Reduced blood loss after total knee arthroplasty with local injection of bupivacaine and epinephrine.

Our goal was to determine by direct measurement of drain output whether intraoperative injection of bupivacaine with epinephrine significantly reduces postoperative blood loss in total knee arthroplasty (TKA). The study and control groups were primary TKAs performed by 1 surgeon using a single-cemented TKA design and a consistent postoperative protocol. The study group comprised 37 sequential TKAs injected intraoperatively with bupivacaine and epinephrine (one-third pericapsular, two-thirds peri-incisional). The control group included 71 sequential TKAs. The study group had 32% (95% confidence interval, 11%-48%), or 195 mL, less drain output (P = .006). There were no statistically significant differences in the transfusion rate or bleeding indices. Control and study groups were comparable regarding tourniquet times, intraoperative soft-tissue releases, preoperative anticoagulant use, and overall postoperative complications. Our study demonstrated a statistically significant decrease in TKA postoperative drain output with intraoperative injection of bupivacaine with epinephrine.

An unusual case of Erdheim-Chester disease with features of Langerhans cell histiocytosis.

Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are both exceedingly rare histiocytic proliferations that can involve the skeletal system. We report on a case of ECD with some features suggestive of LCH. Radiographs demonstrated a large lytic lesion in the left femur, with multiple lesions of sclerosis involving both distal femurs and tibias. Both the lytic lesion and a sclerotic lesion were biopsied and demonstrated distinctive histologic features characteristic of ECD in the tibia and features of LCH in the femur. The clinical/radiologic and pathologic features that distinguish ECD and LCH as distinct entities are reviewed, and the underlying biological connection between them is discussed.

Articular cartilage adjacent to experimental defects is subject to atypical strains.

We tested the hypothesis that articular cartilage adjacent to experimental osteochondral defects is not subject to unusual strains under load. A 2.5-mm drill hole was made in the medial femoral condyle of 15 knees from 10 adult rabbits. Experimental joints were loaded with simulated quadriceps force, then frozen under load and preserved by freeze-substitution fixation. Deformation in the region of the defect was evaluated by scanning electron and light microscopy and compared with nondrilled and nonloaded control knees. To simulate blood clot, alginate was placed into some defects before loading. In loaded knees, articular cartilage at the edge of the drill hole was abnormally flattened and folded into the defect. Opposing tibial cartilage or meniscus intruded into the femoral defect beyond the cement line. Alginate did not prevent incursion of opposing cartilage. In this standard drill-hole model, the articular cartilage defect is occupied by the opposing surface when a joint is loaded. Any tissue growing or surgically implanted in the defect is subject to loading and displacement, therefore complicating attempts to characterize the healing or regenerative potential in similar drill-hole models. Deformation of cartilage at the defect edge suggests load concentration or increased compliance. Either phenomenon would contribute to subsequent degeneration of the cartilage adjacent to defects.

Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy.

BACKGROUND: Patients with high-grade soft tissue sarcomas are at high risk of developing local disease recurrence and metastatic disease. [F-18]-fluorodeoxy-D-glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect histopathologic response to therapy and to predict risk of tumor progression in patients with various malignancies. Serial FDG-PET scans were taken to determine the correlation between FDG uptake and patient outcomes in patients receiving multimodality treatment of extremity sarcomas. METHODS: Forty-six patients with high-grade localized sarcomas were studied. The maximum standardized uptake values (SUVmax) of tumors were measured before receipt of neoadjuvant chemotherapy and again before surgery. Resected specimens were examined for residual viable tumor. Patients were followed up at least annually for evidence of local and distant recurrence of disease and survival. RESULTS: Patients with a baseline tumor SUVmax >/= 6 and < 40% decrease in FDG uptake were at high risk of systemic disease recurrence estimated to be 90% at 4 years from the time of initial diagnosis. Patients whose tumors had a >/= 40% decline in the SUVmax in response to chemotherapy were at a significantly lower risk of recurrent disease and death after complete resection and adjuvant radiotherapy. CONCLUSIONS: The FDG-PET scan was found to be a useful method with which to predict the outcomes of patients with high-grade extremity soft tissue sarcomas treated with chemotherapy. The pretreatment tumor SUVmax and change in SUVmax after neoadjuvant chemotherapy independently identified patients at high risk of tumor recurrence. The FDG-PET scan showed promise as a tool to identify the patients with sarcoma who are most likely to benefit from chemotherapy.

Targeting of EWS/FLI-1 by RNA interference attenuates the tumor phenotype of Ewing's sarcoma cells in vitro.

