Craniopharyngioma Patients Research Articles

6819 Adult-Onset Craniopharyngioma Patients Are at High Risk for Hepatic and Metabolic Dysfunction in the First Year After Surgery

Abstract Disclosure: O. Cooper: None. V.S. Bonert: None. M. Noureddin: Advisory Board Member; Self; GlaxoSmithKline, Novo Nordisk, Merck, Takeda, Altimmune, BI, Northsea Therapeutics, Terns, 89BIO, Madrigal, Cytodyn, Corcept. Research Investigator; Self; Bristol-Myers Squibb, Akero, BI, GlaxoSmithKline, Allergan, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis Pharmaceuticals, Novo Nordisk, Shire, Takeda, Terns, Viking, Zudus, Gilead, Corcept. Stock Owner; Self; Rivus Pharma, CIMA, Cytodyn, ChronWell. M. Ader: None. M.O. Goodarzi: Advisory Board Member; Self; Nestle Health Science, Organon Laboratories. A.N. Mamelak: None. Background: Observational studies of adult-onset craniopharyngioma (AoCP) suggest that hepatic and metabolic dysfunction begin perioperatively, but rigorous evidence is lacking. We assessed prevalence of these sequelae in AoCP to better understand their long-term impact. Methods: The retrospective study included all patients with AoCP who underwent surgery at our center from 1993 to 2017. In the prospective study, newly diagnosed patients were assessed preoperatively and at 3 and 12 months postoperatively with MRI-PDFF/elastography, frequently sampled intravenous glucose tolerance test (FSIGT), and cardiometabolic biomarkers. The primary endpoint was hepatic fat fraction change from baseline. Secondary endpoints were changes in fibrosis, glucose/insulin metabolism, hypertension (HTN), and lipids. Data are summarized as median (IQR) or mean ± SD. Results: 35 patients were followed retrospectively for a mean of 116 months. After surgery, 73% had new-onset obesity. Mean BMI increased by 5.0 ± 5.8 kg/m2 and 40% progressed from overweight to obese. 43% had new-onset type 2 diabetes mellitus (T2DM) and 39% hyperlipidemia. In 16 patients with liver imaging, 11 had metabolic dysfunction-associated steatotic liver disease (MASLD), 5 metabolic dysfunction-associated steatohepatitis (MASH), and 4 cirrhosis. In the prospective study, data from 6 patients were analyzed, 4 for ≥12 months. Median age was 48.5 (40.5, 59); 50% were female. At baseline, 17% had HTN, 50% hyperlipidemia, 67% prediabetes, 50% obesity class 1, and 17% class 2. 40% had mild steatosis and none had fibrosis. Median A1C was 5.9% (5.3, 6.1). By 3 months postop, 83% had elevated liver enzymes and median hepatic fat fraction increased 213%, with steatosis in 67%. BMI increased by 4% (-1.8, 12.5); 1 patient remained normal weight, 1 progressed to overweight, 3 remained class 1 obesity and 1 class 2. By 12 months, 50% had elevated liver enzymes and all had steatosis, with fibrosis grade 3 in 1 patient. Median hepatic fat fraction increased 670% from baseline and 62% from month 3. 50% had T2DM and 50% prediabetes. Median A1C was 6.4% (5.9, 7.3). On FSIGT, disposition index decreased by 69% (-91, 50) and insulin sensitivity decreased by 51% (-70, 46). Median BMI was 30.8 kg/m2 (25.3, 37.1); 1 patient remained normal weight, 1 was overweight, 1 class 1 obesity, and 1 class 2. 50% had HTN and 50% had hyperlipidemia. Conclusion: By 10 years after surgery, most patients with AoCP have MASLD, with some progressing to MASH, fibrosis, and cirrhosis. T2DM, hyperlipidemia, and obesity are prevalent. In our small prospective cohort, by 1 year after surgery, all patients had developed MASLD, and BMI, blood pressure, and insulin and lipid profiles worsened. These results underscore the need for early interventions to halt progression of metabolic sequelae in patients with AoCP undergoing surgical resection and impede long-term comorbidity development. Presentation: 6/3/2024

Obesity in patients with craniopharyngioma in the South Asian region – A distinct phenotype

