Pediatric adamantinomatous craniopharyngioma (ACP) is the most common tumor of the diencephalic-pituitary axis in children. Although histologically benign, pediatric ACP is frequently associated with substantial endocrine dysfunction and neurological complications. The gold-standard treatment is complete surgical resection; however, because of the tumor's location, total removal is often not feasible. Consequently, several authors recommend radiotherapy as an adjuvant option. Nevertheless, partial resections are frequently followed by recurrence, and repeated surgical interventions increase morbidity and impair quality of life. Thus, adjuvant therapeutic strategies capable of controlling this tumor should be encouraged. We analyzed seven fresh tumor specimens ACP from patients < 18years of age using a chemoresistance platform (Bioverso Test, Ziel Biosciences, São Paulo, Brazil). These cases demonstrated widespread resistance to most chemotherapeutic agents tested. Temozolomide (500µM) was the only drug that showed consistent and significant sensitivity. Based on these findings, we initiated treatment in a 14-year-old patient with recurrent ACP who had previously undergone multiple surgical procedures and radiotherapy. The tumor involved the left cavernous sinus and extended into the sphenoid sinus. Clinically, the patient was amaurotic and presented with panhypopituitarism. The patient received temozolomide (200mg/m2/day for 5 consecutive days in 28-day cycles). After completing 12 cycles of chemotherapy, there was a notable regression of the lesion, with approximately 50% reduction in total tumor volume. These findings suggest that temozolomide may represent a promising therapeutic option for controlling ACP.

Adamantinomatous craniopharyngioma (ACP) is an uncommon and anatomically variable tumor in children. The balance between critical treatment objectives, including the pursuit of gross total surgical resection and the reduction of hypothalamic injury and tumor recurrence, remains difficult and controversial. In this retrospective observational study, we compare the management and outcome of ACP in two large paediatric neurosurgical centres to determine how variations in tumor characteristics and management influence long-term outcomes. In this retrospective observational study, consecutive children (aged ≤ 18years) diagnosed with primary ACP between 1997 and 2023 at two tertiary paediatric neurosurgical centres (Great Ormond Street Hospital (GOSH), United Kingdom, and Universidade de São Paulo (USP), Brazil) were evaluated. Functional outcomes related to pituitary function, hypothalamic injury, cognition, and vision were analysed. Scans were independently reviewed for tumor size, characteristics, and relationship to the optic apparatus and hypothalamus. Extent of surgery was documented. 123 patients (USP = 52; GOSH = 71) were included.Mean follow-up was 10.1 ± 5.6years at USP and 7.5 ± 4.8years at GOSH. There were no demographic differences. Rates of growth hormone deficiency (USP = 62.5%; GOSH = 35%; p = 0.009) and visual deficits(p < 0.05)were higher in the USP cohort at initial presentation.Patients at GOSH presented with predominantly cystic lesions (n = 46/60; 76.7%) while at USP solid tumors (n = 24/32; 75%) (p = 0.05) were more prevalent. Paris grade for hypothalamic involvement was higher in the GOSH cohort (p = 0.01). Although gross total resection (GTR) was similar in the two groups, cyst aspiration plus radiotherapy was commoner at GOSH, whereas debulking was commoner at USP (p < 0.001). Post-treatment hypothalamic scores were better in the GOSH cohort (p < 0.04). Patients at GOSH had earlier recurrences(25.5 ± 32months) compared to patients treated at USP (37.4 ± 59.5months) (p = 0.01).In multivariate analysis, STR/GTR (OR 0.17; 95%CI:0.05-0.55, p < 0.01) and older age at diagnosis (OR 0.91, 95%CI:0.82-0.99, p = 0.04)were associated with longer progression-free survival. Comparative analysis of two large series of ACP in children identified different paradigms of surgical management driven by distinct clinical-radiological presentations. While cyst aspiration plus radiotherapy protects against hypothalamic injury, this may occur at the cost of earlier tumour recurrence. Further studies to define this balance are urgently needed. 21st International Symposium on Pediatric Neuro-Oncology. June 29-July 2, 2024.

