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1.
Neuroophthalmology ; 48(4): 272-278, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933752

RESUMEN

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases.

2.
Front Surg ; 11: 1375567, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881706

RESUMEN

Introduction: Chordomas are aggressive tumors that are thought to arise from remnants of the embryological notochord. They can arise along the ventromedial aspect of the sacrum, mobile spine, and clivus-with most cases occurring in the sacrum or skull base. Despite surgery and radiation, chordomas often progress and become refractory to further treatment. The high recurrence rate of chordomas has created an urgent need to develop new systemic treatment options. Recent case reports and clinical trials have highlighted the use of immunotherapy for refractory chordomas. In this review, we summarize the results of these studies and discuss the potential role of immunotherapy for chordomas. Methods: The PUBMED database was queried for studies mentioning both "Chordoma" and "Immunotherapy." All case series and case reports that involved administration of an immunotherapy for chordoma were included. Additional studies that were found during literature review were added. ClinicalTrials.Gov was queried for studies mentioning both "Chordoma" and "Immunotherapy." The final cohort consisted of all clinical trials that utilized immunotherapy for chordomas of any location. Results: Eight case reports and series detailing the use of immunotherapy for treatment refractory chordoma were identified. Most patients received immunotherapy targeting the PD-1/PD-L1 interaction, and two patients received therapy targeting this interaction along with the tyrosine kinase inhibitor pazopanib. One patient received a vaccine derived from autologous tumor cells, and one patient received a viral vector that downregulated the effect of TGF-beta. One clinical trial utilized a brachyury vaccine in conjunction with standard of care radiotherapy. Conclusions: Immunotherapy for chordoma is a promising area of investigation with increasing, but small, numbers of case series and clinical trials. Despite challenges in patient accrual, future directions in chordoma immunotherapy may lie in vaccine-based therapies and immune checkpoint inhibitors. Understanding chordoma heterogeneity and microenvironment will likely elucidate important chordoma features that will inform future clinical trial design.

4.
World Neurosurg ; 182: e742-e754, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38092351

RESUMEN

BACKGROUND: Stereotactic radiosurgery (SRS) and recently, hypofractionated radiosurgery (hSRS) are increasingly utilized as treatment for vestibular schwannomas (VS). We performed a meta-analysis of literature comparing these modalities. METHODS: The PubMed database of articles was searched for studies that compared SRS and hSRS in patients with VS. Variables analyzed include tumor control, hearing preservation, facial nerve preservation, trigeminal nerve preservation, and total complications. Heterogeneity across the studies was gauged using Higgins's inconsistency index. Funnel plots and Egger's regression intercept test were used to address the publication bias. RESULTS: Thirteen studies that satisfied the search criteria were selected for meta-analysis. The studies identified in our study included 353 SRS and 511 hSRS-treated patients. Analysis of heterogeneity showed that hSRS is employed for relatively larger tumor sizes in comparison to SRS. Pooled meta-analysis estimates showed no significant differences between SRS and hSRS in terms of tumor control (odds ratio [OR], 0.620; 95% confidence interval [CI], 0.21-1.86, P = 0.39), hearing preservation (OR, 1.07; 95% CI, 0.59-1.93, P = 0.83), facial nerve preservation (OR, 0.53; 5% CI, 0.23-1.21, P = 0.13), or trigeminal nerve preservation (OR, 0.67; 95% CI, 0.24-1.89, P = 0.49) at a mean follow-up of 39 months. Statistically significant heterogeneity was found across the studies only for tumor diameter (Higgins's inconsistency index = 65.69%, P = 0.003) but not for other variables. CONCLUSIONS: Meta-analysis of thirteen studies comparing SRS and hSRS as treatment for VS showed comparable tumor control, hearing preservation, facial nerve preservation, and trigeminal nerve preservation.


Asunto(s)
Neuroma Acústico , Radiocirugia , Humanos , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Radiocirugia/efectos adversos , Resultado del Tratamiento , Nervio Facial/patología , Audición , Estudios Retrospectivos , Estudios de Seguimiento
6.
Front Immunol ; 14: 1284118, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022656

RESUMEN

Introduction: Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown. Methods: To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment. Results: This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy. Discussion: Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.


