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.

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.

The implication of giant tumor size on surgical resection, oncological, and functional outcomes in craniopharyngioma.

OBJECTIVE: Implication of the tumor size on oncological and functional outcomes of craniopharyngioma is inconsistently reported. The aim of this study is to assess the postoperative outcome of giant craniopharyngiomas (> 4 cm in diameter) and to elucidate the impact of tumor size on various outcome parameters and survival. MATERIAL AND METHODS: Forty-four patients (children aged ≤ 18 years: 25; adults: 16) with giant craniopharyngioma, operated between January 2001 and December 2015, were included in this study. Various outcomes, progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Gross total resection (GTR) was achieved in 17 (39%) and subtotal resection (STR) in 27 (61%) patients. Eleven patients (25%) received radiotherapy (RT) after STR. Postoperatively, new cranial nerve and motor deficits were noted in 12 (27%) and 9 (20%) patients, respectively. Tumor recurrence following GTR and STR without adjuvant RT was diagnosed in 3 (17%), and 5 (38%) patients, respectively. Following STR with RT, one (9%) experienced recurrence. PFS at 5-, and 10- year following GTR, STR, and STR + RT was 80.8%, 45.4%, and 90%, respectively. At 5- and 10- year, OS was 86.5%, 77.9% and 100% following GTR, STR, and STR + RT, respectively. The rate of GTR was significantly lower in patients with giant tumors (39% vs. 62%; Chi-square test, p value 0.008). Postoperatively, neurological deficit (20%), hypopituitarism (95%) and hypothalamic dysfunction (26%) were significantly higher for giant craniopharyngiomas. Hazards of recurrence were not significant between giant and non-giant tumors (hazard ratio 1.86; 95% CI 0.94-3.68; p 0.07). There was no significant difference in OS between the patients with giant and non-giant tumors (log-rank test 2.1; p value 0.14). CONCLUSION: Tumor size should be considered as an important predictor of the postoperative functional outcome. Although the rate of GTR is less than that of small tumors, the recurrence rate, progression-free survival, and overall survival of the patients with giant tumor are comparable to non-giant tumors.

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.

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.

Excess mortality after craniopharyngioma treatment: are we making progress?

PURPOSE: Craniopharyngioma is associated with an increased risk of mortality even after surgical, radiotherapeutic and hormone supplementations. Previous studies using different designs showed a possible trend of decreasing mortality in recent years. This review summarises studies reporting standardised mortality ratio (SMR) after craniopharyngioma treatment, as well as the bias and confounding in these studies to plan further researches. METHODS: PubMed and Embase was searched for manuscripts published before October 2018 using medical subject heading terms ("craniopharyngioma" or "hypopituitarism" and "mortality"). RESULTS: Eight studies reported SMR after craniopharyngioma treatment, with a total of 2802 patients. The subgroup meta-analysis using random effects model was conducted to pool the SMR, which was 6.2 (95% CI 4.1-9.4) before 2010 and 2.9 (95% CI 2.2-3.8) after 2010 (subgroup test p < 0.01), respectively. Misclassification (one study) and selection bias (six studies) either inflated or deflated the result. The trend of increasing survival rate over the time was observed in studies without reporting SMR. Female patients, childhood-onset disease, hydrocephalus, tumour recurrence, body mass index and panhypopituitarism were identified as the important risk factors for excess mortality. CONCLUSIONS: Though bias and confounding existed across studies, the decreasing SMR and increasing survival rate over the time was in favour of a real signal. It is necessary to launch studies to further investigate the morality and risk factors after multidisciplinary treatment of craniopharyngioma in a hospital-based manner, using the modern statistical method to adjust for bias and confounding.

Impact of neutrophil-lymphocyte ratio on long-term outcome in patients with craniopharyngioma.

