RESUMEN
BACKGROUND: Craniopharyngioma (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. METHODS: A 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. RESULTS: Compared 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. CONCLUSION: The 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.
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Craneofaringioma , Mediadores de Inflamación , Leptina , Neoplasias Hipofisarias , Supervivencia sin Progresión , Humanos , Craneofaringioma/metabolismo , Craneofaringioma/patología , Craneofaringioma/mortalidad , Craneofaringioma/complicaciones , Femenino , Masculino , Adulto , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/sangre , Persona de Mediana Edad , Mediadores de Inflamación/metabolismo , Leptina/sangre , Leptina/metabolismo , Pronóstico , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad Mórbida/complicaciones , Obesidad Mórbida/metabolismo , Obesidad Mórbida/mortalidad , Adulto Joven , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/sangre , Edad de Inicio , Factores de Riesgo , Relevancia Clínica , Interleucina-8RESUMEN
OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS: This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50-59, 60-69, and ≥ 70 years. RESULTS: Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50-59 years, 85.0% in those 60-69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01-1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02-1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60-0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90-18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84-0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS: Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.
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Adenoma , Neoplasias Hipofisarias , Supervivencia sin Progresión , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/patología , Femenino , Anciano , Estudios Retrospectivos , Factores de Edad , Adenoma/cirugía , Adenoma/patología , Adenoma/mortalidad , Adulto , Resultado del Tratamiento , Estudios de Seguimiento , Anciano de 80 o más Años , Procedimientos Neuroquirúrgicos/métodos , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Patients with non-functioning pituitary adenoma (NFPA) often present with a variety of clinical manifestations and comorbidities, mainly determined by the local mass effect of the tumor and by hypopituitarism. Whether this has an impact on overall mortality, however, is still unclear. METHODS: PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until May 2023 for studies reporting data either about standardized mortality ratios (SMRs) or about predictors of mortality in patients with NFPA. Effect sizes were pooled through a random-effect model. This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, #CRD42023417782). RESULTS: Eleven studies were eligible for inclusion in the systematic review; among these, five studies reported data on SMRs, with a total follow-up time of approximately 130,000 person-years. Patients with NFPA showed an increased mortality risk compared to the general population (SMR = 1.57 [95%CI: 1.20-1.99], p < 0.01). Age and sex appeared to act as effect modifiers, with a trend towards higher SMRs in females (SMR = 1.57 [95%CI: 0.91-2.41], p = 0.10) than in males (SMR = 1.00 [95%CI: 0.89-1.11], p = 0.97), and in patients diagnosed at age 40 years or younger (SMR = 3.19 [95%CI: 2.50-3.97], p < 0.01) compared to those with later onset of the disease (SMR = 1.26 [95%CI: 0.93-1.65], p = 0.13). The trend towards excess mortality was similar in patients with normal (SMR = 1.22 [95%CI: 0.94-1.53], p = 0.13) or deficient (SMR = 1.26 [95%CI: 0.82-1.79], p = 0.27) pituitary function. CONCLUSIONS: Excess mortality is observed in patients with NFPA, regardless of pituitary function, especially in women and in patients with a younger age at diagnosis.
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/mortalidad , Adenoma/mortalidadRESUMEN
PURPOSE: Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs. METHODS AND MATERIALS: Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible. Late toxicities were analyzed according to the grading system of the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Median follow-up since first diagnosis was 4.3 years (range, 0.8-14.7). In addition, 75.7% of patients received PBT at time of disease progression or recurrence, whereas 24.3% as part of their primary therapy (definitive or adjuvant). Predominantly (85.1%), pencil beam scanning technique was used. The median total dose and initial tumor volume were 5400 cGy relative biologic effectiveness (RBE) and 17.64 cm³ (range, 3.07-300.59), respectively. The estimated (±SE) 3-year overall survival, progression-free, and cystic failure-free survival rate after PBT were 98.2% (±1.7), 94.7% (±3.0), and 76.8% (±5.4), respectively. All local failures (n = 3) were in-field relapses necessitating intervention and occurred exclusively in patients receiving PBT at progression or recurrence. Early cystic enlargements after PBT were typically asymptomatic and self-limiting. Fatigue, headaches, vision disorders, obesity, and endocrinopathies were the predominant late toxicities. No high-grade (≥3) new-onset visual impairment or cognitive deterioration occurred compared with baseline. The presence of cognitive impairments at the end of follow-up correlated with size of the planning target volume (P = .034), Dmean dose to the temporal lobes (P = .032, P = .045) and the number of surgical interventions before PBT (P = .029). CONCLUSIONS: Our findings demonstrate favorable local control rates using modern PBT with acceptable late toxicities. Cyst growth within 12 months after radiation therapy is typically not associated with tumor progression. Longer follow-up must be awaited to confirm results.
