RESUMEN
Anti-angiogenic agents, such as bevacizumab (BEV), can induce normalization of the blood brain barrier, which may influence the penetration and activity of a co-administered cytotoxic drug. However, it is unknown whether this effect is associated with a benefit in overall survival. This study employed intracranial human glioma models to evaluate the effect of BEV alone and in combination with temozolomide (TMZ) and/or radiation therapy (XRT) on overall survival. One hundred eight male athymic rats were intracranially injected with either U251 or U87 human glioma. Ten or eleven days after tumor inoculation, animals bearing U251 and U87, respectively, were treated with: TMZ alone (50 mg/kg for 5 consecutive days, P.O.), BEV alone (15 mg/kg, I.V.), a combination of TMZ and BEV, or a combination of TMZ, BEV, and a single fraction of XRT (20 Gy). Controls received no treatment. The U87 experiment was repeated and the relationship between survival and the extent of anti-angiogenesis via anti-laminin antibodies for the detection of blood vessels was assessed. In both U87 glioma experiments, all of the treatment groups had a statistically significant increase in survival as compared to the control groups. Also, for both U87 experiments the combination groups of TMZ and BEV had significantly better survival when compared to either treatment administered alone, with 75% of animals demonstrating long-term survival (LTS) (defined as animals alive 120 days after tumor implantation) in one experiment and 25% LTS in the repeat experiment. In the U251 glioma experiment, all treated groups (except BEV alone) had significantly improved survival as compared to controls with minimal statistical variance among groups. The percent vessel area was lowest in the group of animals treated with BEV alone. The addition of BEV to TMZ and/or XRT had variable effect on prolonging survival in the two human glioma models tested with reduced tumor vascularity in groups treated with BEV. These results indicate that BEV has anti-angiogenic activity and does not seem to hinder the effect of TMZ.
Asunto(s)
Anticuerpos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Glioma/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/inmunología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Dacarbazina/uso terapéutico , Modelos Animales de Enfermedad , Estudios de Seguimiento , Humanos , Laminina/metabolismo , Masculino , Ratas , Ratas Desnudas , Análisis de Supervivencia , Temozolomida , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Abstract The North America Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that has maintained a prospective SCI registry since 2004, and it has espoused that early surgical intervention is associated with improved outcome. It has previously been shown that initial presentation to a lower acuity center and necessity of transfer to a higher acuity center reduce rates of early surgery. The NACTN database was evaluated to examine the association between interhospital transfer (IHT), early surgery, and outcome, taking into account distance traveled and site of origin for the patient. Data from a 15-year period of the NACTN SCI Registry were analyzed (years 2005-2019). Patients were stratified into transfers directly from the scene to a Level 1 trauma center (NACTN site) versus IHT from a Level 2 or 3 trauma facility. The main outcome was surgery within 24 hours of injury (yes/no), whereas secondary outcomes were length of stay, death, discharge disposition, and 6-month American Spinal Injury Association Impairment Scale (AIS) grade conversion. For the IHT patients, distance traveled for transfer was calculated by measuring the shortest distance between origin and NACTN hospital. Analysis was performed with Brown-Mood test and chi-square tests. Of 724 patients with transfer data, 295 (40%) underwent IHT and 429 (60%) were admitted directly from the scene of injury. Patients who underwent IHT were more likely to have a less severe SCI (AIS D; p = 0.002), have a central cord injury (p = 0.004), and have a fall as their mechanism of injury (p < 0.0001) than those directly admitted to an NACTN center. Of the 634 patients who had surgery, direct admission to an NACTN site was more likely to result in surgery within 24 hours compared with IHT patients (52% vs. 38%) (p < 0.0003). Median IHT distance was 28 miles (interquartile range [IQR] = 13-62 miles). There was no significant difference in death, length of stay, discharge to a rehab facility versus home, or 6-month AIS grade conversion rates between the two groups. Patients who underwent IHT to an NACTN site were less likely to have surgery within 24 hours of injury, compared with those directly admitted to the Level 1 trauma facility. Although there was no difference in mortality rates, length of stay, or 6-month AIS conversion between groups, patients with IHT were more likely be older with a less severe level of injury (AIS D). This study suggests there are barriers to timely recognition of SCI in the field, appropriate admission to a higher level of care after recognition, and challenges related to the management of individuals with less severe SCI.
