Joseph Benevenia

Synovial sarcoma: frequency of nonaggressive MR characteristics.

PURPOSE Our objective was to examine the MR characteristics of synovial sarcoma and determine the frequency of a nonaggressive imaging appearance. METHOD Fifteen patients with histologically confirmed cases of synovial sarcoma and prior MR examinations were seen. Retrospective analysis of imaging features included assessment of size, margins, homogeneity, internal architecture, T1- and T2-weighted signal intensities, and bone invasion. RESULTS Five of 15 patients (33%) had well circumscribed, homogeneous lesions with a mean length of 4.8 cm. The T1-weighted signal intensity was either isointense to muscle or greater in signal intensity than muscle. The T2-weighted images demonstrated signal intensity equal to or greater than fat. The remaining 10 lesions were larger (mean length of 11.3 cm) with mild to complex levels of inhomogeneity and margins that varied from well circumscribed to infiltrating. CONCLUSION There are two sets of MR features seen with synovial sarcoma. Small lesions of -5 cm can demonstrate a nonaggressive appearance with well circumscribed margins and homogeneous signal intensity. These tumors could be confused with benign lesions, resulting in inappropriate surgical intervention like excisional biopsies through transverse incisions. This would make future surgery more difficult. Larger lesions tend to be more heterogeneous in signal intensity.

Treatment of advanced metastatic lesions of the acetabulum using the saddle prosthesis

Current methods of treating advanced patients with metastatic periacetabular disease are complex and result in high complication rates. The purpose of this study was to show whether the implantation of the saddle prosthesis would serve as an additional tool to help treat metastatic disease in these patients. From 1991 to 2003, 20 patients with advanced metastatic periacetabular lesions (Harrington Class III) were treated using the saddle prosthesis. Goals of surgery were a decrease in pain, functional restoration, and ambulation. The mean age was 61 years. Average length of followup was 20 months. Postoperatively, ambulation was achieved in 16 of 20 patients. There were four postoperative complications (20%) in three patients. Surgical goals were met in 18 of 20 patients. The MSTS–ISOLS emotional score was 2.9 of 5. The average total MSTS–ISOLS score was 16.6 of 30 (55%). Using the Allan scoring system consisting of analgesia, independence and ambulation, and mobility, all scores had significant improvements postoperatively. Careful surgical indications and technique should result in a stable, functional reconstruction allowing patients the ability to ambulate outside the house with a cane. Patients can expect to be emotionally satisfied with the procedure while using nonnarcotic analgesia and can expect an improved quality of life despite bone metastasis.

Pathologic supracondylar fracture due to osteolytic pseudotumor of knee following cementless total knee replacement

Wear debris of polyethylene, polymethylmethacrylate, and metal have been recognized to be associated with foreign body reactions, osteolysis, and aseptic prosthetic loosening after joint replacement arthroplasty. Further, foreign body reaction due to the presence of extensive wear debris can cause aggressive granulomatous lesions and pathologic fracture. To our knowledge, there has been no previous report of pathologic fracture of the femur due to an agressive pseudotumor. This report describes a case of pathologic supracondylar fracture of the femur 6 years and 5 months after cementless total knee replacement arthroplasty. The fracture occurred through an aggressive expanding soft tissue mass that was a tumorlike lesion secondary to polyethylene wear debris. The lesion was associated with massive osteolysis around the femoral component of the total knee prosthesis.

Magnetic resonance imaging of intraosseous lipomas: a radiologic-pathologic correlation

Four patients with intraosseous lipomas were studied with magnetic resonance imaging. The imaging features and histology of each tumor were compared. Magnetic resonance imaging was very helpful in establishing a pathologic diagnosis. If a severe degree of involution was present, then the magnetic resonance findings could be ambiguous, making diagnosis more difficult.

