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International Journal of Molecular... Oct 2023Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine... (Review)
Review
Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.
Topics: Animals; Humans; Pituitary Neoplasms; Pituitary Gland; Neuroendocrine Tumors; Aggression; Tumor Microenvironment
PubMed: 37958702
DOI: 10.3390/ijms242115719 -
Acta Neurochirurgica Sep 2023Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery.
METHODS
The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate.
RESULTS
A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59-1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34-1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26-0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI - 119.04-142.27, P = 0.86).
CONCLUSIONS
There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery.
Topics: Humans; Male; Female; Treatment Outcome; Prolactin; Retrospective Studies; Pituitary Neoplasms; Adenoma; Hormones; Postoperative Complications
PubMed: 37555999
DOI: 10.1007/s00701-023-05726-z -
International Journal of Molecular... Jan 2024Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates... (Review)
Review
Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.
Topics: Humans; Ameloblastoma; Craniopharyngioma; Imidazoles; Oximes; Pituitary Neoplasms
PubMed: 38255797
DOI: 10.3390/ijms25020723 -
Hormone and Metabolic Research =... Jul 2023The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to... (Meta-Analysis)
Meta-Analysis
The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to assess the risk of growth, new pituitary endocrinopathies, and surgery in patients with conservatively treated NFPTs. We conducted a bibliographical search identifying studies assessing NFPTs followed conservatively. Estimates were pooled using random-effects meta-analysis reporting events per 100 person years (PYs), in case of high heterogeneity (I2>75%) only the range of observed effects was reported. We identified 30 cohort studies including 1957 patients with a mean follow-up time of 4.0 (SD 1.5) years. The overall risk of tumor growth ranged from 0.0 to 14.2/100 PYs (I2=90%), while the overall risk of new endocrinopathies was 0.9/100 PYs (95% CI. 0.5 to 1.2; I2=: 35%) and risk of surgery ranged from 0.0 to 7.7/100 PYs (I2=: 80%). Compared to microadenomas, macroadenomas had higher risk of growth (p=: 0.002), higher risk of surgery (p=: 0.006), and non-significant differences in risk of new endocrinopathies (p=: 0.15). An analysis of microadenomas found the risk of growth to be 1.8/100 PYs (95% CI. 0.9 to 2.8; I2=: 58%), the risk of new endocrinopathies 0.7/100 PYs (95% CI. 0.0 to 1.6; I2=: 37%) and the risk of surgery 0.5/100 PYs (0.1 to 0.9; I2=: 37%). These data support individualized follow-up strategies of patients with NFPTs and particularly a less rigorous follow-up of patients with microadenomas.
Topics: Humans; Pituitary Neoplasms; Adenoma; Cohort Studies; Pituitary Gland
PubMed: 37494058
DOI: 10.1055/a-2096-1340 -
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 -
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 -
Neurosurgical Review Aug 2023The current knowledge regarding the prevalence and persistence of edematous changes postmeningioma surgery is limited. Our hypothesis was that peritumoral edema is... (Review)
Review
The current knowledge regarding the prevalence and persistence of edematous changes postmeningioma surgery is limited. Our hypothesis was that peritumoral edema is frequently irreversible gliosis, potentially influencing long-term postoperative epilepsy. We conducted a systematic literature search in PubMed, Cochrane Library, and Scopus databases. We included studies with adult patients undergoing first supratentorial meningioma surgery, which reported pre- and postoperative peritumoral brain edema (T2WI and FLAIR hyperintensity on MRI). Risk of bias was assessed based on detailed reporting of five domains: (1) meningioma characteristics, (2) extent of resection, (3) postoperative radiation therapy, (4) neurological outcome, and (5) used MRI sequence. Our loose search strategy yielded 1714 articles, of which 164 were reviewed and seven met inclusion criteria. Persistent edema rates ranged from 39% to 83% with final follow-up occurring between 0, 14, and 157 months. Among patient cohorts exhibiting persistent edema, a smaller portion achieved seizure resolution compared to a cohort without persistent edema. Relatively reliable assessment of persistent T2/FLAIR hyperintensity changes can be made earliest at one year following surgery. All studies were classified as low quality of evidence, and therefore, quantitative analyses were not conducted. Persistent T2/FLAIR hyperintensity changes are frequently observed in MRI imaging following meningioma surgery. The term "edema," which is reversible, does not fully capture pre- and postoperative T2WI and FLAIR hyperintensity changes. Future studies focusing on peritumoral meningioma-related edema, its etiology, its persistence, and its impact on postoperative epilepsy are needed.
Topics: Adult; Humans; Meningioma; Meningeal Neoplasms; Retrospective Studies; Magnetic Resonance Imaging; Brain Edema; Edema; Epilepsy
PubMed: 37541985
DOI: 10.1007/s10143-023-02094-1 -
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 -
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 -
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