Glycogen synthase kinase 3ß as a potential therapeutic target in synovial sarcoma and fibrosarcoma.

Soft tissue sarcomas (STSs) are a rare cancer type. Almost half are unresponsive to multi-pronged treatment and might therefore benefit from biologically targeted therapy. An emerging target is glycogen synthase kinase (GSK)3ß, which is implicated in various diseases including cancer. Here, we investigated the expression, activity and putative pathological role of GSK3ß in synovial sarcoma and fibrosarcoma, comprising the majority of STS that are encountered in orthopedics. Expression of the active form of GSK3ß (tyrosine 216-phosphorylated) was higher in synovial sarcoma (SYO-1, HS-SY-II, SW982) and in fibrosarcoma (HT1080) tumor cell lines than in untransformed fibroblast (NHDF) cells that are assumed to be the normal mesenchymal counterpart cells. Inhibition of GSK3ß activity by pharmacological agents (AR-A014418, SB-216763) or of its expression by RNA interference suppressed the proliferation of sarcoma cells and their invasion of collagen gel, as well as inducing their apoptosis. These effects were associated with G0/G1-phase cell cycle arrest and decreased expression of cyclin D1, cyclin-dependent kinase (CDK)4 and matrix metalloproteinase 2. Intraperitoneal injection of the GSK3ß inhibitors attenuated the growth of SYO-1 and HT1080 xenografts in athymic mice without obvious detrimental effects. It also mitigated cell proliferation and induced apoptosis in the tumors of mice. This study indicates that increased activity of GSK3ß in synovial sarcoma and fibrosarcoma sustains tumor proliferation and invasion through the cyclin D1/CDK4-mediated pathway and enhanced extracellular matrix degradation. Our results provide a biological basis for GSK3ß as a new and promising therapeutic target for these STS types.

Successful treatment of pathologic femoral shaft fracture associated with large arteriovenous malformations using a 3-dimensional external fixator and teriparatide: a case report.

BACKGROUND: Arteriovenous malformations (AVMs) are rare congenital vascular lesions associated with early quiescence, late expansion, and, ultimately, infiltration and destruction of local soft tissue and bone. The extremities are a common location. Incidence of bony involvement by AVM has been reported as high as 31%. However, there are few reports on management of pathologic fracture associated with AVM. Teriparatide is a recombinant parathyroid hormone (PTH) analogue consisting of the 1-34 fragment of PTH. Recently, some reports have shown the ability of teriparatide to improve fracture healing. Here, we present a case of pathologic femoral shaft fracture associated with large AVMs that was treated successfully by external fixation and teriparatide. CASE PRESENTATION: A 68-year-old Japanese woman, previously diagnosed as having large AVMs, sustained a right femoral shaft fracture due to a fall. At the time of admission, she presented with massive swelling and venous varicosities of the right thigh. Plain radiography of the right thigh revealed femoral shaft fracture with bony erosion and calcification of soft tissue. We planned closed reduction and intramedullary nailing with a unilateral external fixator following embolization of the feeding artery. However, closed reduction using the fracture table was difficult. When we attempted open reduction, massive bleeding (1000 mL) after incision of subcutaneous tissue occurred. Finally, we carefully applied a Taylor Spatial Frame. Fracture displacement was corrected successfully and bony union was obtained with administration of teriparatide 15 months after the initial surgery. The patient is able to walk using 1 cane. CONCLUSION: We present the first report of pathologic fracture associated with large AVMs that achieved bony union using a 3-dimensional external fixator and teriparatide.

The usefulness of wide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft for malignant acetabular bone tumors: a report of two cases.

