Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.

BACKGROUND: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. METHODS: European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). RESULTS: Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. CONCLUSIONS: Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.

Comparison of energy expenditure, body composition, metabolic disorders, and energy intake between obese children with a history of craniopharyngioma and children with multifactorial obesity.

UNLABELLED: Craniopharyngioma is a histologically benign brain malformation with a fundamental role in satiety modulation, causing obesity in up to 52% of patients. AIM: To evaluate cardiovascular risk factors, body composition, resting energy expenditure (REE), and energy intake in craniopharyngioma patients and to compare the data with those from children with multifactorial obesity. POPULATION: All obese children and adolescents who underwent craniopharyngioma resection and a control group of children with multifactorial obesity in follow-up between May 2012 and April 2013. MATERIALS AND METHODS: Anthropometric measurements, bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated. RESULTS: Twenty-three patients with craniopharyngioma and 43 controls were included. Children with craniopharyngioma-related obesity had a lower fat-free mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5 vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive association was found between %REE and %fat-free mass in subjects with multifactorial obesity (68±1% in normal REE vs. 62.6±1% in low REE; p=0.04), but not in craniopharyngioma patients (62±2.7 in normal REE vs. 61.2±1.8% in low REE; p=0.8). No differences were found in metabolic involvement or energy intake. CONCLUSIONS: REE was lower in craniopharyngioma patients compared to children with multifactorial obesity regardless of the amount of fat-free mass, suggesting that other factors may be responsible for the lower REE.

Gasto energético, composición corporal, trastornos metabólicos e ingesta energética en pacientes con antecedentes de craneofaringioma / Energy expenditure, body composition, metabolic disorders, and energy intake in patients with a history of craniopharyngioma

Introducción: Los craneofaringiomas son malformaciones histológicamente benignas que se sitúan entre el hipotálamo y la hipófisis, zonas con un rol determinante en la modulación de la saciedad. Aun siendo tumores benignos, presentan una considerable morbilidad. La obesidad está presente hasta en un 52% de los pacientes. Objetivo: evaluar factores de riesgo cardiovascular, composición corporal y gasto energético en pacientes con craneofaringioma, y compararlos con un grupo de obesos multifactoriales. Material y métodos: Se incluyeron todos los pacientes con resección quirúrgica de craneofaringioma, menores de 21 años, en seguimiento en nuestro centro entre mayo 2012 hasta abril 2013 que aceptaron participar por medio del consentimiento informado. Se realizó valoración antropométrica, composición corporal con impedanciometría, gasto energético con calorimetría indirecta y valoración de ingesta energética y de macronutrientes. Se determinó resistencia a la insulina (HOMA-IR) y dislipemia. Se comparó a los pacientes con craneofaringioma con obesidad, con un grupo de pacientes con obesidad multifactorial. Resultados: se estudiaron 39 pacientes. El 59% era obeso y presentó significativamente menor% de masa magra (62.4 vs 67.5 p=0.01) y mayor% de masa grasa (37.5 vs 32.5 p=0.01) comparados con los obesos multifactoriales. No se encontró diferencias en el compromiso metabólico entre los obesos con y sin antecedente de craneofaringioma. Se dividieron los pacientes en tertilos según% de gasto energético para categorizar en gasto bajo vs normal. Se encontró asociación positiva entre% de gasto energético y% de masa magra en obesos multifactoriales (68±1%; en los gasto normal vs 62.6± 1% en los gasto bajo: p 0,04). Sin diferencias dentro de la población de obesos con antecedente de craneofaringioma (62±2.7 en los gasto normal/alto vs 61.2±1.8% en los gasto bajo: p 0,8). El gasto energético basal (REE) fue menor en los pacientes con antecedente de craneofaringioma vs obesos multifactoriales, independientemente de la masa magra, lo que sustenta que existirían otros factores que actuarían disminuyendo el gasto energético. No hubo diferencia con respecto a la ingesta en ambos grupos estudiados. Conclusiones: los pacientes con antecedente de craneofaringioma presentan menor gasto energético no relacionado a la masa magra y similar ingesta energética comparado con obesos multifactoriales. No hubo diferencias en el compromiso metabólico entre los obesos con y sin antecedentes de craneofaringioma (AU)

