Semaglutide as a promising treatment for hypothalamic obesity: a six-month case series on four females with craniopharyngioma.

PURPOSE: Patients with hypothalamic pathology often develop hypothalamic obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Treatments for hypothalamic obesity have not proven very effective, although the glucagon-like peptide-1 receptor agonist semaglutide has been shown to have positive effects. We examined semaglutide's effect on weight loss in a sample of patients with hypothalamic obesity. METHODS: Four female patients with hypothalamic obesity resulting from treatment of craniopharyngiomas were treated with semaglutide for six months. Whole Body Dual-energy x-ray absorptiometry scans were performed, and blood samples drawn at baseline and after six months. Semaglutide dosages were increased monthly along with tracking of body weight and eating behavior (Three Factor Eating Questionnaire, TFEQ-R18). RESULTS: BMI was reduced in all cases, with an average of 7.9 BMI (range: 6.7 to 10.1) corresponding to a weight loss of 17.0% (range: 11.3-22.4%) or 20.2 kg (range 16.2 kg to 23.4 kg). We found a comparable reduction in total fat mass (17.2%, p = 0.006) and lean mass (16.0%, p = 0.05), whereas bone mass was unchanged (2.6%, p = 0.12). All cases reported an increase in energy levels, improved mobility and physical activity. Unfavorable eating behaviors were reduced after 1 month of treatment (emotional eating - 41 points, p = 0.02, uncontrolled eating - 23 points, p = 0.11). HbA1c and total cholesterol were significantly reduced (p = 0.014 for both). CONCLUSION: Semaglutide is a promising and safe treatment option for HO, that improves eating behavior, reduces weight, and improves metabolic markers.

Sporadic and neurofibromatosis type 2-associated meningioma in children and adolescents.

PURPOSE: Pediatric meningioma differs not only in its rare incidence from the adult meningioma, but also in its clinical characteristics. Many treatment approaches of pediatric meningioma are based on the study results of adult meningioma studies. The aim of this study was to explore the clinical and epidemiological characteristics of pediatric meningioma. METHODS: Data on pediatric patients diagnosed between 1982 and 2021 with NF2-associated or sporadic meningioma and recruited in the trials/registries HIT-ENDO, KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 were retrospectively analyzed for clinical characteristics, etiology, histology, therapy, and outcome. RESULTS: One hundred fifteen study participants were diagnosed with sporadic or NF2-associated meningioma at a median age of 10.6 years. There was a 1:1 sex ratio, with 14% of study participants suffering from NF2. 46% of the meningiomas were located hemispherically, 17% at the optic nerve/ intraorbital and 10% ventricularly. Multiple meningiomas were detected in 69% of NF2 patients and in 9% of sporadic meningiomas. 50% of the meningiomas were WHO grade I, 37% WHO grade II and 6% WHO grade III. Progressions or recurrences occurred after a median interval of 1.9 years. Eight patients (7%) died, 3 of them due to disease. The event-free survival was higher for WHO grade I than for WHO grade II meningioma patients (p = 0.008). CONCLUSIONS: The major difference to the preceding literature could be found in the distribution of different WHO grades and their influence on event-free survival. Prospective studies are warranted to assess the impact of different therapeutic regimens. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00258453; NCT01272622; NCT04158284.

SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings.

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.

[Legal Degree of Disability in Childhood-Craniopharyngioma Survivors During Long-Term Follow-Up]. / Anerkannter Grad der Behinderung (GdB) im Langzeitverlauf nach Kraniopharyngeom im Kindes- und Jugendalter.

