Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma.

OPINION STATEMENT: The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.

[Chinese expert consensus on diagnosis and treatment of craniopharyngioma (2024)].

Craniopharyngioma is a sellar tumor with benign pathology and malignant clinical manifestations. Partial resection plus radiotherapy, internal radiation therapy and chemotherapy are the conventional treatment strategies forcraniopharyngioma in most hospitals, which cause many patients to lose the best time to cure and make reoperation more difficult after recurrence. Therefore, the Pediatric Group of Chinese Society of Neurosurgery, Chinese Medical Association organized domestic experts from Pediatrics, Pediatric Neurosurgery, Genetics and Endocrinology to reach a consensus on the following topics: pathological and molecular genetic classification of craniopharyngioma, basic principles of curing tumors, surgical classification of tumors, surgical approach, perioperative and long-term treatment plan. This is expected to improve the quality of life and prognosis of patients, and further standardize the diagnosis and treatment of craniopharyngioma.

Global pediatric craniopharyngioma management modalities and outcomes.

INTRODUCTION: Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies have compared various treatment modalities and outcomes described in different global regions. We conducted a comprehensive systematic review to compare demographics, clinical presentation, treatment approach and outcomes of children diagnosed with craniopharyngioma globally. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "craniopharyngioma" and country-specific terms. Inclusion criteria included full-text studies published between 2000-2022, primarily examining pediatric patients 18-years old or younger diagnosed with craniopharyngioma, and reporting management and outcomes of interest. Data extracted included country of origin, demographical data, initial presentation and treatment modality, and outcomes. Descriptive statistics and between-group comparisons based on country of origin were performed. RESULTS: Of 797 search results, 35 articles were included, mostly originating from high-income countries (HIC) (n = 25, 71.4%). No studies originated from low-income countries (LIC). When comparing HIC to middle-income countries (MIC), no differences in patient demographics were observed. No differences in symptomatology at initial presentation, tumor type, surgical approach or extent of surgical resection were observed. HIC patients undergoing intracystic therapy were more likely to receive bleomycin (n = 48, 85.7%), while the majority of MIC patients received interferon therapy (n = 10, 62.5%). All MIC patients undergoing radiation therapy underwent photon therapy (n = 102). No statistically significant differences were observed in postoperative complications or mean follow-up duration between HIC and MIC (78.1 ± 32.2 vs. 58.5 ± 32.1 months, p = 0.241). CONCLUSION: Pediatric craniopharyngioma presents and is managed similarly across the globe. However, no studies originating from LICs and resource-poor regions examine presentation and management to date, representing a significant knowledge gap that must be addressed to complete the global picture of pediatric craniopharyngioma burden and management.

Pediatric craniopharyngioma: a 20-year study on epidemiological features, clinical presentation, and survival outcomes in a tertiary care center from LMIC.

INTRODUCTION: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. METHODS: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. RESULTS: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2-10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. CONCLUSIONS: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life.

National UK guidelines for the management of paediatric craniopharyngioma.

Although rare, craniopharyngiomas constitute up to 80% of tumours in the hypothalamic-pituitary region in childhood. Despite being benign, the close proximity of these tumours to the visual pathways, hypothalamus, and pituitary gland means that both treatment of the tumour and the tumour itself can cause pronounced long-term neuroendocrine morbidity against a background of high overall survival. To date, the optimal management strategy for these tumours remains undefined, with practice varying between centres. In light of these discrepancies, as part of a national endeavour to create evidence-based and consensus-based guidance for the management of rare paediatric endocrine tumours in the UK, we aimed to develop guidelines, which are presented in this Review. These guidelines were developed under the auspices of the UK Children's Cancer and Leukaemia Group and the British Society for Paediatric Endocrinology and Diabetes, with the oversight and endorsement of the Royal College of Paediatrics and Child Health using Appraisal of Guidelines for Research & Evaluation II methodology to standardise care for children and young people with craniopharyngiomas.

[Etiology, Genetic Features and Clinical Presentations in Craniopharyngiomas].