Tumors of the Sellar and Suprasellar Regions.

Craniopharyngioma (CP) is a rare, recurrent central nervous system tumor with significant hormonal, visual, and metabolic sequelae. This retrospective cohort study analyzes 37 years of experience managing pediatric and adult CP patients at a specialized referral center in Chile, stratified by age at onset. Clinical, biochemical, imaging, and neurosurgical data from 1986 to 2023 were reviewed. A total of 87 patients (1-68 years) were included, with 65 (75%) presenting in childhood (≤ 18 years) and 22 (25%) in adulthood. Mean follow-up was 9.3 years (IQR 3.7-14.1). Histology was adamantinomatous in 84%, papillary in 3%, and unspecified in 13%. The most common symptoms at presentation were headache (77%), visual disturbances (60%), and nausea (45%). At diagnosis, 54% had at least one pituitary dysfunction, most frequently thyrotropic (28.2%) and somatotropic (27.9%). Following initial treatment, pituitary dysfunction increased to 71%, with thyrotropic (59%) and corticotropic (48%) being the most affected axes. Anterior panhypopituitarism occurred in 25%, and permanent AVP deficiency in 32%. Tumor recurrence or progression was observed in 63%. CP carries a high risk of recurrence and neuroendocrine complications. This study, based on 37 years of experience in a reference center, is the first national report on CP patients, with findings consistent with previous literature. The management of these patients is complex and demands a highly experienced multidisciplinary team to achieve optimal long-term outcomes.

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m2; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework.

Malignant transformation of craniopharyngioma is an exceptionally rare and poorly characterized phenomenon. We report a case of a 15-year-old girl who developed symptom recurrence 9 years after undergoing surgery and radiotherapy for adamantinomatous craniopharyngioma. Histology revealed malignant areas comprising highly proliferative basaloid cells with abrupt transitions into ghost cells, resembling ghost cell odontogenic carcinoma. We conducted a literature review and pooled case analysis of 45 cases, which showed a median benign-to-malignant latency of 10 years and a median overall survival of 9 months. The majority of benign diagnoses were adamantinomatous type. Prior radiotherapy was noted in 27 cases (60%). Histological findings of malignant components were reported as unspecified malignant transformation in 20 cases (44.4%), squamous cell carcinoma (SCC) in 16 cases (35.6%), odontogenic-type carcinomas in 5 cases (11.1%), and other types in 4 cases (8.9%). Immunohistochemical analyses showed consistent positivity for pan-cytokeratin, p63, and p40 in all cases performed. The p53 and Ki-67 also consistently exhibited increased or abnormal expression. Due to the overlapping histological and immunohistochemical features of odontogenic-type carcinomas and SCC, careful assessment is recommended when diagnosing recurrent CPs.

Adult-onset craniopharyngiomas (CPs) often present after diagnostic delays, yet the prognostic relevance of duration of history (DOH) and specific clinical manifestations remains unexplored. Data of patients aged > 18 years at CP diagnosis between June 2012 and October 2024 at the First Affiliated Hospital of Nanchang University were retrospectively reviewed. Associations between DOH, specific symptoms, and tumor characteristics at diagnosis, as well as long-term outcomes, were systematically analyzed. Among 151 patients (median follow-up, 71 months) in our cohort, the median DOH was 5 months and showed no significant correlation with tumor volume at diagnosis, hypothalamic involvement, extent of resection, or long-term prognosis including mortality, recurrence, and hypothalamic syndrome at last visit. Patients with amenorrhea/sexual dysfunction in history demonstrated significantly longer DOH (p < 0.001), while those with neurological deficits (p = 0.043) or hydrocephalus (p = 0.044) were associated with shorter DOH. Neurological deficits in history was associated with larger tumor volume at diagnosis (p = 0.016). Headache presented as the first symptom was linked to significantly shorter DOH (p = 0.003) and neurological deficits as the first symptom was associated with worse progression-free survival (p = 0.047). Diagnostic delays are common in adult-onset CP patients but appear unrelated to tumor burden or long-term prognosis. Neurological deficits in history or as the first symptom should trigger prompt diagnostic workup and more rigorous follow-up, while prolonged diagnostic delays in those with endocrine symptoms underscore the need for heightened awareness among clinicians to expedite referral and diagnosis.

