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1.
Anesthesiology ; 131(4): 883-893, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31365367

RESUMO

BACKGROUND: Sympathetic dysfunction may be present in complex regional pain syndrome, and sympathetic blocks are routinely performed in practice. To investigate the therapeutic and predictive values of sympathetic blocks, the authors test the hypotheses that sympathetic blocks provide analgesic effects that may be associated with the temperature differences between the two extremities before and after the blocks and that the effects of sympathetic blocks may predict the success (defined as achieving more than 50% pain reduction) of spinal cord stimulation trials. METHODS: The authors performed a retrospective study of 318 patients who underwent sympathetic blocks in a major academic center (2009 to 2016) to assess the association between pain reduction and preprocedure temperature difference between the involved and contralateral limbs. The primary outcome was pain improvement by more than 50%, and the secondary outcome was duration of more than 50% pain reduction per patient report. The authors assessed the association between pain reduction and the success rate of spinal cord stimulation trials. RESULTS: Among the 318 patients, 255 were diagnosed with complex regional pain syndrome and others with various sympathetically related disorders. Successful pain reduction (more than 50%) was observed in 155 patients with complex regional pain syndrome (155 of 255, 61%). The majority of patients (132 of 155, 85%) experienced more than 50% pain relief for 1 to 4 weeks or longer. The degree and duration of pain relief were not associated with preprocedure temperature parameters with estimated odds ratio of 1.03 (97.5% CI, 0.95-1.11) or 1.01 (97.5% CI, 0.96-1.06) for one degree decrease (P = 0.459 or 0.809). There was no difference in the success rate of spinal cord stimulation trials between patients with or without more than 50% pain relief after sympathetic blocks (35 of 40, 88% vs. 26 of 29, 90%, P > 0.990). CONCLUSIONS: The authors conclude that sympathetic blocks may be therapeutic in patients with complex regional pain syndrome regardless of preprocedure limb temperatures. The effects of sympathetic blocks do not predict the success of spinal cord stimulation.


Assuntos
Bloqueio Nervoso Autônomo/métodos , Síndromes da Dor Regional Complexa/terapia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
2.
Nat Commun ; 9(1): 5410, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575736

RESUMO

Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising in the upper portion of the sinonasal cavity. To better understand the genetic bases for ONB, here we perform whole exome and whole genome sequencing as well as single nucleotide polymorphism array analyses in a series of ONB patient samples. Deletions involving the dystrophin (DMD) locus are found in 12 of 14 (86%) tumors. Interestingly, one of the remaining tumors has a deletion in LAMA2, bringing the number of ONBs with deletions of genes involved in the development of muscular dystrophies to 13 or 93%. This high prevalence implicates an unexpected functional role for genes causing hereditary muscular dystrophies in ONB.

3.
Anesthesiology ; 127(4): 726-728, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28926455
4.
Anesthesiology ; 126(1): 47-65, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27792044

RESUMO

BACKGROUND: How best to characterize intraoperative hypotension remains unclear. Thus, the authors assessed the relationship between myocardial and kidney injury and intraoperative absolute (mean arterial pressure [MAP]) and relative (reduction from preoperative pressure) MAP thresholds. METHODS: The authors characterized hypotension by the lowest MAP below various absolute and relative thresholds for cumulative 1, 3, 5, or 10 min and also time-weighted average below various absolute or relative MAP thresholds. The authors modeled each relationship using logistic regression. The authors further evaluated whether the relationships between intraoperative hypotension and either myocardial or kidney injury depended on baseline MAP. Finally, the authors compared the strength of associations between absolute and relative thresholds on myocardial and kidney injury using C statistics. RESULTS: MAP below absolute thresholds of 65 mmHg or relative thresholds of 20% were progressively related to both myocardial and kidney injury. At any given threshold, prolonged exposure was associated with increased odds. There were no clinically important interactions between preoperative blood pressures and the relationship between hypotension and myocardial or kidney injury at intraoperative mean arterial blood pressures less than 65 mmHg. Absolute and relative thresholds had comparable ability to discriminate patients with myocardial or kidney injury from those without. CONCLUSIONS: The associations based on relative thresholds were no stronger than those based on absolute thresholds. Furthermore, there was no clinically important interaction with preoperative pressure. Anesthetic management can thus be based on intraoperative pressures without regard to preoperative pressure.