Asunto(s)
Traumatismos de la Médula Espinal , Humanos , Tiempo de Internación , América del Norte , Estudios Prospectivos , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Resultado del Tratamiento , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: Minimally invasive surgical techniques have resulted in improved patient outcomes. One drawback has been the increased reliance on fluoroscopy and subsequent exposure to ionizing radiation. We have previously shown the efficacy of a novel instrument tracking system in cadaveric and preliminary clinical studies for commonplace orthopedic and spine procedures. In the present study, we examined the radiation and operative time using a novel instrument tracking system compared with standard C-arm fluoroscopy for patients undergoing minimally invasive lumbar fusion. METHODS: The radiation emitted, number of radiographs taken, and time required to complete 2 tasks were recorded between the instrument tracking systems and conventional C-arm fluoroscopy. The studied tasks included placement of the initial dilator through Kambin's triangle during percutaneous lumbar interbody fusion and placement of pedicle screws during both percutaneous lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion with or without instrument tracking. RESULTS: A total of 23 patients were included in the analysis encompassing 31 total levels. For the task of placing the initial dilator into Kambin's triangle, an average of 4.21 minutes (2.4 vs. 6.6 minutes; P = 0.002), 15 fluoroscopic images (5.4 vs. 20.5; P = 0.002), and 8.14 mGy (3.3 vs. 11.4; P = 0.011) were saved by instrument tracking. For pedicle screw insertion, an average of 5.69 minutes (3.97 vs. 9.67; P < 0.001), 14 radiographs (6.53 vs. 20.62; P < 0.001), and 7.89 mGy (2.98 vs. 10.87 mGy; P < 0.001) were saved per screw insertion. CONCLUSIONS: Instrument tracking, when used for minimally invasive lumbar fusion, leads to significant reductions in radiation and operative time compared with conventional fluoroscopy.
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Fluoroscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Neuronavegación/métodos , Tempo Operativo , Exposición a la Radiación/prevención & control , Fusión Vertebral/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fluoroscopía/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Neuronavegación/instrumentación , Tornillos Pediculares , Estudios Prospectivos , Fusión Vertebral/instrumentación , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodosRESUMEN
STUDY DESIGN: Retrospective review. OBJECTIVE: To determine if adjuvant radiation therapy (RT) improves overall survival (OS) following surgical resection of chordomas. SUMMARY OF BACKGROUND DATA: The role of RT for the treatment of chordomas remains incompletely described. Previous studies have not found adjuvant RT to improve OS, but these studies did not group patients based on surgical margin status or radiation dose or modality. We used the National Cancer Database to investigate the role of RT in chordomas following surgical resection. METHODS: Patients were stratified based on surgical margin status (positive vs. negative). Utilizing the Kaplan-Meier method, OS was compared between treatment modalities (surgical resection alone, therapeutic RT alone, and surgical resection plus therapeutic RT). OS was subsequently compared between patients treated with palliative dose (<40âGy), low dose (40-65âGy), and high dose (>65âGy) RT. Similarly, OS was compared between advanced RT modalities including proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and external beam radiation therapy (EBRT). A multivariable model was used to determine adjusted variables predictive of mortality. RESULTS: One thousand four hundred seventy eight chordoma patients were identified; skull base (nâ=â567), sacral (nâ=â551), and mobile spine (nâ=â360). Surgical resection and therapeutic adjuvant RT improved 5-year survival in patients with positive surgical margins (82% vs. 71%, Pâ=â0.03). No clear survival benefit was observed with the addition of adjuvant RT in patients with negative surgical margins. High dose RT was associated with improved OS compared with palliative and low dose RT (Pâ<â0.001). Advanced RT techniques and SRS were associated with improved OS compared with EBRT. In the multivariate analysis high dose advanced RT (>65âGy) was superior to EBRT. CONCLUSION: Patients with positive surgical margins benefit from adjuvant RT. Optimal OS is associated with adjuvant RT administered with advanced techniques and cumulative dose more than 65âGy. LEVEL OF EVIDENCE: 4.
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Cordoma/radioterapia , Cordoma/cirugía , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia de Protones , Dosificación Radioterapéutica , Radioterapia Adyuvante , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Sacro , Base del CráneoRESUMEN
Intradural spinal arachnoid cysts (ISACs) have been reported in the current literature as either an idiopathic disease or exceedingly rare sequelae after lumbar puncture, spinal trauma, or meningitis. Other studies have more appropriately termed the iatrogenic pathology as a spinal subdural extra-arachnoid hygroma (SSEH), as there is not often a clear cyst wall as in a true arachnoid cyst. However, to the best of our knowledge, none of the previous studies described an SSEH following uncomplicated posterior lumbar surgery, as they have previously involved clear durotomies during the initial operation. Here, we report the case of a 53-year-old woman who presented to the emergency department with a persistent severe orthostatic headache and worsening leg pain, six days following an uneventful L5-S1 discectomy and left L4-5 laminoforaminotomy, without intraoperative durotomy. Lumbar magnetic resonance imaging (MRI) scan revealed a pseudomeningocele and an SSEH extending from the S1 up to the lower thoracic spine, compressing and displacing the cauda equina. Although the hygroma extended up to the lower thoracic spine, surgical exploration was performed only at the index surgical site with bilateral L5 laminectomy, wide durotomy, and wide fenestration of the arachnoid layer. Postoperatively, her headaches dissipated and her pain improved with complete radiographic resolution of the collection. Iatrogenic SSEH is an exceedingly rare complication of posterior lumbar decompression and can occur in the absence of a durotomy during the index surgery. Although these hygromas may span multiple levels, the initial surgical site or the site of known durotomy should be explored first. They can potentially be treated with only a limited durotomy and arachnoid fenestration at a single level rather than at a multilevel arachnoid fenestration.