RESUMEN
BACKGROUND: Neurologic deficit is known as a rare complication of thoracic spinal cord stimulator (SCS) paddle lead implantation, but many believe its incidence after SCS paddle lead placement is under-reported. It is possible that imaging characteristics may be used to help predict safe paddle lead placement. OBJECTIVE: This imaging study was undertaken to determine the minimum canal diameter required for safe paddle lead placement. METHODS: Patients who underwent thoracic laminotomy for new SCS paddle lead placement from January 2018 to March 2023 were identified retrospectively. Preoperative thoracic canal diameter was measured in the sagittal plane perpendicular to the disc space from T5/6 to T11/12. These thoracic levels were chosen because they span the most common levels targeted for SCS placement. Patients with and without new neurologic deficits were compared using a Mann-Whitney U-test. RESULTS: Of 185 patients initially identified, 180 had thoracic imaging available for review. One (0.5%) and 2 (1.1%) of 185 patients complained of permanent and transient neurologic deficit after thoracic SCS placement, respectively. Patients with neurologic deficits had average canal diameters of <11 mm. The average canal diameter of patients with and without neurologic deficits was 10.2 mm (range 6.1-12.9 mm) and 13.0 mm (range 5.9-20.2), respectively (p < 0.0001). CONCLUSION: Postoperative neurologic deficit is an uncommon complication after thoracic laminotomy for SCS paddle lead placement. The authors recommend ensuring a starting thoracic canal diameter of at least 12 mm to accommodate a SCS paddle lead measuring 2 mm thick to ensure a final diameter of >10 mm. If canal diameter is <12 mm, aggressive undercutting of the lamina, a second laminotomy, or placement of smaller SCS wire leads should be considered.
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Terapia por Estimulación Eléctrica , Estimulación de la Médula Espinal , Humanos , Estudios Retrospectivos , Electrodos Implantados/efectos adversos , Médula Espinal , Terapia por Estimulación Eléctrica/métodos , Canal Medular/diagnóstico por imagen , Canal Medular/cirugía , Estimulación de la Médula Espinal/efectos adversos , Estimulación de la Médula Espinal/métodosRESUMEN
QUESTION: What is the optimal role of biopsy in the initial management of presumptive low-grade glioma in adults? TARGET POPULATION: Adult patients with imaging suggestive of a low-grade glioma. LEVEL III: Stereotactic biopsy is recommended when definitive surgical resection is limited by lesions that are deep-seated, not resectable, and/or located within eloquent cortex, or in patients unable to undergo craniotomy due to medical co-morbidities to obtain the critical tissue diagnosis needed for targeted treatment planning for patients with low-grade gliomas. QUESTION: What is the best technique for brain biopsy? TARGET POPULATION: Adult patients with imaging suggestive of a low-grade glioma. LEVEL III: Frameless and frame-based stereotactic brain biopsy for low-grade gliomas are recommended based on clinical circumstances as they provide similar diagnostic yield, diagnostic accuracy, morbidity, and mortality. It is recommended the surgeon consider advanced imaging techniques (e.g., perfusion, spectroscopy, metabolic studies) to target specific regions of interest to potentially improve diagnostic accuracy.