Malignant craniopharyngiomas, de novo or via malignant transformation, are exceedingly rare with a dismal prognosis and unclear treatment standards. Little is known about the factors involved in their pathogenesis. A natural language search, performed in our institutional CoPath system, identified 65 adamantinomatous craniopharyngiomas from 56 patients (25 males, 31 females; median age at initial diagnosis = 22 years). Among those, a unique case of malignant craniopharyngioma was identified in a 36-year-old male initially diagnosed with a benign adamantinomatous craniopharyngioma 16 years prior. A literature review identified 44 cases of malignant craniopharyngiomas (current case included) with a median age of 28 years and a median overall survival of 6 months, independent of sex, age, histologic variant, tumor size, or radiation therapy. Eighteen (41%) malignant craniopharyngiomas occurred in patients without a history of radiation, suggesting mechanisms other than radiation contribute to their pathogenesis. Since BRCA1-Associated Protein 1 (BAP1) and TP53 mutations have recently been reported in a case of malignant craniopharyngioma, we assessed these genes in the current case. Next-generation sequencing identified variants in BAP1 (c.1850delGinsCA;p.R617fs), TP53 (c.428delT;p.V143fs), and CTNNB1 (c.110C>T;p.S37F). In conclusion, our results demonstrate that malignant craniopharyngioma tends to occur in young adults with a median overall survival of only 6 months. The current case is the second reported to harbor BAP1 and TP53 mutations by sequencing. BAP1 and TP53 mutations may play an important role in the pathogenesis of malignant craniopharyngioma and may offer potential targets for therapeutic intervention.

This study investigated epidemiologic characteristics and analyzed postoperative complications on craniopharyngioma (CP) patients in China with an aim to provide a theoretical basis for the postoperative care of CP patients. A total of 598 CP patients was divided into two groups based on the age and postoperative complications including visual impairment and endocrine dysregulation. The WISC IV scoring system was used to measure the cognitive functions of the pediatric patients. In addition, patients with two major CP types, the papillary and adamantinomatous CPs, were also compared with regard to postoperative complications. The Children group had a higher probability of developing severe visual impairment. Moreover, the Children group had a significantly higher occurrence rate of uremia and arginine vasopressin deficiency, thyroid disorder, dysregulated cortisol and growth hormones than the adult group. On the other hand, the mean time to the first recurrence was shorter in patients with the papillary CP than in those with the adamantinomatous CP. After secondary and more surgeries, 22.27% of patients developed amnesia. Patients with the adamantinomatous CP developed amnesia at a higher rate than patients with the papillary CP. Hypopituitarism did not correlate with patient age, gender, and disease duration, but correlated with the follow-up time. Statistically significant differences between the intracranial infection and the duration of surgery, and between intracranial hematoma and hydrocephalus, were observed. Reduced operative time and enhanced postoperative follow-up can reduce the occurrence of postoperative complications in CP patients.

Adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive tumor arising from Rathke's pouch remnants, which is molecularly distinct from the other subtype, papillary craniopharyngioma (PCP). Despite advancements in surgery and radiotherapy, treatment outcomes remain unsatisfactory due to the tumor's invasiveness and resistance to conventional therapies. This review systematically examines the molecular pathogenesis of ACP and evaluates current and emerging therapeutic strategies to improve clinical management. ACP is driven by CTNNB1 mutations and dysregulated Wnt/β-catenin signaling, alongside inflammatory and senescence-associated pathways. Current pharmacological approaches, including interferon-α, IL-6 inhibitors (e.g., tocilizumab), and intracystic agents (e.g., bleomycin), exhibit limited efficacy. Promising emerging therapies target the angiogenesis (e.g., bevacizumab) and MAPK/ERK pathway, which is activated by somatic BRAF V600E mutations in PCP, has been successfully targeted with BRAF/MEK inhibitors, demonstrating significant efficacy in the majority of treated PCP patients. whereas immune checkpoint inhibitors and SHH pathway modulators face significant challenges. Additionally, ACP-related endocrine dysfunction and hypothalamic obesity require tailored interventions, such as GLP-1 receptor agonists and MC4R-targeted therapies. Precision medicine, informed by molecular subtyping and multi-omics data, holds transformative potential for ACP treatment. Future strategies should focus on combinatorial therapies to address tumor heterogeneity, microenvironment modulation, and senolytic approaches. Collaborative multidisciplinary efforts are crucial to translating these insights into clinical practice, ultimately enhancing patient outcomes and quality of life.

BackgroundDifferentiating craniopharyngiomas (CPs) from Rathke's cleft cysts (RCCs) is challenging due to overlapping features. RCCs with squamous metaplasia (SM) may represent a transition to CPs, complicating diagnosis. This study presents a recurrent RCC later confirmed as papillary CP, prompting a systematic review to identify early diagnostic markers. The goal is to improve RCC and CP differentiation, preventing radical resection of true RCCs, and predicting recurrence or transformation to CPs.MethodsA systematic review was performed with adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using the PubMed/Medline databases, a search string was created with the keywords “RCC transformation or (RCC and CP) or (RCC to CP) or (RCC to CP) or (Rathke's and CP).” The initial search yielded 489 papers, narrowed by key data points including RCC recurrence with histologic CP confirmation.ResultsThe final review included five studies, which detailed cases of initial pathological diagnosis of RCC that were later diagnosed as a CP upon repeat surgery and tissue sampling. Histological examination of primary and secondary surgical resections revealed RCC recurrence with transformation to CPs (two adamantinomatous CPs, two papillary CPs, and one ciliated CP).ConclusionRCCs and CPs share overlapping features, complicating preoperative diagnosis and treatment. RCC recurrence with subsequent CP is rare, as our review identified only five recorded cases. Definitive diagnosis requires pathology, though sampling bias poses challenges. Advanced imaging (contrast-enhanced 3D T2-FLAIR MRI) and biomarkers (BRAF V600E, beta-catenin, p53, Ki-67) show promise in improving diagnosis, predicting recurrence, and guiding treatment.

Patients with adamantinomatous craniopharyngiomas (aCP) often present hypothalamic involvement (HI) either by the tumor or therapeutic interventions, resulting in hypothalamic obesity (HyOb). This study aims to investigate how appetite sensations and orexigenic and anorexigenic hormones response may contribute to the HyOb pathogenesis in these subjects. Fifteen patients with aCP submitted to surgical resection (31,1 ± 12 years; 9 women) and 15 controls (31 ± 11,7 years) paired by sex, age and BMI were included in this cross-sectional study. Leptin and adiponectin were measured in basal conditions (T0'). Glucose, insulin, ghrelin, GLP-1, and PYY levels were assessed at T0', T30', T60', T120', and T180' minutes after a standard meal test. Sensations of hunger, fullness and prospective food consumption were measured using a visual analogic scale at the same time points. Intergroup differences on appetite sensations and biochemical variables were not significant between patients with aCP and controls. Intragroup analyses revealed distinct post-meal dynamics: compared to matching controls, patients with aCP showed earlier increase in hunger, and decrease in fullness (both P = 0.005) and prospective food consumption (P = 0.06) ratings from T0' to T180'. There was a tendency towards higher fasting leptin concentrations (P = 0.06), while adiponectinemia was significantly lower (P = 0.002). Insulin and HOMA-IR (both P < 0.01) were higher at T180', whereas the anorexigenic hormones GLP-1 (P = 0.03) and PYY (P = 0.02) were higher at T120'. PYY and ghrelin showed earlier postprandial rise and fall, respectively, in patients with aCP. Although intergroup differences were limited, our intragroup analyses revealed reduced satiety persistence and earlier appetite rebound, particularly in patients with HyOb and severe HI, providing new insights into the complex, multifactorial pathophysiology of HyOb associated with aCP.