BACKGROUND: Cranioparyngiomas are rare low-grade embryonic malformational tumors of the sellar/parasellar region. The prognosis after diagnosis during childood and adolescence is influenced by (neuro)endocrine long-term sequelae. A legal status of the degree of disability (GdB), according to the German Social Code Book V that is worthy of support provides financial means for psychosocial integration and participation of craniopharyngioma survivors. PATIENTS AND METHODS: HIT-Endo is a German registry study on craniopharyngioma patients aged≤18 years at diagnosis . In a sample of 108 patients, the degree of disability and the association with endocrine, ophthalmological, neuropsychological (QLQ-C30; MFI-20; FMH-scale) and psychosocial parameters was analyzed after a mean follow-up period of 16 years. RESULTS: 47 patients (43%) did not receive a GdB or received a GdB of 30-40, 43 patients (40%) a GdB of 50-90 and 18 patients (17%) the maximal GdB of 100. Higher GdB were associated with lower education, higher body mass index standard deviation and a higher degree of visual impairment and hypothalamic involvement of the craniopharyngioma. Patients with a GdB of 100 reported loss in physical and cognitive function, dyspnea, and pain (QLQ-C30), as well as fatigue (MFI-20), and limitations in social and occupational contexts. They further had a lower functional capacity (German daily life ability scale (FMH)) compared to those with a smaller GdB. CONCLUSION: The GdB is associated with psychosocial and physical impairments and reflects the long-term consequences of craniopharyngioma. A low functional capacity may indicate a high GdB in later life of craniopharyngioma survivors.

Molecular profiling of pediatric meningiomas shows tumor characteristics distinct from adult meningiomas.

In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

Pregnancies after Childhood Craniopharyngioma: Results of KRANIOPHARYNGEOM 2000/2007 and Review of the Literature.

BACKGROUND: Data on female fertility, pregnancy, and outcome of offspring after childhood-onset craniopharyngioma (CP) are rare. STUDY DESIGN: Observational study on pregnancy rate and offspring outcome in female CP patients recruited in KRANIOPHARYNGEOM 2000/2007 since 2000. RESULTS: A total of 451 CP patients (223 female) have been recruited, and 269 (133 female) were postpubertal at study. Six of 133 female CP patients (4.5%) with a median age of 14.9 years at CP diagnosis had 9 pregnancies, giving birth to 10 newborns. Three patients achieved complete surgical resections. No patient underwent postoperative irradiation. Five natural pregnancies occurred in 3 CP patients without pituitary deficiencies. Four pregnancies in 3 CP patients with hypopituitarism were achieved under assisted reproductive techniques (ART) (median 4.5 cycles, range: 3-6 cycles). Median maternal age at pregnancy was 30 years (range: 22-41 years). Six babies (60%) were delivered by caesarean section. Median gestational age at delivery was 38 weeks (range: 34-43 weeks); median birth weight was 2,920 g (range: 2,270-3,520 g), the rate of preterm delivery was 33%. Enlargements of CP cysts occurred in 2 women during pregnancy. Other complications during pregnancy, delivery, and postnatal period were not observed. CONCLUSIONS: Pregnancies after CP are rare and were only achieved after ART in patients with hypopituitarism. Close monitoring by an experienced reproductive physician is necessary. Due to a potentially increased risk for cystic enlargement, clinical, ophthalmological, and MRI monitoring are recommended in patients at risk. Severe perinatal complications, birth defects, and postnatal morbidity of mothers and offspring were not observed.

Cardiac remodeling in patients with childhood-onset craniopharyngioma-results of HIT-Endo and KRANIOPHARYNGEOM 2000/2007.

Hypothalamic obesity caused by childhood-onset craniopharyngioma results in long-term cardiovascular morbidity. Knowledge about clinical markers and risk factors for cardiovascular morbidity is scarce. A cross-sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 craniopharyngioma patients. BMI correlated with the thickness of interventricular septum in diastole (IVSd) (r = 0.604, p < 0.001) and left ventricular posterior wall thickness in diastole (LVPWd) (r = 0.460, p = 0.011). In multivariate analyses on risk factors for cardiac remodeling, sex hormone replacement therapy, BMI, and male gender were positively correlated with increased left ventricular internal diameter in diastole (LVIDd), R2 = 0.596, F = 10.323, p < 0.001. BMI and insulin resistance were selected as significant independent determinants of IVSd, produced R2 = 0.655, F = 29.441, p < 0.001. Due to a wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥ 18 years), BMI correlated with IVSd (r = 0.707, p = 0.003), LVPWd (r = 0.592, p = 0.020), and LVIDd (r = 0.571, p = 0.026). In the pediatric subgroup (age at study < 18 years), no correlation between transthoracic echocardiography (TTE) parameters and BMI was observed. Only LVIDd correlated with disease duration (r = 0.645, p < 0.001). All cardiac functions were within the normal range, indicating no association with functional impairments.Conclusion: Cardiac remodeling in patients with craniopharyngioma correlated with the degree of hypothalamic obesity, disease duration, sex hormone replacement therapy, male gender, and insulin resistance. As echocardiography has limited sensitivity in patients with obesity, further research on more sensitive techniques for cardiac diagnostics in craniopharyngioma patients is warranted. What is Known: •Long-term prognosis in survivors of craniopharyngioma is impaired by obesity and cardiovascular disease. •Associations between echocardiographic findings and clinical and anthropometric parameters after craniopharyngioma are not yet analyzed. What is New: •In patients with childhood-onset craniopharyngioma, cardiac remodeling was associated with hypothalamic obesity, duration of disease, male gender sex hormone replacement, and insulin resistance. •Due to reduced echocardiographic sensitivity caused by obesity-related technical limitations, more sensitive cardiac diagnostics should be considered.