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Biopsia , Neoplasias Encefálicas , Encéfalo , Glioma , Humanos , Biopsia/métodos , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Manejo de la Enfermedad , Medicina Basada en la Evidencia , Glioma/diagnóstico , Glioma/patología , Glioma/terapia , Clasificación del Tumor , Procedimientos Neuroquirúrgicos/métodosRESUMEN
OBJECT: The authors evaluated the efficacy of posterior instrumentation for the management of spontaneous spinal infections. Standard surgical management of spontaneous spinal infection is based on debridement of the infected tissue. However, this can be very challenging as most of these patients are medically debilitated and the surgical debridement requires a more aggressive approach to the spine either anteriorly or via an expanded posterior approach. The authors present their results using an alternative treatment method of posterior-only neuro-decompression and stabilization without formal debridement of anterior tissue for treating spontaneous spinal infection. METHODS: Fifteen consecutive patients were treated surgically by 2 of the authors. All patients had osteomyelitis and discitis and were treated postoperatively with intravenous antibiotics for at least 6 weeks. The indications for surgery were failed medical management, progressive deformity with ongoing persistent spinal infection, or neurological deficit. Patients with simple epidural abscess without bony instability were treated with laminectomy and were not included in this series. Fourteen patients were treated with posterior-only decompression and long-segment rigid fixation, without formal debridement of the infected area. One patient was treated with staged anterior and posterior surgery due to delay in treatment related to medical comorbidities. The authors examined as their outcome the ambulatory status and recurrence of deep infection requiring additional surgery or medical treatment. RESULTS: Of the initial 15 patients, 10 (66%) had a minimum 2-year follow-up and 14 patients had at least 1 year of followup. There were no recurrent spinal infections. There were 3 unplanned reoperations (1 for loss of fixation, 1 for early superficial wound infection, and 1 for epidural hematoma). Nine (60%) of 15 patients were nonambulatory at presentation. At final followup, 8 of 15 patients were independently ambulatory, 6 required an assistive device, and 1 remained nonambulatory. CONCLUSIONS: Long-segment fixation, without formal debridement, resulted in resolution of spinal infection in all cases and in significant neurological recovery in almost all cases. This surgical technique, when combined with aggressive antibiotic therapy and a multidisciplinary team approach, is an effective way of managing serious spinal infections in a challenging patient population.
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Discitis/cirugía , Osteomielitis/cirugía , Fusión Vertebral/métodos , Anciano , Desbridamiento , Descompresión Quirúrgica , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vértebras Torácicas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Cervical spine clearance in severely injured children after trauma is often difficult because of unique injury patterns, concerns about radiation exposure to growing tissue, and unfamiliarity with unstable cervical injuries. We prospectively assessed the utility of four radiographic modalities to clear the cervical spine in children after severe trauma. METHODS: Twenty-four comatose, intubated children with severe traumatic injuries underwent radiographic evaluation to clear the cervical spine. Each patient had plain radiographs, flexion-extension radiographs under fluoroscopy, computed tomography (CT), and magnetic resonance (MR) imaging within 10 days of admission. Patients underwent cervical spine flexion-extension radiographs 2-3 months after trauma to detect late instability. Sensitivity and specificity for each radiographic modality was determined. RESULTS: Plain cervical spine radiographs demonstrated sensitivity of 100% and specificity of 95%; flexion-extension radiographs had "indeterminate" sensitivity and specificity of 100%. For CT, sensitivity was 100% and specificity was 95%, and for MR imaging, sensitivity was 100% and specificity was 74%. CONCLUSIONS: There was a low prevalence of cervical instability in this high-risk group. Plain radiographs, flexion-extension radiographs, and CT all had high sensitivities and specificities. MR imaging had a high false-positive rate, making it sensitive but not specific. The data support using either CT or plain radiographs as the initial cervical spine screening study, but CT is recommended because of its superior ability to detect critical injuries. To definitively rule out ligamentous instability after a negative screening CT scan or cervical spine X-ray, these data support using flexion-extension X-rays with fluoroscopy and not MR imaging.
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Vértebras Cervicales/diagnóstico por imagen , Puntaje de Gravedad del Traumatismo , Inestabilidad de la Articulación/diagnóstico por imagen , Traumatismos Vertebrales/diagnóstico por imagen , Índices de Gravedad del Trauma , Adolescente , Vértebras Cervicales/lesiones , Niño , Preescolar , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/normas , Masculino , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normasRESUMEN
In this article, we provide a brief description of the current understanding of aberrant signaling pathways in meningiomas. Cell signaling pathways are responsible for cellular differentiation, development, growth, growth inhibition, and death. In fact, signaling pathways can affect multiple intracellular functions, including those responsible for development, angiogenesis, and apoptosis. Ultimately, a further understanding of the signaling pathways involved in meningioma tumorigenesis will lead to the development and application of novel molecular treatments, such as small molecule inhibitors or interfering ribonucleic acid technologies.