To develop and validate a Pediatric Anatomo-Endocrine (PAE)-based nomogram for predicting severe postoperative endocrine dysfunction in children undergoing craniopharyngioma (CP) resection, integrating anatomical classification, surgical factors, and baseline endocrine status.This retrospective study included 370 pediatric CP patients (≤ 18 years) who underwent primary resection at a single center between 2017 and 2024. Patients were randomly divided into a primary (n = 300) and a validation (n = 70) cohort. Endocrine dysfunction was assessed based on the number and severity of hypothalamic-pituitary axis abnormalities. A novel three-tier PAE classification was developed from preoperative MRI. Logistic regression was used to identify predictors of severe dysfunction. A nomogram was constructed and validated via ROC, calibration, and decision curve analyses.In the primary cohort, 83.4% of patients had worsened endocrine dysfunction postoperatively, with severe dysfunction increasing from 20.3% to 79.3%. Independent predictors included PAE classification, baseline endocrine status, and pituitary stalk sacrifice. The nomogram demonstrated strong performance (AUC 0.84 in primary; 0.82 in validation). Among PAE subtypes, the Global subtype posed the highest risk, with an odds ratio of 16.30 versus the Sella-Infundibulum subtype.The PAE classification stratifies hypothalamic-pituitary involvement and serves as an independent predictor of endocrine outcomes. Although validated internally in a large single-center cohort, its long-term benefit remains to be confirmed. The proposed nomogram may provide a practical, non-invasive tool for individualized risk prediction and surgical planning, but requires external multicenter validation to establish generalizability.

Craniopharyngiomas (CPs) pose significant surgical challenges due to their proximity to critical neurovascular structures and their high recurrence rates. The endoscopic endonasal approach (EEA) has emerged as a reliable alternative to craniotomy, offering unique advantages. This study aimed to summarize management experience by analyzing the largest single-team cohort of the EEA for CPs, providing insights for optimizing treatment and guiding surgical decision-making. A retrospective analysis of 604 patients with CP (ages 2-76 years) treated via the EEA from 2019 to 2023 was conducted. A new tumor classification based on the relationship between the tumor and key anatomical interfaces in the EEA (sellar diaphragm and third ventricle floor) was proposed. Three surgical corridors were used: chiasm-pituitary, suprachiasmatic translamina terminalis, and transclival. Intraoperative visual evoked potential (VEP) monitoring was assessed for visual protection. Risk factors for complications and progression-free survival (PFS) were analyzed. Gross-total resection (GTR) was achieved in 89.7% of cases (93.7% in primary vs 78.8% in recurrent tumors). CSF leak rates declined from 7.35% in 2019 to 1.63% in 2023, with hypoalbuminemia and larger dural defects emerging as independent risk factors in adults. VEP monitoring reduced visual deterioration (6.74% vs 12.62%, p = 0.015). Recurrent tumors (odds ratio [OR] 5.397, 95% CI 2.984-9.763; p < 0.001), larger tumor volume (OR 1.038, 95% CI 1.018-1.06; p < 0.001), Puget grade II (OR 2.35, 95% CI 1.249-4.42; p = 0.008), and massive calcification (OR 2.541, 95% CI 1.333-4.841; p = 0.005) were independent risk factors for non-GTR (NGTR). Multivariate Cox analysis showed that NGTR (hazard ratio [HR] 9.181, 95% CI 5.143-16.392; p < 0.001), Puget grade I (HR 3.306, 95% CI 1.385-7.895; p = 0.007), Puget grade II (HR 2.918, 95% CI 1.260-6.755; p = 0.012), cystic tumor (HR 1.794, 95% CI 1.065-3.021; p = 0.028), and calcification (HR 2.249, 95% CI 1.206-4.195; p = 0.011) were independently associated with decreased PFS. Pediatric patients had higher GTR and lower CSF leak incidence rates than adults. The EEA could be considered the first-line surgical treatment modality for most adult and pediatric patients with CP. For large CPs invading the hypothalamus, the EEA allows for sharp dissection of the tumor from the hypothalamus under direct visualization, enabling complete resection while minimizing hypothalamic damage. Intraoperative VEP monitoring aids in reducing visual deterioration. The proposed tumor classification and experience can enhance surgical quality, reduce complications, and guide patient counseling.