Neutrophil-lymphocyte ratio (NLR) is a poor prognostic factor in many tumors including glioblastoma multiforme (GBM), colorectal, and prostate cancer. The aim of this study was to investigate the prognostic value of preoperative NLR in patients with craniopharyngioma.Around 149 patients of craniopharyngioma surgically were treated at the Department of Neurosurgery, West China Hospital from January 2008 to December 2010, including 84 males and 65 females aged from 6 to 70 years were retrospectively reviewed, and preoperative NLR was analyzed. Overall survival (OS), progression free survival (PFS), and quality of life (QOL) were evaluated.The 5-year OS and PFS rates were 81.21% and 75.84%. Preoperative NLR was significantly correlated with OS (HR = 1.44, 95% CI 1.16-1.79, P = .001) and PFS (HR = 1.46, 95% CI 1.22-1.74, P < .001). The best cut-off value of NLR was found to be 4 based on the receiver operator characteristics (ROC) curve. Patients with NLR ≥4 had a significantly worse QOL (P = .039), lower OS rate (P = .009), and PFS rate (P < .001).Preoperative NLR may be a simple, readily available, and valid predictor of long-term outcome in craniopharyngioma. We suggest that the NLR can provide effective guidance to neurosurgeons for more information about the tumor and prognostic evaluation.

Long-term Effects of Growth Hormone Replacement Therapy in Childhood-onset Craniopharyngioma: Results of the German Craniopharyngioma Registry (HIT-Endo).

OBJECTIVE: Quality of survival, prognosis and long-term outcome are often severely impaired in childhood-onset craniopharyngioma patients (CP). Identification of risk factors for sequelae such as growth hormone (GH) deficiency is important for appropriate treatment and rehabilitation. DESIGN: In a cross-sectional study, 79 CP recruited in HIT-Endo before 2000 were analyzed according to GH substitution: a. CP never GH-treated (noGH); b. CP GH-treated only during childhood (pedGH); c. CP under GH, initiated at adulthood (adultGH); d. CP under GH during childhood and continued during adulthood (contGH). METHODS: Progression-free (PFS) and overall survival (OS), height, body mass index (BMI), psychosocial and neuropsychological status (EORTC QLQ-C30, MFI-20). RESULTS: OS and PFS rates were similar in all subgroups. ContGH and pedGH CP presented with increases in height (p=0.002; p=0.0001) during long-term follow-up when compared with baseline. In all subgroups except for pedGH, increases in BMI were observed when compared with BMI at diagnosis. For emotional functionality and physical fatigue, adultGH CP showed worse (p=0.037; p=0.034) response (mean: 61.4%; 12.5%) when compared with pedGH CP (mean: 83.5%; 7.7%). Observed differences were not related to irradiation and hypothalamic involvement. In terms of psychosocial status, no differences were observed between subgroups. CONCLUSIONS: We conclude that GH substitution was safe with regard to risk of tumor progression/relapse in CP. Growth was improved by GH, whereas the development of obesity was not influenced by GH substitution. However, early initiation of GH substitution after CP diagnosis might have beneficial effects on weight development and neuropsychological outcome.

Comparing survival outcomes of gross total resection and subtotal resection with radiotherapy for craniopharyngioma: a meta-analysis.

BACKGROUND: Recent studies suggest that subtotal resection (STR) followed by radiation therapy (RT) is an appealing alternative to gross total resection (GTR) for craniopharyngioma, but it remains controversial. We conducted a meta-analysis to determine whether GTR is superior to STR with RT for craniopharyngioma. MATERIALS AND METHODS: A systematic search was performed for articles published until October 2017 in the PubMed, Embase, and Cochrane Central databases. The endpoints of interest are overall survival and progression-free survival. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using a fixed or random-effects model. The data were analyzed using Review Manager 5.3 software. RESULTS: A total of 744 patients (seven cohort studies) were enrolled for analyses. There were no significant differences between the GTR and STR with RT groups when the authors compared the pooled HRs at the end of the follow-up period. Overall survival (pooled HR = 0.76, 95% CI: 0.46-1.25, P = 0.28) and progression-free survival (pooled HR = 1.52, 95% CI: 0.42-5.44, P = 0.52) were similar between the two groups. CONCLUSIONS: The current meta-analysis suggests that GTR and STR with RT have the similar survival outcomes for craniopharyngioma.

