Disruption of crosstalk between mesenchymal stromal and tumor cells in bone marrow as a therapeutic target to prevent metastatic bone disease.

Skeletal metastasis is a serious complication of many primary cancers. A common feature of tumor cells that metastasize to the bone marrow microenvironment is that they initiate a cascade of events, recruiting and presumably/potentially altering the phenotype of bone marrow mesenchymal stromal cells (MSC) to produce an environment that allows for tumor growth and in some cases, drug-resistant dormancy of latent cancer cells. Consequently the MSC population can contribute to metastatic disease through several distinct mechanisms by differentiating into cancer-associated fibroblasts (CAFs). Understanding the expression and epigenetic changes that occur as normal MSCs become associated with metastatic tumors would reveal possible therapeutic targets for treating skeletal metastasis.

What is the best material for molding casts in children?

BACKGROUND: Casts are used to treat clubfeet, developmental dysplasia of the hip (DDH), forearm fractures, and femur fractures. The ability of a cast to maintain a desired shape is termed moldability. Clinicians use plaster, fiberglass, and soft casts. To our knowledge the biomechanical molding characteristics of these 3 materials have never been reported. We hypothesized that moldability of plaster would be better than fiberglass and fiberglass would be better than soft cast. METHODS: We compared 12.7 cm wide casts of plaster, fiberglass, and soft cast. Casts were 5 layers thick, prepared in 40°C water, and placed over 2 layers of cotton padding on 5.1 cm and 15.2 cm diameter foam cylinders. A loading device simulated loads applied by clinicians when molding casts for 4 conditions: clubfoot (thumb-shaped 50 N load on 5.1 cm model), DDH (thumb-shaped 100 N load on 15.2 cm model), forearm fracture (palm-shaped 50 N load on 5.1 cm model), and femur fracture (palm-shaped 100 N load on 15.2 cm model). The loading device applied molding for 7 minutes. Five casts of each material were made for each model. Casts were removed, photographed, and the area of maximal deformation was compared with an unmolded cast. A large area of maximal deformation meant that the deformation was spread out over a large area, less precise molding. RESULTS: In the clubfoot model, plaster was more precise than fiberglass (P=0.002) and soft cast (P<0.0001). In the DDH model, plaster was more precise than fiberglass (P<0.0001) and soft cast (P<0.0001) and fiberglass was more precise than soft cast (P<0.0001).In the femur fracture model, plaster was more precise than fiberglass (P=0.001) and soft cast (P=0.001). CONCLUSIONS: The moldability of plaster is better than fiberglass and soft cast and fiberglass is better than soft cast. CLINICAL RELEVANCE: If precise molding is required, plaster has the best moldability. In cases not requiring precise molding, fiberglass and soft cast are lightweight, waterproof, and available in child-friendly colors.

Physical activity assessment in adolescents with limb salvage.

OBJECTIVES: To evaluate ambulatory activity differences between youth with limb salvage procedures and typically developing youth (TDY) and assess differences in self-reported activity levels in the 2 groups, to provide a basis for physical activity assessment in patients who had undergone limb salvage surgery and treatment planning that incorporates regaining normal physical and daily living activities. STUDY DESIGN: In this cohort comparison study, we compared ambulatory and self-reported activity levels in 20 youth (aged 11.7-20.8 years) who had undergone limb salvage surgery and a sex- and age-matched comparison cohort of 20 TDY. StepWatch activity monitor and Activity Scale for Kids data were used to answer these questions. RESULTS: Significant differences were found between the youth who had undergone limb salvage surgery and the TDY in total time active each day (43% vs 48%; P = .03), median total strides per day (4487 vs 7671; P = .001), and amount of time per day at high activity levels (20 minutes vs 47 minutes; P = .001). Self-reported overall physical activity, locomotion, and standing Activity Scale for Kids subscale scores were significantly lower in the youth undergoing limb salvage surgery compared with the TDY (summary score, 88.3 vs 97.7; P = .001). CONCLUSION: Patients undergoing limb salvage surgery exhibit reduced physical activity compared with normal age-matched controls.

Single-Shot Spinal Anesthesia in an Infant Requiring Magnetic Resonance Imaging and Open Lower-Extremity Surgery: A Case Report.

