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Melvin Field, Timothy F. Witham, John C. Flickinger, Douglas Kondziolka and L. Dade Lunsford

Object. Stereotactic brain biopsy has played an integral role in the diagnosis and management of brain lesions. At most centers, imaging studies following biopsy are rarely performed. The authors prospectively determined the acute hemorrhage rate after stereotactic biopsy by performing immediate postbiopsy intraoperative computerized tomography (CT) scanning. They then analyzed factors that may influence the risk of hemorrhage and the diagnostic accuracy rate.

Methods. Five hundred consecutive patients undergoing stereotactic brain biopsy underwent immediate postbiopsy intraoperative CT scanning. Before surgery, routine preoperative coagulation studies were performed in all patients. All medical charts, laboratory results, preoperative imaging studies, and postoperative imaging studies were reviewed.

In 40 patients (8%) hemorrhage was detected using immediate postbiopsy intraoperative CT scanning. Neurological deficits developed in six patients (1.2%) and one patient (0.2%) died. Symptomatic delayed neurological deficits developed in two patients (0.4%), despite the fact that the initial postbiopsy CT scans in these cases did not show acute hemorrhage. Both patients had large intracerebral hemorrhages that were confirmed at the time of repeated imaging. The results of a multivariate logistic regression analysis of the risk of postbiopsy hemorrhage of any size showed a significant correlation only with the degree to which the platelet count was below 150,000/mm3 (p = 0.006). The results of a multivariate analysis of a hemorrhage measuring greater than 5 mm in diameter also showed a correlation between the risk of hemorrhage and a lesion location in the pineal region (p = 0.0086). The rate at which a nondiagnostic biopsy specimen was obtained increased as the number of biopsy samples increased (p = 0.0073) and in accordance with younger patient age (p = 0.026).

Conclusions. Stereotactic brain biopsy was associated with a low likelihood of postbiopsy hemorrhage. The risk of hemorrhage increased steadily as the platelet count fell below 150,000/mm3. The authors found a small but definable risk of delayed hemorrhage, despite unremarkable findings on an immediate postbiopsy head CT scan. This risk justifies an overnight hospital observation stay for all patients after having undergone stereotactic brain biopsy.

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Norimoto Nakahara, Hideho Okada, Timothy F. Witham, Jason Attanucci, Wendy K. Fellows, William H. Chambers, Ajay Niranjan, Douglas Kondziolka and Ian F. Pollack

Object. To determine if the combination of radiosurgery and tumor cell vaccine would enhance the therapy of metastatic lesions of the central nervous system (CNS), the authors examined the antitumoral effects of radiosurgery and cytokine-transduced tumor cell vaccine.

Methods. Fifty-five rats underwent intracranial implantation of 5 × 103 MADB106 cells. On Day 3 after tumor implantation, 34 rats were inoculated in the flank with nonirradiated MADB106 cells that had been retrovirally transduced to express granulocyte-macrophage colony-stimulating factor or interleukin-4. Twenty-seven rats (17 animals that had received the vaccine and 10 that had not) underwent radiosurgery performed using a gamma knife at maximum doses of 32 Gy on Day 5.

No animals in the untreated group or in the vaccine-alone groups survived longer than 21 days. Animals treated by radiosurgery alone displayed prolonged survival in comparison with untreated animals (p < 0.0001), but only one of 10 animals survived longer than 55 days. In contrast, 14 of 17 animals that received the combination therapy of radiosurgery and vaccination survived longer than 55 days (p = 0.0003 compared with animals that underwent radiosurgery alone). On Day 55, the long-term survivors were challenged by parental MADB106 cells, which were implanted in the contralateral hemisphere. All animals from the combination therapy groups survived longer than 50 days after this challenge, but the single survivor from the radiosurgery-alone group died of tumor growth in 27 days.

Conclusions. The combination of radiosurgery and cytokine gene—transduced tumor cell vaccine markedly prolonged animal survival and protected animals from a subsequent challenge by parental tumor cells placed in the CNS. The data provided by this study indicate that this combination therapy represents a strategy that may have clinical applicability for single and/or multiple metastatic brain tumors.