Clinical study on microsurgical treatment for craniopharyngioma in a single consecutive institutional series of 335 patients.

OBJECTIVES: The optimal management of craniopharyngioma is still controversial. The aim of this study is to explore microsurgical outcomes of craniopharyngioma in 335 cases. PATIENTS AND METHODS: Clinical data of 335 consecutive patients with craniopharyngioma between March 2011 and March 2017 were retrospectively analyzed. RESULTS: Gross total resection (GTR) was achieved in 265 cases (79.1%), subtotal resection (STR) was obtained in 70 cases (20.9%). The GTR rate was 81.93% in pediatric group and 78.17% in adult group respectively, no significant difference regarding the GTR rate was found in adult group compared with in pediatric group (p > 0.05). However, there was a noticeable difference in the elevated hypothalamic obesity in children group compared with in adult group after operation (p < 0.05). Multivariate analysis indicated that the tumor recurrence and surgical times played a negative role in the resection extent, the odds ratio and 95% confidence interval of the tumor recurrence and surgical times is [0.306 (0.155-0.603), (p < 0.01)] and [2.135 (1.101-4.142), (p < 0.05)] respectively. There was significant difference on panhypopituitarism between GTR and STR group (p < 0.05). However, No significant difference regarding the postoperative visual dysfunction and indepent quality of life respectively between GTR and STR group was found (p > 0.05). Additionally, there were no statistically significant differences for recurrence-free curves between GTR and STR plus adjuvant radiotherapy (p > 0.05). CONCLUSIONS: Present findings demonstrated that tumor recurrence and surgical times contribute to negative total resection for craniopharyngioma. Postoperative precise adjuvant radiotherapy was considered in selected cases if pursuit of GTR was rather dangerous under disadvantageous removal factors.

Outcome of Surgical Resection of Craniopharyngioma:Single Center 12 Years' Experience.

Background Craniopharyngiomas (CPs) are rare epithelial tumors arising from the Rathke's pouch remnant located along the path of the craniopharyngeal duct accounting for 1.2-4% of all primary intracranial brain tumors, the primary treatment of which is surgery. Objective Whether radical surgical resection or partial resection followed by radiotherapy is a topic of debate. We presented our 12 years single center experience on surgical resection of craniopharyngioma. Method This was a descriptive cross-sectional study conducted among forty-five patients who underwent transcranial resection of craniopharyngioma during a period of 12 years. Data were collected from medical record archives. Glassgow outcome score (GOS), electrolyte imbalance and visual complications were assessed as outcome measure. GOS > 3 was considered favorable while score ≤ 3 was considered unfavorable. Recurrence of tumors were analyzed. Result Out of 45 patients, 28 patients were male with male to female ration of 1.64. Mean age was 32.22±16.42 years. Supra-sellar craniopharyngioma were the most common location. Gross total resection was accomplished in 32 patients (71.1%) while subtotal resection among 13 patients (28.9%). Post-operative Diabetes Insipidus was developed among 35 patients (77.7%). Adamantinomatous craniopharyngioma was the most common histopathological type. Postoperative MRI with contrast was repeated to ascertain the completeness of resection. All patient with subtotal resection received radiotherapy. Follow up period ranged from 3 months to 8 years with mean of 4.2 years. Favorable outcome (GOS>3) was seen among 41 patients while unfavorable among 4 patients. Recurrence seen among 4 patients (8.9%). Overall mortality was 4 (8.8%). Conclusion Gross total excision of craniopharyngioma has a favorable outcome with acceptable morbidity.

Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study.

OBJECTIVE: Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma. DESIGN: Hospital-based retrospective cohort study conducted between 1987 and 2014. METHODS: We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups. RESULTS: Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality. CONCLUSIONS: Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.

Subtemporal Approach for Gross Total Resection of Retrochiasmatic Craniopharyngiomas: Our Experience on 30 Cases.

