Bone metastases from renal cell carcinoma are aggressive, osteolytic lesions that often require operative intervention for fracture prophylaxis, fracture fixation or palliation. The lesions are hypervascular and intraoperative bleeding is a serious challenge for the orthopaedic surgeon. The purpose of this study was to determine the efficacy of preoperative tumour embolization in reducing blood loss during operative management of renal cell carcinoma metastases to bone. Patients were identified from a prospectively accumulated database (1996–2006). Inclusion criteria included operative management for renal cell metastasis to the pelvis or appendicular skeleton. Patients that were not embolised preoperatively due to renal insufficiency or obesity were excluded. Embolizations were performed the day of surgery by an interventional radiologist. Post-embolization runs were used to determine the percentage of blood flow reduction to the tumour. Variables analyzed included patient age, gender, location of tumour, surgical procedure, surgical time, number of units of packed red blood cells (PRBC) transfused, estimated intraoperative blood loss (EBL) and percentage embolised according to the post-embolization run. Student’s t-test was used to determine the effects of percentage embolization on EBL and number of units of transfused PRBCs. Thirty-five cases (twenty-eight patients) met the inclusion criteria. There were twenty males and eight females with an average age of sixty-five years (range, forty-three to eighty-nine years). The most common metastatic sites were the femur (nineteen cases), humerus (seven cases) and pelvis (six cases). There were ten cases of intramedullary nailing and twenty-five cases of tumor resection and reconstruction. Average surgical time was 4.5 hours (range, 0.75–10 hours) and average EBL was 1.5 litres (range, 0.25–12 litres). Embolization that successfully blocked at least 75% of the blood flow to the tumour significantly decreased surgical EBL (3.2 vs 0.6 litres, P<
0.05) and units of PRBCs transfused (5.6 vs 1.9, P=0.05) compared to those that did not. Two embolization-associated complications occurred including one case of toe gangrene and one case of muscle ischemia. Preoperative embolization significantly reduces blood loss and red blood cell transfusions resulting from surgical stabilization of renal cell metastases to bone. Close communication between the orthopaedic surgeon and interventional radiologist is imperative to maximise these benefits.
Giant cell tumor (GCT) of bone is an osteolytic tumor that is locally aggressive and potentially metastatic. The pathogenesis of GCT is poorly understood. The purpose of this study was to harvest and culture primary cell lines from clinical specimens of GCT of bone and identify specific bone degradation proteases (matrix metalloproteinases: MMP-2, MMP-9) produced by the neoplastic stromal cells in vitro. With approval by the McMaster University Biohazards and Ethics Review Boards, we acquired consent from five patients with GCT of bone, and harvested specimens intraoperatively. The specimens were chopped in DMEM containing 10% Fetal Bovine Serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. The cell suspensions were incubated at thirty-seven degrees (5% CO2 and 95% air) and cultivated. The cells were grown to confluence and taken through several passages until only proliferative cells were present. Immunocytochemistry with TRAP (Tartrate Resistant Acid Phosphatase) was used to confirm the stem cell origin of the propagative cells. Protein electrophoresis with embedded gelatin was used for detecting protease activity (MMP-2, MMP-9) on cell lysates and medium. P-aminophenyl mercuric acetate (APMA) was used to activate and ethylenediaminetetraacetic acid (EDTA) was used to block MMP-2 and MMP-9 activity. Our controls included serum free media, Human Osteosarcoma and Fibroblast cell lines. Immunocytochemistry with TRAP confirmed that our propagative cells were not hematopoietic in origin but rather mesenchymal. Protein electrophoresis on cell lysates and medium identified the protease activity of MMP-2 and MMP-9 with lytic bands at appropriate molecular weights. APMA activated MMP-2 more than MMP-9, as indicated by increased relative density of bands. EDTA blocked the activity of both MMPs. Our study confirmed the ability to cultivate the neoplastic stromal cells of GCT of bone from clinical specimens. Protein electrophoresis showed that activated MMP-2 and MMP-9 are secreted from the neoplastic stromal cells in vitro, suggesting a role for the tumor cells in bone destruction. These results are intriguing, as novel therapies in specific MMP inhibitors are currently underway for numerous disease processes.