Gerald M. Y. Quan

Eight-year clinical and radiological follow-up of the Bryan cervical disc arthroplasty.

Study Design. Single institution, prospective cohort study of 21 patients who underwent single- or bilevel cervical disc arthroplasty for radiculopathy. Objective. To evaluate the long-term outcome of cervical disc arthroplasty. Summary of Background Data. There is an increasing trend in the use of cervical arthroplasty; however, no long-term outcome studies exist to verify their safety, functionality, and durability. Methods. A total of 21 patients underwent 27 total disc arthroplasties using the Bryan cervical disc (Medtronic Sofamor Danek Inc, Memphis, TN) after anterior cervical discectomy. Clinical and radiological data were obtained from the 8-year postoperative review. Results. Nineteen of twenty-one patients were able to perform daily activities without limitation. Twenty of twenty-one patients reported fair to excellent outcome according to Odom criteria and 21 of 27 (78%) operated segments were mobile. Functional prostheses moved an average of 10.6°, which was similar to the range of movement of the adjacent nonoperated segments of the cervical spine. Heterotopic ossification was evident in 13 of the 27 (48%) operated segments and restricted movement of the prosthesis in nine cases. Five of the six patients who received bilevel arthroplasties developed heterotopic ossification. There was one case of posterior migration of the prosthesis, which did not have any clinical repercussion. No other case showed evidence of migration, subsidence, loosening, or wear. Radiological evidence of adjacent segment degeneration was observed in four patients (19%); however, each of these patients had pre-existing degenerative disc disease at these levels on preoperative imaging. Conclusion. At 8-year follow-up, the Bryan cervical disc arthroplasty maintains favorable clinical and radiological results, with preservation of movement and satisfactory clinical outcome in the majority of cases. However, the incidence of heterotopic ossification causing restricted range of movement of the prosthesis appears to increase with time, especially in bilevel procedures.

Localization of Pigment Epithelium-Derived Factor in Growing Mouse Bone

Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor found in a wide range of fetal and adult tissues, where it is thought to play a role in the regulation of angiogenesis during development. The temporal expression of PEDF during endochondral bone formation has not previously been reported. In this study, we analysed the expression pattern of PEDF in growing mouse hindlimbs from newborn day one through to maturation at week 9, using immunohistochemistry and in situ hybridization. PEDF expression was demonstrated in chondrocytes within the resting, proliferative and upper hypertrophic zones of the epiphyseal growth plate. The pattern of expression was consistent throughout the developmental stages of the mouse. In addition, PEDF was expressed by osteoblasts lining the bone spicules in the ossification zone of metaphyseal bone, as well as by osteoblasts lining cortical periosteum. These novel results demonstrate that PEDF is developmentally expressed in both cartilage and bone cells during endochondral bone formation, and strongly suggest that it may play a regulatory role in the processes of chondrocyte and osteoblast differentiation, endochondral ossification, and bone remodelling during growth and development of long bones.

Correction of Main Thoracic Adolescent Idiopathic Scoliosis Using Pedicle Screw Instrumentation: Does Higher Implant Density Improve Correction?

Study Design. Single institution, retrospective cohort study of 49 consecutive patients with Lenke I adolescent idiopathic scoliosis, all operated by a single surgeon using identical surgical technique and type of instrumentation. Objective. To evaluate the early coronal and sagittal correction of main thoracic adolescent idiopathic scoliosis using all-pedicle screw instrumentation and to determine whether implant density influences correction. Summary of Background Data. There is an increasing trend in the use of pedicle screws in scoliosis correction surgery, particularly in using segmental all-pedicle screw constructs. No previous studies have investigated whether higher pedicle screw implant density improves correction of scoliosis in vivo. Methods. Forty-nine consecutive patients with Lenke I main thoracic adolescent idiopathic scoliosis underwent single stage posterior correction and instrumented spinal fusion with pedicle screw fixation between 2006 and 2008. Pre- and postoperative radiographs were analyzed. Mean patient age at the time of operation was 14.4 years (range: 11−19.7 years). Results. The preoperative main thoracic curve of 60.0° ± 13.4° was corrected to 17.4° ± 6.9° (69.9% correction) on the postoperative radiographs. The preoperative thoracic kyphosis of 20.0° ± 10.2° decreased to 11.6° ± 4.9° after surgery. There was a significant correlation between decrease in sagittal kyphosis and magnitude of coronal Cobb angle correction (P = 0.002). There was no correlation between implant density and magnitude of coronal or sagittal curve correction, with and without curve flexibility taken into consideration. Conclusion. Pedicle screw constructs provided excellent coronal correction of thoracic idiopathic scoliosis, however, this was at the expense of sagittal contour. Bilateral segmental pedicle screw fixation did not improve curve correction compared with unilateral or alternate segmental fixation.

Resistance of Epiphyseal Cartilage to Invasion by Osteosarcoma Is Likely to Be Due to Expression of Antiangiogenic Factors

Objectives: Epiphyseal cartilage is a barrier to osteosarcoma invasion, however the mechanisms behind this resistance remain unclear. The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage. Methods: We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression. We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis; proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium-derived factor (PEDF). Results: Epiphyseal cartilage remained intact across its entire length in all sections examined, despite increasing tumor size as well as intra- and extraosseous destruction. In the most advanced cases, only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded. This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF. In contrast, the resting, proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases. This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF. Conclusion: Epiphyseal cartilage is resistant to local invasion by osteosarcoma. The balance of angiogenesis, influenced by pro- and antiangiogenic factors, is likely to play an important role in this resistance.

