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Child's Nervous System : ChNS :... Jan 2024Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies...
INTRODUCTION
Pediatric craniopharyngioma is a complex pathology, with optimal management involving a multidisciplinary approach and thoughtful care coordination. To date, no studies have compared various treatment modalities and outcomes described in different global regions. We conducted a comprehensive systematic review to compare demographics, clinical presentation, treatment approach and outcomes of children diagnosed with craniopharyngioma globally.
METHODS
A systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms included "craniopharyngioma" and country-specific terms. Inclusion criteria included full-text studies published between 2000-2022, primarily examining pediatric patients 18-years old or younger diagnosed with craniopharyngioma, and reporting management and outcomes of interest. Data extracted included country of origin, demographical data, initial presentation and treatment modality, and outcomes. Descriptive statistics and between-group comparisons based on country of origin were performed.
RESULTS
Of 797 search results, 35 articles were included, mostly originating from high-income countries (HIC) (n = 25, 71.4%). No studies originated from low-income countries (LIC). When comparing HIC to middle-income countries (MIC), no differences in patient demographics were observed. No differences in symptomatology at initial presentation, tumor type, surgical approach or extent of surgical resection were observed. HIC patients undergoing intracystic therapy were more likely to receive bleomycin (n = 48, 85.7%), while the majority of MIC patients received interferon therapy (n = 10, 62.5%). All MIC patients undergoing radiation therapy underwent photon therapy (n = 102). No statistically significant differences were observed in postoperative complications or mean follow-up duration between HIC and MIC (78.1 ± 32.2 vs. 58.5 ± 32.1 months, p = 0.241).
CONCLUSION
Pediatric craniopharyngioma presents and is managed similarly across the globe. However, no studies originating from LICs and resource-poor regions examine presentation and management to date, representing a significant knowledge gap that must be addressed to complete the global picture of pediatric craniopharyngioma burden and management.
Topics: Humans; Child; Adolescent; Craniopharyngioma; Postoperative Complications; Immunotherapy; Pituitary Neoplasms
PubMed: 37466685
DOI: 10.1007/s00381-023-06088-8 -
Endocrine Dec 2023Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological manifestations, postoperative complications, and patient outcomes of SCTs with other non-functioning pituitary neuroendocrine tumor (NFT) and functioning corticotroph tumor (FCT) or so-called Cushing disease adenoma.
METHODS
We searched PubMed and Web of Science for data of interest. Odds ratio (OR), mean difference (MD), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model.
RESULTS
Twenty-nine studies with 985 SCTs were included in meta-analyses. In comparison to other NFTs, SCTs were more commonly associated with female gender, younger age, cavernous sinus invasion, apoplexy, and radiotherapy administration. Postoperatively, SCT patients were more likely to experience hypocortisolism, new-onset visual disturbances, and a higher risk for tumor progression than other NFTs. We did not find any significant differences between SCT type I and type II. Compared to FCTs, SCTs were more likely male, older age, and had larger tumor sizes. The prevalence of a USP8 mutation was significantly higher in FCT than in SCT.
CONCLUSION
SCT was demographically, clinicopathologically, and prognostically distinct from other NFTs and FCTs. These tumors should be considered high-risk; appropriate treatment decisions and more stringent follow-up should be tailored to improve patient outcomes.
Topics: Humans; Male; Female; Corticotrophs; Adenoma; Pituitary Neoplasms; Pituitary ACTH Hypersecretion; Prognosis; ACTH-Secreting Pituitary Adenoma
PubMed: 37462809
DOI: 10.1007/s12020-023-03449-w -
International Journal of Molecular... Jun 2023Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to... (Review)
Review
Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.
Topics: Humans; MAP Kinase Signaling System; Proto-Oncogene Proteins c-akt; Pituitary Neoplasms; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases; Mitogen-Activated Protein Kinase Kinases; Carcinogenesis
PubMed: 37446128
DOI: 10.3390/ijms241310952 -
The Lancet. Diabetes & Endocrinology Aug 2023Cyclic Cushing's syndrome is a subentity of Cushing's syndrome in which phases of biochemical hypercortisolism (peaks) are followed by spontaneous periods of... (Review)
Review
Cyclic Cushing's syndrome is a subentity of Cushing's syndrome in which phases of biochemical hypercortisolism (peaks) are followed by spontaneous periods of physiological or even hypocortisolaemic cortisol secretion (troughs). To identify common features of cyclic Cushing's syndrome, we systematically reviewed single case reports and case series in MEDLINE from database inception to Oct 10, 2022, and identified 707 articles, of which 149 articles were assessed for eligibility and 118 articles (covering 212 cases) were included in the analysis. Pituitary tumours accounted for 67% of cases of cyclic Cushing's syndrome (n=143), ectopic tumours for 17% (n=36), and adrenal tumours for 11% (n=23). Occult tumours accounted for 2% of cases (n=4), and 3% of cases were unclassified (n=6). We compared the clinical symptoms and comorbidities of patients with cyclic Cushing's syndrome with those of patients with non-cyclic Cushing's syndrome and observed no major difference. In adrenocorticotropic hormone (ACTH)-dependent cyclic Cushing's syndrome, bilateral inferior petrosal sinus sampling had a positive (ie, true pituitary) and negative (ie, true ectopic) predictive value of 100% when performed during periods of hypercortisolism, versus a positive predictive value of 73% and a negative predictive value of 86% when performed, irrespective of cortisolaemic status. Overall, 6% of patients (n=12) with cyclic Cushing's syndrome had unnecessary surgery due to misclassification. Remission rates were significantly lower and the time to remission significantly longer in patients with cyclic Cushing's syndrome compared with patients with non-cyclic Cushing's syndrome (p<0·001). Variations in biochemical test results due to unpredictable cycle duration and frequency might cause diagnostic challenges resulting in misdiagnoses and missed diagnoses.
