✓ Molecular biological techniques have begun to transform modern medicine. These techniques have shown promise in the pathological diagnosis of difficult or uncommon tumors. Accurate molecular diagnosis of the small round-cell tumors, for example, is especially important because divergent therapies may be required to eradicate such disparate lesions as neuroblastoma, lymphoma, rhabdomyosarcoma, central primitive neuroectodermal tumors/medulloblastoma, or Ewing sarcoma (ES). The authors present an unusual case of a primary, extraosseous ES arising from the intramedullary spinal cord, in which molecular studies were required for specific diagnosis and therapeutic guidance.
Robert J. Weil, Zhengping Zhuang, Svetlana Pack, Shimareet Kumar, Lee Helman, Brian G. Fuller, Crystall L. Mackall and Edward H. Oldfield
Carys Thomas, Salvatore Di Maio, Roy Ma, Emily Vollans, Christina Chu, M.Math., Brenda Clark, Richard Lee, Michael McKenzie, Montgomery Martin and Brian Toyota
The goal in this study was to evaluate hearing preservation rates and to determine prognostic factors for this outcome following fractionated stereotactic radiotherapy (FSRT) of vestibular schwannoma.
Thirty-four consecutive patients with serviceable hearing who received FSRT between May 1998 and December 2003 were identified. Clinical and audiometry data were collected prospectively. The prescription dose was 45 Gy in 25 fractions prescribed to the 90% isodose line. The median follow-up duration was 36.5 months (range 12–85 months). The actuarial 2- and 4-year local control rates were 100 and 95.7%, respectively. Permanent trigeminal and facial nerve complications were 0 and 6%, respectively. The actuarial 2- and 3-year serviceable hearing preservation rates were both 63%. The median loss in speech reception threshold was 15 dB (range −10 to 65 dB). The radiotherapy dose to the cochlea was the only significant prognostic factor for hearing deterioration. Radiotherapy dose to the cochlear nucleus, patient age, sex, pre-FSRT hearing grade, tumor volume, and intracanalicular tumor volume failed to show any significance as prognostic factors.
Five cases were replanned with four different radiotherapy techniques (namely arcs, dynamic arcs, static conformal fields, and intensity-modulated radiotherapy), with the cochlea defined as an organ at risk. In all cases, replanning resulted in statistically significant reduction in radiation to the cochlea (p = 0.001); however, no single replanning technique was found to be superior.
The radiation dose to the cochlea is strongly predictive for subsequent hearing deterioration. It is essential for the cochlea to be outlined as an organ at risk, and for radiation techniques to be optimized, to improve long-term hearing preservation.
J. Brett Fleming, Brian L. Hoh, Scott D. Simon, Babu G. Welch, Robert A. Mericle, Kyle M. Fargen, G. Lee Pride, Phillip D. Purdy, Chevis N. Shannon and Mark R. Harrigan
Postprocedural rebleeding is a significant source of morbidity following endovascular treatment of ruptured intracranial aneurysms. Previous large-scale reports include the Cerebral Aneurysm Rerupture After Treatment trial, the International Subarachnoid Aneurysm Trial, and the study on Early Rebleeding after Coiling of Ruptured Cerebral Aneurysms, which reported nonprocedural rebleeding rates within 30 days of treatment of 2.7%, 1.9%, and 1.4%, respectively. However, coiling of intracranial aneurysms is in a state of continual change due to advancing device design and evolving techniques. These studies included only patients initially treated prior to 2004. In the present study the authors assess the most recent short-term results with endovascular treatment of ruptured aneurysms.
A multicenter retrospective chart review was conducted of patients undergoing endovascular treatment for ruptured intracranial aneurysms between July 2004 and October 2009. The technique used, including the use of stent or balloon assistance, was evaluated. Demographic and clinical factors, such as sex, age, initial clinical presentation, aneurysm size, aneurysm location, and modified Raymond Classification following initial treatment, were also evaluated and compared between the groups in which rebleeding did and did not occur.
A total of 469 patients underwent endovascular treatment for a ruptured aneurysm; nonprocedural rehemorrhage occurred within 30 days of the initial coiling in 4 cases (0.9%). Two patients (50%) died after rehemorrhage. Stent-assisted coiling was used during the original treatment in 1 (25%) of the 4 patients with a rerupture. However, no technical, clinical, or demographic factors were found to be statistically significant in association with rebleeding.