Craniopharyngiomas are among the most challenging intracranial tumors for neurosurgeons. Their management is complicated due to growth patterns such as infiltration into the pituitary stalk, chiasma, and hypothalamus. Therefore, patients may present with various conditions such as endocrine disorders, visual disturbances, or hypothalamic dysfunction in the first medical examination. Moreover, surgical management is challenging because of the high risk of recurrence. Two well-known histological subtypes include adamantinomatous and papillary craniopharyngiomas, and recent advances in genetic analysis have provided significant findings about these subtypes. The adamantinomatous subtype can be distinguished by mutations in CTNNB1, whereas the V600E mutation of the BRAF gene characterizes the papillary subtype. This review describes the etiology, genetic features, and clinical presentations of craniopharyngiomas.

Craniopharyngioma in Pediatrics and Adults.

Craniopharyngiomas are rare malignancies of dysembryogenic origin, involving the sellar and parasellar areas. These low-grade, epithelial tumors account for two main histological patterns (adamantinomatous craniopharyngioma and papillary craniopharyngioma), which differ in epidemiology, pathogenesis, and histomorphological appearance. Adamantinomatous craniopharyngiomas typically show a bimodal age distribution (5-15 years and 45-60 years), while papillary craniopharyngiomas are limited to adult patients, especially in the fifth and sixth decades of life. Recently, craniopharyngioma histological subtypes have been demonstrated to harbor distinct biomolecular signatures. Somatic mutations in CTNNB1 gene encoding ß-catenin have been exclusively detected in adamantinomatous craniopharyngiomas, which predominantly manifest as cystic lesions, while papillary craniopharyngiomas are driven by BRAF V600E mutations in up to 95% of cases and are typically solid masses. Despite the benign histological nature (grade I according to the World Health Organization classification), craniopharyngiomas may heavily affect long-term survival and quality of life, due to their growth pattern in a critical region for the presence of eloquent neurovascular structures and possible neurological sequelae following their treatment. Clinical manifestations are mostly related to the involvement of hypothalamic-pituitary axis, optic pathways, ventricular system, and major blood vessels of the circle of Willis. Symptoms and signs referable to intracranial hypertension, visual disturbance, and endocrine deficiencies should promptly raise the clinical suspicion for sellar and suprasellar pathologies, advocating further neuroimaging investigations, especially brain MRI. The optimal therapeutic management of craniopharyngiomas is still a matter of debate. Over the last decades, the surgical strategy for craniopharyngiomas, especially in younger patients, has shifted from the aggressive attempt of radical resection to a more conservative and individualized approach via a planned subtotal resection followed by adjuvant radiotherapy, aimed at preserving functional outcomes and minimizing surgery-related morbidity. Whenever gross total removal is not safely feasible, adjuvant radiotherapy (RT) and stereotactic radiosurgery (SRS) have gained an increasingly important role to manage tumor residual or recurrence. The role of intracavitary therapies, including antineoplastic drugs or sealed radioactive sources, is predominantly limited to monocystic craniopharyngiomas as secondary therapeutic option. Novel findings in genetic profiling of craniopharyngiomas have unfold new scenarios in the development of targeted therapies based on brand-new biomolecular markers, advancing the hypothesis of introducing neoadjuvant chemotherapy regimens in order to reduce tumor burden prior to resection. Indeed, the rarity of these neoplasms requires a multispecialty approach involving an expert team of endocrinologists, neurosurgeons, neuro-ophthalmologists, neuroradiologists, radiotherapists, and neuro-oncologists, in order to pursue a significant impact on postoperative outcomes and long-term prognosis.

Single-cell RNA sequencing highlights intratumor heterogeneity and intercellular network featured in adamantinomatous craniopharyngioma.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPGco / Estudio multicéntrico colaborativo del manejo neuroquirúrgico del craneofaringioma pediátrico en España: S-PedCPGco

Purpose To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. Methods We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. Results The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7–357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. Conclusions Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity (AU)

