Is routine MRI of the spine necessary in trauma patients with ankylosing spinal disorders or is a CT scan sufficient?

BACKGROUND: Ankylosing spinal disorder (ASD) patients are at a greater risk for spinal fractures due to osteoporosis and rigidity of the spinal column. These fractures are associated with a high risk of neurologic compromise resulting from delayed or missed diagnoses. Although computed tomography (CT) is usually the initial imaging modality, magnetic resonance imaging (MRI) has been proposed as mandatory to help identify spinal injuries in ASD patients with unexplained neck or back pain or known injuries to help identify noncontiguous fractures. However, some studies have also shown that neurological injury can result from the required patient transfer and positioning for an MRI. PURPOSE: The purpose of our study was to assess the frequency with which an MRI identified an injury not previously identified with CT, and whether this affected the treatment and outcome of the patient. Secondarily, we attempted to identify clinical or CT findings that may render an MRI particularly useful. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: Patients with ASD who sustained acute spine fractures from 2005 to 2015. OUTCOME MEASURES: Acute fractures identified by CT scan and MRI upon admission; neurologic status upon admission and discharge, mode of injury, type of fracture, and final intervention before and after MRI assessment. METHODS: A total of 124 patients with a diagnosis of diffuse idiopathic skeletal hyperostosis (DISH) or ankylosing spondylitis (AS) were identified by searching the radiology database of a level I trauma center with diagnosis keywords. Final radiology reports were assessed to determine presence and type of fracture(s) from CT. MRI report was then reviewed to assess if additional fractures or injuries were identified beyond that already known from the CT. Neurologic status upon admission and discharge, mode of injury, type of fracture, and final intervention were determined by inpatient notes and/or operative reports. No source funding or conflict of interest was present pertaining to this study. RESULTS: In the designated time frame, 124 ASD patients with injuries of the spine were identified who had obtained both a baseline CT and MRI. Six patients (4.8%) had additional injuries on MRI that had not been identified with CT. Four of these six patients had a change in treatment plan (three operative and one nonoperative) based on subsequent MRI findings. These included a (1) C4-5 hyperextension injury, (2) C6-7 hyperextension injury, (3) C7 bony fracture with C5-T4 epidural hematoma, and (4) C5-C6 hyperextension injury treated in a brace. Two of the six patients that had additional injuries identified on MRI had no change in their treatment plan. One patient had an additional lumbar extension injury identified above a previously diagnosed injury on CT, which was managed with a Thoracolumbosacral Orthosis (TLSO) according to the original plan. One patient died who had a known odontoid fracture and a suspected C6-7 hyperextension injury, and was identified on MRI as also having a C3-C4 hyperextension injury and a C2 spinal cord transection. CONCLUSIONS: In this study, 3.2% (4/124) of patients with ASD who presented to a level I trauma center with an acute spine injury identified with CT required a change in their treatment plan based on subsequent MRI findings. Only one fracture was missed on CT imaging, with the other missed injuries all being either disco-ligamentous hyperextension injuries through mobile discs or intracanal pathology. Our recommendation is that the routine use of MRI be limited to patients with nonankylosed levels in which a disco-ligamentous injury may have occurred, and in patients with neurological deficits that require investigation of the spinal canal to assess for causes of neurological injury.

Short Versus Long Intramedullary Nails in the Treatment of Pertrochanteric Hip Fractures: Incidence of Ipsilateral Fractures and Costs Associated With Each Implant.

OBJECTIVES: Both short intramedullary nails (SIMNs) and long intramedullary nails (LIMNs) are routinely used in the surgical treatment of pertrochanteric hip fractures. The purpose of this study was to assess the incidence of ipsilateral femur fractures after the surgical treatment of hip fractures and the overall costs associated with each implant. DESIGN: Retrospective cohort study. SETTING: Level I trauma center and 2 community hospitals. PATIENTS/PARTICIPANTS: A total of 609 patients with pertrochanteric hip fractures treated with an SIMN or LIMN from 2005 to 2011. INTERVENTION: Review of patient demographics and clinical outcomes over a 5-year follow-up period. MAIN OUTCOME MEASUREMENTS: Ipsilateral femur refracture rates were recorded for both groups, and a cost analysis was then performed to compare SIMNs and LIMNs while accounting for their observed refracture rates and surgical/hospital costs to determine the overall cost of each implant. RESULTS: Union rates were equivalent between groups and averaged over 97%. The incidence of ipsilateral femur fractures in both groups steadily increased with greater follow-up time to reach nearly 10% at 5 years. Although only 47% of all nails were locked distally, 15 of the 16 refractures occurred in nails that were not distally locked. Cost analysis revealed no significant difference in the use of short versus LIMNs over a 5-year period (P = 0.76). CONCLUSIONS: The incidence of ipsilateral femur refractures steadily rose with greater follow-up in both SIMN and LIMNs. Distally locking the initial fixation seems to protect against future femur fractures and may also affect the refracture location when using LIMNs. No differences in overall costs were seen at 1, 2, or 5 years between SIMNs and LIMNs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Neuropilin-2 expression is inhibited by secreted Wnt antagonists and its down-regulation is associated with reduced tumor growth and metastasis in osteosarcoma.

