Carlos A. Bagley

Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model

OBJECTnSpinal 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.nnnMETHODSnFemale 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 microL 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 microL 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.nnnRESULTSnThere 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.nnnCONCLUSIONSnThese 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.

Fractionated, single-port radiotherapy delays paresis in a metastatic spinal tumor model in rats

OBJECTnSpinal 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.nnnMETHODSnAfter 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 animals death.nnnRESULTSnFunctional 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.nnnCONCLUSIONSnThese 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.

A novel model of intramedullary spinal cord tumors in rats: functional progression and histopathological characterization.

OBJECTIVEnIntramedullary spinal cord tumors are difficult lesions to treat given their recurrence rate and limited treatment options. The absence of an adequate animal model, however, has hindered the development of new treatment paradigms. In this study, we describe the technique for intramedullary injection of two experimental rodent gliomas (9L and F98) and present the methodology for functional and histopathological analysis of tumor progression.nnnMETHODSnF344 rats (n = 24) were randomized into three groups. Group 1 (n = 8) received a 5 microl intramedullary injection of Dulbeccos modified Eagle medium, Group 2 received a 5 microl intramedullary injection of 9L gliosarcoma (100,000) cells, and Group 3 received a 5 microl intramedullary injection of F98 glioma (100,000) cells. The animals were anesthetized, a 2 cm incision was made in the dorsal mid-thoracic region, and the spinous process of the T5 vertebrae was removed to expose the intervertebral space. The ligamentum flavum was removed, and an intramedullary injection was made into the spinal cord. The animals were evaluated daily for signs of paralysis using the Basso, Beattie, and Bresnahan scale and sacrificed after the onset of deficits for histopathological analysis.nnnRESULTSnAnimals injected with 9L-gliosarcoma had a median onset of hind limb paresis at 12 +/- 2.9 days. Animals injected with F98 glioma had a median onset of hind limb paresis at 19 +/- 3 days. Animals injected with Dulbeccos modified Eagle medium did not show neurological deficits. Hematoxylin-eosin cross sections confirmed the presence of intramedullary 9L and F98 tumor invading the spinal cord. Control animals had no significant histopathological findings.nnnCONCLUSIONnAnimals injected with 9L or F98 consistently developed hind limb paresis in a reliable and reproducible manner. The progression of neurological deficits is similar to that seen in patients with intramedullary spinal cord tumors. These findings suggest that this model mimics the behavior of intramedullary spinal cord tumors in humans and may be used to examine the efficacy of new treatment options for both low- and high-grade intramedullary tumors.

A novel intravertebral tumor model in rabbits.

OBJECTIVE:Although the majority of human epidural spinal metastases originate in the vertebral body, current animal models of spinal epidural tumors are limited to extraosseous tumor placement. We investigated the onset of paraparesis, radiographic changes (magnetic resonance imaging [MRI] and computed tomographic [CT] scans), and histopathological findings after intraosseous injection of VX2 carcinoma cells into the lower thoracic vertebrae of rabbits. METHODS:New Zealand white rabbits (n = 23) were injected with a 15-&mgr;l suspension containing 300,000 VX2 carcinoma cells in the lowest thoracic vertebral body. Lower extremity motor function was assessed daily. For the first 3 animals, MRI scans (T2-weighted and T1-weighted ± gadolinium) were acquired at postoperative day (POD) 14 and at the onset of paraparesis. Noncontrast CT scans were obtained on POD 7 and at the time of paraparesis. At the onset of paraparesis, the animals ware killed and the spines were dissected. After demineralization, hematoxylin and eosin cross sections were obtained. RESULTS:Before the onset of paraparesis, the CT and MRI scans revealed no gross tumor. At the onset of paraparesis, CT scans demonstrated an osteolytic tumor centered at the junction of the left pedicle and vertebral body, and MRI scans demonstrated epidural tumor arising from the body and compressing the spinal cord. Histopathological examination confirmed carcinoma arising from the body and extending into the canal, with widespread osteolytic activity. By POD 28, 72% of the animals had become paraparetic, and by the termination of the experiment on POD 120, 89% had become paraparetic. CONCLUSION:We established a novel intraosseous intravertebral tumor model in rabbits and characterized it with respect to onset of paraparesis, imaging features, and histopathological findings.