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases

Abstract Purpose. The objective of this study was to evaluate synovial sarcomas for the expression of oncogenic proteins (Her2/neu, EGFR, Bcl-2, p53) and proliferation markers (Ki-67, Topoisomerase 2α), as possible markers of prognostic significance. Methods. From 17 patients with synovial sarcomas 19 tumors (15 primary, 2 recurrent, and 2 metastatic) were selected on the basis of characteristic histology, the expression of at least one epithelial marker, and/or the presence of t(X;18). Adequate follow-up was available in all cases. Results. The tumors were tested immunohistochemically and were found to express multiple oncogenic proteins. Four of 19 synovial sarcomas (21%) demonstrated nuclear over-expression of p53 protein; 18 of 19 tumors (94%) stained positive for Bcl-2; and 13 of 19 tumors (68%) were immunoreactive with EGFR. Of particular interest was the frequent expression of Her2/neu, an oncogenic protein more commonly observed in epithelial neoplasms. Ten of 19 tumors (52%, 7 monophasic and 3 biphasic) showed positive cytoplasmic and membranous staining with Her2/neu (HercepTest, DAKO). The staining intensity ranged from 1+ to 2+. Cellular expression of Her2/neu was independent of EGFR positivity and showed no association with proliferative activity of the tumors. FISH analysis of eight positive cases showed no evidence of Her2/neu gene amplification. Among the non-metastatic tumors, we found a significant correlation between Ki-67 and Topoisomerase 2α. Spearmans correlation co-efficient was 0.86 with P=0.001 (n=17). Conclusions. In this relatively small series of cases, we found no definite correlation between the over-expression of Her2/neu and clinical outcome. The over-expression of p53 was significantly associated with clinical outcome (Fishers exact test, P=0.02).

Mesenchymal stem cells accelerate bone allograft incorporation in the presence of diabetes mellitus

Allograft (Allo) incorporation in the presence of a systemic disease like diabetes mellitus (DM) is becoming a major issue in the orthopedic community. Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from adult, whole bone marrow and have been shown to induce bone formation in segmental defects when combined with the appropriate carrier/scaffold. The objectives of this study were to analyze the effect of DM upon Allo incorporation in a segmental rat femoral defect and to also investigate MSC augmentation of Allo incorporation. Segmental (5 mm) femoral defects were created in non‐DM and DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature bone in the DM/DBM group compared to its non‐DM counterpart (p < 0.001). However, there was significantly more mature bone in the DM/MSC group when compared to the DM/DBM group at both 4 and 8 weeks (p < 0.001 and p = 0.004). Furthermore, significantly more bone formation was observed in the DM/MSC group compared to the DM/DBM group at the 4‐week time point (p < 0.001). The results of this study suggest that MSC are a potential adjunct for bone regeneration when implanted in an orthotopic site in the presence of DM.

HER-2/neu and p53 in Osteosarcoma: An Immunohistochemical and Fluorescence In Situ Hybridization Analysis

The overexpression of HER-2/neu and p53 has been associated with poor outcome in many neoplasms. Their role in patients with osteosarcoma is unclear. We studied the expression of HER-2/neu and p53 in 22 osteosarcoma samples (from 20 patients—2 had locally recurrent disease) biopsied at the University of Medicine and Dentistry of New Jersey (UMDNJ) from 1996–2000 using both immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Fourteen patients (14 samples) presented with Stage II and 6 patients (8 samples) presented with Stage III disease. Median follow-up is two years (range one year to five years). Four of 22 (18%) samples showed focal membranous or cytoplasmic positivity for HER-2/neu and six of 22 samples (27%) showed nuclear positivity for p53 by IHC analysis. In contrast, none of 22 tested samples showed gene amplification for HER-2/neu by FISH analysis. Seven of 13 HER-2/neu and p53 negative patients (54%) are currently disease free (between one year to five years). In this sample of patients, the HER-2/neu oncogene is not overexpressed or amplified in osteosarcoma; six of 22 samples (27%) showed overexpression of p53 by IHC analysis. By FISH, none of the samples demonstrated deletion of p53. Neither HER2/neu nor p53 expression was important for the biology of osteosarcoma in this population.