BACKGROUND: Neuropilin 2 (NRP2) isa multi-functional co-receptor to many receptors, including VEGF receptor, c-Met and others. NRP2 has recently been implicated in tumor angiogenesis, growth, and metastasis of many other cancers. However, its role in osteosarcoma remains poorly understood. RESULTS: NRP2 was overexpressed in osteosarcoma cell lines and tissues, and associated with poor survival of osteosarcoma patients. Knockdown of NRP2 expression by short-hairpin (Sh) RNA resulted in reduced tumor growth, metastasis, and blood vessel formation of osteosarcoma. Knockdown of NRP2 expression by ShRNA also inhibited the recruitment of HUVEC cells to osteosarcoma cells. Inhibition of Wnt signaling by overexpression of secreted Wnt antagonists soluble LRP5, Frzb, and WIF1 markedly down-regulated mRNA and protein expression of NRP2 in osteosarcoma cell lines. CONCLUSIONS: Regulation of NRP2 receptor expression may represent a novel approach for treatment of osteosarcoma through retarding osteosarcoma growth, metastasis and blood vessel formation. In addition, down-regulation of NRP2 expression can be achieved by expression of secreted Wnt antagonists.

Dkk-3, a secreted wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/ ß -catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy.

The Wnt signaling pathway: implications for therapy in osteosarcoma.

Osteosarcoma is the most common primary bone malignancy, with a high propensity for local invasion, early metastasis and relapse. While the molecular mechanisms behind osteosarcoma development and metastasis have not yet been fully elucidated, research has highlighted an important role for Wnt signaling. Several Wnt ligands, receptors and coreceptors are highly expressed in osteosarcoma cell lines, while Wnt inhibitors are downregulated. As a result, research has begun to identify mechanisms with which to inhibit Wnt signaling. The use of Wnt pathway inhibitors and the targeting of c-Met, a Wnt regulated proto-oncogene, may be two possible mechanisms for treatment of osteosarcoma. In addition, as the Wnt signaling pathway is a regulator of stem cells, reagents that function as Wnt inhibitors are currently under investigation as inhibitors of cancer stem cell proliferation. Research involving the Wnt signaling pathway and cancer stem cells holds promise for novel treatment options in the future.

The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition.

BACKGROUND: Aberrations in the Wnt pathway have been reported to be involved in the metastasis of prostate cancer (PCa) to bone. We investigated the effect and underlying mechanism of a naturally-occurring Wnt inhibitor, WIF1, on the growth and cellular invasiveness of a bone metastatic PCa cell line, PC3. RESULTS: The WIF1 gene promoter was hypermethylated and its expression down-regulated in the majority (7 of 8) of PCa cell lines. Restoration of WIF1 expression in PC-3 cells resulted in a decreased cell motility and invasiveness via up-regulation of epithelial markers (E-cadherin, Keratin-8 and-18), down-regulation of mesenchymal markers (N-cadherin, Fibronectin and Vimentin) and decreased activity of MMP-2 and -9. PC3 cells transfected with WIF1 consistently demonstrated reduced expression of Epithelial-to-Mesenchymal Transition (EMT) transcription factors, Slug and Twist, and a change in morphology from mesenchymal to epithelial. Moreover, WIF1 expression significantly reduced tumor growth by approximately 63% in a xenograft mouse model. This was accompanied by an increased expression of E-cadherin and Keratin-18 and a decreased expression of vimentin in tumor tissues. CONCLUSION: These data suggest that WIF1 regulates tumor invasion through EMT process and thus, may play an important role in controlling metastatic disease in PCa patients. Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients.