224 results on '"Camelo-Piragua, Sandra"'
Search Results
202. Sudden Death Due to Calcifying Pseudoneoplasm of the Neuraxis: A Case Report and a Review of Sudden Death Due to Undiagnosed Central Nervous System Mass Lesions.
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Conway KS, Jentzen J, Pratt D, and Camelo-Piragua S
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- Brain Diseases diagnostic imaging, Calcinosis diagnostic imaging, Frontal Lobe diagnostic imaging, Frontal Lobe pathology, Humans, Male, Seizures etiology, Tomography, X-Ray Computed, White Matter pathology, Young Adult, Brain Diseases pathology, Calcinosis pathology, Death, Sudden etiology
- Abstract
We present a case of a 22-year-old man who died unexpectedly after a seizure due to a previously undiagnosed calcifying pseudoneoplasm of the neuraxis (CAPNON). Calcifying pseudoneoplasm of the neuraxis is a rare entity, and this is, to our knowledge, the first described case of sudden death due to CAPNON. Sudden death due to undiagnosed central nervous system mass lesions is rare, and most cases are attributable to hemorrhage, hydrocephalus, or increased intracranial pressure due to mass effect. Seizure is a rare cause of sudden death due to central nervous system mass lesions. This case highlights that mass lesions may cause sudden death due to seizure, even without other pathologic evidence of a cause of death, such as hemorrhage or edema. Furthermore, benign, reactive, and low-grade mass lesions may cause sudden death due to seizure. Seizure should remain in the autopsy differential as a cause of death, even where there is no pathologically evident mechanism by which a mass lesion caused death.
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- 2020
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203. Neuroimaging features of CNS histiocytosis syndromes.
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Wang Y, Camelo-Piragua S, Abdullah A, Ibrahim M, and Parmar HA
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- Central Nervous System pathology, Erdheim-Chester Disease diagnostic imaging, Histiocytosis, Langerhans-Cell diagnostic imaging, Histiocytosis, Langerhans-Cell pathology, Histiocytosis, Sinus diagnostic imaging, Histiocytosis, Sinus pathology, Humans, Neuroimaging, Syndrome, Central Nervous System diagnostic imaging
- Abstract
Histiocytosis syndromes (HS) are group of heterogeneous disorders characterized by abnormal accumulation and infiltration of histiocytes, cells derived from hematopoietic cells of monocyte/macrophage lineage. Overall these disorders are rare. When they do occur they involve many organ systems including the central nervous system (CNS). While imaging findings can provide important clues, diagnosis of this disorder is challenging and definitive diagnosis often necessitates pathologic examination. In this review, we describe imaging features of HS involving the CNS, with the aim to increase our understanding of these disorders. The entities discussed in this review will include: Langerhans cell histiocytosis (LCH), Rosai-Dorfman Disease (RDD), Erdheim Chester Disease (ECD), hemophagocytic lymphohistiocytosis (HLH), and crystal-storing histiocytosis (CSH)., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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204. Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.
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Hollon TC, Pandian B, Adapa AR, Urias E, Save AV, Khalsa SSS, Eichberg DG, D'Amico RS, Farooq ZU, Lewis S, Petridis PD, Marie T, Shah AH, Garton HJL, Maher CO, Heth JA, McKean EL, Sullivan SE, Hervey-Jumper SL, Patil PG, Thompson BG, Sagher O, McKhann GM 2nd, Komotar RJ, Ivan ME, Snuderl M, Otten ML, Johnson TD, Sisti MB, Bruce JN, Muraszko KM, Trautman J, Freudiger CW, Canoll P, Lee H, Camelo-Piragua S, and Orringer DA
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- Algorithms, Brain Neoplasms diagnostic imaging, Clinical Trials as Topic, Deep Learning, Humans, Image Processing, Computer-Assisted, Probability, Brain Neoplasms diagnosis, Computer Systems, Monitoring, Intraoperative, Neural Networks, Computer, Spectrum Analysis, Raman
- Abstract
Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery
1 . The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3 . Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4 . In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7 , a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2 . In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.- Published
- 2020
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205. Polysomy is associated with poor outcome in 1p/19q codeleted oligodendroglial tumors.
