP patients recruited in HIT Endo, KRANIOPHARYNGEOM 2000 were retrospectively evaluated for DOH, symptoms, and characteristics. The effect of specific manifestations and DOH on clinical presentation and tumor characteristics at time of initial CP diagnosis and long-term outcome were analyzed. Main outcome measures were 10-year OS and progression-free survival (PFS), FC, and BMI during longitudinal follow-up. RESULTS: Median DOH was 6 months (range: 0.1-108 months) and correlated with age at diagnosis. Tumor size, HI, degree of resection, and BMI at diagnosis were not related to DOH. In multivariate analysis adjusted for age at diagnosis, only hydrocephalus was found to have a relevant influence on DOH. Visual and neurological deficits were associated with larger initial tumor size and impaired 10-year OS. Weight gain and growth failure were observed with longest DOH. PFS and FC were not related to any specific symptom. Endocrine deficits at diagnosis were associated with long DOH. CONCLUSIONS: CP is frequently diagnosed after long DOH, especially in older children. However, DOH was not associated with tumor size, HI, survival, or FC. Visual and neurological deficits necessitate rapid diagnostic workup.

Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients.

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma.

OBJECTIVE: Hypothalamic obesity in childhood craniopharyngioma (CP) patients carries a high risk for development of metabolic syndrome. In metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is known. The aim of this study is to detect the risk for NAFLD in childhood-onset CP. DESIGN: This cross-sectional study included liver computed tomography (CT); ultrasound analysis of abdomen; measurements of serum parameters, height, weight and body composition; and daily medication of patients with childhood-onset CP. METHODS: A total of 384 patients recruited in trials HIT Endo and KRANIOPHARYNGEOM 2000 were analyzed. Ninety-four survivors were included by fulfilling the criteria of proven hypothalamic involvement (HI), a minimum time interval of 5 years between diagnosis and study, and a minimum age of 18 years at the time of evaluation. A total of 19 patients agreed to participate. To quantify the degree of steatosis hepatis, analyses of liver density were performed once by non-contrasted CT of liver sections. RESULTS: NAFLD occurs in about 50% of CP patients with HI and is associated with elevated liver enzymes and homeostasis model assessment index. BMI is not an effective predictive factor but body fat mass measured by near-infrared spectroscopy (NIRS) is. Over half of CP patients (60%) with NAFLD are treated with stimulating agents, with risk of hepatic side effects. CONCLUSIONS: NAFLD is a major adverse late effect in childhood-onset CP. NIRS rather than BMI should be used to measure body composition and predict NAFLD. Stimulating agents for treatment of fatigue and daytime sleepiness in CP should be prescribed judiciously.

Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (<5 y at diagnosis) (n = 30; 0.39 ± 0.10) compared with patients aged 5-10 years (n = 66; 0.52 ± 0.08) and older than 10 years (n = 72; 0.77 ± 0.06) at diagnosis. PFS was not associated with HI, degree of resection, or sex. HI led to severe weight gain during the first 8-12 years of follow-up (median BMI increase: +4.59SD) compared with no HI (median increase: +1.20SD) (P = .00). During >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. CONCLUSIONS: 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.