Netson KL, Conklin HM, Wu S, et al.
Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma.
Int J Radiat Oncol Biol Phys. 2013; 85(5):1301-6 [PubMed]

PURPOSE: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated.
METHODS AND MATERIALS: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period.
RESULTS: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group.
CONCLUSIONS: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

Merchant TE, Kun LE, Hua CH, et al.
Disease control after reduced volume conformal and intensity modulated radiation therapy for childhood craniopharyngioma.
Int J Radiat Oncol Biol Phys. 2013; 85(4):e187-92 [PubMed] Article available free on PMC after 15/03/2014

PURPOSE: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression.
METHODS AND MATERIALS: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years.
RESULTS: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression.
CONCLUSIONS: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating the differences in outcome based on host factors to explain the results.

Yeung JT, Pollack IF, Panigrahy A, Jakacki RI
Pegylated interferon-α-2b for children with recurrent craniopharyngioma.
J Neurosurg Pediatr. 2012; 10(6):498-503 [PubMed]

OBJECT: Previous studies of systemic and intralesional administration of nonpegylated interferon have shown efficacy against craniopharyngioma. Pegylaion of interferon-α-2b (PI) prolongs the half-life, allowing sustained exposure of the drug over time, and enhances efficacy. The authors report the results of the use of PI in 5 children with recurrent craniopharyngiomas.
METHODS: Five children, ranging in age from 9 to 15 years, with recurrent craniopharyngiomas were treated for up to 2 years with subcutaneous injections of PI at a dose of 1-3 μg/kg/week. Tumor response was assessed using MRI.
RESULTS: All patients had stable disease or better in response to PI. One patient experienced a recurrence after gross-total resection (GTR). She initially showed an increase in the predominantly cystic tumor after 3 months of treatment, followed by a complete response. She required no further intervention and remains without evidence of disease 10 years after starting treatment. Another patient experienced recurrence 3.3 years after subtotal resection (STR) and radiation therapy. He had complete disappearance of the predominantly cystic component after 4 months of treatment, and a small residual calcified mass remains 5 years later. The third patient experienced recurrence after 3 GTRs. He had a complete response after 7 months of treatment and remains without evidence of disease 19 months after starting treatment. The fourth patient experienced recurrence after 2 STRs. He had a 30% decrease in tumor size after 4 months of treatment, which was maintained for 12 months at which point the cyst began to increase in size. The final patient experienced recurrence after GTR and has stable disease 6 months after starting treatment with PI.
CONCLUSIONS: The use of PI in children with recurrent craniopharyngiomas can result in significant and durable responses and potentially delay or avoid the need for radiation therapy.

Müller HL, Gebhardt U, Faldum A, et al.
Xanthogranuloma, Rathke's cyst, and childhood craniopharyngioma: results of prospective multinational studies of children and adolescents with rare sellar malformations.
J Clin Endocrinol Metab. 2012; 97(11):3935-43 [PubMed]

CONTEXT: Craniopharyngioma (CP), Rathke's cyst (RC), and xanthogranuloma (XG) are closely related rare sellar masses. Treatment strategies in children lack consensus.
OBJECTIVE: Our objective was to study clinical manifestations and treatment-related outcome in RC, XG, and CP patients.
DESIGN: We conducted a multicenter surveillance trial.
PATIENTS: Inclusion criteria were 1) histological diagnosis of CP, XG, or RC and 2) diagnosis at age of 18 yr or less. A total of 117 CP, 14 XG (2001-2006), and 14 RC (1996-2006) were recruited.
MAIN OUTCOME: Overall survival (OS), event-free survival (EFS), and quality of life (QoL) were evaluated.
RESULTS: The 5-yr OS rates were 1.00 ± 0.00 in RC and XG and 0.97 ± 0.02 in CP. The 5-yr EFS rates were 0.85 ± 0.10 in RC, 1.00 ± 0.00 in XG, and 0.50 ± 0.05 in CP. Surgical resection of XG results in complete remission without recurrence. Recurrences occur in RC (14%) and CR (59%) but can be efficiently treated by irradiation, reoperation, and/or intracystic treatment. Severe hypothalamic sequelae such as obesity and others affecting QoL are predominant in CP due to presurgical involvement (59%) and postsurgical lesions (44%) of posterior hypothalamic structures. Centers with lower neurosurgery patient load use more radical surgical approaches to treat CP, resulting in higher rates of obesity and reduced QoL. Despite 46% anterior hypothalamic involvement, severe obesity is not encountered in XG.
CONCLUSIONS: Treatment of choice in XG and RC is radical surgery. In CP involving hypothalamic structures, less radical surgical approaches preserving hypothalamic integrity are recommended. Due to frequent relapses, regular imaging during follow-up is recommended for CP and RC. Treatment of patients with sellar masses should be confined to experienced multidisciplinary teams.