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Chen H, Thomas C, Munoz FA, Alexandrescu S, Horbinski CM, Olar A, McGuone D, Camelo-Piragua S, Wang L, Pentsova E, Phillips J, Aldape K, Chen W, Iafrate AJ, Chi AS, Zagzag D, Golfinos JG, Placantonakis DG, Rosenblum M, Ohman-Strickland P, Hameed M, and Snuderl M
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- Adolescent, Adult, Aged, Aged, 80 and over, Brain Neoplasms therapy, Chemotherapy, Adjuvant, Child, Chromosomal Instability, Chromosome Deletion, Female, Humans, In Situ Hybridization, Fluorescence, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Neoadjuvant Therapy, Neurosurgical Procedures, Oligodendroglioma therapy, Prognosis, Progression-Free Survival, Radiotherapy, Adjuvant, Survival Rate, Young Adult, Aneuploidy, Brain Neoplasms genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 19 genetics, Oligodendroglioma genetics
- Abstract
Background: Chromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p/19q status., Methods: We analyzed 412 histologic oligodendroglial tumors with use of 1p/19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p/19q was performed. Polysomy was defined as more than two 1q and 19p signals in cells. Tumors were divided into groups on the basis of their 1p/19q status and polysomy and were compared for progression-free survival (PFS) and overall survival (OS)., Results: In our cohort, 333 tumors (81%) had 1p/19q loss; of these, 195 (59%) had concurrent polysomy and 138 (41%) lacked polysomy, 79 (19%) had 1p/19q maintenance; of these, 30 (38%) had concurrent polysomy and 49 (62%) lacked polysomy. In agreement with prior studies, the group with 1p/19q loss had significantly better PFS and OS than did the group with 1p/19q maintenance (P < 0.0001 each). Patients with 1p/19q loss and polysomy showed significantly shorter PFS survival than patients with 1p/19q codeletion only (P < 0.0001), but longer PFS and OS than patients with 1p/19q maintenance (P < 0.01 and P < 0.0001). There was no difference in survival between tumors with >30% polysomic cells and those with <30% polysomic cells. Polysomy had no prognostic significance on PFS or OS in patients with 1p/19q maintenance., Conclusions: The presence of polysomy in oligodendroglial tumors with codeletion of 1p/19q predicts early recurrence and short survival in patients with 1p/19q codeleted tumors., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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206. Pediatric craniopharyngioma in association with familial adenomatous polyposis.
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Dahl NA, Pratt D, Camelo-Piragua S, Kumar-Sinha C, Mody RJ, Septer S, Hankinson TC, Chinnaiyan AM, Koschmann C, and Hoffman L
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- Adenomatous Polyposis Coli genetics, Child, Craniopharyngioma diagnostic imaging, Craniopharyngioma genetics, Female, Genes, APC, Germ-Line Mutation, Humans, Phenotype, Pituitary Neoplasms diagnostic imaging, Pituitary Neoplasms genetics, Point Mutation, beta Catenin metabolism, Adenomatous Polyposis Coli complications, Craniopharyngioma complications, Pituitary Neoplasms complications, beta Catenin genetics
- Abstract
Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome driven by germline loss-of-function of the APC gene and phenotypically manifests with intestinal polyposis and a variety of extra-intestinal bone and soft tissue tumors. Craniopharyngioma is not a well-described FAP-associated tumor, however, six cases have been reported in adults, all demonstrating ectopic location and adamantinomatous histology. We report the first case of craniopharyngioma associated with FAP in a pediatric patient. A seven-year-old girl who presented with headache and vomiting was found on magnetic resonance imaging to have a suprasellar mass with cystic extension to the pre-pontine space. The tumor represented an adamantinomatous craniopharyngioma (aCP) with nuclear β-catenin expression. Whole exome sequencing confirmed a CTNNB1 activating point mutation and a germline APC frameshift variant. This case represents the first FAP-associated craniopharyngioma in childhood…. expanding our understanding of the molecular underpinnings driving tumorigenesis in this unique patient.
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- 2019
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207. In vivo histotripsy brain treatment.
