Galectin-3 and Estrogen Receptor Alpha as Prognostic Markers in Prolactinoma: Preliminary Results From a Pilot Study.

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.

Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004-2016.

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.

High Prevalence of Weight Gain in Childhood Brain Tumor Survivors and Its Association With Hypothalamic-Pituitary Dysfunction.

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.

Incidence, mortality, and cardiovascular diseases in pituitary adenoma in Korea: a nationwide population-based study.

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.

Craniopharyngioma in the Elderly: A Multicenter and Nationwide Study in Spain.

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.

Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study.

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 33 ±â€…11 years, female predominance (n = 154, 89.5%), majority of them with microadenoma (n = 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 SMR = 3.1, 95% confidence interval (CI) 1.9-4.8, P < 0.001. Cardiovascular disease was the main cause of death (SMR = 4.2, 1.5-9.3, P = 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HR = 5.2, IC 95% 1.8-15.4, P = 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, P = 0.02), and active CD (7.5, 3.8-17.3, P = 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.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

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.

Clinical Outcomes and Complications of Pituitary Blastoma.

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.

Identification of a multidimensional transcriptome signature predicting tumor regrowth of clinically non­functioning pituitary adenoma.

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.

Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study.

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.

Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centers.

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.

Predictive modeling for pituitary adenomas: single center experience in 501 consecutive patients.

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.

[Pituitary adenomas in elderly patients]. / Adenomas hipofisarios en pacientes añosos.

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.

Lower all-cause mortality rates in patients harboring pituitary carcinoma following the introduction of temozolomide.

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.

Adenomas hipofisarios en pacientes añosos / Pituitary adenomas in elderly patients

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.

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.

Pituitary adenomas in elderly patients

Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenomas. 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 adenomas 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 ± 38.1 months). We did not observe tumor progression in elderly patients with non-functioning adenomas 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 retrospecti vo 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.

Patterns of Care in Pediatric Craniopharyngioma: Outcomes Following Definitive Radiotherapy.

BACKGROUND/AIM: Few data are available on the utility of definitive radiation therapy (RT) for pediatric craniopharyngioma. This study sought to evaluate practice patterns and patient outcomes using the Surveillance Epidemiology and End Results database from 2004-2014. MATERIALS AND METHODS: Overall survival (OS) was compared between five treatment groups, definitive radiation therapy (RT), gross total resection (GTR), subtotal resection (STR), STR+RT, and observation/biopsy only, using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards modeling determined variables independently associated with OS. RESULTS: A total of 373 patients met the study criteria. GTR and definitive RT conferred superior OS than observation/biopsy (p=0.008 and 0.029), but were equivalent to STR+RT (p=0.350 and 0.200). GTR was associated with a higher OS than STR (p=0.027). On multivariate analysis, STR+RT, GTR, and definitive RT were associated with statistically equivalent OS (p=0.990). CONCLUSION: Definitive RT for pediatric craniopharyngioma affords similar outcomes to established modalities of therapy such as GTR and STR+RT.

A two­circRNA signature predicts tumour recurrence in clinical non­functioning pituitary adenoma.

Clinical non­functioning pituitary adenoma (NFPA) accounts for >30% of all pituitary adenomas, and the recurrence rate is notably high. The ability to predict tumour recurrence during initial surgery will aid in determining if adjunctive therapy is required to reduce recurrence. With the aim of developing a circular RNA (circRNA) signature to improve prognosis prediction in NFPA, the present study examined the circRNA expression profiles in 73 patients with NFPA from Beijing Tiantan Hospital using high­throughput RNA chip technology. The dataset was randomly separated into a training group and a test group using an R program. In the training group (n=37), a Cox proportional hazards regression model was used to analyse the genes associated with the recurrence and progression­free survival (PFS) of patients with NFPA. Meanwhile, a random survival forest algorithm, Kaplan­Meier and receiver operating characteristic curve (ROC) analyses were used to determine the multi­circRNA signature with the largest area under the ROC curve (AUROC) and verify its efficacy in the test group (n=36). In the training and test groups, the signatures of two circRNAs (hsa_circ_0000066 and hsa_circ_0069707) were specifically associated with the PFS of patients with NFPA (log­rank P<0.05). Furthermore, the two­circRNA signature had a high prediction accuracy for tumour recurrence, with an AUROC of 0.87 and 0.67 in the training and test groups, respectively; and the discriminative power of the signature was greater compared with that of age. The present study is the first to suggest a circRNA signature with a clinical application value for predicting recurrence/progression in patients with NFPA.

Postoperative use of somatostatin analogs and mortality in patients with acromegaly.

Objective To assess the effect of somatostatin analogs (SSAs) on mortality in relation to disease control of acromegaly after pituitary surgery. Design A retrospective study in two large tertiary referral centers in The Netherlands. Methods Overall, 319 patients with acromegaly in whom pituitary surgery was performed as primary therapy between January 1980 and July 2017 were included. Postoperative treatment with SSA was prescribed to 174 (55%) patients because of persistent or recurrent disease. Disease control at last visit was assessed by IGF1 standard deviation score (SDS). Adequate disease control was defined as IGF1 SDS ≤2. Univariate determinants of mortality and standardized mortality ratios (SMRs) were calculated for groups with and without SSA at any moment postoperatively and at last visit. Results In total, 27 deaths were observed. In univariate analysis, determinants of mortality were inadequate disease control (relative risk (RR): 3.41, P = 0.005), surgery by craniotomy (RR: 3.53, P = 0.013) and glucocorticoid substitution (RR: 2.11, P = 0.047). There was a strong trend toward increased mortality for patients who used SSA (RR: 2.01, P = 0.067) and/or dopamine agonists (RR: 2.54, P = 0.052) at last visit. The SMR of patients with adequate disease control who used SSA at any moment postoperatively (1.07, P = 0.785) and at last visit (1.19; P = 0.600) was not increased. Insufficiently controlled patients had a significantly raised SMR (3.92, P = 0.006). Conclusions Postoperative use of SSA is not associated with increased mortality in patients with acromegaly who attain adequate disease control. In contrast, inadequate disease control, primary surgery by craniotomy and glucocorticoid substitution are associated with increased mortality.