BackgroundCraniopharyngiomas are rare benign tumors located in the sellar and suprasellar region, with an incidence of 0.5–2 cases per million as reported in Western studies. Post-treatment, including surgery and/or radiotherapy, many patients develop significant obesity, primarily due to hypothalamic damage and associated complications such as hypopituitarism. In the South Asian population, genetic predisposition to obesity at lower BMIs, coupled with a carbohydrate-rich diet, may exacerbate obesity in craniopharyngioma patients, presenting a unique challenge. MethodsThis submission is a commentary based on a comprehensive literature review. The authors conducted the review using PubMed to focus on English-language articles covering hypothalamic obesity, craniopharyngioma and obesity in the South Asian population from 1939 to the present. ResultsThe literature review revealed that 50–60 % of patients treated for craniopharyngioma develop obesity, predominantly linked to hypothalamic damage, although these data are mainly derived from Western studies. Hypopituitarism was frequently observed, further contributing to the obesity. Despite a caloric intake appropriate for the age and gender, these patients exhibited reduced physical activity as measured by wrist accelerometers. Patients with hypothalamic obesity due to craniopharyngioma are at risk for metabolic syndrome and cardiovascular morbidity. Additionally, visual impairment was common, leading to a decreased quality of life. The South Asian population, genetically predisposed to visceral obesity and a carbohydrate-rich diet, may display a distinct phenotype. Although multiple treatment modalities have been tried, there is no definite treatment modality available to counteract this condition at present. ConclusionSouth Asian phenotype of craniopharyngioma-related obesity is characterized by significant metabolic and hormonal dysregulation, influenced by both dietary and genetic factors. Nevertheless, there may be a lot to be still understood about this devastating, rapid, relentless hypothalamic obesity syndrome. Also, a higher morbidity rate within this population, underscores the need for further research to develop targeted interventions.

Analysis of the different pathways of ectopic recurrence of craniopharyngioma in pediatric patients: presentation of cases and review of the literature.

Craniopharyngioma is a tumor derived from the squamous epithelium of Rathke's pouch. Despite successful excision, recurrence is common, typically occurring at the original tumor site. More rarely, recurrences can manifest at distant locations. This article reports on three distinct types of ectopic recurrence and reviews the existing literature. We reviewed clinical records and neuroimaging data of craniopharyngioma patients at our institution, identifying three cases of ectopic recurrence. Additionally, we conducted a literature review of similar cases published between 1975 and 2023, focusing on historical background, pathophysiology, clinical and radiological features, and treatment options. We identified nineteen articles detailing ectopic recurrence of craniopharyngiomas in pediatric patients. The right frontal lobe was the most frequently reported site of recurrence. The shortest interval to recurrence was 11months, while the longest was 14years. Most cases were managed with surgical resection, yielding positive outcomes. In our cases, the recurrence sites were temporal intraparenchymal, intraosseous orbital, and occipital intraventricular. All were successfully treated with surgery, with no subsequent recurrences. Although craniopharyngiomas are histologically benign, they can recur locally and, more rarely, at distant sites. Surgical intervention is generally well-tolerated. Further research into tumor cell dissemination mechanisms is essential to develop strategies for preventing ectopic recurrence.

Non-contrast MRI Surveillance of Craniopharyngiomas using a balanced steady state free precession (bSSFP) sequence.