The Diagnosis and Treatment of Craniopharyngioma.

Craniopharyngioma (CP) is a rare embryonic malformation of the sellar/parasellar region with a low histological grade. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Recent insight into the molecular pathogenesis of CP opens new perspectives on targeted therapy in papillary CP harboring BRAF-V600E mutations. Further research to elucidate pathogenic mechanisms and hopefully prevent hypothalamic involvement of CP is warranted. If the tumor is favorably localized, the therapy of choice is complete resection, with care taken to preserve the optical and hypothalamic functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), the recommended therapy is a limited hypothalamus-sparing surgical strategy followed by local irradiation. Surgical treatment strategies should be based on a multidisciplinary approach involving experienced teams. Centralizing the treatment of CP in experienced "centers of excellence" and multicenter-based networks for reference assessments should be considered to assure a high standard of treatment quality. CP recurrence and progression are frequent. Irradiation has proven effective in reducing recurrences and progression. Proton beam therapy, available in a wider range in the near future, will help to avoid radio-oncological side effects. Anatomical involvement and/or surgical lesions of posterior hypothalamic areas can result in serious sequelae that compromise quality of life (QoL), such as hypothalamic obesity and psychopathological symptoms. Novel insights into neuropsychological sequelae after CP occurrence should be the basis for the development of therapeutic neuropsychological interventions. CP should be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' clinical and QoL consequences by experienced multidisciplinary teams.

Impact of motion artefacts and motion-artefact correction on diagnostic accuracy of apical periodontitis in CBCT images: an ex vivo study in human cadavers.

AIM: To assess the impact of motion artefacts and motion-artefact correction on diagnostic accuracy of apical periodontitis (AP) in CBCT images. METHODOLOGY: Based on clinical and radiographic inspection of 40 formalin-fixated human jaw specimens, 77 roots in 45 teeth (molars and premolars), with various disease and treatment state, were selected. The specimens were mounted on a robot simulating 3-mm movement types (nodding, lateral rotation and tremor). CBCT images with and without (controls) movements were acquired in four CBCT units: without motion-artefact correction in Cranex 3Dx, Orthophos SL 3D, and Promax 3D Mid, and with motion-artefact correction in Promax 3D Mid and X1. Three observers blindly assessed (i) whether the images were interpretable and (ii) if AP was present (5-step probability index). Histopathology provided the reference standard for presence of AP. Weighted Kappa statistics described inter-observer agreement. Estimates of diagnostic accuracy were assessed by means of receiver operator characteristic (ROC) curve analysis. Area under the curve (AUC) provided a measure of accuracy, and paired-sample AUC difference tests compared differences amongst the CBCT units and movement types. RESULTS: Observer agreement was substantial for control images, moderate for motion-artefact corrected images and fair for images without motion-artefact correction. When movement was present, motion-artefact correction reduced the percentage of images scored as noninterpretable or with uncertain disease state (score 3 in the 5-step probability index). Control images were not perfectly accurate (both false-positive and false-negative results were present; AUC 0.750-0.799). Images acquired with movement and without motion-artefact correction (AUC 0.541-0.709) were associated with significantly lower accuracy than control images (P < 0.05). With motion-artefact correction, accuracy was comparable to that observed in control images (AUC 0.732-0.790). CONCLUSIONS: Diagnostic accuracy of apical periodontitis in CBCT images was dependent on the presence of motion artefacts (i.e. lower accuracy associated with the presence of movement). Motion-artefact correction systems positively influenced image interpretability and diagnostic accuracy.