Surgically resected cystic lesions in the sellar-suprasellar region: Value of qualitative, semiquantitative, and quantitative imaging variables in the diagnostic work-up.

Adamantinomatous craniopharyngioma (ACP), a benign yet clinically challenging neoplasm situated in sellar‐suprasellar region, frequently causes hypothalamic dysfunction. Despite the identification of molecular alterations in ACP, the absence of robust research models has impeded the advancement of targeted therapies. Herein, the development of a large‐scale ACP biobank comprising 54 patient‐derived organoids (PDOs) is presented, achieves with a notable 90% success rate. Comprehensive characterization using hematoxylin and eosin (H&E) staining, immunofluorescence staining, and whole‐exome sequencing (WES) demonstrates that PDOs faithfully recapitulate key histoarchitectural features, molecular marker expression profiles, and somatic mutational landscapes of corresponding parental tumors. Drug sensitivity screening reveals diverse responses of PDOs to the drugs tested, with Ceritinib exhibiting potent and consistent anti‐tumor activity across seventeen PDOs evaluated. Further mechanistic investigations utilizing RNA transcriptomic sequencing have elucidated that Ceritinib inhibits PDO growth by downregulating the IGF‐1R/PI3K/AKT/GSK‐3β/β‐catenin signaling axis. Additionally, a retrospective analysis of two Ceritinib‐treated clinical cases reveals tumor growth with treatment before any possible therapeutic effects are observed, highlighting the need for caution and careful monitoring in treating ACP patients. Collectively, these findings demonstrate that ACP PDOs effectively preserve the biological characteristics of original tumors, thereby providing a valuable platform for developing precision therapies for ACP patients.

Abstract BACKGROUND Childhood adamantinomatous craniopharyngiomas (ACP) are low-grade brain tumors associated with significant morbidity and treatment-related complications. Tocilizumab (TCZ), a monoclonal antibody targeting the IL-6 receptor, may mitigate tumor-associated inflammation, as IL-6 is elevated in both cystic and solid components of ACPs. Preliminary data suggests that TCZ may reduce or stabilize cystic volume within 3–6 months. This two-center retrospective series evaluated the impact of TCZ on tumor volume and clinical outcomes. METHODS Children with ACP received TCZ (10-12 mg/kg every 2-4 weeks) at different disease stages at UCSF (n=9) and the Princess Máxima Center (n=5). Tumor response was assessed by MRI at baseline and approximately every 3 months during treatment. Clinical effects were monitored through evaluations of vision, hypothalamic-pituitary function and adverse events. RESULTS Fourteen children (median age 7.5 years (1–16y), 57% female) received TCZ with a median duration of 10.6 months (6months - 4 years). Thirteen had undergone surgery and/or cyst fenestration and five received radiation therapy prior TCZ initiation. A reduction in the cystic component was observed in 9 patients (64%), with 5 demonstrating stable solid components. Among these, 2 underwent cyst drainage during TCZ treatment, and 1 additionally received bevacizumab. The median time to best response was 6 months (3–12m). Cystic progression occurred in 5 patients (36%), 3 of these exhibited growth in the solid component after a median time of six months. One patient initially received tocilizumab monotherapy; bevacizumab was added after 1.5-3 years in response to cystic growth, resulting in sustained cyst stabilization. All patients had regular ophthalmologic evaluations. Two showed mild visual field improvement. Hypothalamic-pituitary function remained stable. CONCLUSION Tocilizumab was well tolerated and associated with cystic volume reduction in a subset of patients. The addition of bevacizumab led to ongoing responses after single agent TCZ failed. Volumetric MRI assessment is ongoing.