Contrast-enhanced MRI (CEMRI) is a commonly used imaging modality for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non-contrast enhanced MRI (NCMRI) with a balanced steady state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. 29 craniopharyngioma patients (16 female/13 male, mean age=21.5± 4.3 years) with CEMRIs including a bSSFP sequence were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on noncontrast and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated using paired t-tests. Diagnostic confidence levels for NC-and CE evaluations were measured using a 3-point scale (2=confident,1=adequate,0=unsure). Analyses of tumor involvement of cranial nerves and adjacent vasculature and diagnostic confidence were performed using Fisher's exact and chi-square tests. No significant difference was observed between residual tumor volumes in both studies (18.86±21.67 cm3 vs 17.64±23.85 cm3, p=0.55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71±3.47 cm3 vs 3.95±5.51 cm3, p=0.10; 2.5±1.5 vs 2.9±1.5, p=0.10; 7.61±13.41 vs 6.84±13.37 cm3, p=0.22, respectively). Tumoral involvement of cranial nerves II (p=0.64), III (p=0.42), and adjacent vasculature (p=0.05) showed no significant differences in detection. Diagnostic confidence was comparable evaluating cranial nerve II, vascular structures, and third ventricle (p>0.05) involvement. Higher levels of confidence were observed with bSSFP sequences for detection of cranial nerve III involvement (p=0.0001) and with ce-T1W for cavernous sinus involvement (p=0.02). NCMRI techniques using a bSSFP sequence provides similar characterization of craniopharyngiomas as contrast enhanced techniques. 3D DRIVE, 3-dimensional driven equilibrium; ACA, anterior cerebral artery; bSSFP, balanced steady-state free precession; ce-T1W, contrast-enhanced T1-weighted imaging; CN, cranial nerve; GTR, gross total resection; STR, subtotal resection.

Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas

ObjectiveThis study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. MethodsNinety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. ResultsThe seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. ConclusionsOur study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

CP-02. DAYTIME SLEEPINESS AND HEALTH-RELATED QUALITY OF LIFEIN PATIENTS WITH CHILDHOOD-ONSET CRANIOPHARYNGIOMA

Abstract BACKGROUND Adamantinomatous craniopharyngioma (CP) is a rare embryonal malformation originating from remnants of the craniopharyngeal duct and located in the sellar and/or parasellar area. Overall survival rates are high (92%), but frequently quality of life (QoL) is severely impaired in patients with CP involving hypothalamic structures. Tumor- and/or treatment-related hypothalamic lesions result in disturbances of circadian rhythms including increased daytime sleepiness. METHODS After a median follow-up interval of 10 years (range: 1-39 years), 119 patients (63 female/ 56 male) with CP, recruited in KRANIOPHARYNGEOM 2000/2007 and KRANIOPHARYNGEOM Registry 2019 between 2000 and 2022, were analysed for daytime sleepiness by Epworth scale (ES) and for QoL by EORTC QLQ-C30 questionnaire. RESULTS CP patients (n= 85) with pathologically increased ES score (ES score > 12) had worse QoL (p = 0.003), when compared with CP patients with normal ES score (n= 34). Pathologically increased daytime sleepiness (ES score) was negatively correlated with QoL (r= -0.395; p< 0.001). Surgical hypothalamic lesions (71% of patients) were associated with higher ES scores, whereas such impact could not be observed for presurgical hypothalamic involvement of CP (73% of patients). CONCLUSIONS As increased daytime sleepiness plays an important role for QoL in survivors of CP, treatment of disturbances of circadian rhythms with medication such as central stimulating agents is recommended. For prevention of increased daytime sleepiness, hypothalamus-sparing surgical treatment strategies should be considered as state of the art in patients with CP.

Serum Metabolomic and Lipidomic Profiling Reveals the Signature for Postoperative Obesity among Adult-Onset Craniopharyngioma.

Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.

Use of moderate hypofractionated radiotherapy in craniopharyngioma

External beam radiation therapy is used for inoperable, residual, or recurrent disease after surgery for craniopharyngioma. At present, conventional radiotherapy, hypofractionated radiotherapy (HFRT), and stereotactic radiotherapy (SRT) are available options. However, there are limited data on HFRT and SRT using modern radiotherapy (RT) devices. This paper presents the findings of a retrospective study conducted at a single institution based on our long-term experiences with eight craniopharyngioma patients who had underwent RT. The median time between the operation and RT was 8.5 months (ranging from 2.6 to 11 months). Six patients were treated with CyberKnife® (CK®), and two were treated with Tomotherapy® (HT®) using the helical intensity-modulated RT technique (H-IMRT). Patients treated with HT received a mean of 50 and 55 Gy RT in 25 and 30 fractions (conventional RT scheme), respectively. Out of the six patients treated with CK, three received a mean of 22 – 25 Gy in five fractions, and the other three received a mean of 40 – 42 Gy in 15 fractions. The median follow-up was 6 years (range: 2 – 9.1 years), and no progression was observed. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 85.7% and 85.7%, respectively. OS and PFS at 5 years were likewise 85.7% and 85.7%, respectively. Of the two patients (25%) who were alive with a complete response, one received 50 Gy in 25 fractions with H-IMRT, and the other received RT through CyberKnife with five fractions. Five patients (62.5%) were alive with stable residual disease and one patient had died with a complete response. HFRT may be considered as a preferable option in the treatment of craniopharyngioma, in addition to conventional or SBRT treatment options.