Clark AJ, Cage TA, Aranda D, et al.
Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review.
J Neurosurg Pediatr. 2012; 10(4):293-301 [PubMed]

OBJECT: Craniopharyngiomas are benign tumors but their close anatomical relationship with critical neurological, endocrine, and vascular structures makes gross-total resection (GTR) with minimal morbidity difficult to achieve. Currently, there is controversy regarding the extent, timing, and modality of treatment for pediatric craniopharyngioma.
METHODS: The authors performed a systematic review of the published literature on pediatric craniopharyngioma to determine patterns of clinical practice and the reported outcomes of standard treatment strategies. This yielded 109 studies, which contained data describing extent of resection for a total of 531 patients. Differences in outcome were examined based upon extent of resection and choice of radiation treatment.
RESULTS: Gross-total resection was associated with increased rates of new endocrine dysfunction (OR 5.4, p < 0.001), panhypopituitarism (OR 7.8, p = 0.006), and new neurological deficits (OR 9.9, p = 0.03) compared with biopsy procedures. Subtotal resection (STR) was not associated with an increased rate of new neurological deficits. Gross-total was associated with increased rates of diabetes insipidus (OR 7.7, p = 0.05) compared with the combination of STR and radiotherapy (RT). The addition of RT to STR was associated with increased rates of panhypopituitarism (OR 9.9, p = 0.01) but otherwise similar rates of morbidities.
CONCLUSIONS: Although subject to the limitations of a literature review, this report suggests that GTR is associated with increased rates of endocrinopathies compared with STR + RT, and this should be considered when planning goals of surgery.

Liu W, Fang Y, Cai B, et al.
Intracystic bleomycin for cystic craniopharyngiomas in children (abridged republication of cochrane systematic review).
Neurosurgery. 2012; 71(5):909-15 [PubMed]

BACKGROUND: Craniopharyngiomas are the most common benign histological tumors to involve the hypothalamopituitary region in childhood. When the tumor location is unfavorable, a gross total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents the risk of morbidity, especially for children. Intracystic bleomycin has been used to potentially delay the use of radiotherapy or radical resection to decrease morbidity.
OBJECTIVE: To determine the benefit and harm of intracystic bleomycin vs other treatments for cystic craniopharyngiomas in children.
METHODS: We searched the electronic databases of CENTRAL, MEDLINE/PubMed, and EMBASE/Ovid with prespecified terms. In addition, we searched reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases.
RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a randomized, controlled trial comparing intracystic bleomycin with intracystic P (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference in cyst reduction, neurological status, third nerve paralysis, fever, or total adverse effects between the treatment groups. There was a significant difference in favor of the P group for the occurrence of headache and vomiting.
CONCLUSION: Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality randomized, controlled trials are needed.

Catli G, Abaci A, Demir K, et al.
Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.
J Pediatr Endocrinol Metab. 2012; 25(5-6):499-502 [PubMed]

AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI).
METHODS: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years.
RESULTS: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021).
CONCLUSIONS: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Di Pinto M, Conklin HM, Li C, Merchant TE
Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma.
Int J Radiat Oncol Biol Phys. 2012; 84(3):e363-9 [PubMed] Article available free on PMC after 01/11/2013

PURPOSE: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning.
METHODS AND MATERIALS: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years.
RESULTS: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy.
CONCLUSIONS: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.

Ogilvy CS, Tawk RG, Mokin M, et al.
Stent-assisted coiling treatment of pediatric traumatic pseudoaneurysm resulting from tumor surgery.
Pediatr Neurosurg. 2011; 47(6):442-8 [PubMed]

BACKGROUND: Traumatic intracranial pseudoaneurysms in children are typically the result of blunt or penetrating head injury. There are isolated reports of pseudoaneurysm as the result of intracranial aneurysm surgery in both adults and children. Treatment of these lesions, both surgically and endovascularly, can be complicated due to the known variability of arterial wall thickness in traumatic pseudoaneurysms.
CASE REPORT: We describe a child who underwent successful craniopharyngioma resection following staged surgical procedures. Follow-up imaging 8 months after the operation demonstrated an enlarging pseudoaneurysm of the left supraclinoid carotid artery. The lesion was successfully treated with stenting of the vessel and coil placement between the stent and the aneurysmal segment of the artery. Follow-up angiographic imaging 6 months later revealed complete obliteration of the aneurysm and normalization of the carotid artery lumen.
CONCLUSION: To our knowledge, this is the first report of a pseudoaneurysm secondary to a surgical intervention in childhood that was treated with stent-assisted coiling. This strategy of vascular reconstruction is increasingly used in adults and appears safe to implement in the pediatric population. However, the long-term outcomes and the value of using an antiplatelet regimen in this young population are still to be determined.

