No abstract

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.

A djAcent-segment lumbar disease (ASLD) refers to the development of pathology in the mobile segment proximal or distal to a previous lumbar fusion. Adjacent pathology includes disc degeneration, disc herniation, listhesis, instability, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. 7,13 The prevalence of ASLD is widely variable in the literature as some studies refer to radiographic rather than symptomatic disease.3 A recent meta-analysis review reports the prevalence of symptomatic ASLD to be 8.5%.24 A large portion of these patients will require reoperation to address symptomatic ASLD. 4 Subsequent operative intervention to treat ASLD usually includes decompression and fusion of adjacent spinal levels. During surgery for ASLD, it is not unusual to expose all of the preexisting hardware, which leads to significant pain and may potentially increase the risk of infection and need for perioperative blood transfusion. The cortical bone trajectory (CBT) technique can be used to avoid extensive tissue dissection by limiting the surgical corridor to the levels adjacent to the existing hardware. Cortical bone trajectory was developed to increase screw-bone purchase during posterior pedicle fixation. 10,16Because the starting point for CBT screws is at the lateral aspect of the pars interarticularis, there is less need Novel placement of cortical bone trajectory screws in previously instrumented pedicles for adjacent-segment lumbar disease using CT image-guided navigation Object. Symptomatic adjacent-segment lumbar disease (ASLD) after lumbar fusion often requires subsequent surgical intervention. The authors report utilizing cortical bone trajectory (CBT) pedicle screw fixation with intraoperative CT (O-arm) image-guided navigation to stabilize spinal levels in patients with symptomatic ASLD. This unique technique results in the placement of 2 screws in the same pedicle (1 traditional pedicle trajectory and 1 CBT) and obviates the need to remove preexisting instrumentation.Methods. The records of 5 consecutive patients who underwent lumbar spinal fusion with CBT and posterior interbody grafting for ASLD were retrospectively reviewed. All patients underwent screw trajectory planning with the O-arm in conjunction with the StealthStation navigation system. Basic demographics, operative details, and radiographic and clinical outcomes were obtained.Results. The average patient age was 69.4 years (range 58-82 years). Four of the 5 surgeries were performed with the Minimal Access Spinal Technologies (MAST) Midline Lumbar Fusion (MIDLF) system. The average operative duration was 218 minutes (range 175-315 minutes). In the entire cohort, 5.5-mm cortical screws were placed in previously instrumented pedicles. The average hospital stay was 2.8 days (range 2-3 days) and there were no surgical complications. All patients had more than 6 months of radiographic and clinical follow-up (range 10-15 months). At last follow-up, all patients reported improved symptoms from their preoperative state....

The use of intraoperative neuraxial anesthesia does not appear to decrease the incidence of postoperative cognitive dysfunction when compared with general anesthesia. There are methodologic and study-design issues present in many studies, and further elucidation of the pathophysiology of postoperative cognitive dysfunction may provide a direction for future studies.