Adult craniopharyngioma concomitant with unruptured intracranial aneurysms: incidence, risk factors, and treatment strategies.

Concomitant unruptured intracranial aneurysms (UIAs) in patients with craniopharyngioma (CP) pose a challenge for surgical management. This study presents the largest known single-institution case series to investigate the incidence of UIA in CP patients, with the aim of exploring the potential risk factors for the occurrence of UIA in CP patients and proposing treatment strategies. The authors retrospectively reviewed the records of 289 adult CP patients treated in their department between January 2020 and August 2022. Routine CT angiography (CTA) was performed preoperatively in all cases. Logistic regression analysis was used to identify the risk factors for the occurrence of aneurysms. Aneurysms with the following characteristics were considered to have a high risk of intraoperative rupture and required treatment before tumor resection: 1) preliminary assessment of a high inherent risk of rupture (risk of rupture in their natural progression); and 2) location close to the tumor, irregular shape, and/or growth toward the tumor, even if the preliminary assessment indicated a low inherent risk of rupture. Twenty-three of 289 CP patients (7.96%, 95% CI 5.36-11.6) were diagnosed with both CP and UIA (CP-UIA). Hypertension (OR 4.148, 95% CI 1.654-10.398; p = 0.002), estrogen deficiency (OR 3.097, 95% CI 1.241-7.731; p = 0.015), and suprasellar tumor (OR 4.316, 95% CI 1.596-11.67; p = 0.004) were independent risk factors for intracranial aneurysms (IAs) in CP patients. Among the 23 CP-UIA patients, 6 (26.1%) with a high risk of aneurysm rupture underwent endovascular treatment (EVT) before tumor resection. Seventeen (73.9%) patients with a low risk of rupture underwent tumor resection only. The incidence rate of IA in patients with CP was higher than that in the general population. Routine preoperative CTA is advised for adult CP patients. Patients with papillary CP exhibited a higher proportion of CP-UIAs. Older age, hypertension, estrogen deficiency, and suprasellar tumor were independent risk factors for the occurrence of IAs in CP patients. IAs in CP patients are predominantly located in the C6 and C7 segments of the internal carotid artery and are often suitable for EVT. When treating CP-UIAs, tumor-related symptoms, risk of aneurysm rupture, the spatial relationship between the tumor and IA, and the approach for tumor resection should be considered.

Long-term outcomes of neuroendoscopic cyst partial resection combined with stereotactic radiotherapy for craniopharyngioma.

The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas. In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated. ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87months (median, 33months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension. Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.

Preoperative peripheral inflammatory markers are predictors of postoperative central diabetes insipidus in craniopharyngioma patients: a retrospective study

BackgroundPostoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs.MethodsThe clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis.ResultsPreoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups.ConclusionsPreoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.

Comparison of central diabetes insipidus (antidiuretic hormone deficiency) and stalk effect in patients with adamantinomatous and papillary craniopharyngioma.

Craniopharyngioma (CP), a rare benign intracranial tumor, is still a major clinical challenge. There are two major histologic phenotypes: papillary CP (PCP) and adamantinomatous CP (ACP). This research aimed to assess the occurrence of central diabetes insipidus (antidiuretic hormone deficiency), the level of prolactin, and the stalk effect between PCP and ACP subtypes prior to and after surgery. Clinical data of CP patients before and after surgical resection of the tumor were analyzed retrospectively. These patients were divided into PCP and ACP groups, in accordance with the pathologic classification. The data of prolactin level, 24-h urinary volume, urine specific gravity and electrolyte status before and after surgery were evaluated in these two CP subtypes. A total of 86 CP patients were included, among which 28 patients were PCP and 58 were ACP. Compared to those prior to surgery, 24-h urine volume, serum sodium and serum chlorine concentrations were obviously increased, while prolactin and urine specific gravity were remarkably decreased in all the CP patients after surgery. Compared to those before operation, prolactin level and urine specific gravity were decreased, and 24-h urine volume, serum sodium and serum chlorine were elevated after operation in ACP patients. Moreover, after surgery, 24-h urine volume in PCP patients was higher than that in ACP group. The central diabetes insipidus in patients with CP was aggravated after surgical resection, especially in ACP patients. Moreover, the central diabetes insipidus of PCP subtype was more serious than that of ACP subtype.

