[Show abstract][Hide abstract] ABSTRACT: Background Undifferentiated pleomorphic sarcoma (UPS) is a heterogeneous tumor group, and little is known about molecular target therapy for UPS. Heat shock protein 90 (HSP90) is an expressed chaperone that refolds certain denatured proteins under stress conditions. One of these proteins is Akt. The disruption of Akt signaling plays an important role in tumor progression. The present study’s purpose was to analyze the HSP90 expression, Akt/mTOR pathway activation and the correlation between HSP90 expression and its pathway activation in UPS. Methods The status of HSP90 and the profiles of the Akt/ mTOR pathway were assessed by immunohistochemistry in 79 samples of UPS, and these data were compared with clinicopathological and histopathological findings. The expressions of indicated proteins were assessed by Western blotting in five frozen samples. After treating UPS cells with the HSP90 inhibitor, we assessed the antitumor effect of the inhibitor. Results Immunohistochemically, phosphorylated Akt (p-Akt), p-mTOR, p-S6RP and p-4EBP were positive in 57.3, 51.9, 54.5 and 57.1 % of the UPS samples, respectively. The expressions of those phosphorylated proteins were correlated with each other. HSP90 expression was elevated in 56.4 % of the samples and was correlated with p-Akt, p-mTOR and p-S6RP. The immunohistochemical results were confirmed by Western blotting. The HSP90 inhibitor led to decreased viability and invasiveness of the cells and inactivated the AKT/mTOR pathway in vitro. Conclusion Elevated expression of HSP90 is a poor-prognosis factor and is involved in the activation of the Akt/mTOR pathway in UPS. HSP90 inhibition is a potential treatment option for UPS.
BMC Cancer 12/2015; 15(1). DOI:10.1186/s12885-015-1830-8 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Study design:
A computed tomography study.
To clarify the position of the aorta relative to the spine in patients with Lenke type 1 adolescent idiopathic scoliosis.
Summary of background data:
Several authors have examined the position of the aorta in patients with scoliosis. However, their analysis included several types of curve. There is a possibility that the position of the aorta differs according to the scoliosis curve type.
Thirty-eight patients with Lenke type 1 were analyzed. The angle (LtP-Ao angle) and distance (LtP-Ao distance) from the insertion point of the left pedicle screw to the aorta were measured from T4 through L2. The measured data were evaluated from four levels above to four levels below the apical vertebra. The difference between lumbar modifiers A and C was examined. Dangerous pedicles, which were defined as those in which the aorta entered the expected area based on the screw direction error and length, were counted from T10 to L2.
The aorta located posterolaterally and adjacent to the vertebra at the middle thoracic level, and anteromedially and distant at the thoracolumbar level. LtP-Ao angle was largest at one level above the apical vertebra, and LtP-Ao distance was shortest at two levels above. LtP-Ao angle of Lenke 1A was significantly larger than 1C from T11 to L2, and LtP-Ao distance of 1A was significantly shorter than 1C from T11 to L1. When the screw length was 40 mm and the direction error was within 10°, there were a large number of dangerous pedicles at T11, regardless of the lumbar modifier.
The direction error has a potential risk of injuring the aorta around the apical vertebra. The selection of screws of the proper length is necessary to avoid a breach of the anterior vertebral wall at thoracolumbar level, especially at T11.
Level of evidence:
[Show abstract][Hide abstract] ABSTRACT: Background:
When spinal kyphosis increases, the compensatory mechanism activates and the pelvic position changes. Increasing the pelvic tilt, which is the orientation of the pelvis with respect to the femoral head, is known to associate with the clinical symptoms in kyphosis in the aging population. It is often difficult to detect the femoral head on radiographs, limiting the ability to determine the pelvic tilt. Therefore, there is a need to establish another parameter independent of the femoral head which closely correlates with the pelvic tilt.