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Gary L. Gallia, Raqeeb Haque, Ira Garonzik, Timothy F. Witham, Yevgeniy A. Khavkin, Jean Paul Wolinsky, Ian Suk and Ziya L. Gokaslan

✓ Although radical resection prolongs the disease-free survival period, surgical management of primary sacral tumors is challenging because of their location and often large size. Moreover, in cases of lesions for which a radical resection necessitates total sacrectomy, reconstruction is required. The authors have previously described a modified Galveston technique in which a liaison between the spine and pelvis is achieved using lumbar pedicle screws and Galveston rods embedded into the ilia; additionally, a transiliac bar reestablishes the pelvic ring. Although this reconstruction technique achieves stabilization, several biomechanical limitations exist. In the present report the authors present the case of a patient who underwent spinal pelvic reconstruction after a total sacrectomy was performed to remove a giant sacral chordoma. They describe a novel spinal pelvic reconstruction technique that addresses some of the biomechanical limitations.

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Daniel M. Sciubba, Gaurav G. Mavinkurve, Philippe Gailloud, Ira M. Garonzik, Pablo F. Recinos, Matthew J. McGirt, Graeme F. Woodworth, Timothy Witham, Yevgeniv Khavkin, Ziya L. Gokaslan and Jean-Paul Wolinsky

✓ Angiography is often performed to identify the vascular supply of hemangioblastomas prior to resection. Conventional two-dimensional (2D) digital subtraction (DS) angiography and three-dimensional (3D) DS angiography provides high-resolution images of the vascular structures associated with these lesions. However, such 3D DS angiography often does not provide reliable anatomical information about nearby osseous structures, or when it does, resolution of vascular anatomy in the immediate vicinity of bone is sacrificed. A novel angiographic reconstruction algorithm was recently developed at The Johns Hopkins University to overcome these inadequacies. By combining two separate sequences of images of bone and blood vessels in a single 3D representation, 3D fusion DS (FDS) angiography provides precise topographic information about vascular lesions in relation to the osseous environment, without a loss of resolution.

In this paper, the authors present the cases of two patients with cervical spine hemangioblastomas who underwent preoperative evaluation with FDS angiography and then successful gross-total resection of their tumors. In both cases, FDS angiography provided high-resolution 3D images of the hemangioblastoma anatomy, including each tumor’s topographic relationship with adjacent osseous structures and the location and size of feeding arteries and draining veins. These cases provide evidence that FDS angiography represents a useful adjunct to magnetic resonance imaging and 2D DS angiography in the preoperative evaluation and surgical planning of patients with vascular lesions in an osseous environment, such as hemangioblastomas in the spinal cord.

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Gary L. Gallia, Daniel M. Sciubba, Ali Bydon, Ian Suk, Jean-Paul Wolinsky, Ziya L. Gokaslan and Timothy F. Witham

✓The authors describe a technique for total L-5 spondylectomy and reconstruction of the lumbosacral junction. The technique, which involves separately staged posterior and anterior procedures, is reported in two patients harboring neoplasms that involved the L-5 level. The first stage consisted of a posterior approach with removal of all posterior bone elements of L-5 and radical L4–5 and L5–S1 discectomies. Lumbosacral and lumbopelvic instrumentation included pedicle screws as well as iliac screws or a transiliac rod. The second stage consisted of an anterior approach with mobilization of vascular structures, completion of L4–5 and L5–S1 discectomies, and removal of the L-5 vertebral body. Anterior lumbosacral reconstruction included placement of a distractable cage and tension band between L-4 and S-1. Allograft bone was used for fusion in both stages. No significant complications were encountered. At more than 1 year of follow-up, both patients were independently ambulatory, without evidence of recurrent or metastatic disease, and adequate lumbosacral alignment was maintained. The authors conclude that this technique can be safely performed in appropriately selected patients with neoplasms involving L-5.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan and Timothy F. Witham

Object.

Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column.

Methods.

Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 μL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 μL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL-1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed.

Results.

There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups.

Conclusions.

