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Camilo A. Molina, Rachel Sarabia-Estrada, Ziya L. Gokaslan, Timothy F. Witham, Ali Bydon, Jean-Paul Wolinsky, and Daniel M. Sciubba

Object

Recombinant human bone morphogenetic proteins (rhBMPs) are FDA-approved for specific spinal fusion procedures, but their use is contraindicated in spine tumor resection beds because of an unclear interaction between tumor tissue and such growth factors. Interestingly, a number of studies have suggested that BMPs may slow the growth of adenocarcinomas in vitro, and these lesions represent the majority of bony spine tumors. In this study, the authors hypothesized that rhBMP-2 placed in an intraosseous spine tumor in the rat could suppress tumor and delay the onset of paresis in such animals.

Methods

Twenty-six female nude athymic rats were randomized into an experimental group (Group 1) or a positive control group (Group 2). Group 1 (tumor + 15 μg rhBMP-2 sponge, 13 rats) underwent transperitoneal exposure and implantation of breast adenocarcinoma (CRL-1666) into the L-6 spine segment, followed by the implantation of a bovine collagen sponge impregnated with 15 μg of rhBMP-2. Group 2 (tumor + 0.9% NaCl sponge, 13 rats) underwent transperitoneal exposure and tumor implantation in the lumbar spine but no local treatment with rhBMP-2. An additional 8 animals were randomized into 2 negative control groups (Groups 3 and 4). Group 3 (15 μg rhBMP-2 sponge, 4 rats) and Group 4 (0.9% NaCl sponge, 4 rats) underwent transperitoneal exposure of the lumbar spine along with the implantation of rhBMP-2– and saline-impregnated bovine collagen sponges, respectively. Neither of the negative control groups was implanted with tumor. The Basso-Beattie-Bresnahan (BBB) scale was used to monitor daily motor function regression and the time to paresis (BBB score ≤ 7).

Results

In comparison with the positive control animals (Group 2), the experimental animals (Group 1) had statistically significant longer mean (25.8 ± 12.2 vs 13 ± 1.4 days, p ≤ 0.001) and median (20 vs 13 days) times to paresis. In addition, the median survival time was significantly longer in the experimental animals (20 vs 13.5 days, p ≤ 0.0001). Histopathological analysis demonstrated bone growth and tumor inhibition in the experimental animals, whereas bone destruction and cord compression were observed in the positive control animals. Neither of the negative control groups (Groups 3 and 4) demonstrated any evidence of neurological deterioration, morbidity, or cord compromise on either gross or histological analysis.

Conclusions

This study shows that the local administration of rhBMP-2 (15 μg, 10 μl of 1.5-mg/ml solution) in a rat spine tumor model of breast cancer not only fails to stimulate local tumor growth, but also decreases local tumor growth and delays the onset of paresis in rats. This preclinical experiment is the first to show that the local placement of rhBMP-2 in a spine tumor bed may slow tumor progression and delay associated neurological decline.

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Dimitrios Mathios, Paul Edward Kaloostian, Ali Bydon, Daniel M. Sciubba, Jean Paul Wolinsky, Ziya L. Gokaslan, and Timothy F. Witham

Reconstruction of the lumbosacral junction is a considerable challenge for spinal surgeons due to the unique anatomical constraints of this region as well as the vectors of force that are applied focally in this area. The standard cages, both expandable and nonexpendable, often fail to reconstitute the appropriate anatomical alignment of the lumbosacral junction. This inadequate reconstruction may predispose the patient to continued back pain and neurological symptoms as well as possible pseudarthrosis and instrumentation failure. The authors describe their preoperative planning and the technical characteristics of their novel reconstruction technique at the lumbosacral junction using a cage with adjustable caps. Based precisely on preoperative measurements that maintain the appropriate Cobb angle, they performed reconstruction of the lumbosacral junction in a series of 3 patients. All 3 patients had excellent installation of the cages used for reconstruction. Postoperative CT scans were used to radiographically confirm the appropriate reconstruction of the lumbosacral junction. All patients had a significant reduction in pain, had neurological improvement, and experienced no instrumentation failure at the time of latest follow-up. Taking into account the inherent morphology of the lumbosacral junction and carefully planning the technical characteristics of the cage installation preoperatively and intraoperatively, the authors achieved favorable clinical and radiographic outcomes in all 3 cases. Based on this small case series, this technique for reconstruction of the lumbosacral junction appears to be a safe and appropriate method of reconstruction of the anterior spinal column in this technically challenging region of the spine.

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Paul E. Kaloostian, Patricia L. Zadnik, Jennifer E. Kim, Mari L. Groves, Jean-Paul Wolinsky, Ziya L. Gokaslan, Timothy F. Witham, Ali Bydon, and Daniel M. Sciubba

blockade if en bloc resection achieved * ICU = intensive care unit. Conclusions No standard paradigm exists for the surgical management of symptomatic spinal pheochromocytomas. In addition to a full analysis of the extent of metastasis and life expectancy, careful preoperative workup in coordination with endocrine services must be done. Management should include preoperative embolization of the vascular supply to these tumors if it can be safely achieved, chemotherapy and/or radiation therapy in consultation with radiation oncology services, and/or resection

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Matthew J. McGirt, Beril Gok, Starane Shepherd, Joseph Noggle, Giannina L. Garcés Ambrossi, Ali Bydon, and Ziya L. Gokaslan

forebrain ischemia . Free Radic Biol Med 27 : 1033 – 1040 , 1999 27 Loblaw DA , Perry J , Chambers A , Laperriere NJ : Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group . J Clin Oncol 23 : 2028 – 2037 , 2005 28 Mantha A , Legnani FG , Bagley CA , Gallia GL , Garonzik I , Pradilla G : A novel rat model for the study of intraosseous metastatic spine cancer . J Neurosurg Spine 2 : 303 – 307

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Ann Liu, Eric W. Sankey, C. Rory Goodwin, Thomas A. Kosztowski, Benjamin D. Elder, Ali Bydon, Timothy F. Witham, Jean-Paul Wolinsky, Ziya L. Gokaslan, and Daniel M. Sciubba

OBJECT

Spinal metastases from gynecological cancers are rare, with few cases reported in the literature. In this study, the authors examine a series of patients with spinal metastases from gynecological cancer and review the literature.