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Sukovich JR, Cain CA, Pandey AS, Chaudhary N, Camelo-Piragua S, Allen SP, Hall TL, Snell J, Xu Z, Cannata JM, Teofilovic D, Bertolina JA, Kassell N, and Xu Z
- Abstract
Objective: Histotripsy is an ultrasound-based treatment modality relying on the generation of targeted cavitation bubble clouds, which mechanically fractionate tissue. The purpose of the current study was to investigate the in vivo feasibility, including dosage requirements and safety, of generating well-confined destructive lesions within the porcine brain utilizing histotripsy technology., Methods: Following a craniectomy to open an acoustic window to the brain, histotripsy pulses were delivered to generate lesions in the porcine cortex. Large lesions with a major dimension of up to 1 cm were generated to demonstrate the efficacy of histotripsy lesioning in the brain. Gyrus-confined lesions were generated at different applied dosages and under ultrasound imaging guidance to ensure that they were accurately targeted and contained within individual gyri. Clinical evaluation as well as MRI and histological outcomes were assessed in the acute (≤ 6 hours) and subacute (≤ 72 hours) phases of recovery., Results: Histotripsy was able to generate lesions with a major dimension of up to 1 cm in the cortex. Histotripsy lesions were seen to be well demarcated with sharp boundaries between treated and untreated tissues, with histological evidence of injuries extending ≤ 200 µm from their boundaries in all cases. In animals with lesions confined to the gyrus, no major hemorrhage or other complications resulting from treatment were observed. At 72 hours, MRI revealed minimal to no edema and no radiographic evidence of inflammatory changes in the perilesional area. Histological evaluation revealed the histotripsy lesions to be similar to subacute infarcts., Conclusions: Histotripsy can be used to generate sharply defined lesions of arbitrary shapes and sizes in the swine cortex. Lesions confined to within the gyri did not lead to significant hemorrhage or edema responses at the treatment site in the acute or subacute time intervals.
- Published
- 2018
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208. Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma.
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Akgül S, Li Y, Zheng S, Kool M, Treisman DM, Li C, Wang Y, Gröbner S, Ikenoue T, Shen Y, Camelo-Piragua S, Tomasek G, Stark S, Guduguntla V, Gusella JF, Guan KL, Pfister SM, Verhaak RGW, and Zhu Y
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- Adult, Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Carcinogenesis pathology, Cell Differentiation, Cell Proliferation, Child, Genome, Human, Glioma genetics, Glioma pathology, Humans, Medulloblastoma genetics, Medulloblastoma pathology, Mice, Mutation genetics, Protein Binding, Proteolysis, Proto-Oncogene Proteins c-akt metabolism, Treatment Outcome, Tumor Suppressor Protein p53 genetics, Glioma metabolism, Hedgehog Proteins metabolism, Mechanistic Target of Rapamycin Complex 2 metabolism, Medulloblastoma metabolism, Rapamycin-Insensitive Companion of mTOR Protein metabolism, Signal Transduction
- Abstract
Most human cancers arise from stem and progenitor cells by the sequential accumulation of genetic and epigenetic alterations, while cancer modeling typically requires simultaneous multiple oncogenic events. Here, we show that a single p53 mutation, despite causing no defect in the mouse brain, promoted neural stem and progenitor cells to spontaneously accumulate oncogenic alterations, including loss of multiple chromosomal (chr) regions syntenic to human chr10 containing Pten, forming malignant gliomas with PI3K/Akt activation. Rictor/mTORC2 loss inhibited Akt signaling, greatly delaying and reducing glioma formation by suppressing glioma precursors within the subventricular zone stem cell niche. Rictor/mTORC2 loss delayed timely differentiation of granule cell precursors (GCPs) during cerebellar development, promoting sustained GCP proliferation and medulloblastoma formation, which recapitulated critical features of TP53 mutant sonic hedgehog (SHH) medulloblastomas with GLI2 and/or N-MYC amplification. Our study demonstrates that Rictor/mTORC2 has opposing functions in neural stem cells and GCPs in the adult and the developing brain, promoting malignant gliomas and suppressing SHH-medulloblastoma formation, respectively., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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209. Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis.
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Sahinoz M, Khairi S, Cuttitta A, Brady GF, Rupani A, Meral R, Tayeh MK, Thomas P, Riebschleger M, Camelo-Piragua S, Innis JW, Bishr Omary M, Michele DE, and Oral EA
- Abstract
Background: Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome., Case Presentation: A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation., Conclusions: This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA , and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted., Competing Interests: Informed assent and consent were obtained from the patient and her mother for genetic testing and fibroblast collection, as well as from the control patient with Duchenne muscular dystrophy under approval from the Institutional Review Board of the University of Michigan Medical School.Consent for publication has been obtained from the patient and her mother, as well as the control subject. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.EAO received grant support from and served as an advisor to Amylin Pharmaceuticals LLC, Bristol-Myers-Squibb, and AstraZeneca. She currently receives grant support and is an advisor to Aegerion Pharmaceuticals, Akcea Therapeutics and Ionis Pharmaceuticals. Other authors have no financial relationships relevant to this article to disclose.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2018
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210. BRAF activating mutations involving the β3-αC loop in V600E-negative anaplastic pleomorphic xanthoastrocytoma.