Recent data suggest that the periprocedural rebleeding rate may be improving over time.
Claire F. Jones, Jae H. T. Lee, Brian K. Kwon and Peter A. Cripton
Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may “cushion” the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.
A custom weight-drop device was used to apply thoracic contusion SCI to 17 Yucatan miniature pigs. Impact load and velocity were measured. Using fiber optic pressure transducers implanted in the thecal sac, CSF pressures resulting from 2 injury severities (caused by 50-g and 100-g weights released from a 50-cm height) were measured.
The median peak impact loads were 54 N and 132 N for the 50-g and 100-g injuries, respectively. At a nominal 100 mm from the injury epicenter, the authors observed a small negative pressure peak (median −4.6 mm Hg [cranial] and −5.8 mm Hg [caudal] for 50 g; −27.6 mm Hg [cranial] and −27.2 mm Hg [caudal] for 100 g) followed by a larger positive pressure peak (median 110.5 mm Hg [cranial] and 77.1 mm Hg [caudal] for 50 g; 88.4 mm Hg [cranial] and 67.2 mm Hg [caudal] for 100 g) relative to the preinjury pressure. There were no significant differences in peak pressure between the 2 injury severities or the caudal and cranial transducer locations.
A new model of contusion SCI was developed to measure spinal CSF pressures during the SCI event. The results suggest that the Yucatan miniature pig is an appropriate model for studying CSF, spinal cord, and dura interactions during injury. With further development and characterization it may be an appropriate in vivo largeanimal model of SCI to answer questions regarding pathological changes, therapeutic safety, or treatment efficacy, particularly where humanlike dimensions and physiology are important.
Brian Lee and Patrick C. Hsieh
Intradural, extramedullary schwannomas have long been treated with open midline incision, laminectomy, and dural opening to expose and resect the lesion. While this technique is well established, today new surgical techniques can be utilized to perform the same procedure while minimizing pain, size of incision, and trauma to adjacent tissues. In cases of intradural surgery, minimally invasive surgery limits the degree of soft tissue disruption. As a result, there is significant decreased dead space within the surgical cavity that may decrease the rate of CSF leak complications. Minimally invasive techniques have continuously improved over the years and have reached a point where they can be used for intradural surgeries. In this case presentation, we demonstrate a minimally invasive approach to the lumbar spine with resection of an intradural schwannoma. Surgical techniques and the nuances of the minimally invasive approach to intradural tumors compared to the standard open procedure will be discussed.
The video can be found here: http://youtu.be/XXrvAIq_H48.
Jie Lu, Alexander Ksendzovsky, Chunzhang Yang, Gautam U. Mehta, Raymund L. Yong, Robert J. Weil, Deric M. Park, Harry M. Mushlin, Xueping Fang, Brian M. Balgley, Dae-Hee Lee, Cheng S. Lee, Russell R. Lonser and Zhengping Zhuang
Tumor-initiating cells are uniquely resilient to current treatment modalities and play an important role in tumor resistance and recurrence. The lack of specific tumor-initiating cell markers to identify and target these cells presents a major obstacle to effective directed therapy.
To identify tumor-initiating cell markers in primary brain tumors, the authors compared the proteomes of glioma tumor-initiating cells to their differentiated progeny using a novel, nongel/shotgun-based, multidimensional liquid-chromatography protein separation technique. An in vivo xenograft model was used to demonstrate the tumorigenic and stem cell properties of these cells. Western blot and immunofluorescence analyses were used to confirm findings of upregulated ciliary neurotrophic factor receptor subunit–α (CNTFRα) in undifferentiated tumor-initiating cells and gliomas of increasing tumor grade. Sequencing of the CNTFRα coding regions was performed for mutation analysis. Finally, antibody-dependent cell-mediated cytotoxicity was used to establish the role of CNTFRα as a potential immunotherapeutic target.
Ciliary neurotrophic factor receptor subunit–α expression was increased in tumor-initiating cells and was decreased in the cells' differentiated progeny, and expression levels increased with glioma grade. Mutations of CNTFRα are not common in gliomas. Functional studies using CNTF treatment in glioma tumor-initiating cells showed induction of differentiation through the CNTFRα pathway. Treatment with anti-CNTFRα antibody resulted in increased antibody-dependent cell-mediated cytotoxicity in CNTFRα expressing DAOY cells but not in cell lines that lack CNTFRα.
These data indicate that CNTFRα plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target.