Adult-onset Craniopharyngioma 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

The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma

BackgroundCraniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP.MethodsA total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored.ResultsCompared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF.ConclusionThe present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for 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.

THU219 Vascular Damage After Craniopharyngioma

Abstract Disclosure: J. Beckhaus: None. S. Boekhoff: None. B. Bison: None. C. Friedrich: None. H.L. Muller: None. Craniopharyngiomas are rare, embryonic, malformational tumors of the (supra-)sellar region. Due to tumor and/or treatment-related hypothalamic lesions, patients develop morbid obesity. Obesity is a major vascular risk factor, leading to reduced 20-year overall survival and a 3- to 19-fold higher cardiovascular mortality after craniopharyngioma compared to the general population. An analysis within the Childhood Cancer Survivor Study (CCSS) revelaed a 10-fold higher relative risk for stroke in adult survivors of childhood/young adult cancers compared to their siblings. To study craniopharyngioma-specific risk factors for vascular damages we searched three databases (Pubmed, CINAHL and Web of Science) and included 49 articles after title and abstract screening. Eligible studies were case reports, cohort and cross-sectional studies. Neurovascular damages due to surgical interventions included cerebral infarcts, stroke, aneurysms, anterior/middle cerebral artery syndrome (ACA/MCA), cerebral venous sinus thrombosis, and seizures. Radiation-induced vascular disease described Moyamoya syndrome, radionecrosis and thrombosis. Tumor-induced inflammation is suspected to play a causal role in the etiology of vascular complications in proximity of the tumor. Therefore, early diagnostics such as echocradiography or cardial MRI and risk-adapted prevention and treatment options for vascular disease are needed to improve long-term prognosis after craniopharyngioma treatment. This review summarizes the available evidence for vascular disease after pediatric- and adult-onset craniopharyngioma to derive possible treatment pathways. Individualized, tertiary prevention programs are required for craniopharyngioma patients and survivors to overcome or reduce the risk of vascular complications and elevate their quality of survival. Presentation: Thursday, June 15, 2023

The psychological impact of adult-onset craniopharyngioma: A qualitative study of the experience of patients and clinicians.

Individuals who experience social and emotional difficulties struggle to maintain successful social relationships and incur an increased risk of developing mood disorders. These, in turn, have a significant impact on psychological and physical wellbeing. A small number of medical studies suggest that patients with adult-onset craniopharyngioma (AoC) report poorer quality of life, however, no in-depth psychological research has been carried out. The present study aimed to capture a rich understanding of whether patients with AoC experience a psychological impact from their diagnosis and whether psychological factors may contribute to a poorer quality of life. Both patients with AoC and clinicians with experience of working with patients with AoC were invited to take part in a semi-structured interview. Participants were recruited from three geographically disperse National Health Service (NHS) units across the United Kingdom (UK). Eight patients and 10 clinicians took part in the study. Interviews were recorded and transcribed verbatim and analysed using inductive thematic analysis. Two key themes, with multiple subthemes, were identified: 1) Patients experience psychological impacts of AoC; and 2) Patients also experience common physical symptoms. Patients and clinicians recognised significant psychological impact as a result of AoC, and these impacts contributed to overall poorer quality of life. Crucially, both parties also felt that further research into psychological impact of AoC was both interesting and useful.

Effects of Craniotomy and Endoscopic Endonasal Transsphenoidal Surgery on Bodyweight in Adult-Onset Craniopharyngioma: A Single-Center Retrospective Study.

Craniopharyngioma (CP) is a histologically benign tumor with high mortality and morbidity. Although surgical treatment is essential in managing CP, the best surgical approach is debated. A retrospective cohort of 117 patients with adult-onset CP (AOCP) treated between 2018 and 2020 in Beijing Tiantan Hospital was identified and examined. The effects of traditional craniotomy (TC) and endoscopic endonasal transsphenoidal surgery (EETS) on the extent of surgical resection, hypothalamic involvement (HI), postoperative endocrine function, and postoperative weight were compared in the cohort. The cohort comprised 43 males and 74 females, divided into the TC (n = 59) and EETS (n = 58) groups. The EETS group possessed a higher rate of gross total resection (GTR) (adjusted odds ratio (aOR) = 4.08, p = 0.029) and improved HI (aOR = 2.58, p = 0.041) than the TC group. Worse postoperative HI was only observed in the TC group (5 patients). The EETS was associated with fewer adverse hormonal outcomes, including posterior pituitary dysfunction (aOR = 0.386, p = 0.040) and hypopituitarism (aOR = 0.384, p = 0.031). Additionally, multivariate logistic regression analysis confirmed that EETS was related to fewer cases of weight gain >5% (aOR = 0.376, p = 0.034), significant weight change (aOR = 0.379, p = 0.022), and postoperative obesity (aOR = 0.259, p = 0.032). Compared to TC, EETS shows advantages in accomplishing GTR, hypothalamus protection, postoperative endocrine function reservation, and postoperative weight control. These data suggest that the EETS deserves more application in managing patients with AOCP.