Assuntos
Lesão Renal Aguda/epidemiologia , Hipotensão/epidemiologia , Complicações Intraoperatórias/epidemiologia , Infarto do Miocárdio/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios , Lesão Renal Aguda/fisiopatologia , Idoso , Pressão Arterial/fisiologia , Estudos de Coortes , Comorbidade , Feminino , Humanos , Hipotensão/fisiopatologia , Complicações Intraoperatórias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Infarto do Miocárdio/fisiopatologia , Ohio/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
5.
Anesth Analg ; 123(3): 749-57, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27537762

RESUMO

BACKGROUND: Clonidine is an α2-adrenoceptor agonist, which has analgesic properties. However, the analgesic efficacy of perioperative clonidine remains unclear. We, therefore, tested the hypothesis that clonidine reduces both pain scores and cumulative opioid consumption during the initial 72 hours after noncardiac surgery. METHODS: Six hundred twenty-four patients undergoing elective noncardiac surgery under general and spinal anesthesia were included in this substudy of the PeriOperative ISchemia Evaluation-2 trial. Patients were randomly assigned to 0.2 mg oral clonidine or placebo 2 to 4 hours before surgery, followed by 0.2 mg/d transdermal clonidine patch or placebo patch, which was maintained until 72 hours after surgery. Postoperative pain scores and opioid consumption were assessed for 72 hours after surgery. RESULTS: Clonidine had no effect on opioid consumption compared with placebo, with an estimated ratio of means of 0.98 (95% confidence interval, 0.70-1.38); P = 0.92. Median (Q1, Q3) opioid consumption was 63 (30, 154) mg morphine equivalents in the clonidine group, which was similar to 60 (30, 128) mg morphine equivalents in the placebo group. Furthermore, there was no significant effect on pain scores, with an estimated difference in means of 0.12 (95% confidence interval, -0.02 to 0.26); 11-point scale; P = 0.10. Mean pain scores per patient were 3.6 ± 1.8 for clonidine patients and 3.6 ± 1.8 for placebo patients. CONCLUSIONS: Clonidine does not reduce opioid consumption or pain scores in patients recovering from noncardiac surgery.


Assuntos
Analgésicos Opioides/administração & dosagem , Clonidina/administração & dosagem , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Manejo da Dor/métodos , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/tratamento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Idoso , Analgésicos/administração & dosagem , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Adesivo Transdérmico
6.
PLoS One ; 11(3): e0150271, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27028405

RESUMO

OBJECTIVE: Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. METHODS: Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. RESULTS: Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. CONCLUSIONS: We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.


Assuntos
Linhagem Celular Tumoral , Glioblastoma/patologia , Adulto , Idoso , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Criopreservação , Feminino , Humanos , Masculino , Camundongos Nus , Repetições de Microssatélites , Pessoa de Meia-Idade , Transplante de Neoplasias , Adulto Jovem
7.
J Clin Anesth ; 27(4): 325-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25837495

RESUMO

BACKGROUND: Optimum positioning of the nerve catheter is crucial for a successful nerve block. We present a novel technique for confirmation of catheter position. METHODS: We are describing a novel technique for localization of the shaft and tip of the peripheral nerve catheter. After introduction of the catheter 3 to 5 cm beyond the needle tip and removal of the needle, the guide wire was reintroduced and was moved inward and outward rapidly. This movement produced the color Doppler effect along the track of the catheter and the catheter tip that helped us verify the proper positioning of the catheter. RESULTS: We used our technique in a cadaveric study for bilateral supraclavicular brachial plexus block, followed by a series of 5 patients undergoing femoral, sciatic (anterior approach), popliteal (2 patients), and brachial plexus blocks. Catheters were also identified on M-Mode sonography during pumping maneuver and during the injection of medications. CONCLUSION: Pumping maneuver and M-Mode can be additional tools in the array of modalities applied to verify proper positioning of a nerve catheter.