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Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Transducción de Señal , Animales , Humanos , Neoplasias Meníngeas/patología , Meningioma/patologíaRESUMEN
For a physician has the worth of many other warriors, both for the excision of arrows and for the administration of soothing drugs. Homer, Iliad XI.514-515 Ever since armed conflict has been used as a means to settle disputes among men, there have been those who have been tasked to mend the wounds that ravage a soldier's body from the weapons of war. The Iliad portrays the pivotal 10th year of the legendary Trojan War, during which a schism in the Greek leadership prolongs the extended siege of the city of Troy. In the midst of this martial epic come the lines quoted above, quietly attesting to the value of the military physician, even under the crude conditions of the Greek Dark Age. They are uttered by Idomeneus, one of the foremost Greeks, when he is enjoining one of his comrades, Nestor, to rescue the injured Greek physician Machaon and take him back from the line to treat his wounds. He is afraid that Machaon will be captured by the Trojans, a loss far greater than that of any other single warrior. Duty to country has helped shape the careers of many neurosurgeons, including iconic US figures such as Harvey Cushing and Donald Matson. This issue of Neurosurgical Focus celebrates the rich history of military neurosurgery from the wars of yesterday to the conflicts of today. We have been humbled by the tremendous response to this topic. The 25 articles within this issue will provide the reader with both a broad and an in-depth look at the many facets of military neurosurgery. We have attempted to group articles based on their predominant topic. We also encourage our audience to read other recently published articles. The first 8 articles relate to the current conflicts in Afghanistan and Iraq. The lead article, written by Randy Bell and colleagues from the National Naval Medical Center and Walter Reed Army Medical Center, discusses what is arguably one of the most important contributions by military neurosurgeons from these 2 conflicts: the rapid and aggressive use of decompressive craniectomies. This is followed by articles on decompressive craniectomy techniques by Ragel and colleagues and cranioplasty outcomes by Stephens and colleagues. After reading these articles, the reader will come away with an appreciation of the often complex nature of wartime penetrating and closed-head injuries and the remarkable recovery that many injured soldiers make with time.
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Medicina Militar/historia , Neurocirugia/historia , Afganistán , Historia del Siglo XXI , Humanos , Irak , Masculino , Medicina Militar/métodos , Neurocirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Estados Unidos , GuerraRESUMEN
OBJECT: Penetrating spinal injury (PSI), although an infrequent injury in the civilian population, is not an infrequent injury in military conflicts. Throughout military history, the role of surgery in the treatment of PSI has been controversial. The US is currently involved in 2 military campaigns, the hallmark of both being the widespread use of various explosive devices. The authors reviewed the evidence for or against the use of decompressive laminectomy to treat PSI to provide a triservice (US Army, Navy, and Air Force) consensus and treatment recommendations for military neurosurgeons and spine surgeons. METHODS: A US National Library of Medicine PubMed database search that identified all literature dealing with acute management of PSI from military conflicts and civilian urban trauma centers in the post-Vietnam War period was undertaken. RESULTS: Nineteen retrospective case series (11 military and 8 civilian) met the study criteria. Eleven military articles covered a 20-year time span that included 782 patients who suffered either gunshot or blast-related projectile wounds. Four papers included sufficient data that analyzed the effectiveness of surgery compared with nonoperative management, 6 papers concluded that surgery was of no benefit, 2 papers indicated that surgery did have a role, and 3 papers made no comment. Eight civilian articles covered a 9-year time span that included 653 patients with spinal gunshot wounds. Two articles lacked any comparative data because of treatment bias. Two papers concluded that decompressive laminectomy had a beneficial role, 1 paper favored the removal of intracanal bullets between T-12 and L-4, and 5 papers indicated that surgery was of no benefit. CONCLUSIONS: Based on the authors' military and civilian PubMed literature search, most of the evidence suggests that decompressive laminectomy does not improve neurological function in patients with PSI. However, there are serious methodological shortcomings in both literature groups. For this and other reasons, neurosurgeons from the US Air Force, Army, and Navy collectively believe that decompression should still be considered for any patient with an incomplete neurological injury and continued spinal canal compromise, ideally within 24-48 hours of injury; the patient should be stabilized concurrently if it is believed that the spinal injury is unstable. The authors recognize the highly controversial nature of this topic and hope that this literature review and the proposed treatment recommendations will be a valuable resource for deployed neurosurgeons. Ultimately, the deployed neurosurgeon must make the final treatment decision based on his or her opinion of the literature, individual abilities, and facility resources available.