Integrated analysis of long-term growth and bone development in pediatric and adolescent patients receiving bevacizumab.

BACKGROUND: We conducted an integrated analysis of clinical data to describe long-term effects of bevacizumab on growth and bone development in pediatric and adolescent patients with solid tumors. PROCEDURE: Clinical data were pooled from five phase I/II trials of bevacizumab versus chemotherapy: BERNIE, HERBY, and AVF4117s enrolled newly diagnosed patients, AVF3842s and AVF2771s enrolled patients with relapsed/refractory disease. Height, weight, body mass index (BMI), and bone-age data were pooled by treatment group. Growth charts were used to track and monitor growth in relation to a reference population of healthy children. Bone age was measured based on X-ray of the left hand and wrist. Analyses were exploratory/descriptive. RESULTS: Overall, 268 patients received bevacizumab ± chemotherapy and 135 received chemotherapy alone. Baseline characteristics were generally balanced. Median duration of long-term follow-up was 41.8 months (range, 2.4-75.1) with bevacizumab and 22.9 months (range, 2.8-69.2) with chemotherapy alone. Patients had age-appropriate baseline height and weight. Mean height and weight percentiles decreased over time in both treatment groups, but remained within the normal range (height: mean standard deviation score [SDS] range -2 to +3; weight: mean SDS range -2 to +1). Similar trends were seen in BMI. A tendency for reduced growth velocity relative to the reference population was observed at 6 months and 1 year in both groups, but there was no additional decrease for patients receiving bevacizumab. CONCLUSION: Bevacizumab did not appear to have additional negative effects on growth or development of pediatric and adolescent patients with solid tumors.

Craniopharyngiomas presenting as incidentalomas: results of KRANIOPHARYNGEOM 2007.

PURPOSE: Childhood-onset craniopharyngiomas (CP) are diagnosed due to clinical symptoms (symCP) or incidentally (incCP). We investigated clinical manifestations and outcome in incCPs and symCPs. METHODS: IncCP were discovered in 4 (3 m/1 f) and symCP in 214 (101 m/113 f) CP recruited 2007-2014 in KRANIOPHARYNGEOM 2007. Age, sex, height, body mass index (BMI), tumor volume, degree of resection, pre- and postsurgical hypothalamic involvement/lesions, pituitary function and outcome were compared between both subgroups. RESULTS: Reasons for imaging in incCP were cerebral palsy, head trauma, nasal obstruction, and tethered-cord syndrome, whereas headache (44%), visual impairment (25%), and growth retardation (17%) lead to imaging in symCP. Tumor volume at diagnosis was smaller in incCP (median 2.39 cm3; range 0.14-4.10 cm3) when compared with symCP (15.86 cm3; 0.002-286.34 cm3). Age, gender, BMI, height, hydrocephalus, tumor location, and hypothalamic involvement at diagnosis of incCP were within the range of these parameters in symCP. Complete resections were achieved more frequently (3/4 patients) in incCP when compared with symCP (20%). Surgical hypothalamic lesions were distributed similar in incCP and symCP. Irradiation was performed only in symCP (33%). No noticeable differences were observed concerning survival rates, endocrine deficiencies, BMI, height, functional capacity and quality of life of the 4 incCP cases when compared with the symCP cohort. CONCLUSIONS: IncCP are rare (1.8%) and characterized by lack of endocrine deficiencies, resulting in normal height and BMI, no hydrocephalus, and smaller tumor volume at diagnosis when compared with symCPs. Outcome of the observed incCP is similar with symCP. CLINICAL TRIAL REGISTRATION NUMBER: NCT01272622.

Self- and informant-rated apathy in patients with childhood-onset craniopharyngioma.