These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

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Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, Jean-Paul Wolinsky and Timothy F. Witham

Object

Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases.

Methods

After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animal's death.

Results

Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose.

Conclusions

These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.

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Matthew J. McGirt, Kaisorn L. Chaichana, April Atiba, Ali Bydon, Timothy F. Witham, Kevin C. Yao and George I. Jallo

Object

Gross-total resection of pediatric intramedullary spinal cord tumor (IMSCT) can be achieved in the majority of cases while preserving long-term neurological function. Nevertheless, postoperative progressive spinal deformity often complicates functional outcome years after surgery. The authors set out to determine whether laminoplasty in comparison with laminectomy has reduced the incidence of subsequent spinal deformity requiring fusion after IMSCT resection at their institution.

Methods

The first 144 consecutive patients undergoing resection of IMSCTs at a single institution underwent laminectomy with preservation of facet joints. The next 20 consecutive patients presenting for resection of IMSCTs underwent osteoplastic laminotomy regardless of patient or tumor characteristics. All patients were followed up with telephone interviews corroborated by medical records for the following outcomes: 1) neurological and functional status (modified McCormick Scale [MMS] score and Karnofsky Performance Scale [KPS] score); and 2) development of progressive spinal deformity requiring fusion. The incidence of progressive spinal deformity and the long-term neurological function were compared between the laminectomy and osteoplastic laminotomy cohorts. The means are expressed ± the standard deviation.

Results

Overall, the patients' mean age was 8.6 ± 5 years, and they presented with median MMS scores of 2 (interquartile range [IQR] 2–4). A > 95% resection was achieved in 125 cases (76%). There were no differences (p > 0.10) between patients treated with osteoplastic laminotomy and those treated with laminectomy in terms of the following characteristics: age; sex; duration of symptoms; location of tumor; incidence of preoperative scoliosis (Cobb angle > 10°: 7 [35%] with laminoplasty compared with 49 [34%] with laminectomy); involvement of the cervicothoracic junction (7 [35%] compared with 57 [40%]); thoracolumbar junction (4 [20%] compared with 36 [25%]); tumor size; extent of resection; radiation therapy; histopathological findings; or mean operative spinal levels (7.5 ± 2 compared with 7.5 ± 3). Nevertheless, patients who underwent osteoplastic laminotomy had better median preoperative MMS scores than those treated with laminectomy (2 [IQR 2–2] compared with 2 [IQR 2–4]; p = 0.04). A median of 3.5 years (IQR 1–7 years) after surgery, only 1 patient (5%) in the osteoplastic laminotomy cohort required fusion for progressive spinal deformity, compared with 43 (30%) in the laminectomy cohort (p = 0.027). Adjusting for the inter-cohort difference in preoperative MMS scores, osteoplastic laminotomy was associated with a 7-fold reduction in the odds of subsequent fusion for progressive spinal deformity (odds ratio 0.13, 95% confidence interval 0.02–1.00; p = 0.05). The median MMS and KPS scores were similar between patients who underwent osteoplastic laminotomy and those in whom laminectomy was performed (MMS Score 2 [IQR 2–3] for laminotomy compared with 2 [IQR 2–4] for laminectomy, p = 0.54; KPS Score 90 [IQR 70–100] for laminotomy compared with 90 [IQR 80–90] for laminectomy, p = 0.545) at a median of 3.5 years after surgery.

Conclusions

In the authors' experience, osteoplastic laminotomy for the resection of IMSCT in children was associated with a decreased incidence of progressive spinal deformity requiring fusion but did not affect long-term functional outcome. Laminoplasty used for pediatric IMSCT resection may decrease the incidence of progressive spinal deformity requiring subsequent spinal stabilization in some patients.

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Beril Gok, Daniel M. Sciubba, Gregory S. McLoughlin, Matthew McGirt, Selim Ayhan, Jean-Paul Wolinsky, Ali Bydon, Ziya L. Gokaslan and Timothy F. Witham

Object

In patients with cervical spondylotic myelopathy (CSM), ventral disease and loss of cervical lordosis are considered to be relative indications for anterior surgery. However, anterior decompression and fusion operations may be associated with an increased risk of swallowing difficulty and an increased risk of nonunion when extensive decompression is performed. The authors reviewed cases involving patients with CSM treated via an anterior approach, paying special attention to neurological outcome, fusion rates, and complications.