ODP365 The Psychological Impact of Adult-Onset Craniopharyngioma: The Experience of Patients and Clinicians

Abstract Introduction Individuals who experience social and emotional difficulties struggle to maintain successful social relationships and incur an increased risk of developing mood disorders. These, in turn, have been found to have a significant impact on both psychological and physical wellbeing. A small number of medical studies suggest that patients with adult-onset craniopharyngioma (AoC) report a poorer quality of life, however, no psychological research has been carried out. The present study aimed to capture, for the first time, a detailed description of AoC patients’ lives outside the clinic. Specifically, whether they experience a psychological impact from their diagnosis and whether psychological factors may contribute to a poorer quality of life. Methods Both patients with AoC and clinicians with experience of working with patients with AoC were invited to take part in a semi-structured interview. Clinicians were recruited with the view to providing an alternative viewpoint and the possibility to assess potential (mis)matches in perceptions of AoC patients’ social strengths and difficulties. Participants were recruited from three geographically disperse NHS units across the UK. Eight patients and 11 clinicians took part in the study. Interviews were analysed using inductive thematic analysis wherebycodes are identified which represent statements centring on a similar topic that are endorsed by multiple participants. Codes that are frequently used are compiled into larger themes, reflecting broader topics. Results The central theme of 'symptoms’ was consistent across patients and clinicians and consisted of three sub-themes: physical symptoms, psychological symptoms, and the tendency for patients to hide symptoms. Both cohorts stated that weight gain and fatigue were the most common physical symptoms, but these were also closely related to psychological symptoms, such as changing lifestyle patterns and a shrinking social network. Crucially, both cohorts stated that low mood, anxiety, and low self-esteem were common and significant experiences. Both cohorts discussed instances of specific mental health disorders. Conversely, some patients tried to hide symptoms with diminishing or contradictory statements or acknowledged that others had encouraged them to seek help, a theme that was also found with clinicians. In addition to these similarities there were also important differences in perceptions. Firstly, while clinicians believed they were open to or actively discussed a patient's psychological wellbeing during consultations, many patients felt they had never been asked about this. Secondly, while some clinicians were very clear on the extreme negative impact of the condition, patients also described more subtle social impacts. Finally, clinicians felt a sense of frustration regarding poor, unspecialised, under resourced psychological support, a feeling that was not common among patients. Conclusion In conclusion, both patients and clinicians recognised significant psychological impact as a result of AoC. Further research is planned to quantitively assess the topics raised in the present study. Presentation: No date and time listed

Long-term outcomes in patients with adult-onset craniopharyngioma.

PurposeCraniopharyngiomas are nonmalignant sellar and parasellar tumors exhibiting a bimodal age distribution. While the outcomes following treatment in patients with childhood-onset craniopharyngiomas are well characterized, similar information in adult-onset craniopharyngiomas is limited. We aimed to describe the long-term outcomes (weight and metabolic parameters, mortality) in patients with adult-onset craniopharyngioma following treatment.MethodsPatients with adult-onset craniopharyngioma with initial treatment (1993–2017) and >6 months of follow-up at our institution were retrospectively identified. Body mass index (BMI) categories included obese (BMI ≥ 30 kg/m2), overweight (BMI 25–29.9 kg/m2), and normal weight (BMI < 25 kg/m2).ResultsFor the 91 patients with adult-onset craniopharyngioma (44% women, mean diagnosis age 48.2 ± 18 years) over a mean follow-up of 100.3 ± 69.5 months, weight at last follow-up was significantly higher than before surgery (mean difference 9.5 ± 14.8 kg, P < 0.001) with a higher percentage increase in weight seen in those with lower preoperative BMI (normal weight (20.7 ± 18%) vs. overweight (13.3 ± 18.0%) vs. obese (6.4 ± 15%), P = 0.012). At last follow-up, the prevalence of obesity (62 vs. 40.5%, P = 0.0042) and impaired glucose metabolism (17.4% vs. 34%, P = 0.017) increased significantly. All-cause mortality was 12%, with the average age of death 71.9 ± 19.7 years (average U.S. life expectancy 77.7 years, CDC 2020).ConclusionPatients with adult-onset craniopharyngioma following treatment may experience weight gain, increased prevalence of obesity, impaired glucose metabolism, and early mortality. Lower preoperative BMI is associated with a greater percentage increase in postoperative weight.