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma

BackgroundEmerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches.MethodsWe enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients.ResultsThe composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly.ConclusionsThe gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Vascular complications in craniopharyngioma-resected paediatric patients: a single-center experience.

Craniopharyngioma (CP), although slow growing and histologically benign, has high morbidity, mostly related to hypothalamus-pituitary dysfunction and electrolyte imbalance. Increased risk of vascular complications has been described. However, data are still poor, especially in the paediatric population. The aim of our study was to evaluate the occurrence, timing, and predisposing factors of deep venous thrombosis (DVT) and other vascular alterations in neurosurgical paediatric CP patients. In a single-centre, retrospective study, we investigated 19 CP patients (11 males, 8 females, mean age 10.5 ± 4.3 years), who underwent neurosurgery between December 2016 and August 2022, referred to Meyer Children's Hospital IRCCS in Florence. Five patients (26.3%) presented vascular events, which all occurred in connection with sodium imbalances. Three DVT (two with associated pulmonary embolism, in one case leading to death) developed in the post-operative period, most frequently at 7-10 days. Elevated D-dimers, a reduced partial activated thrombin time and a prolonged C-reactive protein increase were highly related to thrombotic vascular events. One case of posterior cerebral artery pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting. Superficial vein thrombophlebitis was a late complication in one patient with other predisposing factors. CP patients undergoing neurosurgery are at risk of developing DVT and vascular alterations, thus careful follow-up is mandatory. In our study, we found that the phase of transition from central diabetes insipidus to a syndrome of inappropriate antidiuretic hormone secretion may be a period of significant risk for DVT occurrence. Careful vascular follow-up is mandatory in CP-operated patients.

Arginine Vasopressin Deficiency in Children with Craniopharyngioma and Cerebral Germ Cell Tumour: Two Sides of the Same Coin – Clinical and Radiological Features

Introduction: Paediatric brain tumours in the sellar-suprasellar region are often associated with arginine vasopressin peptide deficiency (AVPD), either at diagnosis caused by the tumour itself or during follow-up as a consequence of treatments. The purpose of this research was to retrospectively describe the neuroradiological characteristics and the timing of AVPD development in a cohort of paediatric patients with craniopharyngioma (CP) or germ cell tumours (GCTs). Methods: We evaluated brain MRI at tumour diagnosis and at the onset of AVPD, as well as recorded clinical, endocrinological, and histopathological data, treatments, and outcome. Results: Seventy-two patients with AVPD were included: 46 CPs (M:F = 25:21) and 26 GCTs (M:F = 18:8). CPs were suprasellar (63%), sellar (4%), or both (33%). GCTs were suprasellar (65%), pineal (24%), or bifocal (11%). No statistically significant differences were noted in tumour size between CP and GCT. Posterior pituitary bright spot absence was reported at diagnosis or at follow-up (as surgery consequence) in all patients with AVPD, indicating that the absence of hyper-intensity is a cardinal feature of AVPD. When measurable, pituitary stalk was thickened in most GCT patients (61.5%). At AVPD diagnosis in GCT, the mean age was 11.9 years; 18 (69%) patients had AVPD at the time of tumour diagnosis, 5 (19.3%) before the diagnosis with a latency of 24.4 months (range 4–48), and 3 (11.5%) during follow-up (mean 24 months, range 4–60) due to tumour recurrence. GCT patients presented with severe endocrinological manifestations (18/26), headache and vomiting (10/26), visual impairment (5/26), and behavioural changes with fatigue (1/26). In CP, the mean age at AVPD diagnosis was 10.3 years; 7 (15.2%) patients had AVPD at time of tumour diagnosis, 37 (80.5%) developed it shortly after neurosurgery, and 2 patients (4.3%) after 2 and 4 months from surgery, respectively. Clinically, headache and visual abnormalities were the most frequent clinical symptoms at diagnosis of CP (39/46, 84.8%), with hydrocephalus (16/46, 35%) and displacement of optic chiasm (29/46, 63%) at the initial MRI. While the vast majority of CP patients (93%) received only surgery, all GCT patients received radiation therapy in addition to or instead of surgery. Conclusion: An early differential diagnosis in children with AVPD and brain tumours is supported by a good understanding of the clinical features and imaging findings. Expert follow-up is necessary.