Eighty-two adult patients with full-length lateral standing spine radiographs were recruited (mean age: 73.0 years). A new parameter, the iliac cortical density line (a component of the arcuate line of the ilium) and the iliac tilt (defined as the angle between the iliac cortical density line and the vertical), was analyzed to determine the correlation with the pelvic tilt.
Both the pelvic tilt (PT) and iliac tilt (IT) could be identified in 67 patients, and a significant correlation was observed between the PT and IT (r = 0.86, P < 0.0001). The PT could be estimated using the following formula: PT = IT - 12.9 (in females), PT = IT - 16.7 (in males).
The iliac tilt, which can be easily and directly measured using the iliac cortical density line, is a new parameter that can reliably estimate the pelvic tilt even when the femoral head is not detectable on the radiograph.
Journal of Orthopaedic Surgery and Research 07/2015; 10(1):115. DOI:10.1186/s13018-015-0262-0 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence of and to identify independent predictors associated with scoliosis in patients with multiple hereditary exostoses (MHE).
Fifty patients with MHE were clinically examined, and the diagnosis of scoliosis was made based on radiographs. To classify disease severity, three classes based on the presence of deformities and functional limitations were defined. Significant independent predictors of scoliosis in MHE were statistically analyzed.
Scoliosis was present in 36 patients (MHE-scoliosis) (72 %). In the MHE-scoliosis group, the mean primary curve was 15.3° ± 5.7° (range 10°-34°) and the mean minor curve was 10.6° ± 7° (range 6°-32°). Left curve was predominant (72 %), and the apex was located in the thoracolumbar or lumbar spine in 64 % of patients. Univariable and multivariable analyses confirmed that MHE severity was a significant predictor of moderate scoliosis (≥20°).
Our study confirmed that scoliosis is a common feature of MHE and disease severity is a predictor of moderate scoliosis (≥20°).
European Spine Journal 03/2015; 24(7). DOI:10.1007/s00586-015-3883-4 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Marked neurological deterioration within a few days of traumatic spinal cord injury, known as subacute posttraumatic ascending myelopathy, is rare. Although several hypotheses regarding the pathogenesis of this condition have been proposed, the details remain elusive.
The spine journal: official journal of the North American Spine Society 09/2014; 14(12). DOI:10.1016/j.spinee.2014.08.449 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Right thoracic curvature, rib cage deformities and aortic left shift are features of adolescent idiopathic scoliosis that are correlated with each other. We recently reported that disturbance of ribcage development results in progressive thoracic scoliosis in mice. Recently, it has been confirmed that the normal spine exhibits right thoracic curvature and rib cage deformities and that these deformities worsen during the adolescent period. The purpose of this study was to examine whether rib cage deformities correlate with thoracic side curvature in the normal spine, as observed in scoliosis, which is important basic knowledge needed to elucidate the causative factors of adolescent idiopathic scoliosis.
To examine the relationship between rib cage deformities and thoracic side curvature in the normal spine, CT scans of 148 consecutive adult females were examined. The anteroposterior chest dimension, aortic location and rib cage rotation were measured on CT scans obtained at the T8 level. The thoracic side curvature (T5-T12) was also measured on chest radiographs.
The anteroposterior chest dimension exhibited a significant correlation with aortic left shift. The aortic location and rib cage rotation were correlated, and the rib cage rotation and thoracic side curvature were correlated.
There was a significant correlation between a shallow chest and the aortic position, between the aortic position and the rib cage rotation and between the rib cage rotation and the thoracic side curvature in the normal spine. These findings suggest the possibility that rib cage development is one of the causative factors of adolescent idiopathic scoliosis.
[Show abstract][Hide abstract] ABSTRACT: Study Design Retrospective cohort study.
Objectives The mechanism underlying the pain relief observed following balloon kyphoplasty (BKP) to vertebral compression fractures is reported to involve stabilization of the fractured vertebrae. However, whether fixation of the vertebrae was achieved immediately after BKP has not been investigated. The purpose of this study was to assess fixation of the vertebrae immediately after BKP and whether the instability was related to visual analog scale (VAS) scores.