Assuntos
Cateterismo/métodos , Cateteres , Bloqueio Nervoso/métodos , Ultrassonografia Doppler em Cores/métodos , Bloqueio do Plexo Braquial/métodos , Cadáver , Cateterismo/instrumentação , Humanos , Nervos Periféricos/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos
8.
Anesthesiology ; 122(2): 276-85, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25603202

RESUMO

BACKGROUND: Core temperature patterns in patients warmed with forced air remain poorly characterized. Also unknown is the extent to which transient and mild intraoperative hypothermia contributes to adverse outcomes in broad populations. METHODS: We evaluated esophageal (core) temperatures in 58,814 adults having surgery lasting >60 min who were warmed with forced air. Independent associations between hypothermic exposure and transfusion requirement and duration of hospitalization were evaluated. RESULTS: In every percentile subgroup, core temperature decreased during the first hour and subsequently increased. The mean lowest core temperature during the first hour was 35.7 ± 0.6°C. Sixty-four percent of the patients reached a core temperature threshold of <36°C 45 min after induction; 29% reached a core temperature threshold of <35.5°C. Nearly half the patients had continuous core temperatures <36°C for more than an hour, and 20% of the patients were <35.5°C for more than an hour. Twenty percent of patients had continuous core temperatures <36°C for more than 2 h, and 8% of the patients were below 35.5°C for more than 2 h. Hypothermia was independently associated with both transfusions and duration of hospitalization, although the prolongation of hospitalization was small. CONCLUSIONS: Even in actively warmed patients, hypothermia is routine during the first hour of anesthesia. Thereafter, average core temperatures progressively increase. Nonetheless, intraoperative hypothermia was common, and often prolonged. Hypothermia was associated with increased transfusion requirement, which is consistent with numerous randomized trials.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Temperatura Corporal/fisiologia , Tempo de Internação , Reaquecimento/métodos , Adulto , Ar , Transfusão de Eritrócitos/métodos , Esôfago/fisiologia , Feminino , Humanos , Hipotermia/terapia , Período Intraoperatório , Masculino
9.
Head Neck ; 37(6): E74-80, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25352487

RESUMO

BACKGROUND: Although uncommon, esthesioneuroblastomas may produce clinically significant amounts of catecholamines. METHODS: We report a patient with a catecholamine-secreting esthesioneuroblastoma who developed an intraoperative hypertensive crisis. RESULTS: A patient with a history of hypertension was referred to our skull base center for management of a residual esthesioneuroblastoma. A staged endonasal endoscopic approach was planned. At the conclusion of the first stage, a hypertensive crisis occurred. Workup revealed elevated levels of serum and urinary catecholamines. The patient was treated with alpha adrenoceptor blockade before the second stage. Serum catecholamine levels after this second stage were normal. On immunohistochemical analysis, the tumor cells were found to be positive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, and achaete-scute homologue 1, a transcription factor essential in the development of olfactory and sympathetic neurons. CONCLUSION: Catecholamine production should be considered in the differential of unexpected extreme hypertension during surgical resection of esthesioneuroblastoma.


Assuntos
Catecolaminas/metabolismo , Estesioneuroblastoma Olfatório/cirurgia , Hipertensão Maligna/diagnóstico , Complicações Intraoperatórias/fisiopatologia , Cavidade Nasal/cirurgia , Neoplasias Nasais/cirurgia , Anti-Hipertensivos/administração & dosagem , Biópsia por Agulha , Endoscopia/efeitos adversos , Endoscopia/métodos , Estesioneuroblastoma Olfatório/diagnóstico , Estesioneuroblastoma Olfatório/metabolismo , Seguimentos , Humanos , Hipertensão Maligna/tratamento farmacológico , Imuno-Histoquímica , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/patologia , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/metabolismo , Doenças Raras , Medição de Risco , Neoplasias da Base do Crânio/sangue , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/cirurgia , Resultado do Tratamento
10.
Oncotarget ; 4(10): 1737-47, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24077805