Asunto(s)
Glioblastoma , Humanos , Glioblastoma/radioterapia , Glioblastoma/patología , Resultado del Tratamiento , Estudios Retrospectivos , Hipofraccionamiento de la Dosis de Radiación , Leucocitos/patología , Microambiente Tumoral
8.
Otolaryngol Clin North Am ; 56(3): 459-469, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37024332

RESUMEN

Decision-making in management of sporadic vestibular schwannoma aims to identify the most appropriate options based on tumor characteristics, symptoms, health, and goals for each patient. Advances in knowledge of tumor natural history, improvements in radiation techniques, and achievements in neurologic preservation with microsurgery have shifted emphasis toward maximizing quality of life using a personalized approach. To empower patients to make informed decisions, we present a framework to help match patient values and priorities with reasonable expectations from modern management options. Introduced herein are practical examples of communication strategies and decision aids to support shared decision-making in modern practice.


Asunto(s)
Neuroma Acústico , Humanos , Neuroma Acústico/cirugía , Calidad de Vida
9.
Neuroophthalmology ; 47(2): 106-109, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36891405

RESUMEN

Transient visual obscurations (TVOs) represent brief ischaemic events of the optic nerve. These most commonly occur in the setting of raised intracranial pressure or more localised aetiologies within the orbit that result in decreased perfusion pressure. Transient vision loss has rarely been associated with pituitary tumours or optic chiasm compression, but details are lacking. We describe classic TVOs that completely resolved following resection of a pituitary macroadenoma causing chiasmal compression with a relatively normal eye examination. Clinicians should consider neuro-imaging in patients with TVOs and a normal evaluation.

10.
World Neurosurg ; 173: e132-e139, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36773809

RESUMEN

OBJECTIVE: To examine the demographics, tumor characteristics, treatments, and clinical outcomes of a large adult craniopharyngioma population. METHODS: The 2004-2018 National Cancer Database was queried to investigate adult patients with craniopharyngioma. Univariable and multivariable Cox hazard ratio analysis was conducted to analyze the overall survival (OS) impact of demographic and clinical variables. RESULTS: A total of 666 adult patients with craniopharyngioma were identified with a mean age of 51 years (standard deviation 16 years). On multivariable analysis, independent of demographic and clinical variables, increased age, uninsured status, Medicaid, Medicare, Charlson-Deyo Comorbidity Index of 2, and tumor size greater than 40 mm were independently associated with worse OS. There was no significant difference in survival between histologic subtypes. Gross total resection (GTR) (hazard ratio [HR] 0.602, 95% confidence interval [CI] 0.384-0.942, P = 0.026) and subtotal resection (STR) with adjuvant radiotherapy (HR 0.316, 95% CI 0.140-0.710, P = 0.005) were independently associated with improved OS. GTR with radiotherapy trended towards improved OS (HR 0.601, 95% CI 0.334-1.083, P =0.090), but STR alone and radiotherapy alone demonstrated no significant difference in survival compared with no treatment on multivariable analysis. Kaplan-Meier survival models demonstrated improved survival with GTR, GTR + radiation therapy, and STR + radiation therapy. Patients undergoing endoscopic resection had significantly lower GTR rates and greater rates of adjuvant radiotherapy compared with open approaches but no difference in OS. CONCLUSION: Adult patients with craniopharyngioma who underwent GTR or STR with adjuvant radiotherapy had significantly improved overall survival. Endoscopic approaches had lower rates of GTR but no difference in OS.


Asunto(s)
Craneofaringioma , Neoplasias Hipofisarias , Adulto , Humanos , Anciano , Estados Unidos/epidemiología , Persona de Mediana Edad , Craneofaringioma/cirugía , Craneofaringioma/patología , Resultado del Tratamiento , Pronóstico , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Medicare , Radioterapia Adyuvante , Estudios Retrospectivos
11.
World Neurosurg ; 170: 149-156.e3, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36400356