METHODS

The cases of 6 consecutive patients who underwent spine surgery for metastatic gynecological cancer between 2007 and 2012 at a single institution were retrospectively reviewed. The recorded demographic, operative, and postoperative factors were reviewed, and the functional outcomes were determined by change in Karnofsky Performance Scale and the American Spine Injury Association (ASIA) score during follow-up. A systematic review of the literature was also performed to evaluate outcomes for patients with similar gynecological metastases to the spine.

RESULTS

In this series, details regarding metastatic gynecological cancers to the spine are as follows: 2 patients with cervical cancer (both presented at age 46 years, mean postoperative survival of 32 months), 2 patients with endometrial cancer (mean age of 40 years, mean postoperative survival of 26 months), and 2 patients with leiomyosarcoma (mean age of 44 years, mean postoperative survival of 20 months). All patients presented with pain, and no complications were noted following surgery. All patients with known follow-up had stable or improved neurological outcomes, performance status, and improved pain, without local recurrence of tumor. Overall median survival after diagnosis of metastatic spine lesions for all cases in the literature as well as those treated by the authors was 15 months. When categorized by type, median survival of patients with cervical cancer (n = 2), endometrial cancer (n = 26), and leiomyosarcoma (n = 16) was 32, 10, and 22.5 months, respectively.

CONCLUSIONS

Gynecological cancers metastasizing to the spine are rare. In this series, overall survival following diagnosis of spinal metastasis and surgery was 27 months, with cervical cancer, endometrial cancer, and leiomyosarcoma survival being 32, 26, and 20 months, respectively. Combined with literature cases, survival differs depending on primary histology, with decreasing survival from cervical cancer (32 months) to leiomyosarcoma (22.5 months) to endometrial cancer (10 months). Integrating such information with other patient factors may more accurately guide decision making regarding management of such spinal lesions.

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Patricia Zadnik, Rachel Sarabia-Estrada, Mari L. Groves, Camilo Molina, Christopher Jackson, Edward McCarthy, Ziya L. Gokaslan, Ali Bydon, Jean-Paul Wolinsky, Timothy F. Witham, and Daniel M. Sciubba

, European Spine Journal, Nature Reviews in Neurology, World Neurosurgery, Journal of Surgical Oncology, and US Spine . The Johns Hopkins School of Medicine Dean's Research Fellowship provided stipend support. Dr. Bydon serves as a consultant for Medimmune and receives non–study-related support from Depuy Spine. Author contributions to the study and manuscript preparation include the following. Conception and design: Zadnik. Acquisition of data: Sciubba, Zadnik, Sarabia-Estrada, Jackson, McCarthy. Analysis and interpretation of data: Sciubba, Zadnik, Sarabia

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Patricia L. Zadnik, C. Rory Goodwin, Kristophe J. Karami, Ankit I. Mehta, Anubhav G. Amin, Mari L. Groves, Jean-Paul Wolinsky, Timothy F. Witham, Ali Bydon, Ziya L. Gokaslan, and Daniel M. Sciubba

, proposed by the Spine Oncology Study Group incorporates tumor location, patient pain, the degree of osteolysis, spinal alignment, vertebral body collapse, and posterolateral involvement of the spinal elements in the determination of spinal instability from a neoplastic process. 9 This scoring system has been validated in a recent study that demonstrated high inter- and intra-observer reliability and predictability for identifying spinal instability. 10 In this case series, no patient underwent surgery with a SINS predicting stability (score range 0–6). Among patients

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Benjamin D. Elder, Wataru Ishida, C. Rory Goodwin, Ali Bydon, Ziya L. Gokaslan, Daniel M. Sciubba, Jean-Paul Wolinsky, and Timothy F. Witham

concern related to fusion procedures in spinal oncology is the influence of perioperative radiation therapy (RT) and chemotherapy on bone mineral density (BMD) and fusion outcomes. For instance, Hobusch et al. 33 retrospectively reviewed 127 long-term survivors of chondrosarcoma who underwent RT and/or chemotherapy and concluded that they appear to be at greater risk for having low BMD and suffering from fractures than the healthy population. Proton beam therapy (PBT), which is often used in the treatment of chordomas, is also associated with decreased BMD. 3 , 43

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

adjacent lateral mass or occipital condyle. Their postoperative courses were similarly uncomplicated by infection or other issues. Of the 7 patients, 2 patients with malignant pathologies (chordoma and chondrosarcoma) had postoperative instrumentation-related complications. Following surgery, both patients were referred to the radiation oncology department for consideration of adjuvant therapy; 1 patient (Case 2) ultimately underwent proton-beam radiation therapy and the other patient (Case 1) underwent IMRT when the tumor recurred. The latter patient experienced

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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

disease progression despite chemotherapy or radiation therapy or a chemo- and/or radio-insensitive tumor, rapidly progressive neurological deterioration, severe intractable pain, or evidence of spinal mechanical instability. Patients were excluded from the study if they were not sufficiently stable for intervention, if they refused surgery, or if their projected life expectancy was less than 3 months. A multidisciplinary team including radiation and medical oncology personnel determined life expectancy, which incorporated considerations of functional status, presence of