Methods Thirty-eight patients with vertebrae that were evaluated on lateral roentgenkymography within 1 week after BKP were recruited. Instability was defined as a cleft observed between the cement and end plate of the vertebra in the supine position that disappeared in the sitting position, and the posterior wall height of the vertebra was reduced in the sitting position.
Results Instability of the vertebrae immediately after BKP was observed in 17 cases. VAS scores improved in all cases, and no significant differences were observed with or without instability.
Conclusions The mechanism of rapid pain relief following BKP was not strong fixation but some degree of stabilization or other factors. We suggest that more research is needed about the mechanism of pain relief following BKP in the future.
Global Spine Journal 06/2014; 4(2):89-92. DOI:10.1055/s-0034-1370790
[Show abstract][Hide abstract] ABSTRACT: Although a substantial percentage of patients with rheumatoid arthritis (RA) experience low back pain, the characteristics of lumbar spine pathology in RA patients has been poorly investigated. In our institutions, lumbar spine radiographs indicated scoliosis in 26 patients. The present study aimed to clarify the characteristics of lumbar scoliosis in RA patients.
This is a retrospective study of 26 RA patients with lumbar scoliosis. Patient characteristics such as disease duration, disease stage and class according to Steinbrocker's classification, and medication for RA and osteoporosis were reviewed. Radiologic evaluation of scoliosis was performed at two different time points by measuring Cobb angles. The progression of scoliosis per year was calculated by dividing the change in Cobb angles by the number of years. Apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at the first observation were also measured. The correlation between different factors and changes in the Cobb angles per year was analyzed.
Majority of the patients had a long disease duration and were classified as stage 3 or 4 according to Steinbrocker's classification. During the observation period, most patients were treated with glucocorticoids. Unlike the previous studies on degenerative scoliosis, apical vertebral rotation, lateral listhesis, and the level of the intercrestal line at initial observation were not significantly related to the progression of scoliosis. Initial Cobb angles were inversely related to the progression of scoliosis. Patients who were treated with bisphosphonates showed slower progression of scoliosis.
Our results indicate that the characteristics of lumbar scoliosis in RA patients differ from those of degenerative lumbar scoliosis. Bone fragility due to the long disease duration, poor control of disease activity, and osteoporosis is possibly related to its progression.
Journal of Orthopaedic Surgery and Research 04/2014; 9(1):30. DOI:10.1186/1749-799X-9-30 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathomechanism underlying idiopathic scoliosis remains unclear, and, to our knowledge, a consistent and relevant animal model has not been established previously. The goal of this study was to examine whether a disturbance of rib cage development is a causative factor for scoliosis and to establish a nonsurgical mouse model of progressive scoliosis.
To examine the relationship between rib cage development and the pathogenesis of progressive scoliosis, a plastic restraint limiting anteroposterior rib cage development was placed on the chest of four-week-old mice. All mice were evaluated with whole-spine radiographs, and the severity of scoliosis was consecutively measured. The rib cage rotation angle and the anteroposterior chest dimension were measured with use of micro-computed tomography scanning. To examine whether the imbalanced load transmission through the ribs to the vertebral body was involved in our model, we performed a rib-neck osteotomy in a subgroup of the mice.
The thoracic restraint did not provoke spinal curvature immediately after it was applied, but nine of ten mice that wore the restraint but did not have rib osteotomy gradually developed progressive scoliosis. Radiographs and computed tomography images showed a right thoracic curvature, vertebral rotation, and narrow chest in the mice that had worn the restraint for eleven weeks but did not have rib osteotomy even after the restraint was removed. The anteroposterior chest dimension was significantly correlated with both the curve magnitude and the rib cage rotation angle. The progression of spinal deformity was observed only during the adolescent growth spurt, and it plateaued thereafter. The left-side rib osteotomy led to the development of progressive left-thoracic curvature, whereas the bilateral rib osteotomy did not cause scoliosis, even with restraint wear.