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Craneofaringioma , Neoplasias Hipofisarias , Terapia de Protones , Sistema de Registros , Humanos , Craneofaringioma/radioterapia , Craneofaringioma/mortalidad , Terapia de Protones/efectos adversos , Niño , Masculino , Femenino , Estudios Prospectivos , Preescolar , Adolescente , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/mortalidad , Resultado del Tratamiento , Carga Tumoral , Recurrencia Local de Neoplasia , Dosificación Radioterapéutica , Lactante , Efectividad Biológica RelativaRESUMEN
CONTEXT: Prolactin (PRL) is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data have outlined the potential prognostic value of PRL in various clinical settings. OBJECTIVE: This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum PRL levels and risk of mortality in adults without prolactinoma. METHODS: A systematic literature search was conducted up to June 10, 2023, to identify studies reporting the association of serum PRL levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death (CVD) during follow-up. RESULTS: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum PRL levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23 596 individuals. Each unit of PRL increase was independently associated with increased risk of all-cause (pooled aHR = 1.17 [1.08-1.27]; I2 = 48%) and CV mortality (pooled aHR = 1.54 [1.14-2.09]; I2 = 89%). Individuals belonging to the highest PRL category had significantly higher risk for all-cause (pooled aHR = 1.81 [1.43-2.30]; I2 = 65%) and CV (pooled aHR = 1.59 [1.04-2.42]; I2 = 82%) mortality compared to their lowest-PRL category counterparts. The association between PRL levels and in-hospital death did not reach statistical significance. CONCLUSION: PRL levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk-stratification tool can be delineated in clinical practice.
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Prolactina , Humanos , Prolactina/sangre , Adulto , Prolactinoma/sangre , Prolactinoma/mortalidad , Pronóstico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Mortalidad , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/mortalidadRESUMEN
Introduction: Prolactin-secreting pituitary tumors (PRL-omas) are generally benign neoplasia. However, a percentage of cases show aggressive behavior. Prognostic markers may allow for the identification of aggressive cases. In this study, we investigated the prognostic role of galectin-3 and the estrogen receptor alpha (ERα), as predictive biomarkers of aggressiveness and poor prognosis. Patients and Methods: A mono-centric and retrospective study was conducted on consecutive cases of PRL-omas that underwent first line treatment with surgery and were followed-up for at least five years. The immunohistochemical expression of ERα and galectin-3 was investigated in each case. Results: 36 patients were enrolled. Galectin-3 resulted positive in 11 patients (30.6%). The median expression of ERα was 85% (IQR: 37). Among the group of 21 patients who underwent radical surgery (58.3%), recurrence occurred in 12 cases (33.3%). 27 patients were treated post-surgery with a dopamine agonist (DA) (12 for recurrence and 22 for a history of partial surgery). 13 patients (48.1%) were responsive to DA. Six of 11 cases positive for galactin-3 underwent partial surgery (54.5%, p<0.001). Recurrence occurred in all five cases that underwent radical surgery, which were also positive for galectin-3 (p=0.03). Galectin-3 resulted positive in 9 patients resistant to DA treatment (81.1%, p=0.01). ERα expression was lower in tumors positive for galectin-3 (p<0.001), with mitotic activity (p=0.012), with higher Ki67 Li (p<0.001), and in males with post-surgical recurrence (p<0.001). Conclusion: Galectin-3 and ERα play as markers of aggressiveness and prognosis in PRL-omas and may be tested to identify the aggressive forms of the disease.