Objetivo Presentar un análisis descriptivo de los craneofaringiomas pediátricos tratados en varios hospitales españoles, definiendo los factores relacionados con la recurrencia y realizando un análisis crítico de los resultados. Métodos Estudio retrospectivo multicéntrico de los craneofaringiomas pediátricos tratados entre 2000-2017. Se recogieron variables epidemiológicas, clínicas y radiológicas, el objetivo de la primera cirugía, la tasa de recurrencia y su abordaje, los tratamientos adyuvantes, así como las complicaciones y la morbilidad permanente. Se estudió la relación estadística entre la progresión y el número de progresiones con las variables independientes. Resultados Se incluyeron 69 niños tratados en 8 hospitales españoles. La mayoría de los tumores se extendían por varios compartimentos intracraneales al diagnóstico, con invasión hipotalámica en el 41,3%. Habitualmente, la primera estrategia de tratamiento fue la resección radical (71%), con algunos pacientes tratados con radioterapia o quimioterapia intraquística. La tasa de progresión tras la primera cirugía fue del 53% en un seguimiento medio de 88,2 meses (rango 7-357). En el grupo de resección radical recurrieron un 38,8% de los tumores, un 40% en el de resección subtotal o biopsia y un 93,3% en el de fenestración quística±reservorio Ommaya. La mortalidad fue de un 7,2%. Las variables relacionadas de forma significativa con progresión fueron el tiempo de seguimiento, el tamaño del tumor y el objetivo de la primera cirugía. Conclusiones Los resultados obtenidos fueron aceptables en control de la enfermedad, secuelas hormonales o visuales y mortalidad, aunque hay varias áreas susceptibles de mejora. Nuestros objetivos a corto plazo deberían estar orientados a crear un registro nacional de craneofaringiomas pediátricos, alcanzar un consenso respecto al algoritmo de tratamiento y mejorar el diagnóstico de la disfunción hipotalámica para evitar morbilidad (AU)

Unusual circumstance for craniopharyngioma discovery on meningoencephalitis: a pediatric case report.

BACKGROUND: Craniopharyngioma is a rare condition in children, but it is the most frequent tumor that occurs in the hypothalamic pituitary region. Chemical meningitis has been described as an uncommon postoperative complication, but no chemical meningitis due to a spontaneous rupture leading to craniopharyngioma diagnosis in children has been reported. CASE PRESENTATION: This is a case of a 13-year-old boy presenting with fever, vomiting and headache for two days. The CT scan revealed a suprasellar lesion, and lumbar puncture showed aseptic meningitis. The cerebral MRI suggested a craniopharyngioma and the cerebrospinal fluid cholesterol concentration was abnormally high. A thorough medical history indicated some visual disturbance, which improved at the onset of meningitis, and an inflection of the growth curve. The anatomopathological analysis of the tumor confirmed the diagnosis of craniopharyngioma. CONCLUSIONS: This case is the first to report the discovery of a craniopharyngioma with meningoencephalitis caused by the rupture of a craniopharyngioma cyst in a child. Diagnosis was facilitated by determining the cholesterol level in the cerebrospinal fluid, as well as fine anamnesis to identify visual and growth disturbances.

Outcome after pediatric craniopharyngioma: the role of age at diagnosis and hypothalamic damage.

OBJECTIVE: Craniopharyngiomas (CP) are rare malformational tumors. Clinical presentation and outcome of pediatric patients with CP with specific regard to age at diagnosis is not clear. The aim of this cohort study was to determine clinical presentation and outcome in these patients diagnosed at different ages at diagnosis. DESIGN: Seven hundred and nine patients diagnosed with CP were recruited from 1999 to 2021 in HIT-Endo and KRANIOPHARYNGEOM 2000/2007/Registry 2019 and prospectively observed. METHODS: Age at diagnosis was categorized as infants and toddlers (<2 years), early childhood (2-6 years), middle childhood (6-12 years), and early adolescence (12-18 years). Overall and event-free survival (EFS), functional capacity (FMH), and quality of life (QoL) (PEDQOL) were assessed. RESULTS: Severe obesity (body mass index [BMI] >3 standard deviation score [SDS]) was prevalent in 45.4% at last visit. A lower EFS but better QoL was observed in children with age at diagnosis <6 years compared with ≥6 years. Reduced functional capacity percentiles were associated with increased BMI-SDS at last visit (rho = -0.125, 95% confidence interval [CI; -0.21; -0.04]) and age at diagnosis <2 years. Posterior hypothalamic involvement and hypothalamic lesion (HL) were independent risk factors for reduced EFS (hazard ratio = 1.59, 95% CI [1.12-2.26]) and obesity at last visit (odds ratio = 2.94, 95% CI [1.73-5.08]). Age at diagnosis did not contribute to severe obesity and reduced QoL. CONCLUSIONS: Diagnosis of CP at age <6 years may help patients to adapt early to disabilities but may lead to a higher probability of CP relapse. Not age at diagnosis but posterior HL may be the contributing factor to severe obesity and a reduced QoL. CLINICAL TRIAL REGISTRATION NUMBERS: NCT00258453; NCT01272622; NCT04158284.

