Rajiv Rajani

Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing.

Thrombospondin‐2 (TSP2) is a matricellular protein with increased expression during growth and regeneration. TSP2‐null mice show accelerated dermal wound healing and enhanced bone formation. We hypothesized that bone regeneration would be enhanced in the absence of TSP2. Closed, semistabilized transverse fractures were created in the tibias of wildtype (WT) and TSP2‐null mice. The fractures were examined 5, 10, and 20 days after fracture using μCT, histology, immunohistochemistry, quantitative RT‐PCR, and torsional mechanical testing. Ten days after fracture, TSP2‐null mice showed 30% more bone by μCT and 40% less cartilage by histology. Twenty days after fracture, TSP2‐null mice showed reduced bone volume fraction and BMD. Mice were examined 5 days after fracture during the stage of neovascularization and mesenchymal cell influx to determine a cellular explanation for the phenotype. TSP2‐null mice showed increased cell proliferation with no difference in apoptosis in the highly cellular fracture callus. Although mature bone and cartilage is minimal 5 days after fracture, TSP2‐null mice had reduced expression of collagen IIa and Sox9 (chondrocyte differentiation markers) but increased expression of osteocalcin and osterix (osteoblast differentiation markers). Importantly, TSP2‐null mice had a 2‐fold increase in vessel density that corresponded with a reduction in vascular endothelial growth factor (VEGF) and Glut‐1 (markers of hypoxia inducible factor [HIF]‐regulated transcription). Finally, by expressing TSP2 using adenovirus starting 3 days after fracture, chondrogenesis was restored in TSP2‐null mice. We hypothesize that TSP2 expressed by cells in the fracture mesenchyme regulates callus vascularization. The increase in vascularity increases tissue oxemia and decreases HIF; thus, undifferentiated cells in the callus develop into osteoblasts rather than chondrocytes. This leads to an alternative strategy for achieving fracture healing with reduced endochondral ossification and enhanced appositional bone formation. Controlling the ratio of cartilage to bone during fracture healing has important implications for expediting healing or promoting regeneration in nonunions.

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

IntroductionChondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.Case presentationWe present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.ConclusionsOur findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.

Treatment of Bone Tumors

In this article, the authors summarize the state of the art and future potential in the management of Osteosarcoma, Ewings sarcoma, and Chondrosarcoma. They cover systemic therapy, surgical therapy, and radiotherapy, along with targeted therapies to inhibit signal transduction pathways. They discuss staging and the role of imaging evaluation to provide an overview of bone tumor treatment. Images presenting pathologic-radiologic correlations are included.

Giant Cell Tumors of the Foot and Ankle Bones: High Recurrence Rates After Surgical Treatment

Giant cell tumor (GCT) of the bone is a benign primary bone tumor most often treated with intralesional surgery. Most cases occur around the knee; however, rarely, GCT of bone can occur in the foot and ankle. Limited data exist about the outcomes after treatment of GCT in this location. We retrospectively reviewed an orthopedic oncology database from 1970 to 2010 for cases of GCT of the bone, specifically within the foot and ankle bones. After exclusionary criteria were applied, a total of 19 disease sites in 18 patients were included for analysis. Of the 19 disease sites, 10 recurred. Patients, on average, required 1.7 operations per disease site. Of the 18 patients, 10 required ≥2 operations, 3 required ≥3 operations, and 1 required 4 operations. A total of 4 amputations were performed, including 2 below the knee amputations. Of the 10 patients with recurrence, 2 also had evidence of metastatic disease. The recurrence rates of GCT in the foot and ankle bones appear to be greatest after intralesional curettage without the use of cement. Although the recurrence rates are high, intralesional operations with multiple adjuvant therapy can eventually result in cure.

How much tumor surgery do early-career orthopaedic oncologists perform?

BackgroundThere are few data on the types of procedures orthopaedic oncologists perform in their first years of practice. Because fellowships are graduating fellows each year and the number of tumor patients is limited, defining the practice patterns of early-career orthopaedic oncologists may help diminish early employment discontent and enhance workforce discussions.Questions/purposesThe aim of the study was to use the objective case log volumes of a cross-section of early career orthopaedic oncologists to describe (1) the number of operations performed annually; (2) the proportion of tumor, trauma, adult reconstruction, and other operations for individual participants, (3) individual practice characteristics that were associated with the number of tumor procedures; and (4) the sources of satisfaction and challenges in each individual’s career and surgical practice.MethodsFifteen fellowship-trained orthopaedic oncologists out of a potential pool of 33 (45%) in their first 4 years of practice responded to a survey by submitting complete operative case lists for a 2-year period. We recorded the type of procedure and determined associations between the annual number of tumor operations and total operative caseload, years in practice, and some details of individual practice patterns. Each participant completed a survey regarding practice-related sources of stress and satisfaction. A total of 5611 surgical cases were available for review. For the entire cohort, there were 3303 (59%) tumor procedures, 973 (17%) trauma, 890 (16%) adult reconstruction, and 445 (8%) other.ResultsThe median annual number of total operations was 214 (range, 63–356) and median annual number of tumor operations was 135 (range, 47–216). The median proportion of tumor operations in an individual practice was 56% (range, 43%–94%). The annual number of tumor operations correlated with the total annual number of operations (r = 0.73, p < 0.001). Sources of stress and satisfaction were similar to the general membership of the Musculoskeletal Tumor Society (MSTS), apart from more early-career surgeons regarding case volume as important (29 of 104 [28%] of MSTS versus 11 of 15 [73%] of early-career, p < 0.001).ConclusionsThe typical early-career orthopaedic tumor surgeon had fewer than 60% of his or her operative procedures directly related to the subject of his or her fellowship training in orthopaedic oncology. Overall, the challenges and rewards of clinical practice are similar to oncologic surgeons later in their career. This study is a first step in assessing early practice characteristics and may be of value to the prospective orthopaedic oncologist, fellowship educators, and the society in workforce discussions. Early-career practice patterns have not been previously presented, to our knowledge, for any subspecialty of orthopaedic surgery, and we hope that this study will stimulate similar efforts throughout the field.Level of EvidenceLevel IV, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence.

Denosumab Therapy for Giant Cell Tumor of Bone Pulmonary Metastasis

Case A 68-year-old female was diagnosed with giant cell tumor of bone (GCTB) metastatic to her lungs. The patient was treated with IV denosumab for the course of 4.5 years for these metastases. The metastatic tumor burden decreased significantly after only 3 months of therapy. The size of the metastases has been stable for over 4 years. Conclusion Denosumab therapy has promise in the treatment of GCTB, including pulmonary metastasis. However, the long-term role of denosumab for pulmonary metastases is yet to be determined.

Oncogenic Osteomalacia From a Primary Phosphaturic Mesenchymal Tumor of the Toe: A Case Report

Oncogenic osteomalacia is an acquired, rare paraneoplastic syndrome characterized by renal phosphate wasting and subsequent hypophosphatemic osteomalacia. The condition is usually associated with a phosphaturic mesenchymal tumor, which produces fibroblast growth factor 23, the primary circulating factor responsible for reduced tubular phosphate reabsorption. Clinically, adult patients typically present with bone pain, myalgia, recurrent and/or multiple stress fractures, and fatigue, with serum levels typified by low 1,25-(OH)2 vitamin D3, increased alkaline phosphatase, and normal calcium, parathyroid hormone, calcitonin, 25-OH-vitamin D3, and 25,25-(OH)2 vitamin D3 levels. The tumor in question is typically benign and can be of little clinical significance apart from its role in causing hypophosphatemic osteomalacia. Detection of the tumor, therefore, can often be delayed and requires an astute index of suspicion.

Epiphysiolysis of the femoral neck due to closed reduction of an adolescent hip dislocation with a 4-year follow-up: a case report and review of the literature.

This case study discusses a 13-year-old girl diagnosed with a displaced Salter Harris II fracture of the proximal femoral epiphysis post reduction of a dislocated hip. Radiographs before reduction revealed a small fracture of the inferomedial femoral head. This, however, did not induce concern before reduction. The patient underwent reparative surgery of the epiphysis only to develop a collapsed femoral head, which was remedied through total hip arthroplasty. A decrease in blood flow, the delicacy in reduction, and unknown predispositions might have been contributing factors toward the unique development in this case.

Abstract A51: Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients

Introduction: Racial and ethnic disparities in limb-salvage surgery have been reported among adult sarcoma patients. The purpose of this work was to explore treatment patterns by ethnicity and gender in a cohort of pediatric sarcoma patients Methods: A retrospective review was conducted of all consecutive patients under the age of 18 treated for sarcoma at the study institution with diagnoses from 1999 to 2011 who underwent surgery for limb salvage or amputation. Statistical analysis of patient demographics (age, sex, ethnicity and BMI) was performed to assess for factors associated with limb salvage surgery. Results: 51 records were identified as pediatric patients who underwent surgery for extremity sarcoma in the defined study period. 5 records were excluded due to inadequate availability of body site or surgery type documentation, leaving a cohort of 46 patients. Hispanic patients were more likely to undergo amputation (10 of 36) compared to non-Hispanics (5 of 10; p = 0.03). Female patients were more likely to have had limb salvage (8 of 17) than males (7 of 29; p = 0.04). Logistic regression analysis showed no difference between likelihood of limb salvage and amputation when stratified by BMI or age. Conclusions: Hispanic ethnicity and male gender were predictors of amputation in a cohort of pediatric sarcoma patients undergoing surgical treatment. Further study should be devoted to identifying underlying factors for ethnic and gender discrepancies between treatment groups. Citation Format: Jeremy Somerson, Isaac Kim, Rajiv Rajani. Ethnic and gender disparities in limb-salvage rates among pediatric sarcoma patients. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A51.