Spinal anesthesia (SA) is a safe and effective anesthetic technique for lower abdominal and lower extremity surgery in neonates and infants and is associated with an apparent state of sedation. We report the use of single-shot SA in a 6-week-old infant for a combined magnetic resonance imaging and open surgical biopsy of a deep soft tissue lower extremity mass. By leveraging the unique qualities of SA (sedation and surgical blockade), we avoided the need for general anesthesia. To our knowledge, this is the first reported use of single-shot SA for an infant undergoing two procedures in the same day.

Kaposiform hemangioendothelioma in multiple spinal levels without skin changes.

Kaposiform hemangioendothelioma is a rare vascular tumor of childhood that is locally aggressive but has little metastatic potential and by itself is not known to be lethal. It most commonly presents as a superficial or deep soft tissue mass with associated cutaneous lesions. Kasabach-Merritt phenomenon, a condition characterized by profound thrombocytopenia and life-threatening hemorrhage, often is associated with kaposiform hemangioendothelioma. Six cases of kaposiform hemangioendothelioma have been reported in bone, two of which were located in extracraniofacial bones. We report a diagnostically challenging case of a 6-year-old girl with kaposiform hemangioendothelioma of the thoracolumbar spine without Kasabach-Merritt phenomenon or cutaneous lesions.

Risk assessment based on FDG-PET imaging in patients with synovial sarcoma.

UNLABELLED: Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of (18)F-FDG-PET-derived maximum standard uptake value (SUV(max)) for predicting survival in patients with synovial sarcoma. (18)F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUV(max) was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUV(max) ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUV(max) predicted overall survival and progression-free survival. Patients presenting with a SUV(max) greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease. LEVEL OF EVIDENCE: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Metastatic osteosarcoma gene expression differs in vitro and in vivo.

An understanding of differential gene expression in highly metastatic osteosarcoma could provide gene targets for treatment of metastases. We compared gene expression profiles of high- (LM7) and low- (LM2) metastatic SaOS2-derived cell lines in an in vitro tissue culture model and examined several differentially regulated genes in vivo in a murine orthotopic xenograft model. We hypothesized an orthotopic inoculation of LM2 and LM7 cells would establish a primary lesion and the gene expression profile of cells grafted in this fashion would resemble the gene expression profile observed in an in vitro model. Thirty-five days after inoculation, animals were euthanized and both tibiae were harvested and rapidly frozen in liquid nitrogen. Human-specific GAPDH mRNA was present in two of four tibias inoculated with LM2 cells and three of four tibias inoculated with LM7 cells. Tibiae displaying the presence of human cells were assayed by semiquantitative reverse transcriptase polymerase chain reaction. We observed poor correspondence of in vitro to in vivo gene expression for either cell line. Accordingly, in vitro osteosarcoma gene expression data must be interpreted with caution until confirmed in vivo. Our orthotopic injection model allowed in vivo study of differential gene expression between these two cell lines but did not show radiographic evidence of an established primary lesion.

Percutaneous in Situ Fixation of Slipped Capital Femoral Epiphysis.

Slipped capital femoral epiphysis (SCFE), a common cause of adolescent hip pain, is a displacement of the femoral head through the proximal femoral physis. The exact etiology of SCFE is unknown, but both biochemical and biomechanical factors, including obesity, femoral retroversion, increased physeal obliquity, puberty, and endocrinopathies, play a role. Patients often present with hip, groin, or knee pain and an antalgic gait. On physical examination, obligate external rotation of the lower limb with passive hip flexion is a hallmark of SCFE. The diagnosis is confirmed with radiographs, with advanced imaging reserved for atypical presentations. Any degree of SCFE is an indication for internal stabilization. Percutaneous in situ fixation remains the gold-standard treatment for slipped capital femoral epiphysis. The procedure is performed with the following steps: (1) the patient is positioned supine on a fracture table with the contralateral lower limb in the hemilithotomy position; (2) a 1-cm longitudinal incision is made over the anterolateral aspect of the proximal part of the femur; (3) under fluoroscopic guidance, a guidewire is advanced freehand into the "center-center" of the epiphysis, stopping approximately 3 mm short of the articular surface; (4) the guidewire is overdrilled, and a 6.5-mm partially threaded cannulated screw of appropriate length is inserted into the epiphysis; (5) the proximal part of the femur is brought through a full range of internal-external rotation under fluoroscopy to confirm that the screw has not violated the joint cavity; and (6) the wound is closed in layers and a sterile dressing is applied. Postoperatively, the patient's weight-bearing status is advanced on the basis of the stability of the SCFE. Radiographic follow-up is performed at six-month intervals to monitor the contralateral hip until skeletal maturity. Treatment outcomes and complications such as osteonecrosis and chondrolysis correlate with the severity and stability of the slip on presentation. Long-term follow-up has shown good-to-excellent outcomes after in situ screw fixation of stable slips.