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Pratt D, Camelo-Piragua S, McFadden K, Leung D, Mody R, Chinnaiyan A, Koschmann C, and Venneti S
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- Astrocytoma diagnostic imaging, Astrocytoma pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology, Child, Preschool, Glutamic Acid genetics, Humans, Male, Proto-Oncogene Proteins B-raf chemistry, Valine genetics, Young Adult, Astrocytoma genetics, Brain Neoplasms genetics, Mutation genetics, Proto-Oncogene Proteins B-raf genetics
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- 2018
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211. Fast and slide-free imaging.
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Orringer DA and Camelo-Piragua S
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- Fluorescent Dyes, Histological Techniques, Humans, Image Processing, Computer-Assisted, Microscopy, Ultraviolet methods, Optical Imaging methods, Pathology methods
- Published
- 2017
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212. Clinical Application of Whole Genome Array Improves the Diagnosis of Pediatric Brain Tumors.
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Shao L, Miller S, Koschmann C, and Camelo-Piragua S
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- Adolescent, Child, Child, Preschool, Female, Humans, Male, Brain Neoplasms diagnosis, Brain Neoplasms genetics, Genome-Wide Association Study methods
- Abstract
Pediatric brain tumors are the leading cause of childhood cancer mortality. Recurring genetic abnormalities play an essential role in the diagnosis and prognosis of pediatric brain tumors. However, clinical workup has not routinely included whole genome assessment. Here, we present high resolution whole genome array results in 11 pediatric brain tumors. Array identified clinically relevant abnormalities in all samples. Copy number aberrations with targeted therapy implication, GOPC-ROS1 fusion, CDK4 amplification, and NF1 deletion, were detected in 3 cases. In addition, array detected recurring genetic abnormalities, including KIAA1549-BRAF fusion, 19q13.42 amplification, i(17q), and monosomy 6, which assisted accurate histological diagnosis in pediatric brain tumors. In conclusion, our results show that whole genome high-resolution array detects diagnostic and treatment-relevant copy number abnormalities in pediatric brain tumors.
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- 2017
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213. Loss of CDKN1C in a Recurrent Atypical Teratoid/Rhabdoid Tumor.
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Tran D, Camelo-Piragua S, Gupta A, Gowans K, Robertson PL, Mody R, and Koschmann C
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- Biopsy, Brain pathology, Combined Modality Therapy, Female, Humans, Immunohistochemistry, Infant, Magnetic Resonance Imaging, Recurrence, Rhabdoid Tumor therapy, Sequence Analysis, DNA, Teratoma therapy, Treatment Outcome, Cyclin-Dependent Kinase Inhibitor p57 genetics, Mutation, Rhabdoid Tumor diagnosis, Rhabdoid Tumor genetics, Teratoma diagnosis, Teratoma genetics
- Abstract
Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that is commonly associated with biallelic alterations of SMARCB1. Recurrent or refractory AT/RT has not been molecularly characterized as well. We present the case of a child with recurrent AT/RT who underwent clinically integrated molecular profiling (germline DNA and tumor DNA/RNA sequencing). This demonstrated a somatic lesion in CDKN1C alongside hallmark loss of SMARCB1. This data allowed us to explore potential personalized therapies for this patient and expose a molecular driver that may be involved in similar cases.
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- 2017
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214. Blood-brain barrier-adapted precision medicine therapy for pediatric brain tumors.