Bereket A, Kiess W, Lustig RH, et al.
Hypothalamic obesity in children.
Obes Rev. 2012; 13(9):780-98 [PubMed]

Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in addition to acquired or congenital functional defects in central energy homeostasis in children with the so-called common obesity. The pathogenetic mechanisms underlying hypothalamic obesity are complex and multifactorial. Weight gain results from damage to the ventromedial hypothalamus, which leads, variously, to hyperphagia, a low-resting metabolic rate; autonomic imbalance; growth hormone-, gonadotropins and thyroid-stimulating hormone deficiency; hypomobility; and insomnia. Hypothalamic obesity did not receive enough attention, as evidenced by rarity of studies in this group of patients. A satellite symposium was held during the European Congress of Obesity in May 2011, in Istanbul, Turkey, to discuss recent developments and concepts regarding pathophysiology and management of hypothalamic obesity in children. An international group of leading researchers presented certain aspects of the problem. This paper summarizes the highlights of this symposium. Understanding the central role of the hypothalamus in the regulation of feeding and energy metabolism will help us gain insights into the pathogenesis and management of common obesity.

Yokota H, Yokoyama K, Nishioka T, et al.
Anterior cerebral artery notching on anterior optic pathways in a child with craniopharyngioma and progressive blindness.
Pediatr Neurosurg. 2011; 47(5):376-8 [PubMed]

We report the clinical significance of anterior cerebral artery (ACA) notching on the optic nerve and chiasm in a 3.5-year-old girl with a craniopharyngioma and progressive blindness. She presented with a headache and vomiting, followed by binocular blindness. Magnetic resonance imaging (MRI) studies demonstrated severely distended A1 segments and ill-depicted ACAs. Surgical decompression via a right subfrontal approach was performed to reverse blindness. Postoperative MRI studies showed good ACA visualization. A second operation via a right pterional approach revealed ACA notching, which appeared as a transverse groove on the right optic nerve and chiasm. ACA notching should be considered as a possible cause of progressive visual disturbance and a potential risk of ACA infarction in a child with a craniopharyngioma.

Fang Y, Cai BW, Zhang H, et al.
Intracystic bleomycin for cystic craniopharyngiomas in children.
Cochrane Database Syst Rev. 2012; 4:CD008890 [PubMed]

BACKGROUND: Craniopharyngiomas are the commonest benign histological tumours to involve the hypothalamo-pituitary region in childhood. Cystic craniopharyngiomas occur in more than 90% of tumours. The optimal treatment of cystic craniopharyngioma remains controversial. Radical resection is the treatment of choice in patients with favourable tumour localization. When the tumour localization is unfavourable, a gross-total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents risk of morbidity especially for children. Intracystic bleomycin has been utilized to potentially delay the use of radiotherapy or radical resection to decrease morbidity.
OBJECTIVES: To determine the benefits and harms of intracystic bleomycin versus other treatments for cystic craniopharyngiomas in children.
SEARCH METHODS: We searched the electronic databases of CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE/PubMed (from 1966 to Oct 2010), and EMBASE/Ovid (from 1980 to Oct 2010) with pre-specified terms. In addition, we searched reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases.
SELECTION CRITERIA: Randomised controlled trials (RCTs) quasi-randomised trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).
DATA COLLECTION AND ANALYSIS: Two review authors independently performed the data extraction and the 'Risk of bias' assessment. We used risk ratio (RR) for binary data and mean difference (MD) for continuous data. We planned that if one of the treatment groups experienced no events and there was only one study available for the outcome, we would use the Fischer's exact test.
MAIN RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a RCT comparing intracystic bleomycin with intracystic (32)P (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference in cyst reduction (MD = -0.15, 95% confidence interval (CI) -0.69 to 0.39, P= 0.59), neurological status (Fisher's exact P = 0.429), 3rd nerve paralysis (Fischer's exact P = 1.00), fever (RR = 2.92, 95% CI 0.73 to 11.70, P = 0.13) and total adverse effects (RR = 1.75, 95% CI 0.68 to 4.53, P = 0.25 ) between the treatment groups. There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer's exact P = 0.029 for both outcomes).
AUTHORS' CONCLUSIONS: Since no RCTs, quasi-randomised trials or CCTs in which only the use of intracystic bleomycin differed between the treatment groups in the treatment of cystic craniopharyngiomas in children, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High quality RCTs are needed.