RESUMO

Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade and progressive gliomas and are characterized by the production of 2-hydroxyglutarate (2-HG) from α-ketoglutarate by the mutant enzyme. 2-HG is an "oncometabolite" that competitively inhibits α-KG dependent dioxygenases resulting in various widespread cellular changes including abnormal hypermethylation of genomic DNA and suppression of cellular differentiation. Despite the growing understanding of IDH mutant gliomas, the development of effective therapies has proved challenging in part due to the scarcity of endogenous mutant in vivo models. Here we report the generation of an endogenous IDH1 anaplastic astrocytoma model which rapidly grows in vivo, produces 2-HG and exhibits DNA hypermethylation. Using this model, we have demonstrated the preclinical efficacy and mechanism of action of the FDA approved demethylating drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in reduction of DNA methylation of promoter loci, induction of glial differentiation, reduction of cell proliferation and a significant reduction in tumor growth. Tumor regression was observed at 14 weeks and subsequently showed no signs of re-growth at 7 weeks despite discontinuation of therapy. These results have implications for clinical trials of demethylating agents for patients with IDH mutated gliomas.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/enzimologia , Glioma/tratamento farmacológico , Glioma/enzimologia , Isocitrato Desidrogenase/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Diferenciação Celular/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Metilação de DNA/efeitos dos fármacos , Feminino , Glioma/genética , Glioma/patologia , Humanos , Imuno-Histoquímica , Isocitrato Desidrogenase/metabolismo , Masculino , Camundongos , Camundongos Nus , Mutação , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncotarget ; 4(4): 572-83, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23592488

RESUMO

A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.


Assuntos
Astrocitoma/genética , Neoplasias do Sistema Nervoso Central/genética , Ependimoma/genética , Glioblastoma/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto Jovem
12.
Cancer Immunol Res ; 1(5): 296-302, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24777967

RESUMO

Meningiomas are the most common primary intracranial tumors. Surgical resection remains the treatment of choice for these tumors. However, a significant number of tumors are not surgically accessible, recur, or become malignant, necessitating the repetition of surgery and sometimes radiation. Chemotherapy is rarely used and is generally not recognized as an effective treatment. Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in patients with cancer and this feature makes them attractive targets for immunotherapy-based approaches. We analyzed mRNA expression of 37 testis-restricted CT genes in a discovery set of 18 meningiomas by reverse transcription PCR. The overall frequency of expression of CT genes ranged from 5.6% to 27.8%. The most frequently expressed was NY-ESO-1, in 5 patients (27.8%). We subsequently analyzed NY-ESO-1 protein expression in a larger set of meningiomas by immunohistochemistry and found expression in 108 of 110 cases. In some cases, NY-ESO-1 expression was diffused and homogenous, but in most instances it was heterogeneous. Importantly, NY-ESO-1 expression was positively correlated with higher grade and patients presenting with higher levels of NY-ESO-1 staining had significantly worse disease-free and overall survival. We have also shown that NY-ESO-1 expression may lead to humoral immune response in patients with meningioma. Considering the limited treatment options for patients with meningioma, the potential of NY-ESO-1-based immunotherapy should be explored.


Assuntos
Antígenos de Neoplasias/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias Meníngeas/imunologia , Neoplasias Meníngeas/terapia , Meningioma/imunologia , Meningioma/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antineoplásicos/biossíntese , Anticorpos Antineoplásicos/genética , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Neoplasias Meníngeas/genética , Meningioma/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Adulto Jovem
13.
J Clin Neurosci ; 19(10): 1437-41, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22836036

RESUMO

The co-existence of pituitary adenomas (PA) and carotid artery aneurysms has been described and may be particularly frequent in acromegaly. The co-occurrence of an intracranial aneurysm in the setting of a PA presents significant risk to the patient, particularly when the aneurysm is within or near the operative field. We describe a 48-year-old, right-handed female patient with a large skull base lesion who had a left cavernous carotid artery aneurysm detected on her preoperative imaging studies. This patient was managed using a staged approach. She first underwent endovascular stent-assisted coiling of the aneurysm followed, six months later, by resection of the tumor via an expanded endonasal endoscopic approach. Histopathological analysis revealed a pituitary macroadenoma with neuronal metaplasia. Angiographic embolization followed by an expanded endonasal endoscopic approach is a safe and effective treatment for such lesions. Vascular imaging studies and a low index for suspicion are required for preoperative identification of such complex situations.