Introduction: Craniopharyngiomas are histologically benign malformations located between hypothalamus and the pituitary gland, areas that play an important role in satiety modulation. Although the tumors are benign, they may cause significant morbidity. Obesity is found in up to 52% of patients. Aim: To assess cardiovascular risk factors, body composition, and energy expenditure in patients with craniopharyngioma, and to compare them to results in a group of children with multifactorial obesity. Material and methods: All patients who underwent surgical resection of craniopharyngioma, younger than 21 years of age, who were being followed-up at our center between May 2012 and April 2013 who gave their informed consent to participate were enrolled in the study. Anthropometric measurements, body composition with impedanciometer, energy expenditure with indirect calorimetry, and energy and macronutrient intake were evaluated. Insulin resistance (HOMA-IR) and dyslipidemia were determined. Patients with craniopharyngioma associated with obesity were compared to patients with multifactorial obesity. Results: Of 39 patients studied, 59% were obese and a significantly lower percentage of lean mass (62.4 vs 67.5 p=0.01) and a higher percentage of fat mass (37.5 vs 32.5 p=0.01) compared to multifactorial obese subjects. No differences were found in metabolic involvement between obese subjects with and those without a history of craniopharyngioma. Patients were divided into tertiles according to percentage of energy expenditure to categorize low versus normal expenditure. A positive correlation was found between percentage of energy expenditure and lean mass percentage in subjects with multifactorial obesity (68±1%; in those with normal energy expenditure versus 62.6±1% in those with low energy expenditure: p 0.04). No difference was found within the group of obese patients with a history of craniopharyngioma (62±2.7 in those with normal/high expenditure versus 61.2±1.8% in those with low expenditure: p 0.8). Baseline energy expenditure (BEE) was lower in craniopharyngioma patients than in those with multifactorial obesity, regardless of lean mass percentage, supporting the hypothesis that other factors may be involved in the decrease of energy expenditure. There was no difference in the food intake between both groups. Conclusions: Patients with a history of craniopharyngioma had a lower energy expenditure unrelated to lean mass and a similar energy intake compared to subjects with multifactorial obesity. No differences were found in metabolic involvement between obese subject with and those without a history of craniopharyngioma (AU)

Comparative immunohistochemical assessment of craniopharyngioma and related lesions.

Craniopharyngiomas (CP), Rathke's cleft cysts (RCC), and sellar xanthogranulomas (XG) are closely related lesions. As expression of cytokeratins 8 (CK8) and 20 (CK20) was reported in RCC but not in CP, the present study investigates the reproducibility of immunohistochemical distinction between CP and RCC, attempting to identify the relationship of XG to these lesions. A comparative study of 55 patient specimens (25 CP, 28 RCC, and 2 XG) was analyzed for the histological features of xanthomatous changes and squamous metaplasia, and expression of CK8 and CK20. In the 25 CP cases, xanthomatous changes were seen in 5 (20%), with CK8 reactivity demonstrated in all 25 cases. A prominent xanthomatous component was identified in 13 of 28 RCC (46%), and squamous metaplasia was seen in 11 (39%), 9 of which also contained xanthomatous features. CK8 reactivity was demonstrated in all 28 RCC cases, whereas CK20 was seen only in 9 cases (32%). Of the two cases diagnosed as XG, none contained epithelium, and immunohistochemistry for cytokeratins was not observed. Overall, differential expression of cytokeratins cannot reliably distinguish CP from RCC. Furthermore, expression of CK20 in RCC is generally seen within a background of prominent squamous metaplasia and reactive xanthomatous changes.