Laffond C, Dellatolas G, Alapetite C, et al.
Quality-of-life, mood and executive functioning after childhood craniopharyngioma treated with surgery and proton beam therapy.
Brain Inj. 2012; 26(3):270-81 [PubMed]

PRIMARY OBJECTIVE: Childhood craniopharyngioma, a benign tumour with a good survival rate, is associated with important neurocognitive and psychological morbidity, reducing quality-of-life (QoL).
METHOD: This retrospective study analysed QoL, mood disorders, everyday executive functioning and disease's impact on family life in 29 patients (mean age at diagnosis 7 years 10 months (SD = 4.1); mean follow-up period 6 years 2 months (SD = 4.5)) treated for childhood craniopharyngioma by surgery combined with radiotherapy using proton beam. Assessment included a semi-structured interview and standardized scales evaluating self-report of QoL (Kidscreen 52) and depression (MDI-C) and proxy-reports of QoL (Kidscreen 52), executive functioning (BRIEF) and disease's impact (Hoare and Russel Questionnaire).
RESULTS: Twenty-three families answered the questionnaires completely. Overall QoL self-report was within the normal range. QoL proxy-report was lower than self-report. Eleven patients reported depression; 24-38% had dysexecutive symptoms. A majority of families felt 'very concerned' by the disease. Depression and low parental educational level were associated with lower QoL and higher levels of executive dysfunction.
CONCLUSION: Given the high morbidity of childhood craniopharyngioma, screening for psychosocial outcome, cognitive functioning, including executive functions, mood and QoL should be systematic and specific interventions should be developed and implemented.

Harrington MH, Casella SJ
Pituitary tumors in childhood.
Curr Opin Endocrinol Diabetes Obes. 2012; 19(1):63-7 [PubMed]

PURPOSE OF REVIEW: This review focuses on recently published literature on pituitary tumors in children with special focus on craniopharyngioma and prolactinoma. Although most pituitary masses are benign neoplasms, they are associated with high morbidity and mortality related to their proximity to vital neurologic structures including the optic chiasm, hypophysis and hypothalamus, resulting in disruption of pituitary hormone secretion.
RECENT FINDINGS: The role of Wingless/β-beta catenin signaling and aryl hydrocarbon receptor-interacting protein mutations in pituitary tumor formation has been recognized. There is general agreement on optimal treatment of prolactinomas, although duration of medical therapy in children deserves more specific attention. Advances in imaging, medical, surgical and radiotherapy techniques have greatly increased survival rates for all pituitary tumors, but high recurrence rates after attempted complete resection and high progression rates after incomplete resection of craniopharyngioma remain troublesome. Long-term morbidity and late mortality of all pituitary tumors have become better appreciated with recent focus placed on severe obesity. A trend toward a more multidisciplinary approach for craniopharyngioma, including radiotherapy and chemotherapy, particularly when tumor burden involves the hypothalamus, continues.
SUMMARY: A vast amount of literature has been recently published, focusing on the management and long-term sequelae of all pituitary tumors in children. Craniopharyngioma remains the most challenging mass arising within sellar and parasellar areas, and optimal treatment continues to be hotly debated. Recognizing the rarity of pediatric pituitary tumors, the field would greatly benefit from more prospective multicenter trials, as well as from standardization of the assessment of preoperative function and post-treatment outcomes.

Piguel X, Abraham P, Bouhours-Nouet N, et al.
Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement.
Eur J Endocrinol. 2012; 166(2):215-22 [PubMed]

OBJECTIVE: Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects.
DESIGN AND METHODS: Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3±2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO(2max) to fat-free mass (VO(2max)/FFM), a measure independent of age and fat mass in children.
RESULTS: VO(2max)/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO(2max)/FFM (P<0.05), whereas children without hypothalamic involvement had VO(2max)/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia.
CONCLUSIONS: Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined.

Pinho RS, Andreoni S, Silva NS, et al.
Pediatric central nervous system tumors: a single-center experience from 1989 to 2009.
J Pediatr Hematol Oncol. 2011; 33(8):605-9 [PubMed]

The objective of this study was to determine the epidemiology of primary tumors of the central nervous system (CNS) in pediatric patients from a Brazilian oncology institute. We retrospectively analyzed 741 charts (415 males and 326 females) of patients under 21 years of age who were diagnosed with a CNS tumor. The analysis included patients from 1989 to 2009 and was performed using the World Health Organization criteria. We evaluated the distribution of age, sex, topography, clinical symptoms, symptom intervals, and classification of the tumors. Patients with clinical/radiologic diagnoses were included. Seven hundred forty-one patients with tumors in the CNS were reviewed, and 83% of the patients presented a histologic diagnosis. Males (56%) were more prevalent than females. In children under the age of 1 year, the supratentorial compartment was the predominant region involved (62.0%). Astrocytoma was the most frequent tumor type (37.0%), followed by medulloblastoma (13.6%), craniopharyngioma (10.5%), and ependymoma (6.8%). Headaches were the most common symptom, and the symptom intervals varied from 1 to 5010 days. Approximately 4% of the patients had associated genetic syndromes. Although it was not a population study and selection bias may have occurred, this study supplies important epidemiologic data from an emerging country in which population studies are rare.

