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Neurosurgery Dec 2016Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation,...
BACKGROUND
Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense.
OBJECTIVE
To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease.
METHODS
Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue.
RESULTS
NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71).
CONCLUSION
With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity.
ABBREVIATIONS
5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.
Topics: Adult; Aminolevulinic Acid; Brain Neoplasms; Coloring Agents; Contrast Media; Female; Fluorescence; Gadolinium; Ganglioglioma; Glioma; Humans; Indocyanine Green; Magnetic Resonance Imaging; Male; Middle Aged; Optical Imaging; Spectroscopy, Near-Infrared
PubMed: 27741220
DOI: 10.1227/NEU.0000000000001450 -
Neuro-oncology Practice Dec 2014Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly...
BACKGROUND
Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBTs). The aim of this study was to analyze the clinicoradiological features and report the clinical outcomes of PRES in PBT patients.
METHODS
We identified 4 cases with PBT who developed PRES at MD Anderson Cancer Center (MDACC) between 2012 and 2014. Clinical and radiological data were abstracted from their records. In addition, we also solicited 8 cases from the literature.
RESULTS
The median age at PRES onset was 19 years, male-to-female ratio was 1:1, and the syndrome occurred in patients with ependymoma ( = 4), glioblastoma ( = 3), diffuse intrinsic pontine glioma (DIPG; = 3), juvenile pilocytic astrocytoma ( = 1), and atypical meningioma ( = 1). Two glioblastomas and 2 DIPG cases received bevacizumab and vandetanib before the onset of symptoms, respectively. The most common clinical presentation was seizures ( = 7). Three MDACC patients recovered completely in 3-4 weeks after the onset of symptoms. One patient died due to active cancer and several comorbidities including PRES.
CONCLUSIONS
Hypertension seems to be the most important coexisting risk factor for development of PRES; however, the potential effects of chemotherapeutic agents in the pathogenesis of PRES should also be examined. The clinicoradiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. PRES must be considered as part of the differential diagnosis in patients with PBTs presenting with seizures or acute encephalopathy.
PubMed: 26034631
DOI: 10.1093/nop/npu024 -
Journal of Neuro-oncology Jun 2017Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae....
Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA -0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.
Topics: Adolescent; Brain Neoplasms; Cerebral Cortex; Chemoradiotherapy; Child; Child, Preschool; Female; Functional Laterality; Humans; Infant; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medulloblastoma; Radiation Injuries; Retrospective Studies; Young Adult
PubMed: 28534154
DOI: 10.1007/s11060-017-2453-5 -
Orphanet Journal of Rare Diseases Jun 2020Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with many manifestations, and it involves any organ. In this study, we report a TSC patient...
OBJECTIVE
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with many manifestations, and it involves any organ. In this study, we report a TSC patient with new type skin lesions.
METHODS
A 7-month-old TSC boy with multiple cutaneous nodules was admitted in our hospital. We collected the clinical data of the patient. We performed biopsy of cutaneous nodules and whole-exome sequencing in both paraffin block tissue and blood samples.
RESULTS
The patient presented with a 2 month history of gradual growth multiple cutaneous nodules. He had cardiac rhabdomyoma, subependymal giant cell astrocytoma (SEGA) and hypomelanotic macules. The pathological finding of cutaneous nodules was consistent with juvenile xanthogranuloma (JXG). After 3 months of sirolimus treatment, the multiple nodules disappeared. The whole-exome sequencing identified TSC1 (c.2356C > T, p.R786*) mutation in both paraffin block tissue and blood samples. We overturned the original pathological diagnosis and finally identified JXG as a new type of skin lesions in TSC.
CONCLUSION
This is the first report on the occurrence of JXG skin lesions in TSC patient. Genetic testing is necessary in JXG. These findings expand the phenotype of skin in patients with TSC and contribute to the elucidation of JXG pathogenesis and treatment.
Topics: Genetic Testing; Humans; Hypopigmentation; Infant; Male; Sirolimus; Tuberous Sclerosis; Xanthogranuloma, Juvenile
PubMed: 32532290
DOI: 10.1186/s13023-020-01396-7 -
Free Neuropathology Jan 2023Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience,...
Pathological perspectives in pilocytic astrocytomas: Extent of resection as the sole critical factor for recurrence-free survival, and the challenge of evaluating conclusions derived from limited data.
Pilocytic astrocytoma (PA) is one of the most common primary intracranial neoplasms in childhood with an overall favorable prognosis. Despite decades of experience, there are still diagnostic and treatment challenges and unresolved issues regarding risk factors associated with recurrence, most often due to conclusions of publications with limited data. We analyzed 499 patients with PA diagnosed in a single institution over 30 years in order to provide answers to some of the unresolved issues. We identified pilocytic astrocytomas diagnosed at the University of California, San Francisco, between 1989 and 2019, confirmed the diagnoses using the WHO 2021 essential and desirable criteria, and performed a retrospective review of the demographic and clinical features of the patients and the radiological, pathologic and molecular features of the tumors. Among the patients identified from pathology archives, 499 cases fulfilled the inclusion criteria. Median age at presentation was 12 years (range 3.5 months - 73 years) and the median follow-up was 78.5 months. Tumors were predominantly located in the posterior fossa (52.6%). There were six deaths, but there were confounding factors that prevented a clear association of death to tumor progression. Extent of resection was the only significant factor for recurrence-free survival. Recurrence-free survival time was 321.0 months for gross total resection, compared to 160.9 months for subtotal resection (log rank, p <0.001). Multivariate analysis was able to identify extent of resection as the only significant variable to influence recurrence-free survival. We did not find a statistically significant association between age, status, tumor location, molecular alterations, and outcome. Smaller series with apparently significant results may have suffered from limited sample size, limited variables, acceptance of univariate analysis findings as well as a larger p value for biological significance. PA still remains a predominantly surgical disease and every attempt should be made to achieve gross total resection since this appears to be the most reliable predictor of recurrence-free survival.