Vascular Morbidity and Mortality in Craniopharyngioma Patients-A Scoping Review.

Craniopharyngioma (CP) treatment, including surgery and radiotherapy, can have short- and long-term vascular side effects. Hypothalamic damage is related to morbid obesity and may increase the lifelong risk of experiencing vascular events in CP patients. This review summarized the available evidence regarding vascular complications in adamantinomatous or papillary CP patients, whatever their age at diagnosis. Three databases (Medline, CINAHL, Web of Science) were searched (06/2023) to retrieve eligible articles. The search was limited to peer-reviewed articles. Titles, abstracts, and full texts were screened by two independent reviewers, and data were extracted using a self-developed grid. Seventy-two studies were included in this review; the majority were case reports. Reported vascular sequela that occurred due to surgery were fusiform dilation of the carotid artery, stroke, vasospasm, hemorrhage, and aneurysm. Related conditions that emerged due to radiotherapy included Moyamoya syndrome and cavernoma. Cardiovascular morbidity and mortality often lead to hypothalamic obesity and metabolic syndrome in CP patients. Vascular damage is a rare complication of CP treatment. Surgical strategies should protect the surrounding hypothalamic and vascular structures. Patients receiving radiotherapy, particularly at a young age, should undergo magnetic resonance angiography monitoring to identify possible neurovascular sequela during post-treatment care.

Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database.

Craniopharyngiomas are rare tumors originating in the sellar region, with limited information on their somatic mutational landscape. In this study, we utilized a publicly available genomic database to profile the somatic mutational landscape of craniopharyngioma patients and interrogate differences based on histologic subtype. We utilized the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE)® database accessed from cBioPortal (v13.1-public) to query all patients with craniopharyngiomas. Of the 336 patients with sellar tumors, 51 (15.2%) had craniopharyngiomas. Of these 51 patients, 42 (82.4%) were adamantinomatous subtype and 9 (17.6%) were papillary subtype. In this cohort, 32 (62.7%) patients were pediatric, while 19 (37.3%) were adult. The top mutations in the cohort were: CTNNB1 (n = 37; 73%), BRAF (n = 7; 14%), ARID1B (n = 5; 10%), KMT2D (n = 4; 8%), FANCA (n = 4; 8%), ATM (n = 4; 8%), and TERT (n = 3; 8%). Of the 37 patients with CTNNB1 mutations, 8 (21.6%) had S33X, 9 (24.3%) had S37X, 7 (18.9%) had T41X, and 5 (13.5%) had D32X. In this cohort, CTNNB1 mutations tended to co-occur with ATM (n = 4; 10.8%), KMT2C (n = 4; 10.8%), TERT (n = 3; 8.1%), BLM (n = 3; 8.1%), and ERBB2/3 (n = 3; 8.1%), suggesting CTNNB1 mutations tended to co-occur with mutations in genes important in cell growth and survival, chromatin accessibility, and DNA damage response pathways. CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.

Long-term clinical sequelae and socio-professional performance in craniopharyngioma patients.