RESUMEN

OBJECTIVE: Tympanojugular paragangliomas (TJPs) are slow-growing tumors arising within the middle ear or jugular foramen. The development of modified skull base approaches and the increasing use of stereotactic radiosurgery have provided more modern techniques in the management of TJPs. Several factors dictating approach selection, and resulting clinical outcomes have been inconsistently described. METHODS: A systematic review of the literature describing modern management of complex TJPs was performed and summarized. A random-effects meta-analysis was performed to describe the rate of tumor control, complications, and symptom improvement in patients undergoing radiosurgery or surgical resection. RESULTS: Nineteen studies were identified with a total of 852 TJP patients. A minority (153 patients) underwent radiosurgery while 699 underwent surgery. On meta-analysis, there was a 3.5% (95% confidence interval [CI]: 0.5%-6.4%) tumor growth rate following radiosurgery and 3.9% (95% confidence interval [CI]: 1.8%-6.0%) recurrence rate in surgical resection, with no significant moderator effect between the 2 groups (P = 0.9046). Complication rate for radiosurgery was 7.6% (95% CI: 2.8%-12.4%), differing significantly from surgical complication rates of 29.6% (95% CI: 17.1-42.0%, P = 0.0418). CONCLUSIONS: Stereotactic radiosurgery and surgical resection for TJPs have similar rates of tumor recurrence. Radiation is associated with less risk and lower morbidity, yet there is comparably modest reduction of the tumor size. In sum, the data suggest that radiosurgery is a reasonable management option for patients with minimal symptoms who are high risk for surgery. Microsurgical resection should be reserved for patients with lower cranial neuropathies or those who have failed radiation treatment.


Asunto(s)
Enfermedades de los Nervios Craneales , Tumor del Glomo Yugular , Paraganglioma , Radiocirugia , Humanos , Tumor del Glomo Yugular/cirugía , Recurrencia Local de Neoplasia/cirugía , Paraganglioma/cirugía , Enfermedades de los Nervios Craneales/etiología , Radiocirugia/métodos , Resultado del Tratamiento , Estudios Retrospectivos
12.
Lancet ; 400(10368): 2063-2073, 2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36502844

RESUMEN

BACKGROUND: Disparities in treatment and outcomes disproportionately affect minority ethnic and racial populations in many surgical fields. Although substantial research in racial disparities has focused on outcomes, little is known about how surgeon recommendations can be influenced by patient race. The aim of this study was to investigate racial and socioeconomic disparities in the surgical management of primary brain tumors. METHODS: In this registry-based cohort study, we used data from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) and the American College of Surgeons National Cancer Database (NCDB) in the USA for independent analysis. Adults (aged ≥20 years) with a new diagnosis of meningioma, glioblastoma, pituitary adenoma, vestibular schwannoma, astrocytoma, and oligodendroglioma, with information on tumour size and surgical recommendation were included in the analysis. The primary outcome of this study was the odds of a surgeon recommending against surgical resection at diagnosis of primary brain neoplasms. This outcome was determined using multivariable logistic regression with clinical, demographic, and socioeconomic factors. FINDINGS: This study included US national data from the SEER (1975-2016) and NCDB (2004-17) databases of adults with a new diagnosis of meningioma (SEER n=63 674; NCDB n=222 673), glioblastoma (n=35 258; n=104 047), pituitary adenoma (n=27 506; n=87 772), vestibular schwannoma (n=11 525; n=30 745), astrocytoma (n=5402; n=10 631), and oligodendroglioma (n=3977; n=9187). Independent of clinical and demographic factors, including insurance status and rural-urban continuum code, Black patients had significantly higher odds of recommendation against surgical resection of meningioma (adjusted odds ratio 1·13, 95% CI 1·06-1·21, p<0·0001), glioblastoma (1·14, 1·01-1·28, p=0·038), pituitary adenoma (1·13, 1·05-1·22, p<0·0001), and vestibular schwannoma (1·48, 1·19-1·84, p<0·0001) when compared with White patients in the SEER dataset. Additionally, patients of unknown race had significantly higher odds of recommendation against surgical resection for pituitary adenoma (1·80, 1·41-2·30, p<0·0001) and vestibular schwannoma (1·49, 1·10-2·04, p=0·011). Performing a validation analysis using the NCDB dataset confirmed these significant results for Black patients with meningioma (1·18, 1·14-1·22, p<0·0001), glioblastoma (1·19, 1·12-1·28, p<0·0001), pituitary adenoma (1·21, 1·16-1·25, p<0·0001), and vestibular schwannoma (1·19, 1·04-1·35, p=0·0085), and indicated and indicated that the findings are independent of patient comorbidities. When further restricted to the most recent decade in SEER, these inequities held true for Black patients, except those with glioblastoma (meningioma [1·18, 1·08-1·28, p<0·0001], pituitary adenoma [1·20, 1·09-1·31, p<0·0001], and vestibular schwannoma [1·54, 1·16-2·04, p=0·0031]). INTERPRETATION: Racial disparities in surgery recommendations in the USA exist for patients with primary brain tumours, independent of potential confounders including clinical, demographic, and select socioeconomic factors. Further studies are needed to understand drivers of this bias and enhance equality in surgical care. FUNDING: None.