PubMed: 37901684
DOI: 10.17879/freeneuropathology-2023-5116 -
PloS One 2017Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define...
BACKGROUND
Growth monitoring of apparently healthy children aims at early detection of serious conditions through the use of both clinical expertise and algorithms that define abnormal growth. Optimization of growth monitoring requires standardization of the definition of abnormal growth, and the selection of the priority target conditions is a prerequisite of such standardization.
OBJECTIVE
To obtain a consensus about the priority target conditions for algorithms monitoring children's growth.
METHODS
We applied a formal consensus method with a modified version of the RAND/UCLA method, based on three phases (preparatory, literature review, and rating), with the participation of expert advisory groups from the relevant professional medical societies (ranging from primary care providers to hospital subspecialists) as well as parent associations. We asked experts in the pilot (n = 11), reading (n = 8) and rating (n = 60) groups to complete the list of diagnostic classification of the European Society for Paediatric Endocrinology and then to select the conditions meeting the four predefined criteria of an ideal type of priority target condition.
RESULTS
Strong agreement was obtained for the 8 conditions selected by the experts among the 133 possible: celiac disease, Crohn disease, craniopharyngioma, juvenile nephronophthisis, Turner syndrome, growth hormone deficiency with pituitary stalk interruption syndrome, infantile cystinosis, and hypothalamic-optochiasmatic astrocytoma (in decreasing order of agreement).
CONCLUSION
This national consensus can be used to evaluate the algorithms currently suggested for growth monitoring. The method used for this national consensus could be re-used to obtain an international consensus.
Topics: Algorithms; Child; Consensus; Growth and Development; Humans; Interdisciplinary Studies; Pilot Projects
PubMed: 28448550
DOI: 10.1371/journal.pone.0176464 -
Neuro-oncology Advances 2022Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the...
BACKGROUND
Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells.
METHODS
We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patient-derived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells.
RESULTS
We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior.
CONCLUSION
Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types.
PubMed: 35669012
DOI: 10.1093/noajnl/vdac049 -
Journal of Clinical Oncology : Official... Apr 2016Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of...
PURPOSE
Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified.
PATIENTS AND METHODS
Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation.
RESULTS
At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL.
CONCLUSION
SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.
Topics: Acoustic Impedance Tests; Adolescent; Age Factors; Astrocytoma; Audiometry; Brain Neoplasms; Child; Child, Preschool; Cranial Irradiation; Craniopharyngioma; Ependymoma; Female; Follow-Up Studies; Hearing Loss, Sensorineural; Humans; Incidence; Infant; Kaplan-Meier Estimate; Longitudinal Studies; Male; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Risk Factors; Severity of Illness Index; United States; Young Adult
PubMed: 26811531
DOI: 10.1200/JCO.2015.63.6738 -
Cureus Oct 2017The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological...
The resection of deep-seated brain tumors has been associated with morbidity due to injury to critical neural structures during the approach. Recent technological advancements in navigation and stereotaxy, surgical planning, brain tractography and minimal-access brain ports present the opportunity to overcome such limitations. Here, we present the case of a pediatric patient with a left thalamic/midbrain juvenile pilocytic astrocytoma (JPA). The tumor displaced the corticospinal fibers posteriorly and resulted in hemiparesis. Using whole brain tractography to plan a corridor for the approach, neuronavigation, a tubular retractor and an exoscope for visualization, we obtained gross total resection of the tumor, while minimizing injury to white matter bundles, including the corticospinal fibers. We propose that surgical planning with whole brain tractography is essential for reducing morbidity while accessing deep-lying brain lesions via retractor tubes, by means of sparing critical fiber tracts.
PubMed: 29234572
DOI: 10.7759/cureus.1768 -
Surgical Neurology International 2021Low-grade gliomas (LGG) are described by the World Health Organization as Grades I and II. Among LGGs, the most common primary brain tumor is pilocytic astrocytoma (PA)...
BACKGROUND
Low-grade gliomas (LGG) are described by the World Health Organization as Grades I and II. Among LGGs, the most common primary brain tumor is pilocytic astrocytoma (PA) and carries an excellent prognosis when treated with complete surgical resection. Cases, in which this is not possible, are associated with less favorable outcomes and worse progression-free survival.
CASE DESCRIPTION
This report describes a case of a 22-year-old male, who presented with progression of a primary brainstem tumor previously treated with stereotactic radiosurgery and chemotherapy. Patient underwent surgical exploration and was diagnosed with juvenile PA, but debulking was limited by the very dense and fibrous tumor. Complete surgical resection was not possible at this time. Despite efforts to treat with chemotherapy, the patient presented a year later with clinical deterioration and severe neurologic deficits, prompting surgical re-exploration. During the second operation, the tumor was found to have undergone very significant softening in consistency, allowing for gross total resection (GTR).
CONCLUSION
Aggressive treatment of brainstem LGG should be pursued whenever possible, given its generally favorable prognosis. Repeat microsurgical resection, even with a different approach, might be reasonable and safe. Finally, chemotherapy may be associated with changes in the tumor consistency that can render previously unresectable lesions amenable to successful aggressive resection.
PubMed: 33500827
DOI: 10.25259/SNI_594_2020