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Descompresión Quirúrgica/métodos , Laminectomía/métodos , Medicina Militar/métodos , Procedimientos Neuroquirúrgicos/métodos , Traumatismos Vertebrales/cirugía , Adulto , Traumatismos por Explosión/cirugía , Femenino , Cirugía General/métodos , Humanos , Masculino , Ortopedia/métodos , PubMed/estadística & datos numéricos , Columna Vertebral/cirugía , Resultado del Tratamiento , Heridas por Arma de Fuego/cirugía , Heridas Penetrantes/cirugíaRESUMEN
OBJECT: Decompressive craniectomy (DC) with dural expansion is a life-saving neurosurgical procedure performed for recalcitrant intracranial hypertension due to trauma, stroke, and a multitude of other etiologies. Illustratively, we describe technique and lessons learned using DC for battlefield trauma. METHODS: Neurosurgical operative logs from service (October 2007 to September 2009) in Afghanistan that detail DC cases for trauma were analyzed. Illustrative examples of frontotemporoparietal and bifrontal DC that depict battlefield experience performing these procedures are presented with attention drawn to the L.G. Kempe hemispherectomy incision, brainstem decompression techniques, and dural onlay substitutes. RESULTS: Ninety craniotomies were performed for trauma over the time period analyzed. Of these, 28 (31%) were DCs. Of the 28 DCs, 24 (86%) were frontotemporoparietal DCs, 7 (25%) were bifrontal DCs, and 2 (7%) were suboccipital DCs. Decompressive craniectomies were performed for 19 penetrating head injuries (13 gunshot wounds and 6 explosions) and 9 severe closed head injuries (6 war-related explosions and 3 others). CONCLUSIONS: Thirty-one percent of craniotomies performed for trauma were DCs. Battlefield neurosurgeons use DC to allow for safe transfer of neurologically ill patients to tertiary military hospitals, which can be located 8-18 hours from a war zone. The authors recommend the L.G. Kempe incision for blood supply preservation, large craniectomies to prevent brain strangulation over bone edges, minimal brain debridement, adequate brainstem decompression, and dural onlay substitutes for dural closure.
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Lesiones Encefálicas/cirugía , Craniectomía Descompresiva/métodos , Guerra , Adolescente , Adulto , Campaña Afgana 2001- , Afganistán , Preescolar , Duramadre/cirugía , Cirugía General/métodos , Hemisferectomía/métodos , Humanos , Hipertensión Intracraneal/cirugía , Medicina Militar/métodos , Procedimientos Neuroquirúrgicos/métodos , Colgajos Quirúrgicos , Resultado del Tratamiento , Heridas por Arma de Fuego/cirugía , Heridas Penetrantes/cirugíaRESUMEN
OBJECT: "Operation Enduring Freedom" is the US war effort in Afghanistan in its global war on terror. One US military neurosurgeon is deployed in support of Operation Enduring Freedom to provide care for both battlefield injuries and humanitarian work. Here, the authors analyze a 24-month neurosurgical caseload experience in Afghanistan. METHODS: Operative logs were analyzed between October 2007 and September 2009. Operative cases were divided into minor procedures (for example, placement of an intracranial pressure monitor) and major procedures (for example, craniotomy) for both battle injuries and humanitarian work. Battle injuries were defined as injuries sustained by soldiers while in the line of duty or injuries to Afghan civilians from weapons of war. Humanitarian work consisted of providing medical care to Afghans. RESULTS: Six neurosurgeons covering a 24-month period performed 115 minor procedures and 210 major surgical procedures cases. Operations for battlefield injuries included 106 craniotomies, 25 spine surgeries, and 18 miscellaneous surgeries. Humanitarian work included 32 craniotomies (23 for trauma, 3 for tumor, 6 for other reasons, such as cyst fenestration), 27 spine surgeries (12 for degenerative conditions, 9 for trauma, 4 for myelomeningocele closure, and 2 for the treatment of infection), and 2 miscellaneous surgeries. CONCLUSIONS: Military neurosurgeons have provided surgical care at rates of 71% (149/210) for battlefield injuries and 29% (61/210) for humanitarian work. Of the operations for battle trauma, 50% (106/210) were cranial and 11% (25/210) spinal surgeries. Fifteen percent (32/210) and 13% (27/210) of operations were for humanitarian cranial and spine procedures, respectively. Overall, military neurosurgeons in Afghanistan are performing life-saving cranial and spine stabilization procedures for battlefield trauma and acting as general neurosurgeons for the Afghan community.