Assuntos
Adenoma/cirurgia , Doenças das Artérias Carótidas/cirurgia , Endoscopia/métodos , Hormônio do Crescimento/metabolismo , Aneurisma Intracraniano/cirurgia , Neoplasias Hipofisárias/cirurgia , Adenoma/complicações , Doenças das Artérias Carótidas/complicações , Feminino , Humanos , Aneurisma Intracraniano/complicações , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Hipófise/patologia , Hipófise/cirurgia , Neoplasias Hipofisárias/complicações
14.
Can J Anaesth ; 59(8): 758-65, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22638675

RESUMO

BACKGROUND: Preoperative chemotherapy is frequently given to shrink or decrease the chance of metastasis. However, chemotherapy has well-recognized side effects that may complicate the perioperative period. We therefore tested the hypotheses that chemotherapy within 30 days before cancer surgery is associated with an increased risk of mortality and with a composite of major morbidities within 30 postoperative days. METHODS: We evaluated 971,455 patients from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were defined as having chemotherapy when they were given any chemotherapy for malignancy within 30 days before surgery. We successfully matched 1,348 pairs of chemotherapy recipients and non-recipients. RESULTS: Twenty-one of the 1,348 (1.6%) non-chemotherapy patients died within 30 days after surgery compared with 30 of the 1,348 (2.2%) chemotherapy patients. The odds of mortality were not statistically different between groups based on our logistic regression model [odds ratio (OR) = 1.47; 95% confidence interval (CI) 0.82 to 2.64; P = 0.19]. The most common complication observed was wound infection in 13.1% of non-chemotherapy patients compared with 14.2% of the chemotherapy patients. There was similarly no difference between groups for the collapsed composite of major morbidities [OR = 1.17; 95% CI 0.97 to 1.42; P = 0.09]. CONCLUSION: Preoperative use of neoadjuvant chemotherapy in cancer patients undergoing resection surgeries was not associated with a higher rate of early postoperative complications or mortality.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias/cirurgia , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Bases de Dados Factuais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Fatores de Tempo
15.
J Neurosurg ; 116(4): 801-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22283186

RESUMO

OBJECT: Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient's tumor are essential for the development and evaluation of effective therapeutics. Currently, there are only a few established chordoma cell lines and no primary xenograft model. In this study, the authors aimed to develop a primary chordoma xenograft model. METHODS: The authors implanted independent tumor samples from 2 patients into athymic nude mice. The resulting xenograft line was characterized by histopathological analysis and immunohistochemical staining. The patient's tumor and serial passages of the xenograft were genomically analyzed using a 660,000 single-nucleotide polymorphism array. RESULTS: A serially transplantable xenograft was established from one of the 2 patient samples. Histopathological analysis and immunohistochemical staining for S100 protein, epithelial membrane antigen, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed that the xenografts were identical to the original chordoma obtained from the patient. Immunohistochemical staining and western blot analysis confirmed the presence of brachyury, a recently described marker of chordomas, in the tumor from the patient and each of the xenografts. Genome-wide variation was assessed between the patient's tumor and the xenografts and was found to be more than 99.9% concordant. CONCLUSIONS: To the best of their knowledge, the authors have established the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.