Rigante M, Massimi L, Parrilla C, et al.
Endoscopic transsphenoidal approach versus microscopic approach in children.
Int J Pediatr Otorhinolaryngol. 2011; 75(9):1132-6 [PubMed]

OBJECTIVES: To confirm the efficacy and safeness of the endoscopic endonasal transsphenoidal (ETS) approach in the treatment of sellar and parasellar lesions in children compared with the conventional microscopic transsphenoidal approach (CTS).
STUDY DESIGN: Case series with chart review.
SETTING: A. Gemelli - University Hospital - Catholic University of Sacred Heart - Rome.
SUBJECT AND METHODS: We retrospectively evaluate 21 children (mean age 8.3 years) affected by sellar/parasellar lesions: 11 were treated via microscopic sublabial approach between 1995 and 2005 and 10 were treated with ETS approach between 2006 and 2009.
RESULTS: The past series (group A) comprised all sellar/suprasellar lesions and we observed: gross total surgical excision in 81.2% of cases, permanent morbidity in 1/11 patients, CSF fistula in 1/11 patients, mean hospitalization time of 5.8 days and PICU was required. The present series (group B) included 8 sellar/suprasellar and 2 clival lesions and we observed: GTS excision in 80% of the cases, no permanent morbidity, a mean hospitalization time of 4.1 days (P=0.01), CSF fistula in 2/10 patients and the PICU was not required. 10/11 patient of group A underwent to blood transfusion vs 4/10 of the group B (P=0.008). The mean pain score of group A was 5.8 ± 1.7 on the contrary in the group B it was 4.1 ± 1.5 (P=0.006).
CONCLUSION: The ETS approach to the sellar and parasellar region has proved its reliability and effectiveness in the adults. The minimal invasiveness makes it ideal for the treatment of pediatric lesion of this region, in which it is essential to preserve the integrity of the hypothalamic-pituitary axis and of the naso-facial structures to assure the correct growth of the child.

Qi S, Pan J, Lu Y, et al.
The impact of the site of origin and rate of tumour growth on clinical outcome in children with craniopharyngiomas.
Clin Endocrinol (Oxf). 2012; 76(1):103-10 [PubMed]

OBJECTIVES: Data on many predictors of hypothalamic-pituitary axis dysfunction associated with childhood craniopharyngioma (CP) are rather inconsistent, probably reflecting the variable but as yet unclarified growth pattern of these tumours. The aim of this study was to define the determinative role of tumour growth pattern on hypothalamic-pituitary axis function and outcomes for childhood CPs.
PATIENTS AND METHODS: The authors retrospectively analysed the records of 81 consecutive children with primary CP who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. The patients were divided into two subgroups based on tumour location and growth patterns: group A (infra-diaphragmatic sellar tumours: 34 cases) and group B [third ventricular floor (3rd VF) tumours: 47 cases]. The children's pre- and postsurgical endocrinological and hypothalamic disturbances were compared. Pituitary function and hypothalamic statues were quantitatively assessed using classification systems proposed in the previous studies.
RESULTS: Preoperative pituitary function was more severely compromised in patients in group A than those in group B and deteriorated significantly following resection in both groups. (Average pituitary function scores increased from 2·19 ± 0·83 to 3·31 ± 0·74, P < 0·001). At the last follow-up, children with 3rd VF tumours had more prevalent weight gain (median body mass index: 23·1 kg/m(2) in group B vs 19·7 kg/m(2) in group A, P < 0·001) and increased hypothalamic dysfunction (average hypothalamic status scores: 2·04 ± 0·97 in group B vs 1·29 ± 0·57 in group A, P < 0·001). Children with 3rd VF tumours had a significantly lower probability of recurrence-free survival than those with sellar tumours (at 5 years: 74%vs 49%, respectively; at 10 years: 66%vs 32%, respectively; P = 0·02).
CONCLUSIONS: Substantial differences in the outcome of childhood CP with different tumour growth patterns and locations were found, which suggested that diverse therapeutic considerations, especially endocrinological substitution, might be emphasized.