Postoperative hypothalamic damage predicts postoperative weight gain in patients with adult-onset craniopharyngioma.

This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma. The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p=0.005 and p=0.002) and with HO (p=0.001 and p=0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p=0.008) could predict postoperative weight gain ≥5%. Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.

Clinical Implication of Individually Tailored Segmentation Method for Distorted Hypothalamus in Craniopharyngioma

ObjectiveSeveral attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP.MethodsWe included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements.ResultsThe corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P<0.01). However, HT volume was overestimated using T1-weighted images owing to obscured MR signal of the thalamus in patients with severe HT damage. Therefore, we used T2-weighted images to evaluate its clinical implications in 72 patients with available medical data. Postoperative HT volume was negatively associated with preoperative body weight and preoperative tumor volume (r=–0.25 [95% CI -0.45 to -0.04], P=0.04 and r=–0.26 [95% CI -0.40 to -0.15], P=0.03, respectively). In the subgroup analysis of CP patients who underwent primary surgery (n=56), pre- and postoperative body weights were negatively associated with HT volume (r=–0.30 [95% CI -0.53 to -0.03], P=0.03 and r=–0.29 [95% CI -0.53 to -0.02], P=0.03, respectively).ConclusionsAdult-onset CP patients showed negative associations between postoperative HT volume and preoperative/postoperative body weight using a new method of HT volume measurement based on T2-weighted images.

Exploring eating behavior and psychological mechanisms associated with obesity in patients with craniopharyngioma: a scoping review protocol.

The objective of the review is to explore the evidence on the behavioral and psychological mechanisms underlying the development of obesity in patients with craniopharyngioma. The review will map the available evidence, identify gaps in the literature, and find avenues of future intervention. Craniopharyngiomas are low-grade intracranial tumors of the supersellar region. Obesity is associated with the tumor or surgery or radiotherapy to treat the tumor; however, the behavioral and psychological processes contributing to that association are not clear. This review will provide a synthesized evidence base of the relevant research. This review will consider published studies with all types of study designs, including patients with childhood- or adult-onset craniopharyngioma. Articles assessing factors that may impact eating behavior will be included based on the following categories: eating behavior, obesity, neuroimaging, endocrine response, energy expenditure, sleep, and neuropsychology. MEDLINE, Embase, and PsycINFO will be searched, in addition to the Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov, NICE evidence search, and International Standard Randomised Controlled Trial Number (ISRCTN). No limits will be placed on the scope of the search. The methodology will follow a three-stage process with two independent reviewers at each stage, including an initial database search, screening of titles and abstracts of retrieved studies, full-text assessment for inclusion criteria, and hand-searching of reference lists. Data will be extracted using a standardized charting form and summarized in tables. The data will be synthesized using a narrative summary and diagrammatic map and will be based on the evidence for each of the proposed research categories.

Risk Factors for Hypothalamic Obesity in Patients With Adult-Onset Craniopharyngioma: A Consecutive Series of 120 Cases.

ContextHypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse.ObjectiveThe objective of the study was to describe weight changes after surgical treatment in adult-onset craniopharyngioma patients and to analyze risk factors for postoperative weight gain and HO.Subjects and MethodA retrospective analysis was conducted of 120 adult-onset patients who underwent surgery for craniopharyngioma and follow-up at the institution of the authors between January 2018 and September 2020. Clinical characteristics, anthropometric data, image features, treatment modalities, and endocrine indices were collected. Multivariable logistic regression analysis was used to identify independent risk factors for postoperative weight gain and HO.ResultsForty-nine (40.8%) patients had clinically meaningful weight gain (≥5%) in a median follow-up time of 12.0 months (range 1.0–41.0 months) after surgery. The mean postoperative weight gain in this subgroup was 17.59 ± 12.28 (%). Weight gain continued in the first year following surgery. Patients with lower preoperative BMI [OR 0.78, 95% CI (0.67–0.90), P = 0.001] and the adamantinomatous subtype [OR 3.46, 95% CI (1.02–11.76), P = 0.047] were more likely to experience postoperative weight gain ≥5%. The prevalence of HO was 19.2% preoperatively and increased to 29.2% at last follow-up postoperatively. Only preoperative BMI [OR 2.51, 95% CI (1.64–3.85), P < 0.001] was identified as an independent risk factor for postoperative HO.ConclusionsHO is a common complication in patients with adult-onset craniopharyngioma. Patients with higher preoperative BMI had a greater risk for developing HO postoperatively.