We established a nonsurgical experimental model of progressive scoliosis and also demonstrated that a rib cage deformity with an imbalanced load to the vertebral body resulted in progressive structural scoliosis.
The Journal of Bone and Joint Surgery 09/2013; 95(18):e1301-7. DOI:10.2106/JBJS.L.01381 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant peripheral nerve sheath tumor is a malignant tumor showing nerve sheath differentiation. Approximately one-half of malignant peripheral nerve sheath tumors arise from a benign peripheral nerve sheath tumor, which is commonly a neurofibroma in patients with neurofibromatosis type 1. Malignant peripheral nerve sheath tumor arising in a sporadic schwannoma of soft tissue is extremely rare. In this condition, malignant cells usually show epithelioid morphology, meeting the diagnostic criteria for epithelioid malignant peripheral nerve sheath tumor. Here, we present an extraordinary case of spindle cell-type malignant peripheral nerve sheath tumor arising in a schwannoma on the back of a 58-year-old woman without neurofibromatosis. The malignant component showed hypercellular spindle cell proliferation with high mitotic activities; in contrast, the benign component showed hypocellular spindle cell proliferation in a palisading pattern and with Verocay bodies. Immunohistochemical S-100 protein staining showed a clear contrast between the malignant (negative) and benign (positive) components, which was useful for differentiating cellular schwannoma. Recognizing this rare condition is helpful in the pathologic diagnosis of schwannoma showing cellular proliferation in part.
Human pathology 09/2013; 44(12). DOI:10.1016/j.humpath.2013.05.021 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intraosseous hemangioma (IH) is commonly seen in the vertebral column and skull: however, IH occurring in the appendicular skeleton, including the clavicle, is uncommon. We herein report the case of a 69-year-old female presenting with IH of the left clavicle. The findings of preoperative imaging studies, including radiographs, computed tomography (CT), magnetic resonance imaging, fluorine-18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT and ultrasonography, are described. In particular, (18)F-FDG PET/CT showed an ill-defined osteolytic lesion with abnormally high FDG uptake. Surgical en bloc resection with preoperative embolization was carried out and a histopathological examination confirmed the presence of an intraosseous cavernous hemangioma in the clavicle.
[Show abstract][Hide abstract] ABSTRACT: Dedifferentiated chondrosarcoma (DDCS) is a rare and aggressive bone tumor with poor prognosis. Primary DDCS of the mobile spine is extremely rare, particularly in the cervical spine. We herein describe a first case of cervical DDCS in an 81-year-old male presenting with a slowly growing mass. Radiographs showed an expansion of the cortical contour of the C2 lamina and a soft tissue mass with punctate calcification. Magnetic resonance imaging demonstrated a lobulated lesion expanding over the entire lamina and pedicles of C2 with the tumor protuberant to the adjacent soft tissue. A complete tumor resection was performed. Histologically, the majority of the tumor was a low-grade chondrosarcoma component. However, atypical spindle cells that had proliferated in a fascicular pattern with a collagenous stroma, mimicking fibrosarcoma, were focally observed without a transitional zone, and these features confirmed that the tumor was DDCS.
World Journal of Surgical Oncology 02/2013; 11(1):32. DOI:10.1186/1477-7819-11-32 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Dedifferentiated chondrosarcomas consist of two distinguishable components: low-grade chondrosarcoma components and high-grade dedifferentiated components.
Materials and methods
Nine cases (4 males, 5 females) of dedifferentiated chondrosarcoma were treated in our institute. The average age was 58.6 (range, 37–86) years. The tumor location was the long bone in 7 cases (femur, n=5; humerus, n=1; tibia, n=1) and the pelvic bone in 2 cases. The average time from appearance of symptoms to treatment was 9.4 (range, 1–40) months.