BACKGROUND: Surgical treatment of retrochiasmatic craniopharyngiomas is associated with higher rates of complications, mortality, failure of complete removal, and recurrence compared with craniopharyngiomas located elsewhere. These tumors lie behind the optic chiasm and when large can extend upward into the third ventricle and downward along the brain stem, making their adequate exposure challenging. Most of the proposed techniques either use a translamina terminalis route or require wide bony exposures. In this study, we assessed the feasibility of a subtemporal approach for achieving gross total resection of retrochiasmatic craniopharyngiomas. METHODS: Thirty patients with retrochiasmatic craniopharyngioma underwent surgery via a subtemporal approach. The technique and surgical and preoperative and postoperative endocrinologic outcomes are described in detail. RESULTS: Gross total resection was achieved in all cases. The average tumor volume was 7.59 mL. The average postsurgical observation time was 73.8 months. During this time, 3 recurrences were observed (10.7%). The perioperative mortality was 6.6%. The pituitary stalk was preserved in 13 cases. Partial preservation of the pituitary stalk did not offer any advantage in terms of pituitary function. No postoperative vision worsening or new fixed neurologic deficits were observed. Among the 22 patients with preoperative vision impairment, 18 reported a significant improvement. The most common abnormalities within the temporal lobe on the side of the exposure seen on control magnetic resonance imaging were mild temporal horn enlargement (13 cases) and T2 hyperintensity (7 cases). CONCLUSIONS: A subtemporal approach can be an attractive alternative approach to accessing retrochiasmatic craniopharyngiomas. Outcomes are comparable to those associated with other widely used and time-consuming exposures.

[Radiotherapy and radiosurgery in treatment of craniopharyngiomas]. / Luchevaia terapiia i radiokhirurgiia v lechenii kraniofaringiom.

Craniopharyngiomas are benign epithelial tumors having a dysembryogenetic origin, which are usually located in the sellar/parasellar and/or third ventricle regions. Gross total resection is the modern standard of treatment for these tumors because of a low recurrence rate. However, this surgery in some patients with craniopharyngioma often leads to the development or worsening of diencephalic disorders poorly responding to treatment. Perhaps, in these cases, subtotal or partial tumor resection or implantation of an Ommaya reservoir into the tumor cyst followed by stereotactic radiotherapy/radiosurgery may provide better functional outcomes and higher life quality in patients, with tumor growth control being reasonable (according to the published data, the mean 10-year disease-free survival is 66.9% after total tumor resection and 79.6% after combined treatment). The paper presents a review of the literature on radiological treatment of craniopharyngiomas. We discuss the issues of indications, optimal timing of radiotherapy/radiosurgery, its efficacy, and treatment outcomes in terms of complications and quality of life. Particular attention is paid to enlargement of craniopharyngioma cysts during and after radiological treatment.

Visceral adiposity index as an indicator of cardiometabolic risk in patients treated for craniopharyngioma.

PURPOSE: Craniopharyngioma is associated with metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index has been proposed as a marker of visceral adipose tissue dysfunction and of the related cardiometabolic risk. The role of the visceral adiposity index has never been explored in craniopharyngioma patients. We assessed the cardiometabolic risk on the basis of the visceral adiposity index in craniopharyngioma patients. METHODS: We evaluated data of 24 patients treated for craniopharyngioma in a single-centre. We investigated the relationship among patients' clinical and biochemical features, cardiovascular risk -assessed by the Framingham and the atherosclerotic cardiovascular disease risk scores-, visceral adiposity index and adipose tissue dysfunction severity. RESULTS: Increased visceral adiposity index was found in 8 patients (33%). Adipose tissue dysfunction resulted to be severe, moderate or mild in 5, 2 and 1 cases. Increased visceral adiposity index significantly correlated with the occurrence of metabolic syndrome (p 0.027), IRI (p 0.001), triglycerides (p < 0.001), HOMA-IR (p < 0.001) and with lower ISI-Matsuda (p 0.005) and HDL-cholesterol (p < 0.001). Higher degree of adipose tissue dysfunction associated with increased insulin resistance. No gender difference was found for visceral adiposity index, adipose tissue dysfunction severity, and cardiovascular risk scores. Patients with adulthood onset craniopharyngioma showed higher Framingham risk score (p 0.004), atherosclerotic cardiovascular disease 10-year (p < 0.001) and lifetime (p 0.018) risk scores than those with childhood onset disease. CONCLUSIONS: Visceral adiposity index is increased in one third of our patients with craniopharyngioma, even if metabolic syndrome does not occur. Increased visceral adiposity index and adipose tissue dysfunction severity correlate with insulin sensitivity parameters, do not correlate with Framingham or atherosclerotic cardiovascular disease risk scores, and are not influenced by gender and age of disease onset.