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Marini BL, Benitez LL, Zureick AH, Salloum R, Gauthier AC, Brown J, Wu YM, Robinson DR, Kumar C, Lonigro R, Vats P, Cao X, Kasaian K, Anderson B, Mullan B, Chandler B, Linzey JR, Camelo-Piragua SI, Venneti S, McKeever PE, McFadden KA, Lieberman AP, Brown N, Shao L, Leonard MAS, Junck L, McKean E, Maher CO, Garton HJL, Muraszko KM, Hervey-Jumper S, Mulcahy-Levy JM, Green A, Hoffman LM, Dorris K, Vitanza NA, Wang J, Schwartz J, Lulla R, Smiley NP, Bornhorst M, Haas-Kogan DA, Robertson PL, Chinnaiyan AM, Mody R, and Koschmann C
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- Antineoplastic Agents pharmacokinetics, Child, Gene Expression Regulation, Neoplastic, Humans, Molecular Targeted Therapy, Patient Selection, Predictive Value of Tests, Antineoplastic Agents therapeutic use, Blood-Brain Barrier, Brain Neoplasms drug therapy, Brain Neoplasms metabolism, Precision Medicine methods
- Abstract
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated. Four of five of the patients had potential clinical benefit (partial response or stable disease greater than 6 months on therapy). We further describe the specific drug properties of each agent chosen and discuss characteristics relevant in their evaluation for therapeutic suitability. Finally, we summarize both tumor and drug characteristics that impact the ability to successfully incorporate targeted therapies into CNS malignancy management., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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215. Cerebral Air Embolism: A Clinical, Radiologic and Histopathologic Correlation.
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Roquero LP, Camelo-Piragua S, and Schmidt C
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- Brain Infarction pathology, Coronary Artery Bypass adverse effects, Embolism, Air pathology, Humans, Intracranial Embolism pathology, Male, Middle Aged, Postoperative Complications, Subcutaneous Emphysema pathology, Tomography, X-Ray Computed, Embolism, Air diagnostic imaging, Intracranial Embolism diagnostic imaging
- Abstract
Cerebral air embolism is a recognized life-threatening complication, sometimes iatrogenic. Its timely diagnosis is essential because it can result in neurologic deficits or death. We report a case of a 58-year-old man who died from cerebral air embolism diagnosed by nonenhanced computed tomography scan of the head after a cardiac bypass surgery with Biventricular Assist Device and multiple vascular line placements. Autopsy revealed extensive subcutaneous emphysema, intravascular and perivascular air bubbles in the central nervous system and associated cerebral and cerebellar hemorrhagic infarction. The autopsy was helpful in documenting the extent of the air embolism and its appearance in soft tissue and central nervous system.
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- 2016
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216. Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study.
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Kim MM, Camelo-Piragua S, Schipper M, Tao Y, Normolle D, Junck L, Mammoser A, Betz BL, Cao Y, Kim CJ, Heth J, Sagher O, Lawrence TS, and Tsien CI
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- Adult, Aged, Brain Neoplasms drug therapy, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms pathology, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Disease-Free Survival, Drug Administration Schedule, Female, Glioma drug therapy, Glioma genetics, Glioma mortality, Glioma pathology, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neutropenia etiology, Neutropenia pathology, Radiation-Sensitizing Agents adverse effects, Radiotherapy Dosage, Young Adult, Gemcitabine, Brain Neoplasms radiotherapy, Deoxycytidine analogs & derivatives, Glioma radiotherapy, Radiation-Sensitizing Agents administration & dosage
- Abstract
Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG)., Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m(2) during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity., Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m(2)/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen., Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG., (Published by Elsevier Inc.)
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- 2016
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217. Post-Mortem evaluation of amyloid-dopamine terminal positron emission tomography dementia classifications.
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Albin RL, Fisher-Hubbard A, Shanmugasundaram K, Koeppe RA, Burke JF, Camelo-Piragua S, Lieberman AP, Giordani B, and Frey KA
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- Aged, Aged, 80 and over, Alzheimer Disease diagnostic imaging, Autopsy, Biomarkers, Cognitive Dysfunction diagnostic imaging, Female, Humans, Lewy Body Disease pathology, Male, Middle Aged, Neuropsychological Tests, Parietal Lobe pathology, Positron-Emission Tomography, TDP-43 Proteinopathies pathology, Amyloid metabolism, Dementia classification, Dementia diagnostic imaging, Dopamine metabolism
- Abstract
Clinical classification of early dementia and mild cognitive impairment (MCI) is imprecise. We reported previously that molecular imaging classification of early dementia and MCI with dual amyloid and dopamine terminal positron emission tomography differs significantly from expert clinical classification. We now report pathological diagnoses in a substantial subset of our previously imaged subjects. Among 36 subjects coming to autopsy, imaging classifications and pathological diagnosis were concordant in 33 cases (κ = 0.85). This approach enhanced specificity of Alzheimer's disease diagnosis. The strong concordance of imaging-based classifications and pathological diagnoses suggests that this imaging approach will be useful in establishing more accurate and convenient classification biomarkers for dementia research., (© 2015 American Neurological Association.)
