Clinical and radiological long-term results after operative treatment of chondroblastoma.

INTRODUCTION: The aim of this study was the investigation of radiological and clinical long-term results after surgery for chondroblastoma in a single orthopedic oncological center. METHOD: As much as 24 patients were enrolled in the study using an in-house tumor data-base (age, sex, patient history, clinical symptoms, type of surgery, complications, and histological results), radiological findings (localization/size of the lesion, Lodwick-classification, Enneking-stages, and local recurrence), and clinical investigation (Enneking score). Mean follow-up was 8 years. RESULTS: Preferred sites were the knee-joint (distal femur 6, proximal tibia 6), followed by the proximal humerus (8), and the proximal femur. As much as 3 lesions were judged inactive, 13 active, and 8 aggressive. Apart from one case, all lesions were treated by curettage and filling of the defect by bone cement and/or cancellous bone chips. Only one patient suffered local recurrence after primary resection of the tumor (4.2%). About 87.5% of our patients reached a very good or good functional result (Enneking score 28-30). CONCLUSION: Our results further support curettage and defect filling even of active/aggressive chondroblastoma. If performed betimes, the surgical therapeutic concept of accurate intralesional curettage with or without local adjuvant therapy and defect packing with cancellous bone grafts and/or bone cement assures a high chance of joint preservation along with a low rate of recurrence and good functional long-term results.

Silencing of the UCHL1 gene in giant cell tumors of bone.

Giant cell tumors are heterogeneous tumors consisting of multinucleated giant cells, fibroblast-like stromal cells and mononuclear histiocytes. The stromal cells have been identified as the neoplastic cell population, which promotes the recruitment of histiocytes and the formation of giant cells. Strong evidence exists that these cells develop from mesenchymal stem cells (MSCs) but little is known about the molecular mechanisms involved in GCT tumorigenesis. The aim of our study was the identification of cancer-related genes differentially expressed in GCTs compared to MSCs in order to identify possible targets for aberrant promoter methylation, which may contribute to MSC transformation and GCT development. Gene expression of 440 cancer-related genes was analyzed by DNA microarrays in GCT stromal cells and bone marrow-derived MSCs (BMSCs) isolated from the same patient (n = 3) to avoid interindividual variations. Differential expression was identified for 14 genes, which could be confirmed by quantitative PCR in further 21 GCT and 10 BMSC samples. The most pronounced difference in gene expression was detected for UCHL1, an important regulator of the ubiquitin proteasome pathway. Methylation-specific PCR and bisulfite sequencing revealed a strong methylation of the CpG island covering the UCHL1 promoter in GCT stromal cells, whereas methylation was completely absent in BMSCs. UCHL1 expression in stromal cells could be restored by the methylation inhibitor 5-aza-dC. These data demonstrate that the UCHL1 gene is inactivated in GCTs but not in MSCs, suggesting a possible role of UCHL1 in MSC transformation and GCT development.

Ten-year survival of the cemented MS-30 femoral stem: increased revision rate in male patients.

This retrospective study evaluated the clinical and radiographic results of 337 consecutive matte surfaced, straight cemented MS-30 femoral stems implanted with first -to second-generation cementing technique. The median age of the patients at time of surgery was 72 (27-91) years. The median duration of follow-up was 10 (0.1-14) years. A Kaplan Meier survival analysis was performed. At follow-up, 113 patients (120 stems) had died and 13 (13 hips) were lost to follow-up. Twenty-one hips had undergone femoral revision, 13 for aseptic loosening, five for infection, two for dislocation and one for periprosthetic fracture. Survival analysis with revision of the femoral component for any reason as the end point was 91% (95% CI: 87-96) and for aseptic loosening 94% (95% CI: 90-97) at 12 years. Females (n = 245) with 99% (95% CI: 97-100) had significantly better survival compared to males (n = 92) showing 80% stem survival (95% CI: 67-91) at 12 years (p < 0.001). Median Harris Hip score (HHS) was 82 (25-100) points. Male patients had a higher activity score than female patients (p = 0.04). Femoral Dorr type A was associated with a higher risk of failure. THA with the MS-30 stem revealed satisfactory midterm results despite relatively crude cementing techniques. However, the higher revision rate in males and Dorr Type A is of concern.

Prognostic significance of drug-regulated genes in high-grade osteosarcoma.

About 25-45% of patients with high-grade osteosarcoma poorly respond to chemotherapy with an increased risk of relapse and the development of metastasis. Therefore, the aim of this study was the evaluation of the prognostic value of eight previously identified drug-regulated candidate genes on osteosarcoma therapy outcome. Gene expression of 8 candidate genes was analyzed in 35 formalin-fixed, paraffin-embedded, laser-microdissected osteosarcoma biopsies. The prognostic value of these genes was evaluated by the correlation of gene expression with therapy outcome, overall survival and event-free survival in univariate and multivariate analysis. Upon univariate analysis, the expression of MALAT-1, IMPDH2, FTL and RHOA significantly correlated with response to chemotherapy. Expression of all four genes was increased in the poor responder group. Upon multivariate analysis, IMPDH2 maintained its independent prognostic value (P=0.025). Concerning the overall survival of the patients, we observed a significant association with the expression of FTL, PHB, ATAD2, ACTN1 and RRM2 as well as lactate dehydrogenase serum levels. In the subgroups of patients with high expression of these genes and those with elevated lactate dehydrogenase levels, the mean overall survival was decreased 1.7-, 1.9-, 2.2-, 2.4-, 1.5- and 4.5-fold, respectively. Except RRM2, all genes and lactate dehydrogenase serum levels remained significant in the multivariate analysis. In addition, the event-free survival was significantly decreased in the subgroups of patients with high FTL, ATAD2 and IMPDH2 expression (1.8-, 6.3- and 2.4-fold, respectively). These data demonstrate that among the identified genes are valuable markers for the prediction of osteosarcoma therapy outcome. Especially IMPDH2 and FTL are promising candidates for the stratification of osteosarcoma patients into low- and high-risk groups. Owing to their involvement in drug action these genes may further be potential targets for the modulation of drug sensitivity.