A novel surgical approach to lipomatous tumours of the deltoid region.

Resection of large lipomatous tumours in the subdeltoid region remains technically challenging due to the risk of injury to the axillary neurovascular bundle. We describe a novel deltoid release and reinsertion technique for resection of large lipomatous tumours of the sub-deltoid region and report the functional and oncologic outcomes of six patients who underwent this procedure. Three cases were diagnosed histologically as atypical lipoma and three cases were diagnosed as lipoma. There was one local recurrence in a case of an atypical lipoma. Rotator cuff function was comparable to that of the contralateral side in all cases and the average Constant Score adopted by the European Shoulder and Elbow Society was 84 (range 81 to 92) out of 100. We conclude that patients with large sub-deltoid lipomatous tumours who undergo resection through a previously undescribed deltoid release and reinsertion technique have excellent functional outcome with a low risk for recurrence.

Upregulation of MMP-13 via Runx2 in the stromal cell of Giant Cell Tumor of bone.

Giant Cell Tumor of bone (GCT) is an aggressively osteolytic and cytokine-rich bone tumor. Previous work in our lab has shown that matrix metalloproteinase-13 (MMP-13) is the principal proteinase expressed by the mesenchymal stromal cells of GCT. The Runx2 transcription factor is known to have a binding site in the MMP-13 promoter region, and we have previously found this transcription factor to be constitutively expressed in GCT stromal cells. The purpose of this study was to determine the role of Runx2 in MMP-13 regulation in GCT stromal cells. Following in vitro stimulation of GCT stromal cells with incremental concentrations of cytokine IL-1beta or TNF-alpha, the level of MMP-13 mRNA expression increased dramatically over 100-fold with a concomitant increase in MMP-13 protein expression. Inhibition of the ERK and JNK signaling pathways inhibited the upregulation of MMP-13 in these cells. Runx2 siRNA knockdown resulted in MMP-13 knockdown, and this effect was amplified following cytokine stimulation. Our study provides the first evidence that Runx2 may play a crucial role in cytokine-mediated MMP-13 expression in GCT stromal cells.

Collagenase expression and activity in the stromal cells from giant cell tumour of bone.

The characteristic bone destruction in giant cell tumour of bone (GCT) is largely attributed to the osteoclast-like giant cells. However, experimental analyses of bone resorption by cells from GCT often fail to exclude the neoplastic spindle-like stromal cells, and several studies have demonstrated that bone resorption by GCT cells is increased in the presence of stromal cells. The spindle-like stromal cells from GCT may therefore actively contribute to the bone resorption observed in the tumour. Type I collagen, a major organic constituent of bone, is effectively degraded by three matrix metalloproteinases (MMPs) known as the collagenases: MMP-1, MMP-8 and MMP-13. We established primary cell cultures from nine patients with GCT and the stromal cell populations were isolated in culture. The production of collagenases by primary cultures of GCT stromal cells was determined through real-time PCR, western blot analysis and a multiplex assay system. Results show that the cells produce MMP-1 and MMP-13 but not MMP-8. Immunohistochemistry confirmed the presence of MMP-1 and MMP-13 in paraffin-embedded GCT tissue samples. Medium conditioned by the stromal cell cultures was capable of proteolytic activity as determined by MMP-1 and MMP-13-specific standardized enzyme activity assays. The spindle-like stromal cells from GCT may therefore actively participate in the bone destruction that is characteristic of the tumour.

Matrix Metalloproteinase Activity in the Stromal Cell of Giant Cell Tumor of Bone.

Giant cell tumor of bone (GCT) is a destructive and potentially metastatic bone tumour in which the characteristic giant cells have classically been considered the culprits in bone destruction. However, the neoplastic element of the tumour consists of propagative osteoblast-like stromal cells that may play a role in bone resorption. The objectives of this study were to determine the expression and activity of the gelatinases, matrix metalloproteinase (MMP)-2 and -9, in GCT stromal cells, and to determine if these cells have bone-resorbing capabilities. We performed immunohistochemistry on clinical specimens, and real-time polymerase chain reaction (PCR) and zymography on cell lysates and conditioned media from cultured clinical GCT specimens in order to evaluate the expression and activity of MMP-2 and-9 in GCT stromal cells. Our results support the fact that GCT stromal cells express MMP-2 and MMP-9 and are capable of gelatin degradation in vitro. These cells may therefore play a role in bone destruction in GCT.

A systematic meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma.

BACKGROUND: The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival. METHODS: A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model. RESULTS: Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy. CONCLUSIONS: This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.

The use of free vascularized fibular grafts in skeletal reconstruction for bone tumors in children.