Mortality in adults with hypopituitarism: a systematic review and meta-analysis.

PURPOSE: Hypopituitarism is a rare disorder with significant morbidity. To study the evidence on the association of premature mortality and hypopituitarism. METHODS: A comprehensive search of multiple databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August, 2015. Eligible studies that evaluated patients with hypopituitarism and reported mortality estimates were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. RESULTS: We included 12 studies (published 1996-2015) that reported on 23,515 patients. Compared to the general population, hypopituitarism was associated with an overall excess mortality (weighted SMR of 1.55; 95 % CI 1.14-2.11), I 2 = 97.8 %, P = 0.000. Risk factors for increased mortality included younger age at diagnosis, female gender, diagnosis of craniopharyngioma, radiation therapy, transcranial surgery, diabetes insipidus and hypogonadism. CONCLUSION: Hypopituitarism may be associated with premature mortality in adults. Risk is particularly higher in women and those diagnosed at a younger age.

Endoscopic Endonasal Transsphenoidal Surgery, A Reliable Method for Treating Primary and Recurrent/Residual Craniopharyngiomas: Nine Years of Experience.

OBJECTIVE: Craniopharyngioma resection is one of the most challenging surgical procedures. Herein, we describe our extended endoscopic endonasal transsphenoidal surgery (EETS) technique, and the results of 9 years of use on primary and recurrent/residual craniopharyngiomas. METHODS: This study reviewed 28 EETSs in 25 patients with craniopharyngiomas between January 2006 and September 2015. The patients were divided into 2 groups, newly diagnosed patients (group A, n = 15), and patients having residual or recurrent tumors (group B, n = 10). There was no significant difference between the groups in terms of the largest tumor diameter (P = 0.495), and all patients underwent EETS. The clinical and ophthalmologic examinations, imaging studies, endocrinologic studies, and operative findings for these cases were reviewed retrospectively. RESULTS: The number of gross total resections in group A was 13/15, and 7/10 in group B. Three of the patients developed postoperative cerebrospinal fluid leakage (all in group A). There were no neurovascular or ophthalmologic complications, and no meningitis or mortality was observed. CONCLUSIONS: There has been a notable increase in the use of EETS in the treatment of craniopharyngiomas during the last decade. Despite its increased use in the treatment of primary craniopharyngiomas, its implementation for recurrent or residual craniopharyngiomas has been viewed with suspicion. In this study, the results have been presented separately for primary and recurrent/residual craniopharyngiomas, so that the results can be compared. Overall, EETS is a reliable and successful surgical treatment method for primary and recurrent/residual craniopharyngiomas.

Extended Transsphenoidal Endoscopic Endonasal Surgery of Suprasellar Craniopharyngiomas.