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.

Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease.

INTRODUCTION: Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies. METHODS: Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Children's Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to understand their experiences throughout diagnosis and treatment. RESULTS: The CBTN repository revealed a large proportion of patients (40 - 70%) with specimens that are available for sequencing but lacked relevant quality of life (QoL) and functional outcomes. Frequencies of reported patient comorbidities ranged from 20-35%, which is significantly lower than historically reported. Survey results from 159 patients/families identified differences in treatment considerations at time of diagnosis versus time of recurrence. In retrospective review, patients and families identified preference for therapy that would improve QoL, rather than decrease risk of recurrence (mean 3.9 vs. 4.4 of 5) and identified endocrine issues as having the greatest impact on patients' lives. CONCLUSIONS: This work highlights the importance of prospective collection of QoL and functional metrics alongside robust clinical and molecular correlates in individuals with craniopharyngioma. Such comprehensive measures will facilitate biologically relevant therapeutic strategies that also prioritize patient needs.

Contemporary Biological Insights and Clinical Management of Craniopharyngioma.

Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding ß-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close to the optic pathways, hypothalamus, and pituitary gland, such as increased intracranial pressure, endocrine deficiencies, and visual defects. Treatment is not specific and mostly noncurative, and frequently includes surgery, which may achieve gross total or partial resection, followed by radiotherapy. In cystic tumors, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in PCP, but also now in ACP and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumor and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients who bear tumors with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome, hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of CP, with emphasis on recent advances in the understanding of tumor pathogenesis, clinical consequences, management, and therapies.

Approach to the Patient With Hypothalamic Obesity.

Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a classic cause of HO. HO often goes unnoticed initially as patients, families, and medical teams are focused on oncologic treatments and management of panhypopituitarism. HO is characterized by rapid weight gain in the first year after hypothalamic destruction followed by refractory obesity due to an energy imbalance of decreased energy expenditure without decreased food intake. Currently available pharmacotherapies are less effective in HO than in common obesity. While not a cure, dietary interventions, pharmacotherapy, and bariatric surgery can mitigate the effects of HO. Early recognition of HO is necessary to give an opportunity to intervene before substantial weight gain occurs. Our goal for this article is to review the pathophysiology of HO and to discuss available treatment options and future directions for prevention and treatment.

Surgical Treatment of Craniopharyngiomas in Adults: Comparison between Primary Surgery and Surgery for Recurrence.

OBJECTIVE: Few studies have investigated the differences in outcomes between primary and repeat surgery for a craniopharyngioma in adults. As a result, a treatment concept for adult patients with a craniopharyngioma has not yet been established. The present study aimed to retrospectively analyze adult patients with craniopharyngioma to compare surgical outcomes between primary surgery and surgery for recurrence. METHODS: The demographic and clinical data of 68 adult patients with craniopharyngioma who had primary surgery (n=50) or surgery for recurrence (n=18) were retrospectively analyzed. In addition, the patients were followed up for an average of 38.6 months (range: 1-133 months). RESULTS: The cohorts of patients undergoing primary surgery or repeat surgery did not differ preoperatively in terms of demographic data, or radiological tumor features. However, patients with recurrent craniopharyngioma had significantly more pituitary hormone deficits and hypothalamo-pituitary disorders before surgery compared with patients with newly diagnosed craniopharyngioma. The success rate of complete resection in primary surgery was 53.2%. Even after repeat surgery, a satisfactory rate of complete resection of 35.7% was achieved. Operative morbidity was increased neither in patients with repeat surgery compared with those with primary surgery (postoperative bleeding P=0.560; meningitis P=1.000; CSF leak P=0.666; visual disturbance P=0.717) nor in patients with complete resection compared with those with partial resection. We found no difference in recurrence-free survival between initial surgery and repeat surgery (P=0.733). The recurrence rate was significantly lower after complete resection (6.9%) than after partial resection (47.8%; P<0.001). CONCLUSION: Attempting complete resection is justified for not only those with newly diagnosed craniopharyngioma but also for those with recurrent craniopharyngioma. However, the surgeon must settle for less than total resection if postoperative morbidity is anticipated.