Topics: Humans; Cushing Syndrome; Adrenocorticotropic Hormone; Petrosal Sinus Sampling; Pituitary Neoplasms; Predictive Value of Tests; Diagnosis, Differential
PubMed: 37429301
DOI: 10.1016/S2213-8587(23)00150-X -
Pituitary Aug 2023Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis.
METHODS
An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed.
RESULTS
Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301).
CONCLUSIONS
This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis.
REGISTRATION
PROSPERO CRD42022374034.
Topics: Humans; Pituitary Neoplasms; Frailty; Progression-Free Survival; Prognosis; Endoscopy; Treatment Outcome; Retrospective Studies
PubMed: 37389776
DOI: 10.1007/s11102-023-01335-2 -
Pituitary Aug 2023Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and partial surgical excision. Despite the cavernous sinus's complexity and risks, new research has improved the surgical procedure and made excision safer. This comprehensive review and single-arm meta-analysis evaluates endocrinological remission and resection rates in pituitary adenomas to determine the benefits and risks of MWCS resection.
METHODS
Databases were systematically searched for studies documenting the resection of the medial wall of the cavernous sinus. The primary outcome was endocrinological remission in patients who underwent resection of the MWCS.
RESULTS
Eight studies were included in the final analysis. The pooled proportion of endocrinological remission (ER) was 63.3%. The excision of MWCS pooled a gross total resection (GTR) proportion of 72.9%. Finally, ICA injury attained a pooled ratio of 0.5%, indicating minimal morbidity in the procedure.
CONCLUSION
The cavernous sinus was ruled out, proving the MWCS excision is safe. Limiting population selection to Knosp 3A or lower enhanced GTR frequencies and lowered recurrence, according to subgroup analyses. This meta-analysis shows that MWCS resection can be a beneficial treatment option for pituitary tumors, when there is no macroscopic medial wall invasion and careful patient selection is done, especially for GH- and ACTH-producing tumors that can cause life-threatening metabolic changes.
Topics: Humans; Pituitary Neoplasms; Cavernous Sinus; Quality of Life; Neoplasm Recurrence, Local; Adenoma; Treatment Outcome; Retrospective Studies
PubMed: 37382779
DOI: 10.1007/s11102-023-01332-5 -
Orphanet Journal of Rare Diseases Jun 2023Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting...
BACKGROUND
Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting symptoms, radiological findings, endocrine abnormalities and mortality.
AIM
To identify presenting symptoms, radiological findings, endocrinological abnormalities and predictors of mortality for PA.
METHODS
We systematically reviewed the literature to identify all case reports of PA. Data regarding presentation, mortality, radiological findings, endocrinological abnormalities and treatment was extracted.
RESULTS
We identified 488 patients from 218 articles meeting the inclusion criteria. Mortality was 5.1%, with days to presentation (OR 1.0005, 95% CI 1.0001-1.0008, p < 0.01) being the only identified independent predictor of mortality. Mortality rates have decreased over time, with cases published prior to 2000 having higher mortality rates (OR 6.92, 95% CI 2.80-17.90, p < 0.001). The most common symptom was headache (76.2%), followed by visual field defects (47.3%). Classical signs of infection were only present in 43%. The most common imaging feature on magnetic resonance imaging (MRI) was high T2 and low T1 signal of the pituitary gland with peripheral contrast enhancement. Over half (54.8%) were culture negative, with the most common bacterial organism being staphylococcus aureus (7.8%) and fungal organism being aspergillus (8.8%). The most common endocrine abnormality was hypopituitarism (41.1%), followed by diabetes insipidus (24.8%). Whilst symptoms resolved in most patients, persistent endocrine abnormalities were present in over half of patients (61.0%).
CONCLUSION
PA is associated with significant mortality, with delayed presentation increasing risk of mortality. Ongoing endocrinological abnormalities are common. Given the non-specific clinical presentation, the appearance of high T2, low T1 and peripheral contrast enhancement of the pituitary on MRI should prompt consideration of this rare disease.
