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Daniel K. Fahim, Claudio E. Tatsui, Dima Suki, Joy Gumin, Frederick F. Lang and Laurence D. Rhines

Object

There is currently no reproducible animal model of human primary malignant bone tumors in the spine to permit laboratory investigation of the human disease. Therefore, the authors sought to adapt their previously developed orthotopic model of spinal metastasis to a model for primary malignant bone tumors of the spine.

Methods

A transperitoneal surgical approach was used to implant osteosarcoma (Krib-1) into the L-3 vertebral body of nude mice via a drill hole. Motor function was evaluated daily using the previously validated qualitative key milestones of tail dragging, dorsal stepping, hindlimb sweeping, and paralysis. A subset of these animals was euthanized upon reaching the various milestones, and the spines were removed, sectioned, and stained. The degree of spinal cord compression was correlated with the occurrence of milestones and assessed by a ratio between the neural elements divided by the area of the spinal canal. Another subset of animals received stably transfected Krib-1 cells with the luciferase gene, and bioluminescence was measured at 10, 20, and 30 days postimplantation.

Results

Osteosarcoma xenografts grew in all animals according to a reliable and reproducible time course; the mean time for development of behavioral milestones was noted in relation to the day of implantation (Day 1). Tail dragging (Milestone 1) occurred on Day 19.06 (95% CI 16.11–22.01), dorsal stepping (Milestone 2) occurred on Day 28.78 (95% CI 26.79–30.77), hindlimb sweeping (Milestone 3) occurred on Day 35.61 (95% CI 32.9–38.32), and paralysis of the hindlimb (Milestone 4) occurred on Day 41.78 (95% CI 39.31–44.25). These clinically observed milestones correlated with increasing compression of the spinal cord on histological sections. The authors observed a progressive increase in the local bioluminescence (in photons/cm2/sec) of the implanted level over time with a mean of 2.17 (range 0.0–8.61) at Day 10, mean 4.68 (range 1.17–8.52) at Day 20, and mean 5.54 (range 1.22–9.99) at Day 30.

Conclusions

The authors have developed the first orthotopic murine model of a primary malignant bone tumor in the spine, in which neurological decline reproducibly correlates with tumor progression as evidenced by pathological confirmation and noninvasive bioluminescence measurements. Although developed for osteosarcoma, this model can be expanded to study other types of primary malignant bone tumors in the spine. This model will potentially allow animal testing of targeted therapies against specific primary malignant tumor types.

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Julie E. York, Garrett L. Walsh, Frederick F. Lang, Joe B. Putnam, Ian E. McCutcheon, Stephen G. Swisher, Ritsuko Komaki and Ziya L Gokaslan

Traditionally, superior sulcus tumors of the lung that involve the chest wall and spinal column have been considered to be unresectable, and historically, patients harboring these tumors have been treated with local radiation therapy with, at best, modest results. The value of gross-total resection remains unclear in this patient population; however, with the recent advances in surgical technique and spinal instrumentation, procedures involving more radical removal of such tumors are now possible. At The University of Texas M. D. Anderson Cancer Center, the authors have developed a new technique for resecting superior sulcus tumors that invade the chest wall and spinal column. They present a technical description of this procedure and results in nine patients in whom stage IIIb superior sulcus tumors extensively invaded the vertebral column. These patients underwent gross-total tumor resection via a combined approach that included posterolateral thoracotomy, apical lobectomy, chest wall resection, laminectomy, vertebrectomy, anterior spinal column reconstruction with methylmethacrylate, and placement of spinal instrumentation. There were six men and three women, with a mean age of 55 years (range 36–72 years). Histological examination revealed squamous cell carcinoma (three patients), adenocarcinoma (four patients), and large cell carcinoma (two patients). The mean postoperative follow-up period was 16 months. All patients are currently ambulatory or remained ambulatory until they died. Pain related to tumor invasion improved in four patients and remained unchanged in five. In three patients instrumentation failed and required revision. There was one case of cerebrospinal leak that was treated with lumbar drainage and one case of wound breakdown that required revision. Two patients experienced local tumor recurrence, and one patient developed a second primary lung tumor. The authors conclude that in selected patients, combined radical resection of superior sulcus tumors of the lung that involve the chest wall and spinal column may represent an acceptable treatment modality that can offer a potential cure while preserving neurological function and providing pain control.

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Ziya L. Gokaslan, Julie E. York, Garrett L. Walsh, Ian E. McCutcheon, Frederick F. Lang, Joe B. Putnam Jr., David M. Wildrick, Stephen G. Swisher, Dima Abi-Said and Raymond Sawaya

Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

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Marcos V. C. Maldaun, Shumaila N. Khawja, Nicholas B. Levine, Ganesh Rao, Frederick F. Lang, Jeffrey S. Weinberg, Sudhakar Tummala, Charles E. Cowles, David Ferson, Anh-Thuy Nguyen, Raymond Sawaya, Dima Suki and Sujit S. Prabhu

Object

The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex.

Methods

From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome.

Results

Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0–13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR ≥ 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%).

Conclusions

There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month.