Analysis of Prognostic Factors, Extent of Resection, and Long-Term Outcome of Craniopharyngioma in Adults and Children.

Introduction: Surgical management of craniopharyngioma is debatable and still lacks clear guidelines. Long-term complications are attributed to radical resection of the tumor. Extent of resection may not be the only factor which determines the functional outcome, because studies have reported hypothalamic and visual morbidities even with conservative resection. In this article, we analyze the extent of resection, long-term outcome, and various prognostic factors in adults and children. Materials and Methods: Newly diagnosed cases of craniopharyngioma operated between 2001 and 2013 were reviewed retrospectively. PFS and OS were calculated. Predictors of various outcome parameters were analyzed. Results: Of 140 patients, 41% were children and 59% were adults. Postoperatively, vision has improved in 63% and worsened in 12%. GTR was achieved in 66%. The median follow-up was 67 months. PFS at 5 and 10 years was 95% and 41.5%, respectively. OS at 5 and 10 years was 92.6% and 89.5%, respectively. Symptoms of raised ICP and hypothalamic involvement, extensive calcifications, tumor size >5 cm, and multi-compartmental tumors were associated with presence of residual tumor. Regression analysis showed symptoms of hypothalamic involvement, size of the tumor > 5 cm, and hydrocephalus predicted postoperative hypothalamic morbidities. No significant difference was found in postoperative visual, endocrinological, hypothalamic, and functional outcomes between GTR and STR. Conclusion: Conservative resection should be carried out in patients with preoperative hypothalamic symptoms and imaging evidence of extensive hypothalamic involvement. Size of the tumor and invasiveness are the other factors should be considered before radical excision of craniopharyngiomas.

Immune infiltration in aggressive papillary craniopharyngioma: High infiltration but low action.

Papillary craniopharyngiomas (PCPs) are biologically benign but clinically aggressive lesions hence affect the quality of life. The expression of inflammatory mediators and regulation of the immune microenvironment in PCPs have not been investigated much. In this study, for the first time, we assessed the immune cell infiltration and immune cell signatures in PCPs by analyzing the bulk-RNA sequencing data and immunohistochemical staining. Additionally, we performed qRT-PCR analysis to detect inflammatory mediators interleukin-1α (IL1A) and interleukin-6 (IL6) in different aggressive groups and then developed the IL1A and IL6 prediction models for defining the degree of hypothalamic invasion. Lastly, we defined differentially expressed genes related to invasiveness and implemented enrichment analysis to them. Our results indicated that PCPs are in a state of high immune infiltration but low action with abundant inflammatory cells. High infiltration of neutrophils may lead a low active immune microenvironment. Furthermore, the high expression level of IL1A and IL6 was positively correlated with the invasion of PCP tumors in the hypothalamus. These findings provide new pathological insights into the underlying mechanism of the immune microenvironment in PCP tumors. Moreover, IL1A and IL6 might serve as potential therapeutic targets for PCP tumors, especially to prevent their invasion into the hypothalamus.

Hub genes for early diagnosis and therapy of adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a subtype of craniopharyngioma, a neoplastic disease with a benign pathological phenotype but a poor prognosis in the sellar region. The disease has been considered the most common congenital tumor in the skull. Therefore, this article aims to identify hub genes that might serve as genetic markers of diagnosis, treatment, and prognosis of ACP. METHODS: The procedure of this research includes the acquisition of public data, identification and functional annotation of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and the mining and analysis of hub genes by Spearman-rho test, multivariable linear regression, and receiver operator characteristic curve analysis. Quantitative real-time polymerase chain reaction was used to detect the level of mRNA of relative genes. RESULTS: Among 2 datasets, a total of 703 DEGs were identified, mainly enriched in chemical synaptic transmission, cell adhesion, odontogenesis of the dentin-containing tooth, cell junction, extracellular region, extracellular space, structural molecule activity, and structural constituent of cytoskeleton. The protein-protein interaction network was composed of 4379 edges and 589 nodes. Its significant module had 10 hub genes, and SYN1, SYP, and GRIA2 were significantly down-regulated with ACP. CONCLUSION: In a word, we find out the DEGs between ACP patients and standard samples, which are likely to play an essential role in the development of ACP. At the same time, these DEGs are of great value in tumors' diagnosis and targeted therapy and could even be mined as biological molecular targets for diagnosing and treating ACP patients.