The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

Despite the clinical implication and high incidence of bone and spinal metastases, the molecular mechanisms behind prostate cancer metastasis to bone and spine are not well understood. In this review the molecular mechanisms that may contribute to the highly metastatic phenotype of prostate cancer are discussed. Proangiogenic factors such as vascular endothelial growth factor (VEGF) have been shown to not only aid in the metastatic capabilities of prostate cancer but also encourage the colonization and growth of prostate tumour cells in the skeleton. The importance of VEGF in the complex process of prostate cancer dissemination to the skeleton is discussed, including its role in the development of the bone premetastatic niche, metastatic tumour cell recognition of bone, and bone remodeling. The expression of VEGF has also been shown to be upregulated in prostate cancer and is associated with clinical stage, Gleason score, tumour stage, progression, metastasis, and survival. Due to the multifaceted effect VEGF has on tumour angiogenesis, tumour cell proliferation, and bone destruction, therapies targeting the VEGF pathways have shown promising clinical application and are being investigated in clinical trials.

Anti-angiogenic therapy for osteosarcoma

Even in tumor centers using established protocols, the survival rate of patients with osteosarcoma has not improved significantly in recent years. Novel therapies are urgently needed as an adjunct to conventional treatment modalities, to reduce the dose and subsequent toxicity associated with current chemotherapy, improve local disease control, prevent development of metastases, and offer an alternative treatment for those tumors that are poorly responsive to chemotherapy. Anti-angiogenic therapy currently holds great potential in conjunction with conventional treatment modalities for osteosarcoma. Specifically, anti-angiogenic factors derived from cartilage, a natural barrier to osteosarcoma invasion, may have important therapeutic applications in osteosarcoma.

Multidisciplinary Treatment and Survival of Patients with Vertebral Metastases from Thyroid Carcinoma

BACKGROUND Distant metastases from differentiated thyroid carcinoma occur in up to 20% of cases and represent the most frequent cause of thyroid cancer-related death. Metastatic disease to the spine has the potential to cause severe morbidity, including pain, neurological deficit, and paraplegia. SUMMARY We present a case series of eight consecutive patients with symptomatic spinal metastases due to thyroid carcinoma treated by our multidisciplinary team consisting of spinal surgeons, oncologists, and radiologists, with management of each case determined by our surgical algorithm. Four patients underwent surgical decompression and stabilization for spinal metastases causing instability, spinal cord compression, neurological deficit, or intractable pain. Three patients underwent vertebroplasty for focal mechanical pain due to osteolytic metastases in the absence of significant spinal cord compression or spinal instability; one of these patients required subsequent surgical decompression for spinal cord compression. One patient was nonoperatively treated. All patients underwent total thyroidectomy for the primary cancer and adjuvant radioiodine-131 treatment. The only patient with poorly differentiated thyroid cancer, which was refractory to radioiodine-131 died at 6 months after vertebroplasty procedures for symptomatic spinal metastases. One patient with medullary thyroid carcinoma died at 18 months after vertebroplasty. All remaining six patients who had well-differentiated papillary or follicular thyroid carcinoma were alive at an average of 50 months (range: 17-96 months) after diagnosis and treatment of symptomatic spinal metastases and were ambulant, independent, and able to perform activities of daily living and had no significant pain or neurologic symptoms. CONCLUSION The potential for long-term survival of several years following development of spinal metastases should be considered during the counseling and decision-making process for patients with thyroid cancer.

Outcomes of palliative surgery in metastatic disease of the cervical and cervicothoracic spine

OBJECT This prospective study was undertaken to assess the clinical outcome of 26 consecutive patients who underwent surgery for symptomatic metastases of the cervical or cervicothoracic spine. METHODS All patients suffered axial or radicular pain, with or without neurological deficit, including radicular weakness (23%), quadriplegia or paraplegia (12%), and urinary sphincter dysfunction (8%). All patients underwent palliative decompression and stabilization surgery via an anterior (18 patients), posterior (7 patients) or combined approach (1 patient) depending on the topography of the metastases, and were prospectively followed up for 1 year. Thirteen patients received adjuvant chemotherapy and 7 patients received radiotherapy to the cervical lesion. Clinical data as well as data from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire were obtained pre- and postoperatively and at regular follow-up intervals. RESULTS Median survival was 6 months and 10 patients were known survivors at 12 months. Postoperatively, 1 patient developed neurological deterioration and died while an inpatient. There were no other early postoperative complications in any patients. From pre- to postoperatively there was an immediate and significant improvement in axial and radicular pain and overall quality of life. There was also overall improvement in cognitive, emotional, social, role, and physical functioning. The observed improvement in pain, functioning, and quality of life was maintained for the duration of the follow-up period. Furthermore, neurological function was improved or preserved until death in the majority of patients. CONCLUSIONS Together with adjuvant medical management, surgery for cervical metastases produces low morbidity and can achieve good symptomatic palliation in the majority of patients for their remaining lifetime.

Animal Cancer Models of Skeletal Metastasis

The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

In vivo animal models of spinal metastasis

The vertebral column is the commonest site for skeletal metastases, with breast, prostate and lung cancers being the most common primary sources. The spine has structural and neural-protective properties thus involvement by metastatic cancer often causes bony instability and fracture, intractable pain and neurological deficit. In vivo animal models which resemble the human condition are essential in order to improve understanding of the pathophysiology behind the spread of metastatic cancer to the spine and its subsequent local growth and invasion, to enable in-depth analysis of the interaction between host and tumour cells and the molecular processes behind local cancer invasion and barriers to invasion as well as to allow assessment of novel treatment modalities for spinal metastases. This review summarizes the current status of the animal models specifically used for the study of spinal metastasis, their relevance, advantages and limitations, and important considerations for the development of future in vivo animal models.