Abstract BACKGROUND AND OBJECTIVES Although most diseases affecting the sella and suprasellar region are benign, critical neurovascular structures contribute to early symptoms and potential for postoperative morbidity. We assessed the role of intraoperative ultrasound (IOUS) in surgical decision making and detecting inadvertent residual during resection. MATERIAL AND METHODS This is a retrospective study of 108 patients with sellar and suprasellar pathologies who underwent 110 endoscopic endonasal surgeries. The clinical details, magnetic resonance images (MRI), IOUS images, surgical videos, and operative notes were collected from patient records. RESULTS The mean age of the cohort was 57 years, 53.6% were males. Non-secreting pituitary adenomas were the predominant entity (43.6%); secreting adenomas (31.8%), Rathke’s cleft cyst (11.8%), craniopharyngiomas (5.3%), abscess (2.7%), tuberculum sellae meningiomas (1.8%) and others (hypophysitis, teratoma and collision tumor). Tumors involving the sella were 86.5%, 12.7% were suprasellar and 0.9% involved the cavernous sinus. Three cases that were suspected to be cystic adenomas on preoperative MRI underwent IOUS-guided cyst aspiration, which demonstrated mucinous content suggesting Rathke’s cleft cyst, and hence, marsupialization was deemed adequate. Another 3 cases suspected to be papillary craniopharyngiomas (PCP) on preoperative MRI demonstrated calcific shadows on IOUS, suggestive of adamantinomatous craniopharyngioma, precluding a conservative resection, which could suffice for PCP in the era of BRAF inhibitors. An extent of resection of more than 90% was obtained in 85.5% patients.. The mean residual volume was 3.68 cc. Intraoperative USG done just before closure identified residue in 17 (15.4%) patients, with a positive predictive value of 82.4% and a negative predictive value of 82.8%. The sensitivity of IOUS in detecting residual was 46.7% whereas specificity was 96.2%. The most common sites where residual as missed were lateral compartment of cavernous sinus followed by posterior and superior compartment CONCLUSION IOUS helps in surgical decision-making intraoperatively to achieve maximum safe resection.

Disruption of the Wnt-antagonist APC in the pituitary stem cells is a driver of adamantinomatous craniopharyngioma

AimsAcquired hypothalamic obesity (aHO) following craniopharyngioma (CP) is a challenging condition with limited therapeutic options. This study aimed to assess the real‐world effectiveness and safety of GLP‐1 RAs in this population.Materials and MethodsCranioGLP1 is a retrospective multicentre study including 116 adults with aHO treated with one or more GLP‐1 RAs across 16 French obesity centres. Demographic, clinical, and therapeutic data were collected from medical records. Weight outcomes, adverse events, and predictors of response were analysed.ResultsPatients had a mean age of 44.4 ± 13.5 years and a mean BMI of 40.1 ± 8.6 kg/m2, 42% had type 2 diabetes. Over a mean follow‐up of 44 months, mean weight loss was −4.6% (±12.5), with high interindividual variability; 51% achieved ≥5% weight loss, and 28% ≥10%. Semaglutide (mean dose 1.2 mg/week) was associated with the greatest reduction (−6.8%), particularly in patients without diabetes (−8.5% ± 12.3 vs. −3.9% ± 10.0 in those with diabetes; p = 0.032). Endocrine adverse events occurred in 12% and 10% of patients with adrenal or vasopressin deficiency decompensation, respectively, with 8% requiring hospitalisation. Gastrointestinal intolerance led to treatment discontinuation in 13% of cases.ConclusionsGLP‐1 RAs at submaximal doses induce moderate, yet clinically meaningful weight loss in adults with aHO, with semaglutide showing the highest efficacy. Given the non‐negligible risk of hormonal decompensation, specific endocrine monitoring is essential.