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- 2015
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218. Extensive survey of STAT6 expression in a large series of mesenchymal tumors.
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Demicco EG, Harms PW, Patel RM, Smith SC, Ingram D, Torres K, Carskadon SL, Camelo-Piragua S, McHugh JB, Siddiqui J, Palanisamy N, Lucas DR, Lazar AJ, and Wang WL
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- Cell Nucleus metabolism, Child, Child, Preschool, Humans, Immunohistochemistry, Liposarcoma pathology, Sarcoma pathology, Sensitivity and Specificity, Soft Tissue Neoplasms pathology, Solitary Fibrous Tumors pathology, Tissue Array Analysis, Biomarkers, Tumor metabolism, Liposarcoma metabolism, STAT6 Transcription Factor metabolism, Sarcoma metabolism, Soft Tissue Neoplasms metabolism, Solitary Fibrous Tumors metabolism
- Abstract
Objectives: Expression of strong nuclear STAT6 is thought to be a specific marker for solitary fibrous tumors (SFTs). Little is known about subtle expression patterns in other mesenchymal lesions., Methods: We performed immunohistochemical studies against the C-terminus of STAT6 in tissue microarrays and whole sections, comprising 2366 mesenchymal lesions., Results: Strong nuclear STAT6 was expressed in 285 of 2,021 tumors, including 206 of 240 SFTs, 49 of 408 well-differentiated/dedifferentiated liposarcomas, eight of 65 unclassified sarcomas, and 14 of 184 desmoid tumors, among others. Expression in SFTs was predominately limited to the nucleus. Other positive tumors typically expressed both nuclear and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative, respectively)., Conclusions: Strong nuclear STAT6 is largely specific for SFTs. Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal neoplasia and is of uncertain significance., (Copyright© by the American Society for Clinical Pathology.)
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- 2015
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219. Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa).
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Korytnaya E, Liu J, Camelo-Piragua S, Sullivan S, Auchus RJ, and Barkan A
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- Female, Gastrointestinal Neoplasms complications, Gastrointestinal Neoplasms pathology, Humans, Hyperprolactinemia pathology, Middle Aged, Perivascular Epithelioid Cell Neoplasms complications, Perivascular Epithelioid Cell Neoplasms pathology, Gastrointestinal Neoplasms metabolism, Hyperprolactinemia etiology, Perivascular Epithelioid Cell Neoplasms metabolism, Prolactin metabolism
- Abstract
Background: The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor, and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far., Case Report: A 47-year-old woman presented with amenorrhea and galactorrhea of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 × 13 × 8-cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis and secretion., Conclusion: We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/mL and negative sellar MRI.
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- 2014
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220. CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity.
- Author
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Spence T, Sin-Chan P, Picard D, Barszczyk M, Hoss K, Lu M, Kim SK, Ra YS, Nakamura H, Fangusaro J, Hwang E, Kiehna E, Toledano H, Wang Y, Shi Q, Johnston D, Michaud J, La Spina M, Buccoliero AM, Adamek D, Camelo-Piragua S, Peter Collins V, Jones C, Kabbara N, Jurdi N, Varlet P, Perry A, Scharnhorst D, Fan X, Muraszko KM, Eberhart CG, Ng HK, Gururangan S, Van Meter T, Remke M, Lafay-Cousin L, Chan JA, Sirachainan N, Pomeroy SL, Clifford SC, Gajjar A, Shago M, Halliday W, Taylor MD, Grundy R, Lau CC, Phillips J, Bouffet E, Dirks PB, Hawkins CE, and Huang A
- Subjects
- Adolescent, Age of Onset, Brain Neoplasms diagnosis, Brain Neoplasms therapy, Cell Line, Tumor, Child, Child, Preschool, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA Methylation, Diagnosis, Differential, Female, Gene Expression Regulation, Neoplastic, Humans, Infant, Male, Multigene Family, Neuroectodermal Tumors, Primitive diagnosis, Neuroectodermal Tumors, Primitive therapy, DNA Methyltransferase 3B, Brain Neoplasms genetics, Brain Neoplasms metabolism, MicroRNAs genetics, Neuroectodermal Tumors, Primitive genetics, Neuroectodermal Tumors, Primitive metabolism, RNA-Binding Proteins metabolism
- Abstract
Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity.