INTRODUCTION: The current study aimed to assess whether childhood-onset craniopharyngioma patients suffer from symptoms of apathy, as assessed by patients themselves and their close others. We further analyzed whether apathy scores are related to symptoms of depression. METHODS: Childhood-onset craniopharyngioma patients (n = 35, 16 female, median age = 22) and matched healthy controls (n = 35, 19 female, median age = 21) were asked to complete self-ratings of the Apathy Evaluation Scale, whereas informant-ratings were obtained from their close others. Depression was assessed by self-ratings using the German version of the Center for Epidemiological Studies Depression Scale. As primary outcome measures, self- and informant-rated apathy scores were compared between patients and healthy controls. As secondary outcome measures, differences between self- and informant-rated apathy within the single groups and associations between apathy and depression were analyzed. RESULTS: Compared to healthy controls, patients displayed significantly higher apathy levels in informant-ratings (medianpatients = 18, mediancontrols = 12, p = .021), but not in self-ratings (medianpatients = 11, mediancontrols =12, p = .68). In patients, there was a significant discrepancy between self- and informant-rated apathy and self-rated apathy was related to symptoms of depression. CONCLUSIONS: This is the first study to show that childhood-onset craniopharyngioma patients may be at high risk for apathy. Noteworthy, apathy levels in the patient group were judged to be high by their close others but not by the patients themselves, indicating that many patients were not fully aware of their impairments. As apathy is associated with numerous adverse outcomes affecting everyday life and vocational opportunities, future investigations are needed to identify specific risk factors for apathy. Clinical Trial Registration No: NCT00258453.

Pediatric prolactinoma: initial presentation, treatment, and long-term prognosis.

Prolactinoma is a rare pituitary adenoma secreting prolactin. Studies on diagnostics, treatment, and prognosis in pediatric prolactinoma patients are rare. We analyzed clinical presentation, response to treatment, and prognosis of 27 pediatric prolactinoma patients (10 m/17 f. based on patients' records. Tumors included 6 microadenomas (tumor volume: median 0.2 cm3, range 0.01-0.4 cm3; serum prolactin at diagnosis: median 101 ng/ml, range 33-177 ng/ml), 15 macroadenomas (volume: median 3.3 cm3, range 0.4-25.8 cm3; prolactin: median 890 ng/ml, range 87-8624), and 3 giant adenomas (volume: median 44.5 cm3, range 38.6-93.5 cm3; prolactin: median 4720 ng/ml, range 317-10,400); data for 3 patients were not available. Dopamine agonist treatment (n = 22) was safe and effective, leading to reductions in tumor size (p < 0.01) and prolactin levels (p < 0.01). Threat to vision was the indication for decompressing surgery in three of seven operated patients. No patient was irradiated. Long-term functional capacity was not impaired when compared with other sellar masses (n = 235). CONCLUSION: In pediatric prolactinoma, diagnosis is based on hyperprolactinemia and imaging. Dopamine agonist treatment is effective and safe. Overall survival and functional capacity as a measure of quality of survival were not impaired, indicating an optimistic prognosis. Surgery should be considered only in emergency situations of threatened visual function, not presenting a fast response to dopamine agonist treatment. Severe side effects of medication and lack of efficacy should be considered as contraindications. What is Known: • In pediatric prolactinoma-a very rare pediatric neuroendocrinological disease-gender-related differences in terms of clinical presentation at initial diagnosis are known. • Due to the rareness of the disease, reports on long-term outcome and prognosis after childhood-onset prolactinoma based on prospective follow-up are not published. What is New: • Dopamine agonist treatment is efficient and safe for tumor volume reduction in pediatric prolactinoma and surgical interventions are recommended only for decompression of the optic chiasm in case of threat to vision. In case of inefficient response to medication, side effects or parental refuse, alternative therapeutic options should be considered. • Quality of life in terms of survival and functional capacity was not impaired in pediatric prolactinoma patients when compared with 235 long-term survivors of different sellar masses.

Low concordance between surgical and radiological assessment of degree of resection and treatment-related hypothalamic damage: results of KRANIOPHARYNGEOM 2007.

