Surgery (Austin & Northern Health) - Research Publications
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ItemThe role of vascular endothelial growth factor in metastatic prostate cancer to the skeleton.(Hindawi Limited, 2013)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.
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ItemNo Preview AvailableThe osteoblastic and osteoclastic interactions in spinal metastases secondary to prostate cancer.(SAGE Publications, 2013)Prostate cancer (PC) is one of the most common cancers arising in men and has a high propensity for bone metastasis, particularly to the spine. At this stage, it often causes severe morbidity due to pathological fracture and/or metastatic epidural spinal cord compression which, if untreated, inevitably leads to intractable pain, neurological deficit, and paralysis. Unfortunately, the underlying molecular mechanisms driving growth of secondary PC in the bony vertebral column remain largely unknown. Further investigation is warranted in order to identify therapeutic targets in the future. This review summarizes the current understanding of PC bone metastasis in the spine, highlighting interactions between key tumor and bone-derived factors which influence tumor progression, especially the functional roles of osteoblasts and osteoclasts in the bone microenvironment through their interactions with metastatic PC cells and the critical pathway RANK/RANKL/OPG in bone destruction.
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ItemNo Preview AvailableAnimal cancer models of skeletal metastasis.(SAGE Publications, 2013)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.
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ItemFractured neck of femur below long spinopelvic fixation for Charcot spine: a case report.(Springer Science and Business Media LLC, 2013-12-30)INTRODUCTION: We present a case of a patient with a previously undescribed complication: intertrochanteric femoral neck insufficiency fracture after long-segment instrumented spinopelvic fusion to the ilium for Charcot spine. CASE PRESENTATION: A 42-year-old Caucasian man with post-traumatic complete T6 paraplegia presented to our institution after developing Charcot spinal arthropathy at L3 and L4 and symptoms of autonomic dysreflexia 21 years after his original spinal cord injury. Multiple anterior and posterior surgeries were required to eventually achieve stabilization of his thoracolumbar spine to his pelvis and resolution of symptoms. The most distal fixation point was two iliac wing screws bilaterally. At 10 weeks after the final spinal surgery and after posterior spinal bony consolidation had occurred, he sustained an intertrochanteric femoral neck fracture, distal to the iliac fixation, whilst bending forward in his wheelchair. His proximal femoral fracture was internally fixed with an intramedullary device. CONCLUSIONS: Spinal Charcot's arthropathy is a rare condition that may occur in patients with post-traumatic spinal cord injury. Although associated with high risk of complications, circumferential instrumented fusion in Charcot spine can restore spinal stability. Insufficiency fractures of the proximal femur are possible complications of long spinopelvic fusions.
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ItemLessons learnt from the painful shoulder; a case series of malignant shoulder girdle tumours misdiagnosed as frozen shoulder.(Springer Science and Business Media LLC, 2005-01-12)Adhesive capsulitis or frozen shoulder is a common condition characterized by shoulder pain and stiffness. In patients in whom conservative measures have failed, more invasive interventions such as arthrographic or arthroscopic distension can be very effective in relieving symptoms and improving range of movement. However, absolute contraindications to these procedures include the presence of neoplasia around the shoulder girdle. We present five cases referred to our institution where the diagnosis of shoulder joint malignancy was delayed, following prolonged, ineffective treatment for frozen shoulder. These cases highlight the importance of careful review of the radiology and the need for reconsideration of the diagnosis in refractory "frozen shoulder".
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ItemAn in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia(SPRINGER, 2013-11)The spine is the commonest site of skeletal metastatic disease and uncontrolled growth of cancer in the spine will inevitably cause pain and neurologic compromise. Improved understanding of the pathobiology behind this devastating condition is urgently needed. For this reason, the aim of this study was to establish a clinically relevant, animal model of spinal cancer. A percutaneous orthotopic injection of human breast (MDA-MB-231) or human prostate (PC-3) cancer cells was administered into the upper lumbar spine of nude mice (n = 6). Animals were monitored twice daily for general welfare, gait asymmetry or disturbance, and hindlimb weakness. After sacrifice, plain radiographs, micro-CT imaging and histological analysis of the spines were performed on each mouse. All mice recovered fully from the inoculation procedure and displayed normal gait and behaviour patterns for at least 3 weeks post-inoculation. Subsequently, between 3 and 5 weeks post-inoculation, each mouse developed evolving paralysis in their hindlimbs over 48-72 h. All followed the same pattern of decline following onset of neurological dysfunction; from gait asymmetry and unilateral hindlimb weakness, to complete unilateral hindlimb paralysis and finally to complete bilateral hindlimb paralysis. Plain radiographs, micro-CT scanning and histological analysis confirmed local tumour growth and destruction of the spine in all six mice. An in vivo mouse model of human intraosseous spinal cancer has been established forming cancers that grow within the spine and cause epidural spinal cord compression, resulting in a reproducible, evolving neurological deficit and paralysis that closely resembles the human condition.
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ItemMultidisciplinary Treatment and Survival of Patients with Vertebral Metastases from Thyroid Carcinoma(MARY ANN LIEBERT, INC, 2012-02)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.