BACKGROUND: Difficult resection of tumors from regions with complex local anatomy, such as the pelvis and sacrum, is likely to result in inadequate surgical margins (intralesional or marginal); this is because three-dimensional osteotomy is difficult particularly around the acetabulum. Additionally, removal of the joint makes reconstruction very difficult; thus, retention of good function also becomes difficult. In musculoskeletal oncology, computer navigation systems are still not widely used to prevent tumor-positive margins. We performed wide excision with guidance from a computer navigation system and reconstruction using frozen bone autografts for malignant pelvic bone tumors in two patients, and we obtained excellent functional and oncological outcomes. Here we present these patients and discuss our approach. CASE PRESENTATION: Case 1: A 12-year-old girl presented with Ewing sarcoma of the left pelvis (PI-II). We performed wide excision assisted by a computer navigation system with the osteotomy of the load surface of acetabulum and reconstruction using a frozen bone autograft. At the final follow-up, she showed excellent function and was alive without the disease. Moreover, she did not have osteoarthritis of the left hip joint. Case 2: A 71-year-old woman presented with dedifferentiated chondrosarcoma of the right pelvis (PII-III). We performed wide excision assisted by a computer navigation system with osteotomy avoiding load surface of the acetabulum and reconstruction using a frozen bone autograft; there was no tumor at the load surface. At the final follow-up, she showed good function, was alive without the disease, and did not have osteoarthritis of the left hip joint. CONCLUSIONS: Wide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft are very useful for the management/treatment of extremely difficult cases such as malignant pelvic bone tumors, particularly those including the acetabulum.

Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues?

BACKGROUND: The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs. QUESTIONS/PURPOSES: We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients. METHODS: During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations. RESULTS: In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency values (normal adipose tissue versus ALT/WDL) (± SD) were 0.34 (SD, ± 0.13; 95% CI, 0.24-0.44) versus 0.25 (SD, ± 0.10; 95% CI, 0.18-0.33; p = 0.22). By contrast, we found greater osteogenic differentiation potency in MSCs derived from ALT/WDL than in MSCs derived from normal fat. The mean differentiation potency values (normal adipose tissue versus ALT/WDL) (±SD) based on ALP staining was 1.0 versus 17 (SD, ± 36; 95% CI, -2.8 to 38; p = 0.04). However, we found no differences based on alizarin red S staining; mean differentiation potency value (normal adipose tissue versus ALT/WDL) (± SD) was 1.0 versus 4.2 (SD, ± 4.8; 95% CI, 1.3-7.2; p = 0.58). The gap of osteogenic differentiation potency between MSCs from normal adipose tissue and ALT/WDL was decreased as MDM2-inhibitor Nutlin-3 concentration increased. CONCLUSIONS: MSCs derived from ALT/WDL had higher osteogenic differentiation potency based on ALP staining, which disappeared as Nutlin-3 concentration increased, suggesting that could be caused by amplified MDM2 in ALT/WDL. Future laboratory studies might mechanistically confirm the gene and protein expression, and based on the mechanism of the gap of differentiation potency, if p53 contrast between MSCs in tumor and normal tissue could be stimulated, less-toxic and more-effective differentiation therapy to MSCs in malignancies might be developed.

An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change.

BACKGROUND: Simple bone cysts (SBC) have been documented to occur in adults with closed physeal plates, most commonly affecting the calcaneus in this patient subset. Although most authors theorize an association to trauma, etiology of simple bone cysts remains an enigma up to now. CASE PRESENTATION: A 26-year-old kickboxing coach sought consult for a painful right shoulder which on radiographs and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs of ossification. The patient was lost to follow-up but again sought consult after 3 years for the recurring complaint. On repeat radiographs, computed tomography (CT) scan, and MR images, tumor enlargement with cystic findings typical of simple bone cyst were documented. Diagnostic aspiration of the lesion was firstly done, revealing straw-colored fluid. The patient then underwent intralesional curettage with alpha-tricalcium phosphate cement reconstruction of the lytic defect. No perioperative complications were incurred, and on latest follow-up at 3 years postoperatively, Musculoskeletal Tumor Society (MSTS) and visual analog scale (VAS) pain scores were 30/30 and 0/10, respectively. CONCLUSIONS: The authors believe their report provides support to a possible association to trauma of simple bone cysts occurring in the adult population with closed physes and suggest this subset of patients may require a different treatment approach from that for juvenile simple bone cysts.

Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen.

PURPOSE: To preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma. METHODS: Between 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy. RESULTS: Among the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone. CONCLUSIONS: Joint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma.

A case of infected schwannoma mimicking malignant tumor.

