Management of sarcomas possibly involving the knee joint when to perform extra-articular resection of the knee joint and is it safe?

We reviewed the oncological and functional outcomes of patients treated for a primary sarcoma possibly involving the knee joint and present an algorithm to guide treatment. The records of 76 patients who had a primary bone or soft tissue sarcoma possibly invading the knee between 1996 and 2012 were identified. Mean age and follow-up was 32 years (9-74) and 64 months (12-195), respectively. Patients were grouped according to the resection (Intra-articular [IAR] vs. Extra-articular [EAR] vs. Amputation/rotationplasty) for survival and functional outcomes. Overall 5 and 10 year survival was 61% and 53%, respectively. No differences in survival were found between the 3 groups (p = 0.55). Sixteen patients developed local recurrence with no difference between the groups. Mean MSTS score was 24.5 (12-30). Mean flexion at final follow-up was 106° (70-130°). We conclude that EAR of the knee allows for good oncologic and functional outcomes but with an increased risk of complications compared to IAR. Intra-operative assessment of joint involvement can be done in patients where joint infiltration by the tumour is not clear to avoid an unnecessary EAR. For chondrosarcoma patients with joint involvement, an EAR should be carefully considered because they present a significantly higher local recurrence risk.

Surface-associated protein from Staphylococcus aureus stimulates osteoclastogenesis: possible role in S. aureus-induced bone pathology.

OBJECTIVE: Staphylococcus aureus is the cause of bone destruction in osteomyelitis, bacterial arthritis and orthopaedic implant failure. We have previously shown that gentle saline extraction of S. aureus has revealed the presence of an extremely potent stimulator of osteoclast activation in both the murine calvarial bone resorption assay and the isolated chick osteoclast resorption assay. In order to investigate the mechanism of action of this surface-associated material (SAM), we have investigated its capacity to recruit osteoclasts. METHODS: The murine bone marrow osteoclast recruitment assay was used. The ability of the recruited cells to resorb dentine slices was also investigated. Results. The SAM from S. aureus dose dependently stimulated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and pit formation on dentine slices. Neutralization of the cytokines tumour necrosis factor alpha and interleukin (IL)-6 totally inhibited, but antagonism of IL-1 only partially blocked, the stimulated maturation of osteoclast-like cells. CONCLUSION: These findings suggest that bone destruction associated with local infection by S. aureus is due to the stimulation of osteoclast formation induced by the action of the easily solubilized SAM, and could explain the large numbers of osteoclasts found in infarcted bone in osteomyelitis.

Frequency of germline and somatic BRCA1 mutations in ovarian cancer.

Germline mutations in the BRCA1 tumor suppressor gene are thought to be the most common cause of hereditary ovarian cancer. The aim of this study was to explore further the role of BRCA1 alterations in the development of ovarian cancers. We sought to determine whether somatic BRCA1 mutations are ever present in ovarian cancers and whether mutation is always accompanied by loss of the wild-type allele. The entire coding region and intronic splice sites of BRCA1 were sequenced using genomic DNA samples from 103 unselected ovarian cancers. Thirteen clearly deleterious BRCA1 mutations and two variants of uncertain significance were found. Blood DNA was available in all but two cases and demonstrated that 4 of 13 mutations and both variants of uncertain significance were germline alterations, whereas in seven cases the mutation was a somatic change present only in the cancer. Using four microsatellite markers, loss of heterozygosity at the BRCA1 locus was found in all 15 ovarian cancers with BRCA1 sequence alterations, compared with only 58% of ovarian cancers that did not have BRCA1 mutations. BRCA1-associated ovarian cancers were characterized by serous histology and moderate histological grade. These data confirm prior reports suggesting that germline mutations in BRCA1 are present in about 5% of women with ovarian cancer. In addition, somatic mutations in BRCA1 occur in the development of some sporadic cases. The finding that both germline and somatic BRCA1 mutations are accompanied by loss of heterozygosity, suggests that loss of this tumor suppressor gene is a critical event in the development of these cancers.

Mycobacterium tuberculosis chaperonin 10 stimulates bone resorption: a potential contributory factor in Pott's disease.

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95-103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931-939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone-forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65-70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.