Asunto(s)
Glioblastoma , Neuroma Acústico , Neoplasias Hipofisarias , Adulto , Humanos , Población Blanca , Disparidades en Atención de Salud , Estudios de Cohortes , Glioblastoma/epidemiología , Glioblastoma/cirugía
13.
J Neurol Surg B Skull Base ; 83(Suppl 2): e152-e159, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35832980

RESUMEN

Background Pituitary apoplexy after resection of giant pituitary adenomas is a rare but often cited morbidity associated with devastating outcomes. It presents as hemorrhage and/or infarction of residual tumor in the postoperative period. Because of its rarity, its incidence and consequences remain ill defined. Objective The aim of this study is to estimate the rate of postoperative pituitary apoplexy after resection of giant pituitary adenomas and assess the morbidity and mortality associated with apoplexy. Methods A systematic review of literature was performed to examine extent of resection in giant pituitary adenomas based on surgical approach, rate of postoperative apoplexy, morbidities, and mortality. Advantages and disadvantages of each approach were compared. Results Seventeen studies were included in quantitative analysis describing 1,031 cases of resection of giant pituitary adenomas. The overall rate of subtotal resection (<90%) for all surgical approaches combined was 35.6% (95% confidence interval: 28.0-43.1). Postoperative pituitary apoplexy developed in 5.65% ( n = 19) of subtotal resections, often within 24 hours and with a mortality of 42.1% ( n = 8). Resulting morbidities included visual deficits, altered consciousness, cranial nerve palsies, and convulsions. Conclusion Postoperative pituitary apoplexy is uncommon but is associated with high rates of morbidity and mortality in subtotal resection cases. These findings highlight the importance in achieving a maximal resection in a time sensitive fashion to mitigate the severe consequences of postoperative apoplexy.

14.
World Neurosurg X ; 13: 100115, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35028557

RESUMEN

BACKGROUND: The ClearPoint neuronavigation system affords real-time magnetic resonance imaging (MRI) guidance during stereotactic procedures. While such information confers potential clinical benefits, additional operative time may be needed. METHODS: We conducted a retrospective analysis of procedural time associated with ClearPoint Stereotaxis, with hypothesis that this procedural time is comparable with that associated with frame-based biopsy. RESULTS: Of the 52 patients evaluated, the total procedural time for ClearPoint stereotactic biopsy averaged 150.0 (±40.4) minutes, of which 111.5 (±16.5) minutes were dedicated to real-time MRI acquisition and trajectory adjustment. This procedural time is within the range of those reported for frame-based needle biopsies. Approximately 5 minutes of the procedural time is related to the mounting of the MRI-compatible stereotactic frame. Based on the procedural time, we estimate that four cases are required in the learning curve to achieve this efficiency. Efficient algorithms for distortion corrections and isocenter localization are keys to ClearPoint stereotaxis. Routine quality assurance/control after each MRI software update and institutional information technology maintenance also contribute to efficiency. Real-time MRI is essential for definitive diagnosis in select cases. CONCLUSIONS: ClearPoint stereotactic needle biopsy can be achieved in time frames comparable to frame-based stereotaxis. However, procedural efficiency requires 4 "learning curve" cases as well as vigilance in terms of MR distortion correction and information technology maintenance.