BACKGROUND: Assessment of presurgical hypothalamic involvement (psHI) and treatment-related hypothalamic damage (trHD) is relevant for the decision on risk-adapted treatment and rehabilitation strategies in craniopharyngioma. PATIENTS AND METHODS: 129 surgical reports of childhood-onset craniopharyngioma patients recruited 2007-2014 in KRANIOPHARYNGEOM 2007 were analyzed. Data on psHI were available based on surgeon's (63%), reference neuroradiologist's (95%), and local radiologist's (23%) assessment. The surgical degree of resection (DoR) was assessed by neurosurgeon (95%), reference neuroradiologist (73%), and local radiologist (61%). TrHD was assessed by neurosurgeon (33%), by reference neuroradiologist (95%), and by local radiologist (2%). Neurosurgical center size was categorized based on patient load. RESULTS: Surgical assessments on psHI (n = 78), DoR (n = 89) and trHD (n = 42) as documented in surgical reports could be compared with the assessment of respective parameters by reference neuroradiologist. Differences with regard to DoR (p = 0.0001) and trHD (p < 0.0001) were detectable between surgeon's and reference neuroradiologist's assessment, whereas psHI was assessed similarly. Concordance for DoR and trHD was observed in 48 and 62%, respectively. Surgeons estimated a higher rate of complete resections and a lower rate of trHD. Neuroradiological reference assessment of trHD had higher predictive value for hypothalamic sequelae then surgical assessment. Observed differences were not related to neurosurgical center size. CONCLUSIONS: Observed differences between surgical and neuroradiological estimation of risk factors in craniopharyngioma support the necessity of neuroradiological reference review to assure standards of quality. This could be established by central internet-based neuroradiological review in KRANIOPHARYNGEOM 2007. Standardization of surgical reports including specific assessment of tumor/damage location is recommended.

Risk-adapted, long-term management in childhood-onset craniopharyngioma.

PURPOSE: This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management. METHODS: Literature search on Pubmed for paper published after 1994. RESULTS: Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome. CONCLUSIONS: It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' by experienced multidisciplinary teams in the context of multicenter trials.

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.

A systematic review of cognitive performance in patients with childhood craniopharyngioma.

Craniopharyngiomas are rare brain tumors of the sellar/suprasellar region, often adversely affecting patients' physical and psychosocial functioning. Until a few years ago, knowledge on cognitive deficits in craniopharyngioma patients was based on little valid evidence, with considerable inconsistencies across studies. Findings from recent research, with partly larger sample sizes, add to existing evidence to provide a more clear and reliable picture. The current review aims to summarize and systemize current findings on cognitive deficits in childhood craniopharyngioma, taking account of patient- and treatment-related variables where possible. Those studies were included that reported results of childhood craniopharyngioma patients tested with formalized neuropsychological tests (irrespective of their age at study, group size ≥10). A systematic assignment of test results to subcomponents of broader cognitive domains (e.g. to specific memory systems and processes) allows for a first comprehensive overview of patterns of spared and impaired cognitive functions. We show that episodic memory recall in particular is impaired, largely sparing other memory components. In accordance with recent knowledge on mammillary function, patients with hypothalamic involvement appear to be at particular risk. Deficits in higher cognitive processes, relying on the integrity of the prefrontal cortex and its subcortical pathways, may also occur, but results are still inconsistent. To gain deeper insight into the pattern of deficits and their association with patient- and treatment-related variables, further multi-site research with larger cohorts is needed.

Osteosarcoma in patients with Rothmund-Thomson syndrome.

BACKGROUND: Rothmund-Thomson syndrome (RTS) is associated with an increased risk of osteosarcoma, but information about affected patients is limited. PROCEDURE: Seven patients with osteosarcoma, treated in the Cooperative Osteosarcoma Study Group-trials, had a diagnosis of RTS. Their patient-, tumor- and treatment-related variables and outcome were reviewed retrospectively. RESULTS: Median age at diagnosis of osteosarcoma was 13 years (range 7-16), five were female, two male. Tumor involved proximal tibia (n = 4), distal tibia (n = 1), distal fibula (n = 1) and proximal ulna (n = 1). Three patients had metastatic disease at diagnosis. All patients received surgery and chemotherapy. Four of seven patients required dose modifications and three of them terminated treatment prematurely. Complete resection of the primary tumor was achieved in all individuals. Two of three affected patients failed to achieve surgical clearance of their primary metastases and died. The third patient relapsed with multiple metastases and died. Two of four patients with localized disease were alive in first complete remission, a third patient in second complete remission after recurrence and a fourth patient died of acute leukemia, while still in first complete remission of osteosarcoma. CONCLUSIONS: Patients with RTS and osteosarcoma may be cured of their cancer with appropriate multimodal therapy. They should be treated like other osteosarcoma patients but preexisting disorders, needs for special support and development of toxicities have to be considered.