- Published
- 2014
- Full Text
- View/download PDF
221. Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy.
- Author
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Baker GJ, Yadav VN, Motsch S, Koschmann C, Calinescu AA, Mineharu Y, Camelo-Piragua SI, Orringer D, Bannykh S, Nichols WS, deCarvalho AC, Mikkelsen T, Castro MG, and Lowenstein PR
- Subjects
- Algorithms, Angiogenesis Inhibitors pharmacology, Animals, Antineoplastic Agents pharmacology, Biopsy, Brain metabolism, Brain pathology, Brain Neoplasms drug therapy, Brain Neoplasms mortality, Brain Neoplasms ultrastructure, Cell Line, Tumor, Disease Models, Animal, Disease Progression, Glioma drug therapy, Glioma mortality, Glioma ultrastructure, Humans, Mice, Mice, Transgenic, Models, Biological, Neoplasm Invasiveness, Rats, Brain Neoplasms etiology, Brain Neoplasms pathology, Drug Resistance, Neoplasm, Glioma etiology, Glioma pathology, Neovascularization, Pathologic, Vascular Endothelial Growth Factor A metabolism
- Abstract
As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM), and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
222. The role of CD133+ cells in a recurrent embryonal tumor with abundant neuropil and true rosettes (ETANTR).
- Author
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Hervey-Jumper SL, Altshuler DB, Wang AC, He X, Maher CO, Robertson PL, Garton HJ, Fan X, Muraszko KM, and Camelo-Piragua S
- Subjects
- AC133 Antigen, Antigens, CD metabolism, Brain Neoplasms diagnosis, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms surgery, Child, Preschool, Chromosomes, Human, Pair 19, Female, Gene Amplification genetics, Glycoproteins metabolism, Humans, Neoplasms, Germ Cell and Embryonal diagnosis, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Neuroblastoma diagnosis, Neuroblastoma genetics, Neuroblastoma pathology, Neuroectodermal Tumors, Primitive diagnosis, Neuroectodermal Tumors, Primitive genetics, Neuroectodermal Tumors, Primitive pathology, Neuroectodermal Tumors, Primitive surgery, Peptides metabolism, Recurrence, Brain Neoplasms metabolism, Neoplasms, Germ Cell and Embryonal metabolism, Neuroblastoma surgery, Neuroectodermal Tumors, Primitive metabolism, Neuropil pathology
- Abstract
Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently described embryonal neoplasm of the central nervous system, consisting of a well-circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropil-like islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein (GFAP) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell (TSC) marker CD133, CD15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD133 was richly expressed after chemotherapy in recurrent ETANTR, while CD15 is depleted compared with that expressed in the original tumor, suggesting that CD133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor., (© 2013 International Society of Neuropathology.)
- Published
- 2014
- Full Text
- View/download PDF
223. Case records of the Massachusetts General Hospital. Case 11-2010. A 69-year-old woman with lethargy, confusion, and abnormalities on brain imaging.
- Author
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Venna N, Gonzalez RG, and Camelo-Piragua SI
- Subjects
- Adrenal Cortex Hormones therapeutic use, Aged, Confusion etiology, Connective Tissue Diseases drug therapy, Depressive Disorder diagnosis, Diagnosis, Differential, Female, Humans, Lethargy etiology, Leukoencephalopathy, Progressive Multifocal complications, Magnetic Resonance Imaging, Opportunistic Infections, Brain pathology, Connective Tissue Diseases complications, Immunocompromised Host, Leukoencephalopathy, Progressive Multifocal pathology
- Published
- 2010
- Full Text
- View/download PDF
224. Images in HIV/AIDS. Painful oral ulcerations in a patient with AIDS.
- Author
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Skiest DJ, Camelo-Piragua S, and Meade L
- Subjects
- AIDS-Related Opportunistic Infections pathology, Adult, Antiretroviral Therapy, Highly Active, Candidiasis drug therapy, Candidiasis etiology, Candidiasis pathology, Esophageal Diseases drug therapy, Esophageal Diseases etiology, Esophageal Diseases pathology, Female, Humans, Oral Ulcer drug therapy, Stomatitis, Aphthous drug therapy, AIDS-Related Opportunistic Infections drug therapy, Acquired Immunodeficiency Syndrome complications
- Published
- 2006
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