Results and discussion
On plain radiographs, matrix mineralization was seen in all 9 cases (100%). Bone destruction was observed in 5 of 9 cases (56%), while pathological fracture was seen in one femur case (11%). Lung metastasis was observed in all cases (initially in 5 cases; during the treatment course in 4 cases). Surgery was performed in 8 cases, with local recurrence occurring in 2 of those cases (time to recurrence, 2 and 10 months). Chemotherapy was administered in 4 cases, but did not result in significant improvement. All 9 cases died of lung metastases, with a median survival time of 10 (range, 3.4-18.8) months. The presence of initial metastasis at diagnosis was a significant unfavorable prognostic factor.
The prognosis of dedifferentiated chondrosarcoma is dismal. With the lack of convincing evidence of the benefit of chemotherapy, complete surgical excision is the initial recommended treatment.
Journal of Orthopaedic Surgery and Research 12/2012; 7(1):38. DOI:10.1186/1749-799X-7-38 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Myxoid liposarcoma occurs in middle age, and is characterized by extrapulmonary metastasis, including bone metastasis. Bone scans and [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) are widely used for assessment of tumor extension, including vertebral metastasis. However, both methods have a low positive rate with regard to vertebral metastasis arising from myxoid liposarcoma. This is particularly true for bone scans for intramedullary lesions that have no cortical involvement.
We present the case of a 53-year-old male with myxoid liposarcoma in the leg. He had been treated for multiple metastases over a ten-year period, and was experiencing back pain due to a pathological fracture in the second lumbar vertebra (L2). Magnetic resonance imaging of all the vertebrae showed abnormal signal intensity suggestive of metastasis in eight vertebrae, and revealed extraskeletal extension in three vertebrae. Bone scans and FDG-PET were negative except for the L2 fracture which was indicated on a bone scan.
Both bone scans and FDG-PET can be negative in cases of vertebral metastasis that arise from myxoid liposarcoma, even when extraskeletal extensions are present. Similarly, even a fractured vertebra may not always be visible on FDG-PET.
World Journal of Surgical Oncology 10/2012; 10(1):214. DOI:10.1186/1477-7819-10-214 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An in vivo animal study to examine the influence of pre-existing or concurrent spinal canal stenosis (SCS) on the functional recovery after spinal cord injury (SCI).
To clarify whether spinal cord compression before or after SCI results in less favorable neurological recovery.
The influence of spinal cord compression on the neurological recovery after SCI remains unclear.
We created mice with SCS using an extradural spacer before or after producing SCI and statistically analyzed the correlation between the extent of SCS and neurological outcomes. The extent of SCS was calculated by micro-computed tomography, and the spinal cord blood flow (SCBF) was measured serially with laser Doppler flowmetry. Molecular and immunohistochemical examinations were performed to evaluate the neovascularization at the site of cord compression.
Spacer placement (<300 μm) alone in the control mouse resulted in no neurological deficits. Even with spacer placement that caused asymptomatic SCS, the functional recovery after SCI was progressively impaired as spacer sizes increased in the mice with SCS co-occurring with SCI, whereas no significant impact was observed in the mice with pre-existing SCS, irrespective of the spacer sizes. The SCBF progressively decreased immediately after SCS was produced, but it fully recovered at the later time points. Angiogenesis-related genes were upregulated, and neovascular vessels were observed after producing the SCS. We found that concurrent SCS resulted in a significant reduction and impaired the subsequent recovery of the SCBF, whereas pre-existing SCS did not affect the hemodynamics of the spinal cord after SCI.
The dynamic reduction of the SCBF occurring immediately after spinal cord compression is a significant factor that impairs the neurological recovery after SCI, whereas pre-existing SCS is not always an impediment due to the potentially restructured SCBF.
[Show abstract][Hide abstract] ABSTRACT: The purpose of current study was to evaluate recurrence of diffuse pigmented villonodular synovitis (DPVNS), functional outcome, and osteoarthritic change of the knee.