Finken MJ, Zwaveling-Soonawala N, Walenkamp MJ, et al.
Frequent occurrence of the triphasic response (diabetes insipidus/hyponatremia/diabetes insipidus) after surgery for craniopharyngioma in childhood.
Horm Res Paediatr. 2011; 76(1):22-6 [PubMed]

BACKGROUND/AIMS: It is not exactly known how many children develop the triphasic response (diabetes insipidus (DI)/hyponatremia/DI) immediately after surgery for childhood craniopharyngioma; neither is it known which factors predict this. We studied the occurrence of the triphasic response after primary surgery for craniopharyngioma in children, and aimed to identify possible predictors.
METHODS: Patients <18 years old who had undergone a primary craniopharyngioma resection between January 1990 and February 2010 in either of the 2 academic centers in Amsterdam were studied retrospectively.
RESULTS: Twenty-one patients (5 males) fulfilled the inclusion criteria. Median age at surgery was 9.1 (range: 4.0-15.1) years. Six patients developed a triphasic response (29%). Of all factors, only the duration of surgery was found to be a predictor of a triphasic response: 8.5 (6.0-11.0) versus 4.6 (3.5-11.5) h in patients who did not develop a triphasic response (p = 0.03).
CONCLUSION: After primary surgery for a craniopharyngioma, a considerable number of patients develop a triphasic response in the regulation of the sodium and water balance. This is predicted by (factors associated with) a longer duration of surgery. Other predictors could not be identified, which may be due to the small sample size.

Beltran C, Roca M, Merchant TE
On the benefits and risks of proton therapy in pediatric craniopharyngioma.
Int J Radiat Oncol Biol Phys. 2012; 82(2):e281-7 [PubMed] Article available free on PMC after 01/11/2013

PURPOSE: Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients.
METHODS AND MATERIALS: For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment.
RESULTS: CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm(3), and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R(2) values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01).
CONCLUSIONS: Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not.

Müller HL
Consequences of craniopharyngioma surgery in children.
J Clin Endocrinol Metab. 2011; 96(7):1981-91 [PubMed]

CONTEXT: Childhood craniopharyngioma, a rare embryogenic tumorous malformation of the sellar region, is characterized by survival rates ranging from 91 to 98%. However, quality of survival is frequently impaired due to proximity to optical, pituitary, and hypothalamic structures. Long-term sequelae substantially reduce the quality of life of approximately 50% of long-term survivors, notably extreme obesity owing to hypothalamic involvement and/or surgical- or radiation-induced lesions. EVIDENCE ACQUISITION AND SYNTHESIS: This report reviews the current understanding of diagnostic and treatment options and their consequences on the prognosis and quality of life in patients with childhood craniopharyngioma based on publications from PubMed, Science Citation Index Expanded, EMBASE, and Scopus from the year 1980 onward.
CONCLUSIONS: Total resection is the treatment of choice in patients with favorable tumor localization, with extreme care taken to preserve hypothalamic-pituitary and optical nerve functions. When tumor localization is unfavorable, i.e. involvement of hypothalamic or optic structures, a limited resection followed by local irradiation is recommended. Optimal timing of recurrence-inhibiting irradiation after incomplete resection is currently under investigation in an international trial. The rarity of the disease, coupled with limited surgical options, dictates that treatment and long-term monitoring of consequences should be confined to experienced multidisciplinary teams.

Holmer H, Popovic V, Ekman B, et al.
Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma.
Eur J Endocrinol. 2011; 165(1):25-31 [PubMed]

CONTEXT: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment.
OBJECTIVE: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures.
DESIGN AND PARTICIPANTS: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls.
RESULTS: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only.
CONCLUSIONS: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.

Elliott RE, Jane JA, Wisoff JH
Surgical management of craniopharyngiomas in children: meta-analysis and comparison of transcranial and transsphenoidal approaches.
Neurosurgery. 2011; 69(3):630-43; discussion 643 [PubMed]

BACKGROUND: Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas.
OBJECTIVE: We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid.
METHODS: Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria.
RESULTS: Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages.
CONCLUSION: Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification.

Müller HL, Gebhardt U, Teske C, et al.
Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up.
Eur J Endocrinol. 2011; 165(1):17-24 [PubMed]

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.

Winkfield KM, Tsai HK, Yao X, et al.
Long-term clinical outcomes following treatment of childhood craniopharyngioma.
Pediatr Blood Cancer. 2011; 56(7):1120-6 [PubMed]

PURPOSE: To review our institution's experience with treatment of craniopharyngioma in children, and to report long-term treatment outcomes stratified by treatment era to assess whether modern treatment techniques result in improvements in local control and survival.
MATERIALS AND METHODS: We retrospectively reviewed the records of 100 children who underwent surgery for craniopharygioma at Children's Hospital Boston (CHB) from August 1976 to March 2003. Of these, 79 children (median age 8.5 years) had initial treatment at CHB and sufficient follow-up data to be included in this analysis. We report their treatment course, recurrence rates, and treatment-related morbidity. We compared the results in two different treatment eras based on changes in surgical approach at CHB.
RESULTS: Thirty-six patients underwent initial treatment with surgery alone; 63% treated prior to 1988 recurred and 36% treated after 1988 recurred. Recurrence rates following combined modality therapy (CMT) with limited surgery followed by radiation were 21 and 5% in the pre- and post-1988 eras, respectively. Accounting for treatment era, patients treated with surgery alone were 7.7 times as likely to recur as those treated with CMT (95%CI: 2.0, 28.7). In the Cox regression model, there was no significant difference in local control or overall survival based on treatment era; initial treatment remained the only statistically significant variable (P = 0.02).
CONCLUSIONS: Advancements in treatment techniques have improved local control in children diagnosed with craniopharyngioma. The excellent survival rates necessitate long-term patient follow-up to identify and manage any treatment-related effects, including second tumors, vascular abnormalities, and endocrinopathies.

