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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 -
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 -
Frontiers in Endocrinology 2021Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory...
Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.
Topics: Acromegaly; Biomarkers; Cadherins; Cytoskeleton; Drug Resistance; Endocrine Gland Neoplasms; Epithelial-Mesenchymal Transition; Growth Hormone-Secreting Pituitary Adenoma; Humans; Ligands; Phenotype; Pituitary Neoplasms; Receptors, Somatostatin; Somatostatin
PubMed: 33790868
DOI: 10.3389/fendo.2021.646210 -
Cancer Medicine Dec 2019With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life-threatening pituitary-adrenal dysfunctions, particularly for hypopituitarism,... (Meta-Analysis)
Meta-Analysis
With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life-threatening pituitary-adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary-adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta-analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%-3.22%) for all-grade adrenal insufficiency and 3.25% (95% CI, 2.15%-4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious-grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious-grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI-based treatment, particularly for CTLA-4 inhibitors, which were associated with a higher incidence of pituitary-adrenal dysfunction than PD-1/PD-L1 inhibitors.
Topics: Adrenal Insufficiency; Antineoplastic Agents, Immunological; Biomarkers, Tumor; CTLA-4 Antigen; Clinical Trials as Topic; Humans; Hypopituitarism; Neoplasms; Odds Ratio; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Programmed Cell Death 1 Receptor; Severity of Illness Index
PubMed: 31679184
DOI: 10.1002/cam4.2661 -
Pituitary Aug 2021Residual tumor tissue after pituitary adenoma surgery, is linked with additional morbidity and mortality. Intraoperative magnetic resonance imaging (ioMRI) could improve... (Meta-Analysis)
Meta-Analysis Review
Impact of intraoperative magnetic resonance imaging on gross total resection, extent of resection, and residual tumor volume in pituitary surgery: systematic review and meta-analysis.
BACKGROUND
Residual tumor tissue after pituitary adenoma surgery, is linked with additional morbidity and mortality. Intraoperative magnetic resonance imaging (ioMRI) could improve resection. We aim to assess the improvement in gross total resection (GTR), extent of resection (EOR), and residual tumor volume (RV) achieved using ioMRI.
METHODS
A systematic review was carried out on PubMed/MEDLINE to identify any studies reporting intra- and postoperative (1) GTR, (2) EOR, or (3) RV in patients who underwent resection of pituitary adenomas with ioMRI. Random effects meta-analysis of the rate of improvement after ioMRI for these three surgical outcomes was intended.
RESULTS
Among 34 included studies (2130 patients), the proportion of patients with conversion to GTR (∆GTR) after ioMRI was 0.19 (95% CI 0.15-0.23). Mean ∆EOR was + 9.07% after ioMRI. Mean ∆RV was 0.784 cm. For endoscopically treated patients, ∆GTR was 0.17 (95% CI 0.09-0.25), while microscopic ∆GTR was 0.19 (95% CI 0.15-0.23). Low-field ioMRI studies demonstrated a ∆GTR of 0.19 (95% CI 0.11-0.28), while high-field and ultra-high-field ioMRI demonstrated a ∆GTR of 0.19 (95% CI 0.15-0.24) and 0.20 (95% CI 0.13-0.28), respectively.
CONCLUSIONS
Our meta-analysis demonstrates that around one fifth of patients undergoing pituitary adenoma resection convert from non-GTR to GTR after the use of ioMRI. EOR and RV can also be improved to a certain extent using ioMRI. Endoscopic versus microscopic technique or field strength does not appear to alter the impact of ioMRI. Statistical heterogeneity was high, indicating that the improvement in surgical results due to ioMRI varies considerably by center.
Topics: Adenoma; Disease Progression; Humans; Magnetic Resonance Imaging; Neoplasm, Residual; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome; Tumor Burden
PubMed: 33945115
DOI: 10.1007/s11102-021-01147-2 -
European Archives of... Sep 2023We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery.
METHODS
Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed.
RESULTS
The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting.
CONCLUSION
Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.
Topics: Humans; Retrospective Studies; Epistaxis; Surgical Flaps; Endoscopy; Pituitary Gland; Skull Base; Pituitary Diseases; Pituitary Neoplasms; Postoperative Complications; Treatment Outcome
PubMed: 36988686
DOI: 10.1007/s00405-023-07934-w -
Neurosurgical Review Oct 2022The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the... (Review)
Review
The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.