Seventeen cases in 17 patients who had DPVNS of the knee that had not been previously treated were reviewed to determine the outcomes of surgical treatment. There were 10 males and 7 females, and their average age was 33.2 years (SD 17.2) at the time of first operation. Magnetic resonance imaging (MRI) was performed preoperatively to estimate the extent of the lesion. All patients were operated with open synovectomy. The mean postoperative follow-up period was 65.4 months (range 10.2 to 145.8; SD 48.3).
Two of 17 patients had posterior extra-articular lesions and recurrence. Two knees slightly reduced range of motion (from 145 to 130, from 145 to 125) and four knees progressed osteoarthritic changes, but overall postoperative results were satisfactory.
Because DPVNS sometimes exists out of knee joint, we should adequately check the location of the lesions using preoperative MRI, and synovectomy should be performed throughout knee joint including extra-articular lesion, especially around ligaments, meniscus, and suprapatellar was completely resected.
The Knee 01/2012; 19(5):684-7. DOI:10.1016/j.knee.2011.12.002 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Leukocytosis associated with secretion of granulocyte colony-stimulating factor (G-CSF) has been reported in various tumors, primarily poorly differentiated epithelial tumors, but is extremely rare in bone tumors. An 84-year-old woman experienced swelling and pain in the shoulder for 1 month. Leukocytosis and elevated serum G-CSF were observed, but resolved following tumor resection. A diagnosis of leiomyosarcoma of the bone with expression of G-CSF was confirmed immunohistochemically. Histological diagnosis of leiomyosarcoma showed it to be differentiated, which is unusual for G-CSF-secreting tumors.
[Show abstract][Hide abstract] ABSTRACT: Retrospective study.
To identify the clinical significance of coexistence of lumbar spinal stenosis (LSS) with thoracic ossification of ligamentum flavum (OLF), and to study the surgical outcome of the thoracic OLF patients with or without LSS.
The OLF at the thoracic level (thoracic OLF) is a rare disease that causes acquired thoracic spinal canal stenosis. Thoracic OLF is frequently combined with other spinal disorders, such as LSS, and it is not uncommon for thoracic OLF to be misdiagnosed as LSS, resulting in delayed diagnosis. However, clinical impacts of the coexistence of LSS with thoracic OLF remain unknown.
In the present study, 36 patients who underwent posterior decompression for OLF-induced thoracic myelopathy were retrospectively reviewed, and the adverse influence of the copresence of LSS with thoracic OLF was studied with regard to clinical features such as clinical symptoms and surgical outcome.
Out of 36 patients, 18 patients had LSS (combined group: C-group), and the remaining 18 patients had thoracic OLF only (thoracic group: T-group). No significant inter-group differences were found in terms of gender, age, follow-up period, and preoperative duration of symptoms. Regarding the etiology of LSS in the C-group, 12 cases had degenerative LSS, two cases had lumbar OLF, one case had degenerative LSS with lumbar OLF, one case had had degenerative LSS with lumbar OPLL, and two cases had traumatic LSS due to lumbar kyphosis after vertebral fracture. Clinical examination revealed that the T-group was significantly more likely to demonstrate Achilles hyper-reflexia, while the C-group was significantly more likely to demonstrate Achilles hypo-reflexia. The mean preoperative and postoperative JOA scores were not statistically different between the two groups. However, the mean recovery rate of the JOA score was 17.3% in the C-group, and 30.4% in the T-group. Statistical analysis revealed that the recovery rate of the C-group was significantly lower than that of the T-group.
Thoracic OLF with LSS will show a more severe clinical manifestation than that without LSS. In this study, we clearly indicated that the coexisting LSS in thoracic OLF will have adverse effects on the surgical results in thoracic OLF.
Archives of Orthopaedic and Trauma Surgery 12/2011; 132(4):465-70. DOI:10.1007/s00402-011-1438-7 · 1.60 Impact Factor