15.
J Clin Neurosci ; 94: 186-191, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34863436

RESUMEN

INTRODUCTION: There is increased appreciation of racial disparities in the delivery of neurosurgical care. Here, we explore whether race influences surgical recommendations in the management of skull base chondrosarcomas. METHODS: We identified 493 patients with skull base chondrosarcoma using the Surveillance, Epidemiology, and End Results (SEER) registry (November 2017 submission). Regression analyses were performed to identify demographic variables associated with recommendation against surgery. Univariate and multivariate cox proportional hazards models were used for survival analysis. RESULTS: In a univariate analysis, we found that the African-American race was associated with an increased likelihood of surgeon recommendation against surgery (OR = 4.416, 95% CI = 1.893-10.302, p = 0.001). This association remained robust in the multivariate model that controlled for other covariates, including age of diagnosis (OR = 5.091, 95% CI = 2.127-12.187, p < 0.001). For patients who received a recommendation against surgery, the likelihood of dying from non-chondrosarcoma causes was comparable between Caucasian and African-American patients, suggesting that the prevalence and severity of medical conditions that increase the risk of death were comparable between these cohorts (HR = 0.466, 95% CI = 0.057-3.802, p = 0.475). The likelihood of dying from chondrosarcoma was comparable between Caucasian and African-American patients who underwent surgery (HR = 0.982, 95% CI = 0.353-2.732, p = 0.973), suggesting absence of race-specific surgical benefits. CONCLUSION: We identified a racial disparity against African-Americans in recommendations for surgical resection of skull base chondrosarcomas.


Asunto(s)
Condrosarcoma , Negro o Afroamericano , Condrosarcoma/epidemiología , Condrosarcoma/cirugía , Humanos , Programa de VERF , Base del Cráneo , Población Blanca
16.
J Neurooncol ; 154(1): 1-11, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34251602

RESUMEN

BACKGROUND: Stereotactic needle biopsy remains the cornerstone for tissue diagnosis for tumors located in regions of the brain that are difficult to access through open surgery. OBJECTIVE: We perform a meta-analysis of the literature to examine the relation between number of samples taken during biopsy and diagnostic yield, morbidity and mortality. METHODS: We identified 2416 patients from 28 cohorts in studies published in PubMed database that studied stereotactic needle biopsies for tumor indications. Meta-analysis by proportions and meta-regression analyses were performed. RESULTS: On meta-analysis, the morbidity profile of the published needle biopsy studies clustered into three groups: studies that performed < 3 samples (n = 8), 3-6 samples (n = 13), and > 6 samples during biopsy (n = 7). Pooled estimates for biopsy related morbidity were 4.3%, 16.3%, and 17% for studies reporting < 3, 3-6, and > 6 biopsy samples, respectively. While these morbidity estimates significantly differed (p < 0.001), the diagnostic yields reported for studies performing < 3 biopsies, 3-6 samples, and > 6 samples were comparable. Pooled estimates of diagnostic yield for these three groups were 90.4%, 93.8%, and 88.1%, respectively. Mortality did not significantly differ between studies reporting differing number of samples taken during biopsy. CONCLUSIONS: Our meta-analysis suggests that morbidity risk in needle biopsy is non-linearly associated with the number of samples taken. There was no association between the number of biopsies taken, and diagnostic yield or mortality.


Asunto(s)
Biopsia con Aguja , Neoplasias Encefálicas , Técnicas Estereotáxicas , Biopsia con Aguja/efectos adversos , Biopsia con Aguja/estadística & datos numéricos , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Humanos , Técnicas Estereotáxicas/efectos adversos , Resultado del Tratamiento
17.
Neurosurgery ; 89(4): 712-719, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34320218

RESUMEN

BACKGROUND: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma. OBJECTIVE: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR. METHODS: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates. CONCLUSION: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma.


Asunto(s)
Neoplasias Encefálicas , Colaboración de las Masas , Glioblastoma , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Consenso , Glioblastoma/diagnóstico por imagen , Glioblastoma/cirugía , Humanos , Procedimientos Neuroquirúrgicos , Estudios Prospectivos
18.
Pituitary ; 24(6): 859-866, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34041660

RESUMEN

PURPOSE: Pituitary apoplexy is a rare endocrine emergency. The purpose of this study is to characterize physiological changes involved in pituitary apoplexy, especially during the acute phase. METHODS: A Cushing's disease patient experienced corticotroph releasing hormone (CRH)-induced pituitary apoplexy during inferior petrosal sinus sampling (IPSS). The IPSS blood samples from the Cushing's disease patient were retrospectively analyzed for cytokine markers. For comparison, we also analyzed cytokine markers in blood samples from two pituitary ACTH-secreting microadenoma patients and one patient with an ectopic ACTH-secreting tumor. RESULTS: Acute elevation of interleukin 6 (IL-6) and matrix metalloproteinase 9 (MMP9) was observed in the IPSS blood sample on the apoplectic hemorrhagic site of the tumor. In contrast, such a change was not observed in the blood samples from the contralateral side of the apoplexy patient and in other IPSS samples from two non-apoplexy Cushing's disease patient and a patient with ectopic Cushing's syndrome. CONCLUSION: IL-6 and MMP9 may be involved in the acute process of pituitary apoplexy in Cushing's disease.