Prognosis of hepatoid yolk sac tumor in women: what's up, Doc?

Ovarian yolk sac tumors are highly malignant germ cell tumors that commonly occur in young women. The hepatoid yolk sac tumor is a variant form of yolk sac tumor in which there has been extensive tumor differentiation to early liver tissue. Hepatoid differentiation is traditionally considered to signify a poor prognosis. This review focuses on diagnostic criteria and establishes the optimal treatment for patients with hepatoid yolk sac tumor. Immunohistochemical stains are useful for distinguishing hepatoid yolk sac tumor from the other hepatoid-appearing tumors. With a multidisciplinary treatment approach using platinum-based regimens, the outcome is similar to those of any yolk sac tumor.

Ultraporous ß-tricalcium phosphate alone or combined with bone marrow aspirate for benign cavitary lesions: comparison in a prospective randomized clinical trial.

BACKGROUND: Ultraporous ß-tricalcium phosphate (TCP) synthetic graft material (Vitoss; Orthovita) persists for a year or longer in some cases. In this study, we prospectively examined healing of cavitary defects filled with TCP versus TCP and bone marrow aspirate (TCP/BM) with the hypothesis that bone-marrow aspirate speeds incorporation of bone graft substitute. METHODS: Fifty-five patients with a benign bone lesion undergoing surgical curettage were randomized to receive TCP (N = 26; mean duration of follow-up [and standard deviation], 20.2 ± 7.2 months) or TCP/BM (N = 29; mean duration of follow-up, 18.0 ± 7.7 months). There were no significant differences between the groups with regard to demographic or defect parameters. Clinical and radiographic evaluations were done at 1.5, three, six, twelve, eighteen, and twenty-four months, and computed tomography [CT] scans were performed at twelve months. An independent radiographic review was done to evaluate six parameters. RESULTS: There was a significant (p < 0.001) increase in trabeculation through the defect and graft resorption with decreases in the persistence of the graft in both soft tissue and the defect as well as a decreased radiolucent rim around the graft over time. No significant differences were observed between the TCP and TCP/BM groups in terms of any radiographic parameter. No complications related to the graft material or BM were identified. CONCLUSIONS: While significant improvements in radiographic parameters were observed in both TCP groups over two years of follow-up, the addition of BM was not found to provide any significant benefit. Results should not be extrapolated to other bone graft substitutes used for this purpose.

Ankle fractures in children.

Computed tomography is useful for preoperative planning and postreduction assessment for intra-articular pediatric ankle fractures. Nondisplaced pediatric ankle fractures can be effectively managed with cast immobilization and close radiographic follow-up evaluation. Physeal ankle injuries in younger children with considerable growth remaining should be followed closely for at least one year after injury as growth arrest may result in substantial angular deformity. Open reduction and internal fixation should be strongly considered when an articular step-off of <2 mm cannot be maintained by closed means for Salter-Harris type-III and IV and transitional ankle fractures.

Measurement of walking activity throughout childhood: influence of leg length.

The aim of this study was to describe walking (stride) activity frequency and intensity in 428 children ages 2-15 years with a single accelerometer-based device. With comparison with published pedometer-determined data, the influence of leg length was examined. Decline in stride frequency and intensity throughout childhood increased with adjustment for leg length. The accelerometer-based device documented higher stride counts than published pedometer-based data with the greatest discrepancy in 4-5 year olds. Recommended walking levels for optimal weight throughout childhood should be examined with knowledge of the device measurement differences and the natural history of walking activity changes with age.