Topics: Astrocytoma; Brain; Brain Neoplasms; Colloid Cysts; Humans; Neuroendoscopy; Pituitary Neoplasms; Ultrasonics
PubMed: 35896917
DOI: 10.1007/s10143-022-01837-w -
Pituitary Apr 2023Transsphenoidal surgery is an established treatment for pituitary adenomas. We examined outcomes and time points following transsphenoidal surgery for pituitary adenoma...
PURPOSE
Transsphenoidal surgery is an established treatment for pituitary adenomas. We examined outcomes and time points following transsphenoidal surgery for pituitary adenoma to identify reporting heterogeneity within the literature.
METHODS
A systematic review of studies that reported outcomes for transsphenoidal surgery for pituitary adenoma 1990-2021 were examined. The protocol was registered a priori and adhered to the PRISMA statement. Studies in English with > 10 patients (prospective) or > 500 patients (retrospective) were included.
RESULTS
178 studies comprising 427,659 patients were included. 91 studies reported 2 or more adenoma pathologies within the same study; 53 studies reported a single pathology. The most common adenomas reported were growth hormone-secreting (n = 106), non-functioning (n = 101), and ACTH-secreting (n = 95); 27 studies did not state a pathology. Surgical complications were the most reported outcome (n = 116, 65%). Other domains included endocrine (n = 104, 58%), extent of resection (n = 81, 46%), ophthalmic (n = 66, 37%), recurrence (n = 49, 28%), quality of life (n = 25, 19%); and nasal (n = 18, 10%). Defined follow up time points were most reported for endocrine (n = 56, 31%), extent of resection (n = 39, 22%), and recurrence (n = 28, 17%). There was heterogeneity in the follow up reported for all outcomes at different time points: discharge (n = 9), < 30 days (n = 23), < 6 months (n = 64), < 1 year (n = 23), and > 1 year (n = 69).
CONCLUSION
Outcomes and follow up reported for transsphenoidal surgical resection of pituitary adenoma are heterogenous over the last 30 years. This study highlights the necessity to develop a robust, consensus-based, minimum, core outcome set. The next step is to develop a Delphi survey of essential outcomes, followed by a consensus meeting of interdisciplinary experts. Patient representatives should also be included. An agreed core outcome set will enable homogeneous reporting and meaningful research synthesis, ultimately improving patient care.
Topics: Humans; Pituitary Neoplasms; Retrospective Studies; Prospective Studies; Quality of Life; Treatment Outcome; Adenoma; Patient Reported Outcome Measures
PubMed: 36862265
DOI: 10.1007/s11102-023-01303-w -
PloS One 2016Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective.
METHODS
We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992-2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0.
RESULTS
Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p<0.05) than the mononostril group. However, the mononostril group had less rate of epistaxis (0.4% vs. 1.5%, p = 0.008) than the binostril group. For invasive macroadenomas, the binostril group seem to demonstrate a tendency towards better outcomes though there was no subgroup analysis between the two groups.
CONCLUSION
The binostril approach had less temporary diabetes insipidus, anterior pituitary insufficiency, and a shorter length of hospital stay, although they demonstrated a higher rate of epistaxis than the mononstril group. Additionally, the binostril group seemed to suggest a tendency towards better outcomes for invasive macroadenomas.
Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Child; Endoscopy; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Nose; Pituitary Neoplasms; Treatment Outcome; Young Adult
PubMed: 27124276
DOI: 10.1371/journal.pone.0153397 -
Neuro-oncology Mar 2020This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management.
METHODS
Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words "radiosurgery" and "pituitary" and/or "adenoma." Weighted random effects models were used to calculate pooled outcome estimates.
RESULTS
Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5-35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12-25 Gy, delivered in 3-5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0-96.0%) and 97.0% (95% CI: 93.0-98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0-88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0-27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0-7%).
CONCLUSIONS
SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
Topics: Adenoma; Disease Management; Humans; Pituitary Neoplasms; Radiation Dose Hypofractionation; Radiosurgery; Societies, Medical; Treatment Outcome
PubMed: 31790121
DOI: 10.1093/neuonc/noz225