The defining cytogenetic abnormality of Ewing's sarcoma is the presence of a balanced t(11;22) translocation expressing the EWS/FLI-1 chimeric fusion protein. The effect of EWS/FLI-1 appears to be dominant negative since over-expression of EWS does not overcome the sarcoma phenotype. Previous studies have shown that EWS/FLI-1 as well as related sarcoma fusion proteins are necessary and sufficient to induce transformation both in vitro and in vivo. In this study we report that synthetic small interfering RNA (siRNA) specifically suppresses EWS/FLI-1 fusion gene expression in SK-ES Ewing's sarcoma cells. Knockdown of the EWS/FLI-1 fusion protein is correlated with decreased cell proliferation and increased apoptosis. We demonstrate that Ewing's sarcoma tumors as well as Ewing's sarcoma cell lines predominantly express the CXCR4 chemokine receptor. Using an in vitro invasion assay, the SDF-1 ligand of CXCR4 was shown to be a potent stimulus of invasion by SK-ES cells. Knockdown of EWS/FLI-1 by RNA interference abrogates the invasiveness of SK-ES cells. These experiments suggest that targeted silencing of the EWS/FLI-1 fusion gene by siRNA represents a promising strategy to study the loss of EWS/FLI-1 protein in Ewing's sarcoma cells of otherwise identical genetic background.

Child abuse in infants with proximal physeal injuries of the femur.

OBJECTIVE: Child abuse has been recognized to be a common cause of femur fractures in infants. Fractures of the proximal femoral physis in abused infants have been less emphasized. Our report seeks to highlight this infrequent but clinically important inflicted injury. METHODS: Report of 2 cases and a literature review of fractures of the proximal femoral physis in infants, including the role of abuse in this injury. CONCLUSION: Proximal femoral physeal injuries occur infrequently in infants but often result from abuse. Diagnosis may be difficult due to lack of femoral head ossification before 4 months of age and clinical findings suggesting developmental dysplasia of the hip. Current imaging modalities can differentiate physeal injuries from developmental dysplasia of the hip. Early recognition and treatment can minimize sequelae.

Molecular targeting of platelet-derived growth factor B by imatinib mesylate in a patient with metastatic dermatofibrosarcoma protuberans.

PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet-derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase. We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate. PATIENTS AND METHODS: A patient with unresectable, metastatic dermatofibrosarcoma protuberans received imatinib mesylate (400 mg bid). Response to therapy was assessed by [18F]fluorodeoxyglucose (FDG) positron emission tomography, magnetic resonance imaging, and histopathologic and immunohistochemical evaluation. RESULTS: The patient was treated for 4 months with imatinib mesylate. The hypermetabolic uptake of FDG fell to background levels within 2 weeks of treatment, and the tumor volume shrank by over 75% during the 4 months of therapy, allowing for resection of the mass. There was no residual viable tumor in the resected specimen, indicating a complete histologic response to treatment with imatinib mesylate. CONCLUSION: Imatinib mesylate is highly active in dermatofibrosarcoma protuberans. The dramatic response seen in this patient demonstrates that inhibition of PDGFB receptor tyrosine kinase activity can significantly impact viability of at least one type of solid tumor.

Sarcoma tumor FDG uptake measured by PET and patient outcome: a retrospective analysis.

In a retrospective analysis of patients with sarcoma who underwent fluorodeoxyglucose positron emission tomography (FDG PET) imaging, tumor maximum FDG uptake was analyzed for ability to predict patient survival and disease-free interval. Two hundred and nine patients with sarcoma were imaged prior to treatment with neoadjuvant chemotherapy or resection. Tumor FDG uptake expressed as maximum standard uptake value (SUV(max)) was compared with disease-free and overall survival. A multivariate Cox regression analysis was applied to examine the role of SUV(max) in predicting time to death or disease progression, after adjusting for standard clinical prognostic factors. The multivariate analyses showed that the SUV(max) information is a statistically significant independent predictor of patient survival. Tumors with larger SUV(max) have a significantly poorer prognosis. This retrospective analysis indicates that the sarcoma tumor SUV(max) value determined by PET is an independent predictor of survival and disease progression.

Evaluation of chemotherapy response in pediatric bone sarcomas by [F-18]-fluorodeoxy-D-glucose positron emission tomography.

BACKGROUND: Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT). Conventional radiographic imaging does not discriminate between responding and nonresponding osseous tumors. [F-18]-fluorodeoxy-D-glucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that accurately predicts histopathologic response in patients with various malignancies. To describe the FDG PET imaging characteristics and to determine the correlation between FDG PET imaging and chemotherapy response in children with bone sarcomas, we reviewed our single institution experience. METHODS: Thirty-three pediatric patients with OS or ESFT with osseous primary sites were evaluated by FDG PET. All patients received standard neoadjuvant chemotherapy. FDG PET standard uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with chemotherapy response assessed by histopathology in surgically excised tumors. Twenty-six patients had SUV1, SUV2, and surgical excision. RESULTS: Although the mean SUV1 in children with OS or ESFT were similar (8.2. vs. 5.3, P = 0.13), mean SUV2 for OS patients was greater than the values for ESFT patients (3.3 vs. 1.5, P = 0.01). All ESFT patients and 28% of OS patients had a favorable histologic response to chemotherapy (>or= 90% necrosis). Combining ESFT and OS patients, both SUV2 and the ratio of SUV2 to SUV1 (SUV2:SUV1) were correlated with histologic response (P = 0.01 for both comparisons). CONCLUSION: FDG PET evaluation of pediatric bone sarcomas demonstrated significant alteration in response to neoadjuvant chemotherapy. SUV2 and SUV2:SUV1 correlated with histopathologic assessment of response and potentially could be used as a noninvasive surrogate to predict response in patients.