Early Treatment of Hypothalamic Hypogonadism With LH-RH Analog Improved the Long-Term Prognosis of Hypogonadism of Adult-Onset Craniopharyngioma

Object: Craniopharyngiomas frequently grow on the cisternal surface of the hypothalamic region. The survival rate for childhood craniopharyngioma has been improving with more long-term survivors. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. GnRH neurons in hypothalamus that send axons to portal blood system in median eminence fire in coordinated, repetitive, episodic manner, producing distinct pulses of GnRH in the portal blood system. In 2001, we experienced the case of hypothalamic hypogonadism after the radical surgery of craniopharyngioma located in the right basal ganglia and hypothalamus. During the operation, pituitary gland and stalk were preserved. The patient had developed panhypopituitarism and hypothalamic hypogonadism after transcranial surgery. The diagnosis of oligospermia and asthenospermia was made. We hypothesized that the hypogonadism was due to the lack of distinct pulses of GnRH after the surgery. The aim of this program was to demonstrate the efficacy of the pulsatile subcutaneous LH-RH therapy for the recovery of gonadal function from hypothalamic hypogonadism and to observe the long-term prognosis after recovery.Method: After a diagnosis of hypothalamic hypogonadism, low dose LH-RH treatment was given to a 29-year-old male with small portable automatically-timed infusion pump, connected to a subcutaneous (s.c.) catheter. Gonadorelin acetate was prepared to the concentration of 0.8mg/ml. Sixteen micrograms of LH-RH s.c. was given every 120 min. Serum levels of gonadotropin and testosterone were monitored. The treatment was continued until his gonadal function normalized. Long-term follow up was continued after low dose LH-RH treatment.Result: After the six months of pulsatile LH-RH treatment, serum level of testosterone turned normal. Then the treatment was paused in 2003. His wife became pregnant with in-vitro fertilization (IVF) in 2007 and gave birth in 2008. Moreover, his wife became pregnant naturally without IVF in 2009 and gave birth in 2010, suggesting the recovery from oligospermia and asthenospermia of her husband. Early recovery from hypothalamic hypogonadism maintained normal gonadal function in 2020.Clinical Lessons: We demonstrated a case of successful treatment of the hypothalamic hypogonadism after the surgery of craniopharyngioma. The pulsatile subcutaneous LH-RH therapy is efficacious for the case with the lack of the distinct pulses of GnRH after radical surgery of craniopharyngioma. Early treatment of hypothalamic hypogonadism with LH-RH analog improved the long-term prognosis of hypogonadism of adult-onset craniopharyngioma.

Preoperative BMI Predicts Postoperative Weight Gain in Adult-onset Craniopharyngioma.

Craniopharyngiomas, while benign, have the highest morbidity of all nonmalignant sellar tumors. Studies on weight and metabolic outcomes in adult-onset craniopharyngioma (AOCP) remain sparse. To examine postsurgical weight and metabolic outcomes in AOCP and to identify any clinical predictors of weight gain. Retrospective chart review of patients with AOCP who underwent surgery between January 2014 and May 2019 in a single pituitary center. The study included 45 patients with AOCP with a minimum follow-up of 3 months. Median follow-up time was 26 months (interquartile range [IQR] 10-44). Main outcome measures were the changes in weight/body mass index (BMI), metabolic comorbidities, and pituitary deficiencies between preoperative and last follow-up. Both weight and BMI were higher at last follow-up, with a mean increase of 3.4 kg for weight (P = .015) and 1.15 kg/m2 for BMI (P = .0095). Median % weight change was 2.7% (IQR -1.1%, 8.8%). Obesity rate increased from 37.8% at baseline to 55.6% at last follow-up. One-third of patients had ~15% median weight gain. The prevalence of metabolic comorbidities at last follow-up was not different from baseline. Pituitary deficiencies increased postoperatively, with 58% of patients having ≥3 hormonal deficiencies. Preoperative BMI was inversely associated with postoperative weight gain, which remained significant after adjusting for age, sex, race, tumor, and treatment characteristics. Patients with ≥3 hormonal deficiencies at last follow-up also had higher postoperative weight gain. In this AOCP cohort, those with a lower BMI at the preoperative visit had higher postoperative weight gain. Our finding may help physicians better counsel patients and provide anticipatory guidance on postoperative expectations and management.