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Biomarcadores de Tumor/metabolismo , Proteínas Sanguíneas/metabolismo , Receptor alfa de Estrógeno/metabolismo , Galectinas/metabolismo , Neoplasias Hipofisarias/metabolismo , Prolactinoma/metabolismo , Adulto , Agonistas de Dopamina/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia , Proyectos Piloto , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapia , Pronóstico , Prolactinoma/mortalidad , Prolactinoma/patología , Prolactinoma/terapia , Estudios RetrospectivosRESUMEN
Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Extensive clinical and demographic characteristics were extracted and submitted to group comparisons. The standardized incidence rate was calculated and stratified by year at diagnosis, age/sex and age/treatment groups. The Kaplan-Meier analysis and multivariable regressions were performed to identify the factors associated with overall survival. A total of 47,180 pituitary tumors were identified, including 47,030 typical adenomas, 111 uncertain behavior pituitary adenomas, and 39 pituitary carcinomas. The overall standardized incidence rate was 4.8 cases per 100,000 person-years and the annual incidence rate continually trended upwards, with a peak seen in 2015. We noticed a bimodal age-related distribution in females and a unimodal distribution in males. In the multivariate regression analysis, the factors associated with prolonged survival included typical adenoma, younger age, and smaller tumor size. Whereas, black and male patients had worse overall survival. Our study provides a reliable estimate on the incidence of pituitary adenoma and confirms that the annual standardized incidence rate is increasing. Pituitary adenomas have a satisfactory long-term prognosis and age, tumor size, and tumor subtypes are related to overall survival. Though statistically significant, our inferential findings should be constrained within the limitations of SEER database.
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Adenoma/epidemiología , Neoplasias Hipofisarias/epidemiología , Adenoma/mortalidad , Adolescente , Adulto , Factores de Edad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Hipofisarias/mortalidad , Programa de VERF , Factores Sexuales , Adulto JovenRESUMEN
PURPOSE: Childhood brain tumor survivors (CBTS) are at risk for developing obesity, which negatively influences cardiometabolic health. The prevalence of obesity in CBTS may have been overestimated in previous cohorts because of inclusion of children with craniopharyngioma. On the contrary, the degree of weight gain may have been underestimated because of exclusion of CBTS who experienced weight gain, but were neither overweight nor obese. Weight gain may be an indicator of underlying hypothalamic-pituitary (HP) dysfunction. We aimed to study prevalence of and risk factors for significant weight gain, overweight, or obesity, and its association with HP dysfunction in a national cohort of noncraniopharyngioma and nonpituitary CBTS. METHODS: Prevalence of and risk factors for significant weight gain (body mass index [BMI] change ≥ +2.0 standard deviation score [SDS]), overweight, or obesity at follow-up, and its association with HP dysfunction were studied in a nationwide cohort of CBTS, diagnosed in a 10-year period (2002-2012), excluding all craniopharyngioma and pituitary tumors. RESULTS: Of 661 CBTS, with a median age at follow-up of 7.3 years, 33.1% had significant weight gain, overweight, or obesity. Of the CBTS between 4 and 20 years of age, 28.7% were overweight or obese, compared with 13.2% of the general population between 4 and 20 years of age. BMI SDS at diagnosis, diagnosis of low-grade glioma, diabetes insipidus, and central precocious puberty were associated with weight gain, overweight, or obesity. The prevalence of HP dysfunction was higher in overweight and obese CTBS compared with normal-weight CBTS. CONCLUSION: Overweight, obesity, and significant weight gain are prevalent in CBTS. An increase in BMI during follow-up may be a reflection of HP dysfunction, necessitating more intense endocrine surveillance.
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Neoplasias Encefálicas/complicaciones , Enfermedades Hipotalámicas/complicaciones , Neoplasias Hipofisarias/complicaciones , Aumento de Peso/genética , Adolescente , Adulto , Neoplasias Encefálicas/mortalidad , Niño , Preescolar , Femenino , Humanos , Enfermedades Hipotalámicas/mortalidad , Masculino , Neoplasias Hipofisarias/mortalidad , Prevalencia , Factores de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
CONTEXT: Cushing's disease (CD) is a life-threating disease, with increased mortality in comparison with the general population. OBJECTIVE: This study aimed to evaluate standardized mortality ratios (SMRs) in CD patients. We also analyzed independent risk factors related to increased mortality. DESIGN: We conducted a longitudinal cohort study in a 3rd level specialty center, from 1979 to 2018, in patients with CD. RESULTS: From 1375 cases with a pathology diagnosis of pituitary adenoma, 191 cases had the confirmed diagnosis of CD (14%). A total of 172 patients completed follow-up, with a mean age at diagnosis of 33â ±â 11 years, female predominance (nâ =â 154, 89.5%), majority of them with microadenoma (nâ =â 136, 79%), and a median follow-up of 7.5 years (2.4-15). Eighteen patients (10.5%) died, 8 of them (44%) were with active CD, 8 (44%) were under remission, and 2 (11%) were under disease control. Estimated all-cause SMRâ =â 3.1, 95% confidence interval (CI) 1.9-4.8, Pâ <â 0.001. Cardiovascular disease was the main cause of death (SMRâ =â 4.2, 1.5-9.3, Pâ =â 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HRâ =â 5.2, IC 95% 1.8-15.4, Pâ =â 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, Pâ =â 0.02), and active CD (7.5, 3.8-17.3, Pâ =â 0.003) significantly increased the risk of mortality. CONCLUSIONS: Main cause of CD mortality was cardiovascular disease. Main risk factors for mortality were uncontrolled diabetes, persistently high cortisol levels after 1600 hours at diagnosis, and active disease at last follow-up.