Asunto(s)
Adenoma , Interleucina-6 , Metaloproteinasa 9 de la Matriz , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Apoplejia Hipofisaria , Neoplasias Hipofisarias , Hormona Liberadora de Corticotropina , Humanos , Muestreo de Seno Petroso , Estudios Retrospectivos
19.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33846242

RESUMEN

Precision medicine in oncology leverages clinical observations of exceptional response. Toward an understanding of the molecular features that define this response, we applied an integrated, multiplatform analysis of RNA profiles derived from clinically annotated glioblastoma samples. This analysis suggested that specimens from exceptional responders are characterized by decreased accumulation of microglia/macrophages in the glioblastoma microenvironment. Glioblastoma-associated microglia/macrophages secreted interleukin 11 (IL11) to activate STAT3-MYC signaling in glioblastoma cells. This signaling induced stem cell states that confer enhanced tumorigenicity and resistance to the standard-of-care chemotherapy, temozolomide (TMZ). Targeting a myeloid cell restricted an isoform of phosphoinositide-3-kinase, phosphoinositide-3-kinase gamma isoform (PI3Kγ), by pharmacologic inhibition or genetic inactivation disrupted this signaling axis by reducing microglia/macrophage-associated IL11 secretion in the tumor microenvironment. Mirroring the clinical outcomes of exceptional responders, PI3Kγ inhibition synergistically enhanced the anti-neoplastic effects of TMZ in orthotopic murine glioblastoma models. Moreover, inhibition or genetic inactivation of PI3Kγ in murine glioblastoma models recapitulated expression profiles observed in clinical specimens isolated from exceptional responders. Our results suggest key contributions from tumor-associated microglia/macrophages in exceptional responses and highlight the translational potential for PI3Kγ inhibition as a glioblastoma therapy.


Asunto(s)
Glioblastoma/metabolismo , Microglía/metabolismo , Temozolomida/farmacología , Adulto , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase Ib/metabolismo , Resistencia a Antineoplásicos/fisiología , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Humanos , Interleucina-11/inmunología , Interleucina-11/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Desnudos , Microglía/fisiología , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Transducción de Señal/efectos de los fármacos , Temozolomida/metabolismo , Microambiente Tumoral/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/fisiología
20.
J Neurol Surg B Skull Base ; 82(Suppl 1): S41-S42, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33717815

RESUMEN

Aneurysms of the posterior circulation pose a unique challenge due to higher rupture rates, higher recurrence rates following endovascular treatment, and extended open cranial base approaches required to reach the ventrally located brainstem circulation. While endovascular therapy has made tremendous strides in successful treatment for most posterior circulation aneurysms, open microscopic approaches remain essential in specific circumstances. Here, we present a case of a patient who presented with acute, severe headache, and sixth nerve palsies, and who was found to have hydrocephalus and a dissecting aneurysm at the anterolateral medullary segment of the posterior inferior cerebellar artery (PICA). Interestingly, this patient had a history of alpha-1 antitrypsin deficiency that has been linked with spontaneous aortic and cervical arterial dissections. The fusiform geometry of the dissecting aneurysm was deemed suboptimal for endovascular treatment, so an open microsurgical approach for occipital artery to PICA bypass and aneurysm trapping was planned. Because this patient had cerebral edema in the setting of a ruptured aneurysm and hydrocephalus, a far lateral craniotomy combined with drilling of the occipital condyle and jugular tubercle was critical to enhance exposure of the first segment of the PICA and to minimize brain retraction. In this video, we highlight the key steps and nuances for harvest of the occipital artery, achieving control of the extracranial vertebral artery, performing the transcondylar and transtubercular far lateral approach, and bypass with trapping technique for these challenging posterior circulation aneurysms. The link to the video can be found at: https://youtu.be/dqgblwX6t0Q .

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