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Campaña Afgana 2001- , Medicina Militar , Neurocirugia/métodos , Neurocirugia/estadística & datos numéricos , Heridas y Lesiones/cirugía , Adolescente , Adulto , Altruismo , Craniectomía Descompresiva/métodos , Femenino , Hospitales Militares , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Colgajos Quirúrgicos , Heridas Penetrantes/cirugíaRESUMEN
PURPOSE: Anterior vertebral body reconstruction (AVBR) for trauma or tumor involves corpectomy and placement of hardware to reconstitute the anterior weight-bearing stability of the spine. We report our clinical experience with thoracoscopic techniques for AVBR. METHODS: We retrospectively analyzed patients who underwent thoracoscopic AVBR surgery for expandable cage placement. We report pathological condition, patient age, vertebral body level, operative time, estimated blood loss (EBL), and need for blood transfusion. RESULTS: Twenty-one expandable cages were placed thoracoscopically in 15 fractures and six tumors. In fracture cases, mean age, operative time, EBL, and transfusion rate were 36.7 years, 4.9 h, 543 mL, and 7% (1/15), respectively. In tumor cases, mean age, operative time, EBL, and transfusion rate were 61.9 years, 4.9 h, 758 mL, and 17% (1/6), respectively. CONCLUSIONS: Thoracoscopic AVBR with expandable cages can be accomplished safely with acceptable operative times and blood loss and low transfusion rates.
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Pérdida de Sangre Quirúrgica/fisiopatología , Transfusión Sanguínea , Fracturas Espontáneas/cirugía , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Prótesis e Implantes , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Toracoscopía/métodos , Titanio , Adolescente , Adulto , Anciano , Descompresión Quirúrgica/métodos , Femenino , Fracturas Espontáneas/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Radiografía , Fracturas de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/secundario , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/lesiones , Adulto JovenRESUMEN
The authors report the case of laparoscopic-induced pneumocephalus in a ventriculoperitoneal shunt (VPS) patient undergoing a transperitoneal laparoscopic procedure. This case represents the first instance, to our knowledge, of forced retrograde air through a Holter valve placed 20 years ago. Abdominal laparoscopic surgery is a minimally invasive procedure utilized for a wide spectrum of abdominal and pelvic disorders. VPS systems for cerebrospinal fluid diversion are used to treat hydrocephalus. We present a case of laparoscopic-induced pneumocephalus in a VPS patient undergoing a transperitoneal laparoscopic procedure.
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Laparoscopía/efectos adversos , Neumocéfalo/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Derivación Ventriculoperitoneal , Femenino , Humanos , Neumocéfalo/etiología , Complicaciones Posoperatorias/etiología , Adulto JovenRESUMEN
Higher-grade gliomas are distinguished by increased vascular endothelial cell proliferation and peritumoral edema. These are thought to be instigated by vascular endothelial growth factor, which in turn is regulated by cellular oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) is a main responder to intracellular hypoxia and is overexpressed in many human cancers, including gliomas. Here we present methods for investigating the role of HIF-1alpha in glioma growth in vivo and in vitro using RNA interference in U251, U87, and U373 glioma cells.
Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Interferencia de ARN , ARN Interferente Pequeño/uso terapéutico , Animales , Western Blotting , Neoplasias Encefálicas/genética , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica/efectos de los fármacos , Terapia Genética/métodos , Glioma/genética , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Hipoxia , Técnicas para Inmunoenzimas , Ratones , Ratones Desnudos , Reacción en Cadena de la Polimerasa , Transfección , Ubiquitina-Proteína Ligasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: Neurosurgeons at David Grant Medical Center (DGMC) have had low surgeon case volumes. Meanwhile, veterans have had long waits because of inadequate neurosurgical coverage. DGMC and Department of Veteran Affairs (VA) agreed to share resources to treat an underserved VA patient population. We analyzed number of cases, admissions, relative weighted product (RWP), and outpatient visits before and after this unique military-VA agreement. METHODS: Number of operations, hospital admissions, RWP, and outpatient visits (January 2004-November 2007) were noted before or after October 2006. To normalize data, metric (e.g, number of cases) totals were divided by number of months neurosurgeons were available. RESULTS: Before the agreement, two neurosurgeons performed 210 operations over 52 months (4.0 cases/month). After the agreement, two neurosurgeons performed 177 cases over 26 months (6.8 cases/month). This corresponded to a 2.2-, 2.2-, and 2.0-fold increase in hospital admissions, RWP, and outpatient visits, respectively. CONCLUSIONS: The sharing agreement resulted in 1.7-fold increase in operative cases. This military-VA venture provides military neurosurgeons with more surgical cases and provides neurosurgical care to a previously underserved patient population.
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Hospitales Militares , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , United States Department of Veterans Affairs/organización & administración , Carga de Trabajo , California , Humanos , Neurocirugia , Estados Unidos , Veteranos , Listas de Espera , Recursos HumanosRESUMEN
OBJECT: Meningioma research has been hindered by the inability to sequentially measure intracranial tumor growth in a cost-effective, efficient manner. Recently, the luciferase gene has been transfected into cancer lines to obtain cells that express the luciferase enzyme, which oxidizes luciferin in a reaction that releases photon energy that can be measured noninvasively by bioluminescence imaging (BLI) systems. The authors describe a mouse model of intracranial meningioma that uses this novel BLI system. METHODS: The immortal meningioma cell lines CH-157-MN and IOMM-Lee were transfected with luciferase and neomycin phosphotransferase (LucNeo) and selected with G418. These cells were stereotactically implanted at skull base and cerebral convexity locations in nude mice. Animals were imaged for bioluminescence biweekly, and 5 mice underwent magnetic resonance (MR) imaging. Tumors were harvested for immunohistochemical and ultrastructural analysis. RESULTS: The CH-157-MN-LucNeo and IOMM-Lee-LucNeo cell lines were successfully implanted intracranially in mice. The tumor induction rate for CH-157-MN-LucNeo skull base tumors was 90% (36 of 40 procedures). Statistical analysis of CH-157-MN-LucNeo skull base tumor volume measured on MR imaging correlated with the results of BLI showed an R value of 0.900. The tumors exhibited characteristics of aggressive meningiomas by insinuating along arachnoid planes and invading brain. CONCLUSIONS: Noninvasive BLI was successfully used to image intracranial meningiomas in mice. The tumors grew in a fashion similar to that of aggressive meningiomas in humans, and exhibited the microscopic, immunohistochemical, and ultrastructural features characteristic of meningiomas. This animal model overcomes the main obstacle in studying intracranial meningiomas by enabling sequential noninvasive tumor measurement in a cost-effective manner.
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Luciferasas/metabolismo , Sustancias Luminiscentes/metabolismo , Meningioma/patología , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/análisis , Humanos , Kanamicina Quinasa/genética , Antígeno Ki-67/análisis , Luciferasas/genética , Luminiscencia , Imagen por Resonancia Magnética , Ratones , Ratones Desnudos , Mucina-1/análisis , Invasividad Neoplásica , Trasplante de Neoplasias , Neoplasias de la Base del Cráneo/patología , Transfección , Trasplante Heterólogo , Vimentina/análisisRESUMEN
PURPOSE: Higher-grade gliomas are distinguished by increased vascular endothelial cell proliferation and peritumoral edema. These are thought to be instigated by vascular endothelial growth factor, which, in turn, is regulated by cellular oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) is a main responder to intracellular hypoxia and is overexpressed in many human cancers, including gliomas. EXPERIMENTAL DESIGN: We investigated the role of HIF-1alpha in glioma growth in vivo using RNA interference (RNAi) in U251, U87, and U373 glioma cells. RESULTS: We found that RNAi can be used to significantly attenuate glioma growth by reducing HIF-1alpha levels constitutively using short hairpin RNAs and transiently using small interfering RNAs (siRNA). HIF-1alpha levels on average were reduced 55% in normoxia and 71% in hypoxia. Vascular endothelial growth factor and GLUT-1 levels were reduced 81% and 71%, respectively, in the stable HIF-1alpha-reduced clones. These clones showed significant growth attenuation (up to 73%) compared with negative controls when grown in vivo in mouse flanks. Cellular proliferation was also reduced significantly, as determined by MIB-1 staining. Treating gliomas grown in mouse flank transiently with siRNA against HIF-1alpha by intratumoral injection resulted in a significant reduction of HIF-1alpha activity. This activity was followed using a hypoxia-responsive luciferase construct that enabled hypoxia imaging in vivo. Tumor volume in these siRNA injection experiments was reduced by 50% over the negative controls. CONCLUSIONS: These results indicate that transient RNAi directed against HIF-1alpha can effectively curb glioma growth in vivo.