Methods

Retrospectively, 67 cases involving consecutive patients with CSM requiring an anterior decompression were reviewed: 46 patients underwent anterior surgery only (1-to3-level anterior cervical discectomy and fusion [ACDF] or 1-level corpectomy), and 21 patients who required > 3-level ACDF or ≥ 2-level corpectomy underwent anterior surgery supplemented by a posterior instrumented fusion procedure.

Results

Postoperative improvement in Nurick grade was seen in 43 (93%) of 46 patients undergoing anterior decompression and fusion alone (p < 0.001) and in 17 (81%) of 21 patients undergoing anterior decompression and fusion with supplemental posterior fusion (p = 0.0015). The overall complication rate for this series was 25.4%. Interestingly, the overall complication rate was similar for both the lone anterior surgery and combined anterior-posterior groups, but the incidence of adjacent-segment disease was greater in the lone anterior surgery group.

Conclusions

Significant improvement in Nurick grade can be achieved in patients who undergo anterior surgery for cervical myelopathy for primarily ventral disease or loss of cervical lordosis. In selected high-risk patients who undergo multilevel ventral decompression, supplemental posterior fixation and arthrodesis allows for low rates of construct failure with acceptable added morbidity.

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Daniel M. Sciubba, Clarke Nelson, Beryl Gok, Matthew J. McGirt, Gregory S. McLoughlin, Joseph C. Noggle, Jean Paul Wolinsky, Timothy F. Witham, Ali Bydon and Ziya L. Gokaslan

Object

Resection of sacral tumors has been shown to improve survival, since the oncological prognosis is commonly correlated with the extent of local tumor control. However, extensive soft-tissue resection in close proximity to the rectum may predispose patients to wound complications and infection. To identify potential risk factors, a review of clinical outcomes for sacral tumor resections over the past 5 years at a single institution was completed, paying special attention to procedure-related complications.

Methods

Between 2002 and 2007, 46 patients with sacral tumors were treated with surgery. Demographic data, details of surgery, type of tumor, and patient characteristics associated with surgical site infections (SSIs) were collected; these data included presence of the following variables: diabetes, obesity, smoking, steroid use, previous surgery, previous radiation, cerebrospinal fluid leak, number of spinal levels exposed, instrumentation, number of surgeons scrubbed in to the procedure, serum albumin level, and combined anterior-posterior approach. Logistic regression analysis was implemented to find an association of such variables with the presence of SSI.

Results

A total of 46 patients were treated for sacral tumor resections; 20 were male (43%) and 26 were female (57%), with an average age of 46 years (range 11–83 years). Histopathological findings included the following: chordoma in 19 (41%), ependymoma in 5 (11%), rectal adenocarcinoma in 5 (11%), giant cell tumor in 4 (9%), and other in 13 (28%). There were 18 cases of wound infection (39%), and 2 cases of repeat surgery for tumor recurrence (1 chordoma and 1 giant cell tumor). Factors associated with increased likelihood of infection included previous lumbosacral surgery (p = 0.0184; odds ratio [OR] 7.955) and number of surgeons scrubbed in to the operation (p = 0.0332; OR 4.018). Increasing age (p = 0.0864; OR 1.031), presence of complex soft-tissue reconstruction (p = 0.118; OR 3.789), and bowel and bladder dysfunction (p = 0.119; OR 2.667) demonstrated a trend toward increased risk of SSI.

Conclusions

Patients undergoing sacral tumor surgery may be at greater risk for developing wound complications due to the extensive soft-tissue resections often required, especially with the increased potential for contamination from the neighboring rectum. In this study, it appears that previous lumbosacral surgery, number of surgeons scrubbed in, patient age, bowel and bladder dysfunction, and complex tissue reconstruction may predict those patients more prone to developing postoperative SSIs.