Intracavernous trigeminal ganglion amyloidoma: Case report

OBJECTIVEIsolated amyloidomas rarely manifest in nervous system tissues. To the authors knowledge, there have been 52 documented cases of primary amyloid tumors of the central nervous system and closely associated structures. The authors present a case of a woman with a history of presumptive trigeminal neuralgia who was found to have an amyloidoma of the trigeminal ganglion. CLINICAL PRESENTATIONA 32-year-old Caucasian patient presented with a chief complaint of severe numbness and pain throughout the right side of her face. Her symptoms had been progressive over the previous 3 years. Medical management of her presumptive diseases with Zoloft (Pfizer Inc., New York, NY) and Neurontin (Pfizer Inc.) failed to improve or halt her right facial numbness and pain. Brain magnetic resonance imaging was acquired, demonstrating abnormal contrast enhancement and enlargement of the right trigeminal ganglion. The lesion abutted and indented the right internal carotid artery and extended from Meckels cave into the inferior cavernous sinus and distally to the foramen ovale. INTERVENTIONThe patient underwent a right frontotemporal craniotomy for resection of the gasserian ganglion lesion. A delicate incision was made in the wall of the cavernous sinus, allowing confirmatory biopsy of the lesion. With the site of the tumor within the cavernous sinus verified by pathology, the remainder of the tumor was removed. A final pathological review of the resected tumor confirmed a diagnosis of amyloidoma of the trigeminal ganglion. CONCLUSIONWe present the case of a patient with a rare trigeminal ganglion amyloidoma that closely mimicked idiopathic trigeminal neuralgia. Even in the absence of systemic signs of amyloidosis, this benign protein deposition disease should be considered in the differential for atypical dysesthesias of the trigeminal dermatomes. Furthermore, central and peripheral nervous system amyloidomas respond well to surgical resection and rarely recur.

Concomitant conus medullaris ependymoma and filum terminale lipoma: Case report

OBJECTIVE:Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary lesions. In this report, we describe the clinical presentation, radiographic findings, operative details, and pathological features of a patient with a conus medullaris ependymoma and a filum terminale lipoma. CLINICAL PRESENTATION:A 40-year-old woman presented with increasing low back pain and bowel and bladder dysfunction. Magnetic resonance imaging revealed a partially cystic enhancing lesion at the conus medullaris and a T1-weighted hyperintense mass within the filum terminale. INTERVENTION:An L2-L3 laminotomy/laminoplasty was performed for gross total resection of the mass. Histopathological examination demonstrated a conus medullaris ependymoma and filum terminale lipoma. The patient experienced complete resolution of her preoperative symptoms. CONCLUSION:Spinal cord ependymomas are almost exclusively single lesions and their coexistence with other pathological entities is rare. In this report, we describe a patient with a concomitant conus medullaris ependymoma and filum terminale lipoma.Received, April 28, 2005. Accepted, February 9, 2006. OBJECTIVE: Ependymomas of the conus medullaris-cauda equina-filum terminale region are typically solitary lesions. In this report, we describe the clinical presentation, radiographic findings, operative details, and pathological features of a patient with a conus medullaris ependymoma and a filum terminale lipoma. CLINICAL PRESENTATION: A 40-year-old woman presented with increasing low back pain and bowel and bladder dysfunction. Magnetic resonance imaging revealed a partially cystic enhancing lesion at the conus medullaris and a T1-weighted hyperintense mass within the filum terminale. INTERVENTION: An L2–L3 laminotomy/laminoplasty was performed for gross total resection of the mass. Histopathological examination demonstrated a conus medullaris ependymoma and filum terminale lipoma. The patient experienced complete resolution of her preoperative symptoms. CONCLUSION: Spinal cord ependymomas are almost exclusively single lesions and their coexistence with other pathological entities is rare. In this report, we describe a patient with a concomitant conus medullaris ependymoma and filum terminale lipoma.

Harms titanium mesh cage fracture

Interbody fusion has become a mainstay of surgical management for lumbar fractures, tumors, spondylosis, spondylolisthesis and deformities. Over the years, it has undergone a number of metamorphoses, as novel instrumentation and approaches have arisen to reduce complications and enhance outcomes. Interbody fusion procedures are common and successful, complications are rare and most often do not involve the interbody device itself. We present here a patient who underwent an anterior L4 corpectomy with Harms cage placement and who later developed a fracture of the lumbar titanium mesh cage (TMC). This report details the presentation and management of this rare complication, as well as discusses the biomechanics underlying this rare instrumentation failure.

Epidural Tumors and Metastases

Cancer affects approximately 1.4 million Americans every year. Despite recent advancements and improvements in the care of these patents, approximately half will eventually succumb to their disease, a rate that has remained relatively unchanged over the last half century. In 2001, cancer ranked second to only heart disease in terms of mortality in the USA, accounting for approximately 23% of all deaths. The most common causes of death in oncology patients are complications related to metastasis of their primary disease [52]. The skeletal system is the third most common site for metastases, behind the lung and liver. Within the skeletal system, the spinal column is the most commonly affected site [6]. In fact, metastases are the most common type of neoplastic lesion found in the spinal column, comprising up to 90% of all spinal tumors in some series. Autopsy studies also demonstrate that upwards of 90% of cancer patients will have spinal metastatic deposits at the time of death. Of those with spinal metastases, up to 50% will require some form of treatment for their spinal metastasis and 5–10% will require surgery [3, 5, 47, 52].