Reconstruction of musculoskeletal defects following oncologic resection in 76 patients.

Between 1990 and 2002, 76 patients underwent 102 muscle flap reconstructions for extremity sarcomas. The patients had radical resection with immediate reconstruction. Reconstructions were performed by the Musculoskeletal Oncology and Plastic Surgery services. The mean age of our patients was 39.1 years. Patients were studied for a mean of 25.4 months. There were 79 pedicle flaps and 23 free flaps. Complications occurred in 23.7% of patients, including wound necroses, seromas, postoperative bleeding, postoperative infections, and flap loss. Five patients required a secondary flap procedure. The overall flap survival rate was 98%. Three patients had local recurrences. Sixteen patients (21.1%) have died of their disease. Five patients are alive with metastases. In 54 patients, Musculoskeletal Tumor Society (MSTS) functional evaluation scores averaged 27.1 (range, 12–30). In this large series of patients, we have demonstrated that, although minor complications are common, functional limbs can be salvaged following oncologic resection from the extremities.

Prophylactic antibiotic regimens in tumour surgery (PARITY): protocol for a multicentre randomised controlled study

Introduction Limb salvage with endoprosthetic reconstruction is the standard of care for the management of lower-extremity bone tumours in skeletally mature patients. The risk of deep postoperative infection in these procedures is high and the outcomes can be devastating. The most effective prophylactic antibiotic regimen remains unknown, and current clinical practice is highly varied. This trial will evaluate the effect of varying postoperative prophylactic antibiotic regimens on the incidence of deep infection following surgical excision and endoprosthetic reconstruction of lower-extremity bone tumours. Methods and analysis This is a multicentre, blinded, randomised controlled trial, using a parallel two-arm design. 920 patients 15 years of age or older from 12 tertiary care centres across Canada and the USA who are undergoing surgical excision and endoprosthetic reconstruction of a primary bone tumour will receive either short (24 h) or long (5 days) duration postoperative antibiotics. Exclusion criteria include prior surgery or infection within the planned operative field, known colonisation with methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at enrolment, or allergy to the study antibiotics. The primary outcome will be rates of deep postoperative infections in each arm. Secondary outcomes will include type and frequency of antibiotic-related adverse events, patient functional outcomes and quality-of-life scores, reoperation and mortality. Randomisation will be blocked, with block sizes known only to the methods centre responsible for randomisation, and stratified by location of tumour and study centre. Patients, care givers and a Central Adjudication Committee will be blinded to treatment allocation. The analysis to compare groups will be performed using Cox regression and log-rank tests to compare survival functions at α=0.05. Ethics and dissemination This study has ethics approval from the McMaster University/Hamilton Health Sciences Research Ethics Board (REB# 12-009). Successful completion will significantly impact on clinical practice and enhance patients’ lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in Orthopaedic Oncology will follow.

Role of local insulin augmentation upon allograft incorporation in a rat femoral defect model

Each year, over one million orthopedic operations are performed which a bony defect is presence, requiring the use of further augmentation in addition to bony fixation. Application of autogenous bone graft is the standard of care to promote healing of these defects, but several determents exist in using autogenous bone graft exist including limited supply and donor site morbidity. Prior work has demonstrated that local insulin application to fracture sites promote fracture healing, but no work has been performed to date in its effects upon defect healing/allograft incorporation. The goal of this study was to examine the potential role of local insulin application upon allograft incorporation. Microradiographic, histologic, and histomorphometric analysis outcome parameters showed that local insulin significantly accelerated new bone formation. Histological comparisons using predetermined scoring systems demonstrated significantly greater healing in femora treated with insulin compared to control femora (p < 0.001). Quantitatively more bone production was also observed, specifically in areas of endosteal (p = 0.010) and defect (p = 0.041) bone in femora treated with local insulin, compared to control femora, 6 weeks after implantation. This study demonstrates the potential of local insulin as an adjunct for the treatment of segmental defect and allograft incorporation.