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Hidrocortisona/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/mortalidad , Adenoma/sangre , Adenoma/complicaciones , Adenoma/diagnóstico , Adenoma/mortalidad , Adulto , Ritmo Circadiano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Estudios Longitudinales , Masculino , México/epidemiología , Persona de Mediana Edad , Mortalidad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/etiología , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/mortalidad , Pronóstico , Adulto JovenRESUMEN
PURPOSE: Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. METHODS: This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3 years (range: 0-10 years). Cox regression analysis was used to evaluate the associations between CVD and mortality. RESULTS: The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. CONCLUSION: South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.
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Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Hipopituitarismo/epidemiología , Hipopituitarismo/mortalidad , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/mortalidad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Craniopharyngioma (CP) is a rare tumor in the elderly whose clinical features and prognosis are not well known in this population. AIM: To evaluate the clinicopathological features and therapeutic outcomes of CP diagnosed in the elderly. PATIENTS AND METHODS: This was a retrospective, multicenter, national study of CP patients diagnosed over the age of 65 years and surgically treated. RESULTS: From a total of 384 adult CP patients, we selected 53 (13.8%) patients (27 women [50.9%], mean age 72.3 ± 5.1 years [range 65-83 years]) diagnosed after the age of 65 years. The most common clinical symptoms were visual field defects (71.2%) followed by headache (45.3%). The maximum tumor diameter was 2.9 ± 1.1 cm. In most patients, the tumor was suprasellar (96.2%) and mixed (solid-cystic) (58.5%). The surgical approach most commonly used was transcranial surgery (52.8%), and more than half of the patients (54.7%) underwent subtotal resection (STR). Adamantinomatous CP and papillary CP were present in 51 and 45.1%, respectively, with mixed forms in the remaining. Surgery was accompanied by an improvement in visual field defects and in headaches; however, pituitary hormonal hypofunction increased, mainly at the expense of an increase in the prevalence of diabetes insipidus (DI) (from 3.9 to 69.2%). Near-total resection (NTR) was associated with a higher prevalence of DI compared with subtotal resection (87.5 vs. 53.6%, p = 0.008). Patients were followed for 46.7 ± 40.8 months. The mortality rate was 39.6% with a median survival time of 88 (95% CI: 57-118) months. DI at last visit was associated with a lower survival. CONCLUSION: CP diagnosed in the elderly shows a similar distribution by sex and histologic forms than that diagnosed at younger ages. At presentation, visual field alterations and headaches are the main clinical symptoms which improve substantially with surgery. However, surgery, mainly NTR, is accompanied by worsening of pituitary function, especially DI, which seems to be a predictor of mortality in this population.
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Envejecimiento , Craneofaringioma , Neoplasias Hipofisarias , Anciano , Anciano de 80 o más Años , Craneofaringioma/diagnóstico , Craneofaringioma/mortalidad , Craneofaringioma/patología , Craneofaringioma/terapia , Femenino , Humanos , Masculino , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/mortalidad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapia , Estudios Retrospectivos , España/epidemiologíaRESUMEN
Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.
