What should we do as orthopedic surgeons in catastrophic disasters?

AbstractOn March 11, 2011, Japan was consecutively hit by three unprecedented disasters caused by The Great East Japan (Tohoku) Earthquake: an earthquake of magnitude 9.0, an incredibly powerful tsunami, and a nuclear power plant breakdown. As Japan had experienced The Great Hanshin-Awaji Earthquake in 1995, we were prepared to provide the victims with appropriate medical care to some extent. Nevertheless, providing medical treatment after the Tohoku earthquake was extremely difficult due to the fact that the types of injuries in Tohoku were quite different from those in Hanshin. Based on our experiences in Hanshin and Tohoku, I would like to send a message to the world concerning the role of orthopedic surgeons in catastrophic disasters

Current Status and Perspectives Regarding the Treatment of Osteosarcoma: Chemotherapy

Osteosarcoma is the most common primary bone tumor in childhood and adolescence. The use of combination chemotherapy and surgery enables long-term survival in approximately 60-70% of cases. However, the necessity for surgery, the poor prognosis of patients with metastatic or recurrent disease (long-term survival in only about 20% of cases), and the lack of establishment of second-line chemotherapy suggest that improvements in chemotherapy are desperately needed. Currently, in an effort to extend the protocol with the chemotherapy drugs that already exist, high-dose chemotherapy with/without autologous peripheral blood stem cell transplantation, and tumor-targeted drug delivery systems are under investigation. Future drug developments will no doubt lie in the direction of immunotherapy and anti-angiogenic therapy, as well as the use of cytotoxic drugs. Identifying the genes and signal transduction pathways responsible for the development of osteosarcoma or for the occurrence of malignancy in cases of osteosarcoma will undoubtedly lead to the identification of pathway-specific agents, or possible gene therapy. Furthermore, as increased light is shed on the character of osetoblastic differentiation in osteosarcoma, this will certainly give rise to new treatments utilizing differentiation therapy. This article reviews the current status and perspectives regarding the treatment of osteosarcoma in terms of chemotherapy

Establishment of an animal model of a pasteurized bone graft, with a preliminary analysis of muscle coverage or FGF-2 administration to the graft

<p>Abstract</p> <p>Background</p> <p>Pasteurized bone grafting is used following the excision of a bone tumor for the purpose of eliminating neoplastic cells while preserving bone-inducing ability. In the hopes of guaranteeing the most favourable results, the establishment of an animal model has been urgently awaited. In the course of establishing such a model, we made a preliminary examination of the effect of muscle coverage or fibroblast growth factor 2 (FGF-2) administration radiographically.</p> <p>Methods</p> <p>Forty pasteurized intercalary bone grafts of the Wistar rat femur treated at 60°C for 30 min were reimplanted and stabilized with an intramedullary nail (1.1 mm in diameter). Some grafts were not covered by muscle after the implantation, so that they could act as a clinical model for wide resection, and/or these were soaked with FGF-2 solution prior to implantation. The grafts were then divided into 3 groups, comprising 12 grafts with muscle-covering but without FGF-2 (MC+; FGF2-), 12 grafts without muscle-covering and without FGF-2 (MC-; FGF2-) and 16 grafts without muscle covering but with FGF-2 (MC-; FGF2+).</p> <p>Results</p> <p>At 2 weeks after grafting, the pasteurized bone model seemed to be successful in terms of eliminating living cells, including osteocytes. At 4 weeks after grafting, partial bone incorporation was observed in half the (MC+; FGF2-) cases and in half the (MC-; FGF2+) cases, but not in any of the (MC-; FGF2-) cases. At 12 weeks after grafting, bone incorporation was seen in 3 out of 4 in the (MC+; FGF2-) group (3/4: 75%) and in 3 out of 8 in the (MC-; FGF2+) group (3/8: 38%). However, most of the grafted bones without FGF-2 were absorbed in all the cases, massively, regardless of whether there had been muscle-covering (MC+; FGF2-; 4/4: 100%) or no muscle-covering (MC-; FGF2-; 4/4: 100%), while bone absorption was noted at a lower frequency (2/8: 25%) and to a lower degree in the (MC-; FGF2+) group.</p> <p>Conclusion</p> <p>In conclusion, we have established an animal pasteurized bone graft model in rats. Pasteurized bone was able to maintain bone induction ability. Despite the low number of cases in each group, the results of each group suggest that muscle-covering has an effect on bone incorporation, but that it is not able to prevent bone absorption to the pasteurized bone. However, an application of FGF-2 may have a positive effect on bone incorporation and may be able to prevent bone absorption of the graft in cases of pasteurized bone graft.</p

Diastematomyelia: A Surgical Case with Long-Term Follow-Up

Few reports have described the involvement of syringomyelia associated with diastematomyelia in the etiology of neurological deficits. We reported a case with syringomyelia associated with diastematomyelia. A female patient with diastematomyelia was followed up clinically over 14 years. At the age of 8, she developed clubfoot deformity with neurological deterioration. Motor function of the right peroneus demonstrated grade 2 in manual muscle tests. Continuous intracanial bony septum and double cords with independent double dura were observed at upper thoracic spine. Magnetic resonance imaging revealed a tethering of the spinal cord and syringomyelia distal to the level of diastematomyelia. Extirpation of the osseum septum and duralplasty were performed surgically. She grew without neurological deterioration during 7 years postoperatively. A long-term followed up case with syringomyelia that was possibly secondary to the tethering of the spinal cord associated with diastematomyelia, and effective treatment with extirpation of the osseum septum and duralplasty was described

Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

BACKGROUND: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway. METHODS: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry. RESULTS: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK. CONCLUSIONS: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs

Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.

Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury

Metastasis to the gluteus maximus muscle from renal cell carcinoma with special emphasis on MRI features

<p>Abstract</p> <p>Background</p> <p>The skeletal muscle is an unusual site for metastasis from renal cell carcinoma (RCC). Metastatic RCC must be differentiated from benign primary soft-tissue tumors because aggressive surgical resection is necessary.</p> <p>Case presentation</p> <p>We present the case of a 65-year-old man with metastatic RCC in the gluteus maximus muscle (3.8 cm in diameter) found on enhanced computed tomography (CT) 6 years after nephrectomy. Retrospectively, the small mass (1 cm in diameter) was overlooked 5 years earlier on enhanced CT. Because the growth of the lesion was slow, benign tumor was a differential diagnosis. However, magnetic resonance imaging (MRI) showed that the mass had high-signal intensity on T1- and T2-weighted images (WIs) compared to that of skeletal muscle, with mild enhancement by Gadolinium. The MRI features were unusual for most soft-tissue tumors having low-signal intensity on T1-WI and high-signal intensity on T2-WI. Therefore, under a diagnosis of metastatic RCC, the lesion was resected together with the surrounding skeletal muscle. The histology was confirmed to be metastatic RCC.</p> <p>Conclusion</p> <p>MRI features of metastatic RCC may be beneficial in differentiating it from primary soft-tissue tumor.</p