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Silenciador del Gen , Glioma/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Animales , División Celular/genética , Línea Celular Tumoral , Glioma/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Ratones , Ratones Desnudos , Reacción en Cadena de la Polimerasa , Interferencia de ARN , Transfección , Trasplante Heterólogo , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
BACKGROUND: Immortal cell lines and cell lines derived from operative specimens transplanted into animal models are used in meningioma research. We address 2 criticisms of the mouse xenograft flank tumor model: Why are tumor induction rates derived from operative specimens low and inconsistent? Are flank tumors meningiomas? METHODS: Meningioma cell cultures were processed for Giemsa-band karyotyping and flow cytometry. Mouse flank tumors induced subcutaneously were analyzed microscopically, immunohistochemically, and ultrastructurally. Giemsa-band studies identified meningiomas with simple karyotype (< or =1 chromosomal abnormality) or complex karyotype (multiple chromosomal abnormalities). RESULTS: Cell cultures with complex karyotypes (IOMM-Lee, CH-157 MN, 2 operative specimens) grew rapidly in vitro and induced tumors in 49 (98%) of 50 animals. Meningioma cell cultures with simple karyotypes grew slowly in vitro and showed small, nongrowing tumors in mouse flanks (10/10). Meningioma flank tumors were vimentin-positive with ultrastructural features consistent with meningiomas. Cell cultures with complex karyotypes grew faster in cell culture and consistently induced flank tumors, unlike meningiomas with simple karyotypes. CONCLUSIONS: Meningioma cell lines transplanted into flanks of nude mice exhibit microscopic, immunohistochemical, and ultrastructural features of meningiomas. The ease of monitoring tumor growth in the subcutaneous mouse flank model is its primary advantage, although we recognize an intracranial location is more biologically desirable.
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Neoplasias Meníngeas/fisiopatología , Meningioma/fisiopatología , Ensayos Antitumor por Modelo de Xenoinjerto/estadística & datos numéricos , Adulto , Anciano , Animales , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Línea Celular Transformada , Línea Celular Tumoral , Aberraciones Cromosómicas , Modelos Animales de Enfermedad , Femenino , Genotipo , Supervivencia de Injerto/fisiología , Humanos , Antígeno Ki-67/inmunología , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/genética , Meningioma/patología , Ratones , Ratones Desnudos , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Invasividad Neoplásica/genética , Vimentina/análisis , Vimentina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/normasRESUMEN
BACKGROUND: An Afghani man presented to a U.S. military facility in Afghanistan with a 3-month history of clear fluid from his left naris and frequent sinusitis. Eleven years earlier, he had been struck in the forehead by an object falling from the sky. MATERIALS AND METHODS: Neurologic examination revealed decreased sensation in V1 and V2 on the left side. Imaging revealed a large bullet lodged in the left maxillary sinus. FINDINGS: The bullet was removed via sublabial incision and opening of the anterior bony wall of the maxillary sinus. CONCLUSIONS: In Afghanistan, indirect gunshot wounds to the head are not uncommon because of the constant war conditions since the invasion by the former Soviet Union in 1979 and the tradition of firing rounds into the air during cultural celebrations.