Nielsen EH, Feldt-Rasmussen U, Poulsgaard L, et al.
Incidence of craniopharyngioma in Denmark (n = 189) and estimated world incidence of craniopharyngioma in children and adults.
J Neurooncol. 2011; 104(3):755-63 [PubMed]

We studied the incidence of craniopharyngioma in Denmark during the period 1985-2004 and estimated worldwide incidence rates (IR) of craniopharyngioma based on a literature review. Craniopharyngioma patients diagnosed during the period 1985-2004 were identified from the Danish National Patient Registry, the Danish Cancer Registry and regional registries. Medical records were reviewed. Danish population data were obtained from Statistics Denmark. European and World population data were obtained from EU and WHO homepages. Prior studies providing data on craniopharyngioma IRs were identified via PubMed and, if appropriate, were included in a weighted analysis estimating overall and children's IRs of craniopharyngioma. IRs are given as new cases per million per year. We identified 189 patients with new verified (162) or probable craniopharyngioma. The overall WHO World-standardised incidence rate was 1.86 (1.60-2.14) for all ages and 2.14 (1.53-2.92) for children (age <15 years). Peak incidence rates were observed in age groups 5-9 and 40-44 years. Fifteen prior studies (including 1,232 craniopharyngioma cases) were identified. Seven and 11 studies, respectively, were eligible for weighted all-ages and childhood population IR analyses, yielding summary IRs of 1.34 (1.24-1.46) (all ages) and 1.44 (1.33-1.56) (children). We have provided a detailed survey of the incidence of craniopharyngioma in Denmark during a recent 20-year period. Overall IR of craniopharyngioma in Denmark was 1.86 (1.60-2.14) as compared to 2.14 (1.53-2.92) among children. Weighted estimates of craniopharyngioma world IRs were 1.34 (1.24-1.46) in all ages and 1.44 (1.33-1.56) among children.

Boehling NS, Grosshans DR, Bluett JB, et al.
Dosimetric comparison of three-dimensional conformal proton radiotherapy, intensity-modulated proton therapy, and intensity-modulated radiotherapy for treatment of pediatric craniopharyngiomas.
Int J Radiat Oncol Biol Phys. 2012; 82(2):643-52 [PubMed]

PURPOSE: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas.
METHODS AND MATERIALS: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms.
RESULTS: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%*), dentate gyrus (27.3, 75.0%*), and subventricular zone (4.5, 57.8%*). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3*, 100.0%*; middle cerebral arteries, 25.9%*, 100%*; anterior communicating arteries, 30.8*, 41.7%*; and carotid arteries, 51.5*, 77.6*). Relative reduction of integral dose to the infratentorial brain (190.7*, 109.7%*), supratentorial brain without PTV (9.6, 26.8%*), brainstem (45.6, 22.4%*), and whole brain without PTV (19.4*, 34.4%*) were recorded with the use of proton therapy. (*Differences were significant based on Friedman's test with Bonferroni-Dunn correction, α = 0.05)
CONCLUSIONS: The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.

Mortini P, Losa M, Pozzobon G, et al.
Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series.
J Neurosurg. 2011; 114(5):1350-9 [PubMed]

OBJECT: Craniopharyngioma accounts for 2%-5% of all primary intracranial neoplasms. The optimal management of craniopharyngioma remains controversial. The authors evaluated the early results of surgery and the longterm risk of tumor recurrence in a large series of patients undergoing resection of craniopharyngiomas.
METHODS: Between 1990 and 2008, 112 consecutive patients (57 male and 55 female patients with a mean [± SEM] age of 33.3 ± 1.8 years) underwent resection of craniopharyngiomas at the authors' hospital. Recurrence or growth of residual tumor tissue during follow-up was assessed using MR imaging.
RESULTS: There were 3 perioperative deaths (2.7%). Severe adverse events were more frequent in patients who underwent operations via the transcranial route (37%) than the transsphenoidal approach (5.6%; p < 0.001). Magnetic resonance imaging showed radical resection of the tumor in 78 (71.6%) of the remaining 109 patients. Previous surgery and maximum tumor diameter were associated with persistence of disease after surgery. Craniopharyngioma recurred in 26 (24.5%) of 106 patients. Presence of residual tumor on the first postoperative MR imaging, male sex, and no postoperative radiation therapy were associated with a risk of tumor recurrence. Quality-of-life data were assessed in the 91 patients who attended the authors' institution for follow-up visits. Among them, 8.8% patients were partially or completely dependent on others for daily living activities before surgery. This percentage increased to 14.3% at the last follow-up visit. The 5- and 10-year overall survival rates were 94.4% (95% CI 90.0%-98.8%) and 90.3% (95% CI 83.4%-97.3%), respectively.
CONCLUSIONS: Complete surgical removal of craniopharyngioma can be achieved with reasonable safety in more than 70% of patients. Recurrence of craniopharyngioma may occur even after apparent radical excision. Prompt management of residual or recurring disease by radiotherapy, repeat surgery, or a combination of both is usually successful in controlling further tumor growth.