Assuntos
Cordoma/patologia , Modelos Animais de Doenças , Transplante de Neoplasias , Neoplasias da Medula Espinal/patologia , Transplante Heterólogo , Animais , Biomarcadores Tumorais/análise , Cordoma/genética , Feminino , Genótipo , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
16.
Childs Nerv Syst ; 28(1): 151-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22041975

RESUMO

Benign smooth muscle tumors rarely occur in the head and neck and, to the best of our knowledge, have not been reported in the pterygopalatine fossa. In this report, we describe a 15-year-old adolescent who presented with facial pain and was found to have a large skull base tumor centered in the pterygopalatine fossa. The patient underwent an expanded endonasal endoscopic approach for complete resection of this lesion with resolution of his symptoms. Pathology revealed a well-differentiated smooth muscle neoplasm consistent with a leiomyoma. This case adds to the growing body of literature supporting a role for endoscopic procedures in the treatment of skull base pathologies in pediatric patients.


Assuntos
Neoplasias de Tecido Muscular/cirurgia , Neoplasias da Base do Crânio/cirurgia , Adolescente , Humanos , Masculino , Cavidade Nasal/cirurgia , Estadiamento de Neoplasias , Neoplasias de Tecido Muscular/patologia , Neoplasias da Base do Crânio/patologia
17.
Neurosurg Rev ; 34(4): 465-75, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21655908

RESUMO

Esthesioneuroblastoma is an uncommon malignant tumor originating in the upper nasal cavity. The surgical treatment for this tumor has traditionally been via an open craniofacial resection. Over the past decade, there has been tremendous development in endoscopic techniques. In this report, we performed a retrospective analysis of patients with esthesioneuroblastomas treated with a purely endonasal endoscopic approach and resection at the Johns Hopkins Hospital between January 2005 and April 2010. A total of eight patients with esthesioneuroblastoma, five men and three women, were identified. Six patients were treated for primary disease, and two were treated for tumor recurrence. The modified Kadish staging was A in one patient (12.5%), B in two patients (25%), C in four patients (50%), and D in one patient (12.5%). All patients had a complete resection with negative intraoperative margins. One patient had intraoperative hypertension; there were no perioperative complications. With a mean follow-up of over 27 months, all patients are without evidence of disease. In addition, we reviewed the literature and identified several overlapping case series of patients with esthesioneuroblastoma treated via a purely endoscopic technique. Our series adds to the growing experience of expanded endonasal endoscopic surgery in the treatment of skull base tumors including esthesioneuroblastoma. Longer follow-up on a larger number of patients is required to further demonstrate the utility of endoscopic approaches in the management of this malignancy.


Assuntos
Endoscopia , Estesioneuroblastoma Olfatório/cirurgia , Cavidade Nasal/cirurgia , Neoplasias Nasais/cirurgia , Adulto , Idoso , Desbridamento , Dura-Máter/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Procedimentos Neurocirúrgicos , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Neoplasias da Base do Crânio/cirurgia , Tomografia Computadorizada Espiral , Resultado do Tratamento
18.
Childs Nerv Syst ; 27(4): 649-56, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21132434

RESUMO

Aneurysmal bone cysts (ABCs) are uncommon non-neoplastic, hemorrhagic, and expansile osseous lesions. These lesions most commonly occur in the first two decades of life and affect the long bones and spinal column. Skull base involvement is rare. The authors report the case of a 16-year-old boy who presented with acute visual decline and was found to have a large skull base ABC centered in the sphenoid sinus. In addition, the patient had extensive cranial fibrous dysplasia. The patient underwent a staged expanded endonasal endoscopic approach for complete resection of this lesion with excellent return of his vision. This case adds to the growing body of evidence supporting a role for expanded endonasal endoscopic procedures in pediatric patients with skull base pathologies.


Assuntos
Cistos Ósseos Aneurismáticos/cirurgia , Encefalopatias/cirurgia , Displasia Fibrosa Poliostótica/complicações , Neuroendoscopia/métodos , Base do Crânio/cirurgia , Adolescente , Cistos Ósseos Aneurismáticos/etiologia , Cistos Ósseos Aneurismáticos/patologia , Encefalopatias/etiologia , Encefalopatias/patologia , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/patologia , Humanos , Masculino , Mutação de Sentido Incorreto , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Base do Crânio/patologia , Campos Visuais
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