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BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
World Journal of Surgical Oncology May 2024Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients,... (Meta-Analysis)
Meta-Analysis Review
Endoscopic endonasal transsphenoidal approach improves endocrine function and surgical outcome in primary craniopharyngioma resection: a systematic review and meta-analysis.
BACKGROUND
Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs.
OBJECT AND METHOD
We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management.
RESULT
Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21-22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31-0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12-0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06-0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24-9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26-0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51-0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24-0.42, p < 0.001).
CONCLUSION
Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.
Topics: Humans; Craniopharyngioma; Pituitary Neoplasms; Postoperative Complications; Prognosis; Treatment Outcome; Neoplasm Recurrence, Local; Endoscopy
PubMed: 38790064
DOI: 10.1186/s12957-024-03411-8 -
BMC Cancer May 2024Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs.
MATERIALS AND METHODS
The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.
RESULTS
According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level.
CONCLUSION
In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
Topics: Humans; Brachytherapy; Craniopharyngioma; Follow-Up Studies; Pituitary Neoplasms; Treatment Outcome; Progression-Free Survival
PubMed: 38790011
DOI: 10.1186/s12885-024-12397-1 -
BMC Surgery May 2024The endoscopic endonasal transsphenoidal approach (EETA) has revolutionized skull-base surgery; however, it is associated with a steep learning curve (LC), necessitating...
BACKGROUND
The endoscopic endonasal transsphenoidal approach (EETA) has revolutionized skull-base surgery; however, it is associated with a steep learning curve (LC), necessitating additional attention from surgeons to ensure patient safety and surgical efficacy. The current literature is constrained by the small sample sizes of studies and their observational nature. This systematic review aims to evaluate the literature and identify strengths and weaknesses related to the assessment of EETA-LC.
METHODS
A systematic review was conducted following the PRISMA guidelines. PubMed and Google Scholar were searched for clinical studies on EETA-LC using detailed search strategies, including pertinent keywords and Medical Subject Headings. The selection criteria included studies comparing the outcomes of skull-base surgeries involving pure EETA in the early and late stages of surgeons' experience, studies that assessed the learning curve of at least one surgical parameter, and articles published in English.
RESULTS
The systematic review identified 34 studies encompassing 5,648 patients published between 2002 and 2022, focusing on the EETA learning curve. Most studies were retrospective cohort designs (88%). Various patient assortment methods were noted, including group-based and case-based analyses. Statistical analyses included descriptive and comparative methods, along with regression analyses and curve modeling techniques. Pituitary adenoma (PA) being the most studied pathology (82%). Among the evaluated variables, improvements in outcomes across variables like EC, OT, postoperative CSF leak, and GTR. Overcoming the initial EETA learning curve was associated with sustained outcome improvements, with a median estimated case requirement of 32, ranging from 9 to 120 cases. These findings underscore the complexity of EETA-LC assessment and the importance of sustained outcome improvement as a marker of proficiency.
CONCLUSIONS
The review highlights the complexity of assessing the learning curve in EETA and underscores the need for standardized reporting and prospective studies to enhance the reliability of findings and guide clinical practice effectively.
Topics: Humans; Learning Curve; Skull Base; Endoscopy; Pituitary Neoplasms; Neurosurgical Procedures
PubMed: 38705991
DOI: 10.1186/s12893-024-02418-y -
Pituitary Jun 2024Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of...
BACKGROUND
Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma.
METHODS
A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria.
RESULTS
A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery.
CONCLUSION
Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma.
Topics: Prolactinoma; Humans; Quality of Life; Pituitary Neoplasms; Dopamine Agonists
PubMed: 38656635
DOI: 10.1007/s11102-024-01392-1 -
Turkish Neurosurgery 2024To investigate the possible relationship between intracranial aneurysms and brain neoplasms.
AIM
To investigate the possible relationship between intracranial aneurysms and brain neoplasms.
MATERIAL AND METHODS
A comprehensive literature review involving a search of the databases PubMed and Embase to identify relevant articles was conducted in March 2021. The initial search retrieved 451 articles. After deduplication and screening of abstracts, 56 articles were selected. After reading of the full texts, 19 articles were included in the review.
RESULTS
There insufficient evidence to support that people with brain neoplasms have a higher incidence rate of IAs. However, the prevalence of IAs appears to be higher in patients with pituitary tumors than in the general population. The key factors affecting prognosis were tumor type in patients with unruptured aneurysms and progression of subarachnoid hemorrhage in individuals with ruptured aneurysms. Treatment should be individualized according to patient age, tumor pathology, location, and aneurysm rupture risk.