Topics: Humans; Abscess; Pituitary Diseases; Hypopituitarism; Pituitary Neoplasms; Magnetic Resonance Imaging
PubMed: 37365629
DOI: 10.1186/s13023-023-02788-1 -
Journal of Neurosurgery. Pediatrics Sep 2023Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very...
OBJECTIVE
Delayed cerebral ischemia (DCI) associated with vasospasm is well described in the setting of aneurysmal subarachnoid hemorrhage (SAH). In addition, DCI is very infrequently encountered in patients who have undergone resection of a brain tumor with unclear pathophysiology. The occurrence of DCI in the pediatric population is exceedingly rare, and outcomes in this population have, to the authors' knowledge, never been systematically reviewed. Therefore, the authors present what is to their knowledge the largest series of pediatric patients with this complication and systematically reviewed the literature for individual participant data.
METHODS
The authors conducted a retrospective review of 172 sellar and suprasellar tumors in pediatric patients who underwent surgery at the Montreal Children's Hospital between 1999 and 2017 to identify cases of vasospasm occurring after tumor resection. Descriptive statistics, including patient characteristics, intraoperative and postoperative findings, and outcome status, were collected. A systematic review was also conducted using three databases (PubMed, Web of Science, Embase) to identify reported cases available in the literature of vasospasm after tumor resection in children and collect individual participant data on these patients for further analysis.
RESULTS
Six patients treated at Montreal Children's Hospital were identified, with an average age of 9.5 years (range 6-15 years). The prevalence of vasospasm after tumor resection was 3.5% (6/172). Vasospasm in all 6 patients occurred after craniotomy was performed to treat a suprasellar tumor. The average interval from surgery to symptoms was 3.25 days (range 12 hours-10 days). The most common tumor etiology was craniopharyngioma, seen in 4 cases. Extensive tumor encasement of blood vessels requiring significant operative manipulation was described in all 6 patients. A rapid decrease in serum sodium (exceeding 12 mEq/L/24 hrs or below 135 mEq/L) was seen in 4 patients. On final follow-up, 3 patients were left with significant disability, and all patients had persistent deficits. A systematic review of the literature revealed a total of 10 other patients whose characteristics and treatment were compared with those of the 6 patients treated at Montreal Children's Hospital.
CONCLUSIONS
Vasospasm after tumor resection in children and youth is likely a rare entity, with a prevalence of 3.5% in this case series. Suprasellar tumor location (particularly craniopharyngioma tumor etiology), significant encasement of blood vessels by the tumor, and postoperative hyponatremia may be predictive factors. Outcome is poor, with most patients having significant persistent neurological deficits.
Topics: Adolescent; Humans; Child; Craniopharyngioma; Subarachnoid Hemorrhage; Brain Ischemia; Brain Neoplasms; Craniotomy; Pituitary Neoplasms; Vasospasm, Intracranial
PubMed: 37327188
DOI: 10.3171/2023.3.PEDS22373 -
Neuroendocrinology 2023Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement...
INTRODUCTION
Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence.
METHODS
A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis.
RESULTS
Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors.
CONCLUSION
Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.
Topics: Humans; Cohort Studies; Craniopharyngioma; Human Growth Hormone; Neoplasm Recurrence, Local; Hormone Replacement Therapy; Pituitary Neoplasms; Growth Hormone
PubMed: 37231961
DOI: 10.1159/000531226 -
European Journal of Radiology Jul 2023Predicting the consistency of benign central nervous system (CNS) tumors prior to surgery helps to improve surgical outcomes. This review summarizes and analyzes the... (Review)
Review
PURPOSE
Predicting the consistency of benign central nervous system (CNS) tumors prior to surgery helps to improve surgical outcomes. This review summarizes and analyzes the literature on using radiomics and/or machine learning (ML) for consistency prediction.
METHOD
The Medical Literature Analysis and Retrieval System Online (MEDLINE) database was screened for studies published in English from January 1st 2000. Data was extracted according to the PRISMA guidelines and quality of the studies was assessed in compliance with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS
Eight publications were included focusing on pituitary macroadenomas (n = 5), pituitary adenomas (n = 1), and meningiomas (n = 2) using a retrospective (n = 6), prospective (n = 1), and unknown (n = 1) study design with a total of 763 patients for the consistency prediction. The studies reported an area under the curve (AUC) of 0.71-0.99 for their respective best performing model regarding the consistency prediction. Of all studies, four articles validated their models internally whereas none validated their models externally. Two articles stated making data available on request with the remaining publications lacking information with regard to data availability.
CONCLUSIONS
The research on consistency prediction of CNS tumors is still at an early stage regarding the use of radiomics and different ML techniques. Best-practice procedures regarding radiomics and ML need to be followed more rigorously to facilitate the comparison between publications and, accordingly, the possible implementation into clinical practice in the future.
Topics: Humans; Prospective Studies; Retrospective Studies; Central Nervous System; Brain Neoplasms; Pituitary Neoplasms; Machine Learning; Meningeal Neoplasms
PubMed: 37207398
DOI: 10.1016/j.ejrad.2023.110866