Crom DB, Smith D, Xiong Z, et al.
Health status in long-term survivors of pediatric craniopharyngiomas.
J Neurosci Nurs. 2010; 42(6):323-8; quiz 329-30 [PubMed]

Craniopharyngiomas are the third most common pediatric brain tumor and most common pediatric suprasellar tumor. Contemporary treatment of craniopharyngiomas uses limited surgery and radiation in an effort to minimize morbidity, but the long-term health status of patients treated in this fashion has not been well described. The purpose of this study was to analyze the health status of long-term survivors of pediatric craniopharyngioma treated primarily with radiation and conservative surgical resection. Medical records of all long-term survivors of craniopharyngioma treated at St. Jude Children's Research Hospital and then transferred to the long-term follow-up clinic were reviewed. The initial cohort comprised 55 patients. Of these, 51 (93%) were alive at the time of this analysis. The median age at diagnosis was 7.1 years (range, 1.2-17.6 years), and 29 (57%) were male. At the time of analysis, the median survival was 7.6 years (range, 5.0-21.3 years). Diagnosis and treatment included surgical biopsy, resection (n = 50), and radiation therapy (n=48). Only 1 patient received chemotherapy. Polyendocrinopathy was the most common morbidity, with hypothyroidism (96%), adrenocorticotropic hormone deficiency (84%), and diabetes insipidus (53%) occurring most frequently. Half of the patients were hypogonadal, and 33 (65%) were overweight or obese. The most common neurologic problems included shunt dependence (37%), seizures (28%), and headaches (39%). Psychological and educational deficits were also identified in a significant number of these individuals. Despite efforts to reduce morbidity in these patients, many survivors remain burdened with significant medical complications. In a small percentage of patients, complications may result in death even during extended remission of craniopharyngioma. Because of the broad spectrum or morbidities experienced, survivors of craniopharyngioma continue to benefit from multidisciplinary care.

Gucev ZS, Danilovski D, Tasic V, et al.
Childhood craniopharyngioma in Macedonia: incidence and outcome after subtotal resection and cranial irradiation.
World J Pediatr. 2011; 7(1):74-8 [PubMed]

BACKGROUND: craniopharyngioma is a frequent tumor in children with challenging surgical, endocrine, and visual consequences. We evaluated our experience in treating craniopharyngioma and its incidence in Macedonia.
METHODS: Thirteen children (9 male and 4 female) with craniopharyngioma (age 9.55 ± 3.74 years; range 2.90-15.11) who had been treated between 1989 and 2008 in Macedonia were reviewed.
RESULTS: initial signs were vision disturbances (10 children), seizures (1), growth retardation (13), and diabetes insipidus (DI) (2). All children were subjected to subtotal surgical removal. Cranial irradiation was performed in 12 of the 13 children, and intracystic bleomycin was given to one child. The patients were followed up for 6-229 months (mean ± SD: 107.00 ± 74.04 months). All children had multiple pituitary deficiencies after surgical removal of the tumor. Body mass index increased from 16.93 ± 6.34 standard deviation scores (SDS) at diagnosis to 26.33 ± 5.91 SDS (P>0.005) at the last follow-up. DI was permanent in 9 of the 13 children, and multiple pituitary deficiencies were seen in all children. Treatment with growth hormone resulted in normalization of adult height from -1.27 ± 1.52 SDS at the start of the treatment to -0.13 ± 1.39 SDS at the last followup. The final height was not significantly lower than the genetic target height (P>0.005). The permanent deficit was visual impairment: blindness in one or both eyes in 4 children, bitemporal hemianopsia in 4, and other defects in 2. Recurrence of the disease was ruled out in one child after 31 months. No mortality was observed in the observation period of 104.92 ± 76.11 months.
CONCLUSIONS: the overall incidence of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000 000 person-years. Subtotal resection and systematic irradiation showed good life quality of survivors.