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Craneofaringioma/diagnóstico , Craneofaringioma/genética , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/genética , Proteínas Proto-Oncogénicas B-raf/genética , beta Catenina/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Craneofaringioma/mortalidad , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Hipofisarias/mortalidad , Pronóstico , España , Tasa de Supervivencia , Adulto JovenRESUMEN
CONTEXT: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. OBJECTIVE: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases. DESIGN AND SETTING: A multi-institutional case series is presented from tertiary pediatric oncology centers. PATIENTS: Patients included children with pituitary blastoma. INTERVENTIONS: Genetic testing, surgery, oncologic therapy, endocrine support are reported. OUTCOME MEASURES: Outcome measures included survival, long-term morbidities, and germline and tumor DICER1 genotypes. RESULTS: Seventeen pituitary blastoma cases were studied (10 girls and 7 boys); median age at diagnosis was 11 months (range, 2-24 months). Cushing syndrome was the most frequent presentation (n = 10). Cushingoid stigmata were absent in 7 children (2 with increased adrenocorticotropin [ACTH]; 5 with normal/unmeasured ACTH). Ophthalmoplegia and increased intracranial pressure were also observed. Surgical procedures included gross/near-total resection (n = 7), subtotal resection (n = 9), and biopsy (n = 1). Six children received adjuvant therapy. At a median follow-up of 6.7 years, 9 patients were alive; 8 patients died of the following causes: early medical/surgical complications (n = 3), sepsis (n = 1), catheter-related complication (n = 1), aneurysmal bleeding (n = 1), second brain tumor (n = 1), and progression (n = 1). Surgery was the only intervention for 5 of 9 survivors. Extent of resection, but neither Ki67 labeling index nor adjuvant therapy, was significantly associated with survival. Chronic complications included neuroendocrine (n = 8), visual (n = 4), and neurodevelopmental (n = 3) deficits. Sixteen pituitary blastomas were attributed to DICER1 abnormalities. CONCLUSIONS: Pituitary blastoma is a locally destructive tumor associated with high mortality. Surgical resection alone provides long-term disease control for some patients. Quality survival is possible with long-term neuroendocrine management.
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Crisis Blástica/mortalidad , ARN Helicasas DEAD-box/genética , Mutación de Línea Germinal , Neoplasias Hipofisarias/mortalidad , Complicaciones Posoperatorias/mortalidad , Ribonucleasa III/genética , Crisis Blástica/patología , Crisis Blástica/cirugía , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Clinically nonfunctioning pituitary adenoma (NFPA) represents approximately one third of all pituitary adenomas. Tumor regrowth is an important feature of NFPA; however, the effective methods with which to predict this are limited. The present study analyzed the expression of proteincoding genes and long noncoding RNA in 66 patients with NFPA. Cox regression analysis was performed to identify genes associated with regrowth or progressionfree survival (PFS). KaplanMeier, random survival forest analysis and receiver operating characteristic curve (ROC) analyses were performed to generate a multiproteincoding gene (PCG) and long noncoding RNA (lncRNA) signature with a maximum area under the ROC curve (AUC). In total, 1 PCG (CHST12) and 2 lncRNAs (COA6AS1 and RP1123N2.4) were identified that were significantly associated with tumor regrowth. The multitranscriptome signature exhibited a high predictive accuracy for tumor regrowth, with an AUC of 0.869/0.726 in the training/testing set, and the discriminative power of this signature was better than that of age. On the whole, the present study indicates that the combined PCG and lncRNA signature may be beneficial as a marker for the prediction of the prognosis of patients with NFPA.
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Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , ARN Largo no Codificante/genética , Adulto , Factores de Edad , Anciano , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/mortalidad , Pronóstico , Curva ROC , Sulfotransferasas/genética , TranscriptomaRESUMEN
BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.
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Craneofaringioma/mortalidad , Neoplasias Hipofisarias/mortalidad , Terapia de Protones/mortalidad , Radioterapia Conformacional/mortalidad , Adulto , Craneofaringioma/patología , Craneofaringioma/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/radioterapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
PURPOSE: The 2017 World Health Organization classification of pituitary tumors redefined pituitary null cell adenomas (NCAs) by restricting this diagnostic category to pituitary tumors that are negative for pituitary transcription factors and adenohypophyseal hormones. The clinical behavior of this redefined entity has not been widely studied, and this is a major shortcoming of the classification. This study evaluated the imaging and clinical features of NCAs from two pituitary centers and compared them with those of gonadotroph adenomas (GAs). METHODS: Imaging, pathologic, and clinical characteristics of NCAs and GAs were retrospectively reviewed. Tumor immunohistochemistry was performed to confirm absence of adenohypophyseal hormones and pituitary transcription factor expression. RESULTS: Thirty-one NCAs were compared with 38 GAs. NCAs were more likely to invade the cavernous sinus (15/31 [48%] vs. 5/38 [13%], P = .003) and had a higher proliferative index (i.e., MIB-1 > 3%, 11/31 [35%] vs. 5/38 [13%], P = .04). Gross total resection was less likely in the NCA group (19/31 [61%] vs. 33/38 [87], P = .02). Progression-free survival was worse in the NCA cohort (5-year progression-free survival, 0.70 vs. 1.00; P = .011, by log-rank test). CONCLUSIONS: Compared with GAs, NCAs are more invasive at the time of presentation and have a more aggressive clinical course. This study provides evidence that NCAs represent a distinct clinicopathologic entity with behavior that differs adversely from that of GAs. This may inform clinical decision-making, including frequency of postoperative tumor surveillance and timing of adjunctive treatments.
