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  • Author or Editor: Wesley Hsu x
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Wesley Hsu, Ryan M. Kretzer, Michael J. Dorsi and Ziya L. Gokaslan

Wrong-site surgery (WSS) is a rare occurrence that can have devastating consequences for patient care. There are several factors inherent to spine surgery that increase the risk of WSS compared with other types of surgery. Not only can a surgeon potentially operate on the wrong side of the spine or the wrong level, but there are unique issues related to spinal localization that can be challenging for even the most experienced clinicians. The following review discusses important issues that can help prevent WSS during spinal procedures.

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Wesley Hsu, Thomas A. Kosztowski, Hasan A. Zaidi, Ziya L. Gokaslan and Jean-Paul Wolinsky

Chordomas are rare tumors that arise from the sacrum, spine, and skull base. Surgical management of these tumors can be difficult, given their locally destructive behavior and predilection for growing near delicate and critical structures. En bloc resection with negative margins can be difficult to perform without damaging adjacent structures and causing significant clinical morbidity. For chordomas of the upper cervical spine, surgical options traditionally involve transoral or submandibular approaches. The authors report the use of the image-guided, endoscopic, transcervical approach to the upper cervical spine as an alternative to traditional techniques for addressing upper cervical spine tumors, particularly for tumors where gross-total resection is not feasible.

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Wesley Hsu, I-Mei Siu, Gustavo Pradilla, Ziya L. Gokaslan, George I. Jallo and Gary L. Gallia

Object

Advances in the diagnosis and management of patients with spinal cord tumors have been limited because of the rarity of the disease and the limitations of current animal models for spinal cord glioma. The ideal spinal cord tumor model would possess a number of characteristics, including the use of human glioma cells that capture the growth pattern and local invasive nature of their human counterpart. In this study, the authors' goal was to develop a novel spinal cord tumor model using a human neurosphere cell line.

Methods

Eighteen female athymic rats were randomized into 3 experimental groups. Animals in the first group (6 rats) received a 3-ml intramedullary injection containing DMEM and were used as controls. Animals in the second group (6 rats) received a 3-ml intramedullary injection containing 100,000 glioblastoma multiforme (GBM) neurosphere cells in 3 ml DMEM. Animals in the third group (6 rats) received a 3-ml intramedullary injection containing 9L gliosarcoma cells in 3 ml DMEM. Functional testing of hindlimb strength was assessed using the Basso-Beattie-Bresnahan (BBB) scale. Once the functional BBB score of an animal was less than or equal to 5 (slight movement of 2 joints and extensive movement of the third), euthanasia was performed.

Results

Animals in the GBM neurosphere group had a mean survival of 33.3 ± 2.0 days, which was approximately twice as long as animals in the 9L gliosarcoma group (16.3 ± 2.3 days). There was a significant difference between survival of the GBM neurosphere and 9L gliosarcoma groups (p < 0.001). None of the control animals died (p < 0.001 for GBM neurosphere group vs controls and 9L vs controls). Histopathological examination of the rats injected with 9L gliosarcoma revealed that all animals developed highly cellular, well-circumscribed lesions causing compression of the surrounding tissue, with minimal invasion of the surrounding gray and white matter. Histopathological examination of animals injected with GBM neurospheres revealed that all animals developed infiltrative lesions with a high degree of white and gray matter invasion along with areas of necrosis.

Conclusions

The authors have established a novel animal model of spinal cord glioma using neurospheres derived from human GBM. When injected into the spinal cords of athymic nude rats, neurospheres gave rise to infiltrative, actively proliferating tumors that were histologically identical to spinal cord glioma in humans. On the basis of their results, the authors conclude that this is a reproducible animal model of high-grade spinal cord glioma based on a human GBM neurosphere line. This model represents an improvement over other models using nonhuman glioma cell lines. Novel therapeutic strategies can be readily evaluated using this model.

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Michelle J. Clarke, Patricia L. Zadnik, Mari L. Groves, Hormuzdiyar H. Dasenbrock, Daniel M. Sciubba, Wesley Hsu, Timothy F. Witham, Ali Bydon, Ziya L. Gokaslan and Jean-Paul Wolinsky

Object

Traditionally, hemisacrectomy and internal hemipelvectomy procedures have required both an anterior and a posterior approach. A posterior-only approach has the potential to complete an en bloc tumor resection and spinopelvic reconstruction while reducing surgical morbidity.

Methods

The authors describe 3 cases in which en bloc resection of the hemisacrum and ilium and subsequent lumbopelvic and pelvic ring reconstruction were performed from a posterior-only approach. Two more traditional anterior and posterior staged procedures are also included for comparison.

Results

In all 3 cases, an oncologically appropriate surgery and spinopelvic reconstruction were performed through a posterior-only approach.

Conclusions

The advantage of a midline posterior approach is the ability to perform a lumbosacral reconstruction, necessary in cases in which the S-1 body is iatrogenically disrupted during tumor resection.

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Wesley Hsu, Ahmed Mohyeldin, Sagar R. Shah, Colette M. ap Rhys, Lakesha F. Johnson, Neda I. Sedora-Roman, Thomas A. Kosztowski, Ola A. Awad, Edward F. McCarthy, David M. Loeb, Jean-Paul Wolinsky, Ziya L. Gokaslan and Alfredo Quiñones-Hinojosa

Object

Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo.

Methods

Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed.

Results

The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro.

Conclusions

This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.