BACKGROUND: Infected schwannoma has been reported, this being one of the four cases published in the literature. Infected schwannoma has proven to be a tough diagnostic challenge to the treating tumor surgeon, mimicking infectious entities and most essentially, a malignant tumor. CASE PRESENTATION: The authors report the case of a 64-year-old male with a soft tissue mass in his right gluteal area that presented initially with right leg pain, then later with signs of inflammation on the tumor area. Magnetic resonance imaging (MRI), computed tomography (CT), and thallium-201 scintigraphy studies confirm the presence of soft tissue mass which had continuity with sciatic nerve, with subsequent serial MRI findings suggesting tumor enlargement with cystic degeneration. Increased level of C-reactive protein (CRP) was observed before surgery. During an open biopsy upon tissue sampling, exudates with necrotic tissue were seen. Increased level of CRP and necrotic change suggested the possibility of malignant tumor. Histopathological diagnosis was schwannoma, and group B Streptococcus was detected by culture. After the confirmation of infected schwannoma, enucleation of the tumor was performed. CONCLUSIONS: The report concludes that establishment of a benign pathology is essential when presented with similar clinical findings prior to definitive enucleation of an infected schwannoma.

Risk factors of recurrent lumbar disk herniation: a single center study and review of the literature.

BACKGROUND: The recurrence of lumbar disk herniation (LDH) is a major problem in the treatment of LDH. The purpose of this study was to investigate the risk factors for recurrent LDH. METHODS: Between April 2005 and March 2008, 298 patients with LDH, who underwent surgical treatment, were enrolled in this study. The patients were divided into a nonrecurrent group (N group) and a recurrent group (R group). We compared their clinical parameters including age, sex, body mass index, smoking, alcohol, sports activity, occupational lifting, and occupational driving. The relationships between the variables and recurrent LDH were evaluated by univariate analysis and multiple logistic regression analysis. RESULTS: The N group had 266 patients (89.3%) and the R group had 32 patients (10.7%). Univariate analysis showed that current smoking (P<0.001) and occupational lifting (P=0.02) significantly correlated with recurrent LDH. Multivariate analysis showed that current smoking significantly related with recurrent LDH (OR, 3.47; 95% CI, 1.55-7.80; P=0.003). CONCLUSIONS: Our study suggests that smoking cessation and restraining from lifting may significantly decrease the incidence of recurrent LDH.

Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases.

BACKGROUND: Low-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist. PATIENTS AND METHODS: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively. RESULTS: Duration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts. CONCLUSION: Low-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas.

Pedicle versus free frozen autograft for reconstruction in malignant bone and soft tissue tumors of the lower extremities.

BACKGROUND: Of the biological reconstruction methods for malignant bone and soft tissue tumors, reconstruction with liquid nitrogen has the advantage of maintaining continuity on the distal side of the tumor bone site (pedicle freezing procedure; PFP). This method is expected to result in early blood flow recovery, with early union and low complication rate. The purpose of this study was to compare the outcomes of the PFP and free freezing procedure (FFP) in the lower extremities. METHODS: The study included 20 patients (12 men and 8 women) with frozen autografts (FFP, 13 cases; PFP, 7 cases). The mean age of the subjects was 36.3 years (range 11-79 years), and the mean follow-up period was 56.4 months (range 12-142 months). RESULTS: Final bone union occurred in 11 patients in the FFP group (84.6%) and in 7 patients in the PFP group (100%). The mean union period in patients who did not need additional surgery was 9.8 months (range 4-21 months) in the FFP group and 4.8 months (range 2-7 months) in the PFP group. Postoperative complications occurred in 8 cases: infection in 3 cases, fracture in 3 cases, and joint destruction in 2 cases. Six FFP patients, and 2 PFP patients (two cases of fracture), developed postoperative complications. CONCLUSIONS: The union period was shorter and the rate of postoperative complications was lower with the PFP than with the FFP. We considered that early blood flow recovery might have led to the above results in the PFP.

Conjoined lumbosacral nerve root: a case report.

BACKGROUND: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. CASE PRESENTATION: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5-S disc degeneration. L5-S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. CONCLUSIONS: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.

Decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy: a case report.

BACKGROUND: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported. CASE PRESENTATION: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy. CONCLUSIONS: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter.

Bilateral simultaneous asymmetric hip fracture without major trauma in an elderly patient: a case report.

BACKGROUND: Simultaneous bilateral hip fractures without major trauma in the elderly are rare and usually symmetrical. To the best of our knowledge, only two cases of bilateral simultaneous asymmetric hip fracture in the elderly without major trauma have been reported. CASE PRESENTATION: We present the case of a 90-year-old Japanese man with simultaneous bilateral asymmetric hip fractures with trochanteric fracture on the right side and greater trochanteric fracture on the left side. He complained of dyspnea at midnight and was referred to our emergency department. He was admitted to the internal medicine department for bacterial pneumonia treatment. On the 8th day of hospitalization, he was referred to our orthopedic surgery department for hip pain and was found to have fractures of both hips. Computed tomography findings showed that the left femoral neck fracture was an old fracture, while the left greater trochanteric fracture and the right trochanteric fracture were fresh fractures. He was surgically treated through open reduction and internal fixation with an intramedullary nail on the right and hemiarthroplasty on the left in supine position, performed during the same surgical sessions on the 12th day of hospitalization. CONCLUSIONS: We report a new form of simultaneous bilateral asymmetric hip fracture in the elderly. The fracture types of the case were femoral trochanteric fracture and greater trochanteric fracture of the femur, which were different from the fracture types in the previously reported two cases. Clinicians should be aware of the possibility of simultaneous bilateral hip fractures, especially in the elderly.

Treatment of a Malignant Soft Tissue Tumor Arising in the Vicinity of the Sciatic Nerve with an In-Situ Preparation Technique and Intensive Multidisciplinary Therapy.

Preservation of the sciatic nerve is difficult in cases of highly malignant soft tissuetumors closely surrounding the nerve. Herein, we present the first case of preservation of thisnerve by combining an in-situ preparation technique (ISP; a technique enabling the preparation ofneurovascular bundles without contamination by tumor cells) with intensive concurrent neoadjuvantchemo-radiotherapy with hyperthermia (RHC; radio-hyperthermo-chemotherapy). A 62-year-oldman presented with a soft tissue mass in the right thigh and was diagnosed with undifferentiatedpleomorphic sarcoma. The tumor arose in the multi-compartment areas of the posterior thigh musclesand was closely intertwined with the sciatic nerve. As preoperative therapy, RHC was performedfor surgical down-staging and the tumor partially responded. Afterwards, wide resection of thetumor with preservation of the sciatic nerve using ISP was performed. Following the surgery, therehas not been recurrence in the affected site and the functional outcomes of the lower extremityachieved 80% in the Musculoskeletal Tumor Society score. The patient is still alive with disease fiveyears postoperatively. This is the first case in which ISP and RHC procedures were combined forthe preservation of the neurovascular structure. Further study is needed for the validation of thefeasibility of this method.

Satisfaction After Joint-preservation Surgery in Patients With Musculoskeletal Knee Sarcoma Based on Various Scores.

BACKGROUND/AIM: At our institute, we prioritize joint-preservation whenever possible in cases of musculoskeletal knee sarcoma. This study aimed to evaluate patient satisfaction after joint-preservation surgery using different scales. PATIENTS AND METHODS: Surveys were mailed to 62 patients with musculoskeletal knee sarcoma. We analyzed the responders' data based on the Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), and three component scores (physical, mental, and role/social) of the 36-Item Short-Form Health Survey according to whether they belonged to patients in the joint-preservation or in the joint-replacement groups. RESULTS: The survey response rate was 67.7%. MSTS and TESS scores were higher in the patients in the joint-preservation group than in the joint-replacement group, although the differences lacked statistical significance. CONCLUSION: Better physical outcomes improve patient satisfaction, as demonstrated by the high satisfaction in the group with joint-preservation.

Determining Patient Satisfaction and Treatment Desires in Patients With Musculoskeletal Sarcoma of the Knee After Joint-preservation Surgery Using a Questionnaire Survey.