CONCLUSION
There is a lack of evidence to affirm that the existence of brain neoplasm plays a role in the formation and rupture of intracranial aneurysms. Additionally, there is insufficient evidence to confirm a greater prevalence of intracranial aneurysms in individuals with brain tumors. The association of these two disorders does not appear to worsen patient outcome. Prognosis depends on tumor pathology for malignant cases and on subarachnoid hemorrhage in patients with ruptured aneurysms.
Topics: Humans; Intracranial Aneurysm; Brain Neoplasms; Aneurysm, Ruptured; Subarachnoid Hemorrhage; Prognosis; Prevalence; Risk Factors
PubMed: 38650567
DOI: 10.5137/1019-5149.JTN.43614-23.4 -
Frontiers in Endocrinology 2024Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical...
OBJECTIVE
Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure.
METHODS
Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission.
RESULTS
Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients.
CONCLUSIONS
The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.
Topics: Adult; Female; Humans; Male; Middle Aged; Acromegaly; Adenoma; Cushing Syndrome; Pituitary ACTH Hypersecretion; Pituitary Neoplasms
PubMed: 38628582
DOI: 10.3389/fendo.2024.1373869 -
Medical Sciences (Basel, Switzerland) Mar 2024Pituitary adenomas are benign brain tumors that impose a heavy burden on patients worldwide. The local burden of disease is yet to be established due to scarcity of... (Review)
Review
BACKGROUND
Pituitary adenomas are benign brain tumors that impose a heavy burden on patients worldwide. The local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines.
METHODS
A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted.
RESULTS
The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications, and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines.
CONCLUSION
There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.
Topics: Humans; Pituitary Neoplasms; Philippines; Adenoma; Brain Neoplasms; Government
PubMed: 38535157
DOI: 10.3390/medsci12010016 -
Medicina (Kaunas, Lithuania) Feb 2024Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and... (Review)
Review
Skull base reconstruction is a crucial step during transsphenoidal surgery. Sphenoid mucosa is a mucosal membrane located in the sphenoid sinus. Preservation and lateral shifting of sphenoid mucosa as sphenoid mucosal flap (SMF) during the transsphenoidal exposure of the sella may be important for later closure. This is the first systematic review to evaluate the utility of sphenoid mucosal flap for sellar reconstruction after transsphenoidal surgery. A systematic literature search was performed in January 2023: Cochrane, EMBASE, PubMed, Scopus, and Web of Science. The following keywords and their combinations were used: "sphenoid mucosa", "sphenoid sinus mucosa", "sphenoid mucosal flap", "sphenoid sinus mucosal flap". From a total number of 749 records, 10 articles involving 1671 patients were included in our systematic review. Sphenoid sinus mucosa used to be applied for sellar reconstruction as either a vascularized pedicled flap or as a free flap. Three different types of mucosal flaps, an intersinus septal flap, a superiorly based flap and an inferiorly based flap, were described in the literature. Total SMF covering compared to partial or no SMF covering in sellar floor reconstruction resulted in fewer postoperative CSF leaks ( = 0.008) and a shorter duration of the postoperative lumbar drain ( = 0.003), if applied. Total or partial SMF resulted in fewer local complications ( = 0.012), such as fat graft necrosis, bone graft necrosis, sinusitis or fungal infection, in contrast to no SMF implementation. SMF seems to be an effective technique for skull base reconstruction after transsphenoidal surgery, as it can reduce the usage of avascular grafts such as fat along with the incidence of local complications, such as fat graft necrosis, bone graft necrosis, sinusitis and fungal infection, or it may improve the sinonasal quality of life by maintaining favorable wound healing through vascular flap and promote the normalization of the sphenoid sinus posterior wall. Further clinical studies evaluating sphenoid mucosal flap preservation and application in combination with other techniques, particularly for higher-grade CSF leaks, are required.
Topics: Humans; Plastic Surgery Procedures; Sphenoid Sinus; Quality of Life; Pituitary Neoplasms; Postoperative Complications; Surgical Flaps; Sinusitis; Necrosis; Osteonecrosis; Mycoses; Retrospective Studies
PubMed: 38399569
DOI: 10.3390/medicina60020282 -
Journal of Neuro-oncology Mar 2024Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional... (Review)
Review
BACKGROUND
Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment.
METHODS
A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed.
RESULTS
Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported.
CONCLUSIONS
This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-CRD42016036802.
Topics: Child; Humans; Young Adult; Proton Therapy; Quality of Life; Central Nervous System Neoplasms; Central Nervous System; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38294638
DOI: 10.1007/s11060-023-04510-4