MON-276 Post-Surgical Metabolic Outcomes in Adult-Onset Craniopharyngioma: A Single Pituitary Center Experience

Background:Craniopharyngiomas, while benign, have the highest morbidity of all pituitary tumors. Hypothalamic obesity (HO), one of the most devastating consequences, is commonly studied in the pediatric population, but few data are available on weight and other metabolic outcomes in adult-onset craniopharyngiomas (AOCP).Methods:We conducted a retrospective chart review of 49 adult patients with AOCP who underwent surgery between 1/2014 and 5/2019 at an academic pituitary center. Weight, BMI, metabolic diseases (type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, OSA), and pituitary hormone deficiencies were recorded pre-surgery and at last follow up and analyzed using paired t-tests or McNemar’s test.Results:Median age was 56 years (51% women), 45% had >1 surgery (range 1-5), and 49% had radiotherapy. Of 72 total surgeries, 54% were craniotomies and 68% of surgeries resulted in subtotal resections. Median follow up was 25 months. Median BMI was 29.2 and 30.5 kg/m2 at baseline and at last follow up, respectively. Weight was higher at last follow up (mean increase 2.7 kg; p=0.043), with an average of 4% weight gain. Patients with baseline normal and overweight BMI had significant weight gain (mean increase 5.1 kg, p=0.045; mean increase 5.5 kg, p=0.015 respectively), while those who were obese at baseline did not (mean increase 2.0 kg, p=0.302). The proportion of patients with obesity (BMI>30) increased from 37% to 53% (p=0.008). 31% of patients had >5% weight gain, with mean increase in BMI of 4.1 kg/m2 (p<0.0001) and mean weight gain of 13.1 kg (p<0.0001). 24.5% had an increase in the total number of metabolic diseases (p=0.07). Of 43 patients who were overweight or obese at last follow up, obesity was addressed in 51%, most commonly through lifestyle counseling (49%) and adjustment of hormone replacement in response to weight gain (23%). Two patients had bariatric surgery within one year of pituitary surgery. The proportion of patients with ≥3 hormone deficiencies increased from 18% to 55% (p=0.0003). At last follow-up, only one patient had GHD, diagnosed by low age-adjusted IGF-1 level. 14 of 15 patients with ≥3 hormone deficiencies had normal age-adjusted IGF-1 levels and one patient had normal GH provocative testing.Conclusion:Weight significantly increased after surgery for AOCP, with mean weight gain of 4%. 31% of patients had a marked increase in BMI and weight, suggesting possible HO. GHD is likely under-diagnosed in AOCP, and IGF-1 may not be a sensitive tool. Obesity-directed treatment is under-utilized in this patient population.

Advances in the management of craniopharyngioma in children and adults.

BackgroundChildhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient’s quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor’s molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity.ConclusionsCraniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.

Clinical Situation, Therapy, and Follow-Up of Adult Craniopharyngioma.

Craniopharyngioma is a rare neoplastic entity of the central nervous system. Childhood-onset craniopharyngioma is the subject of frequent research whereas the information on adult-onset craniopharyngioma is scarce. The objective of this study was to examine the level of daily impairment in adult patients suffering from craniopharyngioma. Noninterventional patient registry indexed as PV4842 with the local ethics committee. The study is set in a hospitalized and ambulatory setting. 148 patients with adult-onset craniopharyngioma were recruited from 8 centers, 22 prospectively and 126 retrospectively. Mean follow-up was 31 months. No interventions performed. Complications, symptoms, body mass index (BMI), and quality of life (QoL; EORTC QLQ C30 and BN20) were recorded preoperatively and at follow-up. The hypotheses tested were generated after data collection. Complications were more frequent after transcranial than transsphenoidal approaches (31 % vs. 11%; P < 0.01). Preoperative obesity was present in 0% papillary and in 38% of all adamantinomatous craniopharyngiomas (P = 0.05), and diabetes insipidus was more frequent for papillary craniopharyngioma (36.8% vs. 16,7%; P < 0.05). Hormone deficits at follow-up were reduced in 16.9%, equal in 31.4%, and increased in 63.6% (P < 0.001). BMI increased from 28.7 ± 7.4 kg/m2 before surgery to 30.2 ± 7.4 kg/m2 at follow-up (P < 0.001). In QoL, a decrease of future uncertainty (62.5 vs. 36.8; P = 0.02) and visual disorders (38.9 vs. 12.0; P = 0.01) were observed in the prospective collective after surgery. Adult craniopharyngioma is associated with a complex sociological and psychological burden and hypothalamic dysfunction, warranting further investigation and emphasizing the need for a wider treatment approach.

