Evaluation of chemotherapy response in osteosarcoma with FDG-PET.

OBJECTIVE: The objective of this study is to evaluate the utility of positron emission tomography (PET) with 2-deoxy-[(18)F] fluoro-D-glucose (FDG) in the assessment of the chemotherapy response of osteosarcoma when compared with the degree of necrosis determined histologically. METHODS: Whole-body FDG-PET scan was performed on 11 patients with osteosarcoma. All patients received neoadjuvant chemotherapy. The tumor size changes on magnetic resonance imaging; FDG-PET standardized uptake values prior to (SUV(1)) and following (SUV(2)) chemotherapy were analyzed and correlated with response to chemotherapy as assessed using histopathology in surgically excised tumors. Nine patients underwent FDG-PET scan both prior to and following neoadjuvant chemotherapy. The remaining two patients were examined only prior to surgery. RESULTS: Histologically, five patients had a good histologic response to chemotherapy (>==90% necrosis). The changes in tumor size did not correlate with histologic response (P > 0.05). SUV(2) with good response was significantly lower than that with poor response (1.93 +/- 0.50, 5.86 +/- 2.55, respectively). Both the positive and negative predictive values of the SUV(2) of less than 2.5 for a good response were 100%. Patients with good response showed a significantly higher ratio of SUV2 to SUV1 (SUV(2:1)) than patients with poor response (0.74 +/- 0.11, 0.26 +/- 0.39, respectively, P < 0.05). The positive and negative predictive values of SUV(2:1)

Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification.

Leptin has been suggested to mediate a variety of actions, including bone development, via its ubiquitously expressed receptor (Ob-Rb). In this study, we investigated the role of leptin in endochondral ossification at the growth plate. The growth plates of wild-type and ob/ob mice were analyzed. Effects of leptin on chondrocyte gene expression, cell cycle, apoptosis and matrix mineralization were assessed using primary chondrocyte culture and the ATDC5 cell differentiation culture system. Immunohistochemistry and in situ hybridization showed that leptin was localized in prehypertrophic chondrocytes in normal mice and that Ob-Rb was localized in hypertrophic chondrocytes in normal and ob/ob mice. Growth plates of ob/ob mice were more fragile than those of wild-type mice in a mechanical test and were broken easily at the chondro-osseous junction. The growth plates of ob/ob mice showed disturbed columnar structure, decreased type X collagen expression, less organized collagen fibril arrangement, increased apoptosis and premature mineralization. Leptin administration in ob/ob mice led to an increase in femoral and humeral lengths and decrease in the proportional length of the calcified hypertrophic zone to the whole hypertrophic zone. In primary chondrocyte culture, the matrix mineralization in ob/ob chondrocytes was stronger than that of wild-type mice; this mineralization in both types of mice was abolished by the addition of exogenous leptin (10 ng/ml). During ATDC5 cell differentiation culture, exogenous leptin at a concentration of 1-10 ng/ml (equivalent to the normal serum concentration of leptin) altered type X collagen mRNA expression and suppressed apoptosis, cell growth and matrix calcification. In conclusion, we demonstrated that leptin modulates several events associated with terminal differentiation of chondrocytes. Our finding that the growth plates of ob/ob mice were fragile implies a disturbance in the differentiation/maturation process of growth plates due to depletion of leptin signaling in ob/ob mice. These findings suggest that peripheral leptin signaling plays an essential role in endochondral ossification at the growth plate.

Osteosarcoma after bone marrow transplantation for acute lymphoblastic leukemia.

A male patient initially diagnosed with acute lymphoblastic leukemia at age 9 years received chemotherapy (total body irradiation, 12 Gy) followed by allogeneic bone marrow transplantation. Since then, he had been in complete remission. Three years after the bone marrow transplantation, he complained of increasing pain in the right knee. Radiological and histological examinations led to a diagnosis of conventional osteosarcoma. We performed intensive chemotherapy and wide local excision of the osteosarcoma. Intensive chemotherapy was accomplished as planned, although recovery from myelosuppression was delayed during some cycles. Polymerase chain reaction-single-strand conformation polymorphism analysis revealed a p53 gene mutation in exon 7 in the tumor cells, but not in skin or blood cells. This is an extremely rare case of osteosarcoma after bone marrow transplantation.