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Traumatismos Penetrantes de la Cabeza/diagnóstico , Seno Maxilar/lesiones , Sinusitis Maxilar/etiología , Personal Militar , Heridas por Arma de Fuego/diagnóstico , Adulto , Afganistán , Hueso Frontal/diagnóstico por imagen , Hueso Frontal/lesiones , Hueso Frontal/patología , Traumatismos Penetrantes de la Cabeza/diagnóstico por imagen , Traumatismos Penetrantes de la Cabeza/patología , Humanos , Masculino , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/patología , Sinusitis Maxilar/patología , Sinusitis Maxilar/cirugía , Procedimientos Neuroquirúrgicos , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Radiografía , Procedimientos de Cirugía Plástica , Trastornos de la Sensación/etiología , Trastornos de la Sensación/patología , Trastornos de la Sensación/fisiopatología , Base del Cráneo/diagnóstico por imagen , Base del Cráneo/lesiones , Base del Cráneo/patología , Fractura Craneal Basilar/diagnóstico por imagen , Fractura Craneal Basilar/patología , Fractura Craneal Basilar/cirugía , Resultado del Tratamiento , Enfermedades del Nervio Trigémino/etiología , Enfermedades del Nervio Trigémino/patología , Enfermedades del Nervio Trigémino/fisiopatología , Heridas por Arma de Fuego/diagnóstico por imagen , Heridas por Arma de Fuego/patologíaAsunto(s)
Neoplasias Encefálicas/cirugía , Carcinoma de Células Renales/cirugía , Quiste Coloide/cirugía , Neoplasias Renales/cirugía , Tercer Ventrículo/cirugía , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Carcinoma de Células Renales/patología , Quiste Coloide/diagnóstico , Quiste Coloide/patología , Quiste Coloide/secundario , Diagnóstico Diferencial , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Tercer Ventrículo/patología , Resultado del TratamientoRESUMEN
OBJECT: Atlantoaxial and occipitocervical instability in children have traditionally been treated with posterior bone and wire fusion and external halo orthoses. Recently, successful outcomes have been achieved using rigid internal fixation, particularly C1-2 transarticular screws. The authors describe flow diagrams created to help clinicians determine which method of internal fixation to use in complex anatomical circumstances when bilateral transarticular screw placement is not possible. METHODS: The records of children who underwent either atlantoaxial or occipitocervical fixation with rigid internal fixation over an 11-year period were retrospectively reviewed to define flow diagrams used to determine treatment protocols. RESULTS: Among the 95 patients identified who underwent atlantoaxial or occipitocervical fixation, the craniocervical anatomy in 25 patients (six atlantoaxial and 19 occipitocervical fixations [26%]) required alternative methods of internal fixation. Types of screw fixation included loop or rod constructs anchored by combinations of C1-2 transarticular screws (15 constructs), C-1 lateral mass screws (11), C-2 pars screws (24), C-2 translaminar screws (one), and subaxial lateral mass screws (six). The mean age of the patients (15 boys and 10 girls) was 9.8 years (range 1.3-17 years). All 22 patients with greater than 3-month follow-up duration achieved solid bone fusion and maintained stable constructs on radiographic studies. Clinical improvement was seen in all patients who had preoperative symptoms. CONCLUSIONS: Novel flow diagrams are suggested to help guide selection of rigid internal fixation constructs when performing pediatric C1-2 and occipitocervical stabilizations. Use of these flow diagrams has led to successful fusion in 25 pediatric patients with difficult anatomy requiring less common constructs.
Asunto(s)
Articulación Atlantoaxoidea/cirugía , Articulación Atlantooccipital/cirugía , Inestabilidad de la Articulación/cirugía , Complicaciones Posoperatorias/diagnóstico , Fusión Vertebral/métodos , Adolescente , Articulación Atlantoaxoidea/patología , Articulación Atlantooccipital/patología , Tornillos Óseos , Vértebras Cervicales/patología , Vértebras Cervicales/cirugía , Niño , Preescolar , Árboles de Decisión , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/etiología , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
In this article the authors discuss the rationale and research supporting the hypothesis that meningioma tumorigenesis may, in part, be driven by overexpression of cyclooxygenase-2 (Cox-2) and that treatment with celecoxib, a selective Cox-2 inhibitor, may hold therapeutic promise. Because therapies for recurrent or aggressive meningiomas (atypical or malignant subtypes) such as chemotherapy and radiotherapy generally offer little therapeutic benefit, interest in targeting Cox-2 has grown. This rate-limiting enzyme of prostaglandin synthesis can be inhibited with nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen and celecoxib. Treatment with NSAIDs has been shown to curb the tumorigenic properties of prostaglandins in several cancer models via both Cox-2-dependent and -independent mechanisms. In addition, celecoxib is well tolerated in humans, making its use as a chronic therapy for meningiomas attractive.