Adult Craniopharyngioma: Case Series, Systematic Review, and Meta-Analysis.

The optimal therapeutic approach for adult craniopharyngioma remains controversial. Some advocate for gross total resection (GTR), while others advocate for subtotal resection followed by adjuvant radiotherapy (STR + XRT). To conduct a systematic review and meta-analysis assessing the rate of recurrence in the follow-up of 3 yr in adult craniopharyngioma stratified by extent of resection and presence of adjuvant radiotherapy. MEDLINE (1946-July 1, 2016) and EMBASE (1980-June 30, 2016) were systematically reviewed. From1975 to 2013, 33 patients were treated with initial surgical resection for adult onset craniopharyngioma at our center and were reviewed for inclusion in this study. Data from 22 patients were available for inclusion as a case series in the systematic review. Eligible studies (n = 21) were identified from the literature in addition to a case series of our institutional experience. Three groups were available for analysis: GTR, STR + XRT, and STR. The rates of recurrence were 17%, 27%, and 45%, respectively. The risk of developing recurrence was significant for GTR vs STR (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.15-0.38) and STR + XRT vs STR (OR: 0.20, 95% CI: 0.10-0.41). Risk of recurrence after GTR vs STR + XRT did not reach significance (OR: 0.63, 95% CI: 0.33-1.24, P = .18). This is the first and largest systematic review focusing on the rate of recurrence in adult craniopharyngioma. Although the rates of recurrence are favoring GTR, difference in risk of recurrence did not reach significance. This study provides guidance to clinicians and directions for future research with the need to stratify outcomes per treatment modalities.

Adult Craniopharyngioma: Case Series, Systematic Review, and Meta-analysis

Background The optimal therapeutic approach for adult craniopharyngioma remains controversial. Some advocate for gross total resection (GTR), while others advocate for subtotal resection followed by adjuvant radiotherapy (STR + XRT). Objective To conduct a systematic review and meta-analysis assessing the rate of recurrence in the follow-up of 3 yr in adult craniopharyngioma stratified by extent of resection and presence of adjuvant radiotherapy. Methods MEDLINE (1946-July 1, 2016) and EMBASE (1980-June 30, 2016) were systematically reviewed. From1975 to 2013, 33 patients were treated with initial surgical resection for adult onset craniopharyngioma at our center and were reviewed for inclusion in this study. Results Data from 22 patients were available for inclusion as a case series in the systematic review. Eligible studies (n = 21) were identified from the literature in addition to a case series of our institutional experience. Three groups were available for analysis: GTR, STR + XRT, and STR. The rates of recurrence were 17%, 27%, and 45%, respectively. The risk of developing recurrence was significant for GTR vs STR (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.15-0.38) and STR + XRT vs STR (OR: 0.20, 95% CI: 0.10-0.41). Risk of recurrence after GTR vs STR + XRT did not reach significance (OR: 0.63, 95% CI: 0.33-1.24, P = .18). Conclusion This is the first and largest systematic review focusing on the rate of recurrence in adult craniopharyngioma. Although the rates of recurrence are favoring GTR, difference in risk of recurrence did not reach significance. This study provides guidance to clinicians and directions for future research with the need to stratify outcomes per treatment modalities.

Recurrent aseptic meningitis in squamous-papillary craniopharyngioma: Case report

Background: Craniopharyngiomas are divided into two categories; adamantinomatous and squamous-papillary. Adamantinomatous craniopharyngioma, which shows often cysts and calcifications, typically occurs in childhood. On the other hand, adult onset craniopharyngioma usually presents with a squamous-papillary type, sometimes without cysts or calcifications. Aseptic meningitis is a rare complication of the adamantinomatous craniopharyngioma due to spontaneous rupture of the cyst. However, as far as we are aware, reports about aseptic meningitis in squamous-papillary craniopharyngioma are very few.