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Hipófisis/diagnóstico por imagen , Hipófisis/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfocitos Nulos/patología , Masculino , Enfermedades de la Hipófisis/diagnóstico por imagen , Enfermedades de la Hipófisis/mortalidad , Enfermedades de la Hipófisis/patología , Neoplasias Hipofisarias/mortalidad , Supervivencia sin Progresión , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
BACKGROUND: Personalized postoperative management of patients with pituitary adenomas requires an early risk stratification system. METHODS: We reviewed 501 cases operated between 10/27/2011 and 5/5/2016 by a single neurosurgeon. We determined biochemical remission and tumor resection at 3 months, and biochemical recurrence, tumor recurrence, radiation and reoperation during follow-up. We considered age, gender, tumor diameter, cavernous sinus invasion (CSI) by MRI, diagnostic category (clinical, biochemical and immunohistochemical), and proliferation markers in a Cox proportional hazards model. We built predictive models with the significant parameters and used Kaplan-Meier survival curves for time-dependent analyses. RESULTS: The 501 cases comprised 141 functional and 360 nonfunctional adenomas. Tumor diameter, CSI, and ki-67 index predicted long-term events. Model 1 (CSI, diameter ≥ 2.9 cm and ki-67 > 3%) identified 18 (3.6%) adenomas and predicted persistent hypersecretory syndrome and residual tumor with 98.7% specificity (OR 8.6; CI 3.0-24.7). Model 2 (ki-67 > 3% and CSI) identified 48 (9.6%) adenomas and had 93.1% specificity (OR 3.3; CI 1.8-6.0). Model 3 (ki-67 > 3%, mitoses and p53, former "atypical" adenoma) identified 26 (5.2%) adenomas and had 96.0% specificity (OR 2.3; CI 1.0-5.0). Model 1 best predicted the long-term event-free survival and was strengthened when Knosp 3-4 CSI grades were used. Model 2 better identified the smaller adenomas at risk. Among the WHO 2017 special PA subtypes, patients with silent corticotroph adenoma had a lower event-free survival than ACTH-negative nonfunctional adenomas. CONCLUSION: Use of CSI, ki-67 and tumor diameter in prediction models facilitates tailored surveillance and management of patients with pituitary adenomas.
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Adenoma/cirugía , Neoplasias Hipofisarias/cirugía , Adenoma/mortalidad , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias/mortalidad , Modelos de Riesgos ProporcionalesRESUMEN
Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.
Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.
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Adenoma/terapia , Neoplasias Hipofisarias/terapia , Adenoma/diagnóstico , Adenoma/mortalidad , Adenoma/cirugía , Anciano , Anciano de 80 o más Años , Causas de Muerte , Estudios Transversales , Femenino , Humanos , Masculino , Hormonas Hipofisarias , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/mortalidad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the impact of temozolomide (TMZ) introduction on the survival of patients with pituitary carcinoma (PC) compared to aggressive pituitary adenoma (APA). METHODS: Retrospective analysis of the Surveillance Epidemiology and End-Results database (SEER), including patients diagnosed with PC or APA between 1973 and 2015. Age-adjusted Kaplan-Meier analyses were performed, comparing all-cause mortality (ACM) rates before the year 2006, the time of TMZ introduction ("period 1"), and afterwards ("period 2"), in patients harboring PC and APA. RESULTS: Among 107 patients, 18 (16.8%) harbored PC. The prevalence of PC and APA was comparable between genders, ethnicities and age strata. Patients harboring any pituitary tumor (PC or APA) had comparable risk for ACM and disease-specific mortality between the two time periods. However, among patients harboring PC, the risk for ACM was significantly lower in period 2 vs. period 1 (p = 0.021), becoming comparable to the risk of ACM in patients diagnosed with APA (p = 0.48). CONCLUSIONS: In this large cancer-database-based analysis we observed improved overall survival in patients harboring PC in the years following the introduction of TMZ.