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Background: Difficult resection of tumors from regions with complex local anatomy, such as the pelvis and sacrum, is likely to result in inadequate surgical margins (intralesional or marginal); this is because three-dimensional osteotomy is difficult particularly around the acetabulum. Additionally, removal of the joint makes reconstruction very difficult; thus, retention of good function also becomes difficult. In musculoskeletal oncology, computer navigation systems are still not widely used to prevent tumor-positive margins. We performed wide excision with guidance from a computer navigation system and reconstruction using frozen bone autografts for malignant pelvic bone tumors in two patients, and we obtained excellent functional and oncological outcomes. Here we present these patients and discuss our approach.Case Presentation: Case 1: A 12-year-old girl presented with Ewing sarcoma of the left pelvis (PI-II). We performed wide excision assisted by a computer navigation system with the osteotomy of the load surface of acetabulum and reconstruction using a frozen bone autograft. At the final follow-up, she showed excellent function and was alive without the disease. Moreover, she did not have osteoarthritis of the left hip joint. Case 2: A 71-year-old woman presented with dedifferentiated chondrosarcoma of the right pelvis (PII-III). We performed wide excision assisted by a computer navigation system with osteotomy avoiding load surface of the acetabulum and reconstruction using a frozen bone autograft; there was no tumor at the load surface. At the final follow-up, she showed good function, was alive without the disease, and did not have osteoarthritis of the left hip joint.Conclusions: Wide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft are very useful for the management/treatment of extremely difficult cases such as malignant pelvic bone tumors, particularly those including the acetabulum. [ABSTRACT FROM AUTHOR]

Abstract: Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a ligand‐activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti‐inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity. [ABSTRACT FROM AUTHOR]

Background: The p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs.Questions/purposes: We compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients.Methods: During tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations.Results: In terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency values (normal adipose tissue versus ALT/WDL) (± SD) were 0.34 (SD, ± 0.13; 95% CI, 0.24-0.44) versus 0.25 (SD, ± 0.10; 95% CI, 0.18-0.33; p = 0.22). By contrast, we found greater osteogenic differentiation potency in MSCs derived from ALT/WDL than in MSCs derived from normal fat. The mean differentiation potency values (normal adipose tissue versus ALT/WDL) (±SD) based on ALP staining was 1.0 versus 17 (SD, ± 36; 95% CI, -2.8 to 38; p = 0.04). However, we found no differences based on alizarin red S staining; mean differentiation potency value (normal adipose tissue versus ALT/WDL) (± SD) was 1.0 versus 4.2 (SD, ± 4.8; 95% CI, 1.3-7.2; p = 0.58). The gap of osteogenic differentiation potency between MSCs from normal adipose tissue and ALT/WDL was decreased as MDM2-inhibitor Nutlin-3 concentration increased.Conclusions: MSCs derived from ALT/WDL had higher osteogenic differentiation potency based on ALP staining, which disappeared as Nutlin-3 concentration increased, suggesting that could be caused by amplified MDM2 in ALT/WDL. Future laboratory studies might mechanistically confirm the gene and protein expression, and based on the mechanism of the gap of differentiation potency, if p53 contrast between MSCs in tumor and normal tissue could be stimulated, less-toxic and more-effective differentiation therapy to MSCs in malignancies might be developed. [ABSTRACT FROM AUTHOR]