The reconstruction of large skeletal defects in children following resection of a bone tumor presents a unique challenge to the orthopaedic surgeon. Issues in this population that are not present in the adult population include significant remaining growth potential, the desire for biologic preservation of the joint surface, and the need for a long-term viable reconstruction in patients who are anticipated to survive for decades. The use of a free vascularized fibular graft, supplied by the peroneal vessels in intercalary fibular grafts and the anterior tibial vessels in proximal fibular grafts, has been shown to provide biologic reconstruction that successfully addresses these issues in the pediatric population. Specific techniques are applied in the upper and lower extremity to provide long-term excellent functional results. Experience in microvascular surgery and careful postoperative care are required for the success of these procedures.

Properties of the stromal cell in giant cell tumor of bone.

The histiogenesis and mechanisms of bone destruction in giant cell tumor (GCT) of bone are not well understood. We asked whether the spindle-like stromal cells of GCT of bone exhibit osteoblastic properties, and whether the stromal cells produce active matrix-degrading proteases in vitro. We performed immunohistochemistry on 17 paraffin-embedded archival specimens with a pathologic diagnosis of GCT with monoclonal antibodies for the osteoblastic lineage markers osteopontin, osteonectin, and osteocalcin. The average staining grade for the 17 specimens was highest for osteonectin, followed by osteopontin, and osteocalcin. Primary cell cultures of GCT stromal cells were prepared from two fresh tumor specimens. Western blots were used on the cell lysates and media to detect osteocalcin precursor and the matrix-degrading proteases MMP-2 and MMP-9. We found the stromal cells in culture produce osteocalcin precursor, indicating osteoblastic lineage. The cells also express both the active and inactive isoforms of MMP-2 and MMP-9. Gelatinase assays confirmed the activity of the proteases in vitro. The spindle like stromal cells of GCT have characteristics of osteoblast progenitors and produce active matrix-degrading proteases. These cells may therefore play a central role in bone destruction.

Outcomes of an anatomically based approach to metastatic disease of the acetabulum.

Metastatic disease of the acetabulum is a common and challenging surgical problem. We asked whether acetabular reconstruction for metastatic bone disease improves functional outcome with an acceptable risk of surgical morbidity. We also asked if primary tumor type and the presence of visceral metastases predicted patient survival. We analyzed prospectively accumulated records of 62 consecutive patients who underwent 63 hip arthroplasties with acetabular reconstruction. Operative technique was guided by the extent of dome and column involvement. Demographics, functional status in the form of the Eastern Cooperative Oncology Group (ECOG) score, and survival data were analyzed. Functional scores improved from an average of 2.6 preoperatively to 1.1 postoperatively. Four patients had postoperative complications for which we performed further surgery. Mean survival for the patients with breast cancer was longer at 21 months compared to 9 months for the patients with other primary malignancies. Patients who did not present with visceral metastases had longer survival than those with visceral metastases. Despite the moderate risk of operative complications, an anatomically based approach to reconstruction of acetabular defects from metastatic disease improves functional outcome. Breast cancer as the primary malignancy and the absence of visceral metastases predicted longer survival.

Transfusion practices for elective orthopedic surgery.

BACKGROUND: Use of blood conservation techniques in elective surgery reduces the risk of infection and transfusion reactions that result from using allogeneic blood products. We examined the transfusion practice and blood conservation strategies for elective orthopedic procedures in 19 Canadian hospitals. METHODS: We reviewed the medical records of patients who underwent total hip or knee joint arthroplasty between June 1998 and January 1999 in a convenience sample of 19 hospitals to determine the pre- and postoperative hemoglobin concentrations, concurrent medical conditions, participation status in an autologous blood donation program, use of other blood conservation techniques, and occurrence of allogeneic and autologous transfusions. Patients were considered eligible for autologous blood donation if they weighed at least 25 kg, were in good general health without major cardiac conditions and had a hemoglobin concentration of at least 110 g/L. RESULTS: We reviewed 4535 medical records. Of the 4422 patients whose eligibility status was known, 2561 (57.9%) were eligible to participate in an autologous blood donation program. Only 842 (18.6%) of the patients predonated blood. Patients who did not predonate blood were older (mean age 70.1 v. 63.8 years) and were more likely to have concomitant medical conditions (60.3% v. 37.9%) than those who did predonate. Overall, 30.6% (95% confidence interval [CI] 29.1%-32.1%) of the patients who did not predonate blood received allogeneic transfusions. For patients who predonated, the rate of allogeneic transfusion was 14.1% (95% CI 11.8%-16.5%). The frequency with which blood conservation techniques other than autologous blood donation were used was minimal (in 2.4% of all cases). INTERPRETATION: The use of blood conservation techniques among hospitals in Canada remains low. Only a minority of eligible patients participated in an autologous blood donation program.