BACKGROUND/AIM: For cases of musculoskeletal sarcoma of the knee presenting to our institute, we prioritize joint preservation whenever possible. To investigate patient satisfaction and desire for joint preservation, a questionnaire survey was performed. PATIENTS AND METHODS: Surveys were mailed to 62 patients with musculoskeletal sarcoma of the knee. Responses concerning the patient and their families' satisfaction were evaluated on a 5-point Likert scale and their priorities for the surgery were noted as well. RESULTS: The survey response rate was 67.7%. All but one person were above neutral for the 5-point Likert scale. Overall, the first priority was tumor removal followed by preservation of function. CONCLUSION: Patients identified tumor removal as their first priority, which could increase satisfaction. Following that, better preservation of function could also increase patient satisfaction. Joint-preservation was consistent with these priorities.

Efficacy and Limitations of F-18-fluoro-2-deoxy-D-glucose Positron Emission Tomography to Differentiate Between Malignant and Benign Bone and Soft Tissue Tumors.

BACKGROUND/AIM: Positron emission tomography (PET) using 18fluorine-labelled fluorodeoxyglucose (FDG), is the most widely applied molecular imaging technique in oncology. The present study assessed the efficacy and limitations of FDG-PET by comparing FDG accumulation in bone and soft tissue lesions, as well as histopathological features. PATIENTS AND METHODS: The study included 122 patients with 165 lesions, as assessed by histopathological examinations. The maximum standardized uptake values (SUVmax) of benign lesions were compared to those of primary, recurrent, or metastatic sarcomas, as well as those of other malignancies. RESULTS: The sensitivity, specificity, and accuracy of SUVmax for differentiation between benign lesions and primary sarcomas were 67.9%, 92.9%, and 80.4%, respectively. There were no significant differences between benign lesions and recurrent or metastatic sarcomas. CONCLUSION: Although FDG-PET is a useful imaging modality to differentiate primary sarcomas from benign lesions, it is difficult to differentiate residual or metastatic sarcomas from benign lesions.

Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression.

Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti-inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti-tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ-responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase-2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity.

Risk factors for postoperative deep infection in bone tumors.

BACKGROUND: Postoperative deep infection after bone tumor surgery remains a serious complication. Although there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection. METHODS: We reviewed data of 681 patients (844 bone tumors) who underwent surgery. Associations between variables, including age, recurrent tumor, pathological fracture, surgical site (pelvis/other), chemotherapy, biological reconstruction, augmentation of artificial bone or bone cement, the use of an implant, intraoperative blood loss, operative time, additional surgery for complications, and postoperative deep infection were evaluated. RESULTS: The rate of postoperative deep infection was 3.2% (27/844 tumors). A pelvic tumor (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0-11.3) and use of an implant (OR: 9.3, 95% CI: 1.9-45.5) were associated with an increased risk of deep infection. CONCLUSIONS: This retrospective study showed that pelvic tumor and use of an implant were independent risk factors for deep infection. This information will help surgeons prepare an adequate surgical plan for patients with bone tumors.

Surgical management of proximal fibular tumors: A report of 12 cases.

BACKGROUND/AIM: Aggressive benign or malignant tumors in the proximal fibula may require en bloc resection of the fibular head, including the peroneal nerve and lateral collateral ligament. Here, we report the treatment outcomes of 12 patients with aggressive benign or malignant proximal fibula tumors. PATIENTS AND METHODS: Four patients with osteosarcoma and 1 patient with Ewing's sarcoma were treated with intentional marginal resections after effective chemotherapy, and 4 patients underwent fibular head resections without ligamentous reconstruction. Clinical outcomes were investigated. RESULTS: The mean Musculoskeletal Tumor Society scores were 96% and 65% in patients without peroneal nerve resection and those with nerve resection, respectively. No patients complained of knee instability. CONCLUSION: Functional outcomes after resection of the fibular head were primarily influenced by peroneal nerve preservation. If patients are good responders to preoperative chemotherapy, malignant tumors may be treated with marginal excision, resulting in peroneal nerve preservation and good function.