OBJECTIVE: The endoscopic extended transsphenoidal approach for suprasellar craniopharyngiomas may be a really alternative to the transcranial approach in many cases. The authors present their experience with this technique in 136 patients with craniopharyngiomas. METHODS: From the past 7 years 204 patients with different purely supradiaphragmatic tumors underwent removal by extended endoscopic transsphenoidal transtuberculum transplanum approach. Most of the patients (136) had craniopharyngiomas (suprasellar, intra-extraventricular). The patients were analyzed according to age, sex, tumor size, growth and tumor structure, and clinical symptoms. Twenty-five patients had undergone a previous surgery. The mean follow-up was 42 months (range, 4-120 months). The operation is always performed with the bilateral endoscopic endonasal anterior extended transsphenoidal approach. RESULTS: A gross-total removal was completed in 72%. Improvement of vision or absence of visual deterioration after operation was observed in 89% of patients; 11% had worsening vision after surgery. Endocrine dysfunction did not improve after surgery, new hypotalamopituitary dysfunction (anterior pituitary dysfunction or diabetes insipidus) or worsening of it was observed in 42.6%. Other main complications included transient new mental disorder in 11%, temporary neurological postoperative deficits in 3.7%, bacterial meningitis in 16%, cerebrospinal fluid leaks in 8.8%. The recurrence rate was 20% and the lethality was 5.8%. CONCLUSIONS: Resection of suprasellar craniopharyngiomas using the extended endoscopic approach is a more effective and less traumatic technology, able to provide resection of the tumor along with high quality of life after surgery, and relatively rare postoperative complications and mortality.

Magnetic resonance imaging as predictor of functional outcome in craniopharyngiomas.

Quality of life of craniopharyngioma patients can be severely impaired by derangement of hypothalamic function. A classification, taking into account preoperative hypothalamic damage, evaluated by magnetic resonance imaging (MRI), and correlating it with postoperative weight change is still missing in the literature. The aim of our study is to identify objective radiological criteria as preoperative prognostic factors for hypothalamic damage. Pre- and post-operative MRI and clinical data of 47 patients, treated at our Institution for craniopharyngioma, were retrospectively analyzed, based on radiological variables, identified as prognostic factor for hypothalamic involvement. Main factors associated with postoperative obesity were hypothalamic hyperintensity in T2-weighted/FLAIR imaging (p < 0.033), mammillary body involvement according to Müller classification (p < 0.020), unidentifiable pituitary stalk (p < 0.001), dislocated chiasm (p < 0.038), either not visible infundibular recess (p < 0.019) or unrecognizable supra-optic recess (p < 0.004), and retrochiasmatic tumor extension (p < 0.019). Accordingly, postoperative hypothalamic syndrome was associated with peritumoral edema in T2-weighted/FLAIR images (p < 0.003), unidentifiable hypothalamus (p < 0.024), hypothalamic compression (p < 0.006), fornix displacement (p < 0.032), and unrecognizable supra-optic recess (p < 0.031). Ultimately, variables identified as predictive factors of postoperative hypothalamic syndrome were the degree of hypothalamic involvement according to the classification described by Sainte-Rose and Puget (p < 0.002; grade 0 vs 2 p < 0.001), Van Gompel (p < 0.002; grade 0 vs 1, p < 0.027; and grade 0 vs 2, p < 0.002), and Muller (p < 0.006; grade 0 vs 1, p < 0.05; and grade 0 vs 2, p < 0.004). The identification of these predictive factors will help to define and score the preoperative hypothalamic involvement in craniopharyngioma patients.

Craniopharyngioma: long-term consequences of a chronic disease.

Childhood-onset craniopharyngiomas (CP) are rare embryonal malformations of low-grade histological malignancy. Hypothalamic involvement and/or treatment-related lesions result in impaired physical and social functionality and severe neuroendocrine sequelae. Quality of life in CP with hypothalamic involvement is impaired by severe obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and non-optimal psychosocial development. 567 CI patients have been recruited between 1998 and 2010 in the German Craniopharyngioma Registry. Only 5 of 567 patients (<1%) presented without confirmed signs of relapse/progression, visual impairment, and endocrine deficiencies during longitudinal follow-up of more than 5 years. Hypothalamic obesity in CP is associated with a severe increase in BMI during the early post-operative period. Patients with CP involving hypothalamic structures show reduced 10-years overall survival, whereas overall and progression-free survival rates are not related to the degree of surgical resection. Accordingly, gross-total resection should be avoided in cases of hypothalamic involvement to prevent further hypothalamic damage. As surgical expertise has been shown to have impact on postoperative morbidity, medical societies should establish criteria of adequate professional expertise for the treatment of CP. Based on these criteria, health authorities should organize the certification of centers of excellence authorized for treatment and care of patients with this chronic disease.