Craniopharyngioma (CP) is a rare tumor, leading to several post-treatment sequelae which may have significant clinical and social implications, including impaired academic performance or employability. We conducted a retrospective study involving CP patients followed at our center between 1986 and 2020. Data on demographics, clinical, imaging, and treatment characteristics were collected from the clinical records. There were 33 patients (current mean age of 49.8±18.7 years), being 22 diagnosed in adulthood. The average follow-up duration was 16.03±9.3 years. Twelve patients were treated with surgery alone, while 21 underwent surgery and radiotherapy. Pituitary and hypothalamic deficits were more frequent in treated with surgery, whereas visual defects and metabolic diseases were more frequent in treated with surgery and radiotherapy. There were no differences between age of onset groups and type of sequelae. After diagnosis, nine patients concluded their academic training. In childhood-onset group, after diagnosis, one patient was retired, three continue studying and the others concluded schooling. In the other group, six patients were retired and two concluded schooling. There was no association between academic performance or employability and the type of treatment. CP patients academic performance was not worse comparing with general Portuguese population. Long-term sequelae may not be related with the age of CP onset, but may vary according to the type of treatment. There was a wide variety of clinical sequelae with extended follow-up, however academic performance and employability seemed not affected. CP diagnosis in an early period of life may not compromise the academic success of patients.

Performance and symptom validity indicators among children undergoing cognitive surveillance following treatment for craniopharyngioma.

Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to neuropsychological evaluations, helping ensure findings reflect true abilities or concerns. It is unclear how PVTs and SVTs perform in children who received radiotherapy for brain tumors. Accordingly, we investigated the rate of noncredible performance on validity indicators as well as associations with fatigue and lower intellectual functioning. Embedded PVTs and SVTs were investigated in 98 patients with pediatric craniopharyngioma undergoing proton radiotherapy (PRT). The contribution of fatigue, sleepiness, and lower intellectual functioning to embedded PVT performance was examined. Further, we investigated PVTs and SVTs in relation to cognitive performance at pre-PRT baseline and change over time. SVTs on parent measures were not an area of concern. PVTs identified 0-31% of the cohort as demonstrating possible noncredible performance at baseline, with stable findings 1 year following PRT. Reliable digit span (RDS) noted the highest PVT failure rate; RDS has been criticized for false positives in pediatric populations, especially children with neurological impairment. Objective sleepiness was strongly associated with PVT failure, stressing need to consider arousal level when interpreting cognitive performance in children with craniopharyngioma. Lower intellectual functioning also needs to be considered when interpreting task engagement indices as it was strongly associated with PVT failure. Embedded PVTs should be used with caution in pediatric craniopharyngioma patients who have received PRT. Future research should investigate different cut-off scores and validity indicator combinations to best differentiate noncredible performance due to task engagement versus variable arousal and/or lower intellectual functioning.

The Role of Tumor-Associated Hypothalamic Involvement in Surgical Treatment and Long-Term Outcome in Adult Patients with Craniopharyngioma

IntroductionHypothalamic invasion in pediatric patients with craniopharyngioma negatively influences clinical outcomes. It has been demonstrated that radiological classification of hypothalamic invasion can effectively predict surgical strategies to minimize postoperative comorbidities in pediatric patients 1. However, no comparative analysis has been performed in adult craniopharyngioma patients. This study implements the previously established radiological classification to characterize postoperative morbidity, surgical outcome, and distress in adult craniopharyngioma patients. MethodsElectronic medical records of 22 adult craniopharyngioma patients were used to analyze patient demographics, surgical data, endocrinological and ophthalmological status and histopathology in a retrospective, single center study. Questionnaires regarding postoperative distress (NCCN Distress Thermometer and Problem List), comorbidities (Charlston Comorbidity Index (CCI), employment status and need for supportive care were distributed. MRI scans were categorized according to Puget et al. ResultsPatients with hypothalamic involvement display significantly higher rates of postoperative Diabetes Inspidus and higher scores on the NCCN Distress. This significant difference was lost when considering postoperative Puget grades. Puget grades 1 and 2 were found to be associated with use of subfrontal surgical approach (HR 4.080 [CI 1.153-14.431]; p = 0.029). ConclusionOur results point towards a possible predictive role of preoperative hypothalamic invasion for postoperative diabetes insipidus as well as higher perceived levels of distress following surgery which may be established in larger patient cohorts. Furthermore, a subfrontal surgical approach appears to be predicted by tumors with hypothalamic invasion. In this case, preoperative MRI grading may help guide planning of an optimal surgical strategy for adults with craniopharyngioma to reduce postoperative morbidity.